ES2560657T3 - Glicosilación con unión en O de péptidos G-CSF - Google Patents

Glicosilación con unión en O de péptidos G-CSF Download PDF

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ES2560657T3
ES2560657T3 ES05711345.8T ES05711345T ES2560657T3 ES 2560657 T3 ES2560657 T3 ES 2560657T3 ES 05711345 T ES05711345 T ES 05711345T ES 2560657 T3 ES2560657 T3 ES 2560657T3
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p61lssc
sequence
group
mutant peptide
galnac
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Shawn Defrees
David A. Zopf
Zhi-Guang Wang
Henrik Clausen
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Ratiopharm GmbH
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Abstract

Un polipéptido G-CSF aislado que comprende una secuencia de péptido mutante, en el que la secuencia de péptido mutante codifica un sitio de glicosilación con unión en O que no existe en un polipéptido de tipo silvestre correspondiente al polipéptido aislado, en donde la secuencia de péptido mutante se selecciona del grupo que consiste en MVTPLGP, MQTPLGP, MIATPLGP, MATPLGP, MPTQGAMPLGP, MVQTPLGP, MQSTPLGP, MGQTPLGP, MAPTSSSPLGP y MAPTPLGPA, o en donde la secuencia de péptido mutante se selecciona del grupo que consiste en MTPTLGP, MTPTQLGP, MTPTSLGP, MTPTQGP, MTPTSSP, M1TPQTP, M1TPTGP, M1TPLTP, M1TPNTGP, MTPLGP, M1TPVTP, M1TPMVTP y MT1P2TQGL3G4P5A6S7, o en donde la secuencia de péptido mutante se selecciona del grupo que consiste en P129ATQPT, P129TLGPT, P129TQGPT, P129TSSPT, P129TQGAPT, P129NTGPT, PALQPTQT, P129ALTPT, P129MVTPT, P129ASSTPT, MAP129ATQPTQGAM y MP129ATTQPTQGAM, o en donde la secuencia de péptido mutante se selecciona del grupo que consiste en LGIPTA P61LSSC, LGIPTQ P61LSSC, LGIPTQG P61LSSC, LGIPQT P61LSSC, LGIPTS P61LSSC, LGIPTS P61LSSC, LGIPTQP61LSSC, LGTPWAP61LSSC, LGTPFA P61LSSC y SLGAP58TAP61LSS, o en donde la secuencia de péptido mutante se selecciona del grupo que consiste en RHLAQTP175, RHLAGQTP175, QP175TQGAMP, RHLAQTP175AM, QP175TSSAP, QP175TSSAP, QP175TQGAMP, QP175TQGAM, QP175TQGA, QP175TVM, QP175NTGP y QP175QTLP, o en donde la secuencia de péptido mutante se selecciona del grupo que consiste en P133TQTAMP139, P133TQGTMP, P133TQGTNP, P133TQGTLP, PALQP133TQTAMPA, P129TTQP, P129NTLP, P129TLQP, P61TSSC, P61TSSAC, P61FTP y LGSTLGI.

Description

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secuencia indicada explícitamente. En concreto, las sustituciones de codones degenerados se pueden realizar generando secuencias en las que la tercera posición de uno o más codones seleccionados (o de todos) está sustituida con restos de base mixta y/o desoxiinosina (Batzer et al., Nucleic Acid Res. 19: 5081 (1991); Ohtsuka et al., J. Biol. Chem. 260: 2605-2608 (1985); y Rossolini et al., Mol. Cell. Probes 8: 91-98 (1994)). La expresión ácido nucleico se usa indistintamente con gen, ADNc y ARNm codificado por un gen.
El término "gen" significa el segmento de ADN implicado en la producción de una cadena polipeptídica. Puede incluir regiones precedentes y siguientes a la región de codificación (líder y remolque), así como secuencias intermedias (intrones) entre segmentos individuales de codificación (exones).
El término "aislado", cuando se aplica a un ácido nucleico o a una proteína, indica que el ácido nucleico o la proteína está sustancialmente exento de otros componentes celulares con los que se asocia en el estado natural. Está preferentemente en un estado homogéneo, aunque puede estar en una solución bien seca o acuosa. Por lo general, la pureza y la homogeneidad se determinan usando técnicas de química analítica, tales como electroforesis en gel de poliacrilamida o cromatografía de líquidos de alto rendimiento. Una proteína que es la especie predominante presente en una preparación está sustancialmente purificada. En particular, un gen aislado se separa de los marcos de lectura abierta que flanquean el gen y que codifican una proteína que no sea el gen de interés. El término "purificado" indica que un ácido nucleico o una proteína da lugar a sustancialmente una banda en un gel electroforético. En particular, significa que el ácido nucleico o la proteína que tiene una pureza del al menos 85 %, más preferentemente del al menos 95 % y lo más preferentemente del al menos 99 %.
El término "aminoácido" se refiere a aminoácidos de origen natural y sintéticos, así como a análogos de aminoácidos y miméticos de aminoácidos que funcionan de una manera similar a los aminoácidos de origen natural. Los aminoácidos de origen natural son los codificados por el código genético, así como aquellos aminoácidos que se modifican posteriormente, por ejemplo, hidroxiprolina, γ-carboxiglutamato y O-fosfoserina. Análogos de aminoácidos se refiere a compuestos que tienen la misma estructura química básica que un aminoácido de origen natural, es decir, un carbono α que está unido a un hidrógeno, un grupo carboxilo, un grupo amino y un grupo R, por ejemplo, homoserina, norleucina, sulfóxido de metionina, metilsulfonio de metionina. Dichos análogos tienen grupos R modificados (por ejemplo, norleucina) o cadenas principales peptídicas modificadas, pero conservan la misma estructura química básica que un aminoácido de origen natural. "Miméticos de aminoácidos" se refiere a compuestos químicos que tienen una estructura que es diferente de la estructura química general de un aminoácido, pero que funcionan de una manera similar a un aminoácido de origen natural.
En la técnica, existen diversos métodos conocidos que permiten la incorporación de un derivado de aminoácido no natural o análogo en una cadena polipeptídica de una manera específica de sitio, véase, por ejemplo, el documento WO 02/086075.
En el presente documento, los aminoácidos se pueden indicar bien por los símbolos de tres letras comúnmente conocidos o por los símbolos de una letra recomendados por la Comisión de Nomenclatura Bioquímica de la IUPAC-IUB. Del mismo modo, los nucleótidos, se pueden indicar mediante sus códigos de una sola letra comúnmente aceptados.
"Variantes modificadas de manera conservadora" se aplica tanto a secuencias de aminoácidos como de ácido nucleico. Con respecto a las secuencias de ácido nucleico en particular, "variantes modificadas de manera conservadora" se refiere a los ácidos nucleicos que codifican secuencias de aminoácidos idénticas o sustancialmente idénticas, o en las que el ácido nucleico no codifica una secuencia de aminoácidos, a secuencias sustancialmente idénticas. Debido a la degeneración del código genético, hay un gran número de ácidos nucleicos funcionalmente idénticos que codifican cualquier proteína dada. Por ejemplo, todos los codones GCA, GCC, GCG y GCU codifican el aminoácido alanina. Por lo tanto, en cada posición en la que una alanina está especificada por un codón, el codón se puede modificar a cualquiera de los codones correspondientes descritos sin alterar el polipéptido codificado. Dichas variaciones de ácido nucleico son "variaciones silenciosas", que son una especie de variaciones modificadas de manera conservadora. En el presente documento, cada secuencia de ácido nucleico que codifica un polipéptido también describe cada variación silenciosa posible del ácido nucleico. Un experto reconocerá que todos los codones de un ácido nucleico (a excepción de AUG, que es habitualmente el único codón para la metionina y TGG, que es habitualmente el único codón para el triptófano) se pueden modificar para producir una molécula funcionalmente idéntica. Por consiguiente, cada variación silenciosa de un ácido nucleico que codifica un polipéptido está implícita en cada secuencia descrita.
En cuanto a las secuencias de aminoácidos, un experto reconocerá que sustituciones, eliminaciones o adiciones individuales de un ácido nucleico, péptido, polipéptido o secuencia de proteínas que altera, añade o elimina un solo aminoácido o un pequeño porcentaje de aminoácidos en la secuencia codificada es una "variante modificada de forma conservadora", en la que la modificación genera la sustitución de un aminoácido con un aminoácido químicamente similar. Las tablas de sustituciones conservadoras que proporcionan aminoácidos funcionalmente similares son bien conocidas en la técnica. Dichas variantes modificadas de manera conservadora se suman a y no excluyen variantes polimórficas, homólogos entre especies y alelos de la invención.
