Antibodies for t-cell activation

TWI933781BActive Publication Date: 2026-08-01AP BIOSCIENCES INC
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Patent Information

Authority / Receiving Office
TW · TW
Patent Type
Patents
Current Assignee / Owner
Filing Date
2020-06-24
Publication Date
2026-08-01

AI Technical Summary

Technical Problem

Current anti-CD137 antibodies used in cancer therapy face hepatotoxicity issues, and there is a need for a therapy that can activate the 4-1BB:4-1BBL pathway without causing liver toxicity, while also enhancing T cell effector functions and inhibiting tumor growth.

Method used

Development of bispecific antibodies that target CD137 and PD-L1, which are designed to activate T cells through cross-linking, avoiding hepatotoxicity and maintaining antitumor potency by binding to tumor-specific antigens like PD-L1, Her2, or tumor-specific glycans.

Benefits of technology

The bispecific antibodies enhance T cell effector functions and inhibit tumor growth effectively, reducing hepatotoxicity and improving treatment outcomes in various cancers, including prostate, lung, melanoma, and other solid tumors.

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Patent Text Reader

Abstract

This article provides antibodies including an antigen-binding region that binds to CD137. This article also provides bispecific antibodies including a first antigen-binding region that binds to CD137 and a second antigen-binding region that binds to an immune checkpoint molecule, an immunostimulatory molecule, or a tumor antigen. This article provides pharmaceutical compositions including such antibodies and methods for treating cancer.
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Description

Technical field

Prior technology

Content of invention

Implementation

Sequence Listing

Claims

1. An anti-CD137 antibody or an antigen-binding fragment thereof, comprising: (a) V HCDR-H1, CDR-H2 and CDR-H3, wherein CDR-H1 contains an amino acid sequence of SEQ ID NO:19, CDR-H2 contains an amino acid sequence of SEQ ID NO:20, and CDR-H3 contains an amino acid sequence of SEQ ID NO:21; and (b) V LCDR-L1, CDR-L2 and CDR-L3, wherein CDR-L1 contains an amino acid sequence of SEQ ID NO:22, CDR-L2 contains an amino acid sequence of SEQ ID NO:23, and CDR-L3 contains an amino acid sequence of SEQ ID NO:

24.

2. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 1, wherein the VH region contains an amino acid sequence containing SEQ ID NO:17, and wherein the VL region contains an amino acid sequence containing SEQ ID NO:

18.

3. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 1, wherein the antibody contains an Fc domain.

4. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 3, wherein the Fc domain is an IgG domain, an IgE domain, an IgM domain, an IgD domain, an IgA domain, or an IgY domain.

5. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 4, wherein the IgG domain is an IgG1 domain, an IgG2 domain, an IgG3 domain or an IgG4 domain.

6. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 5, wherein the IgG1 domain comprises the amino acid sequence of SEQ ID NO:

26.

7. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 5, wherein the IgG4 domain comprises the amino acid sequence of SEQ ID NO:

25.

8. The anti-CD137 antibody or its antigen-binding fragment as claimed in claim 1, wherein the antigen-binding fragment comprises scFv, F(ab')2 or Fab.

9. A pharmaceutical composition comprising an anti-CD137 antibody or an antigen-binding fragment thereof as claimed in any one of claims 1 to 8 and a pharmaceutically acceptable carrier.

10. The pharmaceutical composition of claim 9, wherein the pharmaceutically acceptable carrier is bound to the C-terminus of one or more polypeptides of the anti-CD137 antibody or its antigen-binding fragment.

11. Use of an anti-CD137 antibody or an antigen-binding fragment thereof as claimed in any one of claims 1 to 8, or a pharmaceutical composition as claimed in claim 9 or 10, for the manufacture of a medicine for the treatment of cancer in an individual.

12. As claimed in claim 11, wherein the cancer is selected from prostate cancer, lung cancer, melanoma, lymphoma, breast cancer, head and neck cancer, renal cell carcinoma (RCC), ovarian cancer, kidney cancer, urinary tract cancer, bladder cancer, uterine cancer, cervical cancer, ovarian cancer, liver cancer, stomach cancer, colon cancer, rectal cancer, oral cancer, pharyngeal cancer, pancreatic cancer, thyroid cancer, skin cancer, brain cancer, bone cancer, hematopoietic cancer, or leukemia.

13. A bispecific antibody comprising a first antigen-binding region and a second antigen-binding region, wherein the first antigen-binding region binds to CD137, wherein the first antigen-binding region comprises (i) a VH region comprising an amino acid sequence containing the amino acid sequence of SEQ ID NO:17; and (ii) a VL region comprising an amino acid sequence containing 100 to 120 amino acids of the N-terminal sequence of SEQ ID NO:18; and wherein the second antigen-binding region binds to an immune checkpoint molecule, an immunostimulatory molecule, or a tumor antigen.

