Bristol-myers Squibb Compnay

Oncogen Limited Partnership

George J Schreiber

Karl E Hellstrom

Kim Folger Bruce

Ingegerd E Hellstrom

Clay B Siegall

Stephen McAndrew

Ingegerg Hellstrom

The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab').sub.2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab').sub.2 -LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

Methods for determining the presence of carcinoma using the antigen

Antibodies reactive with human carcinomas

Antibody conjugates reactive with human carcinomas

The present invention relates to novel antibodies reactive with human carcinoma cells. More particularly, the antibodies of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; and a F(ab').sub.2 fragment of BR96. These antibodies are reactive with a cell membrane antigen on the surface of human carcinomas. The antibodies display a high degree of selectivity for carcinoma cells and possess the ability to mediate ADCC and CDC activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

Monoclonal antibody BR 96 and chimeric monoclonal antibodies having the

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Seattle, WA, United States of America

George J Schreiber