US2022298254A1PendingUtilityA1

Cd47 antigen-binding molecules

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Assignee: HUMMINGBIRD BIOSCIENCE HOLDINGS PTE LTDPriority: Nov 1, 2017Filed: Nov 1, 2018Published: Sep 22, 2022
Est. expiryNov 1, 2037(~11.3 yrs left)· nominal 20-yr term from priority
Inventors:Jerome Douglas Boyd-KirkupDipti ThakkarPiers IngramZhihao WuKonrad PaszkiewiczPeter BrauerSiyu Guan
C07K 2317/31C07K 16/2803A61K 39/39558C07H 21/00C12N 15/11C07K 2317/76C07K 2317/55C07K 16/2896A61P 35/00C12N 15/09C07K 2317/24C07K 2317/92C07K 2317/622A61K 2039/505C07K 2317/565C12N 15/62
50
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Claims

Abstract

CD47 antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods using, the CD47 antigen-binding molecules.

Claims

exact text as granted — not AI-modified
1 .- 39 . (canceled) 
     
     
         40 . An antigen-binding molecule which binds to CD47, comprising:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:169 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:170 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:171 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:172 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:173. 
   
     
     
         41 . The antigen-binding molecule according to  claim 40 , wherein the antigen-binding molecule comprises: 
       (a)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (b)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (c)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (d)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (e)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (f)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (g)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (h)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:142. 
 
 
     
     
         42 . The antigen-binding molecule according to  claim 40 , 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:132, 23, 39, 178, 127, 129, 130 or 131; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128, 31, 44, 179, 133, 134, 135 or 136.   
     
     
         43 . The antigen-binding molecule according to  claim 40 , wherein the antigen-binding molecule comprises:
 (i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
   
       or
 (ii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:23; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:31; 
 
 
       or
 (iii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:44; 
 
 
       or
 (iv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:178; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:179; 
 
 
       or
 (v) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:127; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:129; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:130; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (viii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (ix) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (x) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (xi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xiii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:135; 
 
 
       or
 (xiv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:136. 
 
 
     
     
         44 . The antigen-binding molecule according to  claim 40 , wherein the antigen-binding molecule inhibits interaction between CD47 and SIRPα. 
     
     
         45 . The antigen-binding molecule according to  claim 40 , wherein the antigen-binding molecule is a multispecific antigen-binding molecule, and further comprises an antigen-binding domain specific for a target antigen other than CD47. 
     
     
         46 . A nucleic acid, or a plurality of nucleic acids, encoding an antigen-binding molecule which binds to CD47, comprising:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:169 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:170 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:171 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:172 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:173. 
   
     
     
         47 . The nucleic acid or plurality of nucleic acids according to  claim 46 , wherein the antigen-binding molecule comprises: 
       (a)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (b)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (c)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (d)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (e)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (f)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (g)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (h)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:142. 
 
 
     
     
         48 . The nucleic acid or plurality of nucleic acids according to  claim 46 , 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:132, 23, 39, 178, 127, 129, 130 or 131; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128, 31, 44, 179, 133, 134, 135 or 136   
     
     
         49 . The nucleic acid or plurality of nucleic acids according to  claim 46 , wherein the antigen-binding molecule comprises:
 (i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
   
       or
 (ii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:23; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:31; 
 
 
       or
 (iii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:44; 
 
 
       or
 (iv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:178; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:179; 
 
 
       or
 (v) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:127; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:129; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:130; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (viii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (ix) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (x) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (xi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xiii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:135; 
 
 
       or
 (xiv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:136. 
 
 
     
     
         50 . The nucleic acid or plurality of nucleic acids according to  claim 46 , wherein the antigen-binding molecule inhibits interaction between CD47 and SIRPα. 
     
     
         51 . The nucleic acid or plurality of nucleic acids according to  claim 46 , wherein the antigen-binding molecule is a multispecific antigen-binding molecule, and further comprises an antigen-binding domain specific for a target antigen other than CD47. 
     
     
         52 . A method of treating or preventing a cancer, comprising administering to a subject a therapeutically or prophylactically effective amount of an antigen-binding molecule which binds to CD47, comprising:
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:169 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:170 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
   (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:171 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:172 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:173. 
   
     
     
         53 . The method according to  claim 52 , wherein the antigen-binding molecule comprises: 
       (a)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (b)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (c)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (d)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:139 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (e)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:24 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:25 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (f)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:140 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (g)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:141 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:34; 
 
 
       or 
       (h)
 (i) a heavy chain variable (VH) region incorporating the following CDRs:
 HC-CDR1 having the amino acid sequence of SEQ ID NO:137 
 HC-CDR2 having the amino acid sequence of SEQ ID NO:138 
 HC-CDR3 having the amino acid sequence of SEQ ID NO:26; and 
 
 (ii) a light chain variable (VL) region incorporating the following CDRs:
 LC-CDR1 having the amino acid sequence of SEQ ID NO:32 
 LC-CDR2 having the amino acid sequence of SEQ ID NO:33 
 LC-CDR3 having the amino acid sequence of SEQ ID NO:142. 
 
 
     
     
         54 . 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:132, 23, 39, 178, 127, 129, 130 or 131; and   a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128, 31, 44, 179, 133, 134, 135 or 136.   
     
     
         55 . The method according to  claim 52 , wherein the antigen-binding molecule comprises:
 (i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
   
       or
 (ii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:23; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:31; 
 
 
       or
 (iii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:44; 
 
 
       or
 (iv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:178; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:179; 
 
 
       or
 (v) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:127; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:129; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (vii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:130; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (viii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:128; 
 
 
       or
 (ix) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (x) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:133; 
 
 
       or
 (xi) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:131; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:134; 
 
 
       or
 (xiii) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:135; 
 
 
       or
 (xiv) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:132; and
 a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:136. 
 
 
     
     
         56 . The method according to  claim 52 , wherein the antigen-binding molecule inhibits interaction between CD47 and SIRPα. 
     
     
         57 . The method according to  claim 52 , wherein the antigen-binding molecule is a multispecific antigen-binding molecule, and further comprises an antigen-binding domain specific for a target antigen other than CD47. 
     
     
         58 . The method according to  claim 52 , wherein the cancer is selected from: a hematologic malignancy, a myeloid hematologic malignancy, a lymphoblastic hematologic malignancy, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), bladder cancer, brain cancer, glioblastoma, ovarian cancer, breast cancer, colon cancer, liver cancer, hepatocellular carcinoma, prostate cancer, lung cancer, Non-small Cell Lung Cancer (NSCLC), skin cancer and melanoma.

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