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ES2659829T3 - Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos - Google Patents

Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos Download PDF

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ES2659829T3
ES2659829T3 ES12178200.7T ES12178200T ES2659829T3 ES 2659829 T3 ES2659829 T3 ES 2659829T3 ES 12178200 T ES12178200 T ES 12178200T ES 2659829 T3 ES2659829 T3 ES 2659829T3
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reduction
antibody
protein
prevention
disulfide bonds
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Yung-Hsiang Kao
Melody Trexher Schmidt
Michael W. Laird
Rita L. Wong
Daniel P. Hewitt
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    • C07K1/14—Extraction; Separation; Purification
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Abstract

Un metodo para la prevencion de la reduccion de un enlace disulfuro en un polipeptido expresado en una celula hospedadora recombinante durante el procesamiento posterior a la fermentacion, que comprende, despues de la fermentacion: disminuir el pH del liquido de cultivo celular recogido de dicha celula hospedadora recombinante, en donde dicha celula hospedadora recombinante es una celula de ovario de hamster chino (CHO).

Description

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limitantes.
Un "fragmento biológicamente funcional" de un anticuerpo comprende solo una parte de un anticuerpo intacto, en donde la parte conserva al menos una, y tantas como la mayoría o todas, de las funciones normalmente asociadas a
5 esa parte cuando están presentes en un anticuerpo intacto. En una realización, un fragmento biológicamente funcional de un anticuerpo comprende un sitio de unión a antígeno del anticuerpo intacto y, por lo tanto, conserva la capacidad de unirse al antígeno. En otra realización, un fragmento biológicamente funcional de un anticuerpo, por ejemplo uno que comprende la región Fc, conserva al menos una de las funciones biológicas normalmente asociadas a la región Fc cuando está presente en un anticuerpo intacto, tal como la unión a FcRn, la modulación de la semivida del anticuerpo, la función CCDA y unión al complemento. En una realización, un fragmento biológicamente funcional de un anticuerpo es un anticuerpo monovalente que tiene una semivida in vivo sustancialmente similar a la de un anticuerpo intacto. Por ejemplo, dicho fragmento biológicamente funcional de un anticuerpo puede comprender un brazo de unión a antígeno unido a una secuencia de Fc capaz de conferir estabilidad in vivo al fragmento.
15 Las expresiones "inhibidor de tiorredoxina" e "inhibidor de Trx" se utilizan indistintamente, e incluyen todos los agentes y medidas efectivos para inhibir la actividad de la tiorredoxina. Por lo tanto, los inhibidores de tiorredoxina (Trx) incluyen todos los agentes y medidas que bloquean cualquier componente de los sistemas de enzimas Trx, G6PD y / o hexocinasa. En este contexto, la "inhibición" incluye la eliminación completa (bloqueo) y la reducción de la actividad de la tiorredoxina y, en consecuencia, la eliminación completa o parcial de la reducción del enlace disulfuro en una proteína, tal como un anticuerpo.
Un anticuerpo "aislado" es uno que se ha identificado y separado y / o recuperado de un componente de su entorno natural. Los componentes contaminantes de su entorno natural son materiales que interferirían con la investigación, 25 el diagnóstico o los usos terapéuticos del anticuerpo, y pueden incluir enzimas, hormonas y otros solutos proteicos o no proteicos. En algunas realizaciones, un anticuerpo se purifica (1) a más de 95 % en peso de anticuerpo como se determina mediante, por ejemplo, el método Lowry, y en algunas realizaciones, hasta más de 99 % en peso; (2) a un grado suficiente para obtener al menos 15 restos de la secuencia de aminoácidos N-terminal o interna utilizando, por ejemplo, un secuenciador de copa giratoria, o (3) a homogeneidad mediante SDS-PAGE en condiciones reductoras
o no reductoras utilizando, por ejemplo, tinción con azul de Coomassie o plata. El anticuerpo aislado incluye el anticuerpo in situ dentro de células recombinantes ya que al menos un componente del entorno natural del anticuerpo no estará presente. Sin embargo, habitualmente, el anticuerpo aislado se preparará mediante al menos una etapa de purificación.
