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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 6580. Отображено 100.
05-04-2012 дата публикации

Biomarkers, Methods and Kits for the Diagnosis of Rheumatoid Arthritis

Номер: US20120083423A1
Автор: Isabelle Auger, Jean Roudier
Принадлежит: Universite de la Mediterranee Aix Marseille II

The present invention relates to peptides biomarkers that are specifically recognized by autoantibodies present in the sera of patients with Rheumatoid Arthritis (RA). More specifically, the invention provides epitopes of PAD4, of BRAF, and of calpastatin as well as methods and kits for using these sequences for the diagnosis of RA, in particular for the diagnosis of RA in CCP-negative subjects.

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Номер записи: 1
17-05-2012 дата публикации

Superoxide dismutase variants and methods of use thereof

Номер: US20120121568A1
Автор: Danica Chen, Xiaolei Qiu
Принадлежит: UNIVERSITY OF CALIFORNIA

The present disclosure provides variant superoxide dismutase polypeptides, compositions comprising the polypeptides, and nucleic acids comprising nucleotide sequences encoding the polypeptides. The present disclosure provides methods of reducing oxidative damage in a cell, tissue, or organ. The present disclosure provides methods of identifying agents that increase superoxide dismutase activity.

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Номер записи: 2
17-05-2012 дата публикации

Test for Predicting Neutralization of Asparaginase Activity

Номер: US20120121570A1
Автор: Yann Godfrin
Принадлежит: Individual

Method of in vitro measurement of the presence of factors that are able to neutralize asparaginase activity in a sample of blood, plasma, serum or derived medium that may contain asparaginase neutralizing factors, obtained from a patient, comprising mixing of said sample with asparaginase, incubation of said mixture, then measurement of the residual asparaginase activity in the mixture and determination or quantification of the presence of said neutralizing factors. Method for predicting the efficacy of a treatment with asparaginase.

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Номер записи: 3
16-08-2012 дата публикации

Low-fat or fat-free yoghurt, and process for production thereof

Номер: US20120207878A1
Автор: Noriko Miwa, Wakako Ohashi
Принадлежит: Ajinomoto Co Inc, Amano Enzyme Inc

A fat-free or low-fat yoghurt having a rich and creamy texture like yoghurts produced using whole-fat milk may be produced by adding a proper amount of a milk protein, such as a defatted milk powder, that has been deamidated with a protein deamidating enzyme to a fat-free or low-fat raw material milk. Alternatively, a proper amount of a milk protein, such as a defatted milk powder, is added to a fat-free or low-fat raw material milk, and the resulting mixture is subjected to a deamidation treatment with a protein deamidating enzyme so that the deamidation ratio reaches a proper level. In this manner, a fat-free or low-fat milk raw material having a milk protein mass and a deamidation ratio both falling within proper ranges can be prepared, and yoghurt may be produced using the milk raw material.

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Номер записи: 4
28-02-2013 дата публикации

Arginine deiminase mutant and preparation and application thereof

Номер: US20130052179A1
Автор: Jiwan Qiu, Min Fan, Xiaoyu Fu, Yanshan Huang, Yefei Wang, Yujiao Wang
Принадлежит: Jiangsu T-Mab Biopharma Co Ltd

The present invention relates to an arginine deiminase mutant with partial lysine-deficient and preparation and application thereof. The arginine deiminase mutant of the present invention has enzymatic activity of degrading arginine into citruline; compared with the arginine deiminase with the amino acid sequence of SEQ ID NO: 1, the amino acid sequence comprises one or more of K9N, T, K59Q, K66R, A, K93E, A, Q, K111R, A, K119Q, L, M, K121Q, I, K122E, L, K126E, S, R, K178I, E, D, K196I, R, K209G, T, D, K243E, V, R, K249D, Q, K263N, Q, K279Y, T, K293R, H, E, K325V, I, K380T, R, E, and K406E, D, S substitutions. Compared with PEG modified natural derived arginine deiminase, the PEG modified arginine deiminase mutant of the present invention retain better bioactivity; and because the quantity of lysine in arginine deiminase is reduced, the PEG modified products are more uniform and can be applied to clinical treatment of hepatoma, melanoma and the like.

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Номер записи: 5
04-04-2013 дата публикации

DEACETYLATION HYDROLASE OF HYALURONIC ACID, HYALURONIC ACID DEACETYLATED BY SAME AND DERIVATIVE THEREOF

Номер: US20130085187A1
Автор: Kim Chun-Ho, KIM Jong-Il
Принадлежит: Korea Institute of Radiological & Medical Sciences

The present disclosure relates to a deacetylation hydrolase of a hyaluronic acid a hyaluronic acid deacetylated by same and a derivative thereof. The deacetylated hyaluronic acid and the derivative thereof have the following characteristic: a delayed initial decomposition rate on a living body; minimized decrease of molecular weight and viscosity; accelerated gelation due to a lower gelation temperature than the gelation temperature for a non-deacetylated hyaluronic acid; and an hMSC survival rate that is hardly affected by increased concentration of the deacetylated hyaluronic acid and the derivative thereof in a culture medium. As a result, the deacetylated hyaluronic acid and the derivative thereof can be useful as a bioingredient such a delivery system for a cell, gene, drug, and the like, or a support for tissue engineering, etc. 17.-. (canceled)8Scopulariopsis brevicaulis. A deacetylation hydrolases isolated from or encoded by a gene having a nucleotide sequence of SEQ ID NO: 1.9. A method of preparing a deacetylated hyaluronic acid or a derivative thereof , the method comprising:{'claim-ref': {'@idref': 'CLM-00008', 'claim 8'}, 'contacting the deacetylation hydrolase of with hyaluronic acid.'}10. The method of claim 9 , wherein said contacting comprises:dissolving the hyaluronic acid in a solvent to provide a solution; andincubating the solution in the presence of the deacetylation hydrolase.11. The method of claim 9 , wherein the solvent has pH ranging 3.0 to 9.0.12. The method of claim 9 , wherein the solution is incubated at temperature of 10-70° C.13. The method of claim 9 , wherein the solution is incubated for 0.001-24 hours.14. A deacetylated hyaluronic acid composition prepared by the method of claim 9 , the composition comprises the deacetylated hyaluronic acid and at least one derivative thereof.15. A carrier for delivering a cell claim 14 , a gene or a drug claim 14 , the carrier comprising the deacetylated hyaluronic acid composition of .16. A ...

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Номер записи: 6
22-08-2013 дата публикации

Modified beta-lactamases and methods and uses related thereto

Номер: US20130216622A1
Автор: Katja Valimaki, Pertti Koski, Ulla Airaksinen
Принадлежит: PREVABR LLC

The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

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Номер записи: 7
26-09-2013 дата публикации

Use of glycosidase in preparation of a milk product

Номер: US20130251848A1
Автор: Jonas Jacobsen, Karsten Bruun Qvist, Sandra Lykke Wind
Принадлежит: Chr Hansen AS

A method for making a milk product (e.g. a yogurt) comprising adding an effective amount of an N-linked glycosidase and/or an O-linked glycosidase to milk.

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Номер записи: 8
03-10-2013 дата публикации

Enhanced Antimicrobial Lytic Activity of a Chimeric Ply187 Endolysin

Номер: US20130259849A1
Автор: David M. Donovan, Jinzhe Mao
Принадлежит: US Department of Agriculture USDA

Peptidoglycan hydrolases are an effective new source of antimicrobials. A chimeric fusion protein of the Ply187 endopeptidase domain and LysK SH3b cell wall binding domain is a potent agent against Staphylococcus aureus in three functional assays.

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Номер записи: 9
03-10-2013 дата публикации

Means of controlling infection persistence of helicobacter pylori

Номер: US20130259888A1
Автор: Alma Fulurija, Barry J. Marshall, Douglas E. Berg, Mohammed Benghezal, Tobias Schoep
Принадлежит: ONDEK PTY LTD

The present invention relates to a means of controlling infection persistence of Helicobacter pylori ( H. pylori ). In particular, the present invention relates to an isolated, genetically modified Helicobacter pylori comprising a functional urease, wherein the contiguous amino acid sequence between amino acid 529 and amino acid 555 of SEQ ID NO:1 is altered to produce said modified Helicobacter pylori which is unable to establish or maintain a persistent infection.

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Номер записи: 10
26-12-2013 дата публикации

Peptide deformylase inhibitors

Номер: US20130345120A1
Автор: Andrew B. Benowitz, Andrew Nicholson Knox, Dongchuan Shi, Donghui Qin, James Hoffman, Jared T. Spletstoser, Joseph M. Karpinski, Kelly M. Aubart, Xiangmin Liao, Yuhong Fang
Принадлежит: GlaxoSmithKline LLC

The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

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Номер записи: 11
16-01-2014 дата публикации

Superoxide Dismutase Variants and Methods of Use Thereof

Номер: US20140017221A1
Автор: Danica Chen, Xiaolei Qiu
Принадлежит: UNIVERSITY OF CALIFORNIA

The present disclosure provides variant superoxide dismutase polypeptides, compositions comprising the polypeptides, and nucleic acids comprising nucleotide sequences encoding the polypeptides. The present disclosure provides methods of reducing oxidative damage in a cell, tissue, or organ. The present disclosure provides methods of identifying agents that increase superoxide dismutase activity.

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Номер записи: 12
07-01-2016 дата публикации

OLIGOMERIC INFLUENZA IMMUNOGENIC COMPOSITIONS

Номер: US20160000900A1
Автор: DU Lanying, Jiang Shibo, Zhao Guangyu, Zhou Yusen
Принадлежит:

Embodiments are provided for network resource allocation considering user experience, satisfaction, and operator interest. An embodiment method by a network component for allocating network resources includes evaluating, for a user, a QoE for each flow of a plurality of flows in network traffic in according with a QoE model, and further evaluating, for an operator, a revenue associated with the flows in accordance with a revenue model. A plurality of priorities that correspond to the flows are calculated in accordance with the QoE for the user and the revenue for the operator. The method further includes identifying a flow of the flows with a highest value of the priorities, and allocating a network resource for the flow. In an embodiment, the QoE model is a satisfaction model that provides a measure of user satisfaction for each flow in accordance with a subscription or behavior class of the user. 1. A fusion protein comprising:an immunogen sequence including an influenza A virus matrix protein M2e domain, or a fragment thereof, and an influenza A virus hemagglutinin fusion peptide (FP) domain, or a fragment thereof; andan immunopotentiator sequence.2. The fusion protein of claim 1 , wherein the FP domain is from influenza A virus hemagglutinin subtype 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , 16 claim 1 , 17 claim 1 , or 18.3. The fusion protein of claim 1 , wherein the FP domain and the M2e domain are independently from an influenza A virus selected from an H1N1 virus claim 1 , an H1N2 virus claim 1 , an H2N2 virus claim 1 , an H3N2 virus claim 1 , an H5N1 virus claim 1 , an H7N2 virus claim 1 , an H7N3 virus claim 1 , an H7N7 virus claim 1 , an H7N9 virus claim 1 , an H9N2 virus claim 1 , or an H10N8 virus.4. The fusion protein of claim 1 , wherein the amino acid sequence of the FP domain is at least 90% identical to one ...

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Номер записи: 13
07-01-2021 дата публикации

MODRNA ENCODING SPHINGOLIPID-METABOLIZING PROTEINS

Номер: US20210000975A1
Автор: ELIYAHU Efrat, HADAS Yoav, VINCEK Adam, ZANGI Lior
Принадлежит:

The present disclosure pertains to the use of a modified RNA (modRNA) that encodes a sphingolipid-metabolizing protein such as acid ceramidase to achieve expression of the sphingolipid-metabolizing protein in a mammalian cell or group of cells. Expression of the protein from the (modRNA) reduces high levels of ceramide in the cell that lead to cell death or senescence. 1. A method to inhibit cell death and/or cell senescence and/or promote survival of a mammalian cell or group of mammalian cells , comprising contacting said cell or cells with a modified RNA (modRNA) that encodes a sphingolipid-metabolizing protein.2. The method of claim 1 , wherein said sphingolipid-metabolizing protein is selected from the group consisting of (1) a ceramidase; (2) a sphingosine kinase (SPHK); (3) sphingosine-1-phosphate receptor (SIPR) or a combination of (1) claim 1 , (2) claim 1 , and (3) claim 1 , a combination of (1) and (2) claim 1 , a combination of (1) and (3) claim 1 , or a combination of (2) and (3).3. The method of claim 1 , wherein said mammalian cell or group of mammalian cells are selected from the group consisting of primary cells claim 1 , stems cells and gametes.4. The method of claim 3 , wherein said mammalian cell or group of mammalian cells is selected from the group consisting of cardiac cells claim 3 , muscle cells claim 3 , epithelial cells claim 3 , endothelial cells claim 3 , oocytes claim 3 , sperm claim 3 , and embryos.5. A composition comprising (1) a modRNA that encodes a ceramidase; (2) a modRNA that encodes sphingosine kinase (SPHK); (3) a modRNA that encodes sphingosine-1-phosphate receptor (SIPR) or a combination of (1) claim 3 , (2) claim 3 , and (3) claim 3 , a combination of (1) and (2) claim 3 , a combination of (1) and (3) claim 3 , or a combination of (2) and (3) and a pharmaceutically acceptable carrier.6. The method of claim 1 , wherein the sphingolipid-metabolizing protein is a ceramidase.7. The method of claim 6 , wherein the ceramidase is ...

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Номер записи: 14
04-01-2018 дата публикации

MULTILAMELLAR LIPID VESICLE COMPOSITIONS INCLUDING A CONJUGATED ANAPLASTIC LYMPHOMA KINASE (ALK) VARIANT AND USES THEREOF

Номер: US20180000906A1
Автор: DEMUTH Peter C., EBY Jackson, LI Adrienne
Принадлежит: Vedantra Pharmaceuticals, Inc.

The invention provides compositions including stabilized multilamellar lipid vesicles having crosslinked lipid bilayers (referred to herein as interbilayer-crosslinked multilamellar vesicles or ICMV) and including an ALK variant, pharmaceutical compositions containing vesicles (e.g., ICMV) including an ALK variant, and methods of treatment using such compositions. The invention provides compositions including stabilized multilamellar lipid vesicles with crosslinked lipid bilayers (e.g., an interbilayer-crosslinked multilamellar vesicle or ICMV) containing an Anaplastic lymphoma kinase (ALK) variant as an antigen that is associated with solid tumor cancers. 1. A composition comprising:(a) a multilamellar lipid vesicle having crosslinks between lipid bilayers; and(b) an anaplastic lymphoma kinase (ALK) variant.2. The composition of claim 1 , wherein said ALK variant is conjugated to a lipid.3. The composition of or claim 1 , wherein said composition further comprises a nucleophosmin (NPM) protein or a fragment thereof.4. The composition of claim 3 , wherein said fragment of said NPM protein is an extracellular domain of said NPM protein.5. The composition of or claim 3 , wherein said NPM protein is fused to said ALK variant.6. The composition of or claim 3 , wherein said composition further comprises a tropomyosin (TMP3) protein or a fragment thereof.7. The composition of claim 6 , wherein said fragment of said TMP3 protein is an extracellular domain of said TMP3 protein.8. The composition of or claim 6 , wherein said TMP3 protein is fused to said ALK variant.9. The composition of or claim 6 , wherein said composition further comprises a 5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) protein or a fragment thereof.10. The composition of claim 9 , wherein said fragment of said ATIC protein is an extracellular domain of said ATIC protein.11. The composition of or claim 9 , wherein said ATIC protein is fused to said ALK variant. ...

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Номер записи: 15
03-01-2019 дата публикации

COMPOSITIONS OF ENGINEERED HUMAN ARGINASES AND METHODS FOR TREATING CANCER

Номер: US20190000939A1
Автор: GEORGIOU George, STONE Everett
Принадлежит: AERASE, Inc.

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. 1. A protein comprising an amino acid sequence of human Arginase I or an amino acid sequence of human Arginase II and a non-native metal cofactor , wherein the non-native metal cofactor is cobalt.2. The protein of claim 1 , wherein the amino acid sequence is further defined as Arginase I.3. The protein of claim 2 , wherein the human Arginase I comprises SEQ ID NO:1.4. The protein of claim 1 , wherein the amino acid sequence is further defined as Arginase II.5. The protein of claim 4 , wherein the Arginase II comprises SEQ ID NO:2.6. The protein of claim 1 , wherein the amino acid sequence comprises a truncated Arginase I or Arginase II sequence.7. The protein of claim 6 , wherein the amino acid sequence lacks an N-terminal methionine.8. The protein of claim 6 , wherein the amino acid sequence lacks the first 21 amino acids of the wild-type sequence.9. The protein of claim 1 , wherein the protein displays a k/Kbetween 400 mMsand 4 claim 1 ,000 mMsat pH 7.4.10. The protein of claim 9 , wherein the protein displays a k/Kbetween 400 mMsand 2 claim 9 ,500 mMsat pH 7.4.11. The protein of claim 1 , further comprising at least one amino acid substitution at the metal binding site.12. The protein of claim 11 , wherein the at least one amino acid substitution is at His101 claim 11 , Asp124 claim 11 , His126 claim 11 , Asp128 claim 11 , Asp232 claim 11 , Asp234 claim 11 , Trp122 claim 11 , Asp181 claim 11 , Ser230 claim 11 , His120 claim 11 , Asp143 claim ...

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Номер записи: 16
03-01-2019 дата публикации

METHOD OF TREATING A MAMMAL, INCLUDING HUMAN, AGAINST CANCER USING METHIONINE AND ASPARAGINE DEPLETION

Номер: US20190000941A1
Автор: AGUERA Karine, BERLIER Willy, GAY Fabien, GODFRIN Yann
Принадлежит:

The invention is related to a new method for treating liquid and solid cancers, in a mammal, including human, wherein methioninase is administered before asparaginase. The invention also encompasses the use of a dietary methionine deprivation, possibly combined with methioninase administration, in advance of asparaginase treatment. Methioninase and asparaginase may be used in particular under free form, pegylated form or encapsulated into erythrocytes. 125-. (canceled)26. A pharmaceutical composition or kit for use in treating cancer in a mammal comprising asparaginase and methioninase for at least one sequential administration with methioninase being administered before asparaginase.27. The composition of claim 26 , wherein the methioninase and the asparaginase are under free form claim 26 , pegylated form or encapsulated inside erythrocytes.28. The composition of claim 26 , wherein the methioninase is under free form or is pegylated and the delay between the end of the methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 7 days claim 26 , between about 3 h and about 6 days claim 26 , or between about 1 day and about 5 days.29. The composition of claim 26 , wherein the methioninase is encapsulated into erythrocytes and the delay between the end of methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 30 days claim 26 , between about 1 day and about 20 days claim 26 , or between about 1 day and about 10 days.30. The composition claim 29 , wherein the methioninase is administered once or more in an amount of between about 100 and about 100 claim 29 ,000 IU claim 29 , between about 500 and about 50 claim 29 ,000 IU claim 29 , or between about 500 and about 5 claim 29 ,000 IU; and wherein the asparaginase is administered once or more in an amount of between about 500 and about 100 claim 29 ,000 IU claim 29 , between about 1 claim 29 ,000 and about 50 ...

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Номер записи: 17
07-01-2016 дата публикации

LABELED GLUTAMINASE PROTEINS, ISOLATED GLUTAMINASE PROTEIN MUTANTS, METHODS OF USE, AND KIT

Номер: US20160002619A1
Автор: Cerione Rick, Erickson Jon W., RAMACHANDRAN Sekar, STALNECKER Clint A.
Принадлежит:

The present invention relates to a labeled glutaminase (GLS) protein comprising a GLS protein and a fluorescent reporter group attached to the GLS protein, wherein the fluorescent reporter group is attached to the GLS protein within the glutaminase domain pfam04960 of GLS. The present invention also relates to isolated glutaminase protein mutants. Also disclosed is a method of screening for compounds that allosterically bind to a glutaminase protein. The present invention also relates to a method of identifying compounds that inhibit or stabilize tetramer formation of glutaminase protein. The present invention further relates to a screening kit for compounds that inhibit or stabilize tetramer formation. 1. A labeled glutaminase (GLS) protein comprising:a GLS protein anda fluorescent reporter group attached to the GLS protein, wherein the fluorescent reporter group is attached to the GLS protein within the glutaminase domain pfam04960 of GLS.2. The labeled GLS protein according to claim 1 , wherein the GLS protein is a wild type protein.3. The labeled GLS protein according to claim 1 , wherein the GLS protein is a GLS isoform selected from the group consisting of glutaminase C (GAC) and KGA.4. The labeled GLS protein according to claim 1 , wherein the GLS protein is GLS isoform GAC claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:3.5. The labeled GLS protein according to claim 1 , wherein the GLS protein is GLS isoform KGA claim 1 , having an amino acid sequence selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:7.6. The labeled GLS protein according to claim 1 , wherein the GLS protein is a mutated GLS protein.7. The labeled GLS protein according to claim 6 , wherein the mutated GLS protein has an amino acid sequence selected from the group consisting of SEQ ID NO:9 claim 6 , SEQ ID NO:10 claim 6 , SEQ ID NO:11 claim 6 , and SEQ ID NO:12.8. The labeled GLS protein according to claim 6 , wherein the ...

