US Pat. No. 9,220,631

SYRINGE

Novartis AG, Basel (CH)

1. A pre-filled, terminally sterilized syringe for intravitreal injection, the syringe comprising a glass body forming a barrel,
a stopper and a plunger and containing an ophthalmic solution which comprises a VEGF-antagonist, wherein:
(a) the syringe has a nominal maximum fill volume of between about 0.5 ml and about 1 ml,
(b) the syringe barrel comprises from about 1 ?g to 100 ug silicone oil,
(c) the VEGF antagonist solution comprises no more than 2 particles >50 ?m in diameter per ml and wherein the syringe has
a stopper break loose force of less than about 11N.

US Pat. No. 9,365,552

PYRIDINE AND PYRAZINE DERIVATIVE FOR THE TREATMENT OF CF

Novartis AG, Basel (CH)

1. A method for promoting mucus clearance in a subject with Chronic Obstructive Pulmonary Disorder (COPD) or Cystic Fibrosis
(CF), comprising:
administering at least one compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein:
A is N or CR4a;

R1 is H; C1-C8 alkyl optionally substituted by one or more halogen atoms; C2-C8 alkenyl; C2-C8 alkynyl; C3-C10 cycloalkyl; C5-C10 cycloalkenyl; —C1-C4 alkyl-C3-C8 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen atoms; halogen; SO2NR8R9; SO2R10; S—C1-C8alkyl optionally substituted by one or more halogen atoms; S—C6-C14 aryl; CN; NR11R12; C(O)NR13R14; NR13SO2R15; NR13C(O)R15; CO2R15; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S; wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups are each optionally substituted by one or more
Z substituents;

R2 is C1-C4 haloalkyl;

R3 and R4a are each independently H or C1-C8 alkyl optionally substituted by one or more halogen atoms;

R4 is H, or C1-C8 alkyl optional substituted with one or more halogen;

R5 is —(CH2)m—NR17R18, —(CH2)m—OR?; C1-C8 alkoxy optionally substituted by one or more halogen atoms; —(C0-C4 alkyl)-CO2R15; —(C0-C4 alkyl)-C6-C14 aryl or -3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S; wherein the —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclic group are each optionally substituted by one or more Z substituents;

R6 is C1-C8 alkyl optionally substituted by one or more halogen atoms; C3-C10 cycloalkyl; —C1-C4 alkyl-C3-C8 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen atoms; OH; CN; halogen; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S; wherein the cycloalkyl, cycloalkenyl, —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclic group are each optionally substituted by one or more Z substituents; or

R6 is H, and R5 is —(CH2)m—NR17R18, —(CH2)m—OR, C1-C8 alkoxy optionally substituted by one or more halogen atoms; —(C0-C4 alkyl)-C6-C14 aryl; —(C0-C4 alkyl)-3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S; or —(C0-C4 alkyl)-CO2R15, wherein —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclic group groups are each optionally substituted by one or more Z substituents; or

R4 and R6 together with the carbon atoms to which they are bound form a 3 to 8 membered carbocyclic ring system; or

R4 and R5 together form an oxo group (C?O) and R6 is C1-C4 alkyl optionally substituted by one or more halogen atoms; C1-C4 alkoxy optionally substituted by one or more halogen atoms; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S, wherein the aryl and heterocyclyl groups are each optionally substituted by one or more Z substituents; or

R5 and R6 together with the carbon atoms to which they are bound a 5 to 8 membered heterocyclic ring system containing one or more heteroatoms
selected from N, O and S, wherein the ring system is optionally substituted by one or more Z substituents; or

R4 and R5 and R6 together with the carbon atoms to which they are bound form a 5 to 8 membered heterocyclic ring system containing one or more
heteroatoms selected from N, O and S, wherein the ring system is optionally substituted by one or more Z substituents;

R? is H, or C1-C0 alkyl optional substituted with one or more halogen;

m is 0, 1, 2 or 3;
R8, R11, R13 and R17 are each independently H, C1-C8 alkyl optionally substituted by one or more halogen atoms, C3-C10 cycloalkyl or —(C1-C4 alkyl)-C3-C8 cycloalkyl;

R9, R10, R12, R14, R15, R16 and R18 are each independently H; C1-C8 alkyl optionally substituted by one or more halogen atoms; C2-C8 alkenyl; C2-C8 alkynyl; C3-C10 cycloalkyl; C5-C10 cycloalkenyl; —C1-C4 alkyl-C3-C8 cycloalkyl; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected from
N, O and S, wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups are each optionally substituted by one or more
Z substituents; or

R8 and R9, R11 and R12, R13 and R14, and R17 and R18 together with the nitrogen atom to which they are attached may form a 4 to 14 membered heterocyclic group optionally substituted
by one or more Z substituents;

Z is independently OH, aryl, O-aryl, benzyl, O-benzyl, C1-C6 alkyl optionally substituted by one or more OH groups or NH2 groups, C1-C6 alkyl optionally substituted by one or more halogen atoms, C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy, (SO2)NR19R21, (SO2)R21, C(O)NR19R21, NR19R21, C(O)OR19, C(O)R19, SR19, OR19, oxo, CN, NO2, halogen or a 3 to 14 membered heterocyclic group, wherein the heterocyclic group contains at least one heteroatom selected
from N, O and S;

R19 and R21 are each independently H; C1-C8 alkyl; C3-C8 cycloalkyl; C1-C4 alkoxy-C1-C4 alkyl; (C0-C4 alkyl)-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; (C0-C4 alkyl)-3- to 14-membered heterocyclic group, the heterocyclic group including one or more heteroatoms selected from N, O and
S, optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl; (C0-C4 alkyl)-O-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; and (C0-C4 alkyl)-O-3- to 14-membered heterocyclic group, the heterocyclic group including one or more heteroatoms selected from N, O
and S, optionally substituted by one or more groups selected from halogen, C1-C6 alkyl or C(O)C1-C6 alkyl; wherein the alkyl groups are optionally substituted by one or more halogen atoms, C1-C4 alkoxy, C(O)NH2, C(O)NHC1-C6 alkyl or C(O)N(C1-C6 alkyl)2; or

R19 and R21 together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclic group, the heterocyclic group
including one or more further heteroatoms selected from N, O and S, the heterocyclic group being optionally substituted by
one or more substituents selected from OH; halogen; aryl; 5- to 10-membered heterocyclic group including one or more heteroatoms
selected from N, O and S; S(O)2-aryl; S(O)2—C1-C6 alkyl; C1-C6 alkyl optionally substituted by one or more halogen atoms; C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy; and C(O)OC1-C6 alkyl, wherein the aryl and heterocyclic substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy to a subject in need of such treatment.

US Pat. No. 9,103,965

AMPHIPHILIC SILOXANE-CONTAINING VINYLIC MONOMERS AND USES THEREOF

Novartis AG, Basel (CH)

1. An amphiphilic siloxane-containing vinylic monomer, comprising: one sole ethylenically unsaturated group (Q), one sole
bulky siloxane-containing group BSi, and one hydrophilic linkage (hL) between Q and BSi, wherein the amphiphilic siloxane-containing
vinylic monomer is represented by formula (I)
Q-X1-hL-X2—BSi  (I)
In which:
Q is an ethylenically unsaturated group of formula (II)

in which
R12 is hydrogen or C1-C4 alkyl,

Z1 is a linear or branched C1-C12 alkylene radical, —O—, or —NH—,

Z2 is a direct bond or a linear or branched C1-C12 alkylene radical,

A is —O— or —NH—,
q1 and q2 independent of each other are an integer of 0 or 1;

X1 and X2 independent of each other are a direct bond or a cross linkage of formula (III)

—X3—R?1?4-E-X5—R?2—X6-  (III)

in which
X3, X4, X5, and X6 independent of one other are a linkage selected from the group consisting of a direct bond, —O—, —NR?—, —CO—NR?—, —NR?—CO—,
—NR?—CO—NH—, —NH—CO—NR?—, —O—CO—NH—, —NH—CO—O—, —S—CO—NH—, —O—CO—, —CO—O—, —S—, and —NH—CO—S— in which R? is H or C1-C4 alkyl,

E is a linear or branched alkylene, cycloalkane diradical or arene diradical with up to 40 carbon atoms,
R?1 and R?2 independent of each other is a direct bond, a linear or branched C1-C10 alkylene divalent radical, or a divalent radical of —R?3—X4-E-X5—R?4— in which E, X4 and X5 are as defined above and R?3 and R?4 independent of each other are a direct bond or a linear or branched C1-C10 alkylene radical;

hL is a hydrophilic oligomeric segment selected from the group consisting of (1) polyoxazoline (—[(N(COR?)C2H4— in which R? is H, methyl or ethyl) which is obtained in a ring-opening polymerization of oxazoline, (2) a polypeptide segment
composed of at least one amino acid selected from the group consisting of asparagine, glutamine, alanine, glycine, and combinations
thereof, and (3) a hydrophilic polymer segment composed of hydrophilic monomeric units derived from at least one hydrophilic
vinylic monomer selected from the group consisting of (meth)acrylamide, N,N-dimethyl(meth)acrylamide, dimethylaminoethyl(meth)acrylate,
dimethylaminoethyl(meth)acrylamide, N-vinyl-2-pyrrolidone, N-vinyl-N-methyl isopropylamide, N-vinyl-N-methyl acetamide, N-vinyl
formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,
1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,
1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone,
1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, and mixtures thereof; BSi is a monovalent radical
of formula (1A) or (1B)


in which
Y is a C1-C6 alkylene radical or a C1-C6 substituted alkylene radical containing one or more hydroxyl groups,

B1 and B2 independent of each other are C1-C6 alkyl, phenyl, or benzyl,

T is a C1-C12 alkyl or an alkoxyalkyl radical having 3 to 8 carbon atoms,

m is an integer of 0 to 3,
p is an integer of 1 to 6,
r is an integer of 2 to 20,
A1, A2 and A3 independent of each other are C1-C6 alkyl, phenyl, benzyl, or a radical of formula (2)


in which B3, B4 and B5 independent of each other are C1-C6 alkyl, phenyl, or benzyl, provided that at least two of A1, A2 and A3 are radicals of formula (2).

US Pat. No. 9,274,350

OPHTHALMIC LENS COMPRISING A UNIQUE LENS IDENTIFICATION CODE

NOVARTIS AG, (CH)

1. An ophthalmic lens (1) having a front surface (2) and a rear surface, each of the front and rear surfaces comprising a central optical zone (4) which is surrounded by a peripheral zone (3), the ophthalmic lens (1) further comprising a unique lens identification code being arranged in the peripheral zone (3) of one of said front and rear surfaces, the unique lens identification code having the form of an N×M dot matrix (5) comprising N rows and M columns of matrix elements (50), the N×M dot matrix (5) representing a binary code, and
wherein the binary code represented by the N×M dot matrix (5) comprises two types of matrix elements (50), the two types of matrix elements (50) being two types of ink dots having a distinct transparency to light; and

wherein a corner element (53) of the matrix elements of the N×M dot matrix (5) is blank.

US Pat. No. 9,382,212

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Array BioPharma, Inc., B...

1. A process for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid
(2-hydroxyethyoxy)-amide (Compound A):
the process comprising the steps of:
a) dissolving Compound A in a solution comprising (i.) a solvent system comprising an ether and optionally an alcohol, and
(ii.) water to provide a solution;

b) adding a seed crystal suspension to the solution to provide a suspension mixture;
c) cooling the suspension mixture to provide a cooled suspension mixture;
d) adding water to the cooled suspension mixture to provide a treated mixture; and
e) cooling the treated mixture, to provide the crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic
acid (2-hydroxyethyoxy)-amide.

US Pat. No. 9,233,961

COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES

Novartis AG, Basel (CH) ...

1. A compound of Formula I:
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof; wherein
X1 is N or O, or NR5;

X2 is N or NR7, provided that one of X1 and X2 is N;

W is CR6 or N;

L1 is a bond, —C(O)— or —S(O)2—,

L2 is selected from a bond, —CR9a,R9b—, —NR10—, and —O—, wherein R9a is hydrogen, halo or C1-4alkyl, R9b is selected from hydrogen, halo, hydroxyl, C1-4alkyl, and C1-4alkoxy; and R10 is hydrogen or C1-4alkyl;

R1 is selected from hydrogen, C1-6alkyl, C1-4alkoxy, C6-10aryl, C5-10heteroaryl, C3-7cycloalkyl, C5-6heterocycloalkyl, and C9-10heterocyclyl, wherein

the C1-6alkyl or C1-4alkoxy is unsubstituted or substituted with 1 to 2 substituents independently selected from halo, hydroxy, C1-4alkoxy, C5-6aryloxy, hydroxycarbonyl, C1-4alkoxycarbonyl, amino, C1-4alkyamino, C1-4alkoxycarbonylamino, C5-6aryl, and C5-6heterocycloalkyl; and

the C6-10aryl and C5-10heteroaryl, C3-7cycloalkyl, C5-6heterocycloalkyl or C9-10heterocyclyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halo, cyano, hydroxyl, oxo,
C1-4alkyl, benzyl, haloC1-4alkyl, C1-4alkoxyC1-4alkyl, C1-4alkylaminoC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, amino, C1-4alkylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulfonyl, C5-6heteroaryl, haloC5-6heteroaryl, C3-6cycloalkyl, and C5-6heterocycloalkyl; or —N(R2)-L1-L2-R1 together forms a nitro group;

R2 is hydrogen, C1-4alkyl or —C(O)C5-6heteroaryl;

R3 is hydrogen, halo or C1-4alkyl;

R4 is selected from hydrogen, halo, C1-4alkyl, haloC1-4alkyl, C1-4alkylsulfonyl, C5-6heteroaryl, and C5-6heterocycloalkyl;

R5 is selected from hydrogen, C1-4alkyl, —C(O)OC1-4alkyl, wherein the C1-4alkyl portion of C1-4alkyl or —C(O)OC1-4alkyl is unsubstituted or substituted by amino, C1-4alkylamino, or C5-6heterocycloalkyl;

R6 is selected from halo, cyano, C1-4alkyl, C1-4alkenyl, C1-4alkoxy, C1-4alkylsulfonyl, C3-6cycloalkylsulfonyl, C1-4alkylphosphinyl oxide, C1-4alkylcarbonylamino, phenyl, C5-6heteroaryl, C5-6heteraryl, C4-6heterocycloalkyl, and C6-10heterocyclyl, wherein

the C1-6alkyl, C1-4alkenyl or C1-4alkoxy of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, amino, C1-4alkylamino, and hydroxyl-substituted C1-4alkylamino;

the pheny or C5-6heteroaryl of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkylaminoC1-4alkyl, aminoC1-4alkyl, C4-6heterocycloalkyC1-4alkyl, C1-4alkylsilanylC1-4alkoxyC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkoxyC1-4alkoxy, aminoC1-4alkoxy, phenylC1-4alkoxy, C5-6heteroarylC1-4alkoxy, C3-6cycloalkyC1-4alkoxy, C3-6heterocycloalkyC1-4alkoxy, C1-4alkylcarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, C1-4alkoxycarbonyl, amino, C1-4alkylamino, C4-6heterocycloalkyC1-4alkylamino, C4-6heterocycloalkyC1-4alkylamino, —NHC(O)R14 S(O)2R15, phenyl, C5-6heteraryl, C5-6heterocycloalkyl, and C9-10heterocyclyl,

the C3-6heterocycloalkyl or C6-10heterocyclyl of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from C1-4alkyl, oxo, and C1-4alkoxycarbonyl, wherein

R14 is selected from C1-4alkyl, aminoC1-4alkyl, amino, C1-4alkylamino, cyclopropylamino, C1-4alkoxy, C1-4alkylsulfonyl, and C1-4alkylaminosulfonyl

R15 is selected from C1-4alkyl, amino, C3-6cycloalkyl, and C5-6heterocycloalkyl; and

the phenyl, C5-6heteraryl, C5-6heterocycloalkyl or C9-10heterocyclyl substituent of the phenyl or C5-6heteroaryl of R6 is unsubstituted or substituted by 1 to 3 substituents independently selected from Cl-4alkyl and oxo;

R7 is selected from hydrogen, C1-4alkyl and —C(O)C5-6heteroaryl; and

R8 is hydrogen or halo.

US Pat. No. 9,238,057

METHOD FOR TREATING OCULAR NEOVASCULARIZATION

Novartis AG, Basel (CH)

1. A method for ameliorating or reducing the rate of ocular neovascularization in an individual afflicted with ocular neovascularization,
comprising:
directly administering to the eye or eyes of the individual a replication-defective viral vector that operably encodes and
expresses a functionally active endostatin wherein the administering ameliorates or reduces the rate of ocular neovascularization,

wherein the viral vector is administered to the eye or eyes of the individual intraocularly or subretinally.

US Pat. No. 9,290,533

?-L-2?-DEOXY-NUCLEOSIDES FOR THE TREATMENT OF HEPATITIS B

Novartis AG, Basel (CH) ...

1. A method for the treatment of a hepatitis B infection in a human, said method comprising administering an effective amount
of 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt thereof, of the formula:
wherein R is selected from the group consisting of, (C?O)-alkyl, (C?O)-aryl, (C?O)-alkoxyalkyl, (C?O)-aryloxyalkyl, alkylsulfonyl,
arylsulfonyl, aralkylsulfonyl, amino acid acyl residue, and a stabilized nucleotide or nucleoside prodrug, wherein the stabilized
nucleotide or nucleoside prodrug is a 5?- or N6-alkylated derivative, a 5?-phospholipid, or a 5?-ether lipid.

US Pat. No. 9,233,956

BENZENE SULFONAMIDE THIAZOLE AND OXAZOLE COMPOUNDS

Novartis AG, Basel (CH)

1. A method for treating a susceptible neoplasm selected from melanoma and non-small cell lung cancer in a mammal in need
thereof comprising the steps of:
(a) analyzing a sample from said neoplasm to determine whether an activating mutation is present in the coding sequence for
B-Raf in cells of said neoplasm;

(b) selecting a mammal having said neoplasm with an activating mutation in the coding sequence for B-Raf; and
(c) administering a therapeutically effective amount the compound of formula
or a pharmaceutically acceptable salt thereof to the mammal selected in step (b).

US Pat. No. 9,261,626

CONTACT LENSES WITH ENZYMATICALLY DEGRADABLE COATINGS THEREON

Novartis AG, Basel (CH)

1. A disposable contact lens, comprising:
a preformed silicone hydrogel contact lens composed of a silicone hydrogel material; and a top lubricious hydrophilic coating
thereon, wherein the top lubricious hydrophilic coating is made from a hydrophilic polymeric material including dangling hydrophilic
polymer chains covalently linked to the hydrophilic polymeric material through up to two oligo-caprolactone linkages susceptible
to cleavage by enzymes present in tear fluid, wherein the oligo-caprolactone linkages independent of one another are a divalent
radical of

in which n is an integer of 12 or less, wherein the disposable contact lens is characterized by having a controlled, wearing-induced
deterioration in surface hydrophilicity and/or lubricity over a replacement schedule period.

US Pat. No. 9,119,450

CONTACT LENS PACKAGE

Novartis AG, Basel (CH)

1. A method for packaging a hydrogel contact lens, comprising the steps of:
(a) providing a plastic container having a cavity and a flat flange that horizontally extends in a plane around the perimeter
of the cavity, wherein the flange having a sealing area surrounding circumferentially and adjacently about of the cavity,
wherein the sealing area having a micro-texture pattern,

(b) placing an amount of a packaging solution and the hydrogel contact lens in the container, wherein the amount of the packaging
solution is sufficient to have the hydrogel contact lens to be fully immersed;

(c) heat sealing the container using a heated flat seal plate with a flexible cover sheet which is a laminate material comprising
a metal foil layer and at least one polymer layer to form a storage package of the soft contact lens;

wherein during the step of heat sealing, the micro-texture pattern engages a laminate foil cover and displaces water beads
present between the laminate foil cover and the plastic container in the sealing area to form a heat seal, provided that after
heat sealing the sealing area is smooth and leveled to the flange wherein the micro-texture pattern comprises a step height
rough surface, wherein the step height rough surface pattern thereon has an overall root mean square surface roughness of
between 5 ?m to 50 ?m.

US Pat. No. 9,403,810

CARBOXAMIDE DERIVATIVES

Novartis AG, Basel (CH)

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein
R1 is (C3-C6)alkyl or (C3-C6)cycloalkyl;

R2 is methyl;

R3 is selected from (C6-C10)branched alkyl, (C6-C10)branched alkenyl, (C5-C8)cycloalkenyl, (C5-C8)cycloalkyl, or Het; wherein the (C5-C8)cycloalkenyl or (C5-C8)cycloalkyl is unsubstituted or is substituted by one, two, three or four substituents R4; and wherein Het is substituted by one, two, three or four substituents R4;

each R4 is independently selected from halo, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, or halo(C1-C4)alkoxy; or

two R4 groups, when attached to the same carbon atom, may be taken together with the carbon atom to which they are attached to form
a cyclopentyl, tetrahydrofuran or dioxolane ring; wherein Het is a 5 or 6 membered fully saturated or partially saturated
heterocyclic ring comprising a) 1 oxygen atom in the 2- or 3-position, or b) 2 oxygen atoms in the 2- and 5-, or 2- and 6-positions,
wherein the numbering is relative to the point of attachment; and

(C5-C8)cycloalkyl may be a monocyclic ring or a bridged ring system containing 5, 6, 7 or 8 carbon atoms.

US Pat. No. 9,411,171

SILICONE HYDROGEL LENSES WITH WATER-RICH SURFACES

Novartis AG, Basel (CH)

1. A hydrated silicone hydrogel contact lens, comprising:
a silicone hydrogel material which is obtained by copolymerization of a polymerizable composition comprising at least one
silicone-containing vinylic monomer or at least one silicone-containing vinylic macromer or at least one silicone-containing
prepolymer having ethylenically unsaturated groups;

an anterior surface; and
an opposite posterior surface,wherein the hydrated silicone hydrogel contact lens has an oxygen transmissibility of at least about 40 barrers/mm, a water
content of from about 10% to about 75% by weight, an elastic modulus of from about 0.3 MPa to about 1.8 MPa, a surface wettability
characterized by having an averaged water contact angle of about 80 degrees or less, and a surface hydrophilicity characterized
by having a WBUT of at least about 10 seconds,wherein the hydrated silicone hydrogel contact lens has a cross-sectional surface-modulus profile which comprises, along a
shortest line between the anterior and posterior surfaces on the surface of a cross section of the hydrated silicone hydrogel
contact lens, an anterior outer zone including and near the anterior surface, an inner zone including and around the center
of the shortest line, and a posterior outer zone including and near the posterior surface, wherein the anterior outer zone
has an average anterior surface modulus (designated as SMAnt) while the posterior outer zone has an average posterior surface modulus (designated as SMPost), wherein the inner zone has an average inner surface modulus (designated as SMInner) wherein at least one of
is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about
35%, most preferably at least about 40%, wherein the anterior and posterior outer zones covers a span of at least about 0.1
?m.

US Pat. No. 9,181,238

N-(PYRIDIN-2-YL)SULFONAMIDES AND COMPOSITIONS THEREOF AS PROTEIN KINASE INHIBITORS

NOVARTIS AG, Basel (CH)

8. A pharmaceutical composition comprising a compound of claim 1, admixed with at least one pharmaceutically acceptable excipient.
US Pat. No. 9,061,012

USES OF DGAT1 INHIBITORS

Novartis AG, Basel (CH)

1. A method for the delay of progression or treatment of chylomicronemia due to familial chylomicronemia syndrome comprising
administration of a therapeutically effective amount of the DGAT1 inhibitor trans-4-[4-[5-[[6-(trifluoromethyl)-3-pyridinyl]amino]-2-pyridinyl]phenyl]cyclohexane
acetic acid, or a pharmaceutically acceptable salt or ester thereof, to a human subject in need of such treatment.

US Pat. No. 9,240,043

REPRODUCIBLE QUANTIFICATION OF BIOMARKER EXPRESSION

NOVARTIS AG, Basel (CH)

1. A method of reproducibly quantifying biomarker expression in a slide-mounted tissue sample, the method comprising:
(a) obtaining a slide-mounted tissue sample, which has been stained to permit localization of at least one cellular compartment
and at least one biomarker;

(b) obtaining one or more pixel-comprised images of the stained tissue sample using a microscope, and analyzing the one or
more pixel-comprised images to obtain one or more data sets;

(c) automatically analyzing the one or more data sets derived from the image pixels to differentiate data signal from noise;
(d) automatically analyzing the one or more data sets derived from the image pixels to differentiate data signal attributable
to each of said at least one cellular compartment;

(e) optionally automatically analyzing the one or more data sets derived from the image pixels to differentiate data signal
attributable to said at least one biomarker for each of said at least one cellular compartment;

(f) quantifying the amount of biomarker expressed in each of said at least one cellular compartment to arrive at a standardized
score, which is a product of a raw score and one or more factors selected from the group consisting of a calibration cube
factor, a light source factor and an optical path factor,

whereby a run comprises steps (a)-(f), and the biomarker expression in the same slide-mounted tissue sample is quantified
in a manner having a level of reproducibility above 80 percent for separate runs,

in which each automatic analysis step is carried out in an unsupervised manner and comprises an unsupervised pixel-based clustering
algorithm, and

whereby the microscope allows for automatic adjustment of exposure time to provide an optimized dynamic range of data captured
in the image pixels.

US Pat. No. 9,372,282

STYRENIC OPHTHALMIC AND OTORHINOLARYNGOLOGICAL MATERIALS AND DEVICES FORMED THEREWITH

Novartis AG, Basel (CH)

1. A polymeric ophthalmic or otorhinolaryngological device material comprising:
at least 85 w/w % of a polystyrene of structure (I):

wherein:
ntot represents values of n, which are separate integer values n=1 through n=ntot;

mtot represents values of m, which are separate integer values m=1 through m=mtot;

ptot represents values of p, which are separate integer values p=1 through p=ptot;

R1 independently=H, CH3, or CH2CH3;

R2 independently=H or R3; and

R3 is independently=linear alkyl, branched alkyl, alkyl ether, alkoxy, ester or any combination thereof for each separate combination
of values of n and p and m and p;

A=independently, nothing or a connector moiety;
B=independently, nothing or a connector moiety;
ntot=is independently 1 or greater for each value of p;

mtot=is independently 1 or greater for each value of p; and

ptot=5 or greater; and

wherein, numerically, R2=R3 at least 50% of the time and wherein the device material is shaped into a device selected from the group consisting of intraocular
lenses; contact lenses; keratoprostheses; corneal inlays or rings; otological ventilation tubes; and nasal implants; and

wherein the polystyrene of structure (I) is formed by the polymerization of styrene monomers of the following structure (II):
and
wherein the polystyrene of structure (I) is formed from at least 90% but no greater than 97% of the monomers of structure
(II) polymerized to form the device material;

wherein the device material has a refractive index in the dry state of at least 1.47, an elongation of at least 150% and a
Young's modulus of less than 6.0 MPa.

