US Pat. No. 9,718,803

UNSATURATED NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS

Amgen Inc., Thousand Oak...

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
the group

R1 is L1 or C1-4alk-L1;

Y is a bond or —C(?O);
each R2 and R3 is independently H, halo, CN, OH, —OC1-4alk, C1-4alk, C1-4haloalk, —C1-6alkORa, —C(?O)C1-4alk, —C(?O)NRaRa, or —C0-4alkNH—C(?O)Ra;

R4a is H, OH, halo, C1-4alk, or C1-4haloalk;

R4b is halo, CN, OH, OC1-4alk, C1-4alk, C1-4haloalk, or oxo;

R5 is 5- to 6-membered heteroaryl or unsaturated 9- to 10-membered bicyclo-heterocyclic ring; wherein each R5 ring is substituted by 0, 1, 2, 3, or 4 R8 groups;

R6 is independently H, halo, CN, OH, OC1-4alk, C1-4alk or C1-4haloalk;

m is 0;
each of p and q is independently 2; wherein the sum of p and q is 4;
the ring containing p and q contains 0 or 1 double bonds;
Ra is independently H or Rb;

Rb is independently phenyl, benzyl, or C1-6alk, wherein said phenyl, benzyl, and C1-6alk are substituted by 0, 1, 2 or 3 substituents which are, independently, halo, C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(?O)C1-4alk, or —N(C1-4alk)C1-4alk;

Rc is L2 or C1-4alk-L2;

each L1 is independently a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered
monocyclic ring or a saturated, partially-saturated or unsaturated 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring,
said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms which are O or S; L? is independently substituted by 0, 1,
2 or 3 R9 groups;

each L2 is independently a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered
monocyclic ring or a saturated, partially-saturated or unsaturated 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring,
said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms which are 0 or S; L2 is independently substituted by 0, 1, 2 or 3 R11 groups;

R8 is halo, CN, OH, C1-4alk, C1-4haloalk, —OC1-4haloalk, —C(?O)Rb, —C(?O)Rc, —C(?O)NHRb, —C(?O)NHRc, —S(?O)2Rb, —S(?O)2Rc, —S(?O)2NRaRa, Rb, Rc, NO2, ORb, or ORc;

R9 is halo, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —C(?O)Rb, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —OC(?O)Rb, —OC(?O)NRaRa, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(?O)Rb, —S(?O)2Rb, —S(?O)2NRaRa, —NRaRa, —N(Ra)C(?O)Rb, —N(Ra)C(?O)ORb, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Rb, —N(Ra)S(?O)2NRaRa, —NRaC1-6alkNRaRa, —NRaC1-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6alkN(Ra)C(?O)Rb, —C1-6alkOC(?O)Rb, —C1-6alkC(?O)NRaRa, —C1-6alkC(?O)ORa, oxo, or Rc;

and
R11 is halo, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —C(?O)Rb, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —OC(?O)Rb, —OC(?O)NRaRa, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(?O)Rb, —S(?O)2Rb, —S(?O)2NRaRa, —NRaRa, —N(Ra)C(?O)Rb, —N(Ra)C(?O)ORb, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Rb, —N(Ra)S(?O)2NRaRa, —NRaC1-6alkNRaRa, —NRaC1-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6alkN(Ra)C(?O)Rb, —C1-6alkOC(?O)Rb, —C1-6alkC(?O)NRaRa, —C1-6alkC(?O)ORa, or oxo.

US Pat. No. 9,145,450

THROMBOPOIETIC COMPOUNDS

AMGEN INC., Thousand Oak...

1. An isolated polynucleotide encoding a compound that binds to an myeloproliferative leukemia (mpl) receptor, wherein the
compound comprises the structure
(FC)_(L2)_TPO Mimetic Peptide (TMP)1—(L1)n—TMP2
wherein TMP1 and TMP2 are each independently selected from the group of core compounds comprising the structure:

X2—X3—X4—X5—X6—X7—X8—X9—X10 (SEQ ID NO: 48),

wherein,
X2 is selected from the group consisting of Glu, Lys, and Val;

X3 is selected from the group consisting of Gly and Ala;

X4 is Pro;

X5 is selected from the group consisting of Thr and Ser;

X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

X7 is selected from the group consisting of Arg and Lys;

X8 is selected from the group consisting of Gln, Asn, and Glu;

X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

L1 is a peptide linker, and L2 is a peptide linker; and

n is 0 or 1;
and physiologically acceptable salts thereof.

US Pat. No. 9,296,759

AMINO-OXAZINE AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of Formula I:
or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A1 is CR6;

A2 is CR5;

A3 is CR4;

A4 is N;

A5 is CR1;

A6 is CR8;

L is —C(?O)NH—, —C(?O)N(CH3)—, —NH—, —N(CH3)— or —O—;

each of R1, R4, R5 and R8, independently, is H, F, Cl, Br, CF3, OCF3, C1-6-alkyl, CN, OH, —OC1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein the C1-6-alkyl and C1-6-alkyl portion of —OC1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-3 substituents of F, oxo or OH;

each of R2 and R7, independently, is F, Cl, Br, I, haloalkyl, haloalkoxyl, C1-6-alkyl, C2-6alkenyl, C2-6alkynyl, CN, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl, —Si(CH3)3 or a ring selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, thienyl, pyrazolyl,
imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, diazolyl, triazolyl, tetrazolyl, pyranyl, dihydropyranyl, tetrahydropyranyl,
furanyl, dihydrofuranyl, tetrahydrofuranyl, pyrrolyl, dihydropyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl,
azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl, cyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl, wherein the C1-6-alkyl, C2-6alkenyl, C2-6alkynyl, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl and ring are optionally substituted, independently, with 1-3 substituents of R9;

R6 is H, halo, haloalkyl, haloalkoxyl, C1-6-alkyl, CN, OH, OC1-6-alkyl, NHC1-6-alkyl or C(O)C1-6-alkyl;

each R9, independently, is halo, haloalkyl, haloalkoxyl, CN, OH, NO2, NH2, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, piperazinyl, oxetanyl or dioxolyl, wherein
each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetanyl or dioxolyl, is optionally substituted
independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl,
butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl or oxetanyl;

X is —O— or —S—;
Y is —CH2; and

Z is CH2.

US Pat. No. 9,061,097

DRUG DELIVERY DEVICE

AMGEN INC., Thousand Oak...

1. A drug delivery device comprising:
a disposable housing having an interior surface defining an interior space, and an exterior surface;
a needle having a retracted state wherein the needle is withdrawn inside of the interior space and a deployed state wherein
a pointed end of the needle projects beyond the exterior surface of the housing;

an injector coupled to the needle to move the needle between the retracted and deployed states;
a reservoir disposed within the interior space, the reservoir configured to receive a volume of a drug and to be in fluid
communication with the needle; and

a controller coupled to the injector and the reservoir, the controller being configured to actuate the injector to move the
needle from the retracted state to the deployed state only once, to only once determine when a preselected time period has
elapsed after initiation of action of the controller, and to actuate the reservoir to deliver the volume of the drug to the
patient as a single bolus after the preselected time period has elapsed after the initiation of the action of the controller,
the controller disposed within the interior space and configured prior to being disposed within the interior space,

wherein the delivery device is wearable, disposable, and single-use.
US Pat. No. 9,283,260

LYOPHILIZED THERAPEUTIC PEPTIBODY FORMULATIONS

AMGEN INC., Thousand Oak...

1. A stable lyophilized therapeutic peptibody composition comprising a buffer, a bulking agent, a stabilizing agent, and a
surfactant wherein;
said buffer is 10 mM histidine;
the pH is 5.0;
said bulking agent is 4% w/v mannitol;
said stabilizing agent is 2% w/v sucrose;
said surfactant is 0.004% w/v polysorbate-20; and
said therapeutic peptibody is a dimer that comprises a structure of the formula
F1-(L1)e-P1(L2)f-P2 wherein:
F1 is an Fc domain, wherein the Fc domain is attached at the N-terminus of -L1-P1-L2-P2;

P1 and P2 are each independently selected from Table 6;

L1 and L2 are each independently linkers; and

e and f are each independently 0 or 1.

US Pat. No. 9,096,615

BRIDGED BICYCLIC AMINO THIAZINE DIOXIDE COMPOUNDS AS INHIBITORS OF BETA-SECRETASE AND METHODS OF USE THEREOF

AMGEN INC., Thousand Oak...

1. A compound of Formula I
or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A4 is CR4 or N;

A5 is CR5 or N;

A6 is CR6 or N;

A8 is CR8 or N, provided that no more than one of A4, A5, A6 and A8 is N;

each R1, independently, is H, F, Cl, C1-4alkyl, CH2OC1-4alkyl, cyclopropyl or CN, wherein the C1-4alkyl and CH2OC1-4alkyl are optionally substituted with 1-3 substituents of F;

R2 is C1-4alkyl, CH2OC1-4alkyl, CH2OH, CH2CN, C3-6cycloalkyl or CN, wherein each of the C1-4alkyl, CH2OC1-4alkyl and C3-6cycloalkyl is optionally substituted with 1-4 substituents of F;

each R3, independently, is H, halo, C1-4alkyl, OC1-4alkyl, CH2OC1-4alkyl, CH2OH, C1-4haloalkyl, cyclopropyl or CN, wherein each of the OC1-4alkyl, CH2OC1-4alkyl and cyclopropyl is optionally substituted with 1-4 substituents of F;

each of R4, R5, R6 and R8, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, S(O)oC1-4-alkyl, NHC1-4-alkyl or C(O)C1-4-alkyl;

R7 is —NH—R9, —NHC(?O)—R9, —C(?O)NH—R9, —O—R9 or —S—R9;

R9 is acetyl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl or a fully or partially unsaturated 5-, 6- or 7-membered monocyclic or 8-, 9- or 10-membered bicyclic ring formed
of carbon atoms, said ring optionally including 1-4 heteroatoms if monocyclic or 1-5 heteroatoms if bicyclic, said heteroatoms
selected from O, N or S, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl and ring are optionally substituted, independently, with 1-5 substituents of R10;

each R10, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propynyloxy, 2-butynyloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, tetrahydropyrrolyl,
piperazinyl, oxetan-3-yl, dioxolyl, —NHC(O)R11— or —C(O)NHR11, wherein each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propynyloxy, 2-butynyloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl or
dioxolyl, is optionally substituted independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, cyclopropylmethoxy, butyl,
butoxyl, isobutoxy, tert-butoxy, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, oxetan-3yl or a ring selected from oxazolyl, isoxazolyl, pyrazolyl, thiazolyl, isothiazolyl or oxadiazolyl wherein
the ring is optionally substituted independently with 1-5 substituents of F, Cl, CN or CH3;

R11 is C1-6alkyl, C1-6alkoxyl or C3-6cycloalkyl; and

n is 0, 1 or 2.

US Pat. No. 9,394,297

AMIDES AS PIM INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula 11d

wherein R is

wherein R1 is H, halo, C1-6 alkyl, amino, C1-6 alkylamino, C2-6 alkenylamino, C1-6 haloalkylamino, C1-6 alkylsulfonyl-C1-6 alkylamino, aminocarbonyl-C1-6 alkylamino, amino-C1-6 alkylamino, hydroxy-C1-6 alkylamino, C1-6 alkylsulfonylamino, carboxy-C1-6 alkylamino, C1-6 alkoxycarbonyl-C1-6 alkylamino, C1-6 alkoxy-C1-6 alkylamino, C1-6 alkoxycarbonylamino-C1-6 alkylamino, C1-6 alkoxy-C1-6 alkoxy-C1-6 alkylamino, C1-6 alkoxy-C1-6 alkylamino-C1-6 alkylamino, C1-6 alkylsulfonyl-C1-6 alkylamino-C1-6 alkylamino, substituted or unsubstituted C3-6 cycloalkylamino, substituted or unsubstituted C3-6 cycloalkyl-C1-6 alkylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted phenyl-C1-3 alkylamino, substituted or unsubstituted 3-7-membered heterocyclylamino, substituted or unsubstituted 3-7-membered heterocyclyl-C1-6 alkylamino, guanidinyl, —CONHRb, —NHC?ORb, —ORb, —S(?O)nRb, —CORc, unsubstituted or substituted aryl, unsubstituted or substituted aryl-C1-6 alkyl, unsubstituted or substituted aryl-C2-4 alkenyl, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted C3-6 cycloalkyl-C1-6 alkyl, unsubstituted or substituted 3-7-membered heterocyclyl-C1-6 alkyl or substituted or unsubstituted 3-7-membered heterocyclyl;

wherein n is 0, 1 or 2;
wherein Rb is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 aminoalkyl, C1-6 alkoxy-C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alksulfonyl-C1-6 alkyl, C2-6 alkenyl, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl-C1-2-alkyl or unsubstituted or substituted 5-6 membered heterocyclyl;

wherein Rc is H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl-C1-2-alkyl or unsubstituted or substituted 5-6 membered heterocyclyl;

wherein Re is H or Boc;

wherein Rf is H or methyl;

wherein Rg is H, fluoro or chloro;

wherein R2 is H or fluoro;

wherein R4 is H or methyl;

wherein R5 is H, C1-4 alkyl, C3-6 cycloalkyl, C1-4 aminoalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy-C1-4 alkyl, benzyloxy-C14 alkyl, C2-4 alkynyl, C3-6 cycloalkyl or benzyl; or wherein R4 and R5 together form C3-6 cycloalkyl or 4-6 membered saturated heterocyclyl;

wherein R6 is H; and

wherein R7 is H, or C1-3 alkyl; or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,365,522

PYRAZOLE AMIDE DERIVATIVE

AMGEN INC., Thousand Oak...

1. A compound represented by formula (I) or a pharmaceutically acceptable salt thereof:

wherein:
R1 is selected from F, Cl, Br, a C1 to C6 alkyl group substituted by 0, 1, 2 or 3 Ra groups and a C3 to C8 cycloalkyl group substituted by 0, 1, 2 or 3 Ra groups;

Y is selected from a C4 to C6 cycloalkyl group, a C6 to C9 bicycloalkyl group and a C6 to C9 spiroalkyl group, all of which are substituted by a R2 group, 0 or 1 R6 group and 0, 1, 2 or 3 R7 groups;

R2 is selected from —OH, —CO2H, —SO3H, —CONH2, —SO2NH2, a (C1 to C6 alkoxy)carbonyl group substituted by 0, 1, 2 or 3 Rc groups, a (C1 to C6 alkyl)aminocarbonyl group substituted by 0, 1, 2 or 3 Rc groups, a C1 to C6 alkylsulfonyl group substituted by 0, 1, 2 or 3 Rc groups, a C1 to C6 alkylaminosulfonyl group substituted by 0, 1, 2 or 3 Rc groups, a (hydroxycarbonyl)(C1 to C3 alkyl) group substituted by 0, 1, 2 or 3 Rc groups, a (C1 to C6 alkoxy)carbonyl(C1 to C3 alkyl) group substituted by 0, 1, 2 or 3 Rc groups, a (C1 to C6 alkyl)sulfonyl(C1 to C3 alkyl) group substituted by 0, 1, 2 or 3 Rc groups and a (C2 to C6 alkenyl)(C1 to C3 alkyl) group substituted by 0, 1, 2 or 3 Rc groups;

R6 and R7 are independently selected from H, F, —OH, —NH2, —CN, a C1 to C6 alkyl group substituted by 0, 1, 2 or 3 Rb groups and a C1 to C6 alkoxy group substituted by 0, 1, 2 or 3 Rb groups;

R3 is selected from H, F, Cl, —CH3 and —CF3;

R4 is selected from a C1 to C6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C2 to C6 alkenyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C2 to C6 alkynyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C1 to C6 alkoxy)(C2 to C4 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C6 to C10 aryl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a (5- to 10-membered heteroaryl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a C3 to C8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C3 to C8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C3 to C8 cycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C3 to C8 cycloalkenyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups and a (3- to 8-membered heterocycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 spiroalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C6 to C9 spiroalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 spiroheteroalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C5 to C9 bicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C5 to C9 bicycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 heterobicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, and a (C6 to C9 heterobicycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups;

R5 is selected from a C6 to C10 aryl group substituted by 0, 1, 2, 3, 4 or 5 Ri groups, a 5- to 10-membered heteroaryl group substituted by 0, 1, 2, 3, or 4 Ri groups, a C3 to C8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5Rj groups, a C3 to C8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5Rj groups and a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rj groups;

R8 and R9 are independently selected from H, F, —OH, —NH2, a C1 to C3 alkyl group substituted by 0, 1, 2 or 3 Rh groups, and a C1 to C6 alkoxy group substituted by 0, 1, 2 or 3 Rh groups; or R8 and R9 together form an oxo group or a thioxo group;

R12 is H; or R4 and R12 together are —CRmRm—CR13R14—CRmRm— or —CR13R14—CRmRm—CRmRm— to form a pyrrolidine ring;

R13 is selected from H, a C1 to C6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a C6 to C10 aryl group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a C6 to C10 aryloxy group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a (C2 to C6 alkenyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C2 to C6 alkynyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C1 to C6 alkoxy)(C2 to C4 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Re groups, a (C6 to C10 aryl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a (5- to 10-membered heteroaryl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rf groups, a C3 to C8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C3 to C8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C3 to C8 cycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C3 to C8 cycloalkenyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups and a (3- to 8-membered heterocycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 spiroalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C6 to C9 spiroalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 spiroheteroalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 bicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a (C5 to C9 bicycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, a C6 to C9 heterobicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 Rg groups, and a (C6 to C9 heterobicycloalkyl)(C1 to C3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 Rg groups;

R14 is independently selected from H and a C1 to C6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 Re groups; or R13 and R14 together form a C3 to C8 cycloalkane ring substituted by 0, 1, 2, 3, 4 or 5 Rg groups, C3 to C8 cycloalkene ring substituted by 0, 1, 2, 3, 4 or 5 Rg groups, or a 3- to 8-membered heterocycloalkane ring substituted by 0, 1, 2, 3, 4 or 5 Rg groups;

Rm is independently selected from H, F, Cl, —CH3 and —CF3;

Rg and Rj are, independently selected from F, Cl, a C1 to C6 alkyl group, —OH, —CN, —NH2, —NO2, —CO2H, a C1 to C6 alkoxy group, a mono(C1 to C6 alkyl)amino group, a di(C1 to C6 alkyl)amino group, —CF3, a C1 to C6 alkylene group substituted by 0, 1, 2 or 3 R1 groups, a C2 to C6 alkenylene group substituted by 0, 1, 2 or 3 R1 groups and an oxo group;

Rf and Ri are independently selected from F, Cl, Br, —OH, —CN, —NO2, —CO2H, a C1 to C6 alkyl group substituted by 0, 1, 2 or 3 Rk groups, a C2 to C6 alkenyl group substituted by 0, 1, 2 or 3 Rk groups, a C2 to C6 alkynyl group substituted by 0, 1, 2 or 3 Rk groups, a C3 to C8 cycloalkyl group substituted by 0, 1, 2 or 3 Rk groups, a C1 to C6 alkoxy group substituted by 0, 1, 2 or 3 Rk groups, a C3 to C8 cycloalkyloxy group substituted by 0, 1, 2 or 3 Rk groups, —SH, a C1 to C6 alkylthio group substituted by 0, 1, 2 or 3 Rk groups, a C3 to C8 cycloalkylthio group substituted by 0, 1, 2 or 3 Rk groups, a (C1 to C6 alkyl)carbonyl group substituted by 0, 1, 2 or 3 Rk groups, a (C1 to C6 alkoxy)carbonyl group substituted by 0, 1, 2 or 3 Rk groups, a (C1 to C6 alkyl)aminocarbonyl group substituted by 0, 1, 2 or 3 Rk groups, a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2 or 3 Rk groups, a C1 to C6 alkylsulfonyl group substituted by 0, 1, 2 or 3 Rk groups, —NH2, a mono(C1 to C6 alkyl)amino group substituted by 0, 1, 2 or 3 Rk groups and a di(C1 to C6 alkyl)amino group substituted by 0, 1, 2 or 3 Rk groups; and

Ra, Rb, Rc, Re, Rh, Rk and Rl are independently selected from F, a C1 to C4 alkyl group, —OH, —CN, —NO2, —NH2, —CO2H, a C1 to C6 alkoxy group, a mono(C1 to C6 alkyl)amino group, a di(C1 to C6 alkyl)amino group, —CF3 and an oxo group.

US Pat. No. 9,249,230

ANTIBODIES DIRECTED TO HER-3 AND USES THEREOF

U3 Pharma GmbH, Martinsr...

1. An isolated binding protein that binds to HER-3, comprising a heavy chain amino acid sequence that comprises a CDRH1 having
the sequence of SEQ ID NO: 236, a CDRH2 having the sequence of SEQ ID NO: 258, and a CDRH3 having the sequence of SEQ ID NO:
283; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID No: 320, a CDRL2 having the
sequence of SEQ ID NO: 343, and a CDRL3 having the sequence of SEQ ID NO: 360.

US Pat. No. 9,376,450

HETEROARYLOXYHETEROCYCLYL COMPOUNDS AS PDE10 INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X1 is CR6;

X2 is N;

X3 is CR3;

X4 is N;

X5 is CR6;

the ring containing X1, X2, X3, X4, and X5 can be fused to ring A, ring B, or ring C; each having the formula:

wherein each said ring A, ring B, or ring C is a fused 4- to 6-membered-saturated, -partially saturated, or -unsaturated-carbocyclic
or -heterocyclic ring containing 0, 1, 2, or 3 heteroatoms; and is substituted by 0, 1, or 2 R10 groups; which are oxo, C1-6alk, C1-3haloalk, —OH, —OC1-4alk, —NH2—NHC1-4alk, —OC(?O)C1-4alk, or —N(C1-4alk)C1-4alk;
W is —O—;
m is 0, 1, 2, 3, or 4;
each of p and q is independently 0, 1, 2, 3, 4, 5, or 6; wherein the sum of p and q is 2 to 6;
the ring containing p and q contains 0 or 1 double bond;
R1 is halo, C1-8alk, C1-4haloalk, —ORc, —N(Ra)C(?O)Rb, —C(?O)Ra, —C(?O)Rc, —C(?O)—O—Ra, —NRaRc, —N(Rc)C(?O)Rb, —N(Ra)C(?O)Rc, —C(?O)NRaRb, —C(?O)NRaRc, or C0-4alk-L1; wherein said C1-8alk group is substituted by 0, 1, 2 or 3 groups which are halo, C1-3 haloalk,
—OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(?O)C1-4alk, or —N(C1-4alk)C1-4alk;
R2 is quinolinyl, quinazolinyl, or quinoxalinyl;

each of R3 and R6 is independently R1, H, halo, CN, OH, OC1-4alk, C1-4alk, or C1-4haloalk; wherein 1 or 2 of R3 and R6 must be R1;

R4a is H, C1-4alk, or C1-4haloalk;

each R4b is independently F, Cl, Br, CN, OH, OC1-4alk, C1-4alk, or C1-4haloalk;

Ra is independently H or Rb;

Rb is independently phenyl, benzyl, or C1-6alk, wherein said phenyl, benzyl, and C1-6alk are being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(?O)C1-4alk, or —N(C1-4alk)C1-4alk;

Rc is C0-4alk-L4; and

each of L1, L3, and L4 is independently a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered
monocyclic ring or a saturated, partially-saturated or unsaturated 8-, 9-, 10-, 11-, or 12-membered bicyclic ring; each said
ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms which are O or S; each L1, L3, and L4 is independently substituted by 0, 1, 2 or 3 R7 groups which are independently F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk,
CN, —C(?O)Rb, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —OC(?O)Rb, —OC(?O)NRaRa, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(?O)Rb, —S(?O)2Rb, —S(?O)2NRaRa, —NRaRa, —NRaRc, —N(Ra)C(?O)Rb, —N(Ra)C(?O)ORb, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Rb, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkNRaRa, —NRaC1-6 alkORa, —C1-6 alkNRaRa, —C1-6 alkORa, —C1-6 alkN(Ra)C(?O)Rb, —C1-6alkOC(?O)Rb, —C1-6alkC(?O)NRaRa, —C1-6alkC(?O)ORa, or oxo.
US Pat. No. 9,308,258

STABLE AND AGGREGATION FREE ANTIBODY FC MOLECULES THROUGH CH3 DOMAIN INTERFACE ENGINEERING

Amgen Inc., Thousand Oak...

1. A polypeptide homodimer comprising an IgG CH3 domain homodimer, wherein said CH3 domain comprises the amino acid sequence
set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5 comprising an alanine substitution at Ser364.

US Pat. No. 9,359,435

METHODS FOR MODULATING MANNOSE CONTENT OF RECOMBINANT PROTEINS

Amgen Inc., Thousand Oak...

1. A method of producing a recombinant antibody, or an antigen-binding fragment thereof, comprising culturing a host-cell
which expresses the recombinant antibody or antigen-binding fragment thereof in a culture medium having an osmolality of about
400 mOsm/Kg or less, wherein (i) the culture medium comprises a salt selected from the group consisting of potassium at a
concentration of about 70 mM or less, sodium at a concentration of about 200 mM or less, and combinations thereof, (ii) the
culture medium is substantially free of one or more amino acids selected from the group consisting of alanine, arginine, aspartic
acid and glutamic acid, (iii) the culture medium comprises an osmoprotectant selected from the group consisting of betaine,
glycine, L-threonine, L-proline, and derivatives thereof, and (iv) fewer than about 10% of the recombinant antibody molecules
in the composition have more than 4 mannose residues.

US Pat. No. 9,114,175

MODIFIED FC MOLECULES

AMGEN INC., Thousand Oak...

1. A composition of matter of the formula

wherein:
F1 is a monomer of the monomeric or multimeric Fc domain;

X1 is covalently bound to the N-terminus of F1 through the ?-amino site of F1;

X2 is covalently bound to the C-terminus of F1 through the ?-carboxy site of F1;

X3 is covalently bound to the one or more specifically selected internal conjugation site(s) in F1 through the side chain of an amino acid residue selected from the group consisting of D46, S48, H49, E50, E53, K55, D61, G62,
Q76, K107, K121, G122, Q123, R136, D137, T140, K141, N142, N170, K173, S181, G183, D194, K195, R197, and Q199, relative to
reference sequence SEQ ID NO: 599, or, if g>1, any combination of these members;

X1, X2, and X3 are each independently selected from -(L1)c-P0, -(L1)c-P1, -(L1)c-P1-(L2)d-P2, -(L1)c-P1-(L2)d-P2-(L3)e-P3, and -(L1)c-P1-(L2)d-P2-(L3)e-P3-(L4)f-P4;

P0, P1, P2, P3, and P4 are each independently selected from the group consisting of:

i) a pharmaceutically acceptable polymer or dextran;
ii) a pharmacologically active polypeptide, peptide, peptidomimetic, or non-peptide organic moiety;
iii) a radioisotope, an enzyme, a biotinyl moiety, a fluorophore, or a chromophore; and
iv) an immobilized substrate, provided that in a chain comprising more than one additional functional moieties, the immobilized
substrate is the moiety most distal from F1, and there can be no more than one immobilized substrate in the chain;

L1, L2, L3, and L4 are each independently linkers;

a, b, c, d, e, and f are each independently 0 or 1; and
g is 1, 2, 3, or 4.
US Pat. No. 9,266,965

NUCLEIC ACID ENCODING ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

AMGEN INC., Thousand Oak...

1. A monoclonal antibody that binds to PCSK9, wherein the monoclonal antibody binds an epitope on PCSK9 comprising at least
one of amino acid residues 374, 380, or 381 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding interaction
between PCSK9 and EGFa domain of LDLR.
US Pat. No. 9,279,013

FGF-21 MUTANTS COMPRISING POLYETHYLENE GLYCOL AND USES THEREOF

Amgen Inc., Thousand Oak...

1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide of SEQ ID NO: 4 having a lysine
residue substitution at position 36 and at least one amino acid substitution that is: an arginine residue substitution at
position 56, 59, 69, or 122; and wherein the isolated polypeptide comprises no more than five amino acid substitutions.
US Pat. No. 9,156,911

APELIN ANTIGEN-BINDING PROTEINS AND USES THEREOF

AMGEN INC., Thousand Oak...

1. An isolated antigen-binding protein comprising a light chain variable region and a heavy chain variable region, wherein
the light chain variable region comprises three complementarity determining regions (CDRs) designated L1, L2, and L3 and the
heavy chain variable region comprises three CDRs designated H1, H2, and H3, wherein L1, L2, and L3 have the amino acid sequence
of SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25, respectively, and wherein H1, H2, and H3 have the amino acid sequence
of SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively.
US Pat. No. 9,315,577

ANTI-HEPCIDIN ANTIBODIES AND METHODS OF USE

AMGEN INC., Thousand Oak...

1. An isolated antibody comprising SEQ ID NOs: 334-339 wherein the antibody binds to human hepcidin of SEQ ID NO: 9 with an
affinity KD of less than about 10?8M and which exhibits at least one of the properties selected from the group consisting of:
(a) at least about a 50-fold higher KD at a pH of about 5.5 compared to its KD for said hepcidin at a pH of about 7.4;

(b) at least about a 5-fold faster clearance of said hepcidin compared to antibody 1S1 having the heavy chain variable region
of SEQ ID NO: 202 and the light chain variable region of SEQ ID NO: 128; and

(c) an off rate of about 6×10?2 s?1 or higher at about pH 5.5.

US Pat. No. 9,296,736

PIPERIDINONE DERIVATIVES AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER

Amgen INC., Thousand Oak...