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un proceso altamente regulado que muestra un alto grado de conservación entre los organismos multicelulares.
La primera etapa de la glicosilación con unión en O de tipo mucina está catalizada por uno o más miembros de una gran familia de UDP-GalNAc: las N-acetilgalactosaminiltransferasas polipeptídicas (GalNAc-transferasas) (EC 2.4.1.41), que transfieren GalNAc a sitios aceptores de serina y de treonina (Hassan et al., J. Biol. Chem. 275: 38197-38205 (2000)). Hasta la fecha, se han identificado y caracterizado doce miembros de la familia de GalNActransferasa de mamíferos (Schwientek et al., J. Biol. Chem. 277: 22623-22638 (2002)) y se han predicho varios supuestos miembros adicionales de esta familia genética a partir del análisis de bases de datos del genoma. Las isoformas de la GalNAc-transferasa tienen diferentes propiedades cinéticas y muestran patrones de expresión diferenciales temporal y espacialmente, lo que sugiere que tienen funciones biológicas distintas (Hassan et al., J. Biol. Chem. 275: 38197-38205 (2000)). El análisis de secuencias de GalNAc-transferasas ha conducido a la hipótesis de que estas enzimas contienen dos subunidades distintas: una unidad catalítica central y una unidad Cterminal con similitud en la secuencia con la de la lectina ricina vegetal, denominada "dominio de lectina" (Hagen et al., J. Biol. Chem. 274: 6797-6803 (1999); Hazes, Protein Eng. 10: 1353-1356 (1997); Breton et al., Curr. Opin. Struct. Biol. 9: 563-571 (1999)). Experimentos previos que implican mutagénesis específica del sitio de restos conservados seleccionados confirmaron que mutaciones en el dominio catalítico eliminaban la actividad catalítica. Por el contrario, las mutaciones en el "dominio de lectina" no tenían efectos significativos en la actividad catalítica de la isoforma de GalNAc-transferasa, GalNAc-T1 (Tenno et al., J. Biol. Chem. 277(49): 47088-96 (2002)). Por lo tanto, se creía que el "dominio de lectina" C-terminal no era funcional y no desempeñaba papeles para las funciones enzimáticas de las GalNAc-transferasas (Hagen et al., J. Biol. Chem. 274: 6797-6803 (1999)).
No obstante, pruebas recientes demuestran que algunas GalNAc-transferasas presentan actividades únicas con glicopéptidos parcialmente GalNAc-glicosilados. Las acciones catalítica de al menos tres isoformas de GalNActransferasa, GalNAc-T4, -T7 y -T10, actúan selectivamente en los glicopéptidos que corresponden a dominios de repetición en tándem de mucina en los que solamente algunas de las secuencias de glicosilación potencial agrupadas han sido glicosiladas con GalNAc por otras GalNAc-transferasas (Bennett et al., FEBS Letters 460: 226230 (1999); Ten Hagen et al., J. Biol. Chem. 276: 17395-17404 (2001); Bennett et al., J. Biol. Chem. 273: 3047230481 (1998); Ten Hagen et al., J. Biol. Chem. 274: 27867-27874 (1999)). GalNAc-T4 y -T7 reconocen diferentes polipéptidos glicosilados con GalNAc y catalizan la transferencia de GalNAc a sitios de sustrato aceptor además de los que se han utilizado anteriormente. Se predice que una de las funciones de dichas actividades de GalNActransferasa representa una etapa de control de la densidad de ocupación de O-glicano en mucinas y en glicoproteínas de tipo mucina con alta densidad de glicosilación con unión en O.
Un ejemplo de ello es la glicosilación de la mucina asociada con el cáncer MUC1. La MUC1 contiene una región glicosilada con unión en O de repetición en tándem de 20 restos (HGVTSAPDTRPAPGSTAPPA) con cinco posibles sitios de glicosilación con unión en O. GalNAc-T1, -T2 y -T3 pueden iniciar la glicosilación de la repetición en tándem de MUC1 y se pueden incorporar solamente en tres sitios (HGVTSAPDTRPAPGSTAPPA, se subrayan los sitios de unión a GalNAc). La GalNAc-T4 es única en que es la única isoforma de GalNAc-transferasa identificada hasta el momento que puede completar la unión del glicano con unión en O a los cinco sitios aceptores en la secuencia de repetición en tándem de 20 aminoácidos de la mucina asociada con el cáncer de mama. MUC1. GalNAc-T4 transfiere GalNAc a al menos dos sitios no usados por otras isoformas de GalNAc-transferasa en el glipopéptido GalNAc4TAP24 (TAPPAHGVTSAPDTRPAPGSTAPP, los sitios de unión a GalNAc-T4 únicos están en negrita) (Bennett et al., J. Biol. Chem. 273: 30472-30481 (1998). Parece que una actividad tal como la que presenta GalNAc-T4 es necesaria para la producción de la glicoforma de MUC1 expresada por células cancerosas cuando todos los sitios potenciales están glicosilados (Muller et al., J. Biol. Chem. 274: 18165-18172 (1999)). La MUC1 normal de las glándulas mamarias lactantes tiene aproximadamente 2,6 glicanos con unión en O por repetición (Muller et al., J. Biol. Chem. 272: 24780-24793 (1997) y la MUC1 derivada de la línea celular de cáncer T47D tiene 4,8 glicanos con unión en O por repetición (Muller et al., J. Biol. Chem. 274: 18165-18172 (1999)). La forma de MUC1 asociada al cáncer está asociada, por tanto, con una mayor densidad de ocupación de glicano con unión en O y esto se consigue mediante una actividad de GalNAc-transferasa idéntica o similar a la de GalNAc-T4.
Las GalNAc-transferasas polipeptídicas, que no han presentado especificidades aparentes hacia GalNAcglicopéptido, también parecen estar moduladas por sus supuestos dominios de lectina (documento PCT WO 01/85215 A2). Recientemente, se encontró que las mutaciones en el supuesto dominio de lectina de GalNAc-T1, al igual que las que se han analizado anteriormente en GalNAc-T4 (Hassan et al., J. Biol. Chem. 275:38197-38205 (2000)), modificaban la actividad de la enzima de una forma similar a GalNAc-T4. Por lo tanto, aunque la GalNAc-T1 de tipo silvestre añadía múltiples restos de GalNAc consecutivos a un sustrato peptídico con múltiples sitios aceptores, la GalNAc-T1 mutada no añadía más de un resto de GalNAc al mismo sustrato (Tenno et al., J. Biol. Chem. 277(49): 47088-96 (2002)).
Dado que se ha demostrado que las mutaciones de las GalNAc transferasas se pueden utilizar para producir patrones de glicosilación que sean distintos de los producidos por las enzimas de tipo silvestre, la utilización de una
o más GalNAc-transferasas mutantes en la preparación de los péptidos glicosilados con unión en O de la invención pertenece al alcance de la presente invención.
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Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5545553A (en) * 1994-09-26 1996-08-13 The Rockefeller University Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them
US7795210B2 (en) 2001-10-10 2010-09-14 Novo Nordisk A/S Protein remodeling methods and proteins/peptides produced by the methods
US7173003B2 (en) * 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
US7696163B2 (en) * 2001-10-10 2010-04-13 Novo Nordisk A/S Erythropoietin: remodeling and glycoconjugation of erythropoietin
US8008252B2 (en) * 2001-10-10 2011-08-30 Novo Nordisk A/S Factor VII: remodeling and glycoconjugation of Factor VII
US7157277B2 (en) 2001-11-28 2007-01-02 Neose Technologies, Inc. Factor VIII remodeling and glycoconjugation of Factor VIII
US7179617B2 (en) * 2001-10-10 2007-02-20 Neose Technologies, Inc. Factor IX: remolding and glycoconjugation of Factor IX
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
MXPA04012496A (es) 2002-06-21 2005-09-12 Novo Nordisk Healthcare Ag Glicoformos del factor vii pegilados.