35 Las expresiones "Proteína A" y "ProA" se utilizan indistintamente en la presente memoria y abarcan Proteína A recuperada de una fuente nativa de la misma, Proteína A producida sintéticamente (p. ej. mediante síntesis peptídica
o mediante técnicas recombinantes) y variantes de la misma que conservan la capacidad de unir proteínas que tienen una región CH2/CH3, tal como una región Fc. La proteína A se puede adquirir en el comercio en Repligen, GE Healthcare y Fermatech. La proteína A generalmente se inmoviliza sobre un material de soporte en fase sólida. El término "ProA" también se refiere a una resina o columna de cromatografía de afinidad que contiene una matriz de soporte sólida cromatográfica a la que está unida de manera covalente la Proteína A.
El término "cromatografía" se refiere al proceso mediante el cual un soluto de interés en una mezcla se separa de otros solutos en una mezcla como resultado de las diferencias en las velocidades a las que los solutos individuales
45 de la mezcla migran a través de un medio estacionario bajo la influencia de una fase de movimiento, o en procesos de unión y elución.
Las expresiones “cromatografía de afinidad" y "cromatografía de afinidad de proteínas" se utilizan indistintamente en la presente memoria y se refieren a una técnica de separación de proteínas en la que una proteína o un anticuerpo de interés se une de forma reversible y específica a un ligando bioespecífico. Preferiblemente, el ligando biespecífico se une de manera covalente a un material cromatográfico en fase sólida y es accesible a la proteína de interés en la solución cuando la solución entra en contacto con el material cromatográfico en fase sólida. La proteína de interés (por ejemplo, anticuerpo, enzima o proteína receptora) conserva su afinidad de unión específica por el ligando bioespecífico (antígeno, sustrato, cofactor u hormona, por ejemplo) durante las etapas cromatográficas, mientras
55 que otros solutos y / o proteínas en la mezcla no se unen apreciable o específicamente al ligando. La unión de la proteína de interés al ligando inmovilizado permite que las proteínas contaminantes o las impurezas de proteínas pasen a través del medio cromatográfico mientras que la proteína de interés permanece específicamente unida al ligando inmovilizado en el material de fase sólida. La proteína de interés específicamente unida se elimina después en forma activa del ligando inmovilizado con ligando competidor de bajo pH, alto pH, alto contenido en sal y similares, y se hace pasar a través de la columna cromatográfica con el tampón de elución, carente de las proteínas contaminantes o impurezas de proteínas que antes se les permitía pasar a través de la columna. Como ligando puede utilizarse cualquier componente para purificar su respectiva proteína de unión específica, por ejemplo, anticuerpo.
65 Las expresiones "cromatografía de no afinidad" y "purificación de no afinidad" se refieren a un proceso de purificación en el que no se utiliza la cromatografía de afinidad. La cromatografía de no afinidad incluye técnicas
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recogida.
Como alternativa o adicionalmente, también pueden utilizarse otros métodos inespecíficos para impedir la reducción del enlace disulfuro después de la fermentación durante la producción recombinante de proteínas recombinantes, tal como la inyección de aire o el ajuste del pH. En la siguiente Tabla 1, se enumeran determinados métodos de inhibición de la reducción contemplados en este documento.
