US2004131616A1PendingUtilityA1

Methods of inhibiting proliferative diseases

57
Assignee: BETH ISRAEL DEACONNESS MEDICALPriority: Jul 6, 1998Filed: Nov 6, 2003Published: Jul 8, 2004
Est. expiryJul 6, 2018(expired)· nominal 20-yr term from priority
Inventors:Vikas P. Sukhatme
C07K 14/4703A61K 39/395A61K 45/06C07K 2317/73A61K 38/00A61P 43/00G01N 2333/495C07K 16/22C07K 14/495A61K 38/1709A61K 38/1793G01N 33/6872G01N 33/5758
57
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Disclosed are methods of inhibiting proliferative diseases characterized by TGF-β-mediated angiogenesis.

Claims

exact text as granted — not AI-modified
1 . A method of inhibiting a proliferative disease in a vertebrate, wherein the proliferative disease is characterized by increased production of endogenous TGF-β by the proliferating cells relative to non-proliferating cells, 
 wherein the disease is further characterized by endogenous TGF-β mediated angiogenesis,  
 wherein the disease is also characterized by cells that do not express TGF-β type II receptor molecules, or cells that express non-functional TGF-β type II receptor molecules,  
 said method comprising inhibiting endogenous TGF-β activity by contacting the proliferating cells with a molecule that inhibits endogenous TGF-β mediated angiogenesis, thereby inhibiting the proliferative disease.  
 
     
     
         2 . The method of  claim 1 , wherein the proliferative disease is selected from the group consisting of benign tumors and malignant tumors.  
     
     
         3 . The method of  claim 1  wherein the inhibition of TGF-β mediated angiogenesis results in the inhibition of tumor growth.  
     
     
         4 . The method of  claim 1  wherein the inhibition of TGF-β mediated angiogenesis results in the regression of an established tumor.  
     
     
         5 . The method of  claim 1  wherein the proliferative disease is a clear-cell renal carcinoma.  
     
     
         6 . The method of  claim 1  wherein the TGF-β is selected from the group consisting of: TGF-β1, TGF-β2, and TGF-β3.  
     
     
         7 . The method of  claim 1  wherein the TGF-β mediated angiogenesis is inhibited by contacting the proliferating cells with a molecule that inhibits TGF-β-mediated angiogenesis.  
     
     
         8 . The method of  claim 1  wherein the TGF-β mediated angiogenesis is inhibited by contacting the proliferating cells with an antibody, or antibody fragment that specifically binds to TGF-β.  
     
     
         9 . The method of  claim 8  wherein the antibody is a polyclonal antibody.  
     
     
         10 . The method of  claim 8  wherein the antibody is a monoclonal antibody.  
     
     
         11 . The method of  claim 1  wherein the TGF-β mediated angiogenesis is inhibited by contacting the cell with a molecule that binds to TGF-β protein.  
     
     
         12 . A method of inhibiting a proliferative disease in a vertebrate, 
 wherein the proliferative disease is characterized by cells that secrete endogenous TGF-β and,    wherein the disease is further characterized by angiogenesis,    wherein the disease is also characterized by cells that do not express TGF-β type II receptor molecules, or cells that express non-functional TGF-β type II receptor molecules,    said method comprising inhibiting endogenous TGF-β activity by contacting the proliferating cells with a molecule that inhibits endogenous TGF-β-mediated angiogenesis in combination with one, or more, additional anti -angiogenic molecules, resulting in the inhibition of endogenous TGF-β mediated angiogenesis and thereby inhibiting the proliferative disease.    
     
     
         13 . The method of  claim 12 , wherein the anti-angiogenic molecule is selected from the group consisting of: angiostatin, endostatin, restin, apomigren, arresten, canstatin and tumstatin.  
     
     
         14 . A method of inhibiting a proliferative disease in a vertebrate, 
 wherein the proliferative disease is characterized by cells that secrete endogenous TGF-β   wherein the disease is further characterized by angiogenesis,    wherein the disease is also characterized by cells that do not express TGF-β type II receptor molecules, or cells that express non-functional TGF-β type II receptor molecules,    said method comprising inhibiting endogenous TGF-β activity by contacting the proliferating cells with a molecule that inhibits endogenous TGF-β activity resulting in inhibition of TGF-β mediated angiogenesis in combination with a chemotherapeutic agent or an immunotherapeutic agent.    
     
