Granted Patent B2

US 12,365,734 · App. 17/441,028 · Granted Jul 22, 2025

Inventor: Huawei Qiu (Bridgewater, NJ)

Assignee: GENZYME CORPORATION

C07K16/2809C07K2317/24C07K2317/565C07K2317/76C07K2317/92C07K2317/94

Abstract

Claims (26)

1. A binding polypeptide that specifically binds human αβTCR/CD3 complex, comprising a heavy chain variable region, a light chain variable region, and a constant region, wherein:

the light chain variable region comprises three complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 26, 27, and 28, respectively;

SEQ ID NO: 28 comprises the amino acid sequence Q-Q-W-S-S-X 1 -X 2 -L-T, wherein X 1 is an amino acid selected from the group consisting of Q, D, H, S, Y, and A, and X 2 is an amino acid selected from the group consisting of P and A;

wherein the light chain variable region further comprises a human light chain framework region set forth in SEQ ID NO: 14;

wherein the heavy chain variable region comprises any one of an amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 12, 13, 15, and 16; and

the constant region is of human origin.

2. The binding polypeptide of claim 1 , wherein X 1 is S.

3. The binding polypeptide of claim 1 , wherein X 2 is P.

4. The binding polypeptide of claim 1 , wherein the heavy chain variable region comprises the sequences set forth in SEQ ID NO: 16.

5. The binding polypeptide of claim 1 , wherein the binding polypeptide has increased stability at pH greater than 5.0 compared to a humanized anti-αβTCR antibody, VH31.

6. The binding polypeptide of claim 1 , wherein the binding polypeptide has increased stability at a temperature greater than 4° C. compared to a humanized anti-αβTCR antibody, VH31.

7. The binding polypeptide of claim 1 , wherein the constant region comprises an Fc modification with a modified glycosylation pattern that reduces Fcγ receptor binding, optionally wherein the Fcγ receptor is selected from the group consisting of FcγRIIIa and FcγRI.

8. The binding polypeptide of claim 7 , wherein the Fc modification is selected from the group consisting of N297Q/S298N/Y300S, S298N/T299A/Y300S, and S298N/Y300S.

9. The binding polypeptide of claim 1 , wherein the binding polypeptide is humanized.

10. The binding polypeptide of claim 1 , wherein the binding polypeptide is a monoclonal antibody.

11. The binding polypeptide of claim 1 , wherein the binding polypeptide is multispecific, optionally wherein the binding polypeptide is bispecific.

12. A pharmaceutical composition, comprising the binding polypeptide of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. A formulation comprising the pharmaceutical composition of claim 12 , wherein the formulation is selected from the group consisting of a lyophilized formulation and a liquid formulation.

14. A nucleic acid encoding the binding polypeptide according to claim 1 .

15. A vector comprising the nucleic acid according to claim 14 .

16. A cell which expresses the nucleic acid according to claim 14 .

17. The cell according to claim 16 , wherein the cell is a mammalian cell, optionally wherein the mammalian cell is selected from the group consisting of a Chinese hamster ovary (CHO) cell and a human embryonic kidney (HEK) cell.

18. A method of treating a subject for a T-cell-mediated disease or disorder, wherein the T cell mediated disease, or disorder arises due to transplantation of a cell, tissue, body part, or organ comprising administering to the subject an effective amount of the binding polypeptide of claim 1 .

19. A method of treating a subject for a T-cell-mediated disease or disorder, wherein the T cell mediated disease, or disorder arises due to an autoimmune disease comprising administering to the subject an effective amount of the binding polypeptide of claim 1 .

20. A method of treating a subject for a T-cell-mediated disease or disorder, wherein the T cell mediated disease, or disorder is multiple sclerosis comprising administering to the subject an effective amount of the binding polypeptide of claim 1 .

21. A method of treating a subject for a T-cell-mediated disease or disorder, wherein the T cell mediated disease, or disorder is type I diabetes comprising administering to the subject an effective amount of the binding polypeptide of claim 1 .

Assignments (1)

Continuity (2)

References Cited (400)