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
1988-11-23
1992-04-21
Nucker, Christine
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...
530402, 530403, 530404, 530405, 530406, 530408, 530409, 530410, 5303913, 5303917, C07K 1702
Patent
active
051069555
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for production of antibody conjugates from an antibody and a specific compound. Particularly, the present invention relates to a process for production of antibody conjugates by binding a compound having a specific function to an antibody at its amino group with retention of the antigen-binding activity of the antibody.
BACKGROUND OF THE ART
Conjugates resulting from covalent modification of an antibody which can specifically bind to its antigen, at its amino groups with a variety of substances have been used over a wide range of application. For example, a conjugate of a specific antibody and an insoluble support is used in affinity chromatography to isolate a specific substance from its mixture. Another conjugate of an antibody with specificity to a certain tissue in vivo, for example, to a malignant tumor, and a radioactive isotope can accumulate the radioactivity on the tumors to enable diagnostic imaging of cancers. In addition, conjugates of antibodies and biologically active substances can be medicines with high selectivity. For example, a conjugate of an antitumor antibody and an antitumor substance or other cytotoxic substances can act on the tumor with high selectivity as a therapeutic agent. Conjugates of a fluorescent substance or an enzyme with an antibody can be used as an immunological or biochemical reagent or diagnostic agent. Further, new types of conjugates will be created in compliance with future needs.
One of the essential requisites common to the production of these conjugates is that the process can allow a required substance to bind to the antibody satisfactorily with retention of the original function of the antibody to bind to the antigen specifically.
One of the most widely used methods is to bond a substance to an antibody at an amino group (contained in lysine and the N-terminal amino acid) or a carboxyl group (contained in glutamic acid and aspartic acid) in the amino acids constituting the antibody. Particularly, the binding at the amino group has been widely utilized. For example, the conjugate of an antibody with an insoluble support for the separation and purification of a certain substance by affinity chromatography is prepared by introducing a group reactive with the amino groups, namely epoxy, activated carboxylic acid ester, acid azide, or bromoacetyl group or an activated group derived from cyanogen bromide into the support, then binding an antibody to the support at its amino group [see Affinity Chromatography: pages 19 and 87, edited by Makoto Yamazaki, Shinichi Ishii and Koichi Iwai, published by Kodansha (Tokyo), 1975]. Another conjugate of a radioactive substance with an antibody is formed by reaction between a compound bearing an activated carboxylic acid ester group and an antibody at the latter's amino groups, for example, by reaction between an antibody and Bolton-Hunter reagent, a reagent for introduction of radioactive iodine [see A. E. Bolton and W. M. Hunter; Biochem. J. 133, 529-539 (1973)], or by binding such a type of chelating agent as typified by diethylenetriaminepentaacetic acid (abbreviated to DTPA) at its carboxyl group to an antibody at its amino group followed by chelating a radioactive metal exemplified by .sup.111 In [see B. A. Khaw, J. T. Fallon, H. W. Strauss, E. Haber; Science, 209, 295 (1980)]. Further, conjugates of an antibody and a biologically active substance are also formed by binding the substance at its carboxyl group to the antibody at its amino group, as exemplified by conjugation of methotrexate, an antitumor agent [see P. N. Kulkarni, A. H. Blair, T. I. Ghose; Cancer Res., 41, 2700-2706 (1981)]. Conjugates of an antibody and ricin A chain are prepared, as described by K. A. Krolick, C. Villemez, P. Isakson, J. W. Uhr, and E. S. Vitetta [Proc. Natl. Acad. Sci. U.S.A.; 77, 5719-5423 (1980)], by reaction of N-succinimidyl 3-(2-pyridylthio)propionate, a crosslinking agent for introduction of an activated disulfide group with an antibody at its amino group followed by
REFERENCES:
patent: 4671958 (1987-06-01), Rodwell et al.
Blair et al., (1983) J. Immunol. Methods 59:129-143.
Endo et al., (1981) J. Immunol. Methods 104:253-258.
Gibbons et al., (1970) Brochem J. 116:843-849.
Keller et al. (1975) Helvetica Chiahaica Acta 58, Fasc 2-Nr62-63:531-541.
Chemical Abstracts, vol. 108, No. 5, Feb. 1, 1988, p. 480, abstract no. 36079V, Columbus, Ohio, US; E. Noriaki et al. and J. Immunol. Methods, 1987, 104(1-2), 253-258.
Endo Noriaki
Hara Takeshi
Kato Yoshinori
Takeda Yumiko
Kim Kay
Nucker Christine
Teijin Limited
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