Tissue-protective cytokines for the protection, restoration and enhancement of responsive cells, tissues and organs

Abstract

Methods and compositions are provided for protecting or enhancing a responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of a tissue protective cytokine.

1 .- 49 . (canceled) 
     
     
         50 . A method for treating or protecting against tissue injury in a mammal, comprising administering to a mammal in need thereof a carbamylated erythropoietin having at least one carbamylated lysine residue or carbamylated N-terminal amino group, wherein said carbamylated erythropoietin has: (a) a reduced level of in vivo erythropoietic activity compared to native erythropoietin as determined by the exhypoxic polycythemic mouse bioassay, and (b) tissue protective activity in vivo as determined by the middle cerebral artery occlusion test, and wherein the injury is caused by stroke. 
     
     
         51 . The method of  claim 50  wherein said carbamylated erythropoietin is selected from the group comprising alpha-N-carbamoylerythropoietin; N-epsilon-carbamoylerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylerythropoietin; alpha-N-carbamoylasialoerythropoietin; N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoylhyposialoerythropoietin; N-epsilon-carbamoylhyposialoerythropoietin; or alpha-N-carbamoyl, N-epsilon-carbamoylhyposialoerythropoietin. 
     
     
         52 . A method for treating or protecting against issue injury in a mammal, comprising administering to a mammal in need thereof a carbamylated erythropoietin having at least one carbamylated lysine residue or carbamylated N-terminal amino group, wherein said carbamylated erythropoietin has: (a) a reduced level of in vivo erythropoietic activity compared to native erythropoietin as determined by the exhypoxic polycythemic mouse bioassay, and (b) tissue protective activity in vivo as determined by the middle cerebral artery occlusion test, and wherein the injury is caused by cerebral ischemia. 
     
     
         53 . The method of  claim 52  wherein said carbamylated erythropoietin is selected from the group comprising alpha-N-carbamoylerythropoietin; N-epsilon-carbamoylerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylerythropoietin; alpha-N-carbamoylasialoerythropoietin; N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoylhyposialoerythropoietin; N-epsilon-carbamoylhyposialoerythropoietin; or alpha-N-carbamoyl, N-epsilon-carbamoylhyposialoerythropoietin. 
     
     
         54 . A method for treating or protecting against tissue injury comprising administering to a mammal in need thereof carbamylated erythropoietin having at least one carbamylated lysine residue or carbamylated N-terminal amino group, wherein said carbamylated erythropoietin has: (a) a reduced level of in vivo erythropoietic activity compared to native erythropoietin as determined by the exhypoxic polycythemic mouse bioassay, and (b) tissue protective activity in vivo as determined by the middle cerebral artery occlusion test, and wherein the injury is caused by retinal ischemia. 
     
     
         55 . The method of  claim 54  wherein said carbamylated erythropoietin is selected from the group comprising alpha-N-carbamoylerythropoietin; N-epsilon-carbamoylerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylerythropoietin; alpha-N-carbamoylasialoerythropoietin; N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoyl, N-epsilon-carbamoylasialoerythropoietin; alpha-N-carbamoylhyposialoerythropoietin; N-epsilon-carbamoylhyposialoerythropoietin; or alpha-N-carbamoyl, N-epsilon-carbamoylhyposialoerythropoietin.