The present invention concerns a neuroglobin agonist for use in the treatment or prevention of a mitochondrial disease associated with respiratory chain complex I (RCCI) deficiency and/or respiratory chain complex III (RCCIII) deficiency.

The present invention concerns a neuroglobin agonist for use in the treatment or prevention of a mitochondrial disease associated with respiratory chain complex I (RCCI) deficiency and/or respiratory chain complex III (RCCIII) deficiency.

The present invention refers to an oxygen carrier, preferably hemoglobin or myoglobin, for use in the treatment of an unpleasant feeling of a body surface due to a disease or a disorder.

The present invention refers to an oxygen carrier, preferably hemoglobin or myoglobin, for use in the treatment of an unpleasant feeling of a body surface due to a disease or a disorder.

The invention relates to hemoglobin derivative, particularly hemoglobin which is co-conjugated with both fatty acid-linked polyethylene glycol (FA-PEG) derivatives and alkoxy polyethylene glycol (alkoxy-PEG) derivatives, and a method for making such hemoglobin derivative. Various embodiments of the invention include crosslinked hemoglobin which is co-conjugated with both FA-PEG derivatives and alkoxy-PEG derivatives. Such hemoglobin derivative according to the invention exhibit non-toxicity and extended intravascular retention time.

The invention relates to hemoglobin derivative, particularly hemoglobin which is co-conjugated with both fatty acid-linked polyethylene glycol (FA-PEG) derivatives and alkoxy polyethylene glycol (alkoxy-PEG) derivatives, and a method for making such hemoglobin derivative. Various embodiments of the invention include crosslinked hemoglobin which is co-conjugated with both FA-PEG derivatives and alkoxy-PEG derivatives. Such hemoglobin derivative according to the invention exhibit non-toxicity and extended intravascular retention time.

Certain aspects of the present invention relate to modified proteins e.g. oxygen-carrying proteins, comprising at least one modification for homogenous conjugation of one or more polymeric moieties e.g. polyethylene glycol or derivatives thereof.

Certain aspects of the present invention relate to modified proteins e.g. oxygen-carrying proteins, comprising at least one modification for homogenous conjugation of one or more polymeric moieties e.g. polyethylene glycol or derivatives thereof.

The present invention relates to succinimide-activated nitroxyl compounds and methods for the synthesis of such compounds. The present invention also relates to the use of succinimide-activated nitroxyl compounds to prepare nitroxylated proteins, for example nitroxylated heme proteins (e.g., nitroxylated hemoglobin and nitroxylated myoglobin). The nitroxylated proteins are optionally also conjugated to a polyalkylene oxide (PAO), for example to a polyethylene glycol (PEG). Polynitroxylated heme proteins are useful as oxygen therapeutic agents (OTAs). The invention further relates to pharmaceutical compositions of the nitroxylated proteins and methods for the use of nitroxylated proteins in the treatment of various conditions.

The present invention relates to succinimide-activated nitroxyl compounds and methods for the synthesis of such compounds. The present invention also relates to the use of succinimide-activated nitroxyl compounds to prepare nitroxylated proteins, for example nitroxylated heme proteins (e.g., nitroxylated hemoglobin and nitroxylated myoglobin). The nitroxylated proteins are optionally also conjugated to a polyalkylene oxide (PAO), for example to a polyethylene glycol (PEG). Polynitroxylated heme proteins are useful as oxygen therapeutic agents (OTAs). The invention further relates to pharmaceutical compositions of the nitroxylated proteins and methods for the use of nitroxylated proteins in the treatment of various conditions.