     
         15 . A method of inhibiting a proliferative disease in a vertebrate, 
 wherein the proliferative disease is characterized by cells that secrete endogenous TGF-β,    wherein the disease is further characterized by angiogenesis,    wherein the disease is also characterized by cells that do not express TGF-β type II receptor molecules, or cells that express non-functional TGF-β type II receptor molecules,    said method comprising inhibiting endogenous TGF-β activity by contacting the proliferating cells with a molecule that inhibits endogenous TGF-β activity resulting in inhibition of endogenous TGF-β mediated angiogenesis in combination with radiation therapy.    
     
     
         16 . A method of inhibiting tumor metastasis in a vertebrate, 
 wherein the tumor is characterized as secreting endogenous TGF-α,    wherein the tumor is also characterized by cells that do not express TGF-β type II receptor molecules, or cells that express non-functional TGF-β type II receptor molecules,    said method comprising inhibiting angiogenesis, wherein the angiogenesis is mediated by endogenous TGF-β.    
     
     
         17 . A method of inhibiting a proliferative disease in a vertebrate, 
 wherein the proliferative disease is characterized by cells that secrete endogenous TGF-β,    wherein the disease is further characterized by angiogenesis,    wherein the disease is also characterized by cells that do not express TGF-β type II receptor,    said method comprising inhibiting endogenous TGF-β activity by contacting the proliferating cells with less than 5 mg of an anti-TGF-β antibody, resulting in the inhibition of endogenous TGF-β-mediated angiogenesis, thereby inhibiting the proliferative disease.    
     
     
         18 . The method of  claim 17 , wherein the proliferative disease is selected from the group consisting of benign tumors and malignant tumors.  
     
     
         19 . The method of  claim 17 , wherein the inhibition of the TGF-β-mediated angiogenesis results in the inhibition of tumor growth.  
     
     
         20 . The method of  claim 17 , wherein the inhibition of TGF-β-mediated angiogenesis results in the regression of an established tumor.  
     
     
         21 . The method of  claim 17 , wherein the inhibition of TGF-β-mediated angiogenesis results in the inhibition of metastasis.  
     
     
         22 . The method of  claim 17 , wherein the TGF-β is selected from the group consisting of: TGF-β1, TGF-β2 and TGF-β3.  
     
     
         23 . The method of  claim 17 , wherein the antibody is a polyclonal antibody.  
     
     
         24 . The method of  claim 17 , wherein the antibody is a monoclonal antibody.  
     
     
         25 . The method of  claim 17 , wherein the anti-TGF-β antibody is administered in combination with a chemotherapeutic agent or an immunotherapeutic agent.  
     
     
         26 . The method of  claim 17 , wherein the anti-TGF-β antibody is administed in combination with radiation therapy.  
     
     
         27 . A method of inhibiting renal cell carcinoma in a vertebrate, wherein the renal cell carcinoma is characterized by increased production of TGF-β by the renal cell carcinoma cells relative to non-renal cell carcinoma cells and wherein the renal cell carcinoma is further characterized by TGF-β-mediated angiogenesis, said method comprising inhibiting TGF-β activity by contacting the renal cell carcinoma cells with a molecule that inhibits TGF-β-mediated angiogenesis, thereby inhibiting the renal cell carcinoma.  
     
     
         28 . The method of  claim 27  wherein the inhibition of TGF-β-mediated angiogenesis results in the inhibition of tumor growth.  
     
     
         29 . The method of  claim 27  wherein the inhibition of TGF-β-mediated angiogenesis results in the regression of an established tumor.  
     
     
         30 . The method of  claim 27  wherein the TGF-β is selected from the group consisting of: TGF-β1, TGF-β2 and TGF-β3.  
     
     
         31 . The method of  claim 27 , wherein the TGF-β-mediated angiogenesis in inhibited by contacting the renal cell carcinoma cells with a molecule that inhibits TGF-β-mediated angiogenesis.  
     
