New 5-D-fructose dehydrogenase in combination with an enzyme, e.g. glucose isomerase, useful for preventing or treating adiposity

A 5-D-fructose dehydrogenase, optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase (CGTase), for use in medicine, is new. Independent claims are: (1) a pharmaceutical composition comprising 5-D-fructose dehydrogenase optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase; (2) a medical device comprising 5-D-fructose dehydrogenase optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase; (3) a foodstuff comprising 5-D-fructose dehydrogenase in combination ...

USE OF SEKRETIERTER OF PROTEIN PRODUCTS FOR PREVENTION AND TREATMENT OF ILLNESSES OF THE PANCREAS AND/OR THE ADIPOSITY AND/OR THE METABOLIC SYNDROME

PROTEIN DISULPHIDE ISOMERASEN ABSTENTION PHARMACEUTICAL COMPOSITIONS

Use of low pH active alpha-1,4/1,6-glycoside hydrolases as a feed additive for ruminants to enhance starch digestion

Disclosed are uses at least one alpha-1,4/1,6-glycoside hydrolase (GLCH) as a feed additive for a ruminant wherein said hydrolase: (a) has at least 20% activity at pH less than or equal to 3 in the presence of pepsin as compared to activity of the hydrolase at pH 6 in the presence of pepsin, (b) said hydrolase is active in at least two of three digestive chambers of a ruminant comprising a rumen, an abomasum and a small intestine and (c) the hydrolase works with pancreatic amylase to increase glucose yield.

Extracts isolated from electroporated ambhibian oocytes and use thereof in treating diseases and disorders

Methods for preparing a composition containing extracts of activated amphibian oocytes, the method where the composition is a pharmaceutical composition comprising an equal volume of the extra-oocyte composition and the intra-oocyte composition, and a method for treating a disease, disorder, condition or injury characterized by a damaged or a cancerous differentiated cell including: (a) preparing the composition by the described method; (b) formulating a pharmaceutical composition comprising an equal volume of the extra-oocyte composition and the intra-oocyte composition, and optionally a carrier; and { c) administering a therapeutic amount of the pharmaceutical composition of (b) to a subject in need thereof, where the therapeutic amount as effective to reprogram the damaged or cancerous cells into iPSC-like cells capable of differentiating into cells capable of repairing the damaged or cancerous cells, thereby treating the disease, disorder, injury or condition.

Methods for controlled elimination of therapeutic cells

The technology relates in part to methods for controlling elimination of therapeutic cells, for example, cells that express a chimeric antigen receptor. The technology further relates to a two-step method of controlling destruction of therapeutic cells in a patient following an adverse event. The two-step system may include a rapamycin or rapamycin analog-based level of control and a second, rimiducid, level of control. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide and the rapamycin-sensitive polypeptide, where the proportion of therapeutic cells eliminated by apoptosis is related to the choice and amount of the administered ligand.

METHOD OF TREATING OR RETARDING THE DEVELOPMENT OF BLINDNESS

The claimed invention is drawn to a method for treating an ocular disease disorder in a human or animal subject characterized by the defect or absence or a normal gene in the ocular cells.

METHOD AND COMPOSITION FOR PROTECTING NEURONAL TISSUE FROM DAMAGE INDUCED BY ELEVATED GLUTAMATE LEVELS

A method of reducing extracellular brain glutamate levels. The method comprises administering to a subject in need thereof a therapeutically effective amount of an agent capable of reducing blood glutamate levels thereby reducing extracellular brain glutamate levels.

ISOMERASES, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR MAKING AND USING THEM

This invention relates generally to enzymes, polynucleotides encoding the enzymes, the use of such polynucleotides and polypeptides and more specifically to enzymes having isomerase activity, e.g., racemase activity, e.g., amino acid racemase activity, alanine racemase activity, and/or epimerase activity, and/or catalyze the re¬ arrangement of atoms within a molecule, catalyze the conversion of one isomer into another, catalyze the conversion of an optically active substrate into a raceme, which is optically inactive, catalyze the interconversion of substrate enantiomers, catalyze the stereochemical inversion around the asymmetric carbon atom in a substrate having only one center of asymmetry, catalyze the stereochemical inversion of the configuration around an asymmetric carbon atom in a substrate having more than one asymmetric center, and/or catalyze the racemization of amino acids. Thus, the invention provides enzymes, compositions, methods for production of pharmaceutical compositions ...

DESENSITIZERS

Allergic reaction suppressors comprising a peptide which originates in the same antigenic substance as the antigenic substance inducing the allergic reaction, contains an epitope different from the epitope participating in the induction of the allergic reaction and yet does not induce the allergic reaction; preventives and/or remedies or medicinal compositions for type I allergic diseases containing the above suppressors; a method of suppressing allergic reactions, a desensitizing method, and a method of preventing/treating type I allergic diseases with the use of the same; a cancer vaccine containing a tumor rejection antigen-origin peptide which has a cytotoxic T lymphocyte inducing activity but inducing an allergy reaction and another peptide which originates in the same antigen as the above peptide, has an epitope different from the epitope of the above peptide and exhibits an effect of suppressing the allergic reaction; remedies for cancer containing the above vaccine; and a method ...

PROTEIN MARKERS FOR PHARMACEUTICALS AND RELATED TOXICITY

Protein markers of toxicity and efficacy for drugs are determined. For example, methods and reagents are disclosed for determining whether a patient receiving an antilipemic drug, especially a statin or HMGCoA reductase inhibiting drug, is experiencing drug efficacy and/or toxicity. Individual susceptibility is also determined prior to treatment. Also, drug discovery of similar acting candidates and their likelihood of being toxic or effective is determined by analysis of all proteins in a sample simultaneously by 2-dimensional gel elecrotphoresis.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

The present invention refers to an agent for use in the case of fructose intolerance and any form of impairment and affliction of health and well being which is caused by the administration of fructose or fructose containing foodstuffs or by the release of fructose in the digestive tract of humans or animals from other substances, such as e.g. sucrose. The agent according to the invention comprises 5-D-fructose dehydrogenase, optionally in combination with invertase and/or maltase and/or glucose isomerase, which enzyme or combination of enzymes is/are used in the medical field for the first time. Preferably the agent is in the form of a pharmaceutical composition which is useful for treatment of fructose intolerance.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

The present invention refers to an agent for use in the case of fructose intolerance and any form of impairment and affliction of health and well being which is caused by the administration of fructose or fructose containing foodstuffs or by the release of fructose in the digestive tract of humans or animals from other substances, such as e.g. sucrose. The agent according to the invention comprises 5-D-fructose dehydrogenase, optionally in combination with invertase and/or maltase and/or glucose isomerase, which enzyme or combination of enzymes is/are used in the medical field for the first time. Preferably the agent is in the form of a pharmaceutical composition which is useful for treatment of fructose intolerance. © KIPO & WIPO 2008 ...

APOPTOSIS METHODS, GENES AND PROTEINS

A W303a Saccharomyces cerevisiae yeast cell which contains a polynucleotide that encodes a functional Bax polypeptide under the control of a galactose- inducible promoter that is integrated at the LEU2 chromosomal locus. A kit of parts comprising the yeast cells and a yeast plasmid vector suitable for transforming a cDNA library into the yeast cells. Use of the yeast cell for screening a cDNA library for a polynucleotide that is or encodes an inhibitor of B ax-mediated apoptosis. Genes and polypeptides that inhibit Bax-mediated apoptosis and which were identified from a human hippocampus cDNA library screened in the yeast cells. A method of combating Bax-mediated apoptosis in a cell using an inhibitor of Bax-mediated apoptosis which was identified from a human hippocampus cDNA library screened in the yeast cells. A method of promoting Bax-mediated apoptosis in a cell using an inhibitor or antagonist of the anti-apoptotic polypeptides identified from a human hippocampus cDNA library screened ...

Methods and compositions for modulating somatolactogenic functions

Compositions containing cyclophilin B, mutants of cyclophilin B or inhibitors of cyclophilin B and methods of using these compositions to modulate somatolactogenic function are provided.

Coupling endonucleases with end-processing enzymes drives high efficiency gene disruption

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

СИСТЕМНАЯ ДОСТАВКА И РЕГУЛИРУЕМАЯ ЭКСПРЕССИЯ ПАРАКРИННЫХ ГЕНОВ ДЛЯ ЛЕЧЕНИЯ СЕРДЕЧНО-СОСУДИСТЫХ И ИНЫХ ЗАБОЛЕВАНИЙ

FIELD: medicine. SUBSTANCE: group of inventions can be used to treat heart failure with congestive heart failure (CHF), diabetes or prediabetes in vivo in a patient in need thereof. To this end, a vector is administered to a subject comprising a nucleic acid encoding a paracrine polypeptide or a peptide selected from the group consisting of cardiotonic peptide, urocortin-2 (UCn-2), urocortin-1 (UCn-1), urocortin-3 (UCn-3), brain natriuretic peptide and prostacyclin synthase, wherein the said nucleic acid encoding a paracrine polypeptide or peptide is operably linked to a promoter, wherein the vector is an adeno-associated virus (AAV), and wherein the paracrine polypeptide or peptide is expressed in a cell. EFFECT: group of inventions provides treatment or improvement of CHF, diabetes or prediabetes in a patient. 24 cl, 20 dwg, 3 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) (19) RU (11) (13) 2 642 605 C2 (51) МПК A61K 48/00 (2006.01) A61K 38/17 (2006.01) A61K 38/16 (2006.01) A61K 9/08 (2006.01) A61K 9/06 (2006.01) A61P 17/00 (2006.01) A61P 9/00 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 48/00 (2017.08); A61K 38/17 (2017.08); A61K 38/16 (2017.08); A61K 9/08 (2017.08); A61K 9/06 (2017.08); A61K 2121/00 (2017.08) (21)(22) Заявка: 2014137169, 13.02.2013 13.02.2013 (73) Патентообладатель(и): ТЕ РИДЖЕНТС ОФ ТЕ ЮНИВЕРСИТИ ОФ КАЛИФОРНИЯ (US) Дата регистрации: 25.01.2018 (56) Список документов, цитированных в отчете о поиске: WO 0134208 A1, 17.05.2001. RU 14.02.2012 US 61/598,772 (43) Дата публикации заявки: 10.04.2016 Бюл. № 10 2278871 C2, 27.06.2006. WO 2006086402 A2, 17.08.2006. WO 2009140657 A2, 19.11.2009. (45) Опубликовано: 25.01.2018 Бюл. № 3 (86) Заявка PCT: US 2013/025997 (13.02.2013) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 15.09.2014 (87) Публикация заявки PCT: 2 6 4 2 6 0 5 WO 2013/123094 (22.08.2013) R U 2 6 4 2 6 0 5 Приоритет(ы): (30) Конвенционный приоритет: R U (24) Дата начала ...

ПРИМЕНЕНИЕ АКТИВНЫХ ПРИ НИЗКОМ ЗНАЧЕНИИ pH АЛЬФА-1,4/1,6-ГЛИКОЗИДГИДРОЛАЗ В КАЧЕСТВЕ КОРМОВОЙ ДОБАВКИ ДЛЯ ЖВАЧНЫХ ЖИВОТНЫХ ДЛЯ УЛУЧШЕНИЯ ПЕРЕВАРИВАНИЯ КРАХМАЛА

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2019 111 908 A (51) МПК A23K 20/189 (2016.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2019111908, 15.09.2017 (71) Заявитель(и): ДЮПОН НЬЮТРИШН БАЙОСАЙЕНСИЗ АПС (DK) Приоритет(ы): (30) Конвенционный приоритет: 23.09.2016 US 62/398,741 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 23.04.2019 R U (43) Дата публикации заявки: 23.10.2020 Бюл. № 30 (72) Автор(ы): ЮЙ, Шукунь (SE), КРАГХ, Карстен Маттиас (DK), ЛИ, Вэньтин (GB) (86) Заявка PCT: (87) Публикация заявки PCT: WO 2018/057420 (29.03.2018) R U (54) ПРИМЕНЕНИЕ АКТИВНЫХ ПРИ НИЗКОМ ЗНАЧЕНИИ pH АЛЬФА-1,4/1,6ГЛИКОЗИДГИДРОЛАЗ В КАЧЕСТВЕ КОРМОВОЙ ДОБАВКИ ДЛЯ ЖВАЧНЫХ ЖИВОТНЫХ ДЛЯ УЛУЧШЕНИЯ ПЕРЕВАРИВАНИЯ КРАХМАЛА (57) Формула изобретения 1. Способ увеличения перевариваемости крахмала и выхода глюкозы у жвачного животного, который включает добавление по меньшей мере одной альфа–1,4/ 1,6–гликозидгидролазы (GLCH) в качестве кормовой добавки в корм для жвачного животного, где указанная гидролаза (a) характеризуется по меньшей мере 20% активностью при значении pH, равном 3 или меньше, в присутствии пепсина по сравнению с активностью гидролазы при значении pH 6 в присутствии пепсина, (b) указанная гидролаза активна в по меньшей мере двух из трех пищеварительных камер жвачного животного, включающих рубец, сычуг и тонкую кишку, и (c) гидролаза действует совместно с пищеварительными ферментами, присутствующими в пищеварительных камерах жвачного животного, с обеспечением увеличения перевариваемости крахмала и выхода глюкозы. 2. Гидролидаза по п.1, где по меньшей мере один фермент GLCH способен к гидролизу сырого крахмала в условиях, сравнимых с условиями, обнаруженными в рубце или сычуге. 3. Гидролидаза по п.1, где указанная гидролаза выбрана из группы, состоящей из альфа–амилаз, глюкоамилаз и альфа–глюкозидаз. 4. Гидролаза по п.2, где указанная гидролаза выбрана из группы, состоящей из Стр.: 1 A 2 0 1 9 1 1 1 9 0 8 A ...

Signalling system

PROTEINDISULFIDISOMERASE AND ABC TRANSPORTER HOMOLOGOUS PROTEINS, WHICH ARE INVOLVED TO OF THE ADJUSTMENT THE ENERGY HOMEOSTASE ONES

METHOD AND COMPOSITION FOR PROTECTING NEURONAL TISSUE FROM DAMAGE INDUCED BY ELEVATED GLUTAMATE LEVELS

Methods and compositions for regulating protein-protein interactions

Regulating chimeric antigen receptors

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions

In alternative embodiments, the invention provides methods for treating, ameliorating or protecting (preventing) an individual or a patient against a disease, an infection or a condition responsive to an increased paracrine polypeptide level in vivo comprising: providing a 5 paracrine polypeptide-encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence; or an expression vehicle, a vector, a recombinant virus, or equivalent, having contained therein a paracrine-encoding nucleic acid or gene, and the expression vehicle, vector, recombinant virus, or equivalent can express the paracrine-encoding nucleic acid or gene in a cell or in vivo; and administering or delivering the paracrine polypeptide 10 encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence, or the expression vehicle, vector, recombinant virus, or equivalent, to an individual or a patient in need thereof, thereby treating, ameliorating or protecting (preventing) ...

Compositions and methods for treating diabetes

Compositions containing an FKBP 11 peptide (i.e., FKBP11 polypeptide, a variant or a fragment thereof), a fusion protein containing an FKBP11 peptide, or a nucleic acid encoding an FKBP 11 peptide are disclosed. Also disclosed are methods of reducing blood glucose levels, improving glucose tolerance, decreasing hepatic gluconeogenic activity and/or improving insulin sensitivity in a subject, by administering a composition containing an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide. The methods can include administering nucleic acids encoding an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide, to the subject, or cells expressing the nucleic acids. Kits containing an FKBP 11 peptide, are also provided.

Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

METHOD AND KIT FOR EFFECTING SCREENING AND IMMUNOGENIC TREATMENT USING CRT AND/OR ERP57 TRANSLOCATION

Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) and/or ERP57 to the cell surface. Knock down of CRT and/or ERP57 suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT and/or ERP57 translocation was mimicked by inhibition of the protein phosphatase1/GADD34 complex. Administration of recombinant calreticulin, and not recombinant ERP57, or inhibitors of protein phosphatase1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify calreticulin and/or ERP57 as a key feature determining anti-cancer immune responses and delineate a possible ...

METHODS OF TREATING CANCER OF THE CENTRAL NERVOUS SYSTEM

A method of treating a cancer of the central nervous system in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of an agent which reduces blood glutamate levels and enhances brain to blood glutamate efflux to thereby treat the cancer of the central nervous system in the subject.

HYDROXYALKYL STARCH DERIVATIVES AS REACTANTS FOR COUPLING TO THIOL GROUPS

The present invention relates to a hydroxyalkyl starch (HAS) derivative of formula (I) wherein F1 is a functional group comprising the group -NR'-, with R' being H or alkyl; L is a spacer bridging F1 and S; wherein HAS' is the remainder of the HAS molecule, Rb and Rc are -[(CR1R2)mO]n-H and are the same or different from each other; Ra is -[(CR1R2)mO]n- H with HAS' being the remainder of the hydroxyalkyl starch molecule, or Ra is HAS" with HAS' and HAS" together being the remainder of the hydroxyalkyl starch molecule; R1 and R2 are independently hydrogen or an alkyl group having from 1 to 4 carbon atoms, m is 2 to 4, wherein R1 and R2 are the same or different from each other in the m groups CR1R2; n is from 0 to 6.

USE OF SECRETED PROTEIN PRODUCTS FOR PREVENTING AND TREATING PANCREATIC DISEASES AND/OR OBESITY AND/OR METABOLIC SYNDROME

This invention relates to the use of secreted SF01-SF13 proteins, to the use of polynucleotides encoding these, and to the use of effectors/modulators thereof in the diagnosis, study, prevention, and treatment of pancreatic diseases (e.g. diabetes mellitus), obesity and/or metabolic syndrome and to the use in regeneration of tissues such as pancreatic tissues and others.

METHOD AND COMPOSITION FOR PROTECTING NEURONAL TISSUE FROM DAMAGE INDUCED BY ELEVATED GLUTAMATE LEVELS

A method of reducing extracellular brain glutamate levels. The method comprises administering to a subject in need thereof a therapeutically effective amount of an agent capable of reducing blood glutamate levels thereby reducing extracellular brain glutamate levels.

Phospholipase C homolog

The present invention provides nucleotide and amino acid sequences that identify and encode a novel phospholipase C homolog (plch and PLCH). The present invention also provides for antisense molecules to the plch nucleotide sequences, expression vectors for the production of purified PLCH, antibodies capable of binding specifically to PLCH, hybridization probes or oligonucleotides for detecting excess PLCH-encoding nucleotide sequences, genetically engineered host cells for the expression of PLCH, diagnostic tests for activated, inflamed, diseased, and hydroxyurea-resistant cells and/or tissues based on PLCH-encoding nucleic acid molecules and antibodies capable of binding specifically to PLCH.

