US2004006212A1PendingUtilityA1

Antibody and antibody fragments for inhibiting the growth of tumors

60
Priority: Jun 7, 1995Filed: Feb 25, 2003Published: Jan 8, 2004
Est. expiryJun 7, 2015(expired)· nominal 20-yr term from priority
Inventors:Neil I. GoldsteinNicholas A. GiorgioSteven JonesJose Saldanha
C07K 16/2863C07K 2319/00C07K 2317/24A61K 2039/505A61K 38/00C07K 2317/73
60
PatentIndex Score
0
Cited by
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References
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Claims

Abstract

Chimerized and humanized versions of anti EGF receptor antibody 225 and fragments thereof for treatment of tumors.

Claims

exact text as granted — not AI-modified
What we claim is:  
     
         1 . A polypeptide lacking the constant region and the variable light chain of an antibody, the polypeptide comprising the amino acid sequence NYGVH, GVIWSGGNTDYNTPFTSR, or VIWSGGNTDYNTPFTS.  
     
     
         2 . A polypeptide according to  claim 1 , comprising amino acid sequences NYGVH and GVIWSGGNTDYNTPFTSR or VIWSGGNTDYNTPFTS.  
     
     
         3 . A polypeptide consisting of the amino acid sequence NYGVH or GVIWSGGNTDYNTPFTSR.  
     
     
         4 . A polypeptide consisting of the amino acid sequence NYGVH or VIWSGGNTDYNTPFTS.  
     
     
         5 . A polypeptide according to  claim 1  conjugated to an effector molecule.  
     
     
         6 . A polypeptide according to  claim 5  wherein the effector molecule inhibits tumor growth.  
     
     
         7 . A polypeptide according to  claim 5  wherein the effector molecule is cytotoxic.  
     
     
         8 . A polypeptide according to  claim 5  wherein the effector molecule is doxorubicin.  
     
     
         9 . A polypeptide according to  claim 5  wherein the effector molecule is cisplatin.  
     
     
         10 . A polypeptide according to  claim 5  wherein the effector molecule is taxol.  
     
     
         11 . A polypeptide according to  claim 5  wherein the effector molecule is a signal transduction inhibitor.  
     
     
         12 . A polypeptide according to  claim 5  wherein the effector molecule is a ras inhibitor.  
     
     
         13 . A polypeptide according to  claim 5  wherein the effector molecule is a cell cycle inhibitor.  
     
     
         14 . DNA encoding a polypeptide lacking the constant region and the variable light chain of an antibody, the polypeptide comprising the amino acid sequence NYGVH, GVIWSGGNTDYNTPFTSR or VIWSGGNTDYNTPFTS.  
     
     
         15 . DNA encoding the polypeptide of  claim 14  comprising amino acid sequences NYGVH and GVIWSGGNTDYNTPFTSR or VIWSGGNTDYNTPFTS.  
     
     
         16 . DNA encoding a polypeptide according to  claim 14  conjugated to an effector molecule.  
     
     
         17 . DNA encoding a polypeptide according to  claim 16  wherein the effector molecule inhibits tumor growth.  
     
     
         18 . A molecule having the constant region of a human antibody and the hypervariable region of monoclonal antibody 225 conjugated to an effector molecule.  
     
     
         19 . A molecule according to  claim 18  wherein the effector molecule is a cytotoxic agent.  
     
     
         20 . A molecule according to  claim 19  wherein the cytotoxic agent is doxorubicin.  
     
     
         21 . A molecule according to  claim 19  wherein the cytotoxic agent is taxol.  
     
     
         22 . A molecule according to  claim 19  wherein the cytotoxic agent is cisplatin.  
     
     
         23 . A molecule comprising: a constant region of a human antibody; a variable region other than the CDRs of a human antibody, the variable region comprising a kappa light chain and a heavy chain, and the CDRs of monoclonal antibody 225.  
     
     
         24 . A molecule according to  claim 23  wherein the constant region has an amino acid sequence of an IgG.  
     
     
         25 . A molecule according to  claim 24  wherein the IgG is IgG1.  
     
     
         26 . A molecule according to  claim 23  that is reshaped according to Example IV.  
     
     
         27 . A molecule according to  claim 23 , wherein the heavy chain has at least one amino acid, according to the Kabat numbering system, at an amino acid position selected from the group consisting of 24, 28, 29, 30, 41, 48, 49, 67, 68, 70, 71 and 78, substituted with a murine amino acid selected from the corresponding Kabat amino acid position.  
     
     
         28 . A molecule according to  claim 23 , wherein the kappa light chain has an amino acid, according to the Kabat numbering system, at position 49 substituted with a murine amino acid selected from the corresponding Kabat amino acid position.  
     
     
         29 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence selected from 225RK A  or 225RK B .  
     
     
         30 . A molecule according to  claim 23  wherein the heavy chain variable region has an amino acid sequence selected from 225RH A , 225RH B , 225RH C , 225RH D , or 225RH E .  
     
     
         31 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH A .  
     
     
         32 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH B .  
     
     
         33 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH C .  
     
     
         34 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH D .  
     
     
         35 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH E .  
     
     
         36 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH A .  
     
     
         37 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH B .  
     
     
         38 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH C .  
     
     
         39 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH D .  
     
     
         40 . A molecule according to  claim 23  wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH E .  
     
     
         41 . A molecule according to  claim 23 , wherein the molecule is attached to an effector molecule.  
     
