Novel Peptides for Development of Diagnostic and Therapeutic Agents and Methods of Using Same

• US 20090252735A1
• Filed: 03/30/2009
• Published: 10/08/2009
• Est. Priority Date: 10/18/1999
• Status: Active Grant

• Current Assignee: Prince Henry's Institute of Medical Research (Hudson Institute of Medical Research)
• Original Assignee: Prince Henry's Institute of Medical Research (Hudson Institute of Medical Research)
• Inventors: CAHIR, Nicholas Francis, MILNE-ROBERTSON, David Mark, STANTON, Peter Gordon
• Granted Patent: US 8,399,202 B2
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 33/57449 of ovaries
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/813 Cancer
• CPC Class Codes: Y10S 530/828 Cancer
• CPC Class Codes: Y10S 530/85 Reproductive organs or embryos

Abstract

Novel immuno-interactive fragments of the αC portion of a mammalian inhibin α subunit, together with their variants and derivatives, produce antigen-binding molecules that are interactive with the αC portion, and which are chemically well defined and which can be produced in commercially significant quantities. The antigen-binding molecules of the invention can be used for the detection of a mammalian inhibin and for the treatment and/or prevention of conditions associated with aberrant levels of a mammalian inhibin.

Claims

1. An antigen-binding molecule that is a monoclonal antibody and that binds specifically to an immuno-interactive fragment of the α

C portion of a mammalian inhibin α

-subunit, wherein the immuno-interactive fragment is a fragment defined by or contained within residues 73-96 of SEQ ID NO;

2.

2. An antigen-binding molecule according to claim 1, wherein the immuno-interactive fragment is selected from any one of SEQ ID NOs:

55-60.

3. A method of detecting a mammalian inhibin in a biological sample suspected of containing it, comprising:

(a) contacting the biological sample with an antigen-binding molecule as defined in claim 1; and

(b) detecting the presence of a complex comprising the antigen-binding molecule and the mammalian inhibin in the contacted sample.

4. A method of diagnosing a condition associated with an aberrant concentration of a mammalian inhibin in a biological sample obtained from a patient, comprising:

(a) contacting the biological sample with an antigen-binding molecule as defined in claim 1;

(b) measuring the concentration of a complex comprising the antigen-binding molecule and the mammalian inhibin in the contacted sample; and

(c) relating the measured complex concentration to the concentration of mammalian inhibin in the sample, wherein the presence of the aberrant concentration is indicative of the condition.

5. A method according to claim 4, wherein the condition is a cancer.

6. A method according to claim 5, wherein the cancer is a cancer of a tissue selected from the group consisting of ovary, uterus, breast, pituitary, testis and prostate.

7. A method according to claim 5, wherein the cancer is ovarian cancer.

8. A method of diagnosing a condition associated with an aberrant concentration of a mammalian inhibin and an aberrant concentration of another antigen in a biological sample of a patient, comprising:

(a) contacting a biological sample of the patient with an antigen-binding molecule as defined in claim 1;

(b) contacting the biological sample or another biological sample obtained from the patient with another antigen-binding molecule that is immuno-interactive with the other antigen;

(c) measuring the concentration of a first complex comprising the antigen-binding molecule and the mammalian inhibin in the contacted sample;

(d) measuring the concentration of a second complex comprising the other antigen-binding molecule and the other antigen in the contacted sample; and

(e) relating the measured complex concentrations to the concentration of mammalian inhibin and the concentration of the other antigen in the sample, wherein the presence of the aberrant concentrations is indicative of the condition.

9. A method according to claim 8, wherein the condition is ovarian cancer.

10. A method according to claim 9, wherein the other antigen is an ovarian cancer marker.

11. A method according to claim 10, wherein the ovarian cancer marker is CA125.

12. A method according to claim 8, wherein the mammalian inhibin is human inhibin.

13. A method for treating or preventing a condition associated with an aberrant concentration of a mammalian inhibin in a mammal, the method comprising administering an antigen-binding molecule as defined in claim 1.

14. A method according to claim 13, wherein the condition is a cancer.

15. A method according to claim 14, wherein the cancer is a cancer of a tissue selected from the group consisting of ovary, uterus, breast, pituitary, testis and prostate.

16. A method according to claim 15, wherein the cancer is ovarian cancer.