Immuno-interactive fragments of the alpha-C subunit of inhibin
First Claim
1. An antigen-binding molecule that binds specifically to an immuno-interactive fragment that is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), with the proviso that said antigen-binding molecule is other than a member selected from the group consisting of a polyclonal antibody and the R1 monoclonal antibody described by Groome et al (1993, J. Immunol. Meth. 165;
167-176;
1994, Clin. Endocrinol. 40;
717-723).
2 Assignments
0 Petitions
Accused Products
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.
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Citations
30 Claims
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1. An antigen-binding molecule that binds specifically to an immuno-interactive fragment that is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), with the proviso that said antigen-binding molecule is other than a member selected from the group consisting of a polyclonal antibody and the R1 monoclonal antibody described by Groome et al (1993, J. Immunol. Meth. 165;
167-176;
1994, Clin. Endocrinol. 40;
717-723). - View Dependent Claims (2, 3, 4, 5)
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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6. An immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793).
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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7. A method of producing a variant of an immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), said method comprising;
(a) combining a polypeptide whose sequence is distinguished from the immuno-interactive fragment by substitution, deletion and/or addition of at least one amino acid with at least one antigen-binding molecule that binds to said immuno-interactive fragment; and
(b) detecting the presence of a conjugate comprising said polypeptide and said antigen-binding molecule, which indicates that said polypeptide is said variant.
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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8. A method of producing an antigen-binding molecule that binds specifically to an immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), said method comprising;
(a) producing an antigen-binding molecule against inhibin (alpha)C or fragment thereof;
(b) combining the antigen-binding molecule with said immuno-interactive fragment, variant or derivative; and
(c) detecting the presence of a conjugate comprising said antigen-binding molecule and said fragment. - View Dependent Claims (9)
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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10. A composition for use in eliciting an immune response in a mammal which response includes production of elements that specifically bind the (alpha)C portion of a mammalian inhibin alpha subunit, said composition comprising an immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), together with a pharmaceutically acceptable carrier.
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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11. A method for eliciting an immune response in a mammal which response includes production of elements that specifically bind the (alpha)C portion of a mammalian inhibin alpha subunit, comprising administering to said mammal an immunogenically effective amount of a composition comprising an immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), together with a pharmaceutically acceptable carrier.
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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12. An isolated polynucleotide encoding immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793).
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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13. An expression vector comprising a polynucleotide encoding immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), wherein the polynucleotide is operably linked to a regulatory polynucleotide. - View Dependent Claims (14)
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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15. A method of detecting a mammalian inhibin in a biological sample suspected of containing it, comprising:
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(a) contacting the biological sample with an antigen-binding molecule that binds specifically to an immuno-interactive fragment that is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81;
669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), with the proviso that said antigen-binding molecule is other than a member selected from the group consisting of a polyclonal antibody and the R1 monoclonal antibody described by Groome et al (1993, J. Immunol. Methods 165;
167-176;
1994, Clin. Endocrinol. 40;
717-723); and
(b) detecting the presence of a complex comprising the said antigen-binding molecule and the mammalian inhibin in said contacted sample.
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16. A method of diagnosing a condition associated with an aberrant concentration of a mammalian inhibin in a biological sample of a patient, comprising:
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(a) contacting the biological sample with an antigen-binding molecule that binds specifically to an immuno-interactive fragment that is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81;
669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), with the proviso that said antigen-binding molecule is other than a member selected from the group consisting of a polyclonal antibody and the R1 monoclonal antibody described by Groome et al (1993, J. Immunol. Meth. 165;
167-176;
1994, Clin. Endocrinol. 40;
717-723);
(b) measuring the concentration of a complex comprising said antigen-binding molecule and said mammalian inhibin in said contacted sample; and
(c) relating said measured complex concentration to the concentration of mammalian inhibin in said sample, wherein the presence of said aberrant concentration is indicative of said condition.
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17. 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:
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(a) contacting a biological sample of the patient with a first antigen-binding molecule that binds specifically to an immuno-interactive fragment that is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81;
669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), with the proviso that said first antigen-binding molecule is other than a member selected from the group consisting of a polyclonal antibody and the R1 monoclonal antibody described by Groome et al (1993, J. Immunol. Meth. 165;
167-176;
1994, Clin. Endocrinol. 40;
717-723);
(b) contacting said biological sample or another biological sample obtained from said patient with a second antigen-binding molecule that is immuno-interactive with said other antigen;
(c) measuring the concentration of a first complex comprising the first antigen-binding molecule and the mammalian inhibin in said contacted sample;
(d) measuring the concentration of a second complex comprising the second antigen-binding molecule and the other antigen in said contacted sample; and
(e) relating said measured complex concentrations to the concentration of mammalian inhibin and the concentration of the other antigen in said sample, wherein the presence of said aberrant concentrations is indicative of said condition.
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18. A method for treating or preventing a condition associated with an aberrant concentration of a mammalian inhibin in a mammal, comprising administering to said mammal a therapeutically effective amount of a composition comprising an immuno-interactive fragment of the (alpha)C portion of a mammalian inhibin alpha subunit, wherein said fragment is interactive with an ovine polyclonal antibody selected from the group consisting of As #41 and As #128 described by Robertson et al. (1996, J. Clin. Endocrinol. Metab. 81:
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
790-793), together with a pharmaceutically acceptable carrier. - View Dependent Claims (25, 26, 27, 28, 29, 30)
- 669-676) and As #1989 described by Lapphorn et al. (1989, New England J. Med. 321;
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19. A polypeptide that induces an anti-inhibin alpha subunit immune response when the polypeptide is administered to a mammal, wherein the amino acid sequence of the polypeptide comprises at least 6 contiguous residues of an immuno-interactive sequence selected from the group consisting of SEQ ID NOs:
- 3-6, 18-23, 30-32, 35-40, 55-60, and 68-73.
- View Dependent Claims (20, 21, 22, 23, 24)
Specification