     
         42 . A molecule according to  claim 39 , wherein the effector molecule is a cytotoxic agent.  
     
     
         43 . A molecule according to  claim 40 , wherein the cytotoxic agent is doxorubicin.  
     
     
         44 . A molecule according to  claim 40 , wherein the cytotoxic agent is taxol.  
     
     
         45 . A molecule according to  claim 40 , wherein the cytotoxic agent is cisplatin  
     
     
         46 . A method for significantly inhibiting the growth of tumor cells in a human comprising administering to the human an effective amount of the polypeptide according to  claim 1 .  
     
     
         47 . A method for significantly inhibiting the growth of tumor cells in a human comprising administering to the human an effective amount of the polypeptide according to  claim 3  or  claim 4 .  
     
     
         48 . A method for significantly inhibiting the growth of tumor cells in a human comprising administering to the human an effective amount of a molecule having the constant region of a human antibody and the variable region of monoclonal antibody 225.  
     
     
         49 . A method for significantly inhibiting the growth of tumor cells in a human comprising administering to the human an effective amount of a molecule having a constant region of a human antibody; a variable region other than the CDRs of a human antibody, the variable region comprising a kappa light chain and heavy chain, and the CDRs of monoclonal antibody 225.  
     
     
         50 . A method according to  claim 47 , wherein the kappa light chain variable region has an amino acid sequence selected from 225RK A  or 225RK B .  
     
     
         51 . A method according to  claim 47 , wherein the heavy chain variable region has an amino acid sequence selected from 225RH A , 225RH B , 225RH C , 225RH D , or  225 RH E .  
     
     
         52 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH A .  
     
     
         53 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH B .  
     
     
         54 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH C .  
     
     
         55 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH D .  
     
     
         56 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK A  and the heavy chain variable region has amino acid sequence 225RH E .  
     
     
         57 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH A .  
     
     
         58 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH B .  
     
     
         59 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH C .  
     
     
         60 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH D .  
     
     
         61 . A method according to  claim 47 , wherein the kappa light chain variable region has amino acid sequence 225RK B  and the heavy chain variable region has amino acid sequence 225RH E .  
     
     
         62 . A method according to any of claims  44 - 47 , further comprising administering a cytotoxic agent.  
     
     
         63 . A molecule according to  claim 60 , wherein the cytotoxic agent is doxorubicin.  
     
     
         64 . A molecule according to  claim 60 , wherein the cytotoxic agent is taxol.  
     
     
         65 . A molecule according to  claim 60 , wherein the cytotoxic agent is cisplatin  
     
     
         66 . The method according to  claim 44  or  claim 45 , wherein the polypeptide is conjugated to an effector molecule.  
     
     
         67 . The method according to  claim 46  or  claim 47 , wherein the molecule is conjugated to an effector molecule.  
     
     
         68 . The method according to  claim 64 , wherein the effector molecule is cytotoxic.  
     
     
         69 . The method according to  claim 64 , wherein the effector molecule is doxorubicin  
     
     
         70 . The method according to  claim 64 , wherein the effector molecule is cisplatin.  
     
     
         71 . The method according to  claim 64 , wherein the effector molecule is taxol.  
     
     
         72 . The method according to  claim 64 , wherein the effector molecule is a signal transduction inhibitor.  
     
     
         73 . The method according to  claim 64 , wherein the effector molecule is a ras inhibitor.  
     
     
         74 . The method according to  claim 64 , wherein the effector molecule is a cell cycle inhibitor.  
     
     
         75 . The method according to  claim 65 , wherein the effector molecule is cytotoxic.  
     
     
         76 . The method according to  claim 65 , wherein the effector molecule is doxorubicin.  
     
     
         77 . The method according to  claim 65 , wherein the effector molecule is cisplatin.  
     
     
         78 . The method according to  claim 65 , wherein the effector molecule is taxol.  
     
     
         79 . The method according to  claim 65 , wherein the effector molecule is a signal transduction inhibitor.  
     
     
         80 . The method according to  claim 65 , wherein the effector molecule is a ras inhibitor.  
     
     
         81 . The method according to  claim 65 , wherein the effector molecule is a cell cycle inhibitor.  
     
     
         82 . The method according to any of claims  44 - 47 , wherein the tumor cells are prostatic tumor cells.  
     
     
         83 . The method according to  claim 80 , wherein the prostatic tumor cells are late stage prostatic tumor cells.  
     
     
         84 . A nucleic acid molecule that encodes a molecule comprising: a constant region of a human antibody; a variable region other than the CDRs of a human antibody, the variable region comprising a kappa light chain and a heavy chain, and the CDRs of monoclonal antibody 225.  
     
     
         85 . A vector comprising the nucleic acid molecule claim of  84 .  
     
     
         86 . A vector according to  claim 85 , wherein the vector is an expressible vector.  
     
     
         87 . A vector according to  claim 86 , wherein the vector is expressible in a prokaryotic cell.  
     
     
         88 . A vector according to  claim 86 , wherein the vector is expressible in a eukaryotic cell.  
     
     
         89 . A prokaryotic cell comprising the expressible vector of  claim 87 .  
     
     
         90 . An eukaryotic cell comprising the expressible vector of  claim 88 .  
     
     
         91 . A pharmaceutical composition, comprising the molecule of  claim 23  and a pharmaceutically acceptable carrier.

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