IP Library › Patent Application 16760899
Patent Application
App. No. 16/760,899

CD47 ANTIGEN-BINDING MOLECULES

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Patent No.
US None
App. No.
16/760,899
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 (410)

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.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2022
From: HUMMINGBIRD BIOSCIENCE HOLDINGS LIMITED
To: HUMMINGBIRD BIOSCIENCE PTE. LTD.
Reel/Frame 059519/0410 →
CHANGE OF NAME Recorded Jul 12, 2021
From: HUMMINGBIRD BIOSCIENCE HOLDINGS PTE. LTD.
To: HUMMINGBIRD BIOSCIENCE HOLDINGS LIMITED
Reel/Frame 056832/0875 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2021
From: BOYD-KIRKUP, JEROME; BRAUER, PETER; INGRAM, PIERS; PASZKIEWICZ, KONRAD; WU, ZHIHAO; GUAN, SIYU; DIPTI, THAKKAR
To: HUMMINGBIRD BIOSCIENCE HOLDINGS PTE. LTD.
Reel/Frame 056501/0964 →