EP0282501A1 - Regulation de la reproduction animale - Google Patents

Regulation de la reproduction animale

Info

Publication number
EP0282501A1
EP0282501A1 EP87904825A EP87904825A EP0282501A1 EP 0282501 A1 EP0282501 A1 EP 0282501A1 EP 87904825 A EP87904825 A EP 87904825A EP 87904825 A EP87904825 A EP 87904825A EP 0282501 A1 EP0282501 A1 EP 0282501A1
Authority
EP
European Patent Office
Prior art keywords
hormone
protein
contraceptive
conjugate
fragment
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.)
Withdrawn
Application number
EP87904825A
Other languages
German (de)
English (en)
Other versions
EP0282501A4 (fr
Inventor
Malcolm Roy Brandon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bunge Australia Pty Ltd
Original Assignee
Bunge Australia Pty Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bunge Australia Pty Ltd filed Critical Bunge Australia Pty Ltd
Publication of EP0282501A1 publication Critical patent/EP0282501A1/fr
Publication of EP0282501A4 publication Critical patent/EP0282501A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]

Definitions

  • the present invention relates to a method of regulating the reproductive function of animals and to a veterinary composition for use in such a method. 5 It is known in the prior art to regulate reproductive functions in animals in a variety of ways. Artificial and natural products such as prostaglandins, pregnant mare serum gonadotrophin, melatonins and the like have been proposed for regulation of reproduction in ⁇ _ Q animals. However, such treatments have proved to be of limited value in reduced or suppressing ovulation in female animals in particular. In relation to male animals, surgical castration is still the preferred contraceptive technique. However, there are a number of disadvantages associated with ⁇ ic castration, including possible haemorrhage, infection, weight loss and reduced growth rate.
  • LH-RH immunization is not equally effective in all species of animals and a large proportion of immunized animals fail to respond with an effective suppression of reproductive function. Ineffectiveness of LH-RH immunization as a replacement for surgical desexing is especially evident in cattle (Schanbacher 1984) .
  • LH-RH by itself is not antigenic because of its small size (approx. 1200 daltons) and, in order to .obtain antibodies against it, it is necessary to attach LH-RH to much larger natural or synthetic carrier molecules.
  • Numerous techniques for attachment of LH-RH to various carrier molecules including glutaraldehyde condensation, diisocyanate toluene, benzidine derivatives and carbodiimide. These techniques are not easy to control and it is very difficult to obtain conjugates of a predictable composition and of consistent quality.
  • the most widely used technique for LH-RH conjugation to the carrier molecules is carbodiimide reaction and this reaction is particularly unpredictable (Schanbacher 1984) .
  • the inconsistent quality of conjugates and unpredictable configuration of created antigen molecules contribute to the difficulties of obtaining sufficient titres of specific antibodies to neutralize circulating endogenous hormones.
  • a contraceptive veterinary vaccine including
  • LH luteinizing hormone
  • FSH follicle stimulating hormone
  • Components (a) and (b) of the contraceptive vaccine may be present in any suitable relative amounts.
  • the weight ratio of (a) to (b) may range from approximately 1:2 to 2:1.
  • Techniques utilising immunisation against a single element of reproductive control mechanism (e.g. LH-RH) in order to be effective should be substantially 100% effective in all individuals. There is ample evidence that it is not possible to achieve this level of control via a single element.
  • the contraceptive vaccine according to the present invention utilizing immunization against two interdependent hormones e.g. LH-RH and LH
  • the contraceptive vaccine according to the present invention may be utilised with any animal species.
  • Animal species including cattle, sheep, goats, cats, guinea pigs, pigs, dogs, reindeer, horses and primates may be so treated.
  • the contraceptive vaccine is particularly applicable to domestic pets such as dogs and cats.
  • the hormone-protein conjugates may be formed utilising conventional techniques.
  • heterobifunctional agents such as SPDP, carbodiimide, glutaraldehyde or biotin/avadin systems may be used.
