Methods for identifying targeting domains and method and compositions comprising the same

Abstract

The present invention is directed to a method of identifying tissue targeting domains. In particular, the invention relates to methods for identifying a polynucleotide encoding a targeting domain which directs tumor cell localization to secondary sites, to methods of utilizing the polynucleotide and corresponding polypeptide or fragments thereof and compositions comprising the same.

1 - 37 . (canceled) 
     
     
         38 . A method of targeting delivery of a therapeutic agent or a detection moiety to the liver or lung of a subject comprising administering to the subject a targeting domain that is associated with liver metastasis or lung metastasis and is operably linked to the therapeutic agent or the detection moiety, thereby targeting delivery of the therapeutic agent or the detection moiety to the liver or lung of the subject. 
     
     
         39 . The method of  claim 38 , wherein the targeting domain comprises a polypeptide sequence selected from the group consisting of: SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, and SEQ ID NO:36. 
     
     
         40 . The method of  claim 38 , wherein the targeting domain is encoded by:
 (a) a polynucleotide selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9; or   (b) a polynucleotide that hybridizes under highly stringent conditions to a polynucleotide selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.   
     
     
         41 . The method of  claim 38 , wherein the therapeutic agent is a radioisotope, a cytotoxic agent, a clotting factor, or a thrombolytic factor. 
     
     
         42 . The method of  claim 38 , wherein the detection moiety is a radioisotope, a dye, a pigment, or a fluorescent molecule. 
     
     
         43 . An antibody directed against a targeting domain of a polypeptide
 (a) comprising a polypeptide sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, and SEQ ID NO:36;   (b) encoded by a polynucleotide selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9; or   (c) encoded by a polynucleotide that hybridizes under highly stringent conditions to a polynucleotide selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9,   wherein the targeting domain of the polypeptide is associated with metastasis.   
     
     
         44 . The antibody of  claim 43 , wherein the antibody is a polyclonal antibody or a monoclonal antibody. 
     
     
         45 . The antibody of  claim 43 , wherein the antibody is derived from a mouse or a human. 
     
     
         46 . The antibody of  claim 43 , wherein the antibody is a chimeric antibody or a humanized antibody. 
     
     
         47 . A method of treating metastasis in a subject in need of such treatment comprising administering to the subject the antibody of  claim 43  coupled to a therapeutic agent in an amount effective to treat the metastasis. 
     
     
         48 . The method of  claim 43 , wherein the therapeutic agent is a radioisotope, a cytotoxic agent, a clotting factor, or a thrombolytic factor. 
     
     
         49 . The method of  claim 43 , wherein the metastasis is liver metastasis or lung metastasis. 
     
     
         50 . A method of detecting metastasis in a subject having the metastasis comprising administering to the subject the antibody of  claim 43  coupled to an imaging moiety and detecting the metastasis. 
     
     
         51 . The method of  claim 50 , wherein the imaging moiety is a radioisotope, a dye, a pigment, or a fluorescent molecule. 
     
     
         52 . The method of  claim 50 , wherein the metastasis is liver metastasis or lung metastasis. 
     
     
         53 . A method of treating liver metastasis or lung metastasis in a subject in need of such treatment comprising administering to the subject a targeting domain associated with liver metastasis or lung metastasis, respectively, in an amount effective to treat the liver metastasis or lung metastasis, wherein the targeting domain is operably linked to a therapeutic agent. 
     
     
         54 . The method of  claim 53 , wherein the therapeutic agent is a radioisotope, a cytotoxic agent, a clotting factor, or a thrombolytic factor. 
     
     
         55 . A method of treating liver metastasis or lung metastasis in a subject in need of such treatment comprising administering to the subject a composition in an amount effective to treat the liver or lung metastasis wherein the composition comprises:
 (a) a targeting domain associated with the liver metastasis or lung metastasis and operably linked to a therapeutic agent; or   (b) an antibody coupled to a therapeutic agent and directed against a targeting domain that is associated with the liver metastasis or lung metastasis.   
     
     
         56 . The method of  claim 55 , wherein the therapeutic agent is a radioisotope, a cytotoxic agent, a clotting factor, or a thrombolytic factor. 
     
     
         57 . The method of  claim 55 , wherein the antibody is a polyclonal antibody or a monoclonal antibody. 
     
     
         58 . The method of  claim 55 , wherein the antibody is derived from a mouse or a human. 
     
     
         59 . The method of  claim 55 , wherein the antibody is a chimeric antibody or a humanized antibody.