Tabla 1: Métodos de inhibición de la reducción
Método1
Propósito
Adición de EDTA, EGTA o citrato
Para inhibir hexocinasa
Adición de sorbosa-1-fosfato, polifosfatos, 6-desoxi-6fluoroglucosa, 2-C-hidroxi-metilglucosa, xilosa o lixosa
Para inhibir hexocinasa
Adición de epiandrosterona o deshidropiandrosterona (DHEA)
Para inhibir G6PD
Adición de piridoxal 5'-fosfato o 1-fluor-2,4-dinitrobenceno
Para inhibir G6PD
Adición de iones metálicos, tales como, Cu2+, Zn2+ Hg2+ , Co2+ o Mn2+
Para inhibir el sistema Trx
Adición de disulfuros de alquil-2-imidazolilo y compuestos relacionados (por ejemplo, disulfuro de 1 metilpropil-2imidazolilo)2 o derivados de naftoquinona espirocetales (p. ej. palmarumicina CP12)
Para inhibir Trx
Adición de aurotioglucosa (ATG) o aurotiomalato (ATM)
Para inhibir TrxR
Inyección de aire
Para reducir G6P y NADPH; agente oxidante
Cistina
Agente oxidante
Glutatión oxidada
Agentes oxidantes
Ajuste de pH por debajo de 6,0
Para reducir la tasa de intercambio de tioldisulfuro y la actividad del sistema Trx
1 Aplicado al LCC antes de la recogida o en el LCCR inmediatamente después de la recogida.
2 Actualmente no disponible en el comercio.
10 Como "inhibidores de Trx" para uso en los métodos de la presente divulgación, se incluyen, sin limitación, (1) inhibidores directos de Trx, tales como disulfuros de alquil-2-imidazolilo y compuestos relacionados (por ejemplo, disulfuro de 1 metilpropil-2-imidazolilo) (Kirkpatrick et al., 1998 y 1999, citados anteriormente) y derivados de naftoquinona espirocetales (por ejemplo, palmarumicina CP1 ) (Wipf et al., 2001, citados anteriormente); (2) inhibidores específicos de TrxR, que incluyen complejos de oro, tales como aurotioglucosa (ATG) y aurotiomalato
15 (ATM) (véase, por ejemplo, la revisión de Gromer et al., 2004), que son ejemplos de inhibidores irreversibles de TrxR; (3) iones metálicos, tales como Hg2+, Cu2+, Zn2+, Co2+ y Mn2+, que pueden formar fácilmente complejos con tioles y selenoles, y de este modo se puede utilizar en realizaciones de la presente invención como inhibidores de TrxR o Trx; (4) inhibidores de G6PD, tales como, por ejemplo, piridoxal 5'-fosfato y 1 fluor-2,4-dinitrobenceno (Milhausen y Levy 1975, citados anteriormente), ciertos esteroides, tales como deshidroepiandrosterona (DHEA) y
20 epiandrosterona (EA) (Gordon et al., 1995, citados anteriormente); y (4) inhibidores de la actividad de hexocinasa (y por lo tanto de la producción de G6P para la G6PD), incluidos los quelantes de iones metálicos, por ejemplo, Mg2+ , tales como EDTA, y compuestos que reaccionan con grupos SH, sorbosa-1-fosfato, polifosfatos, 6-desoxi-6fluoroglucosa, 2-C-hidroxi-metilglucosa, xilosa y lixosa (Sols et al., 1958, citados anteriormente; McDonald, 1955, citado anteriormente); en la patente de estados unidos Nº 5.854.067 titulada "Inhibidores de hexocinasa", se
25 desvelan otros inhibidores de hexocinasa. Se entenderá que estos inhibidores se enumeran solo con fines ilustrativos. Existen otros inhibidores de Trx y pueden utilizarse, solos o en diversas combinaciones.
Los "inhibidores de Trx" para utilizar en los métodos de la presente divulgación también incluyen reactivos por los cuales la reducción de anticuerpos o proteínas producidos por medios recombinantes, puede disminuirse o 30 impedirse disminuyendo los niveles de enzimas del sistema Trx, la ruta de la pentosa fosfato o hexocinasa, en varios puntos durante la campaña de producción. En algunas realizaciones, esta reducción de los niveles de enzima se puede lograr utilizando ARNip, nucleótidos antisentido o anticuerpos. Para diseñar RNAip o nucleótidos antisentido dirigidos a los genes que se encuentran en células CHO, estas secuencias génicas están disponibles en bases de datos públicas para seleccionar secuencias para dirigir enzimas en diferentes organismos. Para ejemplos de genes
35 del sistema Trx de E. coli y de ratón véase más adelante el Ejemplo 9.
