WO1997012038A1 - Novel peptides useful in enhancement of fsh action - Google Patents
Novel peptides useful in enhancement of fsh action Download PDFInfo
- Publication number
- WO1997012038A1 WO1997012038A1 PCT/GB1996/002365 GB9602365W WO9712038A1 WO 1997012038 A1 WO1997012038 A1 WO 1997012038A1 GB 9602365 W GB9602365 W GB 9602365W WO 9712038 A1 WO9712038 A1 WO 9712038A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- peptide
- fsh
- sheep
- humans
- fsh activity
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 83
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 29
- 230000000694 effects Effects 0.000 claims abstract description 62
- 230000002708 enhancing effect Effects 0.000 claims abstract description 24
- 230000001965 increasing effect Effects 0.000 claims abstract description 8
- 230000035558 fertility Effects 0.000 claims abstract description 3
- 241001494479 Pecora Species 0.000 claims description 42
- 241000283690 Bos taurus Species 0.000 claims description 30
- 241000282412 Homo Species 0.000 claims description 29
- 241000283086 Equidae Species 0.000 claims description 27
- 241000282887 Suidae Species 0.000 claims description 27
- 241000124008 Mammalia Species 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 150000007523 nucleic acids Chemical group 0.000 claims description 7
- 235000002198 Annona diversifolia Nutrition 0.000 claims description 6
- 241000282832 Camelidae Species 0.000 claims description 6
- 241000282472 Canis lupus familiaris Species 0.000 claims description 6
- 241000283707 Capra Species 0.000 claims description 6
- 241000282326 Felis catus Species 0.000 claims description 6
- 241000282838 Lama Species 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 6
- 241001416177 Vicugna pacos Species 0.000 claims description 6
- 229960005486 vaccine Drugs 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 abstract description 149
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 abstract description 149
- 229940028334 follicle stimulating hormone Drugs 0.000 abstract description 149
- 210000002966 serum Anatomy 0.000 description 29
- 239000002953 phosphate buffered saline Substances 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 230000002611 ovarian Effects 0.000 description 18
- 108010091748 peptide A Proteins 0.000 description 18
- 230000004044 response Effects 0.000 description 16
- 229940088597 hormone Drugs 0.000 description 15
- 239000005556 hormone Substances 0.000 description 15
- 101800005149 Peptide B Proteins 0.000 description 13
- 238000011282 treatment Methods 0.000 description 10
- 238000011121 vaginal smear Methods 0.000 description 10
- 241000894007 species Species 0.000 description 8
- 238000002649 immunization Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000002788 anti-peptide Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 2
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229940015047 chorionic gonadotropin Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000016087 ovulation Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940023041 peptide vaccine Drugs 0.000 description 2
- 230000021595 spermatogenesis Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010042573 Superovulation Diseases 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 230000008217 follicular development Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Definitions
- the present invention relates to novel peptides useful in enhancement of follicle stimulating hormone (FSH) bioactivity in mammals.
- FSH follicle stimulating hormone
- the invention relates to such peptides and their use in stimulating FSH activity in, inter alia , humans, sheep, cattle, pigs, goats, cats, dogs, horses, camels, llamas and alpacas.
- Follicle stimulating hormone belongs to a family of glycoprotein hormones which includes lutenising hormone
- LH thyrotropin
- CG chorionic gonadotropin
- FSH plays a key role in the control of folliculogenesis and spermatogenesis.
- the presence of FSH is fundamental to the recruitment of quiescent primary follicles and their development into antral follicles (for a review see Hillier, Human Reproduction, 9:188-191 (1994) ) .
- These biological effects are mediated by the binding of FSH to specific cellular receptors; such receptors bind to specific sites on the FSH molecule termed receptor recognition sites (Combarnous, supra) .
- receptor recognition sites Combarnous, supra
- Different animal models have been used to study the effects of FSH on follicular growth and ovulation. These include hypophysectomized mice (Wang and Greenwald,
- the present invention provides a peptide having the following sequence:
- the peptides of the invention are useful in eliciting antibody responses in mammals, the antibody causing an enhancement of either endogenous or exogenous FSH activity. This in turn leading to enhanced ovulation or spermatogenesis and hence fertility.
