US Pat. No. 9,315,575

METHODS OF TREATMENT USING HUMAN ANTIBODY MOLECULES FOR IL-13

MEDIMMUNE LIMITED, Cambr...

1. A method of treatment of a disease or disorder selected from the group consisting of asthma, atopic dermatitis, allergic
rhinitis, fibrosis and Hodgkin's lymphoma, the method comprising administering a specific binding member to a patient with
the disease or disorder, wherein the specific binding member binds interleukin-13 (IL-13) and comprises an antibody antigen-binding
site which is composed of a human antibody heavy chain variable region (VH) and a human antibody light chain variable region
(VL) comprising a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the
VH comprises HCDR1, HCDR2 and HCDR3 and the VL comprises LCDR1, LCDR2 and LCDR3, wherein:
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12.

US Pat. No. 9,387,258

PYRROLOBENZODIAZEPINES AND TARGETED CONJUGATES

SEATTLE GENETICS, INC., ...

1. A Conjugate having formula IV:
L-(LU-D)p  (IV)

or a pharmaceutically acceptable salt thereof;
wherein L is a Ligand unit selected from an antibody and an antigen-binding fragment of an antibody,
LU is a Linker unit which is -A1-L1-, wherein A1 is selected from the group consisting of:


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and

L1 comprises an amino acid sequence which is cleavable by the action of an enzyme,

p is 1 to 20; and
D is selected from the group consisting of:

where
(a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically
acceptable cation, and the asterisk indicates the point of attachment to the Linker Unit.

US Pat. No. 9,447,192

ANTI-SIGLEC-15 ANTIBODIES AND USES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. An isolated antibody or antigen-binding fragment thereof that specifically binds to Siglec-15 comprising: VH-CDR1, VH-CDR2,
VH CDR3, VL-CDR1, VL-CDR2 and VL CDR3 sequences identical to the VH-CDR1, VH-CDR2, VH CDR3, VL-CDR1, VL-CDR2 and VL CDR3 sequences
corresponding to SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, respectively.

US Pat. No. 9,399,073

PYRROLOBENZODIAZEPINES

SEATTLE GENETICS, INC., ...

1. A compound of formula I:

wherein:
R2 is of formula II:


wherein X is selected from the group consisting of: OH, SH, CO2H, COH, N?C?O, NHNH2, CONHNH2,


and NHRN, wherein RN is selected from the group consisting of H and C1-4 alkyl;

RC1, RC2 and RC3 are independently selected from the group consisting of H and unsubstituted C1-2 alkyl;

R12 is selected from the group consisting of:

(ia) phenyl, naphthyl, and C5-10 heteroaryl group, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
C1-7 alkyloxy, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;

(id)

wherein each of R21, R22 and R23 are independently selected from the group consisting of H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, wherein the total number of carbon atoms in the R12 group is no more than 5;

(ie)

wherein one of R25a and R25b is H and the other is selected from the group consisting of: pyridyl, thiophenyl and phenyl, which phenyl is optionally substituted
by a substituent selected from the group consisting of halo, methyl, and methoxy; and

(if)

wherein R24 is selected from the group consisting of: H C1-3 saturated alkyl C2-3 alkenyl C2-3 alkynyl cyclopropyl pyridyl, thiophenyl and phenyl, which phenyl is optionally substituted by a substituent selected from
the group consisting of halo, methyl, and methoxy;

R6 and R9 are H;

R7 is a C1-4 alkoxy group, optionally substituted by a C5 heteroaryl or phenyl group; either:

(a) R10 is H, and R11 is OH, ORA, wherein RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, optionally interrupted by one or more aromatic rings;

Y and Y? are selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, respectively, wherein if R11 and R11? are SOzM, each M is a monovalent pharmaceutically acceptable cation or together represent a divalent pharmaceutically acceptable
cation,

wherein the term C3-7 heterocyclyl refers to a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compounds
which has from 3 to 7 ring atoms of which 1 to 4 are ring heteroatoms selected from the group consisting of N, O and S,

wherein the term C5-10 heteroaryl refers to a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heteroaromatic compound
which has from 5 to 10 ring atoms of which 1 to 4 are ring heteroatoms selected from the group consisting of N, O and S.

US Pat. No. 9,242,013

TARGETED PYRROLOBENZODIAZAPINE CONJUGATES

SEATTLE GENETICS INC., B...

1. A conjugate having formula I:
L-(LU-D)p  (I)

or a pharmaceutically acceptable salt thereof;
wherein L is a Ligand unit selected from an antibody, an antigen-binding fragment of an antibody or a Fc fusion protein,
LU is a Linker unit which is of formula 1a:
-A1-L1-,  (1a)

wherein:
-A1- is selected from the group consisting of:


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30;

L1 is an amino acid sequence, and is cleavable by the action of an enzyme;

p is 1 to 20; and
D is a Drug unit wherein the Drug unit is a PBD dimer having the following formula II:

wherein:
R2 is of formula III:


wherein A is a C5-7 aryl group, X is connected to the Linker unit and is selected from the group consisting of —O—, —S—, —C(O)O—, —C(O)—, —NH(C?O)—,
and —N(RN)—, wherein RN is selected from the group consisting of H, C1-4 alkyl and (C2H4O)mCH3, where m is 1 to 3, and either:

(i) Q1 is a single bond, and Q2 is selected from the group consisting of a single bond and —Z—(CH2)n—, wherein Z is selected from the group consisting of a single bond, O, S and NH and n is from 1 to 3; or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

R12 is a C5-10 aryl group optionally substituted by one or more substituents selected from the group consisting of halo, nitro, cyano, C1-7 alkoxy, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

R6 and R9 are independently selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

wherein R and R? are independently selected from the group consisting of optionally substituted C1-12 alkyl, C3-20 heterocyclyl, and C5-20 aryl groups;

either:
(a) R10 is H, and R11 is OH, ORA, wherein RA is C1-4 alkyl, or

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound, or

(c) R10 is H and R11 is SOzM, wherein z is 2;

R? is a C3-12 alkylene group, which chain is optionally interrupted by one or more heteroatoms selected from the group consisting of O,
S, and NH, or an aromatic ring;

Y and Y? are selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively, and R10? and R11? are the same as R10 and R11, and each M is a monovalent pharmaceutically acceptable cation or both M groups together are a divalent pharmaceutically
acceptable cation;

wherein C3-20 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom of a heterocyclic compound which has 3 to 20 ring
atoms, of which 1 to 10 are heteroatoms selected from the group consisting of N, O and S; and

wherein C3-7 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom of a heterocyclic compound which has 3 to 7 ring
atoms, of which 1 to 4 are heteroatoms selected from the group consisting of N, O and S.

US Pat. No. 9,376,440

PYRROLOBENZODIAZEPINES AS ANTIPROLIFERATIVE AGENTS

MEDIMMUNE LIMITED, Cambr...

1. A compound of formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:
the dotted double bond indicates the presence of a single or double bond between C2 and C3;
R2 is selected from —H, —OH, ?O, ?CH2, —CN, —R, OR, halo, dihalo, ?CHR, ?CRR?, —O—SO2—R, CO2R and COR;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

R10 and R11 either together form a double bond, or are selected from H and QRQ respectively,

where Q is selected from O, S and NH and RQ is H or C1-7 alkyl or H and SOxM, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation;

A is either:

where X and Y are selected from: CH and NMe; C—OH and NMe; CH and S; N and NMe; N and S;
B is either a single bond or:

Where X and Y are as defined above; and
R1 is C1-4 alkyl.

US Pat. No. 9,255,144

ANTI-IL-18 ANTIBODIES AND THEIR USES

MedImmune Limited, Cambr...

1. An isolated antibody molecule for human Interleukin-18(IL-18) which specifically binds to an epitope of human IL-18 which
wholly or partially overlaps with the IL-18BP binding site on human IL-18, wherein the antibody molecule comprises:
(a) a HCDR1 having an amino acid sequence identical to or comprising 3 or fewer amino acid residue substitutions relative
to SEQ ID NO: 153;

(b) a HCDR2 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative
to SEQ ID NO: 154;

(c) a HCDR3 having an amino acid sequence identical to or comprising 5 or fewer amino acid residue substitutions relative
to SEQ ID NO: 155;

(d) a LCDR1 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative
to SEQ ID NO: 158;

(e) a LCDR2 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative
to SEQ ID NO: 159; and

(f) a LCDR3 having an amino acid sequence identical to or comprising 9 or fewer amino acid residue substitutions relative
to SEQ ID NO: 160.

US Pat. No. 9,107,945

METHODS OF PURIFYING ANTI-INTERLEUKIN-13 ANTIBODIES

MedImmune Limited, Cambr...

1. A process for purifying an IL-13 antibody comprising more than one chromatographic separation steps, wherein each of said
separation steps comprises elution with a single acetate buffer comprising 50 mM sodium acetate and 85 mM sodium chloride
buffered to a pH of 3.5-7.0.
US Pat. No. 9,283,274

RSV SPECIFIC BINDING MOLECULE

MedImmune Limited, Cambr...

1. An isolated nucleic acid molecule comprising:
a nucleic acid sequence encoding a heavy chain CDR1 comprising the amino acid sequence KLSIH (SEQ ID NO:4), and/or
a nucleic acid sequence encoding a heavy chain CDR2 comprising the amino acid sequence GYEGEVDEIFYAQKFQH (SEQ ID NO:8), and/or
a nucleic acid sequence encoding a heavy chain CDR3 comprising the amino acid sequence LGVTVTEAGLGIDDY (SEQ ID NO:12), and/or
a nucleic acid sequence encoding a light chain CDR1 comprising the amino acid sequence RASQIVSRNHLA (SEQ ID NO:20), and/or
a nucleic acid sequence encoding a light chain CDR2 comprising the amino acid sequence GASSRAT (SEQ ID NO:24), and/or
a nucleic acid sequence encoding a light chain CDR3 comprising the amino acid sequence LSSDSSI (SEQ ID NO:28).
US Pat. No. 9,200,074

ANTIBODIES TO IL-1 R1 AND METHODS OF MAKING THEM

MEDIMMUNE LIMITED, Cambr...