US Pat. No. 9,206,116

PROCESS FOR PREPARING 5-BIPHENYL-4-AMINO-2-METHYL PENTANOIC ACID

NOVARTIS AG, Basel (CH)

1. A process for producing a compound according to formula (18) or a salt thereof

comprising the steps
a) providing a compound according to formula (1), or tautomer, or salt thereof,

b) methylating the compound according to formula (1), or tautomer, or salt thereof, to obtain a compound according to formula
(2), or tautomer, or salt thereof,


c) reacting the compound according to formula (2), or tautomer, or salt thereof, with a ring opening agent to obtain a compound
according to formula (3) or a salt thereof


d) reacting a compound according to formula (3) or a salt thereof to obtain a compound according to formula (18) or a salt
thereof,

wherein in the above formulae R1 and R2 are independently, of each other, hydrogen or a nitrogen protecting group and R3 is
hydrogen or alkyl.

US Pat. No. 9,084,781

MEK MUTATIONS CONFERRING RESISTANCE TO MEK INHIBITORS

Novartis AG, Basel (CH) ...

1. A method of optimizing treatment of a subject having cancer, comprising:
(a) extracting nucleic acid from cells of the cancer;
(b) assaying a nucleic acid molecule encoding a MEK polypeptide and identifying the nucleotide sequence of a nucleic acid
molecule encoding a MEK polypeptide to identify an alteration of an amino acid residue at one or more amino acids of the encoded
MEK polypeptide that confers resistance to a MEK inhibitor and identifying the presence of nucleotides that alter the identity
of an amino acid residue at one or more amino acids of the encoded MEK polypeptide relative to the amino acid at one or more
positions selected from the group consisting of I103N, I111N, L115R, L115P, H119P, P124L, P124S, F129L and V211D of SEQ ID
NO:2, the altered identity of the amino acid residue at one or more amino acids of the encoded MEK polypeptide confers resistance
to a MEK inhibitor and indicates a need to treat the subject with a MEK inhibitor and a RAF inhibitor; and

(c) administering a MEK inhibitor and a RAF inhibitor to the subiect when the nucleic acid molecule includes nucleotides that
alter the identity of an amino acid residue at one or more amino acid of the encoded MEK polypeptide relative to the amino
acid at one or more positions selected from the group consisting I103N, I111N, L115R, L115P, H119P, P124L, P124S, F129L and
V211D of SEQ ID NO:2, and the altered identity of the amino acid residue at one or more amino acids of the encoded MEK polypeptide
confers resistance to a MEK inhibitor.

US Pat. No. 9,394,368

TREATMENT OF CANCER USING HUMANIZED ANTI-EGFRVIII CHIMERIC ANTIGEN RECEPTOR

NOVARTIS AG, Basel (CH) ...

1. An isolated nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein said CAR comprises an anti-EGFRvIII
binding domain, a transmembrane domain, and an intracellular signaling domain comprising a primary signaling domain, a costimulatory
domain, or both a primary signaling domain and a costimulatory domain, wherein the encoded anti-EGFRvIII binding domain comprises
an amino acid sequence with greater than 99% sequence identity to SEQ ID NO:68 comprising:
(a) a heavy chain immunoglobulin variable region comprising:
(i) a CDR1 comprising the sequence DYYIH (SEQ ID NO: 22);
(ii) a CDR2 comprising the sequence RIDPENDETKYGPIFQG (SEQ ID NO: 23); and
(iii) a CDR3 comprising the sequence RGGVY (SEQ ID NO: 24); and
(b) a light chain immunoglobulin variable region comprising:
(i) a CDR1 comprising the sequence KSSQSLLDSDGKTYLN (SEQ ID NO: 26);
(ii) a CDR2 comprising the sequence LVSKLDS (SEQ ID NO: 27); and
(iii) a CDR3 comprising the sequence WQGTHFPGT (SEQ ID NO: 28).

US Pat. No. 9,238,627

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Array BioPharma, Inc., B...

1. A process for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide:

the process comprising the steps of:
a) reacting a compound of Formula (I):

with a suitable base to form an intermediate; and
b) reacting said intermediate with a compound of Formula (II):

to provide a compound of Formula (III):

or a hydrate thereof, wherein P1 is a protecting group;

c) dissolving said compound of Formula (III) or a hydrate thereof in a suitable solvent or solvent system; and
d) deprotecting said compound of Formula (III) or a hydrate thereof with a suitable deprotecting reagent, wherein P1 in each occurrence may be the same or different, and is a suitable protecting group, to provide Compound A.

US Pat. No. 9,193,732

SALT(S) OF 7-CYCLOPENTYL-2-(5-PIPERAZIN-1-YL-PYRIDIN-2-YLAMINO)-7H-PYRROLO[2,3-D]PYRIMIDINE-6-CARBOXYLIC ACID DIMETHYLAMIDE AND PROCESSES OF MAKING THEREOF

Novartis AG, Basel (CH) ...

1. Succinate salt of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide
characterized by the initial X-ray Powder Diffraction (XRPD) illustrated in FIG. 2.

US Pat. No. 9,056,874

COMPLEMENT PATHWAY MODULATORS AND USES THEREOF

NOVARTIS AG, Basel (CH)

1. A compound, or salt or a tautomer thereof, according to Formula (I):

Wherein
is a single or double bond;
X is N;
Y is N(H);
one occurrence of R is cyano and the other occurrence of R is hydrogen or R4;

R1 is halogen, hydroxyl, C1-C6alkyl, C2-C6alkenyl, C3-C6cycloalkyl, C1-C6alkoxy, haloC1-C6alkyl, hydroxyC1-C6alkyl, aminoC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, C1-C6alkoxyC1-C6alkoxy, C3-C6cycloalkylC1-C6alkoxy, haloC1-C6alkoxy, S(O)pC1-C6alkyl, CH2NHC(O)C1-C4alkyl or OCH2C(O)R7;

p is 0, 1, or 2;
R2 is C1-C6alkyl, C1-C6alkoxy, hydroxyC1-C6alkyl or halogen;

R3 is hydrogen, halogen, cyano, C1-C4alkyl, haloC1-C4alkyl, CH2C(O)R7, phenyl or 5 or 6 member heteroaryl having 1, 2 or 3 ring heteroatoms independently selected from N, O or S, wherein the
phenyl or heteroaryl is optionally substituted with 0, 1, or 2 C1-C4alkyl groups, and wherein the alkyl and haloalkyl is optionally substituted with 0 or 1 hydroxy groups;

R4 is 0, 1, or 2 substitutents independently selected at each occurrence from halogen and C1-C6alkyl;

R5 is hydrogen, C1-C6alkyl, haloC1-C6alkyl, C3-C6cycloalkyl, phenyl or 5 or 6 member heteroaryl having 1, 2 or 3 ring heteroatoms independently selected from N, O or S;

or R3 and R5 taken in combination form a divalent —CH2—CH2— or —CH2—N(H)— group;

R6 is hydrogen, hydroxy, amino, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxyC1-C6alkoxy, mono- and di-C1-C4alkylamino, amino C1-C6alkylamino, [CRA2]nR7, [CRA2]nC(O)R7, O[CRA2]nR7, NHC(O)C1-C6alkyl, NHS(O2)C1-C6alkyl, (CH2)nR9, O(CH2)nR9, C(O)R7, N(H)[CRA2]nR7, O[CRA2]nC(O)R7, N(H)[CRA2]nC(O)R7 or tetrazolyl;

or CR5R6, taken in combination, form a divalent carbonyl group, a divalent ?CH2 group or cyclopropyl which cyclopropyl is optionally substituted by CO2H or CH2OH;

n is 1, 2, 3 or 4;
RA is independently selected at each occurrence from hydrogen, halogen or C1-C4alkyl;

R7 is hydroxy, C1-C4alkoxy, amino or mono- and di-C1-C4alkylamino;

R8 is hydrogen or halogen; and

R9 is a 5 member heteroaryl having 1 to 4 ring heteroatoms selected from N, O or S and optionally substituted with 0, 1, or 2
C1-C4alkyl groups.

US Pat. No. 9,386,918

OPHTHALMIC SURGICAL SYSTEM WITH BLUE LIGHT FILTERING

NOVARTIS AG, Basel (CH)

1. An ophthalmic surgical system, comprising:
a light source configured to generate a light beam;
a filter wheel disposed between the light source and an intraocular illumination device, the filter wheel including
an unfiltered area;
a first filtered area configured to limit the transmission of a first range of wavelengths of the light beam to the intraocular
illumination device; and

a second filtered area configured to limit the transmission of a second range of wavelengths of the light beam to the intraocular
illumination device;

an actuator configured to selectively move the filter wheel to cause the light beam to pass through one or more of the unfiltered
area, the first filtered area, and the second filtered area of the filter wheel; and

a computing device in communication with the actuator and configured to
monitor the transmission of blue light by the intraocular illumination device within the eye; and
output, in response to the monitoring the transmission of blue light by the intraocular illumination device, control signals
to the actuator to limit the transmission of blue light within the eye to minimize retinal phototoxicity by causing the actuator
to selectively move the filter wheel such that the light beam passes through one or more of the unfiltered area, the first
filtered area, and the second filtered area.

US Pat. No. 9,358,735

METHOD OF TREATING A LENS FORMING SURFACE OF AT LEAST ONE MOLD HALF OF A MOLD FOR MOLDING OPHTHALMIC LENSES

NOVARTIS AG, (CH)

1. Method of molding a silicon hydrogel soft contact lens, the method comprising the steps of providing a mold comprising
a male mold half and a female mold half, each of the male and female mold halves having a lens forming surface, introducing
a silicon hydrogel lens forming material into the male mold half or the female mold half, assembling the male and female mold
halves, exposing the lens forming material arranged between the lens forming surfaces of the male and female mold halves to
polymerizing and/or crosslinking energy to form the silicon hydrogel soft contact lens, disassembling the male and female
mold halves to open the mold, and removing the silicon hydrogel soft contact lens from the male mold half or from the female
mold half,
wherein the lens forming surface of either both the male and female mold halves or of only one of the male and female mold
halves is treated by a plasma treatment prior to introducing the lens forming material into the male mold half or the female
mold half,

wherein the plasma is generated with the aid of a plasma torch comprising a plasma gun and a tubular plasma concentrator,
the plasma concentrator sealingly surrounding the space between the plasma gun and the lens forming surface of the mold or
mold half, wherein the plasma treatment is under atmospheric pressure thereby hydrophilizing the lens forming surface without
depositing any material on the lens forming surface.

US Pat. No. 9,278,981

COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1

Novartis AG, Basel (CH)

1. A compound of formula (Ia):
in which:
R4 is selected from the group consisting of —SF5 and —Y2—CF2—Y3;

R6 at each occurrence is independently selected from the group consisting of hydrogen, methyl, methoxy, cyano, trifluoromethyl,
methoxy-carbonyl, 2-hydroxypropan-2-yl, hydroxy-methyl, halo, amino, fluoro-ethyl, ethyl and cyclopropyl;

R7 at each occurrence is independently selected from the group consisting of hydroxy, methyl, methoxy, hydroxy-methyl, amino,
methyl-amino, amino-methyl, trifluoromethyl, 2-hydroxypropan-2-yl, methyl-carbonyl-amino, dimethyl-amino, cyano and amino-carbonyl;
or two R7 groups combine with the atom to which they are attached to form a ring selected from the group consisting of cyclopropyl,
pyrrolo[3,4-c]pyrazol-5(1H,4H,6H)-yl and 3-azabicyclo[3.1.0]hexan-3-yl; wherein said 3-azabicyclo[3.1.0]hexan-3-yl can be
optionally substituted with amino;

Y1 is selected from the group consisting of N and CR5; wherein R5 is selected from the group consisting of hydrogen, methoxy and imidazolyl; wherein said imidazolyl is unsubstituted or substituted
with methyl;

Y2 is selected from the group consisting of CF2, O and S(O)0-2; and

Y3 is selected from the group consisting of hydrogen, halo, methyl, difluoromethyl and trifluoromethyl;

Y4 is selected from the group consisting of CR6 and N; or the pharmaceutically acceptable salts thereof.

US Pat. No. 9,392,936

SYSTEMS AND METHODS FOR DUAL VITREOUS AND RETINA IMAGING

Novartis AG, (CH)

1. A method for imaging vitreous and retina in an eye comprising:
receiving as an input optical coherence tomography (OCT) data for an eye;
determining a vitreoretinal boundary in the OCT data between the retina and vitreous region;
processing the OCT data for the retina based on retina characteristics;
processing the OCT data for the vitreous based on vitreous characteristics;
enhancing the OCT data for the retina based on retina characteristics;
enhancing the OCT data for the vitreous based on vitreous characteristics; and
fusing the OCT data for the retina with the OCT data for the vitreous to obtain a combined image of the retina, vitreous,
and the vitreoretinal boundary.

US Pat. No. 9,359,307

AMINO PYRIMIDINE DERIVATIVES

Novartis AG, Basel (CH)

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof;

wherein,
R1 is hydrogen or C1-C6 alkyl optionally substituted by hydroxy;

R2 is hydrogen or halogen;
R3 is hydrogen or halogen;
R4 is hydrogen;
R5 is hydrogen or halogen;
or R4 and R5 are attached to each other and stand for a bond, —CH2—, —CH2—CH2—, —CH?CH—, —CH?CH—CH2—; —CH2—CH?CH—; or —CH2—CH2—CH2—;

R6 and R7 stand independently from each other for H, C1-C6 alkyl optionally substituted by hydroxyl, C3-C6 cycloalkyl optionally substituted by halogen or hydroxy, or halogen;

R8, R9, R, R?, R10 and R11 independently from each other stand for H, or C1-C6 alkyl optionally substituted by C1-C6 alkoxy; or any two of R8, R9, R, R?, R10 and R11 together with the carbon atom to which
they are bound may form a 3-6 membered saturated carbocyclic ring;

R12 is hydrogen or C1-C6 alkyl optionally substituted by halogen or C1-C6 alkoxy;

or R12 and any one of R8, R9, R, R?, R10 or R11 together with the atoms to which they are bound may form a 4, 5, 6 or 7 membered
azacyclic ring, which ring may optionally be substituted by halogen, cyano, hydroxyl, C1-C6 alkyl or C1-C6 alkoxy;

n is 0 or 1; and
R13 is C2-C6 alkenyl optionally substituted by C1-C6 alkyl, C1-C6 alkoxy or N,N-di-C1-C6 alkyl amino; C2-C6 alkynyl optionally substituted by C1-C6 alkyl or C1-C6 alkoxy; or C2-C6 alkylenyl oxide optionally substituted by C1-C6 alkyl.

US Pat. No. 9,283,209

ORAL FORMULATIONS OF DEFERASIROX

NOVARTIS AG, Basel (CH)

1. A tablet for oral administration consisting of 90 mg deferasirox;
53.61 mg microcrystalline cellulose;
3.65 mg poly vinyl pyrrolidone K-30;
11.34 mg crospovidone;
0.16 mg poloxamer;
0.81 mg fumed silica;
2.43 mg magnesium stearate; and
4.86 mg seal-coat.

US Pat. No. 9,283,115

PASSIVE TO ACTIVE STAGED DRAINAGE DEVICE

Novartis AG, Basel (CH)

1. An IOP control system for implantation in an eye of a patient, comprising:
a drainage device sized for implantation into the eye of the patient and comprising:
a housing including an inlet port and an outlet port;
a fluid flow passageway extending through the housing from the inlet port to the outlet port to allow the flow of fluid from
the inlet port to the outlet port; and

at least one valve disposed within the drainage device, the at least one valve including a first side, an opposing second
side, the at least one valve configured to affect flow through the fluid flow passageway from the inlet port to the outlet
port by moving in response to pressure differentials acting on the opposing first and second sides; and

a control device comprising an actuator including an activated mode and a deactivated mode, wherein the actuator in the activated
mode is configured to selectively adjust flow through the drainage device in response to changes in intraocular pressure wherein
the at least one valve comprises a sealing portion attached to the housing and being shaped and configured to control flow
of aqueous humor through the fluid flow passageway by deflecting in response to pressure differentials acting across the sealing
portion, and wherein the at least one valve is in a closed condition when the sealing portion contacts a valve seat in the
housing; wherein the sealing portion is movable relative to the valve seat in response to pressure differentials acting on
the opposing first and second sides, is movable relative to the housing in response to activation of the actuator, and includes
a responsive element that is configured to interact with the actuator and move the sealing portion relative to the valve seat
when the actuator is in an activated mode; wherein the responsive element comprises a magnetic element and the actuator comprises
an electromagnet configured to attract the magnetic element when the actuator is in an activated mode.

US Pat. No. 9,079,889

KINASE INHIBITORS AND METHODS OF THEIR USE

NOVARTIS AG, Basel (CH)

1. A method for treating multiple myeloma,
wherein the method comprises the step of: administering to a patient in need of such treatment an effective amount of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide
of Formula or a pharmaceutically acceptable salt thereof,


US Pat. No. 9,315,500

BICYCLIC HETEROARYL CYCLOALKYLDIAMINE DERIVATIVES

NOVARTIS AG, Basel (CH)

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.

US Pat. No. 9,284,284

OXAZINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE

NOVARTIS AG, Basel (CH)

1. A compound of the formula (I), or a pharmaceutically acceptable salt thereof:

wherein
n represents 0 or 1;
X represents CH or N;
R1 represents:

phenyl, optionally substituted by 1, 2 or 3 substituents independently selected from R10;

a group G1 selected from furan-2-yl, pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl and pyrazin-2-yl, wherein G1 is optionally substituted by 1, 2 or 3 substituents independently selected from R10; or

a group G2 selected from isothiazolo[4,5-b]pyridin-3-yl, isothiazolo[4,5-b]pyrazin-3-yl, benzo[d]isothiazol-3-yl, indazol-3-yl, benzo[d]isoxazol-3-yl,
pyrido[3,2-d]pyrimidin-4-yl, [1,7]naphthyridin-8-yl and imidazol[1,2-a]pyrazin-8-yl, wherein G2 is optionally substituted by 1, 2 or 3 substituents independently selected from R11;

R2, R3 and R4 independently represent hydrogen, halogen or C1-3alkyl;

R5 represents C1-3alkyl, halogen-C1-3alkyl or C1-3alkoxy-C1-3alkyl;

R6 and R7 independently represent hydrogen or C1-3alkyl;

R8 and R9 independently represent hydrogen, C1-3alkyl, halogen-C1-3alkyl or C1-3alkoxy; or R8 and R9 taken together are cyclopropyl;

R10 represents halogen, cyano, hydroxy, halogen-C1-3alkoxy, C1-3alkoxy, C1-3alkoxy-C1-3alkoxy, nitro or amino; and

R11 represents halogen, cyano, hydroxy, halogen-C1-3alkyl, halogen-C1-3alkoxy, C1-3alkoxy, C1-3alkoxy-C1-3alkyl or C1-3alkoxy-C1-3alkoxy.

US Pat. No. 9,351,923

EXTENDED-RELEASE COMPOSITION COMPRISING A SOMATOSTATIN DERIVATIVE IN MICROPARTICLES

Novartis AG, Basel (CH)

1. A pharmaceutical composition for extended release comprising microparticles comprising a polymer matrix comprising a linear
and a branched polylactide-o-glycolide polymer and pasireotide pamoate as an active ingredient produced by suspending pasireotide
pamoate in a polymer solution, wherein said polymer solution comprises methylene chloride and a polymer mixture of said linear
and said branched polylactide-co-glycolide polymer, wherein the concentration of the polymer mixture in methylene chloride
is 15.9% weight of polymer per weight of polymer solution, preparing an aqueous solution comprising a stabilizer, mixing the
suspended pasireotide pamoate in polymer solution with the stabilizer solution, evaporating off the methylene chloride, and
filtering off the microparticles.

US Pat. No. 9,416,136

PYRROLOPYRIMIDINE COMPOUNDS AND THEIR USES

Novartis AG, Basel (CH) ...

1. A method for the treatment of cancer by inhibiting cyclin-dependent kinase 4 comprising administering a compound of formula
I, or a pharmaceutically acceptable salt thereof, to a subject in need thereof:
wherein
X is CR9;

R1 is CONR5R6, and R5 and R6 are C1-8alkyl;

R2 is C3-14cycloalkyl;

L is a bond, C1-8alkylene, C(O), or C(O)NH, and wherein L may be substituted or unsubstituted;

Y is H, OH, or Y is part of the following group

where Y is N and W is CR9, or N;
where 0-2 R8 may be present, and R8 is C1-8alkyl, oxo, or two or more R8 may form a bridged alkyl group;
R3 is H, C1-8alkyl, C3-14cycloalkyl, C(O)C1-8 alkyl, C1-8alkylOH, C1-8cyanoalkyl, C0-8alkylC(O)C0-8alkylNR14R15, C0-8alkylC(O)OR14, NR14R15, C1-8alkylC3-14cycloalkyl, C(O)C1-8alkylC3-14cycloalkyl, C1-8alkylR14, C1-8haloalkyl, or C(O)R14, which may be substituted with one or more of OH, CN, F, or NH2 , and wherein R14 and R15 are each independently selected from H, C1-8alkyl, C3-14cycloalkyl, alkoxy, C(O)C1-3alkyl, C1-8alkylNH2, or C1-6 alkylOH;

R9 is H or halogen;

m and n are independently 0-2; and
wherein L may be substituted with one or more of C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-14cycloalkyl, 5-14 membered heteroaryl group, C6-14aryl group, a 3-14 membered cycloheteroalkyl group, OH, (O), CN, alkoxy, halogen, or NH2.

US Pat. No. 9,403,827

SUBSTITUTED PURINONE COMPOUNDS

NOVARTIS AG, Basel (CH)

1. A compound of formula (I), or a salt thereof,
wherein
R1 is

(a) a phenyl substituted with one to five substituents each independently selected from halo, (C1-C4)alkyl and —O—(CH2)n—N(CH3)2, wherein n is 1 or 2; or

(b) a 6-oxo-1,6-dihydropyridin-3-yl having Formula (Ia) or a 2-oxo-1,2-dihydropyridin-3-yl having Formula (Ib),

 wherein R1a is H, halo or (C1-C4)alkyl, and R1b is H, (C1-C4)alkyl, —(CH2)m—N(CH3)2, or —(CH2)m—OR1c, where R1c is H or (C1-C4)alkyl, and m is 1 or 2;

R2 is a phenyl substituted with one substituent in the para position selected from chloro, fluoro, trifluoromethyl, methyl and
cyano and optionally one additional substituent selected from halo and (C1-C4)alkyl-, optionally substituted with (C1-C4)alkoxy;

R3 is selected from isopropyl, cyclopropyl, isobutyl, cyclobutyl and cyclopentyl;

R4 is halo, —(CH2)q-pyridyl, —(CH2)q-pyrimidyl, —(CH2)q-phenyl, where said pyridyl, said pyrimidyl, and said phenyl moieties are optionally substituted with one, two or three substituents
each independently selected from halo, (C1-C4)alkoxy, cyano, —NH2, (C1-C4)alkyl-NH—, ((C1-C4)alkyl)2-N—, —(CH2)—OH, —C(O)—NH2, —C(O)—NH—(C1-C4)alkyl, —C(O)—N((C1-C4)alkyl)2, —C(O)—NH—(CH2)p—OH, —(CH2)—NH2, —(CH2)—NH—C(O)CH3 and —(CH2)—NH—C(O)H;

p is 1 or 2, and q is 0 or 1.

US Pat. No. 9,273,026

CARBAMATE/UREA DERIVATIVES

Novartis AG, Basel (CH)

1. A method of treating a disorder mediated through antagonism or inverse agonism of the H3 receptor wherein the disorder
is a disorder of sleep and wakefulness with excessive daytime sleepiness or a disorder associated with increased fatigue or
hypersomnolence comprising administration of 1-(6-oxo-1,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate
having the following formula
or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

US Pat. No. 9,265,754

USE OF 1-{4-[1-(4-CYCLOHEXYL-3-TRIFLUOROMETHYL-BENZYLOXYIMINO)-ETHYL]-2-ETHYL-BENZYL}-AZETIDINE-3-CARBOXYLIC ACID IN TREATING SYMPTOMS ASSOCIATED WITH RETT SYNDROME

Novartis AG, Basel (CH)

1. A method for treating one or more symptoms associated with Rett Syndrome, in a subject in need thereof, comprising administering
to said subject a therapeutically effective amount of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic
acid.

US Pat. No. 9,403,833

CARBOXAMIDE DERIVATIVES

Novartis AG, Basel (CH)

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein
R1 is (C3-C6)alkyl or (C3-C6)cycloalkyl;

R2 is methyl;

R3 is


R4 and R5 are independently selected from hydrogen, halo, (C3-C6)cycloalkyl, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy or —(C1-C2)alkyl(C1-C2)alkoxy; or

R2 and R4 may be taken together with the carbon atoms to which they are attached to form an azepine ring and R5 is H;

R6 is halo, (C3-C6)cycloalkyl, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy or —(C1-C2)alkyl(C1-C2)alkoxy;

OR
R1 is 2-fluorophenyl;

R2 is methyl; and

R3 is phenyl, substituted with one or two substituents independently selected from chloro and cyclopropyl.

US Pat. No. 9,295,389

SYSTEMS AND METHODS FOR PRIMING AN INTRAOCULAR PRESSURE SENSOR IN AN INTRAOCULAR IMPLANT

Novartis AG, Basel (CH)

1. An intraocular pressure (TOP) sensing device for implantation in an eye of a patient, comprising:
a pressure sensor;
a pressure sensor cap comprising:
a recess having an inner surface, the recess configured to receive the pressure sensor such that a chamber is formed by the
pressure sensor and the inner surface, and

at least one chamber inlet permitting a fluid to communicate with the chamber; and
at least one tube coupled to the at least one chamber inlet, the at least one tube allowing fluid communication between an
anterior chamber of the eye and the chamber.

