Method of treating or preventing ischemia-reperfusion injury

Abstract

The present disclosure relates to a method for preventing or treating ischemia-reperfusion injury in a subject the method comprising administering a compound that inhibits granulocyte colony stimulating factor (G-CSF) signaling. In some examples, the ischemia-reperfusion injury is due to or associated with tissue or organ transplantation. In some examples, the compound is an antibody.

1 . A method for preventing or treating ischemia-reperfusion injury in a subject, the method comprising administering a compound that inhibits granulocyte colony stimulating factor (G-CSF) signaling. 
     
     
         2 . The method of  claim 1 , wherein the ischemia-reperfusion injury is due to or associated with tissue or organ transplantation. 
     
     
         3 . The method of  claim 2 , wherein the organ transplantation is a kidney transplantation. 
     
     
         4 . The method of  claim 2 , wherein the compound that inhibits G-CSF signaling is administered to the subject, wherein the subject is a tissue or organ transplantation recipient. 
     
     
         5 . The method of  claim 2 , wherein the compound that inhibits G-CSF signaling is administered to a tissue or organ transplantation donor prior to organ collection and/or to a tissue or organ prior to transplantation. 
     
     
         6 . A method of tissue or organ transplantation or for improving outcome of a tissue or organ transplantation or improving function of a transplanted tissue or organ or for preventing delayed graft function, the method comprising:
 a) administering a compound that inhibits G-CSF signaling to a tissue or organ transplant recipient prior to or at the time of transplanting the tissue or organ and then transplanting the tissue or organ into the tissue or organ transplant recipient   b) administering a compound that inhibits G-CSF signaling to a tissue or organ transplant donor prior to collection of the tissue or organ; collecting the tissue or organ and transplanting the tissue or organ into a tissue or organ transplant recipient; or   c) administering a compound that inhibits G-CSF signaling to a harvested tissue or organ ex vivo and transplanting the harvested tissue or organ into a tissue or organ transplant recipient.   
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the compound that inhibits G-CSF signaling is administered before ischemia or reperfusion. 
     
     
         10 . The method of  claim 9 , wherein the compound that inhibits G-CSF signaling is administered between 0 and 48 hours before ischemia or reperfusion. 
     
     
         11 . The method of  claim 9 , wherein the compound that inhibits G-CSF signaling is administered about 24 hours before ischemia or reperfusion. 
     
     
         12 . The method of  claim 1 , wherein the ischemia-reperfusion injury is due to or associated with one or more of the following:
 (i) organ transplantation;   (ii) surgery;   (iii) trauma;   (iv) sepsis;   (v) a tumor; and   (vi) stroke.   
     
     
         13 . The method of  claim 1 , wherein the compound that inhibits G-CSF signaling is administered in an amount sufficient to reduce or prevent inflammation. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the compound that inhibits G-CSF signaling binds to G-CSF or G-CSF receptor (G-CSFR). 
     
     
         18 . The method of  claim 17 , wherein the compound that inhibits G-CSF signaling is a protein comprising an antibody variable region that binds to or specifically binds to G-CSF or G-CSFR and neutralizes G-CSF signaling. 
     
     
         19 . The method of  claim 18 , wherein the compound that inhibits G-CSF signaling is a protein comprising a Fv. 
     
     
         20 . The method of  claim 19 , wherein the protein is selected from the group consisting of:
 (i) a single chain Fv fragment (scFv);   (ii) a dimeric scFv (di-scFv); or   (iv) a diabody;   (v) a triabody;   (vi) a tetrabody;   (vii) a Fab;   (viii) a F(ab′) 2 ;   (ix) a Fv;   (x) one of (i) to (ix) linked to a constant region of an antibody, Fc or a heavy chain constant domain (C H ) 2 and/or C H 3;   (xi) one of (i) to (ix) linked to albumin or a functional fragment or variants thereof or a protein that binds to albumin; or   (xii) an antibody.   
     
     
         21 . The method of  claim 18 , wherein the protein comprises an antibody variable region that binds to or specifically binds to G-CSFR and competitively inhibits the binding of antibody C1.2G comprising a heavy chain variable region (V H ) comprising a sequence set forth in SEQ ID NO: 4 and a light chain variable region (V L ) comprising a sequence set forth in SEQ ID NO: 5 to G-CSFR. 
     
     
         22 . The method of  claim 18 , wherein the protein binds to an epitope comprising residues within one or two or three or four regions selected from 111-115, 170-176, 218-234 and/or 286-300 of SEQ ID NO: 1. 
     
     
         23 . The method of  claim 18 , wherein the protein is an antibody comprising a heavy chain variable region (VH) comprising an amino acid sequence set forth in SEQ ID NO: 4 and a light chain variable region (VL) comprising an amino acid sequence set forth in SEQ ID NO: 5. 
     
     
         24 . The method of  claim 18 , wherein the protein is an antibody comprising a VH comprising an amino acid sequence set forth in SEQ ID NO: 2 and a VL comprising an amino acid sequence set forth in SEQ ID NO: 3. 
     
     
         25 . The method of  claim 18 , wherein the protein is an antibody comprising a VH comprising three CDRs of a VH comprising an amino acid sequence set forth in SEQ ID NO: 4 and a VL comprising three CDRs of a VL comprising an amino acid sequence set forth in SEQ ID NO: 5. 
     
     
         26 . (canceled)