Anti-CD20 antibodies and fusion proteins thereof and methods of use
The present invention provides humanized, chimeric and human anti-CD20 antibodies and CD 20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis.
1. A chimeric or humanized monoclonal antibody that binds to CD20, said antibody having a light chain variable region CDR1 comprising the sequence RASSSVSYIH (SEQ ID NO:1); CDR2 comprising the sequence ATSNLAS (SEQ ID NO:4); and CDR3 comprising the sequence QQWTSNPPT (SEQ ID NO:5); and said antibody having a heavy chain variable region CDR1 comprising the sequence SYNMH (SEQ ID NO:8); CDR2 comprising the sequence AIYPGNGDTSYNQKFKG (SEQ ID NO:9); and CDR3 comprising the sequence STYYGGDWYFDV (SEQ ID NO:10) or the sequence VVYYSNSYWYFDV (SEQ ID NO: 13).
2. An antibody according to claim 1 , wherein said antibody is a chimeric monoclonal antibody.
3. An antibody according to claim 1 , wherein said antibody is a humanized monoclonal antibody.
4. An antibody according to claim 1 , wherein CDR3 comprises the sequence STYYGGDWYFDV (SEQ ID NO:10).
5. An antibody according to claim 1 , wherein CDR3 comprises the sequence VVYYSNSYWYFDV (SEQ ID NO: 13).
6. An antibody fusion protein, comprising at least two monoclonal antibodies, wherein at least one of said antibodies is an antibody according to claim 1 .
7. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets an antigen other than CD20.
8. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets CD22.
9. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets CD37.
10. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets CD74.
11. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets CD19.
12. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets CD52.
13. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets HLA-DR.
14. An antibody fusion protein according to claim 6 , comprising at least one monoclonal antibody that targets MUC-1.
15. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets an antigen other than CD20.
16. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets CD22.
17. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets CD37.
18. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets CD74.
19. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets CD19.
20. A composition comprising a chimeric humanized antibody according to claim 1 and at least one monoclonal antibody that targets CD52.
21. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets HLA-DR.
22. A composition comprising a chimeric or humanized antibody according to claim 1 and at least one monoclonal antibody that targets MUC-1.
23. A composition comprising a chimeric or humanized antibody according to claim 1 , packaged for subcutaneous administration.
24. A composition comprising a chimeric or humanized antibody according to claim 23 , including dosage instructions which specify administration over a period of less than about 3 hours.
25. A composition comprising a chimeric or humanized antibody according to claim 24 , wherein said dosage instructions specify administration of from 25 to 50 mg of the dose within the first 15-30 minutes, and specifying that the remainder of the dose is to be give over a period of 2-3 hours.
26. A composition comprising a chimeric or humanized antibody according to claim 1 , packaged in doses of about 1 mg/kg.