ANTI-GCC ANTIBODY MOLECULES AND METHODS FOR USE OF SAME

• US 20130287783A1
• Filed: 04/27/2013
• Published: 10/31/2013
• Est. Priority Date: 04/27/2012
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: O'Keefe, Theresa L., Frank, Helen Alison, McDonald, Alice A.
• Granted Patent: US 9,000,129 B2
• Time in Patent Office: Days
• US Class Current: 424/139.1
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: G01N 2333/988 Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

Claims

1. An anti-GCC antibody molecule, wherein the light chain variable region and the heavy chain variable region of the anti-GCC antibody molecule are selected from:

the light and heavy chain sequences disclosed in Table 2 for any one of the following antibodies;

MIL-44-148-2 or MIL-44-67-4.

2. The anti-GCC antibody molecule of claim 1, wherein said anti-GCC antibody molecule is a rabbit monoclonal antibody.

3. The anti-GCC antibody molecule of claim 1, wherein said anti-GCC antibody molecule is conjugated to a detectable label.

6. Isolated nucleic acid sequences that encode an antibody molecule of claim 1 or 4.

7. A cell comprising the isolated nucleic acid sequences of claim 6.

8. A method of producing an antibody molecule of claim 1 or 4, comprising culturing the cell of claim 8 under conditions that allow production of an antibody molecule, thereby producing the antibody molecule of claim 1 or 4.

9. A vector comprising one or both of the light chain and heavy chain of an antibody molecule of claim 1 or 4.

10. A method of detecting a GCC molecule comprising contacting the molecule with an antibody molecule of claim 1 or 4 and determining if said antibody molecule binds to said GCC molecule.

11. The method of claim 10, wherein said method comprises an immunohistochemistry assay using a biological sample derived from a patient suspected of having a GCC expressing cancer.

12. The method of claim 11, wherein said biological sample is a tumor biopsy.

13. The method of claim 11, further comprising the step of quantifying GCC expression in said biological sample.

14. The method of claim 13, wherein said quantification of GCC expression comprises apical GCC expression, cytoplasmic GCC expression, or both.

15. The method of claim 13, wherein said quantification step comprises an H-score approach.

16. The method of claim 11, wherein said GCC expressing cancer is selected from the group consisting of:

colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer, liver cancer, ovarian cancer, lung cancer, a gastrointestinal neuroendocrine tumor, and a bronchopulmonary neuroendocrine tumor.

17. A kit comprising the anti-GCC antibody molecule of claim 1 and instructions for use.

4. An anti-GCC antibody molecule, comprising light chain CDR1, CDR2, and CDR3, and heavy chain CDR1, CDR2, and CDR3, disclosed in Table 5 for any one of the following antibodies:

MIL-44-148-2 or MIL-44-67-4.

5. The anti-GCC antibody molecule of claim 4, further comprising rabbit or rabbit derived light and heavy variable region frameworks.

18. A method of treating a patient having cancer characterized by GCC-expressing tumor cells, comprising:

a. detecting GCC expression on a sample of tumor cells from the patient; and

b. administering a therapeutic anti-GCC antibody molecule if the tumor cells express GCC on the cell surface.