Protein Disulfide Isomerase and ABC Transporter Homologous Proteins Involved in the Regulation of Energy Homeostasis

The present invention discloses three novel proteins regulating the energy homeostasis and the metabolism of triglycerides, and polynucleotides, which identify and encode the proteins disclosed in this invention. The invention also relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides of the invention. The invention also relates to the use of these sequences in the diagnosis, study, prevention, and treatment of diseases and disorders related to body-weight regulation, for example, but not limited to, metabolic diseases such as obesity, as well as related disorders such as adipositas, eating disorders, wasting syndromes (cachexia), pancreatic dysfunctions (such as diabetes mellitus), hypertension., pancreatic dysfunctions, arteriosclerosis, coronary artery disease (CAD), coronary heart disease, hypercholesterolemia, dyslipidemia, osteoarthritis, gallstones, cancer, e.g. cancers of the reproductive organs, sleep apnea, and others ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

NEGATIVE IMMUNOMODULATION OF IMMUNE RESPONSES BY NKG2D-POSITIVE CD4-POSITIVE CELLS

Method and composition for protecting neuronal tissue from damage induced by elevated glutamate levels

The present invention concerns a glutamate modifying transaminase for use in the treatment of a medical condition selected from the group consisting of brain anoxia, brain ischemia, stroke, perinatal brain damage, traumatic brain injury, bacterial meningitis, subarachnoid haemorhage, migraine, stress, hemorrhagic shock, epilepsy, acute liver failure, glaucoma, HIV, dementia, amyotrophic lateral sclerosis (ALS), spastic conditions, open heart surgery, aneurism surgery, coronary artery bypass grafting and Alzheimer's disease.

Use of glucose isomerase in therapy or diagnosis of diabetes and metabolic syndrome, preferably insulin resistance syndrome, and as food product, preferably dietary food, a dietary supplement or a food additive

Use of glucose isomerase in therapy or diagnosis of diabetes and metabolic syndrome, is claimed. ACTIVITY : Anabolic; Antidiabetic; Metabolic. MECHANISM OF ACTION : None given.

PHARMACEUTICAL PREPARATIONS TO THE ANGIOGENIC SE THERAPY

MEDICAL COMPOSITIONS TO THE ANGIOGENIC THERAPY

Medicinal compositions for angiogenic therapy

Ant-1 as drug target

Compositions and methods for treating diabetes

Compositions containing an FKBP 11 peptide (i.e., FKBP11 polypeptide, a variant or a fragment thereof), a fusion protein containing an FKBP11 peptide, or a nucleic acid encoding an FKBP 11 peptide are disclosed. Also disclosed are methods of reducing blood glucose levels, improving glucose tolerance, decreasing hepatic gluconeogenic activity and/or improving insulin sensitivity in a subject, by administering a composition containing an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide. The methods can include administering nucleic acids encoding an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide, to the subject, or cells expressing the nucleic acids. Kits containing an FKBP 11 peptide, are also provided.

NEUROPROTECTIVE AGENTS AND METHODS OF THEIR USE

REGULATING CHIMERIC ANTIGEN RECEPTORS

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

An agent is described that, with the help of glucose isomerase, converts fructose into glucose and thus, alone or in combination with 5-D-fructose dehydrogenase, reduces the bioavailability of fructose in the human or animal body. This agent can be used in particular in the therapy of fructose intolerance.

METHODS AND COMPOSITIONS FOR INCREASING SIALIC ACID PRODUCTION AND TREATING SIALIC RELATED DISEASE CONDITIONS

Disclosed herein are methods of expressing UDP-G1cNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3, wherein upon the delivering into the cell of the subject, the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof. Also disclosed are methods of producing a GNE peptide in a cell comprising infecting the cell with an isolated nucleic acid construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

An agent is described that, with the help of glucose isomerase, converts fructose into glucose and thus, alone or in combination with 5-D-fructose dehydrogenase, reduces the bioavailability of fructose in the human or animal body. This agent can be used in particular in the therapy of fructose intolerance.

COUPLING ENDONUCLEASES WITH END-PROCESSING ENZYMES DRIVES HIGH EFFICIENCY GENE DISRUPTION

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

PHOSPHOLIPASE C HOMOLOG

The present invention provides nucleotide and amino acid sequences that identify and encode a novel phospholipase C homolog (plch and PLCH). The present invention also provides for antisense molecules to the plch nucleotide sequences, expression vectors for the production of purified PLCH, antibodies capable of binding specifically to PLCH, hybridization probes or oligonucleotides for detecting excess PLCH-encoding nucleotide sequences, genetically engineered host cells for the expression of PLCH, diagnostic tests for activated, inflamed, diseased, and hydroxyurea-resistant cells and/or tissues based on PLCH-encoding nucleotide sequences or antibodies specific for PLCH.

METHODS AND COMPOSITIONS FOR TREATING DISEASES WITH CARBOHYDRATE MODIFYING ENZYMES

The invention provides methods and compositions for the treatment and/or prevention or a variety of disease conditions. The methods involve the administration of an effective amount of a therapeutic catalyst to a patient. A therapeutic catalyst is an enzyme, or other catalyst, capable of catalyzing a chemical reaction employing a carbohydrate or a carbohydrate portion of a glycoconjugate as a substrate. Therapeutic catalysts are selected so as to catalyze reaction that results in the structural alteration of at least one member of a receptor binding pair of molecules, whereby the interaction between receptor binding pair members is disrupted. The invention also provides compositions containing therapeutic catalysts for use in the subject methods. Diseases that may be treated by therapeutic catalysts include infections diseases, cancer, and autoimmune diseases.

Use of Secreted Protein Products for Preventing and Treating Pancreatic Diseases and/or Obesity and/or Metabolic Syndrome

This invention relates to the use of secreted SF01-SF13 proteins, to the use of polynucleotides encoding these, and to the use of effectors/modulators thereof in the diagnosis, study, prevention, and treatment of pancreatic diseases (e.g. diabetes mellitus), obesity and/or metabolic syndrome and to the use in regeneration of tissues such as pancreatic tissues and others.

СИСТЕМНАЯ ДОСТАВКА И РЕГУЛИРУЕМАЯ ЭКСПРЕССИЯ ПАРАКРИННЫХ ГЕНОВ ДЛЯ ЛЕЧЕНИЯ СЕРДЕЧНО-СОСУДИСТЫХ И ИНЫХ ЗАБОЛЕВАНИЙ

... 1. Способ лечения, улучшения состояния или защиты (предохранения) индивидуума или пациента от болезни, инфекции или состояния, чувствительного к повышенному или устойчивому уровню паракринного пептида или полипептида in vivo, включающий:(a) (i) (i) предоставление нуклеиновой кислоты или гена, кодирующих паракринный полипептид, функционально связанных с последовательностью регулирующей транскрипцию; или средства для экспрессии, вектора, рекомбинантного вируса или эквивалента, содержащих в себе кодирующую паракринный фактор нуклеиновую кислоту или ген, или экспрессирующую паракринный полипептид нуклеиновую кислоту, транскрипт или мРНК, при этом средство для экспрессии, вектор, рекомбинантный вирус, или эквивалент может экспрессировать кодирующую паракринный фактор нуклеиновую кислоту, ген, транскрипт или мРНК в клетке или in vivo; и(ii) введение или доставку кодирующей паракринный полипептид нуклеиновой кислоты, гена, транскрипта или мРНК, функционально связанных с последовательностью регулирующей ...

Agent, useful to treat diabetes, comprises 5-D-fructose-dehydrogenase and glucose isomerase

Agent (A), to reduce the glucose content of food and other materials, comprises 5-D-fructose-dehydrogenase and glucose isomerase. ACTIVITY : Antidiabetic. MECHANISM OF ACTION : None given.

Compositions and uses thereof

ANT-1 AS THERAPEUTIC GOAL MOLECULE

GLUCOSEISOMERASE FOR THE TREATMENT OF FRUCTOSEUNVERTRÄGLICHKEIT

Partial agonists at the glycine modulatory site of the nmda receptor for treating cognitive dysfunction

Methods And Compositions For Increasing Sialic Acid Production And Treating Sialic Related Disease Conditions

Disclosed herein are methods of expressing UDP-G1cNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter 5 operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3, wherein upon the delivering into the cell of the subject, the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof. Also disclosed are methods of producing a 10 GNE peptide in a cell comprising infecting the cell with an isolated nucleic acid construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3.

PHARMACEUTICAL COMPOSITIONS FOR ANGIOGENIC THERAPY

Medicinal compositions for angiogenic therapy which contain as the active ingredients at least one member selected from among substances having a vasodilating effect and/or a platelet aggregation inhibitory effect and substances producing the same, and a gene encoding an angiogenesis factor; agents for potentiating the angiogenic effect of a gene encoding an angiogenesis factor which contain as the active ingredient at least one member selected from among substances having a vasodilating effect and/or a platelet aggregation inhibitory effect and substances producing the same; an angiogenic agent which contains prostacyclin synthase gene as the active ingredient; medicinal compositions for angiogenic therapy which contain ets-1 gene and another gene encoding an angiogenesis factor as the active ingredients; an agent for potentiating the angiogenic effect of a gene encoding an angiogenesis factor which contain ets-1 gene as the active ingredient; and an angiogenic agent which contains ets ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

Method and Pharmaceutical Composition for Use in the Treatment of Neurodegenerative Disorders

The invention relates to compounds which activate the BASIGIN signalling pathway, preferably agonists of BASIGIN, for the treatment of neurodegenerative disorders.

NEGATIVE IMMUNOMODULATION OF IMMUNE RESPONSES BY NKG2D-POSITIVE CD4+ CELLS

The present invention relates to methods of treating immune disorders, particularly autoimmune diseases and cancers having an immune-deficient aspect involving NKG2D-positive CD4+ cells. In addition, the invention provides screening methods that assess the ability of compositions to modulate the negative immunomodulatory effects of NKG2D-positive CD4+ cells. Also provided is a new target for inhibition of signaling by soluble MIC ligand, namely, the ERP-5 disulphide isomerase that interacts with MICA/MICB on the surface of tumor cells.

Formation of novel erythropoietin conjugates using transglutaminase

Method for Regulating Protein Function in Cells In Vivo Using Synthetic Small Molecules

Methods and compositions for the rapid and reversible destabilizing of specific proteins in vivo using cell-permeable, synthetic molecules are described.

SYSTEMIC DELIVERY AND REGULATED EXPRESSION OF PARACRINE GENES FOR CARDIOVASCULAR DISEASES AND OTHER CONDITIONS

SUBSTANCE INHIBITING AGGREGATION OF AMYLOID PROTEIN AND ACTION THEREOF

PROBLEM TO BE SOLVED: To inhibit the aggregation of an amyloid protein and to inhibit/ameliorate symptoms of Alzheimer's diseases. SOLUTION: A drug comprising a polypeptide selected from the group consisting of (1) an L-PGDS (lipocalin-type prostaglandin D synthase), (2) a mutant of the L-PGDS in which at least one cysteine residue of the L-PGDS is substituted with alanine or serine, (3) β-lactoglobulin and (4) a substance selected from the group consisting of estrogen, glucocorticoid, interleukin-1β and thyroid hormone and enhancing expression of the L-PGDS protein as an active ingredient is administered. The polypeptide binds to the β-amyloid protein and inhibits the aggregation thereof. COPYRIGHT: (C)2008,JPO&INPIT ...

Agent for use in the case of fructose intolerance

Protein markers for pharmaceuticals and related toxicity

Non-disruptive gene therapy for the treatment of MMA

Methods and technologies for the treatment of methylmalonic acidemia.

Modified caspase polypeptides and uses thereof

The technology relates in part to compositions comprising modified caspase-9 polypeptides, compositions comprising nucleic acids coding for modified caspase-9 polypeptides, chimeric modified caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified caspase-9 protein, with reduced basal activity in the absence of the inducer.

NON-DISRUPTIVE GENE THERAPY FOR THE TREATMENT OF MMA

Methods and technologies for the treatment of methylmalonic acidemia.

USE OF LOW PH ACTIVE ALPHA-1,4/1,6-GLYCOSIDE HYDROLASES AS A FEED ADDITIVE FOR RUMINANTS TO ENHANCE STARCH DIGESTION

Disclosed are uses at least one alpha-1,4/1,6-glycoside hydrolase (GLCH) as a feed additive for a ruminant wherein said hydrolase: (a) has at least 20% activity at pH less than or equal to 3 in the presence of pepsin as compared to activity of the hydrolase at pH 6 in the presence of pepsin, (b) said hydrolase is active in at least two of three digestive chambers of a ruminant comprising a rumen, an abomasum and a small intestine and (c) the hydrolase works with pancreatic amylase to increase glucose yield.

COMPOSITIONS AND METHODS FOR TREATING DIABETES

Compositions containing an FKBP 11 peptide (i.e., FKBP11 polypeptide, a variant or a fragment thereof), a fusion protein containing an FKBP11 peptide, or a nucleic acid encoding an FKBP 11 peptide are disclosed. Also disclosed are methods of reducing blood glucose levels, improving glucose tolerance, decreasing hepatic gluconeogenic activity and/or improving insulin sensitivity in a subject, by administering a composition containing an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide. The methods can include administering nucleic acids encoding an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide, to the subject, or cells expressing the nucleic acids. Kits containing an FKBP 11 peptide, are also provided.

CASPASE POLYPEPTIDES HAVING MODIFIED ACTIVITY AND USES THEREOF

The technology relates in part to compositions comprising modified caspase-9 polypeptides, compositions comprising nucleic acids coding for modified caspase-9 polypeptides, chimeric modified caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified caspase-9 protein, with reduced basal activity in the absence of the inducer.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

The present invention refers to an agent for use in the case of fructose intolerance and any form of impairment and affliction of health and well bei ng which is caused by the administration of fructose or fructose containing foodstuffs or by the release of fructose in the digestive tract of humans or animals from other substances, such as e.g. sucrose. The agent according to the invention comprises 5-D-fructose dehydrogenase, optionally in combinati on with invertase and/or maltase and/or glucose isomerase, which enzyme or c ombination of enzymes is/are used in the medical field for the first time. P referably the agent is in the form of a pharmaceutical composition which is useful for treatment of fructose intolerance.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

An agent is described that, with the help of glucose isomerase, converts fructose into glucose and thus, alone or in combination with 5-D-fructose dehydrogenase, reduces the bioavailability of fructose in the human or animal body. This agent can be used in particular in the therapy of fructose intolerance.

METHOD OF TREATING OR RETARDING THE DEVELOPMENT OF BLINDNESS

A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Thioester Cationic Lipids

Disclosed are cationic lipids which are compounds of Formula (I), (II), (III), (IV), (V), or (VI). Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

METHOD OF TREATING OR RETARDING THE DEVELOPMENT OF BLINDNESS

A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

APOPTOSIS INDUCER FOR CANCER CELL

The present invention revealed that by suppressing the expression of the WRN gene, the BLM gene, or the RecQ1 gene, which belong to the RecQ helicase family, apoptosis is induced in various cancer cells and their proliferation is suppressed. Compounds that suppress the expression of RecQ helicase family genes or the functions of RecQ helicase proteins are thought to have the activity of inducing apoptosis.

COUPLING ENDONUCLEASES WITH END-PROCESSING ENZYMES DRIVES HIGH EFFICIENCY GENE DISRUPTION

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

ANT-1 ALS THERAPEUTISCHES ZIELMOLEKÜL

Methods And Compositions For Increasing Sialic Acid Production And Treating Sialic Related Disease Conditions

Disclosed herein are methods of expressing UDP-G1cNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter 5 operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3, wherein upon the delivering into the cell of the subject, the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof. Also disclosed are methods of producing a 10 GNE peptide in a cell comprising infecting the cell with an isolated nucleic acid construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3.

Compositions and methods for selective elimination and replacement of hematopoietic stem cells

Disclosed are methods of eliminating at least one target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).

REGULATION OF MATRIX METALLOPROTEINASES BY PSP94 FAMILY MEMBERS

Matrix metalloproteinases (MMPs) play an important role in morphogenesis, angiogenesis, wound healing, and in certain disorders such as rheumatoid arthritis, tumor invasion and metastasis. MMPs are thought to be regulated by a variety of cytokines, growth factors, hormones and phorbol esters. This regulation occurs on three levels; alteration of gene expression, activation of the latent zymogen and inhibition by the tissue inhibitors of metalloproteinases (TIMP). We report here a new agent that regulates the level of MMPs in patient. More particularly, members of the PSP94 family, when administered to patients having metastatic hormone resistant prostate cancer, promote a significant decrease in MMP plasma levels. The invention therefore relates to the use of a PSP94 family member for the treatment of a condition related to the activity or expression of MMPs.

TREATMENT OF FRUCTOSE-MALABSORPTION

The present invention relates to a composition comprising crystalline xylose isomerase (EC 5.3.1.5) and at least one salt of a metal and/or alkaline earth metal.

METHODS OF TREATING CANCER OF THE CENTRAL NERVOUS SYSTEM

The blood-brain barrier (BBB), mediated by endothelial tight junctions, is defective in malignant gliomas such as glioblastoma, resulting in cerebral edema and contrast enhancement upon neuroradiological examination. The mechanisms underlying BBB breakdown are essentially unknown. Since non-neoplastic astrocytes are required to induce BBB features of cerebral endothelial cells, it is conceivable that malignant astrocytes have lost this ability due to dedifferentiation. Alternatively, glioma cells might actively degrade previously intact BBB tight junctions. To examine the latter hypothesis, we have employed a transepithelial electrical resistance breakdown assay using monolayers of the C7 subclone of Madin-Darby canine kidney (MDCK-C7) cells forming tight junctions similar to those of BBB endothelial cells. We found that glioblastoma primary cells co-cultured with the MDCK-C7 monolayer (without direct contact of the two cell types) resulted in marked breakdown of electrical resistance, ...

SYSTEMIC DELIVERY AND REGULATED EXPRESSION OF PARACRINE GENES FOR CARDIOVASCULAR DISEASES AND OTHER CONDITIONS

Treatment of fructose malabsorption

COMPOSITION COMPRISING CYCLOPHILIN A FOR PREVENTING ALOPECIA OR IMPROVING HAIR RESTORATION

The present invention relates to a composition comprising a cyclophilin A (cyp A) protein, a nucleic acid having a nucleotide sequence coding for the cyp A protein, or a recombinant vector for expressing the cyp A protein for preventing alopecia or improving hair restoration. The composition of the present invention is administered to skin cells in order to suppress the IL-1 expression of skin cells, regulate the activity of ERK and c-jun, and increase the expression of NF-κB p65, thereby promoting growth and development of hair follicles. Thus, the present invention can be valuable in the use thereof for the preventing and treatment of alopecia-related diseases.

