Method for obtaining modified immunoglobulins with reduced immun

Details Method for obtaining modified immunoglobulins with reduced immun Method for obtaining modified immunoglobulins with reduced immun

1995-06-30

1998-01-27

Scheiner, Toni R.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

435 7021, 435 711, 435328, 435 697, 5303873, 536 2353, 4241331, 4241358, C12N 1513, C07K 1600, C07H 2104, A61K 39395

Patent

active

057121206

ABSTRACT:
Modified chimaeric antibodies, and antibody heavy and light chains, which comprise variable domains derived from a first mammalian species, usually mouse, and constant domains from a second mammalian species, usually human. Modification concerns the variable domains, in particular the framework regions of the variable domains. The modifications are made only in T-cell antigenic structures present in framework regions, and do not cover canonical structures or Vernier zone. The modifications adapt the amino acid sequences concerned to those occurring in corresponding antibodies derived from said second mammalian species. Thus, the modified chimaeric antibodies retain the original antigen recognition and binding properties but become less immunogenic to said second mammalian species, which improves their therapeutical utility with said second mammalian species. Recombinant DNA technology may be used to construct and produce the modified chimaeric antibodies.

REFERENCES:
Article entitled: A Possible Procedure for Reducing the Immunogenicity of Antibody Variable Domains While Preserving Their Ligand-Binding Properties. Author: Eduardo A. Padlan Published in Molecular Immunology, vol. 28, No. 4/5, pp. 489-498, 1991.
Reyes, VE et al. Methods in Enzymology 202:225-238 (1991).
Margalit, H. et al. Journal of Immunology 138(7):2213-2229 (1987).
Foote J. et al Journal of Molecular Biology 224:487-499 (1992).
Chothia C. et al. Journal of Molecular Biology 196:901-917 (1987).

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