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Q is a bond or optionally can be selected from O, NR7 or S(O)v, when n* is an integer from 1 to 6;

Z is S(?O)2;

Ra at each occurrence is independently selected from H, (C1-C3)alkyl, (halo)(C1-C3)alkyl, (hydroxy)(C1-C3)alkyl, (alkoxy)(C1-C3)alkyl, or cyano;

Rb is H, halo, (C1-C3)alkyl, (halo)(C1-C3)alkyl, (hydroxy)(C1-C3)alkyl, (alkoxy)(C1-C3)alkyl, or cyano;

Rc and Rd are independently selected from H, halo, (C1-C3)alkyl, (C1-C3)alkoxy, (halo)(C1-C3)alkyl, (halo)(C1-C3)alkoxy, (alkoxy)(C1-C3)alkyl, or (hydroxy)(C1-C3)alkyl,

or Rc and Rd may optionally combine to form a spiro-cycloalkyl or heterocyclo ring system;

Re is

(a) H or halo; or
(b) (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)heterocyclo, cyano, halogen, hydroxyl, —OR5, NR7R8, or heterocycloalkyl, any of which may be optionally substituted with 1 or more Rx groups as allowed by valence;

R? and R? at each occurrence, respectively, are independently H, halo, (C1-C3)alkyl, (C1-C3)alkoxy, (halo)(C1-C3)alkyl, (halo)(C1-C3)alkoxy, (alkoxy)(C1-C3)alkyl, (hydroxy)(C1-C3)alkyl, —S—(C1-C3)alkyl, C(O)(C1-C3)alkyl, —NR7R8, or hydroxyl, or R? and R? bound to the same carbon atom may optionally combine to form ?O;

R1 is

(a) —COOH, —C(O)OR10, —C(O)NHOH, —C(O)NH—NH2, —C(O)NHS(O)2R10, —S(O)2NHC(O)R10, —S(O)2NR7R8, —NR7C(O)R10, —NR7C(O)OR5, —C(O)NR7R8, —NR7S(O)2R10, —NR7C(O)NR7R8, —S(O)vR10, hydroxylalkyl, -cyclopropyl-COOH, or CN; or

(b) heteroaryl or heterocyclo, either of which may be optionally independently substituted with one or more Rx groups as allowed by valence;

R2 is

(a) —NR7R8, NR7C(O)OR10, NR7C(O)NR7R10, or —C(Ra)R5R6; or

(b) aryl, heteroaryl, cycloalkyl, or heterocyclo, any of which may be optionally independently substituted with one or more
Rx groups as allowed by valence;

R3 and R4 are independently aryl or heteroaryl, either of which may be optionally independently substituted with one or more Rx groups as allowed by valence;

R5 and R6 at each occurrence, respectively, are independently selected from

(a) H or CN;
(b) -(alkylene)t-OH, -(alkylene)t-OR9, -(alkylene)t-SR9, -(alkylene)t-NR10R11, -(alkylene)t-C(O)R9, -(alkylene)t-C(O)OR9, -(alkylene)t-OC(O)R9, -(alkylene)t-S(O)vR9, -(alkylene)t-NHS(O)2R10, -(alkylene)t-N(R11)S(O)2R10, -(alkylene)t-S(O)2NR10R11, -(alkylene)t-N(R11)S(O)2NR10R11, —NR10C(O)R9, —C(O)NR10R11, —NR10S(O)2R9, S(O)2NR10, or NR10C(O)NR10R11; or

(c) haloalkyl, haloalkoxy, C1-6-alkyl, C2-6alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, (C3-8-cycloalkyl)(C1-3alkyl), C4-8-cycloalkenyl, aryl, aryl(C1-3-alkyl), heteroaryl, heteroaryl(C1-3-alkyl), heterocyclo or heterocyclo(C1-3-alkyl), any of which may be optionally independently substituted with one or more Rx groups as allowed by valence;

R7 and R8 at each occurrence, respectively, are independently selected from H, cyano, —OC1-6-alkyl, C1-6-alkyl, halo(C1-6)-alkyl, cycloalkyl, C2-6-alkenyl, C2-6-alkynyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocyclo(C1-10alkyl), or (C3-8-cycloalkyl)(C1-3alkyl), any of which may be optionally substituted as allowed by valence with one or more Rx, or R7 and R8 may combine to form a C4-C8-heterocyclo ring optionally substituted with one or more Rx;

R9 is haloalkyl, haloalkoxy, C1-6-alkyl, C2-6alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, (C3-8-cycloalkyl)(C1-3alkyl), C4-8-cycloalkenyl, aryl, heteroaryl, heterocyclo, or heterocycloalkyl, any of which may be optionally independently substituted
with one or more Rx groups as allowed by valence;

R10 and R11 at each occurrence, respectively, are independently selected from H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, aryl,
heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, or cycloalkylalkyl, any of which may be optionally
substituted as allowed by valence with one or more Rx, or R10 and R11 may combine to form a heterocyclo ring optionally substituted with one or more Rx;

Rx at each occurrence is independently, deuterium, halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,
heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, -(alkylene)t-OR*, -(alkylene)t-S(O)vR*, -(alkylene)t-NR+R++, -(alkylene)t-C(?O)R*, -(alkylene)t-C(?S)R*, -(alkylene)t-C(?O)OR*, -(alkylene)t-OC(?O)R*, -(alkylene)t-C(?S)OR*, -(alkylene)t-C(?O)NR+R++, -(alkylene)t-C(?S)NR+R++, -(alkylene)t-N(R+)C(?O)NR+R++, -(alkylene)t-N(R+)C(?S)NR+R++, -(alkylene)t-N(R+)C(?O)R*, -(alkylene)t-N(R+)C(?S)R*, -(alkylene)t-OC(?O)NR+R++, -(alkylene)t-OC(?S)NR+R++, -(alkylene)t-SO2NR+R++, -(alkylene)t-N(R+)SO2R*, -(alkylene)t-N(R+)SO2NR+R++, -(alkylene)t-N(R+)C(?O)OR*, -(alkylene)t-N(R+)C(?S)OR*, or -(alkylene)t-N(R+)SO2R*, wherein said alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl,
cycloalkylalkyl, and heterocycloalkyl groups may be further independently substituted with one or more halo, cyano, oxo, -(alkylene)t-OR*, -(alkylene)t-S(O)vR*, -(alkylene)t-NR+R++, -(alkylene)t-C(?O)R*, -(alkylene)t-C(?S)R*, -(alkylene)t-C(?O)OR*, -(alkylene)t-OC(?O)R*, -(alkylene)t-C(?S)OR*, -(alkylene)t-C(?O)NR+R++, -(alkylene)t-C(?S)NR+R++, -(alkylene)t-N(R+)C(?O)NR+R++, - (alkylene)t-N(R+)C(?S)NR+R++, -(alkylene)t-N(R+)C(?O)R*, -(alkylene)t-N(R+)C(?S)R*, -(alkylene)t-OC(?O)NR+R++, -(alkylene)t-OC(?S)NR+R++, -(alkylene)t-SO2NR+R++, -(alkylene)t-N(R+)SO2R*, -(alkylene)t-N(R+)SO2NR+R++, -(alkylene)t-N(R+)C(?O)OR*, -(alkylene)t-N(R+)C(?S)OR*, or -(alkylene)t-N(R+)SO2R*;

R* is H, haloalkyl, haloalkoxy, C1-6-alkyl, C2-6alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C4-8-cycloalkenyl, aryl, heteroaryl, or heterocyclo;

R+ and R++ are independently H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl,
heterocycloalkyl, or cycloalkylalkyl, or R+ and R++ bound to the same nitrogen atom may optionally combine to form a heterocyclo ring system;

n and n* are each independently selected from 0 or an integer from 1 to 6;
t at each occurrence is independently 0 or an integer from 1 to 6; and
v at each occurrence is independently 0, 1 or 2.
US Pat. No. 9,260,514

METHODS OF TREATING CONDITIONS CAUSED BY INCREASED EXPRESSION OF NERVE GROWTH FACTOR (NGF) OR INCREASED SENSITIVITY TO NGF USING ANTI-NGF NEUTRALIZING ANTIBODIES AS SELECTIVE NGF PATHWAY INHIBITORS

Amgen Inc., Thousand Oak...

1. A method of treating a condition caused by increased expression of nerve growth factor (NGF) or increased sensitivity to
NGF, comprising administering to a patient, through subcutaneous injection, a pharmaceutically effective amount of a pharmaceutical
composition comprising a pharmaceutically acceptable carrier and an isolated antibody or antibody fragment thereof,
wherein the antibody comprises a light chain comprising SEQ ID NO: 44 and a heavy chain comprising SEQ ID NO: 40 and the antibody
or antibody fragment specifically binds to NGF, wherein the condition is pain caused by osteoarthritis, and wherein the pharmaceutically
effective amount of the NGF antibody or antibody fragment is from about 1 mg to about 30 mg per subcutaneous injection.

US Pat. No. 9,228,168

FEED MEDIA

Amgen Inc., Thousand Oak...

1. A method for stabilizing a concentrated feed medium for feeding a mammalian cell culture comprising adding pyruvate to
the feed medium,
wherein the concentration of pyruvate after addition is at least 10 mM and not more than 100 mM,
wherein the feed medium comprises cysteine at a concentration from 7 mM to 30 mM,
wherein the feed medium comprises tyrosine at a concentration that is at least 1 mM and less than or equal to 4.6 mM,
wherein the feed medium further comprises tryptophan at a concentration of 0.2-11 mM, histidine at a concentration of 0.6-67
mM, methionine at a concentration from 0.6-31 mM, phenylalanine at a concentration of 0.7-46 mM, isoleucine at a concentration
of 1.6-80 mM, proline at a concentration of 2.6-130 mM, valine at a concentration of 2.5-128 mM, threonine at a concentration
of 2.5-126 mM, serine at a concentration of 1.1-143 mM, lysine at a concentration of 2.4-165 mM, and leucine at a concentration
of 2.2-115 mM,

wherein cystine is not added to the feed medium at a concentration of more than 1.0 mM,
wherein the pH of the feed medium is from 5.8 to about 7.4, and
wherein the feed medium with the added pyruvate is stable for at least 1 week at 4-8° C.
US Pat. No. 9,133,272

BISPECIFIC BINDING AGENTS

AMGEN INC., Thousand Oak...

1. A binding molecule that specifically binds sclerostin and DKK-1 and comprises first and second polypeptide chains, wherein
said first polypeptide chain comprises VH1-(X1)n-VH2-C-(X2)n, wherein VH1 comprises the amino acid sequence of SEQ ID NO:
95; wherein VH2 comprises the amino acid sequence of SEQ ID NO: 4086; C is a heavy chain constant domain; (X1)n is a linker
set forth in SEQ ID NO: 440 or SEQ ID NO: 441, and (X2)n is an Fc region and wherein said second polypeptide chain comprises
a VL1-(X1)n-VL2-C, wherein VL1 comprises the amino acid sequence of SEQ ID NO: 94; wherein VL2 comprises the amino acid sequence
of SEQ ID NO: 407; and wherein C is a light chain constant domain.
US Pat. No. 9,056,915

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Amgen Inc., Thousand Oak...

1. A monoclonal antibody that binds to an epitope on PCSK9, wherein the epitope comprises at least one of the following residues:
S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein said
monoclonal antibody comprises:
a heavy chain variable region; and
a light chain variable region; wherein the monoclonal antibody blocks binding interaction between PCSK9 and EGFa domain of
LDLR.

US Pat. No. 9,242,961

AURORA KINASE MODULATORS AND METHOD OF USE

Amgen Inc., Thousand Oak...

1. A method of making compound 1 having the structure
, or a pharmaceutically acceptable salt thereof, the method comprising the step of reacting compound 2
with a compound 3
wherein X is a halogen, to make compound 1.
US Pat. No. 9,320,797

PHARMACEUTICAL FORMULATIONS

AMGEN INC., Thousand Oak...

1. A liquid pharmaceutical formulation comprising in acetate buffer a therapeutic protein at a concentration of at least 70
mg/ml and an excipient consisting of creatine, creatinine, carnitine or mixtures thereof,
wherein, the liquid pharmaceutical formulation does not comprise an excipient or stabilizer that is an amino acid.
US Pat. No. 9,102,731

HUMAN CGRP RECEPTOR BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. An isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof specifically
binds the human CGRP receptor and comprises a CDRH1 having the sequence of SEQ ID NO:73, a CDRH2 having the sequence of SEQ
ID NO:74, a CDRH3 having the sequence of SEQ ID NO:75, a CDRL1 having the sequence of SEQ ID NO:42, a CDRL2 having the sequence
of SEQ ID NO:43, and a CDRL3 having the sequence of SEQ ID NO:44.

US Pat. No. 9,359,355

FUSED TRICYCLIC DUAL INHIBITORS OF CDK 4/6 AND FLT3

AMGEN INC., Thousand Oak...

1. A method of treating acute myeloid leukemia, the method comprising: administering to a subject an effective amount of a
compound selected from
or a pharmaceutically acceptable salt or a hydrate thereof.
US Pat. No. 9,133,493

METHOD FOR CULTURING MAMMALIAN CELLS TO IMPROVE RECOMBINANT PROTEIN PRODUCTION

AMGEN INC., Thousand Oak...

1. A method of culturing Chinese Hamster Ovary (CHO) cells expressing a recombinant protein, comprising growing the CHO cells
in a defined serum-free culture medium during a growth phase and maintaining the CHO cells in the cell culture medium during
a production phase by supplementing the cell culture with a concentrated defined serum-free feed medium that does not contain
tyrosine, cysteine or cystine, and further supplementing the cell culture with an independent tyrosine and cystine feed, wherein
viability was prolonged, specific productivity and titer was not diminished by the independent tyrosine and cystine feed.

US Pat. No. 9,187,486

BICYCLIC PYRIDAZINE COMPOUNDS AS PIM INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula 1?
wherein
X is CH;
R is H, halo, alkyl, cycloalkyl, optionally substituted aryl, optionally substituted 5-membered heterocyclyl, or optionally
substituted 6-membered heterocyclyl;

R1 is optionally substituted 5-membered nitrogen containing heteroaryl, or optionally substituted 6-membered nitrogen containing
heteroaryl; and

R2 is H;

and a pharmaceutically acceptable salt thereof;
provided R1 is not unsubstituted 3-pyridyl when, X is CH and R is 2,6-difluorophenyl; further provided R1 is not 5-methyl-3-phenyl-4-isoxazolyl when, X is CH and R is 2,6-difluorophenyl; further provided R is not H if X is CH; further
provided R1 is not 4-(5-methyl-4-isoxazolyl)-3-pyridinyl when X is N and R is 2,6-difluorophenyl; further provided R1 is not substituted 4-pyridinyl; and further provided R1 is not 4-chloro-3-pyridyl when, X is CH and R is 2,6-difluorophenyl.

US Pat. No. 9,382,318

ST2 ANTIGEN BINDING PROTEINS

Amgen Inc., Thousand Oak...

1. An isolated ST2 antigen binding protein comprising:
a) a light chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:96;
b) a heavy chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:30; or
c) a light chain variable domain of a) and a heavy chain variable domain of b).
US Pat. No. 9,371,554

FLOCCULATION METHOD

AMGEN INC., Thousand Oak...

1. A mammalian cell culture harvest method comprising
culturing mammalian cells expressing a recombinant protein in a cell culture medium for a predetermined time or until a desired
cell density and/or packed cell volume is achieved,

adding a cationic polymer selected from the group consisting of: a polymer of diallyldimethyammonium chloride and a polymer
of polydiallyldimethyammonium chloride, and a non-ionic polymer selected from the group consisting of: polyethyleneglycol
and dextran to the cell culture medium initiating flocculation,

mixing the cell culture medium during flocculation,
allowing the flocculent to settle for a primary settle, and
recovering the primary clarified supernatant.
US Pat. No. 9,353,174

EPITOPES

AMGEN INC., Thousand Oak...

1. An isolated polynucleotide encoding a monoclonal antibody that binds to amino acids 138-149 of SEQ ID NO:1 with a binding
affinity (Kd) of less than or equal to 1×10?6 M.
US Pat. No. 9,284,364

ISOLATED NUCLEIC ACID MOLECULE ENCODING A FUSION PROTEIN COMPRISING AN ACTIVIN RECEPTOR

Amgen Inc., Thousand Oak...

1. An isolated nucleic acid molecule comprising a first polynucleotide encoding at least one heterologous protein and a second
polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising a polynucleotide sequence at least 95% identical to the polynucleotide sequence set forth
in SEQ ID NO: 1;

(b) a polynucleotide encoding a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence
set forth in SEQ ID NO: 2, with or without a signal sequence, wherein the polypeptide is capable of binding myostatin, activin
A, or GDF-11; and

(c) a polynucleotide that hybridizes to (a) or (b) or the complete complement of (a) or (b) in the presence of 50% formamide,
6× sodium chloride/sodium citrate (SSC) at 42° C. and washing conditions of 60° C., 0.5×SSC, 0.1% sodium dodecyl sulfate (SDS),
and

wherein the protein encoded by the isolated nucleic acid molecule comprises at least one of the following characteristics:
(1) the protein has activin A neutralizing activity IC50 (nM) vs. 20 nM activin that is less than the activin A neutralizing
activity IC50 (nM) vs. 20 nM activin of a control protein comprising amino acids 1-124 of the sequence set forth in SEQ ID
NO:5 linked to human IgG1 Fc; or (2) the protein has myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin that is
less than the myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin of the control protein.

US Pat. No. 9,200,060

MONOMERIC ANTIBODY FC

AMGEN INC., Thousand Oak...

1. A polypeptide comprising a monomeric Fc region having a CH2 and CH3 domain, wherein said CH3 domain is an IgG CH3 domain
and comprises:
(a) a negatively charged amino acid at EU position 392 and EU position 409; and
(b) an amino acid substitution of EU position 349 or EU position 405 with a polar amino acid residue.
US Pat. No. 9,139,645

PEPTIDES AND RELATED MOLECULES THAT BIND TO TALL-1

Amgen Inc., Tousand Oaks...

1. A method of inhibiting TALL-1-mediated B cell proliferation in a subject in need thereof comprising administering to the
subject a TALL-1 binding molecule comprising the amino acid sequence f1f2f3Kf5Df7Lf9f10Qf12f13f14 (SEQ. ID. NO: 109), wherein:
f1, f2, and f3 are absent or are amino acid residues;

f5 is W;

f7 is an amino acid residue;

f9 is T or I;

f10 is K, R, or H;

f12 is C, c a neutral hydrophobic residue, or a basic residue;

f13 is C, a neutral hydrophobic residue or is absent; and

f14 is any amino acid residue or is absent;

provided that only one of f1, f2, and f3 may be C, and only one of f12, f13, and f14 may be C.

US Pat. No. 9,296,812

SCLEROSTIN BINDING ANTIBODIES

AMGEN INC., Thousand Oak...

1. An IgG antibody that binds sclerostin of SEQ ID NO: 1 and comprises CDRH-1, CDR-H2, CDR-H3, CDR-L1 CDR-L2 and CDR-L3 wherein
CDR-H1 is SEQ ID NO:245, CDR-H2 is SEQ ID NO:246, CDR-H3 is SEQ ID NO:247, CDR-L1 is SEQ ID NO:78, CDR-L2 is SEQ ID NO:79
and CDR-L3 is SEQ ID NO:80.

US Pat. No. 9,493,459

AZETIDINE AND PIPERIDINE COMPOUNDS USEFUL AS PDE10 INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound, or a pharmaceutically acceptable salt thereof, of formula:

wherein each of p and q is independently 1 or 2; and
wherein the sum of p and q is 2 or 4.
US Pat. No. 9,352,043

HIGH CONCENTRATION ANTIBODY FORMULATIONS

AMGEN INC., Thousand Oak...

1. A sterile liquid formulation that has an absolute viscosity of about 10 cP or less consisting essentially of: (a) an anti-sclerostin
immunoglobulin at a concentration of from about 70 mg/mL to about 120 mg/mL, wherein the anti-sclerostin immunoglobulin comprises
the amino acid sequences of SEQ ID NO: 86 and SEQ ID NO: 84; (b) calcium acetate at a concentration ranging from about 1 mM
to about 20 mM; and (c) a polyol in an amount ranging from about 4% w/v to about 6% w/v.

US Pat. No. 9,320,816

METHODS OF TREATING CELL CULTURE MEDIA FOR USE IN A BIOREACTOR

Amgen Inc., Thousand Oak...

1. A method of treating cell culture media for use in a bioreactor comprising: (a) exposing the cell culture media to ultraviolet
C (UVC) light at an energy density of 120-320 J/m2; (b) passing the UVC-treated cell culture media through a sterile filter; and (c) introducing the filtered, UVC-treated cell
culture media into a bioreactor.

US Pat. No. 9,321,756

AZOLE COMPOUNDS AS PIM INHIBITORS

AMGEN INC., Thousand Oak...

15. A composition comprising a therapeutically effective amount of the compound of claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
US Pat. No. 9,273,145

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

AMGEN INC., Thousand Oak...

1. A monoclonal antibody that recognizes a conformational epitope on human PCSK9 comprising amino acid residues: S153, R194,
D238, D374, T377, and F379 of SEQ ID NO: 3, wherein the monoclonal antibody reduces binding between PCSK9 and EGFa domain
of LDLR.
US Pat. No. 9,089,553

METHOD FOR INHIBITING BONE RESORPTION

AMGEN INC., Thousand Oak...

1. A method for inhibiting bone resorption in a human, the method comprising administering to the human an amount from about
1 mg/kg to about 8 mg/kg of an antibody or fragment thereof that (i) demonstrates a binding affinity for sclerostin of SEQ
ID NO: 1 of less than or equal to 1×10?9 M and (ii) comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 378 and a light chain
variable region comprising the amino acid sequence of SEQ ID NO: 376, wherein bone resorption is inhibited.

US Pat. No. 9,090,593

BICYCLIC COMPOUNDS AS PIM INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula 1a

wherein X1 is CH or N;

wherein X2 is CH or N;

wherein X3 is C or N;

wherein R is substituted or unsubstituted aryl, substituted or unsubstituted 5-membered heterocyclyl, substituted or unsubstituted
6-membered heterocyclyl, substituted or unsubstituted 9 membered heterocyclyl, substituted or unsubstituted 10 membered heterocyclyl,
cycloalkylalkenyl, 1,2,2?,3?,5?,6?-hexahydrospiro[indole-3,4?-pyranyl], alkylcarbonylamino, phenylaminocarbonyl, phenylcarbonylamino,
benzylaminocarbonyl, alkylcarbonyl, hydroxyalkyl, haloalkyl, cyanoalkyl, substituted or unsubstituted cycloalkyl, substituted
or unsubstituted arylamino, alkenyl, or haloalkenyl;

wherein R1 is


 and
wherein Rg is H or F;

wherein R1A is H, hydroxy, C1-C3-alkoxy, C1-C3-haloalkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino,
substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy,
alkylamino, C3-C6 cycloalkylamino, substituted or unsubstituted 5-6-membered heterocyclyl-S—, substituted or unsubstituted phenylamino or 9-10
membered nitrogen containing heterocyclyl;

wherein R1B is H, hydroxy or C1-C3-alkoxy;

wherein R1C is H, hydroxy, C1-C3-alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino;

wherein R1E is H, hydroxy, C1-C3-alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino,
substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy
or alkylamino;

wherein R1F is H, or substituted or unsubstituted 6-membered heterocyclyl;

wherein R1G is H, hydroxy or C1-C3-alkoxy;

wherein R1J is H, hydroxy, C1-C3-alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino
or substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino or substituted or unsubstituted 5-6-membered heterocyclyloxy
or alkylamino or substituted or unsubstituted 5-6-membered heterocyclyl-S—, or substituted or unsubstituted phenyl or 9-10
membered nitrogen containing heterocyclyl;

wherein R1H is H, hydroxy or C1-C3-alkoxy;

wherein R1M is H, lower alkyl, lower alkoxy, lower alkylamino, lower dialkylamino, substituted or unsubstituted 5-6-membered heterocyclyloxy,
substituted or unsubstituted 5-6-membered heterocyclyl or substituted or unsubstituted 5-6-membered heterocyclylamino;

wherein R1N is H, or C1-C3-alkoxy; and

wherein R1P substituted or unsubstituted phenylamino, lower alkylamino, substituted or unsubstituted 5-membered nitrogen-containing heterocyclyl,
substituted or unsubstituted 5-membered nitrogen-containing heterocyclylamino, substituted or unsubstituted 6-membered nitrogen-containing
heterocyclylamino, or substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl;

or a pharmaceutically acceptable salt thereof;
provided R1 is not 4-pyridyl when R is 3-pyridyl, when X1 is CH, X2 is CH and X3 is C; further provided R is not 2,6-dimethyl-3,5-dicyano-dihydropyridyl when X1 is N, X2 is CH and X3 is C; further provided R1 is not 2-(4-morpholinyl-4-phenylamino)-4-pyrimidyl when X1 is CH, X2 is CH and X3 is C; further provided R is not 2-(3-furyl)-(5-phenyl-2-aminopropoxy)-3-pyridyl when X1 is N, X2 is CH and X3 is C; further provided R is not triazolyl or tetrazolyl when X1 is N, X2 is CH and X3 is C; further provided R is not 7,9-dicyano-[1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazin-8-yl when X1 is N, X2 is CH and X3 is C; further provided R is not 2-methoxypyridyl when Ry is 2-(4-amino-1-piperidyl)-6-pyrazinyl; and further provided R is
not 3-cyano-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-4-yl when X1 is N, X2 is CH, X3 is C, Rg is H and R1 is 2-isopropoxypyridin-5-yl.

US Pat. No. 9,334,269

CARBOXAMIDES AS INHIBITORS OF VOLTAGE-GATED SODIUM CHANNELS

AMGEN INC., Thousand Oak...

1. A compound of Formula (I):

where:
X is —NH;
S, T and U are independently —CR3— or —N—; selected from:


A is phenyl;
R1 is hydrogen, alkyl, haloalkyl, substituted alkyl, or cycloalkyl, wherein said cycloalkyl is optionally substituted with one
to three substituents-independently selected from alkyl, halo, haloalkyl, alkoxy, hydroxyl, or haloalkoxy;

R1a is hydrogen;

R2 is hydrogen, alkyl, substituted alkyl, aryl, heteroaryl, cycloalkyl, halo, haloalkyl, haloalkoxy, alkoxy, alkoxyalkoxy, hydroxy,
carboxy, alkoxycarbonyl, cyano, amino, monosubstituted or disubstituted amino, sulfonyl, or alkoxyalkyl;

each R3 is hydrogen;

R4 is hydrogen, alkyl, substituted alkyl, halo, alkoxy, hydroxy, carboxy, —CONH2, —CONMe2, cycloalkyl, or dialkylamino;

R5 and R6 together with the nitrogen atom to which they are attached form ring B having the formula:


wherein ring B is a heterocyclyl ring-selected from:
a) azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or piperazin-1-yl;
b) 1,2,3,4-tetrahydroisoquinolin-2-yl substituted with Rb at 6-position with haloalkoxy, cyano, cycloalkyl, halo, alkoxy, haloalkyl, or alkoxyalkoxy; or

c) 3,6-dihydro-1(2H)-pyridinyl;
wherein each aforementioned ring B is substituted with Ra, Rb or Rc;

wherein Ra is hydrogen, alkyl, halo, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, cyano, hydroxy, alkoxy, amino, monosubstituted
amino, disubstituted amino, sulfonyl, thio, acyl, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, hydroxyalkoxy,
hydroxyalkoxyalkyl, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, or acylamino and

Rb and Rc are independently selected from hydrogen, alkyl, substituted alkyl, substituted alkynyl, halo, haloalkyl, haloalkoxy, alkylthio,
cyano, alkoxy, amino, monosubstituted amino, disubstituted amino, sulfonyl, acyl, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl,
aminoalkyl, hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, acylamino, sulfonylamino, aryl, heteroaryl,
cycloalkyl, cycloalkenyl, heterocyclyl, aralkyl, heteroaralkyl, heterocyclylalkyl, aryloxy, heteroaryloxy, cycloalkoxy, aryloxyalkyl,
aralkyloxy, aralkyloxyalkyl, aralkylthio, heteroaralkyloxy, heterocyclylalkyloxy, cycloalkylalkyloxy or cycloalkylalkyloxyalkyl;

where the aromatic or alicyclic ring in Ra, Rb and Rc is optionally substituted with Rd, Re or Rf which are independently selected from alkyl, halo, haloalkyl, haloalkoxy, cyanoalkyl, alkylthio, cyano, hydroxy, alkoxy, amino,
monosubstituted amino, disubstituted amino, sulfonyl, acyl, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl,
hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, acylamino, cycloalkyl, cycloalkenyl, phenyl, phenoxy,
heteroaryl, heterocyclyl, heterocyclylalkyl, aralkyl, aralkyloxy or heteroaralkyl and where the aromatic or alicyclic ring
in Rd, Re or Rf is optionally substituted with one to three substituents independently selected from alkyl, halo, haloalkyl, haloalkyloxy,
hydroxyl, alkoxy, acetylamino, alkylsulfonyl, or cyano; or a pharmaceutically acceptable salt thereof;

provided that the compound is not 3-((4-((3S)-3-benzyl-1-piperidinyl)-1,3,5-triazin-2-yl)amino)-N-methylbenzamide; 3-((4-((3R)-3-benzyl-1-piperidinyl)-1,3,5-triazin-2-yl)amino)-N-methylbenzamide;
or N-methyl-3-((4-(4-(4-morpholinylcarbonyl)-1-piperidinyl)-1,3,5-triazin-2-yl)amino)benzamide.

US Pat. No. 9,273,114

STABILIZED RECEPTOR POLYPEPTIDES AND USES THEREOF

Amgen Inc., Thousand Oak...

1. An isolated protein comprising a polypeptide, wherein the polypeptide has at least 95% sequence identity to the amino acid
sequence set forth in SEQ ID NO:6, wherein the polypeptide has a W or a Y at the position corresponding to position 28 of
SEQ ID NO:2 and a T at the position corresponding to position 44 of SEQ ID NO:2, and wherein the polypeptide is capable of
binding at least one of myostatin, activin A, or GDF-11.

US Pat. No. 9,227,019

PRE-FILLED SYRINGE IDENTIFICATION TAG

AMGEN INC., Thousand Oak...

1. An assembly comprising:
a pre-filled syringe including a barrel with a first end and a second, open end, a plunger disposed within the barrel and
spaced between the first end and the second, open end, a product disposed in the barrel between the first end of the barrel
and the plunger, and an outwardly-directed rim disposed about the barrel at the second, open end; and

an identification tag secured to the outwardly-directed rim of the barrel of the syringe with an outwardly-facing surface
of the tag overlying the second, open end of the barrel, the tag having an identifier disposed on the surface of the tag,
the identifier including data regarding the pre-filled syringe, the product disposed in the barrel, or both, wherein the identification
tag comprises a ring that is received about the barrel and a disk that is disposed over the second, open end of the barrel,
the ring secured to the disk with the rim disposed therebetween to secure the identification tag to the rim.

US Pat. No. 9,126,935

AURORA KINASE MODULATORS AND METHODS OF USE

Amgen Inc., Thousand Oak...

10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an effective dosage amount of the
compound of claim 1.

US Pat. No. 9,346,801

SUBSTITUTED 7-OXO-PYRIDO[2,3-D]PYRIMIDINES AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of Formula I

wherein R1 is


wherein Ring A is 5 membered heteroaryl;
wherein Ring T is phenyl or 6 membered heteroaryl;
wherein R2 is H, F, Cl or methyl;

wherein R3 is H, C1-C6 alkyl or C1-C6 dialkylamino-C1-C6 alkyl;

wherein R5 is unsubstituted or substituted 5-6 membered saturated heterocyclyl or substituted 4-7 membered heterocyclylamino;

wherein R6 is H, C1-C6 alkoxy, C1-C6 haloalkoxy or halo; and

wherein X is CH or N;
provided R5 is not 4-morpholinyl;

and pharmaceutically acceptable salts thereof.
US Pat. No. 9,493,576

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

AMGEN INC., Thousand Oak...

1. A monoclonal antibody that recognizes a conformational epitope on human PCSK9 comprising amino acid residues: S153, R194,
D238, D374, T377, and F379 of SEQ ID NO: 3, wherein the monoclonal antibody reduces binding between PCSK9 and EGFa domain
of LDLR.
US Pat. No. 9,365,653

HUMAN PAC1 ANTIBODIES

AMGEN INC., Thousand Oak...

1. An isolated antibody or antigen-binding fragment thereof that specifically binds human pituitary adenylate cyclase-activating
polypeptide type I receptor (PAC1), comprising (i) a heavy chain variable region comprising complementarity determining regions
CDRH1, CDRH2, and CDRH3, and (ii) a light chain variable region comprising complementarity determining regions CDRL1, CDRL2,
and CDRL3, wherein CDRH1 comprises the sequence of SEQ ID NO: 165, CDRH2 comprises the sequence of SEQ ID NO: 179, CDRH3 comprises
the sequence of SEQ ID NO: 189, CDRL1 comprises the sequence of SEQ ID NO: 139 or SEQ ID NO: 140, CDRL2 comprises the sequence
of SEQ ID NO: 151, and CDRL3 comprises the sequence of SEQ ID NO: 157.
US Pat. No. 9,493,554

METHODS OF TREATING RETINAL DISORDERS WITH ANTI-APELIN ANTIBODIES

AMGEN INC., Thousand Oak...

1. A method for inhibiting retinal neovascularization in a patient in need thereof comprising administering to the patient
a therapeutically effective amount of a monoclonal antibody or fragment thereof, wherein the monoclonal antibody or fragment
thereof specifically binds to human apelin at an epitope with the sequence of SEQ ID NO: 32 and inhibits the binding of human
apelin to the APJ receptor.
US Pat. No. 9,284,372

ANTIGEN BINDING PROTEINS CAPABLE OF BINDING THYMIC STROMAL LYMPHOPOIETIN

AMGEN INC., Thousand Oak...

