The Dow Chemical Company

The United States of America, as Represented by the Secretary, Department of Health and 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