US2003144358A1PendingUtilityA1

Method for inhibiting complement activation

37
Priority: Feb 1, 2000Filed: Dec 2, 2002Published: Jul 31, 2003
Est. expiryFeb 1, 2020(expired)· nominal 20-yr term from priority
Inventors:Richard N. Pierson, IiiGeorge L. Zorn, IiiTodd D. GiorgioSimon RobsonAgnes M. Azimzadeh
A61P 37/06C07K 16/2848A61K 31/00C07K 16/2896A61K 38/1703A61K 35/42A61K 38/58A61K 35/22
37
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Claims

Abstract

A method of inhibiting complement activation, particularly by a transplanted tissue, in a warm-blooded vertebrate. The method includes administering a therapeutically effective amount of a platelet activity modulator to a warm-blooded vertebrate before, during or after a tissue is transplanted to the warm-blooded vertebrate, whereby complement activation by the transplanted tissue is inhibited. The platelet activity modulator can include a combination of a GPIb modulator and a GPIIb/GPIIIa modulator.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of inhibiting complement activation in a warm-blooded vertebrate in which said inhibition is desired, the method comprising administering a therapeutically effective amount of a platelet activity modulator to a warm-blooded vertebrate, whereby complement activation is inhibited.  
     
     
         2 . The method of  claim 1 , wherein the platelet activity modulator is selected from the group consisting of a thrombin modulator, a GPIb modulator, a GPIIb/GPIIIa modulator, and combinations thereof.  
     
     
         3 . The method of  claim 1 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 0.01 mg to about 10,000 mg per day.  
     
     
         4 . The method of  claim 2 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 0.1 mg to about 1,000 mg per day.  
     
     
         5 . The method of  claim 3 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 1 mg to about 300 mg per day.  
     
     
         6 . A method of inhibiting complement activation by a transplanted tissue in a warm-blooded vertebrate, the method comprising administering a therapeutically effective amount of a platelet activity modulator to a warm-blooded vertebrate before, during or after a tissue is transplanted to the warm-blooded vertebrate, whereby complement activation by the transplanted tissue is inhibited.  
     
     
         7 . The method of  claim 6 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 0.01 mg to about 10,000 mg per day.  
     
     
         8 . The method of  claim 7 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 0.1 mg to about 1,000 mg per day.  
     
     
         9 . The method of  claim 8 , wherein the therapeutically effective amount of the platelet activity modulator ranges from about 1 mg to about 300 mg per day.  
     
     
         10 . The method of  claim 6 , wherein the transplanted tissue is a vascularized tissue.  
     
     
         11 . The method of  claim 10 , wherein the vascularized tissue is selected from the group consisting of heart, lung, liver, kidney, pancreas and combinations thereof.  
     
     
         12 . The method of  claim 6 , wherein the transplanted tissue is a xenograft tissue.  
     
     
         13 . The method of  claim 12 , wherein the xenograft tissue is a vascularized xenograft tissue.  
     
     
         14 . The method of  claim 13 , wherein the vascularized xenograft tissue is selected from the group consisting of heart, lung, liver, kidney, pancreas and combinations thereof.  
     
     
         15 . The method of  claim 12 , wherein the xenograft tissue is obtained from a donor animal having a deficient platelet activity pathway.  
     
     
         16 . A method of inhibiting rejection of a transplanted tissue in a warm-blooded vertebrate, the method comprising: administering a therapeutically effective amount of a GPIb modulator and a GPIIb/GPIIIa modulator to a warm-blooded vertebrate before, during or after a tissue is transplanted to the warm-blooded vertebrate, whereby rejection of the transplanted tissue is inhibited.  
     
     
         17 . The method of  claim 16 , wherein the therapeutically effective amount of the GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 0.01 mg to about 10,000 mg per day.  
     
     
         18 . The method of  claim 17 , wherein the therapeutically effective amount of GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 0.1 mg to about 1,000 mg per day.  
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective amount of GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 1 mg to about 300 mg per day.  
     
     
         20 . The method of  claim 16 , wherein the transplanted tissue is a vascularized tissue.  
     
     
         21 . The method of  claim 20 , wherein the vascularized tissue is selected from the group consisting of heart, lung, liver, kidney, pancreas and combinations thereof.  
     
     
         22 . The method of  claim 16 , wherein the transplanted tissue is a xenograft tissue.  
     
     
         23 . The method of  claim 22 , wherein the xenograft tissue is a vascularized xenograft tissue.  
     
     
         24 . The method of  claim 23 , wherein the vascularized xenograft tissue is selected from the group consisting of heart, lung, liver, kidney, pancreas and combinations thereof.  
     
     
         25 . The method of  claim 22 , wherein the xenograft tissue is obtained from a donor animal having a deficient platelet activity pathway.  
     
     
         26 . A method of enhancing tolerance of a xenograft transplant in a recipient, the method comprising: administering a therapeutically effective amount of a GPIb modulator and a GPIIb/GPIIIa modulator to a recipient before, during or after the recipient receives a xenograft transplant, whereby tolerance of the xenograft transplant is enhanced.  
     
     
         27 . The method of  claim 26 , wherein the therapeutically effective amount of the GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 0.01 mg to about 10,000 mg per day.  
     
     
         28 . The method of  claim 27 , wherein the therapeutically effective amount of GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 0.1 mg to about 1,000 mg per day.  
     
     
         29 . The method of  claim 28 , wherein the therapeutically effective amount of GPIb modulator and the therapeutically effective amount of the GPIIb/GPIIIa modulator respectively range from about 1 mg to about 300 mg per day.  
     
     
         30 . The method of  claim 26 , wherein the xenograft tissue is a vascularized xenograft tissue.  
     
     
         31 . The method of  claim 30 , wherein the vascularized xenograft tissue is selected from the group consisting of heart, lung, liver, kidney, pancreas and combinations thereof.  
     
     
         32 . The method of  claim 26 , wherein the xenograft tissue is obtained from a donor animal having a deficient platelet activity pathway.  
     
     
         33 . The method of any of claims  1 ,  6 ,  16  and  26 , further comprising administering a therapeutically effective amount of a complement-modulating agent.  
     
     
         34 . The method of either of claims  16  or  26 , wherein the GPIb modulator further comprises a modulator of GPIb/vWF interaction.

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