US Pat. No. 9,284,331

DIAZEPINONE DERIVATIVES

Novartis AG, Basel (CH)

1. A method for the treatment of a substance-related disorder through mGluR5 antagonism comprising administration of a therapeutically
effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof to a patient in need of treatment
thereof
wherein
A is a fused five- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and
which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur;

R1 is —X2—B2;

X2 is bond or C1-3alkylene, wherein one carbon atom of the C1-3alkylene may be replaced by a group selected from carbonyl; oxygen; sulfur; —S(O)—; —S(O)2—; amino, which may be substituted by C1-4alkyl; —NH—C(O)—; —C(O)—NH—; —C(O)—O—; —O—C(O)—; —NH—S(O)2—; —S(O)2—NH—; and —NHC(O)NH—;

B2 is a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which
may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted
once or more than once by R6;

each R6 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy; or two R6 at the same ring atom together are oxo;

m is 0, 1, 2, 3 or 4;
each R2 independently is halogen, cyano, hydroxy, amino, C1-4alkyl; C1-4halogenalkyl; C1-4hydroxyalkyl; C1-4aminoalkyl; C1-4alkylamino-C1-4alkyl; di-(C1-4alkyl)amino-C1-4alkyl; C1-4alkoxy-C1-4alkyl; C2-4alkenyl; C2-4halogenalkenyl; C2-4alkinyl; C2-4halogenalkinyl; C1-4alkoxy; C1-4halogenalkoxy; C1-4alkyl-amino; di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;

n is 0, 1, 2, 3 or 4;
each R3 independently is halogen, cyano, hydroxy, amino, C1-4alkyl; C1-4halogenalkyl; C1-4hydroxyalkyl; C1-4aminoalkyl; C1-4alkylamino-C1-4alkyl; di-(C1-4alkyl)amino-C1-4alkyl; C1-4alkoxy-C1-4alkyl; C2-4alkenyl; C2-4halogenalkenyl; C2-4alkinyl; C2-4halogenalkinyl; C1-4alkoxy; C1-4halogenalkoxy; C1-4alkyl-amino; di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;

R4 is hydrogen, halogen, cyano, hydroxy, amino, C1-4alkyl; C1-4halogenalkyl; C1-4hydroxyalkyl; C1-4aminoalkyl; C1-4alkylamino-C1-4alkyl; di-(C1-4alkyl)amino-C1-4alkyl; C1-4alkoxy-C1-4alkyl; C2-4alkenyl; C2-4halogenalkenyl; C2-4alkinyl; C2-4halogenalkinyl; C1-4alkoxy; C1-4halogenalkoxy; C1-4alkyl-amino; di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;

B1 is a five- to six-membered aromatic ring system, which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen
and sulfur, wherein the ring system may in turn be substituted once or more than once by R7;

each R7 independently is

halogen, cyano, hydroxy, amino,
C1-4alkyl; C1-4halogenalkyl; C1-4hydroxyalkyl; C1-4aminoalkyl; C1-4alkylamino-C1-4alkyl; di-(C1-4alkyl)amino-C1-4alkyl; C1-4alkoxy-C1-4alkyl;

C2-4alkenyl; C2-4halogenalkenyl; C2-4alkinyl; C2-4halogenalkinyl;

C1-4alkoxy; C1-4alkoxy-C1-4alkoxy C1-4halogenalkoxy;

C1-4alkyl-amino; di-(C1-4alkyl)amino;

C1-4alkoxycarbonyl;

or a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which
may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted
once or more than once by R8;

each R8 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy; or two R8 at the same ring atom together are oxo;

or two R7 at adjacent ring atoms atoms form together with said ring atoms a fused five- to seven-membered monocyclic unsaturated non-aromatic
ring system which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system
may in turn be substituted once or more than once by R9;

each R9 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy; or two R9 at the same ring atom together are oxo.

US Pat. No. 9,216,182

CARBAMATE/UREA DERIVATIVES CONTAINING PIPERIDIN AND PIPERAZIN RINGS AS H3 RECEPTOR INHIBITORS

Novartis AG, Basel (CH)

1. A compound of the formula I

or a salt thereof, wherein
R1 is C1-6alkyl, C2-6alkenyl, C2-6alkinyl, C3-6cycloalkyl, C5-6cycloalkenyl or C3-6cycloalkyl-C1-4alkyl; wherein said C1-6alkyl, C2-6alkenyl, C2-6alkinyl or C3-6cycloalkyl-C1-4alkyl may be substituted once or more than once by halogen, hydroxyl or C1-4alkoxy; and wherein said C3-6cycloalkyl or C5-6cycloalkenyl may be substituted once or more than once by halogen, hydroxyl, C1-4alkyl, C1-4halogenalkyl, C1-4hydroxyalkyl or C1-4alkoxy;

m is 1 or 2;
n is 0, 1, 2, 3 or 4;
each R2 independently is halogen, hydroxyl, amino, cyano, nitro, C1-6alkyl, C1-6halogenalkyl, C1-6hydroxyalkyl, C1-4alkoxy-C1-6alkyl, amino-C1-6 alkyl, C1-4alkyl-amino-C1-6alkyl, di(C1-4alkyl)-amino-C1-6alkyl, C1-6alkoxy, C1-6halogenalkoxy, C1-6alkylamino, di(C1-6alkyl)amino, C2-6alkenyl, C2-6halogenalkenyl, C2-6alkinyl or C2-6halogenalkinyl;

or C3-6cycloalkyl, wherein one carbon atom may be replaced by an oxygen atom, wherein the C3-6cycloalkyl may be attached directly to the methylene or via a C1-2alkylene, and wherein the C3-6cycloalkyl may be substituted once or more than once by halogen;

or two R2 at the same carbon atom form together with said carbon atom a C3-6cycloalkyl;

X1 is oxygen;

p is 1 and q is 1;
p is 0 and q is 1; or
p is 0 and q is 0;
r is 0, 1, 2, 3 or 4;
each R3 independently is halogen, hydroxyl, amino, cyano, nitro, C1-6alkyl, C1-6halogenalkyl, C1-6hydroxyalkyl, C1-4alkoxy-C1-6alkyl, amino-C1-6alkyl, C1-4alkyl-amino-C1-6alkyl, di(C1-4alkyl)-amino-C1-6alkyl, C1-6alkoxy, C1-6halogenalkoxy, C1-6alkylamino, di(C1-6alkyl)amino, C2-6alkenyl, C2-6halogenalkenyl, C2-6alkinyl or C2-6halogenalkinyl;

or C3-6cycloalkyl, wherein one carbon atom may be replaced by an oxygen atom, wherein the C3-6cycloalkyl may be attached directly to the methylene or via a C1-2alkylene, and wherein the C3-6cycloalkyl may be substituted once or more than once by halogen;

or two R3 at the same carbon atom form together with said carbon atom a C3-6cycloalkyl;

A is a five- to six-membered monocyclic or an eight- to ten-membered fused bicyclic aromatic ring system, wherein said ring
system may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, and wherein said ring system may be
substituted once or more than once by R5;

each R5 independently is halogen; cyano; nitro; hydroxy; amino; —C(O)H; —C(O)NH2; —C(O)OH; —X2—R6; or —X3—B1;

X2 is selected from bond; carbonyl; oxygen; sulfur; —S(O)—; —S(O)2—; amino, which may be substituted by C1-4alkyl; —N(Ra)—C(O)—; —C(O)—N(Rb)—; —C(O)—O—; —O—C(O)—; —N(Rc)—S(O)2—; —S(O)2—N(Rd)—; and —NHC(O)NH—;

Ra, Rb, Rc and Rd each independently is hydrogen or C1-4alkyl;

R6 is C1-6alkyl; C1-6halogenalkyl; C1-6cyanoalkyl; C1-6carboxyalkyl; C1-6hydroxyalkyl; C1-4alkoxy-C1-6alkyl; C1-4alkoxy-C1-4alkoxy-C1-6alkyl; C1-4alkylcarbonyl-C1-6alkyl; C1-4alkoxycarbonyl-C1-6alkyl; C1-4alkylcarbonyloxy-C1-6alkyl; C1-6aminoalkyl; C1-4alkylamino-C1-6alkyl; di(C1-4alkyl)amino-C1-6alkyl; aminocarbonyl-C1-6alkyl; C1-4alkylaminocarbonyl-C1-6alkyl; di(C1-4alkyl)aminocarbonyl-C1-6alkyl; C1-4alkylcarbonylamino-C1-6alkyl; C1-4alkylaminosulfonyl-C1-6alkyl; di(C1-4alkyl)aminosulfonyl-C1-6alkyl; C2-6alkenyl; C2-6halogenalkenyl; C2-6alkinyl; C2-6halogenalkinyl;

X3 is bond or C1-3alkylene, wherein one carbon atom of the C1-3alkylene may be replaced by a group selected from carbonyl; oxygen; sulfur; —S(O)—; —S(O)2—; amino, which may be substituted by C1-4alkyl; N(Re)—C(O)—; —C(O)—N(Rf)—; —C(O)—O—; —O—C(O)—; —N(Rg)—S(O)2—; —S(O)2—N(Rh)—; and —NHC(O)NH—;

Re, Rf, Rg and Rh each independently is hydrogen or C1-4alkyl;

B1 is a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which
may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted
once or more than once by R7;

each R7 independently is halogen, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy; or two R7 at the same ring atom together are oxo;

or two R5 at adjacent ring atoms atoms form together with said ring atoms a fused five- to seven-membered monocyclic unsaturated non-aromatic
ring system which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system
may in turn be substituted once or more than once by R8, and wherein each R8 independently is halogen, C1-4alkyl or C1-4alkoxy, or two R8 at the same ring atom together are oxo;

and provided that the compounds
N-[(3R)-1-[7-[[(2,4-dichlorophenyl)methyl]amino]pyrazolo[1,5-a]pyrimidin-5-yl]-3-pyrrolidinyl]-4-methyl-1-piperazinecarboxamide;
4-cyclopentyl-N-[1-[5-(trifluoromethyl)-2-pyridinyl]-3-azetidinyl]-1-piperazinecarboxamide;
4-cyclopentyl-N-[1-[5-(trifluoromethyl)-2-pyridinyl]-3-pyrrolidinyl]-1-piperazinecarboxamide;
4-(1,1-dimethylethyl)hexahydro-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1H-1,4-diazepine-1-carboxamide;
4-ethyl-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1-piperazinecarboxamide;
hexahydro-4-methyl-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1H-1,4-diazepine-1-carboxamide;
4-(2,2-difluoroethyl)-N-[1-(2-pyrimidinyl)-4-piperidinyl]-1-piperazinecarboxamide;
N-(1-(4-acetylphenyl)piperidin-4-yl)-4-cyclopentylpiperazine-1-carboxamide; and
N-(1-(4-acetylphenyl)piperidin-4-yl)-4-cyclobutylpiperazine-1-carboxamide
are excluded.

US Pat. No. 9,335,564

MULTIFOCAL DIFFRACTIVE OPHTHALMIC LENS USING SUPPRESSED DIFFRACTIVE ORDER

NOVARTIS AG, Basel (CH)

1. A multifocal ophthalmic lens, comprising:
an ophthalmic lens having a base curvature corresponding to a base power; and
a diffractive element, the diffractive element producing constructive interference in at least four consecutive diffractive
orders corresponding a range of vision between near and distance vision, wherein the constructive interference produces a
near focus, a distance focus corresponding to the base power of the ophthalmic lens, and an intermediate focus between the
near focus and the distance focus and wherein a diffraction efficiency of at least one of the diffractive orders is suppressed
to less than ten percent.

US Pat. No. 9,323,049

FORWARD SCANNING OPTICAL PROBES WITH ONE OR MORE ROTATING COMPONENTS

Novartis AG, (CH)

1. A scanning system comprising:
a plurality of optical elements comprising:
an optical fiber having a fiber axis, the optical fiber configured to transmit a light ray, the fiber axis extending to an
imaginary fiber axis;

a focusing element having a focusing element optical axis that is substantially aligned with the imaginary fiber axis, the
focusing element configured to receive the light ray from the optical fiber and refract the light ray; and

a prism having a prism optical axis substantially aligned with the imaginary fiber axis, the prism configured to receive the
light ray from the focusing element; and

a movement system coupled to at least the prism and configured to:
rotate the prism separately from the focusing element about the prism optical axis to scan the light ray.

US Pat. No. 9,283,113

ULTRASONIC HAND PIECE

Novartis AG, Basel (CH)

1. A surgical hand piece comprising:
a generally cylindrical horn with a flange on one end, the flange having a central hub and first and second protruding sections,
the first and second protruding sections each having first and second sides;

a first piezoelectric crystal held against the horn, the first piezoelectric crystal having a semicircular shape with an inner
circumference, an outer circumference, and first and second ends;

a second piezoelectric crystal held against the horn, the second piezoelectric crystal having a semicircular shape with an
inner circumference, an outer circumference, and first and second ends;

wherein the inner circumference of the first piezoelectric crystal is held against a periphery of the hub, the first end of
the first piezoelectric crystal is held against the first side of the first protruding section, and the second end of the
first piezoelectric crystal is held against the first side of the second protruding section; and

further wherein the inner circumference of the second piezoelectric crystal is held against a periphery of the hub, the first
end of the second piezoelectric crystal is held against the second side of the first protruding section, and the second end
of the second piezoelectric crystal is held against the second side of the second protruding section.

US Pat. No. 9,174,978

MONOBACTAM ORGANIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS

Novartis AG, Basel (CH)

1. A compound of Formula (IA):

or a pharmaceutically acceptable salt thereof,
wherein:
Z is CH;
the group —O—CR1R2R3 is selected from


and
Het is selected from

US Pat. No. 9,452,990

COMPLEMENT PATHWAY MODULATORS AND USES THEREOF

NOVARTIS AG, Basel (CH)

13. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective
amount of a compound of claim 1.
US Pat. No. 9,309,252

PYRROLOPYRIMIDINE COMPOUNDS AS INHIBITORS OF CDK4/6

Novartis AG, Basel (CH)

1. A method for the treatment of a carcinoma with genetic aberrations that activate CDK 4/6 kinase activity in a patient in
need of treatment thereof comprising administration of an effective amount of a compound selected from the group consisting
of:
7-cyclopentyl-N,N-dimethyl-2-(5-((1R,6S)-9-methyl-4-oxo-3,9-diazabicyclo[4.2.1]nonan-3-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide;
7-Cyclopentyl-2-[5-(3,8-diaza-bicyclo[3.2.1]octane-3-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic
acid dimethylamide;

7-Cyclopentyl-2-[5-((1R,6S)-4-oxo-3,9-diaza-bicyclo[4.2.1]non-3-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic
acid dimethylamide;

7-Cyclopentyl-2-[5-((1R,6S)-4-oxo-3,9-diaza-bicyclo[4.2.1]non-3-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic
acid methylamide; and

7-Cyclopentyl-2-[5-((1R,6S)-4-oxo-3,9-diaza-bicyclo[4.2.1]non-3-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic
acid methylamide; or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,296,733

OXAZOLIDIN-2-ONE-PYRIMIDINE DERIVATIVE AND USE THEREOF FOR THE TREATMENT OF CONDITIONS, DISEASES AND DISORDERS DEPENDENT UPON PI3 KINASES

NOVARTIS AG, Basel (CH)

1. A compound and/or a pharmaceutically acceptable salt and/or solvate thereof, of the formula,

US Pat. No. 9,540,619

MELK REGULATION FOR THE TREATMENT OF BREAST CANCER

Novartis AG, Basel (CH) ...

1. A method for inhibiting growth or proliferation of breast cancer cells comprising administering to a subject in need thereof
in an amount that is effective to inhibit growth or proliferation of the breast cancer cells a MELK inhibitor, the MELK inhibitor
comprising an inhibitory RNA having a MELK target nucleotide sequence selected from the group consisting of SEQ. ID. NO: 1,
SEQ. ID. NO: 2, SEQ. ID. NO: 3 and SEQ. ID. NO: 4wherein the inhibitory RNA comprises a nucleotide sequence selected from the group consisting of SEQ. ID. NOS: 5-12;and wherein the breast cancer cells are estrogen receptor (ER) negative.
US Pat. No. 9,315,669

METHOD FOR MAKING UV-ABSORBING OPHTHALMIC LENSES

Novartis AG, Basel (CH)

1. A method for producing UV-absorbing silicone hydrogel contact lenses which have an UVB transmittance of about 10% or less
between 280 and 315 nanometers, an UVA transmittance of about 30% or less between 316 and 380 nanometers, and an average violet
transmittance of about 70% or less between 381 nm and 440 nm, the method comprising the steps of:
(1) providing a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining
the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface
of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is
formed between said first and second molding surfaces;

(2) introducing a UV-absorbing pre-polymerization mixture of lens-forming materials into the cavity, wherein the pre-polymerization
mixture comprises

(a) at least one hydrophilic vinylic monomer,
(b) at least one siloxane-containing vinylic monomer,
(c) at least one polysiloxane crosslinker with two or more ethylenically-unsaturated groups,
(d) a first UV-absorbing vinylic monomer and a second UV-absorbing vinylic monomer, wherein the first UV-absorbing vinylic
monomer absorbs UV radiation and high-energy-violet-light radiation of from 380 nm to 440 nm, wherein the second UV-absorbing
vinylic monomer absorbs UV radiation, wherein the first and second vinylic monomers are present in the UV-absorbing pre-polymerization
mixture in an amount sufficient to render a contact lens formed from the curing of the UV-absorbing pre-polymerization mixture
an ability of blocking at least 90% of UVB light between 280 and 315 nanometers, at least 70% of UVA light between 316 and
380 nanometers, and at least 30% of high-energy violet light between 381 nm and 440 nm,

(e) at least one visibility-tinting agent, and
(f) from about 0.05% to about 1.5% by weight of at least one germanium-based Norrish Type I photoinitiator capable of initiating
a free-radical polymerization under irradiation with a light source including a light in the region of about 380 to about
550 nm; and

(3) irradiating the pre-polymerization mixture in the mold with a light in a region of from 380 to 550 nm and crosslinking
the lens-forming materials to form an UV-absorbing silicone hydrogel contact lens,

wherein the formed UV-absorbing silicone hydrogel contact lens is substantially free of internal stress and has an UVB transmittance
of about 10% or less between 280 and 315 nanometers, an UVA transmittance of about 30% or less between 316 and 380 nanometers,
and an average violet transmittance of about 70% or less between 381 nm and 440 nm.

US Pat. No. 9,139,633

MESENCHYMAL STEM CELL DIFFERENTIATION

Novartis AG, Basel (CH) ...

1. A method of ameliorating or treating arthritis or joint injury in a mammal, the method comprising administering to a joint
of the mammal a composition comprising an effective amount of a C-terminal fibrinogen like domain (FLD) ANGPTL3 polypeptide
consisting of:
i. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, or
ii. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 fused to a human
serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST),
a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP);
thereby ameliorating or treating arthritis or joint injury in the mammal.
US Pat. No. 9,241,939

COMBINATION OF (A) A PHOSPHOINOSITIDE 3-KINASE INHIBITOR AND (B) A MODULATOR OF RAS/RAF/MEK PATHWAY

Novartis AG, Basel (CH)

1. A method of treating a warm-blooded animal having a pancreatic cancer, comprising simultaneously, sequentially or separately
administering to said animal (a) a phosphoinositide 3-kinase inhibitor compound selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine
and (b) a compound which modulates Mek kinase activity selected from ARRY142886/AZD6244, ARRY162, and GSK1120212, wherein
the active ingredients are present in free form or in the form of a pharmaceutically acceptable salt thereof, in a quantity
which is therapeutically effective against said proliferative disease.
US Pat. No. 9,422,574

MAMMALIAN EXPRESSION VECTOR

Novartis AG, Basel (CH)

1. A vector nucleic acid suitable for expressing at least one polypeptide of interest in a mammalian cell, comprising
(a) at least one expression cassette (POI) suitable for expressing a polypeptide of interest;
(b) an expression cassette (MSM) comprising a mammalian selectable marker gene wherein said mammalian selectable marker gene
is an antibiotic resistance gene; and

(c) an expression cassette (MASM) comprising a mammalian amplifiable, selectable marker gene;
wherein each said expression cassette (POI), (MSM), and (MASM) comprises at least one promoter or promoter/enhancer element,
the expression cassette (POI) is flanked 5? by the expression cassette (MASM), the expression cassette (MSM) is located 3?
from the expression cassette (POI) and the expression cassettes (MASM), (POI), and (MSM) are arranged in the same 5? to 3?
orientation

and wherein
the vector is circular and the expression cassette (MASM) is arranged 3? of the expression cassette (MSM) and wherein said
circular vector comprises a unique linearization restriction site for linearizing the vector which is located between the
expression cassettes (MSM) and (MASM);

or
wherein the vector is linearized via a unique linearization restriction site located between the expression cassettes (MSM)
and (MASM); and

wherein the vector is selected from the group consisting of
(a) a circular or linear vector nucleic acid comprising the following genetic elements in the indicated arrangement, wherein
the 5? to 3? direction is indicated by the ?:

I) Promoter of the (MASM) expression cassette (?)
II) Gene encoding the mammalian amplifiable selectable marker of the (MASM) expression cassette (?)
III) Intron of the (MASM) expression cassette (?)
IV) PolyA site of the (MASM) expression cassette (?)
V) Promoter of the (POI) expression cassette (?)
VI) Intron of the (POI) expression cassette (?)
VII) Polynucleotide encoding a polypeptide of interest, which is inserted in the (POI) expression cassette (?)
VIII) PolyA site of the (POI) expression cassette (?)
IX) Promoter of the (POI?) expression cassette (?)
X) Intron of the (POI?) expression cassette (?)
XI) Polynucleotide encoding an additional polypeptide of interest, which is inserted in the (POI?) expression cassette (?)
XII) PolyA site of the (POI?) expression cassette (?)
XIII) Promoter of the (MSM) expression cassette (?)
XIV) Gene encoding the mammalian selectable marker of the (MSM) expression cassette (?)
XV) PolyA site of the (MSM) expression cassette (?)
XVI) PSM expression cassette (?)or (?)
XVII) Linearization restriction site if the vector nucleic acid is circular; and
(b) a vector nucleic acid as shown as Seq. ID No. 1 or Seq. ID No. 16.

US Pat. No. 9,282,989

METHOD OF CONTROLLING A SURGICAL SYSTEM BASED ON A LOAD ON THE CUTTING TIP OF A HANDPIECE

Novartis AG, Basel (CH)

1. A method of controlling a surgical system, the surgical system having an ultrasound handpiece, the ultrasound handpiece
having a cutting tip for cutting tissue, the method comprising the steps of:
establishing a threshold power level;
monitoring a load on the cutting tip of the ultrasound handpiece by monitoring a voltage and a current drawn by the handpiece
during a non-zero sense power interval, the sense power interval being between cutting power intervals;

comparing the amount of power drawn by the handpiece and the threshold power level; and
adjusting an amount of power delivered to the cutting tip of the ultrasound handpiece if the power drawn by the handpiece
exceeds the threshold power level by enabling torsional vibration of the tip;

determining a rate of change of a first operating parameter of the surgical system; determining a stage of occlusion based
on the rate of change of the first operating parameter; and

adjusting an amount of power delivered to the cutting tip of the ultrasound handpiece based on the determined stage of occlusion.

US Pat. No. 9,242,963

ORGANIC COMPOUNDS

NOVARTIS AG, Basel (CH)

1. A compound of Formula I:

wherein:
R1a is hydrogen;

R2a is hydrogen, halogen, or hydroxy;

R3a is hydrogen, halogen, cyano, or alkoxy;

R4a is hydrogen or halogen;

R5a is hydrogen or alkyl;

R6a and R7a are hydrogen;

R8a is:


L is carbonyl or sulfonyl; and
R11a, R12a, R13a, R14a, and R15a are each independently hydrogen, alkyl, cyano, halogen, alkoxy, alkoxycarbonyl, carboxylate, heteroaryl, or sulfonyl; with
the proviso that at least one of R2a-R5a is other than hydrogen; or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,315,489

COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1

Novartis AG, Basel (CH)

1. A compound of formula (I):

in which:
Y at each occurrence is independently selected from N and CH;
Y1 is CR5; wherein R5 is selected from hydrogen, methoxy and imidazolyl; wherein said imidazolyl is unsubstituted or substituted with methyl;

R1 is pyridinyl unsubstituted or substituted with 1 to 3 R6 groups;

R2 is selected from hydrogen, halo, hydroxy, C1-4alkyl, C1-4alkoxy, methoxy-carbonyl, 3,6-dihydro-2H-pyran-4-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-4-yl-oxy and cyclobutyl;
wherein said C1-4alkyl, C1-4alkoxy, cyclobutyl or tetrahydro-2H-pyran-4-yl of R2 can be unsubstituted or substituted with 1 to 3 groups independently selected from halo, hydroxy, cyano, C1-4alkoxy, morpholino, piperazinyl and NR5aR5b; wherein R5a is selected from hydrogen and C1-4alkyl; and R5b is selected from hydroxy-ethyl; wherein said piperazinyl substituent of R2 can be unsubstituted or further substituted with C1-4alkyl;

R3 is selected from hydrogen and halo;

R4 is selected from —SF5 and —Y2—CF2—Y3;

R6 at each occurrence is independently selected from hydrogen, hydroxy, C1-4alkyl, C1-4alkoxy, cyano, trifluoromethyl, halo, amino, methyl-carbonyl, methoxy-carbonyl, cyclopropyl and pyrrolidinyl-methyl; wherein
said C1-4alkyl or C1-4alkoxy of R6 is unsubstituted or substituted with 1 to 3 groups independently selected from halo and hydroxy;

Y2 is selected from CF2, O and S(O)0-2; and

Y3 is selected from hydrogen, halo, methyl, difluoromethyl and trifluoromethyl;

Y4 is CR2;

Y5 and Y6 are independently CR5; wherein R5 is selected from hydrogen and halo; or the pharmaceutically acceptable salts thereof; with the proviso that the compounds
of formula I do not include 3-(2-aminoquinazolin-6-yl)-4-methyl-N-(4-(trifluoromethoxy)phenyl)-benzamide and 3-(2-aminoquinazolin-6-yl)-5-bromo-N-(4-(trifluoromethoxy)phenyl)-benzamide.

US Pat. No. 9,290,481

MONOCYCLIC HETEROARYL CYCLOALKYLDIAMINE DERIVATIVES

NOVARTIS AG, Basel (CH)

1. A compound according to formula (II) or a pharmaceutically acceptable salt thereof, wherein

X1 is N;
R1 is H, C1-4alkyl, CN, or Hal; and

R2 is H, C1-4alkyl or Hal.

US Pat. No. 9,220,404

OCULAR MODELING METHODS AND APPARATUS

Novartis AG, Basel (CH)

1. A method of modeling a lens of an eye having a cornea, the method comprising:
measuring an anterior shape of the cornea;
performing a first type of direct optical measurement of a first parameter of the cornea and performing a second type of direct
optical measurement of a second parameter of the cornea, the first type of direct optical measurement being different from
the second;

performing the first type of direct optical measurement of a first parameter of the lens and performing the second type of
direct optical measurement of a second parameter of the lens; the first type of direct optical measurement being different
from the second;

determining from the first and second parameters of the cornea and first and second parameters of the lens, a refractive index
of the cornea;

correcting the first and second types of direct optical measurements of the first and second parameters of the cornea and
first and second parameters of the lens to form corrected measurements of the lens parameters and the cornea parameters by
accounting for an effect of the refractive index of the cornea on the first and second type of direct optical measurements
of the cornea parameters and the lens parameters;

measuring at least one of an aberration of the eye and a refraction of the eye;
calculating a refractive index of the lens by combining the corrected first and second types of direct optical measurements
of the first and second parameters of the cornea and first and second parameters of the lens and at least one of the measured
aberration and the refraction of the eye; and

correcting the first and second types of direct optical measurements of the first and second parameters of the cornea and
first and second parameters of the lens to account for an effect of the refractive index of the lens on the direct optical
measurements of the first and second parameters of the cornea and first and second parameters of the lens.

