Glaxo Wellcome Inc.

National Research Development Corporation

Burroughs Wellcome Co.

Stephen Paul Cobbold

Herman Waldmann

Michael Ronald Clark

Scott David Gorman

An altered antibody chain is produced in which the CDR's of the variable domain of the chain are derived from a first mammalian species. The framework-encoding regions of DNA encoding the variable domain of the first species are mutated so that the mutated framework-encoding regions encode a framework derived from a second different mammalian species. The or each constant domain of the antibody chain, if present, are also derived from the second mammalian species. An antibody which is capable of binding to human CD4 antigen is also provided together with a pharmaceutical composition comprising the antibody.

Chimeric antibody, pharmaceutical composition and process of its production

An altered antibody chain is produced in which the CDR's of the variable domain of the chain are derived from a first mammalian species. The framework-encoding regions of DNA encoding the variable domain of the first species are mutated so that the mutated framework-encoding regions encode a framework derived from a second different mammalian species. The or each constant domain of the antibody chain, if present, are also derived from the second mammalian species.

Altered antibodies and their preparation

Tolerance to an antigen is induced in a subject by administering a non-depleting CD4 monoclonal antibody and a non-depleting CD8 monoclonal antibody. Tolerance to the antigen can be induced under cover of these antibodies. A depleting CD4 monoclonal antibody and/or a depleting CD8 monoclonal antibody may be administered prior to the non-depleting antibodies.

Non-depleting anti-CD4 monoclonal antibodies and tolerance induction

Tolerance to an antigen is induced in a subject by administering a non-depleting CD4 monoclonal antibody and a non-depleting CD8 monoclonal antibody. Tolerance to the antigen can be induced under cover of these antibodies. A depleting CD4 monoclonal antibody and/or a depicting CD8 monoclonal antibody may be administered prior to the non-depleting antibodies.

Monoclonal antibodies for inducing tolerance

A monoclonal antibody preparation having a single binding activity, which activity is in respect of a cell surface antigen, comprises IgG antibody molecules in which only one of the two light chains will bind to said antigen, the proportion of such antibody molecules being enhanced relative to IgG antibody molecules having two light chains which will bind to said antigen to thereby produce an enhancement of the binding activity of the preparation. Such preparations containing predominatly 'monovalent antibodies' are of particular value in the areas of transplantation immunity, the treatment of neoplastic disease and cell sorting.

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Cambridge, United Kingdom

Stephen Paul Cobbold