IP Library › Patent Application 16791174
Patent Application
App. No. 16/791,174

Glycan-Interacting Compounds and Methods of Use

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Patent No.
US None
App. No.
16/791,174
Abstract

The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.

Claims (84)

1 .- 7 . (canceled)

8 . An isolated antibody, wherein the antibody binds to both AcSTn and GcSTn.

9 . The isolated antibody of claim 8 , wherein the antibody binds to an unsialyated Tn antigen.

10 . The isolated antibody of claim 8 , wherein the antibody does not bind to an un-sialylated Tn antigen.

11 . The isolated antibody of claim 8 , wherein the antibody binds to glycans Neu5Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5Gcα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5,9Ac2α2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , and Neu5Gc9Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 .

12 . The isolated antibody of claim 9 , wherein the antibody binds to glycans Neu5Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5Gcα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5,9Ac2α2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5Gc9Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , and GalNAcαO(CH 2 ) 2 CH 2 NH 2 .

13 . The isolated antibody of claim 10 , wherein the antibody binds to glycans Neu5Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5Gcα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , Neu5,9Ac2α2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 , and Neu5Gc9Acα2,6GalNAcαO(CH 2 ) 2 CH 2 NH 2 ; and wherein the antibody does not bind to GalNAcαO(CH 2 ) 2 CH 2 NH 2 .

14 . An isolated antibody, wherein the antibody binds to GcSTn and wherein the antibody does not bind to AcSTn.

15 . An isolated antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 108, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 135, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96.

16 . The isolated antibody of claim 15 , wherein the antibody is a monoclonal antibody.

17 . The isolated antibody of claim 16 , wherein the antibody is a humanized antibody.

18 . The isolated antibody of claim 15 , wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 37 and a VL comprising the amino acid sequence of SEQ ID NO: 38.

19 . The isolated antibody of claim 17 , wherein the antibody comprises a human IgG1, IgG2a, IgG2b, IgG2c, IgG3, or IgG4 constant region.

20 . A pharmaceutical composition comprising the antibody of claim 15 and at least one pharmaceutically acceptable excipient.

21 . An isolated nucleic acid that encodes the antibody of claim 15 .

22 . An isolated host cell that comprises the nucleic acid of claim 21 .

23 . An isolated host cell that expresses the antibody of claim 15 .

24 . A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 23 under conditions suitable for expressing the antibody.

25 . The method of claim 24 , further comprising isolating the antibody.

26 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody of claim 15 .

27 . The method of claim 26 , wherein the cancer is selected from breast cancer, colon cancer, pancreatic cancer, lung cancer, cervical cancer, ovarian cancer, stomach cancer, prostate cancer, and liver cancer.

28 . A method of selecting a subject with cancer for treatment with an anti-STn antibody, comprising contacting a sample from the subject with the antibody of claim 15 ; and detecting binding of the antibody to STn-expressing cancer cells.

29 . The method of claim 28 , further comprising administering an anti-STn antibody to the subject.

30 . The method of claim 28 , wherein the sample is a cell, a tissue, a tissue section, a body fluid, serum, or a combination thereof.

31 . A kit for screening a biological sample for the presence of STn-expressing cancer cells, comprising an antibody of claim 15 .

32 . An antibody-drug conjugate comprising the antibody of claim 15 conjugated to a therapeutic agent.

33 . The antibody-drug conjugate of claim 32 , wherein said therapeutic agent is a cytotoxic agent.

34 . The antibody-drug conjugate of claim 33 , wherein said cytotoxic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

35 . A pharmaceutical composition comprising the antibody-drug conjugate of claim 32 and at least one pharmaceutically acceptable excipient.

36 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody-drug conjugate of claim 32 .

37 . The method of claim 36 , wherein the cancer is selected from breast cancer, colon cancer, pancreatic cancer, lung cancer, cervical cancer, ovarian cancer, stomach cancer, prostate cancer, and liver cancer.

38 . A method of killing a STn-expressing cell, comprising contacting the cell with an antibody-drug conjugate of claim 32 .

39 . A method of making an antibody-drug conjugate, comprising contacting the antibody of claim 15 with maleimidocaproyl-valine-citruline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-γc-PAB-MMAE).

40 . An isolated antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises:

a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 127, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 90;

b) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 101, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 116, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 128, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 91;

c) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 102, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 117, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 129, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 92;

d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 103, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 118, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 130, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 86, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 93;

e) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 104, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 119, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 131, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 94;

f) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 105, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 120, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 132, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 87, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 95;

g) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 106, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 121, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 133, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 88, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96;

h) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 107, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 122, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 134, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 97;

i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 109, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 124, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 82, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 89, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 98;

j) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 110, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 137, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96;

k) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 110, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 138, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96;

l) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 103, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 139, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 97;

m) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 127, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99;

n) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 111, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 140, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 97;

o) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 118, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 141, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99;

p) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 127, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 85, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 89;

q) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 100, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 127, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 89, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99; or

r) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 113, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 115, a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 127, a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 89, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 99.

