Methods for treating pancreatic cancer

{
  "publication_number": "US2011171213A1",
  "country": "US",
  "kind": "A1",
  "title": "Methods for treating pancreatic cancer",
  "abstract": "The present disclosure is directed to methods of treating pancreatic cancer in subject using cancer with antibodies that specifically bind to progastrin.",
  "claims": [
    "1. A method for treating pancreatic cancer in a subject, comprising administering to a subject diagnosed with pancreatic cancer an amount of an anti-PG antibody sufficient to provide therapeutic benefit. 2. The method of claim 1, in which the subject is a human and the anti-PG antibody is an anti-hPG monoclonal antibody. 3. The method of claim 2 in which the anti-hPG monoclonal antibody is a humanized anti-hPG monoclonal antibody. 4. The method of claim 2 in which the anti-hPG monoclonal antibody is an N-terminal anti-hPG monoclonal antibody. 5. The method of claim 4 in which the N-terminal anti-hPG monoclonal antibody binds an epitope comprising a sequence selected from the group consisting of DAPLG (SEQ ID NO:28), PDAPLG (SEQ ID NO:29), PRSQQPD (SEQ ID NO:30), WKPRSQQPD (SEQ ID NO:31) and WKPRSQQPDAPLG (SEQ ID NO:32). 6. The method of claim 4 in which the N-terminal anti-hPG monoclonal antibody is raised against an immunogen comprising a peptide having the sequence SWKPRSQQPDAPLG (SEQ ID NO:25). 7. The method of claim 4 in which the N-terminal anti-hPG monoclonal antibody comprises three V H CDRs corresponding in sequence to the V H CDRs of MAb3, MAb4, MAb15, MAb16 or MAb19 and three V L CDRs corresponding in sequence to the V L CDRs of MAb3, Mab4, MAb15, MAb16 or MAb19. 8. The method of claim 4 in which the N-terminal anti-hPG monoclonal antibody comprises CDRs corresponding in sequence to the CDRs of MAb3, MAb4, MAb15, MAb16 or MAb 19. 9. The method of claim 4 in which the anti-hPG monoclonal antibody competes for binding hPG with a reference antibody selected from the group consisting of MAb3, MAb4, MAb15, MAb16 and MAb19. 10. The method of claim 2 in which the anti-hPG monoclonal antibody is a C-terminal anti-hPG monoclonal antibody. 11. The method of claim 10 in which the C-terminal anti-hPG monoclonal antibody binds an epitope comprising a sequence selected from the group consisting of FGRR (SEQ ID NO:33), MDFGR (SEQ ID NO:34), AEDEN (SEQ ID NO:35) and GWMDFGRR (SEQ ID NO:36). 12. The method of claim 10 in which the C-terminal anti hPG monoclonal antibody is raised against an immunogen comprising a peptide having the sequence QGPWLEEEEEAYGWMDFGRRSAEDEN (SEQ ID NO:27). 13. The method of claim 10 in which the C-terminal anti-hPG monoclonal antibody comprises three V H CDRs corresponding in sequence to the CDRs of MAb5, MAb6, MAb7, MAb8, MAb11, MAb12 or MAb13 and three V L CDRs corresponding in sequence to the CDRs of MAb5, MAb6, MAb7, MAb8, MAb11, MAb12 or MAb13. 14. The method of claim 10 in which the C-terminal anti hPG monoclonal antibody comprises CDRs corresponding in sequence to the CDRs of MAb5, MAb6, MAb7, MAb8, MAb11, MAb12 or MAb13. 15. The method of claim 10 in which the C-terminal anti-hPG monoclonal antibody competes for binding hPG with a reference antibody selected from the group consisting of MAb5, MAb6, MAb7, MAb8, MAb11, MAb12 and MAb13. 16. The method of claim 2 in which the pancreatic cancer is primary pancreatic cancer. 17. The method of claim 2 in which the pancreatic cancer is metastatic pancreatic cancer. 18. The method of claim 2 in which the anti-hPG monoclonal antibody is administered adjunctive to surgical resection of the tumor. 19. The method of claim 2 in which the anti-hPG monoclonal antibody is administered adjunctive to chemotherapy. 20. A method of inhibiting proliferation of a pancreatic tumor cell comprising exposing the cell to an amount of an anti-PG antibody sufficient to inhibit its proliferation. 