IP Library › Granted Patent US 12,258,407
Granted Patent B2
US 12,258,407 · App. 17/260,974 · Granted Mar 25, 2025

Anti-PD-1 antibodies, dosages and uses thereof

Inventors: Lieping Chen (Beijing, CN); Liqun Luo (Beijing, CN)
Assignee: Tayu Huaxia Biotech Medical Group Co., Ltd.
C07K16/2818A61K2039/505A61K2039/545C07K2317/52C07K2317/565
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Quick Facts
Patent No.
US 12,258,407
App. No.
17/260,974
Granted
Mar 25, 2025
Kind
B2
Abstract

Provided are anti-PD-1 antibodies or fragments thereof. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer, infection or immune disorders are also provided.

Claims (29)

1. A method of treating a cancer in a human patient in need thereof, comprising administering to the patient one or more doses of an isolated antibody or fragment thereof having specificity to a human programmed cell death protein 1 (PD-1), wherein the antibody comprises a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:

(a) HCDR1 comprises an amino acid sequence of GFTFSSYT (SEQ ID NO: 1), HCDR2 comprises an amino acid sequence of ISHGGGDT (SEQ ID NO: 2), HCDR3 comprises an amino acid sequence of ARHSGYERGYYYVMDY (SEQ ID NO: 3), LCDR1 comprises an amino acid sequence of ESVDYYGFSF (SEQ ID NO: 4), LCDR2 comprises an amino acid sequence of AAS (SEQ ID NO: 5), and LCDR3 comprises an amino acid sequence of QQSKEVPW (SEQ ID NO: 6);

(b) HCDR1 comprises an amino acid sequence of GYTFTSYT (SEQ ID NO: 7), HCDR2 comprises an amino acid sequence of INPTTGYT (SEQ ID NO: 8), HCDR3 comprises an amino acid sequence of ARDDAYYSGY (SEQ ID NO: 9), LCDR1 comprises an amino acid sequence of ENIYSNL (SEQ ID NO: 10), LCDR2 comprises an amino acid sequence of AAK (SEQ ID NO: 11), and LCDR3 comprises an amino acid sequence of QHFWGTPWT (SEQ ID NO: 12); or

(c) HCDR1 comprises an amino acid sequence of GFAFSSYD (SEQ ID NO: 13), HCDR2 comprises an amino acid sequence of ITIGGGTT (SEQ ID NO: 14), HCDR3 comprises an amino acid sequence of ARHRYDYFAMDN (SEQ ID NO: 15), LCDR1 comprises an amino acid sequence of ENVDNYGINF (SEQ ID NO: 16), LCDR2 comprises an amino acid sequence of VSS (SEQ ID NO: 17), and LCDR3 comprises an amino acid sequence of QQSKDVPW (SEQ ID NO: 18); and

wherein each dose is at least about 1 mg/kg and less than 10 mg/kg.

2. The method of claim 1 , wherein each dose is about 1 mg/kg, about 3 mg/kg, or 200 mg.

3. The method of claim 2 , wherein each dose is 3 mg/kg.

4. The method of claim 1 , wherein HCDR1 comprises an amino acid sequence of GFTFSSYT (SEQ ID NO: 1), HCDR2 comprises an amino acid sequence of ISHGGGDT (SEQ ID NO: 2), HCDR3 comprises an amino acid sequence of ARHSGYERGYYYVMDY (SEQ ID NO: 3), LCDR1 comprises an amino acid sequence of ESVDYYGFSF (SEQ ID NO: 4), LCDR2 comprises an amino acid sequence of AAS (SEQ ID NO: 5), and LCDR3 comprises an amino acid sequence of QQSKEVPW (SEQ ID NO: 6).

5. The method of claim 4 , wherein the antibody or fragment thereof further comprises a heavy chain constant region, a light chain constant region, an Fc region, or the combination thereof.

6. The method of claim 5 , wherein the antibody or fragment thereof comprises a light chain constant region, wherein the light chain constant region is a kappa or lambda chain constant region.

7. The method of claim 1 , wherein the antibody or fragment thereof is of an isotype of IgG, IgM, IgA, IgE or IgD.

8. The method of claim 7 , wherein the isotype is IgG1, IgG2, IgG3 or IgG4.

9. The method of claim 1 , wherein the antibody or fragment thereof is a chimeric antibody, a humanized antibody, or a fully human antibody.

