N-КОНЦЕВОЕ ПОЛИСИАЛИЛИРОВАНИЕ

Настоящее изобретение относится к новым полисахаридным производным белка, в частности инсулина, где полисахаридом является полисиаловая кислота, содержащая от 20 до 125 единиц сиаловой кислоты, и где, по меньшей мере, 85% производных инсулина модифицированы только на N-конце В-цепи инсулина, а также к способам их получения. Изобретение обеспечивает повышение стабильности, удлинение времени полужизни, снижение иммуногенности инсулина и может найти применение в фармацевтических композициях для лечения диабета. 2 н. и 19 з.п. ф-лы, 3 табл., 15 ил.

ЦИКЛОПЕПТИДЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ИЛИ АКТИВАТОРОВ АНТИОГЕНЕЗА

Изобретение относится к получению новых циклопептидов общей формулы цикло(R1 -Arg-Ile-Lys-Pro-His-R2), выбранных из следующих соединений: P11: цикло(DPhe-Pro-Gln-Ile-Met-Arg-Ile-Lys-Pro-His-Gln-Gly-Gln-His-Ile-Gly-Glu) (SEQ ID NO: 5), P16: цикло (Arg-Ile-Lys-Pro-His-Gln-Gly) (SEQ ID NO: 8), P17: цикло(Pro-Arg-Ile-Lys-Pro-His-Gln-Gly) (SEQ ID NO: 9), P19: цикло(Gln-Ile-Met-Arg-Ile-Lys-Pro-His-Gln-Gly-Gln-His-Ile-Gly-Glu) (SEQ ID NO: 10), P20: цикло(DPhe-Pro-Gln-Ile-Met-Arg-Ile-Lys-Pro-His-Gln-Gly-Gln-His-Ile-Gly) (SEQ ID NO: 11), Р23: цикло (DPhe-Pro-Arg-Ile-Lys-Pro-His-Gln) (SEQ ID NO: 13), P24: цикло (Gly-Arg-Ile-Lys-Pro-His) (SEQ ID NO: 25), a также соединений P11, P20 и Р23, у которых DPhe заменен на DTyr. Циклопептиды применяют в системах для ингибирования ангиогенеза, включающих подложку, к которой присоединены циклопептиды посредством органической ножки, которая может содержать группировку, подверженную расщеплению какой-либо ферментативной системой. 8 н. и 15 з.п. ф-лы, 4 ил., 3 ...

СПОСОБ ВЫДЕЛЕНИЯ И ОЧИСТКИ ЦЕЛЕВОГО БЕЛКА БЕЗ ПРИМЕСИ ПРИОНОВОГО БЕЛКА PrP

Группа изобретений относится к области биохимии. Предложен способ выделения и очистки целевого белка посредством хроматографии, в котором хроматография удаляет или уменьшает содержание прионов (PrP). Осуществляют взаимодействие потенциально PrP-загрязненного образца, содержащего целевой белок, с комбинированным хроматографическим материалом, содержащим лиганд. Лиганд выбирают из положительно заряженного N-бензил-N-метилэтаноламинового лиганда; отрицательно заряженного лиганда 2-(бензоиламино)бутановой кислоты; фенилпропилового лиганда; N-гексилового лиганда; 4-меркаптоэтилпиридинового лиганда; лиганда 3-[{3-метил-5-((тетрагидрофуран-2-илметил)амино)-фенил}амино]бензойной кислоты. Затем создают буферные условия в хроматографических условиях, таких, чтобы целевой белок связывался с комбинированным хроматографическим материалом, а PrPне связывался с комбинированным хроматографическим материалом. Затем элюируют целевой белок. Также предложена фракция фармацевтически применимого целевого белка ...

РАСШИРЕННАЯ АДОПТИВНАЯ КЛЕТОЧНАЯ ТЕРАПИЯ

Настоящее изобретение относится к биотехнологии. В частности, изобретение относится к терапии злокачественных опухолей человека. Более конкретно, настоящее изобретение относится к онколитическим аденовирусным векторам отдельно или вместе с терапевтическими композициями для терапевтического применения и к способам терапии злокачественных опухолей. В одном из аспектов настоящее изобретение относится к отдельному введению адоптивной клеточной терапевтической композиции и онколитических аденовирусных векторов. Кроме того, настоящее изобретение относится к фармацевтическому набору и фармацевтической композиции, в которых используют онколитические аденовирусные векторы. 3 н. и 2 з.п. ф-лы, 51 ил., 15 пр.

Применение рекомбинантного аналога белка человека SLURP-1 совместно с цитостатиками или препаратами ингибиторами протеасом для торможения роста карцином

Изобретение относится к области биотехнологии, конкретно к сочетанному применению препаратов из групп цитостатиков или ингибиторов протеасом с рекомбинантным аналогом белка SLURP-1 с SEQ ID NO:1 для торможения роста карцином, и может быть использовано в медицине. Данный способ позволяет увеличить эффективность действия препаратов из групп цитостатиков и ингибиторов протеасом, а также понизить их концентрации, необходимые для подавления роста опухоли. 2 н.п. ф-лы, 2 ил., 2 пр.

Способ получения рекомбинантного противоопухолевого модифицированного белка DR5-B человека

Изобретение относится к области биотехнологии, конкретно к рекомбинантному получению терапевтических белков, и может быть использовано для получения рекомбинантного противоопухолевого белка DR5-B в Е. coli. Способ предусматривает трансформацию клеток штамма Е. coli SHuffle В полученной рекомбинантной плазмидной ДНК рЕТ-32а без Trx-, His- и S-тагов, кодирующей DR5-B с последующей экспрессией, выделением и очисткой целевого белка. Изобретение позволяет получить модифицированный противоопухолевый белок Манселан на основе мутантного варианта цитокина TRAIL DR5-B с высоким выходом и степенью очистки от низкомолекулярных белковых примесей и бактериальных эндотоксинов. 2 табл., 6 ил., 4 пр.

НОВЫЙ ЛИГАНД РЕЦЕПТОРА ЦИТОКИНА ZCYTOR17

... 1. Выделенный полипептид, содержащий последовательность аминокислотных остатков, которая по меньшей мере на 90% идентична последовательности аминокислотных остатков, выбранных из следующей группы: (а) полипептид, содержащий остатки с 38 (Val) по 152 (Leu), показанные в SEQ ID NO:2; (b) полипептид, содержащий остатки с 27 (Leu) по 164 (Thr), показанные в SEQ ID NO:2; (с) полипептид, содержащий остатки с 24 (Thr) по 164 (Thr), показанные в SEQ ID NO:2; и (d) полипептид, содержащий остатки с 1 (Met) по 164 (Thr), показанные в SEQ ID NO:2. 2. Выделенный полипептид по п.1, где аминокислотные остатки 73, 133 и 147 являются цистеином. 3. Выделенный полипептид по п.1, который связывается с рецептором zcytor17, показанным в SEQ ID NO:5 или SEQ ID NO:71. 4. Выделенный полипептид, содержащий по меньшей мере 14 смежных аминокислотных остатков SEQ ID NO:2 или SEQ ID NO:11. 5. Выделенный полипептид по п.4, где аминокислотные остатки выбраны из следующей группы: (а) аминокислотные остатки 38-52 SEQ ID ...

АКТИВНАЯ ИММУНОТЕРАПИЯ ПРОТИВ АНГИОГЕНЕЗА

... 1. Иммуногенная композиция, содержащая полипептиды VEGFR1 и их фрагменты или кодирующие их олигонуклеотиды, которую вводят в присутствии или в отсутствие фармацевтически приемлемого адъюванта. 2. Композиция по п.1, в которой антиген является аутологичным, гетерологичным или химерным. 3. Композиция по п.1, в которой антиген является мутантом указанной молекулы. 4. Композиция по п.1, в которой иммуноген получен из синтетических, рекомбинантных или естественных источников. 5. Композиция по пп.1-4, в которой иммуноген вводят в виде части плазмидных или вирусных векторов. 6. Композиция по п. 5, в которой адъювант выбирают из группы, состоящей из рекомбинантной частицы ядерного антигена гепатита В, рекомбинантной частицы ядерного антигена гепатита С, белка ОРС, белка KLH, адъюванта Фрейнда или его производных и монтанида ISA 51. 7. Иммуногенная композиция, содержащая полипептиды VEGFR1 и их фрагменты или кодирующие их олигонуклеотиды, которую вводят ковалентно или нековалентно связанной с препаратами ...

МНОГОФУНКЦИОНАЛЬНЫЕ ХИМЕРНЫЕ АГОНИСТЫ ГЕМОПОЭТИЧЕСКИХ РЕЦЕПТОРОВ

... 1. Гемопоэтический белок, содержащий аминокислотную последовательность формулы R1-L1-R2, R2-L1-R1, R1-R2 или R2-R1, причем R1 является полипептидом агониста рецептора фактора стволовых клеток человека, содержащим модифицированную аминокислотную последовательность фактора стволовых клеток, формулы GluGlyIleCysArgAsnArgValThrAsnAsnValLysAspValThrLysLeuValAla 10 20 AsnLeuProLysAspTyrMetIleThrLeuLysTyrValProGlyMetAspValLeuPro 30 40 SerHisCysTrpIleSerGluMetValValGlnLeuSerAspSerLeuThrAspLeuLeu 50 60 AspLysPheSerAsnIleSerGluGlyLeuSerAsnTyrSerIleIleAspLysLeuVal 70 80 AsnIleValAspAspLeuValGluCysValLysGluAsnSerSerLysAspLeuLysLys 90 100 SerPheLysSerProGluProArgLeuPheThrProGluGluPhePheArgIlePheAsn 110 120 ArgSerIleAspAlaPheLysAspPheValValAlaSerGluThrSerAspCysValVal 130 140 SerSerThrLeuSerProGluLysAspSerArgValSerValThrLysProPheMetLeu 150 160 ProProValAlaAla SEQ ID NO:465 165 где 1-23 аминокислоты необязательно удалены с С-конца указанного полипептида агониста рецептора фактора стволовых клеток человека ...

СПОСОБ ПОЛУЧЕНИЯ МОНОМЕРНЫХ И МУЛЬТИМЕРНЫХ МОЛЕКУЛ И ИХ ПРИМЕНЕНИЕ

... 1. Способ получения полипептида, который является биологически активным в виде n-мера, включающий стадии, на которыха) культивируют клетку, содержащую нуклеиновую кислоту, которая кодирует слитый полипептид формулы Iв которойВ обозначает полипептид, который является биологически активным в виде n-мера,FC обозначает полипептид Fc-области тяжелой цепи,CS обозначает сайт расщепления иI обозначает интронную аминокислотную последовательность,в которой n=1 и m=0 или n=0 и m=1,в которой, если n=1, то о=0 или 1, и если о=0, то р=0 или 1, и если о=1, то р=0 и s=0 или 1, и q=0, и t=0, и r=0,в которой, если m=1, то q=0 или 1, и если q=0, то r=0 или 1, и если q=1, то r=0 и t=0 или 1, и о=0, и s=0, и р=0,в которой u=1 или 2,где FC не обладает выраженной способностью связываться с Fc-рецептором,б) выделяют слитый полипептид из клетки или культуральной среды,в) необязательно расщепляют слитый полипептид протеазой,и тем самым получают полипептид, который является биологически активным в виде n-мера и образует ...

МУТАНТНЫЕ АНТИГЕНЫ GAS57 И АНТИТЕЛА ПРОТИВ GAS57

... 1. Выделенное антитело, которое связывается с полипептидом GAS57, содержащим аминокислотную последовательность SEQ ID NO:1, и снижает или ингибирует способность GAS57 дикого типа расщеплять человеческий IL-8.2. Выделенное антитело, полученное способом, включающим иммунизацию животного, не являющегося человеком, полипептидом GAS57 дикого типа, содержащим аминокислотную последовательность SEQ ID NO:1, где указанное антитело связывается с полипептидом GAS57 дикого типа и за счет этого снижает или ингибирует способность GAS57 дикого типа расщеплять человеческий IL-8.3. Выделенное антитело по п.1 или 2, где антитело является поликлональным антителом.4. Выделенное антитело по п.1 или 2, где антитело является моноклональным антителом.5. Выделенное антитело по п.1 или 2, где антитело используется для снижения или ингибирования способности GAS57 дикого типа расщеплять человеческий IL-8 in vitro.6. Композиция, включающая выделенное антитело по п.1 и фармацевтически приемлемый носитель.7. Композиция ...

СПОСОБ ПОВЫШЕНИЯ ЭФФЕКТИВНОСТИ БЕЛКОВ, МОДИФИЦИРУЮЩИХ БИОЛОГИЧЕСКИЙ ОТВЕТ, И ОБРАЗЦОВЫЕ МУТЕИНЫ

... 1. Вариант белка, модифицирующего биологический ответ, в котором валин замещает остаток фенилаланина в связывающем домене цитокина. 2. Вариант белка по п.1, отличающийся тем, что в качестве цитокина используется 4-альфа-спиральный цитокин. 3. Вариант белка по п.2, отличающийся тем, что 4-альфа-спиральный цитокин выбран из группы: CNTF, ЕРО, Flt3L, G-CSF, GM-CSF, GH, IL-2, IL-3, IL-4, IL-5, IL-6, IL-12p35, LPT, LIF, M-CSF, OSM, PL, SCF, TPO, IFN-α2A, IFN-α2B, IFN-β, IFN-γ, IFN-ω и IFN-τ. 4. Вариант белка по п.3, отличающийся тем, что CNTF, ЕРО, Flt3L, G-CSF, GM-CSF, GH, IL-2, IL-3, L4, IL-5, IL-6, IL-12p35, LPT, LIF, M-CSF, OSM, PL, SCF и TPO изменяются замещением валина вместо остатка фенилаланина аминокислотных остатков между позициями 110 и 180. 5. Вариант белка по п.3, отличающийся тем, что IFN-α2A, IFN-α2B, IFN-β, IFN-γ, IFN-ω и IFN-τ изменяются замещением валина вместо остатка фенилаланина аминокислотных остатков между позициями 1 и 50. 6. Вариант белка по п.3, отличающийся тем, что ...

Полиэпитопная противоопухолевая вакцинная конструкция, содержащая эпитопы опухоль-ассоциированных антигенов, фармацевтическая композиция и ее применение для стимуляции специфического противоопухолевого иммунного ответа

ПАРТНЕРЫ ПО СВЯЗЫВАНИЮ LAG-3

НОВЫЙ ВАРИАНТ АЛЬФА-1-АНТИТРИПСИНА, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ

... 1. Вариант альфа-1-антитрипсина, полученный путем замены аминокислоты в определенном сайте между 1-м и 25-м положениями N-конца альфа-1-антитрипсина с целью добавления сайта гликозилирования.2. Вариант альфа-1-антитрипсина по п. 1, отличающийся тем, что вариант альфа-1-антитрипсина имеет от 1 до 3 добавленных к нему сайтов гликозилирования.3. Вариант альфа-1-антитрипсина по п. 1, отличающийся тем, что определенный сайт присутствует между 3-м и 13-м положениями N-конца.4. Вариант альфа-1-антитрипсина по п. 1, отличающийся тем, что определенный сайт присутствует в 9или 12положении N-конца.5. Вариант альфа-1-антитрипсина по п. 1, отличающийся тем, что определенные сайты присутствуют в 4-м и 9-м положениях, 4-м и 12-м положениях или 9-м и 12-м положениях.6. Способ получения варианта альфа-1-антитрипсина, включающий:a) замену аминокислоты в определенном сайте между 1-м и 25-м положениями N-конца альфа-1-антитрипсина с целью добавления сайта гликозилирования;b) культивирование клеток, трансформированных ...

КОМПОЗИЦИИ RON И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

ПЕПТИД, ОБЛАДАЮЩИЙ СПОСОБНОСТЬЮ РЕГЕНЕРИРОВАТЬ КОСТНУЮ ТКАНЬ И СВЯЗЫВАТЬСЯ С АПАТИТОМ

... 1. Пептид, обладающий способностью регенерировать костную ткань и связывающийся с апатитом, в котором, по меньшей мере, один пептид, выбранный из группы, состоящей из аминокислотных последовательностей с SEQ ID NO:1 по SEQ ID NO:35, и по меньшей мере, один пептид, выбранный из группы, состоящей из аминокислотных последовательностей с SEQ ID NO:36 по SEQ ID NO:39, связаны между собой.2. Пептид, обладающий способностью регенерировать костную ткань и связывающийся с апатитом, в котором пептид представлен аминокислотной последовательностью SEQ ID NO:40.3. Материал костного трансплантата, в котором пептид по п.1 или 2 иммобилизован на поверхности апатита.4. Материал костного трансплантата по п.3, в котором апатит выбран из группы, состоящей из полученных из организма костных минералов гидроксилапатита, синтетического гидроксиапатита, карбонатапатита, трикальцийфосфата и монокальцийфосфата.5. Материал костного трансплантата по п.3, в котором содержание пептида составляет 1~100 мг на единицу веса ...