1. An isolated antibody or antigen binding fragment thereof comprising
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence of SEQ ID NO:13;
ii. a light chain CDR2 sequence comprising the amino acid sequence of SEQ ID NO:60; and
iii. a light chain CDR3 sequence comprising the amino acid sequence of SEQ ID NO:105; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence of SEQ ID NO:145;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence of SEQ ID NO:173, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence of SEQ ID NO:212;
wherein the antibody or antigen binding fragment thereof binds a wild-type TSLP polypeptide consisting of amino acids 29-159
as set forth in SEQ ID NO: 2 with a greater affinity than the antibody or antigen binding fragment thereof binds to a mutated
TSLP polypeptide consisting of amino acids 29-159 as set forth in SEQ ID NO: 2 but comprising a serine to arginine mutation
at position 40 (S40R).

US Pat. No. 9,346,827

5-AMINO-OXAZEPINE AND 5-AMINO-THIAZEPANE COMPOUNDS AS BETA SECRETASE ANTAGONISTS AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of Formula I
or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A1 is CR1 or N;

A3 is CR3 or N;

A4 is CR4 or N;

A5 is CR5 or N;

A6 is CR6 or N;

A8 is CR8 or N, provided that no more than one of A1, A3, A4, A5, A6 and A8 is N;

each of R9, R4, R5 and R8, independently, is H, F, Cl, Br, CF3, OCF3,C1-6-alkyl, CN, OH, —OC1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein the C1-6-alkyl and C1-6-alkyl portion of —OC1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-3 substituents of F, oxo or OH;

R2 is Cl, Br, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, pyranyl, dihydropyranyl,
tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thienyl, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl,
cyclopentyl, cyclohexyl or —Si(CH3)3, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, pyranyl, dihydropyranyl,
tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thienyl, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl,
cyclopentyl and cyclohexyl are optionally substituted, independently, with 1-5 substituents of R9;

each of R3 and R6, independently, is H, halo, haloalkyl, haloalkoxyl, C1-6-alkyl, CN, OH, OC1-6-alkyl, NHC1-6-alkyl or C(O)C1-6-alkyl;

R7 is C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NHC(?O)R9, —C(?O)NHR9, —NHS(O)2R9, —S(O)2NHR9, —NH-phenyl, —NH-benzyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, pyranyl, dihydropyranyl,
tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thienyl, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl,
cyclopentyl or cyclohexyl, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, —OC1-6alkyl, —SC1-6alkyl, —NHC1-6alkyl, —N(C1-3alkyl)2, —NH-phenyl, —NH-benzyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, pyranyl, dihydropyranyl,
tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thienyl, pyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl,
cyclopentyl and cyclohexyl are optionally substituted, independently, with 1-5 substituents of R9;

each R9, independently, is halo, haloalkyl, CN, OH, NO2, NH2, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, morpholinyl, pyrazolyl,
isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, piperazinyl, oxetanyl or dioxolyl, wherein each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, isoxazolyl, thiazolyl, morpholinyl, pyrazolyl,
isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetanyl or dioxolyl, is optionally substituted independently with 1-5 substituents
of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl,
butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, or oxetanyl; and

—X—Y— is —CR10R10—O—, —O—CR10R10—, —CR10R10—S— or —S—CR10R10, wherein each R10, independently, is H or F.

US Pat. No. 9,200,040

SPECIFIC BINDING AGENTS OF HUMAN ANGIOPOIETIN-2

Amgen Inc., Thousand Oak...


and an Fc comprising the amino acid sequence of SEQ ID NO:60,
and physiologically acceptable salts thereof.
US Pat. No. 9,097,729

METHODS OF SELECTING EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) BINDING AGENTS

AMGEN INC., Thousand Oak...

1. A method of selecting a specific binding agent to an epidermal growth factor receptor (EGFr) polypeptide, wherein the specific
binding agent binds to at least a portion of a panitumumab epitope on an EGFr polypeptide, comprising:
a) contacting a first EGFr polypeptide with an agent, wherein the first EGFr polypeptide comprises an L2 domain;
b) determining the affinity of the agent for the first EGFr polypeptide;
c) contacting a second EGFr polypeptide with the agent, wherein the second EGFr polypeptide lacks an L2 domain;
d) determining the affinity of the agent for the second EGFr polypeptide; and
e) selecting the agent if the affinity for the first EGFr polypeptide is greater than the affinity for the second EGFr polypeptide.
US Pat. No. 9,447,165

VARIANT ACTIVIN IIB RECEPTOR

Amgen Inc., Thousand Oak...

1. An isolated protein comprising a variant activin IIB receptor (vActRIIB) polypeptide wherein the polypeptide is selected
from the group consisting of:
(a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 18, wherein the polypeptide comprises an amino
acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E;

(b) a polypeptide comprising the amino acid sequence set forth in amino acids 19 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(c) a polypeptide comprising the amino acid sequence set forth in amino acids 23 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(d) a polypeptide comprising the amino acid sequence set forth in amino acids 25 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E; and

(e) a polypeptide having at least 95% identity to any one of (a) through (d), wherein the polypeptide comprises an amino acid
substitution at the position corresponding to position 28 of SEQ ID NO:18, wherein the substitution at position 28 is A, W,
Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.

US Pat. No. 9,151,761

PREDICTIVE BIOMARKER OF SURVIVAL IN THE TREATMENT OF RENAL CELL CARCINOMA

Amgen Inc., Thousand Oak...

1. A method of treating a patient with renal cell carcinoma (RCC) with a therapeutically effective amount of a vascular endothelial
growth factor (VEGFR) inhibitor and an angiopoietin 2 (Ang2) inhibitor, the method comprising:
measuring the concentration of placental growth factor (PLGF) in an RCC patient sample:
determining that the PLGF concentration in said patient sample is lower than a PLGF concentration parameter; and
administering a therapeutically effective amount of a VEGFR inhibitor and an Ang2 inhibitor to said patient.

US Pat. No. 9,309,263

FUSED MULTI-CYCLIC SULFONE COMPOUNDS AS INHIBITORS OF BETA-SECRETASE AND METHODS OF USE THEREOF

Amgen Inc., Thousand Oak...

18. The compound according to claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a Formula II-B:

wherein
A5 is CR5 or N;

A6 is CR6 or N;

A8 is CR8 or N, provided that no more than one of A5, A6 and A8 is N;

each R1, independently, is H, F, Cl, C1-4-alkyl, C2-4alkenyl, C2-4alkynyl, CN, CH2OC1-3-alkyl, —OC1-3-alkyl, wherein each of the C1-4-alkyl, C2-4 alkenyl, C2-4 alkynyl and C1-3-alkyl portion of —CH2OC1-3-alkyl and —OC1-3-alkyl are optionally substituted with 1-4 substituents of F;

alternatively, each R1 taken together with the carbon atom to which they are attached form a C3-6 spirocarbocyclic ring optionally including one heteroatom selected from O and N and optionally substituted with 1-4 F atoms
on the carbon atoms and a substituent of C1-3alkyl, CH2OC1-2alkyl or C1-3haloalkyl on the nitrogen atom;

R2 is CH3, CH2F or CHF2;

each R3, independently, is halo, C1-4alkyl, CH2OC1-4alkyl, CH2OH, C1-4haloalkyl or cyclopropyl, wherein each of the CH2OC1-4alkyl and cyclopropyl is optionally substituted with 1-4 F atoms;

each of R5, R6 and R8, independently, is H or F;

each R10, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propyn-1-yloxy, 2-butyn-1-yloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl,
piperazinyl, oxetan-3-yl, dioxolyl, —NHC(O)R11— or —C(O)NHR11—, wherein each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propyn-1-yloxy, 2-butyn-1-yloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl
or dioxolyl, is optionally substituted independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, cyclopropylmethoxy, butyl,
butoxyl, isobutoxy, tert-butoxy, 2-butynyloxy, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, oxetan-3yl, oxazolyl, isoxazolyl, imidazolyl or pyrazolyl, wherein each of the oxazolyl, isoxazolyl, imidazolyl
or pyrazolyl is optionally substituted with 1-3 substituents of F or CH3;

each W, independently, is CH, CF, CCl, CCH3 or N;

X is H or F;
Y is —SCR4R4—, —S(O)2CR4R4—, —OCR4R4—, —CR4R4O— or —CR4R4CR4R4—, wherein each R4, independently, is H, F, C1-3alkyl or C1-3haloalkyl; and

o is 0, 1 or 2.

US Pat. No. 9,346,798

DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,
wherein:
Ra is hydrogen, C1-6alkyl or a three to eight membered cycloalkyl group, where the cycloalkyl group may be unsubstituted or substituted with from
1 to 3 substitutents independently selected from halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3 or —OC1-6alkyl;

X is O;
Each of W, Y and Z are independently CR5;

U is absent;
V is absent, —C(Rd)2—, (C?O) or —(C?O)N(Rd)—;

Rb is hydrogen, C1-6alkyl, —(C?O)NRdRd, —S(?O)2NRd or —(C?O)C1-6alkyl;

R1 is a five to six membered heteroaryl group having from one to three heteroatoms independently selected from O, N or S, where
the heteroaryl group may be unsubstituted or substituted with from 1 to 3 substituents independently selected from a B group,
halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3, —OC1-6alkyl or —(CH2)nNRdRd;

R2 is a five to ten membered aryl group or a five to ten membered heteroaryl group having from one to three heteroatoms independently
selected from O, N or S, where the aryl or heteroaryl group may be unsubstituted or substituted with from 1 to 3 substituents
independently selected from an A group, halo, —N3, —CF3, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, —O(CH2)mORc, —NRd five to ten membered aryl, —NRd five to ten membered heteroaryl, —CO2H, —SRd, —S(?O)2Rd, —O-three to eight membered cycloalkyl or —NRd(CH2)mORc, and heteroaryl group having from one to three heteroatoms independently selected from O, N or S, and the aryl, heteroaryl
or cycloalkyl group can be unsubstituted or substituted with from 1 to 3 substituents independently selected from halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3, —OC1-6alkyl or —(CH2)nNRdRd;

A is a five to six membered aryl group, a five to six membered heteroaryl group, a three to six membered cycloalkyl group
or a three to six membered heterocycloalkyl group, wherein the heteroaryl or heterocycloalkyl group has from one to three
heteroatoms independently selected from O, N or S, and where the aryl, heteroaryl cycloalkyl or heterocycloalkyl group may
be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —CF3, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, —O(CH2)mORc, —(C?O)NRdRd, —S(?O)2NRd, NRd(C?O)NRdRd, —NRdS(?O)2NRd, —(C?N)OC1-6alkyl, —S(?O)2Rd or —NRd(CH2)mORc;

B is a five to six membered aryl group, a five to six membered heteroaryl group, a three to six membered cycloalkyl group
or a three to six membered heterocycloalkyl group, wherein the heteroaryl or heterocycloalkyl group has from one to three
heteroatoms independently selected from O, N or S, and where the aryl, heteroaryl cycloalkyl or heterocycloalkyl group may
be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —CF3, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, —O(CH2)mORc, —(C?O)NRdRd, —S(?O)2NRd, —NRd(C?O)NRdRd, —NRdS(?O)2NRd, —(C?N)OC1-6alkyl, —S(?O)2Rd or —NRd(CH2)mORc;

each Rc is independently hydrogen, C1-6alkyl, a three to eight membered cycloalkyl group, a five to 10 membered aryl group, a five to ten membered heteroaryl group
or a three to eight membered heteroacylcoalkyl group; where the heteroaryl or heterocycloalkyl group has from one to three
heteroatoms independently selected from O, N or S, and where the aryl, heteroaryl, cycloalkyl or heterocycloalkyl group may
be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —CF3, —OH, —OCF3, —OH, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, —O(CH2)mORc, —(C?O)NRdRd, —S(?O)2NRd, —N(Rd)2—NRd(C?O)NRdRd, —NRdS(?O)2NRd, —(C?N)OC1-6alkyl, —S(?O)2Rd or —NRd(CH2)mORc;

each Rd is independently hydrogen or C1-6alkyl, -aryl, —Oaryl, heteroaryl, —Oheteroaryl, cycloalkyl or heterocycloalkyl group, where the —Oaryl, heteroaryl, —Oheteroaryl,
cycloalkyl or heterocycloalkyl group may be unsubstituted or substituted with from 1 to 4 substituents independently selected
from halo, —CF3, —OH, —CH2F, —CF2H, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, or —CN;

each R3 is independently hydrogen, C1-6alkyl, —OC1-6alkyl, C1-6haloalkyl, —OC1-6haloalkyl, a five or six membered aryl or —Oaryl group, or a five or six membered heteroaryl or —Oheteroaryl group, a three
to eight membered cycloalkyl group or a three to eight membered heterocycloalkyl group, where the heteroaryl, —Oheteroaryl
or heterocycloalkyl group has from one to three heteroatoms independently selected from O, N or S, and where the aryl, —Oaryl,
heteroaryl, —Oheteroaryl, cycloalkyl or heterocycloalkyl group may be unsubstituted or substituted with from 1 to 4 substituents
independently selected from halo, —CF3, —OH, —CH2F, —CF2H, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, or R3 together with the ring carbon to which it is attached can be a (C?O) group;

each R4 is independently hydrogen, C1-6alkyl, —OC1-6alkyl, C1-6haloalkyl, —OC1-6haloalkyl, a five or six membered aryl or —Oaryl group, or a five or six membered heteroaryl or —Oheteroaryl group, a three
to eight membered cycloalkyl group or a three to eight membered heterocycloalkyl group, where the heteroaryl, —Oheteroaryl
or heterocycloalkyl group has from one to three heteroatoms independently selected from O, N or S, and where the aryl, —Oaryl,
heteroaryl, —Oheteroaryl, cycloalkyl or heterocycloalkyl group may be unsubstituted or substituted with from 1 to 4 substituents
independently selected from halo, —CF3, —OH, —CH2F, —CF2H, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRdRd, or R3 together with the ring carbon to which it is attached can be a (C?O) group;

each R5 is independently hydrogen, halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, —OH, —CF2H, —OCF3,—OCF2H, or —OCFH2;

each n is independently 0 to 3;
each m is independently 1 to 3, and
each p is independently 0 to 3,
provided that the compound of Formula I is not N-(5-chloro-1,3-thiazol-2yl)-4-(2-chloro-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(3-methyl-1,2,4-oxadiazol-5-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(3-cyano-1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(5-methyl-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(5-methyl-4-(trifluoromethyl)-1,3-thiazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-1,3-thiazol-5-yl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(5-methyl-3-isoxazolyl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1-methyl-1H-imidazol-4-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-difluorophenyl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-4-isoxazolyl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-chloro-4-(trifluoromethyl)phenyl)-N-1,3,4-oxadiazol-2-yl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide;
4-(2-bromo-4-(trifluoromethyl)phenyl)-N-1,3-thiazol-5-yl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide; or
4-(2-(1,2,3,6-tetrahydro-4-pyridinyl)-4-(trifluoromethyl)phenyl)-N-1,3-thiazol-5-yl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide.

US Pat. No. 9,096,527

TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS

AMGEN INC., Thousand Oak...

1. A compound of Formula I having the structure:

a pharmaceutically-acceptable salt thereof, a tautomer thereof, a pharmaceutically-acceptable salt of the tautomer, a stereoisomer
thereof, or a mixture thereof, wherein:

m is 0, 1, 2 or 3;
n is 0 or 1;
X1 is C(R4);

X2 is N;

R1 is C1-6alk or a direct-bonded, C1-2alk-linked, C1-2alkO-linked, saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered
bicyclic ring containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O and S, but containing no more than one 0 or S atom,
the C1-6alk and ring being substituted by 0, 1, 2 or 3 substituents independently selected from halo, oxo, C1-6alk, C1-6alkOH, C1-6alk-C(?O)Ra, C1-6alk-C(?O)ORa, C1-4haloalk, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkNRaRa, —OC2-6alkORa, —SRa, ?S, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkNRaRa and —NRaC2-6alkORa, wherein the ring is additionally substituted by 0 or 1 directly bonded, SO2 linked, C(?O) linked or CH2 linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2, 3 or
4 heteroatoms selected from N, O and S, but containing no more than one 0 or S atom, and substituted by 0, 1, 2 or 3 groups
selected from halo, oxo, C1-6alk, C1-4haloalk, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —NRaRa, and —N(Ra)C(?O)Ra;

R2 is —F or —CF3;

R3 is —OCF3 or —CF3;

R4 is independently, at each instance, H, C1-6alk, —C1-3haloalk, —OC1-6alk, —OC1-3haloalk, —N(C1-6alk)C1-6alk, —NHC1-6alk, —NC(?O)C1-6alk, —N(C1-6alk)C1-6alk, F, Cl, Br, CN, OH or NH2; or R3 and R4 together form a four-atom unsaturated bridge containing 0 or 1 N atoms, wherein the bridge is substituted by 0, 1 or 2 R5 substituents;

R5 is independently, in each instance, halo, ORa, CH3 or CF3;

R6 is F, C1-6alk, or ORa;

Ra is independently, at each instance, H or Rb; and

Rb is independently, at each instance, phenyl, benzyl or C1-6alk, the phenyl, benzyl and C1-6alk being substituted by 0, 1, 2 or 3 substituents selected from halo, oxo, C1-4alk, C1-3haloalk, —OC1-4alk, —OH, —NH2, —OC1-4alk, —OC1-4haloalk, —NHC1-4alk, and —N(C1-4alk)C1-4alk.

US Pat. No. 9,441,039

ANTI-ERYTHROPOIETIN ANTIBODIES

Amgen Inc., Thousand Oak...

1. An isolated antibody or fragment of an antibody, wherein the antibody or the fragment specifically binds to human erythropoietin
and comprises:
a. a variable heavy chain complementarity determining region 1 (VH CDR1) of SEQ ID NO: 48;
b. a VH CDR2 of SEQ ID NO: 49;
c. a VH CDR3 of SEQ ID NO: 50;
d. a variable light chain complementarity determining region 1 (VL CDR1) of SEQ ID NO: 18;
e. a VL CDR2 of SEQ ID NO: 19; and
f. a VL CDR3 of SEQ ID NO: 20.
US Pat. No. 9,303,084

HUMAN C-FMS ANTIBODIES

AMGEN INC., Thousand Oak...

1. An isolated antibody or antibody fragment, wherein the antibody or antibody fragment binds human c-fms and comprises a
CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and a CDRL3, wherein:
CDRH1 comprises SEQ ID NO:140, CDRH2 comprises SEQ ID NO:155, CDRH3 comprises SEQ ID NO:169, CDRL1 comprises SEQ ID NO:202,
CDRL2 comprises SEQ ID NO:218, and CDRL3 comprises SEQ ID NO:236; or

CDRH1 comprises SEQ ID NO:140, CDRH2 comprises SEQ ID NO:155, CDRH3 comprises SEQ ID NO:169, CDRL1 comprises SEQ ID NO:201,
CDRL2 comprises SEQ ID NO:218, and CDRL3 comprises SEQ ID NO:236.

US Pat. No. 9,273,110

PRODUCTION OF GLYCOPROTEINS USING MANGANESE

Amgen Inc., Thousand Oak...

1. A product made by a process for producing an erythropoietic composition comprising sialylated erythropoiesis-stimulating
molecules, wherein said erythropoiesis-stimulating molecules comprise analogs of erythropoietin (SEQ ID NO:3) or darbepoetin
(SEQ ID NO:2) with 75% homology to SEQ ID NO:3 or SEQ ID NO:2, respectively, and still retaining erythropoietic activity,
said process comprising the steps of: growing a manganese-responsive host cell transfected with DNA encoding said analog in
a culture medium containing an amount of manganese effective to increase the percentage of sialylated molecules or degree
of sialylation of said erythropoietic composition, wherein the concentration of manganese in said culture medium ranges from
about 0.01 to about 40 ?M; and recovering said erythropoietic composition, wherein less than about 5% of the erythropoiesis-stimulating
molecules are lower sialylated.
US Pat. No. 9,266,945

HUMAN ANTI-B7RP1 NEUTRALIZING ANTIBODIES

AMGEN INC., Thousand Oak...

1. An isolated nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically
to human B7RP1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, the heavy
chain comprising:
a) a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, and a heavy chain CDR3 comprising
SEQ ID NO: 29;

b) a heavy chain CDR1 comprising SEQ ID NO: 30, a heavy chain CDR2 comprising SEQ ID NO: 31, and a heavy chain CDR3 comprising
SEQ ID NO: 32;

c) a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 33, and a heavy chain CDR3 comprising
SEQ ID NO: 34;

d) a heavy chain CDR1 comprising SEQ ID NO: 35, a heavy chain CDR2 comprising SEQ ID NO: 36, and a heavy chain CDR3 comprising
SEQ ID NO: 37;

e) a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 33, and a heavy chain CDR3 comprising
SEQ ID NO: 38; or

f) a heavy chain CDR1 comprising SEQ ID NO: 35, a heavy chain CDR2 comprising SEQ ID NO: 39, and a heavy chain CDR3 comprising
SEQ ID NO: 40.

US Pat. No. 9,145,457

SCLEROSTIN ANTIBODY CRYSTALS AND FORMULATIONS THEREOF

AMGEN INC., Thousand Oak...

1. A crystal of an anti-sclerostin IgG antibody comprising two mature light chains each comprised of SEQ ID NO: 13 and two
mature heavy chains each comprised of SEQ ID NO: 15, wherein said crystals have a length of up to 500 ?m and a shape selected
from the group consisting of ellipsoids, rods and needles or mixtures thereof.
US Pat. No. 9,045,547

METHODS OF USING ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Amgen Inc., Thousand Oak...

1. A method for treating hypercholesterolemia in a patient, said method comprising administering to a patient in need thereof
a therapeutically effective amount of a monoclonal antibody that binds to PCSK9, wherein the monoclonal antibody binds to
an epitope on PCSK9 comprising at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374,
C375, T377, F379, V380, or S381 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding between PCSK9 and an EGFa
domain of LDLR to thereby reduce an elevated serum cholesterol level.

US Pat. No. 9,296,734

PERFLUORINATED 5,6-DIHYDRO-4H-1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of Formula I
or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A4 is CR4 or N;

A5 is CR5 or N;

A6 is CR6 or N;

A8 is CR8 or N, provided that no more than two of A4, A5, A6 and A8 is N;

one R1 is C1-3haloalkyl and the other R1 is H, F, Cl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents of F, oxo or OH;

alternatively, each R1 taken together with the carbon atom to which they are attached form a C3-6 spirocarbocyclic ring optionally including one heteroatom selected from O and N and optionally substituted with 1-4 F atoms
on the carbon atoms and optionally substituted with a substituent of C1-3alkyl, CH2OC1-2alkyl or C1-3haloalkyl on the nitrogen atom;

each of R2, independently, is H, F, Cl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents of F, oxo or OH;

alternatively, each R2 taken together with the carbon atom to which they are attached form a C3-6 spirocarbocyclic ring optionally including one heteroatom selected from O and N and optionally substituted with 1-4 F atoms
on the carbon atoms and optionally substituted with a substituent of C1-3alkyl, CH2OC1-2alkyl or C1-3haloalkyl on the nitrogen atom;

R3 is C1-4alkyl, CH2OC1-4alkyl, CH2OH, C1-4haloalkyl or cyclopropyl, wherein each of the C1-4alkyl, CH2OC1-4alkyl, C1-4haloalkyl and cyclopropyl is optionally substituted with 1-4 F atoms;

each of R4, R5, R6 and R8, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, —S(O)C1-4-alkyl, NHC1-4-alkyl or C(O)C1-4-alkyl;

R7 is —NH—R9, —NH—C(?O)—R9, —C(?O)NH—R9, —NH—C(?S)—R9, —O—R9 or —S—R9;

R9 is acetyl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl or a fully or partially unsaturated 3-, 4-, 5-, 6- or 7-membered monocyclic or 8-, 9- or 10-membered bicyclic ring
formed of carbon atoms, said ring optionally including 1-4 heteroatoms if monocyclic or 1-5 heteroatoms if bicyclic, said
heteroatoms selected from O, N or S, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl and ring are optionally substituted, independently, with 1-5 substituents of R10; and

each R10, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHCH3, oxo, cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, piperazinyl, oxetan-3-yl, imidazo-pyridinyl
or dioxolyl, wherein each of the cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl or dioxolyl, is optionally substituted
independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, CF3, CHF2, CH2F, methyl, methoxy, ethyl, ethoxy, CH2CF3, CH2CHF2, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, butyl, butoxyl, cyclobutyl, isobutoxy, tert-butoxy, isobutyl, sec-butyl,
tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl oxazolyl, or oxetan-3yl,

provided that when A4 is CR4, A5 is CR5, A6 is CR6 and A8 is CR8, and each of R6 and R8, independently, is H, then R5 is not H.

US Pat. No. 9,273,106

FGF MUTANTS WITH REDUCED PROTEOLYSIS AND AGGREGATION

Amgen Inc., Thousand Oak...

1. An isolated fusion protein comprising:
(a) an IgG constant domain;
(b) a linker sequence fused to the IgG constant domain; and
(c) an FGF21 mutant fused to the linker sequence and wherein the FGF21 mutant comprises the amino acid sequence of SEQ ID
NO: 4, wherein an arginine residue has been substituted for the leucine residue at position 98, and wherein a glutamic acid
residue has been substituted for the glycine at position 170.

US Pat. No. 9,598,500

BINDING MOLECULES FOR BCMA AND CD3

Amgen Inc., Thousand Oak...

1. A nucleic acid encoding a binding molecule which is at least bispecific comprising a first and a second binding domain,
wherein
(a) the first binding domain is capable of binding to epitope cluster 3 and to epitope cluster 4 of B cell maturation antigen
(BCMA); and

(b) the second binding domain is capable of binding to the T cell CD3 receptor complex; andwherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002,
and epitope cluster 4 of BCMA corresponds to amino acid residues 42 to 54 of the sequence as depicted in SEQ ID NO: 1002,
and wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising
CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:
(a) CDR-H1 as depicted in SEQ ID NO: 231, CDR-H2 as depicted in SEQ ID NO: 232, CDR-H3 as depicted in SEQ ID NO: 233, CDR-L1
as depicted in SEQ ID NO: 234, CDR-L2 as depicted in SEQ ID NO: 235 and CDR-L3 as depicted in SEQ ID NO: 236;

(b) CDR-H1 as depicted in SEQ ID NO: 241, CDR-H2 as depicted in SEQ ID NO: 242, CDR-H3 as depicted in SEQ ID NO: 243, CDR-L1
as depicted in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245 and CDR-L3 as depicted in SEQ ID NO: 246;

(c) CDR-H1 as depicted in SEQ ID NO: 251, CDR-H2 as depicted in SEQ ID NO: 252, CDR-H3 as depicted in SEQ ID NO: 253, CDR-L1
as depicted in SEQ ID NO: 254, CDR-L2 as depicted in SEQ ID NO: 255 and CDR-L3 as depicted in SEQ ID NO: 256;

(d) CDR-H1 as depicted in SEQ ID NO: 261, CDR-H2 as depicted in SEQ ID NO: 262, CDR-H3 as depicted in SEQ ID NO: 263, CDR-L1
as depicted in SEQ ID NO: 264, CDR-L2 as depicted in SEQ ID NO: 265 and CDR-L3 as depicted in SEQ ID NO: 266;

(e) CDR-H1 as depicted in SEQ ID NO: 271, CDR-H2 as depicted in SEQ ID NO: 272, CDR-H3 as depicted in SEQ ID NO: 273, CDR-L1
as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276;

(f) CDR-H1 as depicted in SEQ ID NO: 281, CDR-H2 as depicted in SEQ ID NO: 282, CDR-H3 as depicted in SEQ ID NO: 283, CDR-L1
as depicted in SEQ ID NO: 284, CDR-L2 as depicted in SEQ ID NO: 285 and CDR-L3 as depicted in SEQ ID NO: 286;

(g) CDR-H1 as depicted in SEQ ID NO: 291, CDR-H2 as depicted in SEQ ID NO: 292, CDR-H3 as depicted in SEQ ID NO: 293, CDR-L1
as depicted in SEQ ID NO: 294, CDR-L2 as depicted in SEQ ID NO: 295 and CDR-L3 as depicted in SEQ ID NO: 296;

(h) CDR-H1 as depicted in SEQ ID NO: 301, CDR-H2 as depicted in SEQ ID NO: 302, CDR-H3 as depicted in SEQ ID NO: 303, CDR-L1
as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 306;

(i) CDR-H1 as depicted in SEQ ID NO: 391, CDR-H2 as depicted in SEQ ID NO: 392, CDR-H3 as depicted in SEQ ID NO: 393, CDR-L1
as depicted in SEQ ID NO: 394, CDR-L2 as depicted in SEQ ID NO: 395 and CDR-L3 as depicted in SEQ ID NO: 396;

(k) CDR-H1 as depicted in SEQ ID NO: 401, CDR-H2 as depicted in SEQ ID NO: 402, CDR-H3 as depicted in SEQ ID NO: 403, CDR-L1
as depicted in SEQ ID NO: 404, CDR-L2 as depicted in SEQ ID NO: 405 and CDR-L3 as depicted in SEQ ID NO: 406;

(l) CDR-H1 as depicted in SEQ ID NO: 411, CDR-H2 as depicted in SEQ ID NO: 412, CDR-H3 as depicted in SEQ ID NO: 413, CDR-L1
as depicted in SEQ ID NO: 414, CDR-L2 as depicted in SEQ ID NO: 415 and CDR-L3 as depicted in SEQ ID NO: 416;

(m) CDR-H1 as depicted in SEQ ID NO: 421, CDR-H2 as depicted in SEQ ID NO: 422, CDR-H3 as depicted in SEQ ID NO: 423, CDR-L1
as depicted in SEQ ID NO: 424, CDR-L2 as depicted in SEQ ID NO: 425 and CDR-L3 as depicted in SEQ ID NO: 426;

(n) CDR-H1 as depicted in SEQ ID NO: 431, CDR-H2 as depicted in SEQ ID NO: 432, CDR-H3 as depicted in SEQ ID NO: 433, CDR-L1
as depicted in SEQ ID NO: 434, CDR-L2 as depicted in SEQ ID NO: 435 and CDR-L3 as depicted in SEQ ID NO: 436;

(o) CDR-H1 as depicted in SEQ ID NO: 441, CDR-H2 as depicted in SEQ ID NO: 442, CDR-H3 as depicted in SEQ ID NO: 443, CDR-L1
as depicted in SEQ ID NO: 444, CDR-L2 as depicted in SEQ ID NO:445 and CDR-L3 as depicted in SEQ ID NO: 446;

(p) CDR-H1 as depicted in SEQ ID NO: 451, CDR-H2 as depicted in SEQ ID NO: 452, CDR-H3 as depicted in SEQ ID NO: 453, CDR-L1
as depicted in SEQ ID NO: 454, CDR-L2 as depicted in SEQ ID NO: 455 and CDR-L3 as depicted in SEQ ID NO: 456;

(q) CDR-H1 as depicted in SEQ ID NO: 461, CDR-H2 as depicted in SEQ ID NO: 462, CDR-H3 as depicted in SEQ ID NO: 463, CDR-L1
as depicted in SEQ ID NO: 464, CDR-L2 as depicted in SEQ ID NO: 465 and CDR-L3 as depicted in SEQ ID NO: 466;

(r) CDR-H1 as depicted in SEQ ID NO: 471, CDR-H2 as depicted in SEQ ID NO: 472, CDR-H3 as depicted in SEQ ID NO: 473, CDR-L1
as depicted in SEQ ID NO: 474, CDR-L2 as depicted in SEQ ID NO: 475 and CDR-L3 as depicted in SEQ ID NO: 476;

(s) CDR-H1 as depicted in SEQ ID NO: 481, CDR-H2 as depicted in SEQ ID NO: 482, CDR-H3 as depicted in SEQ ID NO: 483, CDR-L1
as depicted in SEQ ID NO: 484, CDR-L2 as depicted in SEQ ID NO: 485 and CDR-L3 as depicted in SEQ ID NO: 486;

(t) CDR-H1 as depicted in SEQ ID NO: 491, CDR-H2 as depicted in SEQ ID NO: 492, CDR-H3 as depicted in SEQ ID NO: 493, CDR-L1
as depicted in SEQ ID NO: 494, CDR-L2 as depicted in SEQ ID NO: 495 and CDR-L3 as depicted in SEQ ID NO: 496; and

(u) CDR-H1 as depicted in SEQ ID NO: 501, CDR-H2 as depicted in SEQ ID NO: 502, CDR-H3 as depicted in SEQ ID NO: 503, CDR-L1
as depicted in SEQ ID NO: 504, CDR-L2 as depicted in SEQ ID NO: 505 and CDR-L3 as depicted in SEQ ID NO: 506.