1. An isolated antibody or fragment thereof that binds IL-1R1, comprising a heavy chain variable region (VH) comprising SEQ
ID NO: 62 and a light chain variable region (VL) comprising SEQ ID NO: 67.

US Pat. No. 9,321,774

PYRROLOBENZODIAZEPINES

MEDIMMUNE LIMITED, Cambr...

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
the dotted double bond indicates the presence of a single or double bond between C2 and C3;
R2 is selected from —H, —OH, =0, ?CH2, —CN, —R, OR, halo, dihalo, ?CHR, ?CHRR?, —O—SO2—R, CO2R and COR;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C3-20 heterocyclyl and C5-20 aryl groups, wherein the optional substituents are selected from
—F, —Cl, —Br, —I, —OH, —OR24, —CH(OR21)(OR21), —CH(OH)(OR21), —CR(OR21)(OR21), ?O, ?S, ?NR22, —C(?O)R21, —C(?O)OH, —C(?S)SH, —C(?O)SH, —C(?S)OH, —C(?NH)OH, —C(?NOH)OH, —C(?O)OR21, —OC(?O)R21, —OC(?O)OR21, —NR23R23, —C(?O)NR23R23?, —C(?S)NR23R23?, —NR22C(?O)R21, —OC(?O)NR23R23?, —N(R22)CONR23R23?, —NH—C(?NH)NH2, ?NR22, —C(?NR22)N(R22)2, —NO2, —NO, —N3, —CN, —NC, —OCN, —NCO, —SCN, —NCS, —SH, —SR21, —SS—R21, —S(?O)R21, —S(?O)R21, —S(?O)OH, —S(?O)2OH, —S(?O)OR21, —S(?O)2OR21, —OS(?O)R21, —OS(?O)R21, —OS(?O)2OR21, —S(?O)NR23R23?, —S(?O)2NR23R23?, —NR22S(?O)2OH, —NR22S(?O)2R21, —NR22S(?O)R21, —PR222, —P(?O)2, —P(?O)(R21)2, —P(?O)(OH)2, —P(?O)(OR22)2, —OP(?O)(OH)2, —OP(?O)(OR22)2, —OP(OH)2, —OP(OR22)2, —OP(OR22)—N(R22)2; and —OP(?O)(OR22)—N(R22)2 whereineach R21 is independently selected from C1-7 alkyl, a C3-20 heterocyclyl, or a C5-20 aryl;each R22 is independently selected from hydrogen C1-7 alkyl, a C3-20 heterocyclyl or a C5-20 aryl;each R23 is independently selected from hydrogen C1-7 alkyl a C3-20 heterocyclyl a C5-20 or, in the case of a “cyclic” amino group, R23 and R23?, taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 4 to 8 ring atoms;each R24 is independently alkyl; andeach R25 is independently selected from optionally substituted C1-7 alkyl a C3-20 heterocyclyl, or a C5-20 aryl;
R10 and R11 either together form a double bond, or are selected from H and QRQ respectively, where Q is selected from O, S and NH and RQ is H or C1-7 alkyl or H and SOXM, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation;

A is selected from A1, A2, A3, A4 or A5:

Where
X1 and Y1 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively;

X2 and Y2 are selected from: CH and NH; CH and NMe; N and NMe; CH and S;

N and S; N and O; and CH and O, respectively;
Z1 is selected from O and S;

Z2 is selected from CH and N;

F is selected from a single bond and -(E-F1)m—;

each E is independently selected from a single bond, and —C(?O)—NH—;
each F1 is independently a C5-20 heteroarylene group;

m is 1, 2 or 3;
G is selected from hydrogen, C1-4alkyl, —C(?O)—O—C1-4alkyl, —(CH2)n—C3-20 heterocyclyl, and —O—(CH2)n—C3-20 heterocyclyl group;

each n is 0-4;
wherein C3-20 heterocyclyl pertains to a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compound,
which moiety has from 3 to 20 rings atoms, of which 1 to 10 are ring heteroatoms selected from N, O and S;

wherein C5-20 heteroarylene pertains to a divalent moiety obtained by removing a hydrogen atom from each of two ring atoms of a heteroaromatic
compound, which moiety has from 3 to 20 rings atoms, of which 1 to 10 are ring heteroatoms selected from N, O and S;

provided that A2 is not A2:

where X1 and Y1 of A2? are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and

provided that A3 is not A3?:

where X2 and Y2 of A3? are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively;

B is either a single bond or:

where X and Y of B1 are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and
R1 is C1-4 alkyl.

US Pat. No. 9,284,589

METHODS OF OBTAINING A SPECIFIC BINDING MEMBER THAT BINDS EOTAXIN

Medimmune Limited, Cambr...

1. A method of producing an antibody heavy chain variable region (VH) domain, the method comprising culturing host cells under
conditions for production of said VH domain, wherein said host cells are transformed with a nucleic acid which comprises a
nucleotide sequence encoding a polypeptide comprising a VH domain, wherein said VH domain comprises VH CDRs 1-3 with the amino
acid sequences of SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7, respectively, and wherein when the VH domain is paired with an
antibody light chain variable region (VL) domain comprising VL CDRs 1-3 with the amino acid sequences of SEQ ID NO:8, SEQ
ID NO:9 and SEQ ID NO:10, respectively, an antibody antigen binding site that binds eotaxin is provided.

US Pat. No. 9,266,894

PYRROLOBENZODIAZEPINES AS UNSYMMETRICAL DIMERIC PBD COMPOUNDS FOR INCLUSION IN TARGETED CONJUGATES

MEDIMMUNE LIMITED, Cambr...

1. A compound with the formula I:
wherein:
R2 is of formula II:


where Q is selected from OH, SH and NHRN, and RN is selected from H, methyl and ethyl;

when there is a double bond present between C2? and C3?, R12 is selected from:

(ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether,
C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;


 wherein each of R21 , R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;


 wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl;and


 where R24 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;

when there is a single bond present between C2? and C3?,
R12 is


 where R26a and R26b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R26a and R26b is H, the other is selected from nitrile and a C1-4 alkyl ester;

R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

either:
(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, and/or aromatic rings;

Y and Y? are selected from O, S, or NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, wherein if R11 and R11?are SOZM, M may represent a divalent pharmaceutically acceptable cation.

US Pat. No. 9,321,831

RSV-SPECIFIC BINDING MOLECULES AND MEANS FOR PRODUCING THEM

MedImmune Limited, Cambr...

1. An isolated antibody or functional part, derivative or analogue thereof which specifically binds Respiratory Syncytial
Virus and which comprises:
a heavy chain CDR1 sequence comprising the sequence GFSFSHYA (SEQ ID NO:73), and
a heavy chain CDR2 sequence comprising the sequence ISYDGENT (SEQ ID NO:74), and
a heavy chain CDR3 sequence comprising the sequence ARDRIVDDYYYYGMDV (SEQ ID NO:75), and
a light chain CDR1 sequence comprising the sequence QDIKKY (SEQ ID NO:76), and
a light chain CDR2 sequence comprising the sequence DAS, and
a light chain CDR3 sequence comprising the sequence QQYDNLPPLT (SEQ ID NO:77), and
wherein the antibody, or functional part, derivative, or analogue thereof comprises a single chain antibody, a single chain
variable fragment (scFv), an Fab fragment, or a F(ab')2 fragment, or

wherein the antibody, or functional part, derivative, or analogue thereof comprises a chimeric antibody.

US Pat. No. 9,387,259

PYRROLOBENZODIAZEPINES AND TARGETED CONJUGATES

SEATTLE GENETICS, INC., ...

1. A compound with the formula I:

or a pharmaceutically acceptable salt thereof,
wherein:
R2 is of formula III:


where A is a C5-7 aryl group, X is selected from the group consisting of:


and NHRN, wherein RN is selected from the group consisting of H and C1-4 alkyl and either

(i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from the group consisting of a single bond, O, S and NH and n is from 1 to 3; or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

R12 is a C5-10 aryl group, substituted by a group selected from the group consisting of OH, CO2H, and CO2RO, where RO is selected from C1-4 alkyl;

R6 and R9 are independently selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

either:
(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound, or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain is optionally interrupted by one or more heteroatoms selected from the group consisting of O,
S, and NRN2 where RN2 is H or C1-4 alkyl, and/or an aromatic ring;

Y and Y? are selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, wherein if R11 and R11? are SOzM, M may represent a divalent pharmaceutically acceptable cation.

US Pat. No. 9,388,187

PYRROLOBENZODIAZEPINES

MEDIMMUNE LIMITED, Cambr...

1. A compound with the formula I:

wherein:
R2 is of formula II:


where A is phenyl, naphthyl or a C5-7 heteroaryl group, X is selected from the group consisting of: NHNH2, CONHNH2,

and either:
(i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

R12 is a phenyl, naphthyl, or C5-10 heteroaryl group, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
C1-7 alkoxy, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

R6 and R9 are H;

R7 is a C1-4 alkoxy, optionally substituted by a C5 heteroaryl or phenyl group either:

(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more aromatic rings;

Y and Y? are selected from O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, wherein if R11 and R11? are SOzM, M may represent a divalent pharmaceutically acceptable cation,

wherein the term C3-7 heterocyclyl refers to a monovalent moiety obtained by removing a hydrogen atom for a ring atom of a heterocyclic compounds
which has from 3 to 7 ring atoms of which 1 to 4 are ring heteroatoms selected from N, O and S,

wherein the term C5-10 heteroaryl refers to a monovalent moiety obtained by removing a hydrogen atom for a ring atom of a heteroaromatic compound
which has from 5 to 10 ring atoms of which 1 to 4 are ring heteroatoms selected from N, O and S.

