Gene differentially expressed in breast and bladder cancer, and encoded polypeptides

Abstract

The present invention is directed to antibodies or antigen binding fragments thereof that specifically bind to the cancer specific antigen, C35. This invention also relates to a polynucleotide encoding the antibody or antigen binding fragment thereof as well as vectors and host cells comprising the polynucleotide. The present invention further relates to a composition comprising the antibody or antigen binding fragment thereof or further comprising a chemotherapeutic agent, specifically taxol. The invention is also directed to therapeutic and diagnostic methods of using antibodies against C35, preferably more than one anti-C35 antibody in combination with a chemotherapeutic agent, to treat C35 associated cancer.

1 . An isolated antibody or antigen binding fragment thereof that specifically binds to an epitope of C35 (SEQ ID NO:2).  
     
     
         2 . The antibody or fragment thereof of  claim 1 , wherein said epitope of C35 is selected from the group consisting of: amino acids S-9 to V-17, amino acids V-10 to V-17, amino acids E-16 to V-23, amino acids E-16 to R-24, amino acids E-16 to I-25, amino acids S-21 to F-35, amino acids C-30 to T-38, amino acids E-31 to Y-39, amino acids E-36 to A-43, amino acids A-37 to A-45, amino acids A-37 to V-46, amino acids Y-39 to V-46, amino acids S-44 to I-53, amino acids A-45 to I-53; amino acids G-52 to L-59, amino acids E-54 to T-62, amino acids S-57 to F-75, amino acids R-58 to I-67, amino acids G-61 to I-69, amino acids G-63 to F-83, amino acids E-66 to L-73, amino acids E-66 to V-74, amino acids F-83 to E-103, amino acids D-88 to A-96, amino acids L-89 to A-96, amino acids A-92 to T-101, amino acids R-95 to L-102, amino acids A-96 to K-104, amino acids K-104 to V-113, amino acids I-105 to V-113, amino acids I-105 to I-114, amino acids E-4 to P-12, amino acids S-21 to Y-29, amino acids G-22 to C-30, amino acids I-25 to C-33, amino acids T-38 to V-46, amino acids G-63 to G-71, amino acids F-65 to L-73, amino acids I-67 to F-75, amino acids K-77 to Y-85, amino acids Q-72 to E-86, amino acids G-81 to L-89, and amino acids K-104 to C-112, each of SEQ ID NO:2.  
     
     
         3 . The antibody or fragment thereof of  claim 2 , wherein said epitope of C35 is amino acids A-96 to K-104 of SEQ ID NO: 2.  
     
     
         4 . The antibody or fragment thereof of  claim 2 , wherein said epitope of C35 is amino acids K-104 to V-113 of SEQ ID NO: 2.  
     
     
         5 . The antibody or fragment thereof of  claim 2 , wherein said epitope of C35 is amino acids I-105 to V-113 of SEQ ID NO: 2.  
     
     
         6 . The antibody or fragment thereof of  claim 2 , wherein said epitope of C35 is amino acids I-105 to I-114 of SEQ ID NO: 2.  
     
     
         7 . The antibody or fragment thereof of  claim 2 , wherein said epitope of C35 is K-104 to C-112 of SEQ ID NO: 2.  
     
     
         8 . The antibody or fragment thereof of  claim 1 , wherein said antibody or fragment is selected from the group consisting of: a whole antibody, an Fab fragment, an F(ab′)2 fragment, an scFv fragment, and an Fv fragment.  
     
     
         9 . The antibody or fragment thereof of  claim 1 , wherein said antibody is a fusion protein.  
     
     
         10 . The antibody or fragment thereof of  claim 1 , wherein said antibody or fragment is humanized.  
     
     
         11 . An isolated polynucleotide encoding the antibody or fragment thereof of  claim 1 .  
     
     
         12 . An expression vector comprising the polynucleotide of  claim 11 .  
     
     
         13 . A host cell comprising the expression vector of  claim 12 .  
     
     
         14 . A method for producing an isolated antibody or antigen binding fragment thereof that specifically binds C35 comprising 
 (a) culturing the host cell of  claim 13;  and    (b) recovering said antibody or fragment thereof.    
     
     
         15 . A composition comprising at least one isolated antibody or fragment thereof according to  claim 1 .  
     
     
         16 . The composition of  claim 15 , wherein said composition comprises two antibodies or fragments thereof.  
     
     
         17 . The composition of  claim 15 , further comprising an effective amount of a therapeutic agent.  
     
     
         18 . The composition of  claim 17 , wherein said therapeutic agent is selected from the group consisting of: an anti-tumor drug, a cytotoxin, and a radioactive agent.  
     
     
         19 . The composition of  claim 18 , wherein said therapeutic agent is a cytotoxin.  
     
