Patent application number | Description | Published |
20090238813 | Compositions And Methods For Engineered Human Arginine Deiminases - The present invention discloses the engineering of a human enzyme with arginine hydrolytic activity suitable for human therapy. An enzyme comprising of a human sequence is not likely to induce adverse immunological responses and thus is expected to constitute a superior therapeutic. Since the human genome does not encode arginases with the proper high affinity catalytic properties (i.e., for example, a low Km and high catalytic activity, kcat) an appropriate arginase can be engineered by modifying an enzyme with related catalytic activity. For example, the human enzyme PAD4 can hydrolyze arginine in peptide substrates but does not have activity for free arginine. First, a high throughput assay was developed for detecting arginine activity by monitoring the formation of the hydrolytic product citrulline. Then, using a combination of rational design and iterative mutation and screening PAD4 mutants were identified and isolated exhibiting high affinity free arginine metabolic activity. These mutants did not retain activity for their original substrate, peptidyl arginine. | 09-24-2009 |
20100111925 | Compositions of Engineered Human Arginases and Methods for Treating Cancer - Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I. | 05-06-2010 |
20110200576 | ENGINEERED ENZYMES WITH METHIONINE-GAMMA-LYASE ENZYMES AND PHARMACOLOGICAL PREPARATIONS THEREOF - Methods and composition related to the engineering of a novel protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids. | 08-18-2011 |
20120177628 | ARGINASE FORMULATIONS AND METHODS - Methods and composition for generation of arginase variants with high serum persistence are provided. For example, in certain aspects methods for purifying pegylated arginase are described. Furthermore, the invention provides stabilized arginase multimers or pharmaceutical composition thereof. | 07-12-2012 |
20130273022 | COMPOSITIONS OF ENGINEERED HUMAN ARGINASES AND METHODS FOR TREATING CANCER - Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I. | 10-17-2013 |
20140242060 | COMPOSITIONS OF ENGINEERED HUMAN ARGINASES AND METHODS FOR TREATING CANCER - Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I. | 08-28-2014 |
20140287484 | ENGINEERED ENZYMES WITH METHIONINE-GAMMA-LYASE ENZYMES AND PHARMACOLOGICAL PREPARATIONS THEREOF - Methods and composition related to the engineering of a novel protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids. | 09-25-2014 |
20150064154 | ADMINISTRATION OF KYNURENINE DEPLETING ENZYMES FOR TUMOR THERAPY - Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids. | 03-05-2015 |
20150064159 | ENGINEERED PRIMATE L-METHIONINASE FOR THERAPEUTIC PURPOSES - Methods and compositions relating to the engineering of an improved protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids. | 03-05-2015 |
20150064160 | ENGINEERED PRIMATE CYSTINE/CYSTEINE DEGRADING ENZYMES AS ANTINEOGENIC AGENTS - Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with L-cyst(e)ine using the disclosed proteins or nucleic acids. | 03-05-2015 |