ATE466085T1 (de) * 2002-09-09 2010-05-15 Hanall Pharmaceutical Co Ltd Protease-resistente modifizierte interferon alpha polypeptide
EP1608688B1 (en) 2003-03-14 2013-02-27 BioGeneriX AG Branched water-soluble polymers and their conjugates
US8791070B2 (en) 2003-04-09 2014-07-29 Novo Nordisk A/S Glycopegylated factor IX
CA2522345A1 (en) * 2003-04-09 2004-11-18 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
WO2007022512A2 (en) * 2005-08-19 2007-02-22 Neose Technologies, Inc. Glycopegylated factor vii and factor viia
AU2004240553A1 (en) * 2003-05-09 2004-12-02 Neose Technologies, Inc. Compositions and methods for the preparation of human growth hormone glycosylation mutants
WO2005012484A2 (en) 2003-07-25 2005-02-10 Neose Technologies, Inc. Antibody-toxin conjugates
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
NZ547168A (en) * 2003-11-24 2010-05-28 Biogenerix Ag Glycopegylated erythropoietin
US8633157B2 (en) 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
US20080015142A1 (en) * 2003-12-03 2008-01-17 Defrees Shawn Glycopegylated Follicle Stimulating Hormone
US20060040856A1 (en) 2003-12-03 2006-02-23 Neose Technologies, Inc. Glycopegylated factor IX
US7956032B2 (en) 2003-12-03 2011-06-07 Novo Nordisk A/S Glycopegylated granulocyte colony stimulating factor
US20080318850A1 (en) * 2003-12-03 2008-12-25 Neose Technologies, Inc. Glycopegylated Factor Ix
JP4657219B2 (ja) * 2003-12-03 2011-03-23 バイオジェネリックス アーゲー ＧｌｙｃｏＰＥＧ化された顆粒球コロニー刺激因子
CA2552892C (en) * 2004-01-08 2014-08-05 Neose Technologies, Inc. O-linked glycosylation of peptides
ATE455861T1 (de) * 2004-05-04 2010-02-15 Novo Nordisk Healthcare Ag O-verknüpfte glykoformen von faktor vii und verfahren zu deren herstellung
US20080300173A1 (en) 2004-07-13 2008-12-04 Defrees Shawn Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1]
US20090292110A1 (en) * 2004-07-23 2009-11-26 Defrees Shawn Enzymatic modification of glycopeptides
US8268967B2 (en) * 2004-09-10 2012-09-18 Novo Nordisk A/S Glycopegylated interferon α
WO2006050247A2 (en) 2004-10-29 2006-05-11 Neose Technologies, Inc. Remodeling and glycopegylation of fibroblast growth factor (fgf)
US7998930B2 (en) 2004-11-04 2011-08-16 Hanall Biopharma Co., Ltd. Modified growth hormones
JP2008526864A (ja) * 2005-01-06 2008-07-24 ネオス テクノロジーズ インコーポレイテッド 糖断片を用いる糖結合
WO2006074467A2 (en) 2005-01-10 2006-07-13 Neose Technologies, Inc. Glycopegylated granulocyte colony stimulating factor
JP2006223198A (ja) * 2005-02-17 2006-08-31 National Institute Of Advanced Industrial & Technology 転移酵素による化合物ライブラリーおよびその製造方法
EP1866427A4 (en) * 2005-03-30 2010-09-01 Novo Nordisk As MANUFACTURING PROCESS FOR THE PRODUCTION OF CULTIVE PEPTIDES IN CELL LINES OF INSECTS
US20070154992A1 (en) * 2005-04-08 2007-07-05 Neose Technologies, Inc. Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
US20110003744A1 (en) * 2005-05-25 2011-01-06 Novo Nordisk A/S Glycopegylated Erythropoietin Formulations
WO2006127910A2 (en) * 2005-05-25 2006-11-30 Neose Technologies, Inc. Glycopegylated erythropoietin formulations
EP1891231A4 (en) 2005-05-25 2011-06-22 Novo Nordisk As GLYCOPEGYLATED FACTOR IX
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
WO2007055789A2 (en) 2005-10-31 2007-05-18 Neose Technologies, Inc. Expression of soluble therapeutic proteins
WO2007056191A2 (en) 2005-11-03 2007-05-18 Neose Technologies, Inc. Nucleotide sugar purification using membranes
CU23556A1 (es) * 2005-11-30 2010-07-20 Ct Ingenieria Genetica Biotech Estructura polimérica semejante a dendrímero para la obtención de conjugados de interés farmacéutico
WO2007120638A2 (en) * 2006-04-12 2007-10-25 President And Fellows Of Harvard College Methods and compositions for modulating glycosylation
JP2009534034A (ja) 2006-04-19 2009-09-24 ノヴォ ノルディスク アクティーゼルスカブ 原核微生物におけるｏ−グリコシル化治療用タンパク質の発現
EP2049144B8 (en) * 2006-07-21 2015-02-18 ratiopharm GmbH Glycosylation of peptides via o-linked glycosylation sequences
EP2054521A4 (en) 2006-10-03 2012-12-19 Novo Nordisk As METHODS OF PURIFYING CONJUGATES OF POLYPEPTIDES
DK2068907T3 (en) * 2006-10-04 2018-01-15 Novo Nordisk As GLYCEROL BOND PEGYLED SUGAR AND GLYCOPE Peptides
US8637007B2 (en) 2006-12-15 2014-01-28 Baxter International Inc. Factor VIIa-polysialic acid conjugate having prolonged in vivo half-life
CN101796063B (zh) * 2007-04-03 2017-03-22 拉蒂奥法姆有限责任公司 使用糖聚乙二醇化g‑csf的治疗方法
US9045516B2 (en) 2007-04-16 2015-06-02 Suri Saranathan Iyer Synthetic ligands for the differentiation of closely related toxins and pathogens
WO2008151258A2 (en) * 2007-06-04 2008-12-11 Neose Technologies, Inc. O-linked glycosylation using n-acetylglucosaminyl transferases
EP2170919B8 (en) 2007-06-12 2016-01-20 ratiopharm GmbH Improved process for the production of nucleotide sugars
WO2008156676A1 (en) 2007-06-15 2008-12-24 President And Fellows Of Harvard College Methods and compositions for detecting and modulating o-glycosylation
US7968811B2 (en) * 2007-06-29 2011-06-28 Harley-Davidson Motor Company Group, Inc. Integrated ignition and key switch
PL2197919T3 (pl) 2007-08-27 2014-09-30 Ratiopharm Gmbh Ciekły preparat koniugatu G-CSF
US8207112B2 (en) 2007-08-29 2012-06-26 Biogenerix Ag Liquid formulation of G-CSF conjugate
JP5358840B2 (ja) * 2007-11-24 2013-12-04 独立行政法人産業技術総合研究所 Ｇｆｐ（緑色蛍光蛋白質）の機能賦活・回復方法
EP2242505A4 (en) * 2008-01-08 2012-03-07 Biogenerix Ag GLYCOCONJUGATION OF POLYPEPTIDES USING OLIGOSACCHARYLTRANSFERASES
AU2009219232B2 (en) 2008-02-27 2014-02-27 Novo Nordisk A/S Conjugated Factor VIII molecules
US20100056766A1 (en) * 2008-08-27 2010-03-04 Abbott Laboratories Purification of biological conjugates by size exclusion chromatography
TW201042257A (en) * 2009-05-26 2010-12-01 Baxter Int Detection of antibody that binds to water soluble polymer-modified polypeptides
EP2438046A4 (en) 2009-06-01 2013-04-17 Harvard College O-GLCNAC TRANSFERASE INHIBITORS AND USES THEREOF
EP3093029A1 (en) 2009-07-27 2016-11-16 Baxalta GmbH Blood coagulation protein conjugates
NZ597600A (en) 2009-07-27 2014-05-30 Lipoxen Technologies Ltd Glycopolysialylation of non-blood coagulation proteins
EP2459224B1 (en) 2009-07-27 2016-06-01 Baxalta GmbH Blood coagulation protein conjugates
US8642737B2 (en) 2010-07-26 2014-02-04 Baxter International Inc. Nucleophilic catalysts for oxime linkage
US8809501B2 (en) 2009-07-27 2014-08-19 Baxter International Inc. Nucleophilic catalysts for oxime linkage
WO2011059828A1 (en) * 2009-10-29 2011-05-19 University Of Kansas Methods of producing and purifying proteins
KR101174494B1 (ko) 2009-12-30 2012-08-22 대한민국 인간 과립구 콜로니 자극인자의 생물학적 활성 증가 변이체
EP2536752B1 (en) 2010-02-16 2015-04-08 Novo Nordisk A/S Modified recombinant Factor VIII
CN103501804A (zh) * 2010-12-21 2014-01-08 雷科制药公司 眼泪替代物
SG191298A1 (en) 2010-12-22 2013-07-31 Baxter Int Materials and methods for conjugating a water soluble fatty acid derivative to a protein
WO2013006758A1 (en) 2011-07-06 2013-01-10 President And Fellows Of Harvard College Diphosphate mimetics and uses thereof
CA2858806A1 (en) * 2011-12-23 2013-06-27 Innate Pharma Enzymatic conjugation of polypeptides
WO2013149064A1 (en) * 2012-03-30 2013-10-03 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Uridine diphosphate compounds as mobilizers of hematopoietic progenitor cells