US Pat. No. 9,155,696

PHARMACEUTICAL COMPOSITIONS

Novartis AG, Basel (CH)

1. An injectable in situ forming depot formulation comprising
i) a pharmaceutically active agent, wherein the pharmaceutically active agent is a cyclo [{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Bzl)-Phe] pamoate or di-aspartate,

ii) a poly (ethylene) glycol with a molecular weight 450 at a temperature between 8° to 20° C.,

iii) a biodegradable polymer, and optionally
iv) an additive.
US Pat. No. 9,057,716

BACTERICIDAL ANTIBODY ASSAYS TO ASSESS IMMUNOGENICITY AND POTENCY OF MENINGOCOCCAL CAPSULAR SACCHARIDE VACCINES

Novartis AG, Basel (CH)

1. A method of assessing potency of a batch of a meningococcal capsular saccharide vaccine comprising:
(a) contacting in vitro a sample of the batch of the meningococcal capsular saccharide vaccine or a control saccharide mixed
with the sample, with a bactericidal antibody;

(b) assessing the potency of the batch of the meningococcal capsular saccharide vaccine by measuring the binding of the bactericidal
antibody to the meningococcal capsular saccharide vaccine or to the control saccharide; and

(c) releasing the batch of the meningococcal capsular saccharide vaccine if the potency meets a regulatory potency requirement(s)
for release,

wherein the meningococcal capsular saccharide vaccine comprises at least two saccharides selected from (i) an N. meningitidis serogroup A capsular saccharide, (ii) an N. meningitidis serogroup C capsular saccharide, (iii) an N. meningitidis serogroup W135 capsular saccharide, and (iv) an N. meningitidis serogroup Y capsular saccharide, and wherein the bactericidal antibody binds to one of the at least two saccharides or to
the control saccharide.

US Pat. No. 9,268,064

AMPHIPHILIC SILOXANE-CONTAINING (METH)ACRYLAMIDES AND USES THEREOF

Novartis AG, Basel (CH)

4. A method for making silicone hydrogel contact lenses, comprising the steps of: introducing a lens-forming formulation into
a mold for making contact lenses, wherein the lens-forming formulation comprises
(a) a solvent selected from the group consisting of water, 1,2-propylene glycol, a polyethyleneglycol having a molecular weight
of about 400 Daltons or less, and mixtures thereof,

(b) at least one actinically-crosslinked silicone containing prepolymer which is obtained by polymerixing a polymerizable
composition comprising

(i)

in which
A1, A2, A3 and A4 independent of one another are a C1-C6 alkyl, phenyl or benzyl,

r1 is an integer of 2 or 3,
R? is H or C1-C4 alkyl,

R10 is hydrogen or methyl,

R11 is a linear or branched C2-C6 alkylene divalent radical which may be substituted with one or more hydroxyl groups,

R12 is C1-C4 alkoxy,

Z1 and Z2 independent of each other are a direct bond or a linear or branched C1-C4 alkylene divalent radical,

Z3 is C2-C4 alkylene divalent radical,

Z4, Z5, and Z6 independent of one another are a direct bond or a linear or branched C1-C20 alkylene divalent radical which may have one or more ether, thio, amine, carbonyl, or amido linkages in their main chain,

X1 is —O—CO—NH— or —O—CO—NH—R13—NH—CO—O— in which R13 is a linear or branched C2-C12 alkylene divalent radical or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical,

X2 and X3 independent of each other are selected from the group consisting of direct bond, —O—, —NR?—, —CO—NR?—, —NR?—CO—, —O—CO—NH—,
—NH—CO—O—, —NR?—CO—NH—, —NH—CO—NR?—, —S—CO—NH—, —NH—CO—S—, —S—, —CO—O—, —O—CO—, —O—CO—NH—R13—NH—CO—O—, and —NH—CO—NH—R13—NH—CO—NH—, in which R? and R13 are as defined above,

q1 is an integer from 2 to 50, q2 is an integer from 3 to 20,
(ii) at least one polysiloxane-containing crosslinker and/or at least one non-silicone crosslinker,
(iii) at least one hydrophilic vinylic monomer, and
(iv) a thio-containing chain transfer agent having a first reactive functional group other than the thio group and/or a vinylic
monomer having a second reactive functional group other than ethylenically-unsaturated group, wherein the first reactive functional
group is subsequently ethylenically functionalized; and wherein the second reactive functional group is subsequently ethylenically
functionalized with an ethylenically functionalizing vinylic monomer having a third reactive functional group which reacts
with one second reactive functional in the presence of absence or a crosslinking agent to form a covalent linkage, and wherein
the second and the third reactive functional groups are selected from the group consisting of amino group, hydroxyl group,
carboxyl group, azlactone group, isocyanate group, epoxy group, aziridine group, acid chloride and combinations thereof, and

(c) at least one component selected from the group consisting of a hydrophilic vinylic monomer, a hydrophilized polysiloxane-containing
crosslinker, a hydrophilic crosslinker, a photoinitiator, a thermal initiator, a UV-absorbing vinylic monomer, a visibility
tinting agent, an antimicrobial agent, a bioactive agent, a leachable lubricant, a leachable tear-stabilizing agent, and mixtures
thereof;

polymerizing the lens-forming formulation in the mold to form a silicone hydrogel contact lens, wherein the formed silicone
hydrogel contact lens has a water content of from about 20% to about 75% by weight when fully hydrated, an oxygen permeability
(Dk) of at least about 40 barrers, and an elastic modulus of from about 0.1 MPa to about 2.0 MPa.

US Pat. No. 9,162,784

CONTACT LENS PACKAGING SOLUTIONS

Novartis AG, Basel (CH)

1. A process for making a soft contact lens capable of easing wearer's initial discomfort, comprising the steps of:
a) packaging a hydrogel contact lens in a container containing a packaging solution, wherein the packaging solution comprises
(1) copolymer of vinylpyrrolidone and at least one amino-containing vinylic monomer, wherein the amino-containing vinylic
monomer is selected from the group consisting of alkylaminoalkylmethacrylate having 8-15 carbon atoms, alkylaminoalkylacrylate
having 7-15 carbon atoms, dialkylaminoalkylmethacrylate having 8-20 carbon atoms, dialkylaminoalkylacrylate having 7-20 carbon
atoms, and N-vinylalkylamide having 3-10 carbon atoms,

(2) glycerin or a polyethylene glycol having an average molecular weight of about 600 or less,
(3) an ?-oxo-multi-acid or salt thereof in an amount sufficient to have a reduced susceptibility to oxidation degradation
of the polyethylene glycol in the packaging solution, and

(4) one or more buffering agents in an amount sufficient to provide the solution a pH of from about 6.0 to 8.0,
wherein the copolymer of vinylpyrrolidone is present in an amount sufficient to provide the packaging solution a viscosity
of up to about 5.0 centipoises at 25° C., wherein the copolymer of vinylpyrrolidone has a molecular weight sufficiently large
to form a cushion layer on the soft hydrogel contact lens, wherein the packaging solution has an osmolality of from about
200 to about 450 mOsm/kg; and

b) sterilizing the hydrogel contact lens in the package to obtain the soft contact lens.
US Pat. No. 9,333,234

COMBINATION OF SOMATOSTATIN-ANALOGS WITH 11BETA-HYDROXYLASE INHIBITORS

Novartis AG, Basel (CH)

1. A combination of (a) Compound A (R)-4-(6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-benzonitrile; and (b) a somatostatin
analogue, wherein (a) and (b) are present in each case in free form, complex form or in the form of a pharmaceutically acceptable
salt.

US Pat. No. 9,102,671

COMPOUNDS AND COMPOSITIONS AS TRK INHIBITORS

Novartis AG, Basel (CH)

1. A compound of Formula (I):

wherein:

A is
X1 is CH or N;

R1 is —C(O)NH2, —C(O)N(R7)2, —C(O)N(R8)2, —NR7C(O)R8, —NR7C(O)N(R7)2, —NR7C(O)N(R8)2, —NR7C(O)N(R9)2; —C(O)OR7, —NR7C(O)OR7, —NR7C(O)OR8, —C(O)NR7R8, —C(O)NR7C(O)OR7, —C(O)NR7C(O)NH2, —C(O)NR7C(O) N(R7)2 or H;

each R2 is independently selected from H and C1-C6alkyl;

each R3 is independently selected from H, C1-C6alkyl, —CN, —C(O)N(R7)2, —OR7 and halo, or the two R3 together with the C atom they are attached form a cyclopropyl group spiro attached to the pyrrolidine;

or a R2 and a R3 together with the C atom they are attached form a cyclopropyl ring fused to the pyrrolidine;

each R4 is independently selected from H, halo, —OR7, C1-C6alkyl, C1-C6alkyl substituted with 1-3 halo, C1-C6alkoxy substituted with 1-3 halo, —CN and —C(O)N(R7)2;

each R5 is independently selected from H and C1-C6alkyl;

each R6 is independently selected from H, C1-C6alkyl, —CN, —OR7 and halo;

each R7 is independently selected from H, C1-C6alkyl or C1-C6alkyl substituted with 1-3 —OH;

each R8 is independently selected from H, C1-C6alkyl, phenyl, benzyl, phenyl substituted with 1-3 groups independently selected from R6, benzyl substituted with 1-3 groups independently selected from R6, an unsubstituted 5-6 membered heterocycloalkyl having 1 to 2 heteroatoms independently selected from O and N, a 5-6 membered
heterocycloalkyl having 1 to 2 heteroatoms independently selected from O and N which is substituted with 1-3 groups independently
selected from R6, an unsubstituted C3-C6cycloalkyl, a C3-C6cycloalkyl substituted with 1-3 groups independently selected from R6, an unsubstituted 5-6 membered heteroaryl having 1 to 2 heteroatoms independently selected from O and N, a 5-6 membered heteroaryl
having 1 to 2 heteroatoms independently selected from O and N which is substituted with 1-3 groups independently selected
from R6;

each R9 is a C1-C6alkyl and together with the N atom they are attached form an unsubstituted 5-6 membered heterocycloalkyl or a 5-6 membered
heterocycloalkyl substituted with 1-3 groups independently selected from R6;

m is 0, 1, 2, 3 or 4,
n is 0, 1 or 2,or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,078,744

SINGLE OPTIC ACCOMMODATIVE INTRAOCULAR LENS SYSTEM

NOVARTIS AG, Basel (CH)

1. An intraocular lens system, comprising:
a) a capsular ring defining an opening there through, the capsular ring having a circular outermost surface with one or more
notches therein and one or more interlock features within each of the notches; and

b) an IOL having an optic and a plurality of haptics, each of the haptics configured to fit within a corresponding one of
the notches and comprising one or more haptic recesses corresponding to the one or more interlock features of the corresponding
one of the notches, the haptic recesses configured to engage the one or more interlock features to couple to the capsular
ring to the IOL, wherein:

the haptics are dimensioned to fill the notches to present a continuous surface to the anterior or posterior capsule with
minimal space for lens epithelial cell passage; and

the haptics extend outwardly through the notches beyond an outermost surface of the capsular ring when coupled to the capsular
ring.

US Pat. No. 10,005,836

ANTIBODY DRUG CONJUGATES

Novartis AG, Basel (CH)

1. An antibody or antigen binding fragment thereof that binds P-cadherin comprising:a. a heavy chain variable region (VH) that comprises a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, and a VH CDR3 of SEQ ID NO: 3, wherein the CDR is defined in accordance with the Kabat definition; and a light chain variable region (VL) that comprises a VL CDR1 of SEQ ID NO: 11, a VL CDR2 of SEQ ID NO: 12, and a VL CDR3 of SEQ ID NO: 13, wherein the CDR is defined in accordance with the Kabat definition.
US Pat. No. 9,192,661

DELIVERY OF SELF-REPLICATING RNA USING BIODEGRADABLE POLYMER PARTICLES

Novartis AG, (CH)

1. An immunogenic composition comprising:
(a) positively charged nanoparticles that comprise a biodegradable polymer and greater than 1% (w/w) of a cationic surfactant,
wherein:

(i) the biodegradable polymer is a poly(?-hydroxy acid), and
(ii) the nanoparticles have Z average mean particle size value that is between 100 and 500 nanometers, and a zeta potential
greater than +50 mV;

(b) an RNA replicon comprising at least one polynucleotide encoding at least one antigen adsorbed to said positively charged
nanoparticles; and

(c) a non-ionic surfactant.

US Pat. No. 9,278,908

INTERMEDIATES OF NEUTRAL ENDOPEPTIDASE INHIBITORS AND PREPARATION METHOD THEREOF

Novartis AG, Basel (CH)

1. A process for preparing N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl
ester, or a salt thereof, or the compound N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic
acid comprising
i) reacting a compound of formula (3), or salt thereof,

wherein R1 is hydrogen or a nitrogen protecting group;
first with a base and then with a compound of the formula CO2 or R4COY, wherein Y is halogen or —OR? and wherein R4 and R? are independently selected from alkyl, aryl and arylalkyl, to
obtain a compound of formula (4), or salt thereof,


wherein
R1 is hydrogen or a nitrogen protecting group; and
R4 is selected from hydroxyl, alkyl, aryl and arylalkyl; and
ii) reacting the obtained compound of formula (4), or salt thereof, with a base and formaldehyde, optionally in the presence
of a phase transfer catalyst,

to obtain a compound of formula (1), or salt thereof,

wherein R1 is hydrogen or a nitrogen protecting group; and
iii) subsequently converting the obtained compound of formula (1) to the compound N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl
butanoic acid ethyl ester, or a salt thereof, or the compound N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl
butanoic acid or a salt thereof.

US Pat. No. 9,278,099

PAZOPANIB FORMULATION

Novartis AG, Basel (CH)

1. A composition suitable for reconstitution into an aqueous suspension, comprising 35.0 to 50.0 w/w % micronized 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide
hydrochloride, guar gum, wherein said guar gum is present as from 3% to 12% by weight of the weight of the composition, and
polyvinylpyrrolidone, wherein said polyvinylpyrrolidone is present as from 2% to 14% by weight of the weight of the composition.

US Pat. No. 9,227,934

PROCESSES FOR PRODUCING NEP INHIBITORS OR PRODRUGS THEREOF

NOVARTIS AG, Basel (CH)

1. A process for preparing a compound of formula (4) or salt thereof,

wherein R1 is hydrogen or a nitrogen protecting group,
comprising treating a compound of formula (6), or salt or a tautomer thereof,

wherein R1 is hydrogen or a nitrogen protecting group,
with a reducing agent to obtain the compound of formula (4).

US Pat. No. 9,227,969

COMPOUNDS AND COMPOSITIONS AS INHIBITORS OF MEK

NOVARTIS AG, Basel (CH)

1. A compound of formula I:

wherein
n is selected from 0, 1, 2 and 3;
R1 is selected from:


R2 is selected from chloro, methyl, hydrogen, fluoro and methoxy;

R3a is selected from cyano-methyl, 2-hydroxy-ethyl, 1-hydroxypropan-2-yl, 3-hydroxy-2-(hydroxy-methyl)propanoyl, 2-methoxy-ethyl,
2-fluoropropanoyl, (3-methyloxetan-3-yl)-methyl, methyl-sulfonyl, amino-carbonyl-methyl, cyclopropyl-sulfonyl, isopropyl-sulfonyl,
dimethylcarbamoyl, 3-hydroxy-2-(hydroxy-methyl)propyl, 2-hydroxy-propyl, 2-hydroxyacetyl, 2-acetoxyacetyl, 2-methoxyacetyl,
(2,2,2-trifluoroethyl)carbamoyl, 2-aminoacetyl, oxetan-3-ylmethyl, (S)-2-hydroxypropanoyl, 2-hydroxypropanoyl, acetyl, 2-amino-2-oxoethyl,
carbamoyl, (oxetan-2-yl)-methanoyl, 2-(sulfooxy)acetyl, 2-fluoroethanoyl, 3-hydroxypropanoyl, and N,N-dimethylsulfonamidyl;

each R4 is independently selected from hydrogen, halo, methyl and hydroxy-methyl; and

optionally two R4 groups together with the carbon atoms to which they are attached form —(CH2)2-3—;

R5 is selected from hydrogen and methyl;

R6 is selected from hydrogen, methoxy and halo;

R7 is selected from hydrogen, fluoro, CF3, CH2OH, cyclopropyl and methyl; and

R8 is cyano;

or the pharmaceutically acceptable salts thereof.

US Pat. No. 9,295,385

IMAGING PROBES AND ASSOCIATED DEVICES, SYSTEMS, AND METHODS UTILIZING SPEAKER ACTUATORS

Novartis AG, (CH)

1. An ophthalmic imaging apparatus, comprising:
an optical probe having
a handle sized and shaped for handheld grasping by a user; and
a cannula coupled to the handle, the cannula sized and shaped for insertion into an eye to be treated;
an optical fiber positioned at least partially within the optical probe, the optical fiber configured to receive an imaging
light from an imaging light source and guide the imaging light to an optical element positioned within the cannula of the
optical probe; and

an actuator system configured to impart motion to the optical fiber, the actuator system including a speaker positioned within
the optical probe.

US Pat. No. 9,291,159

PUMP HEAD WITH INDEPENDENTLY SPRUNG OFFSET PICOTING ROLLERS

Novartis AG, Basel (CH)

1. A roller assembly comprising:
a central section with a hub, the central section having a plurality of pivots located around the central section and the
roller assembly rotating about the hub on a rotation axis of the hub, wherein the plurality of pivots are located around a
periphery of the central section:

a plurality of arms, each arm having a roller end and a pivot end, the pivot ends coupled to the central section at the plurality
of pivots such that each arm is capable of pivoting independently with respect to the central section, the roller ends and
pivot ends of each arm located a distance of at least one roller width away from each other;

a plurality of rollers, one roller coupled to each of the roller ends of the plurality of arms, wherein the rollers are located
interior the periphery of the central section:

wherein the plurality of rollers and arms are located around the central section such that the pivot is located a distance
away from the roller; and wherein a rotational axis of each roller is perpendicular to the rotation axis of the hub.

US Pat. No. 9,108,368

APPARATUS AND METHOD FOR TRANSPORTING CONTACT LENSES THROUGH DIPPING BATHS

Novartis AG, (CH)

1. A method for transporting contact lenses through dipping baths, comprising the steps of individually accommodating contact
lenses in respective containers which are capable of enabling a flow of one or more treatment fluids into and out of the container,
holding the containers in carriers, advancing the containers through the dipping baths, subjecting the carriers for the containers
to a reciprocating lowering and raising motion along the transport through the dipping baths, wherein the reciprocating lowering
and raising motion is performed more than once in each dipping bath, and wherein a portion of each container which accommodates
a contact lens remains immersed in the treatment fluid contained in each dipping bath during the reciprocating lowering and
raising motions and while the container held by the carrier is transported through the dipping baths from a starting end to
a leaving end thereof; and wherein a translational and vertical movement of the carriers is controlled such, that a path of
the containers, within each of the baths, follows approximately a sinus curve.
US Pat. No. 9,353,162

DISEASE-ASSOCIATED PROTEINS

NOVARTIS AG, Basel (CH) ...

1. A retinoprotective agent comprising a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:14, wherein
the polypeptide is encapsulated in a microsphere or liposome.
US Pat. No. 9,187,426

ORGANIC COMPOUNDS

Novartis AG, Basel (CH) ...

1. A compound selected from:
2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-(pyridin-2-ylmethyl)isonicotinamide,
2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-N-(pyridin-2-ylmethyl)-isonicotinamide,
2-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)-isonicotinamide, and
2-(2-oxo-3-(4-(trifluoromethoxy)benzyl)imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)-isonicotinamide, or a pharmaceutically acceptable
salt thereof.

US Pat. No. 9,243,224

CELL CULTURE MEDIUM

Novartis AG, Basel (CH)

1. A fed-batch process for the production of a recombinant polypeptide comprising a production phase in which recombinant
Chinese hamster ovary (CHO) cells are cultured and the recombinant polypeptide is expressed in a serum free and protein-free
cell culture medium comprising at least 200 to at least 2500 mg/L of choline chloride or an equivalent amount of another choline
salt and about 6.0 to about 10.0 mM glutamine.

US Pat. No. 9,199,981

COMPOUNDS AND COMPOSITIONS AS C-KIT KINASE INHIBITORS

NOVARTIS AG, Basel (CH)

1. A compound of Formula (I) or Formula (II), or pharmaceutically acceptable salt thereof:

wherein:
m is 1 and R20 is selected from H, halo, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkoxy, deuterium, deuterated C1-C6alkyl, —CN, —(CR92),nOR4, —C(O)R4, —(CR92),nC(?O)OR4, R10 —(CR92)nR10, —((CR92),nO)tR4,—(CR92),nO(CR92)nR7, —(CR92)nC(?O)R4, —C(?O)N(R4)2, —OR4 and -(CR92)nCN;

or m is 4 and R20 is deuterium;

R1 is selected from C1-C6alkyl and halo;

each R11 is independently selected from H, halo, and C1-C6alkyl;

L1 is a bond, —NH— or —C(?O)NH—;

L2 is —(CR92)n—, —CHR6—, —(CR92)nO—, —NH—, —(CR92)nC(?O)—, —C(?O)O(CR92)n—, (CR92)nOC(?O)NR4—, —(CR92)nNR4C(?O)(CR92)n—, —(CR92)nNR4C(?O)— or —(CR92)nNR4C(?O)O—;

R2 is R3 or L2R3;

R3 is selected from an unsubstituted C3-C8cycloalkyl, a cyclobutanone, a cyclopentanone and a substituted C3-C8cycloalkyl,

wherein the substituted C3-C8cycloalkyl of R3 is substituted with 1-4 substituents independently selected from C1-C6alkyl, halo, C1-C6haloalkyl, —OR4, —CN, —C(?O)OR4, —C(?O)R4, —C(?O)R7, —C(?O)OR5, —(CR92)nOR4, —O(CR92)nOR4, —C(?O)O(CR92)nOR4, —N(R4)2, ?N—OR4, ?N—O—(CR92)nR5, —C(?O)NR42, —NR4C(?O)OR4, —NR4C(?O)(CR92)nOR4, —NR4(CR92)nOR4, —NR4S(?O)2R4, —N(C(?O)OR4)2, ?CH2, ?CH(CR92)nOR4, R8, —(CR92)nR8, deuterated C1-C6alkoxy, —S(?O)2R4, —S(?O)2R7, —S(?O)2R8, —S(?O)2N(R4)2, —S(?O)2NHC(?O)OR4, —S(?O)2(CR92)nC(?O)OR4, —S(?O)2(CR92)nOR4, a spiro attached dioxolane, a spiro attached dioxolane which is substituted with C1-C6alkyl, a spiro attached dioxane, a spiro attached tetrahyrofuranly, a spiro attached oxetane, a spiro attached cyclobutanone,
a spiro attached cyclobutanol, a C1 alkyl bridge, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S,
a 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S substituted with 1-3 substituents
independently selected from C1-C6alkyl, halo, C1-C6haloalkyl, C1-C6haloalkoxy, —OR4 and R8;

each R4 is independently selected from H and C1-C6alkyl;

R5 is an unsubstituted C3-C8cycloalkyl , an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N or O or a C3-C8cycloalkyl substituted with 1-3 substituents independently selected from C1-C6alkyl;

each R6 is independently selected from —NHC(O)OR4, —OR4 and —(CR92)nOR4;

each R7 is independently selected from C1-C6haloalkyl;

R8 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected
from N, O or S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered
heterocycloalkyl with 1-2 heteroatoms independently selected from N, O or S, an unsubstituted C3-C8cycloalkyl, a substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O or S, a substituted
phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl
with 1-2 heteroatoms independently selected from N, O or S, a substituted C3-C8cycloalkyl, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one,

wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N,
O or S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C3-C8cycloalkyl and substituted 4-6 membered heterocycloalkyl of R8 are substituted with 1-3 substituents independently selected from C1-C6alkyl, —(C(R9)2)nOR4, —(C(R9)2)nR5, —(C(R9)2)nC(O)OR4, —C(O)OR4 and —S(O)2R4;

each R9 is independently selected from H and C1-C6alkyl;

R1° is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected
from N, O or S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered
heterocycloalkyl with 1-2 heteroatoms independently selected from N, O or S, an unsubstituted C3-C8cycloalkyl, a substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O or S, a substituted
phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl
with 1-2 heteroatoms independently selected from N, O or S, a substituted C3-C8cycloalkyl, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one,

wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N,
O or S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C3-C8cycloalkyl and substituted 4-6 membered heterocycloalkyl of R10are substituted with 1-3 substituents independently selected from C1-C6alkyl, —(C(R9)2)nOR4, —(C(R9)2)nR5, —(C(R9)2)nC(O)OR4 and —S(O)2R4;

t is 1, 2 or 3, and
each n is independently selected from 1, 2, 3 and 4.

US Pat. No. 9,452,998

PROTEIN KINASE C INHIBITORS AND METHODS OF THEIR USE

NOVARTIS AG, Basel (CH)

1. A compound that is selected from:
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,216,219

ANTI-BAFFR ANTIBODY FORMULATION

Novartis AG, Basel (CH)

1. An aqueous composition having a pH of 6.0 and comprising
a hypofucosylated or non-fucosylated anti-B-cell Activating Factor Receptor (BAFFR) antibody wherein the antibody has a concentration
of 150 mg/mL and wherein said anti-BAFFR antibody comprises heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 3, 4 and 5 respectively,
and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8 respectively, and

(a) (i) 220 mM sucrose as a stabilizer,
(ii) 20 mM histidine as a buffering agent,
(iii) 0.04% polysorbate 20 as a surfactant; or
(b) (i) 220 mM trehalose as a stabilizer,
(ii) 20 mM histidine as a buffering agent,
(iii) 0.04% polysorbate 20 as a surfactant; or
(c) (i) 120 mM sucrose as a stabilizer,
(ii) 20 mM histidine as a buffering agent,
(iii) 0.04% polysorbate 20 as a surfactant, and
(iv) 50 mM arginine.
US Pat. No. 9,149,459

SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND THEIR USE TO TREAT MUSCLE INFLAMMATION

Novartis AG, Basel (CH)

1. A method for treating polymyositis in a subject in need thereof, comprising administering to said subject a therapeutically
effective amount of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic
acid
or an N-oxide derivative thereof, a prodrug thereof, an individual isomer or mixtures of isomers thereof; or a pharmacologically
acceptable salt, solvate or hydrate thereof.

US Pat. No. 9,376,489

IL-18 BINDING MOLECULES

Novartis AG, Basel (CH)

1. An isolated antibody or fragment thereof, wherein the isolated antibody or a fragment comprises:
i) a heavy chain variable region H-CDR1 comprising SEQ ID NO: 3 and
ii) a heavy chain variable region H-CDR2 comprising SEQ ID NO: 4 or SEQ ID NO: 9 or SEQ ID NO: 10 or SEQ ID NO: 11 or SEQ
ID NO: 12 or SEQ ID NO: 13 and

iii) a heavy chain variable region H-CDR3 comprising SEQ ID NO: 5 and
iv) a light chain variable region L-CDR1 comprising SEQ ID NO: 6 and
v) a light chain variable region L-CDR2 comprising SEQ ID NO: 7 and
vi) a light chain variable region L-CDR3 comprising SEQ ID NO: 8.

US Pat. No. 9,594,257

MYOPIA CONTROL MEANS

Novartis AG, Basel (CH) ...