Además de utilizar los inhibidores comentados anteriormente, en determinadas realizaciones de la presente
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Claims (1)

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ES12178200.7T 2007-07-09 2008-07-08 Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos Active ES2659829T3 (es)

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ES19181777T Active ES2941738T3 (es) 2007-07-09 2008-07-08 Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos
ES08781481.0T Active ES2655474T3 (es) 2007-07-09 2008-07-08 Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos
ES12178200.7T Active ES2659829T3 (es) 2007-07-09 2008-07-08 Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos
ES17196350T Active ES2751022T3 (es) 2007-07-09 2008-07-08 Prevención de la reducción de enlaces disulfuro durante la producción recombinante de polipéptidos
ES24160370T Active ES3022264T3 (en) 2007-07-09 2008-07-08 Prevention of disulfide bond reduction during recombinant production of polypeptides

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US8911964B2 (en) 2006-09-13 2014-12-16 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
CA2842964A1 (en) 2006-09-13 2008-03-20 Abbvie Inc. Cell culture improvements
EP2188302B1 (en) 2007-07-09 2017-11-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
TWI472339B (zh) 2008-01-30 2015-02-11 Genentech Inc 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物
TW201438738A (zh) 2008-09-16 2014-10-16 建南德克公司 治療進展型多發性硬化症之方法
WO2010048192A2 (en) 2008-10-20 2010-04-29 Abbott Laboratories Viral inactivation during purification of antibodies
RU2520838C2 (ru) 2008-10-20 2014-06-27 Эббви Инк Выделение и очистка антител с использованием аффинной хроматографии на основе белка а
AU2010243551B2 (en) * 2009-04-30 2015-03-26 Ablynx Nv Method for the production of domain antibodies
MX346002B (es) * 2009-06-17 2017-03-01 Abbvie Biotherapeutics Inc Anticuerpos anti-vegf y sus usos.
MX355650B (es) 2009-08-11 2018-04-26 Genentech Inc Produccion de proteinas en medios de cultivo de celulas libres de glutamina.
AR078161A1 (es) 2009-09-11 2011-10-19 Hoffmann La Roche Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento.
ES2594893T3 (es) * 2009-12-16 2016-12-23 Abbvie Biotherapeutics Inc. Anticuerpos anti HER2 y sus usos
JP2013528570A (ja) * 2010-03-31 2013-07-11 ユニベルシテ ドゥ ジュネーブ 安定化された抗体調製物およびその使用
TW201302793A (zh) 2010-09-03 2013-01-16 Glaxo Group Ltd 新穎之抗原結合蛋白
CN101974535B (zh) * 2010-11-03 2012-12-19 北京天广实生物技术股份有限公司 新型抗ErbB2人源化抗体MIL12的制备及其应用
US9067988B2 (en) 2010-12-01 2015-06-30 Alderbio Holdings Llc Methods of preventing or treating pain using anti-NGF antibodies
US11214610B2 (en) 2010-12-01 2022-01-04 H. Lundbeck A/S High-purity production of multi-subunit proteins such as antibodies in transformed microbes such as Pichia pastoris
US9078878B2 (en) 2010-12-01 2015-07-14 Alderbio Holdings Llc Anti-NGF antibodies that selectively inhibit the association of NGF with TrkA, without affecting the association of NGF with p75
US9884909B2 (en) 2010-12-01 2018-02-06 Alderbio Holdings Llc Anti-NGF compositions and use thereof
US9539324B2 (en) 2010-12-01 2017-01-10 Alderbio Holdings, Llc Methods of preventing inflammation and treating pain using anti-NGF compositions
MX359070B (es) 2010-12-01 2018-09-13 Alderbio Holdings Llc Composiciones anti-ngf y uso de las mismas.
