US2012034185A1PendingUtilityA1

Anti-cd20 antibodies and fusion proteins therof and methods of use

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Assignee: HANSEN HANSPriority: Feb 14, 2002Filed: Sep 28, 2011Published: Feb 9, 2012
Est. expiryFeb 14, 2022(expired)· nominal 20-yr term from priority
Inventors:Hans J. HansenZhengxing QuDavid M. Goldenberg
A61P 7/02A61P 7/00A61P 35/02A61P 37/06A61P 7/04A61P 7/06A61P 37/02A61P 3/10A61P 35/00A61P 37/00A61P 29/00A61P 25/14A61P 25/00A61K 2039/507C07K 2317/24A61P 21/00A61K 2039/505A61P 1/16C07K 16/2803A61P 1/04A61P 17/02C07K 16/2887A61P 13/12C07K 2317/56A61P 21/04A61P 19/02A61P 21/02C12N 15/11C07K 16/28G01N 33/53
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Claims

Abstract

The present invention provides humanized, chimeric and human anti-CD20 antibodies and CD20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis.

Claims

exact text as granted — not AI-modified
1 . An isolated nucleic acid encoding a chimeric or humanized monoclonal antibody or antigen-binding fragment thereof that binds to CD20, said antibody having a light chain variable region CDR1 comprising the sequence of RASSSVSYIH (SEQ ID NO:1); CDR2 comprising the sequence of ATSNLAS (SEQ ID NO:4); and CDR3 comprising the sequence of QQWTSNPPT (SEQ ID NO:4); and a heavy chain variable region CDR1 comprising the sequence of SYNMH (SEQ ID NO:8); CDR2 comprising the sequence of AIYPGNGDTSYNQKFKG (SEQ ID NO:9); and CDR3 comprising the sequence of STYYGGDWYFDV (SEQ ID NO:10) or the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         2 . The isolated nucleic acid according to  claim 1 , wherein said antibody is a chimeric monoclonal antibody. 
     
     
         3 . The isolated nucleic acid according to  claim 1 , wherein said antibody is a humanized monoclonal antibody. 
     
     
         4 . The isolated nucleic acid according to  claim 1 , wherein the heavy chain variable region CDR3 comprises the sequence of STYYGGDWYFDV (SEQ ID NO:10). 
     
     
         5 . The isolated nucleic acid according to  claim 1 , wherein the heavy chain variable region CDR3 comprises the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         6 . The isolated nucleic acid according to  claim 1 , wherein said antibody or fragment thereof is a fusion protein. 
     
     
         7 . The isolated nucleic acid according to  claim 6 , wherein said fusion protein comprises a second monoclonal antibody or antigen-binding fragment thereof. 
     
     
         8 . The isolated nucleic acid according to  claim 7 , wherein said second monoclonal antibody or fragment thereof is an anti-CD20 antibody or fragment thereof. 
     
     
         9 . The isolated nucleic acid according to  claim 7 , wherein said second monoclonal antibody or fragment thereof binds to an antigen selected from the group consisting of CD4, CD5, CD8, CD14, CD15, CD19, CD21, CD22, CD23, CD25, CD33, CD37, CD38, CD40, CD40L, CD46, CD52, CD54, CD74, CD80, CD126, B7, MUC1, MUC2, MUC3, MUC4, Ia, HM1.24, HLA-DR, tenascin, VEGF, PlGF, and an oncogene product. 
     
     
         10 . An expression vector comprising the isolated nucleic acid of  claim 1 . 
     
     
         11 . The expression vector according to  claim 10 , wherein the expression vector is a pdHL2 vector. 
     
     
         12 . A host cell comprising the expression vector of  claim 10 . 
     
     
         13 . The host cell according to  claim 12 , wherein the host cell is a bacterial cell, a eukaryotic cell or a mammalian cell. 
     
     
         14 . A method for production of a chimeric or humanized monoclonal antibody or antigen-binding fragment thereof that binds to CD20 comprising:
 a. transfecting a host cell with an expression vector according to  claim 10 ; and   b. culturing the host cell in culture medium so that it produces the chimeric or humanized monoclonal anti-CD20 antibody or fragment thereof or fusion protein.   
     
     
         15 . The method of  claim 14 , wherein the host cell secretes the anti-CD20 antibody or fragment thereof or fusion protein into the culture medium. 
     
     
         16 . The method of  claim 15 , further comprising purifying the anti-CD20 antibody or fragment thereof or fusion protein from the culture medium. 
     
     
         17 . The method of  claim 15 , wherein the host cell is a bacterial host cell, a eukaryotic host cell or a mammalian host cell. 
     
     
         18 . A pharmaceutical composition comprising a chimeric or humanized monoclonal antibody or antigen-binding fragment thereof that binds to CD20, said antibody having a light chain variable region CDR1 comprising the sequence of RASSSVSYIH (SEQ ID NO:1); CDR2 comprising the sequence of ATSNLAS (SEQ ID NO:4); and CDR3 comprising the sequence of QQWTSNPPT (SEQ ID NO:4); and a heavy chain variable region CDR1 comprising the sequence of SYNMH (SEQ ID NO:8); CDR2 comprising the sequence of AIYPGNGDTSYNQKFKG (SEQ ID NO:9); and CDR3 comprising the sequence of STYYGGDWYFDV (SEQ ID NO:10) or the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         19 . The pharmaceutical composition according to  claim 18 , wherein said antibody is a chimeric monoclonal antibody. 
     
     
         20 . The pharmaceutical composition according to  claim 18 , wherein said antibody is a humanized monoclonal antibody. 
     
