Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-01-24
2000-02-01
Kemmerer, Elizabeth
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 2, 514 8, 514 13, 514 14, 514 15, 514 16, 514 17, 514 18, 514 19, 4241921, 4241861, A61K 3804, A61K 3816
Patent
active
060203099
DESCRIPTION:
BRIEF SUMMARY
SUMMARY OF THE INVENTION
The present invention relates to pharmaceuticals based on papillomaviruses.
Papillomaviruses induce a variety of lesions both in humans and in animals. Some papillomas, albeit benign, are themselves a clinical problem, such as laryngeal papillomas of children or penile papillomas of bulls and others are known to be a risk factor in the pathogenesis of cancer, as in the case of flat lesions of the cervix or penile condylomata in humans. Therefore both in human and veterinary medicine, antiviral pharmaceuticals against papillomaviruses e.g. for prophylactic use to protect against the establishment of a serious infection would be of major advantage.
Vaccination studies in humans present several problems. First of all experimentation is ethically unacceptable. Secondly, very limited amounts of virus are available as some lesions, in particular those of the cervix, do not produce viral progeny, and no in vitro system is yet available which allows vegetative replication of virus.
The production of viral proteins in bacteria and the use of synthetic peptides have circumvented this last problem and have allowed the ongoing analysis of the immune response to papillomavirus infection (see for instance Jenison et al, 1988 J. Virol, 62 p. 2115 and Tindle et al, 1990 J. Gen. Virol, 71 p. 1347.
Effective prophylactic vaccines, both natural (Jarrett et al, 1990 The Vet. Record, 126 p. 449) and genetically engineered (Pilachinski et al, 1986 Ciba Foundation Symposium Vol. 120 p. 136) have already been produced against bovine papillomaviruses, and regression of Shope papillomas has been achieved by vaccinating rabbits with tumour tissue extracts (Evans et al, 1962 J. Nat. Cancer Inst. 29 p. 277). The bovine system is an excellent model for papillomavirus induced diseases in the human and for medicaments against such diseases in humans given the several similarities between the bovine and human disease. Namely multiple virus types with high lesion specificity (Jarrett et al, 1984 Virol. 136 p. 255), homology of genetic structure, and progression of some lesions to malignancy. The bovine system also presents several advantages in that cofactors in oncogenesis are known (Campo and Jarrett, 1986 In Papillomaviruses, Ciba Foundation Symposium 120, John Wiley and Sons p. 117) and, above all, direct experimentation is possible (Jarrett, 1985 In advances in Viral Oncology (Ed. G. Klein) 5 p.83).
Vaccination has been traditionally regarded as a prophylactic measure. Hosts are immunised against a pathogen and on subsequent exposure to the same organism, the infection is aborted at a preclinical stage. This is usually accomplished in virus infections by a neutralizing event directed at a superficial epitope on a structural protein. Virus-induced tumours such as papillomas often persist for long periods and are then, in a proportion of cases, rejected. The host may then be immune to reinfection (Jarrett, 1985 supra). The nature of the rejection mechanism and its mediators is unknown, but it is advantageous to induce the rejection mechanism early in a tumour life cycle. In veterinary practice, it has been known for a long time that crude extracts of papillomas could sometimes, but by no means always, cause the rejection of homologous papillomas (Olson et al, 1959 Am. J. Vet. Res. 21 p. 233, Evans et al, 1962 supra). These experiments were carried out before it was known that there were different types of papillomavirus in a species (Jarrett et al, 1984 supra; de Villier, 1989 J. Virol. 63 p. 4898), and that these are probably all immunologically type-specific (Jarrett et al. 1990 The Vet. Record 126 p. 473; Jenison et al, 1988 supra).
Papillomaviruses can infect and cause tumours in both cutaneous and mucous epithelia. In man and animals mucosal papillomas are often serious lesions which tend to run a prolonged course, as in the case of human laryngeal, genital and cervical papillomas (Steinberg, 1987 In the Papovaviride Vol. 2 (ed. N. P. Salzman and P. M. Howley) p. 265; zur Hausen, 1991 Virol. 184 p. 9). The
REFERENCES:
Stedman. Stedman's Medical Dictionary, 24th ed., Williams and Williams, Baltimore, p. 1148, 1982.
Jarrett et al. Virology 184:33-42, 1991.
Christensen et al. Virology 181:572-579, 1991.
Lin et al. Virology 187:612-619, 1992.
"Immunostimulation" (Chedid et al., eds.) Springer-Verlag: Berlin, Heidelberg, New York (1980) pp. 5-22.
Mosmann et al., "The role of IL-10 in crossregulation of T.sub.h 1 and T.sub.h 2 responses," Immunology Today, 12(2):A49-A53 (1991).
British Pharmacopoeia 1998, vol. II:1047 (1998).
Campo Maria Saveria
Jarrett William Fleming Hoggan
Cancer Research Campaign - Technology Limited
Kemmerer Elizabeth
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