41 . The isolated antibody of claim 40 , wherein the antibody is a monoclonal antibody.

42 . The isolated antibody of claim 40 , wherein the antibody is a humanized antibody.

43 . The isolated antibody of claim 40 , wherein the antibody comprises:

a) a VH comprising the amino acid sequence of SEQ ID NO: 31 and a VL comprising the amino acid sequence of SEQ ID NO: 32;

b) a VH comprising the amino acid sequence of SEQ ID NO: 27 and a VL comprising the amino acid sequence of SEQ ID NO: 28;

c) a VH comprising the amino acid sequence of SEQ ID NO: 29 and a VL comprising the amino acid sequence of SEQ ID NO: 30;

d) a VH comprising the amino acid sequence of SEQ ID NO: 21 and a VL comprising the amino acid sequence of SEQ ID NO: 22;

e) a VH comprising the amino acid sequence of SEQ ID NO: 23 and a VL comprising the amino acid sequence of SEQ ID NO: 24

f) a VH comprising the amino acid sequence of SEQ ID NO: 19 and a VL comprising the amino acid sequence of SEQ ID NO: 20;

g) a VH comprising the amino acid sequence of SEQ ID NO: 35 and a VL comprising the amino acid sequence of SEQ ID NO: 36;

h) a VH comprising the amino acid sequence of SEQ ID NO: 51 and a VL comprising the amino acid sequence of SEQ ID NO: 52;

i) a VH comprising the amino acid sequence of SEQ ID NO: 25 and a VL comprising the amino acid sequence of SEQ ID NO: 26;

j) a VH comprising the amino acid sequence of SEQ ID NO: 48 and a VL comprising the amino acid sequence of SEQ ID NO: 49;

k) a VH comprising the amino acid sequence of SEQ ID NO: 48 and a VL comprising the amino acid sequence of SEQ ID NO: 50;

l) a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16;

m) a VH comprising the amino acid sequence of SEQ ID NO: 47 and a VL comprising the amino acid sequence of SEQ ID NO: 32;

n) a VH comprising the amino acid sequence of SEQ ID NO: 39 and a VL comprising the amino acid sequence of SEQ ID NO: 40;

o) a VH comprising the amino acid sequence of SEQ ID NO: 39 and a VL comprising the amino acid sequence of SEQ ID NO: 40;

p) a VH comprising the amino acid sequence of SEQ ID NO: 44 and a VL comprising the amino acid sequence of SEQ ID NO: 45;

q) a VH comprising the amino acid sequence of SEQ ID NO: 42 and a VL comprising the amino acid sequence of SEQ ID NO: 32; or

r) a VH comprising the amino acid sequence of SEQ ID NO: 46 and a VL comprising the amino acid sequence of SEQ ID NO: 32.

44 . An isolated nucleic acid that encodes the antibody of claim 40 .

45 . An isolated host cell comprising the isolated nucleic acid of claim 44 .

46 . A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 45 under conditions suitable for expressing the antibody.

47 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody of claim 40 .

48 . A method of selecting a subject with cancer for treatment with an anti-STn antibody, comprising contacting a sample from the subject with the antibody of claim 40 ; and detecting binding of the antibody to STn-expressing cancer cells.

49 . An antibody-drug conjugate comprising the antibody of claim 40 conjugated to a therapeutic agent.

50 . The antibody-drug conjugate of claim 49 , wherein said therapeutic agent is a cytotoxic agent.

51 . The antibody-drug conjugate of claim 50 , wherein said cytotoxic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

52 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody-drug conjugate of claim 49 .

53 . A method of killing a STn-expressing cell, comprising contacting the cell with an antibody-drug conjugate of claim 49 .

54 . A method of making an antibody-drug conjugate, comprising contacting the antibody of claim 40 with maleimidocaproyl-valine-citruline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-γc-PAB-MMAE).

Assignments (3)
CHANGE OF NAME Recorded Oct 21, 2020
From: SEATTLE GENETICS, INC.
To: SEAGEN INC.
Reel/Frame 054174/0595 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2020
From: SIAMAB THERAPEUTICS, INC.
To: SEATTLE GENETICS, INC.
Reel/Frame 052174/0090 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2020
From: DA SILVA, ANA PAULA GALVAO; GHADERI, DARIUS; ZHANG, MAI; MEETZE, KRISTAN; DESANDER, JULIE; BEHRENS, JEFFREY; EAVARONE, DAVID A.; PRENDERGAST, JILLIAN M.; LUGOVSKOY, ALEXEY ALEXANDROVICH
To: SIAMAB THERAPEUTICS, INC.
Reel/Frame 052193/0773 →