Abstract: A method of reducing a cerebral tissue pathology associated with a sickle cell disease therapy in a subject is provided using (i) a synthetic high-oxygen affinity hemoglobin-containing molecule or (ii) synthetically treated high-oxygen affinity blood.

Abstract: A method of reducing a cerebral tissue pathology associated with a sickle cell disease therapy in a subject is provided using (i) a synthetic high-oxygen affinity hemoglobin-containing molecule or (ii) synthetically treated high-oxygen affinity blood.

Abstract: Described herein are semisynthetic biopolymers comprising: a plurality of polyalkylene glycol chains, a protein, and an antioxidant; wherein the polyalkylene glycol chains are conjugated to the protein through a substituted succinimide linker. In some embodiments, the compounds described herein are conjugated proteins referred to as “semisynthetic supra perfusion agents”, “semisynthetic hybrid biopolymers”, “semisynthetic supra plasma expanders”, or the like. In some embodiments, these compounds mimic the same physiological consequences of high viscosity supra plasma expanders without being highly viscous—i.e. having a viscosity greater than blood.

Abstract: The present invention relates to treatments and therapies for anemia conditions and diseases of the blood, and more particular is a therapy for the acute and chronic treatment of sickle cell diseases and thalassemia by administration of pyridoxamine, or a pharmaceutically acceptable salt thereof, optionally in combination with an additional bioactive agent.

Abstract: A method of improving the efficacy of a blood transfusion into a subject is provided comprising administering a composition comprising an EAF PEGylated-blood protein into the subject, prior to, during, or subsequent to the blood transfusion.

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: A method of improving the efficacy of a blood transfusion into a subject is provided comprising administering a composition comprising an EAF PEGylated-blood protein into the subject, prior to, during, or subsequent to the blood transfusion.

Abstract: A method of improving the efficacy of a blood transfusion into a subject is provided comprising administering a composition comprising an EAF PEGylated-blood protein into the subject, prior to, during, or subsequent to the blood transfusion.

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: Provided are hemoglobins having at least two chemical modifications that lower oxygen affinity, hemoglobins chemically modified by the addition of glyceraldehyde-3-phosphate, and hemoglobins having at least two specific chemical modifications. PEGylated versions of these hemoglobins are also provided, as are certain tetraPEGylated and diPEGylated hemoglobins. Methods of modifying a hemoglobin are additionally provided, as are methods of making a hemoglobin. Pharmaceutical compositions and blood substitutes using these hemoglobins are further provided, as are methods of treating a subject using these pharmaceutical compositions and blood substitutes.

Abstract: A method of improving the efficacy of a blood transfusion into a subject is provided comprising administering a composition comprising an EAF PEGylated-blood protein into the subject, prior to, during, or subsequent to the blood transfusion.

Abstract: The present invention is directed to uses of PEGylated albumins which include methods of treating reduced functional capillary density, reduced blood volume, septic shock and cardiac arrhythmia in a subject, which comprise administering to the subject a therapeutically effective amount of a PEGylated albumin.

Abstract: The present invention is directed to uses of PEGylated albumins which include methods of treating reduced functional capillary density, reduced blood volume, septic shock and cardiac arrhythmia in a subject, which comprise administering to the subject a therapeutically effective amount of a PEGylated albumin.

Abstract: Provided are hemoglobins having at least two chemical modifications that lower oxygen affinity, hemoglobins chemically modified by the addition of glyceraldehyde-3-phosphate, and hemoglobins having at least two specific chemical modifications. PEGylated versions of these hemoglobins are also provided, as are certain tetraPEGylated and diPEGylated hemoglobins. Methods of modifying a hemoglobin are additionally provided, as are methods of making a hemoglobin. Pharmaceutical compositions and blood substitutes using these hemoglobins are further provided, as are methods of treating a subject using these pharmaceutical compositions and blood substitutes.

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: The present invention provides pegylated hemoglobins comprising a maleimide polyethylene glycol (PEG) conjugated to a thiol moiety of a cysteine residue of hemoglobin, methods of preparing the pegylated hemoglobins, compositions and blood substitutes comprising the pegylated hemoglobins, and methods of treating a subject which comprise administering to the subject blood substitutes comprising vasoinactive pegylated hemoglobins.

Abstract: The present invention is directed to pegylated red blood cells comprising a polyethylene glycol (PEG) attached to a thiolated amino group on a membrane protein, and to compositions comprising the pegylated red blood cells. The invention also provides methods of preparing pegylated red blood cells comprising reacting red blood cells with a compound that produces a thiolated amino group on a red blood cell membrane protein, and reacting the thiolated red blood cell with a PEG. The invention further provides methods of treatment using pegylated red blood cells.

Abstract: The present invention provides a hemoglobin molecule (Hb) having six ± one PEG chains, wherein two of said PEG chains are bound to Cys-93 (?) of Hb, and the remaining PEG chains are bound to thiol groups introduced on ?-NH2 of Hb. The present invention also provides a process for preparing a modified hemoglobin molecule (Hb), comprising the steps of: (a) reacting Hb with 8-15 fold excess of iminothiolane to form thiolated Hb; and (b) reacting the thiolated Hb with 16-30 fold excess of PEG functionalized with a maleimide moiety, to form the modified Hb.

Abstract: Novel modified hemoglobins comprising polyalkylene glycols and novel methods for making those hemoglobins are provided. One group of modified hemoglobins comprise polyalkylene glycols bonded to the hemoglobin with an amide linkage at Glu-43(?). Additional polyalkylene glycols can also be bonded to the Glu-22(?) and/or the Asp-47(?). These hemoglobins are made by a novel amidation procedure. A second group of modified hemoglobins comprise a polyalkylene glycol covalently bonded to the hemoglobin at the ?-amino of a Val-1(?) or a Val-1(?). Additional polyalkylene glycols can optionally be covalently bonded to a limited number of ?-amino groups. This second group of hemoglobins is made using a novel reductive alkylation procedure. A third group of modified hemoglobins comprise a polyalkylene glycol bonded to a thiol group of the hemoglobin through a phenylsuccinimido linkage, wherein no polyalkylene glycol is bonded to a Cys-93(?).