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Номер записи: 18
05-01-2017 дата публикации

MICROORGANISMS HAVING ENHANCED L-AMINO ACIDS PRODUCTIVITY AND PROCESS FOR PRODUCING L-AMINO ACIDS USING THE SAME

Номер: US20170002388A1
Автор: HONG Hyeong Pyo, JANG Juno, KOH Eun Sung, KWON Su Yon, LEE Ji Sun, LEE Keun Cheol, Lee Kwang Ho
Принадлежит:

Disclosed are a recombinant microorganism having enhanced L-amino acid productivity, wherein the recombinant microorganism is transformed to have removed or decreased activity of at least one of adenosine deaminase and AMP nucleosidase, and a method of producing an L-amino acid using the recombinant microorganism. The use of the recombinant microorganism may enable the production of the L-amino acid in a highly efficient manner. 1. A recombinant microorganism having enhanced producibility of an L-amino acid , wherein activity of at least one of adenosine deaminase comprising an amino acid sequence of SEQ ID NO: 14 and AMP nucleosidase comprising an amino acid sequence of SEQ ID NO: 16 removed or decreased.2. The recombinant microorganism of claim 1 , wherein the L-amino acid is L-threonine or L-tryptophan.3Escherichia.. The recombinant microorganism of claim 1 , the recombinant microorganism belongs to the genus4Escherichia coli.. The recombinant microorganism of claim 3 , wherein the recombinant microorganism is5. A method of producing L-amino acid claim 3 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'culturing the recombinant microorganism of ; and'}collecting an L-amino acid from the culture.6. The method of claim 5 , wherein the L-amino acid is L-threonine or L-tryptophan.7. A method of producing L-amino acid claim 5 , the method comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'culturing the recombinant microorganism of ; and'}collecting an L-amino acid from the culture.8. A method of producing L-amino acid claim 5 , the method comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'culturing the recombinant microorganism of ; and'}collecting an L-amino acid from the culture.9. A method of producing L-amino acid claim 5 , the method comprising:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'culturing the recombinant microorganism of ; and'}collecting an L-amino acid from the culture. The present invention ...

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Номер записи: 19
02-01-2020 дата публикации

MICROORGANISMS FOR PRODUCING PUTRESCINE OR ORNITHINE AND PROCESS FOR PRODUCING PUTRESCINE OR ORNITHINE USING THEM

Номер: US20200002686A1
Автор: JUNG Hee Kyoung, LEE Baek Seok, LEE Hyo Hyoung, Lee Kyoung Min, LI Hong Xian, Park Su Jin, Um Hye Won, YANG Young Lyeol
Принадлежит:

Disclosed is a modified microorganism producing putrescine or ornithine, and a method for producing putrescine or ornithine using the same. 115-. (canceled)16. A method for producing putrescine or ornithine , comprising:{'i': Corynebacterium', 'E. coli', 'E. coli, '(i) culturing a modified microorganism of the genus producing putrescine or ornithine in a medium, wherein activities of N-acetylglutamate synthase from and acetylornithine deacetylase from are introduced into the microorganism; and'}(ii) recovering putrescine or ornithine from the cultured microorganism or the medium.17CorynebacteriumCorynebacterium glutamicum.. The method according to claim 16 , wherein the microorganism of the genus is18E. coliE. coli. The method according to claim 16 , wherein the N-acetylglutamate synthase from consists of an amino acid sequence of SEQ ID NO: 1 claim 16 , and/or the acetylornithine deacetylase from consists of an amino acid sequence of SEQ ID NO: 3.19. The method according to claim 16 , wherein (a) an activity of phosphotransacetylase and acetate kinase operon (pta-ackA operon); (b) an activity of at least one selected from the group consisting of acetyl gamma glutamyl phosphate reductase (ArgC) claim 16 , acetylglutamate synthase or ornithine acetyltransferase (ArgJ) claim 16 , acetylglutamate kinase (ArgB) claim 16 , and acetyl ornithine aminotransferase (ArgD); and/or (c) an activity of putrescine exporter is further enhanced compared to its endogenous activity.20E. coli. The method according to claim 16 , wherein an activity of acetyl-CoA synthetase (acs) from claim 16 , and/or an activity of ornithine decarboxylase (ODC) is further introduced.21. The method according to claim 16 , wherein (a) an activity of i) ornithine carbamoyltransferase (ArgF) claim 16 , ii) glutamate exporter claim 16 , or iii) ornithine carbamoyltransferase and glutamate exporter and/or (b) an activity of acetyltransferase is further weakened compared to its endogenous activity. This ...

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Номер записи: 20
02-01-2020 дата публикации

ANC80 ENCODING SPHINGOLIPID-METABOLIZING PROTEINS FOR MITIGATING DISEASE-INDUCED TISSUE DAMAGE

Номер: US20200002696A1
Автор: ELIYAHU Efrat, FARAGNOLI Anthony, KATZ Misha, VINCEK Adam
Принадлежит:

The present disclosure relates generally to the use of sphingolipid-metabolizing proteins to mitigate or minimize tissue damage resulting from injury or from disease, for example, pulmonary arterial hypertension (PAH) when the sphingolipid-metabolizing protein is delivered via expression from an Anc80 vector. 1. A method to minimize damage to a cell/group of cells/tissue in a subject as the result of disease or injury comprising administering to the subject a therapeutically effective amount of an Anc80 viral vector that codes for the expression of a sphingolipid-metabolizing protein.2. The method of claim 1 , wherein the disease is selected from the group consisting of pulmonary arterial hypertension (PAH) claim 1 , stroke claim 1 , ischemia and reperfusion injury.3. The method of claim 1 , wherein the damage is to pulmonary tissue as the result of pulmonary arterial hypertension (PAH).4. The method of claim 1 , wherein the damage is to cardiac tissue as the result of pulmonary arterial hypertension (PAH).5. The method of claim 1 , wherein said sphingolipid-metabolizing protein is selected from the group consisting of (1) a ceramidase; (2) sphingosine kinase (SPHK) (3) sphingosine-1-phosphate receptor (SIPR); (4) ceramidase kinase (CERK) or a combination of any of (1) claim 1 , (2) claim 1 , (3) and (4).6. The method of claim 1 , wherein said sphingolipid-metabolizing protein is acid ceramidase.7. The method of claim 1 , wherein said sphingolipid-metabolizing protein is a neutral ceramidase.8. The method of claim 1 , wherein said sphingolipid-metabolizing protein is an alkaline ceramidase.9. The method of claim 1 , wherein the sphingolipid-metabolizing protein is a ceramidase encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1 claim 1 , SEQ ID NO: 6 claim 1 , SEQ ID NO: 7 claim 1 , SEQ ID NO: 8 claim 1 , SEQ ID NO: 9 claim 1 , SEQ ID NO: 10 claim 1 , SEQ ID NO: 11 and SEQ ID NO: 12.10. The method of claim 1 , wherein Anc80 has the ...

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Номер записи: 21
07-01-2021 дата публикации

SPHINGOLIPID-METABOLIZING PROTEINS ENHANCE THE EFFICIENCY OF GENE EDITING IN CELLS

Номер: US20210002668A1
Автор: ELIYAHU Efrat, HADAS Yoav, VINCEK Adam, ZANGI Lior
Принадлежит:

The present disclosure pertains to the use of a modified RNA (modRNA) that encodes a sphingolipid-metabolizing protein such as acid ceramidase to achieve expression of the sphingolipid-metabolizing protein in a mammalian cell or group of cells. Expression of the protein from the (modRNA) reduces high levels of ceramide in the cell that lead to cell death or senescence. 1. A method for improving the efficiency of gene/genome editing in a mammalian cell or group of mammalian cells , the method comprising:a. contacting said cell or group of cells undergoing gene editing with a sphingolipid-metabolizing protein or a modRNA that encodes a sphingolipid-metabolizing protein before or during gene editing; andb. performing gene/genome editing.2. The method of claim 1 , wherein said cells or group of cells are contacted with the sphingolipid-metabolizing protein or modRNA that encodes a sphingolipid-metabolizing protein before gene/genome editing.3. The method of claim 1 , wherein said cells or group of cells are contacted with the sphingolipid-metabolizing protein or modRNA that encodes a sphingolipid-metabolizing protein for a time sufficient for cell uptake of the sphingolipid-metabolizing protein or modRNA that encodes a sphingolipid-metabolizing protein.4. The method of claim 1 , wherein said sphingolipid-metabolizing protein is selected from the group consisting of ceramidase claim 1 , sphingosine kinase (SPHK) claim 1 , and sphingosine-1-phosphate receptor (S1PR).5. The method of claim 4 , wherein said sphingolipid-metabolizing protein is acid ceramidase (AC).6. The method of claim 5 , wherein the acid ceramidase is encoded by the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 7.7. The method of claim 4 , wherein said sphingolipid-metabolizing protein is neutral ceramidase.8. The method of claim 7 , wherein the neutral ceramidase is encoded by the nucleotide sequence of SEQ ID NO: 6 claim 7 , SEQ ID NO: 8 claim 7 , SEQ ID NO: 9 claim 7 , SEQ ID NO: 10 claim 7 , SEQ ...

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Номер записи: 22
03-01-2019 дата публикации

BACTERIAL CELLS WITH IMPROVED TOLERANCE TO POLYAMINES

Номер: US20190002935A1
Автор: Feist Adam, Herrgard Markus, Lennen Rebecca, Mohamed Elsayed Tharwat Tolba, Nielsen Alex Toftgaard, SOMMER Morten
Принадлежит:

Provided are bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as polyamines, and methods of preparing and using such bacterial cells for production of polyamines and other compounds. 1. A bacterial cell comprising a recombinant biosynthetic pathway for producing an aliphatic polyamine and at least one genetic modification which reduces expression of an endogenous gene selected from the group consisting of proV , proW , proX , cspC , ptsP , wbbK , yobF , nagC , nagA , rph , ybeX and mpl , or a combination of any thereof.2. The bacterial cell of claim 1 , comprising a genetic modification which reduces expression of ybeX claim 1 , proV claim 1 , cspC claim 1 , ptsP claim 1 , wbbK claim 1 , mpl or rph.3. The bacterial cell of claim 2 , comprising genetic modifications which reduce the expression ofa) proV and at least one of ptsP, cspC, mpl, and ybeX;b) proV, ptsP, and at least one of mpl and ybeX;c) proV, cspC, and at least one of mpl and ybeX;d) ybeX and at least one of proV, ptsP, cspC, and mpl;e) proV, ptsP, ybeX, and mpl; orf) proV, cspC, ybeX, and mpl.4. The bacterial cell of claim 1 , wherein the genetic modification comprises a knock-down or knock-out of the endogenous gene.5. The bacterial cell of claim 1 , further comprising a mutation in at least one of YgaC claim 1 , RpsG claim 1 , MreB claim 1 , NusA claim 1 , SspA claim 1 , MrdB claim 1 , RpoD claim 1 , RpoC claim 1 , RpoB claim 1 , MurA claim 1 , RpsA claim 1 , SpoT claim 1 , argG claim 1 , rph or the pyrE/rph intergenic region.6. A bacterial cell comprising at least one mutation selected from YgaC-R43L claim 1 , RpsG-L157* claim 1 , MreB-A298V claim 1 , MreB-N34K claim 1 , MreB-E212A claim 1 , MreB-I24M claim 1 , MreB-H93N claim 1 , NusA-L152R claim 1 , NusA-M204R claim 1 , SspA-F83C claim 1 , SspA-V91F claim 1 , MrdB-E254K claim 1 , RpoD-E575A claim 1 , RpoC-V401G claim 1 , RpoC-V453I claim 1 , RpoC-R1140C claim 1 , RpoC-L120P claim 1 , RpoB-R637L ...

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Номер записи: 23
20-01-2022 дата публикации

Functionalized Enzyme-Powered Nanomotors

Номер: US20220016223A1
Автор: Ana Candida LOPES HORTELÃO, Samuel SAÑCHEZ ORDOÑEZ, Tania PATIÑO PADIAL
Принадлежит: Fundacio Institut de Bioenginyeria de Catalunya IBEC, Institucio Catalana de Recerca i Estudis Avancats ICREA

The present invention provides an enzyme-powered nanomotor, comprising a particle with a surface, an enzyme, and a heterologous molecule; characterized in that the enzyme and the heterologous molecule are discontinuously attached over the whole surface of the particle. The invention also provides the nanomotor for use in therapy, diagnosis and prognosis, in particular, for the treatment of cancer. Additionally, the invention provides the use of the nanomotor for detecting an analyte in an isolated sample.

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Номер записи: 24
20-01-2022 дата публикации

RECOMBINANT MICROORGANISM CAPABLE OF GROWING USING ONLY CARBON DIOXIDE AND FORMIC ACID AND METHOD FOR PRODUCING USEFUL SUBSTANCES USING THE RECOMBINANT MICROORGANISM

Номер: US20220017879A1
Автор: Ahn Jung Ho, BANG Junho, HWANG Chang Hun, LEE Jong An, LEE Sang Yup
Принадлежит:

Disclosed is a recombinant microorganism capable of growing using only carbon dioxide and formic acid by introducing and improving a metabolic pathway for synthesizing pyruvic acid from carbon dioxide and formic acid to enhance pyruvic acid synthesis efficiency and performing additional genetic manipulation, and a method for producing useful substances using the same. Advantageously, the recombinant microorganism is capable of synthesizing pyruvic acid, a C3 organic compound, at a remarkably improved rate, and in particular, grows well even in a medium containing only carbon dioxide and formic acid as carbon sources without a glucose supply, and is thereby capable of synthesizing pyruvic acid and various high value-added compounds using the same as an intermediate product in an economically efficient manner. 1. A recombinant microorganism , in which a gene encoding a glycine cleavage system transcriptional repressor , pyruvate formate lyase , or phosphoglycerate dehydrogenase is attenuated or deleted from a host microorganism having a formic acid assimilation pathway ,a gene encoding an enzyme involved in a glycine cleavage system reaction is enhancely expressed in the host microorganism having the formic acid assimilation pathway, anda gene encoding formate-tetrahydrofolate ligase, methenyl tetrahydrofolate cyclohydrolase, or methylene-tetrahydrofolate dehydrogenase is introduced into the host microorganism having the formic acid assimilation pathway.2Escherichia, Mannheimia, RhodobacterMethylobacterium. The recombinant microorganism according to claim 1 , wherein the host microorganism is selected from the group consisting of and genera.3. The recombinant microorganism according to claim 1 , wherein the expression of the gene encoding the enzyme involved in the glycine cleavage system reaction is enhanced by substituting a native promoter with a strong promoter.4. The recombinant microorganism according to claim 3 , wherein the strong promoter is selected from the ...

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Номер записи: 25
20-01-2022 дата публикации

METHOD FOR PRODUCTION OF 4-CYANO BENZOIC ACID OR SALTS THEREOF

Номер: US20220017931A1
Автор: Baldenius Kai-Uwe, Ghislieri Diego, GOETZ Roland, KORADIN Christopher, Schachtschabel Doreen, Seemayer Stefan, Willrodt Christian
Принадлежит:

Described herein are methods for the production of 4-cyano benzoic acid or salts thereof from terephthalonitrile using nitrilase as catalyst. Also described herein are compositions including 4-cyano benzoic acid. 1. An isolated nitrilase capable of catalysing a reaction from terephthalonitrile to ammonium 4-cyano benzoic acid in an aqueous medium comprising water , nitrilase and terephthalonitrile and/or ammonium 4-cyano benzoic acid , wherein the concentration of ammonium 4-cyano benzoic acid in the aqueous medium after incubation is at least 5% (w/w) and the concentration of terephthalonitrile is below 1.0% (w/w).2. The isolated nitrilase of wherein after incubation the aqueous medium comprises below 0.5% (w/w) terephthalic acid.3. The isolated nitrilase of comprising a sequence selected from the group consisting ofa. An amino acid molecule of SEQ ID NO: 2, 4, 6 or 8,b. An amino acid molecule having at least 55% identity to the amino acid molecule of SEQ ID NO: 2, 4, 6 or 8 or a functional fragment thereof,c. An amino acid molecule encoded by a nucleic acid molecule of SEQ ID NO: 1, 3, 5 or 7 or a functional fragment thereof,d. An amino acid molecule encoded by a nucleic acid molecule having at least 70% identity to SEQ ID NO: 1, 3, 5 or 7 or a functional fragment thereof, ande. An amino acid molecule encoded by a nucleic acid molecule hybridizing under stringent conditions to a fragment of at least 250 bases complementary to SEQ ID NO: 1, 3, 5 or 7 or a functional fragment thereof,wherein the amino acid molecule as defined in b., d. and e. catalyzes the reaction from terephthalonitrile to ammonium 4-cyano benzoic acid in an aqueous medium.4. An isolated nitrilase sequence selected from the group consisting ofa. An amino acid molecule of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 20 or 22, andb. An amino acid molecule having at least 55% identity to the amino acid molecule of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 20 or 22 or a functional fragment thereof, andc. An ...

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Номер записи: 26
12-01-2017 дата публикации

METHOD FOR REMEDIATING CONTAMINATED SOIL USING MICROORGANISM STRAIN HAVING ABILITY TO PRODUCE UREASE

Номер: US20170008052A1
Автор: CHON Chul-Min, Kim Jae Gon, NAM In Hyun, PARK Min-Jeong
Принадлежит:

The present invention provides a method of remediating contaminated soil with heavy metal using a microorganism of sp. Contaminated soil is inoculated with the sp. KM-01 (KM-01) strain includes a base sequence of SEQ ID NO. 1, the sp. KM-07 (KM-07) strain includes a base sequence of SEQ ID NO. 2, and the sp. KM-12 (KM-12) strain includes a base sequence of SEQ ID NO. 3. The strains are capable of producing urease. 1. A method for remediating contaminated soil , comprising:{'i': 'Sporosarcina', 'inoculating, soil which is contaminated with heavy metals, with a sp. KM-01 strain which includes a base sequence of SEQ ID NO: 1 and is capable of producing urease; and'}hydrolyzing urea in the soil by the action of the urease generated by the strain to generate a carbonate ion and allowing the carbonate ion to react with a calcium ion in the soil to precipitate calcium carbonate, therebystabilizing heavy metals in the soil and neutralizing acidic soil.2Sporosarcina. The method of claim 1 , further inoculating the soil with a sp. KM-07 strain which includes a base sequence of SEQ ID NO: 2 and is capable of producing urease.3Sporosarcina. The method of claim 1 , further inoculating the soil with a sp. KM-12 strain which includes a base sequence of SEQ ID NO: 3 and is capable of producing urease.4Sporosarcina. The method of claim 1 , wherein the sp. strain is isolated from acidic soil contaminated with heavy metals in an exhausted mine area.5. The method of claim 1 , further comprising spreading a urea agent capable of providing urea to the soil prior to inoculation of the microorganism strain.6. The composition for remediating contaminated soil of claim 1 , further comprising a calcium agent capable of providing calcium.7. The method of claim 1 , comprising additionally providing urease to the soil.8. The method of claim 7 , wherein the additionally provided urease is extracted from bean juice. The present invention disclosed herein relates to a method for remediating ...