N-КОНЦЕВОЕ ПОЛИСИАЛИЛИРОВАНИЕ

... 1. Композиция, содержащая популяцию полисахаридных производных белка, где белок представляет собой инсулин или подобный инсулину белок, а полисахарид является полисиаловой кислотой и содержит от 20 до 125 единиц сиаловой кислоты, и где популяция состоит в основном только из производных белка, модифицированых на N-конце В-цепи. ! 2. Композиция согласно п.1, где полисиаловая кислота состоит в основном только из единиц сиаловой кислоты. ! 3. Композиция согласно п.1, где инсулин или подобный инсулину белок модифицирован полисахаридом в редуцирующей концевой единице полисахарида. ! 4. Композиция согласно п.2, где полисахаридные производные имеют общую формулу (I): ! ! где ! HNB происходит из B-NH2, что является N-концом В-цепи инсулина или подобного инсулину белка; ! L обозначает связь, соединяющую группу или содержит полипептид или синтетический олигомер; ! GlyO представляет собой единицу сиаловой кислоты; ! причем соединяющая группа, если она присутствует, имеет общую формулу -Y-C(O)-R1-C( ...

БЕЛКИ СЛИЯНИЯ НА ОСНОВЕ OX40L И ПУТИ ИХ ПРИМЕНЕНИЯ

КОМБИНИРОВАННАЯ ТЕРАПИЯ ДЛЯ ЛЕЧЕНИЯ СВЯЗАННЫХ С BCMA РАКОВЫХ ЗАБОЛЕВАНИЙ И АУТОИММУННЫХ РАССТРОЙСТВ

Способ получения гликопротеина

Vaskulärer endothelialer Wachstumsfaktor 2

EIN NEUARTIGES, ANTINEOPLASTISCHES CYTOKIN

VERWENDUNG VON MODIFIZIERTEM C-REAKTIVEN PROTEIN ZUR HERSTELLUNG EINES MEDIKAMENTS ZUR BEHANDLUNG VON KREBS

VERFAHREN ZUR HERSTELLUNG REKOMBINANTER, BIOLOGISCH AKTIVER POLYPEPTIDE

REGULIERUNG DER SYSTEMISCHEN IMMUNANTWORTEN MITTELS ZYTOKINEN UND ANTIGENEN

HYBRIDE CYTOKINE

Vakzin gegen Neisseria meningitidis Gruppe-B, Gammaglobulin und Transferfaktor.

LYMPHOKIN, DESSEN HERSTELLUNG UND VERWENDUNGEN.

LYMPHOKIN, DESSEN HERSTELLUNG UND VERWENDUNGEN.

KULTUR DES WACHSTUMSFAKTORS DER VASKULAREN ENDOTHELIALZELLEN UND DNS, DIE DAFÜR KODIERT

EXPRESSIONSVEKTOREN UND ZELLINIEN ZUR EXPRESSION VON VASKULÄREM WACHSTUMSFAKTOR D, SOWIE VERFAHREN ZUR BEHANDLUNG VON MELANOMEN

DIE FREISETZUNG DES HISTAMIN HEMMENDEN FAKTORS SOWIE DIESEN ENTHALTENDE PRÄPARATE

ZU VEGF UND BMP1 HOMOLOGE POLYPEPTIDE

VEGF-C-REZEPTORLIGAND

VERFAHREN ZUR HERSTELLUNG PERMANENTER TIERISCHER UND HUMANER ZELLINIEN UND DEREN VERWENDUNG

Zusammensetzungen und Verfahren zur Krebsbehandlung durch die selektive Hemmung von VEGF

MATERIAL UND VERFAHREN DIE HYBRIDVASKULARENDOTHELWACHSTUMFAKTOREN DNS UND PROTEINE ENTHALTEN UND SCREENINGVERFAHREN FÜR MODULATOREN

MEDIZINISCHE VERWENDUNG VON STAMMZELLEN, DIE VEGFR-1 EXPRIMIEREN

VASKULÄRER ENDOTHELIALER WACHSTUMSFAKTOR X

Cytokine variant polypeptides

LYMPHOKINE, MONOCLONAL ANTIBODY SPECIFIC TO THE LYMPHOKINE, AND THEIR PRODUCTION AND USES

A lymphokine (LK 2), the monoclonal antibody specific to the lymphokine, and their production and uses are disclosed. The lymphokine is a glycoprotein with a molecular weight of 20,000+/-2,000 daltons; isoelectric point pi, 6.2+/-0.3; electrophoretic mobility Rf, 0.29+/-0.02; cytotoxic on L 929 cell; and cytostatic on KB cell. The lymphokine significantly inhibits the growth of malignant human tumours in vivo. The monoclonal antibody is of IgM or IgG class, and neutralizes specifically the cytotoxic activity of the lymphokine.

Regulation of endogenous gene expression in cells using zinc finger proteins

Proteins and methods for their production.

Amphiregulin, a cell growth regulatory factor which demonstrates unusual bifunctional cell growth regulatory activity is described, including the A431 epidermoid corcinoma cell, Amphiregulin inhibits the growth of neoplastic cells line, yet augments the growth of certain normal cells including humanfibroblasts. Amphiregulin is an extremely hydrophilic glycoprotein having a median molecular weight of 22,500 daltons which occurs in two distinct yet functionally equivalent forms, a truncated form and a larger form. Except for the additional six N-terminal residues found in the larger form, the two forms are perfectly homologous at the amino acid level (Fig. 12, not shown). The glycoprotein is released by TPA-treated MCF-7 cells. There is described by way of examples in which Amphiregulin is identified, purified to homogenity, and thoroughly characterized structurally and functionally. On other examples, the isolation and sequencing of both cDNA and genomic clones encoding the Amphiregulin ...

Preparation of antibodies to protein secreted by murine erythroleukaemia (MEL) cells

Protein

Process and system for producing biological materials from encapsulated cells

Cells (10) which produce a substance of interest are encapsulated within semipermeable membranes (12) having an upper limit of permeability sufficient to allow traverse of ions, amino acids and other cell nutrients (20) and then suspended in a culture medium containing these nutrients. Serum components (18) or other high molecular weight materials needed for ongoing viability and normal in vitro metabolism of certain types of cells may be included within the intracapsular volume and may be excluded from the extracapsular medium by limiting the permeability of the membranes (12). The substance of interest (22) to be harvested collects either in the intracapsular volume or the extracapsular medium, depending on the degree of permeability of the membranes and the molecular size of the substance.

Process for producing human immune response suppressor

A process for producing human immune Response Suppressor (hIRS) which comprises in vivo multiplication of human cells capable of producing hIRS, and in vitro production of hIRS with the human cells thus obtained.

Novel proteins

Regulation of endogenous gene expression in cells using zinc finger proteins

Modified human growth hormone polypeptides and their uses

Polypeptides, polynucleotides and uses thereof

Compositions of protein complexes and methods of use thereof

Provided herein are protein complexes comprising a sensor domain and a therapeutic domain linked by a linker, and methods of use thereof. In aspects of the present disclosure, activity of the therapeutic domain comprises a dependence on sensor domain binding to target markers.

Hiv resistance genes

Vascular endothelial cell growth factor antagonists

New polypeptides, their process of obtaining, monoclonal antibodies specific for these polypeptides, and use of these polypeptides.

Hiv resistance genes

HUMAN ALPHA ENDOKIN

GAG-BINDUNGSPROTEINE

ANTI- OSTEOPONTIN MORE ANTIKÖRPER AND ITS USE

TREATMENT OF FIBROSEN

SCREENINGVERFAHREN FOR SUITABLE ACTIVE SUBSTANCES

THERAPEUTIC USES OF IL-17 HOMOLOGOUS POLYPEPTIDE

COMPOSITIONS FOR THE TREATMENT OF VASCULAR INJURIES

EXPRESSION HETEROLOGER PROTEINS

FOR THE SMOOTH MUSCLE OF ARTERIEN AND THE SMOOTH MUSCLE OF VENEN SPECIFIC PROTEINS AND THEIR USE

WAS BASED GENE THERAPY FOR THE LUNG SYSTEM

VERFAHREN ZUR HERSTELLUNG EINES NEUEN LYMPHOKINS (LK 2) SOWIE VERWENDUNG VON LK 2 ZUR HERSTELLUNG EINES PHARMAZEUTISCHEN PRAEPARATES

SYNTHETIC ONE MIMETIKA OF PHYSIOLOGICAL CONNECTION MOLECULES

EXPRESS ION VECTORS AND ZELLINIEN TO EXPRESSION OF VASCULAR GROWTH FACTOR THE D, AS WELL AS PROCEDURE FOR THE TREATMENT OF MELANOMEN

NEUTROKIN ALPHA

NEW POLY (ETHYLENGLYCOL) MODIFIED ERYTHROPOIETINAGONISTEN AND THEIR USES

THAT SHIGA SIMILAR TOXIN ABSTENTION, REKOMBINANTE PROTEINS AND VASCULAR ONE, ENDOTHELIUM-SPECIFIC GROWTH FACTOR FRAGMENTS

MODIFIED VEGF AND PDGF WITH IMPROVED ANGIOGENIC CHARACTERISTICS

MULTI-FUNCTIONAL CYTOKINE

IMMUNE-SPECIFICALLY BINDING ANTIBODIES AGAINST BLYS

FUSION OF PEPTIDEN AND PROTEINS WITH THIOREDOXIN AND THIOREDOXIN SIMILAR MOLECULES

GENETICALLY PROCEDURE FOR THE PRODUCTION OF THESE CELLS AND YOUR USES CHANGED DENDRITI CELLS, WHICH WERE TRANSDUCED WITH ADENO ASSOCIATED VIRUS,

NUCLEIC ACID MOLECULES THE T-CELLS IF CODING (TIF) ISOLATED INDUCE-CASH FACTORS, PROTEINS AND YOUR APPLICATION CODED

ARTIFICIAL, VASCULAR TRANSPLANT AS WELL AS PROCEDURE FOR ITS PRODUCTION AND ITS USE

ZYTOKIN LIGAND FOR THE TREATMENT OF ASTHMA AND BREATH WAY OVER REACTIVITY

PROCEDURES FOR THE PRODUCTION OF A N-TERMINAL MODIFIED CHEMO+TACTICAL FACTOR

VERFAHREN ZUR GEWINNUNG EINES (GLYKOPROTEIDS AUS MENSCHLICHEM URIN)

HETEROLOGES POLYPEPTID OF THE TNF FAMILY

USE OF VEGF 165 AND HOMOLOGOUS ONES FOR THE TREATMENT OF NEUROLOGICAL DISTURBANCES

PRODUCTION OF AMPHIREGULIN BY GENETIC PROCEDURES

ARAB MORE PROMOTER AND PROCEDURES FOR THE PRODUCTION OF POLYPEPTIDEN INCLUDING CECROPINEN OF MEANS OF MICRO-BIOLOGICAL PROCEDURES

NEW IMMUNOREGULATORI PROTEIN LST-1

MPL LIGAND ANALOGUES

DERIVATIVES OF THE GROWTH HORMONE AND USED PROTEINS

PROTEOLYSERESISTENTER ACTIVE VEGF

USE OF A VGEFMUTANTS TO ANTI-ANGIOGENIC THERAPY

ACTIVATED COLLAGEN GERÜSTMATERIALIEN AND YOUR SPECIAL CONDENSED ACTIVE ONES RESTORATIONSFAKTOREN

CYTOKINE

REKOMBINANTER NATURAL KILLER CELL ACTIVATOR.

Novel uses of vegfxxxb

The invention provides VEGF xxx b, or an agent which selectively promotes the expression of VEGF xxx b in preference to VEGF xxx in cells of a subject or in vitro, or an expression vector system which causes the expression of the VEGF xxx b in a host organism, for use in treating or preventing microvascular hyperpermeability disorders, or in regulating the pro-angiogenic pro-permeability properties of VEGF xxx isoforms, or in supporting epithelial cell survival without increased permeability, or in reducing the nature (for example the number density and/or size) of fenestrations of epithelial filtration membranes in vivo or in vitro.

Cell lines producing blocking antibodies to human RANKL

Described herein are cell lines and methods for preparing antibodies that bind RANKL, including cell lines that produce blocking antibodies to human RANKL.

Compositions and methods for the treatment of immune related diseases

The present invention relates to compositions containing novel proteins and methods of using those compositions for the diagnosis and treatment of immune related diseases.

TNF-alpha Antagonists Containing IGFBP5

The present invention relates to: TNF-α antagonists containing IGFBP5 protein, variants thereof, or fragments thereof; and the use of the TNF-α antagonists. More specifically, the present invention relates to: a polynucleotide encoding the protein, variants thereof, or fragments thereof; a vector containing the polynucleotide; a transformant containing the vector; and a method for screening a therapeutic agent for TNF-α overexpression-related diseases by checking whether the mutual reaction thereof is facilitated after treating with candidates to the cell expressing the IGFBP5 protein, variants thereof, or fragments thereof, and the TNER1.

Modified vegf-a with improved angiogenic properties

The present invention is directed to methods and compositions for making and using chimeric polypeptides that comprise a VEGFR-2 ligand. The chimeric molecules of the present invention retain VEGFR-2 binding activity and an enhanced angiogenic activity as compared to native VEGF-A.

Antibodies that immunospecifically bind to b lymphocyte stimulator protein

The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

Therapeutic regimen for treating cancer

The invention provides a method for treating locally advanced resectable esophageal cancer in a human comprising (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-α and operably linked to a promoter, wherein the dose comprises about 4×10 7 to about 4×10 12 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, and (c) administering a dose of one or more chemotherapeutics to the human over the duration of the therapeutic period, whereby the locally advanced resectable esophageal cancer in the human is treated.

Il-17 homologous polypeptides and therapeutic uses thereof

The present invention is directed to novel polypeptides having sequence identity with IL-17 and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders.

Strongly inactivated and still highly immunogenic vaccine and process of manufacturing thereof

An immunogenic product includes TNFα coupled with KLH, wherein the TNFα is strongly inactivated, which means that the product shows less than 30% of cytolytic activity and/or an inactivation factor of more than 15000, in the conditions of TEST A. An emulsion and a vaccine including the immunogenic product and methods for preparing the immunogenic product are also described.

Non-pathogenic and/or attenuated bacteria capable of inducing apoptosis in macrophages, process of manufacturing and uses thereof

The invention relates to an non-pathogenic and/or attenuated bacterium which is capable of inducing apoptosis in macrophages.

Cysteine variants of interleukin-11 and methods of use thereof

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.

Novel Antimicrobial Activity of Chicken NK-2 Peptide Against Apicomplexan Protozoa

NK-2 synthetic peptide derived from cationic core region of porcine NK-lysin has an antimicrobial and antitumor polypeptide that is considered to play a pivotal role in innate defense immunity. To evaluate the antimicrobial properties of synthetic chicken NK-lysin peptides, we investigated cytolytic activity against apicomplexan parasites like Eimeria sporozoites, Neospora tachyzoites and Cryptosporidum sporozoites. The chicken NK-2 (cNK-2) lytic peptide which corresponds to amino acid residues of porcine NK-2 peptide significantly disrupted Eimeria and Cryptosporidum sporozoites and Neospora tachyzoites. In contrast, no bactericidal activity was observed on E. coli BMH71-18. The cNK-2 lytic peptide is novel antimicrobial agent which can be used to intervene and treat economically costly infections in the animal industry.

Expression Vectors and Cell Lines Expressing Vascular Endothelial Growth Factor D, and Method of Treating Melanomas

This invention relates to expression vectors comprising VEGF-D and its biologically active derivatives, cell lines stably expressing VEGF-D and its biologically active derivatives, and to a method of making a polypeptide using these expression vectors and host cells. The invention also relates to a method for treating and alleviating melanomas or tumors expressing VEGF-D and various diseases.

