Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Fusion protein or fusion polypeptide
Patent
1991-06-25
1995-04-04
Draper, Garnette D.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Fusion protein or fusion polypeptide
4241981, 424811, 435 693, 435 694, 435 697, 4352523, 4353201, 536 234, 930130, A61K 3900
Patent
active
054035864
DESCRIPTION:
BRIEF SUMMARY
This application is filed under 35 U.S.C. .sctn.371 claiming priority to PCT application PCT/AU90/00373, filed Aug. 24, 1990 and published Mar. 7, 1991 as WO 91/02799.
TECHNICAL FIELD
This invention relates to fusion proteins useful as components of vaccines for the immunological castration or inhibition of reproductive function of vertebrate hosts in general and domesticated animals in particular.
BACKGROUND ART
The most popular method of preventing reproductive activity in domestic animals, including dogs, horses, sheep, cattle, goats and cats, is surgical ovariohysterectomy or castration.
This method suffers from the problem that it is irreversible and is, technically, a relatively difficult procedure, therefore requiring the skills of trained veterinarians.
One of the alternative methods to surgery is the administration of progestagen steroids which can be used as long term oestrus suppressants (Harris and Wotchuk Am. J. Vet. Res. 24: 1003-1006, 1963) in dogs, but are unfortunately associated with the induction of uterine disorders including pyometritis, endometritis and increased incidence of benign mammary tumours following long term treatment. Their use has therefore tended to become confined to short term suppression of oestrus or postponement of oestrus.
In economically important farm animals there is no commonly used long term contraceptive which has been found to be suitable for routine use in the field.
There is therefore a need for a well-tolerated non-steroidal method of contraception in domestic animals which is applicable to both male and female domestic animals.
One such method would be to immunise against the hormones which control the development and activity of the reproductive organs.
The two gonadotrophic hormones which regulate gonadal steroidogenesis and gametogenesis, and are responsible for reproductive cyclicity are luteinizing hormone (LH) and follicle stimulating hormone (FSH).
Luteinizing hormone releasing hormone (LHRH, also known as GnRH) controls the synthesis and release of LH and FSH from the anterior pituitary gland. Mammalian LHRH is a decapeptide comprised of naturally occurring amino acids in the following sequence (ID NO: 1):
The N and C terminal glutamic acid and glycine residues are modified after translation to pyroglutamic acid and glycinamide respectively. Vaccines which result in the production of antibodies against LHRH by a host will suppress that host's endogenous LH and FSH production and release. This suppression can result in reduction of steroidogenesis and a failure of reproductive cyclicity and fertility in the treated animal. The resultant physiological effects are
(i) a cessation of LH pulsatility,
(ii) a failure of ovulation leading to infertility
(iii) a cessation of oestrus cycles due to the lack of oestrogens,
(iv) regression of the reproductive tract
(v) abortion due to regression of the corpus luteum
A suppression of production of testosterone from the Leydig cells in the testes resulting in lowered peripheral blood serum levels of circulating androgens, causes:
(i) reduced libido,
(ii) regression of the accessory sex glands, and
(iii) diminution in the testicular volume and reduction/cessation of spermatogenesis.
Antibodies against LHRH can be produced in a number of species by chemically conjugating LHRH to a suitable carrier and administering it in the presence of an appropriate adjuvant (Carrelli C. et al, 1982, Proc. Natl. Acad. Sci USA 79 5392-5395). Chemical conjugation is however, difficult to control and often results in a heterogeneous and ill-defined product. Moreover, an oil-based adjuvant is usually required for effective immunisation and this often leads to the formation of unacceptable side effects such as inflammation and granulomatous tissue lesions.
It is desirable to provide a means for producing good titres of antibodies against LHRH without the need to use strong adjuvants.
The TraT protein (TraTp) is coded by the TraT gene. TraTp is an outer membrane lipo-protein produced by certain strains of E. coli and is responsi
REFERENCES:
patent: 4624926 (1986-11-01), Inouye et al.
Russell-Jones Gregory J.
Stewart Andrew G.
Tsonis Con G.
Biotechnology Australia Ptl Ltd.
Draper Garnette D.
Spector L.
LandOfFree
LHRH-TraTp fusion proteins does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with LHRH-TraTp fusion proteins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and LHRH-TraTp fusion proteins will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2379417