US Pat. No. 9,303,028

AZETIDINE AND PIPERIDINE COMPOUNDS USEFUL AS PDE10 INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X1 is N or CR4;

X2 is N or CR5;

wherein 0 to 1 of X1 and X2 are N;

each of p and q is independently; wherein the sum of p and q is 4; and
each R1, R2, R3, R4, and R5 is independently hydrogen or halo.

US Pat. No. 9,632,095

DEVICE AND METHOD FOR DETERMINING REACTION KINETICS

UNIVERSITY OF DELAWARE, ...

1. A method of determining the reaction rate coefficient (kobs) for the degradation of a chemical species at each of a plurality of constant temperatures, comprising in sequence the steps
of
a) simultaneously incubating a plurality of samples of the chemical species in a single unitary device at said plurality of
constant temperatures T, wherein the incubation of each of the plurality of samples is performed for an incubation time t
selected to result in loss of a portion of the chemical species, said portion being at most 20 mol % of the amount originally
present, where the choice of t might or might not be the same for each value of T;

b) quenching each of the samples in a manner sufficient to stop degradation;
c) determining the mole fraction m of the chemical species remaining in each of the quenched samples, relative to the amount
present before incubating; and

d) determining for each sample a reaction rate coefficient kobs according to the equation


US Pat. No. 9,051,311

SULFAMIDE SODIUM CHANNEL INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,
wherein:
R1 is a five to six membered heteroaryl group, where the heteroaryl group can have from one to three heteroatoms independently
selected from O, N or S, and can be unsubstituted or substituted with from 1 to 3 substituents independently selected from
halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3, —OC1-6alkyl, —COO or —(CH2)—NReRe;

R2 is a three to ten membered cycloalkyl, six to ten membered aryl, five to ten membered heteroaryl or three to ten membered
heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have from one to three heteroatoms independently
selected from O, N or S, and where the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group can be unsubstituted or substituted
with from 1 to 3 substituents independently selected from an A group, halo, —N3,
—CF3, —OH, —OCF3, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNReRe, —O(CH2)mORe, —CO2Re, —SRe, —S(?O)2Re or —NRe(CH2)mORe;
A is a three to ten membered cycloalkyl, six to ten membered aryl, five to ten membered heteroaryl or three to ten membered
heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have from one to three heteroatoms independently
selected from O, N or S, and where the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group can be unsubstituted or substituted
with from 1 to 3 substituents independently selected from halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3, —OC1-6alkyl, —CO2Re or —(CH2)—NReRe;

Ra is hydrogen, C1-6alkyl or a three to ten membered cycloalkyl group, where the cycloalkyl group may be unsubstituted or substituted with from
1 to 3 substitutents independently selected from halo, C1-6alkyl, —CN, —CF3, —OH, —OCF3, —OC2Re or —OC1-6alkyl;

Rb is hydrogen, halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, —OH, —CF2H, —OCF3, —OCF2H, —OC2Re, —(?O) or —OCFH2;

Rc is hydrogen, halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, —OH, —CF2H, —OCF3, —OCF2H, —CO2Re or —OCFH2;

W is a bond;
X is CRd or N;

Y is CRd or N;

Z is CRd or N;

each Rd is independently selected from hydrogen, halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, —OH, —CF2H, —OCF3, —OCF2H, —CO2Re or —OCFH2;

each n is independently 0 to 3;
each m is independently 1 to 3; and
each Re is independently hydrogen or C1-6alkyl,

provided that the compound of Formula I is not
5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide
or

5-(1,2,3,6-tetrahydropyridin-4-yl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide.

US Pat. No. 9,174,992

HETEROBICYCLIC COMPOUNDS

Amgen Inc., Thousand Oak...

1. A compound of Formula (I):

or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, wherein:
each p and q is independently 1; wherein the sum of p and q is 2;
m is 0, 1, 2, 3, or 4;
A is a 9- to 10-membered heterocyclic ring having the formula:

wherein the group —W-T-D< is selected from the group consisting of: —N?CR5—N<; NR7—N?C<; —NR7—(C?O)—N<; NR7—CR6R7—(C?O)—N<; —NR7—(SO2)—N<; —CR5?CR5—N<; —CR8?N—N<; —CR6R7—(C?O)—N<; —CR6R7—NR7—(C?O)—N<; —CR6R7—O—(C?O)—N<; —CR6R7—(SO2)—N<; —O—(C?O)—N<; and —O—CR6R7—(C?O)—N<;

J is CR3c; wherein each E, X, Y, and Z is independently N or CR4; wherein 1, 2, or 3 of E, X, Y, and Z are N;

G is R1, —NR1R2; —NH(C?O)R1; —OR 1, —(C?O)R1; or —CHR1R2;

R1 is a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 9- or 10-membered bicyclic ring, wherein
each said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R1 is independently substituted by 0, 1, 2 or 3 R9 groups;

R2 is independently H, OH, C1-4alk, a carbon-linked or nitrogen-linked saturated, partially-saturated, or unsaturated 5- or 6-membered monocyclic ring, wherein
each said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R2 C1-4alk or monocyclic ring is independently substituted by 0, 1, 2 or 3 R9 groups;

each R3a and R3c is independently H, F, OH, C1-4alk, or C1-4haloalk;

R3b is independently F, Cl, Br, CN, OH, OC1-4alk, C1-4alk, C1-4haloalk, or oxo;

R4 is halo, R4a, —SR4a, —OR4a, —NHR4a, or —N(C1-4alk)R4a, wherein —R4a is H, C1-4alk, a saturated, partially-saturated or unsaturated 3-, 4-, 5- or 6-membered monocyclic ring, wherein each said ring contains
0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R4 C1-4alk or monocyclic ring is independently substituted by 0, 1, 2 or 3 R9 groups;

each R5 is independently R5a, —OR5b, —NHR5a, or —N(C1-4alk)R5a, wherein R5a is H or C1-4alk; R5b is C1-4alk, a saturated, partially-saturated or unsaturated 3-, 4-, 5- or 6-membered monocyclic ring, wherein each said ring contains
0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R5 C1-4alk or monocyclic ring is independently substituted by 0, 1, 2 or 3 R9 groups;

each R6 and R7 is independently H, halo, OH, C1-4alk, OC1-4alk, a saturated, partially-saturated or unsaturated 3-, 4-, 5- or 6-membered monocyclic ring, wherein each said ring contains
0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R6 and R7 C1-4alk or monocyclic ring is independently substituted by 0, 1, 2 or 3 R9 groups;

or R6 and R7 may optionally form a saturated or partially-saturated 3-, 4-, 5- or 6-membered monocyclic ring, wherein each said ring contains
0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein said monocyclic ring is independently substituted by 0, 1, 2
or 3 R9 groups;

R8 is R8a, —O—R8a, —NHR8a, or —N(C1-4alk)R8a, wherein R8a is H, C1-4alk, a saturated, partially-saturated or unsaturated 3-, 4-, 5- or 6-membered monocyclic ring, wherein each said ring contains
0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 O or S atoms; wherein each R8 C1-4alk or monocyclic ring is independently substituted by 0, 1, 2 or 3 R9 groups;

R9 is independently F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, ORc, —OC1-4haloalk, CN, —C(?O)Rb, —C(?O)Rc, —C(?O)ORa, —C(?O)NRaRa, —C(?O)NRaRc, —C(?NRa)NRaRa, —OC(?O)Rb, —OC(?O)NRaRa, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(?O)Rb, —S(?O)2Rb, —S(?O)2NRaRa, —NRaRa, —N(Ra)C(?O)Rb, —N(Ra)C(?O)ORb, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Rb, —N(Ra)S(?O)2NRaRa, —NRaC1-6alkNRaRa, —NRaC1-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6 alkN(Ra)C(?O)Rb, —C1-6alkOC(?O)Rb, —C1-6alkC(?O)NRaRa, —C1-6alkC(?O)ORa, or oxo;

R10 is halo, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —C(?O)Rb, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —OC(?O)Rb, —OC(?O)NRa Ra, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(?O)Rb, —S(?O)2Rb, —S(?O)2NRaRa, —NRaRa, —N(Ra)C(?O)Rb, —N(Ra)C(?O)ORb, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Rb, —N(Ra)S(?O)2NRaRa, —NRaC1-6alkNRaRa, —NRaC1-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6alkN(Ra)C(?O)Rb, —C1-6alkOC(?O)Rb, —C1-6alkC(?O))NRaRa, —C1-6alkC(?O)ORa, or oxo;

Ra is independently H or Rb;

Rb is independently phenyl, benzyl, or C1-6alk, wherein said phenyl, benzyl, and C1-6alk are substituted by 0, 1, 2 or 3 substituents which are C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(?O)C1-4alk, or —N(C1-4alk)C1-4alk; and

Rc is independently a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered
monocyclic ring or a saturated, partially-saturated or unsaturated 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring,
said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms which are O or S; Rc is independently substituted by 0, 1, 2 or 3 R10 groups.

US Pat. No. 9,296,698

AMINO HETEROARYL COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of Formula I:
or a stereoisomer or pharmaceutically acceptable salt thereof, wherein
A is a phenyl, pyridine, pyrimidine, triazine or thiophene ring;
each of B1, B2 and B3, independently, is —CF, —CCH3 or CH;

L is —CR2R2—(CR3R3)o— wherein

each R2, independently, is H, C1-3alkyl or halo; and

each R3, independently, is H, C1-6alkyl, C3-6cycloalkyl, —OH, —OC1-4alkyl, halo, haloalkyl, CN, —NH2 or —NHC1-6alkyl and o is 1;

each R1, independently, is F, Cl, Br, CF3, OCF3, C1-6-alkyl, CN, OH, —OC1-6-alkyl, C1-6-alkenyl, C1-6-alkynyl, —S(O)nC1-6-alkyl, —NH2, CN, —NHC1-6-alkyl, —C(O)C1-6-alkyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-heterocyclyl, —C(O)—C3-8-cycloalkyl or —C(O)NRaRb wherein Ra is H or C1-6alkyl and Rb is R6;

alternatively, Ra and Rb taken together with the nitrogen atom to which they are attached form a 4-7 membered monocyclic or 6-10 membered bicyclic
heterocycle,

wherein the C1-6-alkyl, the C1-6-alkyl portion of the —OC1-6-alkyl, the C3-8-cycloalkyl of the —C(O)—C3-8-cycloalkyl, and the monocyclic and bicyclic heterocycle are optionally substituted with 1-3 substituents of R6;

R4 is H;

R5 is C1-6-alkyl, C3-8-cycloalkyl or a ring selected from phenyl, pyridyl, pyrimidyl, thienyl, furanyl, pyrrolidinyl, pyrazolyl, imidazolyl, triazolyl,
tetrazolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, diazolyl, thiodiazolyl, oxadiazolyl, oxazolinyl, isoxazolinyl,
thiazolinyl, pyranyl, pyrazinyl, pyridazinyl, morpholinyl, piperidinyl and piperazinyl, wherein the C1-6-alkyl, C3-8-cycloalkyl and ring are optionally substituted, independently, with 1-5 substituents of R6;

each R6, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, acetyl, oxo, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl or a fully saturated or partially or fully unsaturated 3-8 membered monocyclic or a 6-12 membered bicyclic ring
system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic,
said heteroatoms selected from O, N, or S, wherein each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl and ring of said ring system is optionally substituted independently with 1-5 substituents of halo, haloalkyl,
haloalkoxyl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl,
butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, pentyl, cyclopentyl, hexyl, cyclohexyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-thioalkoxyl, benzyl or phenyl;

m is 0, 1, 2, 3, 4 or 5; and
n is 0, 1 or 2.

US Pat. No. 9,212,182

BICYCLIC SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

Amgen Inc., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,
wherein:
each of A1 and A2 is, independently, CRa or N, provided no more than one of A1 and A2 is N;

wherein each Ra is independently H, halo, —NRcRc, —OH, hydroxyC1-6alkyl, —C1-6alkyl, —OC1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —CN,

R1 is a 6 membered aryl or heteroaryl, wherein the aryl or heteroaryl is substituted with from 1 to 4 substituents independently selected
from halo, OH, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —OC1-6alkylCF3, —OC1-6alkylCN, —(CReRe)mCN,—C1-6alkylOC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —(CReRe)mA, —N(Re)(CReRe)mA, —O(CReRe)mA, —O(CReRe)mOA or —C(?O)A, provided at least one substituent on R1 is —(CReRe)mA, —N(Re)(CReRe)mA, —O(CReRe)mA, —O(CReRe)mOA or —C(?O)A;

A is a 4 to 9 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have
from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 6 membered cycloalkyl group, and the aryl, heteroaryl,
heterocycloalkyl or cycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected
from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CReRe)mOH, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN, —C(?O)NRbRb, —O(CReRe)mB or —(CReRe)mB;

B is a 3 to 5 membered cycloalkyl group that can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from Cl, F, Br, —NHCH3, —N(CH3)2, —C1-4alkyl, —OC1-4alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F or —CN;

R2 is a 5 to 6 membered aryl or heteroaryl, where the heteroaryl can have from 1 to 3 heteroatoms independently selected from
O, N or S, and the aryl and heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CRcRc)nNRbRb, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(?O)NRbRb;

each Rb is independently H or —C1-6alkyl;

each Rc is independently H or —C1-6alkyl; and

each Rd is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —OC1-6alkyl;

each Re is independently H, halo, —CN, —NRcRc, —OH, —C6alkyl or —OC1-6alkyl;

each n is independently 0, 1, 2, 3 or 4; and
each m is independently 0, 1, 2, 3 or 4.
US Pat. No. 9,895,308

HETEROCYCLIC COMPOUNDS AND THEIR USES

AMGEN INC., Thousand Oak...

1. A pharmaceutical tablet formulation comprising:
a drug layer, comprising omecamtiv mecarbil dihydrochloride hydrate;
a sweller layer; and
a semi-permeable membrane coating having at least one delivery port,wherein the semi-permeable membrane coating comprises 80% insoluble polymer and 20% pore forming polymer.

US Pat. No. 9,656,998

INTERMEDIATES FOR PREPARING TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A compound of Formula V, a salt thereof, a tautomer thereof, or a salt of the tautomer:

wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with
1, 2, 3, or 4 R1a substituents;

R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —C(?O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(?O)-(heterocyclyl) or heterocyclyl
group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;

R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b?CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of
which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;

R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or N(C1-C6 alkyl)2;

R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3d and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;

Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected
from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein
the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with
1, 2, 3, or 4 RQ substituent;

RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo substituent;

R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently
selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or
4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents; and

R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), or —C(?O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent.

US Pat. No. 9,820,938

STABLE LIQUID FORMULATION OF AMG 416 (ETELCALCETIDE)

Amgen Inc., Thousand Oak...

1. A pharmaceutical formulation comprising AMG 416 in aqueous solution, wherein the formulation has a pH of 2.0 to 5.0.
US Pat. No. 9,856,287

REFOLDING PROTEINS USING A CHEMICALLY CONTROLLED REDOX STATE

Amgen Inc., Thousand Oak...

1. A method of refolding proteins expressed in a non-mammalian expression system, the method comprising:
contacting the proteins with a preparation that supports the renaturation of at least one of the proteins to a biologically
active form, to form a refold mixture, the preparation comprising:

at least one ingredient selected from the group consisting of a denaturant, an aggregation suppressor and a protein stabilizer;
an amount of oxidant; and
an amount of reductant,
wherein the amounts of the oxidant and the reductant are related through a thiol-pair ratio and a thiol-pair buffer strength,
wherein the thiol-pair ratio is in the range of 0.001-100; and
wherein the thiol-pair buffer strength maintains the solubility of the preparation; and
incubating the refold mixture so that at least about 25% of the proteins are properly refolded.
US Pat. No. 9,534,053

THERAPEUTIC HUMAN ANTI-IL-1R1 MONOCLONAL ANTIBODY

Amgen Inc., Thousand Oak...

1. A method for treating an IL-1 mediated disease selected from the group consisting of: pulmonary disease, chronic obstructive
pulmonary disease or COPD, pulmonary alveolar proteinosis, bleomycin induced pneumopathy, pulmonary fibrosis, idiopathic pulmonary
fibrosis, radiation induced pulmonary fibrosis, cystic fibrosis, collagen accumulation in the lungs, acute respiratory distress
syndrome or ARDS, broncho-pulmonary dysplasia or BPD, chronic obstructive pulmonary diseases selected from emphysema and chronic
bronchitis, chronic fibrotic lung disease, asbestosis, coal worker's pneumoconiosis, silicosis, bronchioliterans organizing
pneumonia, pulmonary sarcoidosis, allergic rhinitis, contact dermatitis, atopic dermatitis, diabetes, inflammatory bowel disease,
rheumatoid arthritis, and asthma, comprising administering to a subject having said IL-1 mediated disease an antibody or an
antigen binding fragment thereof, that specifically binds human interleukin-1 receptor type 1 (IL-1R1), wherein the antibody
or antigen binding fragment comprises:
a) i) human heavy chain framework regions, a heavy chain CDR1 region comprising SEQ ID NO: 63, a heavy chain CDR2 region comprising
SEQ ID NO: 66, and a heavy chain CDR3 region comprising SEQ ID NO: 69; and ii) human light chain framework regions, a light
chain CDR1 region comprising SEQ ID NO: 71, a light chain CDR2 region comprising SEQ ID NO: 73, and a light chain CDR3 region
comprising SEQ ID NO: 75;

b) a heavy chain variable region comprising SEQ ID NO: 80, and a light chain variable region comprising SEQ ID NO: 81; or
c) a heavy chain variable region comprising an N-terminal or C-terminal deletion of SEQ ID NO: 80, and a light chain variable
region comprising an N-terminal or C-terminal deletion of SEQ ID NO: 81, wherein said N-terminal or C-terminal deletion of
SEQ ID NO: 80 comprises at least SEQ ID NO: 63, SEQ ID NO:66, and SEQ ID NO: 69, and wherein said N-terminal or C-terminal
deletion of SEQ ID NO: 81 comprises at least SEQ ID NO: 71, SEQ ID NO: 73, and SEQ ID NO: 75.

US Pat. No. 9,480,624

VIAL ADAPTER AND SYSTEM

AMGEN INC., Thousand Oak...

1. A vial adapter for use with a vial having a neck with a passage in the neck and a rim disposed adjacent the neck, a stopper
disposed over the passage in the neck of the vial to control access through the passage into the vial, and a crimp ring disposed
about the stopper and the rim to maintain the stopper fixed relative to the vial, the vial adapter comprising:
first and second collar sections each having first and second ends that are joined with the opposing first and second ends
of an other one of the first and second collar sections to form a collar having a central passage in which the neck of the
vial is disposed, the central passage extending between opposite axial end surfaces of the collar and being narrowest at an
inwardly depending axially central section of the collar;

each of the first and second collar sections having a hook formed at each end of each of the first and second collar sections,
the hooks of opposing ends of the first and second collar sections joined to each other to join the first and second collar
sections together; and

the first ends of each of the first and second collar sections having at least one tab depending therefrom and the second
ends of each of the first and second collar sections having at least one indent formed therein, the at least one tab of each
of the first and second collar sections disposed within the at least one indent of the other one of the first and second collar
sections with the hooks of opposing ends of the first and second collar sections joined to each other, the at least one tab
of each of the first and second collar sections being located radially outward of an inner portion of the other one of the
first and second collar sections, and the at least one tab of each of the first and second collar sections defining an axial
end surface of its respective collar section.

US Pat. No. 9,458,234

TLR2 ANTAGONISTIC ANTIBODY AND USE THEREOF

Technische Universitat Mu...

1. An isolated cross-reactive antibody or a fragment thereof, which specifically inhibits or blocks mammalian Toll-like Receptor
2 (TLR2)-mediated immune cell activation by specifically binding to the C-terminal portion of the extracellular domains of
at least human and murine TLR2, wherein the antibody or fragment thereof specifically binds through the variable regions of
the heavy and light chains, wherein the heavy chain variable region comprises a complementarity determining region 1 (CDR1)
region wherein the amino acid sequence of the CDR1 region comprises Gly-Phe-Thr-Phe-Thr-Thr-Tyr-Gly (residues 58-65 of SEQ
ID NO:6), a CDR2 region wherein the amino acid sequence of the CDR2 region comprises Ile-Tyr-Pro-Arg-Asp-Gly-Ser-Thr (residues
83-90 of SEQ ID NO: 6) and a CDR3 region wherein the amino acid sequence of the CDR3 region comprises Ala-Arg-Leu-Thr-Gly-Gly-Thr-Phe-Leu-Asp-Tyr
(residues 129-139 of SEQ ID NO:6), and wherein the light chain variable region comprises a CDR1 region wherein the amino acid
sequence of the CDR1 region comprises Glu-Ser-Val-Glu-Tyr-Tyr-Gly-Thr-Ser-Leu (residues 47-56 of SEQ ID NO:7), a CDR2 region
wherein the amino acid sequence of the CDR2 region comprises Gly-Ala-Ser (residues 74-76 of SEQ ID NO:7) and a CDR3 region
wherein the amino acid sequence of the CDR3 region comprises Gln-Gln-Ser-Arg-Lys-Leu-Pro-Trp-Thr (residues 113-121 of SEQ
ID NO:7), wherein the CDRs are identified by the IMGT database.

US Pat. No. 9,458,152

BICYCLIC SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

Amgen Inc., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,

wherein:

wherein each Ra is independently H, halo, —OH, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —CN, and

R1 is a 5 to 10 membered aryl or heteroaryl, wherein the heteroaryl group can have from 1 to 3 heteroatoms independently selected
from O, N or S, and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —OC1-6alkylCF3, —OC1-6alkylCN, —C1-6alkylOC1-6alkyl, —(SO2)C1-6alkyl, —(SO2)NRbRb, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —(CReRe)mCN, —C(?O)NRbRb, —C(?O)ORb, —N(CReRe)mA, —N(Re)(CReRe)mA, —(C?N)OC1-6alkyl, —(C?O)N(Re)(CReRe)mA, (C?O)N(Re)(CReRe)mCF3, —O(CReRe)mA, —O(CReRe)mOA or —C(?O)A;

A is a 4 to 9 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have
from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 6 membered cycloalkyl group, and the aryl, heteroaryl,
heterocycloalkyl or cycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected
from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CReRe)mOH, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN, —C(?O)NRbRb, —O(CReRe)mB or —(CReRe)mB;

B is a 5 to 6 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have
from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 5 membered cycloalkyl group, and the aryl, heteroaryl,
cycloalkyl or heterocycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected
from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(?O)NRbRb;

R2 is a 5 to 10 membered aryl or heteroaryl, where the heteroaryl group can have from 1 to 3 heteroatoms independently selected
from O, N or S, and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, hydroxyC1-6alkyl, —(CRcRc)nNRbRb, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(?O)NRbRb;

each Rb is independently H or —C1-6alkyl;

each Rc is independently H or —C1-6alkyl; and

each Rd is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —OC1-6alkyl;

each Re is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —OC1-6alkyl or a 5 to 6 membered heterocycloalkyl group having from 1 to 3 heteroatoms independently selected from O, N or S;

each n is independently 0, 1, 2, 3 or 4;
each m is independently 0, 1, 2, 3 or 4.
US Pat. No. 9,382,309

VARIANT ACTIVIN IIB RECEPTOR

Amgen Inc., Thousand Oak...

1. An isolated protein comprising a variant activin IIB receptor (vActRIIB) polypeptide wherein the polypeptide is selected
from the group consisting of:
(a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 18, wherein the polypeptide comprises an amino
acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E;

(b) a polypeptide comprising the amino acid sequence set forth in amino acids 19 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(c) a polypeptide comprising the amino acid sequence set forth in amino acids 23 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(d) a polypeptide comprising the amino acid sequence set forth in amino acids 25 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E; and

(e) a polypeptide having at least 95% identity to any one of (a) through (d), wherein the polypeptide comprises an amino acid
substitution at the position corresponding to position 28 of SEQ ID NO:18, wherein the substitution at position 28 is A, W,
Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.

US Pat. No. 9,708,375

INHIBITORY POLYPEPTIDES SPECIFIC TO WNT INHIBITORS

Amgen Inc., Thousand Oak...

1. A polypeptide comprising a non-naturally-occurring monomer domain capable of binding sclerostin, wherein the monomer domain
comprises the amino acid sequence of DVAYAECMDSLEDVDYNCFLPEDQ (SEQ ID NO: 683).

US Pat. No. 9,505,749

QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF

AMGEN INC., Thousand Oak...

49. A pharmaceutical composition, comprising the compound of claim 1 or the pharmaceutically acceptable salt thereof, the tautomer thereof, the pharmaceutically acceptable salt of the tautomer,
the stereoisomer of any of the foregoing, or the mixture thereof, and at least one pharmaceutically acceptable excipient,
carrier, or diluent.

US Pat. No. 9,085,576

PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

AMGEN INC., Thousand Oak...

1. A compound of Formula I

or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein
A4 is CR4 or N;

A5 is CR5 or N;

A6 is CR6 or N;

A8 is CR8 or N, provided that no more than two of A4, A5, A6 and A8 is N;

each of Ra and Rb, independently, is H, F, Cl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents of F, oxo or OH;

each of R1 and R2, independently, is H, F, Cl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)C1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents of F, oxo or OH;

R3 is C1-4alkyl, CH2OC1-4alkyl, CH2OH, C1-4haloalkyl or cyclopropyl, wherein each of the C1-4alkyl, CH2OC1-4alkyl, C1-4haloalkyl and cyclopropyl is optionally substituted with 1-4 F atoms;

each of R4, R5, R6 and R8, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, S(O)C1-4-alkyl, NHC1-4-alkyl or C(O)C1-4-alkyl;

R7 is —NH—R9, —NH—C(?O)—R9, —C(?O)NH—R9, —O—R9 or —S—R9;

R9 is acetyl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl or a fully or partially unsaturated 3-, 4-, 5-, 6- or 7-membered monocyclic or 8-, 9- or 10-membered bicyclic ring
formed of carbon atoms, said ring optionally including 1-4 heteroatoms if monocyclic or 1-5 heteroatoms if bicyclic, said
heteroatoms selected from O, N or S, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl and ring are optionally substituted, independently, with 1-5 substituents of R10; and

each R10, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHCH3, oxo, cyclopropylmethoxy, 2-butynyloxy, C1-6alkyl, C2-6alkenyl, C2-6 alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, tetrahydropyrrolyl, piperazinyl,
oxetan-3-yl, imidazo-pyridinyl or dioxolyl, wherein each of the cyclopropylmethoxy, 2-butynyloxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl or dioxolyl, is optionally substituted
independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, CF3, CHF2, CH2F, methyl, methoxy, ethyl, ethoxy, CH2CF3, CH2CHF2, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, butyl, butoxyl, cyclobutyl, isobutoxy, tert-butoxy, isobutyl, sec-butyl,
tert-butyl, cyclopentyl, cyclohexyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl tetrahydropyranyl, tetrahydropyrrolyl or oxetan-3yl,

provided the compound is not
N-(3-((1R,5R,6R)-3-amino-5-methyl-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-3-methoxy-1,7-naphthyridin-8-amine;
or

N-(3-((1R,5R,6R)-3-amino-5-methyl-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-methoxy-2-pyrazinecarboxamide.

US Pat. No. 9,079,902

HETEROARYL SODIUM CHANNEL INHIBITORS

AMGEN INC., Thousand Oak...

1. A compound of Formula I or II, or a pharmaceutically acceptable salt thereof,
wherein:
each X1, X2 or X3 is independently CRa;

each Ra is independently hydrogen, halo, C1-6alkyl, —OC1-6alkyl, or —CN;

each Rb is independently hydrogen or C1-6alkyl;

R1 is a five or six membered heteroaryl or heterocycloalkyl group having from one to four heteroatoms independently selected
from O, N or S, or a five or six membered aryl or cycloalkyl group, where the heteroaryl, heterocycloalkyl, aryl or cycloalkyl
group is unsubstituted or substituted with from one to four substituents selected from halo, C1-6alkyl, —OH, —OC1-6alkyl or —NRbRb;

R2 is a five to ten membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl group, the heteroaryl or heterocycloalkl group
having from one to four heteroatoms independently selected from O, N or S, and where the cycloalkyl, heterocycloalkyl, aryl
or heteroaryl group is unsubstituted or substituted with from one to four substituents independently selected from —CF3, —CHF2, —CF2H, —OC1-6alkyl, —OCF3, —C1-6alkyl, halo, —C?C—Rb, —CN, —NRbRb, —S(?O)2C1-6alkyl, or Y;

Y is a five or six membered heteroaryl or heterocycloalkyl group having from one to four heteroatoms independently selected
from O, N or S, or six membered aryl or five or six membered cycloalkyl group, which heteroaryl, heterocycloalkyl, aryl or
cycloalkyl group is unsubstituted or substituted with from one to four substituents independently selected from —CF3, —CHF2, —CF2H, —OC1-6alkyl, —OCF3, C1-6alkyl, halo, —C?C—Rb, —CN, —NRbRb, —S(?O)2C1-6alkyl, —C(?O)C1-6alkyl or Z;

Z is a three to six membered heterocycloalkyl group having from one to four heteroatoms independently selected from O, N or
S;

R3 is hydrogen, C1-6alkyl, —C(?O)C1-6alkyl, —C(?O)OC1-6alkyl, or —S(?O)2C1-6alkyl; and

R4 is hydrogen or C1-6alkyl, provided that the compound of Formula I is not

1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-2-pyrimidinyl-1H-indole-6-sulfonamide;
3-(1-(3-azetidinyl)-1H-pyrazol-3-yl)-1-methyl-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide;
3-(2-(5-acetyl-2-thiophenyl)-4-(trifluoromethyl)phenyl)-1-methyl-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide;
1-methyl-3-(5-phenyl-2-thiophenyl)-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide;
N-(4-((1R)-1-methoxyethyl)-1,3-thiazol-2-yl)-1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide;
N-(4-((1S)-1-methoxyethyl)-1,3-thiazol-2-yl)-1-methyl-3-(2(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide;
1-methyl-3-(4-(methylsulfonyl)phenyl)-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide;
N-(3-ethyl-1,2,4-thiadiazol-5-yl)-1-methyl-3-(241-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonamide;
1-methyl-3-(4-((methylsulfonyl)amino)phenyl)-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide; or
3(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-1-methyl-N-1,2,4-thiadiazol-5-yl-1H-indole-6-sulfonamide.
US Pat. No. 9,981,988

POLYMORPHIC FORMS AND CO-CRYSTALS OF A C-MET INHIBITOR

AMGEN INC., Thousand Oak...

