US2009130092A1PendingUtilityA1

Nucleotide phosphate dissipation as a treatment for vascular disorders

38
Individually held — no corporate assignee on recordPriority: Oct 30, 2007Filed: Oct 30, 2008Published: May 21, 2009
Est. expiryOct 30, 2027(~1.3 yrs left)· nominal 20-yr term from priority
Inventors:David PinskyDanica Petrovic-Djergovic
C12Y 301/03005A61K 38/465
38
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Claims

Abstract

The present invention provides a method of treating or preventing immunoinflammatory, vascular, thrombotic or ischemic disorders in a subject, the method comprises administering to the subject an agent which dissipates nucleotide phosphates or generates a product which stimulates adenosine receptors. The present invention also provides a method of treating or preventing immunoinflammatory, thrombotic or ischemic disorders in a subject by inhibiting leukocyte infiltration into a site which comprises administering to the subject an effective amount a described agent. Agents described for use in the methods of the invention include CD73, a fragment a mutant, or a modified form thereof.

Claims

exact text as granted — not AI-modified
1 . A method of treating or preventing a vascular, thrombotic, ischemic, or immunoinflammatory disorder in a subject, the method comprising administering to the subject a composition comprising an effective amount of one or more agents which dissipate nucleotide monophosphate; with the proviso that when said composition comprises only one agent that dissipates nucleotide monophosphate, and said only one agent is soluble CD73, said disorder is not acute myocardial infarction or renal ischemia. 
     
     
         2 . A method according to  claim 1 , wherein the one or more agent is CD73, or a fragment, a mutant, or modified form thereof. 
     
     
         3 . A method according to  claim 1 , wherein the one or more agent is a catalytic antibody which mimics the action of CD73. 
     
     
         4 . A method of treating or preventing a thrombotic, ischemic, or immunoinflammatory disorder in a subject by inhibiting leukocyte infiltration into a site of said disorder in the subject which comprises administering to the subject a composition comprising an effective amount of CD73, a fragment a mutant, or a modified form thereof. 
     
     
         5 . The method according to  claim 4  wherein said leukocyte is a macrophage. 
     
     
         6 . A method for inhibiting leukocyte infiltration into a site in a subject which comprises administering to the subject a composition comprising a compound that increases endogenous CD73 levels in said subject by said administration. 
     
     
         7 . The method according to  claim 6  wherein said leukocyte is a macrophage. 
     
     
         8 . The method according to  claim 1 , wherein said disorder is cerebrovascular ischemia. 
     
     
         9 . The method according to  claim 1 , wherein said subject is recipient of a heart transplant and said disorder is graft rejection. 
     
     
         10 . The method according to  claim 1 , wherein said subject is recipient of a lung transplant and said disorder is graft rejection. 
     
     
         11 . The method according to  claim 1 , wherein said subject is recipient of a heart transplant and said disorder is graft vasculopathy. 
     
     
         12 . The method according to  claim 1 , wherein the agent is a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c).   
     
     
         13 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one A 2a  adenosine receptor agonist. 
     
     
         14 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one A 2B  adenosine receptor agonist. 
     
     
         15 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises and at least one A 2 A receptor agonist; and wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         16 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one agent selected from an A 2B AR receptor agonist; and wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         17 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one A 2 A receptor agonist; and wherein said subject is recipient of a lung transplant and said disorder is graft rejection 
     
     
         18 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one A 2B AR receptor agonist; and wherein said subject is recipient of a heart transplant and said disorder is graft rejection. 
     
     
         19 . The method according to  claim 1 , wherein the composition comprises a polypeptide selected from the group consisting of:
 a) CD73 polypeptide from  Crotalus atrox  venom;   b) CD73 polypeptide set forth in SEQ ID NO: 1,   c) CD73 polypeptide set forth in SEQ ID NO: 3, and   d) a fragment, a mutant, or modified form of a CD73 polypeptide set forth in a), b), or c);   
       and further comprises at least one A 2B AR receptor agonist; and wherein said subject is recipient of a heart transplant and said disorder is graft vasculopathy.

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