The Dow Chemical Company

National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

Liming Shu

Jeffrey Schlom

Eduardo Agustin Padlan

Peter S Mezes

Syed V S Kashmiri

Kimberly S Johnson

Ruth A Richard

Syed V Kashmiri

Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.

Composite antibodies of humanized human subgroup IV light chain capable of binding to TAG-72

Humanized anti-tag-72 monoclonal antibodies using human subgroup 4 kappa light chains

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.

Production of a single-gene-encoded immunoglobulin

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Gaithersburg, MD, United States of America

Liming Shu