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Номер записи: 27
11-01-2018 дата публикации

Cleavable Lipids

Номер: US20180008543A1
Автор: DeRosa Frank, GUILD Braydon Charles, Heartlein Michael, Zhang Jerry Chi
Принадлежит:

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids. 2. (canceled)3. The nanoparticle of claim 1 , wherein Ris imidazole.4. The nanoparticle of claim 1 , wherein{'sub': '1', 'Ris imidazole;'}andn is 1.5. The nanoparticle of claim 1 , wherein Ris guanidinium.6. The nanoparticle-of claim 1 , wherein{'sub': '1', 'Ris guanidinium;'}andn is 1.723.-. (canceled)2629.-. (canceled)30. The nanoparticle of claim 1 , further comprising one or more compounds selected from the group consisting of a cationic lipid claim 1 , a PEG-modified lipid claim 1 , a non-cationic lipid and a helper lipid.31. (canceled)32. The nanoparticle of claim 1 , wherein one or more of the polynucleotides comprises a chemical modification.33. The nanoparticle of claim 1 , wherein the one or more polynucleotides is selected from the group consisting of an antisense oligonucleotide claim 1 , siRNA claim 1 , miRNA claim 1 , snRNA claim 1 , snoRNA and combinations thereof.34. (canceled)35. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise DNA.36. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise RNA.37. (canceled)38. The nanoparticle of claim 36 , wherein the RNA encodes an enzyme.39. The nanoparticle of claim 38 , wherein the enzyme is selected from the group consisting of agalsidase alfa claim 38 , alpha-L-iduronidase claim 38 , iduronate-2-sulfatase claim 38 , N-acetylglucosamine-1-phosphate transferase claim 38 , N-acetylglucosaminidase claim 38 , alpha-glucosaminide acetyltransferase claim 38 , N- ...

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Номер записи: 28
14-01-2021 дата публикации

BETA-LACTAMASE FORMULATIONS AND USES THEREOF

Номер: US20210007994A1
Автор: BRISTOL Andrew, Connelly Sheila, Kaleko Michael
Принадлежит:

The present invention provides, in part, formulations comprising a beta-lactamase. Particularly, modified-release formulations comprising a beta-lactamase are provided which release a substantial amount of the beta-lactamase in the intestines. Therapeutic uses of the beta-lactamase formulations are also provided. 1. A modified-release formulation , comprising a beta-lactamase , wherein the formulation releases a substantial amount of the beta-lactamase in the GI tract.2. The modified-release formulation of claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 1.3. The formulation of any of the above claims claim 1 , wherein the beta-lactamase is substantially released in the small intestine.4. The formulation of any of the above claims claim 1 , wherein the beta-lactamase is substantially released in the large intestine.5. The formulation of any of the above claims claim 1 , wherein the formulation comprises a core particle claim 1 , a base coat over the core particle claim 1 , and wherein the base coat comprises the beta-lactamase.6. The formulation of claim 5 , wherein the core particle comprises sucrose.7. The formulation of any of the above claims claim 5 , wherein the formulation comprises a core particle claim 5 , and wherein the beta-lactamase is encapsulated within the core particle.8. The formulation of - claim 5 , wherein the formulation comprises a plurality of core particles.9. The formulation of any one of the above claims claim 5 , wherein the formulation further comprises a modified-release coating that is substantially stable in gastric fluid.10. The formulation of any one of the above claims claim 5 , wherein the formulation comprises a modified-release coating that is degraded by a microbial enzyme present in the gut flora.11. The formulation of any one of the above claims claim 5 , wherein the formulation comprises a modified-release coating having a solubility that is pH-dependent.12. ...

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Номер записи: 29
08-01-2015 дата публикации

Human arginase and site-directed pegylated human arginase and the use thereof

Номер: US20150010522A1
Автор: Chen Li, Cheng Ning Man
Принадлежит:

The present invention provides a site-directed mutated arginase and the preparation method thereof, and the use of said site-directed mutated arginase in preparing a medicament for treating an arginase-related disease. The present invention also provides a site-directed pegylated arginase and the preparation method thereof, and the use of said pegylated arginase in preparing a medicament for treating an arginase-related disease. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. The pegylated arginase of claim 6 , wherein any one of said cysteines at positions 45 claim 6 , 168 and 303 of said SEQ ID NO:1 is mutated to alanine.9. The pegylated arginase of claim 6 , wherein said arginase is conjugated with polyethylene glycol (PEG): said PEG has an average molecular weight of 20K claim 6 , 30K or 40K.10. The pegylated arginase of claim 6 , wherein said arginase has a half-life of at least 0.5 day.11. (canceled)12. (canceled)13. A pharmaceutical composition for treating an arginase-related disease comprising said pegylated arginase of .14. A method for treating an arginase-related disease claim 6 , comprising administrating said pegylated arginase of .15. The pegylated arginase of claim 6 , wherein said cysteine at position 303 of said SEQ ID NO:1 is mutated to alanine.16. The pegylated arginase of claim 15 , wherein the site-specific pegylation is carried out at Cys45 and Cys168; said PEG has an average molecular weight of 20K or 30K.17. The pegylated arginase of claim 6 , wherein said cysteines at positions 45 and 303 of said SEQ ID NO:1 are mutated to alanine.18. The pegylated arginase of claim 17 , wherein the site-specific pegylation is carried out at Cys168; said PEG has an average molecular weight of 40K.19. The pegylated arginase of claim 6 , wherein said cysteines at positions 168 and 303 of said SEQ ID NO:1 are mutated to alanine.20. The pegylated arginase of claim 19 , wherein the site-specific pegylation is carried out at Cys45 ...

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Номер записи: 30
08-01-2015 дата публикации

Acrylamide-degrading self-cloning aspergillus oryzae

Номер: US20150010676A1
Автор: Hirokazu Tsuboi, Kazuya Iwai, Kenji Ozeki, Motoaki Sano, Taiji Fukunaga, Takayuki Bogaki, Yusaku Narita
Принадлежит: Ozeki Corp, UCC Ueshima Coffee Co Ltd

Provided are self-cloning Aspergillus oryzae that expresses amidase without induction culture exhibiting high amidase degradation activity, and a method for reducing acrylamide in which this self-cloning Aspergillus oryzae is used. Self-cloning Aspergillus oryzae , which has a gene which codes a polypeptide with a specific amino acid sequence indicated in SEQ ID NO:1, or has a base sequence hybridizable to a complementary sequence of the gene encoding SEQ ID No:1 under stringent conditions, has a protein with amidase activity which the gene is expressed without induction culture, the process of reducing acrylamide by contact treatment with the above described self-cloning Aspergillus oryzae and acrylamide-containing matter, and a method of producing reduced acrylamide food or beverage.

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Номер записи: 31
12-01-2017 дата публикации

METABOLIC TRANSISTOR IN BACTERIA

Номер: US20170009241A1
Автор: Bennett George N., San Ka-Yiu, Wu Hui
Принадлежит:

The disclosure relates to a metabolic transistor in microbes such as bacteria and yeast where a competitive pathway is introduced to compete with a product pathway for available carbon so as to control the carbon flux in the microbe. 1) A method of increasing the production of a product in a microbe , said method comprising:a) providing a microbe having a product pathway producing a product, wherein a competitive pathway competes with said product pathway for available carbon, said competitive pathway requiring a cofactor that is not rate limiting and not used in said product pathway;b) adding one or more diverting gene(s) under the control of a promoter to said microbe to directly or indirectly divert said cofactor away from said competitive pathway; and,c) allowing expression of said diverting gene(s) and reducing levels of said cofactor, and thus reducing levels of said competitive pathway;d) thereby increasing said product pathway and said product.4) The method of claim 1 , wherein said promoter is a constitutive promoter.5) The method of claim 1 , wherein said promoter is an inducible promoter.6) A method of controlling aerobic respiration in a microbe in the presence of O claim 1 , said method comprising:a) adding a diverting gene(s) to a microbe to divert substrates away from ubiquinone or thiamine or heme production, wherein said diverting gene(s) is under the control of a promoter; and,{'sub': '2', 'b) inducing said promoter, thereby allowing expression of said diverting gene(s), thus reducing ubiquinone levels and reducing aerobic respiration in the presence of 0.'}7) The method of claim 6 , wherein said diverting gene(s) includes the lycopene synthesis pathway.8) The method of claim 6 , wherein said diverting gene(s) include crtE claim 6 , crtB and crtI.9) The method of claim 6 , wherein said diverting gene encodes geranyl diphosphate:4-hydroxybenzoate geranyltransferase.10) The method of claim 6 , wherein said diverting gene is lePGT-1.11) The method of ...

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Номер записи: 32
14-01-2016 дата публикации

Antibodies to argininosuccinate synthase and related methods

Номер: US20160009821A1
Автор: Bor-Wen Wu, Wei He, Yunyun GUO
Принадлежит: Tdw Group

Provided are antibodies, and antigen-binding fragments thereof, which specifically bind to argininosuccinate synthase, and related compositions, kits, and methods of use thereof, for instance, as companion diagnostics to identify suitable subjects for arginine deprivation or depletion therapies such as ADI-PEG 20 and other arginine deiminase (ADI) polypeptide-based therapies.

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Номер записи: 33
27-01-2022 дата публикации

OPTIMIZED PROTEIN LINKERS AND METHODS OF USE

Номер: US20220025346A1
Автор: GUFFY Sharon Leigh, WATTS Joseph Matthew
Принадлежит:

The invention relates to peptide linkers and fusion proteins comprising linkers designed for optimizing the activity of the proteins comprised therein, and methods for using the same. The invention further relates to newly designed Cas12a-based adenine base editors. 172-. (canceled)73. A polypeptide comprising any one of the amino acid sequences of SEQ ID NOs: 1-24.74. The polypeptide of claim 73 , further comprising a polypeptide of interest linked to any one of the amino acid sequences of SEQ ID NOs: 1-24.75. A polypeptide comprising a Cas12a domain linked to any one of the amino acid sequences of SEQ ID NOs: 1-24.76. A fusion protein comprising a Cas12a domain claim 73 , a polypeptide of interest and any one of the amino acid sequences of SEQ ID NOs: 1-24.77. The polypeptide of claim 76 , wherein the Cas12a domain comprises a mutation in the nuclease active site.78. The fusion protein of claim 76 , wherein the Cas12a domain is linked at its C-terminus and/or its N-terminus to any one of the amino acid sequences of SEQ ID NOs: 1-24.79. The polypeptide of claim 74 , wherein the polypeptide of interest comprises a protein domain having deaminase (deamination) activity (e.g. claim 74 , cytosine deaminase claim 74 , adenine deaminase) claim 74 , nickase activity claim 74 , recombinase activity claim 74 , transposase activity claim 74 , methylase activity claim 74 , glycosylase (DNA glycosylase) activity claim 74 , glycosylase inhibitor activity claim 74 , demethylase activity claim 74 , transcription activation activity claim 74 , transcription repression activity claim 74 , transcription release factor activity claim 74 , histone modification activity claim 74 , nuclease activity claim 74 , single-strand RNA cleavage activity claim 74 , double-strand RNA cleavage activity claim 74 , restriction endonuclease activity claim 74 , nucleic acid binding activity claim 74 , methyltransferase activity claim 74 , DNA repair activity claim 74 , DNA damage activity claim 74 , ...

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Номер записи: 34
11-01-2018 дата публикации

Combination cancer immunotherapies with arginine depletion agents

Номер: US20180010114A1
Автор: Elena Brin, Wei He
Принадлежит: Tdw Group

Provided are arginine depletion agents such as ADI-PEG for use in combination with cancer immunotherapies, for example, immune checkpoint modulators and T-cell adoptive immunotherapies, for treating various cancers. Also provided are related methods, compositions, patient care kits, and cell cultures.

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Номер записи: 35
14-01-2021 дата публикации

SYSTEMS METHODS, AND COMPOSITIONS FOR TARGETED NUCLEIC ACID EDITING

Номер: US20210009972A1
Автор: Abudayyeh Omar, Gootenberg Jonathan, Zhang Feng
Принадлежит:

The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof. 1. An engineered composition for site directed base editing comprising:a. a targeting domain; andb. an adenosine deaminase or catalytic domain thereof, wherein the adenosine deaminase is modified to convert activity to a cytidine deaminase.2. The composition of claim 1 , wherein the adenosine deaminase:is mutated at one or more positions selected from E396, C451, V351, R455, T375, K376, S486, Q488, R510, K594, R348, G593, S397, H443, L444, Y445, F442, E438, T448, A353, V355, T339, P539, V525 and I520;is mutated at one or more positions selected from E488, V351, S486, T375, S370, P462, and N597; orcomprises one or more mutations selected from E488Q, V351G, S486A, T375S, S370C, P462A, and N597I.3. (canceled)4. (canceled)5Drosophila. The composition of claim 1 , wherein the adenosine deaminase protein or catalytic domain thereof is a human claim 1 , cephalopod claim 1 , or adenosine deaminase protein or catalytic domain thereof; or is covalently or non-covalently linked to the targeting domain.6. The composition of claim 1 , wherein said adenosine deaminase protein or catalytic domain thereof has been modified to comprise a mutation at glutamic acidof the hADAR2-D amino acid sequence claim 1 , or a corresponding position in a homologous ADAR protein.7. The composition of claim 6 , wherein said glutamic acid residue at position 488 or a corresponding position in a homologous ADAR protein is replaced by a glutamine residue (E488Q); or said adenosine deaminase protein or catalytic domain thereof is a mutated hADAR2d comprising mutation E488Q or a mutated hADAR1d comprising mutation E1008Q.8. (canceled)9. The composition of claim 1 , ...

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Номер записи: 36
14-01-2021 дата публикации

NITRILASE MUTANT, CONSTRUCTION METHOD THEREFOR, AND APPLICATION THEREOF

Номер: US20210009981A1
Автор: LU XIAFENG, TANG Xiaoling, WU ZHEMING, Zhang Qin, ZHENG Renchao, ZHENG Yuguo
Принадлежит:

The present invention discloses a nitrilase mutant and its construction method and its application in the synthesis of chiral intermediate of pregabalin in the technical field of bioengineering. The present invention, respectively, takes turnip nitrilase BrNIT and arabidopsis nitrilase AtNIT as parent, using peptide fragment displacement method, displaces the sites 226-286 of BrNIT amino acid sequence and sites 225-285 of AtNIT amino acid sequence with sites 225-285 of L. nitrilase AaNIT, obtain nitrilase mutants BrNITand AtNITof which the amino acid sequence is as shown in SEQ ID NO.1 or SEQ ID NO.3. Compared with wild type nitrilase, the activity of the nitrilase mutant provided by the present invention in catalyzing and hydrolyzing racemic IBSN and the stereoselectivity of the product show substantial improvement, it can satisfy the requirements of industrial application, and has good application prospect in efficient catalysis of racemic IBSN to synthesize 3-cyano-5-methylhexanoic Acid. 1. A nitrilase mutant , which is characterized in that , the nitrilase mutant's amino acid sequence is as shown in SEQ ID NO.1 or SEQ ID NO.3.2. A coding gene for coding the nitrilase mutant according to claim 1 , which is characterized in that claim 1 , the coding gene's nucleotide sequence is as shown in SEQ ID NO.2 or SEQ ID NO.4.3. A recombinant vector containing the coding gene according to .4. A recombinant genetic engineering strain containing the recombinant vector according to .5. A method for preparing the nitrilase mutant of claim 1 , which is characterized in comprising the following steps:{'i': Arabis alpina', 'Arabis alpina, '(1) based on turnip nitrilase gene or arabidopsis nitrilase gene sequence, designing a PCR primer by using L. cDNA as a template, utilizing the primer to amplify to obtain a DNA fragment I or a DNA fragment II that contains sites 673-855 of the L. nitrilase nucleotide sequence;'}(2) taking a recombinant plasmid that carries turnip nitrilase ...

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Номер записи: 37
14-01-2021 дата публикации

ASSAYS FOR IMPROVING AUTOMATED ANTIMICROBIAL SUSCEPTIBILITY TESTING ACCURACY

Номер: US20210010053A1
Автор: Flentie Kelly, JR. Nicholas, PHELAN, Somers Mark, Stern Eric
Принадлежит:

Phenotypic antimicrobial susceptibility testing (AST), the gold-standard diagnostic that indicates whether an antimicrobial will be clinically effective, often suffer the slowest times-to-result for the most resistant pathogens. Here we introduce novel assays to be performed in parallel with standard AST assays that enable rapid, same-shift reporting of AST results for a plurality of pathogens. The assays developed here are further capable of detecting resistance to carbapenems, the most powerful class of beta-lactams commonly used as “last-resort” antimicrobials. 1. A method for performing automated antimicrobial susceptibility testing of a carbapenem antimicrobial comprising: [{'sub': '0', 'inoculating a microbial solution to achieve a final concentration Cinto a plurality of fluid wells defining a dilution series of a carbapenem antimicrobial; and'}, 'measuring in each of the plurality of fluid wells a signal associated with microbial growth; and, 'performing a dilution assay, comprising {'sub': R', 'R, 'measuring a signal associated with carbapenem degradation in a first well comprising a carbapenem antimicrobial, a microbial concentration of C, a buffer system at <0.05 M, a pH indicator, and optionally ionic zinc referenced to a second well comprising a similar microbial concentration of C, a buffer system at <0.05 M, a pH indicator, and optionally ionic zinc; and'}, 'in parallel with the dilution assay, performing a carbapenemase assay on the same microbial sample comprisingcombining the data derived from the dilution assay with that derived from the carbapenemase assay to define and label the microorganism as carbapenem susceptible or carbapenem resistant.2. The method of claim 1 , further comprising comparing the signal associated with the first well to a at least one well comprising a carbapenem antimicrobial claim 1 , a microbial concentration of C claim 1 , a buffer system at <0.05 M claim 1 , a pH indicator claim 1 , and a metal ion chelating agent.3. ...

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Номер записи: 38
09-01-2020 дата публикации

PROCESS FOR PREPARING (CYCLOPENTYL[d]PYRIMIDIN-4-YL)PIPERAZINE COMPOUNDS

Номер: US20200010428A1
Автор: Gosselin Francis, Han Chong, Iding Hans, Reents Reinhard, Savage Scott, Wirz Beat
Принадлежит:

The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes. 2. The process of claim 1 , wherein the cyclization is achieved by contacting the compound or salt of Formula VIwith a formamidine salt.3. The process of claim 1 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 1 , or salts thereof claim 1 , with a nitrilase enzyme or a lipase enzyme.4. The process of claim 3 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 3 , or salts thereof claim 3 , with a nitrilase enzyme.5. The process of claim 3 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 3 , or salts thereof claim 3 , with a lipase enzyme.6. The process of any one of to claim 3 , wherein the steps (ii) and (iii) are performed through-process.7. The process of claim 1 , wherein step (ii) is performed at a pH of about 7.8. The process of claim 1 , wherein step (ii) is performed at a pH of about 9. This application is a continuation of U.S. patent application Ser. No. 15/514,188, filed Mar. 24, 2017, which is a national phase entry of International Patent Application No. PCT/US2015/052143, filed Sep. 25, 2015, which claims the benefit of priority U.S. Provisional Application No. 62/055,893, ...

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Номер записи: 39
09-01-2020 дата публикации

INCORPORATION OF UNNATURAL AMINO ACIDS INTO PROTEINS USING BASE EDITING

Номер: US20200010835A1
Автор: Koblan Luke W., Liu David R., Maianti Juan Pablo
Принадлежит: President and Fellows of Harvard College

Provided herein are systems, compositions, and methods for the incorporation of unnatural amino acids into proteins via nonsense suppression or rare codon suppression. Nonsense codons and rare codons may be introduced into the coding sequence of a protein of interest using a CRISPR/Cas9-based nucleobase editor described herein. The nucleobase editors are able to be programmed by guide nucleotide sequences to edit the target codons in the coding sequence of the protein of interest. Also provided are application enabled by the technology described herein. 1. A method of incorporating an unnatural amino acid into a protein of interest at one or more specific position(s) , the method comprising:(i) contacting a polynucleotide encoding the protein of interest with a fusion protein comprising (a) a guide nucleotide sequence-programmable DNA-binding protein domain; and (b) a cytosine deaminase domain, wherein the fusion protein is associated with a guide nucleotide sequence, and whereby the contacting results in changing a target codon to a stop codon or a rare codon via deamination of a cytosine (C) base;(ii) using the polynucleotide containing the stop or rare codon in a translation system, whereby the unnatural amino acids are incorporated into the protein of interest at the suppressible stop codon or rare codon during translation of the protein,wherein the polynucleotide comprises a coding strand and a complementary strand.2. The method of claim 1 , wherein the guide nucleotide sequence-programmable DNA binding protein domain is selected from the group consisting of: nuclease inactive Cas9 (dCas9) domains claim 1 , nuclease inactive Cpf1 domains claim 1 , nuclease inactive Argonaute domains claim 1 , and variants thereof.39-. (canceled)10. The method of claim 1 , wherein the cytosine deaminase domain comprises an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase.11. (canceled)12. The method of claim 1 , wherein the cytosine deaminase comprises an amino ...

