US2012089017A1PendingUtilityA1

Ligands to radiation-induced molecules

56
Assignee: HALLAHAN DENNIS EPriority: Oct 3, 2001Filed: Dec 15, 2011Published: Apr 12, 2012
Est. expiryOct 3, 2021(expired)· nominal 20-yr term from priority
A61K 49/0032A61K 51/088A61K 49/0084A61K 41/0038C07K 16/44A61B 6/508A61K 51/1234A61K 49/0058A61K 51/1045A61K 49/0056C07K 2317/622A61K 51/08A61K 51/082C07K 16/18
56
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Claims

Abstract

A method for identifying a molecule that binds an irradiated tumor in a subject and molecules identified thereby. In some embodiments, the method includes the steps of (a) exposing a tumor to ionizing radiation; (b) administering to a subject a library of diverse molecules; and (c) isolating from the tumor one or more molecules of the library of diverse molecules, whereby a molecule that binds an irradiated tumor is identified. Also provided are targeting ligands that bind an irradiated tumor and therapeutic and diagnostic methods that employ the disclosed targeting ligands.

Claims

exact text as granted — not AI-modified
1 - 57 . (canceled) 
     
     
         58 . A method for detecting a tumor in a subject, the method comprising:
 (a) exposing a target area of the subject where the presence of a tumor is suspected to ionizing radiation;   (b) administering to the subject a composition to detect the presence of TIP-1 in the target area, wherein the composition comprises one or more targeting antibodies, wherein each targeting antibody
 i. is capable of binding to a TIP-1 polypeptide expressed by an irradiated tumor, and 
 ii. is conjugated to a detectable label, and 
 iii. substantially lacks binding to a control tissue; and 
   (c) detecting the detectable label to detect the presence of TIP-1, wherein the presence of TIP-1 indicates the presence of a tumor in the target area of the subject.   
     
     
         59 . The method of  claim 58 , wherein the antibody that binds to a TIP-1 polypeptide is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a scFv antibody, and an antibody fragment that binds to a TIP-1 polypeptide. 
     
     
         60 . The method of  claim 59 , wherein the antibody is humanized. 
     
     
         61 . The method of  claim 58 , wherein the exposing comprises exposing the tumor to less than about 2 Gy ionizing radiation. 
     
     
         62 . The method of  claim 61 , wherein the exposing comprises exposing the tumor to at least about 2 Gy ionizing radiation. 
     
     
         63 . The method of  claim 62 , wherein the exposing comprises exposing the tumor to about 10 Gy to about 20 Gy ionizing radiation. 
     
     
         64 . The method of  claim 58 , wherein the administering comprises administering the targeting antibody by intravascular provision. 
     
     
         65 . The method of  claim 58 , wherein the administering comprises administering the targeting antibody subsequent to radiation exposure. 
     
     
         66 . The method of  claim 65 , wherein the administering comprises administering the targeting antibody 0 hours to about 24 hours following radiation exposure. 
     
     
         67 . The method of  claim 66 , wherein the administering comprises administering the targeting antibody about 4 hours to about 24 hours following radiation exposure. 
     
     
         68 . The method of  claim 58 , wherein the subject is a warm-blooded vertebrate. 
     
     
         69 . The method of  claim 58 , wherein the detecting comprises detecting the radionuclide label using positron emission tomography, single photon emission computed tomography, gamma camera imaging, or rectilinear scanning. 
     
     
         70 . The method of  claim 58 , wherein the tumor comprises a tumor selected from the group consisting of bladder carcinoma, breast carcinoma, cervical carcinoma, cholangiocarcinoma, colorectal carcinoma, gastric sarcoma, glioma, lung carcinoma, lymphoma, melanoma, multiple myeloma, osteosarcoma, ovarian carcinoma, pancreatic carcinoma, prostate carcinoma, stomach carcinoma, a head, a neck tumor, and a solid tumor. 
     
     
         71 . The method of  claim 70 , wherein the tumor is selected from the group consisting of a glioma, a melanoma, a lung carcinoma, and a prostate carcinoma. 
     
     
         72 . The method of  claim 58 , further comprising simultaneously detecting two or more tumors in the subject. 
     
     
         73 . The method of  claim 72 , wherein the two or more tumors in a subject comprise two or more tumor types.

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