Use of NRG4, or inhibitors thereof, in the treatment of colon and pancreatic cancers

• US 7,476,506 B2
• Filed: 02/09/2007
• Issued: 01/13/2009
• Est. Priority Date: 06/03/2002
• Status: Expired due to Fees

• Current Assignee: Novartis Vaccines And Diagnostics Incorporated (Novartis Ag)
• Original Assignee: Novartis Vaccines And Diagnostics Incorporated (Novartis Ag)
• Inventors: Jefferson, Anne B., Abraham, Judith A., Schleyer, Siew C., Kavanaugh, W. Michael
• Primary Examiner(s): Rawlings; Stephen L
• Application Number:
  US11/704,622
• Publication Number:
  US 20070148691A1
• Time in Patent Office: 704 Days
• Field of Search: 435/6, 435/7.21, 435/7.23, 530/350, 530/387.7, 530/388.8, 530/389.7, 530/391.3, 536/23.5, 536/24.3
• US Class Current: 435/6.14
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: C07K 14/4756 Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 2333/485 Epidermal growth factor [EGF] (urogastrone)
• CPC Class Codes: G01N 33/57419 of colon

Abstract

This invention relates to compositions and uses of NRG4, and to variants thereof and to polynucleotides encoding NRG4, for therapeutic and diagnostic purposes, particularly related to colon and pancreatic cancer. This invention also relates to therapeutic agents based on or derived from the polynucleotides and proteins, NRG4 inhibitors, particularly antibodies capable of specifically binding to NRG4.

Claims

1. A method of diagnosing pancreatic cancer in a patient, said method comprising:

(a) determining the amount of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2 in a sample of pancreatic tissue from the patient;

(b) determining the amount of said polypeptide in a sample of normal pancreatic tissue; and

(c) determining that there is an indication that the patient has pancreatic cancer if the amount of said polypeptide in said sample of pancreatic tissue from the patient is less than the amount of said polypeptide in said sample of normal pancreatic tissue.

3. The method of claim 1 or 2, wherein the amount of said polypeptide in the sample of pancreatic tissue from the patient is determined by immunoassay.

4. The method of claim 3, wherein said immunoassay comprises contacting said sample or a fraction thereof with an antibody or antigen binding fragment thereof that specifically binds to a polypeptide selected from the group consisting of a polypeptide comprising the amino acid sequence of SEQ ID NO:

2 and a polypeptide comprising the amino acid sequence of amino acids 4 to 50 of SEQ ID NO;

2.

5. The method of claim 4, wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a humanized antibody, and a single chain antibody.

6. The method of claim 4, wherein said antigen binding fragment is a Fab or a F(ab′

)₂.

7. The method of claim 4, wherein said antibody or antigen binding fragment thereof is detectably labeled.

8. The method of claim 7, wherein said antibody or antigen binding fragment thereof is detectably labeled with an enzyme, a radionuclide, a luminescent moiety, or a fluorescent moiety.

9. The method of claim 4, wherein said antibody or antigen binding fragment thereof is biotinylated.

10. The method of claim 3, wherein said immunoassay is selected from the group consisting of an immunohistochemical analysis, an ELISA, a radioimmunoassay, a Western blot analysis, and a fluorescence-activated cell analysis.

2. A method of diagnosing pancreatic cancer in a patient, said method comprising:

(a) determining the amount of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2 in a sample of pancreatic tissue from the patient; and

(b) determining if there is an indication that the patient has pancreatic cancer by comparing the amount of said polypeptide in said sample of pancreatic tissue from the patient and the amount of said polypeptide in a sample of normal pancreatic tissue,

wherein there is an indication that the patient has pancreatic cancer when the amount of said polypeptide in said sample of pancreatic tissue from the patient is less than the amount of said polypeptide in the sample of normal pancreatic tissue.

11. A method of diagnosing pancreatic cancer in a patient, said method comprising:

(a) determining the amount of a mRNA molecule encoding a polypeptide comprising the amino acid sequence of SEQ ID NO;

2 in a sample of pancreatic tissue from the patient;

(b) determining the amount of said mRNA in a sample of normal pancreatic tissue; and

(c) determining that there is an indication that the patient has pancreatic cancer if the amount of said mRNA in said sample of pancreatic tissue from the patient is less than the amount of said mRNA in said sample of normal pancreatic tissue.

13. The method of claim 11 or 12, wherein the amount of said mRNA molecule in the sample of pancreatic tissue from the patient is determined by an assay selected from a Northern blot analysis, a primer extension analysis, an S1 nuclease protection analysis, a RT-PCR assay, and an in situ hybridization assay.

14. The method of claim 11 or 12, wherein the amount of said mRNA molecule is determined by contacting said sample or a fraction thereof with a polynucleotide probe that hybridizes to said mRNA.

15. The method of claim 14, wherein said polynucleotide probe is detectably labeled.

16. The method of claim 15, wherein said polynucleotide probe is detectably labeled with a radioactive moiety, a chemiluminescent moiety, or a fluorescent moiety.

17. The method of claim 14, wherein said polynucleotide probe is biotinylated.

12. A method of diagnosing pancreatic cancer in a patient, said method comprising:

(a) determining the amount of a mRNA molecule encoding a polypeptide comprising the amino acid sequence of SEQ ID NO;

2 in a sample of pancreatic tissue from the patient; and

(b) determining if there is an indication that the patient has pancreatic cancer by comparing the amount of said mRNA molecule in said sample of pancreatic tissue from the patient and the amount of said mRNA molecule in a sample of normal pancreatic tissue,

wherein there is an indication that the patient has pancreatic cancer when the amount of said mRNA molecule in said sample of pancreatic tissue from the patient is less than the amount of said mRNA molecule in the sample of normal pancreatic tissue.