Anti-PD-1 antibodies and methods of use thereof

• US 10,450,373 B2
• Filed: 04/30/2019
• Issued: 10/22/2019
• Est. Priority Date: 09/01/2015
• Status: Active Grant

• Current Assignee: Agenus Inc., Ludwig Institute for Cancer Research, Ltd., Memorial Sloan-Kettering Cancer Center
• Original Assignee: Agenus Inc.
• Inventors: Van Dijk, Marc, Mundt, Cornelia Anne, Ritter, Gerd, Wolchok, Jedd David, Merghoub, Taha, Zappasodi, Roberta, Holmgaard, Rikke Baek, Schaer, David, Savitsky, David Adam, Wilson, Nicholas Stuart
• Primary Examiner(s): Ouspenski, Ilia I
• Application Number:
  US16/399,262
• Publication Number:
  US 20190256601A1
• Time in Patent Office: 175 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• 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 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• 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

Abstract

The instant disclosure provides antibodies that specifically bind to human PD-1 and antagonize PD-1 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Claims

1. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the amino acid sequences of SEQ ID NOs:

1, 2, and 7, respectively; and

a light chain variable region comprising the amino acid sequence of SEQ ID NO;

16.

2. The isolated antibody of claim 1, wherein the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO:

16.

3. The isolated antibody of claim 1, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:

19.

4. The isolated antibody of claim 3, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO:

19.

24. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.

5. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:

20; and

a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOs;

4, 5, and 6, respectively.

6. The isolated antibody of claim 5, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

20.

25. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier or excipient.

7. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

17; and

a light chain variable region comprising the amino acid sequence of SEQ ID NO;

16.

8. The isolated antibody of claim 7, wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO:

17; and

the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO;

16.

9. The isolated antibody of claim 7, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

53.

10. The isolated antibody of claim 9, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

53.

11. The isolated antibody of claim 7, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

20.

12. The isolated antibody of claim 11, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

20.

13. The isolated antibody of claim 7, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:

19.

14. The isolated antibody of claim 13, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

23.

15. The isolated antibody of claim 13, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO:

19.

26. A pharmaceutical composition comprising the antibody of claim 7 and a pharmaceutically acceptable carrier or excipient.

27. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or excipient.

16. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:

53; and

the light chain comprises the amino acid sequence of SEQ ID NO;

19.

17. The isolated antibody of claim 16, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

53.

18. The isolated antibody of claim 16, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:

20.

19. The isolated antibody of claim 18, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

20.

20. The isolated antibody of claim 16, wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO:

19.

21. The isolated antibody of claim 16, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

53, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO;

19.

22. The isolated antibody of claim 16, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:

20, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO;

19.

23. The isolated antibody of claim 22, wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO:

20, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO;

19.

28. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier or excipient.

29. A pharmaceutical composition comprising the antibody of claim 21 and a pharmaceutically acceptable carrier or excipient.

30. A pharmaceutical composition comprising the antibody of claim 23 and a pharmaceutically acceptable carrier or excipient.