Agent for use in the case of fructose intolerance

There is provided in accordance with embodiments of the invention a method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism, the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase, other than in combination with 5-D-fructose dehydrogenase. Other embodiments are also disclosed.

MODIFIED CASPASE POLYPEPTIDES AND USES THEREOF

The technology relates in part to compositions comprising modified Caspase-9 polypeptides, compositions comprising nucleic acids coding for modified Caspase-9 polypeptides, chimeric modified Caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified Caspase-9 protein, with reduced basal activity in the absence of the inducer. 1. A composition comprising a nucleic acid comprising a nucleotide sequence that encodes a chimeric protein comprising a multimeric ligand binding region and a modified Caspase-9 polypeptide , wherein the modified Caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 9 , and comprises at least one amino acid substitution selected from the group consisting of T317S D330A , F404Y , F406L , F406T , F404W , T317A , S144A , S144D , S196A , S183A , S195A , F404T , F404W , N405F , F406T , D315A , A316G , F319W , 5307A , Y153A , and Y153F.2. The composition of claim 1 , wherein the chimeric protein comprising the modified Caspase-9 polypeptide has decreased basal activity compared to a chimeric protein comprising a Caspase-9 polypeptide comprising the amino acid sequence of SEQ ID NO:9.3. The composition of claim 2 , wherein the basal activity is measured using a secreted alkaline phosphatase (SEAP) reporter-based surrogate killing assay.4. The composition of claim 1 , wherein the least one amino acid substitution is selected from the group consisting of T317S claim 1 , D330A claim 1 , F404Y claim 1 , F406T claim 1 , F404W claim 1 , T317A claim 1 , S195A claim 1 , S144A claim 1 , S144D claim 1 , S196A claim 1 , and S183A.5. The composition of claim 1 , wherein the multimeric ligand binding region is selected from the group consisting of FKBP ligand binding region claim 1 , cyclophilin receptor ligand binding region claim 1 , steroid receptor ligand binding region claim 1 , ...

Werner's syndrome helicase as a target for anti -HIV/AIDS therapy

Werner's Syndrome helicase (WRN) interacts in Tat/TAR-RNA chromatin-remodeling complexes assembled on the HIV-1 LTR to promote transcriptional activation and viral replication. WRN markedly increases basal HIV-1 transcription and synergizes with Tat to support LTR trans-activation. Inhibition of WRN functions, through expression of the trans-dominant-negative WRN_K577M mutant, potently represses HIV-1 LTR trans-activation and prevents intracellular synthesis of p24^Gag and inhibits virus production in HIV-infected H9_HIV-1IIIB lymphocytes. Therefore, the present disclosure provides a novel target for anti-HIV therapy. Methods and compositions of the disclosure may be used to perform high throughput screens for small molecule anti-HIV therapeutics. Such therapeutics may inhibit a stage in the HIV replicative cycle not affected by current anti-HIV drugs.

APOPTOSIS INDUCER FOR CANCER CELL

The present invention revealed that by suppressing the expression of the WRN gene, the BLM gene, or the RecQ1 gene, which belong to the RecQ helicase family, apoptosis is induced in various cancer cells and their proliferation is suppressed. Compounds that suppress the expression of RecQ helicase family genes or the functions of RecQ helicase proteins are thought to have the activity of inducing apoptosis.

Phospholipase C homolog

Agent for use in the case of fructose intolerance

The present invention refers to an agent for use in the case of fructose intolerance and any form of impairment and affliction of health and well being which is caused by the administration of fructose or fructose containing foodstuffs or by the release of fructose in the digestive tract of humans or animals from other substances, such as e.g. sucrose. The agent according to the invention comprises 5-D-fructose dehydrogenase, optionally in combination with invertase and/or maltase and/or glucose isomerase, which enzyme or combination of enzymes is/are used in the medical field for the first time. Preferably the agent is in the form of a pharmaceutical composition which is useful for treatment of fructose intolerance.

Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions

Method and Pharmaceutical Composition for Use in the Treatment of Neurodegenerative Disorders

The invention relates to compounds which activate the BASIGIN signaling pathway, preferably agonists of BASIGIN, for the treatment of neurodegenerative disorders.

Agent for use in the case of fructose intolerance

There is provided in accordance with embodiments of the invention a method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism, the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase, other than in combination with 5-D-fructose dehydrogenase. Other embodiments are also disclosed. There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed. 1. A method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism , the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase , other than in combination with 5-D-fructose dehydrogenase.2. A method according to wherein said condition is fructose intolerance that is selected from the group consisting of (a) hereditary fructose intolerance claim 1 , (b) intestinal fructose intolerance (fructose non-absorption or fructose-malabsorption) claim 1 , (c) fructose intolerance that is due to a lack of fructose 1 claim 1 ,6-diphosphatase and (d) combinations thereof.3. A method according to claim 1 , wherein said glucose isomerase is administered prior to said subject's eating claim 1 , concurrently with said subject's eating or after said subject's eating.4. A method according to claim 1 , wherein said glucose isomerase is administered with a second enzyme which cleaves fructose from a more complex sugar.5. A method according to wherein said second enzyme is selected from the group consisting of invertase claim 4 , maltase and combinations thereof.6. A method according to claim 1 , wherein said administration comprises oral administration.7. A mammalian ingestible ...

Agent for use in the case of fructose intolerance

There is provided in accordance with embodiments of the invention a method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism, the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase, other than in combination with 5-D-fructose dehydrogenase. Other embodiments are also disclosed.

Agent for use in the case of fructose intolerance

There is provided in accordance with embodiments of the invention a method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism, the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase, other than in combination with 5-D-fructose dehydrogenase. Other embodiments are also disclosed. 1. A method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism , the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase , other than in combination with 5-D-fructose dehydrogenase.2. A method according to wherein said condition is fructose intolerance that is selected from the group consisting of (a) hereditary fructose intolerance claim 1 , (b) intestinal fructose intolerance (fructose non-absorption or fructose-malabsorption) claim 1 , (c) fructose intolerance that is due to a lack of fructose 1 claim 1 ,6-diphosphatase and (d) combinations thereof.3. A method according to claim 1 , wherein said glucose isomerase is administered prior to said subject's eating claim 1 , concurrently with said subject's eating or after said subject's eating.4. A method according to claim 1 , wherein said glucose isomerase is administered with a second enzyme which cleaves fructose from a more complex sugar.5. A method according to wherein said second enzyme is selected from the group consisting of invertase claim 4 , maltase and combinations thereof.6. A method according to claim 1 , wherein said administration comprises oral administration.7. A mammalian ingestible composition of matter selected from a pharmaceutical composition and a dietary supplement claim 1 , said composition of matter comprising a glucose isomerase claim 1 , a second enzyme other than 5-D-fructose dehydrogenase claim 1 , ...

Methods and compositions for malic enzyme 2 (me2) as a target for cancer therapy

The present invention relates to methods, compositions, and diagnostic tests for treating and diagnosing cancer and other related diseases that result in dysregulation of malic enzyme 2. In particular, the methods and compositions include combination therapy, such as with a combination of two or more ME2 inhibitors or a combination of an ME2 inhibitor and an anticancer agent.

METHOD OF TREATING OR RETARDING THE DEVELOPMENT OF BLINDNESS

A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method. 1. A composition for treatment of an ocular disorder characterized by a defect or absence of a normal gene in ocular cells of a subject , said composition comprising an effective amount of a recombinant adeno-associated virus (rAAV) carrying a nucleic acid sequence encoding said normal gene under the control of a promoter sequence which expresses the product of said normal gene in said ocular cells.2. The composition according to claim 1 , wherein said normal gene is a retinal pigment epithelium-specific gene.3. The composition according to claim 3 , wherein said normal gene is retinal pigment specific epithelial 65 (RPE65).4. The composition according to formulated with a carrier and additional components suitable for subretinal injection.5. A composition for restoring visual function in a subject having an ocular disorder caused by a defect or absence of a normal retinal pigment specific epithelial 65 (RPE65) in ocular cells of said subject claim 1 , said composition comprising an effective amount of a recombinant adeno-associated virus (rAAV) carrying a nucleic acid sequence encoding said RPE65 gene under the control of a promoter sequence which expresses the product of said RPE65 gene in said ocular cells.6. The composition according to claim 5 , wherein said RPE65 gene ...

MATERIAL COMBINATION FOR TREATING INFLAMMATORY OR INFECTIOUS DISEASES

A material combination is configured to treat or prevent inflammatory and infectious diseases caused by fastidious anaerobic or facultative anaerobic microorganisms, such as bacteria or sp. The material combination includes at least one antimicrobial peptide that can be activated by a reducing substance, and at least one reducing agent. 1. A material combination , comprising:at least one antimicrobial peptide that is activatable by a reducing agent; andat least one reducing agent, wherein the material combination is therapeutically effective in treating or preventing inflammatory and infectious diseases caused by obligate or facultative anaerobes.2. The material combination as claimed in claim 1 , wherein the at least one antimicrobial peptide is a defensin or fragments thereof.3. The material combination as claimed in claim 2 , wherein the defensin or the fragments thereof are selected from a group including one of:natural, isolated and purified defensins,recombinant defensins,synthetic defensins,fragments of natural, isolated and purified defensins,fragments of recombinant defensins, andfragments or synthetic defensins.4. The material combination as claimed in claim 2 , wherein the defensin is selected from human beta-defensin 1 claim 2 , human alpha-defensin 6 claim 2 , a human neutrophil peptide claim 2 , fragments of human beta-defensin 1 claim 2 , fragments of human alpha-defensin 6 claim 2 , and fragments of a human neutrophil peptide.5. The material combination as claimed in claim 1 , wherein the at least one reducing agent is selected from one of chemical reducing agents and enzymatic reducing agents.6. The material combination as claimed in claim 1 , wherein the at least one reducing agent is an oxidoreductase.7. The material combination as claimed in claim 1 , wherein the at least one reducing agent is selected from thioredoxin claim 1 , thioredoxin reductase claim 1 , DTT claim 1 , DTE claim 1 , protein disulfide-isomerase claim 1 , glutaredoxin and ...

METHODS FOR REGULATING PROTEIN FUNCTION IN CELLS IN VIVO USING SYNTHETIC SMALL MOLECULES

Methods and compositions for the rapid and reversible destabilizing of specific proteins in vivo using cell-permeable, synthetic molecules are described. 1. A method for modulating stability of a protein of interest in vivo comprisingintroducing into a eukaryotic cell a nucleic acid comprising a polynucleotide which encodes a fusion protein wherein the fusion protein comprises a secreted protein fused to a single-polypeptide chain, ligand-dependent, stability-affecting FKBP variant protein having F36V and L106P amino acid substitutions, andadministering a Shield1 ligand to the eukaryotic cell, wherein the ligand binds to the single-polypeptide chain, ligand-dependent, stability-affecting FKBP variant protein to modulate stability of the fusion protein.2. The method of claim 1 , wherein the eukaryotic cells are stably transformed with the nucleic acid.3. The method of claim 2 , wherein the stably transformed eukaryotic cells are implanted in an animal.4. The method of claim 1 , wherein the nucleic acid sequence is in a viral vector.5. The method of claim 4 , wherein the animal has tumor cells.6. The method of claim 4 , wherein the viral vector is a vaccinia virus.7. The method of claim 4 , wherein the administering of the Shield 1 ligand to the cell is by injecting the ligand into the animal intraperitoneally or intravenously.8. The method of claim 1 , wherein the secreted protein is TNF-α or IL-2.9. The method of claim 1 , wherein the introducing of the nucleic acid sequence comprises transforming the eukaryotic cell in culture with a plasmid comprising the nucleic acid to produce stably transformed eukaryotic cells claim 1 , and implanting the stably transformed eukaryotic cells into mice.10. A method for modulating cellular proliferation in an animal claim 1 , comprising:administering to the animal a nucleic acid comprising a polynucleotide which encodes a fusion protein wherein the fusion protein comprises a secreted protein fused to a single-polypeptide chain, ...

EXTRACTS ISOLATED FROM ELECTROPORATED AMBHIBIAN OOCYTES AND USE THEREOF IN TREATING DISEASES AND DISORDERS

The described invention provides methods for preparing a composition containing extracts of activated amphibian oocytes, the method where the composition is a pharmaceutical composition comprising an equal volume of the extra-oocyte composition and the intra-oocyte composition, and a method for treating a disease, disorder, condition or injury characterized by a damaged or a cancerous differentiated cell including: (a) preparing the composition by the described method; (b) formulating a pharmaceutical composition comprising an equal volume of the extra-oocyte composition and the intra-oocyte composition, and optionally a carrier; and (c) administering a therapeutic amount of the pharmaceutical composition of (b) to a subject in need thereof, where the therapeutic amount is effective to reprogram the damaged or cancerous cells into iPSC-like cells capable of differentiating into cells capable of repairing the damaged or cancerous cells, thereby treating the disease, disorder, injury or condition. 1. A method for preparing a composition comprising extracts of activated amphibian oocytes comprising:(a) providing a suspension of oocytes harvested from an amphibian, in a buffered oocyte washing solution in an oocyte activation vessel;(b) applying an electroporation stimulus to the suspended oocytes of (a) in the oocyte activation vessel to produce a suspension of activated oocytes;(c) combining an aqueous energy solution with the suspension of activated oocytes to form an aqueous suspension;(d) incubating the aqueous suspension of (c) at an incubation temperature of 16° C. to 20° C., for an incubation time of about 2 to about 4 hours;(e) partitioning the incubated combination of (d) to obtain a portion external to the incubated activated oocytes (extra-oocyte portion), and an activated oocyte portion that includes the incubated activated oocytes of (d);(f) separating the extra-oocyte portion and the activated oocyte portion from each other;(g) filtering the extra-oocyte ...

Chimeric antigen receptor (car) signalling system

The present invention relates to a chimeric antigen receptor (CAR) signalling system comprising; (i) a receptor component comprising an extracellular antigen-binding domain, a transmembrane domain and a intracellular first chemical inducer of dimerization binding domain 1 (CBD1); and (ii) an intracellular signalling component comprising a signalling domain and a second chemical inducer of dimerization binding domain 2 (CBD2); wherein CBD1 and CBD2 are capable of simultaneously binding to a chemical inducer of dimerization (CID); wherein, in the absence of the CID, binding of the antigen-binding component to antigen does not result in signalling through the signalling component; whilst, in the presence of the CID, the receptor component and the signalling component heterodimerize and binding of the antigen-binding domain to antigen results in signalling through the signalling domain.

MODIFIED CASPASE POLYPEPTIDES AND USES THEREOF

The technology relates in part to compositions comprising modified Caspase-9 polypeptides, compositions comprising nucleic acids coding for modified Caspase-9 polypeptides, chimeric modified Caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified Caspase-9 protein, with reduced basal activity in the absence of the inducer. 126-. (canceled)27. A cell transfected or transduced with a nucleic acid comprising a nucleotide sequence that encodes a chimeric protein comprising a FKBP 12 multimeric ligand binding region and a modified Caspase-9 polypeptide , wherein the modified Caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 9 , and comprises at least one amino acid substitution selected from the group consisting of N405Q , D330A , F404Y , F406L , F406T , F404W , T317A , T317S , S144A , S144D , S196A , S183A , S195A , F404T , F404W , N405F , F406T , D315A , A316G , T317S , F319W , 5307A , Y153A , and Y153F.28. The cell of claim 27 , wherein the chimeric protein has a Caspase-9 basal activity less than 50% of the basal activity of a chimeric protein comprising a FKBP 12 multimeric ligand binding region and a Caspase-9 polypeptide lacking the caspase recruitment domain (CARD) and having the amino acid sequence of SEQ ID NO: 9.29. The cell of claim 27 , wherein Caspase-9 activity is induced upon binding of a ligand to the FKBP 12 multimeric ligand region of the chimeric protein.30. The cell of claim 29 , wherein the ligand is AP1903 or AP20187.31. The cell of claim 29 , wherein the FKBP12 region is a modified FKBP12 polypeptide comprising an amino acid substitution at position 36 that binds with higher affinity to AP1903 or AP20187 than the wild type FKBP12 polypeptide.32. The cell of claim 31 , wherein the FKBP12 region is a FKBP12v36 polypeptide.33. The cell of claim 27 , wherein the ...

POLYNUCLEOTIDES ENCODING METHYLMALONYL-CoA MUTASE

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.

Methods for inducing selective apoptosis

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.

METHODS OF USING CYCLOOXYGENASE-PROSTACYCLIN SYNTHASE FUSION GENE

An effective amount of a composition comprising (i) a plasmid having a cyclooxygenase-prostacyclin synthase fusion gene, and (ii) a carrier fluid for use in treating an individual having a vascular disease or at risk of developing a vascular disease. A composition comprising a carrier fluid; and a DNA sequence encoding for a triple catalytic enzyme, a cDNA sequence encoding for a triple catalytic enzyme, a plasmid comprising a DNA sequence encoding for a triple catalytic enzyme, a fusion gene encoding for a triple catalytic enzyme, a cyclooxygenase-prostacyclin synthase fusion gene, or combinations thereof, for use in treating an individual having a vascular disease or at risk of developing a vascular disease. 1. An effective amount of a composition comprising (i) a plasmid having a cyclooxygenase-prostacyclin synthase fusion gene , and (ii) a carrier fluid for use in treating an individual having a vascular disease or at risk of developing a vascular disease.2. The composition of wherein the vascular disease comprises: pulmonary arterial hypertension claim 1 , peripheral arterial disease claim 1 , peripheral vascular disease claim 1 , chronic obstructive pulmonary disease claim 1 , ischemia claim 1 , limb ischemia claim 1 , critical limb ischemia claim 1 , Reynaud's syndrome claim 1 , ischemic stroke claim 1 , myocardial infarction claim 1 , systemic hypertension claim 1 , stroke claim 1 , subarachnoid hemorrhage claim 1 , or combinations thereof.3. The composition of wherein the plasmid comprises a DNA sequence encoding for a triple catalytic enzyme.4. The composition of wherein the triple catalytic enzyme is characterized by a formula COX-linker-PGIS claim 3 , wherein COX comprises a cyclooxygenase (COX) amino acid sequence; PGIS is prostacyclin synthase; and the linker comprises from about 10 to about 22 amino acid residues of a transmembrane sequence; wherein the linker is disposed between the COX and PGIS claim 3 , and wherein the linker directly connects the ...