1. A method of supplying, prescribing or selecting an anti-myopia lens for a myopic eye of a patient, comprising the steps
of:
measuring the central refractive error of the myopic eye,
taking the patient's history to assess the patient's propensity for progressive myopia, including the patient's familial history
of myopia,

without measuring peripheral refractive error in the eye, assessing the level of propensity of the patient for progressive
myopia by having regard to the patent history,

selecting from a set, kit or stock of pre-manufactured lenses a first selected lens having (i) a central corrective refractive
power that best matches the measured central refractive error and (ii) a level of peripheral myopic defocus that best matches
the assessed propensity for progressive myopia,

trying said first selected lens on the myopic eye and determining from the response of the patient whether or not peripheral
blur associated with said myopic defocus of the first selected lens is acceptable,

if the level of myopic defocus is determined to be acceptable, then supplying or prescribing an anti-myopia lens having the
central power and the peripheral defocus of the first selected lens for the patient,

if the level of myopic defocus of the first selected lens is determined to be unacceptable, then selecting a further lens
from said set, kit or stock of lenses having the same the same central corrective power as the first selected lens but having
a reduced level of peripheral myopic defocus, and supplying or prescribing for the patient an anti-myopia lens having the
central corrective refractive power and the reduced level of peripheral myopic defocus of said further selected lens.

US Pat. No. 9,295,646

CATIONIC OIL-IN-WATER EMULSIONS

Novartis AG, Basel (CH)

1. A composition comprising an RNA molecule complexed with a particle of a cationic oil-in-water emulsion,
wherein the particle comprises (a) an oil core that is in liquid phase at 25° C., and (b) a cationic lipid, such that the
overall net charge of the emulsion particle prior to RNA complexation is positive, and

wherein said RNA molecule is a self-replicating RNA that encodes a protein antigen and said RNA is anchored to the surface
of said particle by non-covalent interactions;

wherein, when administered in an effective amount to a mammal, the composition elicits antibody titers to the antigen equal
to or greater than the self-replicating RNA administered to the mammal not complexed with the particle.

US Pat. No. 9,320,646

SYSTEM AND METHOD FOR A PROCEDURE BASED GRAPHICAL INTERFACE

Novartis AG, Basel (CH)

1. A method for conducting a surgical procedure, comprising:
receiving, for a first surgical step, a user-associated functionality and at least one defined parameter;
providing a Graphical User Interface (GUI) for a surgical console, wherein the GUI comprises a representation of each of one
or more surgical steps of the surgical procedure, each of the surgical steps corresponding to a function of the surgical console;

detecting that a representation of the first surgical step of the one or more surgical steps has been selected; and
configuring the surgical console according to the user-associated function and at least one defined parameter corresponding
to the first surgical step;

detecting that a representation of a second surgical step of the one or more surgical steps has been selected; and
configuring the surgical console according to the function corresponding to the second surgical step;
wherein a user is enabled to navigate through the GUI and interact with the surgical console so as to cause the console to
be set up to conduct a multiple step surgical procedure.

US Pat. No. 9,598,376

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Array BioPharma, Inc., B...

1. A method of treating a cancer is selected from melanoma, pancreatic cancer, ovarian cancer, carcinoma of the fallopian
tubes, peritoneal cancer, biliary cancer, colon cancer, or rectal cancer in a patient in need thereof, comprising administering
to said mammal a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic
acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient.
US Pat. No. 9,243,271

FERMENTATION PROCESSES FOR CULTIVATING STREPTOCOCCI AND PURIFICATION PROCESSES FOR OBTAINING CPS THEREFROM

NOVARTIS AG, Basel (CH)

1. A fed batch method for cultivating Streptococcus for production of capsular polysaccharides (cps), wherein said fed batch method comprises (a) providing an inoculum of a strain
of Streptococcus expressing the cps, and (b) cultivating the strain by fermentation, wherein said cultivating comprises a pH-independent linear
addition of a carbon source to a cultivating medium.
US Pat. No. 9,399,021

PHARMACEUTICAL COMPOSITION

Novartis AG, Basel (CH)

1. A pharmaceutical tablet comprising:
a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide
dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg;

wherein,
b) the drug particles are micronized.
US Pat. No. 9,399,066

PROCESS FOR MAKING COMPOSITIONS COMPRISING SPHINGOSINE 1 PHOSPHATE (S1P) RECEPTOR MODULATORS

Novartis AG, Basel (CH)

1. A process for making a pharmaceutical composition in a final dosage form, comprising the steps of:
a) preparing a blend consisting of:
(i) 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or a pharmaceutically acceptable salt thereof; and
(ii) one excipient selected from the group consisting of Sorbitol, dicalcium phosphate, Lactose, Hydroxypropyl methylcellulose
(HPMC), Hydroxypropylcellulose (HPC), Crospovidone, croscarmellose sodium, starch, calcium silicate, colloidal silicone dioxide,
talc, and calcium stearate; and

b) mixing the blend of step a) with additional excipients to prepare the final form wherein the final form is an oral formulation
in form of a tablet, a granular, multiparticulate pellets, a soluble tablet or a capsule.

US Pat. No. 9,205,608

CONTACT LENSES WITH IDENTIFYING MARK

Novartis AG, Basel (CH)

1. A method of making silicone-hydrogel contact lenses, comprising the step of:
(a) providing a mold assembly comprising a female mold half having a molding surface and a male mold half having a molding
surface;

(b) applying at least one identifying mark coat to at least a portion of at least one of the female molding surface and the
male molding surface with an ink, wherein the ink comprises a silicone-containing polymer binder;

(c) irradiating the identifying mark coat on the molding surface with a first high intensity UV light to at least partially
cure the identifying mark coat;

(d) irradiating the molding surfaces of the female mold and the male mold with a second high intensity UV light prior to step
e);

(e) filling a lens-forming fluid material comprising at least one silicone-containing vinylic monomer or macromer and at least
one hydrophilic vinylic monomer into the irradiated mold assembly from step d);

(f) exposing the mold assembly and the lens-forming fluid material to an energy source, wherein the energy source polymerizes
the lens-forming fluid material; wherein emission spectrum of the first high intensity UV light has a higher intensity in
wavelength range 320-390 nm by at least 200 mW/cm2 and a lower intensity in wavelength range 250-260 nm by at least 10 mW/cm2
than the second high intensity UV light.

US Pat. No. 9,187,405

S1P RECEPTOR MODULATORS FOR TREATING RELASPING-REMITTING MULTIPLE SCLEROSIS

Novartis AG, Basel (CH)

1. A method for reducing or preventing or alleviating relapses in Relapsing-Remitting multiple sclerosis in a subject in need
thereof, comprising orally administering to said subject 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, in free form
or in a pharmaceutically acceptable salt form, at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen.

US Pat. No. 9,133,096

PROCESS FOR THE PRODUCTION OF 2-AMINO-2[2-(4-C2-20-ALKYL-PHENYL)ETHYL]PROPANE-1,3-DIOLS, AND TO COMPOUNDS FOR USE THEREIN

Novartis AG, Basel (CH)

1. A process for the production of a compound of the Formula (I) or a pharmaceutically acceptable salt thereof:

wherein R1 is hydrogen or C1-18 alkyl;
which comprises:
(a) reducing a compound of the Formula (III):

wherein R2 is a protecting group; and “----” represents an optional third bond;

to form a compound of the Formula (II):

(b) deprotecting the compound of Formula (II) to form a compound of Formula (I); and
(c) optionally converting the compound of Formula (I) to a pharmaceutically acceptable salt.

US Pat. No. 9,080,978

METHOD AND SYSTEM FOR STANDARDIZING MICROSCOPE INSTRUMENTS

Novartis AG, Basel (CH)

11. A microscope system for obtaining a standardized quantitative measurement, of biological sample data imaged by an optical
system having an excitation light source, an optics portion, an image capture portion and a data storage portion, cooperatively
arranged for obtaining an image of the biological sample, comprising:
means for obtaining for the optical system, an optical system intrinsic factor, based on a calibration surface configured
to produce a standardized response;

means for applying the optical system intrinsic factor to a biological sample data, thereby obtaining a biological sample
data measurement standardized with regards to optical system variability; and

means for determining a quantitative measure of the standardized biological sample data.
US Pat. No. 9,073,921

SALT FORMS OF BICYCLIC HETEROCYCLIC DERIVATIVES

Novartis AG, Basel (CH)

1. A crystalline form of N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide
saccharinate.
US Pat. No. 9,045,546

MOLECULES AND METHODS FOR MODULATING TMEM16A ACTIVITIES

NOVARTIS AG, Basel (CH)

1. An antibody or antigen binding fragment thereof that specifically binds to the extracellular domain 3 (“ECD3”) of transmembrane
protein 16A (“TMEM16A”), wherein said antibody or antigen binding fragment is internalized into the cell upon binding to the
ECD3 and wherein the antibody or antigen binding fragment specifically binds to a peptide consisting of SEQ ID NO:4, and wherein
the antibody or antigen binding fragment comprises a heavy chain CDR1 of SEQ ID NO:8, heavy chain CDR2 of SEQ ID NO:9, heavy
chain CDR3 of SEQ ID NO:10; and a light chain CDR1 of SEQ ID NO:11, light chain CDR2 of SEQ ID NO:12, and a light chain CDR3
of SEQ ID NO:13, respectively.

US Pat. No. 9,315,530

ADSORPTION OF IMMUNOPOTENTIATORS TO INSOLUBLE METAL SALTS

Novartis AG, Basel (CH)

1. A composition, comprising a TLR7 agonist of formula (C) and an insoluble metal salt, wherein at least 50% by mass of the
TLR7 agonist of formula (C) is adsorbed to the metal salt, and wherein formula (C) is:
wherein:
P3 is selected from H, C1-C6alkyl, CF3, —((CH2)pO)q(CH2)pOs— and —Y-L-X—P(O)(ORX)(ORY); and P4 is selected from H, C1-C6alkyl, —C1-C6alkylaryl and —Y-L-X—P(O)(ORX)(ORY); with the proviso that at least one of P3 and P4 is —Y-L-X—P(O)(ORX)(ORY);

RX and RY are independently selected from H and C1-C6alkyl;

RC is selected from H and C1-C6alkyl;

XC is selected from CH and N;

X is selected from a covalent bond, O and NH;
Y is selected from a covalent bond, O, C(O), S and NH;
L is selected from, a covalent bond, C1-C6alkylene, C1-C6alkenylene, arylene, heteroarylene, C1-C6alkyleneoxy and —((CH2)pO)q(CH2)p— each optionally substituted with 1 to 4 substituents independently selected from halo, OH, C1-C4alkyl, —OP(O)(OH)2 and —P(O)(OH)2;

each p is independently selected from 1, 2, 3, 4, 5 and 6;
q is selected from 1, 2, 3 and 4; and
s is selected from 0 and 1.

US Pat. No. 9,303,035

SUBSTITUTED PYRAZINO[1?,2?:1,2]PYRROLO[3,4-D]PYRIMIDINES, PYRIMIDO[4?,5?:3,4]PYRROLO[2,1-C][1,4]OXAZINES AND PYRIMIDO[4?,5?:3,4]PYRROLO[1,2-D][1,4]OXAZEPINES FOR INHIBITING THE CFTR CHANNEL

Novartis AG, Basel (CH)

11. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.

US Pat. No. 9,187,601

WATER-PROCESSABLE SILICONE-CONTAINING PREPOLYMERS AND USES THEREOF

Novartis AG, Basel (CH)

1. A water-processable prepolymer, comprising:
(1) siloxane-containing monomeric units and/or polysiloxane-containing crosslinking units, wherein the siloxane-containing
monomeric units are derived from one or more siloxane-containing vinylic monomers each having at least one hydrophilic polymeric
chain with a molecular weight of up to about 10000 Daltons, wherein the polysiloxane-containing crosslinking units are derived
from at least one hydrophilized polysiloxane crosslinker and/or chain-extended hydrophilized polysiloxane crosslinker each
having one or more pendant hydrophilic polymeric chains;

(2) hydrophilic monomeric units derived from one or more hydrophilic vinylic monomers;
(3) from about 0.05% to about 5% by weight of polymerizable units each having a pendant or terminal, ethylenically-unsaturated
group and free of any polysiloxane segment; and

(4) optionally hydrophobic units derived from at least one hydrophobic vinylic monomer free of silicone,
wherein the prepolymer comprises the polysiloxane-containing crosslinking units derived from a hydrophilized polysiloxane
or chain-extended polysiloxane crosslinker of formula (7) or (8)


In which
d2, d3, d4, ?1, ?2, and ?3 independent of one another are an integer from 0 to 20;
e3, e4, e5, e6, e7, ?1, ?2, ?3, ?4, and ?5 independent of one other are 0, 1, 2 or 3 and (e3+e4+e5+e6+e7)?1 and (?1+?2+?3+?4+?5)?1;
X1 is hydrogen or methyl;

D3, D4, D5, D6, D7, D8, D9 and D10 independently of one other are a divalent group of formula (9)


in which Y28 is as defined below, A8, A8?, A9?, and A9? independent of one other are a direct bond, a linear or branched C1-C10 alkylene divalent radical, —(CH2CH2O)r1—CH2CH2— in which r1 is an integer of 1 to 20, or a C1-C7 alkyleneoxy-C1-C7 alkylene divalent radical, and R1, R2, R3, R4, R5, R6, R7, R8, R1?, R2?, R3?, R4?, R5?, R6?, R7?, and R8? independently of one another, are C1-C4-alkyl, -alk-(OCH2CH2)r2—OR9 in which alk is C1-C6-alkylene divalent radical, R9 is C1-C4 alkyl and r2 is an integer from 1 to 20, f1 is an integer of 0 to 8, m1, m2, p1 and p2 independently of each other are an
integer of from 0 to 150, (m1+p1) and (m2+p2) independent of each other are from 2 to 150;

L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, Y8, Y9, Y10, Y11, Y12, Y13, Y14, Y15, Y16, Y17, Y18, Y19, Y20, Y21, Y22, Y23, Y24, Y25, Y26, Y27, and Y28 independent of one another are a direct bond or a divalent radical of

—Z1—X2—Z2—X3—Z3—X4—Z4— In which X2, X3 and X4 independent of one other are a linkage selected from the group consisting of a direct bond —O—, —NR?— in which R? is H or
C1-C4 alkyl, —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —O—C(O)—NH—, —S—, —NH—C(O)—O—, —C(O)—O—, —O—C(O)—, —NH—C(O)—NH—Z0—NH—C(O)—NH—, —O—C(O)—NH—Z0—NH—C(O)—O—, —O—C(O)—NH—Z0—NH—C(O)—NH—, and —NH—C(O)—NH—Z0—NH—C(O)—O—, Z0 is a linear or branched C2-C12 alkylene divalent radical or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical optionally containing therein one or more linkages of —O—, —NR?—,
—S— and —C(O)—, Z1, Z2, Z3 and Z4 independent of one other are is a direct bond, a linear or branched C1-C12 alkylene divalent radical optionally containing therein one or more linkages of —O—, —NR?—, —S— and —C(O)—, a divalent radical
of —CH2—CH(OH)—CH2— or —(CH2CH2O)r1—CH2CH2— with r1 as defined above, or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical optionally containing therein one or more linkages of —O—, —NR?—,
—S— and —C(O)—;

B5, B6, B7, B8, B9, B10, B11, B12, B13, and B14 independent of one another are hydroxyl or a linear or 3-arm hydrophilic polymer chain having a molecular weight of about
10000 Daltons or less and comprising at least about 60% by weight of one or more hydrophilic monomeric units selected from
the group consisting of ethyleneoxide units, (meth)acrylamide units, C1-C3 alkyl (meth)acrylamide units, di-(C1-C3 alkyl) (meth)acrylamide units, N-vinylpyrrole units, N-vinyl-2-pyrrolidone units, 2-vinyloxazoline units, 4-vinylpyridine
units, mono-C1-C4 alkoxy, mono-(meth)acryloyl terminated polyethyleneglycol units having a molecular weight of 600 Daltons or less, di(C1-C3 alkyl amino)(C2-C4 alkyl) (meth)acrylate units, N—C1-C4 alkyl-3-methylene-2-pyrrolidone units, N—C1-C4 alkyl-5-methylene-2-pyrrolidone units, N-vinyl C1-C6 alkylamide units, N-vinyl-N—C1-C6 alkyl amide units, and combinations thereof, provided that at least one of B5, B6, B7, B8, and B9 and at least one of B10, B11, B12, B13, and B14 are the linear or 3-arm hydrophilic polymer chain; and

T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, and T14 independent of one another are an aliphatic or cycloaliphatic or aliphatic-cycloaliphatic trivalent radical which has up to
15 carbon atoms and can be interrupted by —O—, —NR?—, —C(O)— and/or —S—,

wherein the prepolymer comprises from about 20% to about 50% by weight of silicone relative to the total weight of the prepolymer
and has a high water solubility or dispersibility of at least about 5% by weight in water, wherein the prepolymer is capable
of being actinically crosslinked, in the absence of one or more vinylic monomers, to form a silicone hydrogel contact lens
having a water content of from about 20% to about 75% by weight when fully hydrated, an oxygen permeability (Dk) of at least
about 40 barrers, and optionally a hydrophilic surface characterized by an average water contact angle of about 90 degrees
or less without post-molding surface treatment.

US Pat. No. 9,345,619

DEVICES, SYSTEMS AND METHODS FOR POSTERIOR SEGMENT DRAINAGE

Novartis AG, Basel (CH)

1. A method of implanting a glaucoma drainage device in an eye having a vitreous chamber and a drainage site, the glaucoma
drainage device comprising a tube, the tube including a lumen extending from an inlet end to an outlet end, the drainage device
including a control element that regulates the amount of fluid flow through the glaucoma drainage device, the method comprising:
implanting, from the vitreous chamber, the glaucoma drainage device into pars plana tissue to extend between the vitreous
chamber and the drainage site;

further comprising inserting a cannula into the pars plana at a first location in the pars plana tissue; wherein implanting
a glaucoma drainage device into the pars plana tissue includes advancing the glaucoma drainage device into the vitreous chamber
through the cannula;

further comprising the steps of: providing a delivery device having a distal end;
advancing the distal end through the cannula until the distal end comes into contact with ocular tissue of the pars plana
at a second location in the pars plana separate from the first location;

pushing the distal end through the ocular tissue at the second location so that the delivery device penetrates the tissue
of the pars plana to form a tunnel;

advancing the glaucoma drainage device through the delivery device into the tunnel; and
positioning the glaucoma drainage device in the tunnel so that a desired amount of the outlet end is located in the drainage
site and a desired amount of the net end is located in the vitreous chamber.

US Pat. No. 9,303,067

SUSTAINED RELEASE FORMULATION COMPRISING A SOMATOSTATIN ANALOGUE

Novartis AG, Basel (CH)

1. A liquid pharmaceutical composition for parenteral administration comprising a lactate, acetate, diaspartate, diglutamate,
or discuccinate salt of a somatostatin analogue cyclo[{4-NH2—C2H4NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Bzl)-Phe] and water forming a gelling depot system after injection in contact with body fluid.
US Pat. No. 9,296,813

COMPOSITIONS AND METHODS OF USE FOR ANTIBODIES OF DICKKOPF-1

NOVARTIS AG, Basel (CH)

1. A composition comprising:
(1) an isolated antibody or a functional fragment thereof comprising:
(a) CDR sequences of a variable heavy chain comprising: CDR1 with a sequence comprising amino acids 22 to 35 of SEQ ID NO:
11, CDR2 with a sequence comprising amino acids 47 to 66 of SEQ ID NO: 11, and CDR3 with a sequence comprising amino acids
99 to 105 of SEQ ID NO: 11, and

(b) CDR sequences of a variable light chain comprising: CDR1 with a sequence comprising amino acids 23 to 36 of SEQ ID NO:
30, CDR2 with a sequence comprising amino acids 48 to 58 of SEQ ID NO: 30, and CDR3 with a sequence comprising amino acids
91 to 100 of SEQ ID NO: 30,

wherein the antibody or functional fragment thereof specifically binds to human DKK1 and/or human DKK4; and
(2) a bisphosphonate.

US Pat. No. 9,187,468

TOPICAL OCULAR ANALGESIC AGENTS

NOVARTIS AG, (CH)

7. A topical ocular pharmaceutical composition comprising:
a cyclodextrin or sodium polystyrene sulfonate; and
a therapeutically effect amount of compound of Formula I
wherein:

Y?CH or N;
n=0 or 1, with the proviso that n=0 if Y?N;
X=a direct bond or CH2;

Z=a phenyl or heteroatomic group, optionally substituted with phenyl, methyl; halo, trihalomethyl, or trihalomethoxy; and
R2?H, Me, or F, with the Me or F groups in the 2 or 6 positions on the acetamide-bearing phenyl ring.

US Pat. No. 9,149,541

TYROSINE LIGATION PROCESS

NOVARTIS AG, Basel (CH)

1. A tyrosine containing conjugate of diphtheria toxin mutant CRM197 having a structure:

US Pat. No. 9,050,050

METHOD FOR MONITORING FERTILITY BY MEASURING THE CONCENTRATION OF HORMONES IN TEARS

Novartis AG, Basel (CH)

1. A method for determining a fertility status of a current ovulation cycle of a female human, comprising the steps of:
(a) monitoring variation in tear concentration of at least one hormone of relevance to female fertility; and
(b) evaluating a correspondence of the variation in tear concentration of said hormone to onset of a transition phase, fertile
phase, ovulation, or infertile phase of a menstrual cycle in said female human, wherein the step of monitoring is performed
by periodically collecting a tear fluid from the female human by use of a hydrogel soft contact lens and then determining
the tear concentration of said hormone in the tear fluid;

wherein said hydrogel soft contact lens is capable of binding said hormone;
wherein the hydrogel soft contact lens includes: (1) surface charges present in a density sufficient to impart to the contact
lens an increased adsorption of said hormone;

or (2) molecular imprints for said hormone.
US Pat. No. 9,243,299

AVIAN GROUP D ROTAVIRUS

Novartis AG, Basel (CH)

1. A nucleic acid comprising:
(a) a nucleic acid sequence with at least 90% identity to the nucleic acid sequence as recited in SEQ ID NO: 1;
(b) a nucleic acid sequence with at least 90% identity to the reverse complement of the nucleic acid sequence as recited in
SEQ ID NO: 1;

(c) a fragment of the nucleic acid sequence as recited in SEQ ID NO: 1 that consists of at least 24 consecutive nucleotides
from SEQ ID NO: 1;

(d) a fragment of the reverse complement of the nucleic acid sequence as recited in SEQ ID NO: 1 that consists of at least
10 consecutive nucleotides of the reverse complement SEQ ID NO: 1; or

(e) a nucleic acid sequence which hybridizes under high stringency conditions with a nucleic acid sequence as recited in SEQ
ID NO: 1, wherein the nucleic acid comprises a detectable label selected from a radioisotope, a chromophore, a fluorescent
molecule, a quencher molecule, a biotin molecule, or a hairpin structure.

US Pat. No. 9,206,181

1-AZA-BICYCLO[3.3.1] NON-4-YL)-[5-(1H-INDOL-5-YL)-HETEROARYL]-AMINES AS CHOLINERGIC LIGANDS OF THE N-ACHR FOR THE TREATMENT OF PSYCHOTIC AND NEURODEGENERATIVE DISORDERS

Novartis AG, Basel (CH)

1. A pharmaceutical composition, comprising:
a compound of formula (I)

wherein
n represents 0,
R represents independent from each other hydroxyl, cyano, nitro, halogen, alkyl, alkoxy alkylcarbonyl, alkoxycarbonyl, alkylamine,
dialkylamine, alkylcarbonylamine, alkylcarbamate

Y represents one of the following groups:

in free base or acid addition salt form.

US Pat. No. 9,079,897

IMIDAZO-PYRIDINE DERIVATIVES AS ACTIVIN-LIKE RECEPTOR KINASE (ALK4 OR ALK5) INHIBITORS

NOVARTIS AG, Basel (CH)

1. A compound of Formula I,

or hydrates or pharmaceutically acceptable salts thereof, wherein
X is CRx or N;

R1 is NR7R8;

R2 is selected from aryl, heterocyclyl, C1-C7 alkyl, C3-C10-cycloalkyl, C5-C10 cycloalkenyl, C(O)NR5R6, halo, C1-C7 alkoxy, alkylthio, hydroxyl, C1-C7 alkylcarbonyl, carboxy, carbonyl, cyano and sulfonamide, wherein the alkyl, cycloalkyl, cycloalkenyl, aryl and heterocyclyl
groups are optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl and C1-C6 alkoxy;

R3 is selected from H, halo, NR19R20 and OR21;

R4 is hydrogen;

Rx is selected from H, OH and C1-C3 alkoxy;

R5, R6 and R7 are each independently selected from H, C1-C6 alkyl, C3-C8 cycloalkyl and C1-C3 alkyl-C3-C8 cycloalkyl;

R8 is selected from C3-C10 cycloalkyl and a 5- or 6-membered heterocyclic group, each optionally substituted by one or more groups selected from C1-C6alkyl, C1-C6 alkoxy, OH and C1-C6 alkyl substituted by OH or NH2; and

R19, R20 and R21 are each independently selected from H, C1-C6 alkyl and C3-C6 cycloalkyl; or R19 and R20, together with the nitrogen atom to which they are attached form a 4-, 5- or 6-membered N-containing heterocyclic group.

US Pat. No. 9,555,200

INHALER

Novartis AG, Basel (CH)

1. An inhaler comprising:
a medicament capsule housing for containing a medicament capsule,
an airflow path through which air flows during an airflow event from at least one air inlet to an outlet, the airflow path
passing through the capsule housing,

a first sensor comprising a microphone or piezo element for detecting impact,
a processor, and
a power source for powering the processor,
the medicament capsule housing being defined by at least one wall and configured such that when the medicament capsule is
located in the medicament capsule housing and air flows along the airflow path through the medicament capsule housing, the
medicament capsule moves within the medicament capsule housing wherein said movement comprises impacting said at least one
wall, the first sensor is being arranged on the inhaler so that it is able to detect the impact of the medicament capsule
against said wall of the medicament capsule housing and generate a first signal indicative of said movement, the processor
receiving the first signal from the first sensor and analyzes said first signal using a peak-detection algorithm which determines
whether the calculated peak frequency is within predetermined limits to determine whether the first signal is indicative of
the a presence, or absence, of the medicament capsule in the medicament capsule housing during as the airflow event and to
generate a signal indicative of medicament capsule presence,

the inhaler further comprising memory for storing the signal indicative of medicament capsule presence or absence, and an
output from which the medicament capsule presence or absence signal or the contents of the memory can be accessed, and at
least one actuator which can be actuated by a user to cause an opening element to open the medicament capsule within the inhaler,
the inhaler further including an actuator sensor for sensing actuation of the actuator and generating an actuation signal,
the processor being arranged to receive the actuation signal.

