Immunoconjugates joined by thioether bonds having reduced toxici

Details Immunoconjugates joined by thioether bonds having reduced toxici Immunoconjugates joined by thioether bonds having reduced toxici

1987-09-10

1991-01-01

Kepplinger, Estler M.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

436544, 436547, 530389, 530390, 530391, 530403, 530404, 530405, 548546, 548547, C07D20740, G01N 33536, C07K 100

Patent

active

049819798

ABSTRACT:
Method for producing an immunoconjugate comprising the steps of reacting a toxin or protein with a heterobifunctional reagent having the following general formula: ##STR1## where R.sub.1 is: ##STR2## where n=1 to 10; and where R.sub.2 is selected from the group consisting of o- and p-nitrophenyl, 2-chloro-4-nitrophenyl, cyanomethyl, 2-mercaptopyridyl, hydroxybenztriazole, N-hydroxysuccinimide, trichlorophenyl, tetrafluorophenyl, 2-fluorophenyl, 4-fluoropheyl, 2,4-difluorophenyl, o-nitro-p-sulfophenyl, N-hydroxyphthalimide, N,N-diethylamino, N-hydroxypyrrolidone, tetrafluorothiophenyl, and 2,3,5,6-tetrafluorophenyl, under reactive conditions, thereby forming a derivatized toxin or protein. The derivatized toxin or protein is separated from the reaction mixture and combined with an antibody or antibody fragment under reactive conditions, such that at least one native disulfide bond is reduced to produce at least one thiol group, capable of forming a thioether bond between said thiol group and the maleimide group of said derivatized toxin, or protein thereby forming an immunoconjugate. The preferred heterobifunctional linking group is succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC).

REFERENCES:
patent: 4429008 (1984-01-01), Martin et al.
patent: 4434236 (1984-02-01), Freytag
patent: 4507234 (1985-03-01), Kato et al.
patent: 4520226 (1985-05-01), Neville, Jr. et al.
patent: 4545985 (1985-10-01), Pastan et al.
patent: 4618492 (1986-10-01), Blattler et al.
patent: 4643895 (1987-02-01), Casellas et al.
patent: 4657853 (1987-04-01), Freytag et al.
patent: 4659839 (1987-04-01), Nicolotti et al.
patent: 4678667 (1987-07-01), Meares et al.
patent: 4680338 (1987-07-01), Sundoro
patent: 4816390 (1989-03-01), Kondo et al.
Y. Masuho et al., Biochem. Biophys. Res. Comm. 102:561 (1981).
J. Marsh and D. Neville, Biochem. 25:4461 (1986).
S. Ramakrishnan and L. Houston, Cancer Res. 44:201 (1984).
Y. Masuho et al.,J. Biochem. 91:1583 (1982).
J. Lambert et al., J. Biol. Chem. 260:12035 (1985).
M. Bjorn et al., Cancer Res. 46:3262 (1986).
L. Barbieri and F. Stirpe, Canc. Surv. 1:489 (1982).
Pierce Chemical Co. Catalog (1983).

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