PCan065 Antibody Compositions and Methods of Use

Abstract

The invention provides isolated anti-PCan065 antibodies that bind to PCan065. The invention also encompasses compositions comprising an anti-PCan065 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-PCan065 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-PCan065 antibodies. The invention encompasses a method of producing the anti-PCan065 antibodies. Other aspects of the invention are a method of killing an PCan065-expressing cancer cell, comprising contacting the cancer cell with an anti-PCan065 antibody and a method of alleviating or treating an PCan065-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the anti-PCan065 antibody to the mammal.

1 . An isolated antibody which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of PCan065.A10.3.2, PCan065.B1, PCan065.B2.2.1, PCan065.B3, PCan065.B4, PCan065.B5, PCan065.B16, PCan065.B27 and PCan065.B29.  
     
     
         2 . The antibody of  claim 1  which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridomas PCan065.A10.3.2 or PCan065.B2.2.1.  
     
     
         3 . The antibody of  claim 1  which is a monoclonal antibody.  
     
     
         4 . The antibody of  claim 1  which is an antibody fragment.  
     
     
         5 . The antibody of  claim 1  which is a chimeric or a humanized antibody.  
     
     
         6 . The antibody of  claim 1  which binds a PCan065 peptide selected from the group consisting of Leu30-Ile308, Ala35-Ile308, Ala197-Ile308, Pro207-Ile308, Gly208-Ile308 and Cys211-Ile308 of PCan065.  
     
     
         7 . The antibody of  claim 1  which binds a heterodimer or homodimer complex containing a peptide selected from the group consisting of Leu30-Ile308, Ala35-Ile308, Ala197-Ile308, Pro207-Ile308 and Cys211-Ile308 of PCan065.  
     
     
         8 . The antibody of  claim 6  wherein the PCan065 peptide contains a post translational modification, motif, or domain.  
     
     
         9 . The antibody of  claim 8  wherein the post translational modification, motif, or domain is a transforming growth factor-beta (TGF-beta) domain, N-glycosylation site, or proteolytic cleavage site.  
     
     
         10 . The antibody of  claim 1  where the antibody competes for binding with a molecule that binds a transforming growth factor-beta (TGF-beta) domain.  
     
     
         11 . The antibody of  claim 3  which is produced by a hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         12 . The antibody of  claim 3 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         13 . The antibody of  claim 3  which is conjugated to a growth inhibitory agent.  
     
     
         14 . The antibody of  claim 3  which is conjugated to a cytotoxic agent.  
     
     
         15 . The antibody of  claim 14  wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         16 . The antibody of  claim 15  wherein the cytotoxic agent is a toxin.  
     
     
         17 . The antibody of  claim 16 , wherein the toxin is selected from the group consisting of ricin, saponin, maytansinoid and calicheamicin.  
     
     
         18 . The antibody of  claim 17 , wherein the toxin is a maytansinoid.  
     
     
         19 . The antibody of  claim 1  where the antibody inhibits the growth of PCan065-expressing cancer cells.  
     
     
         20 . The antibody of  claim 19  which is a humanized or human antibody.  
     
     
         21 . The antibody of  claim 20  which is produced by bacterial, insect, or mammalian cells.  
     
     
         22 . The antibody of  claim 19 , which is a humanized form of an anti-PCan065 antibody produced by a hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         23 . The antibody of  claim 19 , wherein the cancer cells are from a cancer selected from the group consisting of ovarian, breast, colon, prostate, pancreatic and lung cancer.  
     
     
         24 . A cell that produces the antibody of  claim 3 .  
     
     
         25 . The cell of  claim 24 , wherein the cell is selected from the group consisting of a hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A 10.3.2 and PCan065.B2.2.1.  
     
     
         26 . A method of producing the antibody of  claim 3  comprising culturing an appropriate cell and recovering the antibody from the cell culture.  
     
     
         27 . A composition comprising the antibody of  claim 19 , and a carrier.  
     
     
         28 . The composition of  claim 27 , wherein the antibody is conjugated to a cytotoxic agent.  
     
     
         29 . The composition of  claim 28 , wherein the cytotoxic agent is a maytansinoid.  
     