     
         20 . The composition of  claim 19 , wherein said cytotoxin is selected from the group consisting of: paclitaxel, ricin, doxorubicin, cytochalasin B, gramicidin D, ethidium bromide, etoposide, tenoposide, colchicin, dihydroxy anthracin dione, 1-dehydrotestosterone, and glucocorticoid.  
     
     
         21 . The composition of  claim 20 , wherein said cytotoxin is paclitaxel.  
     
     
         22 . The composition of  claim 17 , wherein said therapeutic agent is conjugated to or complexed with said antibody or fragment thereof.  
     
     
         23 . The composition of  claim 15 , wherein said composition further comprises a pharmaceutically acceptable carrier.  
     
     
         24 . A method of treating a C35-associated cancer comprising administering the composition of  claim 15  to a host in need of treatment thereof.  
     
     
         25 . The method of  claim 24 , wherein said composition comprises two antibodies or fragments thereof.  
     
     
         26 . The method of  claim 24 , wherein said composition further comprises a therapeutic agent.  
     
     
         27 . The method of  claim 26 , wherein said therapeutic agent is selected from the group consisting of: an anti-tumor drug, a cytotoxin, and a radioactive agent.  
     
     
         28 . The method of  claim 27 , wherein said therapeutic agent is a cytotoxin.  
     
     
         29 . The method of  claim 28 , wherein said cytotoxin is selected from the group consisting of: paclitaxel, ricin, doxorubicin, cytochalasin B, gramicidin D, ethidium bromide, etoposide, tenoposide, colchicin, dihydroxy anthracin dione, 1-dehydrotestosterone, and glucocorticoid.  
     
     
         30 . The method of  claim 29 , wherein said cytotoxin is paclitaxel.  
     
     
         31 . The method of  claim 26 , wherein said therapeutic agent is conjugated to or complexed with said antibody or fragment thereof.  
     
     
         32 . The method of  claim 24 , wherein said cancer is selected from the group consisting of: breast cancer, ovarian cancer, bladder cancer, lung cancer, pancreatic cancer, and colon cancer.  
     
     
         33 . The method of  claim 32 , wherein said cancer is breast cancer.  
     
     
         34 . A method of detecting the presence of C35 in a sample, said method comprising: 
 (a) contacting said sample with the antibody or fragment thereof of  claim 1;  and    (b) assaying for binding of said antibody or fragment thereof to C35.    
     
     
         35 . The method of  claim 34 , wherein said assaying step is performed by an assay selected from the group consisting of: ELISA, radioimmunoassay, immunofluorescence, and immunocytochemistry.  
     
     
         36 . A diagnostic kit for detecting the presence of C35 in a sample, said kit comprising: 
 (a) the antibody or fragment thereof of  claim 1;     (b) a conjugate comprising a specific binding partner for the C35 antibody and a label capable of producing a detectable signal.    
     
     
         37 . An isolated antibody or antigen binding fragment thereof that competitively inhibits binding of an antibody or fragment thereof to an epitope of C35.  
     
     
         38 . The antibody or fragment thereof of  claim 37 , wherein said epitope of C35 is selected from the group consisting of: amino acids S-9 to V-17, amino acids V-10 to V-17, amino acids E-16 to V-23, amino acids E-16 to R-24, amino acids E-16 to I-25, amino acids S-21 to F-35, amino acids C-30 to T-38, amino acids E-31 to Y-39, amino acids E-36 to A-43, amino acids A-37 to A-45, amino acids A-37 to V-46, amino acids Y-39 to V-46, amino acids S-44 to I-53, amino acids A-45 to I-53; amino acids G-52 to L-59, amino acids E-54 to T-62, amino acids S-57 to F-75, amino acids R-58 to I-67, amino acids G-61 to I-69, amino acids G-63 to F-83, amino acids E-66 to L-73, amino acids E-66 to V-74, amino acids F-83 to E-103, amino acids D-88 to A-96, amino acids L-89 to A-96, amino acids A-92 to T-101, amino acids R-95 to L-102, amino acids A-96 to K-104, amino acids K-104 to V-113, amino acids I-105 to V-113, amino acids I-105 to I-114, amino acids E-4 to P-12, amino acids S-21 to Y-29, amino acids G-22 to C-30, amino acids I-25 to C-33, amino acids T-38 to V-46, amino acids G-63 to G-71, amino acids F-65 to L-73, amino acids I-67 to F-75, amino acids K-77 to Y-85, amino acids Q-72 to E-86, amino acids G-81 to L-89, and amino acids K-104 to C-112, each of SEQ ID NO:2.  
     
     
         39 . The antibody or fragment thereof of  claim 38 , wherein said epitope of C35 is amino acids A-96 to K-104 of SEQ ID NO: 2.  
     