US Pat. No. 9,505,184

SILICONE HYDROGEL LENS WITH A CROSSLINKED HYDROPHILIC COATING

Novartis AG, Basel (CH)

1. A method for producing silicone hydrogel contact lenses each having a crosslinked hydrophilic coating thereon, comprising
the steps of:
(a) obtaining a silicone hydrogel contact lens;
(b) applying a layer of carboxyl-containing polymeric material onto the silicone hydrogel contact lens;
(c) placing the silicone hydrogel contact lens with the layer of carboxyl-containing polymeric material thereon into a lens
package containing a packaging solution, wherein the packaging solution comprises from about 0.01% to about 2% by weight of
one or more crosslinkable hydrophilic polymeric materials selected from the group consisting of (i) a water-soluble hydrophilic
polymer polymeric material having epoxide groups, wherein the hydrophilic polymeric material is partial reaction product of
a first multi-arm polyethyleneglycol having terminal epoxide groups and a first hydrophilicity-enhancing agent having at least
one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group,
and combination thereof, (ii) a second multi-arm polyethyleneglycol having terminal epoxide groups, (iii) a mixture of a third
multi-arm polyethyleneglycol having terminal epoxide groups and a second hydrophilicity-enhancing agent having at least one
reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group,
and combination thereof, and (iv) a combination thereof;

(d) sealing the package;
(e) autoclaving the sealed package with the silicone hydrogel contact lens therein at a temperature from about 115° C. to
about 125° C. for at least about twenty minutes, thereby forming a non-silicone hydrogel coating on the silicone hydrogel
contact lens, wherein the non-silicone hydrogel coating is a crosslinked polymeric material composed of the carboxyl-containing
polymeric material crosslinked with the one or more crosslinkable material.

US Pat. No. 9,446,043

PHARMACEUTICAL COMBINATIONS

Novartis AG, Basel (CH)

1. A pharmaceutical combination comprising or consisting of:
a protein kinase C (PKC) inhibitor compound, or a pharmaceutically acceptable salt thereof, wherein the PKC inhibitor compound
is selected from the group consisting of:

3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione,
3-(1H-indol-3-yl)-4-[2-(piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione,
3-[2-chloro-7-[(dimethylamino)methyl]-1-naphthalenyl]-4-[7-[2-(2-methoxyethoxy)ethoxy]-1H-indol-3-yl]-1H-pyrrole-2,5-dione,
3-[3-(4,7-diaza-spiro[2,5]oct-7-yl)-isoquinolin-1-yl]-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione,
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo-[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione,
ruboxistaurin, and
12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole,
or a pharmaceutically acceptable salt thereof; and
a mitogen activated protein kinase (MEK) inhibitor compound, or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,346,194

COLORED CONTACT LENSES AND METHOD OF MAKING THE SAME

NOVARTIS AG, (CH)

1. A method of making colored silicone-hydrogel contact lenses, comprising the steps of:
(a) providing a mold assembly comprising a female mold half having a molding surface and a male mold half having a molding
surface;

(b) applying at least one color coat to at least a portion of at least one of the female molding surface and the male molding
surface with an ink, wherein the ink comprises at least one colorant and a silicone-containing polymer binder;

(c) irradiating the color coat on the molding surface with a first high intensity UV light to at least partially cure the
color coat; and then

(d) irradiating exposed surfaces of the female mold and the male mold with a second high intensity UV light prior to step
(e);

(e) filling a lens-forming fluid material comprising at least one silicone-containing vinylic monomer or macromer and at least
one hydrophilic vinylic monomer into the irradiated mold assembly from step d);

(f) exposing the mold assembly and the lens-forming fluid material to an energy source, wherein the energy source polymerizes
the lens-forming fluid material;

wherein an emission spectrum of the first high intensity UV light has a higher intensity in wavelength range of 320-390 nm
by at least 200 mW/cm2 and a lower intensity in wavelength range of 250-260 nm by at least 10 mW/cm2 than the second high intensity UV light.

US Pat. No. 9,310,625

COLORED CONTACT LENSES AND METHOD OF MAKING THE SAME

Novartis AG, Basel (CH)

1. A colored contact lens, comprising a first print of a first color and a second print of a second color,
wherein the first print is an annular ring of gradient dot matrix,
wherein the second print comprises a limbal ring pattern comprised of evenly spaced circular voids,
wherein the annular ring and the limbal ring have a substantially identical outer diameter and the annular ring has a smaller
inner diameter than that of the limbal ring, wherein the first color and the second color are different or the same,

wherein the first print and the second print are concentric with the center of contact lens.

US Pat. No. 9,295,384

IMAGING PROBES AND ASSOCIATED DEVICES, SYSTEMS, AND METHODS UTILIZING LEVER ARM ACTUATORS

Novartis AG, (CH)

1. An ophthalmic imaging probe, comprising:
a handle;
a cannula coupled to the handle;
an optical fiber positioned at least partially within the handle and the cannula, the optical fiber configured to receive
an imaging light from an imaging light source and guide the imaging light to an optical element positioned within a distal
portion of the cannula; and

an actuator system configured to impart motion to the optical fiber, the actuator system including a mechanical structure
and an electrically energizable member configured to selectively impart motion to the mechanical structure upon the electrically
energizable member being electrically energized.

US Pat. No. 9,181,340

TEM8 ANTIBODIES, CONJUGATES THEREOF, AND THEIR USE

The United States of Amer...

1. An isolated monoclonal antibody or antigen binding fragment thereof, comprising a heavy chain variable region comprising
a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3, and a light chain variable region comprising
a light chain complementarity determining region (LCDR)1, a LCDR2, and a L-CDR3, of the amino acid sequences set forth as
one of:
(a) SEQ ID NO: 1 and SEQ ID NO: 6, respectively (L2);
(b) SEQ ID NO: 2 and SEQ ID NO: 7, respectively (L1);
(c) SEQ ID NO: 3 and SEQ ID NO: 8, respectively (L3);
(d) SEQ ID NO: 4 and SEQ ID NO: 9, respectively (L5); or
(e) SEQ ID NO: 5 and SEQ ID NO: 10, respectively (1D2); and
wherein the monoclonal antibody or antigen binding fragment specifically binds to TEM8.

US Pat. No. 9,108,956

CYCLIC ETHER DGAT1 INHIBITORSCYCLIC ETHER DGAT1 INHIBITORS

NOVARTIS AG, Basel (CH)

1. A compound according to formula (I) or a salt or solvate thereof:

wherein
X is O or CH2;

Y is O or CH2; wherein one of X and Y is O and the other is CH2;

Z1, Z2, Z3 and Z4 are each, independently, N or CH;

L is C(O) or absent; and
A is a substituted oxazole, thiazole, oxadiazole or thiadiazole substituted with at least one C1-6alkyl, C3-7cycloalkyl or C1-6haloalkyl.

US Pat. No. 9,365,565

SALTS OF AZA-BICYCLIC DI-ARYL ETHERS AND PHARMACEUTICALS THEREOF

Novartis AG, Basel (CH)

1. A pharmaceutical composition, which comprises
a salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane, wherein said salt is the fumarate, maleate,
chloride, phosphate, succinate or malonate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane as
active ingredient; and

at least one pharmaceutically acceptable carrier.
US Pat. No. 9,333,716

METHOD FOR CAST MOLDING CONTACT LENSES

NOVARTIS AG, (CH)

1. An improved method of cast molding contact lenses, wherein a lens forming material is cured in a lens-shaped cavity formed
between molding surfaces of a male and female mold sections, wherein the improvement comprises injection molding at least
one of mold sections from a controlled rheology polypropylene, wherein the controlled rheology polypropylene has a higher
melt flow rate of at least about 6 g/10 minutes than that of a corresponding pristine polyprolylene, wherein the corresponding
pristine polypropylene is a starting polypropylene prior to going through a controlled rheology process, wherein the controlled
rheology polypropylene has a melt flow rate of from 12 g/10 minutes to 80 g/10 minutes, wherein the controlled rheology polypropylene
having a tangent delta of at least about 5 at 1 rad/second provides the mold section with a less mold warpage, compared to
a mold material having the corresponding pristine polypropylene having the same melt flow rate.

US Pat. No. 9,326,826

GAS PRESSURE MONITOR FOR PNEUMATIC SURGICAL MACHINE

Novartis AG, Basel (CH)

11. A method for monitoring the state of a filter in a pneumatic module of a surgical machine comprising:
sensing a first pressure of a gas upstream from a filter;
sensing a second pressure of a gas downstream from the filter;
computing a difference between the first pressure and the second pressure;
comparing the difference to a value to determine a state of the filter;
determining if a pressure drop across the filter is acceptable; and
opening an isolation valve if the pressure drop across the filter is acceptable.
US Pat. No. 9,309,229

CRYSTALLINE FORMS OF 5-CHLORO-N2-(2-ISOPROPOXY-5-METHYL-4-PIPERIDIN-4-YL-PHENYL)-N4-[2-(PROPANE-2-SULFONYL)-PHENYL]-PYRIMIDINE-2, 4-DIAMINE

Novartis AG, Basel (CH)

1. A crystalline form of 5-Chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]pyrimidine-2,4-diamine
exhibiting one or more X-ray powder diffraction peaks having maxima at diffraction angles selected from 7.2°, 8.1°, 10.8°,
12.0°, 12.4°, 13.4°, 14.4°, 14.8°, 15.7°, 16.9°, 17.7°, 18.5°, 19.0°, 19.5°, 20.0°, 20.3°, 21.1°, 21.6°, 22.4°, 22.6°, 23.0°,
24.1°, 24.5°, 25.5°, 26.0°, 26.2°, 27.0°, 27.3°, 28.3°, 29.0°, 29.1°, 30.6°, 31.3°, 32.8°, 33.5°, 34.2° and 36.4° (2? degrees).
US Pat. No. 9,290,573

THERAPEUTIC LOW DENSITY LIPOPROTEIN-RELATED PROTEIN 6 (LRP6) MULTIVALENT ANTIBODIES

NOVARTIS AG, BASEL (CH)

1. An isolated multivalent antibody or antigen-binding fragment thereof having at least two receptor binding domains for two
different binding sites of a low density lipoprotein-related protein 6 (LRP6) target receptor, wherein the first receptor
binding domain binds to a first binding site on the target receptor and the second receptor binding domain binds to a second
binding site on the same LRP6 target receptor, wherein the first and second receptor binding domains are linked together such
that the binding of the first and second receptor binding domains to the first and second binding sites of the LRP6 target
receptor inhibits a canonical Wnt signal transduction pathway, and wherein the antibody or antigen binding fragment displays
no significant potentiation of a Wnt signal;
wherein the first receptor binding domain is an IgG antibody and the second receptor binding domain is an scFv fragment, wherein
the IgG antibody and scFv fragment are linked together by a linker with a spatial distribution that permits the IgG antibody
and scFv fragment to bind to the first and second epitopes of LRP6, respectively; and
wherein the heavy chain of the IgG antibody is selected from the group consisting of SEQ ID NO: 18, 66, and 86, and the light
chain is selected from the group consisting of SEQ ID NO: 17, and 85.

US Pat. No. 9,242,927

PROCESS FOR THE MANUFACTURE OF N-ACYLBIPHENYL ALANINE

ZHEJIANG JIUZHOU PHARMACE...

1. A process for preparing a compound of formula (3), or salt thereof,
wherein R1 is C1-7alkyl, or C6-10aryl, comprising treating a compound of formula (2-a), or salt thereof,
wherein R1 is C1-7alkyl, or C6-10aryl, under hydrogenation conditions to provide the compound of formula (3).

US Pat. No. 9,051,279

SUBSTITUTED ISOQUINOLINONES AND QUINAZOLINONES

Novartis AG, Basel (CH)

13. A compound that is 6-((R)-sec-Butoxy)-4-(4-chloro-phenyl)-3-(4-dimethylamino-phenyl)-7-methoxy-3,4-dihydro-1H-quinazolin-2-one,
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,050,267

DRY POWDER FORMULATIONS OF PARTICLES THAT CONTAIN TWO OR MORE ACTIVE INGREDIENTS FOR TREATING OBSTRUCTIVE OR INFLAMMATORY AIRWAYS DISEASES

Novartis AG, Basel (CH)

1. A dry powder formulation for inhalation comprising spray-dried particles that comprise a core of a first active ingredient
in substantially crystalline form that is coated with a layer of a second active ingredient in substantially amorphous form
that is dispersed in a pharmaceutically acceptable hydrophobic excipient.

US Pat. No. 9,554,941

OCULAR IMPLANT DELIVERY SYSTEMS AND METHODS

Novartis AG, Basel (CH)

1. A system for delivering an ocular implant having a fluid channel, the system comprising:
a delivery device comprising:
a handle component having a proximal end, a distal end; and
a flexible wire coupled to the handle and insertable through a fluid channel of an ocular implant; and
a retention element on the flexible wire, the retention element providing an interference fit between an implant and the flexible
wire when an implant is inserted on the flexible wire;

an implant comprising an elongate member having a flow pathway, at least one inflow port communicating with the flow pathway,
and an outflow port communicating with the flow pathway, wherein the elongate member is adapted to be positioned in an eye
such that the inflow port communicates with an anterior chamber and the outflow port communicates with a suprachoroidal space.

US Pat. No. 9,557,579

PRESBYOPIC TREATMENT SYSTEM

NOVARTIS AG, Basel (CH)

1. A multifocal contact lens comprising:
a central optical zone having a power profile that provides an ADD power ranging from a maximum ADD power of between about
0 diopters and about 2.4 diopters and a minimum ADD power of between about 0 diopters and about 0.2 diopters;

a peripheral optical zone having a power profile that provides an amount of negative spherical aberration-between an inner
semi-diameter of about 2 millimeters (mm) and an outer semi-diameter of about 3 mm, wherein the difference between the amount
of negative spherical aberration provided by the power profile of the peripheral optical zone at the inner semi-diameter and
the amount of negative spherical aberration provided by the power profile of the peripheral optical zone at the outer semi-diameter
ranges from a minimum absolute value of about 0.65 diopters and a maximum absolute value of about 1.25 diopters; and

a transition zone interposed between and connected to the central optical zone and the peripheral optical zone, the transition
zone providing a transition between the central optical zone and the peripheral optical zone, the transition zone having a
power profile that is continuous.

US Pat. No. 9,512,199

FIBRONECTIN CRADLE MOLECULES AND LIBRARIES THEREOF

NOVARTIS AG, Basel (CH) ...

1. A 10th fibronectin type III (FnIII10) domain-based cradle polypeptide capable of binding to a target molecule, wherein the cradle
polypeptide comprises the sequence of SEQ ID NO: 44.

US Pat. No. 9,452,139

RESPIRABLE AGGLOMERATES OF POROUS CARRIER PARTICLES AND MICRONIZED DRUG

Novartis AG, Basel (CH)

1. A pharmaceutical composition for pulmonary delivery via a dry powder inhaler, the composition comprising a dry powder comprising
a plurality of small porous carrier particles having a mass median diameter (MMD) of about 1-10 microns and a plurality of
active agent particles having a MMD of less than about 4 microns, wherein the plurality of active agent particles are selected
from the group consisting of particles of indacaterol or a pharmaceutically acceptable salt or ester thereof, particles of
glycopyrronium or a pharmaceutically acceptable salt or ester thereof, and particles of mometasone or a pharmaceutically acceptable
salt or ester thereof, and wherein the small porous carrier particles and the active agent particles form an ordered mixture
of respirable agglomerates.

US Pat. No. 9,393,295

NANOPARTICLES FOR USE IN PHARMACEUTICAL COMPOSITIONS

Novartis AG, Basel (CH)

1. A method of forming nanoparticles comprising:
contacting a first liquid that comprises a biodegradable polymer dissolved in an organic solvent with a second liquid that
comprises an aqueous solvent by minimally intermixing the first and second liquid such that (i) nanoparticles are formed without
particle aggregation without detergent; (ii) the polymeric yield for the nanoparticles is >90% and (iii) the D(v,0.5) value
for the nanoparticles is less than 200 wherein the second liquid is miscible with the organic solvent while being a non-solvent
for the biodegradable polymer.

US Pat. No. 9,388,199

PYRROLIDINE DERIVATIVES AND THEIR USE AS COMPLEMENT PATHWAY MODULATORS

NOVARTIS AG, Basel (CH)

1. A compound, or a salt thereof, according to the formula (I):

Wherein
A is a group selected from:

Z1 is C(R1) or N;

Z2 is C(R2) or N;

Z3 is C(R3) or N, wherein at least one of Z1, Z2 or Z3 is not N;

R1 is selected from the group consisting of hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy, haloC-C6alkyl, haloC-C6alkoxy, C1-C6alkoxycarbonyl, CO2H and C(O)NRARB;

R2 and R3 are independently selected from the group consisting of hydrogen, halogen, hydroxy, NRCRD, cyano, CO2H, CONRARB, SO2C1-C6alkyl, and SO2NH2, SO2NRARB, C1-C6alkoxycarbonyl, —C(NRA)NRCRD, C1-C6alkyl, haloC1-C6alkyl, C2-C6alkenyl, C1-C6alkoxy, haloC1-C6alkoxy, C2-C6alkenyloxy, wherein each alkyl, alkenyl, alkoxy and alkenyloxy is unsubstituted or substituted with up to 4 substitutents
independently selected from halogen, hydroxy, cyano, tetrazole, C1-C4alkoxy, C1-C4haloalkoxy, CO2H, C1-C6alkoxycarbonyl, C(O)NRARB, NRCRD, optionally substituted phenyl, heterocycle having 4 to 7 ring atoms and 1, 2, or 3 ring heteroatoms selected from N, O or
S, optionally substituted heteroaryl having 5 or 6 ring atoms and 1 or 2 or 3 ring heteroatoms selected from N, O or S, and
wherein optional phenyl and heteroaryl substituents are selected from halogen, hydroxy, C1-C4alkyl, C1-C4alkoxy and CO2H;

R4 is selected from the group consisting of hydrogen, halogen, and C1-C6alkyl;

R5 is C1-C4alkyl, hydroxyC1-C4alkyl, C1-C4alkoxyC1-C4alkyl, haloC1-C4alkyl amino, methylamino

X1 is CR9R22 or sulfur;

X2 is CR7R8, oxygen, sulfur, N(H) or N(C1-C6alkyl), wherein at least one of X1 and X2 is carbon; or

X1 and X2, in combination, forms an olefin of the formula —C(R7)?C(H)— or —C(R7)?C(C1-C4alkyl)-, wherein the C(R7) is attached to X3;

X3 is (CR6R21)q or N(H) wherein q is 0, 1 or 2, wherein X3 is CR6R21 or (CR6R21)2 when either X1 or X2 is sulfur or X2 is oxygen; or

X2 and X3, taken in combination, are —N?C(H)— or —N?C(C1-C4alkyl)- in which the C(H) or C(C1-C4alkyl) is attached to X1;

R6 is selected from the group consisting of hydrogen, and C1-C6alkyl,

R7 is hydrogen, halogen, hydroxy, cyano, C1-C6alkyl, C1-C6alkoxy, hydroxyC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, haloC1-C6alkyl, or C1-C6haloalkoxy;

R8 is hydrogen, halogen, hydroxy, azide, cyano, COOH, C1-C6alkoxycarbonyl, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, NRARB, N(H)C(O)C1-C6alkyl, hydroxyC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, or C1-C6alkyl substituted with NRARB, N(H)C(O)H or N(H)C(O)(C1-C4alkyl);

R9 is selected from the group consisting of hydrogen, hydroxy, halogen, C1-C6alkyl, haloC1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, haloC1-C6alkoxy, NRARB, N(H)C(O)C1-C6alkyl, N(H)C(O)OC1-C6alkyl and OC(O)NRCRD each of alkyl, alkoxy, alkenyl, and alkynyl substituents may be substituted with 0, 1, or 2 groups independently selected
at each occurrence from the group consisting of halogen, hydroxy, C1-C6alkyl, C1-C6alkoxy, and NRARB;

R20 is hydrogen or C1-C6alkyl;

R21 is selected from the group consisting of hydrogen, phenyl and C1-C6alkyl, which alkyl group is unsubstituted or substituted with hydroxy, amino, azide, and NHC(O)C1-C6alkyl;

R22 is selected from the group consisting of hydrogen, halogen, hydroxy, amino and C1-C6alkyl;

CR7R8, taken in combination forms a spirocyclic 3 to 6 membered carbocycle which is substituted with 0, 1, or 2 substituents independently
selected from the group consisting of halogen and methyl; or

R7 and R8, taken in combination, form an exocyclic methylidene (?CH2);

R7 and R22 or R8 and R9, taken in combination form an epoxide ring or a 3 to 6 membered carbocyclic ring system which carbocyclic ring is substituted
with 0, 1, or 2 substituents independently selected from the group consisting of halogen, methyl, ethyl, hydroxyC1-C4alkyl, C1-C6alkoxyC1-C4alkyl, C1-C4alkoxycarbonyl, CO2H, and C1-C4alkyl substituted with NRARB;

R6 and R7 or R8 and R21, taken in combination, form a fused 3 membered carbocyclic ring system which is substituted with 0, 1, or 2 substituents
independently selected from the group consisting of halogen, methyl, ethyl, hydroxyC1-C4alkyl, C1-C6alkoxyC1-C4alkyl, C1-C4alkoxycarbonyl, CO2H, and C1-C4alkyl substituted with NRARB; or

R20 and R22 taken in combination form a fused 3 carbocyclic ring system;

R9 and R21 taken in combination form a form 1 to 3 carbon alkylene linker;

R7 and R20 taken in combination form 1 to 3 carbon alkylene linker;

RA and RB are independently selected from the group consisting of hydrogen, and C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, hydroxyC1-C6alkyl, or NRARB, taken in combination, form a heterocycle having 4 to 7 ring atoms and 0 or 1 additional ring N, O or S atoms, which heterocycle
is substituted with 0, 1, or 2 substituents independently selected from the group consisting of C1-C4alkyl, halogen, hydroxy, C1-C4alkoxy;

RC and RD, are each independently selected from the group consisting of hydrogen and C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxyC1-C6alkyl, or hydroxyC1-C6alkyl;

n is an integer selected from 0-4;
R10 is hydrogen, C1-C4alkyl, haloC1-C4alkyl, hydroxyC1-C4alkyl or C1-C4alkoxyC1-C4alkyl;

R11 is hydrogen, halogen, hydroxy or C1-C4alkyl;

R12 is hydrogen, halogen or C1-C4alkyl; or

R12 is absent and R11 is oxo; and

R13 is hydrogen, C1-C4alkyl, haloC1-C4alkyl, hydroxyC1-C4alkyl, haloC1-C4alkoxy, and tri-C1-C4alkylsilyl.

US Pat. No. 9,375,348

SYSTEMS AND METHODS FOR A MEMBRANE-FREE ELECTROLYSIS PUMP FOR AN INTRAOCULAR IMPLANT

Novartis AG, Basel (CH)

10. An intraocular device for regulating pressure within an eye of a patient, the intraocular device comprising:
a plate having a cavity therein;
a flexible tube having a proximal end and a distal end, the proximal end configured to insert into an anterior chamber of
the eye and the distal end coupled to the plate; and
a microfluidic pump configured within the cavity of the plate, the microfluidic pump comprising:
a first substrate portion;
a second substrate portion adjacent to the first substrate portion;
a channel defined by and between the first and second substrate portions and in communication with the flexible tube; and
a chamber having a bottom surface, side surfaces, and a top surface, wherein the top surface is provided by a liquid-permeable
wall, a gas being produced within the chamber that displaces fluid from within the chamber into the channel, the rigid, liquid-permeable
wall being in fluid communication with the channel.

US Pat. No. 9,308,128

MULTI-SPOT LASER PROBE WITH MICRO-STRUCTURED FACETED PROXIMAL SURFACE

NOVARTIS AG, Basel (CH)

1. An optical surgical probe comprising:
a cylindrical cannula;
a light guide within the cannula, the light guide configured to receive a light beam from a light source, to guide the light
beam to a distal end of the light guide, and to emit the light beam at the distal end of the light guide; and

a multi-spot generator at a distal end of the cannula, the multi-spot generator having a faceted proximal surface with oblique
facets, configured to receive the light beam emitted at the distal end of the light guide and to split the received light
beam into multiple beam-components, an a distal surface through which the multiple beam-components exit the multi-spot generator,
wherein the proximal surface of the multi-spot generator is micro-structured with a modulation length smaller than a wavelength
of the light beam.

US Pat. No. 9,301,971

PEPTIDES AND COMPOSITIONS FOR TREATMENT OF JOINT DAMAGE

NOVARTIS AG, Basel (CH)

1. An isolated polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino
acid sequence selected from the group of sequences of TABLE 1, wherein the polypeptide comprises an amino acid that is a polar
amino acid other than K or R at position 423, as determined with reference to SEQ ID NO:1, and wherein the polypeptide has
chondrogenic activity.
US Pat. No. 9,296,826

ANTIBODIES AND METHODS FOR WNT PATHWAY-RELATED DISEASES

NOVARTIS AG, Basel (CH)

1. An isolated antibody or antigen binding fragment thereof comprising one or more polypeptides that specifically binds to
the extracellular domain of the transmembrane E3 ubiquitin ligase ZNRF3, wherein said one or more polypeptides are selected
from the group consisting of:
(a) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 31; a second region having a peptide sequence of SEQ ID NO: 32; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 33; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 34; a second region having a peptide sequence of SEQ ID NO: 35; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 36; and

(b) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 37; a second region having a peptide sequence of SEQ ID NO: 38; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 39; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 40; a second region having a peptide sequence of SEQ ID NO: 41; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 42; and

(c) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 43; a second region having a peptide sequence of SEQ ID NO: 44; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 45; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 46; a second region having a peptide sequence of SEQ ID NO: 47; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 48; and

(d) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 49; a second region having a peptide sequence of SEQ ID NO: 50; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 51; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 52; a second region having a peptide sequence of SEQ ID NO: 53; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 54; and

(e) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 55; a second region having a peptide sequence of SEQ ID NO: 56; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 57; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 58; a second region having a peptide sequence of SEQ ID NO: 59; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 60; and

(f) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 61; a second region having a peptide sequence of SEQ ID NO: 62; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 63; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 64; a second region having a peptide sequence of SEQ ID NO: 65; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 66; and

(g) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 91; a second region having a peptide sequence of SEQ ID NO: 92; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 93; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 94; a second region having a peptide sequence of SEQ ID NO: 95; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 96; and

(h) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 97; a second region having a peptide sequence of SEQ ID NO: 98; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 99; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 100; a second region having a peptide sequence of SEQ ID NO: 101; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 102; and

(i) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 103; a second region having a peptide sequence of SEQ ID NO: 104; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 105; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 106; a second region having a peptide sequence of SEQ ID NO: 107; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 108; and

(j) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 109; a second region having a peptide sequence of SEQ ID NO: 110; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 111; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 112; a second region having a peptide sequence of SEQ ID NO: 113; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 114; and

(k) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 115; a second region having a peptide sequence of SEQ ID NO: 116; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 117; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 118; a second region having a peptide sequence of SEQ ID NO: 119; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 120; and

one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 121; a second region having a peptide sequence of SEQ ID NO: 122; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 123; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 124; a second region having a peptide sequence of SEQ ID NO: 125; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 126; and

(m) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 127; a second region having a peptide sequence of SEQ ID NO: 128; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 129; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 130; a second region having a peptide sequence of SEQ ID NO: 131; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 132; and

(n) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 133; a second region having a peptide sequence of SEQ ID NO: 134; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 135; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 136; a second region having a peptide sequence of SEQ ID NO: 137; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 138; and

(o) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 139; a second region having a peptide sequence of SEQ ID NO: 140; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 141; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 142; a second region having a peptide sequence of SEQ ID NO: 143; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 144; and

(p) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 145; a second region having a peptide sequence of SEQ ID NO: 146; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 147; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 148; a second region having a peptide sequence of SEQ ID NO: 149; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 150; and

(q) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 151; a second region having a peptide sequence of SEQ ID NO: 152; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 153; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 154; a second region having a peptide sequence of SEQ ID NO: 155; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 156; and

(r) one or more polypeptides having six regions, comprising:
(i) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 157; a second region having a peptide sequence of SEQ ID NO: 158; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 159.; and

(ii) three regions from the amino terminus of the antibody or antigen binding fragment to the carboxyl terminus: a first region
of having a peptide sequence of SEQ ID NO: 160; a second region having a peptide sequence of SEQ ID NO: 161; and a third region
having a peptide sequence selected from the group consisting of SEQ ID NO: 162.

