ANTI-ErbB2 ANTIBODIES

Abstract

Anti-ErbB2 antibodies are described which bind to an epitope in Domain 1 of ErbB2 and induce cell death via apoptosis. Various uses for these antibodies are also described.

What is claimed is: 
     
         1 . An isolated antibody which binds to Domain 1 of ErbB2. 
     
     
         2 . The antibody of  claim 1  which binds to epitope 7C2/7F3 on ErbB2. 
     
     
         3 . The antibody of  claim 1  which induces death of a cell which overexpresses ErbB2. 
     
     
         4 . The antibody of  claim 3  which induces cell death via apoptosis. 
     
     
         5 . The antibody of  claim 1  which is a monoclonal antibody. 
     
     
         6 . The antibody of  claim 1  which has nonhuman complementarity determining region (CDR) residues and human framework region (FR) residues. 
     
     
         7 . The antibody of  claim 1  which is labelled. 
     
     
         8 . The antibody of  claim 1  which is immobilized on a solid phase. 
     
     
         9 . An isolated antibody which binds to ErbB2 and induces apoptosis of a cell which overexpresses ErbB2. 
     
     
         10 . The antibody of  claim 9  wherein the call is a BT474 cell. 
     
     
         11 . The antibody of  claim 9  wherein the cell is a SKBR3 cell. 
     
     
         12 . The antibody of  claim 9  wherein the cell is a Calu 3 cell. 
     
     
         13 . The antibody of  claim 1  which has complementarity determining regions (CDRs) of antibody 7C2. 
     
     
         14 . The antibody of  claim 1  which has complementarity determining regions (CDRs) of antibody 7F3. 
     
     
         15 . A composition comprising the antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         16 . The composition of  claim 15  further comprising a second anti-ErbB2 antibody which does not bind to Domain 1 of ErbB2. 
     
     
         17 . The composition of  claim 15  further comprising a second antibody which binds ErbB2 and inhibits growth of SKBR3 cells in cell culture by 50-100%. 
     
     
         18 . The composition of  claim 17  wherein the second antibody binds to epitope 4D5 on ErbB2. 
     
     
         19 . The composition of  claim 18  wherein the second antibody has complementarity determining regions (CDRs) of antibody 4D5. 
     
     
         20 . The composition of  claim 15  that is sterile. 
     
     
         21 . Nucleic acid encoding the antibody of  claim 1 . 
     
     
         22 . A vector comprising the nucleic acid of  claim 21 . 
     
     
         23 . A host cell comprising the nucleic acid of  claim 21 . 
     
     
         24 . The host cell of  claim 23  which is a hybridoma cell line producing antibody 7C2 or 7F3. 
     
     
         25 . A method for making an anti-ErbB2 antibody comprising culturing the host cell of  claim 23  so that the anti-ErbB2 antibody is expressed and recovering the anti-ErbB2 antibody from the host cell culture. 
     
     
         26 . A method for determining the presence of ErbB2 comprising exposing a cell suspended of containing Erb82 to the antibody of claim and determining binding of said antibody to the cell. 
     
     
         27 . A kit comprising the antibody of  claim 1  and instructions for using the antibody to detect ErbB2. 
     
     
         28 . A method for inducing cell death comprising exposing a cell which overexpresses Erb2 to an effective amount of the antibody of  claim 1 . 
     
     
         29 . The method of  claim 28  wherein the cell is a cancer cell. 
     
     
         30 . The method of  claim 28  wherein the cell is in a mammal. 
     
     
         31 . The method of  claim 30  wherein the mammal is human. 
     
     
         32 . The method of  claim 28  further comprising exposing the cell to a second anti-ErbB2 antibody which does not bind to Domain 1 of ErbB2. 
     
     
         33 . The method of  claim 28  further comprising exposing the cell to a second antibody which binds ErbB2 and inhibits growth of SKBR3 cells in cell culture by 50-100%. 
     
     
         34 . The method of  claim 33  wherein the cell is exposed to the antibody which binds to Domain 1 of ErbB2 before the cell is exposed to the second antibody. 
     
     
         35 . The method of  claim 33  wherein the second antibody binds to epitope 4D5 on ErbB2. 
     
     
         36 . The method of  claim 35  wherein the second antibody has complementarity determining regions (CDRs) of antibody 4D5. 
     
     
         37 . The method of  claim 28  further comprising exposing the cell to a growth inhibitory agent. 
     
     
         38 . The method of  claim 28  further comprising exposing the cell to a chemotherapeutic agent. 
     
     
         39 . The method of  claim 28  further comprising exposing the cell to radiation. 
     
     
         40 . A method for inducing cell death comprising exposing a cell which overexpresses ErbB2 to an effective amount of the antibody of  claim 9 . 
     
     
         41 . An article of manufacture, comprising:
 a container;   a label on the container; and   a composition comprising an active agent contained within the container; wherein the composition is effective for inducing cell death, the label on the container indicates that the composition can be used for treating conditions characterized by overexpression of ErbB2 and the active agent in the composition is the antibody of  claim 1 .