US Pat. No. 9,085,628

ANTIBODY MOLECULE FOR HUMAN GM-CSF RECEPTOR ALPHA

MedImmune Limited, Cambr...

1. An isolated binding member for human GM-CSFR?, wherein the binding member comprises an antibody molecule that inhibits
binding of GM-CSF to GM-CSFR? and wherein the binding member binds at least one residue of the sequence Tyr-Leu-Asp-Phe-Gln
at positions 226 to 230 of human GM-CSFR? as shown in SEQ ID NO: 206, and wherein the binding member binds to human GM-CSFR?
extra-cellular domain with an affinity (KD) of less than 4 nM in a surface plasmon resonance assay, said antibody molecule
comprising a heavy chain variable region and a light chain variable region, comprising one of:
(a) a heavy chain complementarity determining region (H-CDR)1, a H-CDR2, and a H-CDR3 of the heavy chain variable region set
forth as SEQ ID NO: 2, and a light chain complementarity determining region (L-CDR)1, a L-CDR2, and a L-CDR3 of the light
chain variable region set forth as SEQ ID NO: 208;

(b) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 12, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(c) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 22, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(d) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 32, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(e) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 42, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(f) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 52 or 248, and a
L-CDR1, a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 218 or 250;

(g) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 62, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(h) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 72, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(i) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 82, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(j) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 92, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 210;

(k) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 102, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 228;

(l) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 22, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 230;

(m) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 22, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 232;

(n) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 132, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 234;

(o) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 142, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 236;

(p) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 152, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 238;

(q) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 152, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 240;

(r) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 172, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 242;

(s) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 182, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable region sequence set forth as SEQ ID NO: 244; or

(t) a H-CDR1, a H-CDR2, and a H-CDR3 of the heavy chain variable region sequence set forth as SEQ ID NO: 192, and a L-CDR1,
a L-CDR2, and a L-CDR3 of the light chain variable sequence region set forth as SEQ ID NO: 246.

US Pat. No. 9,433,664

FACTOR II AND FIBRINOGEN FOR TREATMENT OF HAEMOSTATIC DISORDERS

MEDIMMUNE LIMITED, Cambr...

1. A method of normalizing impaired haemostasis associated with dilutional coagulopathy in a mammal in need thereof comprising
administering a clotting factor treatment selected from the group consisting of: (1) recombinant human FII (rhFII), (2) a
combination of rhFII and recombinant human FVIIa (rhVIIa), (3) a combination of rhFII, rhVIIa, and recombinant human FX (rhFX),
(4) fibrinogen and a combination of rhFII, rhFVIIa, and rhFX, (5) fibrinogen and rhFII, and (6) fibrinogen and a combination
of rhFII and rhVIIa,
wherein administration of said clotting factor treatment is performed without co-administration of any other coagulation factors
selected from human coagulation factors FV-FXIII.

US Pat. No. 9,415,117

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A compound which is A:

where R10 and R11 either

(a) form a double bond between the carbon and nitrogen atoms to which they are bound; or
(b) are H and ORA respectively, where RA is selected from H and C1-4 alkyl;

or a pharmaceutically acceptable salt thereof.
US Pat. No. 9,181,336

BINDING PROTEINS SPECIFIC FOR INSULIN-LIKE GROWTH FACTORS AND USES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. An isolated antibody or antibody fragment thereof, wherein said antibody or antibody fragment thereof comprises:
a heavy chain complementarity determining region 1 (hCDR 1) having the amino acid sequence set forth in SEQ ID NO: 21 (Ser
Tyr Tyr Trp Ser);

a heavy chain complementarity determining region 2 (hCDR2) having the amino acid sequence set forth in SEQ ID NO: 22 (Tyr
Phe Phe Tyr Ser Gly Thr Asn Tyr Asn Pro Ser Leu Lys Ser);

a heavy chain complementarity determining region 3 (hCDR3) having the amino acid sequence set forth in SEQ ID NO: 23 (Ile
Thr Gly Thr Thr Lys Gly Gly Met Asp Val);

a light chain complementarity determining region 1 (1CDR1) having the amino acid sequence set forth in SEQ ID NO: 30 (Thr
Gly Arg Ser Ser Asn Ile Gly Ala Gly Tyr Asp Val His);

a light chain complementarity determining region 2(1CDR2) having the amino acid sequence set forth in SEQ ID NO: 31 (Gly Asn
Ser Asn Arg Pro Ser); and

a light chain complementarity determining region 3 (1CDR3) having the amino acid sequence set forth in SEQ ID NO: 32 (Gin
Ser Tyr Asp Ser Ser Leu Ser Gly Ser Val).

US Pat. No. 9,315,571

SPECIFIC BINDING MEMBERS FOR NGF

Elan Pharma International...

1. An antibody antigen-binding site comprising the 1252A5 VH domain (SEQ ID NO: 392) and the 1252A5 VL domain (SEQ ID NO:
397) wherein said antibody antigen-binding site preferentially blocks NGF binding to TrkA receptor over NGF binding to p75
receptor.

US Pat. No. 9,526,798

PYRROLOBENZODIAZEPINES AND TARGETED CONJUGATES

SEATTLE GENETICS, INC., ...

1. A Conjugate having formula IV:
L-(LU-D)p  (IV)

or a pharmaceutically acceptable salt thereof;
wherein L is a Ligand unit selected from an antibody and an antigen-binding fragment of an antibody,
LU is a Linker unit which is -A1-L1-, wherein A1 is selected from the group consisting of:


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and


where the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and

L1 comprises an amino acid sequence which is cleavable by the action of an enzyme,

p is 1 to 20; and
D is selected from the group consisting of:

where
(a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically
acceptable cation, and the asterisk indicates the point of attachment to the Linker Unit.

US Pat. No. 9,068,198

CHINESE HAMSTER OVARY CELL LINE

MedImmune Limited, Cambr...

1. A Chinese hamster ovary cell line as deposited with the European Collection of Cell Cultures (ECACC) under accession number
10090201 comprising nucleic acid encoding a recombinant polypeptide selected from a therapeutic protein, a recombinant immunoglobulin,
and a recombinant fragment thereof.
US Pat. No. 9,701,746

METHODS OF TREATING NEUROPATHIC PAIN WITH SPECIFIC BINDING MEMBERS FOR NGF

MedImmune Limited, Cambr...

1. A method of treating neuropathic pain, the method comprising administering an isolated specific binding member to a patient
having neuropathic pain, wherein said isolated binding member comprises the 1252A5 VH domain of SEQ ID NO: 392 and the 1252A5
VL domain of SEQ ID NO: 397.

US Pat. No. 9,649,390

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A conjugate of formula (Ia):

wherein:
R2a and R22a are independently selected from the group consisting of:

(ia)

(ib)

(ic)

(id)

(ie)
and
(if)

R7a and R17a are independently selected from methyl and phenyl;

Y is selected from formulae A1, A2, A3, A4, A5 and A6:
L is a linker connected to a cell binding agent and is of formula:
(a) -LA-(CH2)m-  (L1)

where m is from 0 to 6; and
LA is selected from:


where Ar represents a phenylene group;
(b) -LA-(CH2)m—O—  (L2)

Where m is from 0 to 6;
(c) -LA-(CH2)q—O—C(?O)—NH—(CH2)p—  (L3)

Where q is from 1 to 3, and p is from 1 to 3; or
(d)

Where m is from 0 to 6;
X1 and X2 are amino acid groups, selected from natural amino acids, which may be modified;

CBA is the cell binding agent which is an antibody or an active fragment thereof;
n is an integer selected in the range of 0 to 48;
RA4 is a C1-6 alkylene group;

either
(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is OSOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

wherein Z is CH or N;
t1 and t2 are an independently selected from 0, 1 and 2.

US Pat. No. 9,587,027

METHODS FOR BINDING MEMBERS OF INTERLEUKIN-4 RECEPTOR ? (IL-4R?)

MEDIMMUNE LIMITED, Cambr...

1. A method of
inhibiting IL-4 induced cell proliferation in vitro, comprising contacting cells expressing human IL-4 receptor alpha (IL-4R?)
with an isolated antibody or fragment thereof that specifically binds hIL-4R?, the isolated antibody or fragment thereof comprising
a set of CDRs, wherein:

(i) the HCDR1 has amino acid sequence SEQ ID NO: 193;
the HCDR2 has amino acid sequence SEQ ID NO: 194;
the HCDR3 has amino acid sequence SEQ ID NO: 195;
the LCDR1 has amino acid sequence SEQ ID NO: 198;
the LCDR2 has amino acid sequence SEQ ID NO: 199; and
the LCDR3 has amino acid sequence SEQ ID NO: 200; or
(ii) the HCDR1 has the amino acid sequence SEQ ID NO: 363;
the HCDR2 has the amino acid sequence SEQ ID NO: 364;
the HCDR3 has the amino acid sequence SEQ ID NO: 365;
the LCDR1 has the amino acid sequence SEQ ID NO: 368;
the LCDR2 has the amino acid sequence SEQ ID NO: 369; and
the LCDR3 has the amino acid sequence SEQ ID NO: 370; or
(iii) the HCDR1 has the amino acid sequence SEQ ID NO: 233;
the HCDR2 has the amino acid sequence SEQ ID NO: 234;
the HCDR3 has the amino acid sequence SEQ ID NO: 235;
the LCDR1 has the amino acid sequence SEQ ID NO: 238;
the LCDR2 has the amino acid sequence SEQ ID NO: 239; and
the LCDR3 has the amino acid sequence SEQ ID NO: 240.