     
         40 . The antibody or fragment thereof of  claim 38 , wherein said epitope of C35 is amino acids K-104 to V-113 of SEQ ID NO: 2.  
     
     
         41 . The antibody or fragment thereof of  claim 38 , wherein said epitope of C35 is amino acids I-105 to V-113 of SEQ ID NO: 2.  
     
     
         42 . The antibody or fragment thereof of  claim 38 , wherein said epitope of C35 is amino acids I-105 to I-114 of SEQ ID NO: 2.  
     
     
         43 . The antibody or fragment thereof of  claim 38 , wherein said epitope of C35 is amino acids K-104 to C-112 of SEQ ID NO: 2.  
     
     
         44 . The antibody or fragment thereof of  claim 38 , wherein said antibody or fragment thereof is selected from the group consisting of: a whole antibody, an Fab fragment, an F(ab′)2 fragment, an scFv fragment, and an Fv fragment.  
     
     
         45 . The antibody or fragment thereof of  claim 38 , wherein said antibody is a fusion protein.  
     
     
         46 . The antibody or fragment thereof of  claim 38 , wherein said antibody or fragment is humanized.  
     
     
         47 . A method of treating a C35-associated cancer, said method comprising administering to a subject in need thereof a therapeutic amount of an antibody or antigen binding fragment thereof that specifically binds to an epitope of C35.  
     
     
         48 . The method of  claim 47 , wherein said epitope of C35 is selected from the group consisting of: amino acids S-9 to V-17, amino acids V-10 to V-17, amino acids E-16 to V-23, amino acids E-16 to R-24, amino acids E-16 to I-25, amino acids S-21 to F-35, amino acids C-30 to T-38, amino acids E-31 to Y-39, amino acids E-36 to A-43, amino acids A-37 to A-45, amino acids A-37 to V-46, amino acids Y-39 to V-46, amino acids S-44 to I-53, amino acids A-45 to I-53; amino acids G-52 to L-59, amino acids E-54 to T-62, amino acids S-57 to F-75, amino acids R-58 to I-67, amino acids G-61 to I-69, amino acids G-63 to F-83, amino acids E-66 to L-73, amino acids E-66 to V-74, amino acids F-83 to E-103, amino acids D-88 to A-96, amino acids L-89 to A-96, amino acids A-92 to T-101, amino acids R-95 to L-102, amino acids A-96 to K-104, amino acids K-104 to V-113, amino acids I-105 to V-113, amino acids I-105 to I-114, amino acids E-4 to P-12, amino acids S-21 to Y-29, amino acids G-22 to C-30, amino acids I-25 to C-33, amino acids T-38 to V-46, amino acids G-63 to G-71, amino acids F-65 to L-73, amino acids I-67 to F-75, amino acids K-77 to Y-85, amino acids Q-72 to E-86, amino acids G-81 to L-89, and amino acids K-104 to C-112, each of SEQ ID NO:2.  
     
     
         49 . The method of  claim 48 , wherein said epitope of C35 is amino acids A-96 to K-104 of SEQ ID NO: 2.  
     
     
         50 . The method of  claim 48 , wherein said epitope of C35 is amino acids K-104 to V-113 of SEQ ID NO: 2.  
     
     
         51 . The method of  claim 48 , wherein said epitope of C35 is amino acids I-105 to V-113 of SEQ ID NO: 2.  
     
     
         52 . The method of  claim 48 , wherein said epitope of C35 is amino acids I-105 to I-114 of SEQ ID NO: 2.  
     
     
         53 . The method of  claim 48 , wherein said epitope of C35 is K-104 to C-112.  
     
     
         54 . The method of  claim 47 , wherein said method comprises administering two antibodies or fragments thereof.  
     
     
         55 . The method of  claim 47 , wherein said method further comprises administering an effective amount of a therapeutic agent.  
     
     
         56 . The method of  claim 55 , wherein said therapeutic agent is selected from the group consisting of: an anti-tumor drug, a cytotoxin, and a radioactive agent.  
     
     
         57 . The method of  claim 56 , wherein said therapeutic agent is a cytotoxin.  
     
     
         58 . The method of  claim 57 , wherein said cytotoxin is selected from the group consisting of: paclitaxel, ricin, doxorubicin, cytochalasin B, gramicidin D, ethidium bromide, etoposide, tenoposide, colchicin, dihydroxy anthracin dione, 1-dehydrotestosterone, and glucocorticoid.  
     
     
         59 . The method of  claim 58 , wherein said cytotoxin is paclitaxel.  
     
     
         60 . The method of  claim 55 , wherein said therapeutic agent is conjugated to or complexed with said antibody or fragment thereof.