US10132799B2 (en) 2012-07-13 2018-11-20 Innate Pharma Screening of conjugated antibodies
EP2916872B1 (en) 2012-11-09 2019-02-27 Innate Pharma Recognition tags for tgase-mediated conjugation
KR20220103204A (ko) * 2013-03-11 2022-07-21 젠자임 코포레이션 과글리코실화된 결합 폴리펩티드
WO2014140300A1 (en) 2013-03-15 2014-09-18 Innate Pharma Solid phase tgase-mediated conjugation of antibodies
US10071169B2 (en) 2013-06-20 2018-09-11 Innate Pharma Enzymatic conjugation of polypeptides
EP3010548A1 (en) * 2013-06-21 2016-04-27 Innate Pharma Enzymatic conjugation of polypeptides
US9689016B2 (en) 2013-12-18 2017-06-27 Caliber Biotherapeutics, Llc Method for in vivo production of deglycosylated recombinant proteins used as substrate for downstream protein glycoremodeling
US10995148B2 (en) 2014-03-19 2021-05-04 Genzyme Corporation Site-specific glycoengineering of targeting moieties
SG11201703251TA (en) * 2014-10-29 2017-05-30 Teva Pharmaceuticals Australia Pty Ltd INTERFERON α2B VARIANTS
EP3423587B1 (en) 2016-04-05 2020-06-24 Council of Scientific & Industrial Research A multifunctional recombinant nucleotide dependent glycosyltransferase protein and its method of glycosylation thereof
CN112010942B (zh) * 2020-08-28 2022-05-17 深圳大学 一种使用超临界流体色谱制备放线菌素d和x2方法
CN114010765A (zh) * 2021-08-30 2022-02-08 上海延立药业有限公司 一种长效人生长激素

Family Cites Families (287)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1479268A (en) 1973-07-05 1977-07-13 Beecham Group Ltd Pharmaceutical compositions
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
CH596313A5 (es) 1975-05-30 1978-03-15 Battelle Memorial Institute
US4385260A (en) 1975-09-09 1983-05-24 Beckman Instruments, Inc. Bargraph display
US4414147A (en) 1981-04-17 1983-11-08 Massachusetts Institute Of Technology Methods of decreasing the hydrophobicity of fibroblast and other interferons
JPS57206622A (en) 1981-06-10 1982-12-18 Ajinomoto Co Inc Blood substitute
US4438253A (en) 1982-11-12 1984-03-20 American Cyanamid Company Poly(glycolic acid)/poly(alkylene glycol) block copolymers and method of manufacturing the same
US4496689A (en) * 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4565653A (en) * 1984-03-30 1986-01-21 Pfizer Inc. Acyltripeptide immunostimulants
US4879236A (en) 1984-05-16 1989-11-07 The Texas A&M University System Method for producing a recombinant baculovirus expression vector
JPS6238172A (ja) * 1985-08-12 1987-02-19 株式会社　高研 抗血栓性医用材料の製造方法
JPS63502716A (ja) 1986-03-07 1988-10-13 マサチューセッツ・インステチュート・オブ・テクノロジー 糖タンパク安定性の強化方法
US4925796A (en) 1986-03-07 1990-05-15 Massachusetts Institute Of Technology Method for enhancing glycoprotein stability
US4902505A (en) 1986-07-30 1990-02-20 Alkermes Chimeric peptides for neuropeptide delivery through the blood-brain barrier
IL82834A (en) 1987-06-09 1990-11-05 Yissum Res Dev Co Biodegradable polymeric materials based on polyether glycols,processes for the preparation thereof and surgical artiicles made therefrom
US5153265A (en) 1988-01-20 1992-10-06 Cetus Corporation Conjugation of polymer to colony stimulating factor-1
US4847325A (en) 1988-01-20 1989-07-11 Cetus Corporation Conjugation of polymer to colony stimulating factor-1
GB8810808D0 (en) 1988-05-06 1988-06-08 Wellcome Found Vectors
US5169933A (en) 1988-08-15 1992-12-08 Neorx Corporation Covalently-linked complexes and methods for enhanced cytotoxicity and imaging
US5218092A (en) 1988-09-29 1993-06-08 Kyowa Hakko Kogyo Co., Ltd. Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains
US5104651A (en) * 1988-12-16 1992-04-14 Amgen Inc. Stabilized hydrophobic protein formulations of g-csf
CA2006596C (en) 1988-12-22 2000-09-05 Rika Ishikawa Chemically-modified g-csf
US6166183A (en) 1992-11-30 2000-12-26 Kirin-Amgen, Inc. Chemically-modified G-CSF
DE68929551T2 (de) 1988-12-23 2008-03-06 Genentech, Inc., South San Francisco Menschliche DNase
KR910700264A (ko) 1989-01-19 1991-03-14 로버트 에이. 아미테이지 소마토트로핀 유사물
AU620673B2 (en) 1989-01-31 1992-02-20 Pharmacia & Upjohn Company Somatotropin analogs
US5194376A (en) * 1989-02-28 1993-03-16 University Of Ottawa Baculovirus expression system capable of producing foreign gene proteins at high levels
CA2053317C (en) 1989-04-19 1996-03-12 Shmuel Zalipsky Active carbonates of polyalkylene oxides for modification of polypeptides
US5122614A (en) 1989-04-19 1992-06-16 Enzon, Inc. Active carbonates of polyalkylene oxides for modification of polypeptides
US5324844A (en) 1989-04-19 1994-06-28 Enzon, Inc. Active carbonates of polyalkylene oxides for modification of polypeptides
US5342940A (en) 1989-05-27 1994-08-30 Sumitomo Pharmaceuticals Company, Limited Polyethylene glycol derivatives, process for preparing the same
US5672683A (en) 1989-09-07 1997-09-30 Alkermes, Inc. Transferrin neuropharmaceutical agent fusion protein
US5977307A (en) 1989-09-07 1999-11-02 Alkermes, Inc. Transferrin receptor specific ligand-neuropharmaceutical agent fusion proteins
US5182107A (en) * 1989-09-07 1993-01-26 Alkermes, Inc. Transferrin receptor specific antibody-neuropharmaceutical or diagnostic agent conjugates
US5527527A (en) 1989-09-07 1996-06-18 Alkermes, Inc. Transferrin receptor specific antibody-neuropharmaceutical agent conjugates
US5154924A (en) 1989-09-07 1992-10-13 Alkermes, Inc. Transferrin receptor specific antibody-neuropharmaceutical agent conjugates
US5032519A (en) 1989-10-24 1991-07-16 The Regents Of The Univ. Of California Method for producing secretable glycosyltransferases and other Golgi processing enzymes
US5312808A (en) 1989-11-22 1994-05-17 Enzon, Inc. Fractionation of polyalkylene oxide-conjugated hemoglobin solutions
IL96477A0 (en) 1989-12-01 1991-08-16 Amgen Inc Megakaryocyte production
US5595900A (en) 1990-02-14 1997-01-21 The Regents Of The University Of Michigan Methods and products for the synthesis of oligosaccharide structures on glycoproteins, glycolipids, or as free molecules, and for the isolation of cloned genetic sequences that determine these structures
US5324663A (en) 1990-02-14 1994-06-28 The Regents Of The University Of Michigan Methods and products for the synthesis of oligosaccharide structures on glycoproteins, glycolipids, or as free molecules, and for the isolation of cloned genetic sequences that determine these structures
DE4009630C2 (de) * 1990-03-26 1995-09-28 Reinhard Prof Dr Dr Brossmer CMP-aktivierte fluoreszierende Sialinsäuren sowie Verfahren zu ihrer Herstellung
US5583042A (en) 1990-04-16 1996-12-10 Neose Pharmaceuticals, Inc. Apparatus for the synthesis of saccharide compositions
GB9107846D0 (en) * 1990-04-30 1991-05-29 Ici Plc Polypeptides
US5951972A (en) * 1990-05-04 1999-09-14 American Cyanamid Company Stabilization of somatotropins and other proteins by modification of cysteine residues
US5399345A (en) * 1990-05-08 1995-03-21 Boehringer Mannheim, Gmbh Muteins of the granulocyte colony stimulating factor
US5219564A (en) 1990-07-06 1993-06-15 Enzon, Inc. Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon
CU22302A1 (es) 1990-09-07 1995-01-31 Cigb Secuencia nucleotidica codificante para una proteina de la membrana externa de neisseria meningitidis y uso de dicha proteina en preparados vacunales
DE59101397D1 (de) 1990-07-10 1994-05-19 Boehringer Ingelheim Int O-glycosyliertes ifn-alpha.
