Immuno-interactive fragments of the alpha-C subunit of inhibin

• US 7,511,123 B2
• Filed: 04/18/2002
• Issued: 03/31/2009
• 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, Cahir, Nicholas Francis, Milne-Robertson, David Mark
• Primary Examiner(s): Shibuya; Mark L
• Assistant Examiner(s): GRUN, JAMES LESLIE
• Application Number:
  US10/125,187
• Publication Number:
  US 20030162229A1
• Time in Patent Office: 2,539 Days
• Field of Search: 435/7.94, 435/70.21, 435/452, 435/330, 435/331, 435/336, 435/344, 436/518, 436/547, 436/548, 436/64, 436/813, 530/387.3, 530/387.7, 530/387.9, 530/388.24, 530/388.8, 530/828, 530/850
• US Class Current: 530/388.24
• 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

Novels immuno-interactive fragments of the (alpha)C portion of a mammalian inhibin alpha subunit are disclosed, together with their variants and derivatives for producing antigen-binding molecules that are interactive with said (alpha)C portion, 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 ovarian cancer diagnosis kit comprising a first isolated antigen-binding molecule and a second isolated antigen-binding molecule, wherein the first isolated antigen-binding molecule binds specifically to a first immuno-interactive sequence contained within a first region of an (alpha)C portion of a mammalian inhibin alpha subunit, wherein the first region consists of an amino acid sequence selected from residues 3-26 or 109-132 of SEQ ID NO:

2, wherein the second isolated antigen-binding molecule binds specifically to a second immuno-interactive sequence contained within a second region of the (alpha)C portion of the mammalian inhibin alpha subunit, wherein the second region consists of an amino acid sequence selected from residues 73-96 of SEQ ID NO;

2, and wherein at least one of the first and second antigen-binding molecules is other than a polyclonal antibody.

2. The kit of claim 1, wherein the first immuno-interactive sequence consists of the amino acid sequence selected from SEQ ID NOs:

35-40 and wherein the second immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs;

55-60.

3. The kit of claim 1, wherein the first immuno-interactive sequence consists of the amino acid sequence selected from SEQ ID NOs:

68-73 and wherein the second immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs;

55-60.

4. The kit of claim 1, wherein the first and second isolated antigen-binding molecules are monoclonal antibodies.

5. The kit of claim 1, wherein the mammalian inhibin is human inhibin.

6. An ovarian cancer diagnosis kit comprising a first isolated antigen-binding molecule, a second isolated antigen-binding molecule and a third isolated antigen-binding molecule, wherein the first isolated antigen-binding molecule binds specifically to a first immuno-interactive sequence contained within a first region of an (alpha)C portion of a mammalian inhibin alpha subunit, wherein the first region consists of residues 73-96 of SEQ ID NO:

2, wherein the second isolated antigen-binding molecule binds specifically to a second immuno-interactive sequence contained within a second region of the (alpha)C portion of the mammalian inhibin alpha subunit, wherein the second region consists of residues 109-132 of SEQ ID NO;

2, and wherein the third isolated antigen-binding molecule binds specifically to a third immuno-interactive sequence contained within a third region of the (alpha)C portion of the mammalian inhibin alpha subunit, wherein the third region consists of residues 3-26 of SEQ ID NO;

2, and wherein at least one of the first, second and third isolated antigen-binding molecules is other than a polyclonal antibody.

7. The kit of claim 6, wherein the first immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs:

55-60, wherein the second immuno-interactive sequence consists of the amino acid sequence selected from SEQ ID NOs;

68-73 and wherein the third immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs;

35-40.

8. The kit of claim 6, wherein the first and second isolated antigen-binding molecules are adapted for use as capture antibodies and the third isolated antigen-binding molecule is associated with a reporter molecule.

9. An ovarian cancer diagnosis kit comprising a first isolated antigen-binding molecule, a second isolated antigen-binding molecule and a third isolated antigen-binding molecule, wherein the first isolated antigen-binding molecule binds specifically to an immuno-interactive sequence contained within a first region of an (alpha)C portion of the mammalian inhibin, wherein the first region consists of an amino acid sequence selected from residues 3-26, or 109-132 of SEQ ID NO:

2, wherein the second isolated antigen-binding molecule binds specifically to a second immuno-interactive sequence contained within a second region of the (alpha)C portion of the mammalian inhibin alpha subunit, wherein the second region consists of an amino acid sequence selected from residues 73-96 of SEQ ID NO;

2, wherein the first isolated antigen-binding molecule binds to a different region than the second isolated antigen-binding molecule and wherein at least one of the first and second isolated antigen-binding molecules is other than a polyclonal antibody, and wherein the third isolated antigen-binding molecule binds specifically to another antigen that is aberrantly expressed in ovarian cancer.

10. The kit of claim 9, wherein the first immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs:

35-40 and wherein the second immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs;

55-60.

11. The kit of claim 9, wherein the first isolated antigen binding molecule binds specifically to an immuno-interactive sequence that consists of the amino acid sequence selected from SEQ ID NOs:

68-73 and wherein the second immuno-interactive sequence consists of an amino acid sequence selected from SEQ ID NOs;

55-60.

12. The kit of claim 9, wherein the other antigen is ovarian cancer antigen CA125.