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Номер записи: 40
09-01-2020 дата публикации

HIGHLY SENSITIVE IN VITRO ASSAYS TO DEFINE SUBSTRATE PREFERENCES AND SITES OF NUCLEIC-ACID BINDING, MODIFYING, AND CLEAVING AGENTS

Номер: US20200010889A1
Автор: Gehrke Jason Michael, Joung J. Keith, Pattanayak Vikram, Petri Karl, Sasaki Kanae Esther
Принадлежит:

Methods and compositions for performing highly sensitive in vitro assays to define substrate preferences and off-target sites of nucleic-acid binding, modifying, and cleaving agents. 1. (canceled)2. (canceled)3. A method of identifying double stranded DNA sequences that are modified by a base editing enzyme , the method comprising:(i) providing a plurality of linear dsDNA oligonucleotides of known sequences, each oligonucleotide having a 5′ end and a 3′ end and bearing two copies of a unique identifier sequence at or near both the 3′ and 5′ ends of the oligonucleotide, and a common sequence that is present in each one of the oligonucleotides in the plurality;(ii) incubating the plurality linear dsDNA oligonucleotides in the presence of a base editing enzyme under conditions sufficient for modification to occur;(iii) amplifying the oligonucleotides with a polymerase that converts edited base pairs to equal mixtures of canonical base pairs during DNA synthesis, optionally wherein a dATP nucleotide is incorporated across from dU or a dCTP nucleotide is incorporated across from dI), such that an oligonucleotide that has been modified by the base editing enzyme will be amplified as a mixture of the original barcode-linked sequence from the pre-treatment library and also a modified sequence that contains substitutions; and(iv) determining the sequences of the amplified oligonucleotides,;thereby identifying double stranded DNA sequences that are modified by the base editing enzyme.4. A method of identifying double stranded DNA sequences that are modified by a cytidine deaminase base editing enzyme that converts deoxycytidine to deoxyuridine and generates a nick on the opposite strand , the method comprising:(i) providing a plurality of linear dsDNA oligonucleotides of known sequences, each oligonucleotide having a 5′ end and a 3′ end and bearing two copies of a unique identifier sequence at or near both the 3′ and 5′ ends of the oligonucleotide, and a common sequence that ...

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Номер записи: 41
03-02-2022 дата публикации

ARGINASE1 POLYPEPTIDES

Номер: US20220031818A1
Автор: Andersen Mads Hald
Принадлежит:

The present invention relates to novel polypeptides, which are derived from Arginase 1. The invention also relates to polynucleotides encoding the polypeptides. The invention also relates to compositions comprising the polypeptides and polynucleotides. The invention also concerns uses of the polypeptides, polynucleotides, and compositions. 2. The polypeptide of claim 1 , which consists of the amino acid sequence of SEQ ID NO: 1.3. The polypeptide of or claim 1 , in which the C terminal amino acid is replaced with the corresponding amide.4. A composition comprising the polypeptide or polynucleotide of any one of to and an adjuvant.5. A composition according to claim 4 , comprising at least one pharmaceutically acceptable diluent claim 4 , carrier or preservative.6. A composition according to or wherein the adjuvant is selected from the group consisting of bacterial DNA based adjuvants claim 4 , oil/surfactant based adjuvants claim 4 , viral dsRNA based adjuvants claim 4 , imidazochinilines claim 4 , and a Montanide ISA adjuvant.7. A method of treating or preventing a disease or condition in a subject claim 4 , the method comprising administering to the subject the polypeptide or polynucleotide of any one of to or the composition of to .8. The method of wherein the disease or condition is characterized at least in part by inappropriate or excessive immune suppressive function of an Arginase claim 7 , and/or said wherein disease or condition is cancer.9. The method of or wherein the disease or condition is cancer and optionally wherein the method further comprises the simultaneous or sequential administration of an additional cancer therapy claim 7 , preferably an antibody.10. The method of any one of to wherein said cancer is breast claim 7 , lung claim 7 , colon or prostate cancer claim 7 , or is a melanoma claim 7 , or is a leukemia claim 7 , preferably acute myeloid leukemia (AML).11. A method of stimulating arginase1-specific T cells claim 7 , the method ...

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Номер записи: 42
19-01-2017 дата публикации

SUMOYLATION OF SERCA2A AND CARDIOVASCULAR DISEASE

Номер: US20170014494A1
Автор: Hajjar Roger Joseph, Kho Chang Won, Lee Ah Young
Принадлежит:

Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation. 1. A method of treating cardiac dysfunction in a subject comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translational modification to the subject.2. The method according to wherein the cardiac dysfunction is selected from the group consisting of heart failure claim 1 , pressure overload-induced cardiac dysfunction claim 1 , and cardiac dysfunction induced by inhibited calcium decay.3. The method according to wherein the heart failure comprises contractile dysfunction.4. The method according to wherein the heart failure is TAC-induced heart failure.5. The method according to wherein the subject is a human.6. The method according to wherein the modulator modulates SERCA2a post-translational SUMOylation.7. The method according to wherein the modulator is a vector comprising an expressible coding region encoding a protein selected from the group consisting of SERCA2a and SUMO1 claim 6 , and wherein the coding region is operably linked to at least one expression control element.8. The method according to wherein the vector is a recombinant adeno-associated virus.9. The method according to wherein the recombinant adeno-associated virus is rAAV1.10. The method according to wherein the modulator ...

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Номер записи: 43
03-02-2022 дата публикации

Polypeptides having Peptidoglycan Degrading Activity and Polynucleotides Encoding Same

Номер: US20220033799A1
Автор: Baltsen Lillian Eva Tang, Garcia Fabian Barrientos, Oehlenschlaeger Christian Berg, Rosen Christian Bech, Salomon Jesper, Segura Dorotea Raventos
Принадлежит: NOVOZYMES A/S

The present invention relates to cleaning compositions comprising polypeptides having peptidoglycan degradation activity, as well as use of the cleaning compositions for cleaning of an item such as a textile or a surface. 1. A cleaning composition comprising a peptidoglycan degradation enzyme , at least one surfactant , and at least one additional cleaning component selected from builders and bleach components.2. The cleaning composition of claim 1 , comprising a peptidoglycan degradation enzyme claim 1 , at least 5 wt % anionic surfactants claim 1 , and at least one additional cleaning component selected from at least one builder and at least one bleach component.3. The cleaning composition according to claim 1 , wherein the peptidoglycan degrading enzyme has N-acetylmuramyl-L-alanine amidase activity.4. The cleaning composition according to claim 1 , wherein the peptidoglycan degrading enzyme has peptidoglycan lyase activity.5. The cleaning composition according to claim 3 , or wherein the peptidoglycan degradation enzyme has N-acetylmuramyl-L-alanine amidase activity and peptidoglycan lyase activity.6. The cleaning composition according to claim 1 , wherein the peptidoglycan degradation enzyme comprises the motif N[IV]X[AG][GAS]A[AY][LV]L (SEQ ID NO: 111).7. The cleaning composition of claim 6 , wherein the peptidoglycan degradation enzyme is selected from the group consisting of: SEQ ID NO: 3 claim 6 , SEQ ID NO: 6 claim 6 , SEQ ID NO: 9 claim 6 , SEQ ID NO: 12 claim 6 , SEQ ID NO: 15 claim 6 , SEQ ID NO: 18 claim 6 , SEQ ID NO: 21 claim 6 , SEQ ID NO: 24 claim 6 , SEQ ID NO: 27 claim 6 , SEQ ID NO: 42 claim 6 , SEQ ID NO: 45 claim 6 , SEQ ID NO: 48 claim 6 , SEQ ID NO: 51 claim 6 , SEQ ID NO: 54 claim 6 , SEQ ID NO: 60 claim 6 , SEQ ID NO: 63 claim 6 , SEQ ID NO: 66 claim 6 , SEQ ID NO: 69 claim 6 , SEQ ID NO: 75 claim 6 , SEQ ID NO: 87 claim 6 , SEQ ID NO: 96 claim 6 , SEQ ID NO: 99 and SEQ ID NO: 108 claim 6 , and polypeptides having at least at least 60% ...

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Номер записи: 44
18-01-2018 дата публикации

Early Hyperlipidemia Promotes Endothelial Activation via a Caspase-1-Sirtuin 1 Pathway

Номер: US20180015152A1
Автор: Yang Xiaofeng
Принадлежит:

The present invention provides compositions and methods for treating or preventing a disease or disorder associated with endothelial activation, inflammation or atherogenesis, including but not limited to cardiovascular diseases and inflammatory disorders. 1. A method for treating or preventing a disease or disorder associated with at least one of endothelial activation , inflammation and atherogenesis in a subject in need thereof comprising administering to the subject an inhibitor of caspase-1-Sirt1-AP-1 pathway.2. The method of claim 1 , wherein the inhibitor is an inhibitor of at least one of the group consisting of caspase-1 activity and caspase-1 expression.3. The method of claim 1 , wherein the inhibitor is a non-cleavable Sirt1 peptide inhibitor.4. The method of claim 3 , wherein the inhibitor is a human non-cleavable Sirt1 peptide inhibitor.5. The method of claim 3 , wherein the non-cleavable Sirt1 peptide inhibitor comprises a cell membrane permeable protein transduction sequence.7. The method of claim 2 , wherein the inhibitor is selected from the group consisting of a nucleic acid claim 2 , a siRNA claim 2 , an antisense nucleic acid claim 2 , a ribozyme claim 2 , a peptide claim 2 , a small molecule claim 2 , an antagonist claim 2 , an aptamer claim 2 , and a peptidomimetic.8. An inhibitor of caspase-1 activity comprising a non-cleavable Sirt1 peptide inhibitor.9. The inhibitor of claim 8 , wherein the inhibitor is a human non-cleavable Sirt1 peptide inhibitor.10. The inhibitor of claim 9 , wherein the non-cleavable Sirt1 peptide inhibitor comprises a cell membrane permeable protein transduction sequence. This application is the U.S. national phase application filed under 35 U.S.C. §371 claiming benefit to International Patent Application No. PCT/US 16/15964, filed Feb. 1, 2016, which is entitled to priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 62/109,918 filed Jan. 30, 2015, the contents of which are each incorporated ...

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Номер записи: 45
17-01-2019 дата публикации

Formulations of 5-fluorocytosine and uses thereof

Номер: US20190015414A1
Автор: Douglas J. Jolly, Harry E. Gruber, Kay Olmstead
Принадлежит: Tocagen Inc

The disclosure provides an extended release formulation of 5-fluorocytosine. In another aspect, a method of treating a fungal disease is provided. The method comprises administering to a subject in need thereof a fungus-treating effective amount of a composition comprising 5-fluorocytosine. In yet another aspect, a method of treating a cancer is provided. The method comprises administering to a subject in need thereof a sufficient amount of an expression vector to induce expression of cytosine deaminase which is capable of converting 5-fluorocytosine to 5-fluorouracil in cells of the cancer and a cancer-treating effective amount of a composition comprising 5-fluorocytosine.

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Номер записи: 46
21-01-2016 дата публикации

UNIVERSAL PROTEIN OVEREXPRESSION TAG COMPRISING RAMP FUNCTION, AND APPLICATION THEREOF

Номер: US20160017341A1
Автор: KIM Geun-Joong, LEE Eun-Bin, LEE Jin-Young, MIN Sa-Young, PARK Won Ji, YOU Sung-Hwan
Принадлежит: INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY

Provided is a ramp tag capable of solving instability in translation rate resulting from poor compatibility between codons in a foreign gene and a host when expressing a recombinant protein in . Unlike the conventional codon optimization or codon deoptimization method for solving the problem of rare codons, the present invention increases an expression efficiency of a target protein by merely having the ramp tag be fused with a target gene or independently expressed, without changing the original codon sequence, thereby allowing tRNA to be reused. Thus, the present invention provides a novel method for increasing recombinant protein expression which is capable of reducing costs and time in comparison to the codon optimization method that artificially synthesizes DNA sequences. Therefore, it is expected that the method of the present invention will be able to be used in production of high value-added pharmaceuticals or industrial enzymes. 1. A method of producing a ramp tag for controlling translation speed , comprising:making a rare codon table according to a host cell;converting DNA sequence of a target gene into codons;analyzing frequency and position at which rare codons in the rare codon table appear in an open reading frame (ORF) of the target gene; andcollecting and arranging the rare codons.2. The method of claim 1 , wherein the collecting of the rare codons is performed by analyzing frequency of the codons and the number of isoacceptor tRNA genes.3. The method of claim 2 , wherein the frequency of the codons is 0.5 to 3% claim 2 , and the number of isoacceptor tRNA genes is 0 to 2.4. The method of claim 1 , wherein in the arranging of the rare codons claim 1 , the rare codons are arranged in the order in which the rare codon appears in the ORF.5. The method of claim 1 , wherein a preferred codon is arranged between the rare codons.6E. coli. The method of claim 1 , wherein the host cell is selected from the group consisting of claim 1 , yeast claim 1 , a ...

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Номер записи: 47
21-01-2021 дата публикации

OPTIMIZED PROTEIN LINKERS AND METHODS OF USE

Номер: US20210017506A1
Автор: GUFFY Sharon Leigh, WATTS Joseph Matthew
Принадлежит:

The invention relates to peptide linkers and fusion proteins comprising linkers designed for optimizing the activity of the proteins comprised therein, and methods for using the same. The invention further relates to newly designed Cas12a-based cytosine base editors. 1. A polypeptide comprising any one of the amino acid sequences of SEQ ID NOs: 1-24.2. The polypeptide of claim 1 , further comprising a polypeptide of interest linked to any one of the amino acid sequences of SEQ ID NOs: 1-24.3. The polypeptide of claim 1 , further comprising a Cas12 a domain linked to any one of the amino acid sequences of SEQ ID NOs: 1-24.4. A fusion protein comprising the polypeptide of claim 3 , wherein the fusion protein further comprises a polypeptide of interest claim 3 , wherein the Cas12a domain and the polypeptide of interest are linked to one another via any one of the amino acid sequences of SEQ ID NOs: 1-24.5. The polypeptide of claim 3 , wherein the Cas12a domain comprises a mutation in the nuclease active site.6. The polypeptide of claim 3 , wherein the Cas12a domain is linked at its C-terminus and/or its N-terminus to any one of the amino acid sequences of SEQ ID NOs: 1-24.7. The polypeptide of claim 2 , wherein the polypeptide of interest comprises at least one polypeptide or protein domain having deaminase (deamination) activity claim 2 , nickase activity claim 2 , recombinase activity claim 2 , transposase activity claim 2 , methylase activity claim 2 , glycosylase (DNA glycosylase) activity claim 2 , glycosylase inhibitor activity (e.g. claim 2 , uracil-DNA glycosylase inhibitor (UGI)). demethylase activity claim 2 , transcription activation activity claim 2 , transcription repression activity claim 2 , transcription release factor activity claim 2 , histone modification activity claim 2 , nuclease activity claim 2 , single-strand RNA cleavage activity claim 2 , double-strand RNA cleavage activity claim 2 , restriction endonuclease activity (e.g. claim 2 , Fok1) ...

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Номер записи: 48
16-01-2020 дата публикации

BETA-LACTAMASES WITH IMPROVED PROPERTIES FOR THERAPY

Номер: US20200017844A1
Автор: Connelly Sheila, Kaleko Michael
Принадлежит:

This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as infection (CDI). 173-. (canceled)74. A beta-lactamase comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1 and the following mutations according to Ambler classification:an aliphatic hydrophobic residue other than alanine (A) at position 232,a polar and neutral hydrophilic residue other than alanine (A) at position 237,an aliphatic hydrophobic residue other than alanine (A) at position 238,a polar and negative hydrophilic residue other than serine (S) at position 240, anda polar and neutral hydrophilic residue other than (R) at position 244.75. The beta-lactamase of claim 74 , wherein the beta-lactamase has a further mutation of a polar and positive hydrophilic residue other than aspartate (D) at position 276 according to Ambler classification.76. The beta-lactamase of claim 74 , wherein the aliphatic hydrophobic residue is selected from glycine (G) claim 74 , leucine (L) claim 74 , isoleucine (I) claim 74 , methionine (M) claim 74 , and valine (V).77. The beta-lactamase of claim 74 , wherein the polar and neutral hydrophilic residue is selected from asparagine (N) claim 74 , glutamine (Q) claim 74 , serine (S) claim 74 , threonine (T) claim 74 , proline (P) claim 74 , and cysteine (C).78. The beta-lactamase of claim 74 , wherein the polar and negative hydrophilic residue is selected from aspartate (D) and glutamate (E).79. The beta-lactamase of claim 75 , wherein the polar and positive hydrophilic residue is selected from arginine (R) and lysine (K).80. A polynucleotide comprising a polynucleotide sequence encoding the beta-lactamase of .81. A host cell comprising the polynucleotide of .82. A pharmaceutical composition claim 74 , comprising the beta-lactamase of and a pharmaceutically acceptable carrier or excipient.83. The pharmaceutical composition of claim ...

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Номер записи: 49
28-01-2016 дата публикации

INHIBITING OR REDUCING FUNGAL GROWTH

Номер: US20160021890A1
Автор: Crow Sidney, PIERCE GEORGE E.
Принадлежит: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.

Provided are methods and compositions for inhibiting or reducing fungal growth. The methods comprise exposing a location to a composition comprising one or more enzymes, one or more bacteria, and/or an enzymatic extract, wherein the one or more enzymes, one or more bacteria, and/or the enzymatic extract isolated from one or more bacteria are exposed to location in a quantity sufficient to inhibit or reduce fungal growth. 1RhodococcusBrevibacteriumPseudonocardiaNocardiaPseudomonas. A method for inhibiting or reducing fungal growth , comprising exposing a location to a composition comprising one or more bacteria , wherein the one or more bacteria are selected from the group consisting of genus , genus , genus , genus , genus and combinations thereof , and wherein the one or more bacteria are provided in a quantity sufficient to inhibit or reduce fungal growth at the location.2. The method of claim 1 , wherein the one or more bacteria are induced to produce one or more enzymes selected from the group consisting of nitrile hydratases claim 1 , amidases claim 1 , asparaginases claim 1 , ACC deaminases claim 1 , cyanoalanine synthase-like enzymes claim 1 , monooxygenases claim 1 , dioxygenases claim 1 , cyanidases claim 1 , and combinations thereof.3. (canceled)4Rhodococcus rhodochrous, Rhodococcus rhodochrous, Rhodococcus erythropolis. The method of claim 1 , wherein the one or more bacteria are selected from the group consisting of DAP 96253DAP 96622 claim 1 , or combinations thereof.5. The method of claim 2 , wherein the composition further comprises the one or more enzymes or an enzymatic extract produced by the one or more bacteria.6. The method of claim 1 , wherein the composition further comprises an inducing agent selected from the group consisting of urea claim 1 , methyl carbamate claim 1 , methacrylamide claim 1 , acetamide claim 1 , cobalt claim 1 , asparagine or asparagine derivative claim 1 , and combinations thereof.7. (canceled)8. The method of claim 1 , ...

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Номер записи: 50
28-01-2016 дата публикации

Novel process for enzymatic acrylamide reduction in food products

Номер: US20160021896A1
Автор: Lex De Boer
Принадлежит: DSM IP ASSETS BV

The present invention relates to a novel enzyme composition comprising asparaginase and at least one hydrolysing enzyme, the use of such composition to reduce acrylamide levels in food products and a method to produce food products involving at least one heating step, comprising adding: a) asparaginase and b) at least one hydrolyzing enzyme to an intermediate form of said food product in said production process whereby the asparaginase and at least one hydrolyzing enzyme are added prior to said heating step in an amount that is effective in reducing the level of acrylamide of the food product in comparison to a food product whereto no asparaginase and hydrolyzing enzyme were added.

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Номер записи: 51
26-01-2017 дата публикации

COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY RELATED DISEASES OR CONDITIONS USING PEDIOCOCCUS ACIDILACTICI PROBIOTICS

Номер: US20170020929A1
Автор: Lin Jhy-Jhu, Lin Jolinta
Принадлежит:

The present invention provides a method of treating a disease or condition characterized by inflammation in a subject in need thereof, comprising administering to the subject an effective amount of a probiotic. Compositions of probiotic are also provided. 1Pediococcus acidilactici. A method of treating a disease or condition characterized by inflammation in a subject in need thereof , comprising administering to the subject an effective amount of a probiotic.2. The method of claim 1 , wherein the disease or condition selected from the group consisting of malignancy (cancer) claim 1 , arthritis claim 1 , cardiovascular disease claim 1 , hepatitis claim 1 , infection claim 1 , wound healing claim 1 , pancreatitis claim 1 , gastroesophageal reflux disease claim 1 , diabetes claim 1 , inflammatory bowel disease claim 1 , peptic ulcer disease claim 1 , bronchitis claim 1 , cholecystitis claim 1 , appendicitis claim 1 , bursitis claim 1 , dermatitis claim 1 , asthma claim 1 , autoimmune disease claim 1 , pelvic inflammatory disease claim 1 , gout claim 1 , trauma claim 1 , foreign body infection claim 1 , burns claim 1 , dental work claim 1 , tendonitis claim 1 , rhinitis claim 1 , mucositis claim 1 , and exposure to toxins such as chemicals and alcohol.3Pediococcus acidilactici. The method of claim 1 , wherein the probiotic is strain NRRL B-50517.4. The method of claim 1 , wherein the subject is a human.5. The method of claim 1 , wherein the subject is administered greater than 1.0×10cfu of the probiotic.6. The method of claim 1 , wherein the subject is administered greater than 4.0×10cfu of the probiotic.7. The method of claim 1 , wherein the subject is administered one or more additional therapeutic agents.8. The method of claim 1 , wherein the subject is not administered another therapeutic agent.9Pediococcus acidilactici. The method of claim 1 , wherein the probiotic increases the number of anti-inflammatory M2 macrophage cells in the subject.10. The method of claim ...

