Epididymis-specific gene as potential contraceptive target
OwnerChristiane Kirchhoff, Heike Obermann-Pless +4inventors
InventorsChristiane Kirchhoff, Heike Obermann-Pless, Annemarie Samalecos, Caroline Osterhoff, Ulrich Gottwald, Reinhard Nubbemeyer
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Abstract
Isolated splice variant polypeptides from the family of human epididymis-specific receptors called HE6, and related polypeptides from mouse (ME6) and rat (RE6), are described. Also described are isolated polynucleotides encoding the polypeptides, and fragments and variants of the polypeptides and polynucleotides. The polypeptides are involved in maturation of sperm during their passage through the epididymis, and can be used, e.g., to isolate agents for diagnosing and treating male infertility or for male contraception.
Claims58
An isolated human epididymis-specific receptor protein-6 (HE6) polypeptide, comprising
- i) the amino acid sequence encoded by SEQ ID NO:
- 1;
- ii) the amino acid sequence encoded by SEQ ID NO:
- 2;
- iii) the amino acid sequence encoded by SEQ ID NO:
- 3;
- iv) the amino acid sequence encoded by SEQ ID NO:
- 4;
- v) the amino acid sequence encoded by SEQ ID NO:
- 5;
- vi) the amino acid sequence encoded by SEQ ID NO:
- 6;
- or
- vii) the amino acid sequence encoded by SEQ ID NO:
- 7,
- or comprising a functional variant or functional fragment of an amino acid sequence of i) through vii).
An isolated polypeptide encoded by SEQ ID NO:
- 16-22, starting at the codon at 2-4 and terminating at stop codon at positions 3101-3103, 3143-3145, 3173-3175, 3167-3169, 3125-3127, or 3149-3151.
An isolated polypeptide comprising, from N-terminus to C-terminus, the polypeptide sequence represented by amino acids 1 through 54 of SEQ ID NO:
- 22, covalently bound to the polypeptide X81892.
An isolated mouse epididymis-specific receptor protein-6 (ME6) polypeptide, comprising
- i) the amino acid sequence encoded by SEQ ID NO:
- 9;
- ii) the amino acid sequence encoded by SEQ ID NO:
- 10;
- iii) the amino acid sequence encoded by SEQ ID NO:
- 11;
- or
- iv) the amino acid sequence encoded by SEQ ID NO:
- 12;
- or comprising a functional variant or functional fragment of an amino acid sequence of i) through iv).
An isolated polypeptide consisting essentially of amino acids 1 to 1009 of SEQ ID NO:
- 31.
An isolated rat epididymis-specific receptor protein-6 (RE6) polypeptide, comprising
- i) the amino acid sequence encoded by SEQ ID NO:
- 13;
- ii) the amino acid sequence encoded by SEQ ID NO:
- 14;
- or
- iii) the amino acid sequence encoded by SEQ ID NO:
- 15
- or comprising a functional variant or functional fragment of an amino acid sequence of i) through iii).
An isolated polynucleotide which comprises the nucleotide sequence of
- i) SEQ ID NO:
- 1,
- ii) SEQ ID NO:
- 2,
- iii) SEQ ID NO:
- 3,
- iv) SEQ ID NO:
- 4,
- v) SEQ ID NO:
- 5,
- vi) SEQ ID NO:
- 6, or
- vii) SEQ ID NO:
- 7,
- or a functional fragment or variant thereof, provided that said fragment comprises either SQ ID NO:
- 1, 2, 3, 4, 5, 6, or 7.
An isolated polynucleotide which comprises the nucleotide sequence of
- i) SEQ ID NO:
- 9
- ii) SEQ ID NO:
- 10,
- iii) SEQ ID NO:
- 11, or
- iv) SEQ ID NO:
- 12
- or a functional fragment or variant thereof, provided that said fragment comprises either SQ ID NO:
- 9, 10, 11, or 12.
An isolated polynucleotide which comprises the nucleotide sequence of
- i) SEQ ID NO:
- 13,
- ii) SEQ ID NO:
- 14, or
- iii) SEQ ID NO:
- 15
- or a functional fragment or variant thereof, provided that said fragment comprises either SQ ID NO:
- 13, 14, or 15.
An isolated polynucleotide comprising from the 5′ to the 3′ terminus, an oligonucleotide consisting essentially of nucleotides 1-91 of SEQ ID NO:
- 16 covalently bound, in phase, to the polynucleotide X81892.
An isolated polynucleotide which comprises a nucleotide sequence that codes without interruption for the polypeptide of SEQ ID NO:
- 30, or which comprises a nucleotide sequence that codes without interruption for a fragment or variant of the polypeptide of SEQ ID NO:
- 30, or a complement thereof.
A method of making epididymis-specific receptor-6 polypeptides, or functional fragments or variants thereof, comprising incubating a cell of claim 35 under conditions which allow expression of said polypeptides, fragments or variants, and recovering the polypeptides, fragments or variants.
A pharmaceutical composition comprising an antagonist or inhibitor of a polypeptide comprising amino acid sequences encoded by SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21, or 22 and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an antisense nucleotide which can bind with any of the nucleotide sequences shown in SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21, or 22 and a pharmaceutically acceptable carrier.
A pharmaceutical composition for treating a male reproductive disorder comprising administering an effective amount of a polypeptide comprising amino acid sequences encoded by SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21, or 22.
A pharmaceutical composition for diagnosing a male reproductive disorder comprising administering an effective amount of a polypeptide comprising amino acid sequences encoded by SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 27, 28, or 29.
A method for diagnosing infertility in a male mammal, which is associated with under-expression or over-expression of a polynucleotide comprising a sequence of SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21, or 22, comprising contacting a tissue, cell, or polynucleotide from said male with a probe that is specific for said SEQ ID and determining the amount of nucleic acid that hybridizes to the probe wherein said cell or tissue is from a biopsy sample or thin section from the epididymis of said male mammal.
A method for diagnosing infertility in a male mammal comprising measuring antibodies from said male specific for a polypeptide comprising a sequence of SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21 or 22.
A method for treating infertility in a male mammal comprising administering to said mammal an agonist or antagonist of an epididymis-specific receptor comprising administering an effective amount of a polypeptide comprising amino acid sequence encoded by SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21 or 22.
A method for contraception in a male mammal comprising administering to said mammal an antagonist of an epididymis-specific receptor comprising a polypeptide encoded by SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 16, 17, 18, 19, 20, 21 or 22.
A recombinant construct comprising the polynucleotide of SEQ ID NO:33 operatively linked to a regulatory sequence.
An antibody or an antigen-specific fragment specific for human HE6 polypeptide comprising amino acid sequences encoded by SEQ ID NO:33.
A pharmaceutical composition comprising an antagonist or inhibitor of a polypeptide comprising amino acid sequences encoded by SEQ ID NOS:
- 34 or 35.
A pharmaceutical composition for treating a male reproductive disorder comprising administering an effective amount of a polypeptide comprising an amino acid sequence encoded by SEQ ID NO:33.
A composition for diagnosing a male reproductive disorder comprising administering an effective amount of a polypeptide comprising amino acid sequences encoded by SEQ ID NO:33.
Dependencies are inferred from the claim text.