21. The method of claim 20 in which is practiced in vitro. 22. The method of claim 20 which is practiced in vivo. 23. A method of claim 20 in which the anti-PG is an anti-hPG monoclonal antibody. 24. The method of claim 20 in which the anti-PG antibody is an N-terminal anti-hPG monoclonal antibody. 25. The method of claim 20 in which the anti-PG antibody is a C-terminal anti-hPG monoclonal antibody. 26. A method of diagnosing pancreatic cancer in a subject exhibiting at least one symptom of pancreatic cancer, comprising determining whether the subject has a plasma or serum progastrin concentration at or above about 50 pM, where such a concentration, when coupled with at least one other symptom of pancreatic cancer, indicates the subject likely has pancreatic cancer. 27. A method of monitoring the effectiveness of a pancreatic cancer treatment, comprising determining whether a subject being treated for pancreatic cancer has a plasma or serum progastrin concentration below about 10 pM, where such a concentration indicates the treatment is effective. 28. A method of monitoring the effectiveness of a pancreatic cancer treatment, comprising monitoring the plasma or serum progastrin concentration of a patient being treated for pancreatic cancer as a function of time, where a decrease in the plasma or serum progastrin concentration over time indicates the pancreatic cancer treatment is effective."
  ],
  "description_excerpt": "The present disclosure is directed to, among other things, methods of treating subjects with primary and/or metastatic pancreatic cancer by administering to the subject a composition comprising an antibody specific for progastrin.\n\nDespite decades of basic and clinical research, cancer remains one of mankind's greatest scourges. According to statistics collected by the World Health Organization, cancer is one of the leading causes of death worldwide, having killed 7.4 million people in 2004, or about 13% of all deaths that year. While much has been learned regarding what causes cancer, and how cancer works at the molecular level, the greatest reductions in cancer death rates remain attributable to public health interventions, such as anti-smoking campaigns, and earlier diagnosis made possible by advances in imaging technology and molecular diagnostics. When it comes to the hard work of actually killing cancer cells, however, clinicians still rely on therapeutic modalities, such as surgery, radiation and chemotherapy, that would have been familiar to oncologists of a generation ago. Although the efficacy of all these treatments has improved over the years, the improvement in cure rates and the increase in longevity has been incremental. Even the new targeted therapies resulting from the revolution in molecular oncology have, for the most part, improved outcomes modestly.\n\nPancreatic cancer, a malignant neoplasm of the pancreas, is a particularly challenging form of cancer to treat, as it typically goes undetected until no longer treatable ((Jemal et al., 2008, CA Cancer J. Clin. 58(2):71-96)).",
  "cpc": [
    "C07K 16/26",
    "A61K 39/395",
    "A61K 39/39558",
    "A61P 35/00",
    "A61P 35/04",
    "C07K 16/303",
    "C07K 2317/34",
    "C07K 2317/73",
    "G01N 2333/595",
    "G01N 2800/52",
    "G01N 33/57525"
  ],
  "ipc": [
    "A61P 35/00",
    "A61P 35/04",
    "C12N 5/09",
    "G01N 33/74",
    "A61K 39/395",
    "C07K 16/00",
    "C07K 16/26",
    "C07K 16/30",
    "G01N 33/574"
  ],
  "inventors": [
    "Leïla Houhou",
    "Dominique Joubert",
    "Frédéric Hollande"
  ],
  "filing_date": "2011-01-04",
  "publication_date": "2011-07-14",
  "priority_date": "2010-01-08",
  "application_number": "US-98452211-A",
  "family_id": "43607948",
  "cited_by_count": 12,
  "citations": [
    "US6548066B1",
    "US20110117086A1"
  ]
}