Nucleic acid sequences encoding and compositions comprising ige signal peptide and/or il-15 and methods for using the same

Fusion proteins and nucleic acid molecules encoding fusion proteins are disclosed. Fusion proteins comprising non-IL-15 signal peptide linked to IL-15 protein sequences and fusion proteins comprising an IgE signal peptide linked to non-IgE protein sequences are disclosed. Vectors comprising such nucleic acid molecules; and to host cells comprising such vectors are disclosed as well as recombinant vaccines and live attenuated pathogens encoding fusion proteins, and methods of using the same, are disclosed. The immunomodulatory effect following delivery of IL-15 and CD40L, with or without immunogens, is disclosed as are various nucleic acid molecules and compositions thereof used for delivering such proteins and methods of using such compositions.

SDF-1 Delivery For Treating Ischemic Tissue

A method of treating a cardiomyopathy in a subject includes administering directly to or expressing locally in a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject an amount of SDF-1 effective to cause functional improvement in at least one of the following parameters: left ventricular volume, left ventricular area, left ventricular dimension, cardiac function, 6-minute walk test, or New York Heart Association (NYHA) functional classification.

Production of Therapeutic Proteins in Photosynthetic Organisms

The present disclosure relates to methods of expressing therapeutic proteins in photosynthetic organisms and the therapeutic proteins produced by the methods. The therapeutic proteins include high-mobility group box 1 (HMGB1) protein, fibronectin domain (10) (10FN3), fibronectin domain (14) (14FN3), interferon beta (IFNβ), proinsulin and vascular endothelial growth factor (VEGF). The photosynthetic organisms include prokaryotes such as cyanobacteria and eukaryotes such as alga and plants. Transformation of eukaryotes is preferably the plastid genome, more preferably the chloroplast genome.

Antibody Fusion Proteins with Disrupted Heparin-Binding Activity

Disclosed herein are polypeptides which comprise all or part of an antibody linked to all or part of a cytokine. The cytokine sequences of the polypeptides have a modified heparin binding region which disrupts, inhibits, or reduces the ability of the cytokine to bind a heparin compound as compared to a corresponding cytokine having an unmodified heparin binding region. Also disclosed are methods of treating cancer, inducing cell proliferation, and reducing the non-specific binding and/or non-specific localization of the polypeptides.

Peptides for active anti-cytokine immunization

Peptide of a size comprised between 5 and 40 amino acids, originating from a cytokine, in which at least one of its amino acids comprises at least one of its atoms separated by a distance d of less than 5 angströms from an atom of the receptor corresponding to said cytokine, the spacing d being evaluated on the basis of structural data, derivatives, immunogenic compounds comprising them, use of a peptide or peptide derivative or immunogenic compound for the preparation of a curative or preventative medicament intended for the treatment or prevention of diseases linked to an excess or to the presence of cytokines or for the treatment of an auto-immune disease and pharmaceutical compositions which contain at least one abovementioned peptide or peptide derivative or immunogenic compound as active ingredient.

Method and system to remove soluble tnfr1, tnfr2 and il2 in patients

A method, and system, to induce remission in diseases characterized by excess production of sTNR and interleukin 2 has been developed. In the most preferred embodiment, the system consists of antibodies to sTNFR1, sTNFR2 and sIL2R immobilized in a column containing a material such as SEPHAROSE™. The patient is connected to a pheresis machine which separates the blood into the plasma and red cells, and the plasma is circulated through the column until the desired reduction in levels of sTNFR1, sTNFR2, and IL2 is achieved, preferably to less than normal levels. In the preferred method, patients are treated three times a week for four weeks. This process can be repeated after a period of time. Clinical studies showed reduction in tumor burden in patients having failed conventional chemotherapy and radiation treatments.

Methods of identifying obm modulators

Novel proteins and polypeptides binding to osteoclastogenesis inhibitory factor (OCIF) (OCIF-binding molecules, OBMs) and nucleic acids encoding these proteins and polypeptides are provided. Processes for producing these proteins, polypeptides, and nucleic acid molecules by genetic engineering are provided. Medicinal compounds are provided which comprise proteins and nucleic acids according to the invention, as well as proteins which bind to OBM, including anti-OBM antibodies. These compounds may be used for the treatment of bone disease.

Genetically modified mice and engraftment

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

ANTAGONISTS OF LIGANDS AND USES THEREOF

The invention provides multivalent ligand binding agents (traps) for members of the TGF-β superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-β superfamily, the agent having the general structure I: 2. The agent of wherein the member of the TGF-β superfamily to which the binding domains have affinity is selected from the group consisting of: TGF-β1 claim 1 , TGF-β2 claim 1 , TGF-β3 claim 1 , activin βA claim 1 , activin βB claim 1 , activin βC claim 1 , activin βE claim 1 , bone morphogenic protein (BMP) 2 claim 1 , BMP 3 claim 1 , BMP4 claim 1 , BMP 5 claim 1 , BMP 6 claim 1 , BMP 7 claim 1 , BMP 8 claim 1 , BMP 9 claim 1 , BMP 10 claim 1 , BMP 11 claim 1 , BMP 12 claim 1 , BMP 13 claim 1 , BMP 14 claim 1 , BMP 15 claim 1 , growth differentiation factor (GDF) 1 claim 1 , GDF 3 claim 1 , GDF 8 claim 1 , GDF 9 claim 1 , GDF 15 claim 1 , Nodal claim 1 , Inhibin a claim 1 , anti-Mullerian Hormone claim 1 , Lefty 1 claim 1 , Lefty 2 claim 1 , arteman claim 1 , Persephin and Neurturin.3. The agent of wherein the member of the TGF-β superfamily to which the binding domains have affinity is selected from the group consisting of: TGF-β1 claim 2 , TGF-β2 claim 2 , TGF-β3 claim 2 , BMP2 claim 2 , GDF 8 claim 2 , and activin.4. The agent of wherein each linker is between 25 and 60 amino acids in length.5. The agent of wherein bd4 is the same as bd1 claim 1 , bd2 is the same as bd3 claim 1 , h>0 claim 1 , and d claim 1 , f claim 1 , m claim 1 , and n=1.6. (canceled)7. The agent of wherein one of the linkers comprises SEQ ID NO: 37 claim 1 , SEQ ID NO: 38 claim 1 , SEQ ID NO: 39 claim 1 , SEQ ID NO: 40 or SEQ ID NO: 51 and the other linkers comprise one or more of SEQ ...

METHOD OF IMPROVING EFFICACY OF BIOLOGICAL RESPONSE-MODIFYING PROTEINS AND THE EXEMPLARY MUTEINS

Disclosed is a protein variant which substitutes valine for phenylalanine residue in a binding domain having a biological response-modifying function by binding to a receptor, ligand or substrate. Also, the present invention discloses a DNA encoding the protein variant, a recombinant expression vector to which the DNA is operably linked, a host cell transformed or transfected with the recombinant expression vector, and a method of preparing the protein variant comprising cultivating the host cell and isolating the protein variant from the resulting culture. Further, the present invention discloses a pharmaceutical composition comprising the protein variant and a pharmaceutically acceptable carrier. 19-. (canceled)10. A protein variant , wherein a valine residue replaces a phenylalanine residue in a binding domain of a protein having a biological response-modifying function when bound to a receptor , ligand , or substrate.11. The protein variant according to claim 10 , wherein the protein is a cytokine.12. The protein variant according to claim 11 , wherein the cytokine is a 4-alpha helix bundle cytokine.13. The protein variant according to claim 12 , wherein the 4-alpha helix bundle cytokine is selected from the group consisting of CNTF claim 12 , EPO claim 12 , Flt3L claim 12 , G-CSF claim 12 , GM-CSF claim 12 , GH claim 12 , IL-2 claim 12 , IL-3 claim 12 , IL-4 claim 12 , IL-5 claim 12 , IL-6 claim 12 , IL-12p35 claim 12 , LPT claim 12 , LIF claim 12 , M-CSF claim 12 , OSM claim 12 , PL claim 12 , SCF claim 12 , TPO claim 12 , IFN-α2A claim 12 , IFN-α2B claim 12 , IFN-β claim 12 , IFN-γ claim 12 , IFN-ω claim 12 , and IFN-τ.14. The protein variant according to claim 13 , wherein the 4-alpha helix bundle cytokine is CNTF claim 13 , EPO claim 13 , Flt3L claim 13 , G-CSF claim 13 , GM-CSF claim 13 , GH claim 13 , IL-2 claim 13 , IL-3 claim 13 , IL-4 claim 13 , IL-5 claim 13 , IL-6 claim 13 , IL-12p35 claim 13 , LPT claim 13 , LIF claim 13 , M-CSF claim 13 , OSM claim ...

Recombinant production of authentic human proteins using human cell expression systems

The present invention relates to novel expression cassettes and vectors for efficiently producing authentic recombinant human proteins from stable cultures of novel human cell lines, the authentic recombinant proteins produced therefrom, and antibodies raised against those authentic recombinant proteins.

LIGHT TARGETING MOLECULES AND USES THEREOF

LIGHT-targeting molecules (e.g., LIGHT fusion molecules), compositions, e.g., pharmaceutical compositions thereof, are disclosed. Methods of using these molecules to treat, prevent and/or diagnose hyperproliferative, e.g., neoplastic, diseases or conditions, including, but not limited to, cancer and metastasis are also provided. 1. A LIGHT-targeting molecule , comprising at least one extracellular domain of a human LIGHT protein or fragment thereof , and a targeting antibody molecule that binds to a surface protein on a cancer cell or tissue , said LIGHT-targeting molecule comprising a linker connecting the at least one extracellular domain with the targeting antibody molecule , wherein said linker is chosen from one or more of:(i) a linker comprising one or more protease sensitive sites of human LIGHT, e.g., a linker comprising one or more of amino acids 81-84 (EQLI), 85-88 (QERR), or both, of human LIGHT isoform 1 (SEQ ID NO:1);(ii) a linker comprising amino acids 65-92, 70-92, 71-92, 72-92, 73-92, 74-92, 75-92, 76-92, 77-92, 78-92, 79-92, 80-92, of human LIGHT isoform 1 (SEQ ID NO:1), or a fragment or variant thereof, wherein said fragment or variant comprises a protease sensitive site comprising one or more of amino acids 81-84 (EQLI);(iii) a linker comprising amino acids 76 to 92 of human LIGHT isoform 1 (SEQ ID NO:1), or a fragment or variant thereof, comprising 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6 amino acids, wherein said fragment or variant comprises a protease sensitive site comprising one or more of amino acids 81-84 (EQLI);(iv) a linker comprising amino acids a human LIGHT extracellular domain fragment having one or more mutations (e.g., one or more deletions, insertions or substitutions), in amino acids 85-88 (QERR) of human LIGHT isoform 1 (SEQ ID NO:1);(v) a linker comprising one or more glycosylation sites having the glycosylation consensus sequence NXS, where X can be any amino acid;{'sub': '4', '(vi) a linker comprising one, two, three, four or ...

APO-2 LIGAND VARIANTS AND USES THEREOF

The disclosure provides Apo-2 ligand variant polypeptides. Methods of making and chemically modifying Apo-2 ligand variant polypeptides are also provided. In addition, formulations of Apo-2 ligand variant polypeptides are provided. 1. An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide sequence of (SEQ ID NO:1) and has one or more of the following amino acid substitutions at the residue position(s) in (SEQ ID NO:1): S96C; S101C; S111C; V114C; R115C; E116C; N134C; N140C; E144C; N152C; S153C; R170C; R170K; R170S; K179C; D234C; E249C; R255C; E263C; H264C.2. An isolated nucleic acid comprising a nucleotide sequence encoding the Apo-2 ligand variant of .3. A vector comprising the nucleic acid of .4. A host cell comprising the vector of .5E. coli. The host cell of wherein said host cell is claim 4 , a yeast cell or CHO cell.6. A method of making Apo-2 ligand variant polypeptide claim 4 , comprising the steps of: providing a host cell comprising the vector of ; (b) providing culture media; (c) culturing the host cell in the culture media under conditions sufficient to express the Apo-2 ligand variant polypeptide; (d) recovering the Apo-2 ligand variant polypeptide from the host cell or culture media; and (e) purifying the Apo-2 ligand variant polypeptide.7. The Apo-2 ligand variant polypeptide of claim 1 , wherein the Apo-2 ligand variant polypeptide is conjugated or linked to one or more polyol groups that increase the actual molecular weight of the Apo-2 ligand variant polypeptide.8. The Apo-2 ligand variant polypeptide of claim 1 , wherein the Apo-2 ligand variant polypeptide is conjugated or linked to one or more polyol groups that increase the in vivo half-life of the Apo-2 ligand variant polypeptide.9. The Apo-2 ligand variant polypeptide of claim 7 , wherein the one or more polyol groups is poly(ethylene glycol).10. The Apo-2 ligand variant polypeptide of claim 9 , where the ...

Derivatisation of erythropoietin (epo)

The present invention relates to a compound which is a polysaccharide derivative of EPO, or of an EPO like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.

Zcytor17 heterodimeric cytokine receptor polynucleotides

Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytor17-containing multimeric or heterodimer cytokine receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. The present invention also includes methods for producing the multimeric or heterodimeric cytokine receptor, uses therefor and antibodies thereto.

GLYCOSAMINOGLYCAN-ANTAGONISING MCP-1 MUTANTS AND METHODS OF USING SAME

Novel mutants of human monocyte chemoattractant protein 1 (MCP-1) with increased glycosaminoglycan (GAG) binding affinity and knocked-out or reduced GPCR activity compared to wild type MCP-1, and their use for therapeutic treatment of inflammatory diseases. 1. An MCP1 mutant protein with increased GAG binding affinity and reduced GPCR activity compared to wild type MCP-1 protein , wherein the MCP-1 protein is modified in a structure-conserving way by insertion of at least one basic and/or electron donating amino acid or replacement of at least two amino acids by at least two basic and/or electron donating amino acids.2. The MCP-1 mutant protein of claim 1 , wherein at least one amino acid of the first 10 amino acids of the N-terminal region of the wild type MCP-1 protein is modified by addition claim 1 , deletion and/or replacement of at least one amino acid.3. The MCP-1 mutant protein of claim 1 , wherein the amino acids that are replaced by the at least two basic and/or electron donating amino acids are non-basic amino acids.4. The MCP-1 mutant protein of claim 1 , wherein the modification in a structure-conserving way is a deviation of the modified structure from wild type MCP1 structure of less than 30% claim 1 , and preferably less than 20% as measured by far-UV CD spectroscopy.5. The MCP-1 mutant protein of claim 1 , wherein the basic amino acids are selected from the group consisting of R claim 1 , K claim 1 , and H.6. The MCP-1 mutant protein of claim 1 , wherein the electron donating amino acids are selected from the group consisting of N or Q.7. The MCP-1 mutant protein of claim 1 , wherein at least two amino acids at positions 21 claim 1 , 23 and/or 47 are modified.8. The MCP-1 mutant protein of claim 1 , wherein the Y at position 13 is substituted by an A.9. The MCP-1 mutant protein of claim 1 , containing an N-terminal Met.10. The MCP-1 mutant protein of claim 1 , wherein the N-terminal amino acid residues 2-8 are deleted.12. The MCP-1 mutant protein of ...

ANTICANCER FUSION PROTEIN

The fusion protein, especially recombinant, comprising domain (a) which is a functional fragment of soluble hTRAIL protein sequence beginning with an amino acid at a position not lower than hTRAIL95 or a sequence having at least 70% homology thereto; and domain (b) which is a sequence of pro-apoptotic effector peptide, wherein the sequence of domain (b) is attached at C-terminus and/or N-terminus of domain (a). The fusion protein has anticancer activity. The nucleotide sequence coding the fusion protein, expression vector and host cell for the preparation of the fusion protein, and the use of the fusion protein for treating cancer diseases. 1. A fusion protein comprising:domain (a) which is the functional fragment of soluble hTRAIL protein sequence, which fragment begins with an amino acid at a position not lower than hTRAIL95 or a sequence having at least 70% homology thereto; anddomain (b) which is the sequence of a pro-apoptotic effector peptide, which effects its pro-apoptotic action via intrinsic apoptosis pathway, wherein the sequence of domain (b) is attached at the C-terminus and/or the N-terminus of domain (a).2. The fusion protein according to wherein domain (a) is the fragment of soluble hTRAIL protein sequence claim 1 , which fragment begins with an amino acid from the range hTRAIL95 to hTRAIL121 claim 1 , inclusive claim 1 , and ends with the amino acid hTRAIL281.3. The fusion protein according to claim 2 , wherein domain (a) is selected from the group consisting of hTRAIL114-281 (SEQ. No. 27) claim 2 , hTRAIL119-281 (SEQ. No. 28) claim 2 , hTRAIL121-281 (SEQ. No. 29) claim 2 , hTRAIL116-281 and hTRAIL120-281.4. The fusion protein according to claim 1 , wherein domain (a) is the sequence hTRAIL95-281.5. The fusion protein according to claim 1 , wherein domain (b) is selected from the group consisting of:the fragment of BH3 domain of Bax protein of SEQ. No. 30;the fragment of Bid protein of SEQ. No. 31;ribonuclease A of SEQ. No. 32;cytochrome C of SEQ. ...

APO-2 LIGAND/TRAIL VARIANTS AND USES THEREOF

The disclosure provides Apo-2 ligand variant polypeptides. Methods of making and chemically modifying Apo-2 ligand variant polypeptides are also provided. In addition, formulations of Apo-2 ligand variant polypeptides are provided. In addition, therapeutic methods for using Apo-2 ligand variant polypeptides are provided. 1. An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide sequence of (SEQ ID NO:1) and has one or more of the following amino acid substitutions at the residue position(s) in (SEQ ID NO:1): S96C; S101C; S111C; R170C; K179C.2. An isolated Apo-2 ligand variant polypeptide comprising one or more amino acid mutations in the amino acid sequence of native Apo-2 ligand polypeptide sequence of (SEQ ID NO:1) , said mutations comprising one or more amino acid substitutions recited in Table II.3. The Apo-2 ligand variant polypeptide of wherein said Apo-2 ligand variant polypeptide has selective binding affinity for DR4 receptor.4. The Apo-2 ligand variant polypeptide of wherein said Apo-2 ligand variant polypeptide induces apoptosis in at least one type of mammalian cell.5. The Apo-2 ligand variant polypeptide of wherein said mammalian cell is a cancer cell.6. The Apo-2 ligand variant polypeptide of wherein said DR4 receptor comprises amino acids 1 to 218 of (SEQ ID NO:3).7. The Apo-2 ligand variant polypeptide of wherein said one or more amino acid mutations comprises one or more amino acid substitutions at positions 189 claim 2 , 193 claim 2 , 199 claim 2 , or 201 of the native Apo-2 ligand sequence.8. The Apo-2 ligand variant polypeptide of wherein said Apo-2 ligand variant polypeptide retains native residues at positions corresponding to Arg149 claim 2 , Gln205 claim 2 , Val207 claim 2 , Tyr216 claim 2 , Glu236 and/or Tyr237.9. An isolated Apo-2 ligand variant polypeptide comprising an amino acid sequence which differs from the native sequence Apo-2 ligand polypeptide ...

Method for Purifying Antibodies

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains. 1. A composition comprising a heterodimer protein comprising: i) a first variant heavy chain constant region;', 'ii) a first fusion partner; and, 'a) a first monomer comprising i) a second variant heavy chain constant region;', 'ii) a second fusion partner;, 'b) a second monomer comprisingwherein the pIs of said first and second variant heavy chain constant regions are at least 0.5 logs apart.2. A composition according to wherein the pIs of said first and second monomer are at least 0.5 logs apart.3. A composition according to or wherein said first monomer comprises a third fusion partner.4. A composition according to claim 1 , or wherein said second monomer comprises a fourth fusion partner.5. A composition according to claim 1 , and wherein said fusion partners are independently selected from the group consisting of an immunoglobulin component claim 1 , a peptide claim 1 , a cytokine claim 1 , a chemokine claim 1 , an immune receptor and a blood factor.6. A composition according to wherein said immunoglobulin component is selected from the group consisting of Fab claim 5 , VH claim 5 , VL claim 5 , scFv claim 5 , scFv2 claim 5 , dAb.7. A composition according to wherein said cytokine is selected from the group consisting of IL-2 claim 5 , IL-10 claim 5 , IL-12 and GM-CSF.8. A composition according to wherein said chemokine is selected from the group consisting of RANTES claim 5 , CXCL9 claim 5 , CXCL10 and CXCL12.9. A composition according to wherein said immune receptor is selected from the group consisting of CTLA-4 claim 5 , TNFRI claim 5 , TNFRII claim 5 , a TNFSF protein claim 5 , and TNFRSF10. A composition according to wherein said blood factor is selected from the group consisting of Factor VII claim 5 , Factor ...

Tnf superfamily collectin fusion proteins

The present invention refers to a fusion protein comprising a TNF-superfamily (TNFSF) cytokine or a receptor binding domain thereof fused to a collectin trimerization domain, to a nucleic acid molecule encoding the fusion protein, and to a cell comprising the nucleic acid molecule. The fusion protein is present as a trimeric complex or as an oligomer thereof. The fusion protein, the nucleic acid, and the cell is suitable as pharmaceutical composition or for therapeutic, diagnostic and/or research applications.

BIMER OR AN OLIGOMER OF A DIMER, TRIMER, QUADROMER OR PENTAMER OF RECOMBINANT FUSION PROTEINS

The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. Said oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membrane signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence. 1. A bimer or oligomer of dimers , trimers , quadromers or pentamers of recombinant fusion proteins characterized by the recombinant fusion proteins having at least one component A and at least one component B , wherein component A comprises a protein or a protein segment with biological function , in particular with ligand function for antibodies , for soluble or membrane-bound signal molecules or for receptors or an antibody or segment of an antibody and component B comprises a protein or a protein segment selected from the group consisting of the family of C1q proteins and the collectins , which bimerizes or oligomerizes the dimer , trimer , quadromer or pentamer of the recombinant fusion protein without the effect of third molecules.2. The bimer or oligomer of dimers claim 1 , trimers claim 1 , quadromers or pentamers of recombinant fusion proteins according to characterized by the component A of the recombinant fusion proteins in the dimer claim 1 , trimer claim 1 , quadromer or pentamer being identical or different.3. The bimer or ...

Moesin fragments associated with aplastic anemia

The present application provides compositions and methods useful for detecting and monitoring acquired aplastic anemia.

Use of MIF and MIF Pathway Agonists

The present invention relates to novel methods and compositions for increasing AMPK activity and glucose uptake comprising administering a macrophage migration inhibitory factor (MIF) pathway agonist in a subject in need thereof. The invention also relates to methods for selecting a subject for treatment with an agonist of MIF, identifying a subject at risk for developing a condition in which increased AMPK activity is desirable, and for predicting whether a subject is susceptible to a condition in which increased AMPK activity is desirable.

PEPTIDE HAVING THE ABILITY TO REGENERATE BONE TISSUE AND FOR BINDING TO APATITE

The present invention relates to a peptide having bone tissue regeneration capacity and binding to surface of apatite, and more particularly, to a peptide having bone tissue regeneration capacity and specifically binding to a surface of apatite mineral, capable of being stably immobilized to the surface of apatite mineral to retain effective activity and exhibit bone regeneration effects for a long time, by linking an amino acid sequence having bone tissue regeneration capacity and an amino acid sequence having apatite-binding capacity to each other to thereby provide a peptide having both bone-forming effects and binding capacity to the surface of apatite mineral, and a composition for bone tissue regeneration, containing the peptide. The peptide having binding capacity to the apatite mineral and bone tissue regeneration capacity according to the present invention binds to the surface of apatite to thereby be present in a stable state, and thus can be used in a bone replacement material for dental or orthopedic application, and metal, natural polymers, or synthetic polymers, coated with apatite; promote transition, proliferation, and differentiation of cells associated with regeneration and eventually maximize bone tissue regeneration; and can be stably present while maintaining peptide activity when being grafted into the body and thus is useful in development of the bone tissue regeneration therapeutic technology using the peptide. 1. A peptide having bone tissue regeneration capacity and binding to apatite , in which at least one peptide selected from the group consisting of amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 35 and at least one peptide selected from the group consisting of amino acid sequences of SEQ ID NO: 36 to SEQ ID NO: 39 are linked to each other.2. A peptide having bone tissue regeneration capacity and binding to apatite , wherein the peptide is represented by an amino acid sequence of SEQ ID NO: 40.3. A bone graft material in which the ...

METHODS FOR TREATING TWEAK-RELATED CONDITIONS

The present invention provides methods and agents for the treatment of TWEAK-related conditions, including cardiac, liver, kidney, lung, adipose, skeletal, muscle, neuronal, bone and cartilage conditions. The invention also provides methods for identifying TWEAK agonists or antagonists for the treatment of TWEAK-related conditions. Additionally, the invention provides transgenic animals that express an exogenous DNA encoding a TWEAK polypeptide, or fragments, analogs, or muteins thereof, and methods for using such animals to identify TWEAK agonists or antagonists. The invention further provides methods for diagnosing a disease based on TWEAK expression. The invention also provides methods for affecting cellular differentiation of progenitor cells using TWEAK polypeptides, agonists, or antagonists. 1. A method for treating primary glomerular disease in a human subject comprising the step of administering to the subject a therapeutically effective amount of a TWEAK antagonist selected from (a) an antibody that binds human TWEAK (an anti-TWEAK antibody) or an antigen-binding fragment thereof; (b) an antibody that binds human Fn14; and (c) a soluble human TWEAK receptor polypeptide.2. The method of claim 1 , wherein the glomerular disease is selected from glomerulonephritis and glomerular nephropathy.3. The method of claim 1 , wherein the glomerular disease is kidney fibrosis.4. The method of claim 1 , wherein the antibody is human or humanized.5. The method of claim 1 , wherein the antibody is monoclonal or chimeric.6. The method of claim 1 , wherein the antibody is full length.7. The method of claim 1 , wherein the antibody is an antigen-binding fragment.8. The method of claim 1 , wherein the TWEAK antagonist is administered to the subject via a route selected from the group consisting of: injection claim 1 , transmucosal claim 1 , oral claim 1 , inhalation claim 1 , ocular claim 1 , rectal claim 1 , stent implantation claim 1 , topical claim 1 , parenteral claim 1 , ...

Recombinant Production of Heparin Binding Proteins

A process for recovering and purifying refolded heparin binding proteins produced in heterologous host cells includes the step of incubation of the solubilized protein with a polyanionic species such as dextran sulfate.

Complex having tumor vaccine effect, and use thereof

The present invention provides a tumor cell-soluble TNF family member molecule complex containing a tumor cell and an isolated soluble TNF family member molecule, wherein the soluble TNF family member molecule is bound on a surface of the tumor cell such that it binds to a receptor of the TNF family member expressed on a surface of a cell other than the tumor cell, and stimulates the cell other than the tumor cell via the receptor, and a composition and a tumor vaccine, each containing the complex.

VIRAL CHEMOKINE-ANTIGEN FUSION PROTEINS

The present invention relates to a vaccine for increasing the immunogenicity of a tumor antigen thus allowing treatment of cancer, as well as a vaccine that increases the immunogenicity of a viral antigen, thus allowing treatment of viral infection, including immunodeficiency virus (HIV) infection. In particular, the present invention provides a fusion protein comprising a viral chemokine fused to either a tumor antigen or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing viral infection. 1. A fusion polypeptide comprising a viral chemokine and a human tumor antigen , wherein the viral chemokine comprises viral macrophage inflammatory protein III (vMIPIII).2. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises a B cell tumor antigen.3. The fusion polypeptide of claim 2 , wherein the B cell tumor antigen is selected from the group consisting of:(1) an antibody produced by a B cell tumor;(2) a single chain antibody comprising linked VH and VL domains which retain the conformation and specific binding activity of the native idiotype of the antibody produced by a B cell tumor; and(3) an epitope of an idiotype of an antibody produced by a B cell tumor.4. The fusion polypeptide of claim 3 , wherein the B cell tumor antigen comprises sFv38.5. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises gp100.6. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises Muc-1.7. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises the amino acid sequence of SEQ ID NO: 1.8. A composition comprising the fusion polypeptide of in a pharmaceutically acceptable carrier.9. A method of producing an immune response in a subject claim 8 , comprising administering to the subject the composition of .10. The method of claim 9 , wherein the immune response is an effector T cell ...

Antibodies That Inhibit TSLP Activity

The invention is directed to purified and isolated novel TSLP polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above. 1. An isolated nucleic acid molecule selected from the group consisting of:(a) the DNA sequence of SEQ ID NO: 1;(b) an isolated nucleic acid molecule encoding an amino acid sequence comprising the sequence of SEQ ID NO:2;(c) an isolated nucleic acid molecule that hybridizes to either strand of a denatured, double-stranded DNA comprising the nucleic acid sequence of (a) or (b) under condition of moderate stringency in 50% formamide and 6×SSC, at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS;(d) an isolated nucleic acid molecule derived by in vitro mutagenesis from SEQ ID NO:1;(e) an isolated nucleic acid molecule degenerate from SEQ ID NO:1 as a result of the genetic code; and(f) an isolated nucleic acid molecule selected from the group consisting of human TSLP DNA, an allelic variant of human TSLP DNA, and a species homolog of TSLP DNA.2. The nucleic acid molecule of comprising the DNA sequence of SEQ ID NO:1.3. A recombinant vector that directs the expression of the nucleic acid molecule of .4. An isolated polypeptide encoded by the nucleic acid molecule of .5. An isolated polypeptide according to having a molecular weight of approximately 21 claim 4 ,000 Daltons as determined by SDS-PAGE.6. An isolated polypeptide according to in non-glycosylated form.7. An isolated antibody that binds to a polypeptide of .8. An antibody to claim 7 , wherein the antibody is a monoclonal antibody.9. A purified TSLP polypeptide selected from the group consisting of:a) the TSLP polypeptide of SEQ ID NO:2; andb) a fragment of the polypeptide of (a), wherein said fragment is capable of binding TSLP receptors.10. An isolated TSLP polypeptide comprising an ...

Methods, compositions, cells, and kits for treating ischemic injury

The methods, compositions, cells and kits described herein are based on the discovery that stem cells, when injected into ischemic tissue of mammals, can be protected by preconditioning of the ischemic tissue with hypoxia-regulated human VEGF and human IGF-1. Methods, compositions, cells and kits for treating tissue injured by ischemia or at risk of ischemic injury in a subject are thus described herein.

Chimeric protein

A chimeric protein is disclosed for promoting repair and regeneration of neurons damaged by disease or physical injury wherein the chimeric protein is a combination of a first polypeptide possessing matrix modification activity and a second polypeptide possessing regenerating activity for neural cells.

Virus like particle composition

The present invention provides a particle comprising a polypeptide and at least one antigen, and a composition comprising thereof.

VEGF-ACTIVATED FAS LIGANDS

The present invention provides fusion proteins comprising an extracellular domain of a VEGF receptor and a death ligand. The fusion proteins bind to VEGF and to death receptors on tumor cells thereby inhibiting VEGF activation of VEGF receptors and inducing apoptosis in the tumor cells. Fusion proteins of the present invention are useful for inducing apoptosis and cytotoxic effects in cells, treating cancer and diseases or disorders related to unregulated angiogenesis and/or vasculogenesis. Thus, this invention further provides methods for treating angiogenesis related diseases using the fusion proteins, polynucleotides encoding the fusion proteins, vectors containing the polynucleotides, pharmaceutical compositions and kits containing the fusion proteins or the polynucleotides encoding the fusion proteins. 131-. (canceled)32. A fusion protein which binds to a death receptor , the fusion protein comprising:(i) a vascular endothelial growth factor receptor-1 (VEGFR-1) polypeptide that binds a vascular endothelial growth factor (VEGF) polypeptide, wherein the VEGFR-1 polypeptide comprises an amino acid sequence at least 95% identical to amino acid residues 129 to 230 of SEQ ID NO:19; and(ii) a TRAIL ligand comprising an oligomerization domain and a TRAIL receptor binding domain,wherein the C-terminus of the VEGFR polypeptide is linked to the N-terminus of the TRAIL ligand.33. The fusion protein of claim 32 , wherein the VEGFR-1 is a human VEGFR-1.34. The fusion protein of claim 32 , wherein the TRAIL ligand is a human TRAIL ligand.35. The fusion protein of claim 32 , further comprising:(iii) an epitope tag.36. The fusion protein of claim 35 , wherein the epitope tag comprises a FLAG-like tag or an HA tag.37. The fusion protein of claim 36 , wherein the epitope tag can be cleaved off.38. A method of inducing a death receptor-mediated pathway comprising the step of:{'claim-ref': {'@idref': 'CLM-00032', 'claim 32'}, 'contacting a TRAIL receptor expressing cell with a ...

STRONGLY INACTIVATED AND STILL HIGHLY IMMUNOGENIC VACCINE AND PROCESS OF MANUFACTURING THEREOF

An immunogenic product includes TNFα coupled with KLH, wherein the TNFα is strongly inactivated, which means that the product shows less than 30% of cytolytic activity and/or an inactivation factor of more than 15000, in the conditions of TEST A. An emulsion and a vaccine including the product and methods for preparing the immunogenic product are also described. 119-. (canceled)20. An immunogenic product comprising TNFα coupled with KLH , wherein the TNFα is strongly inactivated , which means that the product at a concentration of 100 ng/ml shows less than 30% of cytolytic activity and/or an inactivation factor of more than 15000 , in the conditions of TEST A.21. The immunogenic product according to claim 20 , wherein said product remains inactivated overtime claim 20 , which means that the product at a concentration of 100 ng/ml shows less than 80% of cytolytic activity and/or an inactivation factor of more than 500 claim 20 , in the conditions of TEST B.22. The immunogenic product according to claim 20 , wherein said product may comprise free TNFαhomopolymers of more than 300 kDa and when said product comprises free TNFαhomopolymers of more than 300 kDa claim 20 , the percentage of free TNFαhomopolymers of more than 300 kDa is of less than 30% w/w of total TNFα as calculated in TEST C.23. The immunogenic product according to claim 20 , wherein said product is lyophilized.24. An immunogenic emulsion comprising a product according to and an oil and a surfactant or a mixture thereof; wherein the emulsion is a water-in-oil emulsion or an oil-in-water emulsion claim 20 , and wherein the oil claim 20 , the surfactant and/or the mixture of oil and surfactant are pharmaceutically acceptable excipients.25. The immunogenic emulsion according to claim 24 , comprising a mixture of oil and surfactant which is an adjuvant claim 24 , preferably ISA 51.26. A vaccine composition comprising animmunogenic product according to .27. A vaccine composition comprising an immunogenic ...

Modified polynucleotides for the production of secreted proteins

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Targeting vector-phospholipid conjugates

Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

ANTICANCER FUSION PROTEIN

A fusion protein comprising domain (a) which is a functional fragment of hTRAIL protein sequence, which fragment begins with an amino acid at a position not lower than hTRAIL95, or a homolog of said functional fragment having at least 70% sequence identity; and domain (b) which is a sequence of an anti-angiogenic effector peptide, wherein the sequence of domain (b) is attached at the C-terminus or N-terminus of domain (a). The fusion protein can be used for the treatment of cancer diseases. 2. The fusion protein according to claim 1 , wherein domain (a) comprises a fragment of soluble hTRAIL (SEQ. No. 16) protein sequence starting with amino acid in a range from hTRAIL95 to hTRAIL121 claim 1 , inclusive claim 1 , and ending with amino acid 281.3. The fusion protein according to claim 2 , wherein domain (a) is selected form the group consisting of hTRAIL95-281 claim 2 , hTRAIL119-281 claim 2 , hTRAIL120-281 and hTRAIL121-281.4. The fusion protein according to claim 1 , wherein domain (b) is selected form the group consisting of:an inhibitor of receptors for growth factors selected from the group consisting of receptors for VEGF, PDGF and EGF;fragment of tumstatin, andan inhibitor of aminopeptidase N (CD13).5. The fusion protein according to claim 4 , wherein domain (b) is an inhibitor of receptors for growth factors selected from the group consisting of receptors for VEGF claim 4 , PDGF and EGF claim 4 , and consists of the sequence set forth as SEQ. No. 17 claim 4 , SEQ. No. 22 or SEQ. No. 23.6. The fusion protein according to claim 4 , wherein domain (b) consisting of the sequence set forth as SEQ. No 18 or SEQ. No. 19 representing respectively tumstatin fragment I or tumstatin fragment II.7. The fusion protein according to claim 4 , wherein domain (b) is an inhibitor of aminopeptidase N (CD13) consisting of the sequence set forth as SEQ. No. 20 or SEQ. No. 21.8. The fusion protein according to claim 1 , wherein the fusion protein between the domain (a) and domain ...

Tumor targeted tnf-related apoptosis inducing ligand fusion polypeptide, methods and uses therefor

Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Methods for diagnosis and prognosis of inflammatory bowel disease using cytokine profiles

The present invention relates to the field of inflammatory bowel disease. More specifically, the present invention relates to the use of cytokines to detect, diagnose, and assess inflammatory bowel disease. In one embodiment, a method for diagnosing Crohn's Disease (CD) in a patient comprises the steps of (a) collecting a sample from the patient; (b) measuring the levels of at least one cytokine in the sample collected from the patient; and (c) comparing the levels of the at least one cytokine with predefined cytokine levels, wherein a correlation between the cytokine levels in the patient sample and predefined cytokine levels indicates that the patient has CD. In a specific embodiment, the at least one cytokine comprises Interferon (IFN)-gamma, Interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-17 and CXCL10.

CONJUGATES FOR THE TREATMENT OF MESOTHELIOMA

The present invention provides conjugates of cytokines and targeting peptides that is able to bind to a receptor expressed on tumor-associated vessels or to a component of the extracellular matrix associated to the tumor vessels, for treatment of malignant pleural mesothelioma. In particular, the invention provides conjugates comprising the cytokine TNF linked to a peptide containing the NGR motif. The invention further provides pharmaceutical compositions comprising such conjugate and pharmaceutical formulations comprising conjugates dissolved in appropriate buffers. 112-. (canceled)13. A method for treating mesothelioma in a patient comprising administering to a patient a conjugate comprising a targeting peptide and a cytokine , wherein the targeting peptide is a peptide containing a NGR motif and wherein the cytokine is TNFα.14. The method of wherein the targeting peptide is selected from the group consisting of linear or cyclic CNGRCVSGCAGRC (SEQ ID No. 1) claim 13 , NGRAHA (SEQ ID No. 2) claim 13 , GNGRG (SEQ ID No. 3) claim 13 , CVLNGRMEC (SEQ ID No. 4) claim 13 , CNGRC (SEQ ID No. 5) claim 13 , CNGRCG (SEQ ID No. 6) claim 13 , LNGRE (SEQ ID No. 7) claim 13 , YNGRT (SEQ ID No. 8) claim 13 , LQCICTGNGRGEWKCE (SEQ ID No. 9) claim 13 , LQCISTGNGRGEWKCE (SEQ ID No. 10) claim 13 , CICTGNGRGEWKC (SEQ ID No. 11) claim 13 , CISTGNGRGEWKC (SEQ ID No. 12) claim 13 , MRCTCVGNGRGEWTCY (SEQ ID No. 13) claim 13 , MRCTSVGNGRGEWTCY (SEQ ID No. 14) claim 13 , CTCVGNGRGEWTC (SEQ ID No. 15) and CTSVGNGRGEWTC (SEQ ID No. 16).15. The method of wherein the cytokine is TNFα that is linked to a targeting peptide CNGRC (SEQ ID No. 5) through a spacer G (glycine).16. The method of wherein the conjugate is administered to the patient at a dose of 0.8 μg/mby a 60 minute intravenous infusion every three weeks.17. The method of wherein the conjugate is administered to the patient at a dose of 0.8 μg/mby a 60 minute intravenous infusion every week.18. The method of claim 13 , wherein the ...

PEPTIDE LIBRARY

The present invention provides a peptide selected from the following (i) and (ii): (i) a peptide having the amino acid sequence represented by SEQ ID NO: 1 in the Sequence Listing; and (ii) a peptide having an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO: 1 in the Sequence Listing by the conservative amino acid substitution, deletion, addition, or insertion of 1 to (inclusive) amino acids except at the 1st Xaa to the 11th Xaa counting from the amino terminus. 1. A peptide comprising:(i) a peptide having the amino acid sequence represented by SEQ ID NO: 1 in the Sequence Listing; or(ii) a peptide having an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO: 1 in the Sequence Listing by the conservative amino acid substitution, deletion, addition, or insertion of 1 to 28 (inclusive) amino acids except at the 1st Xaa to the 11th Xaa counting from the amino terminus.2. The peptide according to claim 1 , wherein each of the 1st Xaa to the 11th Xaa counting from the amino terminus is any amino acid other than cysteine.3. The peptide according to claim 1 , wherein each of the 1st Xaa to the 11th Xaa counting from the amino terminus is any amino acid other than proline.4. The peptide according to claim 1 , wherein the conservative amino acid substitution is within any group selected from a hydrophobic amino acid group claim 1 , a neutral hydrophilic amino acid group claim 1 , an acidic amino acid group claim 1 , a basic amino acid group claim 1 , a group of amino acids influencing the direction of the main chain claim 1 , and an aromatic amino acid group.5. The peptide according to claim 1 , wherein the 1st Xaa counting from the amino terminus is an amino acid selected from the group consisting of glutamine claim 1 , methionine claim 1 , histidine claim 1 , serine claim 1 , glutamic acid claim 1 , asparagine claim 1 , tryptophan claim 1 , isoleucine claim 1 , aspartic acid claim 1 , and threonine.6. The ...

ENGINEERED CXCL12 ALPHA LOCKED DIMER POLYPEPTIDE

The present invention provides a novel CXCL12-αlocked dimer polypeptide, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer, inflammatory disorders, autoimmune disease, and HIV/AIDS. 1. A method of treating HIV/AIDS in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising a CXCL12αlocked dimer polypeptide.2. The method of wherein the subject is human. This application is a divisional of U.S. application Ser. No. 12/956,514, filed on Nov. 30, 2010, which is a continuation of U.S. application Ser. No. 12/380,308, filed on Feb. 26, 2009 and issued as U.S. Pat. No. 7,923,016 on Apr. 4, 2011, which claims priority to U.S. Provisional Application No. 61/067,273 filed Feb. 27, 2008. Each of these applications and patents is incorporated by reference herein in its entirety.The present invention was made with United States government support awarded by the following agency: National Institute of Health-NIAID, Grant No. AI058072. The United States Government has certain rights in the invention.The invention relates generally to a novel CXCL12-αlocked dimer polypeptide, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer and autoimmune, inflammatory disease and HIV/AIDS.Chemokines are a superfamily of chemoattractant cytokine proteins which primarily serve to regulate a variety of biological responses and promote the recruitment and migration of multiple lineages of leukocytes and lymphocytes to a body organ tissue. Chemokines are classified into four families according to the relative position of the first two cysteine residues in the protein. In one family, the first two cysteines are separated by one amino acid residue (the CXC chemokines) and in another family the first two cysteines are adjacent (the CC chemokines). In a third family, the first two cysteines are separated by three amino acids (CXC chemokines). In a fourth ...

GELSOLIN ENRICHMENT OF BLOOD SAMPLES USING GOLD PARTICLES

In the method for producing at least one therapeutically effective protein or a protein mixture in a container, the container is filled with a body fluid and gold particles and incubated, and in this process the therapeutically effective protein is formed in the body fluid. 131-. (canceled)32. A medicament composition for creating blood serum comprising:autologous or homologous blood;gold particles; andgelsolin in an amount which is at least twice the corresponding value for standard blood gelsolin.33. The medicament composition for creating blood serum of wherein:the gold particles are of about 1 μm in size.34. The medicament composition for creating blood serum of wherein:the gold particles are about 0.3 mg per 1 ml of blood.35. The medicament composition for creating blood serum of further comprising:cytokines above the relevant standard blood level for cytokines.36. A method for producing autologous proteins comprising:providing a mixture of body fluid and gold particles in a container;incubating the body fluid and gold particles to produce protein-enriched body fluid serum;removing the gold particles from the protein enriched body fluid serum.37. The method for producing autologous proteins of wherein the body fluid is autologous or homologous blood.38. The method for producing autologous proteins of wherein incubating the body fluid and gold particles produces gelsolin enriched blood serum.39. The method for producing autologous proteins of wherein incubating the body fluid and gold particles produces gelsolin enriched blood serum in an amount which is at least twice the corresponding value for standard blood gelsolin.40. The method for producing autologous proteins of wherein incubating the body fluid and gold particles produces gelsolin enriched and cytokine enriched blood serum.41. The method for producing autologous proteins of further comprising:removing the somatic cells and insoluble aggregates from the blood serum.42. A method of treating a patient ...

Chemokine-immunoglobulin fusion polypeptides, compositions, method of making and use thereof

This application is directed to chemokine-immunoglobulin fusion polypeptides and chemokine-polymer conjugates. The fusion polypeptides and conjugates can be used for treating chemokine receptor-mediated disorders and modulating inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival.

CYTOKINE DERIVATIVES

The invention relates to polypeptides comprising an N-terminal portion and a C-terminal portion, wherein said N-terminal portion comprises the signature sequence QGP[P or L] and the amino acid sequence of said C-terminal portion is at least 70% identical to SEQ ID NO: 1, and uses thereof. 167-. (canceled)68. A method of preventing a disorder selected from the group consisting of HIV infection , the transmission of HIV , the transmission of HIV during sexual contact , and the outbreak of acquired immunodeficiency syndrome (AIDS) in a subject , said method comprising the administration of a polypeptide comprising an N-terminal portion and a C-terminal portion , wherein said N-terminal portion comprises the signature sequence QGP[P or L] and the amino acid sequence of said C-terminal portion is at least 70% identical to SEQ ID NO: 1 , or a composition comprising said polypeptide and a pharmaceutically acceptable carrier , to the subject.69. The method according to claim 68 , wherein said method is a method of preventing HIV infection in a subject.70. The method according to claim 68 , wherein said method is a method of preventing the outbreak of acquired immunodeficiency syndrome (AIDS) in a subject.71. The method according to claim 68 , wherein the signature sequence is QGP[P or L][L or G or S or M][M or D or S or Q or G].72. The method according to claim 68 , wherein the signature sequence is QGP[P or L][L or G][M or D or S].73. The method according to claim 68 , wherein the signature sequence is QGP[P or L][L or G or S or M][M or D or S or Q or G]XX[Q or G or L or A or T or S]X claim 68 , wherein X denotes any natural or modified amino acid.74. The method according to claim 68 , wherein the signature sequence is QGP[P or L][L or G][M or D or S]XX[Q or G or L]X claim 68 , wherein X denotes any natural or modified amino acid.75. The method according to claim 68 , wherein the signature sequence is QGP[P or L]LM or QGPPG[D or S].76. The method according to claim 68 , ...

Serpin Fusion Polypeptides And Methods Of Purification Thereof

This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing and purifying such molecules. 1. A method of purifying a fusion protein , the method comprising the steps of:(a) culturing a cell comprising a nucleic acid construct that encodes the fusion protein under conditions that allow for the expression of the fusion protein, an immunoglobulin Fc polypeptide or an amino acid sequence that is derived from an immunoglobulin Fc polypeptide;', 'a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide;', 'a WAP domain containing polypeptide or a sequence derived from a WAP domain containing polypeptide; or', 'an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide;, 'wherein the fusion protein comprises at least one human serpin polypeptide operably linked to a second polypeptide, wherein the second polypeptide comprises at least one the following(b) contacting a supernatant from the cultured cell with an affinity resin under conditions that allow for binding between the affinity resin and the fusion protein, wherein the affinity resin comprises protein A, or an antibody that binds to alpha-1 antitrypsin (AAT) or a fragment of said antibody; and(c) eluting the fusion protein from the ...

Novel Class of Therapeutic Protein Based Molecules

The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of a target cell by a pathogen, such as a virus. The present invention also comprises therapeutic compositions having sialidase activity, including protein-based compounds having sialidase catalytic domains. Compounds of the invention can be used for treating or preventing pathogen infection, and for treating and reducing allergic and inflammatory responses. The invention also provides compositions and methods for enhancing transduction of target cells by recombinant viruses. Such compositions and methods can be used in gene therapy. 1. A fusion protein , comprising at least one catalytic domain of a sialidase and at least one anchoring domain , wherein the catalytic domain sequence comprises:a) the sequence of amino acids extending from amino acid 274 to amino acid 681 of SEQ ID NO:12, inclusive and lacks the sequence that consists of the sequence extending from amino acid 1 to amino acid 273 and from amino acid 682 to amino acid 901 of SEQ ID NO:12;b) the sequence of amino acids extending from amino acid 290 to amino acid 666 of SEQ ID NO:12, inclusive and lacks the sequence that consists of the sequence extending from amino acid 1 to amino acid 289 and from amino acid 667 to amino acid 901 of SEQ ID NO:12; orc) the sequence of amino acids extending from amino acid 290 to amino acid 681 of SEQ ID NO:12, inclusive and lacks the sequence that consists of the sequence extending from amino acid 1 to amino acid 289 and from amino acid 682 to amino acid 901 of SEQ ID NO:12; and the anchoring domain comprises the GAG-binding domain of human platelet factor 4 (SEQ ID NO:2), the GAG-binding domain of human interleukin 8 (SEQ ID NO:3), the GAG-binding ...

Growth factor

VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Methods of treating inflammation

Disclosed herein, in certain embodiments, are peptides for use in inhibiting the interactions of PF4 and RANTES. Further disclosed herein, are methods for treating an inflammatory disease, disorder, condition, or symptom. In some embodiments, the method comprises co-administering an agent that inhibits the interactions of PF4 and RANTES and a second active agent.

Protein-binding peptide isolated from placenta growth factor

Embodiments of the invention are described, including materials and methods for making molecules and materials that have a specific binding domain of a PlGF2. Embodiments include, for instance, medicaments, biomaterials, biomolecules, molecular fusions, and vaccines.

CONTROL AGENT FOR CONTROLLING UNDIFFERENTIATED STATE AND USE THEREOF

The present invention aims to provide a novel undifferentiated state-control agent that maintains and/or improves an undifferentiated state of undifferentiated cells. CCL2 or a protein containing a functional domain thereof is used as the undifferentiated state-control agent. By culturing undifferentiated cells in the presence of the control agent, it is possible to maintain and/or improve an undifferentiated state of the undifferentiated cells. Examples of the undifferentiated cells include embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). The origin of the cells is not particularly limited, and may be a human, mouse, or the like, for example. 1. A control agent for controlling an undifferentiated state of an undifferentiated cell , the control agent comprising:CCL2 or a protein containing a functional domain of the CCL2.4. The control agent according to claim 1 , wherein the undifferentiated cell is an ES cell or an iPS cell.5. The control agent according to claim 1 , further comprising a medium claim 1 , wherein the medium comprises the CCL2 or the protein containing the functional domain of the CCL2 claim 1 , and is a medium for controlling an undifferentiated state of an undifferentiated cell.6. The control agent according to claim 1 , further comprising a culture container claim 1 , wherein the CCL2 or the protein containing the functional domain of the CCL2 is immobilized on the culture container claim 1 , and the culture container is a culture container for controlling an undifferentiated state of an undifferentiated cell.7. A control agent for controlling an undifferentiated state of an undifferentiated cell claim 1 , the control agent comprising:an expression vector that expresses CCL2 or a protein containing a functional domain of the CCL2.8. The control agent according to claim 7 , comprising a transformant transfected with the expression vector.9. The control agent according to claim 8 , wherein the transformant is an ...

PROTEASE RESISTANT MUTANTS OF STROMAL CELL DERIVED FACTOR-1 IN THE REPAIR OF TISSUE DAMAGE

The present invention is directed stromal cell derived factor-1 peptides that have been mutated to make them resistant to digestion by the proteases dipeptidyl peptidase IV (DPPIV) and matrix metalloproteinase-2 (MMP-2) but which maintain the ability of native SDF-1 to attract T cells. The mutants may be attached to membranes formed by self-assembling peptides and then implanted at sites of tissue damage to help promote repair. 1. A method of treating a patient to aid the repair of damaged tissue , comprising: administering locally to said damaged tissue , an isolated mutant stromal cell derived factor-1 comprising a peptide having a formula selected from the group consisting of: Xp-SDF-I , mSDF-1 and Xp-mSDF-1 , wherein:a) X is a proteinogenic amino acid or a protease protective organic group;b) p is an integer between 1 and 4;c) SDF-1 is a peptide comprising the amino acid sequence of at least amino acids 1-8 of SEQ ID NO:52 and which is optionally extended at the C terminus by all, or any portion, of the remaining sequence of SEQ ID NO:52, shown as amino acids 9-68;{'sub': 'p', 'd) X-SDF-I has chemoattractant activity for T cells and is inactivated by dipeptidyl peptidase FV (DPPIV) at a rate that is less than one half of the rate at which SDF-I is inactivated;'}e) mSDF-1 is a form of SDF-I comprising a mutation in the fourth and/or the fifth amino acid from the N terminus of SDF-I;f) mSDF-1 has chemoattractant activity for T cells and is inactivated by matrix metalloproteinase-2 (MMP-2) at a rate that is less than one half of the rate at which SDF-I is inactivated; and{'sub': 'p', 'g) X-mSDF-1 has chemoattractant activity for T cells, is inactivated by DPPIV at a rate that is less than one half of the rate at which SDF-I is inactivated and is inactivated by MMP-2 at a rate that is less than one half of the rate at which SDF-I is inactivated.'}2. The method of claim 1 , wherein said mutant stromal cell derived factor-1 is attached to a biologically compatible ...

Anticancer fusion protein

A fusion protein comprising domain (a) which is the functional fragment of a hTRAIL protein sequence, which fragment begins with an amino acid at a position not lower than hTRAIL95, or a homolog of said functional fragment having at least 70% sequence identity; and at least one domain (b) which is the sequence of an effector peptide having anti-proliferative activity against tumour cells, wherein the sequence of domain (b) is attached at the C-terminus or at the N-terminus of domain (a). The fusion protein can be used for the treatment of cancer diseases.

HIGH LEVEL PRODUCTION OF RECOMBINANT PROTEINS

The present technology relates to the fields of biochemistry, molecular biology and medicine. In particular, the present technology relates to methods and compositions for increased expression of recombinant proteins. 1. A method for producing a recombinant protein comprising:producing a fusion protein in a cell, wherein said fusion protein comprises a protein of interest and a modified protein moiety, wherein said modified protein moiety decreases the solubility of said fusion protein in said cell compared to the solubility of said protein of interest in said cell.2. The method of claim 1 , further comprising cleaving said protein of interest from said modified protein moiety.3. The method of claim 2 , wherein said cleaving comprises utilizing a protease.4. The method of claim 3 , wherein said protease is ubiquitinase.5. The method of claim 4 , wherein said ubiquitinase comprises Usp2-cc.6. The method of claim 1 , further comprising providing conditions for said protein of interest to refold into an active form claim 1 , wherein said protein of interest is cleaved from said modified protein moiety.7. The method of claim 1 , further comprising purifying said fusion protein or said protein of interest.8. The method of claim 1 , wherein said modified protein moiety comprises a modified ubiquitin moiety.9. The method of claim 8 , wherein said modified ubiquitin moiety comprises an increased frequency or number of hydrophobic amino acid residues compared to a wild type ubiquitin moiety.10. The method of claim 8 , wherein said modified ubiquitin moiety comprises a decreased frequency or number of hydrophobic amino acid residues compared to a wild type ubiquitin moiety.11. The method of claim 8 , wherein said modified ubiquitin moiety comprises a ubiquitin sequence with one or more mutations at positions selected from the group consisting of I3 claim 8 , V5 claim 8 , I13 claim 8 , L15 claim 8 , V17 claim 8 , I23 claim 8 , V26 claim 8 , I30 claim 8 , L43 claim 8 , L50 ...

Biological active proteins having increased in vivo and/or in vitro stability

Increased in vivo and/or in vitro stability is imparted to a biologically active protein by fusing to an amino acid sequence consisting of at least about 100 amino acid residues, which consist essentially of Alanine, Serine and Proline, which form a random coil conformation. Specific examples are described. Also described are related nucleic acids, vectors and cells encoding such amino acids; compositions of biologically active proteins fused to a random coil domain, and methods of making and using the compounds and compositions of the invention.

Method for isolating osteopontin using feeds containing cmp or casein species

The present invention pertains to a method for isolating osteopontin from a milk-derived feed containing caseino macropeptide and/or free beta casein, such as e.g. a feed based on milk serum or sweet whey. Particularly, the present method involves the use of a narrow window of pH and specific conductance of the milk-derived feed, which surprisingly has proven to provide a very efficient isolation of osteopontin from chemically complex feeds.

Tnfsf single chain molecules

The present invention refers to single-chain fusion proteins comprising three soluble TNF superfamily (TNFSF) cytokine domains and nucleic acid molecules encoding these fusion proteins. The fusion proteins are substantially non-aggregating and suitable for therapeutic, diagnostic and/or research applications.

ANTI-LYMPHOTOXIN ANTIBODIES

The instant invention is based, at least in part on the identification of a new class of antibodies that result, e.g., in improved LT blocking capabilities. Methods of making the subject binding molecules and methods of using the binding molecules of the invention to antagonize LTβR signaling are also provided. 1. An isolated antibody that binds to lymphotoxin (LT) or antigen binding fragment thereof , wherein said antibody ,(a) blocks an LT-induced biological activity in a cell by at least about 70% under conditions in which a reference antibody, B9, (Produced by the cell line B9.C9.1, deposited with the ATCC under Accession number HB 11962) blocks the LT-induced biological activity in a cell by about 50%;(b) blocks an LT-induced biological activity in a cell at an IC50 of less than 100 nM; or(c) blocks LTβR-Ig binding to a cell by at least 85%.23-. (canceled)4. The isolated antibody or molecule comprising an antigen binding region thereof of claim 1 , wherein the LT-induced biological activity is IL-8 release.56-. (canceled)7. The isolated antibody or molecule comprising an antigen binding region thereof of claim 1 , wherein claim 1 ,(a) the human constant region is an IgG1 constant region that has been altered to reduce binding to at least one Fc receptor or;(b) the human constant region is an IgG1 constant region that has been altered to enhance binding to at least one Fc receptor.815-. (canceled)16. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment binds two sites on LT leaving no site for LTβR binding.1718-. (canceled)19. An isolated antibody claim 1 , or antigen binding fragment thereof claim 1 , that specifically binds to an epitope of LT claim 1 , wherein the binding to the LT epitope by the antibody is competitively blocked in a dose-dependent manner by claim 1 ,(a) the 102 antibody;(b) the AOD9 antibody;(c) 101/103 antibody;(d) the 105 antibody;(e) the 9B4 antibody;(f) the A1D5 antibody ...

Genetically Modified Mice and Engraftment

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Modified Human Thymic Stromal Lymphopoietin

Modified, furin resistant human TSLP polypeptides and polynucleotides encoding the modified human TSLP polypeptides are provided. Pharmaceutical compositions, B and T cell activation agents, assays and methods of use are also described. 1. An isolated nucleic acid encoding a polypeptide comprising at least 90% amino acid sequence identity to amino acids 29-159 of SEQ ID NO: 10 , wherein the polypeptide comprises one or more amino acid substitutions or deletions to inactivate the furin cleavage site RRKRK (SEQ ID NO:6) at position 127-131 of SEQ ID NO:4.2. The nucleic acid of encoding a polypeptide comprising at least 90% amino acid sequence identity to SEQ ID NO: 12 claim 1 , wherein the polypeptide comprises one or more amino acid substitutions or deletions to inactivate the furin cleavage site RRKRK (SEQ ID NO:6) at position 127-131 of SEQ ID NO:4.3. The nucleic acid of encoding a polypeptide comprising at least 90% amino acid sequence identity to SEQ ID NO: 14 claim 1 , wherein the polypeptide comprises one or more amino acid substitutions or deletions to inactivate the furin cleavage site RRKRK (SEQ ID NO:6) at position 127-131 of SEQ ID NO:4.4. The nucleic acid of encoding a polypeptide comprising at least 90% amino acid sequence identity to SEQ ID NO: 16 claim 1 , wherein the polypeptide comprises one or more amino acid substitutions or deletions to inactivate the furin cleavage site RRKRK (SEQ ID NO:6) at position 127-131 of SEQ ID NO:4.5. The nucleic acid of encoding a polypeptide comprising at least 90% amino acid sequence identity to SEQ ID NO: 17 claim 1 , wherein the polypeptide comprises an amino acid substitution or deletion to inactivate the furin cleavage site RRKRK (SEQ ID NO:6) at position 127-131 of SEQ ID NO:4.6. The nucleic acid of encoding a polypeptide comprising at least 90% amino acid sequence identity to SEQ ID NO: 18 claim 1 , wherein the polypeptide comprises one or more amino acid substitutions or deletions to inactivate the furin ...

TNF Family Ligand Variants

The present invention relates to variants of TNF family ligands which have been mutated at the ligand trimerisation interface so that they are not capable of assembling into trimers, and either assemble into dimers or remain as monomers. Such ligands bind to the TNF receptor but are unable to activate it, effectively functioning as competitive inhibitors. The invention also relates to nucleic acids encoding the variants of TNF family ligands, vectors and host cells comprising the nucleic acid and methods for the treatment of diseases associated with aberrant signalling through a TNF receptor. 168.-. (canceled)69. A variant of a TNF family ligand which is mutated such that it is not capable of assembling into a trimer ,wherein the variant ligand retains the ability to bind one or more of its cognate receptor(s), but wherein binding to the receptor does not activate the receptor.70. The variant of a TNF family ligand of claim 69 , wherein the variant does not homotrimerise with itself.71. The variant of a TNF family ligand of claim 69 , wherein the variant is capable of assembling into a dimer with another variant of the same ligand.72. The variant of a TNF family ligand of claim 71 , wherein the variant binds one or more of its cognate receptors within the cleft formed between two assembled ligand monomers claim 71 , and wherein the TNF family ligand is optionally selected from the group consisting of RANKL claim 71 , TRAIL claim 71 , APRIL claim 71 , BAFF claim 71 , TNFalpha claim 71 , CD30L claim 71 , CD40L claim 71 , FasL claim 71 , Light claim 71 , and Tweak.73. The variant of a TNF family ligand of claim 69 , wherein the variant comprises a mutation at one or more of positions 169 claim 69 , 195 claim 69 , 213 claim 69 , 230 claim 69 , 257 claim 69 , 272 and 280 in the human RANKL sequence claim 69 , or an equivalent position as set out in Table 1 herein.74. The variant of a TNF family ligand of claim 73 , wherein the TNF variant comprises one or more of the ...

Genetically Modified Mice and Engraftment

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., or is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia. 117.-. (canceled)18. A method comprising:engrafting a second mouse with human hematopoietic cells isolated from a genetically modified first mouse, wherein the genetically modified first mouse is immunocompromised for a mouse immune system, wherein the genetically modified first mouse comprises an engraftment of human hematopoietic cells and a replacement of each allele of the mouse thrombopoietin (TPO) gene with a human TPO gene at the mouse TPO gene locus, and wherein the second mouse is immunocompromised for a mouse immune system.19. The method of claim 18 , wherein the human hematopoietic cells comprise CD34+ cells.20. The method of claim 18 , wherein the first mouse comprises a replacement of a mouse IL-3 gene with a human IL-3 gene at a mouse IL-3 gene locus claim 18 , and a replacement of a mouse GM-CSF gene with a human GM-CSF gene at a mouse GM-CSF gene locus.21. The method of claim 18 , wherein the first mouse is null for a RAG2 gene claim 18 , and null for a mouse interleukin 2 receptor gamma (IL-2Rg) gene.22. The method of claim 18 , wherein the second mouse comprises a replacement of a mouse IL-3 gene ...

Compositions and Methods for use of CXCL12 in Treatment of Bone Disorders

The present invention provides compositions and methods for treating a disease or disorder associated with bone defects or reduced or abnormal bone formation.

ANTI-CXCL13 ANTIBODIES AND ASSOCIATED EPITOPE SEQUENCES

The invention relates to epitopes of CXCL13 and to binding agents, such as antibodies, that specifically bind to CXCL13. 1. An isolated antibody or antigen-binding fragment thereof that specifically binds to CXCL13 , wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of:(a) a monoclonal antibody that binds to an epitope within the sequence set forth in SEQ ID NO: 26;(b) a monoclonal antibody that binds to an epitope comprising an amino acid sequence having at least 40% identity to SEQ ID NO: 26;(c) a monoclonal antibody that binds to an epitope comprising an amino acid sequence identical to SEQ ID NO: 26, except for 9 or fewer amino acid substitutions; and(d) an antigen-binding fragment of any one of (a)-(c).2. An isolated antibody or antigen-binding fragment thereof that specifically binds to CXCL13 , wherein said antibody or antigen-binding fragment thereof binds to the same CXCL13 epitope as a reference monoclonal antibody or antigen-binding fragment thereof selected from the group consisting of:(a) the monoclonal antibody 5261;(b) the monoclonal antibody 5378;(c) the monoclonal antibody 5080;(d) the monoclonal antibody 1476;(e) the monoclonal antibody 3D2;(f) a monoclonal antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 13 and SEQ ID NO: 15, respectively;(g) a monoclonal antibody comprising a VH and VL comprising the amino acid sequence set forth in SEQ ID NO: 13 and SEQ ID NO: 17, respectively;(h) a monoclonal antibody comprising a VH and VL comprising the amino acid sequence set forth in SEQ ID NO: 3 and SEQ ID NO: 8, respectively;(i) a monoclonal antibody comprising VH domain comprising a Chothia-Kabat heavy chain complementarity determining region-1 (VH-CDR1) amino acid sequence set forth in SEQ ID NO: 4; a Kabat heavy chain complementarity determining region-2 (VH-CDR2) amino acid sequence set forth in SEQ ID ...

Cell Penetrating Peptide, Conjugate Comprising Same, and Composition Comprising Conjugate

The present invention relates to a conjugate of cell penetrating peptide and an active ingredient; and its use. Specifically, a conjugate including a cell penetrating peptide which is a peptide comprising any one amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 6, a fragment of any one sequence of SEQ ID NO: 1 to SEQ ID NO: 6, or a peptide having above 80% homology with the above-mentioned sequence; and a composition comprising the same are disclosed.

Cytokine Fusion Proteins

The present invention relates to cytokine fusion proteins and to nucleic acid molecules encoding such cytokine fusion proteins. The present invention further relates to cells, non-human organisms. pharmaceutical compositions and kits comprising the cytokine fusion proteins or the nucleic acid molecules encoding them, as well as to their use as medicaments. 1. A cytokine fusion protein comprising (i) three extracellular domains or fragments or variants thereof of a first ligand of the tumor necrosis factor (TNF) superfamily forming a first homotrimer capable of binding to a receptor of the first ligand and (ii) three extracellular domains or fragments or variants thereof of a second ligand of the TNF superfamily forming a second homotrimer capable of binding to a receptor of the second ligand , wherein the first ligand and the second ligand are different , and wherein the first homotrimer and the second homotrimer are covalently linked , preferably via one or more peptide linkers.2. The cytokine fusion protein according to claim 1 , wherein the three extracellular domains or fragments or variants thereof of the first ligand and/or the three extracellular domains or fragments or variants thereof of the second ligand are covalently linked.3. The cytokine fusion protein according to or claim 1 , comprising a molecule/structure having the general formula{'br': None, 'sub': A', 'A', 'B', 'B, 'N′-A-L-A-L-A-L-B-L-B-L-B-C′\u2003\u2003(Formula I),'}wherein A comprises the extracellular domain or a fragment or a variant thereof of the first ligand, and B comprises the extracellular domain or a fragment or variant thereof of the second ligand, andwherein L comprises a peptide linker, and{'sub': A', 'B, 'Land Lare, at each occurrence, independently selected from a covalent bond and a peptide linker.'}4. The cytokine fusion protein according to claim 3 , wherein L further comprises a multimerization domain claim 3 , preferably a dimerization domain claim 3 , allowing the ...

MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF ONCOLOGY-RELATED PROTEINS AND PEPTIDES

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of oncology-related polynucleotides, oncology-related primary transcripts and oncology-related mmRNA molecules. 1. An mRNA encoding a polypeptide of interest selected from the group consisting of SEQ ID NOs 4704-9203 , wherein said mRNA comprises a coding region selected from the group consisting of SEQ ID NOs: 9204-33882.2. The mRNA of claim 1 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.3. The mRNA of claim 2 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.4. The mRNA of claim 2 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.5. The mRNA of claim 2 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.6. The mRNA of claim 2 , wherein the mRNA comprises at least two stop codons.7. A pharmaceutical composition comprising the mRNA of and a pharmaceutically acceptable excipient.8. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable excipient is selected from a solvent claim 7 , aqueous solvent claim 7 , non-aqueous solvent claim 7 , dispersion media claim 7 , diluent claim 7 , dispersion claim 7 , suspension aid claim 7 , surface active agent claim 7 , isotonic agent claim 7 , thickening or emulsifying agent claim 7 , preservative claim 7 , lipid claim 7 , lipidoids liposome claim 7 , lipid nanoparticle claim 7 , core-shell nanoparticles claim 7 , polymer claim 7 , lipoplex claim 7 , peptide claim 7 , protein claim 7 , cell claim 7 , hyaluronidase claim 7 , and mixtures thereof.9. The pharmaceutical composition of claim 8 , where the pharmaceutical composition comprises a lipid and wherein said lipid is selected from DLin-DMA claim 8 , DLin-K-DMA claim 8 , DLin-KC2-DMA claim 8 , ...

SERPIN FUSION POLYPEPTIDES AND METHODS OF USE THEREOF

This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules. 1. A method of treating or alleviating a symptom of a disease or disorder associated with aberrant serine protease expression or activity in a subject in need thereof , the method comprising administering an isolated fusion protein comprising at least one alpha-1 antitrypsin (AAT) polypeptide , an Elafin polypeptide , and an immunoglobulin Fc polypeptide , such that at least two of the AAT polypeptide , the Elafin polypeptide , and the immunoglobulin Fc polypeptide are operably linked via a hinge region , a linker region , or both a hinge region and linker region.2. A method of treating or alleviating inflammation or a symptom of an inflammatory disease or disorder while reducing the risk of infection , in a subject in need thereof , the method comprising administering an isolated fusion protein comprising at least one alpha-1 antitrypsin (AAT) polypeptide , an Elafin polypeptide , and an immunoglobulin Fc polypeptide , such that at least two of the AAT polypeptide , the Elafin polypeptide , and the immunoglobulin Fc polypeptide are operably linked via a hinge region , a linker region , or both a hinge region and linker region.3. A method of reducing the risk of infection in a subject in ...

Bimer or an oligomer of a dimer, trimer, quadromer or pentamer of recombinant fusion proteins

The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. The oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membranous signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence.

OSTEOPONTIN ISOFORM A INHIBITORS AND METHODS OF USE

The present invention relates to a therapeutic comprising an osteopontin isoform a (“OPNa”) inhibitor where the OPNa inhibitor blocks activity of extracellular OPNa exon 4. The OPNa inhibitor is selected from the group consisting of (i) an exon-4 specific antibody or binding portion thereof; (ii) a peptide mimic of OPNa exon 4 or a fragment thereof; (iii) a nucleic acid aptamer that specifically binds to OPNa exon 4 or a fragment thereof; and (iv) a peptide inhibitor that binds to OPNa exon 4 or a fragment thereof. The present invention also relates to methods of inhibiting tumor growth and/or metastasis in a subject, treating a subject with chemotherapeutic resistance, and methods of increasing tumor cell sensitivity to a cancer therapeutic by administering an OPNa inhibitor according to the present invention. 1. A therapeutic comprising:an osteopontin isoform a (“OPNa”) inhibitor, wherein the OPNa inhibitor blocks activity of extracellular OPNa exon 4 and is selected from the group consisting of:(i) an exon-4 specific antibody or binding portion thereof;(ii) a peptide mimic of OPNa exon 4 or a fragment thereof;(iii) a nucleic acid aptamer that specifically binds to OPNa exon 4 or a fragment thereof; and(iv) a peptide inhibitor that binds to OPNa exon 4 or a fragment thereof.2. The therapeutic according to claim 1 , wherein the OPNa inhibitor blocks OPNa exon 4 cell surface receptor binding activity.3. The therapeutic according to claim 1 , wherein OPNa exon 4 comprises the amino acid sequence of LYNKYPDAVATWLNPDPSQKQNLLAPQ (SEQ ID NO:3).4. The therapeutic according to claim 1 , wherein the OPNa inhibitor is an exon-4 specific antibody or binding fragment thereof that recognizes at least a portion of OPNa exon 4 comprising the amino acid sequence of PDAV (SEQ ID NO:5).5. The therapeutic according to claim 1 , wherein the OPNa inhibitor is an exon-4 specific antibody or binding fragment thereof that recognizes at least a portion of OPNa exon 4 comprising the amino ...

Atomic Description Of Immune Complex That Causes Heparin-Induced Thrombocytopenia

The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants. The present invention also provides a mutant protein which has the same amino acid sequence of a wild type PF4 monomer except that (i) at least one amino acid of the wild type PF4 monomer has been deleted, (ii) at least one amino acid of the wild type PF4 monomer has been replaced by another amino acid, or (iii) a combination of such changes has been made. The present invention also provides methods of treating or reducing the likelihood of HIT, treating angiogenesis, treating abnormal cell growth, or affecting coagulation pathologies that lead to thrombus formation, by administering such mutant proteins to a patient.

Antibodies That Inhibit TSLP Activity

The invention is directed to purified and isolated novel TSLP polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above. 1. An isolated nucleic acid molecule selected from the group consisting of:(a) the DNA sequence of SEQ ID NO: 1;(b) an isolated nucleic acid molecule encoding an amino acid sequence comprising the sequence of SEQ ID NO:2;(c) an isolated nucleic acid molecule that hybridizes to either strand of a denatured, double-stranded DNA comprising the nucleic acid sequence of (a) or (b) under condition of moderate stringency in 50% formamide and 6×SSC, at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS;(d) an isolated nucleic acid molecule derived by in vitro mutagenesis from SEQ ID NO:1;(e) an isolated nucleic acid molecule degenerate from SEQ ID NO:1 as a result of the genetic code; and(f) an isolated nucleic acid molecule selected from the group consisting of human TSLP DNA, an allelic variant of human TSLP DNA, and a species homolog of TSLP DNA.2. The nucleic acid molecule of comprising the DNA sequence of SEQ ID NO:1.3. A recombinant vector that directs the expression of the nucleic acid molecule of .4. An isolated polypeptide encoded by the nucleic acid molecule of .5. An isolated polypeptide according to having a molecular weight of approximately 21 claim 4 ,000 Daltons as determined by SDS-PAGE.6. An isolated polypeptide according to in non-glycosylated form.7. An isolated antibody that binds to a polypeptide of .8. An antibody to claim 7 , wherein the antibody is a monoclonal antibody.9. A purified TSLP polypeptide selected from the group consisting of:a) the TSLP polypeptide of SEQ ID NO:2; andb) a fragment of the polypeptide of (a), wherein said fragment is capable of binding TSLP receptors.10. An isolated TSLP polypeptide comprising an ...

Methods and Compositions Relating to p62/SQSTM1 for the Treatment and Prevention of Inflammation-Associated Diseases

Provided herein are novel p62 compositions for the modulation of expression of a proinflammatory cytokines, osteogenic transcription factors, a bone resorptive factors and endogenous p62. Consequently, such p62 compositions are useful for prophylaxis and treatment of inflammatory diseases and related methods. In certain embodiments the inflammatory diseases are not cancer-related. In various embodiments, the inflammatory diseases include, but are not limited to osteoporosis, obesity, metabolic syndrome, type 2 diabetes, fat liver, inflammatory bowel disease, chronic pancreatitis, asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), osteoarthritis, multiple sclerosis (MS), psoriasis, congestive heart failure (CHF), atherosclerosis, neurodegenerative diseases (ALS, Parkinson, Alzheimer's, Huntington disease), depression, schizophrenia, gout, asbestosis and silicosis. 117-. (canceled)18. A method for treating , alleviating , ameliorating , relieving , delaying onset of , inhibiting progression of , reducing severity of , and/or reducing incidence of one or more symptoms of a non-cancer-related chronic inflammatory disease in a subject in need ,said method comprising administering to said subject an agent comprising p62/SQSTM1 nucleic acid that encodes a polypeptide at least 90% identical to SEQ ID NO: 2,wherein said agent suppresses the expression of a proinflammatory cytokine in a subject.19. The method of claim 18 ,further comprising administering one or more anti-inflammatory therapies.20. The method of claim 19 ,wherein said one or more anti-inflammatory therapies is selected from the group consisting of: anti-inflammatory chemotherapeutic agent and biological agent.21. The method of claim 20 ,wherein said anti-inflammatory chemotherapeutic agent is selected from the group consisting of: a nonsteroidal anti-inflammatory drug, a glucocorticoid, methotrexate, cyclosporine, and rapamycin.22. The method of claim 20 ,wherein said biological ...

IMMUNOMODULATORY CELLS AND USES THEREOF

Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen. 1. A cell genetically modified to comprise at least one mechanism for inducing immune tolerance to an antigen when administered to a subject , the genetically modified cell comprising a set of transgenes comprising two or more of the following genes: PD-L1 , HLA-G or H2-M3 , Cd47 , Cd200 , FASLG or FasL , Ccl21 or Ccl21b , Mfge8 , and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1 , HLA-G or H2-M3 , Cd47 , Cd200 , FASLG or FasL , Ccl21 or Ccl21b , Mfge8 , or Serpin B9 or Spi6; and a transgene encoding a polypeptide comprising an antigen.2. The cell of claim 1 , wherein the set of transgenes comprises three claim 1 , four claim 1 , five claim 1 , six claim 1 , seven claim 1 , or all eight of the following genes: PD-L1 claim 1 , HLA-G or H2-M3 claim 1 , Cd47 claim 1 , Cd200 claim 1 , FASLG or FasL claim 1 , Ccl21 or Ccl21b claim 1 , Mfge8 claim 1 , and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1 claim 1 , HLA-G or H2-M3 claim 1 , Cd47 claim 1 , Cd200 claim 1 , FASLG or FasL claim 1 , Ccl21 or Ccl21b claim 1 , Mfge8 claim 1 , or Serpin B9 or Spi6.3. The cell of claim 1 , wherein the set of transgenes comprises PD-L1 claim 1 , HLA-G or H2-M3 claim 1 , Cd47 claim 1 , Cd200 claim 1 , FASLG or FasL claim 1 , Ccl21 or Ccl21b claim 1 , Mfge8 claim 1 , and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1 claim 1 , ...

EXPOSED COLLAGEN-TARGETED FUSION CYTOKINE FOR IMMUNE MODULATION IN INVASIVE CANCERS AND LESIONS OF INFECTIONS

Provided herein are new compositions and methods to target pharmaceutical agents to pathological areas by utilizing fusion polypeptides. These fusion polypeptides contain two or more domains: (i) aptamer sequences that bind to exposed collagenous (XC-) proteins present in pathological areas, including cancerous and viral lesions, (ii) immunomodulators, such as cytokines, and optionally (iii) at least one linker joining the two domains or at the terminus of the polypeptide. In some cases, the linker is a rigid linker, e.g., a rigid helical linker. Also provided herein are methods of treating cancer and/or infectious diseases using the new fusion polypeptides. 184-. (canceled)85. A method of treating an infection in a subject comprising administering to a subject in need of such treatment a fusion polypeptide comprising an amino acid sequence selected from the group consisting of:APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGAEAAAKEAAAKAGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 17);APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGSAGSAAGSGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 18);METDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEFEENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGAEAAAKEAAAKA GARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 19);1VIETDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEFEENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGSAGSAAGSGARR GVRVAWREPGRMELNMPHGQE (SEQ ID NO: 40);METDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEHENLYFQGARRGVHVGWREPGRMELN MPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNET VEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT QIITFESFKENLKDFLLVIPFDCWEPVQE (SEQ ID NO: 36); andRRGVHVGWREPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEA ...

Tetrapeptides Derived from Human C-X-C Chemokines Useful for Treatment of Various Skin Conditions

Tetrapeptides consisting of (I or V)—X1-K—X2, where X1 can be selected from E, Q or K, and X2 can be selected from M, F, I, W, or V, exhibit diverse bioactivities. They are multi-functional effector molecules to stimulate keratinocytes migration; neutralize the proinflammatory effect of bacterial cell wall components such as lipoteichoic acids of the Gram-positive S. aureus; and induce angiogenesis in cultured human umbilical vein endothelial cells. The downregulation of pro-inflammatory condition was also demonstrated using SOR-300-FT psoriasis skin model for representative peptide. The bioactivity was also supported by gene profiling study upon treatment of normal skin tissues using EPIDERM™ skin substitutes. The inventive peptides with diverse bioactivities are useful for treating various skin conditions including, but not limited to, acute or chronic wounds, striae distensae, aging skin, hair control, inflammatory skins such as psoriasis, atopic dermatitis and rosacea and for unwanted hair removal or for conditions such as removal of skin tags.

Treatment of right ventricular dysfunction due to pressure overload

A method is disclosed for inducing right ventricular (RV) adaptive remodeling in a patient suffering from pulmonary hypertension (PH) due to pressure overload comprising administering a therapeutically effective amount of a carditrophin-1 polypeptide, recombinant protein or a polynucleotide encoding CT-1 polypeptide or full-length protein.

USE OF MIF AND MIF PATHWAY AGONISTS

The present invention relates to novel methods and compositions for increasing AMPK activity and glucose uptake comprising administering a macrophage migration inhibitory factor (MIF) pathway agonist in a subject in need thereof. The invention also relates to methods for selecting a subject for treatment with an agonist of MIF, identifying a subject at risk for developing a condition in which increased AMPK activity is desirable, and for predicting whether a subject is susceptible to a condition in which increased AMPK activity is desirable. 16.-. (canceled)7. A method of predicting whether a subject is susceptible to a condition in which increased AMPK activity is desirable , comprising genotyping a subject for the presence of a polymorphism associated with decreased MIF expression , wherein a subject having a polymorphism associated with decreased MIF expression is more susceptible to the condition.8. The method of claim 7 , wherein the condition in which increased AMPK activity is desirable is a condition selected from the group consisting of: hypoxia claim 7 , ischemia claim 7 , and type 2 diabetes.9. The method of claim 8 , wherein the ischemia is caused by myocardial infarction claim 8 , coronary revascularization claim 8 , stroke claim 8 , vascular occlusion claim 8 , organ transplant surgery claim 8 , vascular surgery.1017-. (canceled)18. A method of increasing uptake of AMPK-mediated glucose into a cell claim 8 , comprising administering a MIF agonist to a subject in need thereof.1920.-. (canceled)21. A method of increasing AMPK-mediated glycolysis in a cell claim 8 , comprising administering a MIF agonist to a subject in need thereof.2225.-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/751,887, filed Jan. 28, 2013, which is a continuation of U.S. patent application Ser. No. 12/083,131, filed Apr. 3, 2008, which is a U.S. national stage filing under 35 U.S.C. §371 of International Application No. PCT/US2006/039315, ...

ENGINEERED CYTOKINE- AND CHEMOKINE-EXPRESSING CANDIDA ALBICANS STRAINS AND METHODS OF USE

Recombinant nucleic acid constructs for expression of heterologous cytokines or chemokines in , and genetically modified strains comprising the recombinant nucleic acid constructs, are described. The recombinant nucleic acid molecules include a gene promoter sequence, a nucleic acid sequence encoding a secreted protein signal sequence and a heterologous open reading frame (ORF) of a cytokine or chemokine gene. Also described are a method of expressing a heterologous cytokine or chemokine protein in a subject, and a method of treating or inhibiting the development of candidiasis in a subject. These methods include administering a genetically modified containing a recombinant nucleic acid construct for expression of a heterologous cytokine or chemokine. Exemplary cytokines or chemokines include IL8, IL17A, CXCL1, CXCL2 and CXCL5. 1Candida albicansC. albicansC. albicans. A recombinant nucleic acid molecule comprising a (gene promoter sequence , a nucleic acid sequence encoding a secreted protein signal sequence and a heterologous open reading frame (ORF) of a cytokine or chemokine gene , wherein the nucleic acid encoding the secreted protein signal sequence is fused in frame to the heterologous ORF.2C. albicans. The recombinant nucleic acid molecule of claim 1 , wherein the gene promoter sequence is a TDH3 promoter sequence.3. The recombinant nucleic acid molecule of claim 1 , wherein the secreted protein is the secreted aspartyl proteinase 5 (SAP5) protein.4C. albicans.. The recombinant nucleic acid molecule of claim 1 , wherein the heterologous ORF is codon-optimized for expression in5. The recombinant nucleic acid molecule of claim 1 , wherein the cytokine or chemokine gene is human IL8 claim 1 , human IL17A claim 1 , mouse IL17A claim 1 , mouse CXCL1 claim 1 , mouse CXCL2 or mouse CXCL5.6. The recombinant nucleic acid molecule of claim 2 , wherein the TDH3 promoter sequence comprises nucleotides 2758-3737 of SEQ ID NO: 1.7. The recombinant nucleic acid molecule of ...

VACCINE COMPOSITIONS COMPRISING C-C MOTIF CHEMOKINE 22 (CCL22) OR FRAGMENTS THEREOF

The present disclosure relates to CCL22 as a novel T cell target in cancer immunosuppression. 1. A vaccine composition comprising: (i) CCL22 of SEQ ID NO: 12 or of SEQ ID NO: 15 or an immunogenically active peptide fragment of CCL22 comprising a consecutive sequence of amino acids of CCL22 of SEQ ID NO: 12 or SEQ ID NO: 15;', '(ii) an immunogenically active peptide fragment of CCL22, which is an MHC Class I-restricted peptide fragment or MHC Class II-restricted peptide fragment;', '(iii) a functional homologue of the polypeptides under (i) and (ii), wherein said functional homologue shares at least 70% sequence identity with SEQ ID NO: 12 or SEQ ID NO: 15, and/or said functional homologue is an immunogenically active polypeptide consisting of a sequence identical to a consecutive sequence of amino acids of SEQ ID NO: 12 or SEQ ID NO: 15, except that at the most three amino acids have been substituted, such as at the most two amino acids, such as at the most one amino acid;', '(iv) a polypeptide comprising any of the polypeptides under (i), (ii) or (iii));', '(v) a nucleic acid encoding any of the polypeptides under (i), (ii) or (iii); and optionally, 'a) one or more of the followingb) an adjuvant.2. The vaccine composition according to claim 1 , wherein said immunogenically active peptide fragment consists of a consecutive sequence of in the range of from 5 to 24 amino acids of SEQ ID NO: 12 or SEQ ID NO: 15 claim 1 , or a functional homologue sharing at least 70% sequence identity with SEQ ID NO: 12 or SEQ ID NO: 15.3. The vaccine composition according to claim 1 , wherein said immunogenically active peptide fragment comprises or consists ofa) a consecutive sequence in the range of 8 to 11 amino acids of SEQ ID NO: 12 or SEQ ID NO: 15, such as a consecutive sequence of 9 to 10 amino acids of SEQ ID NO: 12 or SEQ ID NO: 15; orb) a consecutive sequence in the range of 20 to 25 amino acids of SEQ ID NO: 12, such as a consecutive sequence of 22 to 24 amino acids of SEQ ...

COMPOSITIONS COMPRISING CHEMERIN AND METHODS OF USE THEREOF

The present disclosure provides compositions comprising chemerin and the methods of use thereof. The compositions of the disclosure are useful in the treatment of cancer. 1. A polynucleotide sequence encoding a polypeptide , the polypeptide comprising chemerin linked via a linker to a targeting moiety , wherein the targeting moiety is capable of directing the chemerin to a target site on a cell.2. The polynucleotide sequence of claim 1 , wherein the chemerin is mature chemerin comprising a nucleotide sequence encoding SEQ ID NO:3 or prochemerin comprising a nucleotide sequence encoding SEQ ID NO:2.3. (canceled)4. The polynucleotide sequence of claim 1 , wherein the chemerin is mature chemerin comprising a nucleotide sequence encoding SEQ ID NO:2 with 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 or 9 amino acids absent from the C-terminus of SEQ ID NO:2.56.-. (canceled)7. The polynucleotide sequence of claim 1 , wherein the targeting moiety is capable of directing the chemerin to a target site on a cancer cell selected from the group consisting of CD20 claim 1 , HER2 claim 1 , EGFR claim 1 , PSCA and PSMA.8. (canceled)9. The polynucleotide sequence of claim 1 , wherein the targeting moiety is selected from the group consisting of an antibody or fragment thereof claim 1 , an aptamer claim 1 , or a binding domain derived from a target protein ligand.10. (canceled)11. The polynucleotide sequence of claim 1 , wherein the targeting moiety is a CD20 scFv comprising a nucleotide sequence encoding SEQ ID NO:4 or PSCA scFv comprising a nucleotide sequence encoding SEQ ID NO:5.1216.-. (canceled)17. The polynucleotide sequence of claim 1 , wherein the linker is a cleavable linker.18. (canceled)19. The polynucleotide sequence of claim 17 , wherein the linker is a MMP cleavable linker and comprises a MMP2 or MMP9 sensitive site.2021.-. (canceled)22. The polynucleotide sequence of claim 17 , wherein the linker comprises a nucleotide sequence encoding SEQ ID NO:8.2326.-. (canceled)27. A ...

FUSOKINES INVOLVING CYTOKINES WITH STRONGLY REDUCED RECEPTOR BINDING AFFINITIES

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases. 18.-. (canceled)9. A composition comprising a fusion protein comprising at least two cytokines ,wherein the cytokines are human chemokine (C motif) ligand (XCL1) and human interferon alpha 2 (IFNα2), andwherein at least one cytokine comprises a mutation that reduces binding activity to its receptor as compared to wild type cytokine and at least one cytokine is a wild-type cytokine which provides cell-specific targeting that restores activity of the mutant cytokine on the targeted cells.10. The composition of claim 9 , further comprising a linker.11. The composition of claim 10 , wherein the linker is one or more GSS repeats.12. The composition of claim 9 , wherein the human IFNα2 comprises the mutation.13. The composition of claim 12 , wherein the wild-type cytokine is the human XCL1.14. A method of stimulating an immune response in a cell claim 12 , comprising contacting the cell with a composition comprising a composition comprising at least two cytokines claim 12 ,wherein the cytokines are human XCL1 and human IFNα2, andwherein at least one of the cytokines has a mutation which provides reduced affinity for its receptor as compared to wild type cytokine and at least one cytokine is a wild-type cytokine that provides cell-specific targeting that restores activity of the mutant cytokine on the targeted cells.15. The method of claim 14 , wherein the composition further comprises a linker.16. The method of claim 15 , wherein the linker is one or more GSS repeats.17. The method of claim 14 , wherein the human IFNα2 comprises the mutation.18. The method of claim 17 , wherein the wild-type ...

MODIFICATION OF IMMUNE CELLS FOR REDUCING TOXICITY AND USES THEREOF IN ADOPTIVE CELL THERAPY

A population of immune cells comprising modified immune cells with reduced inflammatory properties, wherein such modified immune cells may have reduced production of one or more inflammatory cytokines (e.g., interleukin 2) and/or express one or more antagonists of one or more inflammatory cytokines (e.g., interleukin 6). Also provided herein are methods of producing such immune cell populations comprising the modified immune cells and methods of using such in cell therapy (e.g., to treat cancer, infectious diseases or immune diseases).

NOVEL AIMP1 PROTEIN FRAGMENT AND SKIN-PROTECTING COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to novel fragments of AIMP1 protein and a composition comprising the same as an active ingredient for preventing skin-aging, anti-wrinkle, and improving skin flexibility or elasticity. 1. A polypeptide consisting of 4 to 17 consecutive amino acids from the amino acid sequence of SEQ ID NO: 1 , wherein the polypeptide comprises the 9to 12amino acid residue (KGAE) of amino acid sequence of SEQ ID NO: 1 , or a polypeptide consisting of an amino acid sequence having 70% or more sequence homology with the polypeptide.2. The polypeptide of claim 1 , wherein the polypeptide consists of 10 to 15 consecutive amino acids from the amino acid sequence of SEQ ID NO: 1 and comprises the 9to 12amino acid residue (KGAE) of amino acid sequence of SEQ ID NO: 1.3. The polypeptide of claim 1 , wherein the polypeptide consists of amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3.4. A polynucleotide encoding the polypeptide of .5. The polynucleotide of claim 4 , wherein the polynucleotide consists of nucleotide sequence of SEQ ID NO: 7 or SEQ ID NO: 8.6. A composition comprising as an active ingredient a polypeptide consisting of 4 to 17 consecutive amino acids from the amino acid sequence of SEQ ID NO: 1 claim 4 , wherein the polypeptide comprises the 9to 12amino acid residue (KGAE) of amino acid sequence of SEQ ID NO: 1 claim 4 , or a polypeptide consisting of an amino acid sequence having 70% or more sequence homology with the polypeptide.7. The composition of claim 6 , wherein the polypeptide consists of amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3.8. The composition of claim 6 , wherein the composition is 4 a cosmetic composition claim 6 , or a food composition.914-. (canceled)15. A method for anti-wrinkle claim 1 , improving skin flexibility and elasticity claim 1 , the method comprising administering to a subject in need thereof an effective amount of the polypeptide of .16. (canceled)17. A method for preventing skin-aging claim 1 , the ...

METHODS AND REAGENTS FOR MODULATING MACROPHAGE PHENOTYPE

The present invention is directed to methods of inducing a phenotypic change in a population of monocytes and; or macrophages. The method includes administering to the population of monocytes and/or macrophages, a macrophage stimulating agent coupled to a carrier molecule, wherein the carrier molecule facilitates macropinocytic uptake of the agent by monocytes and macrophages in the population and is defective in neonatal Fc receptor binding, wherein the administering induces a phenotypic change in the monocytes and macrophages in the population. 116.-. (canceled)17. A method of treating a tumor in a subject comprising:selecting a subject having a tumor andadministering to the selected subject an anti-tumor agent coupled to a carrier molecule that is defective in neonatal Fc receptor (FcRn) binding, wherein said administering induces a therapeutic tumor cell response in the subject.18. The method of claim 17 , wherein the tumor is characterized by tumor cells expressing FcRn.19. The method of claim 17 , wherein the anti-tumor agent is a chemotherapeutic agent.20. The method of claim 17 , wherein the chemotherapeutic agent is a taxane.21. The method of claim 20 , wherein the taxane is paclitaxel.22. The method of claim 17 , wherein the carrier molecule is a variant human albumin protein or fragment thereof.23. The method of claim 22 , wherein the variant human albumin protein or fragment thereof comprises one or more amino acid modifications at one or more amino acid positions corresponding to 464 claim 22 , 494 claim 22 , 495 claim 22 , 496 claim 22 , 499 claim 22 , 500 claim 22 , 510 claim 22 , 535 claim 22 , 536 claim 22 , 537 claim 22 , 538 claim 22 , and 573 of SEQ ID NO: 1.24. The method of claim 23 , wherein the variant human albumin protein or fragment thereof comprises one or more amino acid modification selected from the group consisting of D494N claim 23 , D494Q claim 23 , D494A claim 23 , E495Q claim 23 , E495A claim 23 , T496A claim 23 , P499A claim 23 , ...

CHIMERIC ANTIGEN RECEPTORS COMPRISING BCMA-SPECIFIC FIBRONECTIN TYPE III DOMAINS AND USES THEREOF

BCMA-specific fibronectin type III (FN3) domains, BCMA-targeting chimeric antigen receptors (CARs) comprising the FN3 domains, and engineered BCMA-targeting immune cells expressing the CARs are described. Also described are nucleic acids and expression vectors encoding the FN3 domains and the CARs, recombinant cells containing the vectors, and compositions comprising the engineered immune cells. Methods of making the FN3 domains, CARs, and engineered immune cells, and methods of using the engineered immune cells to treat diseases including cancer are also described. 113-. (canceled)14. An isolated polynucleotide encoding a chimeric antigen receptor (CAR) comprising:an extracellular domain having an FN3 domain that binds to BCMA;a transmembrane domain; andan intracellular signaling domain.15. The isolated polynucleotide of claim 14 , wherein the FN3 domain comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 1; and wherein the FN3 domain binds to a human BCMA with a KD less than 1×10M as determined by using surface plasmon resonance.16. The isolated polynucleotide of claim 14 , wherein the FN3 domain comprises the amino acid sequence of SEQ ID NO: 7.17. The isolated polynucleotide of claim 14 , wherein the FN3 domain comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 8-44 and 58-145.18. The isolated polynucleotide of claim 14 , wherein the FN3 domain comprises the amino acid sequence of any one of SEQ ID NOs: 8-44 and 58-145.19. The isolated polynucleotide of claim 14 , wherein the CAR further comprises a signal peptide at the amino terminus.20. The isolated polynucleotide of claim 19 , wherein the CAR further comprises a hinge region connecting the extracellular domain and the transmembrane domain.21. The isolated polynucleotide of claim 20 , wherein the hinge region comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 3.22. The isolated polynucleotide of claim 21 , wherein the ...

TETANUS TOXOID AND CCL3 IMPROVE DC VACCINES

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4 T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy. 119-. (canceled)20. A method of immunizing a human , comprising: administering a first acellular immunogen to the human; and administering a second immunogen to the human , whereby administration of the first immunogen increases migration of the second immunogen to vaccine draining lymph nodes (VDLNs) , and wherein the first and second administrations are separated by 1 hour to 4 weeks.21. The method of claim 20 , wherein the first acellular immunogen is selected from the group consisting of tetanus toxoid claim 20 , diphtheria toxoid claim 20 , tetanus and diphtheria toxoids claim 20 , pneumococcal conjugate vaccine (PCV) claim 20 , and haemophilus b conjugate vaccine.22. The method of claim 20 , wherein the second immunogen comprises a cytomegalovirus (CMV) antigen or an RNA encoding a CMV antigen.23. The method of claim 22 , wherein the CMV antigen is pp65.24. The method of claim 20 , wherein the second immunogen comprises dendritic cells pulsed with a CMV integument protein pp65 RNA.25. The method of claim 20 , wherein the method further comprises administering chemokine (C-C motif) ligand 3 (CCL3) to the human.26. The method of claim 20 , wherein the first immunogen ...