US Pat. No. 9,981,908

AMINO ACID DERIVATIVES

MedImmune Limited, Cambr...

1. A pyrrolysine analogue of formula X:
wherein
X=O or S;
Y=CH2, NH, O or S;
Z=CH2, CH—NH2, CH—OH, NH, O or S;
FG azide, alkene, alkyne, ketone, ester, or cycloalkyne;
a=an integer 1-7;
b=an integer 1-7 save that when Z is NH, O or S then b is an integer 2-7;
provided that a+h is in the range 2-8;
and d=an integer 1-4.

US Pat. No. 9,919,056

PYRROLOBENZODIAZEPINE-ANTI-CD22 ANTIBODY CONJUGATES

ADC THERAPEUTICS S.A., E...

1. A conjugate of formula:
ConjE:

wherein Ab is an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID
NO. 1; and

wherein the drug loading is from 1 to 8.

US Pat. No. 9,956,298

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

Medimmune Limited, Cambr...

1. A compound which is B:
or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,931,415

PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES

MEDIMMUNE LIMITED, Cambr...

1. A conjugate of formula ConjA:
where Ab is an antibody which is an antibody that binds to CD25, the antibody comprising:
a VH domain comprising a VH CDR1 with the amino acid sequence of SEQ ID NO. 3, a VH CDR2 with the amino acid sequence of SEQ ID NO. 4, and a VH CDR3 with the amino acid sequence of SEQ ID NO. 5; and
wherein the drug loading is from 1 to about 8.

US Pat. No. 9,713,647

PYRROLOBENZODIAZEPINES AND TARGETED CONJUGATES

SEATTLE GENETICS, INC., ...

1. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
wherein:
(a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically
acceptable cation.

US Pat. No. 9,624,227

UNSYMMETRICAL PYRROLOBENZODIAZEPINE-DIMERS FOR TREATMENT OF PROLIFERATIVE DISEASES

MEDIMMUNE LIMITED, Cambr...

1. A method of treatment of a proliferative disease, comprising administering to a subject in need of treatment a therapeutically-effective
amount of a compound of formula I:

wherein:
R2 is of formula II:


where A is a C5-7 aryl group, X is selected from the group consisting of: OH, SH, CO2H, COH, N?C?O, and NHRN, wherein RN is selected from the group consisting of H, C1-4 alkyl, and (OC2H4)mOCH3, where m is 1 to 3, and either:

(i) Q1 is a single bond, and Q2 is selected from the group consisting of a single bond and —Z—(CH2)n—, wherein Z is selected from the group consisting of a single bond, O, S and NH and n is from 1 to 3, or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

R6 and R9 are independently selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

wherein R and R? are independently selected from the group consisting of optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

either:
(a) R10 is H, and R11 is OH, or ORA, where RA is C1-4alkyl,

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound, or

(c) R10 is H and R11 is SOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms selected from the group consisting of O, S, and
NH, and/or by aromatic rings selected from the group consisting of benzene and pyridine;

Y and/or Y? are independently selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9, respectively, and R10? and R11? are the same as R10 and R11, wherein if R11 and R11? are SOZM, M represents a divalent pharmaceutically acceptable cation selected from the group consisting of Ca2+and Mg2+, wherein the proliferative disease is selected from the group consisting of kidney cancers and breast carcinomas.

US Pat. No. 9,567,340

UNSYMMETRICAL PYRROLOBENZODIAZEPINES-DIMERS FOR USE IN THE TREATMENT OF PROLIFERATIVE AND AUTOIMMUNE DISEASES

MEDIMMUNE LIMITED, Cambr...

1. A compound of formula III:

or a pharmaceutically acceptable salt thereof,
wherein:
R22 is selected from:

(a) formula IVa:

 where A is a phenyl group, and either
(i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

(b) formula IVb:

 where RC1, RC2 and RC3 are independently selected from H and unsubstituted C1-2 alkyl;

(c) formula IVc:

 where Q is selected from OH, SH and NRN, and RN is selected from H, methyl and ethyl

X is selected from the group consisting of: OH, SH, CO2H, COH, N?C?O, NHNH2, CONHNH2,


 and NHRN, wherein RN is selected from the group consisting of H and C1-4 alkyl;

L4 is selected from a single bond and a group of:


wherein n is 0 to 3;

 wherein n is as defined above;

 wherein n is as defined above; and

 wherein n is as defined above, E is O, S or NR, D is N, CH, or CR, and F is N, CH, or CR;
L3 is:

 where X is such that L3 is an amino-acid residue, a dipeptide residue or a tripeptide residue;
Prot is selected from Fmoc (fluorenylmethyloxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) and Boc (t-butoxycarbonyl);
R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively;

when there is a double bond present between C2? and C3?, R12 is selected from the group consisting of:

(ia) phenyl, naphthyl or azulenyl group or C5-10 heteroaryl, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
C1-7 alkoxy, C3-20 heterocyclyloxy, C5-20 aryloxy, carboxy, —C(?O)OC1-7alkyl, —C(?O)OC3-20heterocyclyl, —C(?O)OC5-20aryl, C1-7 alkyl, C3-7 heterocyclyl; and bis-oxy-C1-3 alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;


 wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;


 wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl; and


 where R24 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;

when there is a single bond present between C2? and C3?,
R12 is H or

where R26a and R26b are independently selected form H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R26a and R26b is H, the other is selected from nitrile and a C1-4 alkyl ester;
R? is a C3-12 alkylene group, which chain is interrupted by one or more aromatic rings selected from benzene or pyridine;

Y and Y? are selected from O, S, or NH;
either:
(A) R20 is H or Me and R21a and R21b are both H or together form ?O and either:

(i) R10 is H, R11a is H and R11b is OH or ORA, where RA is C1-4 alkyl; or

(ii) R10 and R11b form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R11a is H; or

(iii) R10 is H, R11a is H and R11b is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; or

(B) R10 is H or Me and R11a and R11b are both H or together form ?O and either:

(i) R20 is H, R21a is H and R21b is OH or ORA, where RA is C1-4 alkyl; or

(ii) R20 and R21b form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R11a is H; or

(iii) R20 is H, R21a is H and R21b is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

wherein the C3-20 heterocyclyloxy group and —C(?O)OC3-20heterocyclyl group independently contain 1 to 10 ring heteroatoms selected from N, O and S;

the C3-7 heterocyclyl group contains 1 to 4 ring heteroatoms selected from N, O and S.

US Pat. No. 9,493,565

TARGETED BINDING AGENTS AGAINST B7-H1

MedImmune Limited, Cambr...

1. An isolated antibody that specifically binds to B7-H1 having an amino acid sequence comprising:
a VH CDR1 having the amino acid sequence of SEQ ID NO: 73; and
a VH CDR2 having the amino acid sequence of SEQ ID NO: 74; and
a VH CDR3 having the amino acid sequence of SEQ ID NO: 75; and
a VL CDR1 having the amino acid sequence of SEQ ID NO: 78; and
a VL CDR2 having the amino acid sequence of SEQ ID NO: 79; and
a VL CDR3 having the amino acid sequence of SEQ ID NO: 80.
US Pat. No. 9,403,901

ANTI-PSEUDOMONAS PSL BINDING MOLECULES AND USES THEREOF

MedImmune, LLC, Gaithers...

1. An isolated antibody or antigen-binding fragment thereof which specifically binds to Pseudomonas Psl polysaccharide, wherein the antibody or antigen-binding fragment thereof promotes opsonophagocytic killing (OPK) of P. aeruginosa, and wherein the isolated antibody or antigen-binding fragment thereof specifically binds to the same Pseudomonas Psl epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and the light
chain variable region (VL) of WapR-004RAD, which comprises SEQ ID NO: 74 and SEQ ID NO: 12, respectively.
US Pat. No. 9,884,902

CTLA-4 VARIANTS

MedImmune Limited, Cambr...

1. An isolated CTLA-4 polypeptide having greater affinity for binding human CD80, greater potency and/or greater stability
compared with wild type CTLA-4 SEQ ID NO: 35, wherein the polypeptide comprises:
amino acid sequence SEQ ID NO: 68, SEQ ID NO: 43, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 36, SEQ ID NO: 42 or SEQ ID NO:
47.

US Pat. No. 9,856,317

HUMAN ANTIBODY MOLECULES FOR IL-13

MEDIMMUNE LIMITED, Cambr...

1. An isolated nucleic acid molecule comprising a polynucleotide encoding an antibody or antigen-binding fragment thereof
that binds human interleukin-13 (IL-13), wherein the antibody or antigen-binding fragment thereof comprises a set of complementarity
determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein:
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12.

US Pat. No. 9,745,303

SYNTHESIS AND INTERMEDIATES OF PYRROLOBENZODIAZEPINE DERIVATIVES FOR CONJUGATION

MEDIMMUNE LIMITED, Cambr...

