US2004077843A1PendingUtilityA1

Antibody/receptor targeting moiety for enhanced delivery of armed ligand

59
Assignee: CT OF MOLECULAR MEDICINE AND IPriority: Jan 15, 1998Filed: Nov 24, 2003Published: Apr 22, 2004
Est. expiryJan 15, 2018(expired)· nominal 20-yr term from priority
Inventors:Jack D. BurtonDavid M. Goldenberg
A61K 47/67B82Y 5/00A61K 47/65A61K 38/00A61K 47/6813C07K 16/3007C07K 2319/00C07K 2317/77A61K 2039/505C07K 7/08C07K 2317/24C07K 2317/622C07K 14/7155
59
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Claims

Abstract

A method for intracellular delivery of drugs or other agents for diagnosis and therapy of malignancies or immune-mediated or inflammatory conditions. A targeting moiety of a an antibody and the ligand-binding region of a selected cytokine receptor is used. The targeting moiety targets surface antigen on a specific cell population. The targeting moiety is administered to a subject, and then, after a specified interval, therapeutic or diagnostic agents linked to the cognate cytokine then are given. The invention provides rapid, efficient internalization of the cytokine receptor antibody/antigen complexes. Targeting of a high-level cell surface antigen with such bispecific fusion molecules substantially increases the number of cytokine receptors over their low background level.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A targeting moiety comprising a conjugate of an antibody linked to a ligand-binding region of a receptor subunit selected from the group consisting of interleukin-2 receptor α(IL-2α), interleukin-4 receptor α(IL-4α), and interleukin-15 receptor α(IL-15Rα), which antibody is specific for a cell marker specific to a targeted cell.  
     
     
         2 . A targeting moiety as claimed in  claim 1 , comprising a covalent conjugate in which the antibody is covalently linked to the ligand-binding region of the receptor.  
     
     
         3 . A targeting moiety as claimed in  claim 1 , comprising a fusion protein of the antibody and the ligand-binding region.  
     
     
         4 . A targeting moiety as claimed in  claim 1 , comprising a bispecific antibody that has a first specificity for a cell marker specific to a targeted cell and a second specificity for the ligand-binding region.  
     
     
         5 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to CEA.  
     
     
         6 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to HLA-DR.  
     
     
         7 . A targeting moiety as claimed in  claim 1 , wherein the receptor subunit is IL-4α.  
     
     
         8 . A targeting moiety as claimed in  claim 1 , wherein the receptor subunit is IL-15Rα.  
     
     
         9 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to HLA-DR and is linked to the ligand-binding region of IL-15Rα.  
     
     
         10 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to CEA and is linked to the ligand-binding region of IL-15Rα.  
     
     
         11 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to HLA-DR and is linked to the ligand-binding region of IL-4Rα.  
     
     
         12 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific to CEA and is linked to the ligand-binding region of IL-4Rα.  
     
     
         13 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to a B-cell.  
     
     
         14 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to a malignant B-cell.  
     
     
         15 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to an activated B-cell.  
     
     
         16 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to a normal B-cell.  
     
     
         17 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to a T-cell.  
     
     
         18 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to a malignant T-cell.  
     
     
         19 . A targeting moiety as claimed in  claim 1 , wherein the antibody is specific for a cell marker specific to an activated T-cell.  
     
     
         20 . A composition comprising a targeting moiety according to  claim 1 , and a pharmaceutically acceptable carrier.  
     
     
         21 . A composition comprising a targeting moiety according to  claim 7 , and a pharmaceutically acceptable carrier.  
     
     
         22 . A composition comprising a targeting moiety according to  claim 8 , and a pharmaceutically acceptable carrier.  
     
     
         23 . A kit comprising a conjugate of IL-15 linked to a drug, radionuclide or toxin, and a targeting moiety comprising an antibody specific for a cell marker specific to a targeted cell, linked to the ligand-binding region of IL-15Rα.  
     
     
         24 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to a B-cell.  
     
     
         25 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to a malignant B-cell.  
     
     
         26 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to an activated B-cell.  
     
     
         27 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to a normal B-cell.  
     
     
         28 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to a T-cell.  
     
     
         29 . A kit as claimed in  claim 23 , wherein the antibody is specific for a cell marker specific to a malignant T-cell.  
     
     
         30 . A method of treatment for cancer or an immunologically-mediated or infectious disease, comprising: 
 first administering to a subject in need of such treatment a targeting moiety comprising a antibody specific for a cell marker specific to a targeted cell, linked to the ligand-binding region of IL-15Rα, and then    administering to the subject a therapeutically effective amount of a conjugate of IL-15 linked to a drug, radionuclide or toxin.    
     
     
         31 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to a B-cell.  
     
     
         32 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to a malignant B-cell.  
     
     
         33 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to an activated B-cell.  
     
     
         34 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to a normal B-cell.  
     
     
         35 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to a T-cell.  
     
     
         36 . A method as claimed in  claim 30 , wherein the antibody is specific for a cell marker specific to a malignant T-cell.  
     
     
         37 . A targeting moiety comprising a conjugate of an antibody linked to a ligand-binding region of interleukin-13 receptor α(IL-13Rα), which antibody is specific to HLA-DR.  
     
     
         38 . A composition comprising a targeting moiety according to  claim 18 , and a pharmaceutically acceptable carrier.

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