  • the hormone-protein conjugates are formed utilising a methodr which is both repeatable and predictable. Because of the repeatability and predictability this technique is particularly suited for large scale production. Creation of properly structured antigens presenting always the same antigenic site to the immunosystem produces a more uniform immune response in the animals.
  • tetanus toxoid tetanus toxoid (TT) is preferred.
  • the protein carrier is activated with 6-maleimido caproic acyl N-hydroxy succinimide ester (MCS) to introduce maleimido reactive groups.
  • MCS 6-maleimido caproic acyl N-hydroxy succinimide ester
  • the maleimido reactive groups are introduced in a ratio of approximately 30 per 100,000 daltons, a desired number of binding sites for the peptide hormones is created.
  • the peptide hormones may in turn be activated by thiolation. Thiolation may be achieved by reaction with, e.g. N-acetyl homocysteine thiolactone (AHTL) .
  • AHTL N-acetyl homocysteine thiolactone
  • a contraceptive vaccine as described above further including
  • the vaccine adjuvant includes a cell wall immunostimulant or mixturs thereof.
  • the cell wall irnmunostimulant may be a cell wall fraction of a mycobacterium phlei or smegmatis.
  • This fraction may be obtained by lysosome digestion of purified mycobacterial cell walls and is capable of replacing, at least in part, standard adjuvants such as described above, in particular the most commonly used, Fruend's Complete Adjuvant.
  • the cell fraction is body tissue compatable, stimulate immune response to the viral and protein antigens and also does not induce sensitivity to tuberculin.
  • a method of inhibiting the reproductive functions of animals which method includes providing a contraceptive vaccine including (a) a protein-hormone conjugate of a luteinizing hormone (LH) , analogue thereof, fragment thereof or derivative thereof, or a follicle stimulating hormone (FSH) analogue thereof, fragment thereof or derivative thereof, and (b) a protein-hormone conjugate of a luteinizing hormone releasing hormone (LH-RH) , analogue thereof, fragment thereof, or derivative thereof; and administering an effective amount of the vaccine to the animal to be treated.
  • the method of inhibiting the reproductive functions of animals may include preventing or suppressing ovulation and/or oestrous cyclicity in female animals and prevention or suppression of sexual behaviour in male animals.
  • the vaccine may be administered parenterally.
  • Parenteral administration may include subcuaneous, intramuscular or intravenous injeciton, oral administration or adsorption through the skin or by mini pump either implanted in the animal or attached to the hide of the animal.
  • Tne dose rates effective will vary with the weight and species of animal. Optimum dose rates for individual species may be selected utilising simple experimentation. However, as a guide for small animals such as domestic dogs or cats each dose may include from approximately 200 to 300
  • c microgram of the luteinising hormone or follicle stimulating hormone conjugate and from approximately 200 to 300 microgram of luteinizing hormone releasing hormone conjugate. Where a vaccine conjugate is used this may be present in amounts of from approximately 150 to 250 micrograms.
  • a single vaccination is only required but a second vaccination may be undertaken for security.
  • MCS-modified TT was dissolved in a small volume of N 2 -saturated 0,1M sodium-phosphate-O,1M EDTA pH. 6.6 buffer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Endocrinology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Reproductive Health (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Un vaccin vétérinaire contraceptif comprend (a) un conjugué de protéines-hormones d'une hormone lutéinisante (LH), d'une hormone analogue, d'un fragment de ladite hormone ou d'un dérivé de ladite hormone ou d'une hormone de stimulation de follicules (FSH), d'une hormone analogue, d'un fragment de ladite hormone ou d'un dérivé de ladite hormone et (b) un conjugué de protéines-hormones d'une hormone de libération d'hormones lutéinisantes (LH-RH), d'une hormone analogue, d'un fragment de ladite hormone ou d'un dérivé de ladite hormone.
EP19870904825 1986-08-18 1987-07-30 Regulation de la reproduction animale. Withdrawn EP0282501A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPH751786 1986-08-18
AU7517/86 1986-08-18

Publications (2)

Publication Number Publication Date
EP0282501A1 true EP0282501A1 (fr) 1988-09-21
EP0282501A4 EP0282501A4 (fr) 1989-11-14

Family

ID=3771764

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19870904825 Withdrawn EP0282501A4 (fr) 1986-08-18 1987-07-30 Regulation de la reproduction animale.