- the peptide or peptides can be provided as a vaccine used to stimulate an immune response which recognises FSH in the subject mammal. Such a vaccine forms a second aspect of the invention.
- the present invention provides a nucleic acid sequence coding for a peptide as described above, or one substantially homologous thereto.
- nucleic acid sequences can either be DNA sequences or RNA sequences.
- nucleic acid sequences include all other nucleic acid sequences which, by virtue of the degeneracy of the genetic code, also code for the given amino acid sequence, or which are substantially homologous to such a sequence.
- substantial homology at the amino acid level refers to peptide sequences having a significant number of constituent amino acids homologous to the peptide sequences described above. For example, at least 40%, 50%, 60%, 70%, 80%, 90%, 95% or even 99%, in increasing order of preference, of the amino acids may be homologous .
- the peptides of the present invention can be used to generate antibodies, these antibodies then being administered to a mammal to elicit enhanced bioactivity of either endogenous or exogenous FSH.
- the present invention provides an antibody having specificity for one or more of the peptides of the present invention.
- the antibody will be a monoclonal antibody.
- the antibody is provided as an antibody preparation, comprising one or more antibodies reactive with one or more of the peptides of the present invention.
- Peptides (i) or (iv) will be used to enhance FSH activity in sheep, or to raise antibodies to enhance FSH activity in sheep;
- Peptide (i) will be used to enhance FSH activity in cattle or pigs, or to raise antibodies to enhance FSH activity in cattle or pigs:
- Peptide (i) will be used to enhance FSH activity in horses or humans, or to raise antibodies to enhance FSH activity in horses or humans;
- Peptide (ii) will be used to enhance FSH activity in sheep or pigs, or to raise antibodies to enhance FS_H activity in sheep or pigs;
- Peptide (ii) will be used to enhance FSH activity in horses, humans or cattle, or to raise antibodies to enhance FSH activity in horses, humans or cattle;
- Peptide (iii) will be used to enhance FSH activity in horses or humans, or to raise antibodies to enhance FSH activity in horses or humans;
- Peptide (iii) will be used to enhance FSH activity in horses or humans, or to raise antibodies
- the present invention provides a pharmaceutical formulation comprising one or more peptides of the present invention, or one or more antibodies or antibody preparations of the present invention, together with one or more pharmaceutically acceptable carriers, diluents or excipients.
- the present invention provides the use of a peptide or antibody of the present invention in enhancing FSH bioactivity in a mammal.
- the bioactivity is enhanced in cattle, sheep, horses, pigs, humans, camels, goats, cats, dogs, llamas or alpacas.
- the present invention provides a method for enhancing FSH bioactivity in mammals, particularly cattle, sheep, horses, pigs, humans, camels, goats, cats, dogs, llamas or alpacas, which comprises the step of administering one or more peptides, or one or more antibodies, of the present invention to the mammal.
