Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Patent
1994-03-17
1997-05-20
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
424520, 424574, 514 21, 530350, 5303871, 5303881, 5303891, 530403, A61K 3900, A61K 3800, A61K 3512, C07K 1600
Patent
active
056310099
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the immunological control of fat in the mammalian body, especially in non-human animals (herein referred to simply as animals).
2. Description of Prior Art
Excess fat in animals is recognised as detrimental to lowering production costs and a health risk to human consumers. One attempt at reducing the deposition of fat in animals has been to incorporate a 5-agonist in the feed. 5-agonists have encountered many problems, particularly that they can adversely affect meat quality and its preservation during storage and that the animals have to be slaughtered within a short period after the compound is withdrawn from the feed. Another attempt has been the use of growth hormones such as bovine somatotrophin (BST). Besides stimulating milk yield, BST improves the protein: fat ratio and feed conversion efficiency in cattle. Although the dairy industry considers BST to be safe, it has been the subject of considerable concern to regulatory authorities and consumer groups.
In view of these problems, D J Flint et al., International Journal of Obesity 1, 69-77 (1986) pioneered the idea of raising antibodies to the plasma membranes of adipocytes and injecting them into animals. It was found that this treatment reduced the amount of fat considerably and that this reduction was maintained for several months without inducing adverse effects. The first published reports, in which crude antisera raised against whole adipocyte plasma membranes from rats were shown to have such an effect, were by D J Flint, H Coggrave, C E Futter, M J Gardner and T Clarke, International Journal of Obesity 1, 69-77 (1986) and by D J Flint and C E Futter, Annual Report of the Hannah Research Institute, Ayr, Scotland 1986. Not only was fat reduced, that there was a body weight gain and an improvement in feed conversion efficiency. In an article "Can obesity be controlled?" by D J Flint, C E Futter and M Peaker, News in Physiological Sciences 2, 1-2 (February 1987), it is reported that similar antibodies have been produced against sheep and pig fat cells and that all are effective against adipocytes in vivo. A more detailed report on the effects of treatment of Fats with anti-adipocyte antibodies is given by D Panton, C E Futter, S Kestin and D J Flint in American Journal of Physiology 258, (Endocrinol. Metab. 21): E985-E989 (1990). See also A P Moloney and P Allen, Proc. Nutrition Society, July 1988 Meeting, page 14. Although J Killefer and C Y Hu, Proc. Soc. Exp. Biol. Med. 194, 172-176 (1990) have reported raising a monoclonal antibody to pig adipocyte plasma membranes, the hybridoma is believed not to be publicly available and the paper contains no evidence that the antibody would lyse fat cells. J T Wright and G J Hausman, Int. J. Obesity 14, 395-409 (1990) report the preparation of monoclonal antibodies against porcine adipocyte plasma membranes of 2-week old pigs. The antibodies are reported to immuno-precipitate proteins of relative molecular mass 77 and 90 kD. These experiments were directed to identifying cell surface antigens useful as markers of differentiating adipocytes.
J. Killefer and C Y Hu, J. Cell. Biochem. 44, 167-175 (1990) describe a 64 kD protein present in the plasma membrane of adipocytes and genetically lean pigs, but not in adipocytes of genetically obese pigs.
Although some of the above work has demonstrated experimentally the possibility of treating fat deposition in vivo by the administration of anti-adipocyte antibodies, it is a problem that the production of such antibodies may be very labour-intensive. The administration of the plasma membranes themselves as antigens could be considered, if they could be conjugated to carrier proteins and could thereby by made "non-self". However, the production of plasma membrane material from slaughterhouses poses difficulty of quality control. If the antigen(s) responsible for the fat reduction could be isolated and purified, the way would be open to making them by a recombinant DNA method or by prot
REFERENCES:
patent: 5096706 (1992-03-01), Flint
patent: 5102658 (1992-04-01), Flint
J. Killefer et al, J. Cell. Biochem., vol.44, No. 3 (1990) 167-175.
A. Nassar et al, Comp. Biochem. Physiol., vol. 98B, No. 213, (1991), 361-367.
Tam. et al. 1989. J. Immunological 124:53-61.
Cryer Anthony
Flint David J.
Kestin Steven C.
British Technology Group Ltd.
Housel James C.
Minnifield N. M.
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