US Pat. No. 9,296,754

COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES

Novartis AG, Basel (CH)

1. A compound of Formula I:
or a pharmaceutically acceptable salt, or stereoisomer thereof; wherein
L1 is —C(O)—or —S(O)2—;

R1 is selected from nitro, C1-4alkyl, C1-6alkoxy, amino, C5-9heteroaryl, C3-6cycloalkyl and C4-6heterocycloalkyl, each of which is optionally substituted by 1-2substituents independently selected from halo, cyano, amino,
C1-4alkyl, haloC1-4alkyl, C1-6alkoxy, and C1-4alkylcarbonyl;

R3 is selected from hydrogen, halo, cyano, C1-4alkyl and haloC1-4alkyl;

R4 is selected from hydrogen, C1-4alkyl, haloC1-4alkyl, and —C(O)R10, wherein R10 is hydroxy, C1-4alkyl, C1-4alkoxy, amino, C1-4alkylamino, C3-6cycloalkyl and C4-6heterocycloalkyl, each of which is optionally substituted by 1-2substituents independently selected from hydroxyl, halo and
C1-4alkyl;

L3 is a bond, phenylene, or C5-6heteroarylene;

R0 is selected from hydroxyl, halo, nitro, —N?CHN(CH3)2, C1-4alkyl, C1-4alkoxy, —NR2aR2b, —NR5C(O) R6, —NR5S(O)2R8, C3-6cycloalkyl, C4-6heterocycloalkyl, C4-6heterocycloalkenyl, phenyl and C5-6heteroaryl; wherein

the C1-4alkyl or C1-4alkoxy is optionally substituted by 1-2 substituents independently selected from C1-4alkoxy, amino, phenyl and C5-6heteroaryl;

wherein the phenyl or C5-6heteroaryl is optionally further substituted by halo or C1-4alkyl;

the C3-6cycloalkyl, C4-6heterocycloalkyl, C4-6heterocycloalkenyl, phenyl and C5-6heteroaryl of R0 is optionally substituted with halo, oxo, C1-4alkyl, hydroxyC1-4alkyl, haloC1-4alkyl, C1-4alkoxy, amino, C1-4alkylamino, and —(CH2)1-4NRaRb, wherein Ra and Rb are each independently hydrogen, C1-4alkyl or C3-6cycloalkyl;

R2a is hydrogen or C1-4alkyl;

R2b is selected from hydrogen, C1-4alkyl, wherein the alkyl is optionally substituted by amino, C4-6heterocycloalkyl, phenyl or C5-6heteroaryl, wherein the C4-6heterocycloalkyl, phenyl or C5-6heteroaryl is further optionally substituted by hydroxyl, halo or C1-4alkyl;

R5 is hydrogen or C1-4alkyl;

R6 is selected from hydrogen, Cl-6alkyl, C1-4alkoxy, C3-6cycloalkoxy, amino, C3-6cycloalkyl, C5-6heterocycloalkyl, and C5-6heteroaryl, wherein

the C1-6alkyl, C1-4alkoxy, C3-6cycloalkoxy, and amino of R6 are each optionally substituted by 1-2 substituents independently selected from halo, hydroxy, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, —NR9aR9b, C3-6cycloalkyl, C5-6heterocycloalkyl, and C5-6heteroaryl, wherein R9a is hydrogen or C1-4alkyl and R9b is selected from hydrogen, C1-4alkyl, C1-4alkylcarbonyl and the C5-6heterocycloalkyl and C5-6heteroaryl substituents are each further optionally substituted by 1-2 substituents independently selected from hydroxyl,
C1-4alkyl and C1-4alkoxycarbonyl,

the C5-6heteroaryl of R6 is optionally substituted with 1-2 substituents selected from hydroxy, C1-4alkyl, and C1-4alkoxycarbonyl,

the C3-6cycloalkyl or C5-6heterocycloalkyl of R6 are each independently optionally substituted by 1-2 substituents independently selected from halo, cyano, hydroxy, C1-4alkyl, haloC1-4alkyl, C1-4alkoxylC1-4alkyl, aminocarbonyl, C1-4alkoxycarbonyl, and C1-4alkoxycarbonylaminoC1-4alkyl, and

R8 is C1-4alkyl or C1-4alkylamino.

US Pat. No. 9,585,561

OPHTHALMIC SURGICAL MICROSCOPE WITH ADAPTIVE OPTICS FOR OPTICAL WAVEFRONT COMPENSATION

Novartis AG, Basel (CH)

1. An ophthalmic surgical microscope disposed in an optical path between an observer and a subject, comprising:
a first light source configured to project a first light beam at an eye of the observer, a reflection of the first light beam
from the eye of the observer including a first reflection wavefront;

a first wavefront sensor disposed in an optical path of a reflection of the first light beam from the eye of the observer,
the optical path of the reflection at least partially overlapping the optical path between the observer and the subject, the
first wavefront sensor being configured to determine aberrations corresponding to the eye of the observer in a first reflection
wavefront of the reflection of the first light beam;

a second light source configured to project a second light beam at an eye of the subject;
a second wavefront sensor disposed in an optical path of a reflection of the second light beam, the second wavefront sensor
being configured to determine aberrations corresponding to the eye of the subject in a second reflection wavefront of the
reflection of the second light beam, the second wavefront sensor distinct from the first wavefront sensor;

an adaptive optical element disposed in the optical path between the observer and the subject, the adaptive optical element
being configured to modify the phase of incident light to compensate for the aberrations in the first reflection wavefront
and the second reflection wavefront in response to a plurality of control signals; and

a computing device in communication with the first wavefront sensor and the adaptive optical element, the computing device
being configured to:

generate a first control signal to compensate for the aberrations in the first reflection wavefront;
provide the first control signal to the adaptive optical element;
generate a second control signal to compensate for the aberrations in the second reflection wavefront;
provide the second control signal to the adaptive optical element.
US Pat. No. 9,428,583

COMPOSITIONS AND METHODS OF USE FOR THERAPEUTIC LOW DENSITY LIPOPROTEIN-RELATED PROTEIN 6 (LRP6) MULTIVALENT ANTIBODIES

NOVARTIS AG, Basel (CH)

1. An antibody or fragment thereof that binds to a low density lipoprotein-related 6 (LRP6) wherein the antibody or fragment
thereof comprises a heavy chain variable region CDR1 of SEQ ID NO: 1; a heavy chain variable region CDR2 of SEQ ID NO: 2;
a heavy chain variable region CDR3 of SEQ ID NO: 3; a light chain variable region CDR1 of SEQ ID NO: 4; a light chain variable
region CDR2 of SEQ ID NO: 5; and a light chain variable region CDR3 of SEQ ID NO: 6.
US Pat. No. 9,393,300

IMMUNOGENIC COMPLEXES OF POLYANIONIC CARBOMERS AND ENV POLYPEPTIDES AND METHODS OF MANUFACTURE AND USE THEREOF

Novartis AG, Basel (CH)

17. A method of generating an immune response in a subject, comprising administering to said subject an immunogenic composition
comprising an Env polypeptide complexed to a polyanionic carbomer polymer, thereby generating the immune response to the Env
polypeptide.
US Pat. No. 9,358,236

COMBINATIONS OF THERAPEUTIC AGENTS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES

Novartis AG, Basel (CH)

1. A method for the treatment of Huntington's disease in a subject in need of such treatment, which method comprises administering
to such subject a synergistically effective amount of a combination of an allosteric mTOR inhibitor and a catalytic mTOR inhibitor,
wherein the allosteric mTOR inhibitor is RAD001 and the catalytic mTOR inhibitor is BEZ235.
US Pat. No. 9,328,174

CHEMOKINE RECEPTOR BINDING POLYPEPTIDES

Novartis AG, Basel (CH)

1. A polypeptide comprising the amino acid sequence of SEQ ID NO:221 and a C-terminal extension consisting of two alanine
residues.

US Pat. No. 9,272,424

GRIPPER FOR A CONTACT LENS AND PROCESS FOR TRANSPORTING A CONTACT LENS

NOVARTIS AG, (CH)

1. A gripper (1) for a contact lens (L) comprising a gripper head (2) having a bearing surface (21) for the contact lens (L) to adhere thereto, and further comprising an ejector (23, 24) for mechanically displacing the contact lens (L), at least partially, away from the bearing surface (21); and wherein the ejector comprises a plurality of elector pins (23), the elector being actuatable such that the ejector pins (23) are movable from a rest position in which the ejector pins (23) do not interfere with the bearing surface (21), to an ejection position in which the ejector pins (23) axially protrude beyond the bearing surface (21), and vice versa.
US Pat. No. 9,271,941

PHARMACEUTICAL COMPOSITION

Novartis AG, Basel (CH)

1. A pharmaceutical tablet comprising:
a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide
dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein,

b) the tablet contains from about 25% to about 89% by weight of one or more excipients, where the excipients are substantially
free of water.

US Pat. No. 9,239,409

SILICONE HYDROGEL LENS WITH A CROSSLINKED HYDROPHILIC COATING

Novartis AG, Basel (CH)

1. A water-soluble and thermally-crosslinkable hydrophilic polymeric material, comprising:
(a) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine
or polyamidoamine;

(b) from about 5% to about 80% by weight of second polymer chains derived from a copolymer which is a polymerization product
of a composition comprising about 50% or less by weight of one or more reactive vinylic monomer and (2) at least one phosphorylcholine-containing
vinylic monomer, wherein said one or more reactive vinylic monomers are vinylic monomers having a carboxyl group or an amino
group, wherein the second polymer chains are covalently attached to the first polymer chains through one or more covalent
linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and
one amino or carboxyl group of the copolymer; and

(c) azetidinium groups which are parts of the first polymer chains or pendant groups covalently attached to the first polymer
chains.

US Pat. No. 9,227,746

METHOD AND APPARATUS FOR MANUFACTURING OPHTHALMIC LENSES

Novartis AG, Basel (CH)

1. A method for manufacturing contact lenses comprising the steps of:
molding in a mass production process a plurality of lenses having different properties; and
transferring the molded lenses that have the same properties to a respective intermediate buffer so as to store therein a
bulk of lenses having the same properties, wherein the intermediate buffer comprises a tube-like container, wherein the diameter
of tube-like container is chosen such that the lenses are stored therein one above the other, wherein the tube-like container
is closed at one end and is open at the other end to allow for the storage of contact lenses with a suitable amount of preserving
liquid contained therein to prevent the lenses from drying and to allow for the molded lenses to sink downwardly and self-orient
during sinking with their convex surface facing downwards.

US Pat. No. 9,220,768

DECREASING POTENTIAL IATROGENIC RISKS ASSOCIATED WITH INFLUENZA VACCINES

Novartis AG, Basel (CH)

1. A process for preparing an influenza vaccine or an influenza vaccine antigen from a culture of a Vero cell line, comprising
(i) testing for the presence of a JC Polyomavirus (a) during manufacture of the vaccine and/or (b) in a seed, the vaccine,
the culture, or combinations thereof, (ii) culturing influenza virus in the culture of the Vero cell line, and (iii) formulating
the vaccine manufactured from the influenza virus cultured in the culture of the Vero cell line, wherein the testing is performed
before, during and/or after the formulating.

US Pat. No. 9,199,973

BICYCLIC HETEROAROMATIC COMPOUNDS AS PROTEIN TYROSINE KINASE INHIBITORS

Novartis AG, Basel (CH)

1. A method of treating breast cancer by administering a pharmaceutical formulation presented in unit dose form comprising
the compound of formula

as an active ingredient,
wherein said active ingredient is present within said unit dose form in an amount from 0.5 mg to 1 g.

US Pat. No. 9,151,873

ACTINICALLY-CROSSLINKABLE AMPHIPHILIC PREPOLYMERS

Novartis AG, (CH)

1. An actinically-crosslinkable prepolymer, comprising; at least one polysiloxane segment; at least one polyoxazoline segment
which is a divalent radical of
in which 1R is hydrogen, methyl or ethyl group, and q is an integer from 3 to 200;
and two terminal ene groups, wherein the prepolymer is defined by formula (1)

in which
B1, B2, B3, B4, and B5 independent of one another are a linear hydrophilic polymer chain of

in which 1R is hydrogen, methyl or ethyl group, A? is C1-C4 alkoxy and q is an integer from 3 to 200, and have a weight average molecular weight of about 10000 Daltons or less;
d1, d2, d3 independent of one another are an integer from 0 to 20 and (d1+d2+d3)?1;
D1, D2, D3, and D4 independently of one other are a divalent group of formula (2)


in which A1 and A2 independent of each other are a direct bond, a linear or branched C1-C10 alkylene radical, —(CH2CH2O)r1—CH2CH2— in which r1 is an integer of 1 to 20, or a C1-C7 alkyleneoxy-C1-C7 alkylene divalent radical, R1, R2, R3, R4, R5, R6, R7, and R8, independently of one another, are C1-C10 alkyl, C1-C4 alkyl- or C1-C4-alkoxy-substituted phenyl, C1-C10 fluoroalkyl, C1-C10 fluoroether, C6-C18 aryl radical, -alk-(OCH2CH2)n—OR9 in which alk is C1-C6-alkylene divalent radical, R9 is hydrogen or C1-C5 alkyl and n is an integer from 1 to 10, m and p independently of each other are an integer of from 0 to 100 and (m+p) is from
1 to 100;

e1, e2, e3, e4, e5 independent of one other are an integer from 0 to 3 and (e1+e2+e3+e4+e5)?1;
L1, L2, L3, L4, and L5 independent of one another are a direct bond or a divalent radical of —Z1—X1—Z2—X2—Z3—X3—Z4—

in which
X1, X2, and X3 independent of one other are a linkage selected from the group consisting of a direct bond, —O—, —NR?— in which R? is H or
C1-C4 alkyl, —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —O—C(O)—NH—, —S—, —NH—C(O)—O—, —C(O)—O—, —O—C(O)—, —NH—C(O)—NH—Z0—NH—C(O)—NH—, —O—C(O)—NH—Z0—NH— C(O)—O—, —O—C(O)—NH—Z0—NH—C(O)—NH—, and —NH—C(O)—NH—Z0—NH—C(O)—O—, Z0 is a linear or branched C2-C12 alkylene divalent radical or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical optionally containing therein one or more linkages of —O—, —NR?—
with R? as defined above, —S— and —C(O)—, Z1, Z2, Z3, and Z4 independent of one other are a direct bond, a linear or branched C1-C12 alkylene divalent radical optionally containing therein one or more linkages of —O—, —NR?—, —S— and —C(O)—, —(CH2CH2O)r1—CH2CH2— with r1 as defined above, or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical optionally containing therein one or more linkages of —O—, —NR?—
with R? as defined above, —S— and —C(O)—;

Y1, Y2, Y3, Y4, Y4, Y6, Y7, Y8, Y9, and Y10 each comprise at least one urethane linkage (—O—C(O)—NH—) and independent of each other are a divalent radical of —Z1—X1—Z2—X2—Z3—X3—Z4— as defined above, or a divalent radical of formula (3)


in which
Z1 to Z4 and X1 to X3 are as defined above,

X4, X5, and X6 independent of one other are a linkage selected from the group consisting of a direct bond, —O—, —NR?— with R? as defined
above, —C(O)—NH—, —NH—C(O)—, —NH—C(O)—NH—, —O—C(O)—NH—, —S—, —NH—C(O)—O—, —C(O)—O—, —O—C(O)—, —NH—C(O)—NH—Z0—NH—C(O)—NH— with Z0 as defined above, —O—C(O)—NH—Z0—NH—C(O)—O— with Z0 as defined above, —O—C(O)—NH—Z0—NH—C(O)—NH— with Z0 as defined above, and —NH—C(O)—NH—Z0—NH—C(O)—O— with Z0 as defined above,

Z5, Z6, Z7, and Z8 independent of one other are a direct bond, a linear or branched C1-C12 alkylene divalent radical optionally containing therein one or more linkages of —O—, —NR?— with R? as defined above, —S— and
—C(O)—, —(CH2CH2O)r1—CH2CH2— with r1 as defined above, or a C5-C45 cycloaliphatic or aliphatic-cycloaliphatic divalent radical optionally containing therein one or more linkages of —O—, —NR?—
with R? as defined above, —S— and —C(O)—,

1R is hydrogen, methyl or ethyl group, and

q is an integer from 3 to 200;
T1, T2, T3, T4, and T5 independent of one another are an aliphatic or cycloaliphatic or aliphatic-cycloaliphatic trivalent radical which has up to
15 carbon atoms and can be interrupted by —O—, —NR?— with R? as defined above, —C(O)— and/or —S—; and

Q is defined by any one of formula (I)-(III)

in which (i) R10-R17, independent of each other, are hydrogen, C1-C10 alkene divalent radical, C1-C10 alkyl, or —(R18)a1—(X7)b1—R19 in which R18 is C1-C10 alkene divalent radical, X7 is an ether linkage, a urethane linkage, a urea linkage, an ester linkage, an amid linkage, or carbonyl, R19 is hydrogen, a single bond, amino group, carboxylic group, hydroxyl group, carbonyl group, C1-C12 aminoalkyl group, C1-C18 alkylaminoalkyl group, C1-C18 carboxyalkyl group, C1-C18 hydroxyalkyl group, C1-C18 alkylalkoxy group, C1-C12 aminoalkoxy group, C1-C18 alkylaminoalkoxy group, C1-C18 carboxyalkoxy group, or C1-C18 hydroxyalkoxy group, a1 and b1 independent of each other is zero or 1, q1 is 1, provided that only one of R10-R17 are divalent radicals; (ii) R20-R25, independent of each other, are hydrogen, C1-C10 alkene divalent radical, C1-C10 alkyl, or —(R18)a1—(X7)b1—R19 in which R18, R19, X7, a1, and b1 are as defined above, provided that at least one of R20-R25 are divalent radicals, t1 and t2 independent of each other are integer number from 0 to 9, provided that (t1+t2) is an integer
number from 2 to 9;

(iii) R26 is hydrogen, or C1-C10 alkyl; R27 and R28 independent of each other are hydrogen, C1-C10 alkyl, or —(R18)a1—(X7)b1—R19 in which R18, R19, X7, a1, and b1 are as defined above, R29 is a C1-C10 alkene divalent radical.

US Pat. No. 9,517,014

OCT PROBE WITH PIVOTING FIBER

Novartis AG, Basel (CH)

1. An OCT probe for imaging patient tissue, comprising:
a cannula having a cannula axis;
a selectively displaceable light-carrying optical fiber disposed within the cannula and having a distal end, the optical fiber
being adapted to emit light from the distal end;

an actuation system arranged to displace the optical fiber within the cannula, the actuation system comprising:
a driver actuatable to displace a portion of the optical fiber, the driver acting in an angled direction relative to the cannula
axis; and

a pivot feature operably engaged with the optical fiber, the optical fiber pivotable about the pivot feature in response to
a displacement of the portion of the optical fiber by the driver; and

a stiffening tube disposed about the optical fiber and separating the optical fiber and the pivot feature, the stiffening
tube directly engaging the pivot feature in a pivot relationship,

wherein the driver is spaced from the pivot feature along the optical fiber by a first distance, and wherein the distal end
of the optical fiber is spaced from the pivot feature by a second distance greater than the first distance.

US Pat. No. 9,504,747

LIPIDS AND LIPID COMPOSITIONS FOR THE DELIVERY OF ACTIVE AGENTS

Novartis AG, Basel (CH)

1. A compound of formula (I):

wherein:
L is C1-6 alkylene, *-C1-4 alkylene-L2-, or *-C1-4 alkylene-L2-C1-4 alkylene-, wherein in the * denotes attachment of the moiety to the NR1R2 group;

L2, attached in either direction, is —C(O)O—;
R1 and R2 are each independently optionally substituted C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted with one or two substituents each independently selected from the group consisting of: OH,
C1-3 alkoxy, COOH, and COO—C1-4 alkyl,

R3 and R4 are each independently chain:

(b) —Z1—Rb—Z2—Ra,

wherein Z1, attached in either direction, is each independently —O— or —C(O)O—;

Z2, attached in either direction, is —C(O)O—;

Ra is C2-22 alkyl, C2-22 alkenyl, or C2-22 alkynyl;

each Rb is independently C1-20 alkylene, C2-20 alkenylene, or C2-20 alkynylene;

provided that chain (b) has at least 12 carbon atoms and no more than 30 carbon atoms;
X is CR6; and

R6 is H, halo, C1-6 alkyl, or R4; or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,474,762

TRIAZOLOPYRIDINE COMPOUNDS

NOVARTIS AG, Basel (CH)

1. A method of treating a c-Met related disorder or disease in a subject wherein the method comprises administering to the
subject in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein
said compound is formula (I)

wherein
R1 is selected from

(i) pyrazolyl, optionally substituted by (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted by one OH group, and

(ii) —CR9?N—O—R10, wherein

R9 is hydrogen or (C1-C4)alkyl; and,

R10 is hydrogen or (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted by one OH group;

R2 is selected from hydrogen and halo; and

R3 is —(C0-C2)alkyl-heterocyclyl1,

wherein heterocyclyl1 is a 4, 5, 6, 7 or 8 membered saturated or partially unsaturated N-heterocyclic ring which is attached via the N-atom and
optionally comprises additional 1 or 2 ring heteroatoms independently selected from N, O and S in a position or positions
other than adjacent to the linking N atom, wherein the total number of ring S-atoms does not exceed 1, and the total number
of ring O-atoms does not exceed 1,

wherein the N-heterocyclic ring is optionally substituted
(i) by one, two or three substituents independently selected from —OH, halo, —CONH2, —CONH(C1-C4)alkyl, —CON((C1-C4)alkyl)2, —COO(C1-C4)alkyl, —NH2, —NH—COO(C1-C4)alkyl, —NH(C1-C3)alkyl, —N((C1-C3)alkyl)2, —O(C1-C4)alkyl, heterocyclyl2, —(C3-C8)cycloalkyl, phenyl and (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted by one, two or three substituents independently selected from OH and halo; wherein heterocyclyl2 is a 5 or 6-membered saturated or partially unsaturated monocyclic group comprising 1 or 2 ring heteroatoms independently
selected from N and O, wherein the total number of ring O atoms does not exceed 1, and which is optionally substituted by
one or two substituents independently selected from OH and (C1-C4)alkyl; or

(ii) by two groups which are attached to the same carbon atom and are combined into a cyclic 4, 5, 6, or 7 membered saturated
or partially unsaturated ring system optionally comprising 1 or 2 ring heteroatoms independently selected from N, O and S,
wherein the total number of ring S atoms does not exceed 1, which cyclic ring system is optionally substituted by —OH or (C1-C4)alkyl;

and wherein the substituted N-heterocyclic ring is optionally substituted by one or two additional (C1-C4)alkyl groups.

US Pat. No. 9,402,534

TWO DIMENSIONAL FORWARD SCANNING PROBE

NOVARTIS AG, Basel (CH)

1. An optical scanning probe, comprising:
a handle, configured to receive a light beam from a light guide;
a cannula, extending from a distal end of the handle;
a fiber, positioned partially inside the handle and partially inside the cannula, configured to guide the received light beam
toward a distal end of the cannula;

a rotating scanner, rotatably positioned at least partially inside the cannula and configured to house a proximal portion
of the fiber; and

a deflecting scanner, movably coupled to a distal end of the rotating scanner, configured to deflect a distal portion of the
fiber,

wherein the distal portion of the fiber is configured to emit and scan the guided light in a target region.
US Pat. No. 9,382,326

COMPOSITIONS AND METHODS OF USE FOR THERAPEUTIC ANTIBODIES

Novartis AG, Basel (CH)

1. An isolated antibody or antigen-binding portion thereof comprising:
(a) an HCDR1 comprising an amino acid sequence of SEQ ID NO: 3;
(b) an HCDR2 comprising an amino acid sequence with amino acid substitutions at the 9th, 11th, or both the 9th and 11th amino acids of SEQ ID NO: 10;

(c) an HCDR3 comprising an amino acid sequence with amino acid substitutions at the 2nd or 12thamino acids of SEQ ID NO: 17;

(d) an LCDR1 comprising an amino acid sequence with amino acid substitutions at the 5th, 7th, 8th, 9th or all of these amino acids of SEQ ID NO: 24,

(e) an LCDR2 comprising an amino acid sequence of SEQ ID NO: 31;and
(f) an LCDR3 comprising an amino acid sequence with amino acid substitutions at the 3rd, 8th, or both the 3rd and 8th amino acids of SEQ ID NO: 38;

and wherein said antibody or antigen-binding portion thereof binds to the BAFFR polypeptide with a KD of 100 nM or less and inhibits BLyS induced human B cell proliferation with an IC50 around 10 nM or less.

