Abstract: Compositions and methods for the preparation of high purity arginase and high efficiency preparation of monosubstituted polyethylene glycol conjugation of arginase are provided, as are methods for using arginase in combination with asparaginase to inhibit cancer cells. High purity arginase is provided by applying an initial high temperature precipitation step, followed by ion exchange to provide arginase at a purity of 90% or greater. Conjugation with either linear or branched polyethylene glycol is performed using a maleimide-derivatized polyethylene glycol at low molar excess relative to arginase and at reduced temperature. Such polyethylene glycol-derivatized arginase is useful in combination with asparaginase in inhibiting the growth of cancer cells, particularly cells that have low endogenous asparaginase expression.

Abstract: A recombinant arginine deiminase including a fluorescent group attached via an optional linker to the side chain of a cysteine residue useful for qualitative and quantitative detection of L-arginine in a sample, and methods of use and preparation thereof.

Abstract: The invention provides a method for treating acute myeloid leukemia (AML) in a subject in need thereof, said method comprising administering a therapeutically effective amount of an arginine-depleting agent to the subject, wherein the AML is of the French-American-British (FAB) subtype M0 (undifferentiated acute myeloblastic leukemia), M2 (acute myeloblastic leukemia with maturation), M4 (acute myeloblastic leukemia with maturation), M4 eos (acute myelomonocytic leukemia with eosinophilia), M5 (acute monocytic leukemia), M6 (acute erythroid leukemia) or M7 (acute megakaryoblastic leukemia).

Abstract: Compositions and methods for the preparation of high purity arginase and high efficiency preparation of monosubstituted polyethylene glycol conjugation of arginase are provided, as are methods for using arginase in combination with asparaginase to inhibit cancer cells. High purity arginase is provided by applying an initial high temperature precipitation step, followed by ion exchange to provide arginase at a purity of 90% or greater. Conjugation with either linear or branched polyethylene glycol is performed using a maleimide-derivatized polyethylene glycol at low molar excess relative to arginase and at reduced temperature. Such polyethylene glycol-derivatized arginase is useful in combination with asparaginase in inhibiting the growth of cancer cells, particularly cells that have low endogenous asparaginase expression.

Abstract: The present disclosure provides methods for inducing intermittent fasting and modulating autophagy in cells or organs in a subject via periodic administration of arginine-depleting agents. Induction of intermittent fasting and modulation of autophagy are useful in preventing and/or treating diseases, including those associated with deficits in autophagy, promoting the clearance of intracellular pathogens and protein aggregates, and promoting regeneration and longevity. The methods can be used alone or in combination with other agents to enhance intermittent fasting and autophagy activity to potentiate the health benefit(s).

Abstract: The present disclosure relates to arginase albumin binding domain (ABD) fusion proteins and methods of preparation and use thereof. Also provided are methods involving arginine depletion for the treatment of obesity, metabolic disorders, and related complications and comorbidities.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase (AAD) fusion protein for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, binds to human serum albumin (HSA) or animal serum albumin and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD fusion protein in the present invention are about 20 and about 19 U/mg (at physiological pH 7.4), respectively. The composition can be used alone or in combination with at least one chemotherapeutic agent to give a synergistic effect on cancer treatment and/or inhibiting metastasis. The AAD fusion protein can also be used as a component for detection and quantitative analysis of arginine in a testing kit for various samples including blood, food and analytical samples.

Abstract: The present invention provides a site-specific pegylated arginase conjugate and method for producing thereof. The site-specific pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method for producing the arginase conjugate comprises genetically modifying the gene encoding an arginase so that the PEG moiety can be attached to the enzyme at a predetermined, specific intended sites. This is achieved by removing the PEG-attaching amino acid residue(s) at undesirable site(s) while keeping or adding cysteine(s) at the desirable site(s) of the enzyme. Two exemplary embodiments of the pegylated arginase conjugate are directed to human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase (AAD) fusion protein for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) or animal serum albumin and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD fusion protein in the present invention are about 20 and about 19 U/mg (at physiological pH 7.4), respectively. The AAD fusion protein used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, melanoma, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases.