- FIGURE 1 is a comparison of the sequences of j ⁇ subunits of FSH from various species
- FIGURE 2 is a comparison between the titre of antibodies against whole bovine FSH (bFSH) in preimmune serum (bleed 0) and in antiserum after four administrations of peptide A (bleed 4) in sheep Al (2-a) and A2 (2-b) , and peptide B in sheep Bl (2- c) ;
- FIGURE 3 shows the mean ( ⁇ SEM) of uterine (3-a) and ovarian (3-b) weights and the keratinisation index (3-c) in groups of Snell dwarf mice given 3.3, 10, 30 and 90 ⁇ g/day of ovine FSH (oFSH) or phosphate buffered saline (hormone diluent, PBS) ;
- oFSH ovine FSH
- PBS phosphate buffered saline
- FIGURE 4 shows an estimation of antibody mediated enhancement of oFSH bioactivity by measurement of uterine (4-a) and ovarian (4-b) weights and the keratinisation index of vaginal smears (4-c) , in five different groups of Snell dwarf mice which received 20 ⁇ g/day oFSH (group FSH) , 20 ⁇ g/day oFSH + peptide A antiserum (group FSH + A) , 20 ⁇ g/day oFSH + preimmune serum (group FSH + p) , peptide A antiserum alone (group A) and PBS control (group C) ; all values are means ⁇ SEM; and FIGURE 5: shows an estimation of antibody mediated enhancement of FSH oioactivity by measurement of uterine (5a) and ovarian (5b) weights and the keratinisation index of vaginal smears (5c) m five different groups of mice which received 20 ⁇ g/day oFSH (group
- Peptides different sequential peptides of FSH were synthesised by F moc chemistry using an upgraded 431A automated peptide synthesiser (Applied Biosystems) . Peptides were synthesised with free amino and carboxytermmi . Peptide identity was confirmed by MALDI (matrix assisted laser desorption ionisation) mass spectroscopy and peptides were estimated at greater than 95% purity by analytical reverse phase chromatography.
- MALDI matrix assisted laser desorption ionisation
- KLH conj ugation 20 ml of 10 mM sodium phosphate buffer pH 6.8 were added to a mixture composed by 5 mg of peptide and 5 mg of Reyhole Lympet Haemocyanin (KLH) ; this solution was stirred with the slow addition of 50 ⁇ l of 25% glutaraldehyde and the stirring was carried on for three hours. The solution was then aliquoted m 20 x 2 ml aliquots and stored at 20°C ready for use.
- HADSLYTYPVAT (labelled C; bFSH sequence 69-80) ; HCSRCDSDSTDC (labelled D; bFSH sequence 83-94) ; and WCAGYCYTRDLVY (labelled E; bFSH sequence 27-39) .
- peptide A sheep Al and A2
- Radioimmunoassay serum samples were taken from each sheep before the __first injection of peptide (preimmune) and ten days after each immunisation. Serial dilutions of each serum sample (1/10-1/6250) were tested for their ability to recognise iodinated bFSH in a liquid phase radioimmunoassay.
- ovine-FSH NIH-FSH-SI (Ovine R041212)
- PBS PBS
- mice Animals and trea tment : snell dwarf mice were bred, maintained and marked as previously described by Holder et al , J. Endocrinol . 85: 35-47 (1980) . Thirty 26 to 35 day old female dwarf mice were randomly allocated to five treatment groups, given 0, 3.3, 10, 30, 90 ⁇ g/day of oFSH using 0.05 ml of solution injected subcutaneously twice a day for five days. Fourteen hours after the last injection, the mice were sacrificed by decapitation under halothane/oxygen anaesthetic.
- Ovarian and uterine weights ovaries and uterus were removed, dissected free of fat under a stereo- microscope, fixed in formalin (3.7%) and weighed, after fixation, using a Cahn microbalance.
- Vaginal smears vaginal cells were collected using a few drops of PBS introduced into the vagina via an ordinary pipette and then extracted by the pipette. The cells were transferred to a microscope slide, fixed in methanol and stained with Wright Giemsa. The smears were analysed under lOOx magnification and the keratinisation index (keratinised cells/total cells x 100) was calculated.
- uterine and ovarian weights (expressed as mg/g body weight) and keratinisation index were used for the statistical analysis.
- Data from each group treated with hormone were compared with the PBS injected control group using Student's t . -Test.
- ovine FSH (NIH-FSH- SI) was dissolved in PBS.
- Preimmune serum or antiserum against peptide A was purified as follows: one volume of 27% sodium sulphate was mixed with 2 volumes of serum and incubated at 37°C for 3.5 h. The precipitated IG fraction was centrifuged and the pellet reconstituted to the volume of serum from which it was derived. This IG fraction was then extensively dialysed against PBS. Equal volumes of FSH and purified serum were combined to give a final concentration of 20 ⁇ g oFSH plus 50 ⁇ l of neat purified antiserum per 100 ⁇ l of injection solution.
