Ornithodoros moubata complement inhibitor for use in the treatment of acute graft versus host disease

Abstract

The present invention relates to methods of treating or preventing acute GVHD, comprising systemically administering to a subject in need thereof a therapeutically or prophylactically effective amount of an agent which is a protein comprising amino acids 19 to 168 of the amino acid sequence in FIG. 2 (SEQ ID NO: 2) or a functional equivalent of this protein.

1 . A method of treating or preventing acute GVHD, comprising systemically administering to a subject in need thereof a therapeutically or prophylactically effective amount of an agent which is a protein comprising amino acids 19 to 168 of the amino acid sequence in  FIG. 2  (SEQ ID NO: 2) or a functional equivalent of this protein. 
     
     
         2 . An agent which is a protein comprising amino acids 19 to 168 of the amino acid sequence in  FIG. 2  (SEQ ID NO: 2) or a functional equivalent of this protein.for treating or preventing acute GVHD in a subject, wherein the agent is administered systemically. 
     
     
         3 . A method of treating or preventing acute GVHD comprising systemically administering to a subject in need thereof a therapeutically or prophylactically effective amount of an agent which is a nucleic acid molecule encoding a protein comprising amino acids 19 to 168 of the amino acid sequence in  FIG. 2  (SEQ ID NO: 2) or a functional equivalent of this protein. 
     
     
         4 . An agent which is a nucleic acid molecule encoding a protein comprising amino acids 19 to 168 of the amino acid sequence in  FIG. 2  (SEQ ID NO: 2) or a functional equivalent of this protein.for treating or preventing GVHD in a subject, wherein the agent is administered systemically. 
     
     
         5 . The method of  claim 1  or  3  or the agent of  claim 2  or  4  wherein the subject does not have or has not been tested for a complement C5 polymorphism. 
     
     
         6 . The method of any one of  claims 1 ,  3  and  5 , or the agent of any one of  claims 2 ,  4 , and  5  wherein the subject does not have or has not been tested for a complement C5 polymorphism which decreases the effectiveness of monoclonal antibody agents in inhibiting activation of one or more of the complement pathways, such as a complement C5 polymorphism which decreases the effectiveness of the monoclonal antibody eculizumab in inhibiting activation of one or more of the complement pathways. 
     
     
         7 . The method of any one of  claims 1 ,  3  and  5 , or the agent of any one of  claims 2 ,  4 , and  5 , wherein the subject does not have or has not been tested for a complement C5 polymorphism which decreases the effectiveness of one or more agents that inhibit the classical complement pathway, the alternative complement pathway and the lectin complement pathway, but does not decrease the effectiveness of Coversin or functional equivalents thereof. 
     
     
         8 . The method of any one of  claims 1  and  3  to  7  or the agent of any one of  claims 2  and  4  to  7 , wherein the subject does not have or has not been tested for a complement C5 polymorphisms which increases the affinity of another agent, such as eculizumab, for the C5 protein. 
     
     
         9 . The method of any one of  claims 1  and  3  to  8  or agent of any one of  claims 2  and  4  to  8 , wherein the subject does not have or has not been tested for resistance to monoclonal antibody agent treatment wherein the treatment is intended to inhibit activation of one or more of the complement pathways, preferably wherein the monoclonal antibody is eculizumab. 
     
     
         10 . The method of any one of  claims 1  and  3  to  9  or agent of any one of  claims 2  and  4  to  9 , wherein the subject has not been treated with a monoclonal antibody agent treatment wherein the monoclonal antibody is intended to inhibit activation of one or more of the complement pathways. 
     
     
         11 . The method of any one of  claims 1  and  3  to  10  or the agent of any one of  claims 2  and  4  to  10 , wherein the subject has not been treated with eculizumab. 
     
     
         12 . The method of any one of  claims 1  and  3  to  11  or the agent of any one of  claims 2  and  4  to  11 , wherein the subject has not been selected for treatment with the agent of the invention on the basis of decreased effectiveness in the subject of a different agent, such as anti C5 antibody. 
     
     
         13 . The method of any one of  claims 1  and  3  to  12  or agent of any one of  claims 2  and  4  to  12 , wherein the subject has a GVHD symptom at stage +, ++, +++ or ++++ and/or the subject has a clinical grading of I, II, III or IV, 
     
     
         14 . The method of any one of  claims 1  and  3  to  12  or agent of any one of  claims 2  and  4  to  12 , wherein the subject has tissue damage, e.g. internal (such as intestinal) tissue damage arising from the GVHD. 
     
     
         15 . The method of any one of  claims 1  and  3  to  14  or agent of any one of  claims 2  and  4  to  14 , wherein the subject
 i. has acute GVHD following allogenic haematopoietic cell transplant (HCT), and/or 
 ii. has received no GVHD prophylaxis, 
 iii. is at least 5 years old, 
 iv. has received HLA-nonidentical stem cells, 
 v. has acute GVHD following solid-organ transplantation, or following transfusion of unirradiated blood products, 
 vi. has acute GVHD after autologous or syngeneic HCT. 
 
     
     
         16 . The method of any one of  claims 1  and  3  to  15  or agent of any one of  claims 2  and  4  to  14 , wherein the subject has hyperacute GVHD. 
     
     
         17 . The method of any one of  claims 1  and  3  to  16  or agent of any one of  claims 2  and  4  to  16 , wherein the treatment is continued
 i. for at least 6 weeks, and/or 
 ii. until the subject is no longer considered to be suffering from acute GVHD, and/or 
 iii. until the subject no longer requires treatment.