US2008199499A1PendingUtilityA1

Method for Making Targeted Therapeutic Agents

52
Assignee: PROTEONOVA INCPriority: Jan 12, 2005Filed: Jan 12, 2006Published: Aug 21, 2008
Est. expiryJan 12, 2025(expired)· nominal 20-yr term from priority
Inventors:Richard B. Williams
C12N 15/1075A61P 35/00G01N 33/6845A61P 37/06A61P 31/18C07K 16/30C07K 2319/30C12P 19/34G01N 33/531C07K 14/00A61P 31/12C12N 15/1068A61P 35/02A61P 43/00A61P 37/02A61P 31/00A61P 37/04
52
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Claims

Abstract

Provided herein are methods and kits for making a targeted therapeutic for treating a disease or condition. The therapeutic agents can be targeted to patient-specific disease markers. In one of these methods, the method includes obtaining a biological sample from a patient having the disease or condition, or who is at risk for developing the disease or condition. In this particular method, the sample includes a population of diseased cells, screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent. Some of the methods further include preparing a library with proteins linked to their cognate mRNAs. In certain of these methods, the preparation of the library includes providing at least two candidate mRNA molecules in which each of the mRNA molecules includes a cross-linker, translating at least two of the candidate mRNA molecules to generate at least one translated protein, and linking at least one of the candidate mRNA molecules to its corresponding translated protein via the cross-linker to form at least one cognate pair.

Claims

exact text as granted — not AI-modified
1 . A method for making a targeted therapeutic for treating a disease or condition, the method comprising:
 obtaining a biological sample from a patient having the disease or condition, or who is at risk for developing the disease or condition, the sample comprising a population of diseased cells;   screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells;   isolating one or more proteins from the identified mRNA-protein pairs; and   conjugating the isolated protein(s) to a therapeutic agent, the therapeutic agent having therapeutic efficacy against the diseased cells.   
     
     
         2 . The method of  claim 1 , further comprising:
 isolating a first sub-population of cells from the sample, the first sub-population comprising diseased cells substantially free from non-diseased cells; and   isolating a second sub-population of cells from the sample, the second population comprising non-diseased cells substantially free of diseased cells, wherein the library is screened to identify mRNA-protein pairs that bind the diseased cells with substantially higher affinity than the non-diseased cells   
     
     
         3 . The method of  claim 1 , wherein the disease or condition is a cancer, and the diseased cells are malignant cells. 
     
     
         4 . The method of  claim 3 , wherein the disease or condition is a hematological cancer, and the malignant cells comprise lymphocytes. 
     
     
         5 . The method of  claim 4 , wherein the malignant cells are B-cells. 
     
     
         6 . The method of  claim 4 , wherein the malignant cells are T-cells. 
     
     
         7 . The method of  claim 1 , wherein the disease or condition is a pathogenic infection, and the diseased cells are cells infected with a pathogen. 
     
     
         8 . The method of  claim 7 , wherein the pathogen is a virus. 
     
     
         9 . The method of  claim 8 , wherein the virus is HIV. 
     
     
         10 . The method of  claim 1 , wherein the therapeutic agent is a cytotoxic agent. 
     
     
         11 . The method of  claim 1 , wherein the therapeutic agent is capable of effecting an immune response in the patient. 
     
     
         12 . The method of  claim 11 , wherein the therapeutic agent is an adjuvant. 
     
     
         13 . The method of  claim 1 , wherein the disease or condition is transplant rejection, and the diseased cells are transplanted cells. 
     
     
         14 . The method of  claim 13 , wherein the therapeutic agent is capable of suppressing an immune response in the patient. 
     
     
         15 . The method of  claim 1 , wherein the disease or condition is transplant rejection, and the diseased cells are lymphocytes that bind to transplanted cells. 
     
     
         16 . The method of  claim 15 , wherein the therapeutic agent is capable of effecting an immune response in the patient. 
     
     
         17 . The method of  claim 14 , wherein the therapeutic agent stimulates complement-mediated immune response. 
     
     
         18 . The method of  claim 17 , wherein the therapeutic agent is C3 convertase. 
     
     
         19 . The method of  claim 1 , wherein the isolating step comprises cloning an oligonucleotide corresponding to the mRNA of the identified mRNA-protein pair, and expressing protein from the oligonucleotide. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 18 , wherein the cross-linker is placed on a codon. 
     
     
         22 . The method of  claim 18 , wherein the cross-linker is placed on a pseudo-stop codon. 
     
     
         23 . The method of  claim 18 , wherein the cross-linker comprises a psoralen cross-linker, and the linking comprises exposing the mRNA to UV light. 
     
     
         24 . The method of  claim 18 , wherein the translating is performed in vitro. 
     
     
         25 . The method of  claim 18 , wherein at least one of the candidate mRNA molecules and at least one the translated proteins is linked by a tRNA molecule selected from the group consisting of tRNA, modified tRNA, and tRNA analogs. 
     
     
         26 . The method of  claim 18 , wherein the disease or condition is a cancer, and the diseased cells are malignant cells. 
     
     
         27 . The method of  claim 24 , wherein the disease or condition is a hematological cancer, and the malignant cells comprise lymphocytes. 
     
     
         28 . The method of  claim 18 , wherein the disease or condition is a pathogenic infection, and the diseased cells are cells infected with a pathogen. 
     
     
         29 . The method of  claim 18 , wherein the disease or condition is transplant rejection, and the diseased cells are transplanted cells. 
     
     
         30 . The method of  claim 27 , wherein the therapeutic agent is capable of suppressing an immune response in the patient. 
     
     
         31 . The method of  claim 18 , wherein the disease or condition is transplant rejection, and the diseased cells are lymphocytes that bind to transplanted cells 
     
     
         32 . The method of  claim 29 , wherein the therapeutic agent is capable of effecting an immune response in the patient. 
     
     
         33 . The method of  claim 18 , wherein the therapeutic agent is a cytotoxic agent. 
     
     
         34 . The method of  claim 18 , wherein the therapeutic agent is capable of effecting an immune response in the patient. 
     
     
         35 - 43 . (canceled)

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