     
         21 . The pharmaceutical composition according to  claim 18 , wherein the heavy chain variable region CDR3 comprises the sequence of STYYGGDWYFDV (SEQ ID NO:10). 
     
     
         22 . The pharmaceutical composition according to  claim 18 , wherein the heavy chain variable region CDR3 comprises the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         23 . The pharmaceutical composition according to  claim 18 , wherein said antibody or fragment thereof is a fusion protein. 
     
     
         24 . The pharmaceutical composition according to  claim 23 , wherein said fusion protein comprises a second monoclonal antibody or antigen-binding fragment thereof. 
     
     
         25 . The pharmaceutical composition according to  claim 24 , wherein said second monoclonal antibody or fragment thereof is an anti-CD20 antibody or fragment thereof. 
     
     
         26 . The pharmaceutical composition according to  claim 24 , wherein said second monoclonal antibody or fragment thereof binds to an antigen selected from the group consisting of CD4, CD5, CD8, CD14, CD15, CD19, CD21, CD22, CD23, CD25, CD33, CD37, CD38, CD40, CD40L, CD46, CD52, CD54, CD74, CD80, CD126, B7, MUC1, MUC2, MUC3, MUC4, Ia, HM1.24, HLA-DR, tenascin, VEGF, PlGF, and an oncogene product. 
     
     
         27 . A kit comprising a chimeric or humanized monoclonal antibody or antigen-binding fragment thereof that binds to CD20, said antibody having a light chain variable region CDR1 comprising the sequence of RASSSVSYIH (SEQ ID NO:1); CDR2 comprising the sequence of ATSNLAS (SEQ ID NO:4); and CDR3 comprising the sequence of QQWTSNPPT (SEQ ID NO:4); and a heavy chain variable region CDR1 comprising the sequence of SYNMH (SEQ ID NO:8); CDR2 comprising the sequence of AIYPGNGDTSYNQKFKG (SEQ ID NO:9); and CDR3 comprising the sequence of STYYGGDWYFDV (SEQ ID NO:10) or the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         28 . The kit according to  claim 27 , wherein said antibody is a chimeric monoclonal antibody. 
     
     
         29 . The kit according to  claim 27 , wherein said antibody is a humanized monoclonal antibody. 
     
     
         30 . The kit according to  claim 27 , wherein the heavy chain variable region CDR3 comprises the sequence of STYYGGDWYFDV (SEQ ID NO:10). 
     
     
         31 . The kit according to  claim 27 , wherein the heavy chain variable region CDR3 comprises the sequence of VVYYSNSYWYFDV (SEQ ID NO:13). 
     
     
         32 . The kit according to  claim 27 , wherein said antibody or fragment thereof is a fusion protein. 
     
     
         33 . The kit according to  claim 32 , wherein said fusion protein comprises a second monoclonal antibody or antigen-binding fragment thereof. 
     
     
         34 . The kit according to  claim 33 , wherein said second monoclonal antibody or fragment thereof is an anti-CD20 antibody or fragment thereof. 
     
     
         35 . The kit according to  claim 33 , wherein said second monoclonal antibody or fragment thereof binds to an antigen selected from the group consisting of CD4, CD5, CD8, CD14, CD15, CD19, CD21, CD22, CD23, CD25, CD33, CD37, CD38, CD40, CD40L, CD46, CD52, CD54, CD74, CD80, CD126, B7, MUC1, MUC2, MUC3, MUC4, Ia, HM1.24, HLA-DR, tenascin, VEGF, PlGF, and an oncogene product. 
     
     
         36 . An immunoconjugate comprising:
 a. a chimeric or humanized monoclonal antibody or antigen-binding fragment thereof that binds to CD20, said antibody having a light chain variable region CDR1 comprising the sequence of RASSSVSYIH (SEQ ID NO:1); CDR2 comprising the sequence of ATSNLAS (SEQ ID NO:4); and CDR3 comprising the sequence of QQWTSNPPT (SEQ ID NO:4); and a heavy chain variable region CDR1 comprising the sequence of SYNMH (SEQ ID NO:8); CDR2 comprising the sequence of AIYPGNGDTSYNQKFKG (SEQ ID NO:9); and CDR3 comprising the sequence of STYYGGDWYFDV (SEQ ID NO:10) or the sequence of VVYYSNSYWYFDV (SEQ ID NO:13); and   b. at least one therapeutic and/or diagnostic agent attached to the chimeric or humanized monoclonal antibody or fragment thereof.   
     
     
         37 . The immunoconjugate according to  claim 36 , wherein said chimeric or humanized anti-CD20 antibody or fragment thereof is a fusion protein. 
     
     
         38 . The immunoconjugate according to  claim 36 , wherein said therapeutic agent is selected from the group consisting of a radioisotope, a cytotoxic agent, a drug, a toxin, a second antibody, a second antigen-binding antibody fragment and an immunomodulator. 
     
     
         39 . The immunoconjugate according to  claim 38 , wherein said immunomodulator is selected from the group consisting of a cytokine, an interferon, a stem cell growth factor, thrombopoietin, a lymphotoxin and a colony stimulating factor. 
     
     
         40 . A method of treating an autoimmune disease or a B-cell lymphoma or leukemia in a subject comprising administering to said subject a pharmaceutical composition according to  claim 18 . 
     
     
         41 . A method of treating an autoimmune disease or a B-cell lymphoma or leukemia in a subject comprising administering to said subject an immunoconjugate according to  claim 39 .

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