CA2302392A1 - Compositions and methods for contraception in or sterilization of mammals - Google Patents
Compositions and methods for contraception in or sterilization of mammals Download PDFInfo
- Publication number
- CA2302392A1 CA2302392A1 CA002302392A CA2302392A CA2302392A1 CA 2302392 A1 CA2302392 A1 CA 2302392A1 CA 002302392 A CA002302392 A CA 002302392A CA 2302392 A CA2302392 A CA 2302392A CA 2302392 A1 CA2302392 A1 CA 2302392A1
- Authority
- CA
- Canada
- Prior art keywords
- recited
- mammal
- domain
- compound
- peptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 241000124008 Mammalia Species 0.000 title claims abstract 37
- 238000000034 method Methods 0.000 title claims 33
- 230000001954 sterilising effect Effects 0.000 title abstract 2
- 238000004659 sterilization and disinfection Methods 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 31
- 230000002101 lytic effect Effects 0.000 claims abstract 24
- 150000001875 compounds Chemical class 0.000 claims abstract 22
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims abstract 16
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims abstract 15
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims abstract 15
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 claims abstract 15
- 210000004027 cell Anatomy 0.000 claims abstract 4
- 230000007774 longterm Effects 0.000 claims abstract 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 4
- 230000036512 infertility Effects 0.000 claims abstract 3
- 229940088597 hormone Drugs 0.000 claims 7
- 239000005556 hormone Substances 0.000 claims 7
- 230000001456 gonadotroph Effects 0.000 claims 4
- 125000000539 amino acid group Chemical group 0.000 claims 3
- 230000035558 fertility Effects 0.000 claims 3
- 230000001817 pituitary effect Effects 0.000 claims 3
- 241000283690 Bos taurus Species 0.000 claims 2
- 108050004290 Cecropin Proteins 0.000 claims 2
- 108010002069 Defensins Proteins 0.000 claims 2
- 108060003100 Magainin Proteins 0.000 claims 2
- 108010036176 Melitten Proteins 0.000 claims 2
- 241001494479 Pecora Species 0.000 claims 2
- 229930003779 Vitamin B12 Natural products 0.000 claims 2
- 244000309464 bull Species 0.000 claims 2
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims 2
- 210000000936 intestine Anatomy 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 210000002569 neuron Anatomy 0.000 claims 2
- 239000011715 vitamin B12 Substances 0.000 claims 2
- 235000019163 vitamin B12 Nutrition 0.000 claims 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 claims 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 claims 1
- 102000009151 Luteinizing Hormone Human genes 0.000 claims 1
- 108010073521 Luteinizing Hormone Proteins 0.000 claims 1
- 101150047731 MTDH gene Proteins 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 229940028334 follicle stimulating hormone Drugs 0.000 claims 1
- 229940040129 luteinizing hormone Drugs 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract 4
- 230000009089 cytolysis Effects 0.000 abstract 2
- 101710112752 Cytotoxin Proteins 0.000 abstract 1
- 239000000556 agonist Substances 0.000 abstract 1
- 230000000890 antigenic effect Effects 0.000 abstract 1
- 210000000170 cell membrane Anatomy 0.000 abstract 1
- 231100000599 cytotoxic agent Toxicity 0.000 abstract 1
- 239000002619 cytotoxin Substances 0.000 abstract 1
- 230000004927 fusion Effects 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
- C12N15/8257—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
-
- 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
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Reproductive Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Gynecology & Obstetrics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pregnancy & Childbirth (AREA)
- Insects & Arthropods (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to induce sterility or long-term contraception in mammals. The peptides act directly on cell membranes, and need not be internalized.
Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in mammals in vivo. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes). The two components --the ligand and the lytic peptide -- may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide.
Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in mammals in vivo. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes). The two components --the ligand and the lytic peptide -- may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide.
Claims (44)
1. A compound comprising: (a) a hormone domain selected from the group consisting of gonadotropin-releasing hormone, and analogues of gonadotropin-releasing hormone; and (b) a lytic peptide domain.
2. A compound as recited in Claim 1, wherein said hormone domain is bonded directly to said lytic peptide domain, without an intermediate linking domain joining said hormone domain to said lytic peptide domain.
3. A compound as recited in Claim 1, wherein said lytic peptide domain is selected from the group consisting of a cecropin peptide, a melittin peptide, a defensin peptide, a magainin peptide, a sarcotoxin peptide, and analogs of said peptides.
4. A compound as recited in Claim 1, wherein said lytic peptide domain comprises hecate.
5. A compound as recited in Claim 1, wherein said hormone domain comprises gonadotropin-releasing hormone.
6. A compound as recited in Claim 1, wherein said compound has the sequence SEQ. ID NO. 3.
7. A compound as recited in Claim 1, wherein said compound has the sequence SEQ. ID NO. 4.
8. A compound as recited in Claim 1, wherein said hormone domain, or said lytic peptide domain, or both comprise D-conformation amino acid residues.
9. A compound as recited in Claim 8, additionally comprising a carrier domain to facilitate uptake by the intestine when the compound is administered orally.
10. A compound as recited in Claim 9, wherein said carrier domain comprises a vitamin B12 domain.
11. A method for producing long-term contraception or sterility in a mammal, comprising administering to the mammal an effective amount of gonadotropin-releasing hormone and an effective amount of a lytic peptide.
12. A method as recited in Claim 11, wherein the lytic peptide is administered after the gonadotropin-releasing hormone is administered.
13. A method as recited in Claim 11, wherein the gonadotropin-releasing hormone, or the lytic peptide, or both comprise D-conformation amino acid residues.