US5529914A (en) 1990-10-15 1996-06-25 The Board Of Regents The Univeristy Of Texas System Gels for encapsulation of biological materials
US5410016A (en) * 1990-10-15 1995-04-25 Board Of Regents, The University Of Texas System Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
CA2073511A1 (en) * 1990-11-14 1992-05-29 Matthew R. Callstrom Conjugates of poly(vinylsaccharide) with proteins for the stabilization of proteins
US5212075A (en) 1991-04-15 1993-05-18 The Regents Of The University Of California Compositions and methods for introducing effectors to pathogens and cells
EP0586549B1 (en) 1991-05-10 2000-09-20 Genentech, Inc. Selecting ligand agonists and antagonists
US5374655A (en) 1991-06-10 1994-12-20 Alberta Research Council Methods for the synthesis of monofucosylated oligosaccharides terminating in di-N-acetyllactosaminyl structures
US5352670A (en) 1991-06-10 1994-10-04 Alberta Research Council Methods for the enzymatic synthesis of alpha-sialylated oligosaccharide glycosides
KR950014915B1 (ko) 1991-06-19 1995-12-18 주식회사녹십자 탈시알로당단백-포함화합물
US5281698A (en) * 1991-07-23 1994-01-25 Cetus Oncology Corporation Preparation of an activated polymer ester for protein conjugation
US6319695B1 (en) 1991-10-15 2001-11-20 The Scripps Research Insitute Production of fucosylated carbohydrates by enzymatic fucosylation synthesis of sugar nucleotides; and in situ regeneration of GDP-fucose
IT1260468B (it) 1992-01-29 1996-04-09 Metodo per mantenere l'attivita' di enzimi proteolitici modificati con polietilenglicole
US5858751A (en) * 1992-03-09 1999-01-12 The Regents Of The University Of California Compositions and methods for producing sialyltransferases
US5962294A (en) 1992-03-09 1999-10-05 The Regents Of The University Of California Compositions and methods for the identification and synthesis of sialyltransferases
US6037452A (en) * 1992-04-10 2000-03-14 Alpha Therapeutic Corporation Poly(alkylene oxide)-Factor VIII or Factor IX conjugate
US5614184A (en) * 1992-07-28 1997-03-25 New England Deaconess Hospital Recombinant human erythropoietin mutants and therapeutic methods employing them
WO1994003191A1 (en) * 1992-08-07 1994-02-17 Progenics Pharmaceuticals, Inc. NON-PEPTIDYL MOIETY-CONJUGATED CD4-GAMMA2 AND CD4-IgG2 IMMUNOCONJUGATES, AND USES THEREOF
WO1994004193A1 (en) 1992-08-21 1994-03-03 Enzon, Inc. Novel attachment of polyalkylene oxides to bio-effecting substances
JP3979678B2 (ja) 1992-08-24 2007-09-19 サントリー株式会社 新規糖転移酵素及びそれをコードする遺伝子並びに該酵素の製造方法
WO1994005332A2 (en) 1992-09-01 1994-03-17 Berlex Laboratories, Inc. Glycolation of glycosylated macromolecules
US6361977B1 (en) * 1992-11-24 2002-03-26 S. Christopher Bauer Methods of using multivariant IL-3 hematopoiesis fusion protein
NZ250375A (en) 1992-12-09 1995-07-26 Ortho Pharma Corp Peg hydrazone and peg oxime linkage forming reagents and protein derivatives
AU6029594A (en) 1993-01-15 1994-08-15 Enzon, Inc. Factor viii - polymeric conjugates
US5349001A (en) 1993-01-19 1994-09-20 Enzon, Inc. Cyclic imide thione activated polyalkylene oxides
US5321095A (en) 1993-02-02 1994-06-14 Enzon, Inc. Azlactone activated polyalkylene oxides
US5202413A (en) 1993-02-16 1993-04-13 E. I. Du Pont De Nemours And Company Alternating (ABA)N polylactide block copolymers
EP0832755B1 (en) 1993-03-15 2000-05-31 King Jim Co., Ltd. Seal making device
WO1994023021A1 (en) 1993-03-29 1994-10-13 Kyowa Hakko Kogyo Co., Ltd. α-1,3-FUCOSYLTRANSFERASE
US5374541A (en) 1993-05-04 1994-12-20 The Scripps Research Institute Combined use of β-galactosidase and sialyltransferase coupled with in situ regeneration of CMP-sialic acid for one pot synthesis of oligosaccharides
WO1994026906A2 (en) 1993-05-14 1994-11-24 The Upjohn Company CLONED DNA ENCODING A UDP-GALNAc:POLYPEPTIDE,N-ACETYLGALACTOS AMINYLTRANSFERASE
WO1994028024A1 (en) 1993-06-01 1994-12-08 Enzon, Inc. Carbohydrate-modified polymer conjugates with erythropoietic activity
US5621039A (en) * 1993-06-08 1997-04-15 Hallahan; Terrence W. Factor IX- polymeric conjugates
DE4325317C2 (de) 1993-07-29 1998-05-20 Univ Dresden Tech Verfahren zur radioaktiven Markierung von Immunglobulinen
JPH0770195A (ja) * 1993-08-23 1995-03-14 Yutaka Mizushima 糖修飾インターフェロン
US5874075A (en) * 1993-10-06 1999-02-23 Amgen Inc. Stable protein: phospholipid compositions and methods
US5919455A (en) 1993-10-27 1999-07-06 Enzon, Inc. Non-antigenic branched polymer conjugates
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
US5446090A (en) 1993-11-12 1995-08-29 Shearwater Polymers, Inc. Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules
US5443953A (en) 1993-12-08 1995-08-22 Immunomedics, Inc. Preparation and use of immunoconjugates
US5369017A (en) 1994-02-04 1994-11-29 The Scripps Research Institute Process for solid phase glycopeptide synthesis
US5837458A (en) 1994-02-17 1998-11-17 Maxygen, Inc. Methods and compositions for cellular and metabolic engineering
US5605793A (en) 1994-02-17 1997-02-25 Affymax Technologies N.V. Methods for in vitro recombination
US5492841A (en) * 1994-02-18 1996-02-20 E. I. Du Pont De Nemours And Company Quaternary ammonium immunogenic conjugates and immunoassay reagents
US5432059A (en) 1994-04-01 1995-07-11 Specialty Laboratories, Inc. Assay for glycosylation deficiency disorders
US5646113A (en) 1994-04-07 1997-07-08 Genentech, Inc. Treatment of partial growth hormone insensitivity syndrome
US5629384A (en) 1994-05-17 1997-05-13 Consiglio Nazionale Delle Ricerche Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces
US5545553A (en) 1994-09-26 1996-08-13 The Rockefeller University Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them
US5824784A (en) * 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
US5834251A (en) 1994-12-30 1998-11-10 Alko Group Ltd. Methods of modifying carbohydrate moieties
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
US5922577A (en) 1995-04-11 1999-07-13 Cytel Corporation Enzymatic synthesis of glycosidic linkages
US5876980A (en) * 1995-04-11 1999-03-02 Cytel Corporation Enzymatic synthesis of oligosaccharides
US6030815A (en) 1995-04-11 2000-02-29 Neose Technologies, Inc. Enzymatic synthesis of oligosaccharides
US5728554A (en) 1995-04-11 1998-03-17 Cytel Corporation Enzymatic synthesis of glycosidic linkages
CA2227326A1 (en) 1995-05-15 1996-11-21 Philip Dehazya Carbohydrate-mediated coupling of peptides to immunoglobulins
US6015555A (en) * 1995-05-19 2000-01-18 Alkermes, Inc. Transferrin receptor specific antibody-neuropharmaceutical or diagnostic agent conjugates
US5824864A (en) 1995-05-25 1998-10-20 Pioneer Hi-Bred International, Inc. Maize gene and protein for insect control
US5858752A (en) 1995-06-07 1999-01-12 The General Hospital Corporation Fucosyltransferase genes and uses thereof
US6251864B1 (en) 1995-06-07 2001-06-26 Glaxo Group Limited Peptides and compounds that bind to a receptor
US6127153A (en) 1995-06-07 2000-10-03 Neose Technologies, Inc. Method of transferring at least two saccharide units with a polyglycosyltransferase, a polyglycosyltransferase and gene encoding a polyglycosyltransferase
WO1996040731A1 (en) 1995-06-07 1996-12-19 Mount Sinai School Of Medicine Of The City University Of New York Pegylated modified proteins
US5672662A (en) 1995-07-07 1997-09-30 Shearwater Polymers, Inc. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications
MX9800482A (es) 1995-07-27 1998-04-30 Cytec Tech Corp Polimeros cationicos sinteticos como promotores para el aprestamiento con anhidrido alquenil-succinico.