Agent for use in the case of fructose intolerance

There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed.

CRYSTALLIZED XYLOSE ISOMERASE IN PREVENTION OF THE DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE

The present invention relates to the composition comprising crystalline xylose-isomerase and at least one salt of a metal and/or alkaline earth metal for the treatment and prevention of non-alcoholic fatty liver disease and other fructose-related disorders. 2. The method of claim 1 , wherein the composition is administered in an enteric form.3. The method of claim 2 , wherein the enteric form is further defined as an enteric coated pellet claim 2 , enteric coated tablet claim 2 , enteric coated capsule claim 2 , enteric coated granule claim 2 , or enteric coated powder.4. The method of claim 1 , wherein the magnesium salt in the composition has a molar ratio to xylose-isomerase ranging from 5:1 to 25:1.5. The method of claim 1 , wherein the magnesium salt is MgCl claim 1 , MgSO claim 1 , MgCO claim 1 , Mg(HCO3)2 claim 1 , or Mg(CHO).6. The method of claim 1 , wherein the xylose-isomerase is present in microcapsules claim 1 , nanoparticles claim 1 , or liposomes.7Streptomyces rubiginosus.. The method of claim 1 , wherein the xylose-isomerase of microbial origin originates from8. The method of claim 1 , wherein the composition is a pharmaceutical composition claim 1 , a food supplement claim 1 , a dietetic food claim 1 , a medicinal product claim 1 , a feeding stuff claim 1 , a supplementary feeding stuff or a dietetic feeding stuff. The present invention relates to a composition for the treatment of Non-Alcoholic Fatty Liver Disease and the treatment or prevention of fructose-related disorders.Non-alcoholic fatty liver disease (NAFLD) is a rapidly-growing and mostly silent chronic liver disease characterised by the accumulation of triglycerides in hepatocytes occurring in people who consume little or no alcohol. This condition comprises a wide spectrum of histological lesions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), a parenchymal liver inflammation which can develop further to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD is ...

METHODS AND COMPOSITIONS FOR INCREASING SIALIC ACID PRODUCTION AND TREATING SIALIC RELATED DISEASE CONDITIONS

Disclosed herein are methods of expressing UDP-GlcNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3, wherein upon the delivering into the cell of the subject, the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof. Also disclosed are methods of producing a GNE peptide in a cell comprising infecting the cell with an isolated nucleic acid construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3. 1. A method of treating hyposialylation in a subject , comprising administering to the subject a composition comprising a net negative charge , and a DNA molecule encoding GNE or a therapeutic fragment thereof.2. The method of claim 1 , wherein the composition comprises hypermorphic GNE.3. The method of claim 1 , wherein the composition is administered by hydrodynamic delivery route.4. The method of claim 1 , wherein the composition is a gene therapy vector or an enzyme replacement therapy.5. The method of claim 1 , wherein GNE has at least one mutation within the allosteric domain.6. The method of claim 1 , wherein subsequent to the administration of the composition claim 1 , the subject experiences an increase in sialic content.7. The method of claim 1 , wherein the subject has at least one mutation in the gene encoding GNE.8. The method of claim 1 , comprising administering the composition to a limb or limbs of the subject.9. The method of claim 1 , wherein subsequent to the administration of the composition claim 1 , the ...

POLYNUCLEOTIDES ENCODING METHYLMALONYL-CoA MUTASE

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide. 215.-. (canceled)17. The lipid nanoparticle of claim 1 , wherein Ris unsubstituted Calkyl.18. The lipid nanoparticle of claim 1 , wherein Ris —(CH)Q or —(CH)CHQR claim 1 , Q is —N(R) claim 1 , and n is selected from 3 claim 1 , 4 claim 1 , and 5.19. The lipid nanoparticle of claim 1 , wherein the compound is selected from the group consisting of Compounds 1 to 147 and salts and stereoisomers thereof.22. The lipid nanoparticle of claim 16 , wherein M and M′ are independently —C(O)O— or —OC(O)—.23. The lipid nanoparticle of claim 1 , wherein Rand Rare the same.24. The lipid nanoparticle of claim 1 , wherein Rand Rare Calkyl.25. The lipid nanoparticle of claim 1 , wherein Rand Rare different.26. The lipid nanoparticle of claim 16 , wherein:(i) n is 2;{'sub': 4', '4', '5', '5', '6', '6', '7', '7', '9', '9', '11', '11', '12', '12', '13', '13', '14', '14', '15', '15', '16', '16', '17', '17', '18', '18, '(ii) R′ is selected from: Calkyl and Calkenyl, Calkyl and Calkenyl, Calkyl and Calkenyl, Calkyl and Calkenyl, Calkyl and Calkenyl, Calkyl and Calkenyl, Calkyl, Calkenyl, Calkyl, Calkenyl, Calkyl, Calkenyl, Calkyl, Calkenyl, Calkyl, Calkenyl, Calkyl, Calkenyl, Calkyl, and Calkenyl; and/or'}(iii) l is selected from 3, 4, and 5.27. The lipid nanoparticle of claim 1 , further comprising a phospholipid claim 1 , a structural lipid claim 1 , and a PEG lipid.28. The lipid nanoparticle of claim 27 , wherein:(i) the phospholipid is selected from the group consisting of:1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC),1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC),1,2-dioleoyl ...

COMPOSITIONS AND METHODS FOR SELECTIVE ELIMINATION AND REPLACEMENT OF HEMATOPOIETIC STEM CELLS

Disclosed are methods of eliminating at least on target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs). 1. A method of eliminating at least one target cell in a subject , comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells , wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell , wherein specifically binding of the one or more CLR(s) to the target ligand activates the immune cell , and wherein the activated immune cell induces death of the target cell.2. The method of claim 1 , further comprising the step of eliminating the plurality of immune cells.3. A method of transplanting an immune system of a subject claim 1 , comprising:(a) administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target ligand activates the immune cell, and wherein the activated immune cell induces death of the target cell;(b) eliminating the plurality of immune cells; and(c) administering to the subject an effective amount of a composition comprising a plurality of therapeutic hematopoietic stem cells ...

TAGGED FORM OF MUT ENZYME, GENETIC CONSTRUCTS INCORPORATING IT, AND ITS USE IN GENE THEREAPY

Disclosed are polynucleotides, polypeptides, and gene therapy vectors relating to biologically active methylmalonyl-CoA mutase enzymes, internally tagged with an immunoaffinity and detection epitope, which has been designed and tested in mouse models of methylmalonic acidemia (MMA). The polypeptides and polynucleotides of the present invention contain a mitochondrial leader sequence fused to tag, such as an HA, 3xFLAG, or V5 tag placed in a region of the methylmalonyl-CoA mutase enzyme that maintains mitochondrial localization and function, e.g., the 5′ end of a methylmalonyl-CoA mutase polynucleotide is replaced with an engineered nucleotide sequence that encodes the endogenous mitochondrial importation sequence, a mitochondrial protease cleavage site, and a tag. The polynucleotides and polypeptides of the invention are useful to treat conditions such as MMA, and to assay both activity and biodistribution after gene therapy in varied models of MMA. 1. A synthetic methylmalonyl-CoA mutase polypeptide comprising an amino acid sequence comprising , in order from the N-terminus: a methylmalonyl-CoA mutase mitochondrial leader amino acid sequence , a tag amino acid sequence , and a methylmalonyl-CoA mutase mature amino acid sequence.2. The synthetic polypeptide of claim 1 , wherein the tag amino acid sequence is flanked by at least one linker amino acid sequence.3. The synthetic polypeptide of claim 1 , wherein the methylmalonyl-CoA mutase mitochondrial leader amino acid sequence comprises a human or a mouse mitochondrial leader amino acid sequence selected from the group consisting of SEQ ID NO:1 claim 1 , SEQ ID NO:2 claim 1 , and an amino acid sequence having at least about 95% identity thereto claim 1 , and having substantially identical activity to the methylmalonyl-CoA mutase mitochondrial leader amino acid sequence.4. The synthetic polypeptide of claim 2 , wherein the linker amino acid sequence comprises an amino acid sequence of from 1 to about 15 amino acids ...

ISOMERASES, NUCLEIC ACIDS ENCODING THEM AND METHODS FOR MAKING AND USING THEM

This invention relates generally to enzymes, polynucleotides encoding the enzymes, the use of such polynucleotides and polypeptides and more specifically to enzymes having isomerase activity, e.g., racemase activity, e.g., amino acid racemase activity, alanine racemase activity, and/or epimerase activity, and/or catalyze the re-arrangement of atoms within a molecule, catalyze the conversion of one isomer into another, catalyze the conversion of an optically active substrate into a raceme, which is optically inactive, catalyze the interconversion of substrate enantiomers, catalyze the stereochemical inversion around the asymmetric carbon atom in a substrate having only one center of asymmetry, catalyze the stereochemical inversion of the configuration around an asymmetric carbon atom in a substrate having more than one asymmetric center, and/or catalyze the racemization of amino acids. Thus, the invention provides enzymes, compositions, methods for production of pharmaceutical compositions, pharmaceutical intermediates, antibiotics, sweeteners, peptide enzymes, peptide hormones, fuel and fuel additive compositions, foods and food additives, beverage and beverage additives, feeds and feed additives, drugs and drug additives, dietary supplements, textiles, wood, paper, pulp, and detergents comprising the polypeptides or polynucleotides in accordance with the invention. 1. An isolated , synthetic or recombinant comprising(a) a nucleic acid (polynucleotide) encoding at least one polypeptide, wherein the nucleic acid comprises a sequence having at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more or complete (100%) sequence identity to the nucleic acid (polynucleotide) sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: ...

DYNAMIC COVALENTLY LINKED HYDROGELS AS STABILIZATION NETWORK PLATFORMS

The present invention provides dynamically covalent polymeric hydrogel systems for encapsulating and stabilizing bioactive therapeutic agents (e.g., proteins, cells, viruses, and vaccines) from environmental stressors, obviating standard refrigeration requirements, and decreasing transportation and storage costs of temperature-sensitive biomolecules. Described herein are dynamic polymeric hydrogel compositions comprising a therapeutic agent and a combination of phenylboronic acid- and 1,2-diol-modified multi-arm polyethylene glycol (PEG) polymer backbones. Methods of encapsulating and stabilizing bioactive therapeutic agents within the dynamic polymeric hydrogel compositions are also provided. Also described are methods for releasing stabilized therapeutic agents from hydrogel encapsulation. The covalently adaptable hydrogel release systems allow for discretionary administration of temperature-sensitive therapeutic agents, as well as the parenteral administration of highly concentrated amounts of therapeutic agents. 2. The method of claim 1 , whereinsubscripts a, a′, b, b′, c, c′, d, and d′ are each independently an integer selected from 10 to 250;{'sub': 1', '2, 'subscripts mand mare each independently an integer selected from 25 to 10,000;'}{'sub': 1-6', '1-6', '1-6', '2', '3', '2', '1-3', '1-3, 'each linker L is selected from a bond, —C(O)—, substituted or unsubstituted Calkylene, and unsubstituted —C(O)—Calkylene, wherein substituted Calkylene is substituted with at least one substituent selected from —OH, —NH, —SH, —CN, —CF, —COOH, —C(O)NH, halogen, unsubstituted Calkyl, and substituted Calkyl; and'}{'sub': 1-6', '1-6, 'each linker L′ is selected from a bond, —C(O)—, unsubstituted Calkylene, and unsubstituted —C(O)—Calkylene.'}4. The method of claim 3 , wherein{'sup': 1', 'a', 'b', 'a', 'b', 'a', 'a', 'a', 'b, 'sub': 1-6', '1-6', '1-6', '2', '2, 'each Ris each independently selected from the group consisting of substituted or unsubstituted Calkyl, Calkoxy, ...

METHODS OF TREATING CANCER OF THE CENTRAL NERVOUS SYSTEM

A method of treating a cancer of the central nervous system in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of an agent which reduces blood glutamate levels and enhances brain to blood glutamate efflux to thereby treat the cancer of the central nervous system in the subject. 1. A method of treating a cancer of the central nervous system in a subject in need thereof , the method comprising administering to the subject a therapeutically effective amount of a glutamate modifying enzyme and optionally a co-factor thereof which reduces blood glutamate levels to thereby treat the cancer of the central nervous system in the subject.2. An article-of-manufacture comprising packaging material and a pharmaceutical composition identified for treating a cancer of the central nervous system being contained within the packaging material , the pharmaceutical composition including , as an active ingredient , an agent capable of reducing blood glutamate levels and an anti cancer agent and a pharmaceutically acceptable carrier.3. The article of manufacture of claim 2 , wherein the anti cancer agent comprises a chemotherapy.4. The method of claim 1 , wherein the glutamate modifying enzyme comprises glutamate oxaloacetate transaminase and the co-factor thereof comprises oxaloacetate.5. The method of claim 1 , wherein the glutamate modifying enzyme comprises pyruvate transaminase and the co-factor thereof comprises pyruvate.6. The method of claim 1 , wherein the cancer is a glioma. This application is a continuation of U.S. patent application Ser. No. 14/685,628 filed on Apr. 14, 2015, which is a division of U.S. patent application Ser. No. 12/994,762 filed on Nov. 25, 2010, now U.S. Pat. No. 9,034,319, which is a national phase of PCT Patent Application No. PCT/IL2008/000711 having International Filing Date of May 26, 2008. The contents of the above Applications are incorporated herein by reference.The ...

METHODS FOR THE TREATMENT AND DIAGNOSIS OF BONE MINERAL DENSITY RELATED DISEASES

The present invention relates to methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, the present invention relates to a method of diagnosing or predicting a hone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. The invention also relates to a compound selected in the group consisting of a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). The invention also relates to a compound selected from the group consisting of an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis). 1. A method of diagnosing or predicting a bone mineral density related disease , or a risk of a bone mineral density related disease , in a subject , which method comprises detecting a mutation in the TBXAS1 gene , wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease , wherein said method comprises the step of detecting a TBXAS1 mutation in a nucleic acid sample obtained from said subject.2. The method according to claim 1 , wherein the bone mineral density related disease is a disease associated with an increased bone mineral density and the mutation in the TBXAS1 gene is associated with a decrease of the Thromboxane synthase activity.3. The method of wherein said disease associated with an increased bone mineral density is Ghosal hematodiaphyseal dysplasia syndrome.4. The method of or wherein the ...

HYBRID PROTEIN THAT CONVERTS ARACHIDONIC ACID INTO PROSTACYCLIN

A recombinant 130-kDa protein is constructed by linking together human cyclooxygenase (COX) isoform-2 (COX-2) and prostacyclin synthase (PGIS), via a 10-20 amino acid residues of a transmembrane sequence. The engineered protein is expressed in cells, and adopts the functions of COX and PGIS, to continually convert arachidonic acid (AA) into prostaglandin G(catalytic step 1), prostaglandin H(catalytic step 2) and prostacyclin (PGI; catalytic step 3). 1. An isolated hybrid protein molecule comprising a cyclooxygenase (COX) amino acid sequence and an eicosanoid-synthesizing (ES) enzyme amino acid sequence with a linker sequence disposed there between and directly connecting said COX enzyme sequence to said ES enzyme sequence.2. The hybrid protein molecule of claim 1 , wherein said linker sequence is about 10 to 22 amino acids long.3. The hybrid protein molecule of wherein said linker sequence is His-Ala-Ile-Met-Gly-Val-Ala-Phe-Thr-Trp (SEQ ID NO. 1) or His-Ala-Ile-Met-Gly-Val-Ala-Phe-Thr-Trp-Val-Met-Ala-Leu-Ala-Cys-Ala-Ala-Pro-Pro-Leu-Val (SEQ ID NO. 2) or residues 1-11 claim 2 , 1-12 claim 2 , 1-13 claim 2 , 1-14 claim 2 , 1-15 claim 2 , 1-16 claim 2 , 1-17 claim 2 , 1-18 claim 2 , 1-19 claim 2 , 1-20 or 1-21 of SEQ ID NO. 2.4. The hybrid protein of claim 1 , comprising cyclooxygenase (COX) claim 1 , a transmembrane linker claim 1 , and a prostacyclin synthase (PGIS) claim 1 , wherein said hybrid protein is either chemically synthesized or recombinantly produced.5. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the hybrid protein of ; and'}a pharmaceutically acceptable carrier.6. A method of treating an individual having a vascular disease claim 5 , or at risk of developing a vascular disease claim 5 , said method comprising microinjecting an effective amount of the pharmaceutical composition of into at least one vascular cell in said individual claim 5 , to cause the production of at least one biologically active compound ...

METHOD FOR INDUCING PRODUCTION OF VASCULAR ENDOTHELIAL GROWTH FACTOR

The present invention relates to a method for inducing production of vascular endothelial growth factor (VEGF). The method includes administering, to an individual, a composition including adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin 1. A method for inducing production of vascular endothelial growth factor (VEGF) , the method comprising: administering , to an individual , a composition comprising an adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin I(PGI).2. The method according to claim 1 , wherein the AAV is of a type selected from the group consisting of type 1 claim 1 , 2 claim 1 , 5 and 83. The method according to claim 1 , wherein the AAV is of a type selected from the group consisting of type 1 and 2.4. The method according to claim 1 , wherein the AAV induces one or more activities selected from the group containing of vasodilation claim 1 , anti-platelet aggregation and angiogenesis.5. The method according to claim 1 , wherein the composition further comprises a pharmaceutically permissible carrier containing the AAV claim 1 , the carrier being selected from the group consisting of water claim 1 , a water-propylene glycol mixed solution claim 1 , a buffered solution claim 1 , and 0.4% saline.6. The method according to claim 1 , wherein the AAV further carries a second gene coding for an angiogenesis factor selected from the group consisting of genes coding for vascular endothelial growth factor (VEGF) and VEGF-2.7. The method according to claim 6 , wherein the second gene coding for an angiogenesis factor is a VEGF.8. The method according to claim 6 , wherein the AAV induces one or more activities selected from the group containing of vasodilation claim 6 , anti-platelet aggregation and angiogenesis.9. The method according to claim 6 , wherein the composition further comprises a pharmaceutically ...