     
         32 . The method of  claim 31 , wherein the TGF-β-mediated angiogenesis is inhibited by contacting the renal cell carcinoma cells with an antibody, or antibody fragment, that specifically binds to TGF-β.  
     
     
         33 . The method of  claim 32  wherein the antibody is a poLyclonal antibody.  
     
     
         34 . The method of  claim 32  wherein the antibody is a monoclonal antibody.  
     
     
         35 . The method of  claim 27  wherein the TGF-β-mediated angiogenesis is inhibited by contacting the renal cell carcinoma cells with a molecule that binds to TGF-β protein.  
     
     
         36 . A method of inhibiting renal cell carcinoma in a vertebrate wherein the renal cell carcinoma is characterized by cells that secrete TGF-β and the renal cell carcinoma is further characterized by angiogenesis, comprising inhibiting TGF-β activity by contacting the renal cell carcinoma cells with a molecule that inhibits TGF-β-mediated angiogenesis in combination with one, or more, additional anti-angiogenic molecules, resulting in the inhibition of TGF-β-mediated angiogenesis, thereby inhibiting the renal cell carcinoma.  
     
     
         37 . The method of  claim 36  wherein the anti-angiogenic molecule is selected from the group consisting of: angiostatin, endostatin, restin, apomigren, arresten, canstatin and tumstatin.  
     
     
         38 . A method of inhibiting renal cell carcinoma in a vertebrate wherein the renal cell carcinoma is characterized by cells that secrete TGF-β and the renal cell carcinoma is further characterized by angiogenesis, comprising inhibiting TGF-β activity by contacting the renal cell carcinoma cells with a molecule that inhibits TGF-β activity resulting in inhibition of TGF-β-mediated angiogenesis in combination with a chemotherapeutic agent or an immunotherapeutic agent.  
     
     
         39 . A method of inhibiting renal cell carcinoma in a vertebrate wherein the renal cell carcinoma is characterized by cells that secrete TGF-β and the renal cell carcinoma is further characterized by angiogenesis, comprising inhibiting TGF-β activity by contacting the renal cell carcinoma cells with a molecule that inhibits TGF-β activity resulting in inhibition of TGF-β-mediated angiogenesis in combination with radiation therapy.  
     
     
         40 . A method of inhibiting metastasis of a renal cell carcinoma tumor in a vertebrate, wherein the tumor is characterized as secreting TGF-β, said method comprising inhibiting angiogenesis, wherein the angiogenesis is mediated by TGF-β.  
     
     
         41 . A method of inhibiting a proliferative disease in a vertebrate, wherein the proliferative disease is characterized by proliferating cells that express a defective receptor for TGF-β and/or do not express a receptor for TGF-β, and wherein the disease is further characterized by TGF-β-mediated angiogenesis, said method comprising inhibiting TGF-β activity by contacting the proliferating cells with a molecule that inhibits TGF-β-mediated angiogenesis, thereby inhibiting the proliferative disease.  
     
     
         42 . The method of  claim 41  wherein the proliferative disease is selected from the group consisting of benign tumors and malignant tumors.  
     
     
         43 . The method of  claim 41  wherein the inhibition of TGF-β-mediated angiogenesis results in the inhibition of tumor growth.  
     
     
         44 . The method of  claim 41  wherein the inhibition of TGF-β-mediated angiogenesis results in the regression of an established tumor.  
     
     
         45 . The method of  claim 42  wherein the proliferative disease is clear-cell renal carcinoma.  
     
     
         46 . The method of  claim 41  wherein the TGF-β is selected from the group consisting of: TGF-β1, TGF-β2 and TGF-β3.  
     
     
         47 . The method of  claim 41  wherein the TGF-β-mediated angiogenesis in inhibited by contacting the proliferating cells with a molecule that inhibits TGF-β-mediated angiogenesis.  
     
     
         48 . The method of  claim 47  wherein the TGF-β-mediated angiogenesis is inhibited by contacting the proliferating cells with an antibody, or antibody fragment, that specifically binds to TGF-β.  
     
     
         49 . The method of  claim 48  wherein the antibody is a polyclonal antibody.  
     