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Номер записи: 52
26-01-2017 дата публикации

CERAMIDE LEVELS IN THE TREATMENT AND PREVENTION OF INFECTIONS

Номер: US20170020998A1
Автор: Futerman Anthony, Gulbins Erich, Pewzner-Jung Yael, Schuchman Edward H.
Принадлежит:

The present invention relates to a method for treating or preventing pathogenic infections in a subject having Cystic Fibrosis, COPD, and/or an open wound. This method involves selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and administering to the selected subject a ceramidase under conditions effective to reduce ceramide and to treat or prevent the pathogenic infection. The method also involves the use of a ceramidase in combination with other drugs to reduce infection, reduce ceramide, or improve lung function in Cystic Fibrosis, COPD, and/or open wound patients. 1. A method for treating or preventing pathogenic infections in a subject having Cystic Fibrosis , COPD , and/or an open wound , said method comprising:selecting a subject having Cystic Fibrosis, COPD, and/or an open wound andadministering to said selected subject a ceramidase under conditions effective reduce ceramide and to treat or prevent said pathogenic infection in said selected subject.2. The method of claim 1 , wherein the subject is selected based on elevated ceramide levels compared to a reference level for a subject not having said Cystic Fibrosis claim 1 , COPD claim 1 , and/or an open wound.3. The method of claim 1 , wherein said selecting is based on ceramide level in lung epithelium claim 1 , nasal epithelium claim 1 , mucus claim 1 , and/or cells isolated from an open wound site.4. The method of claim 1 , wherein said administering is carried out under conditions effective to normalize ceramide levels in the subjects' respiratory epithelia claim 1 , mucus claim 1 , or cells at an open wound site.5. The method of claim 1 , wherein said ceramidase is acid ceramidase.6. The method of claim 1 , wherein one or more additional agents that reduce ceramide levels are administered in combination with said ceramidase.7. The method of claim 6 , wherein said one or more additional agents are selected from the group consisting of one or more additional ceramide reducing agents ...

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Номер записи: 53
10-02-2022 дата публикации

MODULATION OF THE GUT MICROBIOME TO TREAT MENTAL DISORDERS OR DISEASES OF THE CENTRAL NERVOUS SYSTEM

Номер: US20220040242A1
Автор: Lewis Kim, STRANDWITZ Philip
Принадлежит:

The present disclosure relates to methods of treating at least one symptom of a mental disorder or disease of the central nervous system in a subject by modulating the amount of GABA produced in the subject's gut. The present disclosure also relates to methods of culturing the bacterial strain new bacterial strains. Also disclosed are methods of identifying bacterial strains capable of producing GABA, and engineering strains to produce GABA. 1. A method of treating a disease or disorder in a subject in need thereof , the method comprising administering to the subject a therapeutic composition comprising at least one purified bacterial population that produces GABA at a pH range of between 4.5 and 7.5 , the at least one purified bacterial population consisting of bacteria comprising a 16s rDNA sequence at least 98% identical to a 16s rDNA sequence selected from the group consisting of SEQ ID NOs: 1-4 , 8 , 10 , 12 , 16-18 , 28-29 and 81.2. The method of claim 1 , wherein the at least one bacterial population consists of bacteria comprising a 16S rDNA sequence at least 99% identical to a 16S rDNA sequence selected from the group consisting of SEQ ID NOs: 1-4 claim 1 , 8 claim 1 , 10 claim 1 , 12 claim 1 , 16-18 claim 1 , 28-29 and 81.3. The method of claim 1 , wherein the disease or disorder is a mental disease or disorder.4. The method of claim 3 , wherein the mental disease or disorder is selected from the group consisting of depression claim 3 , bipolar disorder claim 3 , schizophrenia claim 3 , anxiety claim 3 , anxiety disorders claim 3 , addiction claim 3 , social phobia claim 3 , treatment-resistant major depressive disorder (TR-MDD) claim 3 , major depressive disorder and its subtypes claim 3 , neurodegenerative amyloid disorders claim 3 , orthostatic tremor claim 3 , Lafora disease claim 3 , restless leg syndrome claim 3 , neuropathic pain claim 3 , pain disorders claim 3 , dementia claim 3 , epilepsy claim 3 , stiff-person syndrome claim 3 , premenstrual ...

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Номер записи: 54
10-02-2022 дата публикации

METHOD OF TREATING A MAMMAL, INCLUDING HUMAN, AGAINST CANCER USING METHIONINE AND ASPARAGINE DEPLETION

Номер: US20220040272A1
Автор: AGUERA Karine, BERLIER Willy, GAY Fabien, GODFRIN Yann
Принадлежит:

The invention is related to a new method for treating liquid and solid cancers, in a mammal, including human, wherein methioninase is administered before asparaginase. The invention also encompasses the use of a dietary methionine deprivation, possibly combined with methioninase administration, in advance of asparaginase treatment. Methioninase and asparaginase may be used in particular under free form, pegylated form or encapsulated into erythrocytes. 125-. (canceled)26. A pharmaceutical composition or kit for use in treating cancer in a mammal comprising an asparagine-reducing means and a methionine-reducing means , wherein the methionine-reducing means is administered before the asparagine-reducing means and wherein there is a delay between the administration of the methionine-reducing means and the asparagine-reducing means.27. The composition or kit of claim 26 , wherein when the methionine-reducing means comprises or consists essentially of a methioninase and/or when the asparagine-reducing means comprises or consists essentially of an asparaginase claim 26 , the methioninase and/or the asparaginase are under free form claim 26 , pegylated form or encapsulated inside erythrocytes.28. The composition or kit of claim 27 , wherein the methioninase is under free form or is pegylated and the delay between the end of the methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 7 days claim 27 , between about 3 h and about 6 days claim 27 , or between about 1 day and about 5 days.29. The composition or kit of claim 27 , wherein the methioninase is encapsulated into erythrocytes and the delay between the end of methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 30 days claim 27 , between about 1 day and about 20 days claim 27 , or between about 1 day and about 10 days.30. The composition or kit claim 29 , wherein the methioninase is administered once ...

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Номер записи: 55
28-01-2016 дата публикации

Modulation of ACC Deaminase Expression

Номер: US20160024516A1
Автор: Kateri Duncan, Nina Lovan
Принадлежит: PIONEER HI BRED INTERNATIONAL INC

Methods and compositions comprise ACC deaminase nucleic acids and their encoded proteins for altering ethylene production and stress response in plants. Recombinant expression cassettes, host cells, and transgenic plants comprise the constructs. The amino acid sequence of the deaminase may be altered to modify enzymatic function. The ACC deaminase may be from Diplodia maydis and the host plant may be maize.

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Номер записи: 56
26-01-2017 дата публикации

Attenuated Mannheimia haemolytica

Номер: US20170022510A1
Автор: Briggs Robert E., Tatum Fred M.
Принадлежит:

This disclosure provides attenuated strains useful for providing immunity against 1M. haemolytica. A deletion mutant bacterium comprising a deletion with the LktCA gene locus encoding acylase (LktC) and leukotoxin A (LktA).2M. haemolyticaM. haemolytica. The deletion mutant bacterium of claim 1 , which is an serotype A1 bacterium.3M. haemolytica. The deletion mutant bacterium of claim 2 , which secretes a truncated form of the LktA protein having an amino acid sequence encoded by the nucleic acid sequence set forth in SEQ ID NO:8 or SEQ ID NO:9.4M. haemolyticaM. haemolytica. The deletion mutant bacterium of claim 1 , which is an serotype A6 bacterium.5M. haemolytica. The deletion mutant bacterium of claim 4 , which secretes a truncated form of the LktA protein having an amino acid sequence encoded by the nucleic acid sequence set forth in SEQ ID NO:8 or SEQ ID NO:9. This application is a continuation-in-part of Ser. No. 14/934,737 filed on Nov. 6, 2015, which is a continuation of Ser. No. 14/075,169 filed on Nov. 8, 2013, which claims priority to Ser. No. 61/723,979 filed on Nov. 8, 2012.This application incorporates by reference the contents of an 11.2 kb text file created on Mar. 21, 2016 and named “sequencelisting.txt,” which is the sequence listing for this application.This disclosure relates generally to attenuated bacteria and their use in vaccines.This disclosure provides attenuated strains which can be used to prepare vaccine compositions useful for protection against . In some embodiments, the is serotype A1 (D153). In other embodiments, the is serotype A6 (D174).To attenuate the bacterium, we deleted nucleotides within the LktCA locus, which encodes an enzyme acylase (LktC) and leukotoxin A (LktA), the bacterium's principal virulence factor. This deletion can be amplified by polymerase chain reaction (PCR) and the secretion of a truncated LktA can be detected on a Western blot to determine if the bacterium is the mutant or wildtype. The genetic engineering ...

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Номер записи: 57
24-01-2019 дата публикации

Compositions and methods for treating or ameliorating fibrosis, systemic sclerosis and scleroderma

Номер: US20190022196A1
Автор: Brian Dean Schreiber, Gianfranco Fornasini, Nadejda SOUKHAREVA, Santosh Kumar Ramamurthy
Принадлежит: Leadiant Biosciences Ltd

Provided are Adenosine Deaminase (ADA), or a polypeptides or peptides having an ADA activity, or an ADA conjugate, pharmaceutical compositions and formulations, products of manufacture and kits, and methods containing them for the prevention and treatment of a scleroderma-associated vasculopathy, in particular proliferative obliterative vasculopathy, progressive obliterative vasculopathy or an idiopathic obliterative vasculopathy and/or preventing or decreasing the progression of scleroderma, wherein optionally the scleroderma comprises a local scleroderma or a diffuse, or a systemic scleroderma.

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Номер записи: 58
25-01-2018 дата публикации

BETA-LACTAMASES WITH IMPROVED PROPERTIES FOR THERAPY

Номер: US20180023072A1
Автор: Connelly Sheila, Kaleko Michael
Принадлежит:

This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as infection (CDI). 173-. (canceled)74. A beta-lactamase comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1 and having a polar and neutral hydrophilic residue other than alanine (A) at position 238 according to Ambler classification.75. The beta-lactamase of claim 74 , further comprising a polar and positively charged hydrophilic residue other than glycine (G) at position 156 according to Ambler classification.76. The beta-lactamase of claim 74 , further comprising a polar and neutral hydrophilic residue other than aspartate (D) at position 276 according to Ambler classification.77. The beta-lactamase of claim 76 , further comprising an aromatic hydrophobic residue other than phenylalanine (F) at position 33 according to Ambler classification.78. The beta-lactamase of claim 74 , wherein the polar and neutral hydrophilic residue is selected from asparagine (N) claim 74 , glutamine (Q) claim 74 , serine (S) claim 74 , threonine (T) claim 74 , proline (P) claim 74 , and cysteine (C).79. The beta-lactamase of claim 75 , wherein the polar and positively charged hydrophilic residue is selected from arginine (R) claim 75 , and lysine (K).80. The beta-lactamase of claim 76 , wherein the polar and neutral hydrophilic residue is selected from asparagine (N) claim 76 , glutamine (Q) claim 76 , serine (S) claim 76 , threonine (T) claim 76 , proline (P) claim 76 , and cysteine (C).81. The beta-lactamase of claim 77 , wherein the aromatic hydrophobic residue is selected from tryptophan (W) claim 77 , and tyrosine (Y).82. The beta-lactamase of claim 74 , wherein the beta-lactamase hydrolyzes one or more of penicillins and cephalosporins.83. The beta-lactamase of claim 82 , wherein the penicillin is ampicillin.84. The beta-lactamase of claim 82 , wherein the cephalosporin is ...

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Номер записи: 59
10-02-2022 дата публикации

PENICILLIN-G ACYLASES

Номер: US20220042004A1
Автор: Banerjee Goutami, Jenne Stephan, Mayo Melissa Ann, Milczek Erika M., Yang Jie, Zhang Xiyun
Принадлежит:

The present disclosure relates to engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes. 1. An engineered penicillin G acylase capable of removing the A1/B1/B29 tri-phenyl acetate protecting groups from insulin to produce free insulin , wherein said penicillin G acylase is at least 95% identical to SEQ ID NO: 6 , and wherein said engineered penicillin G acylase comprises an alanine at position 264 , an asparagine at position 484 , and a lysine at position 547 , wherein said positions are numbered with reference to SEQ ID NO: 6.2. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase further comprises at least one additional substitution as provided in Table 5.1 claim 1 , Table 6.2 claim 1 , and/or Table 6.3.3. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises SEQ ID NO: 6 claim 1 , 8 claim 1 , 10 claim 1 , or 12.4. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase is encoded by a polynucleotide sequence selected from SEQ ID NOS: 5 claim 1 , 7 claim 1 , 9 claim 1 , and 11.5. A vector comprising the polynucleotide sequence of .6. A host cell comprising the vector of .7. A method for producing free insulin claim 1 , comprising: i) providing the engineered penicillin G acylase of claim 1 , and insulin comprising A1/B1/B29 tri-phenyl acetate protecting groups; and ii) exposing said engineered penicillin G acylase to said insulin comprising A1/B1/B29 tri-phenyl acetate protecting groups claim 1 , under conditions such that said engineered penicillin G acylase removes the A1/B1/B29 tri-phenyl acetate protecting groups and free insulin is produced.8. The method of claim 7 , wherein said engineered penicillin G acylase produces more than 90% claim 7 , 91% claim 7 , 92% claim 7 , 93% claim 7 , 94% claim 7 , 95% claim 7 , 96% claim 7 , 97% claim 7 ...

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Номер записи: 60
24-01-2019 дата публикации

METHODS AND COMPOSITIONS FOR MODULATING GENE EXPRESSION

Номер: US20190024086A1
Автор: Berry David Arthur, Karnik Rahul, Lande Laura Gabriela
Принадлежит:

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription. 1. A chimeric protein , comprising:a targeting element comprising a sequence targeting polypeptide; andan effector domain comprising all or a biologically active portion of an epigenetic modifying agent,wherein the chimeric protein modifies an anchor sequence associated with a target anchor sequence-mediated conjunction.2. The chimeric protein of claim 1 , wherein the targeting element comprises a sequence targeting polypeptide that specifically binds a sequence in or around an anchor sequence associated with an anchor sequence-mediated conjunction.3. The chimeric protein of claim 1 , which epigenetically modifies the anchor sequence.4. The chimeric protein of claim 1 , which increases methylation of the anchor sequence.5. The chimeric protein of claim 4 , wherein the increase in methylation of the anchor sequence decreases binding of a nucleating protein to the anchor sequence.6. The chimeric protein of claim 1 , wherein the chimeric protein decreases methylation of the anchor sequence.7. The chimeric protein of claim 6 , wherein the decrease in methylation of the anchor sequence increases binding of a nucleating protein to the anchor sequence.8. The chimeric protein of claim 1 , which modulates the activity and/or expression of one or more target nucleic acid sequences.9. The chimeric protein of claim 1 , wherein the anchor sequence is a CTCF binding site.10. The chimeric protein of claim 1 , wherein the nucleating protein is CTCF.11. The chimeric protein of claim 1 , wherein the epigenetic modifying agent comprises an agent that affects DNA methylation claim 1 , histone acetylation claim 1 , histone methylation claim 1 , or RNA-associated silencing.12. The chimeric protein of claim 1 , wherein the epigenetic modifying agent comprises a DNA methylase.13. The chimeric protein of claim 12 , wherein the epigenetic modifying agent comprises DNMT3a ...

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Номер записи: 61
24-01-2019 дата публикации

Method for modifying genome sequence that specifically converts nucleobase of targeted dna sequence, and molecular complex used in said method

Номер: US20190024098A1
Автор: Akihiko Kondo, Keiji Nishida, Satomi Kojima
Принадлежит: Kobe University NUC

The present invention provides a method of modifying a targeted site of a double stranded DNA in a host cell, the method including introducing (a) a DNA encoding a crRNA containing a sequence complementary to a target strand of a target nucleotide sequence in the given double stranded DNA, and (b) a DNA encoding a protein group constituting Cascade and a nucleic acid base converting enzyme, in which the nucleic acid base converting enzyme is constituted in a form capable of forming a complex with any protein in the protein group, into the host cell to convert one or more nucleotides in the targeted site to other one or more nucleotides, or delete one or more nucleotides, or insert one or more nucleotides into said targeted site, without cleaving the double stranded DNA in the targeted site.

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Номер записи: 62
10-02-2022 дата публикации

DIAGNOSING AND TREATING ALZHEIMERS DISEASE

Номер: US20220043007A1
Автор: Han Peng Cheng, Shi Jiong
Принадлежит:

Described herein are methods, systems and compositions for the diagnosis, prognosis and treatment of dementia and Alzheimer's disease. Also described are methods, systems and compositions to distinguish between Alzheimer's disease and Parkinson's disease. In various embodiments levels of PACAP and/or SIRT3 are analyzed for the diagnosis, prognosis and treatment of dementia and Alzheimer's disease. 1. A method of detecting PACAP protein expression in a human subject suspected of having late onset Alzheimer's disease (LOAD) , the method comprising the steps of:(a) obtaining or having obtained a sample from the human subject suspected of having LOAD, wherein the sample comprises at least one of a brain tissue or cerebrospinal fluid; and(b) detecting, using an antibody-based assay, an expression level of PACAP protein in the sample.2. The method of claim 1 , wherein the expression level of PACAP protein in the sample is detected using at least one of ELISA claim 1 , Western blot claim 1 , and flow cytometry.3. The method of and further comprising comparing the detected expression level of PACAP protein in the subject's sample to a reference level of PACAP protein.4. The method of and further comprising administering a composition comprising PACAP to the subject if the subject's expression level of PACAP is below that of the reference level of PACAP protein.5. A method of monitoring PACAP protein expression in a human subject suspected of having late onset Alzheimer's disease (LOAD) claim 1 , the method comprising the steps of:(a) obtaining or having obtained a first sample from the human subject suspected of having LOAD, wherein the sample comprises at least one of a brain tissue or cerebrospinal fluid;(b) detecting, using an antibody-based assay, an expression level of PACAP protein in the first sample;(c) obtaining or having obtained a second sample from the human subject suspected of having LOAD, wherein the sample comprises at least one of a brain tissue or ...

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Номер записи: 63
28-01-2021 дата публикации

RNA PREPARATIONS COMPRISING PURIFIED MODIFIED RNA FOR REPROGRAMMING CELLS

Номер: US20210024895A1
Автор: Dahl Gary, Jendrisak Jerome, Kariko Katalin, Meis Judith, Person Anthony, Weissman Drew
Принадлежит:

The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs. 118-. (canceled)19. A method for reducing the immunogenicity for mammalian cells of a preparation of in vitro-synthesized RNA molecules comprising:purifying a preparation of in vitro-synthesized RNA molecules obtained by a process comprising in vitro transcription (IVT),{'sup': 1', '5', '5', '2, 'wherein said in vitro-synthesized RNA molecules encode at least one recombinant protein and comprise at least one modified nucleoside selected from ψ, mψ, mU, moU, and sU in place of U,'}wherein said purifying uses a purification process that removes RNA contaminant molecules comprises dsRNA molecules that are toxic to mammalian cells by inducing an innate immune response, and wherein said purifying generates a purified RNA preparation that exhibits reduced immunogenicity,wherein said reduced immunogenicity is detectable using an in vitro MDDC immunogenicity assay by measuring secretion of less IFN-α or TNF-α cytokine secreted by human or murine monocyte-derived dendritic cells (MDDCs) transfected with said purified RNA preparation than is secreted from MDDCs transfected with said preparation of in vitro-synthesized RNA molecules that have not been subjected to said purifying.20. The method of claim 19 , wherein said process comprises replacing at least a portion of the UTP in the IVT reaction mixture by the corresponding ...