Modified caspase-9 polypeptides and methods of use thereof

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

CYCLOPHILIN 40 FOR REDUCTION OF NEUROTOXIC FIBRILS AND TREATMENT OF NEURODEGENERATIVE DISEASES

The present invention concerns the use of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) for reduction of neurotoxic fibrils and treatment and prevention of neurodegenerative diseases associated with amyloid fibril aggregation. Aspects of the invention include compositions, methods, dosage forms, and kits for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation in a human or animal subject, and for disaggregating neurofibrillary aggregates in vitro or in vivo, using CyP40, or a biologically active fragment thereof. 1. A method for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation , said method comprising administering an effective amount of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) , or a biologically-active fragment thereof , to a human or animal subject in need thereof.2. The method according to claim 1 , wherein said method further comprises identifying a subject as one in need of treatment.3. The method according to claim 1 , wherein the disease or condition is characterized by the presence of neurofibrillary aggregates of the microtubule associated protein tau and/or α-synuclein.4. The method according to claim 1 , wherein the disease or condition is Alzheimer' s disease claim 1 , gangliogliomas claim 1 , gangliocytomas claim 1 , argyrophilic grain dementia claim 1 , corticobasal degeneration claim 1 , dementia pugilistica claim 1 , frontotemporal dementia with parkinsonism linked to chromosome17 claim 1 , Pick's disease claim 1 , Hallervorden-Spatz disease claim 1 , myotonic dystrophy claim 1 , Niemann-Pick disease (type C) claim 1 , Parkinsonism-dementia complex of Guam claim 1 , postencephalitic parkinsonism claim 1 , prion diseases claim 1 , progressive subcortical gliosis claim 1 , or progressive supranuclear palsy.5. The method according to claim 1 , wherein the CyP40 claim 1 , or a biologically active fragment thereof claim 1 , is ...

POLYNUCLEOTIDES ENCODING METHYLMALONYL-COA MUTASE

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering a polynucleotide sequence encoding an MCM polypeptide. 2. An isolated polynucleotide comprising an ORF that has(i) at least 99% or 100% sequence identity to nucleotide 97 to nucleotide 2250 of SEQ ID NO: 734, or at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to nucleotide 154 to nucleotide 2307 of SEQ ID NO: 775;(ii) at least 98%, at least 99%, or 100% sequence identity to nucleotide 97 to nucleotide 2250 of SEQ ID NO: 732;(iii) at least 92%, at least 93%, at least 941%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of nucleotides 97 to nucleotides 2250 of SEQ ID NOs: 182, 733, and 741;(iv) at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of nucleotides 97 to nucleotides 2250 of SEQ ID NOs: 735, 736, 738, 743, 744, 748, 749, 750, 754, 755, 758, 762, and 765;(v) at least 90%, at least 913%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of nucleotides 97 to nucleotides 2250 of SEQ ID NOs: 180, 187, 737, 739, 740, 742, 745, 746, 747, 751, 752, 753, 757, 759, 760, 761, 763, and 764;(vi) at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence ...

METABOLIC THERAPY FOR OXIDATIVE STRESS IN THE BRAIN THROUGH TARGETED NEURONAL CATABOLISM OF N-ACETYL-ASPARTIC ACID

The present invention provides a novel method of treatment for treating brain disorders that manifest oxidative stress by providing targeted populations of neurons with the ability to catabolize the acetylated amino acid derivative, N-acetylaspatic acid (NAA) and further supply extraphysiological levels of ATP to neurons via the targeted expression of the NAA catabolic enzyme aspartoacylase (ASPA) in neurons and astrocytes. 111-. (canceled)12. A method of increasing the intracellular concentration of AcCoA from its baseline level in a subject in need thereof , the method comprising (a) administering to the subject an effective amount of a delivery construct comprising an isolated nucleic acid comprising a first sequence that encodes ASPA or a functional fragment thereof under conditions whereby the nucleic acid is expressed in a host cell of the subject (b) measuring the increased level of AcCoA.13. The method of claim 12 , wherein the delivery construct comprises a viral vector or a non-viral vector.14. The method of claim 13 , wherein the viral vector is selected from the group consisting of an AAV1 vector claim 13 , an AAV2 vector claim 13 , an AAV3 vector claim 13 , an AAV4 vector claim 13 , an AAV5 vector claim 13 , an AAV6 vector claim 13 , an AAV7 vector claim 13 , an AAV8 vector claim 13 , an AAV9 vector claim 13 , an AAV10 vector claim 13 , an AAV 11 vector claim 13 , a retroviral vector claim 13 , an alphaviral vector; a vaccinia viral vector; an adenoviral vector claim 13 , and an herpes simplex viral vector.15. The method of claim 13 , wherein the delivery non-viral vector is a lipid claim 13 , a poly-lysine claim 13 , a synthetic polyamino polymer claim 13 , or a plasmid.16. The method of claim 12 , wherein the nucleic acid encoding ASPA comprises a sequence identified as SEQ ID NO: 1.17. The method of claim 14 , wherein the viral vector of the delivery construct is an AAV2 viral vector.18. The method of claim 13 , wherein the delivery construct further ...

METHODS FOR CONTROLLED ELIMINATION OF THERAPEUTIC CELLS

The technology relates in part to methods for controlling elimination of therapeutic cells, for example, cells that express a chimeric antigen receptor. The technology further relates to a two-step method of controlling destruction of therapeutic cells in a patient following an adverse event. The two-step system may include a rapamycin or rapamycin analog-based level of control and a second, rimiducid, level of control. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide and the rapamycin-sensitive polypeptide, where the proportion of therapeutic cells eliminated by apoptosis is related to the choice and amount of the administered ligand. 1. A modified cell , comprisinga) a first polynucleotide encoding a first chimeric polypeptide, wherein the first chimeric polypeptide comprises a membrane-associated polypeptide region and a first multimerizing region; andb) a second polynucleotide encoding a second chimeric polypeptide, wherein the second chimeric polypeptide comprises a pro-apoptotic polypeptide region and a second multimerizing region, wherein the second multimerizing region has a different amino acid sequence than the first multimerizing region;wherein the first and second multimerizing regions bind to a first multimeric ligand.2. The modified cell of claim 1 , wherein the second multimerizing region binds to the first multimeric ligand and binds to a second multimeric ligand that does not significantly bind to the first multimerizing region.3. The modified cell of claim 2 , wherein:the first ligand comprises a first portion,the first multimerizing region binds to the first portion, andthe second multimerizing region does not significantly bind to the first portion.4. The modified cell of claims 2 , wherein the first multimerizing region is not capable of binding to the second multimeric ligand.5. The modified cell of claim 4 , wherein the first and second multimerizing regions bind to a ...

Metabolic therapy for oxidative stress in the brain through targeted neuronal catabolism of n-acetyl-aspartic acid

The present invention provides a novel method of treatment for treating brain disorders that manifest oxidative stress by providing targeted populations of neurons with the ability to catabolize the acetylated amino acid derivative, N-acetylaspatic acid (NAA) and further supply extraphysiological levels of ATP to neurons via the targeted expression of the NAA catabolic enzyme aspartoacylase (ASPA) in neurons and astrocytes.

SUCROSE ISOMERASES AS FOOD AND NUTRITIONAL SUPPLEMENTS

Sucrose isomerase is used as a nutritional supplement, or can be mixed in with a powderous food/beverage formulation. When an animal, including a human, consumes sucrose, the sucrose isomerase will act on the sucrose present in the food, and will convert the sucrose to other sugars. This results in lowering of the glycemic index of the food without changing the formulation of the food. 1. A nutraceutical , pharmaceutical or nutritional supplement composition comprising a sucrose isomerase.2. A composition according to which is suitable for humans.3. A composition according to which is suitable for companion animals.4. A composition according to comprising a sucrose isomerase with at least 60% identity claim 1 , preferably 90% claim 1 , 95% claim 1 , 98% claim 1 , 99% claim 1 , 100% identity claim 1 , to any one of the sequences of SEQ ID NO:1-6.5. A composition according to comprising a sucrose isomerase with at least 60% identity claim 4 , preferably 90% claim 4 , 95% claim 4 , 98% claim 4 , 99% claim 4 , 100% identity claim 4 , to SEQ ID NO: 4.6. A method of lowering the increase of blood glucose levels in an animal claim 1 , including a human ingesting sucrose claim 1 , comprising administering a nutraceutical claim 1 , pharmaceutical or nutritional supplement of to the animal including a human in need thereof.7. A method of lowering the glycemic index of a food or feed which is consumed by a human or companion animal comprising administering to the human or companion animal a nutraceutical claim 1 , pharmaceutical or nutritional supplement comprising a sucrose isomerase according to .8. A method of losing weight or maintaining weight loss in a human or companion animal comprising administering to the human or companion animal a nutraceutical claim 1 , pharmaceutical or nutritional supplement comprising a sucrose isomerase according to .9. Use of a nutraceutical claim 1 , pharmaceutical or nutritional supplement comprising a sucrose isomerase to achieve a ...

AGENT FOR REDUCING THE USEABLE CALORIE CONTENT OF FOOD AND FOR THERAPEUTIC REDUCTION OF WEIGHT, IN PARTICULAR FOR USE IN THE CASE OF ADIPOSITY (OBESITY)

There are disclosed compositions and methods for treating obesity using 5-D-fructose dehydrogenase. Other embodiments are also described. 1262-. (canceled)263. A mammalian ingestible composition which is adapted for oral administration selected from a pharmaceutical composition and a dietary supplement , said composition being in unit dosage form , said composition comprising 5-D-fructose dehydrogenase and a carrier or excipient that is acceptable for use in pharmaceutical compositions or foodstuffs , said composition further comprising a second enzyme selected form the group consisting of a glucose isomerase , maltase , invertase , lactase , alpha-amylase , beta-amylase , glucoamylase , pullulanase , isoamylase amyloglucosidase , cyclomaltodextrin glucanotransferase , and mixtures thereof.264266-. (canceled)267. The composition according to which is in a form selected from (a) the group consisting of a tablet claim 263 , capsule claim 263 , gel cap claim 263 , pellet and dragee claim 263 , (b) powder and (c) liquid form as solution claim 263 , drops suspension or gel.268. The composition according to wherein said 5-D-fructose dehydrogenase is protected by a coating which is stable at pH below 4.269. The composition according to wherein said coating protects the entire dosage unit.270. The composition according to wherein said 5-D-fructose dehydrogenase is microencapsulated.271. The composition according to wherein said 5-D-fructose dehydrogenase constitutes between 5 and 99.9% by weight of the composition.272. The composition according to wherein said unit dosage contains between 50 and 1 million units of 5-D-fructose dehydrogenase activity.273. The composition according to wherein said composition comprises a coating which dissolves at a pH of 5.5 or higher.274. The composition according to wherein said 5-D-fructose dehydrogenase is not contained in an inorganic-based sol-gel biocompatible matrix.275. The composition according to wherein said second enzyme is a ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed. 197-. (canceled)98. A method of treating fructose intolerance or reducing the effects of fructose intolerance , the method comprising administering to a subject in need of such treatment or reduction an amount of a glucose isomerase sufficient to effect such treating or reducing.99. A method of reducing in a subject at least one of (a) the bioavailability of fructose in the body of said subject , (b) the amount of fructose available to the body of said subject and (c) the amount of fructose available to intestinal bacteria colonizing the intestine of said subject , the subject being a person who would benefit from such reducing , the method comprising administering to the subject an amount of a glucose isomerase sufficient to convert fructose to glucose in said subject , thereby reducing at least one of (a) the bioavailability of fructose in the body of said subject , (b) the amount of fructose available to the body of said subject and (c) the amount of fructose available to intestinal bacteria colonizing in the intestine of said subject.100. The method of claim 98 , wherein said subject suffers from intestinal fructose intolerance.101. The method of claim 100 , wherein said intestinal fructose intolerance is caused by a disorder of fructose absorption.102. The method of claim 98 , wherein the administration occurs after the intake by said subject of fructose or a substance or foodstuff containing fructose in pure form or from which fructose can be released in the digestive tract.103. The method of claim 98 , wherein said glucose isomerase is contained in a pharmaceutical composition or a foodstuff.104. The method of claim 103 , wherein said glucose isomerase is contained in a pharmaceutical composition.105. The method of claim 103 , wherein ...

REDUCTION OF LIPASE ACTIVITY IN PRODUCT FORMULATIONS

The invention relates a method for producing a stable recombinant protein, comprising growing a non-naturally occurring host cell in a culture medium to produce a recombinant protein, and making a composition comprising the recombinant protein and a polysorbate. The production of endogenous lipoprotein lipase by the host cell is reduced. The endogenous lipoprotein lipase is present in the composition in a small amount, and is capable of degrading the polysorbate. The invention also relates to the relevant host cells and compositions, and preparation thereof. 1. A non-naturally occurring host cell comprising a nucleic acid sequence encoding a recombinant protein , wherein the host cell expresses the recombinant protein , and wherein at least one copy of an endogenous gene encoding the endogenous lipoprotein lipase is knocked out from the genome of the host cell.2. The non-naturally occurring host cell of claim 1 , wherein the host cell is a mammalian cell selected from the group consisting of CHO claim 1 , 3T3 claim 1 , BHK claim 1 , HeLa claim 1 , NS0 claim 1 , HepG2 claim 1 , and derivatives thereof.36-. (canceled)7. A composition comprising a stable recombinant protein and a polysorbate claim 1 , wherein the recombinant protein is produced by the non-naturally occurring host cell of claim 1 , wherein the endogenous lipoprotein lipase is present in the composition in an amount less than 10% by weight claim 1 , and wherein the endogenous lipoprotein lipase is capable of degrading the polysorbate.8. The composition claim 7 , wherein the recombinant protein is a monoclonal antibody.9. The composition of claim 7 , wherein the polysorbate comprises polysorbate 80 claim 7 , polysorbate 20 claim 7 , polysorbate 40 claim 7 , polysorbate 60 claim 7 , polysorbate 65 claim 7 , or a combination thereof.1020-. (canceled) This application claims the benefit of U.S. Provisional Application No. 61/917,555, filed Dec. 18, 2013, the contents of which are incorporated herein by ...

Method for inducing production of vascular endothelial growth factor

The present invention relates to a method for inducing production of vascular endothelial growth factor (VEGF). The method includes administering, to an individual, a composition including adeno-associated virus (AAV) carrying a hPGIS gene coding for human prostacyclin synthase (hPGIS) which synthesizes prostaglandin I2 (PGI2).

METABOLIC THERAPY FOR OXIDATIVE STRESS IN THE BRAIN THROUGH TARGETED NEURONAL CATABOLISM OF N-ACETYL-ASPARTIC ACID

The present invention provides a novel method of treatment for treating brain disorders that manifest oxidative stress by providing targeted populations of neurons with the ability to catabolize the acetylated amino acid derivative, N-acetylaspatic acid (NAA) and further supply extraphysiological levels of ATP to neurons via the targeted expression of the NAA catabolic enzyme aspartoacylase (ASPA) in neurons and astrocytes. 142.-. (canceled)43. A method of reducing oxidative stress in a subject suffering from Parkinson's disease , the method comprising:(a) identifying a subject suffering from Parkinson's disease; and(b) administering to the subject an effective amount of a formulation comprising an isolated nucleic acid comprising a first sequence that encodes aspartoacylase (ASPA) under conditions whereby the nucleic acid is expressed in a host cell of the subject and whereby expression of ASPA leads to enhanced catabolism of NAA, increased concentration of AcCoA, and reduced oxidative stress.44. The method of claim 43 , wherein the host cell is a nerve cell selected from the group consisting of oligodendrocytes claim 43 , neurons claim 43 , astrocytes claim 43 , and any combination thereof.45. The method of claim 43 , further comprising administration of a secondary therapeutic product selected from the group consisting of an antibody claim 43 , a cultured cell claim 43 , an active substance and a diagnostic agent.46. The method of claim 43 , wherein the formulation further comprises a pharmaceutically acceptable carrier.47. The method of claim 43 , further comprising a step of administering an adjunct immunotherapy claim 43 , a dietary regime claim 43 , or combinations thereof.48. The method of claim 43 , wherein the isolated nucleic acid is in a vector and operatively linked to a promoter.49. The method of claim 48 , wherein the vector is an AAV vector comprising a regulatory element.50. The method of claim 49 , wherein the AAV vector is an AAV 2 vector.51. The ...

METHODS AND COMPOSITIONS FOR INCREASING SIALIC ACID PRODUCTION AND TREATING SIALIC RELATED DISEASE CONDITIONS

Disclosed herein are methods of expressing UDP-GlcNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3, wherein upon the delivering into the cell of the subject, the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof. Also disclosed are methods of producing a GNE peptide in a cell comprising infecting the cell with an isolated nucleic acid construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof, wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3. 1. A method of expressing UDP-GlcNAc 2-Epimerase/ManNAc Kinase enzyme (GNE) peptide in a cell of a subject comprising: delivering into the cell of the subject an isolated nucleic acid expression construct that comprises a promoter operatively linked to a nucleic acid sequence encoding a GNE peptide or a therapeutically active fragment thereof , wherein the GNE peptide has the amino acid sequence of SEQ ID NO:3 , wherein upon the delivering into the cell of the subject , the nucleic acid expression construct initiates expression of the GNE peptide or a therapeutically active fragment thereof.2. The method of claim 1 , wherein the isolated nucleic acid expression construct has the sequence set forth in SEQ ID NO:1 or SEQ ID NO:2.3. The method of claim 1 , wherein the cell of the subject is in a limb of the subject.4. The method of claim 3 , wherein the delivering step comprises a vascular delivery method in conjunction with a temporary vascular occlusion.5. The method of claim 4 , wherein the delivery method comprises:a) infusing ...

Cationic Lipids Comprising a Steroidal Moiety

Disclosed are cationic lipids which are compounds of Formula I. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

COUPLING ENDONUCLEASES WITH END-PROCESSING ENZYMES DRIVES HIGH EFFICIENCY GENE DISRUPTION

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage. 1. A method of increasing mutagenesis at a double-strand DNA (dsDNA) break at a selected dsDNA target site in a eukaryotic cell comprising:a) selecting a dsDNA target site for mutagenesis; andb) introducing into the eukaryotic cell a polynucleotide sequence encoding a homing endonuclease that binds and cleaves the selected dsDNA target site, and an exonuclease; wherein the exonuclease exhibits exonuclease activity at the cleaved dsDNA target site, resulting in increased mutagenesis at the selected dsDNA target site as compared to mutagenesis that occurs in the absence of exonuclease activity.2. The method of claim 1 , wherein the homing endonuclease is a LAGLIDADG homing endonuclease.3. The method of claim 2 , wherein the homing endonuclease is I-OnuI.4. The method of claim 1 , wherein the homing endonuclease is engineered to bind and cleave the selected dsDNA target site.5. The method of claim 1 , wherein the eukaryotic cell is a human cell.6. The method of claim 1 , wherein the mutagenesis is an insertion or deletion at the selected dsDNA target site.7. The method of claim 1 , wherein the exonuclease exhibits 3′ to 5′ exonuclease activity.8. The method of claim 2 , wherein the exonuclease exhibits 3′ to 5′ exonuclease activity.9. The method of claim 3 , wherein the exonuclease exhibits 3′ to 5′ exonuclease activity.10. The method of claim 1 , wherein the exonuclease is Trex2 or a biologically active fragment thereof.11. The method of claim 2 , wherein the exonuclease is Trex2 or a biologically active fragment thereof.12. The method of claim 3 , wherein the exonuclease is Trex2 or a biologically active fragment thereof.13. The method of claim 1 , wherein the exonuclease is Trex2.14. The method of claim 2 , wherein the exonuclease is Trex2.15. The method of claim 3 , ...

