PTK7 modulators and methods of use

Patent metadata

Field	Value
Publication number	US-9914784-B2
Application number	US-201615085223-A
Country	US
Kind code	B2
Filing date	Mar 30, 2016
Priority date	Feb 18, 2011
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

PTK7 modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyper-proliferative disorders are provided.

First claim

The invention claimed is:

1. A method of treating a PTK7-associated neoplastic disorder comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 to a subject having the PTK7-associated neoplastic disorder, wherein the antibody or fragment thereof comprises:
(a) three CDRs of a light chain variable region set forth as SEQ ID NO: 62 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 63; or
(b) three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65,
and wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.

2. The method of claim 1 , wherein the PTK7-associated neoplastic disorder comprises a solid tumor.

3. The method of claim 1 , wherein the PTK7-associated neoplastic disorder is breast cancer, ovarian cancer, colorectal cancer, pancreatic cancer, lung cancer, or melanoma.

4. The method of claim 3 , wherein the PTK7-associated neoplastic disorder is ovarian cancer.

5. The method of claim 3 , wherein the breast cancer is triple-negative breast cancer.

6. The method of claim 3 , wherein the lung cancer is non-small cell lung cancer.

7. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 62 for CDR-L1, residues 50-56 of SEQ ID NO: 62 for CDR-L2, and residues 89-97 of SEQ ID NO: 62 for CDR-L3;
(b) a heavy chain variable region comprising residues 31-35 of SEQ ID NO: 63 for CDR-H1, residues 50-65 of SEQ ID NO: 63 for CDR-H2, and residues 95-102 of SEQ ID NO: 63 for CDR-H3; and
wherein the CDR numbering is according to Kabat.

8. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 62 for CDR-L1, residues 50-56 of SEQ ID NO: 62 for CDR-L2, and residues 89-97 of SEQ ID NO: 62 for CDR-L3; and
(b) a heavy chain variable region comprising residues 26-32 of SEQ ID NO: 63 for CDR-H1, residues 50-58 of SEQ ID NO: 63 for CDR-H2, and residues 95-102 of SEQ ID NO: 63 for CDR-H3;
wherein the CDR numbering is according to Chothia.

9. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 30-36 of SEQ ID NO: 62 for CDR-L1, residues 46-55 of SEQ ID NO: 62 for CDR-L2, and residues 89-96 of SEQ ID NO: 62 for CDR-L3; and
(b) a heavy chain variable region comprising residues 30-35 of SEQ ID NO: 63 for CDR-H1, residues 47-58 of SEQ ID NO: 63 for CDR-H2, and residues 93-101 of SEQ ID NO: 63 for CDR-H3; and
wherein the CDR numbering is according to MacCallum.

10. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 62 and a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 63.

11. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence set forth as SEQ ID NO: 62 and a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO: 63.

12. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 64 for CDR-L1, residues 50-56 of SEQ ID NO: 64 for CDR-L2, and residues 89-97 of SEQ ID NO: 64 for CDR-L3;
(b) a heavy chain variable region comprising residues 31-35 of SEQ ID NO: 65 for CDR-H1, residues 50-65 of SEQ ID NO: 65 for CDR-H2, and residues 95-102 of SEQ ID NO: 65 for CDR-H3; and
wherein the CDR numbering is according to Kabat.

13. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 24-34 of SEQ ID NO: 64 for CDR-L1, residues 50-56 of SEQ ID NO: 64 for CDR-L2, and residues 89-97 of SEQ ID NO: 64 for CDR-L3; and
(b) a heavy chain variable region comprising residues 26-32 of SEQ ID NO: 65 for CDR-H1, residues 50-58 of SEQ ID NO: 65 for CDR-H2, and residues 95-102 of SEQ ID NO: 65 for CDR-H3;
wherein the CDR numbering is according to Chothia.

14. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a light chain variable region comprising residues 30-36 of SEQ ID NO: 64 for CDR-L1, residues 46-55 of SEQ ID NO: 64 for CDR-L2, and residues 89-96 of SEQ ID NO: 64 for CDR-L3; and
(b) a heavy chain variable region comprising residues 30-35 of SEQ ID NO: 65 for CDR-H1, residues 47-58 of SEQ ID NO: 65 for CDR-H2, and residues 93-101 of SEQ ID NO: 65 for CDR-H3; and
wherein the CDR numbering is according to MacCallum.

15. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 64 and a heavy chain variable region having an amino acid sequence that is at least 60% identical to SEQ ID NO: 65.

16. The method of claim 1 , wherein the antibody or fragment thereof comprises a light chain variable region having an amino acid sequence set forth as SEQ ID NO: 64 and a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO: 65.

17. A method of treating a PTK7-associated cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.

18. A method of treating a PTK7-associated ovarian cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.

19. A method of treating a PTK7-associated non-small cell lung cancer comprising administering a therapeutically effective amount of a composition comprising an antibody or a fragment thereof that specifically binds to PTK7 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 64 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 65 to a subject having the PTK7-associated cancer, wherein the antibody or fragment thereof is conjugated or linked to a cytotoxic agent.

Assignees

• Abbvie Stemcentrx Llc

Inventors

• Foord Orit
• Dylla Scott J
• Stull Robert A
• Bankovich Alex
• Lazetic Alexandra Leida Liana
• Bernstein Jeffrey

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title