1. A free base form of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, wherein the free base form is a monohydrate form.

US Pat. No. 9,611,261

PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of formula

or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,499,620

METHODS OF USING AN ALPHA-4-BETA-7 HETERODIMER SPECIFIC ANTAGONIST ANTIBODY

AMGEN INC., Thousand Oak...

1. A method of treating an individual afflicted with a condition characterized by inappropriate trafficking of cells expressing
alpha4beta7 to tissues comprising cells expressing MAdCAM-I, wherein the condition is inflammatory bowel disease, comprising
administering to the individual a composition in an amount sufficient to treat inflammatory bowel disease, wherein said composition
comprises:
(a) an alpha4beta7 heterodimer specific antigen binding protein selected from the group consisting of:
(i) an alpha4beta7 heterodimer specific antigen binding protein having a heavy chain variable region comprising CDR1, CDR2
and CDR3 from SEQ ID NO:37, and a light chain variable region comprising CDR1, CDR2 and CDR3 from SEQ ID NO:9;

(ii) an alpha4beta7 heterodimer specific antigen binding protein wherein the light chain variable region is at least 90% identical
to SEQ ID NO:9, and the heavy chain variable region is at least 90% identical to SEQ ID NO:37; and

(iii) an alpha4beta7 heterodimer specific antigen binding protein wherein the light chain variable region comprises SEQ ID
NO:9, and the heavy chain variable region is selected from the group consisting of a polypeptide that comprises SEQ ID NO:37
and a polypeptide that comprises SEQ ID NO:37 wherein the N-terminal amino acid is converted to pyroglutamic acid; and

(b) a physiologically acceptable diluent, excipient or carrier.

US Pat. No. 9,296,735

METHOD FOR THE PREPARATION OF THIADIAZOLES

Amgen Inc., Thousand Oak...

1. A compound of the structure

Wherein R is alkyl, aryl or the two R groups together form cycloalkyl; and
Rb is an optionally substituted substituent selected from aryl, alkyl, arylalkyl, and 5-6 membered heterocyclyl.

US Pat. No. 9,115,127

BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE

AMGEN INC., Thousand Oak...

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, tautomer thereof, a pharmaceutically acceptable salt of the tautomer, or a
stereoisomer of any of the foregoing, wherein:

R1 is —H;

R2 is —H;

R3 is —H;

X is selected from CR4;

R4 is —H;

Y is selected from a C3-C12 cycloalkyl or a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from O, S, or N; wherein the C3-C12 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic, bicyclic, or tricyclic, and further wherein the C3-C12 cycloalkyl and the 3-10 membered heterocyclyl comprise a substituent selected from C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)NH—(C1-C4)alkylene-CF3, —C(?O)NH—(C1-C4)alkylene-F, —C(?O)NH—(C2-C4)alkenyl, —C(?O)N((C1-C6)alkyl)2, —C(?O)NH—OH, —C(?O)NH—O—(C1-C6)alkyl, —C(?O)NH—Y?, —C(?O)—(C1-C4)alkylene-CF3, —C(?O)N—(C1-C4)alkylene-F, —C(?O)—(C2-C4)alkenyl, —C(?O)—(C1-C4)alkylene-NH2, —C(?O)—(C1-C4)alkylene-NH((C1-C4)alkyl), —C(?O)—(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH—(C1-C4)alkylene-OH, —C(?O)NH—(C1-C4)alkylene-O—(C1-C6)alkyl, —C(?O)NH—(C1-C4)alkylene-Y?, —C(?O)—(C1-C6)alkyl, —C(?O)—Y?, —CO2H, —C(?O)—O—(C1-C6)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C6)alkyl), and —C(?O)NH—(C1-C4)alkylene-N((C1-C6)alkyl)2, —(C1-C4)alkylene-NH—C(?O)—(C1-C6)alkyl; and

wherein Y optionally further comprises 1 or 2 substituents selected from Y?, —F, —Cl, —Br, —I, —C?N, —NO2, —OH, —O-(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl —OCF3, —OCHF2—CF3, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —NHSO2—(C1-C6)alkyl, —NHC(?O)—(C1-C6)alkyl, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)NH—(C1-C4)alkylene-CF3, —C(?O)NH—(C1-C4)alkylene-F, —C(?O)NH—(C2-C4)alkenyl, —C(?O)N((C1-C6)alkyl)2, —C(?O)NH—OH, —C(?O)NH—O—(C1-C6)alkyl, —C(?O)NH—Y?, —C(?O)—(C1-C4)alkylene-CF3, —C(?O)N—(C1-C4)alkylene-F, —C(?O)—(C2-C4)alkenyl, —C(?O)—(C1-C4)alkylene-NH2, —C(?O)—(C1-C4)alkylene-NH((C1-C4)alkyl), —C(?O)—(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH—(C1-C4)alkylene-OH, —C(?O)NH—(C1-C4)alkylene-O—(C1-C6)alkyl, —C(?O)NH—(C1-C4)alkylene-Y?, —C(?O)—(C1-C6)alkyl, —C(?O)—Y?, —CO2H, —C(?O)—O—(C1-C6)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C6)alkyl), and —C(?O)NH—(C1-C4)alkylene-N((C1-C6)alkyl)2, —SO2NH2, —SO2NH((C1-C6)alkyl), —SO2N((C1-C6)alkyl)2, —SO2NH((C2-C4)alkenyl), —SO2NH((C2-C4)alkynyl), —SO2NH—Y?, —SO2NH—(C1-C4)alkylene-OH, —SO2NH—(C1-C4)alkylene-O—(C1-C4)alkyl, —SO2—(C1-C6)alkyl, —SO2—Y?, —SO—(C1-C6)alkyl, —(C1-C4)alkylene-NH—C(?O)—(C1-C6)alkyl, —(C1-C4)alkylene-NH—(C1-C6)alkyl, —(C1-C4)alkylene-N((C1-C6)alkyl)2-(C1-C4)alkylene-OH, —(C1-C4)alkylene-O—(C1-C6)alkyl, —(C1-C4)alkylene-C(?O)—(C1-C6)alkyl, —(C1-C4)alkylene-C(?O)—O—(C1-C6)alkyl, or —(C1-C4)alkylene-C(?O)—OH, wherein two substituents on a carbon ring member of the Y cycloalkyl or heterocyclyl may join to form
a 3-7 membered cycloalkyl group or a 3-7 membered heterocyclyl group that comprises 1 to 3 heteroatoms selected from N, O,
or S; and further wherein 1 or 2 carbon atom ring members of the 3-7 membered cycloalkyl or the 3-7 membered heterocyclyl
group formed from the two substituents on the carbon ring member of the Y cycloalkyl or heterocyclyl may be double bonded
to an O atom;

Y? may be absent or is a C6-C10 aryl, a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, or a 3-7 membered
heterocyclyl comprising 1, 2, or 3 heteroatoms selected from O, S, or N, wherein the C6-C10 aryl, the 5-10 membered heteroaryl, or the 3-7 membered heterocyclyl Y? groups are unsubstituted or are optionally substituted
with 1, 2, or 3 substituents independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C4)alkylene-OH, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C4)alkyl), —C(?O)N((C1-C4)alkyl)2, —SO2NH2, —SO2NH((C1-C4)alkyl), —SO2N((C1-C4)alkyl)2, —NHSO2—(C1-C4)alkyl, —NHC(?O)—(C1-C4)alkyl, —SO2—(C1-C6)alkyl, —SO—(C1-C4)alkyl, —(C1-C4)alkylene-NH—C(?O)—(C1-C4)alkyl, —CF3, —C(?O)—(C1-C4)alkyl, —CO2H, —C(?O)—O—(C1-C4)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C4)alkyl), —C(?O)NH—(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH—(C1-C4)alkylene-OH, —C(?O)NH—(C1-C4)alkylene-CF3, —C(?O)NH—(C1-C4)alkylene-O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—OH, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, or —OCHF2;

Y? may be absent or is selected from a C3-C10 cycloalkyl; a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from N, O, and S; a C6-C10 aryl; or a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; wherein the
C3-C10 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic or bicyclic, and further wherein the C3-C10 cycloalkyl, the 3-10 membered heterocyclyl, the C6-C10 aryl, or the 5-10 membered heteroaryl Y? groups are unsubstituted or are optionally substituted with 1, 2, or 3 substituents
independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C4)alkylene-OH, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C4)alkyl), —C(?O)N((C1-C4)alkyl)2, —SO2NH2, —SO2NH((C1-C4)alkyl), —SO2N((C1-C4)alkyl)2, —NHSO2—(C1-C4)alkyl, —NHC(?O)—(C1-C4)alkyl, —SO2—(C1-C6)alkyl, —SO—(C1-C4)alkyl, —(C1-C4)alkylene-NH—C(?O)—(C1-C4)alkyl, —CF3, —C(?O)—(C1-C4)alkyl, —CO2H, —C(?O)—O—(C1-C4)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C4)alkyl), —C(?O)NH—(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH—(C1-C4)alkylene-OH, —C(?O)NH—(C1-C4)alkylene-CF3, —C(?O)NH—(C1-C4)alkylene-O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—OH, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, or —OCHF2;

W is selected from —(CRaRa?)q—O—(C1-C6)alkyl, —(CRaRa?)q—O—W?, —O—(CRaRa?)q—W?, —O—(CRaRa?)q—OH, —O—(CRaRa?)q—O—(C1-C6)alkyl, —(CRaRa?)q—O—(CRaRa?)q—OH, —(CRaRa?)q—O—(CRaRa?)q—O—(C1-C6)alkyl, —(CRaRa?)q—SH, —(CRaRa?)q—S—(C1-C6)alkyl, —(CRaRa?)q—S—W?, —S—(CRaRa?)q—W?, —(CRaRa?)q—S(O)2—(C1-C6)alkyl, —(CRaRa?)q—S(O)2—W?, —S(O)2—(CRaRa?)q—W?, —(CRaRa?)q—NH2, —(CRaRa?)q—NH—(C1-C6)alkyl, —(CRaRa?)q—N—((C1-C6)alkyl,)2, —(CRaRa?)q—N+-((C1-C6)alkyl,)3, —(CRaRa?)q—NH—W?, —(CRaRa?)q—NH—(CRaRa?)q—OH, —NH—(CRaRa?)q—W?, or —(CRaRa?)q—W?;

W? may be absent or is selected from a C3-C10 cycloalkyl; a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from N, O, and S; a C6-C10 aryl; or a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; wherein the
C3-C10 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic or bicyclic, and further wherein the C3-C10 cycloalkyl, the 3-10 membered heterocyclyl, the C6-C10 aryl, or the 5-10 membered heteroaryl W? groups are unsubstituted or are optionally substituted with 1, 2, 3, or 4 substituents
independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C4)alkylene-OH, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —CH(CF3)(OH), —(C1-C4)alkylene-NH2, —(C1-C4)alkylene-NH((C1-C4)alkyl), —(C1-C4)alkylene-NH—(C1-C4)alkylene-CF3, —(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C4)alkyl), —C(?O)N((C1-C4)alkyl)2, —SO2NH2, —SO2NH((C1-C4)alkyl), —SO2N((C1-C4)alkyl)2, —NHSO2—(C1-C4)alkyl, —NHC(?O)—(C1-C4)alkyl, —SO2—(C1-C6)alkyl, —SO—(C1-C4)alkyl, —(C1-C4)alkylene-NH—C(?O)—(C1-C4)alkyl, —CF3, —C(?O)—(C1-C4)alkyl, —CO2H, —C(?O)—O—(C1-C4)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C4)alkyl), —C(?O)NH—(C1-C4)alkylene-N((C1-C4)alkyl)2, —C(?O)NH—(C1-C4)alkylene-OH, —C(?O)NH—(C1-C4)alkylene-CF3, —C(?O)NH—(C1-C4)alkylene-O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—O—(C1-C4)alkyl, —(C1-C4)alkylene-C(?O)—OH, —(C1-C4)alkylene-OH, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —SO3H, —OCF3, —OCHF2, or —C(?O)—W?; and further wherein W? may include 0, 1, or 2=O groups when W? is a C3-C10 cycloalkyl or a 3-10 membered heterocyclyl, and further wherein the ?O groups may be bonded to a ring carbon atom or a ring
S atom;

W? may be absent or is selected from a C3-C10 cycloalkyl; a 3-10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms selected from N, O, and S; a C6-C10 aryl; or a 5-10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S; wherein the
C3-C10 cycloalkyl and the 3-10 membered heterocyclyl may be monocyclic or bicyclic, and further wherein the C3-C10 cycloalkyl, the 3-10 membered heterocyclyl, the C6-C10 aryl, or the 5-10 membered heteroaryl W? groups are unsubstituted or are optionally substituted with 1, 2, 3, or 4 substituents
independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —OH, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —CF3, —CO2H, —C(?O)—O—(C1-C4)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, or —OCHF2; and further wherein W? may include 0, 1, or 2=O groups when W? is a C3-C10 cycloalkyl or a 3-10 membered heterocyclyl, and further wherein the ?O groups may be bonded to a ring carbon atom or a ring
S atom;

the subscript q is, in each instance, independently selected from 0, 1, 2, 3, or 4;
Ra is, in each instance, independently selected from —H, —CH3, —CH2CH3, —F, —CF3, or —C?N;

Ra? is, in each instance, independently selected from —H, —CH3, —CH2CH3, —F, —CF3, or —C?N; or

Ra and Ra? may join to form a cyclopropyl ring together with the carbon atom to which they are attached;

Z is selected from —OMe or —NH-cyclohexyl; or a phenyl, pyridyl, benzothiophenyl, thiazolyl, pyradizinyl, pyrimidinyl, indolyl,
cyclohexyl, morpholinyl, pyrrolidinyl, piperazinyl, or piperidinyl group; wherein the —NH-cyclohexyl, phenyl, pyridyl, benzothiophenyl,
thiazolyl, pyradizinyl, pyrimidinyl, indolyl, cyclohexyl, morpholinyl, pyrrolidinyl, piperazinyl, or piperidinyl group is
unsubstituted or is optionally substituted with 1, 2, or 3 substituents independently selected from —F, —Cl, —Br, —I, —C?N,
—NO2, —CF3, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C4)alkylene-OH, —NH2, —NH((C1-C6)alkyl), —N((C1-C6)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —SO2NH2, —SO2NH((C1-C6)alkyl), —SO2N((C1-C6)alkyl)2, —SO2NH((C2-C6)alkenyl), —SO2NH((C2-C6)alkynyl), —SO2NH—(C1-C4)alkylene-OH, —SO2NH—(C1-C4)alkylene-O—(C1-C6)alkyl, —NHSO2—(C1-C6)alkyl, —NHC(?O)—(C1-C6)alkyl, —SO2—(C1-C6)alkyl, —SO—(C1-C6)alkyl, —(C1-C4)alkylene-NH—C(?O)—(C1-C6)alkyl, —C(?O)—(C1-C6)alkyl, —CO2H, —C(?O)—O—(C1-C6)alkyl, —C(?O)NH—(C1-C4)alkylene-NH2, —C(?O)NH—(C1-C4)alkylene-NH((C1-C6)alkyl), —C(?O)NH—(C1-C4)alkylene-N((C1-C6)alkyl)2, —(C1-C4)alkylene-C(?O)—(C1-C6)alkyl, —(C1-C4)alkylene-C(?O)—O—(C1-C6)alkyl, —(C1-C4)alkylene-C(?O)—OH, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, or —OCHF2.

US Pat. No. 9,809,638

VARIANT ACTIVIN RECEPTOR

Amgen Inc., Thousand Oak...

1. An isolated protein comprising a variant activin IIB receptor (vActRIIB) polypeptide wherein the polypeptide is selected
from the group consisting of:
(a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 18, wherein the polypeptide comprises an amino
acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E;

(b) a polypeptide comprising the amino acid sequence set forth in amino acids 19 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(c) a polypeptide comprising the amino acid sequence set forth in amino acids 23 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E;

(d) a polypeptide comprising the amino acid sequence set forth in amino acids 25 through 134 of SEQ ID NO: 18, wherein the
polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q,
V, I, L, M, K, or H for E; and

(e) a polypeptide having at least 99% identity to any one of (a) through (d), wherein the polypeptide comprises an amino acid
substitution at the position corresponding to position 28 of SEQ ID NO:18, wherein the substitution at position 28 is A, W,
Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.

US Pat. No. 9,580,486

INTERLEUKIN-2 MUTEINS FOR THE EXPANSION OF T-REGULATORY CELLS

Amgen Inc., Thousand Oak...

1. An Fc-fusion protein comprising a Fc region and a human interleukin-2 (IL-2) mutein, wherein the mutein comprises a V91K
substitution and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:1, and further
wherein the Fc region comprises a substitution at N297, using Eu numbering scheme, and an amino acid sequence having at least
95% identity to the amino acid sequence of SEQ ID NO:3, wherein said Fc-fusion protein preferentially stimulates T regulatory
cells.
US Pat. No. 9,487,580

HUMAN IL-23 ANTIGEN BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. An isolated antigen binding protein that binds IL-23, comprising:
a CDRH1 of SEQ ID NO: 109;
a CDRH2 of SEQ ID NO: 116;
a CDRH3 of SEQ ID NO: 111;
a CDRL1 of SEQ ID NO: 80;
a CDRL2 of SEQ ID NO: 81; and
a CDRL3 of SEQ ID NO: 76.

US Pat. No. 9,328,134

CARBOHYDRATE PHOSPHONATE DERIVATIVES AS MODULATORS OF GLYCOSYLATION

AMGEN INC., Thousand Oak...

7. The compound of claim 2, wherein the compound is

US Pat. No. 9,175,078

FERROPORTIN ANTIBODIES AND METHODS OF USE

AMGEN INC., Thousand Oak...

1. An isolated antibody that binds an epitope with the sequence SITPTKIPEI (amino acids 417-426 of SEQ ID NO: 16) of ferroportin
and that preserves ferroportin activity.
US Pat. No. 9,988,354

SALT OF OMECAMTIV MECARBIL AND PROCESS FOR PREPARING SALT

AMGEN INC., Thousand Oak...

1. A dihydrochloride monohydrate salt of omecamtiv mecarbil.
US Pat. No. 9,562,108

CARRIER IMMUNOGLOBULINS

AMGEN INC., Thousand Oak...

1. An isolated antigen binding protein comprising an immunoglobulin heavy chain variable region and an immunoglobulin light
chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (CDRs)
designated CDRH1, CDRH2 and CDRH3, and the light chain variable region comprises three CDRs designated CDRL1, CDRL2 and CDRL3,
and wherein:
(a) CDRH1 comprises the amino acid sequence of SEQ ID NO:215;
(b) CDRH2 comprises the amino acid sequence of SEQ ID NO:218;
(c) CDRH3 comprises the amino acid sequence of SEQ ID NO:221;
(d) CDRL1 comprises the amino acid sequence of SEQ ID NO:204;
(e) CDRL2 comprises the amino acid sequence of SEQ ID NO:206; and
(f) CDRL3 comprises the amino acid sequence of SEQ ID NO:230.

US Pat. No. 9,340,549

OXAZOLIDINONE COMPOUNDS AND DERIVATIVES THEREOF

AMGEN INC., Thousand Oak...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, a tautomer thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer
of any of the foregoing, or a mixture thereof, wherein:
R1 and R2 are (C1-C6)alkyl;

R3 is —H;

W is selected from pyridyl, phenyl, or phenyl substituted with 1, 2, or 3 substituents independently selected from —F, —Cl,
—Br, —I, —C?N, —NO2, —OH, —O—(C1-C6)alkyl, —OCF3, —CF3, —(C1-C6)alkyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl), —NHSO2, —(C1-C6)alkyl, —NHC(?O)—(C1-C6)alkyl, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —C(?O)—(C1-C6)alkyl, —CO2H, —C(?O)—O—(C1-C6)alkyl, —SO2NH2, —SO2N((C1-C6)alkyl), —SO2N((C1-C6)alkyl)2, —SO2—(C1-C6)alkyl, or —SO—(C1-C6)alkyl;

X is O;
Y is selected from unsubstituted (C4-C7)cycloalkyl, substituted (C4-C7)cycloalkyl, unsubstituted (C4-C7)cycloalkenyl, substituted (C4-C7)cycloalkenyl, unsubstituted (C6-C10)aryl, substituted (C6-C10)aryl, unsubstituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or
N, substituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, unsubstituted
4 to 10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms independently selected from O, S, or N, or substituted 4 to
10 membered heterocyclyl comprising 1, 2, or 3 heteroatoms independently selected from O, S, or N, wherein the substituted
(C4-C7)cycloalkyl and substituted (C4-C7)cycloalkenyl are substituted with 1 or 2 substituents independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —OH, —O—(C1-C6)alkyl, —OCF3, —OCHF2, —CF3, —(C1-C6)alkyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —C(?O)—(C1-C6)alkyl, —CO2H, or —C(?O)—O—(C1-C6)alkyl, and wherein the substituted (C6-C10)aryl, substituted 5 to 10 membered heteroaryl, and substituted 4 to 10 membered heterocyclyl are substituted with 1, 2, or
3 substituents independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —OH, —O—(C1-C6)alkyl, —OCF3, —OCHF2, —CF3, —(C1-C6)alkyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —C(?O)—(C1-C6)alkyl, —CO2H, or —C(?O)—O—(C1-C6)alkyl, and further wherein the substituted 4 to 10 membered heterocyclyl may also be substituted with a ?O;

Z is selected from unsubstituted (C6-C10)aryl, substituted (C6-C10)aryl, unsubstituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or
N, substituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, unsubstituted
5 to 10 membered heterocyclyl comprising 1, 2, 3 or 4 heteroatoms independently selected from O, S, or N, or substituted 5
to 10 membered heterocyclyl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, or Z is selected
from —NRb—Z?, —NRc—C(?O)—Z?, or —C(?O)—NRd—Z?, wherein the substituted (C6-C10)aryl, substituted 5 to 10 membered heteroaryl, and the substituted 5 to 10 membered heterocyclyl are substituted with 1,
2, or 3 Q substituents and may additionally be substituted with 0 or 1 of Z? or —NRe—Z?, and further wherein the substituted 5 to 10 membered heterocyclyl may also be substituted with a ?O;

each Q is independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, —OCHF2, —CH2CHF2, —CF3, —(C1-C6)alkyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —NHSO2—(C1-C6)alkyl, —NHC(?O)—(C1-C6)alkyl, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —C(?O)NH—OH, —C(?O)NH—O—(C1-C6)alkyl, —C(?O)—(C1-C6)alkyl, —CO2H, —C(?O)—O—(C1-C6)alkyl, —SO2NH2, —SO2NH((C1-C6)alkyl), —SO2N((C1-C6)alkyl)2, —SO2—(C1-C6)alkyl, —SO—(C1-C6)alkyl, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-O—(C1-C6)alkyl, unsubstituted (C3-C7)cycloalkyl, unsubstituted 5 to 10 membered heterocyclyl comprising 1, 2, 3, or 4 heteroatoms independently selected from
O, S, or N, or unsubstituted 3 or 4 membered heterocyclyl comprising 1 heteroatom selected from O, S, or N;

Rb is selected from —H or (C1-C6)alkyl;

Rc is selected from —H or (C1-C6)alkyl;

Rd is selected from —H or (C1-C6)alkyl;

Re is selected from —H or (C1-C6)alkyl;

Z? is selected from unsubstituted (C6-C10) aryl, substituted (C6-C10) aryl, unsubstituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or
N, substituted 5 to 10 membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, unsubstituted
5 to 10 membered heterocyclyl comprising 1, 2, 3 or 4 heteroatoms independently selected from O, S, or N, substituted 5 to
10 membered heterocyclyl comprising 1, 2, 3, or 4 heteroatoms independently selected from O, S, or N, unsubstituted 3 or 4
membered heterocyclyl comprising 1 heteroatom selected from O, S, or N, substituted 3 or 4 membered heterocyclyl comprising
1 heteroatom selected from O, S, or N, or unsubstituted (C3-C7)cycloalkyl, wherein, the substituted (C6-C10) aryl, the substituted 5 to 10 membered heteroaryl, the substituted 5 to 10 membered heterocyclyl, and the 3 or 4 membered
heterocyclyl are substituted with 1, 2, or 3 substituents independently selected from —F, —Cl, —Br, —I, —C?N, —NO2, —C(?NH)—NH2, —OH, —O—(C1-C6)alkyl, —SH, —S—(C1-C6)alkyl, —OCF3, —OCHF2, —CH2CHF2, —CF3, —(C1-C6)alkyl, —NH2, —NH((C1-C4)alkyl), —N((C1-C4)alkyl)2, —NHSO2—(C1-C6)alkyl, —NHC(?O)—(C1-C6)alkyl, —C(?O)NH2, —C(?O)NH((C1-C6)alkyl), —C(?O)N((C1-C6)alkyl)2, —C(?O)NH—OH, —C(?O)NH—O—(C1-C6)alkyl, —C(?O)—(C1-C6)alkyl, —CO2H, —C(?O)—O—(C1-C6)alkyl, —SO2NH2, —SO2NH((C1-C6)alkyl), —SO2N((C1-C6)alkyl)2, —SO2—(C1-C6)alkyl, —SO—(C1-C6)alkyl, —(C1-C4)alkylene-OH, or —(C1-C4)alkylene-O—(C1-C6)alkyl, and further wherein the substituted 5 to 10 membered heterocyclyl and the 3 or 4 membered heterocyclyl may also be
substituted with a ?O.

US Pat. No. 9,340,590

POTENT AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7

AMGEN INC., Thousand Oak...


or a pharmaceutically acceptable salt thereof,
wherein:
Xaa1 and Xaa2 are absent; or Xaa1 is any amino acid residue and Xaa2 is any amino acid residue; or Xaa1 is absent and Xaa2 is any amino acid residue;

Xaa4 is an acidic, hydrophobic, basic, or neutral hydrophilic amino acid residue;

Xaa5 is a Gly, Ala, hydrophobic, or basic amino acid residue;

Xaa7 is a Gly, Ala, aromatic, or hydrophobic amino acid residue;

Xaa8 is a basic, acidic, or neutral hydrophilic amino acid residue, or an Ala residue;

Xaa9 is a basic or neutral hydrophilic amino acid residue;

Xaa11 is any amino acid residue;

Xaa12 is a Pro, acidic, neutral, or hydrophobic amino acid residue;

Xaa13 is any amino acid residue;

Xaa14 is any amino acid residue;

Xaa16 is a basic, neutral hydrophilic, or acidic amino acid residue, or an Ala residue;

Xaa19 is any amino acid residue;

Xaa20 is a Pro, Gly, basic, or neutral hydrophilic residue;

Xaa21 is a basic, hydrophobic, or neutral hydrophilic amino acid residue;

Xaa22 is a hydrophobic or basic amino acid residue;

Xaa23 is a hydrophobic, basic, or neutral hydrophilic amino acid residue;

Xaa25 is a Ser, Ala, or a neutral hydrophilic amino acid residue;

Xaa26 is an Ala, acidic, basic, or neutral hydrophilic amino acid residue;

Xaa27 is an acidic, basic, neutral hydrophilic or hydrophobic residue;

Xaa28 is an aromatic or basic amino acid residue;

Xaa29 is an acidic, basic, or neutral hydrophilic amino acid residue;

Xaa30 is a Trp, 5-bromoTrp, 6-bromoTrp, 5-chloroTrp, 6-chloroTrp, 1-Nal, 2-Nal, or thioTrp residue;

Xaa33 is a hydrophobic or aromatic amino acid residue;

Xaa34 is any amino acid residue;

Xaa35 is a hydrophobic amino acid residue;

each of Xaa36, Xm37, and Xaa38 is independently absent or is independently a neutral, basic, or hydrophobic amino acid residue; and

wherein there is a disulfide bond between Cys3 and Cys18, a disulfide bond between Cys10 and Cys24, and a disulfide bond between Cys17 and Cys31.

US Pat. No. 9,066,954

FUSED HETEROCYCLIC DERIVATIVES AND METHODS OF USE

Amgen Inc., Thousand Oak...

1. A compound of formula II

or a pharmaceutically acceptable salt thereof wherein
J is N;
W is CR2b;

Z and Z* are independently —O— or —NR5—;

Ra, Rb, Rc and Rd are each independently H, halo, alkyl, any of which may be optionally independently substituted with one or more R10 groups as allowed by valence;

R1 is aryl, heteroaryl or heterocyclo any of which may be optionally independently substituted with one or more R10 groups as allowed by valence;

R2 is

(i) halo, cyano, nitro, or
(ii) alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl,
cycloalkylalkyl, heterocycloalkyl, —OR4, any of which may be optionally independently substituted with one or more R10 as allowed by valence,

R2a, R2b and R3 are independently selected at each occurrence from H, halo, cyano, nitro, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl,
cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl,

heterocycloalkyl, —OR4, —S(O)vR4, —NR5R5a, —C(?O)R4, —C(?S)R4, —C(?O)OR4, —C(?S)OR4, —C(?O)NR5R5a, —C(?S)NR5R5a, —N(R5)C(?O)NR5R5a, —N(R5)C(?S)NR5R5a, —N(R5)C(?O)R4, —N(R5)C(?S)R4, —OC(?O)NR5R5a, —OC(?S)NR5R5a, —SO2NR5R5a, —N(R5)SO2R4, —N(R5)SO2NR5R5a, —N(R5)C(?O)OR4, —N(R5)C(?S)OR4, —N(R5)SO2R4, any of which may be optionally independently substituted with one or more R10 groups as allowed by valence;

R4 is independently selected at each occurrence from H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo,
arylalkyl, heteroarylalkyl, heterocycloalkyl, and cycloalkylalkyl, any of which may be optionally independently substituted
as allowed by valence with one or more R10 groups;

R5 and R5a are independently selected at each occurrence from H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclo,
arylalkyl, heteroarylalkyl, heterocycloalkyl, and cycloalkylalkyl, any of which may be optionally substituted as allowed by
valence with one or more R10;

R10 at each occurrence is independently, halo, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo,
aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl,

heterocycloalkyl, -(alkylene)m-OR4, -(alkylene)m-S(O)vR4, -(alkylene)m-NR5R5a, -(alkylene)m-C(?O)R4, -(alkylene)m-C(?S)R4, -(alkylene)m-C(?O)OR4, -(alkylene)m-OC(?O) R4, -(alkylene)m-C(?S)OR4, -(alkylene)m-C(?O)NR5R5a, -(alkylene)m-C(?S)NR5R5a, -(alkylene)m-N(R5)C(?O)NR5R5a, -(alkylene)m-N(R5)C(?S)NR5R5a, -(alkylene)m-N(R5)C(?O)R4, -(alkylene)m-N(R5)C(?S)R4, -(alkylene)m-OC(?O)NR5R5a, -(alkylene)m-OC(?S)NR5R5a, -(alkylene)m-SO2NR5R5a, -(alkylene)m-N(R5)SO2R4, -(alkylene)m-N(R5)SO2NR5R5a, -(alkylene)m-N(R5)C(?O)OR4, -(alkylene)m-N(R5)C(?S)OR4,

or -(alkylene)m-N(R5)SO2R4;

wherein said alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl,
cycloalkylalkyl, and heterocycloalkyl groups may be further independently substituted with one or more -(alkylene)m-OR4, -(alkylene)m-S(O)vR4, -(alkylene)m-NR5R5a, -(alkylene)m-C(?O)R4, -(alkylene)m-C(?S)R4, -(alkylene)m-C(?O)OR4, -(alkylene)m-OC(?O)R4, -(alkylene)m-C(?S)OR4,

-(alkylene)m-C(?O)NR5R5a, -(alkylene)m-C(?S)NR5O, -(alkylene)m-N(R5)C(?O)NR5R5a, -(alkylene)m-N(R5)C(?S)NR5R5a, -(alkylene)m-N(R5)C(?O)R4, -(alkylene)m-N(R5) C(?S)R4, -(alkylene)m-OC(?O)NR5R5a, -(alkylene)m-OC(?S)NR5R5a, -(alkylene)m-SO2NR5R5a, -(alkylene)m-N(R5)SO2R4, -(alkylene)m-N(R5)SO2NR5R5a, -(alkylene)m-N(R5)C (?O)OR4, -(alkylene)m-N(R5)C(?S)OR4, or -(alkylene)m-N(R5)SO2R4;

m is 0 or 1;
n is 0, 1 or 2;
q and t are each independently 0 or 1;
v is 0, 1 or 2.