Drug composition for angiogenesis therapy

Drug compositions of angiogenesis therapy contain gene coding for human prostacyclin synthase (hPGIS) synthesizing prostaglandin Iwith activities of vasodialation and/or anti-platelet aggregation; drug compositions contain adeno-associated virus (AAV) inserted with gene for angiogenesis factors. The administration of the drug compositions into the aimed treatment region results in transfer of AAV type 1-hPGIS to skeletal muscles and induces a notable expression of human PGIS gene in skeletal muscles. The PGIis produced by mediation of the gene expression in the muscle cells, secreted, induces vessel-protective, neovascularization and anti-platelet aggregation actions, which lead to an improvement in vascular ischemia. 1. A drug composition of angiogenesis therapy used for treatment and prevention of peripheral arterial disease comprising;an active component, an adeno-associated virus (AAA) inserted with a PGIS gene producing a prostaglandin I2 (PGI2) which induces one or more of the activities selected from the group consisting of vasodialation, anti-platelet aggregation and angiogenesis.2. The drug composition of angiogenesis therapy according to claim 1 , wherein the adeno-associated virus (AAV) is further inserted with a gene coding for an angiogenesis factor.3. A drug composition of angiogenesis therapy used for treatment and prevention of peripheral arterial disease comprising;an active component, a first adeno-associated virus (AAV) inserted with a PGIS gene producing a prostaglandin I2 (PGI2) which induces one or more of the activities selected from the group consisting of vasodialation, anti-platelet aggregation and angiogenesis,and a second adeno-associated virus (AAV) inserted with a gene coding for an angiogenesis factor.4. The drug composition of angiogenesis therapy according to any of claim 1 , wherein the adeno-associated virus (AAV) is of the type selected from the group consisting of type 1 claim 1 , 2 claim 1 , 5 and 8.5. The drug composition of ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed. 197-. (canceled)98. A method of treating fructose intolerance or reducing the effects of fructose intolerance , the method comprising administering to a subject in need of such treatment or reduction a glucose isomerase , wherein said glucose isomerase is not administered in combination with 5-D-fructose-dehydrogenase.99. A method of reducing in a subject at least one of (a) the bioavailability of fructose in the body of said subject , (b) the amount of fructose available to the body of said subject and (c) the amount of fructose available to intestinal bacteria colonizing in the intestine of said subject , the subject being a person who would benefit from such reducing , the method comprising administering to the subject an amount of a glucose isomerase sufficient to effect such reducing in said subject , wherein said glucose isomerase is not administered in combination with 5-D-fructose-dehydrogenase.100. The method of claim 98 , wherein said subject suffers from fructose intolerance.101. The method of claim 100 , wherein said subject suffers from intestinal fructose intolerance.102. The method of claim 101 , wherein said intestinal fructose intolerance is caused by a disorder of fructose absorption.103. The method of claim 98 , wherein the administration occurs after the intake by said subject of fructose or a substance or foodstuff containing fructose in pure form or from which fructose can be released in the digestive tract.104. The method of claim 98 , wherein said glucose isomerase is contained in a pharmaceutical composition or a foodstuff.105. The method of claim 104 , wherein said glucose isomerase is contained in a pharmaceutical composition.106. The method of claim 104 , wherein said glucose isomerase is contained in a foodstuff. ...

Coupling endonucleases with end-processing enzymes drives high efficiency gene disruption

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

METHODS FOR INDUCING SELECTIVE APOPTOSIS

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient. 1. A method of controlling the survival of therapeutic cells in a human patient , comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered , wherein:the therapeutic cells comprise polyclonal T cells;the therapeutic cells have been transfected or transduced with a nucleic acid comprising (i) a promoter region, and (ii) a polynucleotide that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase 9 polypeptide;the promoter region is operatively linked to the polynucleotide;the multimeric ligand binds to the multimeric ligand binding region;the multimeric ligand binding region comprises a modified FKBP12 polypeptide;the modified FKBP12 polypeptide binds with higher affinity to the multimeric ligand than the wild type FKBP12 polypeptide;the modified FKBP12 polypeptide comprises an amino acid substitution at position 36;the number of therapeutic cells that express the caspase 9 polypeptide is reduced at least 90% within 24 hours following administration of the multimeric ligand.2. The method of claim 1 , wherein therapeutic cells that are not undergoing cell division are killed following administration of the multimeric ligand.3. The method of claim 1 , wherein the multimeric ligand is AP1903.4. The method of claim 1 , wherein the multimeric ligand is AP20187.5. The method of claim 1 , wherein the therapeutic cells comprise allogeneic T cells.6. The method of claim 1 , wherein the therapeutic cells are non-allodepleted.7. The method of claim 1 , ...

Compositions and Methods for Diagnosing and Treating Diseases and Disorders Associated With D-DT

The present invention relates to the discovery that altered levels of D-DT (also known as MIF-2) are associated with disorders and diseases. Thus, the present invention relates to compositions and methods useful of the assessment, diagnosis, characterization, prevention and treatment of disorders and diseases associated with an elevated level of D-DT. The present invention also relates to compositions and methods useful of the assessment, diagnosis, characterization, prevention and treatment of disorders and diseases associated with a reduced level of D-DT. 1. A method of diagnosing a disease or disorder in a subject in need thereof , the method comprising:a. determining the level of D-DT in a biological sample from the subject,b. comparing the level of D-DT in the biological sample with a comparator control, anddiagnosing the subject with a disease or disorder when the level of D-DT in the biological sample is different than the level of D-DT of the comparator control.2. The method of claim 1 , wherein the level of D-DT in the biological sample is elevated when compared with the comparator control.3. The method of claim 1 , wherein the level of D-DT in the biological sample is reduced when compared with the comparator control.4. The method of claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the level of D-DT mRNA in the biological sample.5. The method of claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the level of D-DT polypeptide in the biological sample.6. The method of claim 1 , wherein the level of D-DT in the biological sample is determined by measuring an enzymatic activity of D-DT polypeptide in the biological sample.7. The method of claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the binding of a detectable molecule to the D-DT enzyme substrate binding site.8. The method of claim 1 , wherein the level of D-DT in the biological sample is ...

METHODS FOR INDUCING SELECTIVE APOPTOSIS

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient. 123-. (canceled)24. A method of controlling the survival of therapeutic cells in a human patient , comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered , wherein:the therapeutic cells have been transfected or transduced with a nucleic acid comprising (i) a promoter region, and (ii) a polynucleotide that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase-9 polypeptide;the promoter region is operatively linked to the polynucleotide;the multimeric ligand binds to the multimeric ligand binding region;the multimeric ligand binding region comprises an FKBP12 polypeptide;the number of therapeutic cells that express the caspase-9 polypeptide is reduced at least 90% within 24 hours following administration of the multimeric ligand.25. The method of claim 24 , wherein therapeutic cells that are not undergoing cell division are killed following administration of the multimeric ligand.26. The method of claim 24 , wherein the number of therapeutic cells is reduced at least 90% within 30 minutes following administration of the multimeric ligand.27. The method of claim 24 , wherein the therapeutic cells are non-allodepleted.28. The method of claim 24 , wherein the therapeutic cells comprise allogeneic T cells.29. The method of claim 24 , wherein the therapeutic cells comprise polyclonal T cells.30. The method of claim 24 , wherein the therapeutic cells comprise cytotoxic T cells.31. The method of claim 24 , wherein the therapeutic cells comprise T ...

CYCLOPHILIN 40 FOR REDUCTION OF NEUROTOXIC FIBRILS AND TREATMENT OF NEURODEGENERATIVE DISEASES

The present invention concerns the use of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) for reduction of neurotoxic fibrils and treatment and prevention of neurodegenerative diseases associated with amyloid fibril aggregation. Aspects of the invention include compositions, methods, dosage forms, and kits for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation in a human or animal subject, and for disaggregating neurofibrillary aggregates in vitro or in vivo, using CyP40, or a biologically active fragment thereof. 1. A method for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation , said method comprising administering an effective amount of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) , or a biologically-active fragment thereof , to a human or animal subject in need thereof.2. The method according to claim 1 , wherein said method further comprises identifying a subject as one in need of treatment.3. The method according to claim 1 , wherein the disease or condition is characterized by the presence of neurofibrillary aggregates of the microtubule associated protein tau and/or α-synuclein.4. The method according to claim 1 , wherein the disease or condition is Alzheimer's disease claim 1 , gangliogliomas claim 1 , gangliocytomas claim 1 , argyrophilic grain dementia claim 1 , corticobasal degeneration claim 1 , dementia pugilistica claim 1 , frontotemporal dementia with parkinsonism linked to chromosome17 claim 1 , Pick's disease claim 1 , Hallervorden-Spatz disease claim 1 , myotonic dystrophy claim 1 , Niemann-Pick disease (type C) claim 1 , Parkinsonism-dementia complex of Guam claim 1 , postencephalitic parkinsonism claim 1 , prion diseases claim 1 , progressive subcortical gliosis claim 1 , or progressive supranuclear palsy.5. The method according to claim 1 , wherein the CyP40 claim 1 , or a biologically active fragment thereof claim 1 , is ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed. 1. A method of treating fructose intolerance or reducing the effects of fructose intolerance , the method comprising administering to a subject in need of such treatment or reduction an effective amount of an isolated glucose isomerase , wherein said glucose isomerase is not administered in combination with-5-D-fructose-dehydrogenase.2. The method of wherein said fructose intolerance is not hereditary fructose intolerance.3. A kit comprising glucose isomerase and instructions explaining how to use said glucose isomerase to diagnose claim 1 , treat claim 1 , or reduce the effects of a condition selected from fructose intolerance and impaired fructose metabolism.4. A foodstuff which comprises glucose isomerase claim 1 , at least some of said glucose isomerase being present in said foodstuff in a form in which said glucose isomerase will be available in active form after ingestion of said foodstuff and wherein said foodstuff is labeled as being advantageous for persons who suffer from fructose intolerance and/or a fructose metabolism disorder.5. A method of conversion of fructose into glucose in a human subject who would benefit from such conversion claim 1 , which method comprises the oral administration to the subject of a glucose isomerase in an amount effective to convert fructose into glucose in the digestive tract of the subject.6. The method according to wherein the amount of glucose isomerase is an amount effective to convert 10-50 g of fructose into glucose.7. The method of claim 5 , wherein the administration occurs after the intake by said subject of fructose or a substance or foodstuff containing fructose in pure form or from which fructose can be released in the digestive tract.8. The method of claim 5 , wherein said glucose ...

POLYNUCLEOTIDES ENCODING METHYLMALONYL-CoA MUTASE

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide. 115-. (canceled)16. A messenger RNA (mRNA) comprising:(i) a 5′-terminal cap;(ii) a 5′ untranslated region (UTR);(iii) an open reading frame (ORF) encoding the human methylmalonyl-CoA mutase (MCM) polypeptide of SEQ ID NO:213, wherein the ORF is at least 98% identical to the nucleotide sequence of SEQ ID NO:732;(iv) a 3′ UTR; and(v) a poly-A tail.17. The mRNA of claim 16 , wherein the ORF is at least 99% identical to the nucleotide sequence of SEQ ID NO:732.18. The mRNA of claim 16 , wherein the ORF is 100% identical to the nucleotide sequence of SEQ ID NO:732.19. The mRNA of claim 16 , wherein the 5′ UTR comprises the nucleotide sequence of SEQ ID NO:215.20. The mRNA of claim 16 , wherein the mRNA comprises the miR-142-3p binding site depicted in SEQ ID NO:722.21. The mRNA of claim 16 , wherein the 5′ terminal cap is Cap1.22. The mRNA of claim 16 , wherein the poly-A tail is 100 residues in length.23. The mRNA of claim 16 , wherein at least 95% of uridines in the mRNA are 5-methoxyuridines.24. The mRNA of claim 18 , wherein the 5′ UTR comprises the nucleotide sequence of SEQ ID NO:215.25. The mRNA of claim 18 , wherein the mRNA comprises the miR-142-3p binding site depicted in SEQ ID NO:722.26. The mRNA of claim 18 , wherein the 5′ terminal cap is Cap1.27. The mRNA of claim 18 , wherein the poly-A tail is 100 residues in length.28. The mRNA of claim 18 , wherein at least 95% of uridines in the mRNA are 5-methoxyuridines.29. The mRNA of claim 18 , wherein the 5′ UTR comprises the nucleotide sequence of SEQ ID NO:215 claim 18 , wherein the mRNA comprises the miR-142 ...

COMPOSITIONS AND USES THEREOF

The present invention relates to a composition comprising a probiotic extract, wherein the extract comprises a protein fraction derived from a secretion or lysate and having proteins of a molecular weight of up to 100 kDa. The composition may have a number of uses, such as for use in the prevention, management or treatment of bacterial infection or the enhancement and improvement of skin health. 1. A composition comprising a probiotic extract , wherein the extract comprises a protein fraction derived from a secretion or lysate and having proteins of a molecular weight of up to 100 kDa.2. The composition according to claim 1 , wherein the extract is from one or more probiotic strains.3. The composition according to claim 1 , wherein the probiotic strain is a Lactobacilli.4L. rhamnosus.. The composition according to claim 3 , wherein the Lactobacilli is5. The composition according to claim 1 , wherein the proteins have a molecular weight of up to 90 kDa.6. The composition according to claim 5 , wherein the protein fraction comprises the Subtilin biosynthesis protein C (SpaC) and proteins having a molecular weight of up to 50 kDa claim 5 , and optionally one or more exopolysaccharides.7. The composition according to claim 6 , wherein the proteins having a molecular weight of up to 50 kDa comprise one or more of the following: Glyceraldehyde-3 phosphate dehydrogenase (GAPDH); Elongation factor TU (EF-Tu); Triosephosphate isomerase (TPI); and/or Enolase.8. A composition comprising the SpaC protein and one or more of the following proteins: Glyceraldehyde-3 phosphate dehydrogenase (GAPDH); Elongation factor TU (EF-Tu); Triosephosphate isomerase (TPI); Enolase; Acyl carrier protein; Transcription elongation factor greA; Phosphopentomutase; 505 ribosomal protein S11; Dihydroxyecetone kinase; 50s Ribosomal protein; Asparaginyl tRNA synthetase; UPF0342 protein; and/or 505 ribosomal protein L22.9. The composition according to claim 8 , wherein the one or more of the following ...

HYDROXYALKYL STARCH DERIVATIVES AS REACTANTS FOR COUPLING TO THIOL GROUPS

The present invention relates to a hydroxyalkyl starch (HAS) derivative of formula (I) wherein F1 is a functional group comprising the group —NR′—, with R′ being H or alkyl; L is a spacer bridging F1 and S; wherein HAS′ is the remainder of the HAS molecule, Rand Rare —[(CRR)O]—H and are the same or different from each other; Ris —[(CRR)O]—H with HAS′ being the remainder of the hydroxyalkyl starch molecule, or Ris HAS″ with HAS′ and HAS″ together being the remainder of the hydroxyalkyl starch molecule; Rand Rare independently hydrogen or an alkyl group having from 1 to 4 carbon atoms, m is 2 to 4, wherein Rand Rare the same or different from each other in the m groups CRR; n is from 0 to 6. 120-. (canceled)22. The HAS derivative of claim 21 , wherein the HAS is hydroxyethyl starch (HES) claim 21 ,{'sup': 1', '2', '3', '4, 'R, R, R, and Rare hydrogen,'}m is 2;n is 0 to 4.23. The HAS derivative of claim 21 , wherein F1 is selected from the group consisting of —NH— claim 21 , —NH—NH— claim 21 , —NH—NH—C(═O)— claim 21 , and —NH—O—.24. The HAS derivative of claim 21 , wherein the spacer L comprises the moiety —(C(L′L″))- with L′ and L″ in each repeating unit CL′L″ with L′ and L″ in each repeating unit —C(L′L″)- being claim 21 , independently of each other claim 21 , selected from the group consisting of H claim 21 , alkyl claim 21 , aryl claim 21 , alkenyl claim 21 , alkynyl claim 21 , hydroxyl claim 21 , fluorine claim 21 , alkylcarbonyloxy claim 21 , arylcarbonyloxy claim 21 , alkoxycarbonyloxy claim 21 , aryloxycarbonyloxy claim 21 , amide claim 21 , carboxyl claim 21 , alkoxycarbonyl claim 21 , aminocarbonyl claim 21 , alkylaminocarbonyl claim 21 , dialkylaminocarbonyl claim 21 , alkoxy claim 21 , phosphate claim 21 , phosphonato claim 21 , phosphinato claim 21 , tertiary amino claim 21 , acylamino claim 21 , including alkylcarbonylamino claim 21 , arylcarbonylamino claim 21 , carbamoyl claim 21 , ureido claim 21 , nitro claim 21 , alkylthio claim 21 , arylthio claim ...

REDUCTION OF LIPASE ACTIVITY IN PRODUCT FORMULATIONS

The invention relates a method for producing a stable recombinant protein, comprising growing a non-naturally occurring host cell in a culture medium to produce a recombinant protein, and making a composition comprising the recombinant protein and a polysorbate. The production of endogenous lipoprotein lipase by the host cell is reduced. The endogenous lipoprotein lipase is present in the composition in a small amount, and is capable of degrading the polysorbate. The invention also relates to the relevant host cells and compositions, and preparation thereof. 1. A non-naturally occurring host cell for producing a stable recombinant protein , wherein the production of endogenous lipoprotein lipase by the host cell is reduced.2. The non-naturally occurring host cell of claim 1 , wherein the host cell is a mammalian cell selected from the group consisting of CHO claim 1 , 3T3 claim 1 , BHK claim 1 , HeLa claim 1 , NS0 claim 1 , HepG2 claim 1 , and derivatives thereof.3. The non-naturally occurring host cell of claim 1 , wherein the host cell expresses an interfering RNA specific for the lipoprotein lipase.4. The non-naturally occurring host cell of claim 3 , wherein the interfering RNA is selected from the group consisting of small interfering RNAs (siRNAs) claim 3 , short hairpin RNAs (shRNAs) claim 3 , and bifunctional RNAs.5. The non-naturally occurring host cell of claim 3 , wherein the interfering RNA is encoded by the genome of the host cell.6. The non-naturally occurring host cell of claim 1 , wherein at least one copy of an endogenous gene encoding the endogenous lipoprotein lipase is knocked out from the genome of the host cell.7. A composition comprising a stable recombinant protein and a polysorbate claim 1 , wherein the recombinant protein is produced by the non-naturally occurring host cell of claim 1 , wherein the endogenous lipoprotein lipase is present in the composition in an amount less than 10% by weight claim 1 , and wherein the endogenous ...