1. A method of synthesizing a compound of formula III:,

from a compound of formula VI:

which proceeds via a compound of formula VIIa or VI lb:

wherein:
R2 is selected from a group of:

(a) formula IIa:

where A is a phenyl or C5-7 heteroaryl group, and either:

(i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3, or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

(b) formula IIb:

RC1, RC2 and RC3 are independently selected from H and unsubstituted C1-2 alkyl;

(c) formula IIc:

L2 is selected from a single bond and a group of:

(a)

wherein n is 0 to 3;
(b)

 wherein n is as defined above;
(c)

 wherein n is as defined above; and
(d)

 wherein n is as defined above, E is O, S or NR, D is N, CH, or CR, and F is N, CH, or CR;
L1 is:


 where X is such that L1 is an amino-acid residue, a dipeptide residue or a tripeptide residue;

Prot is selected from Fmoc (fluorenylmethyloxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) and Boc (t-butoxycarbonyl);
R12 is selected from:

(a) C5-10 heteroaryl, phenyl, or naphthyl group, optionally substituted by one or more substituents selected from the group consisting
of: halo, nitro, cyano, C1-7 alkoxy, C3-20 heterocyclyloxy, phenoxy, naphthyloxy, C5-20 heteroaryloxy, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

(b) C1-5 saturated aliphatic alkyl;

(c) C3-6 saturated cycloalkyl;

(d)

 wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;

(e)

 wherein one of R25a and R25b is H and the other is selected from:

phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; and
(f)

 where R24 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;

R6, R6 ?, R9 and R9? are H;

R7 is C1-7, alkoxy;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms selected from O, S, NRN2 (where RN2 is H or C1-4 alkyl), and/or aromatic rings selected from benzene and pyridine;

Y and Y? are selected from O, S, and NH;
SEM is 2-((trimethylsilyl)ethoxy)methyl;
OTf is CF3SO3;

C3-20 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compound, which
moiety has from 3 to 20 ring atoms, of which from 1 to 10 are ring heteroatoms selected from O, S, and N;

C3-7 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compound, which
moiety has from 3 to 7 ring atoms, of which from 1 to 4 are ring heteroatoms selected from O, S, and N;

C5-20 heteroaryl is a monovalent moiety obtained by removing a hydrogen atom from an aromatic ring atom of a heteroaromatic compound,
which moiety has from 5 to 20 ring atoms, of which from 1 to 10 are ring heteroatoms selected from O, S, and N;

C5-10 heteroaryl is a monovalent moiety obtained by removing a hydrogen atom from an aromatic ring atom of a heteroaromatic compound,
which moiety has from 5 to 10 ring atoms, of which from 1 to 4 are ring heteroatoms selected from O, S, and N;

C5-7 heteroaryl is a monovalent moiety obtained by removing a hydrogen atom from an aromatic ring atom of a heteroaromatic compound,
which moiety has from 5 to 20 ring atoms, of which from 1 to 4 are ring heteroatoms selected from O, S, and N; and

R7? is selected from the same groups as R7;

wherein the R2 group is introduced by coupling a compound of formula XIa, XIb or XIc:


(a)

(b)

(c)
wherein the R12 group is introduced by coupling a derivative comprising R12 which, when R12 is


 is

 or otherwise the derivative is RB? —R12, where RB represents boronic acid or a boronate and RB? represents boronic acid or a boronate.

US Pat. No. 9,732,084

PYRROLOBENZODIAZEPINES USED TO TREAT PROLIFERATIVE DISEASES

Medimmune Limited, Cambr...

1. A Conjugate having formula IV:
L-(LU-D)p   (IV)

wherein L is a Ligand unit selected from an antibody, an antigen-binding fragment of an antibody or a Fc fusion protein,
LU is a Linker unit which is of formula 1a:
-A1-L1-,  (1a)

wherein:
-A1- is selected from the group consisting of:


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, and n is 0 to 6;


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30; and


wherein the asterisk indicates the point of attachment to L1, the wavy line indicates the point of attachment to the Ligand unit, n is 0 or 1, and m is 0 to 30;

L1 is an amino acid sequence, and is cleavable by the action of an enzyme;

p is 1 to 20; and
D is a Drug unit of formula I:

wherein
R2 is of formula III:


where A is a phenyl or a C5-7 heteroaryl group,

X is selected from the group consisting of: O, S, C(?O), C(?O)O—, NH(C?O), NHNH, CONHNH,

 NRN, wherein RN is selected from the group consisting of H and C1-4 alkyl, wherein * indicates the point of connection to Q2, wherein LU is connected to D via the X substituent of R2;
and either:
(i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

R12 is selected from:

(iia) C1-5 saturated aliphatic alkyl;

(iib) C3-6 saturated cycloalkyl;


 wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;


 wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl; and


 where R24 is selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;

R6 , R7 , and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl, phenyl, naphthyl and C5-20 heteroaryl groups;

either:
(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, and/or aromatic rings;

Y and Y? are selected from O, S, or NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, respectively, wherein if R11 and R11? are SOZM, M optionally represents a divalent pharmaceutically acceptable cation.

US Pat. No. 9,399,641

PYRROLOBENZODIAZEPINES AS UNSYMMETRICAL DIMERIC PBD COMPOUNDS FOR INCLUSION IN TARGETED CONJUGATES

MEDIMMUNE LIMITED, Cambr...

1. A compound with the formula I:
wherein:
R2 is of formula II:


where Q is selected from OH, SH and NHRN, and RN is selected from H, methyl and ethyl;

when there is a double bond present between C2? and C3?, R12 is selected from:

(ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether,
C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;


 wherein each of R21 , R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;


 wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl;and


 where R24 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;

when there is a single bond present between C2? and C3?,
R12 is


 where R26a and R26b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R26a and R26b is H, the other is selected from nitrile and a C1-4 alkyl ester;

R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

either:
(a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl;

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or

(c) R10 is H and R11 is SOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, and/or aromatic rings;

Y and Y? are selected from O, S, or NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively and R10? and R11? are the same as R10 and R11, wherein if R11 and R11?are SOZM, M may represent a divalent pharmaceutically acceptable cation.

US Pat. No. 9,707,301

PYRROLOBENZODIAZEPINES AND TARGETED CONJUGATES

SEATTLE GENETICS, INC., ...

1. A Conjugate having formula IV:
L-(LU-D)p  (IV)

or a pharmaceutically acceptable salt thereof;
wherein L is a Ligand Unit selected from the group consisting of an antibody and an antigen binding fragment of an antibody;
LU is a Linker Unit of formula [X]:

wherein E is a glucuronic acid residue, the asterisk adjacent to the carbonyl carbon atom indicates the point of attachment
of that carbon atom to a Drug Unit, and the wavy line indicates the point of attachment to the Ligand Unit, and

—A1— is selected from the group consisting of:


wherein n is 0 to 6;

wherein n is 0 or 1, and m is 0 to 30; and

wherein the asterisk indicates the point of attachment to the nitrogen atom of Formula [X], and the wavy line indicates the
point of attachment to the Ligand Unit;

p is 1 to 20; and
D is a Drug Unit, wherein the Drug Unit is a PBD compound of formula I:

wherein:
R2 is of formula III;


 wherein
A is C5-7 aryl, and X is selected from the group consisting of:


 wherein RN is selected from the group consisting of H and C1-4 alkyl, the asterisk indicates the point of attachment to Q2, and the wavy line indicates the point of attachment to the Linker Unit; and either

(i) Q1 is a single bond, and Q2 is selected from the group consisting of a single bond and —Z—(CH2)n—, wherein Z is selected from the group consisting of a single bond, O, S and NH, and subscript n is from 1 to 3, or

(ii) Q1 is —CH?CH—, and Q2 is a single bond;

and
R12 is C5-10 aryl having a substituent selected from the group consisting of OH, CO2H, and CO2RO, wherein RO is C1-4 alkyl;

R6 and R9 are independently selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo, wherein R and R? are independently selected from the group consisting of optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl; and either:

(a) R10 is H, and R11 is OH or ORA, wherein RA is C1-4 alkyl, or

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound, or

(c) R10 is H and R11 is SOzM, wherein subscript z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

and
R? is C3-12 alkylene whose carbon chain is optionally interrupted by one or more heteroatoms selected from the group consisting of O,
S, and NRN2, wherein RN2 is H or C1-4 alkyl, and/or by an aromatic ring;

Y and Y? are selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9, respectively, and R10? and R11? are the same as R10 and R11, respectively, wherein if R11 and R11? are SOzM, then each M is a monovalent pharmaceutically acceptable cation or together is a divalent pharmaceutically acceptable cation;
and

wherein LU is attached to D via the X substituent of R2.

US Pat. No. 9,592,240

TARGETED PYRROLOBENZODIAZAPINE CONJUGATES

SEATTLE GENETICS INC., B...

1. A Conjugate having formula I:
L-(LU-D)p  (I)
or a pharmaceutically acceptable salt thereof;
wherein L is a Ligand Unit selected from the group consisting of a full length antibody and an antigen binding fragment of
a full length antibody;

LU is a Linker unit of formula X:

wherein E is of formula:

 the asterisk indicates the point of attachment to a Drug Unit and the wavy line indicates the point of attachment to the
Ligand Unit, and

wherein:
-A1- is selected from the group consisting of:


wherein n is 0 to 6;

wherein n is 0 to 6;

wherein n is 0 or 1, and m is 0 to 30; and

wherein n is 0 or 1, and m is 0 to 30;
wherein the asterisk indicates the point of attachment to the nitrogen atom of Formula X, and the wavy line indicates the
point of attachment to the Ligand unit;

p is 1 to 20; and
D is a Drug unit, wherein the Drug Unit is a PBD dimer of formula I:

wherein:
R2 is of formula II:


wherein A is a C5-7 aryl group, X is attached to the carbonyl carbon of Formula X and is selected from the group consisting of: —O—, —S—, —NH(C?O)—,
and —N(RN)—, wherein RN is selected from the group consisting of H, C1-4 alkyl and (C2H4O)mCH3, wherein m is 1 to 3; and either:

(i) Q1 is a single bond and Q2 is selected from the group consisting of a single bond and —Z—(CH2)n—, wherein Z is selected from the group consisting of a single bond, O, S and NH and n is from 1 to 3, or

(ii) Q1 is —CH?CH— and Q2 is a single bond;

R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group consisting of halo, nitro, cyano, C1-7 alkoxy, C1-7 alkyl, C3-7 heterocyclyl, dimethyl-aminopropyloxy, piperazinyl and bis-oxy-C1-3 alkylene;

R6 and R9 are independently selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

R7 is selected from the group consisting of H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo, wherein R and R? are independently selected from the group consisting of optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; and either:

(a) R10 is H, and R11 is OH or ORA, wherein RA is C1-4 alkyl,

(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound, or

(c) R10 is H and R11 is SOzM, wherein z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

R? is a C3-12 alkylene group, which chain is optionally interrupted by one or more heteroatoms that are selected from the group consisting
of O, S, and NH, or by an aromatic ring;

Y and Y? are selected from the group consisting of O, S, and NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9, respectively, and R10? and R11? are the same as R10 and R11, respectively, wherein if R11 and R11? are SOzM, then each M is a monovalent pharmaceutically acceptable cation or together is a divalent pharmaceutically acceptable cation;
wherein C3-20 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom of a heterocyclic compound which has 3 to 20 ring
atoms, of which 1 to 10 are heteroatoms selected from the group consisting of N, O and S; andwherein C3-7 heterocyclyl is a monovalent moiety obtained by removing a hydrogen atom of a heterocyclic compound which has 3 to 7 ring
atoms, of which 1 to 4 are heteroatoms selected from the group consisting of N, O and S.