- mice were bred, maintained and marked as described previously. Thirty 31 to 40 days old female Snell dwarf mice were randomly allocated to five treatment groups:
- FSH Group 1
- mice Twenty-five 31-40 day old female Snell dwarf mice were randomly allocated to five treatment groups. Mice were bred and maintained as above.
- Hormone and purified antiserum hormone and sera were prepared and purified as described in the previous section.
- FSH Group 1
- Figures 2a, b and c show the comparison between the titre of antibodies against bFSH in preimmune serum (bleed 0) , and in antiserum after four injections (bleed 4), in the two sheep injected with peptide A (Al and A2) and in one of the two sheep immunised against peptide B (Bl) .
- the second animal (B2) died before the end of the present trial.
- sheep injected with peptide A sheep
- Figure 3 illustrates the effects of various doses of oFSH alone, on uterine and ovarian weight (expressed as mg/g body weight; figs 3a and 3b) and on the index of keratinisation in vaginal smears (% keratinised cells; fig 3c) .
- Figure 4 illustrates the ability of antiserum to peptide A to enhance FSH activity, as determined by increased uterine (Fig 4a) and ovarian weight (Fig 4b) and an increased index of keratinisation in vaginal smears (fig 4c) in Snell dwarf mice.
- Figure 5 illustrates the ability of antiserum to peptide A to enhance FSH activity, as determined by increased uterine (Fig 5a) and ovarian weight (Fig 5b) and an increased index of keratinisation in vaginal smears (fig 3c) in Snell dwarf mice.
- FSH enhancing antisera can be produced m a subject animal by active immunisation; alternatively antibody preparation from one animal may be administered to another animal of the same species by passive immunisation.
- This technique can be used to enhance endogenous FSH activity; under these circumstances, circulating levels of FSH remain under pituitary control, thus enhancement only occurs when FSH is produced. This will serve to avoid hyperstimulation of the ovaries which is often caused by current superovulation treatments .
- Both of the active component namely antisera and FSH, are produced by the animal.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Reproductive Health (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP96931894A EP0858508A1 (en) | 1995-09-25 | 1996-09-25 | Novel peptides useful in enhancement of fsh action |
JP9513214A JP2000508293A (en) | 1995-09-25 | 1996-09-25 | Novel peptide useful for promoting FSH action |
AU70900/96A AU704010B2 (en) | 1995-09-25 | 1996-09-25 | Novel peptides useful in enhancement of FSH action |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9519511.1 | 1995-09-25 | ||
GBGB9519511.1A GB9519511D0 (en) | 1995-09-25 | 1995-09-25 | Peptides |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997012038A1 true WO1997012038A1 (en) | 1997-04-03 |
Family
ID=10781220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1996/002365 WO1997012038A1 (en) | 1995-09-25 | 1996-09-25 | Novel peptides useful in enhancement of fsh action |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0858508A1 (en) |
JP (1) | JP2000508293A (en) |
AU (1) | AU704010B2 (en) |
CA (1) | CA2232950A1 (en) |
GB (1) | GB9519511D0 (en) |
WO (1) | WO1997012038A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001047875A1 (en) * | 1999-12-27 | 2001-07-05 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted aminoalkylamide derivatives as antagonists of follicle stimulating hormone |
FR3025517A1 (en) * | 2014-09-10 | 2016-03-11 | Repropharm | LIGANDS POTENTIATING THE BIOACTIVITY OF GONADOTROPHINS |
FR3025516A1 (en) * | 2014-09-10 | 2016-03-11 | Repropharm | LIGAND POTENTIATING THE BIOACTIVITY OF FSH |
-
1995
- 1995-09-25 GB GBGB9519511.1A patent/GB9519511D0/en active Pending
-
1996
- 1996-09-25 JP JP9513214A patent/JP2000508293A/en active Pending