US Pat. No. 9,365,506

COMPOUNDS AND COMPOSITIONS AS TLR2 AGONISTS

NOVARTIS AG, Basel (CH)

1. A compound of Formula (I), or pharmaceutically acceptable salt thereof:

wherein:
R1 is H, —C(O)—C7-C18alkyl or —C(O)—C1-C6alkyl;

R2 is C7-C18alkyl;

R3 is C7-C18alkyl;

L1 is —CH2OC(O)—;

L2 is —OC(O)—;

R4 is -L3R5 or -L4R5;

R5 is —P(O)(OR7)2, —NR7C(O)L3R8, —NR7C(O)L4R8, —OL3R6, —C(O)NR7L3R8, —C(O)NR7L4R8, —S(O)2OR7, —OS(O)2OR7, C1-C6alkyl, a C6aryl, a C10aryl, a C14aryl, 5 to 14 ring membered heteroaryl containing 1 to 3 heteroatoms selected from O, S and N, C3-C8cycloalkyl or a 5 to 6 ring membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, S and N, wherein the
aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R5 are each unsubstituted or the aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R5 are each substituted with 1 to 3 substituents independently selected from —OR9, —OL3R6, —OL4R6, —OR7, and —C(O)OR7;

L3 is a C1-C10alkylene, wherein the C1-C10alkylene of L3 is substituted with 1 to 4 R6 groups, or the C1-C10alkylene of L3 is substituted with 2 C1-C6alkyl groups on the same carbon atom which together, along with the carbon atom they are attached to, form a C3-C8cycloakyl;

L4 is —((CR7R7)pO)q(CR10R10)p— or —(CR11R11)((CR7R7)pO)q(CR10R10)p—, wherein each R11 is a C1-C6alkyl groups which together, along with the carbon atom they are attached to, form a C3-C8cycloakyl;

each R6 is independently selected from halo, —OR7, —N(R7)2, —C(O)N(R7)2, —P(O)(OR7)2, a C6aryl, a C10aryl and a C14aryl;

each R7 is independently selected from H and C1-C6alkyl;

R8 is —SR7, —C(O)OH, —P(O)(OR7)2, or a 5 to 6 ring membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O and N;

R9 is phenyl;

each R19 is independently selected from H and halo;

each p is independently selected from 1, 2, 3, 4, 5 and 6, and
q is 1, 2, 3 or 4.
US Pat. No. 9,358,278

CAPSULAR POLYSACCHARIDE SOLUBILISATION AND COMBINATION VACCINES

Novartis AG, Basel (CH)

1. A process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitating the polysaccharide
using one or more cationic detergents without an inert porous support, followed by (b) solubilising the precipitated polysaccharide
using an alcohol, wherein the bacterial capsular polysaccharide is from Neisseria meningitidis, Haemophilus influenzae or Streptococcus pneumoniae, wherein the process does not comprise precipitating the polysaccharide using one or more cationic detergents on an inert
porous support.

US Pat. No. 9,283,114

SYSTEMS AND METHODS FOR PRIMING A MICROFLUIDIC CHAMBER

Novartis AG, Basel (CH)

1. An intraocular device for implantation in an eye of a patient, comprising:
an inlet tube;
an outlet tube;
a microfluidic chamber comprising:
a chamber inlet coupled to the inlet tube;
a chamber outlet coupled to the outlet tube; and
three fluidic barriers configured such that a front of a fluid injected into the microfluidic chamber coincides with each
fluidic barrier before the fluid passes beyond the fluidic barrier; wherein the first fluidic barrier comprises a linear wall
portion, the second fluidic barrier comprises an arcuate wall portion with a first radius of curvature, and the third fluidic
barrier comprises an arcuate wall portion with a second radius of curvature.

US Pat. No. 9,272,040

5-CNAC AS ORAL DELIVERY AGENT FOR PARATHYROID HORMONE FRAGMENTS

Novartis AG, Basel (CH)

3. A method of treating osteoporosis comprising orally administering to a patient in need of said treatment a pharmaceutical
composition in solid dosage form comprising a therapeutically effective amount of recombinant PTH (1-34) and 5-CNAC disodium
salt.

US Pat. No. 9,227,968

METHOD OF TREATMENT OR PROPHYLAXIS OF INFLAMMATORY PAIN

Novartis AG, Basel (CH)

1. A method for the treatment of inflammatory pain in a subject in need thereof, comprising administering to the subject an
effective amount of an AT2 receptor antagonist,
wherein the AT2 receptor antagonist is selected from compounds represented by the formula (IV):


wherein:
R10 is selected from H, halogen, C1-6alkyl, phenyl, substituted phenyl, substituted C1-6alkyl, or C1-6alkoxy,

R9 is selected from —NR13R14, wherein R13 and R14 are independently selected from C1-6alkyl, substituted C1-6alkyl, aryl, substituted aryl, benzyl, substituted benzyl, C1-6alkylaryl, substituted C1-4alkylaryl, OH, or NH2; a five or six membered, saturated or unsaturated, substituted or unsubstituted, carbocyclic or heterocyclic ring selected
from:


V is selected from CH or a nitrogen atom,
Y is selected from sulfur, oxygen or N—RN,

RN is selected from H, C1-6alkyl, substituted C1-6alkyl, aryl, substituted aryl, benzyl, substituted benzyl, C1-4alkylaryl, substituted C1-4alkylaryl, OH, or NH2,

G is a five or six membered homoaromatic or heterocyclic, unsaturated, substituted ring selected from the following rings
systems:


where the symbol ‘*’ indicates the bond shared between the fused rings ‘A’ and ‘G’,
W is selected from sulfur, oxygen and N—RN,

R5 is selected from C1-6alkyl, phenyl, substituted phenyl, substituted C1-6alkyl, or C1-6alkoxy,

R6 and R8 are independently selected from H, C1-6alkyl, substituted C1-6alkyl, C1-6alkoxy, substituted C1-6alkoxy, phenyl, phenyloxy, benzyl, benzyloxy, benzylamino, biphenyl, substituted biphenyl, biphenyloxy, substituted biphenyloxy,
naphthyl, substituted naphthyl, provided that one of R6 or R8 is not hydrogen, and

R7 is selected from phenyl, substituted phenyl, benzyl, substituted benzyl, biphenyl, substituted biphenyl, biphenylmethylene,
substituted biphenylmethylene, naphthyl, substituted naphthyl, naphthylmethylene, and substituted naphthylmethylene, or a
pharmaceutically acceptable salt thereof, which is optionally in the form of a composition comprising a pharmaceutically acceptable
carrier and/or diluent.

US Pat. No. 10,030,063

PRODUCTION OF THERAPEUTIC PROTEINS IN GENETICALLY MODIFIED MAMMALIAN CELLS

Novartis AG, Basel (CH)

1. A method of producing a protein in a mammalian cell, wherein the cell has been modified to be deficient in expression of a cognate receptor of the protein and has been transformed with a nucleic acid encoding the protein, the method comprising the steps of:(a) Cultivating the cell under conditions allowing the expression of the protein; and
(b) Harvesting the protein from the cell cultivated in step (a),wherein the cell produces at least 1.5-fold more protein than a cell in which the expression of the receptor has not been modified, wherein the protein is Insulin like growth factor 1 (IGF-1) protein or a variant thereof and the receptor is IGF-1 receptor (IGF-1R).

US Pat. No. 9,681,793

SURGICAL PROBE WITH INTERLOCKING ATTACHMENT

Novartis AG, Basel (CH)

1. A method of manufacturing an optical probe for use in ophthalmic procedures, comprising:
positioning a cannula around a distal portion of a ferrule, wherein an optical fiber extends at least partially through the
ferrule towards an optical element disposed within a distal portion of the cannula;

coupling the cannula to the ferrule by applying laser energy to the cannula; and
generating engaged deformations in the cannula and the ferrule.

US Pat. No. 9,580,426

COMPOUNDS THAT EXPAND HEMATOPOIETIC STEM CELLS

Novartis AG, Basel (CH) ...

1. A compound of Formula Ia:

in which:
L is selected from —NR5a(CH2)2-3, —NR5a(CH2)2NR5b—, —NR5a(CH2)2S—, —NR5aCH2CH(OH)— and —NR5aCH(CH3)CH2—; wherein R5a and R5b are independently selected from hydrogen and C1-4alkyl;

R1 is selected from thiophenyl, 1H-benzoimidazolyl, isoquinolinyl, 1H-imidazopyridinyl, benzothiophenyl, pyrimidinyl, pyridinyl,
pyrazinyl, pyridazinyl, and thiazolyl; wherein

said thiophenyl, 1H-benzoimidazolyl, isoquinolinyl, 1H-imidazopyridinyl, benzothiophenyl, pyrimidinyl, pyridinyl, pyrazinyl,
pyridazinyl, or thiazolyl of R1 can be optionally substituted by 1 to 3 radicals independently selected from cyano, hydroxy, C1-4alkyl, C1-4alkoxy, halo, halo-substituted-C1-4alkyl, halo-substituted-C1-4alkoxy, amino, —C(O)R8a, —S(O)0-2R8a, —C(O)OR8a and —C(O)NR8aR8b; wherein R8a and R8b are independently selected from hydrogen and C1-4alkyl;

R2 is selected from —S(O)2NR6aR6b, —NR6aC(O)R6b—, —NR6aC(O)NR6bR6c, phenyl, 1H-pyrrolopyridin-3-yl, 1H-pyrrolopyridin-5-yl, 1H-indolyl thiophenyl, pyridinyl, 1H-1,2,4-triazolyl, 2-oxoimidazolidinyl,
1H-pyrazolyl, 2-oxo-2,3-dihydro-1H-benzoimidazolyl and 1H-indazolyl; wherein

R6a, R6b and R6c are independently selected from hydrogen and C1-4alkyl; and

said phenyl, 1H-pyrrolopyridin-3-yl, 1H-pyrrolo[2,3-b]pyridin-5-yl, 1H-indolyl, thiophenyl, pyridinyl, 1H-1,2,4-triazolyl,
2-oxoimidazolidinyl, 1H-pyrazolyl, 2-oxo-2,3-dihydro-1H-benzoimidazolyl or 1H-indazolyl of R2 is optionally substituted with 1 to 3 radicals independently selected from hydroxy, halo, methyl, methoxy, amino, —O(CH2)2NR7aR7b, —S(O)2NR7aR7b, —OS(O)2NR7aR7b and —NR7aS(O)2R7b; wherein R7a and R7b are independently selected from hydrogen and C1-4alkyl;

R3 is selected from hydrogen, C1-4alkyl and biphenyl; and

R4 is selected from C1-10alkyl, prop-1-en-2-yl, cyclohexyl, cyclopropyl, 2-(2-oxopyrrolidin-1-yl)ethyl, oxetan-2-yl, oxetan-3-yl, benzhydryl, tetrahydro-2H-pyran-2-yl,
tetrahydro-2H-pyran-3-yl, phenyl, tetrahydrofuran-3-yl, and benzyl, (4-pentylphenyl)(phenyl)methyl and 1-(1-(2-oxo-6,9,12-trioxa-3-azatetradecan-14-yl)-1H-1,2,3-triazol-4-yl)ethyl
wherein

said alkyl, cyclopropyl, cyclohexyl, 2-(2-oxopyrrolidin-1-yl)ethyl, oxetan-3-yl, oxetan-2-yl, benzhydryl, tetrahydro-2H-pyran-2-yl,
tetrahydro-2H-pyran-3-yl, phenyl, tetrahydrofuran-3-yl, benzyl, (4-pentylphenyl)(phenyl)methyl or 1-(1-(2-oxo-6,9,12-trioxa-3-azatetradecan-14-yl)-1H-1,2,3-triazol-4-yl)ethyl
can be optionally substituted with 1 to 3 radicals independently selected from hydroxy, C1-4alkyl and halo-substituted-C1-4alkyl;

or a salt thereof.

US Pat. No. 9,504,606

SYSTEMS AND METHODS FOR AN ELECTROCAPILLARY POSITIVE DISPLACEMENT PUMP FOR AN INTRAOCULAR IMPLANT

Novartis AG, Basel (CH)

1. A microfluidic pump for implantation proximate an eye of a patient, the microfluidic pump comprising:
a first substrate that includes a microfluidic actuator, the microfluidic actuator comprising:
a first chamber and a second chamber coupled by a channel;
an electrode in each of the first and second chambers; and
a slug positioned within the channel, the slug being displaceable by applying an electric potential to an electrolytic fluid
in the first and second chambers and the channel;

a first reservoir aligned with the first chamber;
a first membrane portion separating the first reservoir and the first chamber;
a second reservoir aligned with the second chamber;
a second membrane portion separating the second reservoir and the second chamber, wherein each of the first and second reservoirs
has an inlet and an outlet, each of the inlets having a valve that prevents backflow through the inlet, each of the outlets
having a valve that prevents backflow through the outlet;

a second substrate that comprises a pump inlet channel coupling the outlet of the first reservoir to the inlet of the second
reservoir, a first pump outlet channel coupled to the inlet of the first reservoir, and a second pump outlet channel coupled
to the outlet of the second reservoir, wherein the first and second substrates are coupled together, and further wherein the
pump inlet channel, the first pump outlet channel, and the second pump outlet channel are located above the first and second
reservoirs; and

a third substrate, the first and second substrates being coupled by the third substrate, and wherein the third substrate supports
the valves.

US Pat. No. 9,364,141

SHARP FIXATION TARGET

Novartis AG, (CH)

1. Device for stabilizing the constant accommodation of an eye of a patient, comprising:
a target object that is set up to be fixated by the patient along an optical axis;
an optical unit in the light path from the target object to the eye, the optical unit set up along the optical axis in order
to compensate for a spherical ametropia of the eye; and

an additional optical unit in the light path, the additional optical unit set up along the optical axis in order to compensate
for an astigmatic ametropia of the eye, the additional optical unit comprising:

at least two cylindrical lenses, wherein at least one cylindrical lens is rotatably arranged about the optical axis; and
at least four deflection prisms, wherein at least one deflection prism can be adjusted to change the optical path length of
the light path from the target object to the eye.

US Pat. No. 9,353,419

BIOMARKERS FOR IAP INHIBITOR THERAPY

Novartis AG, Basel (CH)

1. A method of analyzing a biological sample of a subject with cancer, comprising determining a level of mRNA expression of
biomarkers TNF and RIPK1 and one or more of the following biomarkers CXLC10, CCL5, NFKBIA, HERC5, CDYL, STK39 and MAPK14 in
the biological sample taken from the subject, wherein the level of expression of the biomarkers in comparison to a control
indicates that the subject has an increased likelihood of response to an Inhibitor of Apoptosis Protein (IAP) inhibitor.

US Pat. No. 9,346,224

METHOD AND APPARATUS FOR TRANSFERRING OBJECTS BETWEEN TWO CONSECUTIVE PROCESSING STATIONS BEING OPERATED WITH DIFFERENT CYCLE SPEEDS

NOVARTIS AG, Basel (CH)

1. An apparatus for transferring contact lenses between two consecutive processing stations being operated at different cycle
speeds, said apparatus comprising:
a transfer device having a fluid means to transport the removed contact lenses from a preceding processing station having
a first cycle speed to a subsequent processing station of said two consecutive processing stations and for introducing them
into a plurality of receptacles consecutively arranged in said subsequent processing station, said receptacles being advanced
through said subsequent processing station with a second cycle speed faster than said first cycle speed, said transfer device
is moved synchronously with and in the direction of advancement of said receptacles in said subsequent processing station,

wherein said preceding processing station is a removal station of a contact lens forming line operated, in which contact lenses
are in contact lens molds comprising male and female mold halves arranged opened in said removal station with each contact
lens resting on one of said male and female mold halves of a respective mold, and wherein said subsequent processing station
to which said contact lenses are transferred is a processing station of a contact lens treatment line,

said transfer device further comprising at least two feed tubes each having an entry port which is aligned with a respective
removal position of said contact lenses in said preceding processing station, each feed tube ending in a respective transfer
nozzle which is arranged in the vicinity of a corresponding one of said receptacles in said subsequent processing station
and which is aligned with an inlet of said corresponding receptacle for introduction of said contact lens into said corresponding
one of said receptacles, said respective transfer nozzle being mounted on a slide movably arranged in a frame in a manner
such that said respective transfer nozzle is moved synchronously with and in the direction of advancement of said receptacles.

US Pat. No. 9,314,464

COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS

Novartis AG, Basel (CH)

1. A method for treating a B-Raf protein kinase mediated cancer, wherein the cancer is selected from the group consisting
of lung carcinoma, pancreatic carcinoma, bladder carcinoma, colon carcinoma, myeloid disorders, prostate cancer, thyroid cancer,
melanoma, adenomas and carcinomas of the ovary, eye, liver, biliary tract, and nervous system, and wherein the method comprises
administering to a subject in need of such treatment an effective amount of a compound of Formula (Ia), or a tautomer, stereoisomer
or pharmaceutically acceptable salt thereof;
wherein the compound of Formula (Ia) is

in which:
Y is selected from N and CR6;

R2, R3, R5 and R6 are independently selected from hydrogen, halo, cyano, C1-4alkyl, halo-substituted-C1-4alkyl, C1-4alkoxy and halo-substituted-C1-4alkoxy; with the proviso that when R5 is fluoro, R3 and R6 are not both hydrogen;

R4 is selected from —R9 and —NR10R11; wherein R9 is selected from C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl and heteroaryl; wherein

said alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl of R9 is optionally substituted with 1 to 3 radicals independently selected from halo, cyano, C1-4alkyl, halo-substituted-C1-4alkyl, C1-4alkoxy and halo-substituted-C1-4alkoxy;

and R10 and R11 are independently selected from hydrogen and R9;

R7 is selected from hydrogen, C1-4alkyl, C3-5cycloalkyl and C3-5heterocycloalkyl;

wherein said alkyl, cycloalkyl or heterocycloalkyl of R7 is optionally substituted with 1 to 3 radicals independently selected from halo, cyano, hydroxyl, C1-4alkyl, halo-substituted-C1-4alkyl, C1-4alkoxy and halo-substituted-C1-4alkoxy.

US Pat. No. 9,278,969

ORGANIC COMPOUNDS

Novartis AG, Basel (CH)

1. A compound of formula (III)

wherein
R is hydrogen, (C1-C4) alkyl, (C2-C4) alkenyl, —C(O)O—R10, or —C(O)N(R11)(R12), said (C1-C4) alkyl and (C2-C4) alkenyl are optionally substituted by one to three substituents independently selected from hydroxyl, (C1-C4) alkoxy, halo, —NH2, or (C1-C4)-[(alkyl)(alkyl)N—];

wherein R10, R11 and R12 are independently hydrogen, (C1-C4) alkyl, (C6-C10) aryl-(C1-C4) alkyl-, (C3-C8) cycloalkyl, or (C2-C4) alkenyl, each of which is optionally substituted by one to three substituents independently selected from halo, hydroxyl,
or (C1-C4) alkoxy;

R1 is a (C1-C4) alkoxy;

R2, R3, R4, and R5 are independently selected from hydrogen, halo, cyano, —NH2, (C1-C4)-[(alkyl)(alkyl)N—], (C1-C4) alkoxy, (C2-C4) alkenyl, (C1-C4) alkyl, (C1-C4) haloalkyl, (C6-C10) aryl, or (5-9)-membered heteroaryl, said (C1-C4) alkoxy, (C2-C4) alkenyl, (C1-C4) alkyl and (C6-C10) aryl being optionally substituted by one to three substituents independently selected from halo, (C1-C4) alkoxy, (C1-C4) alkyl, —NH2, cyano, nitro, (C1-C4) alkoxy-(C1-C4) alkyl-, or (C1-C4) haloalkyl, with the proviso that no more than three of R2, R3, R4, and R5 are simultaneously hydrogen;

R6 and R7 are independently hydrogen, (C1-C4) alkyl, (C3-C8) cycloalkyl, (C1-C4) alkoxy, phenyl, or benzyl, said phenyl and benzyl are optionally substituted by one to three substituents independently
selected from halo, (C1-C4) alkyl, or (C1-C4) alkoxy;

when R6 and R7 are attached to the same carbon atom, they optionally form a moiety (A) represented by the following structure:


wherein Ra and Rb are independently hydrogen, or (C1-C4) alkyl, or Ra and Rb taken together with said carbon atom optionally form a 3-8-membered ring;

or a pharmaceutically acceptable salt thereof; or an optical isomer thereof; or a mixture of optical isomers.
US Pat. No. 9,192,663

ANTIBODIES FOR EPIDERMAL GROWTH FACTOR RECEPTOR 3 (HER3)

NOVARTIS AG, Basel (CH)

1. A method of treating benign prostate hyperplasia comprising:
selecting a patient suffering from benign prostate hyperplasia; and
administering an antibody or fragment thereof that specifically binds to a HER3 receptor, such that the antibody or fragment
thereof binds to a conformational epitope comprising amino acid residues within domain 2 and domain 4 of the HER3 receptor
and blocks both ligand-dependent and ligand-independent signal transduction, wherein the antibody or fragment thereof comprises:

(a) a heavy chain variable region CDR1 of SEQ ID NO: 38; a heavy chain variable region CDR2 of SEQ ID NO: 39; a heavy chain
variable region CDR3 of SEQ ID NO: 40; a light chain variable region CDRI of SEQ ID NO: 41; a light chain variable region
CDR2 of SEQ ID NO: 42; and a light chain variable region CDR3 of SEQ ID NO: 43;

(b) a heavy chain variable region CDR1 of SEQ ID NO: 44; a heavy chain variable region CDR2 of SEQ ID NO: 45; a heavy chain
variable region CDR3 of SEQ ID NO: 46; a light chain variable region CDR1 of SEQ ID NO: 47; a light chain variable region
CDR2 of SEQ ID NO: 48; and a light chain variable region CDR3 of SEQ ID NO: 49;

(c) a variable heavy chain (VH) sequence of SEQ ID NO: 51 and a variable light chain (VL) sequence of SEQ ID NO: 50;
(d) a variable heavy chain (VH) sequence having SEQ ID NO: 141 and a variable light chain (VL) sequence having of SEQ ID NO:
140;

(e) a variable heavy chain (VH) sequence selected from the group consisting of SEQ ID NOs.: 402-423;
(f) a variable light kappa chain (VK) sequence selected from the group consisting of SEQ ID NOs.: 443-461 and SEQ ID NOs.:
479-480; or

(g) a sequence selected from the group consisting of SEQ ID NOs.: 487-492;
thereby treating benign prostate hyperplasia.
US Pat. No. 9,127,090

ARTIFICIAL ANTIBODY POLYPEPTIDES

Novartis AG, Basel (CH)

1. A nucleic acid molecule encoding a protein that comprises a fibronectin type III domain, wherein the fibronectin type III
domain comprises at least two fibronectin type III ?-strand domains with a loop region linked between each ?-strand domain,
wherein the integrin-binding domain has been removed from the FG loop of the fibronectin type III domain, wherein at least
one loop region varies as compared to the wild-type fibronectin type III loop region by deletion of two to twelve amino acids
in the loop region, insertion of at least two to 25 amino acids in the loop region, or replacement of at least two amino acids
in the loop region, wherein at least one loop region binds to a specific binding partner (SBP) to form a polypeptide: SBP
complex.

US Pat. No. 9,119,700

GRAPHICAL USER INTERFACE SYSTEM AND METHOD FOR REPRESENTING AND CONTROLLING SURGICAL PARAMETERS

Novartis AG, Basel (CH)

1. An interface for displaying and controlling parameters related to the operation of a surgical device, the parameters being
displayed on a display screen, the interface comprising:
a graphical user interface, the graphical user interface being displayed on the display screen, the graphical user interface
including representations of the parameters, at least one of the representations being a linear representation having a first
end and a second end, the first end representing a minimum value of the parameter, the second end representing a maximum value
of the parameter, the at least one parameter being adjustable by moving at least one of the first end and the second end from
a first location on the display screen to a second location on the display screen, thereby controlling the operation of the
surgical device.

US Pat. No. 9,412,161

SYSTEMS AND METHODS FOR MEDICAL USE OF MOTION IMAGING AND CAPTURE

Novartis AG, Basel (CH)

1. A touchless system for capturing and evaluating motion data of a subject having a neurological condition, the system comprising:
(a) a motion database for selecting a subject motion appropriate to the subject's condition;
(b) a visual display or audio command, to cue the subject to perform the selected motion;
(c) a plurality of image capture cameras to capture a plurality of images of said motion of said subject wherein said plurality
of images comprise a video;

(d) a processing means to capture a set of image data comprising a depth image representing said motion by said subject wherein
said plurality of cameras and said processing means permit detection of a displacement of 0.5 mm;

(e) data analytic software to analyze at least one said set of data, to yield a set of values associated with said subject;
and wherein

(f) said processing means generates results representative of at least a portion of said processed data, and presents said
results in a human-perceivable format.

US Pat. No. 9,370,508

IMIDAZOQUINOLINES AS DUAL LIPID KINASE AND MTOR INHIBITORS

NOVARTIS AG, Basel (CH)

1. A method of inhibiting mammalian target of rapamycin (mTOR) kinase in a patient with mTOR kinase dependent disease comprising
administering a therapeutically effective amount of a compound 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile,
or a pharmaceutically acceptable salt thereof, to a patient in need thereof wherein said mTOR kinase dependent disease is
selected from the group consisting of muscle wasting, atrophy and cachexia.

US Pat. No. 9,359,400

SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

NOVARTIS AG, (CH)

1. A compound of the formula R1-(Leu)x-Gln-(Gly)y-(A-W-B-R2) z wherein x is 0 or 1; y is 0 or 1; z is 0 or 1;
R1 is selected from the group consisting of:


wherein R4 is selected from —H, —N3, and


W is selected from: C1-C6 linear or branches alkyl or polyethylene glycol having a molecular weight of between about 40 and about 80,000 amu;

A is absent or selected from —O—, —NH—, and —S—;
B is absent or selected from —O—, —C(O)—, —NH—, —C(O)NH—, —NHC(O)—, —NHC(O)O—, —OC(O)NH—, —OC(O)O—, —C?N(OH)—, —S(O2)—, —NHS(O2)—, —S(O2)NH—, —S(O)—, —NHS(O)—, —S(O)NH—; —C(O)O—, —OC(O)—, —S—, ?NH—O—, ?NH—NH— and ?NH—N(C1-C20alkyl)-;

R2 is selected from the group consisting of: a fatty acid, linear or branched C1-C3 alkyl-N3, cyclooctynyl, polysaccharide, —CH(OCH3)2,


each n is an integer independently selected from 0 to 6;
and each Q is selected from H and —NO2.

US Pat. No. 9,139,586

TREATING DISEASES MEDIATED BY BLOCKADE OF THE EPITHELIAL SODIUM CHANNEL WITH PYRAZINE-2-CARBOXAMIDE DERIVATIVES

Novartis AG, Basel (CH)

1. A method of treating a respiratory disease mediated by the blockade of an epithelial sodium channel in a patient in need
thereof, comprising:
administering to said patient a therapeutically effective amount of a compound that is
or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,125,864

OMV VACCINES

Novartis AG, Basel (CH)

1. A bacterium which presents a heterologous antigen from Chlamydia on its surface, wherein the heterologous antigen is a C. trachomatis CT823 antigen, and wherein the bacterium is an ompA mutant and/or which is a mutant in one or more components of the Tol-Pal
complex.
US Pat. No. 9,505,803

WASH SOLUTION AND METHOD FOR AFFINITY CHROMATOGRAPHY

Novartis AG, Basel (CH)

1. A method of producing a purified antibody, antibody fragment, or Fc fusion protein using an affinity chromatography (AC)
matrix to which the antibody, antibody fragment, or Fc fusion protein is bound, the method comprising:
(a) loading a mixture comprising the antibody, antibody fragment, or Fc fusion protein onto the AC matrix; and
(b) washing the AC matrix with one or more wash solutions comprising arginine and a halogen salt selected from the group consisting
of sodium chloride (NaCl), magnesium chloride (MgCl2) and potassium chloride (KCl), wherein the pH of the one or more wash solutions is greater than 8.0, prior to elution of
the antibody, antibody fragment, or Fc fusion protein from the AC matrix.