     
         30 . The composition of  claim 27 , wherein the antibody is a human or humanized antibody and the carrier is a pharmaceutical carrier.  
     
     
         31 . The composition of  claim 30 , wherein the humanized antibody is a humanized form of an anti-PCan065 antibody produced by hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         32 . A method of killing a PCan065-expressing cancer cell, comprising binding PCan065 with the antibody of  claim 10 , thereby inhibition PCan065 activity and killing the cancer cell.  
     
     
         33 . The method of  claim 32 , wherein the cancer cell is selected from the group consisting of ovarian, breast, colon, prostate, pancreatic and lung cancer cells.  
     
     
         34 . The method of  claim 33 , wherein the cancer cell is an ovarian cancer cell.  
     
     
         35 . The method of  claim 33 , wherein the cancer cell is from metastatic ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         36 . The method of  claim 32 , wherein the antibody is an antibody fragment.  
     
     
         37 . The method of  claim 32 , wherein the antibody is a humanized antibody.  
     
     
         38 . The method of  claim 32 , wherein the antibody is conjugated to a cytotoxic agent.  
     
     
         39 . The method of  claim 38 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin.  
     
     
         40 . The method of  claim 38 , wherein the cytotoxic agent is a radioactive isotope.  
     
     
         41 . The method of  claim 32 , wherein the antibody is a humanized form of the antibody produced by hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         42 . A method of alleviating an PCan065-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the antibody of  claim 19  to the mammal.  
     
     
         43 . The method of  claim 42 , wherein the cancer is selected from the group consisting of ovarian, breast, colon, prostate, pancreatic and lung cancer.  
     
     
         44 . The method of  claim 42 , wherein the antibody is a humanized antibody.  
     
     
         45 . The method of  claim 42 , wherein the antibody is conjugated to a cytotoxic agent.  
     
     
         46 . The method of  claim 45 , wherein the cytotoxic agent is a maytansinoid.  
     
     
         47 . The method of  claim 46 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent.  
     
     
         48 . The method of  claim 47  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof.  
     
     
         49 . An article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an antibody of  claim 3 .  
     
     
         50 . The article of manufacture of  claim 49  further comprising a package insert indicating that the composition can be used to treat ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         51 . A method for determining if cells in a sample express PCan065 comprising 
 (a) contacting a sample of cells with an PCan065 antibody of  claim 3  under conditions suitable for specific binding of the PCan065 antibody to PCan065, and    (b) determining the level of binding of the antibody to PCan065 in the sample, or the level of PCan065 antibody internalization by cells in said sample,    wherein PCan065 antibody binding to PCan065 in the sample or internalization of the PCan065 antibody by cells in the sample indicate cells in the sample express PCan065.    
     
     
         52 . The method of  claim 51  wherein said sample of cells are contacted with an antibody produced by a hybridoma deposited with the American Type Culture Collection selected from the group consisting of PCan065.A10.3.2 and PCan065.B2.2.1.  
     
     
         53 . The method of  claim 51  wherein said sample of cells is from a subject who has a cancer, is suspected of having a cancer or who may have a predisposition for developing cancer.  
     
     
         54 . The method of  claim 53  wherein the cancer is a ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         55 . The method of  claim 51  wherein said antibody is a labeled antibody.  
     
     
         56 . A method for detecting PCan065 overexpression in a test cell sample, comprising: 
 (a) combining a test cell sample with an PCan065 antibody of  claim 3  under conditions suitable for specific binding of the PCan065 antibody to PCan065 expressed by cells in said test sample,    (b) determining the level of binding of the PCan065 antibody to the cells in the test sample, and    (c) comparing the level of PCan065 antibody bound to the cells in step (b) to the level of PCan065 antibody binding to cells in a control cell sample,    wherein an increase in the binding of the PCan065 antibody in the test cell sample as compared to the control is indicative of PCan065 overexpression by cells in the test cell sample.    
     
     
         57 . The method of  claim 56  wherein the test cell sample is a cancer cell sample.  
     
     
         58 . The method of  claim 57  wherein the cancer cell sample is of ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         59 . The method of  claim 58  wherein the ovarian, breast, colon, prostate, pancreatic or lung cancer is metastatic ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         60 . The method of  claim 57  wherein the control is a sample of adjacent normal tissue.  
     
