Anti-PD-1 antibodies

• US 9,771,425 B2
• Filed: 04/24/2017
• Issued: 09/26/2017
• Est. Priority Date: 10/27/2014
• Status: Active Grant

• Current Assignee: Agency For Science Technology and Research
• Original Assignee: Agency For Science Technology and Research
• Inventors: Wang, Cheng-i, Oh, Hsueh Ling Janice, Yeo, Siok Ping, Low, Jianrong Lionel, Tan, Hwee Ching
• Primary Examiner(s): Duffy, Brad
• Assistant Examiner(s): Moseley, II, Nelson B
• Application Number:
  US15/495,048
• Publication Number:
  US 20170240635A1
• Time in Patent Office: 155 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 16/005 constructed by phage libraries
• 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 2317/31 multispecific
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/70 characterized by effect upon binding to a cell or to an antigen
• CPC Class Codes: C07K 2317/74 Inducing cell proliferation
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Anti-PD-1 antibodies are disclosed. Also disclosed are pharmaceutical compositions comprising such antibodies, and uses and methods using the same.

Claims

1. A method of treating cancer, comprising administering an antibody or antigen binding fragment to a patient suffering from a cancer, wherein the antibody or antigen binding fragment binds to PD-1, and comprises:

at least one light chain variable region incorporating the following CDRs;

2. The method of claim 1, wherein the antibody or antigen binding fragment comprises a heavy chain variable region sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO:

15, and a light chain variable region sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO;

3.

3. The method of claim 1, wherein the antibody or antigen binding fragment comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

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

3.

4. The method of claim 1, wherein the cancer is a cancer of a tissue selected from the group consisting of lung, kidney, bladder, liver, stomach, cervix, nasopharynx, oral cavity, oesophagus, larynx, salivary gland, tongue, tonsil, trachea, skin, blood, colon and breast.

5. The method of claim 1, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), renal cancer, renal cell carcinoma, bladder cancer, bladder carcinoma, liver cancer, hepatoma, stomach cancer, cervical cancer, nasopharyngeal cancer, oral cavity cancer, oesophageal cancer, laryngeal cancer, salivary gland cancer, tongue cancer, tonsil cancer, tracheal cancer, skin cancer, melanoma, metastatic melanoma, haematologic cancer, lymphoma, Hodgkin'"'"'s lymphoma, colon cancer, colon carcinoma and breast cancer.

6. The method of claim 1, wherein the administration of the antibody or antigen binding fragment is intravenous.

7. The method of claim 1, wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.

8. The method of claim 1, wherein the antigen binding fragment is a Fab fragment or scFv fragment.

9. A method of treating cancer, comprising administering an antibody or antigen binding fragment to a patient suffering from a cancer, wherein the antibody or antigen binding fragment binds to PD-1, and comprises:

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

15, and

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

3.

10. The method of claim 9, wherein the cancer is a cancer of a tissue selected from the group consisting of lung, kidney, bladder, liver, stomach, cervix, nasopharynx, oral cavity, oesophagus, larynx, salivary gland, tongue, tonsil, trachea, skin, blood, colon and breast.

11. The method of claim 9, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), renal cancer, renal cell carcinoma, bladder cancer, bladder carcinoma, liver cancer, hepatoma, stomach cancer, cervical cancer, nasopharyngeal cancer, oral cavity cancer, oesophageal cancer, laryngeal cancer, salivary gland cancer, tongue cancer, tonsil cancer, tracheal cancer, skin cancer, melanoma, metastatic melanoma, haematologic cancer, lymphoma, Hodgkin'"'"'s lymphoma, colon cancer, colon carcinoma and breast cancer.

12. The method of claim 9, wherein the administration of the antibody or antigen binding fragment is intravenous.

13. The method of claim 9, wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.

14. The method of claim 9, wherein the antigen binding fragment is a Fab fragment or scFv fragment.

15. A method of treating cancer in a subject, comprising:

culturing T cells obtained from a blood sample from a subject having a cancer in the presence of an antibody or antigen binding fragment which binds to PD-1 to expand a T cell population; and

administering the expanded T cell population to the subject;

wherein the antibody or antigen binding fragment which binds to PD-1 comprises;

at least one light chain variable region incorporating the following CDRs;

16. The method of claim 15, wherein the antibody or antigen binding fragment comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

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

3.

17. The method of claim 15, wherein the cancer is a cancer of a tissue selected from the group consisting of lung, kidney, bladder, liver, stomach, cervix, nasopharynx, oral cavity, oesophagus, larynx, salivary gland, tongue, tonsil, trachea, skin, blood, colon and breast.

18. The method of claim 15, wherein the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer (NSCLC), renal cancer, renal cell carcinoma, bladder cancer, bladder carcinoma, liver cancer, hepatoma, stomach cancer, cervical cancer, nasopharyngeal cancer, oral cavity cancer, oesophageal cancer, laryngeal cancer, salivary gland cancer, tongue cancer, tonsil cancer, tracheal cancer, skin cancer, melanoma, metastatic melanoma, haematologic cancer, lymphoma, Hodgkin'"'"'s lymphoma, colon cancer, colon carcinoma and breast cancer.

19. The method of claim 15, wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.

20. The method of claim 15, wherein the antigen binding fragment is a Fab fragment or scFv fragment.