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Номер записи: 64
24-04-2014 дата публикации

Methods for treatment of inflammatory and infectious diseases

Номер: US20140112902A1
Автор: Augusto Ochoa, James Milton Hill, Paulo Cesar Rodriguez, Timothy Paul Foster
Принадлежит: Louisiana State University and Agricultural and Mechanical College

Methods and therapeutic treatments of diseases such as viral infections are provided including applying peg-Arginase I. Methods are provided that treat inflammation mediated diseases with peg-Arginase I.

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Номер записи: 65
04-02-2016 дата публикации

Erythrocytes containing arginine deiminase

Номер: US20160030532A1
Автор: Pierre-Olivier Goineau, Yann Godfrin
Принадлежит: Erytech Pharma SA

Use of erythrocytes containing arginine deirainase for the preparation of a medicinal product for lowering the plasma concentration of arginine in vivo. The use relates in particular to the treatment of arginine-dependent tumors, such as hepatocarcinoma and malignant melanoma, or inhibition of the synthesis of nitric oxide, and the prevention and/or treatment of septic shock.

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Номер записи: 66
29-01-2015 дата публикации

Method for Producing an Acidified Milk Drink

Номер: US20150030723A1
Автор: Jeppe Wegener Tams, Preben Nielsen
Принадлежит: Chr Hansen AS, Novozymes AS

The present invention relates to a method for producing an acidified milk drink using an enzyme which reduces the isoelectric point of the milk proteins. The invention also relates to a novel enzyme having deamidase activity and its use in production of an acidified milk drink.

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Номер записи: 67
02-02-2017 дата публикации

Methods, compositions and devices for maintaining chemical balance of chlorinated water

Номер: US20170029304A1
Автор: Vivian I. Teichberg
Принадлежит: Mia Levite, Nof Lyle Teichberg, Yaar Teichberg

A composition-of-matter for use in water treatment, composed of a water-insoluble matrix and one or more amidohydrolase, such as cyanuric acid amidohydrolase, incorporated in or on the matrix, is disclosed. Also disclosed are devices containing same and methods utilizing same for water treatment. The water treatment is effected by an enzymatically-catalyzed reduction of the concentration of an amide-containing compound, such as cyanuric acid, found in chlorinated water of swimming polls, spas and other similar structures.

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Номер записи: 68
04-02-2016 дата публикации

CHARGE-ENGINEERED ANTIBODIES OR COMPOSITIONS OF PENETRATION-ENHANCED TARGETING PROTEINS AND METHODS OF USE

Номер: US20160031985A1
Автор: Bowdish Katherine S., Cooke Heather, Huston James S., LIN Kai, Ross John, Vogan Erik M.
Принадлежит:

The disclosure relates to charge-engineered antibodies and penetration-enhanced targeted proteins and their uses for therapeutic treatment or therapeutics delivery. 1. A charge-engineered antibody comprising:an antigen-binding fragment of a parent antibody, which binds a cell surface target;{'sub': H', 'H', 'H, 'a charge-engineered Fc region variant of a starting Fc region, wherein the starting Fc region is a Fc region of the parent antibody or is a naturally occurring immunoglobulin Fc region, wherein the charge-engineered Fc region variant has an increased surface positive charge relative to the starting Fc region, and wherein the charge-engineered Fc region variant has surface positive charge and an increase in theoretical net charge, relative to the starting Fc region, of at least +6 and less than or equal to +16, wherein the charge-engineered Fc region variant comprises a pair of C3 domains and comprises at least three, at least four, at least five, at least six, at least seven, or eight amino acid substitutions in each C3 domain of the pair of C3 domains that increases net positive charge of the charge-engineered Fc region variant relative to that of the starting Fc region, and wherein each substitution is independently selected from Arginine or Lysine or Glutamine or Asparagine.'}2. A protein entity comprising:a target binding region that binds a cell surface target with a dissociation constant (KD) of greater than 0.01 nM or with an avidity of greater than 0.001 nM, anda charged protein moiety (CPM) that enhances penetration into cells;wherein the CPM has tertiary structure and a molecular weight of at least 4 kDa, wherein the CPM has surface positive charge and a net theoretical charge of less than +20;wherein the cell surface target is distinct from that bound by the CPM;and wherein the protein entity binds the cell surface target with sufficient affinity or avidity to effect penetration of the protein entity into cells that express the cell surface target ...

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Номер записи: 69
04-02-2016 дата публикации

UREASE PURIFICATION FROM JACK BEANS OR OTHER ORGANISMS

Номер: US20160032268A1
Автор: Grovender Eric, Hall Eric, Judd Dianne L., Roberson Cindy
Принадлежит: Medtronic, Inc.

A method for the extraction and purification of urease from jack beans or other natural sources of urease. The method provides an efficient way to obtain purified urease from natural sources. The method can include defatting the natural sources of urease, extracting the urease from impurities, and further purification of the extracted urease. 1. A method for isolating and purifying urease from natural sources of urease comprising the steps of:defatting the natural sources of urease using cold solvent to create defatted natural sources of urease;extracting urease from the defatted natural sources of urease; andpurifying the resulting urease solution.2. The method of wherein the natural source of urease is jack beans.3. The method of claim 2 , wherein the hulls of the jack beans are removed prior to the step of defatting the jack beans.4. The method of claim 3 , wherein the jack beans are ground to make jack bean meal prior to the step of defatting the jack beans.5. The method of claim 1 , wherein the step of defatting the natural sources of urease comprises mixing the natural sources of urease with cold solvent to create a natural sources of urease/cold solvent mixture claim 1 , and mechanically separating the natural sources of urease/cold solvent mixture.6. The method of claim 1 , wherein the step of extracting urease from the defatted natural sources of urease comprises:adding the defatted natural sources of urease to a buffer solution to create a natural sources of urease/buffer mixture;agitating the natural sources of urease/buffer mixture; andmechanically separating the natural sources of urease/buffer mixture wherein the supernatant liquid contains the urease.7. The method of claim 6 , wherein the buffer solution is a cold aqueous buffer.8. The method of claim 1 , wherein the step of purifying the urease solution comprises using any one of size exclusion chromatography claim 1 , hydrophobic interaction chromatography claim 1 , affinity chromatography claim 1 , ...

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Номер записи: 70
01-02-2018 дата публикации

Thermostable asparaginase variants and polynucleotides encoding same

Номер: US20180030428A1
Автор: Aki TOMIKI, Allan Svendsen, Hanne Vang Hendriksen, Keiichi Ayabe, Mary Ann Stringer, Tomoko Matsui
Принадлежит: Novozymes AS

The present invention relates to asparaginase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants. The invention further relates to a process of producing a fermentation product, comprising: liquefying a starch-containing material to dextrins with an alpha-amylase in the presence of an asparaginase of the invention; saccharifying the dextrins to a sugar with a glucoamylase; and fermenting the sugar using a fermenting organism.

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Номер записи: 71
01-02-2018 дата публикации

E. COLI-BASED PRODUCTION OF BETA-LACTAMASE

Номер: US20180030458A1
Автор: BRISTOL Andrew, Kaleko Michael
Принадлежит:

The invention relates to, in part, improved methods for the production of beta-lactamase using () cells. High yield production of beta-lactamase is achieved using methods of the invention. 1Escherichia coliE. coli. A method for the production of a beta-lactamase polypeptide in () , comprising:{'i': 'E. coli', '(a) providing a host cell transformed with a vector comprising a sequence encoding the beta-lactamase polypeptide;'}{'i': 'E. coli', '(b) culturing the cell to induce expression of the beta-lactamase polypeptide in the cytoplasm; and'}{'i': 'E. coli', '(c) recovering the beta-lactamase polypeptide from a soluble fraction prepared from the cell, wherein the method yields more than 10 grams of the beta-lactamase polypeptide per liter of culture.'}2. (canceled)3. (canceled)4. The method of claim 1 , wherein the method yields more than 15 grams of the beta-lactamase polypeptide per liter of culture.5E. coli. The method of claim 1 , wherein the cell is selected from BL21(DE3) or W3110.6. The method of claim 1 , wherein expression of the beta-lactamase polypeptide in the cytoplasm is induced by adding isopropylthiogalactoside (IPTG) to the culture.7. The method of claim 1 , wherein the beta-lactamase polypeptide comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 1.8. The method of claim 1 , wherein the beta-lactamase polypeptide comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 10.9. The method of claim 1 , wherein the beta-lactamase polypeptide comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 5.10. The method of claim 1 , wherein the beta-lactamase polypeptide comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 7.11. (canceled)12. The method of claim 9 , wherein the beta-lactamase polypeptide comprises an amino acid sequence of SEQ ID NO: 5 (P3A).13. The method of claim 8 , wherein the beta-lactamase polypeptide comprises an amino acid sequence of SEQ ID NO ...

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Номер записи: 72
30-01-2020 дата публикации

CHOLIX TOXIN-DERIVED FUSION MOLECULES FOR ORAL DELIVERY OF BIOLOGICALLY ACTIVE CARGO

Номер: US20200030417A1
Автор: Mahmood Tahir, Mrsny Randall J.
Принадлежит: APPLIED MOLECULAR TRANSPORT INC.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A(Cholix) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes. 116.-. (canceled)17. A method for delivering a therapeutic cargo across an epithelium of a subject , the method comprising:orally administering to the subject a pharmaceutical composition comprising a non-toxic Cholix toxin coupled to the therapeutic cargo; anddelivering the therapeutic cargo across the epithelium of the subject.18. The method of comprising delivering the therapeutic cargo via transcytosis through a polarized gut epithelial cell.19. The method of comprising transporting the therapeutic cargo preferentially across a polarized epithelial cell versus a cell comprising a CD91 cell receptor.20. The method of comprising delivering the therapeutic cargo via binding a cell receptor not bound by a non-toxic ExoA.21. The method of claim 17 , wherein the non-toxic Cholix toxin lacks a domain III or lacks a functional domain III.22. The method of claim 17 , wherein the non-toxic Cholix toxin is truncated.23. The method of claim 17 , wherein the non-toxic Cholix ...

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Номер записи: 73
30-01-2020 дата публикации

RNA Containing Modified Nucleosides and Methods of Use Thereof

Номер: US20200030460A1
Автор: Kariko Katalin, Weissman Drew
Принадлежит:

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules. 115-. (canceled)16. A method for reducing the immunogenicity of in vitro-synthesized RNA comprising an open reading frame that encodes a recombinant protein of interest , the method comprising: replacing at least a portion of uridine nucleotides of in vitro-synthesized RNA with a nucleotide comprising the modified nucleoside 5-methoxyuridine (moU) , thereby generating in vitro-synthesized RNA comprising moU in place of at least a portion of uridine nucleotides and reducing the immunogenicity of said in vitro-synthesized RNA compared with the in vitro-synthesized RNA that does not comprise moU in place of uridine.17. The method of claim 16 , wherein the reduced immunogenicity is detected by at least one method selected from the group consisting of:{'sup': 5', '5, '(i) detecting a decrease in immunogenicity such that the in vitro-synthesized RNA comprising moU in place of uridine can be repeatedly administered without eliciting an immune response sufficient to detectably reduce expression of said recombinant protein of interest, whereas repeatedly administering the same quantity of in vitro-synthesized RNA that does not comprise moU in place of uridine does detectably reduce expression of said recombinant protein of interest;'}(ii) measuring less secretion of at least one cytokine in response to administration of{'sup': 5', '5, 'in vitro-synthesized RNA comprising moU in place of uridine compared to the amount of said cytokine secreted in response to administration of the ...

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Номер записи: 74
31-01-2019 дата публикации

USE OF THE REDUCTIVE GLYCINE PATHWAY FOR GENERATING FORMATOTROPHIC AND AUTOTROPHIC MICROORGANISMS

Номер: US20190032027A1
Автор: Bar-Even Arren, Milo Ron, Noor Elad, Yishai Oren
Принадлежит: Yeda Research and Development Co. Ltd.

An isolated microorganism that expresses enzymes of the reductive glycine pathway is disclosed. The microorganism is capable of converting formate to pyruvate or glycerate via the formation of glycine and serine. Methods of generating same are further described. 1. An isolated microoranism that is genetically modifed to express at least one enzyme of the reductive glycine pathway , said microorganism being able to utilize formate as its sole carbon source , wherein the microorganism is capable of converting formate to glycine and serine and further being able of converting said glycine and said serine to pyruvate or glycerate.2. An isolated microorganism that is genetically modifed to express enzymes of the reductive glycine pathway , wherein the microorganism is capable of converting formate to a metabolite of central metabolism via the formation of glycine and without the formation of serine , said metabolite being selected from the group consisting of acetyl CoA , oxaloacetate , glycerate 2-phosphate and glycerate 3-phosphate.3. The microorganism of claim 2 , not expressing EC 2.1.2.1.4. The microorganism of claim 1 , further expressing a formate dehydrogenase which is capable of reducing carbon dioxide to formic acid.5. The microorganism of claim 1 , selected from the group consisting of a bacteria claim 1 , a yeast claim 1 , a fungi or an algae.6. The microorganism of claim 2 , selected from the group consisting of a bacteria claim 2 , a yeast claim 2 , a fungi or an algae.7Escherichia.. The microorganism of claim 5 , wherein said bacteria comprises8Escherichia. The microorganism of claim 7 , wherein said are genetically modified to express a first enzyme NAD-dependent formate dehydrogenase which is capable of oxidizing formate to carbon dioxide and a second enzyme formate-tetrahydrofolate ligase.9Escherichia. The microorganism of claim 8 , wherein said are genetically modified to further express bifunctional methenyltetrahydrofolate-cyclohydrolase-NAD- ...

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Номер записи: 75
31-01-2019 дата публикации

SYSTEMIC SYNTHESIS AND REGULATION OF L-DOPA

Номер: US20190032079A1
Автор: McDonald Michael
Принадлежит:

The present invention relates to an expression system for enzyme replacement therapy with the aim of obtaining or maintaining a steady level of L-DOPA in the blood of an individual, achieved through systemic administration of the expression system. The invention is thus useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including Parkinson's Disease. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. (canceled)30. (canceled)31. (canceled)32. (canceled)33. (canceled)34. (canceled)35. (canceled)36. (canceled)37. (canceled)38. (canceled)39. (canceled)40. (canceled)41. (canceled)42. (canceled)43. (canceled)44. (canceled)45. (canceled)46. (canceled)47. (canceled)48. (canceled)49. (canceled)50. (canceled)51. (canceled)52. (canceled)53. (canceled)54. (canceled)55. (canceled)56. (canceled)57. (canceled)58. (canceled)59. (canceled)60. (canceled)61. (canceled)62. (canceled)63. (canceled)64. (canceled)65. (canceled)66. (canceled)67. (canceled)68. (canceled)69. (canceled)70. (canceled)71. (canceled)72. (canceled)73. (canceled)74. (canceled)75. (canceled)76. (canceled)77. (canceled)78. (canceled)79. (canceled)80. (canceled)81. (canceled)82. (canceled)83. (canceled)84. (canceled)85. (canceled)86. (canceled)87. (canceled)88. (canceled)89. (canceled)90. (canceled)91. (canceled)92. (canceled)93. (canceled)94. (canceled)95. (canceled)96. (canceled)97. (canceled)98. (canceled)99. (canceled)100. (canceled)101. (canceled)102. (canceled)103. (canceled)104. (canceled)105. (canceled)106. (canceled)107. (canceled)108. (canceled)109. (canceled)110. (canceled)111. (canceled)112. (canceled)113. (canceled)114. ( ...

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Номер записи: 76
04-02-2021 дата публикации

METHOD FOR PRODUCTION OF RECOMBINANT ERWINIA ASPARAGINASE

Номер: US20210032640A1
Автор: BRUCK Torben, COLEMAN Russell J.
Принадлежит:

Provided herein are methods of production of recombinant asparaginase. Methods herein produce asparaginase having high expression levels in the periplasm or the cytoplasm of the host cell having activity comparable to commercially available asparaginase preparations. 1. A method for producing a recombinant type II asparaginase , the method comprising culturing a Pseudomonadales host cell in a culture medium and expressing the recombinant type II asparaginase in the cytoplasm of the Pseudomonadales host cell from an expression construct comprising a nucleic acid encoding the recombinant type II asparaginase , wherein the recombinant type II asparaginase comprises an amino acid sequence from about 85% to 100% homologous to SEQ ID NO: 1 , and wherein the recombinant type II asparaginase is produced in the cytoplasm at a yield of about 20% to about 40% total cell protein (TCP) in soluble form.2. The method of claim 1 , wherein the recombinant type II asparaginase is produced in the cytoplasm at a yield of about 10 g/L to about 25 g/L.3. The method of claim 1 , further comprising measuring the activity of an amount of the soluble recombinant type II asparaginase produced claim 1 , using an activity assay.4Erwinia chrysanthemi. The method of claim 1 , wherein the recombinant type II asparaginase is an L-asparaginase type II (crisantaspase).5. The method of claim 1 , wherein the nucleic acid encoding the recombinant type II asparaginase comprises a sequence at least 85% homologous to SEQ ID NO: 2.6. The method of claim 1 , wherein the recombinant type II asparaginase comprises an amino acid sequence as set forth in SEQ ID NO: 1.7Pseudomonas fluorescens. The method of claim 1 , wherein the Pseudomonadales host cell is a cell.8. The method of claim 1 , wherein the host cell is deficient in the expression of one or more native asparaginases.9. The method of claim 8 , wherein the one or more deficiently expressed native asparaginase is selected from: a type I asparaginase; a ...

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Номер записи: 77
05-02-2015 дата публикации

Binding Proteins To The Constant Region Of Immunoglobulin G

Номер: US20150037312A1
Автор: Baker David, Fleishman Sarel Jacob, Strauch Eva-María
Принадлежит:

The present invention provides polypeptides that bind to immunoglobulin G and methods for their use. 1. A polypeptide comprising an amino acid sequence of general formula 1 Z1-Z2-Z3 (SEQ ID NO: 1) , wherein X1 is any four amino acids; and', 'X2 is any nine amino acids;, 'Z1 is a peptide with an amino acid sequence according to general formula 2: X1-S-X2 (SEQ ID NO: 2), wherein'}Z2 is a peptide of between 17 and 50 amino acid residues; and B1 is any four amino acids;', 'B2 is any two amino acids; and', 'B3 is any four amino acids., 'Z3 is a peptide with an amino acid amino acid sequence according to general formula 3: B1-Q-B2-F-Y-B3 (SEQ ID NO: 3)'}2. (canceled)3. The polypeptide of claim 1 , wherein X2 is a peptide of general formula 4: R-J1-V-J2 (SEQ ID NO: 4) claim 1 , whereinJ1 is any two amino acids; andJ2 is any five amino acids.4. The polypeptide of claim 1 , wherein X1 is EY(A/C)V (SEQ ID NO: 10).5. The polypeptide of claim 1 , wherein X2 is RTA(X3)D(A/F)(L/R/K)(K/L)H (SEQ ID NO: 5);wherein X3 is any amino acid.67.-. (canceled)9. (canceled)10. The polypeptide of claim 1 , wherein B1 is (T/S/R/M/P/W/V/T)(M/F)(E/M/K/L/V)(Q) (SEQ ID NO: 6).11. (canceled)12. The polypeptide of claim 1 , wherein B2 is (S/A)(F/L/M/I).1314.-. (canceled)15. The polypeptide of wherein B3 is M(B4)(L/W)(R/K) (SEQ ID NO: 7) claim 1 , wherein B4 is any amino acid.1619.-. (canceled)21. The polypeptide of claim 1 , wherein Z2 is a peptide of between 17 and 32 amino acids.2325.-. (canceled)26. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:88-119.27. The polypeptide of claim 1 , wherein the polypeptides comprises an amino acid sequence of general formula 5 claim 1 , Z4-Z1-Z2-Z3 (SEQ ID NO: 8) claim 1 , wherein Z4 is a peptide of at least between 100-200 amino acids in length.28. The polypeptide of claim 27 , wherein Z4 comprises an amino acid sequence of SEQ ID NO:120.2930.-. (canceled)31. The polypeptide ...