14. A method as recited in Claim 13, wherein the compound containing D-conformation amino acid residues additionally comprises a carrier domain to facilitate uptake by the intestine when the compound is administered orally.
15. A method as recited in Claim 14, wherein the carrier domain comprises a vitamin B12 domain.
16. A method for producing long-term contraception or sterility in a mammal, comprising administering to the mammal a compound comprising a gonadotropin-releasing hormone domain, and a lytic peptide domain.
17. A method as recited in Claim 16, wherein the hormone domain is bonded directly to the lytic peptide domain, without an intermediate linking domain joining the hormone domain to the lytic peptide domain.
18. A method as recited in Claim 16, wherein the lytic peptide domain is selected from the group consisting of a cecropin peptide, a melittin peptide, a defensin peptide, a magainin peptide, a sarcotoxin peptide, and analogs of said peptides.
19. A method as recited in Claim 16, wherein the lytic peptide domain comprises hecate.
20. A method as recited in Claim 16, wherein the compound has the sequence SEQ. ID NO. 3.
21. A method as recited in Claim 16, wherein the compound has the sequence SEQ. ID NO. 4.
22. A method of temporarily restoring fertility in a mammal that had been made sterile by the selective destruction of gonadotropes in the pituitary, comprising administering to the mammal an effective amount of luteinizing hormone and follicle stimulating hormone.
23. A method as recited in Claim 22, wherein fertility is restored in a mammal that had previously been made sterile by administering to the mammal an effective amount of gonadotropin-releasing hormone and an effective amount of a lyric peptide.
24. A method as recited in Claim 22, wherein fertility is restored in a mammal that had previously ban made sterile by administering to the mammal an effective amount of a compound comprising a gonadotropin-releasing hormone domain, and a lytic peptide domain.
25. A method as recited in Claim 11, wherein the mammal is a dog.
26. A method as recited is Claim 11, wherein the mammal is a cat.
27. A method as recited in Claim 11, wherein the mammal is a cow or bull.
28. A method as recited in Claim 11, wherein the mammal is a pig.
29. A method as recited in Claim 11, wherein the mammal is a horse.
30. A method as recited in Claim 11. wherein the mammal is a sheep.
31. A method as recited in Claim 11, wherein the mammal is a human.
32. A method as recited in Claim 16, wherein the mammal is a dog.
33. A method as recited is Claim 16, wherein the mammal is s cat.
34. A method an recited in Claim 16. wherein the mammal a cow or bull.
35. A method as recited in Claim 16, wherein the mammal is a pig.
36. A method as recited in Claim 16, wherein the mammal is a horse.
37. A method as recited in Claim 16, wherein the mammal is a sheep.
38. A method as recited in Claim 16, wherein the mammal is a human.
39. A method for selectively killing gonadotrophic cells in the pituitary of a mammal, comprising administering to the mammal: (a) an effective amount of gonadotropin-releasing hormone, and (b) an effective amount of a lytic peptide.
40. A method for selectively killing gonadotrophic cells in the pituitary of a mammal, comprising administering to the mammal an effective amount of a compound comprising a gonadotropin-releasing hormone domain and a lytic peptide domain.
41. A method for selectively killing neurons having gonadotrophic receptors in a mammal, comprising administering to the mammal: (a) an effective amount of gonadotropin-releasing hormone, and (b) an effective amount of a lytic peptide.
42. A method for selectively killing neurons having gonadotrophic receptors in a mammal, comprising administering to the mammal an effective amount of a compound comprising a gonadotropin-releasing hormone domain and a lytic peptide domain.
43. A method as recited in Claim 11, wherein the mammal is sexually immature.
44. A method as recited in Claim 16, wherein the mammal is sexually immature.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5745697P | 1997-09-03 | 1997-09-03 | |
| US60/057,456 | 1997-09-03 | ||
| PCT/US1998/018117 WO1999011282A1 (en) | 1997-09-03 | 1998-09-01 | Compositions and methods for contraception in or sterilization of mammals |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2302392A1 true CA2302392A1 (en) | 1999-03-11 |
| CA2302392C CA2302392C (en) | 2012-04-10 |
Family
ID=22010643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2302392A Expired - Lifetime CA2302392C (en) | 1997-09-03 | 1998-09-01 | Compositions and methods for contraception in or sterilization of mammals |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2001514231A (en) |
| AU (1) | AU9213898A (en) |
| CA (1) | CA2302392C (en) |
| WO (1) | WO1999011282A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CU23739A1 (en) * | 2008-09-30 | 2011-12-28 | Ct Ingenieria Genetica Biotech | PHARMACEUTICAL COMPOSITION USING COMBINATIONS OF VARIANTS OF THE GONADOTROPIN LIBERATING HORMONE (GNRH) AS IMMUNOGEN |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631007A (en) * | 1990-03-12 | 1997-05-20 | Ciba-Geigy Corporation | Anti-pathogenically effective compositions comprising lytic peptides and hydrolytic enzymes |
-
1998
- 1998-09-01 WO PCT/US1998/018117 patent/WO1999011282A1/en active Application Filing
- 1998-09-01 CA CA2302392A patent/CA2302392C/en not_active Expired - Lifetime
- 1998-09-01 JP JP2000508384A patent/JP2001514231A/en active Pending
- 1998-09-01 AU AU92138/98A patent/AU9213898A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU9213898A (en) | 1999-03-22 |
| WO1999011282A1 (en) | 1999-03-11 |
| WO1999011282A9 (en) | 1999-05-14 |
| CA2302392C (en) | 2012-04-10 |
| JP2001514231A (en) | 2001-09-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20180904 |
|
| MKEX | Expiry |
Effective date: 20180904 |