CHIMERIC FVII-XTEN MOLECULES AND USES THEREOF

摘要

The present invention provides chimeric FVII molecules comprising FVII, an XTEN polypeptide, and an antibody C and antigen-binding molecules thereof which specifically bind the α and/or β subunits of the non-active form of the GPIIb/IIIIa receptor. The antibodies and antigen-binding molecules can be genetically fused and/or conjugated to heterologous moieties, e.g., half-life extending moiety. The invention also includes methods of producing and using the chimeric molecules.

主权项

1. A chimeric molecule comprising Factor VII (“FVII”), an XTEN polypeptide, and an anti-GPIIb/IIIa antibody or antigen-binding molecule thereof, wherein the anti-GPIIb/IIIa antibody or antigen-binding molecule thereof exhibits one or more of the following characteristics:
(a) the anti-GPIIb/IIIa antibody or antigen-binding molecule thereof specifically binds to the same GPIIb/IIIa epitope as an antibody selected from the group consisting of 34D10, 12B2, 2A2, 35D1, 36A8, 4B11, 1H6, 38G8, 21F10, 38A8, 18F7, 38F6, 13C1, 5C4, 23C10, 37C7, 28C2, 9D6, and 28F4; (b) the anti-GPIIb/IIIa antibody or antigen-binding molecule thereof competitively inhibits GPIIb/IIIa binding to an antibody selected from the group consisting of 34D10, 12B2, 2A2, 35D1, 36A8, 4B11, 1H6, 38G8, 21F10, 38A8, 18F7, 38F6, 13C1, 5C4, 23C10, 37C7, 28C2, 9D6, and 28F4; or (c) the anti-GPIIb/IIIa antibody or antigen-binding molecule thereof comprises at least one, at least two, at least three, at least four, at least five, or at least six complementarity determining regions (CDR) or variants thereof selected from the CDRs of 34D10, 12B2, 2A2, 35D1, 36A8, 4B11, 1H6, 38G8, 21F10, 38A8, 18F7, 38F6, 13C1, 5C4, 23C10, 37C7, 28C2, 9D6, or 28F4.