# US 11,028,181 B2 · Glycan-interacting compounds and methods of use

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,028,181 B2
- Document ID: US11028181B2
- Status: Granted
- Kind: B2
- Application number: 15/775,410
- Filed: 2016-11-10
- Published: 2018-11-15
- Granted: 2021-06-08
- Earliest claimed: 2015-11-12
- Assignees: Seagen Inc.
- Applicants: Seagen Inc.
- Inventors: David A. Eavarone; Jillian M. Prendergast; Jeffrey Behrens
- Web page: https://patentgrep.com/patent/US11028181B2

## CPC

- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/6817: {Toxins}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/3084: {against tumour-associated gangliosides}
- C07K 16/3092: {against tumour-associated mucins}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/572: {cytotoxic response}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## 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 humanized antibodies, derivatives and fragments thereof as well as related compositions and kits. Methods of using glycan-interacting antibodies for treatment and diagnosis are included.

## Claims

### Claim 1

An isolated antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 2 (depends on 1)

The isolated antibody of claim 1, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 3 (depends on 1)

The isolated antibody of claim 1, wherein the antibody comprises a human IgG1, IgG2, IgG3, or IgG4 constant region.

### Claim 4 (depends on 1)

The isolated antibody of claim 1, wherein the antibody comprises a human IgG1 constant region.

### Claim 5 (depends on 2)

The isolated antibody of claim 2, wherein the antibody comprises a human IgG1 constant region.

### Claim 6 (depends on 2)

The isolated antibody of claim 2, wherein the antibody binds to cell-associated STn with a half maximal effective concentration (EC50) of from about 0.01 nM to about 30 nM.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1 and at least one pharmaceutically acceptable excipient.

### Claim 8

An isolated nucleic acid that encodes an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 9 (depends on 8)

The isolated nucleic acid of claim 8, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 10 (depends on 8)

The isolated nucleic acid of claim 8, wherein the antibody comprises a human IgG1, IgG2, IgG3, or IgG4 constant region.

### Claim 11 (depends on 8)

The isolated nucleic acid of claim 8, wherein the antibody comprises a human IgG1 constant region.

### Claim 12 (depends on 9)

The isolated nucleic acid of claim 9, wherein the antibody comprises a human IgG1 constant region.

### Claim 13 (depends on 8)

An isolated host cell that comprises the nucleic acid of claim 8.

### Claim 14 (depends on 9)

An isolated host cell that comprises the nucleic acid of claim 9.

### Claim 15 (depends on 1)

An isolated host cell that expresses the antibody of claim 1.

### Claim 16 (depends on 2)

An isolated host cell that expresses the antibody of claim 2.

### Claim 17 (depends on 15)

A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 15 under conditions suitable for expressing the antibody.

### Claim 18 (depends on 17)

The method of claim 17, further comprising isolating the antibody.

### Claim 19 (depends on 16)

A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 16 under conditions suitable for expressing the antibody.

### Claim 20 (depends on 19)

The method of claim 19, further comprising isolating the antibody.

### Claim 21

A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236, wherein the antibody comprises an IgG1 or IgG3 constant region, and wherein the cancer comprises STn-positive cancer cells.

### Claim 22 (depends on 21)

The method of claim 21, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 23 (depends on 21)

The method of claim 21, wherein the antibody comprises a human IgG1 constant region.

### Claim 24 (depends on 22)

The method of claim 22, wherein the antibody comprises a human IgG1 constant region.

### Claim 25 (depends on 22)

The method of claim 22, wherein the antibody binds to cell-associated STn with a half maximal effective concentration (EC50) of from about 0.01 nM to about 30 nM.

### Claim 26 (depends on 21)

The method of claim 21, wherein the cancer is breast cancer, colon cancer, pancreatic cancer, lung cancer, cervical cancer, ovarian cancer, stomach cancer, prostate cancer, or liver cancer.

### Claim 27

A method of selecting a subject with cancer for treatment with an anti-STn antibody, comprising contacting a sample from the subject with an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236; and detecting binding of the antibody to STn-expressing cancer cells.