     
         50 . The method of  claim 48  wherein the antibody is a monoclonal antibody.  
     
     
         51 . The method of  claim 41  wherein the TGF-β-mediated angiogenesis is inhibited by contacting the cell with a molecule that binds to TGF-β protein.  
     
     
         52 . A method of inhibiting a proliferative disease in a vertebrate wherein the proliferative disease is characterized by proliferating cells that express a defective receptor for TGF-β and/or do not express a receptor for TGF-β, and wherein the disease is further characterized by angiogenesis, said method comprising inhibiting TGF-β activity by contacting the proliferating cells with a molecule that inhibits TGF-β-mediated angiogenesis in combination with one, or more, additional anti-angiogenic molecules, resulting in the inhibition of TGF-β-mediated angiogenesis and thereby inhibiting the proliferative disease.  
     
     
         53 . The method of  claim 52  wherein the anti-angiogenic molecule is selected from the group consisting of: angiostatin, endostatin, restin, apomigren, arresten, canstatin and tumstatin.  
     
     
         54 . A method of inhibiting a proliferative disease in a vertebrate wherein the proliferative disease is characterized by proliferating cells that express a defective receptor for TGF-β and/or do not express a receptor for TGF-β, and wherein the disease is further characterized by angiogenesis, said method comprising inhibiting TGF-β activity by contacting the proliferating cells with a molecule that inhibits TGF-β activity resulting in inhibition of TGF-β-mediated angiogenesis in combination with a chemotherapeutic agent or an immunotherapeutic agent.  
     
     
         55 . A method of inhibiting a proliferative disease in a vertebrate wherein the proliferative disease is characterized by proliferating cells that express a defective receptor for TGF-β and/or do not express a receptor for TGF-β, and wherein the disease is further characterized by angiogenesis, said method comprising inhibiting TGF-β activity by contacting the proliferating cells with a molecule that inhibits TGF-β activity resulting in inhibition of TGF-β-mediated angiogenesis in combination with radiation therapy.  
     
     
         56 . A method of inhibiting tumor metastasis in a vertebrate, wherein the tumor is characterized as containing cells that express a defective receptor for TGF-β and/or do not express a receptor for TGF-β, said method comprising inhibiting angiogenesis, wherein the angiogenesis is mediated by TGF-β.  
     
     
         57 . A method of inhibiting renal cell carcinoma in a vertebrate, wherein the renal cell carcinoma is characterized by cells that secrete TGF-β and is further characterized by angiogenesis, said method comprising inhibiting TGF-β activity by contacting the cells with less than 5 mg of an anti-TGF-β antibody, resulting in the inhibition of TGF-β-mediated angiogenesis, thereby inhibiting the renal cell carcinoma.  
     
     
         58 . The method of  claim 57 , wherein the inhibition of TGF-β-mediated angiogenesis results in the inhibition of renal cell carcinoma tumor growth.  
     
     
         59 . The method of  claim 57 , wherein the inhibitor of TGF-β-mediated angiogenesis results in the regression of an established renal cell carcinoma tumor.  
     
     
         60 . The method of  claim 57 , wherein the inhibition of TGF-β-mediated angiogenesis results in the inhibition of renal cell carcinoma metastasis.  
     
     
         61 . The method of  claim 57 , wherein the TGF-β is selected from the group consisting of: TGF-β1, TGF-β2 and TGF-β3.  
     
     
         62 . The method of  claim 57 , wherein the antibody is a polyclonal antibody.  
     
     
         63 . The method of  claim 62 , wherein the antibody is a monoclonal antibody.  
     
     
         64 . The method of  claim 57 , wherein the anti-TGF-β antibody is administered in combination with a chemotherapeutic agent or an immunotherapeutic agent.  
     
     
         65 . The method of  claim 57 , wherein the anti-TGF-β3 antibody is administered in combination with radiation therapy.  
     
     
         66 . The method of  claim 57 , wherein the renal cell carcinoma is characterized by cells that do not express TGF-β type II receptor molecules, or express non-functional TGF-β type II receptor molecules.

Join the waitlist — get patent alerts

Track US2004131616A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.