Abstract: The present invention provides an isolated and substantially purified recombinant human arginase having sufficiently high enzymatic activity and stability to maintain Adequate Arginine Depletion in a patient. The present invention also provides a pharmaceutical composition comprising the modified invention enzyme and method for treatment of diseases using the pharmaceutical composition.

Abstract: The present invention provides a site-specific pegylated arginase conjugate and method for producing thereof. The site-specific pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method for producing the arginase conjugate comprises genetically modifying the gene encoding an arginase so that the PEG moiety can be attached to the enzyme at a predetermined, specific intended sites. This is achieved by removing the PEG-attaching amino acid residue(s) at undesirable site(s) while keeping or adding cysteine(s) at the desirable site(s) of the enzyme. Two exemplary embodiments of the pegylated arginase conjugate are directed to human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Abstract: Mono-pegylated arginase conjugate and method producing thereof. The mono-pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method of producing such arginase conjugate has a main step of genetically modifying the gene encoding an arginase so that the PEG moiety can attach to the enzyme at a predetermined, specific intended site. This is achieved by removing the PEG attaching amino acid residues at undesirable sites while keeping (or adding, if necessary) the one at the desirable site of the enzyme. Two exemplary mono-pegylated arginase conjugates so produced are human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Abstract: Fast and simple method of detecting the presence of chloramphenicol, a harmful compound if present in food products. The method makes use of a mutant chloramphenicol acetyltransferase (CAT) and a fluorophore-linked chloramphenicol in a system where chloramphenicol and the fluorophore-linked chloramphenicol competes for the active site of the mutant CAT. Because the fluorophore-linked chloramphenicol reduces its fluorescence upon binding to the active site and vice versa increases its fluorescence upon being displaced from the active site by the presence of unmodified chloramphenicol in a sample, the increase of fluorescence caused by a testing sample indicates the presence of chloramphenicol.

Abstract: Fast and simple method of detecting the presence of chloramphenicol, a harmful compound if present in food products. The method makes use of a mutant chloramphenicol acetyltransferase (CAT) and a fluorophore-linked chloramphenicol in a system where chloramphenicol and the fluorophore-linked chloramphenicol competes for the active site of the mutant CAT. Because the fluorophore-linked chloramphenicol reduces its fluorescence upon binding to the active site and vice versa increases its fluorescence upon being displaced from the active site by the presence of unmodified chloramphenicol in a sample, the increase of fluorescence caused by a testing sample indicates the presence of chloramphenicol.

Abstract: The present invention provides an isolated and substantially purified recombinant human arginase having sufficiently high enzymatic activity and stability to maintain Adequate Arginine Depletion in a patient. The present invention also provides a pharmaceutical composition comprising the modified invention enzyme and method for treatment of diseases using the pharmaceutical composition.

Abstract: Mono-pegylated arginase conjugate and method producing thereof. The mono-pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method of producing such arginase conjugate has a main step of genetically modifying the gene encoding an arginase so that the PEG moiety can attach to the enzyme at a predetermined, specific intended site. This is achieved by removing the PEG attaching amino acid residues at undesirable sites while keeping (or adding, if necessary) the one at the desirable site of the enzyme. Two exemplary mono-pegylated arginase conjugates so produced are human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fission protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases.

Abstract: The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase (AAD) fusion protein for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, binds to human serum albumin (HSA) or animal serum albumin and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD fusion protein in the present invention are about 20 and about 19 U/mg (at physiological pH 7.4), respectively. The composition can be used alone or in combination with at least one chemotherapeutic agent to give a synergistic effect on cancer treatment and/or inhibiting metastasis. The AAD fusion protein can also be used as a component for detection and quantitative analysis of arginine in a testing kit for various samples including blood, food and analytical samples.