US Pat. No. 9,744,304

PRE-FILLED SYRINGE IDENTIFICATION TAG

AMGEN INC., Thousand Oak...

1. An assembly comprising:
a pre-filled syringe including a barrel with a first end and a second, open end, a plunger disposed within the barrel and
spaced between the first end and the second, open end, a product disposed in the barrel between the first end of the barrel
and the plunger, and an outwardly-directed rim disposed about the barrel at the second, open end; and

an identification tag secured to the outwardly-directed rim of the barrel of the syringe, the identification tag including
a disk and at least one fastener being one-piece with the disk, the at least one fastener attached to the rim to secure the
identification tag to the rim, the disk overlying the second, open end of the barrel, and having an outwardly-facing surface,
the tag further having an identifier disposed on the outwardly-facing surface of the disk, the identifier including data regarding
the pre-filled syringe, the product disposed in the barrel, or both.

US Pat. No. 9,714,276

GROWTH DIFFERENTIATION FACTOR 15 (GDF-15) POLYPEPTIDES

Amgen Inc., Thousand Oak...

1. A fusion protein comprising:
(a) a GDF15 polypeptide comprising the amino acid sequence of SEQ ID NOs: 12, 14 or a variant thereof, wherein the variant
is a GDF15(H6D) variant comprising the amino acid sequence of SEQ ID NO: 38, or a GDF15(N3Q) variant comprising the amino
acid sequence of SEQ ID NO: 42: and

(b) a negatively charged Fc sequence comprising two lysine-to-aspartate mutations.
US Pat. No. 9,574,008

CD27L ANTIGEN BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. A method of treating a CD27L-expressing cancer, said method comprising administering a therapeutically effective amount
of an anti-CD27L antibody or antigen-binding fragment thereof to a patient in need thereof, wherein the antibody or antigen-binding
fragment thereof comprises:
a) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 71; an LCDR2 sequence as set forth
in SEQ ID NO: 79; and an LCDR3 sequence as set forth in SEQ ID NO: 87; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 25; an HCDR2 sequence as set forth in SEQ ID NO: 33; and an HCDR3 sequence as set forth
in SEQ ID NO: 41;

b) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 72; an LCDR2 sequence as set forth
in SEQ ID NO: 80; and an LCDR3 sequence as set forth in SEQ ID NO: 88; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 26; an HCDR2 sequence as set forth in SEQ ID NO: 34; and an HCDR3 sequence as set forth
in SEQ ID NO: 42;

c) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 73; an LCDR2 sequence as set forth
in SEQ ID NO: 81; and an LCDR3 sequence as set forth in SEQ ID NO: 89; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 27; an HCDR2 sequence as set forth in SEQ ID NO: 35; and an HCDR3 sequence as set forth
in SEQ ID NO: 43;

d) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 74; an LCDR2 sequence as set forth
in SEQ ID NO: 82; and an LCDR3 sequence as set forth in SEQ ID NO: 90; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 28; an HCDR2 sequence as set forth in SEQ ID NO: 36; and an HCDR3 sequence as set forth
in SEQ ID NO: 44;

e) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 75; an LCDR2 sequence as set forth
in SEQ ID NO: 83; and an LCDR3 sequence as set forth in SEQ ID NO: 91; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 29; an HCDR2 sequence as set forth in SEQ ID NO: 37; and an HCDR3 sequence as set forth
in SEQ ID NO: 45;

f) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 76; an LCDR2 sequence as set forth
in SEQ ID NO: 84; and an LCDR3 sequence as set forth in SEQ ID NO: 92; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 30; an HCDR2 sequence as set forth in SEQ ID NO: 38; and an HCDR3 sequence as set forth
in SEQ ID NO: 46;

g) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 77; an LCDR2 sequence as set forth
in SEQ ID NO: 85; and an LCDR3 sequence as set forth in SEQ ID NO: 93; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 31; an HCDR2 sequence as set forth in SEQ ID NO: 39; and an HCDR3 sequence as set forth
in SEQ ID NO: 47; or

h) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 78; an LCDR2 sequence as set forth
in SEQ ID NO: 86; and an LCDR3 sequence as set forth in SEQ ID NO: 94; and a heavy chain variable domain comprising an HCDR1
sequence as set forth in SEQ ID NO: 32; an HCDR2 sequence as set forth in SEQ ID NO: 40; and an HCDR3 sequence as set forth
in SEQ ID NO: 48;

i) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth
in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an R24K-S26G mutation; and a heavy chain variable
domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3
sequence as set forth in SEQ ID NO:44, but with an N31S-134M mutation;

j) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth
in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an R24K-S26G mutation; and a heavy chain variable
domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3
sequence as set forth in SEQ ID NO:44;

k) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth
in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an L551-Y58F mutation; and a heavy chain variable
domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3
sequence as set forth in SEQ ID NO:44;

l) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth
in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with a Q95N-T96S mutation; and a heavy chain variable
domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3
sequence as set forth in SEQ ID NO:44, but with an N31S-134M mutation; or

m) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth
in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with a Q95N-T96S mutation; and a heavy chain variable
domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3
sequence as set forth in SEQ ID NO:44.

US Pat. No. 9,562,061

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Amgen Inc., Thousand Oak...

1. A compound having the formula:
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,458,246

PROTEINS SPECIFIC FOR BAFF AND B7RP1

AMGEN INC., Thousand Oak...

1. A bispecific protein comprising:
(a) a polypeptide comprising an amino acid sequence having the following formula: A-L1-P-L2-P, wherein A is an immunoglobulin
heavy chain of an IgG antibody, L1 is a first linker that is absent or is 3 to 40 amino acids long, P is a BAFF-binding peptide
that is 10 to 40 amino acids long, and L2 is a peptide linker that is absent or is 5 to 50 amino acids long, and

(b) an immunoglobulin light chain,
wherein the immunoglobulin heavy chain of (a) and the immunoglobulin light chain of (b) can form an IgG antibody that can
bind human B7RP1,

wherein the protein can inhibit BAFF-mediated proliferation of human B cells and
wherein the protein can inhibit B7RP1-mediated proliferation of human T cells.
US Pat. No. 9,920,114

ANTIBODY FORMULATIONS

AMGEN INC., Thousand Oak...

1. A crystal of an anti-sclerostin IgG antibody comprising two light variable chains each comprised of SEQ ID NO: 23 and two
heavy variable chains each comprised of SEQ ID NO: 25, wherein the crystal has a length of about 100 ?m to about 1000 ?m and
an ellipsoidal shape.

US Pat. No. 9,662,271

VIAL ADAPTER AND SYSTEM

AMGEN INC., Thousand Oak...

1. A system comprising:
a vial having a neck with a passage in the neck and a rim disposed adjacent the neck, a stopper disposed over the passage
in the neck of the vial to control access through the passage into the vial, and a crimp ring disposed about the stopper and
the rim to maintain the stopper fixed relative to the vial;

a vial adapter including:
a collar securely attached to the vial at the neck of the vial and having a continuous inner circumferential surface engaging
the neck of the vial, the collar for receiving one of a pair of opposing axial forces to limit the movement of the stopper
relative to the vial,

a plate for receiving another of the pair of axial opposing forces, the plate being axially spaced apart from the collar,
and

a surface of the crimp ring abutting a surface of the collar and an opposite surface of the crimp ring abutting a surface
of the plate; and

a spike configured to be advanced through a passage in the plate and penetrate the stopper after the collar is securely attached
to the vial.

US Pat. No. 9,517,264

HUMAN FGF RECEPTOR AND ?-KLOTHO BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. An antigen binding protein comprising:
(a) a light chain variable domain comprising; (i) a light chain CDR1 comprising an amino acid sequence of SEQ ID NO: 107;
(ii) a light chain CDR2 comprising an amino acid sequence of SEQ ID NO: 113; (iii) a light chain CDR3 comprising an amino
acid sequence of SEQ ID NO: 121; and

(b) a heavy chain variable domain comprising: (i) a heavy chain CDR1 comprising an amino acid sequence of SEQ ID NO: 84; (ii)
a heavy chain CDR2 comprising an amino acid sequence of SEQ ID NO: 90; and (iii) a heavy chain CDR3 comprising an amino acid
sequence of SEQ ID NO: 99; wherein the antigen binding protein specifically binds ?-Klotho.

US Pat. No. 9,464,139

GITR ANTIGEN BINDING PROTEINS AND METHODS OF USE THEREOF

AMGEN INC., Thousand Oak...

1. An antigen binding protein, wherein said antigen binding protein is an antibody or a functional fragment thereof that agonizes
human glucocorticoid-induced TNFR-related protein (“GITR”), said antigen binding protein comprising:
a) a variant VH comprising a CDRH1, a CDRH2 and a CDRH3, wherein one or more of CDRH1, CDRH2 and CDRH3 differ in sequence
relative to the corresponding CDRH1, CDRH2 and CDRH3 of the VH of any single antigen binding protein selected from the group
of Ab1 to Ab59 inclusive, provided however that the sequence differences in the CDRH1, CDRH2 and CDRH3 of the variant VH relative
to the corresponding CDRs of the VH sequence collectively total no more than 1, 2, 3, 4 or 5 amino acids; and

a variant VL comprising a CDRL1, a CDRL2 and a CDRL3, wherein one or more of CDRL1, CDRL2 and CDRL3 differ in sequence relative
to the corresponding CDRL1, CDRL2 and CDRL3 of the VL of any single antigen binding protein selected from the group of Ab1
to Ab59 inclusive, provided however that the sequence differences in the CDRL1, CDRL2 and CDRL3 of the variant VL relative
to the corresponding CDRs of the VL sequence collectively total no more than 1, 2, 3, 4 or 5 amino acids, provided that the
variant VH and the variant VL are, respectively, variants of the VH and VL of the same antigen binding protein as specified
in Table 1;

b) a VH comprising a CDRH1, a CDRH2 and a CDRH3, wherein CDRH1 comprises the sequence X1YGMX2 (SEQ ID NO:436), wherein X1 is S or N; and X2 is H or Y;

CDRH2 comprises the sequence VIWYX1GSNKYYADSVX2G (SEQ ID NO:437), wherein X1 is E, V, A, P; and X2 is K or R;

CDRH3 comprises the sequence GGX1LX2X3X4YYX5GMDV (SEQ ID NO:438), wherein X1 is Q, L, E, or R; X2 is G, R, or S; X3 is K, Y, L, F, or R; and X4 is Y or D; and X5 is Y
or S; and

a VL comprising a CDRL1, a CDRL2 and a CDRL3, wherein
CDRL1 comprises the sequence RASQX1IRNDLG (SEQ ID NO:439), wherein X1 is G or V;

CDRL2 comprises the sequence X1X2SX3LQS (SEQ ID NO:440), wherein X1 is A or D; X2 is A or T; and X3 is S or T;

CDRL3 comprises the sequence X1QX2X3X4YPX5T (SEQ ID NO:441), wherein X1 is L or Q; X2 is H or L; X3 is N or H; X4 is S, N or T, and X5 is W, L or I;

c) a CDRH1, a CDRH2 and a CDRH3, each from the same VH of an antigen binding protein of Ab1 to Ab59 inclusive as specified
in Table 1; and

the CDRL1, a CDRL2, and a CDRL3, each from the same VL of an antigen binding protein of Ab1 to Ab59 inclusive as specified
in Table 1, wherein the VH and the VL are from the same antigen binding protein;

d) a VH that is at least 80%, 85%, 90%, 95%, 97% or 99% identical in amino acid sequence to the VH sequence of any one of
antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1; and

a VL that is at least 80%, 85%, 90%, 95%, 97% or 99% identical in amino acid sequence to the VL sequence of any one of antigen
binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the VH and the VL are from the same antigen binding
protein as specified in Table 1;

e) a VH comprising the amino acid sequence of the VH of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified
in Table 1; and

a VL comprising the amino acid sequence of the VL of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified
in Table 1, wherein the VH and the VL are from the same antigen binding protein as specified in Table 1;

f) a full length heavy chain (HC) that is at least 90%, 95%, 97% or 99% identical in amino acid sequence to the full length
heavy chain sequence of any one of antigen binding proteins Ab1 to AB59 inclusive as specified in Table 1; and

a full length light chain (LC) that is at least 90%, 95%, 97% or 99% identical in amino acid sequence to the full length light
chain sequence of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the full length
heavy chain and the full length light chain are from the same antigen binding protein as specified in Table 1; or

g) a full length heavy chain comprising the amino acid sequence of the full length heavy chain of any one of the antigen binding
proteins Ab1 to Ab59 inclusive as specified in Table 1; and

a full length light chain comprising the amino acid sequence of the full length light chain of any one of the antigen binding
proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the full length heavy chain and the full length light chain
are from the same antigen binding protein as specified in Table 1.

US Pat. No. 9,453,080

DUAL RECEPTOR ANTAGONISTIC ANTIGEN-BINDING PROTEINS AND USES THEREOF

AMGEN INC., Thousand Oak...

1. An isolated antigen-binding protein comprising a first polypeptide comprising SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO:
5 and a second polypeptide comprising SEQ ID NO:6, SEQ ID NO: 7 and SEQ ID NO:8 wherein the isolated antigen-binding protein
specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18.

US Pat. No. 9,418,416

METHODS AND APPARATI FOR NONDESTRUCTIVE DETECTION OF UNDISSOLVED PARTICLES IN A FLUID

AMGEN INC., Thousand Oak...

1. A method of nondestructive counting and sizing of undissolved particles in a vessel that is at least partially filled with
a fluid, the method comprising:
(a) receiving, by a sensor of an imaging system, at least one image of the particles in the vessel obtained under specified
imaging conditions; and analyzing the at least one image by a processor of the imaging system, the analyzing including (b)-(d):

(b) detecting the particles and determining information indicative of an apparent size of the detected particles in the image;
(c) determining apparent particle size population information indicative of an apparent particle size distribution of the
detected particles; and

(d) determining actual particle size population information indicative of an actual particle size distribution of the detected
particles based on:

(i) the apparent particle size population information; and
(ii) calibration population information indicative of the apparent size distribution of one or more sets of standard sized
particles imaged under conditions corresponding to the specified imaging conditions;

wherein (d) comprises fitting a superposition of apparent size distributions for a plurality of the sets of standard sized
particles to the apparent particle size population of the detected particles; and

wherein fitting the superposition of apparent size distributions for the plurality of sets of standard sized particles conditions
to the apparent particle size population of the detected particles comprises: minimizing a difference between the superposition
and the apparent particle size population of the detected particles by adjusting the weighting of the apparent size distributions
for the plurality of sets of standard sized particles.

US Pat. No. 9,987,428

INJECTOR AND METHOD OF ASSEMBLY

AMGEN INC., Thousand Oak...

1. An injector comprising:a container including a wall with a first interior surface defining a bore and an opening in fluid communication with a first end of the bore;
a stopper disposed in a second end of the bore and movable along the bore;
a seal assembly comprising
a first septum disposed across the opening and fixedly attached to the wall of the container, the first septum having a second interior surface, the first and second interior surfaces defining a closed sterile reservoir filled with a drug product, and
a second septum disposed across the opening and fixedly attached to the wall of the container, the second septum being spaced from the first septum to define an enclosed clean space between the first septum and the second septum;
a fluid delivery system comprising a clean, unsheathed, rigid container needle having a point disposed through the second septum into the clean space in a storage state, and disposed through the first septum into the sterile reservoir in a delivery state; and
an actuator that is adapted to move the container needle from the storage state to the delivery state.
US Pat. No. 9,982,054

ST2 ANTIGEN BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. A method of treating inflammation in a patient with an autoimmune or inflammatory disorder, comprising administering to the patient a therapeutically effective amount of an antibody that binds ST2, wherein the antibody comprises a light chain variable domain that comprises an LCDR1 sequence as set forth in SEQ ID NO: 107; an LCDR2 sequence as set forth in SEQ ID NO: 118; and an LCDR3 sequence as set forth in SEQ ID NO: 129; and a heavy chain variable domain that comprises an HCDR1 sequence as set forth in SEQ ID NO: 41; an HCDR2 sequence as set forth in SEQ ID NO: 52; and an HCDR3 sequence as set forth in SEQ ID NO: 63.
US Pat. No. 9,732,134

METHOD OF TREATING GRAFT VERSUS HOST DISEASE USING IL-2 MUTEINS

Amgen Inc., Thousand Oak...

1. A method of treating graft versus host disease in a subject, said method comprising administering to a subject in need
thereof a therapeutically effective amount of an IL-2 variant comprising a sequence of amino acids that differs from SEQ ID
NO: 1 only at one or more of residues E15, H16, Q22, D84, N88, or E95, wherein said IL-2 variant selectively promotes FOXP3-positive
regulatory T cell growth or survival in vitro.

US Pat. No. 9,656,997

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A method of treating a condition in a subject where it is desired to activate the APJ Receptor, the method comprising:
administering to the subject an effective amount of a compound of Formula I or Formula II or a pharmaceutically acceptable
salt thereof, a tautomer thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer of any of the foregoing,
or a mixture thereof, wherein the condition is obesity, diabetes, or diabetic nephropathy, and further wherein the compound
of Formula I or Formula II has the structure:
wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with
1, 2, 3, or 4 R1a substituents;

R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —C(?O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(?O)-(heterocyclyl) or heterocyclyl
group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;

R2 is selected from —H, or C1-C4 alkyl or is absent in the compounds of Formula II;

R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula —NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b?CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of
which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;

R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;

Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected
from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein
the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with
1, 2, 3, or 4 RQ substituent;

RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo substituent;

R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently
selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or
4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents;

R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), or —C(?O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent; and

further wherein:
if R4 is an unsubstituted or substituted phenyl ring and R3 is a group of formula —(CR3b?CR3c)-Q, then at least one of the following is true:

a) R4 is substituted with at least one —O—(C1-C6 alkyl) group;

b) Q is not an oxadiazole;
c) R3b is not —H;

d) R3c is not —H;

e) R1 is not a 2-pyridyl group; or

f) R4 is substituted with two or more —O—(C1-C6 alkyl) groups.

US Pat. No. 9,623,018

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

Amgen Inc., Thousand Oak...

1. A compound, wherein the compound is

US Pat. No. 9,617,333

SCLEROSTIN ANTIBODY CRYSTALS AND FORMULATIONS THEREOF

AMGEN INC., Thousand Oak...

1. A crystal of an anti-sclerostin IgG antibody comprising two light chains each comprised of SEQ ID NO: 3 and two heavy chains
each comprised of SEQ ID NO: 5, wherein said crystals have a length of up to 500?M and a shape selected from the group consisting
of ellipsoids, rods and needles or mixtures thereof.

US Pat. No. 9,573,936

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A compound of Formula I or Formula II:
or a pharmaceutically acceptable salt thereof, a tautomer thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer
of any of the foregoing, or a mixture thereof,wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with
1, 2, 3, or 4 R1a substituents;

R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —(C?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —C(?O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(?O)-(heterocyclyl) or heterocyclyl
group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;

R2 is selected from —H, or C1-C4 alkyl or is absent in the compounds of Formula II;

R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R1a substituents, a group of formula —(CR3bR3c)-Q, a group of formula —NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b?CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of
which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;

R1a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;

Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected
from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein
the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with
1, 2, 3, or 4 RQ substituent;

RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo RQ substituent;

R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently
selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or
4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents;

R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), or —C(?O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent; and

further wherein:
if R4 is an unsubstituted or substituted phenyl ring and R3 is a group of formula —(CR3b?CR3c)-Q, then at least one of the following is true:

a) R4 is substituted with at least one —O—(C1-C6 alkyl) group;

b) Q is not an oxadiazole;
c) R3b is not —H;

d) R3c is not —H;

e) R1 is not a 2-pyridyl group; or

f) R4 is substituted with two or more —O—(C1-C6 alkyl) groups.

US Pat. No. 9,862,752

GROWTH DIFFERENTIATION FACTOR 15 (GDF-15) CONSTRUCTS

Amgen Inc., Thousand Oak...

1. A fusion protein comprising a GDF15 region and an Fc domain, wherein the Fc domain has the amino acid sequence of SEQ ID
NO: 220 or SEQ ID NO: 220 with a tyrosine to cysteine mutation at position 113.
US Pat. No. 9,803,019

CARRIER IMMUNOGLOBULINS AND USES THEREOF

AMGEN INC., Thousand Oak...

1. An isolated immunoglobulin, comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain
variable region, wherein:
(a) the light chain variable region comprises the amino acid sequence of SEQ ID NO:196 and the heavy chain variable region
comprises the amino acid sequence of SEQ ID NO:335, SEQ ID NO:349, SEQ ID NO:351, SEQ ID NO:353, SEQ ID NO:355, or SEQ ID
NO:359, or

(b) the light chain variable region comprises the amino acid sequence of SEQ ID NO:204 and the heavy chain variable region
comprises the amino acid sequence of SEQ ID NO:349 or SEQ ID NO:355, or

(c) the light chain variable region comprises the amino acid sequence of SEQ ID NO:202 and the heavy chain variable region
comprises the amino acid sequence of SEQ ID NO:349, or

(d) the light chain variable region comprises the amino acid sequence of SEQ ID NO:192 and the heavy chain variable region
comprises the amino acid sequence of SEQ ID NO:357, SEQ ID NO:359, or SEQ ID NO:369, or

(e) the light chain variable region comprises the amino acid sequence of SEQ ID NO:194 and the heavy chain variable region
comprises the amino acid sequence of SEQ ID NO:335, SEQ ID NO:349, or SEQ ID NO:351.

US Pat. No. 9,801,867

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

Amgen Inc., Thousand Oak...

1. A process of making
the process comprising reacting

to form

US Pat. No. 9,657,090

METHOD OF TREATING ALVEOLAR BONE LOSS THROUGH THE USE OF ANTI-SCLEROSTIN ANTIBODIES

AMGEN INC., Thousand Oak...

1. A method for increasing alveolar bone height in a subject suffering from alveolar bone loss comprising administering to
the subject an anti-sclerostin antibody in an amount effective to decrease the distance between the cement-enamel junction
and the alveolar bone crest, at a dose from about 5 mg to about 1,000 mg per week, and wherein the anti-sclerostin antibody
comprises a CDR-H1 of SEQ ID NO:245, a CDR-H2 of SEQ ID NO:246, a CDR-H3 of SEQ ID NO:247, a CDR-L1 of SEQ ID NO:78, a CDR-L2
of SEQ ID NO:79, and a CDR-L3 of SEQ ID NO:80.

US Pat. No. 9,663,508

BIARYL ACYL-SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

Amgen Inc., Thousand Oak...

1. A compound, or a pharmaceutically acceptable salt thereof, of Formula (Ia):
wherein:
Ar is a pyridinyl ring having a structure:
substituted by 1, 2, or 3 R5 groups, wherein said pyridinyl ring is selected from the group consisting of:

T is absent, —N(Rf)—, —(CRdRd)rO(CRdRd)r—, —O(CRdRd)pO(CRdRd)p—, —N(Rd)(CRdRd)p—, S, S(?O), or S(?O)2;

R1 is —NHRe, C1-6alkyl, a 3- to 6-membered cycloalkyl group, a 4-, 5- to 6-membered heterocyclyl group, or a 4-, 5- to 6-membered heteroaryl
group, wherein each C1-6alkyl is independently substituted by 0, 1, 2, 3, or 4 R7 groups; and each said heterocyclyl or heteroaryl group is independently substituted by 0, 1, 2, 3, or 4 C1-6alkyl or R7 groups;

R2 is H or C1-6alkyl;

R3 is a —(CReRe)q(6- to 10-membered aryl) group, a —(CReRe)q(5- to 10-membered heteroaryl) group, a —(CReRe)q(3- to 8-membered cycloalkyl) group, or a —C(ReRe)q(3- to 10-membered heterocycloalkyl) group,

wherein each R3 aryl, heteroaryl, cycloalkyl or heterocycloalkyl group is independently substituted by 0, 1, 2, 3, or 4 R8 substituents independently selected from an A group, —O-A group, halo, —CF3, —CF2H, —CFH2, —OH, —OCF3, —OCHF2, —OCH2F, C1-6alkyl, —OC1-6alkyl, —CN, —(CH2)nNRcRc, —O(CRdRd)pORc, —N(Rc)2, —NRd(CH2)m5- to 10-membered aryl, —NRd(CH2)m5- to 10-membered heteroaryl, —(CH2)mO(CH2)m6-membered aryl, —NRd(CH2)mORc, or oxo;

and each occurrence of R8 C1-6alkyl, —OC1-6alkyl, aryl, or heteroaryl group is independently substituted by 0, 1, 2, 3, or 4 R9 substituents independently selected from a B group, halo, C1-6alkyl, —CN, —CF3, —OH, —OCHF2, —OCH2F, —OCF3, —OC1-6alkyl, or —(CH2)mNRdRd;

Each R4a, R4b, R4c, and R4d is independently H, halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, CF2H, CFH2, —OCF3, —OCF2H, —OCFH2, or —O—CH2CF3; wherein each occurrence of said R4a, R4b, R4c, and R4d C1-6alkyl group is independently substituted by 0, 1, 2, 3, or 4 halo, CN, C1-6alkyl, —OC1-6alkyl, —O(CRdRd)pORc, NH2, OH, or —C(?O)NH2;

each R5 is independently halo, —CN, —OC1-6alkyl, C1-6alkyl, —CF3, —OH, —CF2H, —CFH2, —OCF3, —OCF2H, or —OCFH2;

an A group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group, a 3- to 6-membered cycloalkyl group, or
a 3- to 6-membered heterocycloalkyl group, wherein the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is independently
substituted by 0, 1, 2, 3, or 4 substituents independently selected from a B group or R6;

a B group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group, a 3- to 6-membered cycloalkyl group or a
3- to 6-membered heterocycloalkyl group, wherein the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is independently
substituted by 0, 1, 2, 3, or 4 substituents independently selected from R6;

each R6 is independently halo, haloC1-6alkyl, CN, OH, NO2, NH2, acetyl, —C(O)NHCH3, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, —OC1-6alkyl, —O—B group, —O(CH2)mB group, —(CH2)nNRdRd, —O(CRdRd)pORc, —(C?O)NRdRd, —S(?O)2NRd, —N(Rd)2, —NRd(C?O)NRdRd, —NRdS(?O)2NRd, —S(?O)2Rd, —NRd(CH2)mORc or —SC1-6alkyl, wherein each occurrence of R6 C1-6alkyl, C2-6alkenyl, C2-6alkynyl, or C3-6cycloalkyl is independently substituted by 0, 1, 2, 3, 4, or 5 substituents independently selected from F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, cyclopropylmethoxy, butyl,
butoxyl, isobutoxy, tert-butoxy, 2-butynyloxy, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl or oxetan-3-yl;

R7 is a B group, halo, —CN, or —C1-6alkyl-OC1-6alkyl;

each Rc and Rd is independently H or C1-6alkyl, and wherein the C1-6alkyl is independently substituted by 0, 1, 2, 3, or 4 substituents independently selected from halo, —OH or —CN;

each Re is independently H, C1-6alkyl or a 3- to 6-membered cycloalkyl group; wherein each of the C1-6alkyl and the 3- to 6-membered cycloalkyl group is independently substituted by 0, 1, 2, 3, or 4 substituents independently
selected from halo, —OH or —CN;

each Rf is independently H or C1-6alkyl, and wherein the C1-6alkyl is independently substituted by 0, 1, 2, 3, or 4 substituents independently selected from halo, —OH or —CN;

or alternatively, Rf and R3 together with the nitrogen atom they attach to may form a four-membered, five-membered, or six-membered heterocycloalkyl or
heteroaryl ring, each of which is independently substituted by 0, 1, 2, 3, or 4 substituents independently selected from halo,
—OH or —CN;

each m is independently 0, 1, 2 or 3;
each n is independently 0, 1, 2 or 3;
each p is independently 1, 2, 3, or 4;
each q is independently 0, 1, 2 or 3; and
each r is independently 0, 1, 2 or 3.

US Pat. No. 10,088,660

IMAGING SYSTEM FOR COUNTING AND SIZING PARTICLES IN FLUID-FILLED VESSELS

AMGEN INC., Thousand Oak...

1. A well plate inspection system, comprising:a stage configured to receive a plate including a vessel containing a fluid, the fluid contained within the vessel substantially occupying three dimensions;
a light source configured to generate source light that is incoherent;
an optical element that is separate from the light source and is disposed between the light source and the vessel, the optical element being configured to:
refract the source light to produce refracted source light; and
direct the refracted source light through the fluid contained in the vessel to produce scattered light as a result of an interaction between the refracted source light and particles suspended in the fluid,
wherein the optical element is configured to refract the source light such that, once the refracted source light has passed through the fluid contained within the vessel, the refracted source light does not impinge upon an imager that is configured to acquire images using the scattered light,
wherein the light source and the imager are positioned such that, but for the optical element refracting the source light, the source light would impinge upon the imager, and
wherein each acquired image from among the acquired images corresponds to an entire volume of the fluid contained within the vessel; and
one or more processors configured to perform image analysis on the acquired images to determine a size and a number of particles in the fluid.

US Pat. No. 9,850,297

SECRETED FRIZZLE-RELATED PROTEIN 5 (SFRP5) BINDING PROTEINS

Amgen Inc., Thousand Oak...

1. An antigen binding protein that specifically binds SFRP5 (secreted frizzled-related protein5) and comprises:
i. a CDRH1 of SEQ ID NO:23;
ii. a CDRH2 of SEQ ID NO:24;
iii. a CDRH3 of SEQ ID NO:25;
i. a CDRL1 of SEQ ID NO:26;
ii. a CDRL2 of SEQ ID NO:27; and
iii. a CDRL3 of SEQ ID NO:28.
US Pat. No. 9,822,178

HUMAN PAC1 ANTIBODIES

AMGEN INC., Thousand Oak...

1. A method for treating a headache in a patient in need thereof, comprising administering to the patient an effective amount
of an isolated antibody or antigen-binding fragment thereof that specifically binds to human pituitary adenylate cyclase-activating
polypeptide type I receptor (PAC1), wherein the antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable
region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, and (ii) a light chain variable region comprising
complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein CDRH1 comprises the sequence of SEQ ID NO: 165, CDRH2
comprises the sequence of SEQ ID NO: 179, CDRH3 comprises the sequence of SEQ ID NO: 189, CDRL1 comprises the sequence of
SEQ ID NO: 139 or SEQ ID NO: 140, CDRL2 comprises the sequence of SEQ ID NO: 151, and CDRL3 comprises the sequence of SEQ
ID NO: 157.
US Pat. No. 9,688,756

VARIANT FC-POLYPEPTIDES WITH ENHANCED BINDING TO THE NEONATAL FC RECEPTOR

AMGEN INC., Thousand Oak...