- 1996-09-25 WO PCT/GB1996/002365 patent/WO1997012038A1/en not_active Application Discontinuation
- 1996-09-25 AU AU70900/96A patent/AU704010B2/en not_active Ceased
- 1996-09-25 EP EP96931894A patent/EP0858508A1/en not_active Withdrawn
- 1996-09-25 CA CA002232950A patent/CA2232950A1/en not_active Abandoned
Non-Patent Citations (8)
Title |
---|
B B SAXENA ET AL.: "Chemical synthesis of peptide fragments of the hormone-specific beta-subunit of human follicle stimulating hormone", BIOCHEMISTRY, vol. 24, no. 3, 29 January 1985 (1985-01-29), EASTON, PA US, pages 813 - 816, XP002023257 * |
CHEMICAL ABSTRACTS, vol. 113, no. 21, 19 November 1990, Columbus, Ohio, US; abstract no. 184859t, D D VAKHARIA ET AL.: "Mapping of an assembled epitope of human follicle-stimulating hormone-beta utilizing monoclonal antibodies, synthetic peptides and hormone-receptor inhibition" page 80; XP002023260 * |
ENDOCRINOLOGY, vol. 127, no. 2, 1990, BALTIMORE, pages 658 - 666 * |
M HAGE-VAN NOORT ET AL.: "Synthetic peptides based upon a three-dimensional model for the receptor recognition site of follicle-stimulating hormone exhibit antagonistic or agonistic activity at low concentrations", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 89, no. 9, 1 May 1992 (1992-05-01), WASHINGTON US, pages 3922 - 3926, XP002023259 * |
P GRASSO ET AL.: "An explanation for the disparate effects of synthetic peptides corresponding to human follicle-stimulating hormone beta-subunit receptor binding region (33-53) and (81-95) and their serine analogs on steroidogenesis in cultured rat Sertoli cells", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 190, no. 1, 15 January 1993 (1993-01-15), ORLANDO, FL US, pages 56 - 62, XP002023255 * |
T A SANTA-COLOMA ET AL.: "A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH beta-receptor, stimulates basal estradiol biosynthesis and is a partial antagonist of FSH", BIOCHEMISTRY, vol. 29, no. 5, 6 February 1990 (1990-02-06), EASTON, PA US, pages 1194 - 1200, XP002023256 * |
T A SANTA-COLOMA ET AL.: "Identification of a follicle-stimulating hormone receptor-binding region in h FSH (81-95) using synthetic peptides", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 265, no. 9, 25 March 1990 (1990-03-25), MD US, pages 5037 - 5042, XP002023258 * |
T A SANTA-COLOMA ET AL.: "Serine analogues of hFSH-beta-(33-53) and hFSH-beta-(81-95) inhibit hFSH binding to receptor", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 184, no. 3, 15 May 1992 (1992-05-15), ORLANDO, FL US, pages 1273 - 1279, XP000268961 * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001047875A1 (en) * | 1999-12-27 | 2001-07-05 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted aminoalkylamide derivatives as antagonists of follicle stimulating hormone |
US6583179B2 (en) | 1999-12-27 | 2003-06-24 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted aminoalkylamide derivatives as antagonists of follicle stimulating hormone |
FR3025517A1 (en) * | 2014-09-10 | 2016-03-11 | Repropharm | LIGANDS POTENTIATING THE BIOACTIVITY OF GONADOTROPHINS |
FR3025518A1 (en) * | 2014-09-10 | 2016-03-11 | Repropharm | LIGANDS POTENTIATING THE BIOACTIVITY OF GONADOTROPHINS |
FR3025516A1 (en) * | 2014-09-10 | 2016-03-11 | Repropharm | LIGAND POTENTIATING THE BIOACTIVITY OF FSH |
WO2016038309A1 (en) * | 2014-09-10 | 2016-03-17 | Repropharm | Ligands that potentiate the bioactivity of gonadotropins |
WO2016038310A1 (en) * | 2014-09-10 | 2016-03-17 | Repropharm | Ligand potentializing fsh bioactivity |
WO2016038308A1 (en) * | 2014-09-10 | 2016-03-17 | Repropharm | Ligands that potentiate the bioactivity of gonadotropins |
CN107108732A (en) * | 2014-09-10 | 2017-08-29 | 瑞普罗制药公司 | Strengthen the part of the bioactivity of gonadotropic hormone |
