Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1995-05-26
1998-06-02
Knode, Marian C.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
5303881, 5303883, 530324, 4241331, 4241471, 424800, 424809, 424801, C07K 1600, C12P 2108, A61K 3800, A61K 39395
Patent
active
057601852
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a 371 national stage application of PCT/JP93/01724, filed Nov. 25, 1993.
TECHNICAL FIELD
The present invention relates to a novel feline monoclonal antibody usable for diagnosis, treatment and prevention of feline herpes virus-1 (FHV-1) infection. More particularly, it relates to a felinized anti-FHV-1 recombinant antibody wherein a constant region of a mouse-type anti-FHV-1 neutralizing monoclonal antibody is replaced with a feline antibody constant region, and a gene fragment encoding said antibody.
BACKGROUND ART
A cat is such an animal that has been loved by humans as a pet from ancient times and, in modern times, called as Companion species, is becoming a member of a human society. On the other hand, a cat has hitherto greatly contributed to humans as an experimental animal in various fields such as medicine, pharmaceutics, animal husbandry veterinary and psychology, and in recent years, the contribution of a cat has further increased to be used as an SPF Cat in an effectiveness assay or safety test for drugs. In any case, as a matter of course, more reliable knowledge on feline diseases, especially on infectious diseases, is increasingly needed and the establishment of a method for diagnosis, treatment and prevention of these diseases is required.
Many viral diseases of cats have been known. Among them, an upper tracheal disease caused by FHV-1 is acute and shows a high lethality. For both diseases, there is no specific treating drug and only a symptomatic treatment for preventing a secondary infection by the use of antibiotics, sulfonamide drugs, etc., and hence, there remains a problem in a conventional method for treatment.
Hitherto, a hiperimmune serum or a serum-derived immunoglobulin have been used as a medicament for treatment of viral diseases and have shown satisfactory results. Nowadays, however, feline serum materials are hardly available due to promotion of Be-Kind-to-Animals thought, and hence, we are in a situation that this treating method cannot be used in spite of desire to use this method. Accordingly, in place of the conventional hiperimmune serum, a monoclonal antibody capable of neutralizing FHV-1 will possibly greatly contribute to the treatment of FHV-1 infection.
PRIOR ART
There have been established several neutralizing monoclonal antibodies against FHV-1. However, all the monoclonal antibodies established hitherto are antibodies derived from a mouse hybridoma. When these antibodies are administered to a cat as a medicament, since they are a heterogeneous protein, they will show weaker binding capacity to complement or immunocompetent cells having an Fc receptor present in blood than that of homo species (cat) and appear to hardly induce cell damage by "antibody+complement" or antibody-dependent cellular cytotoxicity, cell-mediated cell damage. It is known that, in addition to the action by an antibody alone, these two immune reactions are also important for prevention of FHV-1 infection and for neutralization of virus (Horimoto T. et al., Jpn. J. Vet. Sci. 51, p1025, 1989). Therefore, it is possible that the conventional mouse antibodies cannot exhibit efficacious results in treatment.
Furthermore, it is also possible that the mouse antibodies recognized as a heterogeneous protein cause a side effect such as anaphylaxic shock or serum disease or show a shortened half-life, resulting in a decreased efficacy in treatment. Accordingly, when administered, the conventional mouse monoclonal antibodies have never been satisfactory but a felinized monoclonal antibody should have been used.
DISCLOSURE OF THE INVENTION
Under the circumstances, the present inventors have established a mouse monoclonal antibody, JH2, which neutralizes FHV-1 viral strain, have identified a nucleotide sequence of a gene encoding a variable region (V region) of said antibody, and have found a specific amino acid sequence in V region of said antibody which is deeply involved in the neutralization of FHV-1. Then, in order to felinize this mouse typ
REFERENCES:
Limcumpao et al. (A) Jap. J. of Veterinary Sci. 52(2): 351-359, 1990.
Horimoto et al. Arch. of Virol. 111:127-132, 1990.
Limcumpao et al (B) J. Veterinary Medical Sci. 53(3): 423-432, 1991.
Limcumpao et al (C) Arch. of Virol. 111:165-176, 1990 Buckel et al. Gene 13-19, 1987.
Kimachi Kazuhiko
Maeda Hiroaki
Nishiyama Kiyoto
Tokiyoshi Sachio
Juridical Foundation The Chemo-Sero-Therapeutic Research Institu
Knode Marian C.
Williams Jay F.
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