1. A variant Fc-polypeptide comprising a human IgG1, IgG2, IgG3, or IgG4 variant Fc-fragment,
wherein the variant Fc-fragment comprises an insertion:
between amino acids 382 and 383, amino acids 383 and 384, amino acids 384 and 385, amino acids 385 and 386, amino acids 386
and 387, amino acids 387 and 388, or amino acids 388 and 389, using the EU numbering system shown in Table 1, or

wherein amino acids 384-386 are deleted and the insertion is between amino acids 383 and 387, using the EU numbering system,
wherein the insertion is 10-16 amino acids and comprises at least one cysteine among the first four inserted amino acids and
at least one cysteine among the last four inserted amino acids,

wherein the variant Fc-polypeptide binds to a human neonatal Fc receptor (hFcRn) with higher binding activity at pH 6.0 than
a control Fc-polypeptide that has the same amino acid sequence as the variant Fc-polypeptide except that it does not contain
the insertion, and

wherein the variant Fc-polypeptide has little or no binding activity for binding to hFcRn at pH 7.4 and any residual binding
response detected at pH 7.4 is no more than 0.1 nanometer more than that detected using the control Fc-polypeptide.

US Pat. No. 9,643,984

METHOD FOR THE PREPARATION OF [1,2,4]-TRIAZOLO[4,3-A]PYRIDINES

AMGEN INC., Thousand Oak...

1. A method comprising;
subjecting (R)—N?-(3-fluoro-5-(1methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-(2-methoxyethoxy)-5-oxo-1,6-naphthyridin-6(5H)yl)propanehydrazide
(“HYDZ”):

to a dehydration reaction with either a thiophosphetane compound or a phosphorus (V) dehydrating agent thereby forming (R)-6-(1-(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one
(“A”):

US Pat. No. 9,562,107

CARRIER IMMUNOGLOBULINS

AMGEN INC., Thousand Oak...

1. An isolated antigen binding protein comprising an immunoglobulin heavy chain variable region and an immunoglobulin light
chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (CDRs)
designated CDRH1, CDRH2 and CDRH3, and the light chain variable region comprises three CDRs designated CDRL1, CDRL2 and CDRL3,
and wherein:
(a) CDRH1 comprises the amino acid sequence of SEQ ID NO:189;
(b) CDRH2 comprises the amino acid sequence of SEQ ID NO:193;
(c) CDRH3 comprises the amino acid sequence of SEQ ID NO:198;
(d) CDRL1 comprises the amino acid sequence of SEQ ID NO:203;
(e) CDRL2 comprises the amino acid sequence of SEQ ID NO:206; and
(f) CDRL3 comprises the amino acid sequence of SEQ ID NO:209.
US Pat. No. 9,474,792

METHOD OF TREATING METABOLIC DISORDERS USING PLA2G12A POLYPEPTIDES AND PLA2G12A MUTANT POLYPEPTIDES

Amgen Inc., Thousand Oak...

1. A method of treating a metabolic disorder comprising administering to a subject in need thereof a therapeutically effective
amount of an isolated human PLA2G12A mutant polypeptide comprising an amino acid sequence that has at least 90% sequence identity
with SEQ ID NO: 1 and comprises an amino acid substitution at position 110.
US Pat. No. 10,047,138

FUSION PROTEIN, CELLS EXPRESSING THE FUSION PROTEIN, AND USES THEREOF

AMGEN INC., Thousand Oak...

1. A fusion protein comprising the following polypeptides:(a) an extracellular region of a costimulatory receptor comprising amino acids 1-121 of SEQ ID NO:5 or amino acids 1-135 of SEQ ID NO:6;
(b) a transmembrane domain comprising amino acids 122-144 of SEQ ID NO:5 or amino acids 136-158 of SEQ ID NO:6;
(c) an intracellular region of the costimulatory receptor, which comprises at least one tyrosine-based signaling motif having the amino acid sequence of Tyr-Met-Phe-Met (SEQ ID NO:2) when the extracellular region is amino acids 1-121 of SEQ ID NO:5, or Tyr-Met-Asn-Met (SEQ ID NO:1) when the extracellular region is amino acids 1-135 of SEQ ID NO:6; and
(d) an intracellular region of a CD3 protein that comprises at least one paired ITAM motif, wherein the intracellular region of the CD3 protein comprises amino acids 138-152 of SEQ ID NO:10, amino acids 138-160 of SEQ ID NO:10, amino acids 166-180 of SEQ ID NO:9, amino acids 128-142 of SEQ ID NO:11, amino acids 51-65 of SEQ ID NO:8, amino acids 90-105 of SEQ ID NO:8, amino acids 121-135 of SEQ ID NO:8, or amino acids 51-135 of SEQ ID NO:8,
wherein a T cell expressing the fusion protein can be induced to secrete at least three times as much IL-2 by a costimulatory ligand as it secretes in the absence of the costimulatory ligand.
US Pat. No. 9,920,134

MONOCLONAL ANTIBODIES TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

AMGEN INC., Thousand Oak...

1. A monoclonal antibody that binds to a PCSK9 protein, wherein the PCSK9 protein comprises the amino acid sequence of SEQ
ID NO: 1, wherein the monoclonal antibody comprises a light chain complementarity determining region (CDR) CDR1 that is a CDR1 in SEQ ID NO:46; a light chain CDR2 that is a CDR2 in SEQ ID NO:46; and a light chain CDR3 that is a CDR3
in SEQ ID NO: 46, and wherein the monoclonal antibody comprises a heavy chain CDR1 that is a CDR1 in SEQ ID NO:60; a light
chain CDR2 that is a CDR2 in SEQ ID NO:60; and a light chain CDR3 that is a CDR3 in SEQ ID NO:60.
US Pat. No. 9,803,166

PRE-PROGRAMMED NON-FEEDBACK CONTROLLED CONTINUOUS FEEDING OF CELL CULTURES

AMGEN INC., Thousand Oak...

1. A method of continuously feeding a mammalian cell culture that does not employ feedback control, comprising:
(a) providing a vessel comprising a mammalian cell culture comprising mammalian cells and media;
(b) determining preferred values for the consumption rate (K1) of a nutrient, growth rate (K21) and growth rate (K22) of the cell culture;

(c) providing an apparatus adapted to impart a continuous feed stream to the cell culture, wherein the apparatus comprises
a controller module adapted to continuously feed the culture at a flow rate F, wherein

F is defined as K1exp(K21t2+K22t);

t is the duration of time from the time the feed stream is added to the bioreactor to the time when the feed stream is stopped;
and

K1, K21 and K22 are the values determined in (a); and

(d) activating the controller module to initiate continuous feeding of the cell culture.
US Pat. No. 9,574,002

HUMAN ANTIGEN BINDING PROTEINS THAT BIND TO A COMPLEX COMPRISING ?-KLOTHO AND AN FGF RECEPTOR

AMGEN INC., Thousand Oak...

1. An isolated antigen binding protein that induces FGF21-mediated signaling, wherein the antigen binding protein comprises
a light chain CDR1 comprising the sequence of SEQ ID NO: 821, a light chain CDR2 comprising the sequence of SEQ ID NO: 900,
a light chain CDR3 comprising the sequence of SEQ ID NO: 954, a heavy chain CDR1 comprising the sequence of SEQ ID NO: 611,
a heavy chain CDR2 comprising the sequence of SEQ ID NO: 664, and a heavy chain CDR3 comprising the sequence of SEQ ID NO:
741.
US Pat. No. 9,534,032

THROMBOPOIETIC COMPOUNDS

AMGEN INC., Thousand Oak...

1. A method of producing a compound comprising growing a host cell comprising a polynucleotide that encodes said compound
in a suitable nutrient medium and isolating said compound from said cell or nutrient medium, wherein said compound binds to
an mpl receptor and comprises a polypeptide having a sequence selected from SEQ ID NOS. 10-34.
US Pat. No. 10,072,090

HUMAN ANTI-B7RP1 NEUTRALIZING ANTIBODIES

AMGEN INC., Thousand Oak...

1. A method of treating an autoimmune disease or inflammatory response in a patient, comprising administering to a patient a pharmaceutically effective amount of an isolated antibody that binds specifically to human B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO: 1-14, 29, 32, 34, 37, 38, 40, 44-58, or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
US Pat. No. 10,059,766

ANTIBODY CONSTRUCTS FOR CDH19 AND CD3

AMGEN INC., Thousand Oak...

1. An isolated multispecific antibody construct or an oligomer thereof comprising a first binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3on the surface of a T cell, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(b) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 102, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(c) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 119, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 154, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 155, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 156, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 322, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 323 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 324;
(e) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 912, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(f) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 913, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(g) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 910, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(h) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 911, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 119, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(j) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 914, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(k) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 154, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 155, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 920, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 322, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 323 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 324;
(l) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 996, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 997, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 998, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 999, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1000 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1001;
(m) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1048, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1049, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1050, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1051, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1052 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1053;
(n) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1087, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1088, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1089, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1090, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1091 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1092;
(o) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1608, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1609, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1610, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1611, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1612 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1613;
(p) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1621, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1622, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1623, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1624, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1625 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1626;
(q) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1634, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1635, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1636, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1637, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1638 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1639;
(r) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1673, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1674, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1675, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1676, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1677 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1678;
(s) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1686, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1687, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1688, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1689, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1690 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1691;
(t) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1699, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1700, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1701, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1702, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1703 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1704;
(u) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1712, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1713, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1714, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1715, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1716 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1717;
(v) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1725, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1726, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1727, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1728, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1729 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1730;
(w) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1738, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1739, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1740, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1741, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1742 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1743;
(x) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1751, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1752, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1753, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1754, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1755 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1756;
(y) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1764, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1765, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1766, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1767, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1768 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1769; and
(z) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1920, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1921, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1922, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1923, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1924 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1925.

US Pat. No. 9,873,701

HETEROCYCLIC COMPOUNDS AND THEIR USES

AMGEN INC., Thousand Oak...

1. A method of treating cancers which are mediated, dependent on or associated with p110? activity, comprising the step of
administering a compound having the structure:
or any pharmaceutically-acceptable salt thereof, wherein:
X1 is C(R9);

X2 is N;

Y is N(R11);

Z is N;
n is 0, 1, 2 or 3;
R1 is a direct bonded or oxygen-linked saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing
0, 1, 2, 3 or 4 atoms selected from N, O and S, but containing no more than one O or S, wherein the available carbon atoms
of the ring are substituted by 0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0 or 1 R2 substituents, and the ring is additionally substituted by 0, 1, 2 or 3 substituents independently selected from halo, nitro,
cyano, C1-4alkyl, OC1-4alkyl, OC1-4haloalkyl, NHC1-4alkyl, N(C1-4alkyl)C1-4alkyl and C1-4haloalkyl;

R2 is selected from halo, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkylNRaRa, —OC2-6alkylORa, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkylNRaRa and —NRaC2-6alkylORa; or R2 is selected from C1-6alkyl, phenyl, benzyl, heteroaryl, heterocycle, —(C1-3alkyl)heteroaryl, —(C1-3alkyl)heterocycle, —O(C1-3alkyl)heteroaryl, —O(C1-3alkyl)heterocycle, —NRa(C1-3alkyl)heteroaryl, —NRa(C1-3alkyl)heterocycle, —(C1-3alkyl)phenyl, —O(C1-3alkyl)phenyl and —NRa(C1-3alkyl)phenyl all of which are substituted by 0, 1, 2 or 3 substituents selected from C1-4haloalkyl, OC1-4alkyl, Br, Cl, F, I and C1-4alkyl;

R3 is selected from H, halo, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkylNRaRa, —OC2-6alkylORa, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkylNRaRa, —NRaC2-6alkylORa, C1-6alkyl, phenyl, benzyl, heteroaryl and heterocycle, wherein the C1-6alkyl, phenyl, benzyl, heteroaryl and heterocycle are additionally substituted by 0, 1, 2 or 3 substituents selected from
C1-6haloalkyl, OC1-6alkyl, Br, Cl, F, I and C1-6alkyl;

R4 is, independently, in each instance, halo, nitro, cyano, C1-4alkyl, OC1-4alkyl, OC1-4haloalkyl, NHC1-4alkyl, N(C1-4alkyl)C1-4alkyl or C1-4haloalkyl;

R5 is, independently, in each instance, H, halo, C1-6alkyl, C1-4haloalkyl, or C1-6alkyl substituted by 1, 2 or 3 substituents selected from halo, cyano, OH, OC1-4alkyl, C1-4alkyl, C1-3haloalkyl, OC1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)C1-4alkyl; or both R5 groups together form a C3-6spiroalkyl substituted by 0, 1, 2 or 3 substituents selected from halo, cyano, OH, OC1-4alkyl, C1-4alkyl, C1-3haloalkyl, OC1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)C1-4alkyl; R6 is selected from H, halo, C1-6alkyl, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa;

R7 is selected from H, halo, C1-6alkyl, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa;

R9 is selected from H, halo, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkylNRaRa, —OC2-6alkylORa, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkylNRaRa, —NRaC2-6alkylORa, C1-6alkyl, phenyl, benzyl, heteroaryl and heterocycle, wherein the C1-6alkyl, phenyl, benzyl, heteroaryl and heterocycle are additionally substituted by 0, 1, 2 or 3 substituents selected from
halo, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkylNRaRa, —OC2-6alkylORa, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkylNRaRa, —NRaC2-6alkylORa; or R9 is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2, 3 or 4 atoms selected
from N, O and S, but containing no more than one O or S, wherein the available carbon atoms of the ring are substituted by
0, 1 or 2 oxo or thioxo groups, wherein the ring is substituted by 0, 1, 2, 3 or 4 substituents selected from halo, C1-4haloalkyl, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkylNRaRa, —OC2-6alkylORa, —SRa, —S(?O)Ra, —S(?O)2Ra, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkylNRaRa and —NRaC2-6alkylORa;

R11 is H or C1-4alkyl;

Ra is independently, at each instance, H or Rb;

Rb is independently, at each instance, phenyl, benzyl or C1-6alkyl, the phenyl, benzyl and C1-6alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alkyl, C1-3haloalkyl, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)C1-4alkyl; and

wherein the cancer is acute myeloid leukaemia, B-cell lymphoma, glioblastoma, prostate cancer, neuroblastoma, or breast cancer.

US Pat. No. 9,845,310

INTERMEDIATES FOR PREPARING TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A compound of Formula VII, a salt thereof, a tautomer thereof, or a salt of the tautomer:

wherein:
R3e? is a —C1-C6 alkyl;

R3g? is selected from —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, or —O—(C1-C6 alkyl)-O—(C1-C6 alkyl);

Q? is a monocyclic 6-membered heteroaryl group with 1, 2, or 3 N heteroatoms, wherein the heteroaryl group is unsubstituted
or is substituted with 1, 2, 3, or 4 RQ? substituent; and

RQ? in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, or —S(?O)2—(C1-C6 alkyl).

US Pat. No. 9,822,388

METHODS FOR INCREASING MANNOSE CONTENT OF RECOMBINANT PROTEINS

Amgen Inc., Thousand Oak...

1. A method for modulating one or more high mannose glycan species on a recombinant protein during mammalian cell culture
comprising;
establishing a mammalian cell culture in a bioreactor with a serum-free defined culture medium containing 5-8 g/L glucose;
growing the mammalian cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free defined
feed medium having from 5-8 g/L glucose;

initiating a production phase in the cell culture by perfusion with a serum-free first perfusion medium having 5-15 g/L glucose;
at a predetermined time point, perfusing the cell culture with a low glucose second perfusion medium containing or supplemented
with an amount of glucose that is decreased relative to the amount of glucose in the first perfusion medium, wherein said
second perfusion medium further contains or is supplemented with galactose.

US Pat. No. 10,144,780

METHODS AND COMPOSITIONS RELATING TO ANTI-IL-21 RECEPTOR ANTIBODIES

AMGEN INC., Thousand Oak...

1. An isolated IL-21 receptor antigen binding protein, wherein said antigen binding protein comprises either:a. the heavy chain variable domain and the light chain variable domain of antibody 30G3; or
b. the CDR1, CDR2, and CDR3 of the light chain variable domain sequence, and the CDR1, CDR2, and CDR3 of the heavy chain variable domain sequence, of antibody 30G3.
US Pat. No. 9,868,721

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A compound or a pharmaceutically acceptable salt thereof, wherein the compound is
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propane
sulfonamide;

(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propane
sulfonamide;

(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrimidinyl)-2-propane
sulfonamide;

(1S,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-2-propane
sulfonamide;

(1S,2R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrazinyl)-2-propane
sulfonamide;

(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrazinyl)-2-propane
sulfonamide;

(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butane sulfonamide;
(1R,2S)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propane
sulfonamide;

(1S,2R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrazinyl)-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(6-methyl-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrimidinyl)-2-propane
sulfonamide;

(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(5-fluoro-2-pyrimidinyl)-1-methoxy-2-propanesulfonamide;
(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrazinyl)-2-butanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-fluoro-2-pyrimidinyl)-2-propanesulfonamide;
(1S,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(1-methylethoxy)-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(1-methylethoxy)-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(1S,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methoxy-2-pyrazinyl)-2-propanesulfonamide;
(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrazinyl)-2-butanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-fluoro-2-pyrimidinyl)-2-propanesulfonamide;
(1R,2S)—N-(4-(4,6-dimethoxy-5-pyrimidinyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(1R,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-2-propanesulfonamide;
or

(1S,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide,
or

the pharmaceutically acceptable salt of any of the above compounds.

US Pat. No. 9,745,286

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A method of treating a cardiovascular condition, the method comprising: administering to a subject having a cardiovascular
condition an effective amount of a compound of Formula I or Formula II or a pharmaceutically acceptable salt thereof, a tautomer
thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer of any of the foregoing, or a mixture thereof,
wherein the cardiovascular condition is heart failure or hypertension, and further wherein the compound of Formula I or Formula
II has the structure:
wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with
1, 2, 3, or 4 R1a substituents;

R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —C(?O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(?O)-(heterocyclyl) or heterocyclyl
group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;

R2 is selected from —H, or C1-C4 alkyl or is absent in the compounds of Formula II;

R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula —NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b?CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of
which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;

R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;

Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected
from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein
the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with
1, 2, 3, or 4 RQ substituent;

RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo substituent;

R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently
selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or
4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents;

R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), or —C(?O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent; and

further wherein:
if R4 is an unsubstituted or substituted phenyl ring and R3 is a group of formula —(CR3b?CR3c)-Q, then at least one of the following is true:

a) R4 is substituted with at least one —O—(C1-C6 alkyl) group;

b) Q is not an oxadiazole;
c) R3b is not —H;

d) R3c is not —H;

e) R1 is not a 2-pyridyl group; or

f) R4 is substituted with two or more —O—(C1-C6 alkyl) groups.

US Pat. No. 9,663,476

GLYCINE TRANSPORTER-1 INHIBITORS

AMGEN INC., Thousand Oak...

20. A pharmaceutical composition comprising a compound of Formula (I) according to any one of the preceding claims, or a pharmaceutically
acceptable salt thereof, and a pharmaceutically acceptable excipient.
US Pat. No. 9,610,327

VARIANT ACTIVIN RECEPTOR POLYPEPTIDES, ALONE OR IN COMBINATION WITH CHEMOTHERAPY, AND USES THEREOF

Amgen Inc., Thousand Oak...

1. A method of reducing the size of a gonadal tumor mass in a subject in need of such treatment comprising administering to
the subject: an effective amount of an isolated protein comprising a variant activin IIB receptor polypeptide (vActRIIB) wherein
vActRIIB comprises a polypeptide sequence having at least 99% identity to the amino acid sequence set forth at amino acids
25 through 134 of SEQ ID NO: 18, wherein the polypeptide comprises an amino acid substitution at position 28, wherein the
substitution at position 28 is selected from the group of amino acids consisting of A, W, and Y for E, and wherein the polypeptide
is capable of binding myostatin, activin A, or GDF-11; and a chemotherapeutic agent.

US Pat. No. 10,053,452

CRYSTALLINE FORMS OF N-(4-((3-(2-AMINO-4-PYRIMIDINYL)-2-PYRIDINYL)OXY)PHENYL)-4-(4-METHYL-2-THIENYL)-1-PHTHALAZINAMINE SALTS AND USES THEREOF

AMGEN INC., Thousand Oak...

1. A crystalline form A of a mesylate salt of AMG 900 having the formulacharacterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 9.89+/?0.16°, 12.96+/?0.10°, 16.52+/?0.10°, 17.84+/?0.16°, 20.05+/?0.10° and 21.55+/?0.19°.
US Pat. No. 9,988,457

HUMAN C-FMS ANTIGEN BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. A nucleic acid encoding an isolated antibody or antibody fragment, wherein the antibody or antibody fragment binds human c-fms and comprises a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and a CDRL3, wherein:CDRH1 comprises SEQ ID NO:140, CDRH2 comprises SEQ ID NO:155, CDRH3 comprises SEQ ID NO:169, CDRL1 comprises SEQ ID NO:202, CDRL2 comprises SEQ ID NO:218, and CDRL3 comprises SEQ ID NO:236;
CDRH1 comprises SEQ ID NO:140, CDRH2 comprises SEQ ID NO:155, CDRH3 comprises SEQ ID NO:169, CDRL1 comprises SEQ ID NO:201, CDRL2 comprises SEQ ID NO:218, and CDRL3 comprises SEQ ID NO:236;
CDRH1 comprises SEQ ID NO:147, CDRH2 comprises SEQ ID NO:163,CDRH3 comprises SEQ ID NO:186, CDRL1 comprises SEQ ID NO:193, CDRL2 comprises SEQ ID NO:214, and CDRL3 comprises SEQ ID NO:228.
US Pat. No. 9,920,121

ANTIBODIES TARGETING CDH19 FOR MELANOMA

AMGEN INC., Thousand Oak...

1. An isolated human antibody or antigen binding fragment thereof that binds to human cadherin 19 (CDH19) on the surface of
a target cell, comprising a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3
selected from the group consisting of:
(a) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 4, CDR-H2 as depicted in SEQ ID NO: 5 and CDR-H3 as depicted in
SEQ ID NO: 6, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 172, CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3
as depicted in SEQ ID NO: 174;

(b) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 10, CDR-H2 as depicted in SEQ ID NO: 11 and CDR-H3 as depicted
in SEQ ID NO: 12, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 178, CDR-L2 as depicted in SEQ ID NO: 179 and
CDR-L3 as depicted in SEQ ID NO: 180;

(c) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29 and CDR-H3 as depicted
in SEQ ID NO: 30, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and
CDR-L3 as depicted in SEQ ID NO: 198;

(d) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 34, CDR-H2 as depicted in SEQ ID NO: 35, CDR-H3 as depicted in
SEQ ID NO: 36, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 202, CDR-L2 as depicted in SEQ ID NO: 203 and CDR-L3
as depicted in SEQ ID NO: 204;

(e) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47 and CDR-H3 as depicted
in SEQ ID NO: 48, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 214, CDR-L2 as depicted in SEQ ID NO: 215 and
CDR-L3 as depicted in SEQ ID NO: 216;

(f) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 59 and CDR-H3 as depicted
in SEQ ID NO: 60, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and
CDR-L3 as depicted in SEQ ID NO: 228;

(g) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 64, CDR-H2 as depicted in SEQ ID NO: 65 and CDR-H3 as depicted
in SEQ ID NO: 66, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 232, CDR-L2 as depicted in SEQ ID NO: 233 and
CDR-L3 as depicted in SEQ ID NO: 234;

(h) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 71 and CDR-H3 as depicted
in SEQ ID NO: 72, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and
CDR-L3 as depicted in SEQ ID NO: 240;

(i) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161 and CDR-H3 as depicted
in SEQ ID NO: 162, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 328, CDR-L2 as depicted in SEQ ID NO: 329 and
CDR-L3 as depicted in SEQ ID NO: 330;

(j) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47 and CDR-H3 as depicted
in SEQ ID NO: 48, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and
CDR-L3 as depicted in SEQ ID NO: 216;

(k) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47 and CDR-H3 as depicted
in SEQ ID NO: 902, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and
CDR-L3 as depicted in SEQ ID NO: 216;

(l) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47 and CDR-H3 as depicted
in SEQ ID NO: 903, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and
CDR-L3 as depicted in SEQ ID NO: 216;

(m) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47 and CDR-H3 as depicted
in SEQ ID NO: 48, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 925, CDR-L2 as depicted in SEQ ID NO: 215 and
CDR-L3 as depicted in SEQ ID NO: 216;

(n) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907 and CDR-H3 as depicted
in SEQ ID NO: 72, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and
CDR-L3 as depicted in SEQ ID NO: 240;

(o) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907 and CDR-H3 as depicted
in SEQ ID NO: 908, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and
CDR-L3 as depicted in SEQ ID NO: 240;

(p) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901 and CDR-H3 as depicted
in SEQ ID NO: 30, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and
CDR-L3 as depicted in SEQ ID NO: 923;

(q) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905 and CDR-H3 as depicted
in SEQ ID NO: 906, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and
CDR-L3 as depicted in SEQ ID NO: 228;

(r) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905 and CDR-H3 as depicted
in SEQ ID NO: 60, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and
CDR-L3 as depicted in SEQ ID NO: 228;

(s) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161 and CDR-H3 as depicted
in SEQ ID NO: 162, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and
CDR-L3 as depicted in SEQ ID NO: 330;

(t) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 921 and CDR-H3 as depicted
in SEQ ID NO: 162, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and
CDR-L3 as depicted in SEQ ID NO: 940;

(u) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161 and CDR-H3 as depicted
in SEQ ID NO: 162, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 941, CDR-L2 as depicted in SEQ ID NO: 329 and
CDR-L3 as depicted in SEQ ID NO: 330;

(v) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29 and CDR-H3 as depicted
in SEQ ID NO: 30, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and
CDR-L3 as depicted in SEQ ID NO: 923;

(w) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29 and CDR-H3 as depicted
in SEQ ID NO: 30, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and
CDR-L3 as depicted in SEQ ID NO: 923; and

(x) a VH region comprising CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29 and CDR-H3 as depicted
in SEQ ID NO: 30, and a VL region comprising CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and
CDR-L3 as depicted in SEQ ID NO: 330.

US Pat. No. 9,922,429

METHODS AND APPARATI FOR NONDESTRUCTIVE DETECTION OF UNDISSOLVED PARTICLES IN A FLUID

AMGEN INC., Thousand Oak...

1. A method for nondestructive detection of an undissolved particle in a vessel that is at least partially filled with a fluid,
the method comprising:
(a) using at least one imager to image the particle;
(b) processing the image to determine position data indicative of a position of the particle in the vessel;
(c) detecting the particle based at least in part on the position data, wherein detecting the particle based at least in part
on the position data comprises identifying the presence of the particle in a sub-region of the vessel;

(d) using a sensor to determine a characteristic of the particle when the particle is located in the sub-region of the vessel,
(e) generating particle characteristic data indicative of the determined characteristic; and
(f) associating the particle characteristic data with data identifying the particle.
US Pat. No. 9,822,173

HETERODIMERIC IMMUNOGLOBULINS

AMGEN INC., Thousand Oak...

1. method of treating a bone gap defect in a mammalian subject comprising administering to the subject an antibody that binds
to a region of sclerostin comprising amino acids 86-111 of SEQ ID NO: 1,
wherein the antibody comprises a first heavy chain and a first light chain comprising a sclerostin-binding portion and a second
heavy chain and a second light chain comprising a DKK1-binding portion, wherein the first heavy chain comprises amino acid
substitutions at EU positions 183, 356 and 399, wherein the second heavy chain comprises amino acid substitutions at EU positions
183 , 392 and 409, and wherein the first and second light chains comprise an amino acid substitution at EU position 176, wherein
the amino acid substitutions introduce a charged amino acid at said positions, wherein the substitution introduce charged
amino acids that are electrostatically unfavorable to homodimer formation and electrostatically favorable to heterodimer formation,
wherein the antibody is administered in an amount effective to treat the gap defect in the subject.

US Pat. No. 9,758,495

HETEROARYL ACID MORPHOLINONE COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER

Amgen Inc., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,

wherein:
X is S(?O)2 or —S(?O)2N(Ra)—;

Z is C1-6alkyl or C3-6cyclolalkyl;

A is a 5 or 6 membered heteroaryl group containing a nitrogen atom, or an N-oxide thereof, and from 0 to 2 additional heteroatoms
independently selected from O, N, or S, where the heteroaryl group may be unsubstituted or substituted with from 1 to 3 substituents
independently selected from, halo, C1-6alkyl, —OC1-6alkyl, —OCF3, —CF3,

—CHF2 or —CH2F;

R1 is hydrogen or C1-6alkyl, where the alkyl group can be unsubstituted or substituted with from 1 to 3 substituents independently selected from
halo, —OH, —OC1-6alkyl,

—OCF3, —CF3, —CN, —CHF2 or —CH2F;

R2 is hydrogen or C1-6alkyl;

R3 is C3-6cycloalkyl or C1-6alkyl, where the cycloalkyl or alkyl group can be unsubstituted or substituted with from 1 to 2 substituents independently
selected from halo, C1-6alkyl, —CH2CF3, —CF3, —OCF3, —CHF2 or —CH2F;

R4 is a phenyl or pyridyl group which is substituted with from one to three substituents independently selected from halo or
C1-6 alkyl;

R5 is a phenyl or pyridyl group which is substituted with from one to three substituents independently selected from halo or
C1-6 alkyl;

n is 0, 1 or 2;
m is 1 or 2; and
Ra is hydrogen, C1-6alkyl, C3-6cycloalkyl or phenyl, where the phenyl or cycloalkyl group is unsubstituted or substituted with from one to three halo groups.

US Pat. No. 9,757,367

CALCIUM PROPANE-2-SULFINATE DIHYDRATE

Amgen Inc., Thousand Oak...

1. A compound, wherein the compound is

US Pat. No. 9,873,704

HETEROCYCLIC COMPOUNDS AND THEIR USES

AMGEN INC., Thousand Oak...

1. A compound having the structure:
or any pharmaceutically-acceptable salt thereof, wherein:
R1 is phenyl or pyridyl, both of which are substituted by 0, 1, 2 or 3 substituents independently selected from halo, C1-6alk, C1-4haloalk, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkNRaRa, —OC2-6alkORa, —SRa, —S(?C)Ra, —S(?O)2Ra and —S(?O)2NRaRa
R2 is H;

R3 is selected from H and halo;

R5 is, independently, in each instance, H or C1-6alk;

R6 is NHR9;

R9 is H;

R11 is selected from H, halo, C1-6alk, C1-4haloalk, cyano, nitro, —C(?O)Ra, —C(?O)ORa, —C(?O)NRaRa, —C(?NRa)NRaRa, —ORa, —OC(?O)Ra, —OC(?O)NRaRa, —OC(?O)N(Ra)S(?O)2Ra, —OC2-6alkNRaRa, —OC2-6alkORa, —SRa, —S(?O)Ra, —S(?O)2Rb, —S(?O)2NRaRa, —S(?O)2N(Ra)C(?O)Ra, —S(?O)2N(Ra)C(?O)ORa, —S(?O)2N(Ra)C(?O)NRaRa, —NRaRa, —N(Ra)C(?O)Ra, —N(Ra)C(?O)ORa, —N(Ra)C(?O)NRaRa, —N(Ra)C(?NRa)NRaRa, —N(Ra)S(?O)2Ra, —N(Ra)S(?O)2NRaRa, —NRaC2-6alkNRaRa, —NRaC2-6alkORa, —NRaC2-6alkCO2Ra, —NRaC2-6alkSO2Rb, —CH2C(?O)Ra, —CH2C(?O)ORa, —CH2C(?O)NRaRa, —CH2C(?NRa)NRaRa, —CH2ORa, —CH2OC(?O)Ra, —CH2OC(?O)NRaRa, —CH2OC(?O)N(Ra)S(?O)2Ra, —CH2OC2-6alkNRaRa, —CH2OC2-6alkORa, —CH2SRa, —CH2S(?O)Ra, —CH2S(?O)2Rb, —CH2S(?O)2NRaRa, —CH2S(?O)2N(Ra)C(?O)Ra, —CH2S(?O)2N(Ra)C(?O)ORa, —CH2S(?O)2N(Ra)C(?O)NRaRa, —CH2NRaRa, —CH2N(Ra)C(?)Ra, —CH2N(Ra)C(?O)ORa, —CH2N(Ra)C(?O)NRaRa, —CH2N(Ra)C(?NRa)NRaRa, —CH2N(Ra)S(?O)2Ra, —CH2N(Ra)S(?O)2NRaRa, —CH2NRaC2-6alkNRaRa, —CH2NRaC2-6alkORa, —CH2NRaC2-6alkCO2Ra, —CH2NRaC2-6alkSO2Rb, —CH2Rc, —C(?O)Rc and —C(?O)N(Ra)Rc;

Ra is independently, at each instance, H or Rb;

Rb is independently, at each instance, phenyl, benzyl or C1-6alk, the phenyl, benzyl and C1-6alk being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk and —N(C1-4alk)C1-4alk; and

Rc is a saturated or partially-saturated 4-, 5- or 6-membered ring containing 1, 2 or 3 heteroatoms selected from N, O and S,
the ring being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alk, C1-3haloalk, —OC1-4alk, —NH2, —NHC1-4alk and —N(C1-4alk)C1-4alk.