US10584166B2 (en) | 2014-09-10 | 2020-03-10 | Repropharm Vet | Ligands that potentiate the bioactivity of gonadotropins |
US10703815B2 (en) | 2014-09-10 | 2020-07-07 | Igyxos | Ligands that potentiate the bioactivity of gonadotropins |
Also Published As
Publication number | Publication date |
---|---|
JP2000508293A (en) | 2000-07-04 |
EP0858508A1 (en) | 1998-08-19 |
AU704010B2 (en) | 1999-04-01 |
GB9519511D0 (en) | 1995-11-29 |
CA2232950A1 (en) | 1997-04-03 |
AU7090096A (en) | 1997-04-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wrathall et al. | Inhibin immunoneutralization by antibodies raised against synthetic peptide sequences of inhibin α subunit: effects on gonadotrophin concentrations and ovulation rate in sheep | |
Sherwood | The GnRH family of peptides | |
Ying | Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone | |
Forage et al. | Immunization against an inhibin subunit produced by recombinant DNA techniques results in increased ovulation rate in sheep | |
Johnson et al. | Active immunization of heifers against luteinizing hormone-releasing hormone, human chorionic gonadotropin and bovine luteinizing hormone | |
Hofferer et al. | Induction of ovulation and superovulation in mares using equine LH and FSH separated by hydrophobic interaction chromatography | |
O'shea et al. | Inhibin immunization for increasing ovulation rate and superovulation | |
McNeilly et al. | Changes in the plasma concentrations of inhibin throughout the normal sheep oestrous cycle and after the infusion of FSH | |
Remy et al. | Are antibodies responsible for a decreased superovulatory response in goats which have been treated repeatedly with porcine follicle-stimulating hormone? | |
Anderson et al. | Increased ovulation rate in Merino ewes immunized against small synthetic peptide fragments of the inhibin α subunit | |
Wheaton et al. | Active and passive immunoneutralization of inhibin increases follicle-stimulating hormone levels and ovulation rate in ewes | |
Yamamoto et al. | Radioimmunoassay of a newt sex pheromone, sodefrin, and the influence of hormones on its level in the abdominal gland | |
EP0260306A1 (en) | Method of assay of inhibin | |
CA1330420C (en) | Compositions containing growth hormone peptide fragments | |
Thau et al. | The mechanism of action of an antifertility vaccine in the rhesus monkey: reversal of the effects of antisera to the β-subunit of ovine luteinizing hormone by medroxyprogesterone acetate | |
D'alessandro et al. | Active immunization with a synthetic fragment of pig inhibin α-subunit increases ovulation rate and embryo production in superovulated ewes but season affects its efficiency | |
JP2802633B2 (en) | Protein | |
AU595295B2 (en) | Method and compositions for increasing mammary parenchyma | |
AU704010B2 (en) | Novel peptides useful in enhancement of FSH action | |
Palta et al. | Peripheral inhibin levels during estrous cycle in buffalo (Bubalus bubalis) | |
HOLLANDER et al. | Levels of corticotropin releasing factor-like immunoreactivity in mammalian hypothalamic and extrahypothalamic brain tissue as determined with a monoclonal antibody to the ovine material. | |
Audhya et al. | Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems. | |
Schalla et al. | Production of anti-idiotypic antibodies resembling bovine somatotrophin by active immunization of lactating cows | |
JPH08154957A (en) | Excessive ovulation inducing method for cow | |
JP2000509964A (en) | Bioactive molecules, especially peptides, that have an enhancing effect on growth hormone biological activity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2232950 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 318822 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996931894 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1996931894 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1996931894 Country of ref document: EP |