US5770420A (en) 1995-09-08 1998-06-23 The Regents Of The University Of Michigan Methods and products for the synthesis of oligosaccharide structures on glycoproteins, glycolipids, or as free molecules, and for the isolation of cloned genetic sequences that determine these structures
DE122006000003I2 (de) * 1995-09-21 2011-01-13 Genentech Inc Varianten des menschlichen wachstumshormons
US5716812A (en) * 1995-12-12 1998-02-10 The University Of British Columbia Methods and compositions for synthesis of oligosaccharides, and the products formed thereby
DE69738368T2 (de) * 1996-03-08 2008-12-04 The Regents Of The University Of Michigan, Ann Arbor MURINE alpha(1,3)-FUCOSYLTRANSFERASE (Fuc-TVII)
JP4410852B2 (ja) 1996-08-02 2010-02-03 オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド 単一の共有結合ｎ末端水溶性ポリマーを有するポリペプチド
EP0953354A4 (en) 1996-08-13 2002-10-23 Fujisawa Pharmaceutical Co HEMATOPOIETIC STEM CELLS PROLIFERING ACTIVE SUBSTANCES
US20020064546A1 (en) 1996-09-13 2002-05-30 J. Milton Harris Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor
WO1998015581A1 (en) 1996-10-10 1998-04-16 Cytel Corporation Carbohydrate purification using ultrafiltration, reverse osmosis and nanofiltration
US6087325A (en) 1996-10-15 2000-07-11 The Liposome Company, Inc. Peptide-lipid conjugates
IL129843A0 (en) 1996-11-08 2000-02-29 Cytel Corp Improved expression vectors
AU736993B2 (en) 1997-01-16 2001-08-09 Novo Nordisk A/S Practical in vitro sialylation of recombinant glycoproteins
US5945314A (en) 1997-03-31 1999-08-31 Abbott Laboratories Process for synthesizing oligosaccharides
JP2002505574A (ja) 1997-04-30 2002-02-19 エンゾン，インコーポレイテッド ポリアルキレンオキシド修飾された単鎖ポリペプチド
JPH10307356A (ja) 1997-05-08 1998-11-17 Konica Corp ハロゲン化銀乳剤およびそれを用いたハロゲン化銀写真感光材料
US6183738B1 (en) 1997-05-12 2001-02-06 Phoenix Pharamacologics, Inc. Modified arginine deiminase
US6075134A (en) 1997-05-15 2000-06-13 The Regents Of The University Of California Glycoconjugates and methods
US6399337B1 (en) 1997-06-06 2002-06-04 The Governors Of The University Of Alberta α1,3-fucosyltransferase
JP2002506353A (ja) 1997-06-24 2002-02-26 ジェネンテック・インコーポレーテッド ガラクトシル化糖タンパク質の方法及び組成物
AU8269898A (en) 1997-06-27 1999-01-19 Regents Of The University Of California, The Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor
US20030027257A1 (en) * 1997-08-21 2003-02-06 University Technologies International, Inc. Sequences for improving the efficiency of secretion of non-secreted protein from mammalian and insect cells
AU759779B2 (en) 1997-10-31 2003-05-01 Genentech Inc. Methods and compositions comprising glycoprotein glycoforms
CA2312843A1 (en) 1997-12-01 1999-06-10 Neose Technologies Inc. Enzymatic synthesis of gangliosides
EP0924298A1 (en) * 1997-12-18 1999-06-23 Stichting Instituut voor Dierhouderij en Diergezondheid (ID-DLO) Protein expression in baculovirus vector expression systems
JP3786832B2 (ja) 1998-01-07 2006-06-14 デビオ ルシェルシュ ファルマシュティーク ソシエテ アノニム 分解性のヘテロ二官能性ポリ（エチレングリコール）アクリレート及びそれから誘導されるゲル及び複合体
CA2323048C (en) 1998-03-12 2006-10-10 Shearwater Polymers, Inc. Poly(ethylene glycol) derivatives with proximal reactive groups
CA2324616A1 (en) 1998-03-25 1999-09-30 Sloan-Kettering Institute For Cancer Research Trimeric antigenic o-linked glycopeptide conjugates, methods of preparation and uses thereof
EP1075282B1 (en) 1998-04-28 2005-06-15 Applied Research Systems ARS Holding N.V. Peg-lhrh analog conjugates
US20030166525A1 (en) 1998-07-23 2003-09-04 Hoffmann James Arthur FSH Formulation
US6258770B1 (en) * 1998-09-11 2001-07-10 Albemarle Corporation Compositions for surface cleaning in aerosol applications
SG110047A1 (en) 1998-10-16 2005-04-28 Biogen Inc Polymer conjugates of interferon beta-a1 and uses
US7304150B1 (en) 1998-10-23 2007-12-04 Amgen Inc. Methods and compositions for the prevention and treatment of anemia
JP2002531067A (ja) 1998-10-30 2002-09-24 ノボザイムス アクティーゼルスカブ 低下したアレルゲン性を有するグリコシル化タンパク質
DE19852729A1 (de) 1998-11-16 2000-05-18 Werner Reutter Rekombinante Glycoproteine, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und ihre Verwendung
US6465220B1 (en) 1998-12-21 2002-10-15 Glycozym Aps Glycosylation using GalNac-T4 transferase
US6949372B2 (en) 1999-03-02 2005-09-27 The Johns Hopkins University Engineering intracellular sialylation pathways
DE60014879T2 (de) 1999-04-22 2005-10-13 Astrazeneca Ab Test zum nachweis der aktivität von phospho-n-acetylmuramyl-pentapeptid-translokase
JO2291B1 (en) 1999-07-02 2005-09-12 اف . هوفمان لاروش ايه جي Erythropoietin derivatives
US6261805B1 (en) 1999-07-15 2001-07-17 Boyce Thompson Institute For Plant Research, Inc. Sialyiation of N-linked glycoproteins in the baculovirus expression vector system
AU6357900A (en) 1999-07-20 2001-02-05 Amgen, Inc. Hyaluronic acid-protein conjugates, pharmaceutical compositions and related methods
US6537785B1 (en) 1999-09-14 2003-03-25 Genzyme Glycobiology Research Institute, Inc. Methods of treating lysosomal storage diseases
US6716626B1 (en) * 1999-11-18 2004-04-06 Chiron Corporation Human FGF-21 nucleic acids
ES2377935T3 (es) 1999-12-02 2012-04-03 Zymogenetics, Inc. Procedimiento para dirigir células que expresan receptor -3 o -2 del factor de crecimiento de fibroblastos
US6348558B1 (en) * 1999-12-10 2002-02-19 Shearwater Corporation Hydrolytically degradable polymers and hydrogels made therefrom
EP1259563B2 (en) * 1999-12-22 2016-08-10 Nektar Therapeutics Method for the preparation of 1-benzotriazolyl carbonate esters of water soluble polymers.
EP1270642B1 (en) 1999-12-24 2011-08-31 Kyowa Hakko Kirin Co., Ltd. Branched polyalkylene glycols
IL150314A0 (en) 1999-12-30 2002-12-01 Maxygen Aps Improved lysosomal enzymes and lysosomal enzyme activators
US6555660B2 (en) * 2000-01-10 2003-04-29 Maxygen Holdings Ltd. G-CSF conjugates
US6646110B2 (en) * 2000-01-10 2003-11-11 Maxygen Holdings Ltd. G-CSF polypeptides and conjugates
AR027509A1 (es) * 2000-01-10 2003-04-02 Maxygen Aps Conjugados g-csf
AU2001231531A1 (en) 2000-02-11 2001-08-20 Maxygen Aps Follicle stimulating hormones
RU2278123C2 (ru) 2000-02-11 2006-06-20 Максиджен Холдингз Лтд. Молекулы, подобные фактору vii или viia
AU2001232337A1 (en) 2000-02-18 2001-08-27 Kanagawa Academy Of Science And Technology Pharmaceutical composition, reagent and method for intracerebral delivery of pharmaceutically active ingredient or labeling substance
EP1263771B1 (en) * 2000-03-16 2006-06-14 The Regents Of The University Of California Chemoselective ligation by use of a phosphine
US6586398B1 (en) 2000-04-07 2003-07-01 Amgen, Inc. Chemically modified novel erythropoietin stimulating protein compositions and methods
US7338932B2 (en) 2000-05-11 2008-03-04 Glycozym Aps Methods of modulating functions of polypeptide GalNAc-transferases and of screening test substances to find agents herefor, pharmaceutical compositions comprising such agents and the use of such agents for preparing medicaments
MXPA02011016A (es) * 2000-05-12 2004-03-16 Neose Technologies Inc Glicopeptidos recombinantes de glucolisacion in vitro.