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Номер записи: 78
05-02-2015 дата публикации

MICROORGANISMS FOR THE PRODUCTION OF 5-HYDROXYTRYPTOPHAN

Номер: US20150037849A1
Автор: Forster Jochen, Knight Eric Michael, Luo Hao, Zhu Jiangfeng
Принадлежит:

Recombinant microbial cells and methods for producing 5-hydroxytryptophan (5HTP) using such cells are described. More specifically, the recombinant microbial cell comprises an exogenous gene encoding an L-tryptophan hydroxylase, and means for providing tetrahydrobiopterin (THB). Related sequences and vectors for use in preparing such recombinant microbial cells are also described. 1. A recombinant microbial cell comprising an exogenous nucleic acid sequence encoding an L-tryptophan hydroxylase (TPH) (EC 1.14.16.4) , and exogenous nucleic acid sequences encoding enzymes of at least one pathway for producing tetrahydrobiopterin (THB).2. The recombinant microbial cell of claim 1 , comprising exogenous nucleic acid sequences encoding enzymes of a first pathway producing THB from guanosin triphosphate (GTP) claim 1 , of a second pathway regenerating THB from 4a-hydroxytetrahydrobiopterin claim 1 , or of both the first and the second pathway.3. The recombinant microbial cell of any one of the preceding claims claim 1 , comprising exogenous nucleic acid sequences encoding(a) optionally, a GTP cyclohydrolase I (EC 3.5.4.16);(b) a 6-pyruvoyl-tetrahydropterin synthase (EC 4.2.3.12); and(c) a sepiapterin reductase (EC 1.1.1.153).4. The recombinant microbial cell of any one of the preceding claims claim 1 , comprising exogenous nucleic acid sequences encoding(a) a 4a-hydroxytetrahydrobiopterin dehydratase (EC 4.2.1.96); and(b) optionally, a dihydropteridine reductase (EC 1.5.1.34).5. The recombinant microbial cell of any one of the preceding claims claim 1 , wherein each one of said exogenous nucleic acid sequences is operably linked to an inducible claim 1 , a regulated or a constitutive promoter.6. The recombinant microbial cell of any one of the preceding claims claim 1 , which comprises a mutation providing for reduced tryptophanase activity.7. The recombinant microbial cell of any one of the preceding claims claim 1 , which is derived from a microbial host cell which is a ...

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Номер записи: 79
11-02-2016 дата публикации

THERAPEUTIC ACID CERAMIDASE COMPOSITIONS AND METHODS OF MAKING AND USING THEM

Номер: US20160038574A1
Автор: Schuchman Edward H.
Принадлежит:

The present invention relates to a therapeutic composition including a ceramidase mixture and a pharmaceutically acceptable carrier, where the ceramidase mixture includes an inactive acid ceramidase precursor and an active acid ceramidase. The invention also relates to a method of acid ceramidase treatment, including formulating the acid ceramidase used in said treatment as a ceramidase mixture, where the ceramidase mixture includes an inactive acid ceramidase precursor and an active acid ceramidase. The invention further relates to a method of producing a therapeutic composition including providing a medium containing an inactive acid ceramidase precursor; incubating the medium under conditions effective to transform a portion of the inactive acid ceramidase precursor to active acid ceramidase; and recovering the incubated medium as a ceramidase mixture comprising the inactive acid ceramidase precursor and an active acid ceramidase. The present invention also relates to preparation of a therapeutic composition of a ceramidase lacking acid sphingomyelinase. 1. A method of producing a therapeutic composition , the method comprising:providing a medium containing an inactive acid ceramidase precursor;incubating the medium under conditions effective to transform a portion of the inactive acid ceramidase precursor to active acid ceramidase; andrecovering the incubated medium as a ceramidase mixture comprising the inactive acid ceramidase precursor and an active acid ceramidase.2. The method of claim 1 , wherein said incubating is carried out under conditions effective to reduce the transformation rate of inactive acid ceramidase precursor to active acid ceramidase compared to the transformation rate achieved when said incubating is carried out at a pH of 4 and a temperature of 4° C. or 37° C. claim 1 , for 24 hours claim 1 , under otherwise consistent conditions.3. The method of claim 2 , wherein the pH of the ceramidase mixture during said incubating is over 4.0 and up ...

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Номер записи: 80
11-02-2016 дата публикации

Novel Polypeptides Having Endolysin Activity and Uses Thereof

Номер: US20160040148A1
Автор: Mayer Melinda, NARBAD Arjan
Принадлежит:

The present invention provides isolated polypeptides comprising a fragment of the amino acid sequence of SEQ ID NO:1, or a variant, derivative or fusion thereof, which is capable of binding specifically to and lysing cells of , wherein the polypeptide exhibits greater lytic activity on cells of than the polypeptide of SEQ ID NO:1. The invention further provides means for producing the same, methods for killing bacterial cells such as cells of , as well as methods for diagnosing, treating and preventing diseases and conditions associated with infection of the same. 1100-. (canceled)101Clostridium difficile. An isolated polypeptide comprising or consisting of an amino acid sequence with at least 95% identity to the amino acid sequence of SEQ ID NO:2 , wherein the polypeptide exhibits greater lytic activity on cells of than the polypeptide of SEQ ID NO:1.102. The isolated polypeptide of claim 101 , wherein the polypeptide consists of amino acids 1 to 179 of SEQ ID NO:1 (i.e. claim 101 , SEQ ID NO:2).103. The isolated polypeptide of claim 101 , consisting of the amino acid sequence of SEQ ID NO:2 claim 101 , 4 claim 101 , or 6.104. An isolated nucleic acid molecule encoding the polypeptide of .105. A vector comprising a nucleic acid molecule encoding the polypeptide of .106. A host cell comprising a nucleic acid molecule encoding the polypeptide of or a vector comprising a nucleic acid molecule encoding the polypeptide of .107. A method for producing the polypeptide of comprising culturing a population of host cells comprising a nucleic acid molecule encoding the polypeptide of or a vector comprising a nucleic acid molecule encoding the polypeptide of under conditions in which the polypeptide is expressed claim 101 , and isolating the polypeptide therefrom.108. A pharmacological composition comprising:{'claim-ref': {'@idref': 'CLM-00101', 'claim 101'}, '(a) the polypeptide of ;'}{'claim-ref': {'@idref': 'CLM-00101', 'claim 101'}, '(b) a nucleic acid molecule encoding ...

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Номер записи: 81
09-02-2017 дата публикации

Methods And Materials For Producing Enhanced Sugar, Starch, Oil, And Cellulose Output Traits In Crop Plants

Номер: US20170037419A1
Автор: Herman Eliot M.
Принадлежит: The Arizona Board of Regents on Behalf of the University of Arizona

Described are crop-related materials and methods for metabolic engineering. Certain aspects of the invention include applications in food production, carbon sequestration, and biofuel production. Described are methods of enhancing plant traits for increased production of sugar, starch, cellulose, and oil. Described methods include altering cytosolic asparagine to promote production of non-nitrogenous plant compounds. 1. A method for redirecting a plant's allocation of fixed carbon toward carbohydrate polymers relative to a control plant , comprising increasing expression in a plant at least a first copy of a nucleic acid having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 2 sufficient to redirect the plant's allocation of fixed carbon toward carbohydrate polymers relative to a control plant.2. (canceled)3. (canceled)4. (canceled)5. The method of claim 1 , wherein the fixed carbohydrate comprises in at least one form of carbohydrate polymer selected from the group consisting of: sugars; starch; cellulose; and oil.6. The method of claim 1 , wherein the redirection of the plant's allocation of fixed carbon towards carbohydrate polymers relative to a control plant occurs under non-stress conditions.7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The method of claim 1 , wherein the first copy of the nucleic acid is operatively linked to a first promoter claim 1 , and further comprising introducing and expressing a second copy of the nucleic acid in the plant claim 1 , wherein the second copy of the nucleic acid is operably linked to a second promoter.14. The method of claim 13 , wherein one copy of the nucleic acid is operably linked to a tissue non-specific promoter and the other copy of the nucleic acid is operably linked to a tissue-specific promoter.15. (canceled)16CamelinaBrachypodium. The method of claim 1 , wherein the plant is selected from the group consisting of: soybean; potato; tomato; tobacco; ...

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Номер записи: 82
08-02-2018 дата публикации

METHODS AND MEANS FOR INCREASING STRESS TOLERANCE AND BIOMASS IN PLANTS

Номер: US20180037903A1
Автор: AMTMANN Anna, Gossele Veronique, Hannah Matthew, LOPEZ-VERNAZA Manuel, PERRELLA Giorgio, VERDUYN Christoph
Принадлежит:

The invention provides methods for producing a plant with increased stress-tolerance and yield, as well as chimeric genes for use according to the methods and plant comprising such chimeric genes. 1. A method for increasing tolerance of a plant , plant part , plant organ or plant cell to stress conditions; or for reducing ABA sensitivity of a plant , plant part , plant organ or plant cell; or for increasing biomass or yield or growth rate of a plant , plant organ or plant part; or for accelerating flowering time of a plant; comprising the step ofa. increasing the expression and/or activity of a protein having the activity of the protein with the amino acid sequence of SEQ ID NO. 6, in said plant, plant part, plant organ or plant cell.2. The method according to claim 1 , wherein said stress condition is a moderate stress condition.3. The method according to or claim 1 , wherein said increasing the expression and/or activity of a protein having the activity of the protein with the amino acid sequence of SEQ ID NO. 6 comprises expressing in said plant cell claim 1 , plant part claim 1 , plant organ or plant a chimeric gene comprising the following operably linked elements:i. A plant-expressible promoterii. A nucleic acid which when transcribed results in an increased activity and/or expression of a protein having the activity of the protein encoded by SEQ ID NO. 6iii. Optionally, a 3′ end region involved in transcription termination and polyadenylation functional in plants4. The method according to claim 3 , wherein said nucleic acid encodes a protein having the activity of the protein with the amino acid sequence of SEQ ID NO.6.5. The method according to or claim 3 , wherein said nucleic acid comprises a nucleic acid sequence encoding a protein having at least 70% sequence identity to SEQ ID NO.6 claim 3 , SEQ ID NO. 8 claim 3 , SEQ ID NO. 10 claim 3 , SEQ ID NO. 12 claim 3 , SEQ ID NO. 14 claim 3 , SEQ ID NO. 16 claim 3 , SEQ ID NO. 18 claim 3 , SEQ ID NO. 20 claim 3 ...

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Номер записи: 83
24-02-2022 дата публикации

ASPARAGINASE-INDUCED GLUTAMINE DEPLETION COMBINED WITH BCL-2 INHIBITION FOR TREATMENT OF HEMATOLOGIC AND SOLID CANCERS

Номер: US20220054606A1
Автор: Emadi Ashkan, LAPIDUS Rena G.
Принадлежит: University of Maryland, Baltimore

Methods of treating cancer and prolonging survival of a subject having cancer, such as acute myeloid leukemia, via administration of therapeutically effective amounts of agents that depletes plasma glutamine and agents that inhibit BCL-2 activity are detailed herein. Suitable agents that depletes plasma glutamine include asparaginase Suitable agents that inhibit BCL-2 activity include Venetoclax. 1. A method of treating cancer in a subject or prolonging survival of a subject having cancer , comprising administering therapeutically effective amounts of a first agent that depletes plasma glutamine and a second agent that inhibits BCL-2 activity to a subject having cancer.2. The method of claim 1 , wherein the first and second agents are administered in any order claim 1 , alone or in any combination claim 1 , sequentially or concurrently claim 1 , with overlapping or non-overlapping periods of administration.3. The method of claim 2 , comprising concurrently administering therapeutically effective amounts of the first and second agents.4. The method of claim 2 , comprising sequentially administering therapeutically effective amounts of the first and second agents claim 2 , in any order.5. The method of claim 1 , wherein one or more of the first and second agents are formulated claim 1 , separately or together claim 1 , in any combination claim 1 , in pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent.6. The method of claim 1 , wherein the combination of the first and second agents has an additive therapeutic effect on the cancer. (original) The method of claim 1 , wherein the combination of the first and second agents has a synergistic therapeutic effect on the cancer.8E. coliE. coliErwinia chrysanthemiErwinia chrysanthemiErwinia chrysanthemi. The method of claim 1 , wherein the agent that depletes plasma glutamine is one or more asparaginase selected from the group consisting of -derived short acting asparaginase claim 1 , ...

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Номер записи: 84
07-02-2019 дата публикации

MESENCHYMAL STEM CELL EXPRESSING TRAIL AND CD, AND USE THEREOF

Номер: US20190038676A1
Автор: KIM Hey-yon, LEE Soon Min, Sung Young Chul
Принадлежит: SLBIGEN INC.

The present invention relates to: a recombinant lentiviral vector comprising a gene encoding a TRAIL protein and a CD protein; and a cell that is transfected with the lentivirus produced by using the vector. A host cell transfected with the recombinant lentivirus of the present invention maintains a high cell proliferation rate and overexpresses a TRAIL protein and a CD protein. Thus, a mesenchymal stem cell transfected with the lentivirus may be usefully employed as a cell therapeutic agent. 1. A recombinant lentiviral vector comprising a gene encoding a TNF-related apoptosis-inducing ligand (TRAIL) protein , and a cytosine deaminase (CD) protein.2. The recombinant lentiviral vector according to claim 1 , wherein the TRAIL protein is a polypeptide having the amino acid sequence of SEQ ID NO: 1.3. The recombinant lentiviral vector according to claim 1 , wherein the CD protein is a polypeptide having the amino acid sequence of SEQ ID NO: 3.4. The recombinant lentiviral vector according to claim 1 , which comprises one or two promoters.5. The recombinant lentiviral vector according to claim 4 , wherein the promoter is a cytomegalovirus (CMV) claim 4 , respiratory syncytial virus (RSV) claim 4 , human elongation factor-1 alpha (EF-1α) or tetracycline response elements (TRE) promoter.6. The recombinant lentiviral vector according to claim 1 , which comprises an internal ribosome entry site (IRES).7. A recombinant lentivirus comprising a gene encoding a TRAIL protein and a CD protein.8. The recombinant lentivirus according to claim 7 , wherein the lentivirus is obtained by a process comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'transforming a host cell with the lentiviral vector according to , a packaging plasmid and an envelope plasmid; and'}isolating the lentivirus from the transformed host cell.9. A host cell transfected with the recombinant lentivirus according to .10. The host cell according to claim 9 , which is a mesenchymal stem cell. ...

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Номер записи: 85
24-02-2022 дата публикации

METHODS FOR PROMOTING PLANT HEALTH USING FREE ENZYMES AND MICROORGANISMS THAT OVEREXPRESS ENZYMES

Номер: US20220055961A1
Автор: AUGUSTIN Jörg, Thompson Brian M.
Принадлежит:

Methods for stimulating plant growth and/or promoting plant health using free enzymes or recombinant microorganisms that overexpress enzymes are provided. Plant seeds coated with free enzymes or recombinant microorganisms that overexpress enzymes are also provided. Compositions comprising a fertilizer and an enzyme or a recombinant microorganism that overexpresses an enzyme are provided. Modified enzymes having ACC deaminase activity, recombinant microorganisms expressing the modified enzymes, plant seeds treated with the modified enzymes or recombinant microorganisms, and methods for stimulating plant growth and/or promoting plant health using the modified enzymes or recombinant microorganisms are also provided. 120-. (canceled)21. A method for stimulating plant growth and/or promoting plant health comprising applying a free enzyme to a plant seed , wherein the enzyme is selected from a phospholipase , a lipase , a xylanase , a xylosidase , a lactonase , a mannanase , a pectinase , a chitosanase , a protease , an acid phosphatase , a glucanase , an ACC deaminase , a phytase , and combinations of any thereof.22. (canceled)23. The method of claim 21 , wherein the enzyme comprises a glucanase claim 21 , and wherein the glucanase comprises a non-cellulolytic glucanase.2466-. (canceled)67. The method of claim 21 , wherein applying the enzyme to the plant seed comprises:(a) applying the enzyme to the plant seed at the time of planting; or (b) coating the plant seed with the enzyme.68. The method of claim 67 , wherein the method comprises coating the plant seed with a seed coating formulation comprising:the enzyme; andan agriculturally acceptable carrier.69. A plant seed treated with a free enzyme claim 67 , wherein the enzyme is selected from a phospholipase claim 67 , a lipase claim 67 , a xylanase claim 67 , a xylosidase claim 67 , a mannanase claim 67 , a pectinase claim 67 , a lactonase claim 67 , a chitosanase claim 67 , a protease claim 67 , a phytase claim 67 , an ...

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Номер записи: 86
24-02-2022 дата публикации

SINGLE-DOMAIN ANTIBODY-CYTOSINE DEAMINASE FUSION PROTEINS

Номер: US20220056149A1
Автор: Chen Pei-Jiun, LEE Shu-Hua
Принадлежит:

The disclosure relates to fusion proteins, methods of making fusion proteins, and methods of using fusion proteins, wherein the fusion proteins comprise a functional single-domain antibody (sdAb) or a functional variant thereof and a cytosine deaminase (CD) protein or a functional variant thereof, optionally connected via a peptide linker. The fusion proteins of the disclosure also have CD activity. The disclosure also relates to pharmaceutical compositions or formulations comprising such fusion proteins and pharmaceutically acceptable excipients, as well as medical uses of these fusion proteins. 2. The fusion protein of claim 1 , wherein n=0 claim 1 , 1 claim 1 , or 2.3. The fusion protein of claim 1 , wherein the sdAb or functional variant thereof binds to a target.4. The fusion protein of claim 3 , wherein the target is selected from the group consisting of EGFR claim 3 , 5T4 claim 3 , A33 claim 3 , AFP claim 3 , Beta-catenin claim 3 , BRCA1 claim 3 , BRCA2 claim 3 , C242 claim 3 , CCR4 claim 3 , CD152 claim 3 , CD19 claim 3 , CD20 claim 3 , CD200 claim 3 , CD22 claim 3 , CD221 claim 3 , CD23 claim 3 , CD30 claim 3 , CD3 claim 3 , CD37 claim 3 , CD40 claim 3 , CD44 claim 3 , CD5 claim 3 , CD51 claim 3 , CD52 claim 3 , CD56 claim 3 , CD64 claim 3 , CD74 claim 3 , CD80 claim 3 , CDCP1 claim 3 , c-KIT claim 3 , COX-2 claim 3 , cMET claim 3 , CSF1R claim 3 , CTLA-4 claim 3 , ErbB2 claim 3 , ErbB3 claim 3 , EGF2 claim 3 , FGFR1 claim 3 , FGFR2 claim 3 , FGFR3 claim 3 , FLT3 claim 3 , HER2 claim 3 , HER3 claim 3 , HIF-Ia claim 3 , HLA-DR claim 3 , IGF-IR claim 3 , mTOR claim 3 , NPC-1C claim 3 , P53 claim 3 , PDGFRα claim 3 , PDGFRβ claim 3 , PLGF claim 3 , PSA claim 3 , RGMa claim 3 , RoN claim 3 , TNF claim 3 , TP53 claim 3 , TPD52 claim 3 , VEGFR1 claim 3 , VEGFR2 claim 3 , VEGFR3 claim 3 , CA-IX claim 3 , αvβ3 claim 3 , α5β1 claim 3 , FAP claim 3 , glycoprotein 75 claim 3 , TAG-72 claim 3 , MUC16 claim 3 , NR-LU-13 claim 3 , SLAMF7 claim 3 , EGP40 claim 3 , BAFF ...

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Номер записи: 87
24-02-2022 дата публикации

Modified L-Asparaginase

Номер: US20220056430A1
Автор: "ODONNELL Anne", FRIEDRICH Lars
Принадлежит:

The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof. 127-. (canceled)28. A method of treating cancer in a human subject in need thereof comprising administering to the human subject a recombinant protein , wherein the recombinant protein is a tetramer , and each monomer of the tetramer comprises:(i) an L-asparaginase subunit having at least 95% sequence identity to SEQ ID NO: 1 fused to (ii) a polypeptide, wherein the polypeptide consists of 200-600 proline and alanine amino acid residues.29. The method according to claim 28 , wherein the L-asparaginase subunit has an amino acid sequence comprising SEQ ID NO: 1.30. The method according to claim 28 , wherein the L-asparaginase subunit has an amino acid sequence consisting of SEQ ID NO: 1.31. The method according to claim 30 , wherein the polypeptide consists of 100 to 600 proline and alanine amino acid residues.32. The method according to claim 30 , wherein the proline amino acid residues constitute more than 10% and less than 70% of the polypeptide.33. The method according to claim 30 , wherein the polypeptide has an amino acid sequence comprising SEQ ID NO: 5.34. The method according to claim 30 , wherein the polypeptide has an amino acid sequence comprising SEQ ID NO: 7.35. The method according to claim 30 , wherein the polypeptide has an amino acid sequence comprising SEQ ID NO: 9.36. The method according to claim 30 , wherein the monomer has an amino acid sequence comprising SEQ ID NO: 11.37. The method according to claim 30 , wherein the monomer has an amino acid sequence comprising SEQ ID NO: 13.38. The method according to claim 28 , wherein the recombinant protein is present in a pharmaceutical formulation with one or more pharmaceutically acceptable carriers or excipients.39. The method of claim 38 , ...

