ANTI-PD-1 ANTIBODY AND USE THEREOF

• US 20170210806A1
• Filed: 08/28/2015
• Published: 07/27/2017
• Est. Priority Date: 07/30/2014
• Status: Active Grant

• Current Assignee: Livzon Mabpharm Inc. (Livzon Pharmaceutical Group Incorporated)
• Original Assignee: Livzon Mabpharm Inc. (Livzon Pharmaceutical Group Incorporated)
• Inventors: LIU, Jie
• Granted Patent: US 10,414,821 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/00115 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• 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 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

A PD-1 antibody or a functional fragment thereof, and use of said antibody in the preparation of a medicament for treating tumors are provided.

Claims

1. An antibody comprising a heavy chain and a light chain, which is capable of specifically binding to PD-1, wherein

(i) the heavy chain comprises H-CDR1, H-CDR2 and H-CDR3 which have the amino sequences represented by SEQ ID NO:

7, 8 and 11 or 9, 10 and 11, respectively; and

(ii) the light chain comprises L-CDR1, L-CDR2 and L-CDR3 which have the amino sequences represented by SEQ ID NO;

12, 13 and 14, respectively.

2. The antibody according to claim 1, wherein

(i) the heavy chain comprises a heavy chain variable region which has the amino sequence represented by SEQ ID NO:

1, 2, 4 or 5; and

(ii) the light chain comprises a light chain variable region which has the amino sequence represented by SEQ ID NO;

3 or 6.

3. The antibody according to claim 1, wherein

(i) the heavy chain comprises a heavy chain variable region which has the amino sequence represented by SEQ ID NO:

4 or 5; and

(ii) the light chain comprises a light chain variable region which has the amino sequence represented by SEQ ID NO;

6.

4. The antibody according to claim 1, wherein the antibody is selected from 10F8, 15H6, BA08-1 and BA08-2.

5. An isolated polynucleotide, which encodes the antibody according to claim 1.

6. A combination of isolated polynucleotides, which comprises a polynucleotide encoding the light chain of the antibody according to claim 1, and a polynucleotide encoding the heavy chain of the antibody.

7. An expression vector, which comprises the polynucleotide according to claim 5, wherein the polynucleotide effectively links to a regulatory sequence which allows the expression of a polypeptide encoded by the polynucleotide in a host cell or a cell-free expression system.

8. A pharmaceutical composition, which comprises the antibody according to claim 1, and a pharmaceutically acceptable carrier.

9. A method for treating or preventing a cancer or an infectious disease in a subject in need thereof, which comprises administering the antibody according to claim 1, to the subject.

10. The method according to claim 9, wherein the cancer is lung cancer or melanoma, and the infectious disease is HIV infection or hepatitis B virus infection.

11. A method for enhancing T cell immune response in a subject in need thereof, which comprises administering the antibody according to claim 1, to the subject.

12. The method according to claim 11, wherein enhancing T cell immune response includes enhancing cytokine production of T cells, preferably, the cytokine includes IL-2 and/or IFN-γ

.

13. The method according to claim 11, wherein the method further comprises administering an anti-CD3 antibody to the subject.