MEP90708A (en) * 2000-05-15 2011-12-20 New pharmaceutical composition
EP2339013B1 (en) 2000-06-28 2014-07-02 GlycoFi, Inc. Methods for producing modified glycoproteins
US6423826B1 (en) 2000-06-30 2002-07-23 Regents Of The University Of Minnesota High molecular weight derivatives of vitamin K-dependent polypeptides
JP2004504016A (ja) 2000-06-30 2004-02-12 マキシゲン・エイピーエス ペプチド拡張されたグリコシル化ポリペプチド
AU2001285020A1 (en) 2000-08-17 2002-02-25 Synapse Technologies, Inc. P97-active agent conjugates and their methods of use
WO2002013843A2 (en) 2000-08-17 2002-02-21 University Of British Columbia Chemotherapeutic agents conjugated to p97 and their methods of use in treating neurological tumours
US20030165849A1 (en) 2000-11-28 2003-09-04 Biliang Zhang Methods and reagents for introducing a sulfhydryl group into the 5'-terminus of RNA
CA2431964C (en) 2000-12-20 2013-09-10 F. Hoffmann-La Roche Ag Conjugates of erythropoietin (pep) with polyethylene glycol (peg)
US7892730B2 (en) 2000-12-22 2011-02-22 Sagres Discovery, Inc. Compositions and methods for cancer
US6531121B2 (en) * 2000-12-29 2003-03-11 The Kenneth S. Warren Institute, Inc. Protection and enhancement of erythropoietin-responsive cells, tissues and organs
PA8536201A1 (es) 2000-12-29 2002-08-29 Kenneth S Warren Inst Inc Protección y mejoramiento de células, tejidos y órganos que responden a la eritropoyetina
EP2080771A3 (en) 2001-02-27 2010-01-06 Maxygen Aps New interferon beta-like molecules
US7235638B2 (en) 2001-03-22 2007-06-26 Novo Nordisk Healthcare A/G Coagulation factor VII derivatives
WO2002092147A2 (en) 2001-05-11 2002-11-21 Aradigm Corporation Optimization of the molecular properties and formulation of proteins delivered by inhalation
AU2002342653A1 (en) 2001-05-14 2002-11-25 The Gouvernment Of The United States Of America, Represented By The Secretary, Department Of Health Modified growth hormone
KR100453877B1 (ko) 2001-07-26 2004-10-20 메덱스젠 주식회사 연쇄체화에 의한 면역 글로블린 융합 단백질의 제조 방법 및 이 방법에 의해 제조된 ＴＮＦＲ/Ｆｃ 융합 단백질, 상기 단백질을 코딩하는 ＤＮＡ, 상기 ＤＮＡ를 포함하는벡터, 및 상기 벡터에 의한 형질전환체
CA2457794A1 (en) 2001-08-29 2003-03-06 Neose Technologies, Inc. Novel synthetic ganglioside derivatives and compositions thereof
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
US7226903B2 (en) 2001-10-10 2007-06-05 Neose Technologies, Inc. Interferon beta: remodeling and glycoconjugation of interferon beta
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
US7179617B2 (en) * 2001-10-10 2007-02-20 Neose Technologies, Inc. Factor IX: remolding and glycoconjugation of Factor IX
US7265084B2 (en) * 2001-10-10 2007-09-04 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
US7297511B2 (en) * 2001-10-10 2007-11-20 Neose Technologies, Inc. Interferon alpha: remodeling and glycoconjugation of interferon alpha
US7157277B2 (en) * 2001-11-28 2007-01-02 Neose Technologies, Inc. Factor VIII remodeling and glycoconjugation of Factor VIII
US7696163B2 (en) * 2001-10-10 2010-04-13 Novo Nordisk A/S Erythropoietin: remodeling and glycoconjugation of erythropoietin
PT2279753E (pt) 2001-10-10 2016-01-15 Novo Nordisk As Remodelação e glicoconjugação de péptidos
US7265085B2 (en) 2001-10-10 2007-09-04 Neose Technologies, Inc. Glycoconjugation methods and proteins/peptides produced by the methods
US8008252B2 (en) * 2001-10-10 2011-08-30 Novo Nordisk A/S Factor VII: remodeling and glycoconjugation of Factor VII
US7399613B2 (en) * 2001-10-10 2008-07-15 Neose Technologies, Inc. Sialic acid nucleotide sugars
US7173003B2 (en) * 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
US7795210B2 (en) * 2001-10-10 2010-09-14 Novo Nordisk A/S Protein remodeling methods and proteins/peptides produced by the methods
US7125843B2 (en) * 2001-10-19 2006-10-24 Neose Technologies, Inc. Glycoconjugates including more than one peptide
US6784154B2 (en) 2001-11-01 2004-08-31 University Of Utah Research Foundation Method of use of erythropoietin to treat ischemic acute renal failure
EP1461445B1 (en) 2001-11-28 2008-08-20 Neose Technologies, Inc. Glycoprotein remodeling using endoglycanases
CA2468230A1 (en) 2001-11-28 2003-06-05 Neose Technologies, Inc. Glycopeptide remodeling using amidases
US7473680B2 (en) * 2001-11-28 2009-01-06 Neose Technologies, Inc. Remodeling and glycoconjugation of peptides
US20060035224A1 (en) * 2002-03-21 2006-02-16 Johansen Jack T Purification methods for oligonucleotides and their analogs
EP1504023A4 (en) 2002-05-03 2006-03-22 Neose Technologies Inc RECOMBINANT GLYCOSYL TRANSFERASE FUSION PROTEINS
UA86744C2 (en) 2002-06-21 2009-05-25 Ново Нордиск Хэлс Кеа Аг Pegylated factor vii glycoforms
MXPA04012496A (es) 2002-06-21 2005-09-12 Novo Nordisk Healthcare Ag Glicoformos del factor vii pegilados.
DE10232916B4 (de) 2002-07-19 2008-08-07 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Vorrichtung und Verfahren zum Charakterisieren eines Informationssignals
CA2493258C (en) 2002-07-23 2015-10-20 Neose Technologies, Inc. Synthesis of oligosaccharides, glycolipids, and glycoproteins using bacterial glycosyltransferases
JP2006508918A (ja) 2002-09-05 2006-03-16 ザ ジェネラル ホスピタル コーポレーション 修飾されたアシアロインターフェロンおよびその使用
EP1539210A4 (en) 2002-09-06 2006-06-07 Bayer Pharmaceuticals Corp GLP-1 RECEPTOR MODIFIED AGONISTS AND THEIR PHARMACOLOGICAL METHODS OF USE
US20040062748A1 (en) 2002-09-30 2004-04-01 Mountain View Pharmaceuticals, Inc. Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
AU2003275952A1 (en) * 2002-11-08 2004-06-07 Glycozym Aps Inactivated ga1 - nac - transferases, methods for inhibitors of such transferases and their use
JP4412461B2 (ja) 2002-11-20 2010-02-10 日油株式会社 修飾された生体関連物質、その製造方法および中間体
US20050064540A1 (en) * 2002-11-27 2005-03-24 Defrees Shawn Ph.D Glycoprotein remodeling using endoglycanases
EP1424344A1 (en) 2002-11-29 2004-06-02 Aventis Behring Gesellschaft mit beschränkter Haftung Modified cDNA factor VIII and its derivates
ES2312523T3 (es) 2002-12-13 2009-03-01 Bioceuticals Arzneimittel Ag Procedimiento para la produccion y purificacion de eritropoyetina.
ES2389183T3 (es) 2002-12-26 2012-10-23 Mountain View Pharmaceuticals, Inc. Conjugados de polietilenglicol de interferón-beta-1b con potencia biológica in vitro potenciada
US7041635B2 (en) 2003-01-28 2006-05-09 In2Gen Co., Ltd. Factor VIII polypeptide
EP1608688B1 (en) 2003-03-14 2013-02-27 BioGeneriX AG Branched water-soluble polymers and their conjugates
US20060276618A1 (en) 2003-03-18 2006-12-07 Defrees Shawn Activated forms of water-soluble polymers
WO2007022512A2 (en) 2005-08-19 2007-02-22 Neose Technologies, Inc. Glycopegylated factor vii and factor viia
CA2522345A1 (en) * 2003-04-09 2004-11-18 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
US7691603B2 (en) * 2003-04-09 2010-04-06 Novo Nordisk A/S Intracellular formation of peptide conjugates
US7718363B2 (en) 2003-04-25 2010-05-18 The Kenneth S. Warren Institute, Inc. Tissue protective cytokine receptor complex and assays for identifying tissue protective compounds
AU2004240553A1 (en) * 2003-05-09 2004-12-02 Neose Technologies, Inc. Compositions and methods for the preparation of human growth hormone glycosylation mutants
WO2005012484A2 (en) 2003-07-25 2005-02-10 Neose Technologies, Inc. Antibody-toxin conjugates
US20060198819A1 (en) 2003-08-08 2006-09-07 Novo Nordisk Healthcare A/G Use of galactose oxidase for selective chemical conjugation of protractor molecules to proteins of therapeutic interest
CN1882355A (zh) 2003-09-09 2006-12-20 沃伦药品公司 保持内源性促红细胞生成素组织保护活性的长效促红细胞生成素
US7524813B2 (en) 2003-10-10 2009-04-28 Novo Nordisk Health Care Ag Selectively conjugated peptides and methods of making the same
NZ547168A (en) 2003-11-24 2010-05-28 Biogenerix Ag Glycopegylated erythropoietin
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
US8633157B2 (en) 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
MXPA06006023A (es) 2003-12-03 2006-08-23 Neose Technologies Inc Factor ix glicopegilado.
