Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1994-09-01
1999-04-06
Eisenschenk, Frank C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
4241301, 435 691, 435 697, 4353201, 435344, 5303873, C07K 1900, C12N 1513, C07H 2104
Patent
active
058920196
ABSTRACT:
Construction of a single gene encoding a signal-chain immunoglobulin-like molecule is described. This single-gene approach circumvents inefficiencies inherent in delivering two genes into a mammalian cell and in the assembly of a functional immunoglobulin molecule. It also facilitates ex vivo transfection of cells for gene-therapy protocols. The single-chain protein comprises the heavy- and light-chain variable (V.sub.H and V.sub.L) domains of a monoclonal antibody covalently joined through a short linker peptide, while the carboxyl end of a V domain is linked to the amino terminus of a human constant region such as .gamma.1 Fc, through the hinge region. The single-chain protein assembles into a dimeric molecule of .apprxeq.120 kDa and is secreted into the culture fluid. The single-chain immunoglobulin-like protein shows similar antigen binding affinity to that of chimeric or parental antibody and mediates ADCC. This single-gene construct approach provides a way of generating an immunoglobulin-like molecule which retains the specificity, binding properties, and cytolytic activity of a parental monoclonal antibody, and thus is a useful therapeutic and diagnostic reagent against a range of antigens, such as human carcinomas.
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Kashmiri Syed V. S.
Schlom Jeffrey
Shu Liming
Eisenschenk Frank C.
The United States of America, as represented by The Department o
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