Her3 antigen-binding molecules

Abstract

HER3 antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods using, the HER3 antigen-binding molecules.

1 .- 44 . (canceled) 
     
     
         45 . An antigen-binding molecule which binds to HER3, comprising:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:41 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:45 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:88 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:92 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:95. 
   
     
     
         46 . The antigen-binding molecule according to  claim 45 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83.   
     
     
         47 . The antigen-binding molecule according to  claim 45 , wherein the antigen-binding molecule further comprises an Fc region. 
     
     
         48 . A method of treating or preventing a cancer in a subject, the method comprising administering to a subject a therapeutically or prophylactically effective amount of an antigen-binding molecule which binds to HER3, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:41 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:45 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:88 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:92 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:95. 
   
     
     
         49 . The method according to  claim 48 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83.   
     
     
         50 . The method according to  claim 48 , wherein the cancer is selected from: a HER3-expressing cancer, gastric cancer, head and neck cancer, breast cancer, ovarian cancer, lung cancer, melanoma, prostate cancer, oral cavity cancer, renal cancer or colorectal cancer, oesophageal cancer, pancreatic cancer, a solid cancer and a liquid cancer. 
     
     
         51 . The method according to  claim 48 , wherein the method further comprises administering an agent capable of inhibiting signalling mediated by an immune checkpoint protein selected from PD-1, CTLA-4, LAG-3, TIM-3, TIGIT and BTLA. 
     
     
         52 . A method for killing or reducing the number of HER3-expressing cells, comprising contacting HER3-expressing cells with an antigen-binding molecule which binds to HER3, wherein the antigen-binding molecule comprises:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:41 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:45 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:88 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:92 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:95. 
   
     
     
         53 . The method according to  claim 52 , wherein the antigen-binding molecule comprises:
 a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83.