US Pat. No. 9,950,078

PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES

Medimmune Limited, Cambr...

1. A conjugate of formulawherein:the drug loading is from 1 to about 8;
Ab is an antibody that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
US Pat. No. 9,884,911

COMPOUNDS AND METHODS FOR TREATING PAIN

MEDIMMUNE LIMITED, Cambr...

1. A binding molecule comprising an NGF antagonist domain and a TNF? antagonist domain, wherein the NGF antagonist domain
comprises an anti-NGF scFv fragment, and the TNF? antagonist domain comprises a soluble, TNF?-binding fragment of TNFR-2;
and wherein the anti-NGF scFV fragment comprises, from N-terminus to C-terminus, a VH comprising the amino acid sequence of
SEQ ID NO: 94, a 20-amino acid linker sequence (GGGGS)4 (SEQ ID NO:19), and a VL comprising the amino acid sequence of SEQ ID NO: 95.

US Pat. No. 9,889,207

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A compound which is selected from the group consisting of A:

and B:
where R10 and R11 either
(a) form a double bond between the carbon and nitrogen atoms to which they are bound; or
(b) are H and ORA respectively, where RA is selected from H and C1-4 alkyl;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,732,367

CELL LINES

MEDIMMUNE LIMITED, Cambr...

1. A process for stabilizing a eukaryotic cell line which expresses PylRS and tRNAPyl, wherein the cell line is capable of
incorporating a gene encoding a target protein and wherein said target protein comprises one or more non-natural amino acids
encoded by an amber codon, wherein said process comprises culturing said cell line in the presence of a decoy amino acid of:
(a) formula VIIA:

wherein K is CO or SO2;

Q=H, C1-6alkyl, aryl, heteroaryl, -OC1-6alkyl, -OCH2aryl, -OCH2heteroaryl, C2-6alkenyl or -OC2-6alkenyl; or

(b) formula VIIB:

wherein G=H;
a=4 or 5; and
R=C1-6alkyl, C2-6alkenyl, CH2aryl, C2-6alkynyl, C1-6haloalkyl or C1-6azidoalkyl,

wherein the viability of said eukaryotic cell line is enhanced in comparison to the viability of said eukaryotic cell line
cultured in the absence of said decoy amino acid.

US Pat. No. 9,562,049

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A compound with the formula I:

or a pharmaceutically acceptable salt thereof, wherein:
when there is a double bond present between C2 and C3, R2 is selected from the group consisting of:

(ia) phenyl, naphthyl, azulenyl, or C5-10 heteroaryl, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
C1-7 alkoxy, C3-20 heterocyclyloxy, C5-20 aryloxy, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;

wherein each of R13a, R13b and R13c are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R2 group is no more than 5;
wherein one of R15a and R15b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl; and
where R14 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;
when there is a single bond present between C2 and C3,
R2 is

where R16a and R16b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R16a and R16b is H, the other is selected from nitrile and a C1-4 alkyl ester;
when there is a double bond present between C2? and C3?, R12 is selected from the group consisting of:

(ia) phenyl, naphthyl, azulenyl or C5-10 heteroaryl, optionally substituted by one or more substituents selected from the group consisting of: halo, nitro, cyano,
C1-7 alkoxy, C3-20 heterocycloxy, C5-20 aryloxy, carboxy, ester, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;

(ib) C1-5 saturated aliphatic alkyl;

(ic) C3-6 saturated cycloalkyl;

wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5;
wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl,
methoxy; pyridyl; and thiophenyl; and
where R24 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl;
and thiophenyl;
when there is a single bond present between C2? and C3?,
R12 is

where R26a and R26b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R26a and R26b is H, the other is selected from nitrile and a C1-4 alkyl ester;
R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo;

where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;

R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo;

R? is a C3-12 alkylene group, which chain is interrupted by one or more aromatic rings selected from the group consisting of benzene and
pyridine;

Y and Y? are selected from O, S, or NH;
R6?, R7?, R9? are selected from the same groups as R6, R7 and R9 respectively;

R20 is H or Me and R21a and R21b are both H or together form ?O;

RL is the group


where the asterisk indicates the point of attachment to the N10 position, G1 is a functional group to form a connection to a cell binding agent, L1 is a linker, L2 is a covalent bond or together with —OC(?O)— forms a self-immolative linker, and L1 or L2 is a cleavable linker;

R11b is selected from OH, ORA, where RA is C1-4 alkyl, and SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation;

the heterocyclyl group in C3-20 heterocycloxy contains 1 to 10 ring heteroatoms selected from N, O and S;

the heteroaryl group in C5-10 heteroaryl contains 1 to 4 ring heteroatoms selected from N, O and S;

the heterocyclyl group in C3-7 heterocyclyl contains 1 to 4 ring heteroatoms selected from N, O and S; and

the heterocyclyl group in C3-20 heterocyclyl contains 1 to 10 ring heteroatoms selected from N, O and S.

US Pat. No. 10,092,645

METHODS OF TREATMENT WITH ANTAGONISTS AGAINST PD-1 AND PD-L1 IN COMBINATION WITH RADIATION THERAPY

MedImmune Limited, Cambr...

1. A method of treating cancer in a patient comprisinga. administering to the patient a fraction of fractionated radiation therapy; and
b. administering to the patient at least one PD-1 and/or PD-L1 antagonist, wherein the at least one PD-1 and/or PD-L1 antagonist is administered on the same day as the fraction of radiation therapy or up to and including 4 days later, wherein the fraction is 2.2 Gy or lower, and wherein the cancer is bladder cancer, breast cancer, colorectal cancer, head and neck cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer or renal cancer.
US Pat. No. 9,796,779

BINDING PROTEINS SPECIFIC FOR INSULIN-LIKE GROWTH FACTORS AND USES THEREOF

MedImmune Limited, Cambr...

1. A nucleic acid molecule encoding an isolated antibody or antibody fragment thereof, wherein said antibody or antibody fragment
thereof comprises:
a heavy chain complementarity determining region 1 (hCDR1) having the amino acid sequence set forth in SEQ ID NO: 21 (Ser
Tyr Tyr Trp Ser);

a heavy chain complementarity determining region 2 (hCDR2) having the amino acid sequence set forth in SEQ ID NO: 22 (Tyr
Phe Phe Tyr Ser Gly Thr Asn Tyr Asn Pro Ser Leu Lys Ser);

a heavy chain complementarity determining region 3 (hCDR3) having the amino acid sequence set forth in SEQ ID NO: 23 (Ile
Thr Gly Thr Thr Lys Gly Gly Met Asp Val);

a light chain complementarity determining region 1 (lCDR1) having the amino acid sequence set forth in SEQ ID NO: 30 (Thr
Gly Arg Ser Ser Asn Ile Gly Ala Gly Tyr Asp Val His);

a light chain complementarity determining region 2 (lCDR2) having the amino acid sequence set forth in SEQ ID NO: 31 (Gly
Asn Ser Asn Arg Pro Ser); and
a light chain complementarity determining region 3 (lCDR3) having the amino acid sequence set forth in SEQ ID NO: 32 (Gin
Ser Tyr Asp Ser Ser Leu Ser Gly Ser Val).
US Pat. No. 9,765,130

GLUCAGON/GLP-1 AGONISTS FOR THE TREATMENT OF OBESITY

MEDIMMUNE LIMITED, Cambr...

1. An isolated peptide comprising the amino acid sequence:
HX2QGTFTSDX10SX12X13LX15X16X17X18AX20X21FX23X24WLX27X28GX30 (SEQ ID NO:4)
wherein,
(1) X2 is S, X10 is Y, X12 is K, X13 is K, X15 is D, X16 is S, X17 is E, X18 is R, X20 is R, X21 is D, X23 is V, X24 is A,
X27 is V, X28 is A, and X30 is G (SEQ ID NO: 16);

(2) X2 is S, X10 is K, X12 is E, X13 is Y, X15 is D, X16 is S, X17 is E, X18 is R, X20 is R, X21 is D, X23 is V, X24 is A,
X27 is V, X28 is A, and X30 is G (SEQ ID NO: 17);

(3) X2 is S, X10 is K, X12 is K, X13 is Y, X15 is E, X16 is G, X17 is Q, X18 is A, X20 is K, X21 is E, X23 is I, X24 is A,
X27 is E, X28 is K, and X30 is R (SEQ ID NO: 22);

(4) X2 is S, X10 is K, X12 is S, X13 is Y, X15 is D, X16 is S, X17 is R, X18 is S, X20 is R, X21 is D, X23 is V, X24 is A,
X27 is E, X28 is A, and X30 is G (SEQ ID NO: 20);

(5) X2 is S, X10 is K, X12 is E, X13 is Y, X15 is D, X16 is S, X17 is E, X18 is R, X20 is R, X21 is D, X23 is V, X24 is A,
X27 is V, X28 is A, and X30 is G (SEQ ID NO: 12); and

(6) X2 is S, X10 is K, X12 is S, X13 is Y, X15 is D, X16 is S, X17 is R, X18 is R, X20 is R, X21 is D, X23 is V, X24 is A,
X27 is E, X28 is A, and X30 is G (SEQ ID NO:21).