WO2012149197A2 (en) 2011-04-27 2012-11-01 Abbott Laboratories Methods for controlling the galactosylation profile of recombinantly-expressed proteins
CN102911265B (zh) * 2011-08-05 2014-02-05 王革 一种人神经生长因子的重组变异体及其制备方法
CA2866753C (en) * 2012-03-27 2020-09-22 Genentech, Inc. Improved harvest operations for recombinant proteins
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
US9150645B2 (en) 2012-04-20 2015-10-06 Abbvie, Inc. Cell culture methods to reduce acidic species
WO2013176754A1 (en) 2012-05-24 2013-11-28 Abbvie Inc. Novel purification of antibodies using hydrophobic interaction chromatography
US9650411B2 (en) 2012-08-07 2017-05-16 Kyowa Hakko Kirin Co., Ltd. Method of purifying protein
US9512214B2 (en) 2012-09-02 2016-12-06 Abbvie, Inc. Methods to control protein heterogeneity
HK1211981A1 (en) 2012-09-02 2016-06-03 Abbvie Inc. Methods to control protein heterogeneity
US9976163B2 (en) 2012-10-03 2018-05-22 Kyowa Hakko Kirin Co., Ltd Method for preventing reduction of polypeptide by adding amino acid to culture solution
US20140154255A1 (en) 2012-11-30 2014-06-05 Abbvie Biotherapeutics Inc. Anti-vegf antibodies and their uses
SG11201507230PA (en) 2013-03-12 2015-10-29 Abbvie Inc Human antibodies that bind human tnf-alpha and methods of preparing the same
WO2014151878A2 (en) 2013-03-14 2014-09-25 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides
US8921526B2 (en) 2013-03-14 2014-12-30 Abbvie, Inc. Mutated anti-TNFα antibodies and methods of their use
US9017687B1 (en) 2013-10-18 2015-04-28 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
CA2907776C (en) 2013-04-16 2020-04-14 Genentech, Inc. Pertuzumab variants and evaluation thereof
US10398682B2 (en) 2013-07-15 2019-09-03 The Board Of Regents Of The University Of Texas System Methods and compositions to prevent or treat bacterial infections
US9598667B2 (en) 2013-10-04 2017-03-21 Abbvie Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US8946395B1 (en) 2013-10-18 2015-02-03 Abbvie Inc. Purification of proteins using hydrophobic interaction chromatography
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US20150139988A1 (en) 2013-11-15 2015-05-21 Abbvie, Inc. Glycoengineered binding protein compositions
KR20160088930A (ko) * 2013-12-04 2016-07-26 이뮤노젠 아이엔씨 항체 생산용 조성물 및 항체 생성 방법
US9620278B2 (en) * 2014-02-19 2017-04-11 General Electric Company System and method for reducing partial discharge in high voltage planar transformers
US10647777B2 (en) * 2014-05-28 2020-05-12 Genzyme Corporation Methods of controlling the formation of disulfide bonds in protein solutions
US9840553B2 (en) 2014-06-28 2017-12-12 Kodiak Sciences Inc. Dual PDGF/VEGF antagonists
AR103172A1 (es) * 2014-12-22 2017-04-19 Novartis Ag Reducción selectiva de residuos de cisteina en anticuerpos il-17
ES2864842T3 (es) * 2015-08-12 2021-10-14 Pfizer Cisteínas de anticuerpos protegidas y no protegidas, y su uso en la conjugación fármaco-anticuerpo
SI4209499T1 (sl) 2015-08-13 2025-01-31 Amgen Inc. Globinsko nabito filtriranje proteinov, ki vežejo antigen
NZ783685A (en) 2015-12-30 2025-09-26 Kodiak Sciences Inc Antibodies and conjugates thereof
KR20190005873A (ko) 2016-04-15 2019-01-16 앨더 바이오파마슈티컬즈, 인코포레이티드 항-pacap 항체 및 그의 용도
SG11201809959PA (en) * 2016-05-10 2018-12-28 Genentech Inc Methods of decreasing trisulfide bonds during recombinant production of polypeptides