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Номер записи: 88
06-02-2020 дата публикации

Urease Purification And Purified Urease Products Thereof And Sorbent Cartridges, Systems And Methods Using The Same

Номер: US20200040323A1
Автор: Mallipalli Harshavardhana Reddy, Yi Jun
Принадлежит:

Methods for purifying urease are described that make use of a precipitating agent such as ammonium sulfate to obtain urease as a precipitate. The method can involve use of a solubilizing agent, such as a citrate-containing solution, to dissolve the precipitate. The method can involve the use of a sugar to provide protected urease in a sugar-urease solution and immobilization of the urease. The method can involve freeze drying of the immobilized urease. A sugar-urease preparation and an immobilized urease, and a sorbent cartridge containing the urease are described as well as methods to conduct dialysis. 1. A method of purifying urease , comprising:a) mechanically separating an extract mixture to provide a separated solution, wherein the extract mixture comprises an extracting agent in solution and a comminuted source of urease;b) combining ammonium sulfate with the separated solution to precipitate urease in the separated solution to provide a precipitate-containing mixture;c) mechanically separating the precipitate-containing mixture to collect the precipitate;d) dissolving the precipitate collected to provide a urease-containing solution;e) combining the urease-containing solution with a sugar to provide a sugar-urease solution;f) combining the sugar-urease solution and a sorbent material to immobilize urease on the sorbent material to provide an immobilized urease preparation; andg) optionally freeze drying the immobilized urease preparation to provide an immobilized urease product.2. The method of claim 1 , wherein the source of urease is a botanical source of urease claim 1 , fungal source of urease claim 1 , algal source of urease claim 1 , bacterial source of urease claim 1 , invertebrate source of urease claim 1 , or any combination thereof.3. The method of claim 1 , wherein the source of urease comprises jack beans claim 1 , sword beans claim 1 , soy beans claim 1 , or any combination thereof.4. The method of claim 1 , wherein the source of urease is jack ...

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Номер записи: 89
07-02-2019 дата публикации

Sensitive Detection of Protein Heterogeneity By Use Of Enzyme Cascades

Номер: US20190041392A1
Автор: Hans Brandstetter, Julia Hollerweger
Принадлежит: SANDOZ AG

The present invention deals with a method for detecting a protein in a protein sample by amplifying and enhancing small differences between proteins contained in the protein sample. In particular, the present invention uses a cascade of enzymatic modification steps to detect and identify a protein in a protein sample by enhancing small differences between the protein and other proteins contained in the protein sample. Further, the present invention provides a method for distinguishing two proteins having substantially identical or similar amino acid sequences but different protein conformations.

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Номер записи: 90
16-02-2017 дата публикации

NOVEL USE OF MULTI-ARM POLYETHYLENE GLYCOL MODIFIER AND APPLICATION OF MULTI-ARM POLYETHYLENE GLYCOL MODIFIER IN L-ASPARAGINASUM MODIFICATION

Номер: US20170043028A1
Автор: MA Bruce Yong, Wang Jun, WANG Yaofang, WU Dinglong, XU Chunlin
Принадлежит:

Methods for use of a multi-arm polyethylene glycol (PEG) modifier in modification of asparaginase. The described multi-arm PEG modifier enhances the subunit interaction of a multimeric protein to maintain the multimeric protein in a polymerized form, thereby improving the stability of the multimeric protein, maintaining the bioactivity of the multimeric protein, and reducing the probability of exposure of the antigen binding site after depolymerization of the subunits, so as to reduce the immunogenicity. 1. A method comprising modifying a multimeric protein with a multi-arm polyethylene (PEG).3. The method according to claim 2 , wherein n is an integer selected from 2 to 500 claim 2 , and preferably an integer selected from 25 to 100; k is 1 claim 2 , m is 4 claim 2 , and p is 2; and the molecular weight of the multi-arm PEG is from 1 to 40 kDa claim 2 , and preferably 5 to 10 kDa.4. The method according to claim 3 , wherein the multi-arm PEG is an aldehyde or ester activated multi-arm PEG derivative claim 3 , wherein the ester activated PEG derivative is any one selected from 4-arm PEG succinimidyl acetate claim 3 , 4-arm PEG succinimidyl propionate or 4-arm PEG succinimidyl carbonate; and the aldehyde activated PEG derivative is any one selected from 4-arm PEG propionaldehyde claim 3 , 4-arm PEG butyraldehyde claim 3 , 4-arm PEG acetaldehyde or 4-arm PEG amylic aldehyde claim 3 , and preferably 4-arm PEG propionaldehyde.5. The method according to claim 1 , wherein the multimeric protein is any one selected from alkaline phosphatase claim 1 , asparaginase or urease.7. The method according to claim 6 , wherein n is an integer selected from 2 to 500 claim 6 , and preferably an integer selected from 25 to 100; k is 1 claim 6 , m is 4 claim 6 , and p is 2; and the molecular weight of the multi-arm PEG is from 1 to 40 kDa claim 6 , and preferably 5 to 10 kDa.8. The method according to claim 7 , wherein the multi-arm PEG is an aldehyde or ester activated multi-arm PEG ...

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Номер записи: 91
16-02-2017 дата публикации

RNA Containing Modified Nucleosides and Methods of Use Thereof

Номер: US20170043037A1
Автор: Drew Weissman, Katalin Kariko
Принадлежит: University of Pennsylvania Penn

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

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Номер записи: 92
06-02-2020 дата публикации

PORTABLE WIDE FIELD FLUORIMETER SYSTEMS

Номер: US20200041413A1
Автор: Hasan Tayyaba, Palanisami Akilan
Принадлежит:

The present disclosure features portable wide field fluorimeter systems, e.g., in the form of low-cost mobile platforms, and methods to perform fluorometric assays to detect a change in fluorescence intensity in liquid samples, e.g., caused by the presence of a target analyte, e.g., a protein, e.g., an enzyme (e.g., β-lactamase) expressed by a target pathogen in a liquid sample in a point-of-care setting. In some implementations, a portable system for detecting a change in fluorescence intensity in a liquid sample includes a microfluidic device, an optical assembly including an emission filter and one or more lenses, and an analyzer device that collects and processes a fluorescent signal for the detection of a target analyte produced by the target pathogen present in the liquid sample. 1. A microfluidic device for detecting a change in fluorescence intensity in a liquid sample , the device comprising: an inlet that receives a liquid sample;', 'an outlet for receiving the liquid sample from the inlet;', 'a filter arranged between the inlet and the outlet and located to retain a target analyte; and', a first channel in fluid communication with the inlet, wherein the first channel extends from the inlet to a first surface of the filter; and', 'a second channel in fluid communication with the outlet, wherein the second channel extends from a second surface of the filter that is opposite to the first surface of the filter to the outlet, and is shaped and dimensioned to collect the liquid sample that has passed through the filter and has a depth that reduces an amount of unreacted detection reagent available to create background fluorescence during detection of the target analyte., 'a fluidic circuit arranged within the housing and comprising], 'a housing comprising2. The device of the claim 1 , wherein the device is constructed from multiple layers.3. The device of claim 2 , wherein the multiple layers comprise:a first layer comprising a first hole corresponding to the ...

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Номер записи: 93
16-02-2017 дата публикации

METHOD FOR REDUCING THE DNA CONTENT OF A FERMENTATION BROTH

Номер: US20170044209A1
Автор: Andersen Heidi Winterberg, Hobel Cedric, Kepka Cecilia Jansson, Pind Peter Frode
Принадлежит: NOVOZYMES A/S

A method for reducing the level of DNA in a fermentation broth is disclosed where the method includes a heating step where the broth is heated to a temperature of at least 70° C. 1. A method for removing DNA from a fermentation broth comprising a protein of interest and a microorganism producing the protein of interest , said method comprising:a) heating the fermentation broth to a temperature of at least 70° C.2. The method according to claim 1 , further comprising the steps of:b) adding a poly aluminium chloride to the fermentation broth, andc) separating the flocculated microorganism from the fermentation broth.3. The method according to claim 1 , wherein the protein of interest is a peptide claim 1 , such as an antimicrobial peptide claim 1 , a lipopeptide or brazzein; or a polypeptide such as an enzyme.4. The method according to claim 3 , wherein the protein of interest is an enzyme selected among: hydrolases claim 3 , lyases claim 3 , proteases claim 3 , amylases glucoamylases claim 3 , pectinases claim 3 , pectate lyases claim 3 , cellulases claim 3 , xylanases claim 3 , arabinases claim 3 , arbinofuranosidases claim 3 , mannanases claim 3 , carrageenanases claim 3 , xanthanases claim 3 , endoglucanases claim 3 , chitinases claim 3 , asparaginases claim 3 , lipases claim 3 , phospholipases claim 3 , cutinases claim 3 , lysozymes claim 3 , phytases claim 3 , peroxidases claim 3 , lactase claim 3 , glucose isomerases claim 3 , xylose isomerases claim 3 , esterases and phosphodiesterases.5. The method according to claim 4 , wherein the enzyme is a thermostable enzyme.6. The method according to claim 5 , wherein the thermostable enzyme has a thermostability measured as halflife at 70° C. and pH 7.0 of at least 30 minutes claim 5 , preferably at least 40 minutes claim 5 , preferably at least 50 minutes; preferably at least 60 minutes claim 5 , preferably at least 70 minutes claim 5 , preferably at least 80 minutes claim 5 , preferably at least 90 minutes claim 5 , ...

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Номер записи: 94
15-02-2018 дата публикации

NOVEL ANTI-PAD4 ANTIBODY

Номер: US20180044434A1
Автор: Kanazawa Satoshi, Saito Kenji, Sato Mamoru, Shoya Yuji, Toyoura Masayoshi, YAMADA Michiyuki, YAMAZAKI Chihiro
Принадлежит:

Provided are anti-PAD4 antibodies having excellent properties and an excellent method for treatment of RA. Used are anti-PAD4 antibodies that specifically bind to an epitope containing positions 345, 347, and 348 of PAD4. These anti-PAD4 antibodies may inhibit the citrullination activity of PAD4. In addition, these anti-PAD4 antibodies may have a KD (M) of 9.0×10or less. Optionally, the anti-PAD4 antibody and a TNFα inhibitor are used in combination. 1. An anti-PAD4 (peptidylarginine deiminase 4) antibody which specifically binds to an epitope containing positions 345 , 347 , and 348 of PAD4.2. The anti-PAD4 antibody according to claim 1 , wherein the antibody inhibits citrullination activity of PAD4.3. The anti-PAD4 antibody according to claim 1 , wherein a KD (M) between the antibody and PAD4 is 9.0×10or less.4. The anti-PAD4 antibody according to claim 1 , wherein the epitope is identified by alanine scan in which a single amino acid is replaced.5. The anti-PAD4 antibody according to claim 1 , wherein the antibody is a monoclonal antibody.6. The anti-PAD4 antibody according to claim 1 , wherein the antibody is a humanized antibody.7. The anti-PAD4 antibody according to claim 1 , wherein the antibody is an antigen-binding fragment.8. A polynucleotide or vector which encodes the anti-PAD4 antibody according to .9. A composition comprising the anti-PAD4 antibody according to .10. A method of inhibiting citrullination activity of PAD4 claim 1 , comprising a step of causing the anti-PAD4 antibody according to to contact PAD4.11. A method of treating RA or arthritis claim 1 , comprising a step of administering to a patient the anti-PAD4 antibody according to .12. A process for producing an anti-PAD4 antibody claim 8 , comprising the step of causing a cell containing the polynucleotide or vector according to to proliferate.13. An anti-PAD4 antibody comprising at least one selected from the group consisting of:an antibody in which heavy chain CDRs 1 to 3 and light chain ...

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Номер записи: 95
16-02-2017 дата публикации

PROTEIN DEAMIDASE

Номер: US20170044513A1
Автор: Hashiro Shuhei, Hiraga Masako, Nakano Mayu, SHIMBO Kazutaka, Tokunaga Ayaka, YOKOYAMA Noriko
Принадлежит: AJINOMOTO CO., INC.

A novel protein deamidase having an activity of directly acting on a side chain amide group of an asparagine residue in a protein to form a side chain carboxyl group and release ammonia, a microorganism that produces the same, a gene encoding the same, a method for producing the same, and use of the same are provided. A bacterium classified into the class Actinobacteria is cultured to generate protein deamidase, and the enzyme is collected from culture. 1. A protein having an activity for catalyzing a reaction of deamidating an asparagine residue in a protein.2. The protein according to claim 1 , which does not substantially have an activity for catalyzing a reaction of hydrolyzing a peptide bond in a protein.3. The protein according to claim 1 , which is a protein defined in (A) claim 1 , (B) claim 1 , or (C) mentioned below:(A) a protein comprising the amino acid sequence of SEQ ID NO: 10 or 11, the amino acid sequence of positions 63 to 1260, 245 to 1378, 245 to 1260, or 131 to 1260 of SEQ ID NO: 10, or the amino acid sequence of positions 47 to 1257, 59 to 1258, 96 to 1101, 241 to 1378, 244 to 1258, 244 to 1257, 244 to 1101, 129 to 1258, 120 to 1257, or 120 to 1101 of SEQ ID NO: 11;(B) a protein comprising the amino acid sequence of SEQ ID NO: 10 or 11, the amino acid sequence of positions 63 to 1260, 245 to 1378, 245 to 1260, or 131 to 1260 of SEQ ID NO: 10, or the amino acid sequence of positions 47 to 1257, 59 to 1258, 96 to 1101, 241 to 1378, 244 to 1258, 244 to 1257, 244 to 1101, 129 to 1258, 120 to 1257, or 120 to 1101 of SEQ ID NO: 11 but including substitution, deletion, insertion, or addition of 1 to 10 amino acid residues, and having an activity for catalyzing a reaction of deamidating an asparagine residue in a protein;(C) a protein comprising an amino acid sequence showing an identity of 90% or higher to the amino acid sequence of SEQ ID NO: 10 or 11, the amino acid sequence of positions 63 to 1260, 245 to 1378, 245 to 1260, or 131 to 1260 of SEQ ID ...

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Номер записи: 96
16-02-2017 дата публикации

RECOMBINANT RNA PARTICLES AND METHODS OF PRODUCING PROTEINS

Номер: US20170044555A1
Автор: BROWN Robert C., Kamrud Kurt I.
Принадлежит:

The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) encoding heterologous proteins, which can be useful for various therapeutic purposes as well as for the production of desired proteins. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that encodes a heterologous protein. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs (or DNA or RNA molecules) of the invention to an organism provides for therapeutic benefits as well as for the production of desired proteins. 1. A double-stranded RNA particle (dsRP) comprisinga recombinant double-stranded RNA molecule (dsRNA) and a capsid or coat protein;the RNA molecule encoding an RNA-dependent RNA polymerase and a polyprotein that forms at least part of the capsid or coat protein, the dsRP able to replicate in a host cell;the RNA molecule further comprising at least one RNA sub-sequence that encodes an additional, functional protein that is translated by the host cell cellular components.2. The dsRP of wherein the dsRP is derived from a virus of the Totiviridae family and wherein the host cell is a yeast and the functional protein is heterologous to the virus the dsRP is derived from.3Saccharomyces cerevesiae.. The dsRP of wherein the host cell is a4. The dsRP of wherein the functional protein performs a function that affects an organism outside of the host cell.5. The dsRP of wherein the affect is to inhibit the growth of or kill a bacterial organism.6. The dsRP of wherein the functional protein is an enzyme that is exported from the host cell.7. The dsRP of wherein the functional protein is an enzyme selected from the group consisting of: a cellulase claim 1 , a hemicellulase claim 1 , ...

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Номер записи: 97
15-02-2018 дата публикации

HYPOCHLORITE RESISTANT CYANURIC ACID HYDROLASES AND METHODS OF USE THEREOF

Номер: US20180044655A1
Автор: Aukema Kelly, Seffernick Jennifer L., Wackett Lawrence P.
Принадлежит:

The present invention relates to engineered cyanuric acid hydrolase enzymes that are resistant to hypochlorite and compositions and devices comprising such enzymes. The present invention also relates to methods of using these enzymes, compositions and devices for the treatment of a liquid, such as water. 1. A hypochlorite resistant cyanuric acid hydrolase (CAH) enzyme comprising an amino acid sequence having at least 70% sequence identity to SEQ ID NO:1 , SEQ ID NO:3 , SEQ ID NO:4 or SEQ ID NO:5.2. The CAH enzyme of claim 1 , wherein the amino acid sequence has at least 90% sequence identity to SEQ ID NO:1 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:4 or SEQ ID NO:5.3. The CAH enzyme of claim 1 , wherein the amino acid sequence has at least 95% sequence identity to SEQ ID NO:1 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:4 or SEQ ID NO:5.4. The CAH enzyme of claim 1 , wherein the amino acid sequence comprises an amino acid at residue 46 that does not block access to the active site of the enzyme and that does not react with hypochlorite to form a reaction product that blocks access to the active site of the enzyme.5. The CAH enzyme of claim 1 , wherein the amino acid sequence comprises an alanine claim 1 , serine claim 1 , glycine claim 1 , dehydroalanine claim 1 , homoserine or an amino acid having a cyclopropyl or an ethyl side chain at residue 46.6. The CAH enzyme of claim 1 , wherein the amino acid sequence comprises a non-oxidizable amino acid at residue 46.7. The CAH enzyme of claim 6 , wherein the side chain of the non-oxidizable amino acid is less than or about 109 Angstrom.8. The CAH enzyme of claim 1 , wherein the amino acid sequence comprises SEQ ID NO:3 claim 1 , SEQ ID NO:4 or SEQ ID NO:5.9. The CAH enzyme of claim 1 , wherein the amino acid sequence consists of SEQ ID NO:3 claim 1 , SEQ ID NO:4 or SEQ ID NO:5.10. The CAH enzyme of claim 1 , wherein the CAH enzyme is an isolated or purified CAH enzyme.11. The CAH enzyme of claim 1 , wherein the CAH enzyme is ...

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Номер записи: 98
03-03-2022 дата публикации

DEVICE FOR DETECTING ORGANOPHOSPHATES

Номер: US20220062906A1
Автор: Rosenberg Yvonne J.
Принадлежит:

This invention relates to a device that can be used is used to detect organophosphates and carbamate on surfaces including food, clothing (including as wearable pesticide detectors) and machinery.

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Номер записи: 99
03-03-2022 дата публикации

INHIBITION OF UNINTENDED MUTATIONS IN GENE EDITING

Номер: US20220064626A1
Автор: Chen Jia, Huang Xingxu, WANG Lijie, YANG BEI, Yang Li
Принадлежит:

Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion proteins may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitory domain, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability. 1. A fusion protein comprising:a first fragment comprising a nucleobase deaminase or a catalytic domain thereof,a second fragment comprising a nucleobase deaminase inhibitor, anda protease cleavage site between the first fragment and the second fragment.2. The fusion protein of claim 1 , wherein the nucleobase deaminase is an adenosine deaminase.3. The fusion protein of claim 2 , wherein the adenosine deaminase is selected from the group consisting of tRNA-specific adenosine deaminase (TadA) claim 2 , adenosine deaminase tRNA specific 1 (ADAT1) claim 2 , adenosine deaminase tRNA specific 2 (ADAT2) claim 2 , adenosine deaminase tRNA specific 3 (ADAT3) claim 2 , adenosine deaminase RNA specific B1 (ADARB1) claim 2 , adenosine deaminase RNA specific B2 (ADARB2) claim 2 , adenosine monophosphate deaminase 1 (AMPD1) claim 2 , adenosine monophosphate deaminase 2 (AMPD2) claim 2 , adenosine monophosphate deaminase 3 (AMPD3) claim 2 , adenosine deaminase (ADA) claim 2 , adenosine deaminase 2 (ADA2) claim 2 , adenosine deaminase like (ADAL) claim 2 , adenosine deaminase domain containing 1 (ADAD1) claim 2 , adenosine deaminase domain containing 2 (ADAD2) claim 2 , adenosine deaminase RNA specific (ADAR) and adenosine deaminase RNA specific B1 (ADARB1).4. The fusion protein of claim 1 , wherein the nucleobase deaminase is a cytidine deaminase.5. The fusion protein of claim 4 , wherein the cytidine deaminase is selected from the group consisting of APOBEC3B (A3B) claim 4 , APOBEC3C ( ...

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Номер записи: 100