Peptides for development of diagnostic and therapeutic agents and methods of using same

• US 8,399,202 B2
• Filed: 03/30/2009
• Issued: 03/19/2013
• Est. Priority Date: 10/18/1999
• Status: Expired due to Fees

• 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: Stanton, Peter Gordon, Milne-Robertson, David Mark, Cahir, Nicholas Francis
• Primary Examiner(s): Gabel, Gailene R.
• Assistant Examiner(s): GRUN, JAMES LESLIE
• Application Number:
  US12/414,180
• Publication Number:
  US 20090252735A1
• Time in Patent Office: 1,450 Days
• Field of Search: 435/7.1, 435/7.23, 435/7.93, 435/7.94, 435/7.95, 435/70.21, 435/330, 435/331, 435/336, 435/344, 436/518, 436/548, 436/64, 436/813, 530/387.3, 530/387.7, 530/387.9, 530/388.8, 530/828, 530/388.24
• US Class Current: 435/7.1
• 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 an α

C portion of a mammalian inhibin α

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

2.

2. The 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 the antigen-binding molecule as defined in claim 1; and

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

wherein the presence of the complex indicates presence of mammalian inhibin in the biological sample and absence of the complex indicates absence of mammalian inhibin in the biological 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, wherein the condition is a cancer of a tissue selected from the group consisting of ovary, uterus, breast, pituitary, testis and prostate, the method comprising:

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

(b) measuring a 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 presence of an aberrant concentration is indicative of the condition.

5. The method according to claim 4, wherein the cancer is ovarian cancer.

6. A method of diagnosing an ovarian cancer in a patient, the method comprising:

(a) contacting a biological sample of the patient with the 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 an ovarian cancer marker;

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

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

(e) relating the measured complex concentrations to the concentration of mammalian inhibin and the concentration of ovarian cancer marker in the sample, wherein presence of an aberrant concentration of the first complex and an aberrant concentration of the second complex is indicative of the ovarian cancer.

7. The method according to claim 6, wherein the mammalian inhibin is human inhibin.

8. A method of diagnosing an ovarian cancer in a patient, the method comprising:

(a) contacting a biological sample of the patient with the 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 CA125;

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

(d) measuring a concentration of a second complex comprising the CA125 antigen-binding molecule and CA125 in the contacted sample; and

(e) relating the measured complex concentrations to the concentration of mammalian inhibin and the concentration of CA125 in the sample, wherein presence of aberrant concentrations of the complexes is indicative of the ovarian cancer.

9. The method according to claim 8, wherein the mammalian inhibin is human inhibin.