MONOCLONAL ANTIBODIES TO PROGRAMMED DEATH 1 (PD-1)

摘要

The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

主权项

1. A monoclonal antibody, or antigen-binding portion thereof, which specifically binds to PD-1 and comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3; and a light chain variable region comprising CDR1, CDR2, and CDR3, wherein the heavy chain CDR1, CDR2, and CDR3 are selected from the group consisting of:
(a) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 15, a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 22, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 29; (b) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 16, a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 23, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 30; (c) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 17, a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 24, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 31; (d) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 18, and a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 25, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 32; (e) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 19, and a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 26, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 33; (f) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 20, and a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 27, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 34; and (g) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 21, a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO: 28, and a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO: 35.