CD80 VARIANT AND CD80 FUSION PROTEIN

Claims

1. A variant of the CD80 protein comprising a functionally active fragment of the CD80 protein or a variant thereof, wherein the variant has mutations in one or more amino acid regions compared to the corresponding functionally active fragment of the wild-type CD80, wherein the amino acid position numbers are determined relative to the amino acid position numbers in SEQ ID NO: 1, wherein the amino acid mutations are selected from any of the groups: 1) N64; 2) N55 and N64; 3) N55, N64 and N152; 4) N55, N64 and N192; 5) N55, N64 and N198; 6) N55, N64, N152 and N198; 7) N55, N64, N152 and N192; 8) N55, N64, N152, N173, N177 and N198; 9) N55, N64, N152, N173 and N198; And 10) N55, N64, N152, N177 and N198, and where the mutations are selected from N55A / Q, N64A, N152A, N173Q, N177A, N192A and N198A / Q.

2. A variant of the CD80 protein according to claim 1, comprising any of the groups of amino acid mutations selected from: 1) N64A; 2) N55A and N64A; 3) N55A, N64A and N152A; 4) N55A, N64A and N192A; 5) N55A, N64A and N198A; 6) N55A, N64A, N152A and N198A; 7) N55A, N64A, N152A and N192A; 8) N55Q, N64A, N152A and N198Q; 9) N55Q, N64A, N152A, N173Q, N177A and N198Q; 10) N55Q, N64A, N152A, N173Q and N198Q; And 11) N55Q, N64A, N152A, N177A and N198Q.

3. A CD80 protein variant according to any one of claims 1, 2, comprising at least one first class amino acid mutation capable of maintaining or increasing the stability of the CD80 protein variant, wherein the first class amino acid mutations are selected from one or more of the following amino acid mutations: N55A / Q, N64A, N152A, N192A and N198A / Q.

4. A protein variant according to any one of paragraphs 1-3, containing any of the groups of mutations of amino acids of the first class, selected from: 1) N64A; 2) N55A and N64A; 3) N55A, N64A and N152A; 4) N55A, N64A and N192A; 5) N55A, N64A and N198A; 6) N55A, N64A, N152A and N198A; 7) N55A, N64A, N152A and N192A; and 8) N55Q, N64A, N152A and N198Q.

5. A CD80 protein variant according to any one of claims 1-4, comprising at least one second class amino acid mutation capable of retaining the binding activity of the CD80 protein variant, wherein the second class amino acid mutations are selected from one or more of the following amino acid mutations: N152A, and N192A, and N198A / Q.

6. A CD80 protein variant according to any one of claims 1-5, comprising at least one second class amino acid mutation capable of retaining the binding activity of the CD80 protein variant, wherein the second class amino acid mutations are selected from N55A / Q and / or N64A.

7. A CD80 protein variant according to any one of claims 1-6, comprising at least one third class amino acid mutation capable of maintaining the binding affinity of the CD80 protein variant, wherein the third class amino acid mutations are selected from one or more of the following amino acid mutations: N55A / Q, N64A, N152A and N198A.

8. A CD80 protein variant according to any one of claims 1 to 7, comprising at least one class three amino acid mutation capable of maintaining the binding affinity of the CD80 protein variant, wherein the class three amino acid mutation is N192A.

9. A CD80 protein variant according to any one of claims 1-8, comprising at least one class four amino acid mutation capable of enhancing the binding of the CD80 protein variant to CD28 and / or PD-L1, wherein the class four amino acid mutations are N173Q and / or N177A.

10. A CD80 protein variant according to any one of claims 1-9, comprising the amino acid sequence indicated by any one of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO:

24.

11. A fusion protein comprising a CD80 protein variant according to any one of claims 1-10.

12. The fusion protein of claim 11, further comprising an immunoglobulin Fc region or a variant thereof, wherein the immunoglobulin Fc region comprises an IgG Fc region.

13. The fusion protein according to any one of claims 11, 12, comprising the amino acid sequence indicated under any one of SEQ ID NO: 27-37.

14. A polypeptide comprising a variant of the CD80 protein according to any one of claims 1-10 or a fusion protein according to any one of claims 11-13.

15. One or more isolated nucleic acid molecules encoding a CD80 protein variant according to any one of claims 1-10, a fusion protein according to any one of claims 11-13, or a polypeptide according to claim 14.

16. A vector containing nucleic acid molecules according to claim 15.

17. A host cell containing nucleic acid molecules according to claim 15 or a vector according to claim 16.

18. A pharmaceutical composition comprising a CD80 protein variant according to any one of claims 1-10, a fusion protein according to any one of claims 11-13, a polypeptide according to claim 14, a nucleic acid molecule according to claim 15, a vector according to claim 16 and / or a host cell according to claim 17 and optionally a pharmaceutically acceptable carrier.

19. A pharmaceutical combination comprising a CD80 protein variant according to any one of claims 1-10, a fusion protein according to any one of claims 11-13 or a polypeptide according to claim 14 and an immune checkpoint inhibitor, wherein the immune checkpoint comprises PD-1, PD-L1, GITR and / or CTLA-4.

20. A method for preventing and / or treating a disease and / or disorder, comprising administering to an individual in need thereof a CD80 protein variant according to any one of claims 1-10, a fusion protein according to any one of claims 11-13, a polypeptide according to claim 14, nucleic acid molecules according to claim 15, a vector according to claim 16, a host cell according to claim 17, a pharmaceutical composition according to claim 18, or a pharmaceutical combination according to claim 19.

21. The method of claim 20, wherein the tumor is selected from one or more of malignant melanoma, breast cancer, gastric cancer, kidney cancer, non-small cell lung cancer, colon cancer, rectal cancer, squamous cell carcinoma of the head and neck, liver cancer, kidney cancer, mesothelioma, bladder cancer, pancreatic cancer, ovarian cancer, endometrial cancer, and lymphoma.