US Pat. No. 10,017,580

HUMANIZED ANTI-TN-MUC1 ANTIBODIES AND THEIR CONJUGATES

ADC Therpeutics S.A., Ep...

1. An isolated humanized antibody that binds to Tn-MUC1, wherein the isolated humanized antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29, a light chain variable region having the amino acid sequence of SEQ ID NO: 31, 32, 33, or 34, and optionally comprises a constant region derived from one or more human antibodies.

US Pat. No. 9,982,061

ANTIBODIES TO TICAGRELOR AND METHODS OF USE

MEDIMMUNE LIMITED, Cambr...

1. An antibody or a fragment thereof that specifically binds a cyclopentyltriazolopyrimidine compound of the Formula (Ia):whereinR1 is selected from the group consisting of C1-C6 alkoxy and C1-C6 alkylthio,
R2 is selected from the group consisting of H, C1-C6 alkyl, substituted C1-C6 alkyl, C3-C6 cycloalkyl, and substituted C3-C6 cycloalkyl, and
R3 is selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 alkanol;wherein the antibody or a fragment thereof comprises a combination of heavy chain variable region (VH) and light chain variable region (VL) sequences selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:7; SEQ ID NO:12 and SEQ ID NO:17; SEQ ID NO:22 and SEQ ID NO:27; SEQ ID NO:32 and SEQ ID NO:37; SEQ ID NO:42 and SEQ ID NO:47; SEQ ID NO:52 and SEQ ID NO:57; SEQ ID NO:62 and SEQ ID NO:67; and SEQ ID NO:72 and SEQ ID NO:77.
US Pat. No. 9,834,598

ANTIBODIES TO AMYLOID BETA

MedImmune Limited, Cambr...

1. An isolated antibody molecule that is selective for binding human amyloid beta 1-42 peptide (A?1-42) over human amyloid
beta 1-40 peptide (A?1-40), wherein the antibody molecule comprises (i) a VH domain comprising the Abet0380 set of HCDRs,
wherein the amino acid sequences of the Abet0380 HCDRs are
HCDR1 SEQ ID NO: 525,
HCDR2 SEQ ID NO: 526, and
HCDR3 SEQ ID NO: 527,or comprising the Abet0380 set of HCDRs with one or two amino acid mutations, and (ii) a VL domain comprising the Abet0380
set of LCDRs, wherein the amino acid sequences of the Abet0380 LCDRs are
LCDR1 SEQ ID NO: 534
LCDR2 SEQ ID NO: 535, and
LCDR3 SEQ ID NO: 536,or comprising the Abet0380 set of LCDRs with one or two amino acid mutations.

US Pat. No. 9,670,521

AMINO ACID DERIVATIVES

MEDIMMUNE LIMITED, Cambr...

1. A pyrrolysine analog of Formula VI:

wherein
Z=NH;
FG=azide, alkene, alkyne, ketone, ester, aryl or cycloalkyne; and
b=an integer 1-4.
US Pat. No. 10,035,843

RSV-SPECIFIC BINDING MOLECULE

MedImmune Limited, Cambr...

1. A method for treating and/or preventing a RSV-related disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of an antibody, or functional part thereof, wherein the antibody or functional part thereof specifically binds to a Respiratory Syncytial Virus (RSV) F protein and comprises:a heavy chain CDR1 sequence comprising the sequence KLSIH (SEQ ID NO:4), a heavy chain CDR2 sequence comprising the sequence GYEGEVDEIFYAQKFQH (SEQ ID NO:8), a heavy chain CDR3 sequence comprising the sequence LGVTVTEAGLGIDDY (SEQ ID NO:12), a light chain CDR1 sequence comprising the sequence RASQIVSRNHLA (SEQ ID NO:20), a light chain CDR2 sequence comprising the sequence GASSRAT (SEQ ID NO:24), and a light chain CDR3 sequence comprising the sequence LSSDSSI (SEQ ID NO:28).
US Pat. No. 9,994,636

ANTI-SIGLEC-15 ANTIBODIES AND USES THEREOF

MedImmune Limited, Grant...

1. An isolated polynucleotide comprising a nucleic acid encoding an antibody or antigen-binding fragment thereof that specifically binds to Siglec-15, wherein the antibody or antigen-binding fragment thereof comprises SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8.

US Pat. No. 9,968,687

ANTI-DLL3 ANTIBODY DRUG CONJUGATES

AbbVie Stemcentrx LLC, N...

1. An antibody drug conjugate (ADC) comprising an anti-DLL3 antibody covalently linked through a linker to one or more pyrrolobenzodiazepines (PBDs), wherein the one or more PBDs is/are

US Pat. No. 9,931,414

PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES

MEDIMMUNE LIMITED, Cambr...

1. A conjugate of formulawhere Ab is an antibody which is an antibody that binds to CD19, the antibody comprising a VH domain having the sequence of SEQ ID NO. 2, optionally further comprising a VL domain having the sequence of SEQ ID NO. 8; andwherein the drug loading is from 1 to 8.

US Pat. No. 10,010,624

PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES

Medimmune Limited, Cambr...

1. A conjugate of formulaConjB:

 or ConjC

wherein:
the drug loading is from 1 to 8;
Ab is an antibody that binds to PSMA, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 3, 5, 7, 8, 9, or 10, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.
US Pat. No. 9,714,277

PEGYLATED GLUCAGON AND GLP-1 CO-AGONISTS FOR THE TREATMENT OF OBESITY

MedImmune Limited, Cambr...

1. An isolated peptide comprising:
HX1QGTFTSDYSKYLDSB4RARDFVAWLV(OCH2CH2)4 (SEQ ID NO:56)

wherein:
X1 is alpha-amino-iso-butyric acid; and

B4 is K((OCH2CH2)4-gE-palm).

US Pat. No. 10,059,757

RSV-SPECIFIC BINDING MOLECULES AND MEANS FOR PRODUCING THEM

MedImmune Limited, Cambr...

1. An isolated nucleic acid molecule which comprises:a nucleic acid sequence encoding a heavy chain CDR1 comprising the amino acid sequence NYIIN (SEQ ID NO:1), and
a nucleic acid sequence encoding a heavy chain CDR2 comprising the amino acid sequence GIIPVLGTVHYAPKFQG (SEQ ID NO:2), and
a nucleic acid sequence encoding a heavy chain CDR3 comprising the amino acid sequence ETALVVSTTYLPHYFDN (SEQ ID NO:3).
US Pat. No. 9,938,356

BINDING MOLECULES SPECIFIC FOR CD73 AND USES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. An isolated binding molecule or antigen-binding fragment thereof which specifically binds to CD73 comprising an antibody VL and an antibody VH, wherein the VL comprises the amino acid sequence comprising SEQ ID NO: 68; and wherein the VH comprises the amino acid sequence comprising SEQ ID NO: 82.
US Pat. No. 10,066,011

ANTIBODIES DIRECTED TO ANGIOPOIETIN-2 AND USES THEREOF

MedImmune Limited, Cambr...

1. A targeted binding agent that binds to Angiopoietin-2 with a Kd of less than 100 picomolar (pM), wherein the targeted binding agent is a full-length antibody or fragment thereof comprising a variable heavy chain CDR1, CDR2, and CDR3 of SEQ ID NO:79; and variable light chain CDR1, CDR2, and CDR3 of SEQ ID NO:81.

US Pat. No. 10,029,018

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A compound which is:C

a pharmaceutically acceptable salt thereof.

US Pat. No. 9,956,299

PYRROLOBENZODIAZEPINE—ANTIBODY CONJUGATES

Medimmune Limited, Cambr...

1. A conjugate of formula
wherein:
the drug loading is an integer from 1 to about 8;
Ab is an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
US Pat. No. 10,117,889

ANTIBODIES SPECIFIC FOR LOX1 AND USE IN TREATMENT OF CARDIOVASCULAR DISORDERS

MedImmune Limited, Cambr...

1. An isolated Lectin-like oxidized low density lipoprotein receptor-1 (LOX1) antibody comprising a set of complementary determining regions (CDRs): heavy chain variable region (VH)-CDR1, VH-CDR2, VH-CDR3, and light chain variable region (VL)-CDR1, VL-CDR2 and VL-CDR3, wherein:(a) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO:1;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO:2;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO:3;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO:30;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:31; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:32;
(b) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO:1;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO:5;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO:14;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO:30;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:31; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:32;
(c) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO:38;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO:39;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO:44;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO:55;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:60; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:61; or
(d) (i) VH-CDR1 has the amino acid sequence of SEQ ID NO:38;
(ii) VH-CDR2 has the amino acid sequence of SEQ ID NO:39;
(iii) VH-CDR3 has the amino acid sequence of SEQ ID NO:40;
(iv) VL-CDR1 has the amino acid sequence of SEQ ID NO:55;
(v) VL-CDR2 has the amino acid sequence of SEQ ID NO:56; and
(vi) VL-CDR3 has the amino acid sequence of SEQ ID NO:57.

US Pat. No. 10,214,761

AMINO ACID DERIVATIVES

MEDIMMUNE LIMITED, Cambr...

