Loading patent…
AssigneeBristol-Myers Squibb Company
InventorsIngegerd Hellstrom, Karl Erik Hellstrom, Kim Folger Bruce, George J. Schreiber, Clay Siegall, Stephen McAndrew
Estimating the term…
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.
An immunoconjugate comprising a molecule containing the antigen-binding region of the BR96 monoclonal antibody (ATCC Accession No. 10036) joined to a therapeutic agent.
An immunoconjugate comprising the BR96 monoclonal antibody (ATCC Accession No. 10036) or antigen binding fragments thereof joined to Pseudomonas exotoxin A.
An immunoconjugate comprising chimeric human/murine BR96 antibody (ATCC Accession No. 100460) joined to Pseudomonas exotoxin A.
An immunoconjugate comprising a Fab' fragment of chimeric human/murine BR96 antibody (ATCC Accession No. 100460) joined to Pseudomonas exotoxin A.
An immunoconjugate comprising a F(ab).sub.2 fragment of chimeric human/murine BR96 antibody (ATCC Accession No. 100460) joined to Pseudomonas exotoxin A.
A recombinant single-chain immunotoxin molecule comprising a cloned heavy chain Fv portion of the BR96 monoclonal antibody (ATCC Accession No. 10036) and a cloned light chain Fv portion of the BR96 monoclonal antibody joined to a cytotoxic agent.
A single-chain immunoconjugate comprising a Fv fragment of BR96 antibody (ATCC Accession No. 10036) joined to Pseudomonas exotoxin A.
A single-chain immunoconjugate comprising a Fv fragment of chimeric human/murine BR96 antibody (ATCC Accession No. 100460) joined to Pseudomonas exotoxin A.
A method for imaging carcinoma characterized by cells having the BR96 antigen on the cell surface comprising administering to a patient intravenously the BR96 monoclonal antibody (ATCC Accession No. 10036) in an amount effective for detection of the carcinoma, allowing the antibody to bind to carcinoma cells and to localize to the site of carcinoma cells and detecting said antibody bound to the carcinoma cells.
Dependencies are inferred from the claim text.