Monoclonal antibodies to fibrin
View Patent ↗The present invention provides an isolated antibody that binds a fibrin or fibrinogen γC domain. In various aspects, the antibody inhibits microglial adhesion to the fibrin or fibrinogen γC domain, inhibits Mac-1 binding to the fibrin or fibrinogen γC domain, and/or suppresses clinical symptoms of Experimental Autoimmune Encephalomyelitis (EAE). Various methods of using the antibodies, pharmaceutical compositions, kits, vectors, cells comprising the vectors, and antibody generating methods are provided.
1. An isolated antibody that binds human fibrin or fibrinogen γC domain, and inhibits Mac-1 binding to fibrin or fibrinogen γC domain, wherein the antibody light chain comprises three complementarity determining regions comprising the amino acid sequences of RSSKSLLHSSGITYLS (SEQ ID NO:2), QMSNLAS (SEQ ID NO:3), and AQNLELPLT (SEQ ID NO:4), respectively, and the antibody heavy chain comprises three complementarity determining regions comprising the amino acid sequences of GYTFTSYWIH (SEQ ID NO:6), LIDPSDSYTNYNQKFRG (SEQ ID NO:7), and SDPTGC (SEQ ID NO:8), respectively.
2. The antibody of claim 1 , wherein the antibody is a humanized antibody.
3. The antibody of claim 1 , wherein the antibody binds an γ 377-395 epitope (SEQ ID NO:18) of the fibrin or fibrinogen γC domain.
4. The antibody of claim 1 , wherein the antibody suppresses clinical symptoms of Experimental Autoimmune Encephalomyelitis (EAE).
5. The antibody of claim 1 , wherein the antibody exhibits greater than 20% inhibition of microglial adhesion to the fibrin or fibrinogen γC domain.
6. The antibody of claim 1 , wherein the antibody exhibits greater than 50% inhibition of Mac-1 binding to the fibrin or fibrinogen γC domain.
7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
8. An isolated antibody, wherein the antibody binds human fibrin or fibrinogen γC domain, and inhibits Mac-1 binding to fibrin or fibrinogen γC domain, and wherein the antibody light chain variable domain comprises the amino acid sequence of SEQ ID NO:1.
9. The antibody of claim 8 , wherein said antibody comprises the heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:5.
10. The antibody of claim 8 , wherein the antibody is a chimeric antibody.
11. The antibody of claim 8 , wherein the antibody binds an γ 377-395 epitope (SEQ ID NO:18) of the fibrin or fibrinogen γC domain.
12. The antibody of claim 8 , wherein the antibody suppresses clinical symptoms of Experimental Autoimmune Encephalomyelitis (EAE).
13. The antibody of claim 8 , wherein the antibody exhibits greater than 20% inhibition of microglial adhesion to the fibrin or fibrinogen γC domain.
14. The antibody of claim 8 , wherein the antibody exhibits greater than 50% inhibition of Mac-1 binding to the fibrin or fibrinogen γC domain.
15. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier.
16. An isolated antibody wherein the antibody binds human fibrin or fibrinogen γC domain, and inhibits Mac-1 binding to fibrin or fibrinogen γC domain, and wherein the antibody heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:5.
17. The antibody of claim 16 , wherein the antibody is a chimeric antibody.
18. The antibody of claim 16 , wherein the antibody binds an γ 377-395 epitope (SEQ ID NO:18) of the fibrin or fibrinogen γC domain.
19. The antibody of claim 16 , wherein the antibody suppresses clinical symptoms of Experimental Autoimmune Encephalomyelitis (EAE).
20. The antibody of claim 16 , wherein the antibody exhibits greater than 20% inhibition of microglial adhesion to the fibrin or fibrinogen γC domain.
21. The antibody of claim 16 , wherein the antibody exhibits greater than 50% inhibition of Mac-1 binding to the fibrin or fibrinogen γC domain.
22. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier.