ТОНКОИЗМЕЛЬЧЕННЫЙ ПЛЕНКООБРАЗУЮЩИЙ ПОРОШОК, СОДЕРЖАЩИЕ ЕГО КОМПОЗИЦИИ, СПОСОБЫ ЕГО ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ

Настоящее изобретение относится к медицине и описывает тонкоизмельченный пленкообразующий порошок, применяемый в фармацевтической, косметической и питательной композициях и имеющий размер частиц не более 100 мкм и включающий смесь, по меньшей мере, одного активного вещества в количестве от 0,001 до 90 мас.%, по меньшей мере, одного биосовместимого адгезионного агента и, по меньшей мере, одного пластификатора в количестве от 0,1 до 30 мас.%. Пленка, которая образуется после нанесения порошка на гидратированную или влажную подложку, обладает хорошими адгезионными и когезионными свойствами. 4 н. и 19 з.п. ф-лы, 10 табл., 2 ил.

ЦИАНОТИЕНОТРИАЗОЛОДИАЗЕПИНЫ И ПУТИ ИХ ПРИМЕНЕНИЯ

Настоящее изобретение относится к соединению формулы (I):(I),или его фармацевтически приемлемым солям, стереоизомеру или таутомеру, где радикалы R1, R2, RA1, RA2, RC, RB, C, X1определены в формуле изобретения. Также предложена фармацевтическая композиция, набор для использования в лечении заболевания, ассоциированного с бромодоменсодержащим белком и/или с бромодоменом, способы лечения заболеваний, ассоциированных с аберрантной активностью бромодомена, способ мужской контрацепции, способы ингибирования активности бромодомена в биологическом образце, способы ингибирования связывания бромодомена бромодоменсодержащего белка с ацетил-лизиновым остатком второго белка у субъекта, способы ингибирования экспрессии гена, способы индуцирования апоптоза, способы индуцирования блокирования G1 в клетке. Технический результат заключается в получении новых органических соединений, которые могут представлять собой средства, обладающие способностью связывать бромодоменсодержащие белки, и могут быть пригодны ...

СПОСОБЫ И ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ ДЛЯ ДОСТОВЕРНОГО ДОСТИЖЕНИЯ ПРИЕМЛЕМЫХ УРОВНЕЙ ТЕСТОСТЕРОНА В СЫВОРОТКЕ

Настоящее изобретение относится к области фармации, а также к области терапевтического применения гормонов в заместительной гормональной терапии мужчин и мужской контрацепции. Предлагаемая композиция для внутримышечной инъекции содержит сложный эфир тестостерона, который выбран из группы сложных эфиров, включающей линейные и разветвленные нонаноаты, деканоаты, ундеканоаты, додеканоаты, тридеканоаты, тетрадеканоаты и пентадеканоаты; и носитель, содержащий касторовое масло в концентрации 25-45 об.% и сорастворитель. Композиции после внутримышечной инъекции обеспечивают достоверные физиологически приемлемые уровни тестостерона в сыворотке в течение продолжительного периода времени. Это позволяет применять их в заместительной гормональной терапии и мужской контрацепции без осуществления лечащим врачом сопутствующего мониторинга уровней тестостерона в сыворотке. Описан также фармацевтический состав, содержащий 1000 мг ундеканоата тестостерона в среде носителя, состоящего из касторового масла ...

Препарат для лечения и/или профилактики инфекционно-воспалительных заболеваний

Изобретение относится к области фармацевтической промышленности, а именно к антисептическому препарату в форме геля, который содержит хлоргексидина глюконат - 0,01-0,5 г, метил-4-гидроксибензоат - 0,01-0,1 г, этил-4-гидроксибензоат - 0,01-0,1 г, пропил-4-гидроксибензоат - 0,01-0,1 г, пропиленгликоль - 5-70 г, гидроксиэтилцеллюлозу - 1,5-5 г и воду - до 100 г. Изобретение обеспечивает создание нового препарата, эффективного в отношении патогенов, вызывающих заболевания, передающиеся половым путем, и не обладающего токсичностью и раздражающим действием. 2 з.п. ф-лы, 8 пр., 2 табл.

КОМПОЗИЦИЯ ДЛЯ ИНГИБИРОВАНИЯ ВИРУСА, НАХОДЯЩЕГОСЯ В ОБОЛОЧКЕ, И В КАЧЕСТВЕ ПРОТИВОЗАЧАТОЧНОГО СРЕДСТВА

Изобретение относится к медицине. Предложено в качестве средства для ингибирования вируса, находящегося в оболочке, и в качестве противозачаточного средства применять смесь высший алкил N-ди(низший алкил)бетаина и высший алкил N,N-ди(низший алкил)аминооксида, где высший алкил имеет C10 - C18 при молярном соотношении 1:5 - 5:1, а также кислоты для установления pH 4 - 8. В предложенной композиции инактивируют вирусы и бактерии при низкой активности по разрушению клеток. 2 с.п. ф-лы, 8 ил., 3 табл.

АГЕНТ ДЛЯ КОНТРОЛЯ ПЛОДОВИТОСТИ И СОДЕРЖАЩАЯ ЕГО ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Предметом изобретения являются соединения формулы I, приведенной в описании, а также их соли с допустимыми с фармацевтической точки зрения кислотами для контроля плодовитости, в частности для контроля мужской плодовитости.

17α-АЛКИЛ-17β-ОКСИЭСТРАТРИЕНЫ И ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ ДЛЯ ИХ ПОЛУЧЕНИЯ, ПРИМЕНЕНИЕ 17α -АЛКИЛ-17β -ОКСИЭСТРАТРИЕНОВ ДЛЯ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ, А ТАКЖЕ ФАРМАЦЕВТИЧЕСКИХ ПРЕПАРАТОВ

... 1. 17α-Алкил-17β-оксиэстратриены общей формулы I в которой Hal обозначает F или Cl и в положении 11β связан с эстратриеновым скелетом; R3 обозначает водород, С1-С4алкил, С1-С4алканоил или простой циклический С3-С7эфир с O-атомом; R17’ обозначает водород, С1-С4алкил или С1-С4алканоил; R17’’ обозначает С1-С4алкил, С1-С4алкинил, а также по меньшей мере частично фторированные алкильные остатки, при этом R17’-О в положении 17β и R17’’ в положении 17α связаны с эстратриеновым скелетом; SK обозначает группировку U-V-W-X-Y-Z-E, которая через U связана в положении 7α с эстратриеновым скелетом, где U представляет собой либо прямоцепочечный или разветвленный С1-С13алкиленовый, -алкениленовый или -алкиниленовый остаток либо группу А-В, при этом А связан с эстратриеновым скелетом и обозначает соединенный через -CH2- с эстратриеновым скелетом бензилиденовый, фениленовый или соединенный через алкильную группу с эстратриеновым скелетом C1-С3алкиларильный остаток, а В обозначает прямоцепочечный или разветвленный ...

VERFAHREN ZUR GEWINNUNG UND ANWENDUNG NEUER HUMANER DEFENSINE ALS BIOLOGISCH AKTIVE EIWEISSTOFFE ZUR BEHANDLUNG VON INFEKTIONEN UND ANDEREN ERKRANKUNGEN

Beta-amino-tetrahydroimidazo (1,2-A)pyrazine und-tetrahydrotriazolo(4,3-A)pyrazine als dipeptidyl peptidase Inhibitoren zur Behandlung oder preventionvon Diabetes

22R-HYDROXYCHOLESTA-8,14-DIENE DERIVATE ZUR HEMMUNG DER MEIOSE

CYANOPYRROLE ALS PROGESTERONREZEPTORAGONISTEN

TESTOSTERON-ESTER FORMULIERUNG ZUR ANWENDUNG AM MENSCHEN

NICHT ANTIGEN WIRKENDE VERZWEIGTE POLYMERKONJUGATE

KONDENSIERTE 1,2,4-THIADIAZINDERIVATE, IHRE HERSTELLUNG UND VERWENDUNG

Compounds

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

METHOD FOR INACTIVATING ENVELOPED VIRUSES AND SPERM

Non-peptide gnrh agents methods and intermediates for their preparation

Method for inactivating enveloped viruses and sperm.

There is provided methods for inhibiting the activity of enveloped viruses, treatment of viral infections and method inactivating sperm. There is provided articles for use in these methods.

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

METHOD FOR INACTIVATING ENVELOPED VIRUSES AND SPERM

No-peptide GnRH agents, methods and intermediates for their preparation.

Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are described. Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent turnors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intrmediates useful in their preparation are also described.

Spiro-pyrimidine-2,4,6-Trione Metalloproteinase inhibitors

The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein said "A" is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflamation, cancer and other disorders.

Imidazole derivatives

The invention provides compounds of formula 1 wherein R1, R2, R3, and R4 are as defined, and their pharmaceutically acceptable salts. Compounds of formula 1 are indicated to have activity inhibiting cdk5,cdk2,and GSK-3.Pharmaceutical compositions and methods comprising compounds of formula 1 for treating and preventing diseases and conditions comprising abnormal cell growth,such as cancer, and neurodegenerative diseases and conditions and those affected by dopamine neurotransmission. Also described are pharmaceutical compositions and methods comprising compounds of formula 1 for treating male fertility and sperm motility; diabetes mellitus; impared glucose tolerance; metabolic sydrome or syndrome X; polycystic ovary syndrome; adipogenesis and obesity; myogenesis and fraity, for example age-related decline in physical performance; acute sarcopenia, for example muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic ...

Non-peptide GnRH agents, methods and intermediatesfor their preparation.

Imidazole derivatives.

2-Aminocarbonyl-9H-purine derivatives.

Method for inactivating enveloped viruses and sperm.

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors.

Non-peptide gnrh agents methods and intermediates for their preparation

METHYLENSTEROIDE AS NEW ANDROGENS

17ALPHA-ALKYL-17BETA-OXY-ESTRATRIENE AND INTERMEDIATE PRODUCTS TO THEIR PRODUCTION, USE of the 17ALPHA-ALKYL-17BETA-OXY-ESTRATRIENE PREPARATIONS PHARMACEUTICAL FOR the PRODUCTION OF DRUGS AS WELL AS

PHARMACEUTICAL EFFECTIVE ONE PIPERIDINDERIVATE

USES FOR THE TREATMENT OF FSH CONNECTED CONDITIONS WITH GNRH ANTAGONIST

2-AMINOCARBONYL-9H-PURINDERIVATIVE

SELECTIVE ONE SUBSTITUTED ANDROGEN RECEPTOR MODULATORS AND OPERATING TECHNIQUES FOR IT SEVERAL TIMES

TREATMENT PROCEDURE USING CTLA-4 ANTIBODIES

STABILIZED SYNTHETIC IMMUNOGEN DELIVERY SYSTEM

2-HYDROXY-3-HETEROARYLINDOLE of DERIVATIVES AS GSK3 INHIBITORS

VERWENDUNG VON AFAMIN

The invention relates to the use of afamin for the manufacture of a pharmaceutical preparation for the prevention or treatment of fertility disorders.

8BETA-SUBSTITUIERTE-11BETA-PENTYL-UND 11BETA HEXYL-ESTRA-1,3,5 (10) - TRI DERIVATIVES

PHENETHYL-5-BROMOPYRIDYLTHIOHARNSTOFF (PBT) DERIVATIVES WITH SPERMIZIDER EFFECT

ANTI-ANGIOGENIC CHARACTERISTICS OF VASCOSTATIN AND FRAGMENTS AND VARIANTS OF IT

CONNECTIONS TO THE ADJUSTMENT OF THE HEDGEHOG OF SIGNAL PATH, COMPOSITIONS AND USES OF IT

DIPEPTIDYLPEPTIDASE HEMMER FOR THE TREATMENT OF DIABETES

BETA AMINO TETRAHYDROIMIDAZO (1,2-A) PYRAZINE AND - TETRAHYDROTRIAZOLO (4,3-A) PYRAZINE AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR TREATMENT OR PREVENTION OF DIABETES

ANDROGEN OF GLYKOSIDE AND THE ANDROGENI ACTIVITY OF IT

7.ALPHA. - METHYL 19-NORTESTOSTERON UNDECANOAT WITH ANDROGENI ACTIVITY

MEDICINE MATERIAL DELIVERY SYSTEM, IN PARTICULAR FOR THE ADMINISTRATION OF ANDROGENS

PYRAZOLOPYRIMIDINE AS DRUGS

PROCEDURE FOR IDENTIFYING SEX SPECIFIC AND SPECIES-SPECIFIC MOLECULES, WITH PROCEDURES IDENTIFIED MOLECULES AND USE OF THE MOLECULES

17ALFA, 21-DIHYDROXYPREGNENE of ESTER AS ANTI-ANDROGENS of ACTIVE SUBSTANCES

RSR ANTAGONIST FOR PREVENTING FOR MEN

KONTRAZEPTIVES IMPLANT FOR MEN

ORALLY EFFECTIVE ANDROGENS

Epididymis-specific proteins with fibronectin type II modules

Gnrh/reduced pseudomonas exotoxin conjugates

Nitrogenated fused ring derivative, pharmaceutical composition comprising the same, and use of the same for medical purposes

... [PROBLEMS] To provide a compound useful as a prophylactic or therapeutic agent for a sex hormone-dependent disease or the like. [MEANS FOR SOLVING PROBLEMS] Disclosed are: a nitrogenated fused ring derivative represented by the general formula (I), or a prodrug, salt or the like thereof, which has a GnRH antagonistic activity; a pharmaceutical composition comprising the derivative or the prodrug, salt or the like thereof; use of the the derivative or the prodrug, salt or the like thereof for medical purposes; and others. In the general formula (I), the rings A and B independently represent an aryl or a heteroaryl; R and R independently represent a halogen, a cyano, an alkyl, an alkylsulfonyl, -OW, -SW, -COW, -NWW, -SONWW, an aryl or the like; R represents H or an alkyl; E represents an oxygen atom or the like; U represetns a single bond or an alkylene; and X represents Y, -CO-Y, -SO-Y, -S-(alkylene)-Y, -O-(alkylene)-Y, -SO-(alkylene)-Y or the like [wherein Y represents Z, an amino or the ...

Substituted acylanilides and methods of use thereof

This invention provides SARM compounds and uses thereof in treating a variety of diseases or conditions in a subject, including, , a muscle wasting disease and/or disorder or a bone-related disease and/or disorder.

N-Bridged selective androgen receptor modulators and methods of use thereof

Methods of treatment using CTLA-4 antibodies

Thioamide derivatives as progesterone receptor modulators

Thioamide compounds, and specifically, thioamide pyrrole compounds, and preparation thereof are provided. These thioamide compounds can be used as progesterone receptor modulators, in contraception, and in the treatment of progesterone-related maladies (formula I).

Methods of treatment using CTLA-4 antibodies

CHANGE INHIBITORS OF DIPEPTIDYL PEPTIDASE IV

Use of oxindole derivatives in the treatment of dementia related diseases, alzheimer's disease and conditions associated with glycogen synthase kinase-3

Methods for treating endocrine disorders

USE OF OXINDOLE DERIVATIVES IN THE TREATMENT OF DEMENTIA RELATED DISEASES, ALZHEIMER'S DISEASE AND CONDITIONS ASSOCIATED WITH GLYCOGEN SYNTHASE KINASE-3

N-bridged selective androgen receptor modulators and methods of use thereof

Method for the production of vaccines against cell surface proteins

Androgen glycosides and androgenic activity thereof

Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

Vanadium (iv) metallocene complexes having spermicidal activity

Compositions and methods of making embryonic stem cells

Androgen receptor modulator compounds and methods

Regulators of the hedgehog pathway, compositions and uses related thereto

14(15)-unsaturated 15- and/or 16- substituted androgens with mixed androgen-progestational profile

USE OF ALKYLUREAS AND HYDROXYUREA AS CONTRACEPTIVE AGENTS

6-azaindole compounds as antagonists of gonadotropin releasing hormone

Methods of making and using 7alpha,11beta-dimethyl-17beta-hydroxy-4-estren-3-one17beta-trans-4-m-butylcyclohexane carboxylate and 7alpha,11beta-dimethyl-17beta -hydroxyestr-4-en-3-one 17-undecanoate

FUSED 1,2,4-THIADIAZINE DERIVATIVES, THEIR PREPARATION AND USE

The present invention relates to 4H-thieno[3,2-e]-1,2,4-thiadiazine derivatives of general formula (I), compositions thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

SPIRO-PYRIMIDINE-2,4,6-TRIONE METALLOPROTEINASE INHIBITORS

The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein said "A" is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflammation, cancer and othter disorders.

ANTI-ANGIOGENIC AND ANTI-TUMOR PROPERTIES OF VASCOSTATIN AND OTHER NIDOGEN DOMAINS

A protein with anti-angiogenic properties is disclosed.

MALE CONTRACEPTIVES

Disclosed are male contraceptives containing a peptide and analogs thereof having an amino acid sequence corresponding to the second extracellular domain of a mammalian occludin. The peptides may be linked to a carrier targeting testicular cells, preferably to a modified follicle stimulating hormone. Methods of producing such a contraceptive, and a method of use are also disclosed.

NEW COMPOUNDS

The present invention provides new compounds of formula Ia and Ib: as well as a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.

8BETA-VINYL-11BETA-(ALPHA-SUBSTITUTED)ALKYL-ESTRA-1,3,5(10)-TRIENES

The invention relates to 8.beta.-vinyl-11.beta.-(.omega.-substituted)alkyl- estra-1,3,5(10)-trienes of general formula (I), which have ER.beta.- antagonistic activity, methods for the production thereof, the intermediate products thereof, pharmaceutical preparations containing the inventive compounds, and the use thereof for producing medicaments. The novel compounds can be used for contraceptive purposes in men and women without influencing other estrogen-sensitive organs such as the uterus or the liver and while also being suitable for the treatment of benign or malignant proliferous ovarian diseases, such as ovarian carcinoma and granulosa cell tumors.

2-AMINOCARBONYL-9H-PURINE DERIVATIVES

The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

INHIBITORS OF DIPEPTIDYL PEPTIDASE IV

Novel inhibitors of dipeptidyl peptidase IV (DPP IV), pharmaceutical compositions comprising therapeutically effective amounts of novel inhibitors of DPP IV, and novel methods of treating medical conditions are provided. The novel inhibitors of DPP IV described herein are useful in the treatment of neurological disorders, diabetes, inflammatory disorders such as arthritis, obesity, osteoporosis, and of such other enumerated conditions as can be treated with inhibitors of DPP IV.

REGULATORS OF THE PCT OR SMOOTHENED PATHWAY, COMPOSITIONS AND USES RELATED THERETO

The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of- function or smoothened gain-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule in an amount sufficient to control the aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. The present invention further makes available methods and reagents for ameliorating the consequences of hedgehog loss-of-function, ptc gain-of-function, or smoothened loss-of- function comprising contacting a cell with a compound, such as a polypeptide or small molecule, in an amount sufficient for amelioration. In certain embodiments, the subject compounds, e.g., a cAMP analog, adenylate cyclase agonist, or cAMP phosphodiesterase inhibitor, regulate cAMP levels, which in turn modulates activity of the hedgehog pathway.

NON-HORMONAL COMPOSITIONS AND METHODS FOR MALE CONTRACEPTION

The present invention relates to the use of a composition in a non-hormonal contraception method for a male subject, comprising administering an alpha-1-adrenoreceptor antagonist; wherein the contraception method includes a once daily administration of said composition at about the same time each day, triggering a continuous reversible aspermia, azoospermia, or severe oligozoospermia in the male subject, and wherein after an initial period of at least two consecutive days, the contraception is not impaired by a delay of the subsequent once daily intake. This invention also relates to the packaging comprising 7, 14, 28, 56, 84, or 168 to 365 unit doses; or 10, 20, 30, 60, 90, or 180 to 360 single doses of the composition to be implemented according to the present invention.

6H-THIENO[2,3-E][1,2,4]TRIAZOLO[3,4-C][1,2,4]TRIAZEPINE DERIVATIVES

This 6H-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,2,4]triazepine derivative or a salt thereof has BRD4 inhibitory activity and is therefore useful as a drug, especially as an agent to prevent and/or treat diseases involving BRD4.

ANDROGENIC 7-SUBSTITUTED 11-HALOGENATED STEROIDS

The invention relates to 11.beta.-halogen steroids with general formula (I), whereby R11 is halogen, X-Y-Z represents a group with one of the two structures CH=C-C or CH2-C=C and the other radicals have the meaning that is indicated in the claims, also the production and use of these compounds for the production of pharmaceutical agents as well as pharmaceutical preparations that contain 11.beta.-halogen steroids.

BRAIN/NEURONAL CELL-PROTECTING AGENT AND THERAPEUTIC AGENT FOR SLEEP DISORDER

A compound represented by the formula (I) or a salt thereof; and an agent for protecting a brain/neuronal cell or a therapeutic agent for sleep disorder comprising the compound or salt: wherein Z represents an oxygen or sulfur; R1 represents an aryl or heterocyclic group which may be substituted, provided that R1 is not a 3-ethyl-6-methoxy-2-methyl-5-naphthalen-1-yl group; R1a represents a hydrogen atom, a hydrocarbon group which may be substituted, a hydroxyl group or the like; R2 represents a pyperidin-1,4-diyl or piperadin- 1,4-diyl which may be substituted; R3 represents a bivalent group which is formed by removing two hydrogen atoms from a benzene ring or 6-membered aromatic heterocyclic ring which may have a substituent, provided that R3 is not a pyridazin-3,6-diyl; and R4 represents a group which is formed by removing one hydrogen atom from a benzene ring or 5- to 6-membered heterocyclic ring which may be substituted, provided that the substituent on the heterocyclic ring is not ...

INHIBITORS OF SOLUBLE ADENYLATE CYCLASE

The invention relates to compounds of general Formula (I), the production thereof, and the use thereof as a medicinal product.

SUBSTITUTED ACYLANILIDES AND METHODS OF USE THEREOF

This invention provides SARM compounds and uses thereof in treating a var iety of diseases or conditions in a subject, including, inter alia, a muscle wasting disease and/or disorder or a bone-related disease and/or disorder.< /SDOAB> ...

SALT OF FUSED HETEROCYCLIC DERIVATIVE AND CRYSTAL THEREOF

The purpose of the present invention is to improve the solubility of a 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)- 4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d] pyrimidine-5-carboxylic acid. Disclosed is a choline salt represented by formula (A), which has excellent solubility and excellent storage stability.

IMMUNIZATION BY INOCULATION OF DNA TRANSCRIPTION UNIT

This invention relates to a method of immunizing a vertebrate, comprising introducing into the vertebrate a DNA transcription unit which comprises DNA encoding a desired antigen or antigens. The uptake of the DNA transcription unit by a host vertebrate results in the expression of the desired antigen or antigens, thereby eliciting humoral or cell-mediated immune responses or both humoral and cell-mediated responses. The elicited humoral and cell-mediated immune response can provide protection against infection by pathogenic agents, provide an anti-tumor response, or provide contraception. The host can be any vertebrate, avian or mammal, including humans.

INACTIVATING ENVELOPED VIRUSES AND SPERM

Disclosed is a composition for inhibiting the activity of an enveloped virus or sperm, the composition comprising a mixture of (a) a betaine selected from an alkyl-N- betaine, alkyl-N-sulfobetaine, acyl-N-betaine, an alkyl-N- substituted aminopropionic acid and an alkylimidazolinium betaine, or a mixture of two or more thereof, (b) an amine oxide selected from an alkyl-N,N-dimethylamine oxide, alkyl-N,N-dihydroxyethylamine oxide, acylamide t-amine oxide, or a mixture of two or more thereof, and (c) acid in an amount to provide the composition with a pH of 4 - 8 as measured when the betaine and amine oxide together comprise 0.5 weight percent of the composition. Also disclosed is a contraceptive device containing the composition as a spermicide.

NON-ANTIGENIC BRANCHED POLYMER CONJUGATES

Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

IMMUNOGENIC LHRH COMPOSITIONS AND METHODS RELATING THERETO

The present invention relates generally to an immunogenic LHRH composition and more particularly to an immunogenic LHRH composition comprising an LHRH C-terminal fragment of at least five amino acids. The present invention is useful, inter alia, as a prophylactic and/or therapeutic agent for the modification of fertility and behaviour patterns of animals, the achievement of livestock production gains such as increasing growth, decreasing feed conversion ratios or the control of unwanted organoleptic characteristics or the treatment of disorders of the reproductive organs.

SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM

Novel polynucleotides and the proteins encoded thereby are disclosed.

Recombinant fusion protein and polynucleotide construct for immunotoxin production

The present invention relates to a polynucleotide construct encoding a fusion protein consisting of a domain which binds the immunoglobulin Fc region, genetically fused to a truncated form of Pseudomonas exotoxin A (PE). In particular, the invention discloses the fusion protein, ZZ-PE38, and further provides immunotoxins, formed from complexes of the fusion protein with antibodies for targeted cell killing.

Triheterocyclic Compounds and Compositions Thereof

The present invention relates to novel Triheterocyclic Compounds, compositions comprising a Triheterocyclic Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a Triheterocyclic Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, treating or preventing a viral infection, or inhibiting the replication and/or infectivity of a virus.

Compositions for bacterial mediated gene silencing and methods of using the same

The invention features compositions and methods for delivering small interfering (siRNAs), e.g., shRNAs, to host cells using non-pathogenic strains of Salmonella bacteria containing nucleic acid expression constructs encoding shRNAs. In this process, shRNA expressed by the Salmonella silences or knocks down genes of interest (target genes) inside target cells. The nucleic acid expression constructs of the invention include an RNA polymerase (e.g., a T7 polymerase), an RNA polymerase promoter (e.g., a T7 polymerase promoter), and an RNA polymerase terminator (e.g., a T7 polymerase terminator). The Salmonella bacteria can also include, on the same or different nucleic acid construct, an endosomal release factor (e.g., HlyA).

Humanized antibodies against west nile virus and therapeutic and prophylactic uses thereof

The present invention relates to compositions comprising humanized antibodies or fragments thereof that immunospecifically bind to one or more antigens of a flavivirus, particularly of West Nile Virus (WNV) and methods for preventing, treating or ameliorating symptoms associated with a flavivirus, particularly of West Nile Virus (WNV) infection utilizing said compositions. In particular, the present invention relates to methods for preventing, treating or ameliorating symptoms associated with WNV infection, said methods comprising administering to a human subject an effective amount of one or more humanized antibodies or fragments thereof that immunospecifically bind to a WNV antigen. The present invention also relates to detectable or diagnostic compositions comprising humanized antibodies or fragments thereof that immunospecifically bind to a WNV antigen and methods for detecting or diagnosing WNV infection utilizing said compositions.

Il-21 variants

IL-21 variants nucleic acid sequences are provided that encode a peptide having deletions and zero to ten conservative amino acid substitutions in the region of amino acid residues 65-96 of SEQ ID. NO:2.

Immunotherapeutic agent

The present invention is directed to adoptive immunotherapy using a lymphocyte in which an antigen-specific receptor and a bioactive material gene such as an IL-2 gene or a water-soluble TGF-beta receptor gene are transferred. The bioactive material is intensively secreted to, for example, a local site of a tumor, thereby reducing systemic side effects as much as possible, and the survival time of the lymphocyte is increased, thereby further improving the effect of the adoptive immunotherapy.

Polyion complex comprising hydrophobized polyamino acid and use of the same

A polyion complex (PIC) or a PIC nanoparticle that may be easily prepared, and that is finally disappeared in vivo due to its suitable biodegradability while exhibiting high stability in vivo, an immunotherapy agent comprising the PIC nanoparticle to which various antigen proteins or peptides may be easily conjugated or incorporated and/or which may be easily mixed with the antigen proteins or peptides, as well as a process for preparing thereof are provided. Specifically, a polyion complex (PIC) comprising a hydrophobized poly(acidic amino acid) and a basic polypeptide, a nanoparticle thereof having a particle shape, an immunotherapy agent comprising the PIC nanoparticle, as well as a process for preparing the PIC, comprising steps of introducing a hydrophobic amino acid to a poly(acidic amino acid) to prepare a hydrophobized poly(acidic amino acid), and dissolving the hydrophobized poly(acidic amino acid) prepared to a buffer, and it is mixed with a basic polypeptide dissolved in a buffer.

Antifungal 1,2,4-triazolyl Derivatives

The present invention relates to novel triazole compounds of the formulae I and II as defined below which carry a sulfur substituent, to agricultural compositions containing them, to their use as fungicides and to intermediate compounds used in the method of producing them.

Rna sequence-specific mediators of rna interference

The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

Lung-targeted drugs

Methods and compositions are provided for treating lung diseases, including but not limited to infections and small cell and non-small cell lung cancer, by conjugating a drug of interest to glycerol ethers or glycerol phosphate ethers.

dsRNA For Treating Viral Infection

The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

Methods of isolating stem cells

The present inventors discovered for the first time that labeling cell nuclei makes it possible to efficiently isolate stem cells. Namely, it was elucidated that stem cells with labeled nuclei remained labeled even after cell division, and showed self-renewing and long-living abilities characteristic of stem cells. Efficient isolation of stem cells is possible, for instance, by labeling the nuclear of each cell in a heterogeneous cellular group followed by selecting those cells that maintain a labeled state even after cell division. The present invention provides methods for enabling visualization of stem cells of animal tissues in a living state by labeling using the essential functions of the stem cells, and methods for simply and easily isolating the stem cells in a fresh state without using at all genetic manipulation or artificial markers.

Chemical method for sexual sterilization and libido elimination in male mammals

A chemical method for sexual sterilisation and libido suppression in male mammals is indicated to achieve the biological sterilisation of male mammals such as bovines, sheep, goats, equines, swine, dogs, cats and humans. The invention consists in a sterile aqueous solution containing an active sclerosing principle (lactic acid) and an enzyme (papain). The enzyme causes digestion of testicle tissue, intensifying the acid's necrosing effect and causing it to act faster and more efficiently. The association of these two active principles provokes an acute inflammatory reaction with a quick resolution characterised by fibrosing of the organ. This effect leads to the loss of the gametogenic and androgenic functions, and causes sterility and libido suppression, respectively. The biological sterilisation process can be easily carried out and does not require additional treatments, requiring less handling of the animals, with less stress and increased weight gain. The process is not painful either during or after administration, owing to the lesion of the testicle nerve endings at the moment of application, and to the fact that the greatest number of sensitive structures is located in the scrotal sac. The meat of thus treated cattle does not require for consumption a waiting period between application and slaughter, since the biological active principles can be easily metabolised by the animal organism. This method has already been successfully used in more than 3,000 animals, and is the only method available today in which naturally available biological active principles are used.

Cyclic di-amp induction of type i interferon

Methods of modulating type-I interferon production in a cell are provided. Aspects of the methods include modulating cytosolic cyclic di-adenosine monophosphate (c-di-AMP) activity in the cell in a manner sufficient to modulate type-I interferon production in the cell. Additional aspects of the invention include c-di-AMP activity modulatory compositions, e.g., c-di-AMP, mutant Listeria bacteria, cyclase and/or phosphodiesterase nucleic acid or protein compositions, etc. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

Intracellular viral vector delivery method employing iron ion/viral vector composite

The present invention relates to an intracellular viral vector delivery method employing an iron ion/viral vector composite. The iron ion/viral vector composite according to the present invention is not dependent on the expression of CAR and so improves the efficiency of delivery of viral vectors and gene expression in cells of diverse types, and has an outstanding virus-neutralizing antibody escape performance, exhibits little cytotoxicity and is outstandingly stable even when subjected to iron ion processing at low concentration, and hence can be used to advantage in recombinant viral vaccine compositions.

Polyethylene glycol-based dendrons

The instant invention relates to polyethylene glycol-based dendrons, otherwise known as PEGtide dendrons, compositions thereof and methods of use.

Inhibitors of hedgehog signaling pathways, compositions and uses related thereto

The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.

Method of treatment of cancer patients

This invention may be used in human and veterinary medicine in combination with traditional methods of treatment of oncological illnesses for the purpose of increasing their effectiveness. It is a method of treating patients with oncological diseases that is distinct in that an antiviral drug is used as an additional component of standard treatment before the beginning of and in parallel with standard treatment, in which Acyclovir, Valacyclovir, alpha interferon, a specific antiviral immunoglobulin or a combination of these substances are used as an antiviral drug, which may be used for inclusion in the standard surgical, radiological, or chemotherapeutic treatment plan for cancer patients. The proposed method allows us to significantly improve the results of the treatment of cancer patients, decrease the number of relapses, improve patients' quality of life, and significantly extend their lives. Because the proposed drugs are already approved for use, there are no technical difficulties facing their inclusion in cancer patients' treatment plans.

Antiviral compositons

A composition which includes a carboxamide, preferably ribavirin, for treating viral diseases in humans. A preferred embodiment of the subject invention comprises a very high dose (>600 mg) of ribavirin, and more preferably between about 800-1200 mg of ribavirin or more per dosage form.

Virucidal properties of various forms of sophorolipids

A method for neutralizing or inactivating a virus, and neutralizing or inactivating HIV using sophorolipids having antiviral properties produced by synthesizing the sophorolipid by fermentation of Candida bombicola in a fermentation media to form a natural mixture of lactonic sophorolipids compounds and non-lactonic sophorolipids compounds and utilizing the natural mixture as an antiviral agent, and/or separating the lactonic sophorolipids from the natural mixture to form a lactonic fraction and mixing all remaining fractions to form a non-lactonic fraction and utilizing the lactonic fraction and/or the non-lactonic fraction as an antiviral agent, and sophorolipid compounds for use as antiviral agents.

Multi-targets interfering rna molecules and their applications

This invention relates to interfering RNA (iRNA) molecules and their applications, especially multi-targets iRNA molecules and their applications. The said multi-targets iRNA molecules comprised of a sense strand annealed onto at least one antisense strand, each strand is at least 30 nucleotides in length, the sense or antisense strand has at least two segments, which can target at least two RNAs of different genes, or can target at least two portions of an RNA, and wherein the iRNA does not induce an interferon-response when transfected into a cell. The iRNA molecule can interfere with the translation procedure post-transcription, and the target gene is inhibited or blocked, the iRNA does not induce an interferon-response in vivo. The RNA molecules are the active ingredient in preparation of the drug which can regulate one or many genes function.

Technical field and industrial applicability of the invention

The present invention is a solution or colloid of fullerene, SWNTs, or graphene in cyclic terpenes, lactones, terpene-alcohol, fatty-acid alcohols, and lactones following ultrasonication and ultracentrifugation processing, for oil-energy, biological, electrical-thermal applications. The compositions are useful as fuel/oil/grease/gels (synthetic included), oil/fuel/additives/propellants, identification dyes, and heat-transfer fluids. Other functions are phase-change fluids for solar energy power plants, antifreeze, electronic dyes, electrolytic fluid/solvent, electrically-thermally conductive material for electrochemical, dielectric, filler/adhesive for semiconductor, eletro-optical, and liquid crystal substrates/coatings for touch sensitive transmissive or reflective displays. When combined with gelatin the formulations can function as dichroic-optical coatings for thin-films/waveguides/holograms. Such formulations may also be used as photovoltaic paint, electrorheological, thermophoretic-thermodiffusion, electrohydrodynamics, electric propulsion, laser enhancement, plasma jets, and magnetohydrodynamics. Energy use includes high-temperature superconductivity, or hydrogen storage using carbon, alumina, or silica supported Pd, Pt, or Zn catalysts. Biological applications include anticancer, antiviral, antifungal, drug delivery, skin permeable agents, and lubricant use.

Mhc peptide complexes and uses thereof in infectious diseases

Novel compounds carrying ligands capable of binding to counter receptors on relevant target cells are disclosed. The compounds possess a number of advantageous features, rendering them very suitable for a wide range of applications, including use as detection systems, detection of relevant target cells as well as a number of other methods. In particular, novel MHC complexes comprising one or more MHC molecules are disclosed. The affinity and specificity of the MHC-peptide complexes are surprisingly high. The possibility of presenting to the target cells a plurality of MHC-peptide complexes makes the MHC complexes according to the present invention an extremely powerful tool e.g. in the field of therapy and diagnosis. The invention generally relates to the field of therapy, including therapeutic methods and therapeutic compositions. Also comprised by the present invention is the sample-mounted use of MHC complexes and MHC multimers.

Novel chimeric polynucleotides and polypeptides enabling the secretion of a polypeptide of interest in combination with exosomes and uses thereof

The present invention provides a chimeric polypeptide comprising a plurality of polypeptide domains that are capable of being secreted in combination with membrane vesicles and in particular exosomes. The invention also concerns the use of polypeptides of the invention and polynucleotides coding for these polypeptides, for the production of immunogenic compositions based on exosomes or DNA, to screen protein interactions. The present invention also concerns exploiting the properties of exosomes comprising a polypeptide of the invention and immunogenic compositions of the invention in immunology. The present invention concerns the use of exosomes comprising a polypeptide of the invention as a diagnostic tool. The present invention also concerns exploiting the properties of membrane vesicles and protein compositions of the invention for the prophylaxis and/or treatment of a disease due to a functional deficit, in particular to transport a protein or a nucleic acid, in particular to compensate for or make up for an enzymatic deficit, or in particular to induce a transcriptional or translational modification in the target cells or organs.

Polymeric conjugates of adenine nucleoside analogs

The present invention relates to polymeric conjugates of adenine nucleoside analogs. In particular, the invention relates to multi-arm polyethylene glycol conjugates of adenine nucleoside analogs and use thereof. The present invention, more specifically, provides polymeric conjugates of toyocamycin and its derivatives. Furthermore, the present invention provides a method for preparing the polymeric conjugates of adenine nucleoside analogs and a method of using the same for treating a cancer, inhibiting the growth or proliferation of cancer cells, treating a viral infection, treating a disease or condition associated with abnormal expression of VEGF. Most polymeric conjugates of toyocamycin was stable in PBS but released toyocamycin in vivo to provided inhibition of cancer cell growth.

Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided.

Combination of a Macrocyclic Inhibitor of HCV, A Non-Nucleoside and a Nucleoside

The present invention relates to a combination of a macrocyclic HCV protease inhibitor, a macrocyclic non-nucleoside HCV polymerase inhibitor and a nucleoside HCV polymerase inhibitor.

Modulating xrn1

The present invention relates to a method for modulating miRNA, said method being characterized in that a modulator of XRN1 is used. Also provided are uses of said method for therapeutical purposes, reagents therefore, as well as screening methods.

Nucleoside Phosphonate Salts

The present invention relates to compounds and methods for treating viral diseases. Some compounds of the invention are described by Formula I: (I), wherein M + is Na + , Li + , K + , Ca 2+ , Mg 2+ , or NR c R d R e R f + and R c , R d , R e and R f are each independently hydrogen or C 1-5 alkyl, or a stereoisomer, a diastereomer, an enantiomer or racemate thereof.

Virus-inactivating composition containing low-molecular weight compound and arginine

The invention provides a virus-inactivating composition with pH of 3.8 to 5.5, containing (A) 0.02 to 0.3 M arginine and (B) a component such as 0.01 to 10 mM flavonoid, polyphenol, or ascorbic acid derivative, 0.005 to 5 mass % of an arginine derivative, and 0.1 to 2.5 mass % of an extract solution of natural product.

Silk-Based Ionomeric Compositions

Disclosed herein are pH-dependent silk fibroin-based ionomeric compositions and colloids, and methods of making the same. The state of the silk fibroin ionomeric compositions is reversible and can transform from a gel-like colloid to a more fluid-like solution, or vice versa, upon an environmental stimulus, e.g., pH. Thus, the silk-based ionomeric compositions and colloids can be applied in various industries, ranging from electronic applications to biomedical applications, such as sensors, gel diodes, absorbent materials, drug delivery systems, tissue implants and contrast agents.

Biologic female contraceptives

This invention provides, inter alia, commensal organisms engineered to express antibody fragments, which inhibit sperm motility or fertilization and compositions comprising the same. The present invention provides for the use of the engineered commensal organisms or compositions comprising the same as effective contraceptive means in females.

Arginine deiminase mutant and preparation and application thereof

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

Combination virotherapy for cancer

One aspect of the present disclosure relates to a method for treating a subject with cancer. The method includes administering an oncolytic virus simultaneously, sequentially, or separately in combination with an immunomodulatory agent in an amount effective to suppress both antiviral immunity and angiogenesis associated with the cancer.

Means and methods for distinguishing fecv and fipv

The invention provides methods and means for distinguishing FECV and FIPV, and methods and means for determining whether FIPV is present in a sample. Further provided are primers and probes for detecting FIPV specific nucleic acid sequences encoding a spike protein, antibodies for detecting a FIPV, and an immunogenic composition and use thereof for eliciting an immune response against a feline coronavirus, preferably a FIPV.

Structural Variants of Antibodies for Improved Therapeutic Characteristics

Substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments are disclosed. They are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Substitution of an aspartate residue at Kabat position 101 of CDR3 V H (CDRH3), produces improved therapeutic properties, including decreased dissociation rates and improved CDC activity, apoptosis, B-cell depletion and therapeutic efficacy at very low dosages. Veltuzumab, a humanized antibody that incorporates such sequence variation, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, preferably 100 mg or less, preferably 80 mg or less, preferably 50 mg or less, most preferably 30 mg or less of naked antibody administered i.v. or s.c.

In-vivo gelling pharmaceutical pre-formulation

Provided herein are in vivo gelling pharmaceutical pre-formulations forming biocompatible hydrogel polymers that are polymerized in vivo and kits comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally at least one therapeutic agent. The biocompatible hydrogel polymer is bioabsorbable and releases the therapeutic agent at a target site, avoiding systemic exposure.

Modulators of sperm hypermobility and uses thereof

The invention provides novel compositions and compounds that inhibit CatSper channel activity, that preferentially inhibits sperm hyperactivity over sperm motility, or both. The compounds of the invention are useful as contraceptive agents that may be adminstered to males, females, or concurrently to both sexual partners. The invention further provides methods of conducting drug discovery business and of conducting a reproductive medicine business. The invention also provides methods of identifying compounds that modulate sperm hypermotility.

Macrophage activating factor for use in the treatment of chronic fatigue syndrome (cfs) and cfs-related diseases and disorders

The present invention relates to Macrophage Activating Factors such as GcMAF and compositions thereof, for use in the treatment of a patient suffering from CFS/ME and/or XMRV infection.

Process for the preparation of amorphus valgancyclovir hydrochloride

Amorphous valgancyclovir hydrochloride has a median particle size of below 100 μm. A process for the preparation of the compound includes dissolving valgancyclovir hydrochloride in at least one solvent, removing the solvents under moisture controlled conditions, and drying the wet mass.

Bis-pyrinidium compounds

A method of treating, inhibiting, or preventing an infection in a subject is described. The method comprises administering to the subject an effective amount of at least one bis-pyridinium compound. The bis-pyridinium compound comprises two aromatic ring structures. Each of the ring structures comprises a pyridine ring, and the ring structures are linked by a linker group of at least 8 atoms in length, said linker group being attached to the nitrogen atoms of the pyridine rings. At least one substituent on at least one of the ring structures is an alkyl group having at least 2 carbon atoms, and no substituent on either of the ring structures is —OH, —SH or an amine group.

Topical antiviral formulations

The disclosure provides antiviral pharmaceutical compositions comprising one or more antiviral compounds and 2-deoxy-D-glucose in the form of lip-balms, creams and ointments. A specific embodiment discloses a lip-balm composition comprising acyclovir and 2-deoxy-D-glucose.

Inhibitors of Serine Proteases

This invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof wherein C* represents a diastereomeric carbon comprising a mixture of R and S isomers wherein the R isomer is greater than 50% of the mixture.

Synergistic biomolecule-polymer conjugates

The synergistic biomolecule-polymer conjugates are the long-acting, in vivo controlled continuous-release and hybrid synergy systems of biomolecules that provide increased biological activities and enhanced pharmacological properties for achieving greater therapeutic efficacies.

Rationally-designed meganucleases with recognition sequences found in dnase hypersensitive regions of the human genome

Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.

Methods of preparing substituted nucleotide analogs

Disclosed herein are methods of preparing a phosphorothioate nucleotide analog, which are useful in treating diseases and/or conditions such as viral infections.

Method of preparation of metaxalone

The present invention relates to a method of preparation of metaxalone comprising reaction of triglycidyl isocyanurate (TGIC) with m-xylenol, characterized in that said reaction is carried out in a solvent mixture comprising an aprotic polar solvent with dielectric constant greater than or equal to 30 and at least one other solvent selected from the group comprising apolar solvents and aprotic polar solvents with dielectric constant below 30 said solvent mixture comprising from 5 to 40 wt. % of said first solvent and from 95 to 60 wt. % of said second solvent, adding the TGIC at a temperature between 30° C. and 50° C., and after adding the TGIC, raising the temperature of the reaction solution to a value between 80° C. and 180° C. in a time between 120 and 180 minutes at a rate of increase not greater that 1.25° C. per minute. The invention also relates to a metaxalone with a reduced content of impurities derived from incomplete reactions and/or side reactions of the method of production.

Methods of preparing substituted nucleotide analogs

Disclosed herein are methods of preparing a phosphorothioate nucleotide analog, which are useful in treating diseases and/or conditions such as viral infections.

Compositions for conferring tolerance to viral disease in social insects, and the use thereof

Compositions and methods for reducing susceptibility to infectious disease in bees using RNA interference technology, and more particularly, prevention and treatment of viral infections in honeybees such as Israel acute paralysis virus (IAPV) by feeding of pathogen-specific dsRNA. Further, multiple-pathogen specific dsRNA is disclosed.

Laglidadg homing endonuclease variants having mutations in two functional subdomains and use thereof

A LAGLIDADG homing endonuclease variant, having mutations in two separate subdomains, each binding a distinct part of a modified DNA target half-site, said LAGLIDADG homing endonuclease variant being able to cleave a chimeric DNA target sequence comprising the nucleotides bound by each subdomain. Use of said herodimeric meganuclease and derived products for genetic engineering, genome therapy and antiviral therapy.

Method of vaccination

The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of an antigen-presenting cell, said method comprising introducing a molecule into the cell cytosol by photochemical internalisation, wherein said molecule, or a part thereof, is subsequently presented on the surface of said cell. Methods of vaccination comprising this method, together with compositions comprising said cells and uses involving said cells expressing antigenic molecules are also provided.

Novel Polymer Derivative Of Cytidine Metabolic Antagonist

[Problem] To provide a novel polymer derivative of a cytidine metabolic antagonist which allows release of a medicament irrespective of enzymes of the living body and is expected to have high therapeutic effects. [Solution] The polymer derivative of a cytidine metabolic antagonist in which a substituent represented by the general formula (I) or the general formula (II) [wherein R 7 and R 8 each independently represent a hydrogen atom or an optionally substituted (C1-C6)alkyl group, R 6 represents a hydrogen atom, an optionally substituted (C1-C40)alkyl group, an optionally substituted (C1-C40)aralkyl group, an optionally substituted aromatic group, an amino acid residue in which the carboxy group is protected, or an optionally substituted sugar residue, CX—CY represents CH—CH or C═C (double bond), and A represents the residue of the cytidine metabolic antagonist except the amino group at the position 4] is bonded to the side-chain carboxy group of a block copolymer of a polyethylene-glycol structural moiety and a polymer having 10 or more carboxy groups.

O-(substituted benzyl) phosphoramidate compounds and therapeutic use

This application discloses novel phosphoramidate and phosphonoamidate prodrugs of nucleosides, nucleotides, C-nucleosides, C-nucleotides, phosphonates, and other alcohol-containing drugs; use of these prodrugs for treatment of infectious diseases and cancers, in particular, liver infections and cancers; and methods of preparing these novel phosphoramidate and phosphonoamidate prodrugs.

Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Bi-specific conjugates

The present invention provides a conjugate comprising: i) at least one first specific binding molecule which binds CD40, wherein said first specific binding molecule is an agonist of CD40; and ii) at least one second specific binding molecule which binds a tag moiety, wherein said tag moiety is not a cancer antigen, wherein said first specific binding molecule and second specific binding molecule are antigen-binding proteins comprising an antigen-binding domain of an antibody and are covalently linked. The conjugate can be combined with a tag construct comprising: i) a tag moiety which is not a cancer antigen; and ii) an antigen, being a cancer antigen or an antigen derived from a pathogen; wherein said antigen is a polypeptide and said tag moiety is covalently linked to said antigen, for use in therapy, to stimulate an immune response by a subject against the antigen in question.

METHODS AND SYNERGIC COMPOSITIONS FOR TREATING VIRAL INFECTIONS

The present invention provides compositions and methods for treating, preventing, and inhibiting viral replication, viral infections and viral diseases and disorders, comprising use of artemisone in combination with at least one antiviral compound selected from maribavir, cidofovir, brincidofovir, valganciclovir, and letermovir, and the combination provides a synergistic anti-viral effect. The invention also provides compositions and methods for treating, preventing, and inhibiting viral replication, viral infections and viral diseases and disorders, comprising the use of artemisone in combination with ganciclovir, wherein the molar ratio between artemisone and ganciclovir is about 1:100 to 100:1, and the combination provides a synergistic anti-viral effect. Pharmaceutical compositions comprising artemisone and at least one of said antiviral compounds are provided as well. 1. A method of treating a viral infection in a subject in need thereof comprising co-administering to said subject artemisone and at least one compound selected from the group consisting of maribavir , brincidofovir , cidofovir , valganciclovir , letermovir , and ganciclovir , wherein said co-administering provides a synergistic antiviral effect and wherein the molar ratio of artemisone to ganciclovir is in the range of from 1:100 to 100:1.2. The method of claim 1 , wherein the method comprises co-administering of artemisone and maribavir claim 1 , and wherein the molar ratio of artemisone to maribavir is in the range of from 1:100 to 100:1.3. The method of claim 1 , wherein the method comprises co-administering of artemisone and letermovir claim 1 , and wherein the molar ratio of artemisone to letermovir is in the range of from 2:1 to 20000:1.4. The method of claim 1 , wherein the method comprises co-administering of artemisone and brincidofovir claim 1 , and wherein the molar ratio of artemisone to brincidofovir is in the range of from 10:1 to 10:1.5. The method of claim 1 , wherein the method ...

COMPOSITIONS AND METHODS FOR INHIBITING PATHOGEN INFECTION

The presently-disclosed subject matter relates to antibodies, compositions, and methods for inhibiting and treating virus infection in the respiratory tract and virus transmission through the respiratory tract. In particular, the presently-disclosed subject matter relates to inhibiting and treating virus infection in a subject using compositions and antibodies that trap viruses in mucus of the respiratory tract, thereby inhibiting transport of virus across or through mucus secretions. 1. A nebulized solution for treating or preventing Respiratory syncytial virus (RSV) in a subject inhaling the nebulized solution , the nebulized solution comprising a recombinant antibody having a human or humanized Fc region and an oligosaccharide having a glycosylation pattern that enhances the trapping potency of the recombinant antibody in mucus , so that the recombinant antibody binds to the RSV to form an antibody/RSV complex that is trapped in the subject's mucus thereby treating or preventing the infection , wherein the nebulized solution comprises particles having a mass median aerodynamic diameter (MMAD) of between 2-6 μm diameter and a concentration of antibody within the particles of between 10 mg/mL and 100 mg/mL.2. The nebulized solution of claim 1 , wherein the pH of the nebulized solution between about 4.5 to 7.3. The nebulized solution of claim 1 , wherein the pH of the nebulized solution approximately neutral.4. The nebulized solution of claim 1 , wherein the nebulized solution is hypertonic relative to the lungs.5. The nebulized solution of claim 1 , wherein the recombinant antibody comprises an N-linked glycosylation site on the Fc region of the antibodies to which the oligosaccharide is attached.6. The nebulized solution of claim 1 , wherein the glycosylation pattern comprises a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch.7. The nebulized solution of claim 1 , wherein the ...

Teat disinfectant composition

Antimicrobially effective compositions comprising lactic acid, salicylic acid, and at least one anionic surfactant are provided. The compositions are effective in controlling pathogen levels, particularly those commonly found on bovine teats to prevent or reduce the incidence of mastitis in lactating cows. In particular, the compositions possess germicidal and/or yeasticidal characteristics. Methods of using the antimicrobial compositions, as a part of a good milking routine, are also provided in which the compositions are applied to bovine teats.

NOVEL NANOPARTICLES OF ANTIRETROVIRAL DRUGS, THEIR PREPARATION AND THEIR USE FOR THE TREATMENT OF VIRAL INFECTIONS

The present application relates to nanoparticles including an antiretroviral drug and chitosan and optionally one or more metal cation, their use for treating viral infections, their process of preparation and the pharmaceutical compositions including the same. 1. A method for treating and/or preventing HIV and/or the symptoms thereof comprising administering by the sub-cutaneous or intramuscular route a nanoparticle comprising an antiretroviral drug encapsulated by an encapsulation complex , said complex comprising chitosan.2. The method according to wherein the administration comprises administering of said nanoparticle in an aqueous suspension.3. The method according to claim 1 , wherein said antiretroviral drug is chosen from AZT-TP claim 1 , enfuvirtide claim 1 , carbotegravir claim 1 , rilpivirine.4. The method according to where said antiretroviral drug is AZT-TP and said encapsulation complex comprises chitosan and one or more metal cation.5. The method according to where said metal cation is Fe.6. A nanoparticle comprising an antiretroviral drug encapsulated by an encapsulation complex claim 1 , said complex comprising chitosan and Fe.7. The nanoparticle according to where said antiretroviral drug is AZT-TP.8. A nanoparticle comprising enfuvirtide encapsulated by an encapsulation complex comprising chitosan.9. The nanoparticle according to where said metal cation is Fe.10. The nanoparticle according to having a mean diameter (in number or in intensity) of less than 300 nm.11. The nanoparticle according to comprising from 20 to 60% of antiretroviral drug in weight.12. The nanoparticle according to where the maximum ratio of the amount of the antiretroviral drug in the nanoparticle relative to the amount of the chitosan in the nanoparticle is comprised between 0.03 and 0.3.13. The process of preparation of a nanoparticle of comprising mixing a S1 aqueous solution of chitosan with a S2 aqueous solution of said antiretroviral drug.14. A pharmaceutical ...

MODIFIED RNAi AGENTS

One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

HEMATOPOIETIC STEM CELLS IN COMBINATORIAL THERAPY WITH IMMUNE CHECKPOINT INHIBITORS AGAINST CANCER

The novel synergistic combination of immune checkpoint blockade and hematopoietic stem cell transplantation and/or hematopoietic stem cell mobilization yield synergistic effects in disease therapy. 1167.-. (canceled)168. A method for treating a cancer comprising administering to a subject having the cancer one or more immune checkpoint inhibitors , and administering to the subject hematopoietic stem cells , in amounts effective to treat the cancer , wherein the one or more immune checkpoint inhibitors are each an antagonist of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) , and/or B7 family inhibitory ligand B7-H3 , and wherein the source of hematopoietic stem cells is autologous or wherein the source of hematopoietic stem cells is allogenic and the donor cells are HLA-matched to the recipient.169. The method of claim 168 , wherein the cancer is resistant to monotherapy treatment with the one or more immune checkpoint inhibitors.170. The method of claim 168 , wherein the CTLA-4 antagonist is an agent that binds to and antagonizes CTLA-4.171. The method of claim 170 , wherein the agent that binds to and antagonizes CTLA-4 is a peptide that binds CTLA-4 or a humanized antibody that selectively binds CTLA-4.1721. The method of claim claim 170 , wherein the B7-H3 antagonist is an agent that binds to and antagonizes B7-H3.173. The method of claim 172 , wherein the agent that binds to and antagonizes B7-H3 is a peptide that binds B7-H3 or a humanized antibody that selectively binds B7-H3.174. The method of claim 168 , wherein the immune checkpoint inhibitor is administered on the same day or on a different day than the hematopoietic stem cell transplantation.175. The method of claim 168 , wherein the immune checkpoint inhibitor is administered within 3 months of the hematopoietic stem cells.176. The method of claim 168 , wherein the immune checkpoint inhibitor is administered within 1 month of the hematopoietic stem cells.177. The method of claim 168 , wherein the ...

HEMICHANNEL EXTRACELLULAR-DOMAIN SPECIFIC AGENTS FOR TREATING SEPSIS

Methods of treating sepsis or endotoxemia in a subject comprising administering to the subject an amount of an antagonist of a Panx1 hemichannel protein or an amount of an antagonist of a Cx43 hemichannel protein. 1. A method of treating sepsis or endotoxemia in a subject or of reducing or inhibiting development of sepsis in a subject , the method comprising administering to the subject an amount of an antagonist of a Cx43 hemichannel protein or an amount of an antagonist of a Panx1 hemichannel protein sufficient to treat sepsis or endotoxemia , or sufficient to reduce or inhibit development of sepsis.2. The method of claim 1 , wherein the amount of the antagonist of a Cx43 hemichannel protein is administered.3. The method of claim 1 , wherein the amount of the antagonist of a Panx1 hemichannel protein is administered.4. A method of treating sepsis or endotoxemia in a subject or of reducing or inhibiting development of sepsis in a subject claim 1 , the method comprising administering to the subject an amount of an inhibitor of a Cx43 hemichannel protein expression or an amount of an inhibitor of a Panx1 hemichannel protein expression sufficient to treat sepsis or endotoxemia claim 1 , or sufficient to reduce or inhibit development of sepsis.5. The method of claim 4 , wherein the amount of the inhibitor of a Cx43 hemichannel protein expression is administered.6. The method of claim 4 , wherein the amount of the inhibitor of a Panx1 hemichannel protein expression is administered.7. The method of claim 1 , wherein the subject already has sepsis and the method is to treat sepsis in the subject.8. The method of claim 1 , wherein the method is to reduce or inhibit development of sepsis in the subject.9. (canceled)10. The method of claim 1 , wherein the antagonist of a Cx43 hemichannel protein is a peptide antagonist.11. The method of claim 1 , wherein the antagonist of a Panx1 hemichannel protein is a peptide antagonist.12. The method of claim 11 , wherein the peptide ...

MALEATE OF SCY-635 AND USES THEREOF IN MEDICINE

The present invention relates to a salt of a compound of formula (I) and uses thereof in medicine. Specifically, it relates to maleate of compound of formula (I) and pharmaceutically compositions thereof. Furthermore, the invention relates to the uses of maleate herein and pharmaceutically compositions thereof disclosed herein in the manufacture of a medicament, especially in the manufacture of a medicament for preventing, managing, treating or lessening hepatitis C virus (HCV) infection. 2. The salt of claim 1 , wherein a mole ratio of the compound of formula (I) to maleic acid in the maleate of the compound of formula (I) is from 1:0.9 to 1.1.2.3. The salt of claim 1 , wherein a mole ratio of the compound of formula (I) to maleic acid in the maleate of the compound of formula (I) is 1:1.4. A pharmaceutical composition comprising the salt of claim 1 , and a pharmaceutically acceptable excipient.5. (canceled)6. A method of preventing claim 1 , managing claim 1 , treating or lessening chronic hepatitis C and hepatitis C infection claim 1 , comprising administering to a patent in need of such treatment a therapeutically effective amount of the salt of .7. (canceled) None.The present invention belongs to the field of medicine. Specifically, it relates to maleate of (3S,6S,9S,12R,15S,18S,21 S,24S,27R,30S,33 S)-27-((2-(dimethylamino)ethyl)thio)-30-ethyl-33-((1R,2R,E)-1-hydroxy-2-methylhex-4-en-1-yl)-24-(2-hydroxy-2-methylpropyl)-6,9,18-triisobutyl-3,21-diisopropyl-1,4,7,10,12,15,19,25,28-nonamethyl-1,4,7,10,13,16,19,22,25,28,31-undecaazacyc lotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecaone (I) (SCY-635), and pharmaceutically composition thereof. Furthermore, it relates to the uses of salt and pharmaceutically compositions thereof in the manufacture of a medicament, especially in the manufacture of a medicament for preventing, managing, treating or lessening chronic hepatitis C and hepatitis C infection in a patient.SCY-635 (the compound of formula (I)) is a novel ...

VIRAL VACCINES

The present invention relates to a composition for raising an immune response in animal which decreases the risk of chikungunya and smallpox infection, Zika virus and smallpox infection, and/or chikungunya, Zika virus and smallpox infection. The composition comprises a pharmaceutically acceptable carrier and an attenuated poxvirus, wherein the poxvirus genome comprises a nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and/or the PrME of Zika virus. 114-. (canceled)15. An immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus , wherein the attenuated poxvirus genome comprises a nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and a nucleic acid sequence encoding the PrME polyprotein of Zika virus.16. An immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus , wherein the attenuated poxvirus genome comprises a nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and further comprises deletion of a gene encoding an endogenous essential assembly or maturation protein , and/or increases immunogenicity of the composition.17. An immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus , wherein the attenuated poxvirus genome comprises a nucleic acid sequence encoding the PrME polyprotein of Zika virus and further comprises deletion of a gene encoding an endogenous essential assembly or maturation protein , and/or increases immunogenicity of the composition.18. The immunogenic composition of claim 15 , wherein the attenuated poxvirus is selected from the group consisting of Modified Vaccinia Ankara (MVA) claim 15 , NYVAC claim 15 , avipox claim 15 , canarypox and fowlpox.19. The immunogenic composition of claim 15 , wherein the attenuated poxvirus is a modified orthopoxvirus claim 15 , wherein the modification comprises deletion of at least one ...

Cyclic dinucleotides as sting agonists

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein B 2 , X 2 , R 2a , R 2b , R 2c , Z-M-Y, Y 1 -M 1 Z 1 , B 1 , X 1 , R 1a , R 1b , R 1c are as defined herein.

NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF

Disclosed is a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections. 3. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein the compound of Chemical Formula 2 is any one selected from the group consisting of N-benzyl-5-chloro-2 claim 1 ,4-dihydroxybenzamide claim 1 , N-benzyl-5-chloro-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-(4-methoxybenzyl)-N-methylbenzamide claim 1 , 5-chloro-N-(3 claim 1 ,4-dimethoxybenzyl)-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , N-(benzo[d][1 claim 1 ,3]dioxol-5-ylmethyl)-5-chloro-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-methyl-N-(3 claim 1 ,4 claim 1 ,5-trimethoxybenzyl)benzamide claim 1 , 5-chloro-N-(2-chloro-3 claim 1 ,4 claim 1 ,5 -trimethoxy benzyl)-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , N-(2-bromo-3 claim 1 ,4 claim 1 ,5-trimethoxybenzyl)-5 -chloro-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-methyl-N-(3-methylbenzyl)benzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-methyl-N-(2-methylbenzyl)benzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-methyl-N-(4-methylbenzyl)benzamide claim 1 , 5-chloro-2 claim 1 ,4-dihydroxy-N-methyl-N-(4-(methylcarbamoyl)benzyl)benzamide claim 1 , 5-chloro-N-(4-(ethylcarbamoyl)benzyl)-2 claim 1 ,4-dihydroxy-N-methylbenzamide claim 1 , 5-chloro-2 claim 1 ,4- ...

Novel immune stimulating macrolides

The present invention provides immune stimulating macrolides of formula (I), wherein the substituents are as defined in the claims. The macrolides have utility in treating viral diseases and cancer.

Anti-bacterial compositions

Antibacterial compositions comprising at least one unsaturated fatty acid or a pharmaceutically acceptable salt thereof; at least one alpha-hydroxy acid or a pharmaceutically acceptable salt thereof; and at least one amino alcohol. The compositions have broad-spectrum antibacterial activity, including on pathogens displaying multi-drug resistance.

Tam receptors as virus entry cofactors

The present invention concerns the use of an inhibitor of an interaction between phosphatidylserine and a TAM receptor for preventing or treating a virus entry cofactors, in particular phosphatidylserine harboring virus infection such as flavivirus infection.

Formulations of 5-fluorocytosine and uses thereof

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

Lipid Disulfide Prodrugs and Uses Related Thereto

This disclosure relates to lipid disulfide prodrugs and in particular to lipid disulfide phosphodiester nucleosides and derivatives thereof, pharmaceutical compositions, and uses related thereto. According to one embodiment of the disclosure there is provided a compound of Formula I, 2. The compound of claim 1 , wherein W is a nucleoside or nucleobase;3. The compound of claim 1 , wherein T is a Cto Calkyl;4. The compound of claim 1 , wherein Z and Y are each O5. The compound of claim 1 , wherein Ris a Cto Clipid.6. The compound of claim 1 , wherein Ris RSST- claim 1 , hydrogen claim 1 , alkyl claim 1 , aryl or phenyl.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl claim 1 , or alkyl.10. A pharmaceutical composition comprising a compound of or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.11. The pharmaceutical composition of in the form of a tablet claim 10 , capsule claim 10 , pill claim 10 , gel claim 10 , or granules.12. The pharmaceutical composition of in the form of an aerosol claim 10 , aqueous buffer or emulsion.13. The pharmaceutical composition of wherein the compound is in a nanoparticle or a liposome.14. A method of treating or preventing a viral infection comprising administering in effective amount of a compound of to a subject in need thereof.15. The method of wherein the subject is at risk of claim 14 , exhibiting symptoms of claim 14 , suffering from claim 14 , or diagnosed with a viral infection.16. The method of wherein the compound is administered in combination with another the antiviral agent.17. A method of treating cancer comprising administering in effective amount of a compound of to a subject in need thereof.18. The method of wherein the compound in administering in combination with another chemotherapy regimen or anti-cancer agent. This application claims the benefit of U.S. Provisional Application No. 62/532,013 filed Jul. 13, 2017. The entirety of this application is hereby ...

Chimeric nucleic acid molecules with non-aug translation initiation sequences and uses thereof

The present disclosure relates to nucleic acid vaccine compositions and methods for preventing or treating pathological conditions, such as cancer or infectious disease. Further, the disclosure provides methods for more efficient production of antigens via mRNA containing one or more non-conventional start codons to promote multiplex initiation of translation in eukaryotic cells.

Novel prodrugs of nucleoside phosphonates

The present invention relates to novel phosphonoamidate prodrugs. The invention also relates to the use of these novel phosphonate-modified nucleosides to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, particularly infections with viruses such as the herpes simplex virus 1, herpes simplex virus 2, human cytomegalovirus, varicella zoster virus, vaccinia virus and adenovirus.

GLA DOMAINS AS THERAPEUTIC AGENTS

The disclosure relates to the recombinant Gla domain proteins and their use targeting phosphatidylserine (PtdS) moieties on the surface of cells, particularly those expressing elevated levels of PtdS, such as cells undergoing apoptosis. 145-. (canceled)46. A polypeptide for targeting phosphatidylserine cell-surface expression said polypeptide comprising:a protein S gamma-carboxyglutamic-acid (Gla) domain, andan EGF domain,wherein said polypeptide is fused to a proteinaceous sequence; andwherein said polypeptide lacks a protease or hormone-binding domain.47. The polypeptide according to claim 46 , comprising an EGF domain from protein S.48. The polypeptide according to claim 47 , wherein the GLA domain has the sequence shown in SEQ ID NO: 1.49. The polypeptide according to claim 46 , wherein the polypeptide is 300 amino acids or less.50. The polypeptide according to claim 46 , comprising SEQ ID NO: 6 or a derivative differing therefrom only by the absence of the HIS-tag.51. The polypeptide according to claim 50 , comprising SEQ ID NO: 6.52. The polypeptide according to claim 46 , wherein the polypeptide is a genetic fusion.53. The polypeptide according to claim 46 , comprising an Fc region.54. The polypeptide according to claim 53 , wherein the polypeptide is a genetic fusion.55. The polypeptide according to claim 54 , wherein the Fc region is conjugated.56. The polypeptide according to claim 46 , comprising a detectable label.57. The polypeptide according to claim 56 , wherein the detectable label is selected from a fluorescent label claim 56 , a chemiluminescent label claim 56 , a radiolabel claim 56 , an enzyme claim 56 , a dye and a ligand.58. The polypeptide according to claim 56 , wherein the label is conjugated to said polypeptide.59. A pharmaceutical composition comprising a polypeptide of and a pharmaceutically acceptable carrier or aqueous medium. This application is a continuation application of U.S. patent application Ser. No. 16/170,131, filed Oct. 25, ...

Polypeptides, cells, and methods involving engineered cd16

This disclosure describes, generally, a modified form of CD16, genetically-modified cells that express the modified CD16, and methods that involve the genetically-modified cells. The modified form of CD16 can exhibit increased anti-tumor and/or anti-viral activity due, at least in part, to reduced susceptibility to ADAM17-mediated shedding upon NK cell stimulation.

USE OF IMMUNE CHECKPOINT MODULATORS IN COMBINATION WITH ANTIGEN-SPECIFIC T CELLS IN ADOPTIVE IMMUNOTHERAPY

Provided herein are methods of treating a human patient, comprising administering to the human patient an inhibitory immune checkpoint inhibitor or stimulatory immune checkpoint activator and administering to the human patient a population of human cells comprising antigen-specific T cells that are derived from a T cell line restricted by a subdominant HLA allele or HLA allele combination. Also provided are methods of selecting such a T cell line and methods of selecting a T cell donor from whom to derive such a T cell line, for therapeutic administration to a human patient in combination with administration of an inhibitory immune checkpoint inhibitor or stimulatory immune checkpoint activator. Also provided are pharmaceutical compositions comprising an inhibitory immune checkpoint inhibitor or stimulatory immune checkpoint activator and a population of human cells comprising antigen-specific T cells that are derived from a T cell line restricted by a subdominant HLA allele or HLA allele combination. 1. A method of treating a human patient having or suspected of having a pathogen or cancer , comprising:(1) administering to the human patient an inhibitory immune checkpoint inhibitor; and(2) administering to the human patient a population of human cells comprising antigen-specific T cells that are specific for an antigen of the pathogen or cancer and are derived from a T cell line restricted by a first HLA allele or HLA allele combination expressed by the diseased cells in the human patient;wherein the first HLA allele or HLA allele combination is a subdominant HLA allele or HLA allele combination among HLA alleles and HLA allele combinations expressed by the diseased cells with respect to activity of T cells restricted by the respective HLA allele or HLA allele combination based on recognition of the antigen.2. The method of claim 1 , wherein the inhibitory immune checkpoint inhibitor is an inhibitor of Programmed Cell Death 1 (PD1) claim 1 , Programmed Death Ligand ...

Purine nucleoside phosphorylase as enzymatic activator of nucleoside prodrugs

A process for inhibiting a mammalian cancerous cell or virally infected cell includes providing a Trichomonas vaginalis purine nucleoside phosphorylase enzyme or a tail mutant purine nucleoside phosphorylase enzyme in proximity to the mammalian cancerous cell or the virally infected cell and exposing the enzyme to a purine nucleoside phosphorylase enzyme cleavable substrate to yield a cytotoxic purine analog. The process includes introducing to the cell a vector containing the phosphorylase enzyme, or a DNA sequence coding for the same and delivering to the cell an effective amount of the substrate such as 9-(β-D-arabinofuranosyl)-2-fluoroadenine (F-araA).

THERAPEUTIC COMPOSITIONS OF DECANOIC ACID AND ARGININE

Compositions including a complex of fatty acids (e.g., including one or more C4 to C40 fatty acids, such as a C4 to C20 fatty acid) and one or more amino acids (and particularly one or more amino acids having electrically charged basic side chains, e.g., Arginine, Lysine, etc.) for use as an anti-pathogenic composition. In particular, described herein are compositions of decanoic acid: Arginine in which the decanoic acid and Arginine for a complex having a lamellar supramolecular structure. 1. A method of treating a patient to destroy a pathogen using an anti-pathogenic composition , the method comprising: administering to said patient a therapeutically effective amount of the anti-pathogenic composition , the anti-pathogenic composition comprising a mixture of decanoic acid: amino acid in a molar ratio of between about 1:0.6 to about 1:1.6 , wherein the amino acid is one or more of: L-Arginine , Lysine and Histidine.2. The method of claim 1 , wherein the amino acid is L-Arginine.3. The method of claim 1 , wherein the molar ratio of undecylenic acid: amino acid is in an approximately 1:1 molar ratio.4. The method of claim 1 , wherein the molar ratio of undecylenic acid: amino acid is in an approximately 5:4 molar ratio.5. The method of claim 1 , wherein the anti-pathogenic composition is an aqueous composition.6. The method of claim 1 , wherein the therapeutic composition does not include cetyl alcohol.7. The method of claim 1 , wherein the pH of the anti-pathogenic composition is between 6 and 10.8. The method of claim 1 , wherein the pH of the anti-pathogenic composition is between 6.9 and 7.8.9. The method of claim 1 , wherein administering comprises applying the anti-pathogenic composition to the patient's skin.10. The method of claim 1 , wherein administering comprises applying the anti-pathogenic composition to the patient's wound.11. The method of claim 1 , wherein administering comprises applying the anti-pathogenic composition systemically to the patient.12 ...

Attenuated Infectious Bronchitis Virus

The present invention provides a live, attenuated coronavirus comprising a mutation in non-structural protein nsp-3 and/or deletion of accessory proteins 3a and 3b. The coronavirus may be used as a vaccine for treating and/or preventing a disease, such as infectious bronchitis, in a subject. 1. A live , attenuated coronavirus comprising a mutation in non-structural protein nsp-3 and/or deletion of accessory proteins 3a and/or 3b.2. The coronavirus according to wherein the mutation in nsp-3 is in the adenosine diphosphate-ribose-1′-phosphatase (ADRP) region.3. The coronavirus according to claim 1 , wherein the nsp-3 gene encodes a protein comprising one or more amino acid mutations selected from the list of:a) Asn (N) to Ala (A) at position 373 in SEQ ID NO: 6; andb) Gly (G) to Ser (S) at position 379 in SEQ ID NO: 6.4. The coronavirus according to claim 1 , wherein i) the nsp-3 gene encodes a protein comprising the amino acid mutation Asn (N) to Ala (A) at position 373 in SEQ ID NO: 6; orii) the nsp-3 gene encodes a protein comprising the amino acid mutation Gly (G) to Ser (S) at position 379 in SEQ ID NO: 6.5. (canceled)6. The coronavirus according to wherein the nsp-3 gene comprises one or more nucleotide substitutions selected from the list of:a) A to G at nucleotide position 1116 and A to C at nucleotide position 1117 compared to the sequence shown as SEQ ID NO: 5; andb) G to A at nucleotide position 1138 compared to the sequence shown as SEQ ID NO: 5.7. A coronavirus according to comprising a deletion from nucleotide position 37 to 384 of the sequence shown as SEQ ID NO: 2.8. The coronavirus according to which is an infectious bronchitis virus (IBV) claim 1 , optionally wherein the IBV is M41.9. (canceled)10. The coronavirus according to claim 8 , which comprises an S protein wherein at least part of which is from an IBV serotype other than M41.11. The coronavirus according to claim 10 , wherein the S1 subunit is from an IBV serotype other than M41.12. The ...

POLYPEPTIDE TARGETING APTAMERS FOR CHARACTERIZATION, CAPTURE, AND CLINICAL MANAGEMENT OF CIRCULATING TUMOR CELLS

Provided herein are new compositions and methods to target and deliver agents to pathological areas by utilizing multifunctional compounds. These compounds include three or more domains: (i) a vimentin-binding peptide, (ii) a linker, and (iii) a drug binding, a capturing reagent, or a detectable moiety. These compounds can be used to detect, isolate, and/or treat cancerous cells such as circulating tumor cells. 1. A compound comprising:a first domain comprising a vimentin-binding peptide;a second domain comprising a linker; anda third domain selected from the group consisting of a detectable moiety, a capture reagent, and a drug binding domain, wherein the linker links the first domain and the third domain.233-. (canceled)3537-. (canceled)38. A method of detecting cancer , a tumor , or circulating tumor cells (CTSs) in a sample , the method comprising:contacting the sample with a compound, wherein the compound comprises (i) a first domain comprising a vimentin-binding peptide; (ii) a second domain comprising a linker; and (iii) a third domain comprising a detectable moiety; anddetecting the compound, to thereby detect cancer, a tumor, or circulating tumor cells CTCs) in the sample.3946-. (canceled)47. A method of diagnosing cancer in a subject , the method comprising: a first domain comprising a vimentin-binding peptide;', 'a second domain comprising a linker; and', 'a third domain comprising a detectable moiety;, 'contacting a sample with a compound, wherein the compound comprisesdetecting the compound in the sample; anddiagnosing the subject as having cancer when the levels of the compound in the sample are increased when compared to a reference sample.48. A method of determining the stage of a cancer , the method comprising: a first domain comprising a vimentin-binding peptide;', 'a second domain comprising a linker; and', 'a third domain comprising a detectable moiety;, 'contacting a sample with a compound, wherein the compound comprisesdetecting the compound in ...

Liposomes Useful for Drug Delivery

The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.

Decontamination solution and its use for denaturation, modification, degradation, solubilisation and removal of proteins, nucleic acid molecules and microorganisms

The invention concerns a three component system comprising surface-active substances, vitamins and metal ions for efficient destruction and removal of contaminating proteins, nucleic acids and microorganisms from surfaces like for example laboratory benches, floors, equipment and instruments. These non-corrosive and non-toxic solutions for removal of proteins, nucleic acids and microorganisms are applied by spraying, rubbing or immersion of contaminated surfaces thereby destroying, solubilizing inactivating and removing proteins and nucleic acids. In that way also microorganisms are killed with high efficiency and at the same time all genetic information is inactivated.

Antiinfective composition

The present invention relates to the use of hydroxymethyl-group-containing glycosaminoglycans, such as in particular hydroxymethyl-hyaluronic acid, for the treatment and prevention of infectious diseases or malignant or premalignant diseases, in particular of the skin or mucosa. The invention additionally provides a preparation method for glycosaminoglycans modified with hydroxymethyl groups.

METHODS FOR THE TREATMENT OF MYELOID DERIVED SUPPRESSOR CELLS RELATED DISORDERS

The invention features methods of treating disorders related to increased levels of myeloid derived suppressor cells such as cancer or infections. The disclosure also provides methods of treating cancer including combinations of LXRβ agonists and immunotherapies such as PD1 inhibitors, PDL1 inhibitors, and adoptive T-cell transfer therapy. 1. A method of treating cancer in a subject , the method comprising:(a) determining the level of myeloid derived suppressor cells and/or the level of activated T-cells in the subject; and(b) administering an effective amount of an LXRβ agonist to the subject if the level of myeloid derived suppressor cells are greater than a predetermined level and/or the level of activated T-cells is lower than a predetermined level.2. The method of claim 1 , wherein step (b) further comprises administering an immunotherapy to the subject.3. The method of claim 2 , wherein the immunotherapy is administered concurrently with the LXRβ agonist.4. The method of claim 2 , wherein the immunotherapy is administered prior to the LXRβ agonist.5. The method of claim 2 , wherein the immunotherapy is administered subsequently to the LXRβ agonist.6. The method of any one of to claim 2 , wherein the activated T-cells are CD8+ T-cells.7. The method of any one of to claim 2 , wherein the level of myeloid derived suppressor cells and/or the level of activated T-cells is determined in the tumor microenviroment.8. The method of any one of to claim 2 , wherein the level of myeloid derived suppressor cells and/or the level of activated T-cells is determined systemically.9. The method of any one of to claim 2 , wherein the subject has not been previously administered an immunotherapy prior to step (a).10. A method of treating cancer in a subject claim 2 , the method comprising:(a) administering an effective amount of an LXRβ agonist to the subject, without concurrently administering an immunotherapy; and(b) administering an effective amount of an immunotherapy to the ...

BIOPHOTONIC COMPOSITIONS FOR THE TREATMENT OF OTITIS EXTERNA

The present disclosure describes methods and uses of biophotonic compositions which comprise at least one oxidant and at least one chromophore capable of activating the oxidant, in association with a pharmacologically acceptable carrier for the treatment of otitis externa. 1. A method of treating otitis extrena or chronic otitis extrena comprisinga) applying a biophotonic composition to a patient in need thereof, wherein the biophotonic composition comprises at least one oxidant and at least one chromophore capable of activating the oxidant andb) exposing said biophotonic composition to actinic light for a time sufficient for said chromophore to cause activation of said oxidant.25.-. (canceled)6. The method according to claim 1 , wherein the composition is applied to an auricle and/or ear canal of a patient.7. The method according to claim 1 , wherein said biophotonic composition is exposed to actinic light for a period of less than about 5 minutes.8. (canceled)9. The method according to claim 1 , wherein said biophotonic composition is exposed to actinic light for a period of less than about 5 minutes per cmof an area to be treated.10. (canceled)11. (canceled)12. The method according to claim 1 , wherein said actinic light is visible light having a wavelength between about 400 nm and about 700 nm.13. The method according to claim 1 , wherein the oxidant is chosen from hydrogen peroxide claim 1 , carbamide peroxide and benzoyl peroxide.14. The method according to claim 1 , wherein the oxidant is carbamide peroxide.15. The method according to claim 1 , wherein the oxidant is chosen from peroxy acid and an alkali metal percarbonate.16. The method according to claim 1 , wherein the oxidant is present in an amount of from about 1% to about 10% by weight of the total composition.1718.-. (canceled)19. The method according to claim 1 , wherein the composition further comprises at least one healing factor chosen from hyaluronic acid claim 1 , glucosamine and allantoin.20. ...

NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF

The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections. 2. The dihydroxyphenyl-based compound represented by following Chemical Formula 1 claim 1 , a stereoisomer thereof claim 1 , a racemic mixture thereof or a pharmaceutically acceptable salt thereof of claim 1 , wherein the dihydroxyphenyl-based compound is a 2 claim 1 ,4-dihydroxybenzoic acid derivative wherein Ris C1-C4 alkyl claim 1 , Ris phenyl and Ris C1-C4 alkyl in the Chemical Formula 1.4. The method of claim 3 , wherein the dihydroxyphenyl-based compound is a 2 claim 3 ,4-dihydroxybenzoic acid derivative wherein Ris C1-C4 alkyl claim 3 , Ris phenyl and Ris C1-C4 alkyl in the Chemical Formula 1.5. The method of claim 3 , wherein the heat shock protein 90-mediated disease is one or more diseases selected from the group consisting of cancer diseases claim 3 , degenerative neurological diseases and viral infections.6. The method of claim 5 , wherein the cancer is selected from the group consisting of non-small cell lung cancer claim 5 , breast cancer claim 5 , ovarian cancer claim 5 , uterine cancer claim 5 , pancreatic cancer claim 5 , lung cancer claim 5 , gastric cancer claim 5 , liver cancer claim 5 , colon cancer claim 5 , skin cancer claim 5 , head or neck cancer claim 5 , brain cancer claim 5 , laryngeal cancer claim 5 , prostate cancer claim 5 , bladder cancer claim 5 , esophageal cancer claim 5 , ...

Derivatives And Methods Of Treating Hepatitis B Infections

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject. 25-. (canceled)6. The compound of claim 1 , wherein Z is —(CRR).7. The compound of claim 1 , whereinm is 0 or 1;{'sup': '5', 'sub': 1', '6, 'Ris H, —OH, or C-C-alkyl; and'}{'sup': '6', 'sub': 1', '6, 'Ris H or C-C-alkyl.'}8. (canceled)9. (canceled)10. The compound of claim 1 , wherein Ris H claim 1 , C-C-alkyl claim 1 , or C-C-alkyl-OH and Ris H or C-C-alkyl.1113-. (canceled)14. The compound of claim 1 , wherein n is 1.1521-. (canceled)22. The compound of claim 1 , wherein Ris H claim 1 , C-C-alkyl claim 1 , or C-C-alkyl-OH; Ris H or C-C-alkyl; and n is 1.2327-. (canceled)29. The compound of claim 28 , wherein Y is —C(O)—.30. The compound of claim 28 , wherein Ris pyrimidyl claim 28 , pyridyl claim 28 , pyrazolyl claim 28 , thienyl claim 28 , thiazolyl claim 28 , isothiazolyl claim 28 , oxazolyl claim 28 , pyridazinyl claim 28 , pyrazinyl claim 28 , or pyrrolyl claim 28 , any of which are optionally substituted by 1 or 2 groups independently selected from —OH claim 28 , halo claim 28 , C-C-alkyl claim 28 , C-C-haloalkyl claim 28 , —O—C-C-alkyl claim 28 , C-C-alkyl-OH claim 28 , CN claim 28 , and C(O)H.31. (canceled)32. The compound of claim 28 , wherein Ris H claim 28 , C-C-alkyl claim 28 , or C-C-alkyl-OH and Ris H or C-C-alkyl.33. The compound of claim 28 , wherein Ris (CRR)—C-aryl claim 28 , which is optionally substituted with 1 claim 28 , 2 claim 28 , or 3 groups claim 28 , each independently selected from —OH claim 28 , halo claim 28 , CN claim 28 , and C-C-alkyl;{'sup': '8', 'sub': 1', '6, 'Ris H or C-C-alkyl;'}{'sup': '9', 'sub': 1', '6, 'Ris H or C-C-alkyl; and'}p is 0 or 1.34. (canceled)3641-. (canceled)43. (canceled)44. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 ...

TLR7 AGONIST TRIFLUOROACETATE SALT AND CRYSTALLINE FORM B THEREOF, PREPARATION METHODS AND USES

The present invention relates to a trifluoroacetate salt of a TLR7 agonist 2-butoxy-7-(4-(pyrrolidin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (formula I), crystalline form B of the trifluoroacetate salt, methods for preparing the trifluoroacetate salt and crystalline form B, and uses of the trifluoroacetate salt and crystalline form B. 2. The trifluoroacetate of the compound of formula I according to claim 1 , wherein the molar ratio of the compound of formula I to trifluoroacetic acid is 1:0.5˜2 claim 1 , preferably 1:1.4. The crystal form B according to claim 3 , wherein when characterized by DSC claim 3 , the initial temperature is 171.4° C.±5° C. and the peak temperature is 173.4° C.±5° C.5. A crystalline composition claim 3 , comprising crystal form B according to claim 3 , wherein based on the weight of the crystalline composition claim 3 , the crystal form B is 50% or more claim 3 , preferably 80% or more claim 3 , more preferably 90% or more claim 3 , and most preferably 95% or more.6. A pharmaceutical composition claim 1 , comprising the trifluoroacetate of the compound of formula I according to in an effective amount.7. A method for treating Toll-like receptor 7 associated disease claim 1 , comprising administering to a subject in need thereof the trifluoroacetate of the compound of formula I according to .9. The preparing process according to claim 8 , wherein the crystallizing solvent is selected from the group consisting of methanol claim 8 , ethanol claim 8 , propanol claim 8 , isopropanol claim 8 , n-butanol claim 8 , isobutanol claim 8 , tertiary butanol claim 8 , acetone claim 8 , ethyl acetate claim 8 , water and mixed solvent thereof; preferably ethanol.10. A pharmaceutical composition claim 3 , comprising the crystal form B according to in an effective amount.11. A pharmaceutical composition claim 5 , comprising the crystalline composition according to in an effective amount.12. A method for treating Toll-like receptor 7 associated ...

