Patent classifications
A61K38/51
CHONDROITINASE ABC MUTANTS AND METHODS OF MANUFACTURE AND USE THEREOF
The present application provides a Chondroitinase ABC (ChABC) mutants. ChABC stimulates axonal regeneration by degrading the inhibitory chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans in the glial scar that forms after traumatic injuries to the central nervous system (CNS). However, the therapeutic utility of this potent, fragile protein is severely limited by rapid aggregation at physiological temperature. To overcome this limitation, the ChABC mutants were engineered to at least 15 point mutations in domain 2 of the wild-type ChABC and/or at least 5 point mutations in domain 3 of the wild-type enzyme. These mutants exhibit improved stability over wild-type ChABC. The present application further provides method and compositions comprising the mutant ChABC for treating conditions associated with excess proteoglycan formation or conditions for which treatment is benefitted by degradation of proteoglycans, including CNS injuries, scarring and cancer.
CHONDROITINASE ABC MUTANTS AND METHODS OF MANUFACTURE AND USE THEREOF
The present application provides a Chondroitinase ABC (ChABC) mutants. ChABC stimulates axonal regeneration by degrading the inhibitory chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans in the glial scar that forms after traumatic injuries to the central nervous system (CNS). However, the therapeutic utility of this potent, fragile protein is severely limited by rapid aggregation at physiological temperature. To overcome this limitation, the ChABC mutants were engineered to at least 15 point mutations in domain 2 of the wild-type ChABC and/or at least 5 point mutations in domain 3 of the wild-type enzyme. These mutants exhibit improved stability over wild-type ChABC. The present application further provides method and compositions comprising the mutant ChABC for treating conditions associated with excess proteoglycan formation or conditions for which treatment is benefitted by degradation of proteoglycans, including CNS injuries, scarring and cancer.
IN VIVO USE OF CHONDROITINASE AND/OR HYALURONIDASE TO ENHANCE DELIVERY OF AN AGENT
Disclosed herein are methods of delivering an agent to a subject. Further disclosed herein are methods of treating a disease or disorder in a subject. The methods may include administering to the subject a chondroitinase polypeptide or a polynucleotide encoding a chondroitinase polypeptide in an amount sufficient to degrade glycosaminoglycans, and administering to the subject the agent. The methods may further include administering a hyaluronidase polypeptide or a polynucleotide encoding a hyaluronidase.
IN VIVO USE OF CHONDROITINASE AND/OR HYALURONIDASE TO ENHANCE DELIVERY OF AN AGENT
Disclosed herein are methods of delivering an agent to a subject. Further disclosed herein are methods of treating a disease or disorder in a subject. The methods may include administering to the subject a chondroitinase polypeptide or a polynucleotide encoding a chondroitinase polypeptide in an amount sufficient to degrade glycosaminoglycans, and administering to the subject the agent. The methods may further include administering a hyaluronidase polypeptide or a polynucleotide encoding a hyaluronidase.
ORALLY ADMINISTERED COMPOSITION TO LOWER SERUM METHIONINE LEVELS AND METHOD OF USE
A composition and method for lowing serum and plasma levels of methionine by oral administration. The composition includes a recombinant methioninase enzyme and a cofactor (pyridoxal-L-phosphate). Methods of use describe methods for treatment of cancer, including malignant melanoma, by oral administration of the methioninase composition. Methods for chronic suppressive therapy of melanoma and other cancers are described. Because reduction of plasma methionine levels is effective in treating other conditions, including diabetes and conditions associated with aging, the use of the methods described herein includes treatment of these and other conditions.
ORALLY ADMINISTERED COMPOSITION TO LOWER SERUM METHIONINE LEVELS AND METHOD OF USE
A composition and method for lowing serum and plasma levels of methionine by oral administration. The composition includes a recombinant methioninase enzyme and a cofactor (pyridoxal-L-phosphate). Methods of use describe methods for treatment of cancer, including malignant melanoma, by oral administration of the methioninase composition. Methods for chronic suppressive therapy of melanoma and other cancers are described. Because reduction of plasma methionine levels is effective in treating other conditions, including diabetes and conditions associated with aging, the use of the methods described herein includes treatment of these and other conditions.
CARBONIC ANHYDRASE II COMPOSITIONS AND METHODS OF USE THEREOF
Provided herein are compositions of carbonic anhydrase and inhibitors thereof for the treatment of subjects with certain conditions such as heart disease.
CARBONIC ANHYDRASE II COMPOSITIONS AND METHODS OF USE THEREOF
Provided herein are compositions of carbonic anhydrase and inhibitors thereof for the treatment of subjects with certain conditions such as heart disease.
CARBONIC ANHYDRASE II COMPOSITIONS AND METHODS OF USE THEREOF
Provided herein are compositions of carbonic anhydrase and inhibitors thereof for the treatment of subjects with certain conditions such as heart disease.
High efficiency oxalate-degrading enzymes for degradation of insoluble and soluble oxalate
Disclosed herein are oxalate inducing enzymes with pH and thermal stability and methods of using for oxalate related conditions for in food processing.