US20080015142A1 (en) * 2003-12-03 2008-01-17 Defrees Shawn Glycopegylated Follicle Stimulating Hormone
JP4657219B2 (ja) 2003-12-03 2011-03-23 バイオジェネリックス アーゲー ＧｌｙｃｏＰＥＧ化された顆粒球コロニー刺激因子
US7956032B2 (en) * 2003-12-03 2011-06-07 Novo Nordisk A/S Glycopegylated granulocyte colony stimulating factor
US20060040856A1 (en) * 2003-12-03 2006-02-23 Neose Technologies, Inc. Glycopegylated factor IX
US20080318850A1 (en) 2003-12-03 2008-12-25 Neose Technologies, Inc. Glycopegylated Factor Ix
CA2552892C (en) * 2004-01-08 2014-08-05 Neose Technologies, Inc. O-linked glycosylation of peptides
US20080058245A1 (en) 2004-01-09 2008-03-06 Johnson Karl F Vectors for Recombinant Protein Expression in E. Coli
US20070105770A1 (en) 2004-01-21 2007-05-10 Novo Nordisk A/S Transglutaminase mediated conjugation of peptides
AU2005208897B2 (en) 2004-01-26 2011-05-19 Ratiopharm Gmbh Branched polymeric sugars and nucleotides thereof
EP1735340A2 (en) 2004-03-17 2006-12-27 Eli Lilly And Company Glycol linked fgf-21 compounds
US20070037966A1 (en) * 2004-05-04 2007-02-15 Novo Nordisk A/S Hydrophobic interaction chromatography purification of factor VII polypeptides
ATE455861T1 (de) 2004-05-04 2010-02-15 Novo Nordisk Healthcare Ag O-verknüpfte glykoformen von faktor vii und verfahren zu deren herstellung
US20080206810A1 (en) 2004-06-03 2008-08-28 Neose Technologies, Inc. Truncated St6galnaci Polypeptides and Nucleic Acids
WO2005121331A2 (en) 2004-06-03 2005-12-22 Neose Technologies, Inc. Truncated galnact2 polypeptides and nucleic acids
WO2006014466A2 (en) 2004-07-02 2006-02-09 The Kenneth S. Warren Institute, Inc. Novel carbamylated epo and method for its production
JP2008505184A (ja) 2004-07-02 2008-02-21 ザ ケネス エス．ウォーレン インスティテュート，インコーポレーテッド 完全にカルバミル化されたエリトロポイエチンを生成する方法
US20080300173A1 (en) 2004-07-13 2008-12-04 Defrees Shawn Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1]
US20090292110A1 (en) 2004-07-23 2009-11-26 Defrees Shawn Enzymatic modification of glycopeptides
WO2006013202A2 (en) 2004-08-02 2006-02-09 Novo Nordisk Health Care Ag Conjugation of fvii
US20060024286A1 (en) * 2004-08-02 2006-02-02 Paul Glidden Variants of tRNA synthetase fragments and uses thereof
US8268967B2 (en) * 2004-09-10 2012-09-18 Novo Nordisk A/S Glycopegylated interferon α
WO2006035057A1 (en) 2004-09-29 2006-04-06 Novo Nordisk Health Care Ag Modified proteins
WO2006050247A2 (en) 2004-10-29 2006-05-11 Neose Technologies, Inc. Remodeling and glycopegylation of fibroblast growth factor (fgf)
US20090054623A1 (en) * 2004-12-17 2009-02-26 Neose Technologies, Inc. Lipo-Conjugation of Peptides
JP2008526864A (ja) 2005-01-06 2008-07-24 ネオス テクノロジーズ インコーポレイテッド 糖断片を用いる糖結合
WO2006074467A2 (en) 2005-01-10 2006-07-13 Neose Technologies, Inc. Glycopegylated granulocyte colony stimulating factor
WO2006078645A2 (en) 2005-01-19 2006-07-27 Neose Technologies, Inc. Heterologous polypeptide expression using low multiplicity of infection of viruses
PA8660701A1 (es) 2005-02-04 2006-09-22 Pfizer Prod Inc Agonistas de pyy y sus usos
MX2007011801A (es) 2005-03-24 2008-02-19 Neose Technologies Inc Expresion de glicosiltransferasas eucarioticas activas, solubles en organismos procarioticos.
EP1866427A4 (en) 2005-03-30 2010-09-01 Novo Nordisk As MANUFACTURING PROCESS FOR THE PRODUCTION OF CULTIVE PEPTIDES IN CELL LINES OF INSECTS
US20070154992A1 (en) 2005-04-08 2007-07-05 Neose Technologies, Inc. Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
EP2311972B1 (en) 2005-05-11 2015-01-21 ETH Zurich Recombinant N-glycosylated proteins from procaryotic cells
EP1891231A4 (en) * 2005-05-25 2011-06-22 Novo Nordisk As GLYCOPEGYLATED FACTOR IX
WO2006127910A2 (en) 2005-05-25 2006-11-30 Neose Technologies, Inc. Glycopegylated erythropoietin formulations
US20110003744A1 (en) * 2005-05-25 2011-01-06 Novo Nordisk A/S Glycopegylated Erythropoietin Formulations
EP1893632B1 (en) 2005-06-17 2015-08-12 Novo Nordisk Health Care AG Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
EP1926817A2 (en) * 2005-09-14 2008-06-04 Novo Nordisk Health Care AG Human coagulation factor vii polypeptides
WO2007056191A2 (en) * 2005-11-03 2007-05-18 Neose Technologies, Inc. Nucleotide sugar purification using membranes
DE202006020194U1 (de) 2006-03-01 2007-12-06 Bioceuticals Arzneimittel Ag G-CSF-Flüssigformulierung
EP2029738A2 (en) 2006-05-24 2009-03-04 Novo Nordisk Health Care AG Factor ix analogues having prolonged in vivo half life
EP2049144B8 (en) 2006-07-21 2015-02-18 ratiopharm GmbH Glycosylation of peptides via o-linked glycosylation sequences
ITMI20061624A1 (it) * 2006-08-11 2008-02-12 Bioker Srl Mono-coniugati sito-specifici di g-csf
ES2531934T3 (es) * 2006-09-01 2015-03-20 Novo Nordisk Health Care Ag Glicoproteínas modificadas
EP2054521A4 (en) * 2006-10-03 2012-12-19 Novo Nordisk As METHODS OF PURIFYING CONJUGATES OF POLYPEPTIDES
DK2068907T3 (en) 2006-10-04 2018-01-15 Novo Nordisk As GLYCEROL BOND PEGYLED SUGAR AND GLYCOPE Peptides
WO2008073620A2 (en) 2006-11-02 2008-06-19 Neose Technologies, Inc. Manufacturing process for the production of polypeptides expressed in insect cell-lines
CN101796063B (zh) 2007-04-03 2017-03-22 拉蒂奥法姆有限责任公司 使用糖聚乙二醇化g‑csf的治疗方法
US20090053167A1 (en) * 2007-05-14 2009-02-26 Neose Technologies, Inc. C-, S- and N-glycosylation of peptides
WO2008151258A2 (en) 2007-06-04 2008-12-11 Neose Technologies, Inc. O-linked glycosylation using n-acetylglucosaminyl transferases
EP2170919B8 (en) 2007-06-12 2016-01-20 ratiopharm GmbH Improved process for the production of nucleotide sugars
US8207112B2 (en) 2007-08-29 2012-06-26 Biogenerix Ag Liquid formulation of G-CSF conjugate
EP2242505A4 (en) 2008-01-08 2012-03-07 Biogenerix Ag GLYCOCONJUGATION OF POLYPEPTIDES USING OLIGOSACCHARYLTRANSFERASES

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