HETEROAROMATIC COMPOUNDS USEFUL IN THERAPY

A compound of formula (I) or a pharmaceutically acceptable salt thereof, useful in therapy, in particular in the treatment of a viral infection or a disease linked to impaired or abnormal autophagy. 2. The compound or pharmaceutically acceptable salt of claim 1 , wherein X is CH.3. The compound or pharmaceutically acceptable salt of claim 1 , wherein Y is N and Z is C.4. The compound or pharmaceutically acceptable salt of claim 1 , wherein Y is C and Z is N.5. The compound or pharmaceutically acceptable salt of claim 1 , wherein X is N.6. The compound or pharmaceutically acceptable salt of claim 1 , wherein ring A is 5- or 6-membered heteroaryl.7. The compound or pharmaceutically acceptable salt of claim 1 , wherein ring A is phenyl or 6-membered heteroaryl.9. The compound or pharmaceutically acceptable salt of claim 8 , wherein Wis N and Wis CR; or Wis CH and Wis CR; or Wis CH and Wis N.10. The compound or pharmaceutically acceptable salt of claim 9 , wherein Wis N and Wis CR; or Wis CH and Wis N.11. A compound according to claim 1 , selected from3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethyl-N-(pyridin-4-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethyl-N-((6-methylpyridin-3-yl)methyl)pyrazolo[1,5-a]pyrimidin-7-amine,3-(1,3-dimethyl-1H-indazol-5-yl)-N-(4-methoxybenzyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine,N-(4-chlorobenzyl)-3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine,3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethyl-N-(4-(methylsulfonyl)benzyl)pyrazolo[1,5-a]pyrimidin-7-amine,4-(((3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)benzenesulfonamide,3-(1,3-dimethyl-1H-indazol-5-yl)-N-((6-methoxypyridin-3-yl)methy)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amine,3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethyl-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,N-(4-(((3-(1,3-dimethyl-1H-indazol-5-yl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl) ...

ARYLNAPHTHALENE COMPOUNDS AS VACUOLAR-ATPASE INHIBITORS AND THE USE THEREOF

Ebola virus and Marburg virus are filoviruses and are responsible for outbreaks that cause up to 90% fatality, including the recent outbreak in West Africa that has resulted in over 11,000 deaths. The present disclosure generally relates to novel arylnaphthalene compounds as a vacuolar-ATPase inhibitor that are useful for the treatment of various viral infections, including those infections caused by filoviruses. Pharmaceutical composition matters and methods of use are within the scope of this invention. 1. (canceled)2. (canceled)5. The compound according to claim 4 , wherein X is 0; B is hydrogen or deuterium.6. (canceled)7. The compound according to claim 4 , wherein X is 0; B is fluorine (F).9. A pharmaceutical composition comprising one or more compounds of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , together with one or more diluents claim 3 , excipients or carriers.10. The compound according to claim 3 , wherein the compound is an antiviral agent.11. The compound according to claim 3 , wherein the compound is an antiviral agent for the treatment of a viral infection by flaviviridae viruses claim 3 , including Dengue virus claim 3 , West Nile virus claim 3 , Yellow fever virus claim 3 , Japanese encephalitis virus claim 3 , Powassan virus claim 3 , Zika virus claim 3 , and Usutu virus; respiratory viruses claim 3 , including MERS coronavirus claim 3 , Influenza A HIN virus claim 3 , Respiratory syncytial virus; Arenaviridae virus claim 3 , including Tacaribe virus claim 3 , Pichinde virus claim 3 , Junin virus claim 3 , Lassa fever virus claim 3 , Lymphocytic Choriomeningitis virus; Filoviridae virus claim 3 , including Ebolavirus claim 3 , Marburgvirus; Togaviridae virus claim 3 , including Venezuelan equine encephalitis virus claim 3 , Eastern equine encephalitis virus claim 3 , Western equine encephalitis virus claim 3 , and Chikungunya virus; Mayarovirus; and Hantavirus.12. A method for treating a patient with a viral infection claim ...

Pharmaceutical compositions of pyridinium and quinolinium derivatives

The present invention relates to pharmaceutical compositions comprising a compound of formula (I) and a cyclodextrin or a liposome, to the process of preparing said compositions and their use for antitumor, antiviral, antiparasitic and antifungal treatment.

Method for producing nk cell-enriched blood preparation

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD3 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.

Oligonucleotide analog and method for treating flavivirus infections

A method of inhibiting replication of a flavivirus in animal cells, and an oligonucleotide compound for use in the method are disclosed. The oligonucleotide analog (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the cells, (iii) contains between 8-40 nucleotide bases, and (iv) has a sequence of at least 8 bases complementary to a region of the virus' positive strand RNA genome that includes at least a portion of SEQ ID NOS:1-4. Exposure of cells infected with a flavivirus to the analog is effective to form within the cells, a heteroduplex structure composed of the virus ssRNA and the oligonucleotide, characterized by a T m of dissociation of at least 45° C., and having disrupted base pairing between the virus's 5′ and 3′ cyclization sequences.

Antiviral epicatechins, epicatechin oligomers, or thiolated epicatechins from theobroma cacao for treatment of genital warts

Epicatechins, Epicatechin Oligomers, or Thiolated Epicatechins are applied (A) directly to a genital wart in the form of a cream, ointment, paste or solution, (B) directly to the genital wart wherein such cream, ointment, paste or solution contains as an additional active ingredient a skin permeabilizing agent, (C) following electrosurgical resection or removal of the genital wart in such form of a cream, ointment, paste or solution, (D) following chemical resection or extirpation of the genital wart in such form, (E) following surgical resection or removal of the genital wart in such form, wherein said Epicatechins, Epicatechin Oligomers, or Thiolated Epicatechins both provide antiviral activity against multiple strains of human pappilomavirus (HPV) and promote healing following resection polymers contained in a vehicle. Disclosed are the compositions, therapeutical kits containing such composition, methods of treatment using such composition, and methods of enhancing the stability of such composition.

ANTI HLA-G SPECIFIC ANTIBODIES

The present invention relates to antibodies, or antigen-binding fragments thereof, directed against human leukocyte antigen-G (HLA-G) protein and raised against an immunogenic peptide derived from the α3 domain of HLA-G protein. The invention further relates to the immunogenic peptide, and methods for producing said anti-HLA-G specific antibodies. 116.-. (canceled)17. A method for treating a cancer in a subject in need thereof , the method comprising administering to the subject an anti-human leukocyte antigen G (HLA-G) antibody or an antigen-binding fragment thereof , wherein the antibody or antigen-binding fragment comprises:(a) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (HC CDR2) of SEQ ID NO: 10, and a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 12; and(b) a light chain variable region (VL), which comprises a light chain complementarity determining region 1 (LC CDR1) of SEQ ID NO: 2, a light chain complementarity determining region 2 (LC CDR2) of sequence KVS and a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 5.18. The method of claim 17 , wherein the VH comprises SEQ ID NO: 64 and the VL comprises SEQ ID NO: 63.19. The method of claim 18 , wherein the antibody is a full-length immunoglobulin G comprising two heavy chains and two light chains.20. The method of claim 17 , wherein the antibody or antigen-binding fragment is humanized or chimeric.21. The method of claim 17 , wherein the VH claim 17 , the VL claim 17 , or both the VH and VL comprise human immunoglobulin framework region sequences.22. The method of claim 17 , wherein the antibody comprises an immunoglobulin constant region.23. The method of claim 17 , wherein the antigen-binding fragment is a Fv claim 17 , a dsFv claim 17 , a scFv claim 17 , a Fab claim 17 , a Fab′ claim 17 , or a F(ab′)2.24. The method of claim 17 ...

Aerosol tyrosine kinase inhibitor compounds and uses thereof

Disclosed herein are formulations of imatinib or a phenylaminopyrimidine derivative compound for aerosolization and use of such formulations for inhaled aerosol administration of imatinib or a phenylaminopyrimidine derivative compound for the prevention or treatment of various fibrotic, carcinogenic, vascular and viral infectious diseases, including diseases associated with the lung, heart, kidney, liver, eye, central nervous system and surgical sites. In some embodiments, formulations and delivery options described herein allow for efficacious local delivery of imatinib or a phenylaminopyrimidine derivative compound or salt thereof. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described. Also included are methods for identifying compounds and indications that may benefit by reformulation and inhalation administration.

TLR7 AGONIST CRYSTALLINE FORM A, PREPARATION METHOD AND USE THEREOF

The present invention relates to crystalline form A of a TLR7 agonist 2-butoxy-7-(4-(pyrrolidin-1-ylmethyl)-benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (formula I), a method for preparing the crystalline form A, and the use thereof. 110.-. (canceled)12. The crystal form A according to claim 11 , wherein the crystal form A is characterized by an X-ray powder diffraction pattern having diffraction peaks (2θ) at 5.5°±0.2° claim 11 , 10.1°±0.2° claim 11 , 13.8°±0.2° claim 11 , 16.4°±0.2° claim 11 , 17.9°±0.2° claim 11 , 19.0°±0.2° claim 11 , 19.7°±0.2° claim 11 , 20.3°±0.2° claim 11 , 21.8°±0.2° claim 11 , 22.1°±0.2° claim 11 , 23.7°±0.2° claim 11 , 24.1°±0.2° claim 11 , 25.5°±0.2° claim 11 , 27.9°±0.2° claim 11 , 32.9°±0.2° claim 11 , and 34.0°±0.2°.13. The crystal form A according to claim 11 , wherein the crystal form A is characterized by an X-ray powder diffraction pattern substantially shown in .14. The crystal form A according to claim 11 , wherein the crystal form A is further characterized by a differential scanning calorimetry thermogram having an initial temperature of 199.0° C.±5° C. and a peak temperature of 200.4° C.±5° C.15. A composition comprising a carrier or excipient and at least 95% w/w of the crystal form A according to claim 11 , based on a total weight of the composition.16. A composition comprising a carrier or excipient and at least 50% w/w of the crystal form A according to claim 11 , based on a total weight of the composition.17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of the crystal form A according to .18. A method for inhibiting toll-like receptor activity in a subject claim 11 , wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of the crystal form A according to .19. The method according to claim 18 , wherein the subject has a viral infection.20. The method according to claim 18 , wherein the ...

Methods and compositions for targeted single-stranded cleavage and targeted integration

Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

ANTIBODIES AGAINST DISEASE CAUSING AGENTS OF CANINES AND FELINES AND USES THEREOF

Described herein are methods and antibodies useful for reducing, eliminating, or preventing infection with a viral population in an animal. Also described herein are antigens useful for targeting by heavy chain antibodies and VHH fragments for reducing a viral population in an animal. 1. A polypeptide comprising at least one variable region fragment of a heavy chain antibody (VH) , wherein the at least one VH specifically binds a parvovirus , wherein the polypeptide: a) prevents red blood cell hemagglutination by canine parvovirus type 2C capsid at a concentration lower than 100 nM; b) prevents red blood cell hemagglutination by canine parvovirus type 2C capsid at a concentration lower than 1 μM; or c) reduces invasion of MDCK cells by canine parvovirus by >50% at 5 μM.24.-. (canceled)5. The polypeptide of claim 1 , wherein the polypeptide comprises a plurality of VHs.68.-. (canceled)9. The polypeptide of claim 1 , wherein the variable region fragment of the heavy chain antibody comprises an amino acid sequence at least 80% identical to any one of SEQ ID NOs: 1 to 18 or 77 to 79.10. The polypeptide of claim 1 , wherein the variable region fragment of the heavy chain antibody comprises a complementarity determining region 1 (CDR1) as set forth in any one of SEQ ID NOs: 19 to 36 or 80 to 82 claim 1 , a complementarity determining region 2 (CDR2) as set forth in any one of SEQ ID NOs: 37 to 54 or 83 to 85 claim 1 , and a complementarity determining region 3 (CDR3) as set forth in any one of SEQ ID NOs: 55 to 72 or 86 to 88.1118.-. (canceled)19. The polypeptide of claim 1 , wherein the VH specifically binds a canine parvovirus virulence factor.20. The polypeptide of claim 1 , wherein the VH specifically binds an antigen or polypeptide at least 80% claim 1 , identical to SEQ IDs NO: 73 or 74 or 75 or 76 or 89.2131.-. (canceled)32. The polypeptide of claim 1 , wherein the parvovirus comprises a swine parvovirus.3346.-. (canceled)47. A method of producing the polypeptide ...

Antimicrobial compositions and uses thereof

In some aspects, provided herein are antimicrobial compositions comprising partially esterified polygalacturonic acid and certain fatty acids (e.g., caprylic acid). In some embodiments, the antimicrobial composition may be administered (e.g., topically or orally) to a subject, such as a human patient to treat an infection (e.g., an infection comprising a biofilm). In some aspects, improved catheters are provided.