Synthetic methylmalonyl-coa mutase transgene for the treatment of mut class methylmalonic acidemia (mma)

Synthetic polynucleotides encoding human methylmalonyl-CoA mutase (synMUT) and exhibiting augmented expression in cell culture and/or in a subject are described herein. An adeno-associated viral (AAV) gene therapy vector encoding synMUT under the control of a liver-specific promoter (AAV2/8-HCR-hAAT-synMUT-RBG) successfully rescued the neonatal lethal phenotype displayed by methylmalonyl-CoA mutase-deficient mice, lowered circulating methylmalonic acid levels in the treated animals, and resulted in prolonged hepatic expression of the product of synMUT transgene in vivo, human methylmalonyl-CoA mutase (MUT).

CASPASE POLYPEPTIDES HAVING MODIFIED ACTIVITY AND USES THEREOF

The technology relates in part to compositions comprising modified caspase-9 polypeptides, compositions comprising nucleic acids coding for modified caspase-9 polypeptides, chimeric modified caspase-9 polypeptides, and methods of use thereof, including methods for cell therapy. Methods for cell therapy include modifying transfused cells to express an inducible modified caspase-9 protein, with reduced basal activity in the absence of the inducer.

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

There is provided a method for treating or reducing the effects of fructose intolerance and health problems associated with excessive fructose intake by administration of glucose isomerase. Other embodiments are also disclosed. 197-. (canceled)98. A method of conversion of fructose into glucose in a human subject who would benefit from such conversion , which method comprises the oral administration to the subject of a glucose isomerase in an amount effective to convert fructose into glucose in the digestive tract of the subject.99. The method according to wherein the amount of glucose isomerase is an amount effective to convert 10-50 g of fructose into glucose.100. The method of claim 98 , wherein the administration occurs after the intake by said subject of fructose or a substance or foodstuff containing fructose in pure form or from which fructose can be released in the digestive tract.101. The method of claim 98 , wherein said glucose isomerase is contained in a pharmaceutical composition.102. The method of claim 98 , wherein said glucose isomerase is contained in a foodstuff.103. The method of claim 102 , wherein the foodstuff is selected from the group consisting of (a) foodstuffs for particular nutritional uses; (b) foods for special medical purposes; (c) medical foods; (d) food supplements; (e) dietary supplements; (f) dietetic food supplements; (g) health foods; (h) nutraceuticals; and (i) food additives.104. The method of claim 103 , wherein the foodstuff is a dietary supplement.105. The method of claim 98 , wherein said glucose isomerase is administered orally.106. The method of claim 105 , wherein the glucose isomerase is administered prior to said subject's eating claim 105 , concurrently with said subject's eating or after said subject's eating.107. The method of claim 105 , wherein the glucose isomerase is formulated in a form selected from the group consisting of (a) coated or non-coated capsules (b) coated or non-coated tablets (c) capsules ...

SYNTHETIC METHYLMALONYL-COA MUTASE TRANSGENE FOR THE TREATMENT OF MUT CLASS METHYLMALONIC ACIDEMIA (MMA)

Synthetic polynucleotides encoding human methylmalonyl-CoA mutase (synMUT) and exhibiting augmented expression in cell culture and/or in a subject are described herein. An adeno-associated viral (AAV) gene therapy vector encoding synMUT under the control of a liver-specific promoter (AAV2/8-HCR-hAAT-synMUT-RBG) successfully rescued the neonatal lethal phenotype displayed by methylmalonyl-CoA mutase-deficient mice, lowered circulating methylmalonic acid levels in the treated animals, and resulted in prolonged hepatic expression of the product of synMUT transgene in vivo, human methylmalonyl-CoA mutase (MUT). 114-. (canceled)15. A method of treating a disease or condition mediated by methylmalonyl-CoA mutase , comprising administering to a subject in need thereof a therapeutic amount of a methylmalonyl-CoA mutase produced using a synthetic methylmalonyl-CoA mutase (MUT) polynucleotide (synMUT) selected from the group consisting of:(a) a polynucleotide comprising the nucleic acid sequence of SEQ ID NO:1; and(b) a codon-optimized polynucleotide comprising a polynucleotide having a nucleic acid sequence with at least about 80% identity to the nucleic acid sequence of SEQ ID NO:1 and encoding a polypeptide according to SEQ ID NO:2, and having equivalent expression in a host to either SEQ ID NO:1 expression or SEQ ID NO:3 expression,wherein the codon-optimized polynucleotide having at least about 80% identity to SEQ ID NO:1 does not have the nucleic acid sequence of SEQ ID NO:3.16. The method of claim 15 , wherein the disease or condition is methylmalonic academia (MMA).17. The method of claim 15 , wherein the polynucleotide has at least about 90% identity to the nucleic acid sequence of SEQ ID NO:1.18. The method of claim 15 , wherein the polynucleotide has at least about 95% identity to the nucleic acid sequence of SEQ ID NO:1.19. The method of claim 15 , wherein the polynucleotide has at least about 97% identity to the nucleic acid sequence of SEQ ID NO:1.20. The method ...

COUPLING ENDONUCLEASES WITH END-PROCESSING ENZYMES DRIVES HIGH EFFICIENCY GENE DISRUPTION

The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage. 1. (canceled)2. A method of increasing mutagenesis at a double-strand DNA (dsDNA) break at a selected dsDNA target site in a primary cell comprising: selecting a dsDNA target site for mutagenesis; selecting a TAL effector nuclease (TALEN) engineered to bind and cleave the selected dsDNA target site; and coupling the activity of the TALEN and the activity of a 3′ to 5′ exonuclease within the primary cell so as to increase mutagenesis at the selected dsDNA target site.3. The method of claim 2 , wherein the dsDNA target site is within a gene.4. The method of claim 2 , wherein the dsDNA target site is within a non-coding sequence of a gene.5. The method of claim 4 , wherein the non-coding sequence is a regulatory sequence.6. The method of claim 5 , wherein the regulatory sequence is a promoter claim 5 , enhancer claim 5 , or splice site.7. The method of claim 2 , wherein the dsDNA target site is within a coding sequence of a gene.8. The method of claim 3 , wherein the gene is CCR-5.9. The method of claim 3 , wherein the gene is Stat-3.10. The method of claim 2 , wherein the primary cell is a mammalian cell claim 2 , optionally a human cell.11. The method of claim 2 , wherein the mutagenesis is an insertion at the selected dsDNA target site.12. The method of claim 2 , wherein the mutagenesis is a deletion at the selected dsDNA target site.13. The method of claim 2 , wherein the TALEN comprises a FokI nuclease domain.14. The method of claim 2 , wherein the 3′-5′ exonuclease is Trex2 or a biologically active fragment thereof.15. The method of claim 2 , wherein the TALEN and the 3′-5′ exonuclease are encoded by a single polynucleotide.16. The method of claim 2 , wherein the TALEN is coupled to the 3′-5′ exonuclease by a linker domain.17. The method of claim 16 , wherein the ...

AGENT FOR USE IN THE CASE OF FRUCTOSE INTOLERANCE

5-D-fructose dehydrogenase, optionally in combination with invertase and/or maltase and/or glucose isomerase, may be used to treat fructose intolerance. Other embodiments are also disclosed. 1139-. (canceled)140. A method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism , the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of 5-D-fructose dehydrogenase.141. A method according to wherein said condition is fructose intolerance that is selected from the group consisting of (a) hereditary fructose intolerance claim 140 , (b) intestinal fructose intolerance claim 140 , (c) fructose intolerance that is due to a lack of fructose 1 claim 140 ,6-diphosphatase and (d) combinations thereof.142. A method according to claim 140 , wherein said 5-D-fructose dehydrogenase is administered prior to said subject's eating claim 140 , concurrently with said subject's eating or after said subject's eating.143. A method according to claim 140 , wherein said 5-D-fructose dehydrogenase is administered with a second enzyme which cleaves fructose from a more complex sugar.144. A method according to wherein said second enzyme is selected from the group consisting of invertase claim 143 , maltase and combinations thereof.145. A method according to claim 140 , wherein said administration comprises oral administration.146. A mammalian ingestible composition of matter selected from a pharmaceutical composition and a dietary supplement claim 140 , said composition of matter comprising 5-D-fructose dehydrogenase and a carrier or excipient that is acceptable for use in pharmaceutical compositions or foodstuffs.147. A composition of matter according to which is in unit dosage form.148. A composition of matter according to which is in an orally administrable form.149. A composition of matter according to which is in a form selected from (a) the group consisting of ...

CHIMERIC ANTIGEN RECEPTOR (CAR) SIGNALLING SYSTEM

The present invention relates to a chimeric antigen receptor (CAR) signalling system comprising; (i) a receptor component comprising an extracellular antigen-binding domain, a transmembrane domain and a intracellular first chemical inducer of dimerization binding domain 1 (CBD1); and (ii) an intracellular signalling component comprising a signalling domain and a second chemical inducer of dimerization binding domain 2 (CBD2); wherein CBD1 and CBD2 are capable of simultaneously binding to a chemical inducer of dimerization (CID); wherein, in the absence of the CID, binding of the antigen-binding component to antigen does not result in signalling through the signalling component; whilst, in the presence of the CID, the receptor component and the signalling component heterodimerize and binding of the antigen-binding domain to antigen results in signalling through the signalling domain. 1. A chimeric antigen receptor (CAR) signalling system comprising;(i) multiple receptor components comprising an extracellular antigen-binding domain, a transmembrane domain, and a intracellular first chemical inducer of dimerization (CID) binding domain (CBD1), wherein the antigen-binding domain of each receptor component binds to a different antigen; and(ii) an intracellular signalling component comprising a signalling domain and a second CID binding domain (CBD2);wherein CBD1 and CBD2 are capable of simultaneously binding to a CID; andwherein, in the absence of CID, binding of the antigen-binding domain to antigen does not result in signalling through the signalling domain; whilst, in the presence of CID, the receptor component and the signalling component heterodimerize and binding of the antigen-binding domain to antigen results in signalling through the signalling domain.211-. (canceled)12. The CAR signalling system according to claim 1 , wherein the CBD1 of the multiple receptor components differ in binding to CID such that each antigen propagates different signalling strengths.13 ...

METHODS FOR INDUCING SELECTIVE APOPTOSIS

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient. 1. A method of controlling the survival of therapeutic cells in a human patient , comprising administering a multimeric ligand to a human patient to whom therapeutic cells have been administered , wherein:the therapeutic cells have been transfected or transduced with a nucleic acid comprising (i) a promoter region, and (ii) a polynucleotide that encodes a chimeric protein comprising a multimeric ligand binding region and a caspase 9 polypeptide;the promoter region is operatively linked to the polynucleotide;the multimeric ligand binding region comprises a modified FKBP12 polypeptide, wherein the modified FKBP12 polypeptide binds with higher affinity to the multimeric ligand than the wild type FKBP12 polypeptide;the multimeric ligand binds to the multimeric ligand binding region; andthe number of therapeutic cells that express the caspase 9 polypeptide is reduced at least 90% within 24 hours following administration of the multimeric ligand.2. The method of claim 1 , wherein therapeutic cells that are not undergoing cell division are killed following administration of the multimeric ligand.3. The method of claim 1 , wherein the multimeric ligand is AP1903 or AP20187.4. (canceled)5. The method of claim 1 , wherein the therapeutic cells are allogeneic T cells.6. The method of claim 1 , wherein the therapeutic cells are non-allodepleted.7. The method of claim 1 , wherein the caspase-9 polypeptide is a truncated caspase-9 polypeptide.8. (canceled)10. The method of claim 1 , wherein the modified FKBP12 polypeptide comprises an amino acid ...

THERAPEUTIC AGENT FOR CEREBRAL INFARCTION

The purpose of the present invention is to provide a novel medicine that is effective in treating cerebral infarction. The present invention provides a pharmaceutical composition that contains a peptidyl-prolyl cis-trans isomerase B (PPIB) protein, a nucleic acid encoding the PPIB protein, or a cell that secretes the PPIB protein. 1. A pharmaceutical composition for treating cerebral infarction , comprising a peptidyl-prolyl isomerase B (PPIB) protein , or a cell which secretes PPIB protein.2. The pharmaceutical composition according to claim 1 , wherein the PPIB protein is:a) a protein comprising the amino acid sequence of SEQ ID NO:3;b) a protein comprising an amino acid sequence in which one or more amino acids are substituted, inserted, deleted and/or added in the amino acid sequence of SEQ ID NO:3;c) a protein comprising an amino acid sequence having 80% or more sequence identity with the amino acid sequence of SEQ ID NO:3;d) a protein encoded by the DNA which hybridizes under stringent conditions with the nucleic acid sequence of SEQ ID NO:4;e) a protein encoded by a nucleic acid sequence having 70% or more sequence identity with the nucleic acid sequence of SEQ ID NO:4;f) a protein comprising an amino acid sequence in which a signal sequence has been removed from an amino acid sequence of a homologue of a protein comprising the amino acid sequence of SEQ ID NO:1; org) a protein comprising an amino acid sequence in which a signal sequence has been removed from an amino acid sequence of an orthologue of a protein comprising the amino acid sequence of SEQ ID NO:1, wherein the protein has 80% or more sequence identity with the amino acid sequence of SEQ ID NO:3.3. A pharmaceutical composition for treating cerebral infarction claim 1 , comprising a nucleic acid encoding PPIB protein.4. The pharmaceutical composition according to claim 3 , wherein the nucleic acid encoding PPIB protein is:i) a nucleic acid comprising the nucleic acid sequence of SEQ ID NO:4;ii) a ...

METHOD OF MAKING PDIA2 AND COMPOSITIONS CONTAINING PDIA2

A method for producing soluble PDIA2, compositions containing it, and methods for its use. 1. A method for treating damaged tissue comprising contacting the damaged tissue with soluble PDIA2.2. The method of claim 1 , wherein the damaged tissue includes conjunctiva of an eyelid and the contacting comprises contacting a gelatin-supported PDIA2-containing composition with a damaged surface of the conjuctiva claim 1 , wherein the damaged surface is a surgical incision.3. The method of claim 1 , wherein the damaged tissue is part of the oral or gastrointestinal lining.4. The method of claim 1 , wherein the damaged tissue is skin.5. The method of claim 1 , wherein the damaged tissue is UV damaged.6. The method of claim 1 , wherein the damaged tissue is damaged by dermatitis.7. The method of claim 1 , wherein the damage tissue has been damaged by over-exposure to estrogen or an estrogen-like compound.8. The method of claim 1 , further comprising:contacting the damaged tissue with superoxide dismutase and/or an antioxidant.9. The method of claim 1 , wherein said soluble PDIA2 comprises GST.10Escherichia coli.. The method of claim 1 , wherein said soluble PDIA2 is expressed in11Escherichia coli. The method of claim 1 , wherein said soluble PDIA2 is expressed in that contains extra copies of argU claim 1 , ileY claim 1 , and leuW tRNA genes.12Escherichia coli. The method of claim 1 , wherein said soluble PDIA2 is expressed by that does not express disulfide bond isomerase protein DsbC.13. The method of claim 1 , wherein expression of the soluble PDIA2 is induced by isopropyl β-D-1-thiogalactopyrano side (IPTG).14. The method of claim 1 , wherein the expression of the soluble PDIA2 is induced by IPTG at a temperature of no more than 30° C.15. A method for making soluble PDIA2 comprising:inducing expression of a GST-PDIA2 fusion protein, which comprises a glutathione-S-transferase (GST) tag and a segment of PDIA2 having disulphide isomerase activity, in host cells, which ...

Regulating chimeric antigen receptors

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

COMPOSITIONS AND METHODS FOR TREATING OR AMELIORATING NEUROINFLAMMATION, NEURODEGENERATION, NEUROPATHIC PAIN, AND MIGRAINE

In alternative embodiments, provided are methods for increasing levels of and/or upregulating the expression of ApoA-I Binding Protein (APOA1BP, AIBP, or AI-BP) to treat, ameliorate, prevent, reverse, decrease the severity or duration of: a neuropathic pain, including an inflammation-induced neuropathic pain, a nerve or CNS inflammation, a, a post nerve injury pain, a post-surgical pain, a chemotherapeutic-induced peripheral neuropathy (CIPN) (e.g., cisplatin-induced allodynia) a neurodegeneration or neurodegenerative disease or condition, a migraine, and/or a hyperalgesia. In alternative embodiments, provided are methods comprising administering formulations and pharmaceutical compositions comprising an APOA1BP polypeptide or protein that is a human or a mammalian APOA1BP, or an AIBP1 or an AIBP2, or a recombinant, peptidomimetic or a synthetic APOA1BP, or a bioisostere of an ApoA-I Binding Protein to treat, ameliorate prevent, reverse, decrease the severity of a neuropathic pain, a TLR4-mediated allodynia and/or a hyperalgesia. 1. A method for treating , ameliorating , reversing or decreasing the severity or duration of a primary headache , wherein the method comprises:(a) providing or having provided a formulation or a pharmaceutical composition comprising: an ApoA-I Binding Protein (APOA1BP) polypeptide compound or composition; and(b) administering or having administered the formulation or the pharmaceutical composition of (a) to a subject in need thereof,thereby treating, ameliorating, reversing or decreasing the severity or duration of the primary headache, or(b) administering the formulation or the pharmaceutical composition comprising: an ApoA-I Binding Protein (APOA1BP) polypeptide compound or composition to a subject in need thereof,thereby treating, ameliorating, reversing or decreasing the severity or duration of the primary headache.2. The method of claim 1 , wherein the primary headache is a migraine.3. The method of claim 1 , wherein the primary ...