US Pat. No. 9,704,239

VIDEO TRIGGER SYNCHRONIZATION FOR IMPROVED PARTICLE DETECTION IN A VESSEL

AMGEN INC., Thousand Oak...

1. A method comprising:
during an agitation period of an agitation profile, applying a motion to a transparent vessel containing a fluid
acquiring, via one or more imagers while applying the motion, a sequence of original images of a portion of the transparent
vessel, the acquisition of the sequence of original images being synchronized to the agitation profile such that each original
image in the sequence of original images corresponds to the transparent vessel being in the same position;

generating, via one or more processors, a background image from the sequence of original images;
generating, via one or more processors, a resultant image from the background image and an original image in the sequence
of original images; and

identifying, via one or more processors, a particle in the fluid from the resultant image.
US Pat. No. 10,011,642

METHODS OF TREATING OF DIABETES AND OBESITY USING FGF21 MUTANTS

AMGEN INC., Thousand Oak...

1. A method for treating diabetes comprising administering to a human patient in need thereof a fusion protein comprising (a) an IgG constant domain; (b) a linker sequence fused to the IgG constant domain; and (c) an FGF21 mutant fused to the linker sequence and comprising the amino acid sequence of SEQ ID NO: 4, wherein an arginine residue has been substituted for the leucine residue at position 98 and a glycine residue has been substituted for the proline residue at position 171.
US Pat. No. 9,932,380

INTERLEUKIN-2 MUTEINS FOR THE EXPANSION OF T-REGULATORY CELLS

Amgen Inc., Thousand Oak...

1. A method of increasing the ratio of regulatory T cells (Tregs) to non-regulatory T cells within a population of T cells within the peripheral blood of a subject, or increasing the ratio of regulatory T cells (Tregs) to natural killer (NK) cells within the peripheral blood of a subject, comprising contacting the population of T cells with an effective amount of a Fc-fusion protein comprising a Fc region and a human interleukin-2 (IL-2) mutein, wherein the mutein comprises a V91K substitution and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:1, and further wherein the Fc region comprises a substitution at N297, using Eu numbering scheme, and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:3.
US Pat. No. 9,862,771

HUMAN CGRP RECEPTOR BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. A method for inhibiting vasodilation in a patient in need thereof comprising administering to the patient an isolated monoclonal
antibody or antigen-binding fragment thereof that selectively inhibits the human calcitonin gene-related peptide (CGRP) receptor
relative to human AM1, AM2, and AMY1 receptors, wherein the isolated monoclonal antibody or antigen-binding fragment thereof
comprises (i) a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3 and (ii)
a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein:
(a) CDRH1, CDRH2, and CDRH3 have the sequence of SEQ ID NOs: 73, 74and 75, respectively, and CDRL1, CDRL2, and CDRL3 have
the sequence of SEQ ID NOs: 42, 43 and 44, respectively;

(b) CDRH1, CDRH2, and CDRH3 have the sequence of SEQ ID NOs: 82, 83 and84, respectively, and CDRL1, CDRL2, and CDRL3 have
the sequence of SEQ ID NOs: 51, 52 and 53, respectively;

(c) CDRH1, CDRH2, and CDRH3 have the sequence of SEQ ID NOs: 76, 91 and 78, respectively, and CDRL1, CDRL2, and CDRL3 have
the sequence of SEQ ID NOs: 45, 61 and 47, respectively;

(d) CDRH1, CDRH2, and CDRH3 have the sequence of SEQ ID NOs: 92, 93 and 94, respectively, and CDRL1, CDRL2, and CDRL3 have
the sequence of SEQ ID NOs: 62, 63 and 64, respectively; or

(e) CDRH1, CDRH2, and CDRH3 have the sequence of SEQ ID NOs: 73, 74 and 96, respectively, and CDRL1, CDRL2, and CDRL3 have
the sequence of SEQ ID NOs: 42, 43 and 44, respectively.

US Pat. No. 9,643,997

CAPTURE PURIFICATION PROCESSES FOR PROTEINS EXPRESSED IN A NON-MAMMALIAN SYSTEM

AMGEN INC., Thousand Oak...

1. A method of purifying a protein expressed in a non-native soluble form in a non-mammalian expression system comprising:
(a) lysing a non-mammalian cell in which the protein is expressed in a nonnative soluble form to generate a cell lysate;
(b) contacting the cell lysate with a separation matrix under conditions suitable for the protein to associate with the separation
matrix;

(c) washing the separation matrix; and
(d) eluting the protein from the separation matrix.
US Pat. No. 9,636,418

POTENT AND SELECTIVE INHIBITORS OF NAV1.7

AMGEN INC., Thousand Oak...


or a pharmaceutically acceptable salt thereof,wherein:
Xaa1 is any amino acid residue and Xaa2 is any amino acid residue; or Xaa1 is absent and

Xaa2 is any amino acid residue; or Xaa1 is absent and Xaa2 is absent;

Xaa3 is any amino acid residue;

Xaa5 is any neutral hydrophilic or basic amino acid residue;

Xaa6 is any basic amino acid residue;

Xaa7 is a Trp, 5-bromoTrp, 6-bromoTrp, 5-chloroTrp, 6-chloroTrp, 1-Nal, 2-Nal, or thioTrp residue;

Xaa8 is a Met, Nle, Nva, Leu, Ile, Val, or Phe residue;

Xaa9 is a Trp, 5-bromoTrp, 6-bromoTrp, 5-chloroTrp, 6-chloroTrp, 1-Nal, 2-Nal, or thioTrp residue;

Xaa10 is a basic or neutral hydrophilic amino acid residue, or an Ala residue;

Xaa13 is any amino acid residue except a hydrophobic residue;

Xaa14 is a basic residue or an Ala residue;

Xaa16 is any amino acid residue;

Xaa19 is any amino acid residue;

Xaa22 is a basic amino acid residue, or Ala residue;

Xaa24 is a basic amino acid;

Xaa31 is an Ile, Trp, Tyr, 5-bromoTrp, 6-bromoTrp, 5-chloroTrp, 6-chloroTrp, 1-Nal, 2-Nal, or thioTrp residue;

each of Xaa32, Xaa33, and Xaa34 is independently absent or is independently a hydrophobic amino acid residue;

and wherein:
there is a disulfide bond between Cys4 and Cys18,

a disulfide bond between Cys11 and Cys23, and

a disulfide bond between Cys17 and Cys27;

the amino-terminal residue is optionally acetylated, biotinylated, 4-pentynoylated, or PEGylated; and
the carboxy-terminal residue is optionally amidated.
US Pat. No. 10,093,711

INTERLEUKIN-2 MUTEINS FOR THE EXPANSION OF T-REGULATORY CELLS

Amgen Inc., Thousand Oak...

1. A Fc-fusion protein comprising the Fc region of a human IgG1 antibody wherein said Fc region comprises a N297G mutation and one or more substitutions of the amino acid sequence set forth in SEP ID NO:3 at position V259, A287, R292, V302, L306, V323, or I332 with a cysteine amino acid residue, using EU numbering scheme, further comprising a deletion of the C-terminal lysine residue, and wherein said Fc region of a human IgG1 comprises at least 95% identity to the amino acid sequence set forth in SEQ ID NO:3.

US Pat. No. 9,855,259

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

Amgen Inc., Thousand Oak...

1. A compound, wherein the compound is crystalline anhydrous

characterized by a powder X-ray diffraction pattern comprising at least three peaks at a diffraction angle 2 theta degrees
selected from a group consisting of peaks at approximately 8.4, 11.6, 12.4, 18.6, 19.0, 23.6, and 30.4.

US Pat. No. 9,842,408

METHODS AND APPARATI FOR NONDESTRUCTIVE DETECTION OF UNDISSOLVED PARTICLES IN A FLUID

AMGEN INC., Thousand Oak...

1. A method of nondestructive counting and sizing of undissolved particles in a vessel that is at least partially filled with
a fluid, the method comprising:
capturing, via an imager, at least one image of the particles in the vessel that has been imaged under specified imaging conditions;
storing, via a processor coupled to a memory, the at least one image in the memory;
analyzing, via the processor, the at least one image to detect the particles and to calculate information indicative of the
apparent size of the detected particles in the at least one image;

calculating, via the processor, apparent particle size population information indicative of a distribution of varying apparent
particle sizes of the detected particles in the at least one image; and

calculating, via the processor, actual particle size population information indicative of a distribution of varying actual
particle sizes of the detected particles in the at least one image based on a comparison between:

(i) the apparent particle size population information; and
(ii) calibration population information indicative of a distribution of varying apparent particle sizes of one or more sets
of standard sized particles imaged under conditions corresponding to the specified imaging conditions.

US Pat. No. 9,796,766

POTENT AND SELECTIVE INHIBITORS OF NAV1.3 AND NAV1.7

AMGEN INC., Thousand Oak...


or a pharmaceutically acceptable salt thereof,wherein:
Xaa1Xaa2 is absent; or Xaa1 is any amino acid residue and Xaa2 is any amino acid residue;

or Xaa1 is absent and Xaa2 is any amino acid residue;

Xaa3 is Cys, if Xaa18 is Cys; or Xaa3 is SeCys, if Xaa18 is SeCys;

Xaa4 is an acidic, hydrophobic, basic, or neutral hydrophilic amino acid residue;

Xaa5 is a Gly, Ala, hydrophobic, or basic amino acid residue;

Xaa6 is a Gly, 2 Abu, 2-Aib, Ile, Leu, Val, Nle, or Nva;

Xaa7 is a Gly, Ala, aromatic, or hydrophobic amino acid residue;

Xaa8 is a basic, acidic, or neutral hydrophilic amino acid residue, or an Ala residue;

Xaa9 is a basic or neutral hydrophilic amino acid residue;

Xaa10 is Cys if Xaa24 is Cys; or Xaa10 is SeCys if Xaa24 is SeCys;

Xaa11 is any amino acid residue;

Xaa12 is a Pro, acidic, neutral, or hydrophobic amino acid residue;

Xaa13 is any amino acid residue;

Xaa14 is any amino acid residue;

Xaa16 is a basic, neutral hydrophilic, or acidic amino acid residue, or an Ala residue;

Xaa17 is a Cys if Xaa31 is Cys; or Xaa17 is a SeCys if Xaa31 is SeCys;

Xaa18 is a Cys or SeCys;

Xaa19 is any amino acid residue;

Xaa20 is a Pro, Gly, basic, or neutral hydrophilic residue;

Xaa21 is a basic, hydrophobic, or neutral hydrophilic amino acid residue;

Xaa22 is a hydrophobic or basic amino acid residue;

Xaa23 is a hydrophobic, basic, or neutral hydrophilic amino acid residue;

Xaa24 is a Cys or SeCys residue;

Xaa25 is a Ser, Ala, or a neutral hydrophilic amino acid residue;

Xaa26 is an Ala, acidic, basic, or neutral hydrophilic amino acid residue;

Xaa27 is an acidic, basic, neutral hydrophilic or hydrophobic residue;

Xaa28 is an aromatic or basic amino acid residue;

Xaa29 is an acidic, basic, or neutral hydrophilic amino acid residue;

Xaa30 is a Trp, 5-bromoTrp, 6-bromoTrp, 5-chloroTrp, 6-chloroTrp, 1-Nal, 2-Nal, or thioTrp residue;

Xaa31 is a Cys or SeCys;

Xaa33 is a hydrophobic or aromatic amino acid residue;

Xaa34 is any amino acid residue;

Xaa35 is a hydrophobic amino acid residue;

each of Xaa36, Xaa37, and Xaa38 is independently absent or is independently a neutral, basic, or hydrophobic amino acid residue;

and wherein:
if Xaa3 and Xaa18 are both Cys residues, there is a disulfide bond between residue Xaa3 and residue Xaa18; or if Xaa3 and Xaa18 are both SeCys residues, there is a diselenide bond between residue Xaa3 and residue Xaa18;

if Xaa10 and Xaa24 are both Cys residues, there is a disulfide bond between residue Xaa10 and residue Xaa24; or if Xaa10 and Xaa24 are both SeCys residues, there is a diselenide bond between residue Xaa10 and residue Xaa24; and

if Xaa17 and Xaa31 are both Cys residues, there is a disulfide bond between residue Xaa17 and residue Xaa31; or if Xaa17 and Xaa31 are both SeCys residues, there is a diselenide bond between residue Xaa17 and residue Xaa31.

US Pat. No. 9,776,995

BICYCLIC SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

Amgen Inc., Thousand Oak...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof,
wherein:
is

wherein each Ra is independently H, halo, —NRcRc, —OH, hydroxyC1-6alkyl, —C1-6alkyl, —OC1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —CN, and

Ra1 is H, —C1-6alkyl or acetyl;

R1 is a 6 membered aryl or heteroaryl, wherein the aryl or heteroaryl is substituted with from 1 to 4 substituents independently
selected from halo, OH, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —OC1-6alkylCF3,—OC1-6alkylCN, —(CReRe)mCN,—C1-6alkylOC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —(CReRe)mA, —N(Re)(CReRe)mA, —O(CReRe)mA, —O(CReRe)mOA or —C(?O)A, provided at least one substituent on R1 is —(CReRe)mA, —N(Re)(CReRe)mA, —O(CReRe)mA, —O(CReRe)mOA or —C(?O)A;

A is a 4 to 9 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have
from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 6 membered cycloalkyl group, and the aryl, heteroaryl,
heterocycloalkyl or cycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected
from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CReRe)mOH, hydroxyC1-6alkyl, —CF3, —CHF2 , —CH2F, —OCF3, —OCHF2, —OCH2F, —CN, —C(?O)NRbRb, —O(CReRe)mB or —(CReRe)mB;

B is a 3 to 5 membered cycloalkyl group that can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from Cl, F, Br, —NHCH3, —N(CH3)2, —C1-4alkyl, —OC1-4alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F or —CN;

R2 is a 5 to 6 membered aryl or heteroaryl, where the heteroaryl can have from 1 to 3 heteroatoms independently selected from
O, N or S, and the aryl and heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently
selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CRcRc)nNRbRb, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(?O)NRbRb;

each Rb is independently H or —C1-6alkyl;

each Rc is independently H or —C1-6alkyl;

each Rd is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —OC1-6alkyl;

each Re is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl or —OC1-6alkyl;

each n is independently 0, 1, 2, 3 or 4; and
each m is independently 0, 1, 2, 3 or 4;
provided that the compound is not
1-(4-fluoro-2-(pyrimidin-5-yl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide;
1-(4-fluoro-2-(pyrimidin-2-yloxy)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide;
5-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinoline-7-sulfonamide;
N-3-isoxazolyl-1-(3-methoxy-1-phenyl-1H-pyrazol-4-yl)-6-isoquinolinesulfonamide;
1-(2-methoxy-6-(tetrahydro-2H-pyran-4-yloxy)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(2-(cyclohexylamino)-6-methoxy-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(2-((4,4-difluorocyclohexyl)amino)-6-methoxy-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(2-methoxy-6-(tetrahydro-2H-pyran-4-ylamino)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(2-(4,4-difluoro-1-piperidinyl)-6-methoxy-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(6-methoxy-2-(1-pyrrolidinyl)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(2-methoxy-6-(4-morpholinyl)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(6-methoxy-2-(4-morpholinyl)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(6-methoxy-2-(1-piperidinyl)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(6-methoxy-2-(tetrahydro-2H-pyran-4-ylamino)-3-pyridinyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide;
1-(3?,5?-difluoro-3-methoxy-4-biphenylyl)-N-(5-methoxy-4-pyrimidinyl)-6-isoquinolinesulfonamide; or
1-(2-methyl-5-(3-oxetanylmethoxy)phenyl)-N-4-pyrimidinyl-6-isoquinolinesulfonamide.

US Pat. No. 9,751,864

METHODS FOR PREPARING TRIAZOLE AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A method for preparing a compound of Formula VI, a salt thereof, a tautomer thereof, or a salt of the tautomer:

the method comprising:
a) cyclizing a compound of Formula V, a salt thereof, a tautomer thereof, or a salt of the tautomer in the presence of an
acid or a base to form the compound of Formula VI, the salt thereof, the tautomer thereof, or the salt of the tautomer,


wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with
1, 2, 3, or 4 R1a substituents;

R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —C(?O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(?O)-(heterocyclyl) or heterocyclyl
group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;

R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b?CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of
which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;

R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;

R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;

Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected
from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein
the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with
1, 2, 3, or 4 RQ substituent;

RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo substituent;

R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently
selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or
4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents; and

R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), or —C(?O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent.

US Pat. No. 9,988,369

HETEROCYCLIC TRIAZOLE COMPOUNDS AS AGONISTS OF THE APJ RECEPTOR

AMGEN INC., Thousand Oak...

1. A compound of Formula I or Formula II:
or a pharmaceutically acceptable salt thereof, a tautomer thereof, a pharmaceutically acceptable salt of the tautomer, a stereoisomer of any of the foregoing, or a mixture thereof,
wherein:
R1 is a 3-, 4-, 5-, 6-, 7-, or 8-membered saturated or partially saturated heterocyclic group that includes 1, 2, or 3 heteroatoms independently selected from N, O, or S that is unsubstituted or is substituted with 1, 2, or 3 R1a substituents;
R1a in each instance is independently selected from —F, —Cl, —Br, —I, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —NHS(?O)2—(C1-C6 alkyl), or —S(?O)2—(C1-C6 alkyl), wherein R1a may also be oxo unless R1 is a 6-membered heterocyclic group that includes one N atom and includes at least one double bond, and further wherein two R1a substituents on adjacent carbon atoms or on an adjacent carbon atom and an adjacent N atom of a 5- or 6-membered heterocyclic R1 group may join to form a 6 membered ring that may be saturated, partially saturated, or aromatic and may include 0, 1, or 2 N atoms and may further optionally be substituted with 1 or 2 R1a? substituent and may include an oxo substituent if the ring is not an aromatic ring and further wherein two R1a substituents on adjacent carbon atoms or on an adjacent carbon atom and an adjacent N atom of a 5- or 6-membered heterocyclic R1 group may join to form a 5 membered ring that may be saturated, partially saturated, or aromatic and may include 0, 1, or 2 heteroatoms selected from N, O, or S and may further optionally be substituted with 1 or 2 R1a? substituent and may include an oxo substituent if the ring is not an aromatic ring;
R1a? is in each instance independently selected from —F, —Cl, —Br, —I, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, C3-C8 cycloalkyl —(C1-C6 alkyl)-O—(C1-C6 alkyl), —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2 or —S(?O)2—(C1-C6 alkyl);
R2 is selected from —H, or C1-C4 alkyl or is absent in the compounds of Formula II;
R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)—C(?O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)—CH(OH)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)—(CR3fR3g)-Q, a group of formula —(C3-C8 cycloalkyl)-Q, a group of formula -(heterocyclyl)-Q, or -Q, wherein the heterocyclyl of the -(heterocyclyl)-Q group has 5 to 7 ring members of which 1, 2, or 3 are heteroatoms independently selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents, and further wherein the C3-C8 cycloalkyl of the —(C3-C8 cycloalkyl)-Q group is unsubstituted or is substituted with 1 or 2 R3h substituents;
R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —C2-C6 alkenyl, —C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —(C1-C6 alkyl)-OH, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-O—(C1-C6 alkyl)-phenyl, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —(C1-C6 alkyl)-OH, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C2-C6 alkenyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(?O)—(C1-C6 alkyl), —C(?O)—(C3-C6 cycloalkyl), —C(?O)—O—(C1-C6 alkyl), oxo, or —C(?O)-(heterocyclyl), wherein the heterocyclyl group of the Rh—C(?O)-(heterocyclyl) has 5 or 6 ring members of which 1 or 2 are heteroatoms independently selected from N, or S or has 3 or 4 ring members of which 1 is a heteroatom selected from N, O, or S;
Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, a C3-C8 cycloalkyl group, a 3 to 10 membered heterocyclyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl, the heteroaryl, the cycloalkyl, and the heterocyclyl Q groups are unsubstituted or are substituted with 1, 2, 3, or 4 RQ substituents; and further wherein the Q heterocyclyl group may additionally be substituted with 1 or 2 oxo substituents, and the Q heteroaryl group may include an N-oxide if the heteroaryl includes a N heteroatom;
RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(?O)(C1-C6 alkyl), —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —S(?O)2—(C1-C6 alkyl), —(C1-C6 alkyl)-OH, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NH2, —(C1-C6 alkyl)-NH—(C1-C6 alkyl), —(C1-C6 alkyl)-N—(C1-C6 alkyl)2, phenyl, a heterocyclyl group, a —(C1-C6 alkyl)heterocyclyl group, or a heteroaryl group with 5 or 6 ring members and 1, 2, or 3, heteroatoms independently selected from N, O, or S, wherein the heterocyclyl groups of the RQ heterocyclyl and —(C1-C6 alkyl)heterocyclyl groups have 3 to 6 ring members of which 1 or 2 are heteroatoms independently selected from N, O, or S, and further wherein the heterocyclyl and the heterocyclyl of the —(C1-C6 alkyl)heterocyclyl RQ groups may be further substituted with one or two oxo substituents and a substituent selected from —F, —Cl, —Br, —I, —CN, —OH, —C1-C6 alkyl, or —C(?O)—(C1-C6 alkyl);
R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, a monocyclic 3-6 membered cycloalkyl group, or a straight or branched chain C1-C6 alkyl group, wherein the C6-C10 aryl, the heteroaryl, and the heterocyclyl R4 group are unsubstituted or are substituted with 1, 2, 3, or 4 R4a substituents, and further wherein the cycloalkyl R4 group is unsubstituted or is substituted with 1, 2, 3, or 4 R4b substituents, and further wherein the straight or branched chain C1-C6 alkyl R4 group is unsubstituted or is substituted with 1, 2, or 3 R4c substituents;
R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —(C1-C6 alkyl)-OH, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NH(C1-C6 alkyl-OH), —N(C1-C6 alkyl-OH)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —S(?O)2—(C1-C6 alkyl), —(C1-C6 alkyl)-heterocyclyl, or heterocyclyl wherein the heterocyclyl of the —(C1-C6 alkyl)-heterocyclyl and heterocyclyl R4a groups is a 3-6 membered ring comprising 1 or 2 heteroatoms independently selected from N, O, or S and is unsaturated or partially unsaturated and is optionally substituted with 1 or 2 oxo substituents, and further wherein the heterocyclyl of the R4 group may be further substituted with 1 oxo substituent;
R4b in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —(C1-C6 alkyl)-OH, oxo, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NH(C1-C6 alkyl-OH), —N(C1-C6 alkyl-OH)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, phenyl, —S(?O)2—(C1-C6 alkyl), —(C1-C6 alkyl)-heterocyclyl, heterocyclyl, a monocyclic 3-6 membered cycloalkyl group, or a 5 or 6 membered heteroaryl ring containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein the heterocyclyl of the —(C1-C6 alkyl)-heterocyclyl and heterocyclyl R4b groups is a 3-6 membered ring comprising 1 or 2 heteroatoms independently selected from N, O, or S and is unsaturated or partially unsaturated and is optionally substituted with 1 or 2 oxo substituents, and further wherein the phenyl and heteroaryl R4b groups are unsubstituted or are substituted with 1 or 2 R4aa substituents;
R4c in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —OH, oxo, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —S—(C1-C6 alkyl), —S—(C1-C6 haloalkyl), —S—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NH(C1-C6 alkyl-OH), —N(C1-C6 alkyl-OH)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)NH(C3-C6 cycloalkyl), —C(?O)N(C1-C6 alkyl)(C3-C6 cycloalkyl), —C(?O)N(C3-C6 cycloalkyl)2, —S(?O)—(C1-C6 alkyl), —S(?O)2—(C1-C6 alkyl), a monocyclic 3-6 membered cycloalkyl group, a 3 to 6 membered heterocyclyl group containing 1 or 2 heteroatoms selected from N, O, or S, a phenyl group, or a 5 or 6 membered heteroaryl ring containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein the a monocyclic 3-6 membered cycloalkyl R4c group, the 3 to 6 membered heterocyclyl R4c group, the phenyl R4c group, or the a 5 or 6 membered heteroaryl R4c ring are unsubstituted or are substituted with 1 or 2 R4aa substituents; and further wherein the 3 to 6 membered cycloalkyl R4c group and the 3 to 6 membered heterocyclyl R4c group may optionally be additionally substituted with an oxo substituent; and
R4aa in each instance is selected from —F, —Cl, —Br, —I, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —S—(C1-C6 alkyl), —S—(C1-C6 haloalkyl), —S—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, NH(C1-C6 alkyl-OH), —N(C1-C6 alkyl-OH)2, —C(?O)—(C1-C6 alkyl), —C(?O)OH, —C(?O)—O—(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)NH(C3-C6 cycloalkyl), —C(?O)N(C1-C6 alkyl)(C3-C6 cycloalkyl), —C(?O)N(C3-C6 cycloalkyl)2, —S(?O)—(C1-C6 alkyl), or —S(?O)2—(C1-C6 alkyl).
US Pat. No. 9,913,900

METHOD OF TREATING ALVELOR BONE LOSS THROUGH THE USE OF ANTI-SCLEROSTIN ANTIBODIES

AMGEN INC., Thousand Oak...

1. A method for increasing alveolar bone height in a subject suffering from alveolar bone loss comprising administering to
the subject an anti-sclerostin antibody in an amount effective to decrease the distance between the cement-enamel junction
and the alveolar bone crest, at a dose from about 5 mg to about 1,000 mg per week, and wherein the anti-sclerostin antibody
comprises a light chain variable region amino acid sequence set forth in SEQ ID NO: 376 and a heavy chain variable region
amino acid sequence set forth in SEQ ID NO: 378.
US Pat. No. 9,914,779

ADMINISTRATION OF ALPHA4BETA7 HETERO-DIMER-SPECIFIC ANTIBODY

AMGEN INC., Thousand Oak...

1. A method of treating a subject afflicted with a condition that is associated with inappropriate trafficking of cells expressing
alpha4beta7 to the gastrointestinal tract, wherein the condition is inflammatory bowel disease, comprising administering to
the subject an alpha4beta7 heterodimer specific antibody 18A11 in an amount and at an interval selected from the group consisting
of:
(a) 5-14 mg every 7-21 days;
(b) 15-54 mg every 14-56 days;
(c) 55-149 mg every 43-126 days;
(d) 150-299 mg every 112-147 days; and
(e) 300-1000 mg every 126-224 days;
wherein 18A11 is an isolated, alpha4beta7 heterodimer-specific antigen binding protein having a heavy chain variable region
comprising CDR1, CDR2 and CDR3 from SEQ ID NO:5, and a light chain variable region comprising CDR1, CDR2 and CDR3 from SEQ
ID NO:2.

US Pat. No. 9,892,523

METHODS AND APPARATI FOR NONDESTRUCTIVE DETECTION OF UNDISSOLVED PARTICLES IN A FLUID

AMGEN INC., Thousand Oak...

1. An apparatus for nondestructive detection of an undissolved particle in a vessel that is at least partially filled with
a fluid, the apparatus comprising:
at least two imagers positioned to image the particle from different perspectives, each imager from among the at least two
imagers configured to respectively acquire one or more two dimensional images of the particle in the fluid;

a memory operably coupled to the imager and configured to store the two dimensional images; and
a processor operably coupled to the memory and configured to detect the particle by:
combining the two dimensional images from the at least two imagers to determine three dimensional position data indicative
of a position of the particle in the vessel; and

detecting the particle based at least in part on the three dimensional position data,
wherein the processor is configured to, when the three dimensional position data comprises at least one blind spot region
corresponding to a region of the vessel not imaged by the at least two imagers, determine blind spot trajectory information
indicative of a path of the particle in the blind spot region based at least in part on a time-series of two dimensional images
of the particle from one of the at least two imagers.

US Pat. No. 9,879,072

DKK1 ANTIBODIES AND METHODS OF USE

AMGEN INC., Thousand Oak...

1. An isolated antibody or fragment thereof that binds to human DKK1 with a kd of 1.30E-03?5 or less and inhibits human DKK1 activity comprising six CDRs comprising:
a) SEQ ID NOs: 115 to 120,
b) SEQ ID NOs: 139 to 144,
c) SEQ ID NOs: 187 to 192,
d) SEQ ID NOs: 217 to 222, or
e) SEQ ID NOs: 223 to 228.
US Pat. No. 10,023,608

PROTEIN PURIFICATION METHODS TO REMOVE IMPURITIES

AMGEN INC., Thousand Oak...

1. A method of reducing high molecular weight (HMW) species in a protein sample comprising adalimumab or a biosimilar thereof comprising:(a) subjecting the protein sample to mixed mode chromatography (MMC) to form a first eluate using a washing buffer comprising Tris-HCl and NaCl, wherein the protein sample subjected to MMC has a pH of about 6.9 to about 7.3 and a conductivity at a temperature between about 18° C. and about 22° C. of about 15 to about 30 mS/cm; and
(b) subjecting the first eluate to hydrophobic interaction chromatography (HIC) to form a second eluate using an elution buffer comprising 3-(N-morpholino) propanesulfonic acid (MOPS), wherein the second eluate has at least 40% fewer HMW species than the protein sample.
US Pat. No. 9,994,923

NEUTRALIZING PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9) VARIANTS AND USES THEREOF

Amgen Inc., Thousand Oak...

1. An isolated neutralizing PCSK9 variant comprising:a Pro/Cat domain that binds to low density lipoprotein receptor (LDLR) wherein the Pro/Cat domain consists of an amino acid sequence starting at position 31 or 61 of SEQ ID NO:3 and ending at position 374, 381, 382, 447, 448, 449, 450, 451, 452, or 453 of SEQ ID NO: 3; and
an inactive V domain, wherein the inactive V domain does not result in the degradation of LDLR, and wherein the inactive V-domain lacks amino acids 454 to 692 of SEQ ID NO:3.
US Pat. No. 9,951,129

HUMAN IL-23 ANTIGEN BINDING PROTEINS

AMGEN INC., Thousand Oak...

1. An isolated nucleic acid molecule encoding one or both variable regions of an antigen binding protein that binds IL-23, wherein the antigen binding protein comprises at least one heavy chain variable region comprising: a CDRH1 of SEQ ID NO: 91, a CDRH2 of SEQ ID NO:92, and a CDRH3 of SEQ ID NO: 93; and at least one light chain variable region comprising: a CDRL1 of SEQ ID NO: 62, a CDRL2 of SEQ ID NO:63, and a CDRL3 of SEQ ID NO:64.