Antigen binding proteins that bind PD-1

• US 9,676,853 B2
• Filed: 05/31/2014
• Issued: 06/13/2017
• Est. Priority Date: 05/31/2013
• Status: Active Grant

• Current Assignee: Sorrento Therapeutics Inc.
• Original Assignee: Sorrento Therapeutics Inc.
• Inventors: Swanson, Barbara A., Gray, John Dixon, Kaufmann, Gunnar F., Gros, Edwige, Zhou, Heyue
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US14/292,866
• Publication Number:
  US 20140356363A1
• Time in Patent Office: 1,109 Days
• Field of Search: None
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/70 characterized by effect upon binding to a cell or to an antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

There is disclosed compositions and methods relating to or derived from anti-PD-1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-1, PD-1-binding fragments and derivatives of such antibodies, and PD-1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PD-1 related disorders or conditions, including various inflammatory disorders and various cancers.

Claims

1. A recombinant fully human anti-PD-1 antibody of an IgG class comprising a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:

23 and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequences of SEQ ID NO. 24.

2. The recombinant fully human anti-PD-1 antibody of claim 1, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO;

24.

3. An anti-PD-1 recombinant fully human antibody Fab fragment comprising a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 23 and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 24.

4. The anti-PD-1 recombinant fully human antibody Fab fragment of claim 3, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO;

24.

5. An anti-PD-1 recombinant single chain human antibody comprising a heavy chain variable domain and a light chain variable domain which are connected by a peptide linker wherein the heavy chain variable domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 23 and the light chain variable domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 24.

6. The anti-PD-1 recombinant single chain human antibody of claim 5, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO;

24.

7. A method for treating a subject having cancer, the method comprising administering an effective amount of a recombinant fully human anti-PD-1 antibody of an IgG class to the subject;

wherein the recombinant fully human anti-PD-1 antibody comprises a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO. 23 and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 24.

8. The method of claim 7, wherein the recombinant fully human anti-PD-1 antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

23 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

24.

9. The method of claim 7, wherein the cancer is selected from the group consisting of ovarian cancer, colon cancer, breast cancer, lung cancer, myeloma, a neuroblastic-derived CNS tumor, monocytic leukemia, B-cell derived leukemia, T-cell derived leukemia, B-cell derived lymphoma, T-cell derived lymphoma, skin cancer, small cell lung cancer, non-small cell lung cancer (NSCLC), head and neck cancer, pancreatic cancer, bladder cancer, brain cancer, colorectal cancer, thyroid cancer, prostate cancer, kidney cancer, stomach cancer, cancer of the testes, and a mast cell derived tumor.

10. A recombinant fully human anti-PD-1 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in the heavy chain variable domain amino acid sequence of SEQ ID NO:

23; and

comprising a light chain variable domain comprising CDRs as set forth in the light chain variable domain amino acid sequence of SEQ ID NO;

24.

11. The anti-PD-1 antibody of claim 10, wherein the antibody is an IgG.

12. The anti-PD-1 antibody of claim 11, wherein the antibody is an IgG1 or an IgG4.

13. The anti-PD-1 antibody of claim 10, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

23 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO;

24.

14. The antigen binding fragment of the anti-PD-1 antibody of claim 10, wherein the fragment is a Fab fragment.

15. A pharmaceutical composition comprising the anti-PD-1 antibody, or antigen-binding fragment thereof, of any one of claims 10-14, and a pharmaceutically acceptable excipient.

16. A method of treating a subject having cancer or an inflammatory disease comprising administering an effective amount of the anti-PD-1 antibody, or antigen binding fragment thereof, of any one of claims 10-14.

17. The method of claim 16, wherein the cancer is selected from the group consisting of skin cancer, small cell lung cancer, non-small cell lung cancer (NSCLC), lung cancer, ovarian cancer, myeloma, colon cancer, head and neck cancer, B-cell derived lymphoma, T-cell derived lymphoma, pancreatic cancer, bladder cancer, brain cancer, monocytic leukemia, B-cell derived leukemia, T-cell derived leukemia, colorectal cancer, thyroid cancer, prostate cancer, breast cancer, kidney cancer, stomach cancer, a neuroblastic-derived CNS tumor, and cancer of the testes.

18. A method for treating a subject having cancer, the method comprising administering an effective amount of an anti-PD-1 Fab fragment or an anti-PD-1 single chain antibody (scFv) to the subject, wherein the anti-PD-1 Fab fragment or the anti-PD-1 scFv comprises a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO. 23, and comprises a light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO. 24.

19. The method of claim 18, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO. 23, and the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO. 24.

20. The method of claim 18, wherein the cancer is selected from the group consisting of skin cancer, small cell lung cancer, non-small cell lung cancer (NSCLC), lung cancer, ovarian cancer, myeloma, colon cancer, head and neck cancer, B-cell derived lymphoma, T-cell derived lymphoma, pancreatic cancer, bladder cancer, brain cancer, monocytic leukemia, B-cell derived leukemia, T-cell derived leukemia, colorectal cancer, thyroid cancer, prostate cancer, breast cancer, kidney cancer, stomach cancer, a neuroblastic-derived CNS tumor, and cancer of the testes.