Anti-vista antibodies and fragments

Patent metadata

Field	Value
Publication number	US-11242392-B2
Application number	US-201916395585-A
Country	US
Kind code	B2
Filing date	Apr 26, 2019
Priority date	Dec 24, 2013
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of making and using same. Methods of use include methods of treatment of cancer, including leukemias, lymphomas, solid tumors and melanomas.

First claim

What is claimed is:

1. A method for treating cancer in a subject in need thereof, said method comprising administering to the subject an effective amount of an antibody or antibody fragment, which antibody comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30.

2. A method for suppressing tumor growth in a subject in need thereof, said method comprising administering to the subject an effective amount of an antibody or antibody fragment, which antibody comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30.

3. A method for eliciting a biological response in a subject in need thereof, said method comprising administering to the subject an effective amount of an antibody or antibody fragment, which antibody comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30, thereby enhancing an immune response, wherein the biological response comprises one or more of:
(a) activation of monocytes;
(b) induction of T-cell proliferation and cytokine secretion;
(c) increased survival of monocytes;
(d) induction of antibody-dependent cell-mediated cytotoxicity (ADCC) in cells-expressing VISTA; and
(e) induction of antibody-dependent cellular phagocytosis (ADCP) in cells-expressing VISTA.

4. The method of claim 1 , wherein the antibody or antibody fragment is administered at least one of:
(i) parenterally or nonparenterally;
(ii) in a dosage range of 0.1-15 mg/kg per administration;
(iii) weekly, once every two weeks, once every three weeks, once every month, once every 2 months, or once every 3 months.

5. The method of claim 1 , wherein the subject is human.

6. The method of claim 1 , wherein the cancer is a leukemia, a lymphoma, a myelodysplastic syndrome, a myeloma, or a combination thereof; or a solid tumor.

7. The method of claim 6 , wherein the leukemia is acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid (myelogenous) leukemia (AML), chronic myelogenous leukemia (CML), hairy cell leukemia, T-cell prolymphocytic leukemia, large granular lymphocytic leukemia, or adult T-cell leukemia.

8. The method of claim 6 , wherein the solid tumor:
(i) is surrounded by a tumor stroma comprising myeloid cells, T-cells, or a combination of myeloid cells and T-cells;
(ii) is infiltrated with myeloid cells, T cells or a combination of myeloid cells and T-cells; and/or
(iii) is lung cancer.

9. The method of claim 8 , wherein the lung cancer is a non-small cell lung carcinoma (NSCLC).

10. The method of claim 1 , further comprising administering a second treatment or therapeutic.

11. The method of claim 10 , wherein the second treatment or therapeutic is a vaccine, surgery, chemotherapy, radiation therapy, biologic therapy, targeted therapy, immunomodulatory therapy, or a combination thereof.

12. The method of claim 2 , wherein the antibody or antibody fragment is administered at least one of:
(i) parenterally or nonparenterally;
(ii) in a dosage range of 0.1-15 mg/kg per administration; and/or
(iii) weekly, once every two weeks, once every three weeks, once every month, once every 2 months, or once every 3 months.

13. The method of claim 2 , wherein the subject is human.

14. The method of claim 2 , wherein the cancer is a leukemia, a lymphoma, a myelodysplastic syndrome, a myeloma, or a combination thereof;
or a solid tumor.

15. The method of claim 14 , wherein the leukemia is acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid (myelogenous) leukemia (AML), chronic myelogenous leukemia (CML), hairy cell leukemia, T-cell prolymphocytic leukemia, large granular lymphocytic leukemia, or adult T-cell leukemia.

16. The method of claim 14 , wherein the solid tumor:
(i) is surrounded by a tumor stroma comprising myeloid cells, T-cells, or a combination of myeloid cells and T-cells;
(ii) is infiltrated with myeloid cells, T cells or a combination of myeloid cells and T-cells; and/or
(iii) is lung cancer.

17. The method of claim 16 , wherein the lung cancer is a non-small cell lung carcinoma (NSCLC).

18. The method of claim 2 , further comprising administering a second treatment or therapeutic.

19. The method of claim 18 , wherein the second treatment or therapeutic is a vaccine, surgery, chemotherapy, radiation therapy, biologic therapy, targeted therapy, immunomodulatory therapy, or a combination thereof.

20. The method of claim 3 , wherein the immune response is an antitumor immune response.

21. The method of claim 1 , wherein the antibody comprises a variable heavy chain polypeptide at least 90% identical to SEQ ID NO:37 and a variable light chain polypeptide at least 90% identical to SEQ ID NO:44.

22. The method of claim 2 , wherein the antibody comprises a variable heavy chain polypeptide at least 90% identical to SEQ ID NO:37 and a variable light chain polypeptide at least 90% identical to SEQ ID NO:44.

23. The method of claim 3 , wherein the antibody comprises a variable heavy chain polypeptide at least 90% identical to SEQ ID NO:37 and a variable light chain polypeptide at least 90% identical to SEQ ID NO:44.

24. The method of claim 1 , wherein the antibody comprises a variable heavy chain polypeptide having the sequence of SEQ ID NO:37 and a variable light chain polypeptide having the sequence of SEQ ID NO:44.

25. The method of claim 2 , wherein the antibody comprises a variable heavy chain polypeptide having the sequence of SEQ ID NO:37 and a variable light chain polypeptide having the sequence of SEQ ID NO:44.

26. The method of claim 3 , wherein the antibody comprises a variable heavy chain polypeptide having the sequence of SEQ ID NO:37 and a variable light chain polypeptide having the sequence of SEQ ID NO:44.

27. The method of claim 1 , wherein the antibody or antibody fragment thereof comprises a human IgG1 constant region.

28. The method of claim 2 , wherein the antibody or antibody fragment thereof comprises a human IgG1 constant region.

29. The method of claim 3 , wherein the antibody or antibody fragment thereof comprises a human IgG1 constant region.

30. The method of claim 21 , wherein the antibody or antibody fragment comprises the heavy chain of SEQ ID NO:61 and the light chain of SEQ ID NO:56.

3

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Snyder Linda
• Powers Gordon

Classifications

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5751

  of the skin, e.g. melanoma · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/04

  Immunostimulants · CPC title