Antibodies against the ectodomain of erbb3 and uses thereof
AssigneeMerrimack Pharmaceuticals, Inc.
InventorsBirgit SCHOEBERL, Ulrik NIELSEN, Michael FELDHAUS, Arumugam MURUGANANDAM, David BUCKLER
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Abstract
The present invention provides a novel class of antibodies and antigen binding fragments thereof that bind the extracellular domain of ErbB3 receptor and inhibit various ErbB3 functions. For example, the antibodies and antigen binding fragments described herein are capable of binding to the receptor designated ErbB3 and inhibiting EGF-like ligand mediated phosphorylation of the receptor. Such antibodies and antigen binding fragments thereof have the useful characteristic of inhibiting the proliferation of cancer cells expressing ErbB3.
Claims24
A composition comprising a first agent that is an anti-ErbB3 antibody and a second agent that is an anti-cancer agent other than the first agent, wherein the anti-ErbB3 antibody comprises heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 10, 11, and 12, respectively.
A composition comprising erlotinib and an anti-ErbB3 antibody comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 10, 11, and 12, respectively.
A composition comprising paclitaxel and an anti-ErbB3 antibody comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 10, 11, and 12, respectively.
A composition comprising cisplatin and an anti-ErbB3 antibody comprising heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 10, 11, and 12, respectively.
A method of treating a cancer in a patient, the method comprising co-administering to the patient, 1) a composition comprising a first agent that is an anti-ErbB3 antibody and 2) a second agent that is an anti-cancer agent other than the first agent, wherein:
- (a) the antibody comprises heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs:
- 10, 11, and 12, respectively, and
- (b) the anti-cancer agent is selected from the group consisting of erlotinib, paclitaxel, and cisplatin.
The method of claim 17, wherein the KRAS mutation is a G12S KRAS mutation.
An anti-ErbB3 antibody comprising CDRH1, CDRH2, and CDRH3 paratope sequences comprising the amino acid sequences set forth in SEQ ID NO:
- 63 or SEQ ID NO:
- 76 (CDRH1), SEQ ID NO:
- 64 (CDRH2), and SEQ ID NO:
- 65 (CDRH3), and CDRL1, CDRL2, and CDRL3 paratope sequences comprising the amino acid sequences set forth in SEQ ID NO:
- 69 or SEQ ID NO:
- 77 (CDRL1), SEQ ID NO:
- 70 (CDRL2), and SEQ ID NO:
- 71 or SEQ ID NO:
- 80 (CDRL3), with the proviso that the antibody is not an antibody comprising VH CDR1, CDR2 and CDR3 sequences as shown in SEQ ID NOs:
- 7, 8 and 9, respectively, and VL CDR1, CDR2 and CDR3 sequences as shown in SEQ ID NOs:
- 10, 11 and 12, respectively.
An isolated monoclonal antibody, or antigen binding portion thereof, which binds an epitope of human ErbB3 comprising residues 92-104 and 129 of SEQ ID NO:
- 73, with the proviso that the antibody is not an antibody comprising VH CDR1, CDR2 and CDR3 sequences as shown in SEQ ID NOs:
- 7, 8 and 9, respectively, and VL CDR1, CDR2 and CDR3 sequences as shown in SEQ ID NOs:
- 10, 11 and 12, respectively.
Dependencies are inferred from the claim text.