REDUCTION OF LIPASE ACTIVITY IN PRODUCT FORMULATIONS

The invention relates a method for producing a stable recombinant protein, comprising growing a non-naturally occurring host cell in a culture medium to produce a recombinant protein, and making a composition comprising the recombinant protein and a polysorbate. The production of endogenous lipoprotein lipase by the host cell is reduced. The endogenous lipoprotein lipase is present in the composition in a small amount, and is capable of degrading the polysorbate. The invention also relates to the relevant host cells and compositions, and preparation thereof. 1. A composition comprising a stable recombinant protein and a polysorbate , wherein the recombinant protein is produced by a host cell , wherein at least one copy of an endogenous gene encoding the endogenous lipoprotein lipase is knocked out from the genome of the host cell , wherein the endogenous lipoprotein lipase is present in the composition in an amount less than 10% by weight , and wherein the endogenous lipoprotein lipase is capable of degrading the polysorbate.2. The composition claim 1 , wherein the recombinant protein is a monoclonal antibody.3. The composition of claim 1 , wherein the polysorbate comprises polysorbate 80 claim 1 , polysorbate 20 claim 1 , polysorbate 40 claim 1 , polysorbate 60 claim 1 , polysorbate 65 claim 1 , or a combination thereof. This application is a divisional of U.S. application Ser. No. 15/897,290, filed Feb. 15, 2018, which is a divisional of U.S. application Ser. No. 15/105,925, filed Jun. 17, 2016, now U.S. Pat. No. 9,932,591, which is a U.S. national phase application of International Application No. PCT/US2014/071234, filed Dec. 18, 2014, claiming the benefit of U.S. Provisional Application No. 61/917,555, filed Dec. 18, 2013, the contents of each of which are incorporated herein in their entireties for all purposes.This work is supported by a grant from the National Science Foundation (NSF) (Award No. CBET-0966644). The United States has certain rights in the ...

Formation of novel erythropoietin conjugates using transglutaminase

The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein a transglutaminase reaction is employed to covalently and site specifically conjugate the EPO molecule to a non-antigenic hydrophilic polymer that can also be covalently linked to an organic molecule either of which modification increases the circulating serum half-life of the composition.

USE OF ALPHA-1,4/1,6-GLYCOSIDE HYDROLASE ACTIVE AT LOW pH AS FEED ADDITIVE FOR RUMINANTS TO IMPROVE STARCH DIGESTION

FIELD: veterinary medicine. SUBSTANCE: proposed method for increasing starch digestibility and glucose yield in a ruminant animal includes the addition of at least one alpha-1,4/1,6-glycoside hydrolase (GLCH) selected from α-amylase from an Aspergillus kawachii (AkAA) source and α-amylase from an Aspergillus Clavatus (AcAA) source as a feed additive in ruminant animal feed. The specified hydrolase (a) is characterized by at least 20% activity at a pH value of 3 or less in the presence of pepsin compared to hydrolase activity at a pH value of 6 in the presence of pepsin; (b) the specified hydrolase is active in at least two of three digestive chambers of the ruminant animal, including the rumen, rennet and small intestine; (c) hydrolase acts together with digestive enzymes present in digestive chambers of the ruminant animal to increase the digestibility of starch and glucose yield. A method for an increase in starch digestibility, increase in glucose yield, increase in the digestion of dry substance and increase in gas formation during fermentation in a ruminant animal is also proposed by adding an enzyme-based composition containing the specified hydrolase and at least one protease selected from pepsin, pancreatin, bacillolysin (P7L) and thermolysin (P14L) to the feed. EFFECT: invention is aimed at increasing the digestibility of starch and glucose yield. 4 cl, 11 dwg, 19 tbl, 19 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 763 378 C2 (51) МПК A23K 20/189 (2016.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A23K 20/189 (2021.08) (21)(22) Заявка: 2019111908, 15.09.2017 (24) Дата начала отсчета срока действия патента: Дата регистрации: (73) Патентообладатель(и): ДЮПОН НЬЮТРИШН БАЙОСАЙЕНСИЗ АПС (DK) 28.12.2021 23.09.2016 US 62/398,741 (43) Дата публикации заявки: 23.10.2020 Бюл. № 30 (45) Опубликовано: 28.12.2021 Бюл. № 1 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 23.04.2019 (56) Список ...

Isomerases, nucleic acids encoding them and processes for their preparation and use

Systemic administration and regulated expression of paracrine genes for cardiovascular diseases and other conditions

Un vector que comprende una secuencia de ácidos nucleicos que codifica una proteína o un péptido paracrino para su uso en un método para tratar, mejorar o proteger a un sujeto que padece una insuficiencia cardiaca congestiva que comprende proporcionar y administrar o suministrar el vector a una célula del sujeto, o a un sujeto en necesidad del mismo en el que la proteína o el péptido paracrino comprende una proteína o un péptido de la Urocortina-2 (UCn-2), y el vector es un virus adenoasociado (AAV). A vector comprising a nucleic acid sequence encoding a protein or a paracrine peptide for use in a method to treat, improve or protect a subject suffering from congestive heart failure comprising providing and administering or delivering the vector to a cell. of the subject, or a subject in need thereof in which the protein or paracrine peptide comprises a protein or a peptide of Urocortin-2 (UCn-2), and the vector is an adeno-associated virus (AAV).

Systemic delivery and controlled expression of the paracrine gene for cardiovascular disease and other conditions

Methods of treating cancer of the central nervous system

A method of treating a cancer of the central nervous system in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of an agent which reduces blood glutamate levels and enhances brain to blood glutamate efflux to thereby treat the cancer of the central nervous system in the subject.

Blockade of Pin1 prevents cytokine production by activated immune cells

The invention provides pharmaceutical compositions and methods of treating immunological disorders. The invention also provides pharmaceutical compositions and methods of inducing eosinophil apoptosis, and methods for treating eosinophil-associated disorders comprising inducing eosinophil apoptosis in an individual in need thereof.

Composition for preventing hair loss and enhancing hair growth comprising cyclophilin A

본 발명은 사이클로필린 A(CypA) 단백질, CypA 단백질을 코딩하는 뉴클레오티드 서열을 갖는 핵산 또는 CypA 단백질 발현 재조합 벡터를 포함하는 탈모 방지 및 발모 개선용 조성물에 관한 것이다. 본 발명의 조성물은 피부 세포내로 투여되어 피부 세포의 IL-1 발현을 억제하고, ERK 및 c-jun의 활성을 조절하며, NF-kB p65 발현을 증가시키고, 이를 통해 모발 모낭의 성장 및 발달을 촉진하여, 탈모 질환의 예방 및 치료에 유용하게 사용될 수 있다. The present invention relates to a composition for preventing hair loss and hair growth comprising a cyclophilin A (CypA) protein, a nucleic acid having a nucleotide sequence encoding a CypA protein, or a CypA protein expression recombinant vector. The composition of the present invention is administered into skin cells to suppress the expression of IL-1 in skin cells, to regulate the activity of ERK and c-jun, to increase the expression of NF-kB p65 and thereby to promote the growth and development of hair follicles And can be useful for prevention and treatment of hair loss diseases.

Methods of administering D-dopachrome tautomerase (D-DT) to treat ischemia-reperfusion injury

The present invention relates to the discovery that reduced levels of D-dopachrome tautomerase (D-DT) (also known as MIF-2) are associated with ischemia-reperfusion injury. Thus, the present invention relates to methods of administering D-DT and recombinant D-DT for the treatment of ischemia-reperfusion injury.

Agent for use in the case of fructose intolerance

An agent is described that, with the help of glucose isomerase, converts fructose into glucose and thus, alone or in combination with 5-D-fructose dehydrogenase, reduces the bioavailability of fructose in the human or animal body. This agent can be used in particular in the therapy of fructose intolerance.

A vaccine composition for preventing tuberculosis comprising chorismate mutase

일 양상은 코리스미산 이성화효소(chorismate mutase)를 포함하는 결핵 예방용 백신 조성물에 관한 것이다. 상기 백신 조성물은 단독으로 결핵균 특이적 면역을 유도할 수 있으며, 면역 어쥬번트 함께 제공될 경우 보다 효과적으로 결핵 특이적 면역을 유도할 수 있다. 나아가, 기존 결핵 백신을 프라임으로 사용하고, 부스터로서 일 양상에 따른 코리스미산 이성화효소(chorismate mutase)를 포함하는 결핵 예방용 백신 조성물이 제공될 경우, 보다 현저하게 효과적으로 결핵 특이적 면역을 유도할 수 있다.

Cationic lipids comprising a steroidal moiety

Disclosed are cationic lipids which are compounds of Formula I. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Agent for use in the case of fructose intolerance

Methods for inducing selective apoptosis

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.

Compositions and methods for treating diabetes

Compositions containing an FKBP 11 peptide (i.e., FKBP11 polypeptide, a variant or a fragment thereof), a fusion protein containing an FKBP11 peptide, or a nucleic acid encoding an FKBP 11 peptide are disclosed. Also disclosed are methods of reducing blood glucose levels, improving glucose tolerance, decreasing hepatic gluconeogenic activity and/or improving insulin sensitivity in a subject, by administering a composition containing an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide. The methods can include administering nucleic acids encoding an FKBP 11 peptide or a fusion protein containing an FKBP11 peptide, to the subject, or cells expressing the nucleic acids. Kits containing an FKBP 11 peptide, are also provided.

Methods and compositions for regulating protein-protein interactions

The invention relates to methods and compositions of WW-domains as phosphoserine and phosphothreonine binding modules. The WW-domain containing polypeptides of the invention can be used, for example, to regulate cell growth; to treat neurodegenerative diseases; to screen for substances that modulated interactions between WW-domain containing polypeptides and phosphorylated ligands; as drug targeting vehicles; to direct protein degradation; and in the treatment of certain diseases or conditions characterized by aberrant WW-domain containing polypeptides or their ligands .

Cell-penetrating phosphoglycerate mutase 1 fusion protein and pharmaceutical Composition containing thereof

An object of the present invention is to provide a phosphoglycerate mutase 1 fusion protein and a pharmaceutical composition comprising the same, which may more efficiently transport phosphoglycerate mutase 1 into cells or tissues, thereby preventing or treating symptoms or diseases such as central nervous system diseases, muscle pains, convulsions, and muscle necrosis, etc., which are symptoms caused by phosphoglycerate mutase 1 deficiency. To solve the above problem, the present inventors selected and tested a number of candidate peptides, and thus found that a peptide consisting of 18 amino acids derived from human adenosine receptor A2a (ADORA2A) and a modified sequence in which several sequences are substituted, added or deleted by using the peptide as a base sequence bind to the mutase 1 protein to smoothly permeate this protein into cells and tissues. The fusion protein, and an oligonucleotide or a vector encoding the same can be applied as a pharmaceutical composition for preventing or treating a phosphoglycerate mutase 1 deficiency disease.

Means for use in fructose intolerance

Es wird ein Mittel beschrieben, das mit Hilfe von Glucose-Isomerase Fructose in Glucose umwandelt und so allein oder in Kombination mit 5-D-Fructose-Dehydrogenase die Bioverfügbarkeit von Fructose im menschlichen oder tierischen Organismus reduziert. Dieses Mittel kann insbesondere in der Therapie der Fructoseintoleranz eingesetzt werden. An agent is described which converts fructose into glucose by means of glucose isomerase and thus, alone or in combination with 5-D-fructose dehydrogenase, reduces the bioavailability of fructose in the human or animal organism. This agent can be used in particular in the therapy of fructose intolerance.

Gene inactivation collateral biomarkers and targets for cancer treatment

Una composición para su uso en el tratamiento del cáncer en un sujeto, donde el cáncer presenta una deleción homocigota en un gen constitutivo y el gen constitutivo tiene un homólogo funcionalmente redundante, comprendiendo la composición un inhibidor del homólogo redundante en una cantidad suficiente para inhibir la actividad del homólogo redundante, donde el gen constitutivo es enolasa 1 (ENO1), el homólogo redundante es endolasa 2 (ENO2) y el inhibidor es un ácido nucleico que inhibe la expresión o actividad del homólogo redundante, un anticuerpo que se une específicamente al homólogo redundante, fosfonoacetohidroxamato, que preferentemente comprende, además, un agente quimioterapéutico, donde el agente quimioterapéutico interfiere preferentemente con la homeostasis del ADN. A composition for use in treating cancer in a subject, where the cancer has a homozygous deletion in a constitutive gene and the constitutive gene has a functionally redundant homolog, the composition comprising a redundant homolog inhibitor in an amount sufficient to inhibit the activity of the redundant homolog, where the constitutive gene is enolase 1 (ENO1), the redundant homolog is endolase 2 (ENO2) and the inhibitor is a nucleic acid that inhibits the expression or activity of the redundant homolog, an antibody that specifically binds the homolog redundant, phosphonoacetohydroxamate, which preferably further comprises a chemotherapeutic agent, where the chemotherapeutic agent preferably interferes with DNA homeostasis.

Use of Cyclophilin As Antioxidant and Prevention of Cyclosporin A-induced Toxicity in Cell Transplantation by Overexpression of Cyclophilin

본 발명은 PPIase 활성을 갖는 사이클로필린 단백질을 포함함을 특징으로 하는 항산화제에 관한 것이다. 또한, 본 발명은 이식 세포에서 면역억제제 사이클로스포린 A 또는 이의 유사체에 의해 발생되는 독성을 감소시키기에 유효한 양의 PPIase 활성을 갖는 사이클로필린 단백질을 발현하는 재조합 발현 벡터를 포함함을 특징으로 하여, 이식 세포에서 상기 사이클로필린 단백질의 과발현을 유도하여 사이클로스포린 A 또는 이의 유사체에 의해 발생되는 독성을 방지하는 약제학적 조성물에 관한 것이다. 또한, 본 발명은 PPIase 활성을 갖는 사이클로필린 단백질의 과발현이 유도되어 사이클로스포린 A 또는 이의 유사체에 대해 내성을 갖는 이식 세포 및 이의 제조 방법에 관한 것이다. The present invention relates to an antioxidant characterized by comprising a cyclophylline protein having PPIase activity. The invention also provides a recombinant cell comprising a recombinant expression vector expressing a cyclophylline protein having an amount of PPIase activity effective to reduce the toxicity caused by the immunosuppressive cyclosporin A or an analog thereof in the transplanted cell. It relates to a pharmaceutical composition for inducing overexpression of the cyclophilin protein in the prevention of toxicity caused by cyclosporin A or an analog thereof. In addition, the present invention relates to a transplanted cell and a method for producing the same, wherein overexpression of a cyclophylline protein having PPIase activity is induced to be resistant to cyclosporin A or an analog thereof. 세포이식, 사이클로스포린 A, 세포독성, 근육분화, 사이클로필린 단백질의 과발현, 항산화제, PPIase 활성 Cell Transplantation, Cyclosporin A, Cytotoxicity, Muscle Differentiation, Overexpression of Cyclophylline Protein, Antioxidant, PPIase Activity

Agent for use in the case of fructose intolerance

There is provided in accordance with embodiments of the invention a method of treating or reducing the effects in a subject of a condition selected from fructose intolerance and impaired fructose metabolism, the method comprising administering to a subject in need of such treatment or reduction an efficacious amount of a glucose isomerase, other than in combination with 5-D-fructose dehydrogenase. Other embodiments are also disclosed.

Fusogenic lipid nanoparticles for the target cell-specific production of rapamycin inducible therapeutic proteins

Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and/or eliminating the growth and/or survival of a cell, such as a senescent cell and/or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

Methods and compositions for increasing sialic acid production and treating sialic related disease conditions

피험체의 세포에서 UDP-GlcNAc 2-에피머라제/ManNAc 키나제 효소(GNE) 펩타이드를 발현하는 방법으로서, GNE 펩타이드 또는 이의 치료학적 활성 단편을 코딩하는 핵산 서열에 작동적으로 결합된 프로모터를 포함하는 단리된 핵산 발현 작제물을 상기 피험체의 세포에게 전달하는 단계를 포함하고, 상기 GNE 펩타이드는 서열 번호 3의 아미노산 서열을 갖고, 상기 피험체의 세포에게 전달 시, 상기 핵산 발현 작제물은 상기 GNE 펩타이드 또는 이의 치료학적 활성 단편의 발현을 개시하는 것인 방법이 본원에 개시되어 있다. 또한, 세포에서 GNE 펩타이드를 제조하는 방법으로서, GNE 펩타이드 또는 이의 치료학적 활성 단편을 코딩하는 핵산 서열에 작동적으로 결합된 프로모터를 포함하는 단리된 핵산 작제물로 상기 세포를 감염시키는 단계를 포함하고, 상기 GNE 펩타이드는 서열 번호 3의 아미노산 서열을 갖는 것인 방법이 개시되어 있다.

Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions

Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

An agent for reducing the useable calorie content of food is described wh ich contains a compound effecting the dehydrogenation of fructose to 5-keto- D-fructose. In addition, a combination agent is described which also contain s a compound that converts glucose to fructose. These agents can be used in particular in the therapy of adiposity (obesity).

Methods for controlled elimination of therapeutic cells

The technology relates in part to methods for controlling elimination of therapeutic cells, for example, cells that express a chimeric antigen receptor. The technology further relates to a two-step method of controlling destruction of therapeutic cells in a patient following an adverse event. The two-step system may include a rapamycin or rapamycin analog-based level of control and a second, rimiducid, level of control. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide and the rapamycin-sensitive polypeptide, where the proportion of therapeutic cells eliminated by apoptosis is related to the choice and amount of the administered ligand.

Agent for use in the case of fructose intolerance

The invention provides the use of an agent comprising glucose isomerase for (a) reducing the bioavailability of fructose in the body of a human or animal or (b) reducing the amount of fructose available to the human or animal body or to intestinal bacteria colonizing therein after the ingestion of a fructose-containing food or substance, but excluding the use of an agent containing 5-D-fructose dehydrogenase.

Agent for use in the case of fructose intolerance

Apoptosis methods, genes and proteins

A W303a Saccharomyces cerevisiae yeast cell which contains a polynucleotide that encodes a functional Bax polypeptide under the control of a galactose- inducible promoter that is integrated at the LEU2 chromosomal locus. A kit of parts comprising the yeast cells and a yeast plasmid vector suitable for transforming a cDNA library into the yeast cells. Use of the yeast cell for screening a cDNA library for a polynucleotide that is or encodes an inhibitor of B ax-mediated apoptosis. Genes and polypeptides that inhibit Bax-mediated apoptosis and which were identified from a human hippocampus cDNA library screened in the yeast cells. A method of combating Bax-mediated apoptosis in a cell using an inhibitor of Bax-mediated apoptosis which was identified from a human hippocampus cDNA library screened in the yeast cells. A method of promoting Bax-mediated apoptosis in a cell using an inhibitor or antagonist of the anti-apoptotic polypeptides identified from a human hippocampus cDNA library screened in the yeast cells.

Methods for inducing selective apoptosis

Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.