     
         61 . A method for detecting PCan065 overexpression in a subject in need thereof comprising, 
 (a) combining a bodily fluid sample of a subject with an PCan065 antibody of  claim 3  under conditions suitable for specific binding of the PCan065 antibody to PCan065 in said bodily fluid sample,    (b) determining the level of PCan065 in the bodily fluid sample, and    (c) comparing the level of PCan065 determined in step (b) to the level of PCan065 in a control sample,    wherein an increase in the level of PCan065 in the bodily fluid sample from the subject as compared to the control is indicative of PCan065 overexpression in the subject.    
     
     
         62 . The method of  claim 61  wherein the subject has cancer, is suspected of having a cancer or who may have a predisposition for developing cancer.  
     
     
         63 . The method of  claim 62  wherein the cancer is ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         64 . The method of  claim 63  wherein the ovarian, breast, colon, prostate, pancreatic or lung cancer is metastatic ovarian, breast, colon, prostate, pancreatic or lung cancer.  
     
     
         65 . The method of  claim 61 , wherein the bodily fluid is selected from the group consisting of blood, serum, plasma, urine, ascites, peritoneal wash, saliva, sputum, seminal fluids, tears, mucous membrane secretions, and other bodily excretions such as stool.  
     
     
         66 . The method of  claim 61  wherein the control is a bodily fluid sample from a subject without a cancer overexpressing PCan065.  
     
     
         67 . The method of  claim 61  wherein the control is a sample of known concentration of PCan065.  
     
     
         68 . A method for detecting the presence of ovarian cancer in an subject comprising: 
 (a) determining the level of PCan065 in a sample from the subject, and    (b) comparing the level of PCan065 determined in step (a) to the level of PCan065 in a control sample,    wherein an increase in the level of PCan065 in the sample from the subject as compared to the control is indicative of the presence of ovarian cancer.    
     
     
         69 . The method of  claim 68  wherein the sample is selected from the group consisting of cells, tissues and bodily fluids.  
     
     
         70 . The method of  claim 69  where in the bodily fluid is selected from the group consisting of blood, serum, plasma, urine, ascites, peritoneal wash, saliva, sputum, seminal fluids, tears, mucous membrane secretions, and other bodily excretions such as stool.  
     
     
         71 . The method of  claim 68  wherein the control sample is from a subject without a cancer overexpressing PCan065.  
     
     
         72 . The method of  claim 68  wherein the control is a sample of known concentration of PCan065.  
     
     
         73 . A screening method for antibodies that bind to an epitope which is bound by an antibody of  claim 3  comprising, 
 (a) combining an PCan065-containing sample with a test antibody and an antibody of  claim 3  to form a mixture,    (b) determining the level of PCan065 antibody bound to PCan065 in the mixture, and    (c) comparing the level of PCan065 antibody bound in the mixture of step (a) to a control mixture,    wherein the level of PCan065 antibody binding to PCan065 in the mixture as compared to the control is indicative of the test antibody's binding to an epitope that is bound by the anti-PCan065 antibody of  claim 3 .    
     
     
         74 . The screening method of  claim 73  wherein the level of PCan065 antibody bound to PCan065 is determined by ELISA or flow cytometry.  
     
     
         75 . The screening method of  claim 74  wherein the control is a mixture of: 
 PCan065;    a monoclonal antibody which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of PCan065.A10, PCan065.B1, PCan065.B2, PCan065.B3, PCan065.B4, PCan065.B5, PCan065.B16, PCan065.B27 and PCan065.B29; and    an antibody known to bind the epitope bound by the monoclonal antibody which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of PCan065.A10, PCan065.B1, PCan065.B2, PCan065.B3, PCan065.B4, PCan065.B5, PCan065.B16, PCan065.B27 and PCan065.B29.    
     
     
         76 . The screening method of  claim 74  wherein the anti-PCan065 antibody is labeled.  
     
     
         77 . The screening method of  claim 76  wherein the PCan065 is bound to a solid support.  
     
     
         78 . The screening method of  claim 77  wherein the solid support is a sepharose bead.