US20190112357A1 (en) * 2016-05-10 2019-04-18 Medimmune, Llc Prevention of protein disulfide bond reduction
WO2017212071A1 (en) 2016-06-10 2017-12-14 Lonza Ltd Method for stabilizing proteins
WO2018002036A1 (en) 2016-06-28 2018-01-04 Zaklady Farmaceutyczne Polpharma Sa Recombinant production of monoclonal antibodies
CN106366160B (zh) * 2016-10-11 2019-06-14 厦门大学 基于二硫键精准配对构建富含二硫键多肽分子骨架的方法
US20190374639A1 (en) 2016-11-21 2019-12-12 Polpharma Biologics S.A. Aqueous pharmaceutical formulations
EP3548071A4 (en) 2016-11-30 2020-07-15 OncoMed Pharmaceuticals, Inc. CANCER TREATMENT METHODS INCLUDING TIGIT BINDING AGENTS
US20190316096A1 (en) 2016-12-28 2019-10-17 Kyowa Hakko Kirin Co Method for selecting cell
US11760777B2 (en) * 2017-04-26 2023-09-19 Bristol-Myers Squibb Company Methods of antibody production that minimize disulfide bond reduction
WO2018208743A1 (en) * 2017-05-09 2018-11-15 Bristol-Myers Squibb Company Method of controlling the formation of pink color during antibody manufacturing
US10913795B2 (en) 2017-05-17 2021-02-09 Immunogen, Inc. Compositions and methods for antibody production
US11697670B2 (en) * 2017-08-22 2023-07-11 Biogen Ma Inc. Methods for purifying antibodies having reduced high molecular weight aggregates
TW201927335A (zh) * 2017-10-02 2019-07-16 美商拜耳保健有限責任公司 防止雙硫鍵於細胞培養收集物中還原之方法
TW201923069A (zh) * 2017-10-02 2019-06-16 美商拜耳保健有限責任公司 以亞硒酸鹽防止細胞培養收獲物中雙硫鍵還原之方法
US11447547B1 (en) 2017-12-13 2022-09-20 Amgen Inc. Method of antigen-binding protein production
SG11202008242XA (en) 2018-03-02 2020-09-29 Kodiak Sciences Inc Il-6 antibodies and fusion constructs and conjugates thereof
EP3788151A4 (en) * 2018-05-04 2022-01-12 Sigma-Aldrich Co. LLC GENE ENGINEERED CELLS WITH MODIFIED HOST CELL PROTEIN PROFILES
WO2020028616A1 (en) * 2018-08-02 2020-02-06 Lonza Ltd Methods for manufacturing recombinant protein comprising a disulfide bond
CN113166717B (zh) 2018-11-08 2024-02-20 苏特罗生物制药公司 具有氧化细胞质的大肠杆菌菌株
WO2020201296A1 (en) 2019-04-01 2020-10-08 The Automation Partnership (Cambridge) Ltd. Operation process for a cell cultivation system
EP4004044A1 (en) 2019-07-24 2022-06-01 H. Lundbeck A/S Anti-mglur5 antibodies and uses thereof
AU2020364071A1 (en) 2019-10-10 2022-05-26 Kodiak Sciences Inc. Methods of treating an eye disorder
US12014835B2 (en) 2020-02-19 2024-06-18 Vanderbilt University Methods for evaluating therapeutic benefit of combination therapies
US12351850B2 (en) 2020-04-30 2025-07-08 Sutro Biopharma, Inc. Methods of producing full-length antibodies using E. coli
CN113480652B (zh) * 2021-07-30 2023-04-07 成都景泽生物制药有限公司 一种重组cho细胞发酵培养生产重组egfr抗体活性分子的方法
WO2023049687A1 (en) 2021-09-21 2023-03-30 Bristol-Myers Squibb Company Methods of controlling the level of dissolved oxygen (do) in a solution comprising a recombinant protein in a storage container
TW202337494A (zh) 2021-11-16 2023-10-01 美商建南德克公司 用莫蘇妥珠單抗治療全身性紅斑狼瘡（ｓｌｅ）之方法及組成物
IL319534A (en) * 2022-09-15 2025-05-01 Sanofi Sa Methods for determining the susceptibility of proteins to redox reactions
TW202504919A (zh) 2023-05-30 2025-02-01 美商派拉岡醫療公司 α4β7整合素抗體組合物及使用方法

Family Cites Families (275)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US524474A (en) * 1894-08-14 Seed-planter
US670534A (en) * 1900-07-27 1901-03-26 Oliver L Carmical Seeding-machine and fertilizer-distributer.
