Recombinant anti-HIV antibody and process for preparing the same

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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43524027, 5303873, 53038835, 536231, C12P 2106, C12P 2108, C12N 500, C07H 2104

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057732477

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BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION

The present invention relates to a novel recombinant anti-HIV antibody which can be expected to be used for treatment and prevention of AIDS provoked by human immunodeficiency virus (HIV). More specifically, the present invention relates to a recombinant anti-HIV antibody (reshaped antibody and chimeric antibody) having a neutralizing activity against HIV, said antibody being expressed using a genetic recombination technique from a mouse immunoglobulin gene and a human immunoglobulin gene, and a novel process for preparing the same. The present invention further relates to DNA fragments coding for H chain and L chain variable region which can be effectively used for expression of such useful recombinant antibody.


BACKGROUND ART

Acquired immunodeficiency syndrome (AIDS) is a viral disease caused by human immunodeficiency virus (HIV) belonging to a retrovirus. This disease, since discovery in the United States in 1981, has rapidly been spreading all over the world but an effective vaccine or a method for treating said disease has not yet been established.
Under such circumstances, there are reports on a relevance between the clinics and a neutralizing antibody in a group of thalassemic patients exhibiting HIV positive through transfusion and in a group of children 138, p3731, (1987); R. Guroff et al., Pediatric Research, inpress!. It is mentioned in both reports that the clinical symptom was mild and benign in such cases where a neutralizing antibody was detectable, whereas it has become malignant in such cases where no neutralizing antibody could be detected. These facts suggest in vivo effectiveness of a neutralizing antibody. Therefore, an anti-HIV neutralizing antibody is expected to be usable for prevention of expansion of infection or for exclusion of infected cells, and to show a more enhanced effect when used in combination with anti-viral agents etc. now currently used clinically.
Though it is possible that the anti-HIV neutralizing antibody as mentioned above is directly obtained or prepared from patients with AIDS, this method is expected to bear a number of difficulties such as an ethical problem, availability of materials or a problem of biohazard. In this respect, as an alternative of such a high titer serum, the use of a monoclonal antibody having a neutralizing activity against HIV virus is considered. Although a basic technique for preparation of a monoclonal antibody has already been established in a mouse-type monoclonal antibody, a mouse antibody is hardly applicable to clinical applications in view of side effects (a mouse monoclonal antibody, when administered to humans, is considered to cause side effects such as anaphylactic shock or serum disease as a heterogeneous protein) etc., and hence, the use of a human monoclonal antibody is eventually preferable.
However, preparation of a human monoclonal antibody provokes many problems to be overcome for preparing an antibody having a desired specificity and is actually quite difficult in comparison to preparation of a mouse-type monoclonal antibody. For overcoming such problems, a method for preparing a chimeric monoclonal antibody utilizing a genetic recombination technique has recently been reported wherein the variable region, which characterizes the specificity of an antibody, has an amino acid sequence derived from a mouse antibody and the constant region has an amino acid sequence derived from a human antibody.
Such chimeric monoclonal antibody is obtained by expressing a mouse(V)-human(C) chimeric antibody gene, comprising a variable (V) gene as a material for V region which is cloned from a mouse hybridoma producing a mouse monoclonal antibody and a constant (C) gene as a material for C region which is cloned from a human cell such as a human antibody-producing cell, in an animal cell or a microorganism cell, etc., the desired chimeric monoclonal antibody being present in a culture supernatant. There have been several reports on a chimeric antibody Publication No. 61-47500! and the present invent

REFERENCES:
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Max, Edward E. et al., "The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse (Kappa).kappa. immunoglobulin in J and C region genes. "Biological Chemistry vol. 256, pp. 5116-5120, (1981).
Sakano, Hitoshi, et al., "Two types of somatic recombinant are necessary for the generation of complete immunoglobul in heavy-chain genes."Nature vol. 286 pp. 676-683 (14 Aug. 1980).
Palm, Walter et al., "Die Primarstruktur einer kristallinen monoklonalen immunoglobulin in-L-kette vom (Kappa).kappa.-typ, subgruppe I (Bence-Jones-Protein Rei.), isolierung und charakerisierung der tryptischen peptide; die vollstandige aminosauresequenz des proteins."Physi. Chem. vol. 356, pp. 167-191 (1975).
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