1. A pyrrolysine analog selected from the group consisting of:(a) a pyrrolysine analog of Formula VI:

wherein
Z=CH2, CH—NH2, CH—OH, O, S;
FG =azide, alkene, alkyne, ketone, ester, aryl or cycloalkyne; and
b=an integer 1-4; and
(b) pyrrolysine analog of Formula V:

wherein
Z=bond, CH—OH, NH, or S;
b is 0 or an integer 1-7; and
FG=alkene, alkyne, aromatic ketone, ester, aryl or cycloalkyne.
US Pat. No. 10,184,008

BLOOD BRAIN BARRIER TRANSPORT MOLECULES AND USES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. An isolated transporter molecule comprising an immunoglobulin polypeptide, wherein the polypeptide comprises an immunoglobulin heavy chain complementarity-determining region-1 (H-CDR1), an immunoglobulin heavy chain complementarity-determining region-2 (H-CDR2), an immunoglobulin heavy chain complementarity-determining region-3 (H-CDR3), an immunoglobulin light chain complementarity-determining region-1 (L-CDR1), an immunoglobulin light chain complementarity-determining region-2 (L-CDR2), and an immunoglobulin light chain complementarity-determining region-3 (L-CDR3); wherein the H-CDR1, H-CDR2, H-CDR3, L-CDR1, L-CDR2, and L-CDR3 comprise, respectively:(a) SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14;
(b) SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 229, SEQ ID NO: 230, and SEQ ID NO: 231;
(c) SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 229, SEQ ID NO: 230, and SEQ ID NO: 231;
(d) SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 66, SEQ ID NO: 67, and SEQ ID NO: 68;
(e) SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 229, SEQ ID NO: 230, and SEQ ID NO: 231;
(f) SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 229, SEQ ID NO: 230, and SEQ ID NO: 231;
(g) SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 229, SEQ ID NO: 230, and SEQ ID NO: 231;
(h) SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 138, SEQ ID NO: 139, and SEQ ID NO: 140;
(i) SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158;
(j) SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 174, SEQ ID NO: 175, and SEQ ID NO: 176;
(k) SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 192, SEQ ID NO: 193, and SEQ ID NO: 194; or
(l) SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 219, SEQ ID NO: 220, and SEQ ID NO: 220; and
wherein the transporter molecule can cross the blood brain barrier.
US Pat. No. 10,287,362

BINDING MOLECULES SPECIFIC FOR CD73 AND USES THEREOF

MedImmune Limited, Cambr...

1. A method of treating a CD73-associated cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to CD73, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain VH domain and a light chain VL domain, the heavy and light chain domains comprising:(a) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36;
(b) a VH CDR2 having the amino acid sequence of SEQ ID NO: 39;
(c) a VH CDR3 having the amino acid sequence of SEQ ID NO: 45;
(d) a VL CDR1 having the amino acid sequence of SEQ ID NO: 46;
(e) a VL CDR2 having the amino acid sequence of SEQ ID NO: 51; and
(f) a VL CDR3 having the amino acid sequence of SEQ ID NO: 56.

US Pat. No. 10,253,345

CELL LINES

MEDIMMUNE LIMITED, Cambr...

1. A process for preparing a target protein containing one or more non-natural amino adds encoded by an amber codon which comprises:(A) introducing into a eukaryotic cell line which expresses PyiRS and tRNAPyl and is capable of incorporating a gene encoding a target protein comprising one or more non-natural amino acids encoded by an amber codon a gene encoding the target protein such that the target protein is stably expressed in the cell line,
(B) culturing the eukaryotic cell line in the presence of a decoy amino add which is a substrate for PylRS but which is incapable of being incorporated into an extending protein chain, wherein the decoy amino acid is selected from:
(a) a compound of formula VIIA:

wherein K is CO or SO2; and
Q=H, C1-6alkyl, aryl, heteroaryl, OC1-6alkyl, OCH2aryl, OCH2heteroaryl, C2-6alkenyl or OC2-6alkenyl; and
(b) a compound of formula VIIB:

wherein G=H;
a=4 or 5; and
R?C1-6alkyl, C2-6alkenyl, —CH2aryl, C2-6alkynyl, C1-6haloalkyl or C1-6azidoalkyl; and
(C) expressing the target protein in the presence of one or more non-natural amino adds and in the absence of the decoy amino add.
US Pat. No. 10,202,447

ANTIBODY DERIVATIVES

MedImmune Limited, Cambr...

1. A bivalent, bispecific construct comprising an anti-IL-6 antibody comprising variable heavy chain complementarity determining regions (VH CDRs) 1-3 and variable light chain complementarity determining regions (VL CDRs) 1-3 and an anti-IL-23 antibody comprising VH CDRs 1-3 and VL CDRs 1-3 wherein the anti-1L-6 antibody comprises VH CDRs comprising SEQ ID NOs: 10-12 and VL CDRs comprising SEQ ID NOs: 13-15 and/or wherein the anti-IL-23 antibody comprises VH CDRs comprising SEQ ID NOs: 90-92 and VL CDRs comprising SEQ ID NOs: 93-95.

US Pat. No. 10,188,746

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

MEDIMMUNE LIMITED, Cambr...

1. A conjugate of formula (A):
and salts and solvates thereof, wherein:
D represents either group D1 or D2:

the dotted line indicates the optional presence of a double bond between C2 and C3;
when there is a double bond present between C2 and C3, R2 is selected from the group consisting of:
(ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, carboxy, ester, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene;
(ib) C1-5 saturated aliphatic alkyl;
(ic) C3-6 saturated cycloalkyl;
(id)
wherein each of R31, R32 and R33 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R2 group is no more than 5;(ie)
wherein one of R35a and R35b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; and(if)
where R34 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl;(ig) halo;
when there is a single bond present between C2 and C3,
R2 is
where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R16a and R16b is H, the other is selected from nitrile and a C1-4 alkyl ester;R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, SnMe3 and halo;
either
(a) R10 is H, and R11 is OH or ORA, where RA is C1-4 alkyl; or
(b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or
(c) R10 is H and R11 is OSOZM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; or
(d) R11 is OH or ORA, where RA is C1-4 alkyl and R10 is selected from:
where Rz is selected from:(z-i)

(z-ii) OC(?O)CH3;
(z-iii) NO2;
(z-iv) OMe;
(z-v) glucoronide;
(z-vi) —C(?O)—X1—NHC(?O)X2—NH—RZC, where —C(?O)—X1—NH— and —C(?O)—X2—NH— represent natural amino acid residues and Rzc is selected from Me, OMe, OCH2CH2OMe;
Y is selected from formulae A1 and A2:

Z1 is a C1-3 alkylene group;
Z2 is a C1-3 alkylene group;
Q is:
where QX is such that Q is an amino-acid residue, a dipeptide residue or a tripeptide residue;L is a linker connected to a cell binding agent;
CBA is the cell binding agent;
n is an integer between 0 and 48;
R and R? are each independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups, and optionally in relation to the group NRR?, R and R? together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring;
R8 is either:
(a) independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, SnMe3 and halo; or
(b) of formula A*:
wherein:D? represents either group D?1 or D2:

wherein the dotted line indicates the optional presence of a double bond between C2? and C3?;
R17 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, SnMe3 and halo;
R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), NMe and/or aromatic rings, e.g. benzene or pyridine, which rings are optionally substituted; and
X and X? are independently selected from O, S and N(H); and
R22, R16, R19, R20 and R21 are as defined for R2, R6, R9, R10 and R11 respectively.

US Pat. No. 10,160,800

ANTIBODIES TO ?-SYNUCLEIN AND USES THEREOF

MedImmune Limited, Cambr...

1. An antibody, or antigen-binding fragment thereof that binds to human ?-synuciein, wherein the antibody or antigen-binding fragment thereof comprises:a) three heavy chain CDRs having sequences:
(i) H-CDR1 of SEQ ID NO: 5,
(ii) H-CDR2 of SEQ ID NO: 15; and
(iii) H-CDR3 of SEQ ID NO: 16, and
b) three light chain CDRs having sequences:
(i) L-CDR1 of SEQ ID NO: 20,
(ii) L-CDR2 of SEQ ID NO: 10; and
(iii) L-CDR3 of SEQ ID NO: 21.
US Pat. No. 10,131,920

NUCLEIC ACID MOLECULES

MEDIMMUNE LIMITED, Cambr...

1. A DNA construct which comprises a tRNApyl gene comprising a tRNApyl coding sequence comprising a functional intragenic RNA polymerase III promoter element comprising a putative A box, a putative B box, or a combination thereof, wherein the tRNApyl gene is capable of expressing functional tRNApyl sufficiently to support amber suppression in a eukaryotic expression system wherein the tRNApyl gene comprises a nucleic acid sequence selected from SEQ ID Nos 7, 8, 9, 10, and 11 derived from Methanosarcina mazei or a sequence of an analogous tRNApyl gene derived from another bacterial species which comprises 1 or 2 mutations in the putative A box, 1 or 2 mutations in the putative B box, or a combination thereof made in positions equivalent to A10G, A52C, T14A, or a combination thereof as shown in SEQ ID Nos 7, 8, 9, 10, or 11, wherein the mutations result in the generation of the functional intragenic promoter element.
US Pat. No. 10,259,842

PURIFICATION OF RECOMBINANTLY PRODUCED POLYPEPTIDES

MedImmune, LLC, Gaithers...

1. A method of reducing host cell protein (HCP) level in a composition comprising a recombinantly produced polypeptide, the method comprising:providing a clarified cell culture supernatant comprising the recombinantly produced polypeptide and one or more HCP;
loading the clarified cell culture supernatant onto a Protein A chromatography column;
washing the Protein A chromatography column with a wash buffer comprising a fatty acid having a chain length of at least about 6 carbon atoms, or a fatty acid salt thereof to remove HCP; wherein the wash buffer comprises between about 25 mM to about 200 mM fatty acid; and wherein the wash buffer comprises sodium chloride present at a concentration of between about 1.0 M to about 2.5 M.