Compounds for the treatment of sexual dysfunction

• US 20020102707A1
• Filed: 07/13/2001
• Published: 08/01/2002
• Est. Priority Date: 07/14/2000
• Status: Active Grant

• Current Assignee: Pfizer Inc., Pfizer Products Incorporated (Pfizer Inc.)
• Original Assignee: Pfizer Inc., Pfizer Products Incorporated (Pfizer Inc.)
• Inventors: Wayman, Christopher Peter, Phillips, Stephen Charles, Walsh, Roderick Thomas, Harrow, Ian Dennis, Stacey, Peter
• Granted Patent: US 6,878,529 B2
• Time in Patent Office: Days
• US Class Current: 435/226
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 5/40 : Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C12N 9/6421 : from mammals
• CPC Class Codes: C12N 9/6489 : Metalloendopeptidases (3.4.24)
• CPC Class Codes: G01N 2800/344 : Disorders of the penis and the scrotum and erectile dysfuncrion

Abstract

Polynucleotide and polypeptide sequences are described. The polypeptide sequences comprise one or more of: (a) a polypeptide having the deduced amino acid sequence translated from the polynucleotide sequence in SEQ ID NO: 1 or SEQ ID NO: 5 and variants, fragments, homologues, analogues and derivatives thereof; (b) a polypeptide of SEQ ID NO: 2 and variants, fragments, homologues, analogues and derivatives thereof (c) a polypeptide encoded by the cDNA of NCIMB 41110 and variants, fragments, homologues, analogues and derivatives thereof; or (d) a polypeptide which has at least 78% identity to (i) the polypeptide encoded by the polynucleotide of SEQ ID NO: 1 or SEQ ID NO: 5, (ii) the polypeptide of SEQ ID NO: 2, or (iii) the polypeptide encoded by the cDNA of NCIMB 41110. Such polypeptide sequences are, inter alia, useful in the prophylaxis and/or treatment of sexual dysfunction, in particular male erectile dysfunction (MED) or female sexual dysfunction (FSD), preferably female sexual arousal disorder (FSAD).

Claims

1. An isolated and/or purified polynucleotide comprising one or more of:

(a) a polynucleotide encoding the polypeptide comprising SEQ ID NO;

2;

(b) a polynucleotide comprising a nucleotide sequence of SEQ ID NO;

1 or SEQ ID NO;

5;

(c) a polynucleotide encoding the polypeptide expressed by the DNA contained in NCIMB 41110;

(d) a polynucleotide, wherein the complement of said polynucleotide hybridizes to the full length coding sequence of (a) (b) or (c) under conditions of moderate stringency;

or

(e) a complement to the polynucleotide of any one of (a) to (d).

2. The polynucleotide of claim 1 which encodes human soluble secreted endopeptidase (SEP).

3. A process for producing a polypeptide comprising culturing a host cell transformed or transfected with a vector comprising the polynucleotide of claim 1 in culture medium under conditions sufficient for the expression of said polypeptide.

4. An isolated and/or purified polypeptide having SEP activity comprising:

(a) an amino acid sequence encoded by the polynucleotide of claim 1;

or

(b) an amino acid sequence comprising SEQ ID NO;

2.

5. An antibody against the polypeptide of claim 4.

6. A compound which inhibits or selectively inhibits the polypeptide of claim 4.

7. A pharmaceutical composition comprising the antibody of claim 5 or the compound of claim 6 and one or more pharmaceutically acceptable carriers, diluents, adjuvants, or excipients.

8. A method for the treatment of a patient in need thereof comprising administering to the patient a therapeutically effective amount of the antibody of claim 5 or the compound of claim 6.

9. The method of claim 8, wherein said patient is treated for sexual dysfunction.

10. The method of claim 9, wherein said patient is treated for female sexual arousal disorder (FSAD).

11. The method of claim 9, wherein said patient is treated for male erectile dysfunction.

12. A method for the prophylactic treatment of a patient in need thereof comprising administering to the patient a therapeutically effective amount of the antibody of claim 5 or the compound of claim 6.

13. A cell genetically engineered ex vivo or in vivo to overexpress, underexpress, or to exhibit targeted insertion or deletion of the polypeptide of claim 4.

14. A non-human animal comprising cells according to claim 13.

15. Cells deposited under Accession Number NCIMB 41110 and variants and mutants derivable therefrom capable of producing a polypeptide according to claim 4.