Antibody drug conjugates (ADC) that bind to 158P1D7 proteins

• US 10,669,348 B2
• Filed: 02/13/2018
• Issued: 06/02/2020
• Est. Priority Date: 08/23/2012
• Status: Active Grant

• Current Assignee: Seagen Inc.
• Original Assignee: Agensys, Inc. (Astellas Pharma Incorporated)
• Inventors: Morrison, Robert Kendall, An, Zili, Morrison, Karen Jane Meyrick, Snyder, Josh, Jia, Xiao-Chi
• Primary Examiner(s): Huff, Sheela J.
• Application Number:
  US15/895,996
• Publication Number:
  US 20180251566A1
• Time in Patent Office: 840 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6813 the drug being a peptidic cytokine, e.g. an interleukin or interferon
• CPC Class Codes: A61K 47/6817 Toxins
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6855 the tumour determinant being from breast cancer cell
• CPC Class Codes: A61K 47/6857 the tumour determinant being from lung cancer cell
• CPC Class Codes: A61K 47/6859 the tumour determinant being from liver or pancreas cancer cell
• CPC Class Codes: A61K 47/6861 the tumour determinant being from kidney or bladder cancer cell
• CPC Class Codes: A61K 47/6865 the tumour determinant being from skin, nerves or brain cancer cell
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3015 Breast
• CPC Class Codes: C07K 16/3023 Lung
• CPC Class Codes: C07K 16/3038 : Kidney, bladder
• CPC Class Codes: C07K 16/3053 : Skin, nerves, brain
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Antibody drug conjugates (ADC'"'"'s) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC'"'"'s of the invention provide a therapeutic composition for the treatment of cancer.

Claims

1. An anti-158P1D7 antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:

7 according to Kabat numbering and a light chain variable region consisting of the amino acid sequence ranging from position 1 to position 113 of SEQ ID NO;

8.

2. The antigen binding fragment thereof of claim 1, wherein the antigen binding fragment is an Fab, F(ab′

)2, Fv, or scFv fragment.

3. The anti-158P1D7 antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is a fully human antibody or antigen binding fragment thereof.

4. The anti-158P1D7 antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is recombinantly produced.

5. An antibody drug conjugate comprising the antibody or antibody binding fragment of claim 1 conjugated to monomethyl auristatin E (MMAE) via a linker.

6. The antibody drug conjugate of claim 5, wherein the linker comprises valine-citrulline.

7. The antibody drug conjugate of claim 5, wherein the antibody drug conjugate has the following structure:

8. The antibody drug conjugate of claim 7, wherein the p ranges from 2 to 5.

9. A pharmaceutical composition comprising a therapeutically effective amount of the antibody drug conjugate of claim 7 and a pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9, wherein the composition is in a human unit dose form.

11. A method of treating cancer in a subject, comprising administering to said subject a therapeutically effective amount of the antibody drug conjugate of claim 7, wherein the cancer expresses 158P1D7.

12. The method of claim 11, wherein the subject is a human subject.

13. The method of claim 11, comprising administering about 1 to about 5 mg/kg of the antibody drug conjugate to the subject.

14. The method of claim 11, wherein the cancer is selected from the group consisting of glioblastoma, lung cancer, bladder cancer, and breast cancer.

15. The method of claim 11, wherein the cancer is bladder cancer.

16. An anti-158P1D7 antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region consisting of the amino acid sequence ranging from position 1 to position 120 of SEQ ID NO:

7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO;

8 according to Kabat numbering.

17. The antigen binding fragment thereof of claim 16, wherein the antigen binding fragment is an Fab, F(ab′

)2, Fv, or scFv fragment.

18. The anti-158P1D7 antibody or antigen binding fragment thereof of claim 16, wherein the antibody or antigen binding fragment thereof is a fully human antibody or antigen binding fragment thereof.

19. The anti-158P1D7 antibody or antigen binding fragment thereof of claim 16, wherein the antibody or antigen binding fragment thereof is recombinantly produced.

20. An antibody drug conjugate comprising the antibody or antibody binding fragment of claim 16 conjugated to monomethyl auristatin E (MMAE) via a linker.

21. The antibody drug conjugate of claim 20, wherein the linker comprises valine-citrulline.

22. The antibody drug conjugate of claim 20, wherein the antibody drug conjugate has the following structure:

23. The antibody drug conjugate of claim 22, wherein the p ranges from 2 to 5.

24. A pharmaceutical composition comprising a therapeutically effective amount of the antibody drug conjugate of claim 22 and a pharmaceutically acceptable excipient.

25. The pharmaceutical composition of claim 24, wherein the composition is in a human unit dose form.

26. A method of treating cancer in a subject, comprising administering to said subject a therapeutically effective amount of the antibody drug conjugate of claim 20, wherein the cancer expresses 158P1D7.

27. The method of claim 26, wherein the subject is a human subject.

28. The method of claim 27, comprising administering about 1 to about 5 mg/kg of the antibody drug conjugate to the subject.

29. The method of claim 27, wherein the cancer is selected from the group consisting of glioblastoma, lung cancer, bladder cancer, and breast cancer.

30. The method of claim 29, wherein the cancer is bladder cancer.