### Claim 28 (depends on 27)

The method of claim 27, further comprising administering an anti-STn antibody to the subject.

### Claim 29 (depends on 27)

The method of claim 27, wherein the sample is a cell, a tissue, a tissue section, a body fluid, serum, or a combination thereof.

### Claim 30 (depends on 1)

A kit for screening a biological sample for the presence of STn-expressing cancer cells, comprising the isolated antibody of claim 1.

### Claim 31

An antibody-drug conjugate comprising an antibody conjugated to a therapeutic agent, wherein the antibody binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 32 (depends on 31)

The antibody-drug conjugate of claim 31, wherein said therapeutic agent is a cytotoxic agent.

### Claim 33 (depends on 32)

The antibody-drug conjugate of claim 32, wherein said cytotoxic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

### Claim 34 (depends on 33)

The antibody-drug conjugate of claim 33, wherein the cytotoxic agent is MMAE.

### Claim 35 (depends on 31)

The antibody-drug conjugate of claim 31, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 36 (depends on 32)

The antibody-drug conjugate of claim 32, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 37 (depends on 33)

The antibody-drug conjugate of claim 33, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 38 (depends on 34)

The antibody-drug conjugate of claim 34, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 39 (depends on 31)

A pharmaceutical composition comprising the antibody-drug conjugate of claim 31 and at least one pharmaceutically acceptable excipient.

### Claim 40

A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of an antibody-drug conjugate comprising an antibody conjugated to a cytotoxic agent, wherein the antibody binds to sialyl(α2,6)N-acetylgalactosamine (STn) and comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236, and wherein the cancer comprises STn-positive cancer cells.

### Claim 41 (depends on 40)

The method of claim 40, wherein said cytotoxic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

### Claim 42 (depends on 41)

The method of claim 41, wherein the cytotoxic agent is MMAE.

### Claim 43 (depends on 40)

The method of claim 40, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 44 (depends on 41)

The method of claim 41, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 45 (depends on 42)

The method of claim 42, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 46 (depends on 40)

The method of claim 40, wherein the cancer is breast cancer, colon cancer, pancreatic cancer, lung cancer, cervical cancer, ovarian cancer, stomach cancer, prostate cancer, or liver cancer.

### Claim 47 (depends on 45)

The method of claim 45, wherein the cancer is breast cancer, colon cancer, pancreatic cancer, lung cancer, cervical cancer, ovarian cancer, stomach cancer, prostate cancer, or liver cancer.

### Claim 48 (depends on 31)

A method of killing a STn-expressing cell, comprising contacting the cell with the antibody-drug conjugate of claim 31.

### Claim 49

A method of making an antibody-drug conjugate, comprising contacting an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn) with maleimidocaproyl-valine-citruline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-γc-PAB-MMAE), wherein the antibody comprises a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 237-241, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 50 (depends on 49)

The method of claim 49, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 51 (depends on 21)

The method of claim 21, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 52 (depends on 40)

The method of claim 40, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 53 (depends on 45)

The method of claim 45, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 54 (depends on 1)

The isolated antibody of claim 1, wherein the antibody binds to cell-associated STn with a half maximal effective concentration (EC50) of from about 0.01 nM to about 30 nM.

### Claim 55 (depends on 2)

A pharmaceutical composition comprising the antibody of claim 2 and at least one pharmaceutically acceptable excipient.

### Claim 56

An isolated nucleic acid that encodes a heavy chain variable domain of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the heavy chain variable domain (VH) comprises an amino acid sequence selected from SEQ ID NOs: 237-241.

### Claim 57 (depends on 52)

The isolated nucleic acid of claim 52, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240.

### Claim 58

An isolated nucleic acid that encodes a light chain variable domain of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the light chain variable domain (VL) comprises an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 59 (depends on 54)

The isolated nucleic acid of claim 54, wherein the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 60 (depends on 56)

The isolated nucleic acid of claim 56, wherein the antibody comprises a human IgG1, IgG2, IgG3, or IgG4 constant region.

### Claim 61 (depends on 52)

The isolated nucleic acid of claim 52, wherein the antibody comprises a human IgG1 constant region.

