Monoclonal antibodies to progastrin and their uses

摘要

The present disclosure is directed to progastrin monoclonal antibodies, fragments thereof, compositions comprising progastrin monoclonal antibodies, and methods of making and using progastrin monoclonal antibodies and compositions thereof. The present disclosure is directed to methods of treating colorectal cancer with progastrin monoclonal antibodies and compositions comprising progastrin monoclonal antibodies or fragments thereof. The present disclosure is further directed to methods comprising detection of progastrin, including methods of diagnosing colorectal cancer and methods of monitoring efficacy of anti-cancer therapy in subjects suffering from colorectal cancer.

主权项

1. A monoclonal antibody that specifically binds a human progastrin (hPG) polypeptide having an amino acid sequence of SEQ ID NO:20, but does not detectably bind to an amidated gastrin 17 consisting of SEQ ID NO:103, a glycine-extended gastrin 17 consisting of SEQ ID NO: 104, or C-terminal Flanking Peptide (CTFP) consisting of SEQ ID NO:105, wherein said monoclonal antibody is a C-terminal anti-hPG monoclonal antibody that specifically binds a C-terminal region of hPG, wherein:
(a) the antibody is obtainable using an immunogen comprising a peptide antigen having an amino acid sequence of SEQ ID NO: 27; and (b) the antibody comprises VH CDRs comprising amino acid sequences of VH CDR 1.8 (SEQ ID NO:37), VH CDR 2.8 (SEQ ID NO:41), VH CDR 3.8 (SEQ ID NO:45) and VL CDRs comprising amino acid sequences of VL CDR 1.8 (SEQ ID NO:49), VL CDR 2.8 (SEQ ID NO:52), and VL CDR 3.8 (SEQ ID NO:55).