IP Library › Granted Patent US 11,242,395
Granted Patent B2
US 11,242,395 · App. 16/108,018 · Granted Feb 8, 2022

Anti-CD137 molecules and use thereof

Inventors: Peter Peizhi Luo (Suzhou, CN); Fangyong Du (Suzhou, CN); Yan Li (Suzhou, CN); Guizhong Liu (Suzhou, CN); Jun Chen (Suzhou, CN); Xiaohong She (Suzhou, CN); Peter Cheung (Suzhou, CN)
Assignee: Adagene Inc.
C07K16/2878A61K39/3955A61K39/39591A61P35/00C07K16/2818A61K45/06A61K2039/505A61K2039/545C07K2317/21C07K2317/33C07K2317/52C07K2317/55C07K2317/56C07K2317/75C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 11,242,395
App. No.
16/108,018
Granted
Feb 8, 2022
Kind
B2
Abstract

The present disclosure provides antibodies that bind to human CD137 or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, and for the treatment of cancer.

Claims (32)

1. An isolated antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CD137, comprising a heavy chain variable region and a light chain variable region,

wherein:

(i) the heavy chain variable region comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO:731, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:755, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:779; and

(ii) the light chain variable region comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO:803, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:827, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:851.

2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds human CD137 with a K D of 0.1 pM to 100 nM, as measured by surface plasmon resonance.

3. The antibody or antigen-binding fragment of claim 2 , wherein the antibody or antigen-binding fragment binds human CD137 with a K D of 0.1 pM to 50 nM, as measured by surface plasmon resonance.

4. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is cross-reactive with a CD137 polypeptide from at least one non-human species selected from the group consisting of cynomolgus monkey, mouse, rat and dog.

5. The antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment binds to cynomolgus monkey CD137.

6. The antibody or antigen-binding fragment of claim 1 , wherein an activity of human CD137 expressed on a human cell is decreased when contacted with the antibody or antigen-binding fragment.

7. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment has a half maximal inhibitory concentration (IC 50 ) of 0.1 pM to 100 nM for blocking binding of human CD137 to human CD137L in vitro.

8. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment completely blocks binding of human CD137 to human CD137L in vitro when the antibody or antigen-binding fragment is provided at a concentration of about 1 μM or greater.

9. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment blocks CD137 signaling stimulated by CD137L in a cell that expresses CD137.

10. The antibody or antigen-binding fragment of claim 1 , wherein an activity of human CD137 expressed on a human cell is increased when contacted with the antibody or antigen-binding fragment.

11. The antibody or antigen-binding fragment of claim 10 , wherein contacting a human cell expressing CD137 with the antibody or antigen-binding fragment results in increased NF-κB-dependent transcription.

12. The antibody or antigen-binding fragment of claim 1 , wherein the antibody comprises a human IgG2 Fc region.

13. The antibody or antigen-binding fragment of claim 1 , wherein the antibody comprises a human IgG4 Fc region.

14. The antibody or antigen-binding fragment of claim 13 , wherein the human IgG4 Fc region comprises an S241P mutation, wherein numbering is according to Kabat.

15. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.

16. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds to one or more amino acid residues within amino acid residues 34-93 of SEQ ID NO:1.

17. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds to one or more amino acid residues selected from the group consisting of amino acid residues 34-36, 53-55, and 92-93 of SEQ ID NO:1.

18. The antibody or antigen-binding fragment of claim 17 , wherein the antibody or antigen-binding fragment binds to one or more of amino acid residues 34-36, one or more of amino acid residues 53-55, and one or more or amino acid residues 92-93 of SEQ ID NO:1.

19. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment does not bind to one or more of amino acid residues selected from the group consisting of amino acid residues 109-112, 125, 126, 135-138, 150 and 151 of SEQ ID NO:1.

20. The antibody or antigen-binding fragment of claim 19 , wherein the antibody or antigen-binding fragment does not bind to amino acid residues 109-112, 125, 126, 135-138, 150 and 151 of SEQ ID NO:1.

21. An isolated antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CD137, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence of SEQ ID NO:71, and the light chain variable region comprises an amino acid sequence of SEQ ID NO:72.

22. An isolated antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CD137, wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 657, and the light chain comprises an amino acid sequence of SEQ ID NO: 658.

23. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment does not induce ADCC effect.

24. The antibody or antigen-binding fragment of claim 1 , wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a Fv fragment, and a single chain antibody (scFv).

25. The antibody or antigen-binding fragment of claim 21 , wherein the antibody comprises a human IgG4 Fc region.

26. The antibody or antigen-binding fragment of claim 25 , wherein the human IgG4 Fc region comprises an S241P mutation, wherein numbering is according to Kabat.

27. The antibody or antigen-binding fragment of claim 21 , wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a Fv fragment, and a single chain antibody (scFv).

28. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 21 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 22 and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 19, 2018
From: LUO, PETER PEIZHI; DU, FANGYONG; LI, YAN; LIU, GUIZHONG; CHEN, JUN; SHE, XIAOHONG; CHEUNG, PETER
To: ADAGENE INC.
Reel/Frame 047236/0278 →
Continuity (2)
Continuation In Part PCTCN2017098332 · Aug 21, 2017
Related Publication 20190055314A1 · Feb 21, 2019
Cited By (2)
US 12,378,319 US 12,472,148