### Claim 62 (depends on 53)

The isolated nucleic acid of claim 53, wherein the antibody comprises a human IgG1 constant region.

### Claim 63

An isolated host cell that comprises a first nucleic acid that encodes a heavy chain variable domain (VH) of an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the VH comprises an amino acid sequence selected from SEQ ID NOs: 237-241, and a second nucleic acid that encodes a light chain variable domain (VL) of the antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the VL comprises an amino acid sequence selected from SEQ ID NOs: 235 and 236.

### Claim 64 (depends on 63)

The isolated host cell of claim 63, wherein the VH comprises the amino acid sequence of SEQ ID NO: 240 and the VL comprises the amino acid sequence of SEQ ID NO: 235.

### Claim 65 (depends on 63)

The isolated host cell of claim 63, wherein the antibody comprises a human IgG1, IgG2, IgG3, or IgG4 constant region.

### Claim 66 (depends on 63)

The isolated host cell of claim 63, wherein the antibody comprises a human IgG1 constant region.

### Claim 67 (depends on 64)

The isolated host cell of claim 64, wherein the antibody comprises a human IgG1 constant region.

### Claim 68 (depends on 63)

A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 63 under conditions suitable for expressing the antibody.

### Claim 69 (depends on 68)

The method of claim 68, further comprising isolating the antibody.

### Claim 70 (depends on 64)

A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of claim 64 under conditions suitable for expressing the antibody.

### Claim 71 (depends on 70)

The method of claim 70, further comprising isolating the antibody.

### Claim 72 (depends on 31)

The antibody-drug conjugate of claim 31, further comprising a linker attaching the therapeutic agent to the antibody.

### Claim 73 (depends on 34)

The antibody-drug conjugate of claim 34, further comprising a linker attaching the therapeutic agent to the antibody.

### Claim 74 (depends on 35)

The antibody-drug conjugate of claim 35, further comprising a linker attaching the therapeutic agent to the antibody.

### Claim 75 (depends on 38)

The antibody-drug conjugate of claim 38, further comprising a linker attaching the therapeutic agent to the antibody.

### Claim 76 (depends on 72)

The antibody-drug conjugate of claim 72, wherein the linker is a cleavable linker.

### Claim 77 (depends on 73)

The antibody-drug conjugate of claim 73, wherein the linker is a cleavable linker.

### Claim 78 (depends on 74)

The antibody-drug conjugate of claim 74, wherein the linker is a cleavable linker.

### Claim 79 (depends on 75)

The antibody-drug conjugate of claim 75, wherein the linker is a cleavable linker.

### Claim 80 (depends on 40)

The method of claim 40, wherein the antibody-drug conjugate comprises a linker attaching the cytotoxic agent to the antibody.

### Claim 81 (depends on 42)

The method of claim 42, wherein the antibody-drug conjugate comprises a linker attaching the cytotoxic agent to the antibody.

### Claim 82 (depends on 43)

The method of claim 43, wherein the antibody-drug conjugate comprises a linker attaching the cytotoxic agent to the antibody.

### Claim 83 (depends on 45)

The method of claim 45, wherein the antibody-drug conjugate comprises a linker attaching the cytotoxic agent to the antibody.

### Claim 84 (depends on 47)

The method of claim 47, wherein the antibody-drug conjugate comprises a linker attaching the cytotoxic agent to the antibody.

### Claim 85 (depends on 80)

The method of claim 80, wherein the linker is a cleavable linker.

### Claim 86 (depends on 81)

The method of claim 81, wherein the linker is a cleavable linker.

### Claim 87 (depends on 82)

The method of claim 82, wherein the linker is a cleavable linker.

### Claim 88 (depends on 83)

The method of claim 83, wherein the linker is a cleavable linker.

### Claim 89 (depends on 84)

The method of claim 84, wherein the linker is a cleavable linker.

### Claim 90 (depends on 82)

The method of claim 82, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 91 (depends on 83)

The method of claim 83, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 92 (depends on 87)

The method of claim 87, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.

### Claim 93 (depends on 88)

The method of claim 88, wherein the cancer is endometrial cancer, gastric cancer, or colorectal cancer.