14. The bispecific antibody of claim 13, wherein the first antigen-binding region comprises a VH region comprising the amino acid sequence of SEQ ID NO:17; and a VL region comprising the amino acid sequence of 100 to 120 amino acids of the N-terminal sequence of SEQ ID NO:

18.

15. The bispecific antibody of claim 13, wherein the second antigen-binding region binds to an antigen selected from: PD-L1, PD-1, CTLA-4, LAG3, CD28, CD40, CD137, CD27, ICOS, Her2, or a glycan.

16. The bispecific antibody of claim 15, wherein the second antigen-binding region is bound to PD-L1, Her2 or a glycan.

17. The bispecific antibody of claim 15, wherein the first antigen-binding region and the second antigen-binding region comprise scFv, F(ab')2, Fab, or any combination thereof.

18. The bispecific antibody of claim 17, wherein the first antigen-binding region comprises scFv and the second antigen-binding region comprises Fab.

19. The bispecific antibody of claim 18, wherein the scFv comprises: a VH region comprising the amino acid sequence of SEQ ID NO:17; and a VL region comprising the amino acid sequence of 100 to 120 amino acids of the N-terminal sequence of SEQ ID NO:

18.

20. The bispecific antibody of claim 19, further comprising a linker between the VH region and the VL region of the scFv.

21. The bispecific antibody of claim 20, wherein the scFv contains the amino acid sequence of SEQ ID NO:

34.

22. The bispecific antibody of claim 18 further includes an Fc domain.

23. The bispecific antibody of claim 22, wherein the Fc domain is an IgG domain, an IgE domain, an IgM domain, and an IgD domain, an IgA domain, or an IgY domain.

24. The bispecific antibody as claimed in claim 23, wherein the Fc domain is an IgG domain.

25. The bispecific antibody of claim 24, wherein the IgG domain is an IgG1 domain, an IgG2 domain, an IgG3 domain, or an IgG4 domain.

26. The bispecific antibody of claim 22, wherein the scFv is linked to the C-terminus of the Fc domain.

27. The bispecific antibody of claim 22 further includes a linker between the Fc domain and the scFv.

28. The bispecific antibody of claim 22, wherein the Fab is linked to the N-terminus of the Fc domain.

29. The bispecific antibody of claim 13, wherein the antibody comprises the heavy chain sequence of SEQ ID NO:32 and the light chain sequence of SEQ ID NO:

30.

30. The bispecific antibody of claim 13, wherein the antibody comprises the heavy chain sequence of SEQ ID NO:36 and the light chain sequence of SEQ ID NO:

35.

31. The bispecific antibody of claim 13, wherein the antibody comprises the heavy chain sequence of SEQ ID NO:38 and the light chain sequence of SEQ ID NO:

37.

32. The bispecific antibody of claim 13, wherein the antibody comprises the heavy chain sequence of SEQ ID NO:40 and the light chain sequence of SEQ ID NO:

39.

33. An antibody-drug conjugate comprising a therapeutic agent and an anti-CD137 antibody or an antigen-binding fragment thereof as claimed in any one of claims 1 to 8, or a bispecific antibody or an antigen-binding fragment thereof as claimed in any one of claims 13 to 32.

34. The antibody-drug conjugate of claim 33, wherein the therapeutic agent is covalently linked to the anti-CD137 antibody or its antigen-binding fragment via a linker.

35. A pharmaceutical composition comprising a bispecific antibody as claimed in any one of claims 13 to 32 and at least one pharmaceutically acceptable carrier.

36. Use of a bispecific antibody or antigen-binding fragment thereof as claimed in any one of claims 13 to 32, for the manufacture of a medicine for the treatment of cancer in an individual.

37. As claimed in claim 36, wherein the cancer is selected from prostate cancer, lung cancer, melanoma, lymphoma, breast cancer, head and neck cancer, renal cell carcinoma (RCC), ovarian cancer, kidney cancer, urinary tract cancer, bladder cancer, uterine cancer, cervical cancer, ovarian cancer, liver cancer, stomach cancer, colon cancer, rectal cancer, oral cancer, pharyngeal cancer, pancreatic cancer, thyroid cancer, skin cancer, brain cancer, bone cancer, hematopoietic cancer, or leukemia.

38. As claimed in claim 12 or 37, wherein the lung cancer is non-small cell lung cancer (NSCLC).

Citation Information

Patent Citations

  • Antibodies targeting CD137 and methods of use thereof

    EP3470428A1

  • Anti-Tenascin-C A2 Antibodies and Methods of Use

    US20120039807A1

  • Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof

    WO2018156740A1