10. The method of claim 9 , wherein the antibody or fragment thereof is a humanized antibody.

11. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 35, SEQ ID NO: 37, or SEQ ID NO: 39, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 41, SEQ ID NO: 43, or SEQ ID NO: 45.

12. The method of claim 1 , wherein the method is for treating a cancer, wherein the cancer is selected from the group consisting of bladder cancer, liver cancer, colon cancer, rectal cancer, endometrial cancer, leukemia, lymphoma, pancreatic cancer, small cell lung cancer, non-small cell lung cancer, breast cancer, urethral cancer, head and neck cancer, gastrointestinal cancer, stomach cancer, esophageal cancer, ovarian cancer, renal cancer, melanoma, prostate cancer and thyroid cancer.

13. A method of treating an infection or Alzheimer's disease, in a human patient in need thereof, comprising administering to the patient one or more doses of an isolated antibody or fragment thereof having specificity to a human programmed cell death protein 1 (PD-1), wherein the antibody comprises a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein:

(a) HCDR1 comprises an amino acid sequence of GFTFSSYT (SEQ ID NO: 1), HCDR2 comprises an amino acid sequence of ISHGGGDT (SEQ ID NO: 2), HCDR3 comprises an amino acid sequence of ARHSGYERGYYYVMDY (SEQ ID NO: 3), LCDR1 comprises an amino acid sequence of ESVDYYGFSF (SEQ ID NO: 4), LCDR2 comprises an amino acid sequence of AAS (SEQ ID NO: 5), and LCDR3 comprises an amino acid sequence of QQSKEVPW (SEQ ID NO: 6);

(b) HCDR1 comprises an amino acid sequence of GYTFTSYT (SEQ ID NO: 7), HCDR2 comprises an amino acid sequence of INPTTGYT (SEQ ID NO: 8), HCDR3 comprises an amino acid sequence of ARDDAYYSGY (SEQ ID NO: 9), LCDR1 comprises an amino acid sequence of ENIYSNL (SEQ ID NO: 10), LCDR2 comprises an amino acid sequence of AAK (SEQ ID NO: 11), and LCDR3 comprises an amino acid sequence of QHFWGTPWT (SEQ ID NO: 12); or

(c) HCDR1 comprises an amino acid sequence of GFAFSSYD (SEQ ID NO: 13), HCDR2 comprises an amino acid sequence of ITIGGGTT (SEQ ID NO: 14), HCDR3 comprises an amino acid sequence of ARHRYDYFAMDN (SEQ ID NO: 15), LCDR1 comprises an amino acid sequence of ENVDNYGINF (SEQ ID NO: 16), LCDR2 comprises an amino acid sequence of VSS (SEQ ID NO: 17), and LCDR3 comprises an amino acid sequence of QQSKDVPW (SEQ ID NO: 18); and

wherein each dose is at least about 1 mg/kg and less than 10 mg/kg.

14. The method of claim 4 , wherein each dose is about 1 mg/kg, about 3 mg/kg, or 200 mg.

15. The method of claim 14 , wherein each dose is 3 mg/kg.

16. The method of claim 13 , wherein HCDR1 comprises an amino acid sequence of GFTFSSYT (SEQ ID NO: 1), HCDR2 comprises an amino acid sequence of ISHGGGDT (SEQ ID NO: 2), HCDR3 comprises an amino acid sequence of ARHSGYERGYYYVMDY (SEQ ID NO: 3), LCDR1 comprises an amino acid sequence of ESVDYYGFSF (SEQ ID NO: 4), LCDR2 comprises an amino acid sequence of AAS (SEQ ID NO: 5), and LCDR3 comprises an amino acid sequence of QQSKEVPW (SEQ ID NO: 6).

17. The method of claim 16 , wherein each dose is about 1 mg/kg, about 3 mg/kg, or 200 mg.

18. The method of claim 17 , wherein each dose is 3 mg/kg.

19. The method of claim 13 , wherein the method is for treating an infection, wherein the infection is viral infection, bacterial infection, fungal infection or infection by a parasite.

20. The method of claim 13 , wherein the method is for treating an infection, wherein the infection is hepatitis.

21. The method of claim 20 , wherein the hepatitis is selected from hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 9, 2021
From: CHEN, LIEPING; LUO, LIQUN
To: TAYU HUAXIA BIOTECH MEDICAL GROUP CO., LTD.
Reel/Frame 056803/0338 →
Priority Claims (1)
WO PCT/CN2018/096206 · Jul 19, 2018 · international
Continuity (1)
Related Publication 20210261665A1 · Aug 26, 2021
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