Country Status (3)

Country Link
EP (1) EP0282501A4 (fr)
JP (1) JPH01500663A (fr)
WO (1) WO1988001176A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5538948A (en) * 1987-01-30 1996-07-23 Novo Nordisk A/S Method for treating infertility comprising administering GnRH analog, gonadotrophins, and growth hormone
US5036047A (en) * 1988-09-29 1991-07-30 Pitman-Moore, Inc. Method and composition for preventing conception
DK272789D0 (da) * 1989-06-02 1989-06-02 Novo Nordisk As Fremgangsmaade og praeparat til behandling af infertilitet
US5378815A (en) * 1989-10-20 1995-01-03 National Research Council Canada Process for indirect targeted immunocytolysis
KR100257214B1 (ko) * 1991-03-01 2000-05-15 데스꼴롱그 티에리 거세되지 않은 수컷가축의 고기의 관능적 품질을 개선하기 위한 방법
DE69230855D1 (de) * 1991-07-26 2000-05-04 Commw Scient Ind Res Org System der bereitstellung eines impfstoffes auf peptidbasis, das sein eigenes adjuvans bildet, und seine herstellung
AUPP977899A0 (en) * 1999-04-15 1999-05-13 Monash University Improvement of t cell mediated immunity
CH698085B1 (it) * 2006-06-28 2009-05-15 Studio Legale Avv Aldo Ferrini Medicamento contraccettivo comprendente l'ormone luteinizzante.

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4526716A (en) * 1981-11-20 1985-07-02 The Ohio State University Antigenic modification of polypeptides
AU503647B2 (en) * 1974-10-14 1979-09-13 All India Institute Of Medical Sciences Antipregnancy vaccine
US4338305A (en) * 1975-03-24 1982-07-06 American Home Products Corporation Use of LRH and LRH agonists
DD142421B1 (de) * 1978-12-29 1982-06-30 Jost Bergfeld Verfahren zur herstellung einer hormonkombination zur ovulationsstimulation
DE3200459A1 (de) * 1982-01-09 1983-07-21 Hoechst Ag, 6230 Frankfurt Verfahren zur behandlung der azyklie bei schafen oder rindern
ZA845550B (en) * 1983-08-09 1986-03-26 American Home Prod Treatment of endometriosis

Also Published As

Publication number Publication date
WO1988001176A1 (fr) 1988-02-25
EP0282501A4 (fr) 1989-11-14
JPH01500663A (ja) 1989-03-09

Similar Documents

Publication Publication Date Title
Thompson Jr Immunization against GnRH in male species (comparative aspects)
EP1140165B1 (fr) Compositions adjuvantes ameliorees a base de saponine et procedes en rapport
AU619239B2 (en) Antigen antibody conjugate
JPH02113A (ja) ＧｎＲＨに対する免疫応答を刺激し、哺乳動物を免疫的に生殖不能化するための剤及び方法
US20040213817A1 (en) Vaccine compositions and adjuvant
Kemp et al. Continuous antigen delivery from controlled release implants induces significant and anamnestic immune responses
Vassilev Aluminium phosphate but not calcium phosphate stimulates the specific IgE response in guinea pigs to tetanus toxoid
Finnerty et al. Immunization of bull calves with a GnRH analogue–human serum albumin conjugate: effect of conjugate dose, type of adjuvant and booster interval on immune, endocrine, testicular and growth responses
CA1297003C (fr) Composition et methode pour traiter les animaux
US5897863A (en) LHRH hormones
EP0282501A1 (fr) Regulation de la reproduction animale
AU625561B2 (en) Method and composition for preventing conception
EP0274496A1 (fr) Composition et procede de castration et de sterilisation immunologiques
TAUSSIG Antigenic competition
Talwar et al. Birth control vaccines inducing antibodies against chorionic gonadotropin
Carelli et al. Immunological castration by a totally synthetic vaccine: modification of biological properties of LH-RH after conjugation to adjuvant-active muramyl peptide
US6355256B1 (en) Compositions containing a p53 derived protein or peptide, an adjuvant, and interleukin-12 and uses thereof
Talwar Immunological approaches to contraception: the need, basic premise, and overview
Stone et al. Tick‐paralysis toxoid: an effective immunizing agent against the toxin of Ixodes holocyclus
Fraser LHRH immunoneutralization: basic studies and prospects for practical application
WO2001034192A2 (fr) Procede relatif a une amelioration de l'immunisation
RAIKOW et al. Humoral response of normal and athymic (nude) mice to human choriogonadotropin immunogens
AU7642387A (en) Composition and method for immunological castration and spaying
US20220016225A1 (en) Vaccine compositions and adjuvant
Chang THE REGULATION OF REPRODUCTION IN CATTLE BY AN ANTIESTROGEN, OR ACTIVE IMMUNIZATION AGAINST PROSTAGLANDIN F (2ALPHA) AND OVARIAN STEROIDS

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19880421

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

A4 Supplementary search report drawn up and despatched

Effective date: 19891114

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19910201