US1369649A (en) * 1920-01-02 1921-02-22 George A Gieseler Pneumatic conveying mechanism
US2062295A (en) * 1932-11-22 1936-12-01 Niagara Sprayer And Chemical C Crop duster
US2171205A (en) * 1937-08-26 1939-08-29 Louis A Zinke Powder distributing attachment for tractors
US2193738A (en) * 1938-05-21 1940-03-12 Nat Conveyors Co Inc Pneumatic conveyer
US2559183A (en) * 1946-12-10 1951-07-03 Lawton L Barnett Transplanter drill set
US2671690A (en) * 1948-02-21 1954-03-09 Ehrenkrook Karl Von Forced air sprayer and duster
US2937049A (en) * 1949-10-18 1960-05-17 Osawa Hirosaburo Method of and an apparatus for carrying coals out of a vertical shaft with the aid of heavy liquid in the coal mine
US2814531A (en) * 1956-04-27 1957-11-26 Clough Equipment Co Balanced pneumatic conveying systems for pulverulent material
US3207560A (en) * 1962-12-26 1965-09-21 Monsanto Co Unloading device
US3197261A (en) * 1964-03-09 1965-07-27 Simpson Herbert Corp System for feeding and transporting materials
US3386474A (en) * 1965-05-26 1968-06-04 Chemagro Corp Diverter valve for finely divided solids
US3515315A (en) * 1966-01-24 1970-06-02 Kidd Designs Ltd Archie Combined seed and fertilizer drills for agricultural use
US3387895A (en) * 1966-12-29 1968-06-11 Combustion Eng Non-clogging splitter unit for dividing the flow of fluid-conveyed material
FR1558490A (es) * 1967-12-27 1969-02-28
US3543704A (en) * 1968-08-05 1970-12-01 Deere & Co Seed planter
US3845702A (en) 1970-04-01 1974-11-05 Mies Filter Prod Inc Apparatus for cooking chicken
DE2440888C3 (de) * 1974-08-27 1978-11-23 Waeschle Maschinenfabrik Gmbh, 7980 Ravensburg Anlage zum aufeinanderfolgenden Beschicken mehrerer, hintereinander an eine pneumatische Förderleitung über Abscheider angeschlossener Entnahmestationen mit Schüttgut
US4049494A (en) 1975-09-04 1977-09-20 The United States Of America As Represented By The Secretary Of Agriculture Vaccine production process
US4036408A (en) * 1975-12-24 1977-07-19 Acf Industries, Incorporated Hopper having means for directing blasts of gas to a discharge outlet or the hopper
US4280419A (en) * 1977-03-21 1981-07-28 International Harvester Company Pneumatic system for conveying granular material
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
FR2413974A1 (fr) 1978-01-06 1979-08-03 David Bernard Sechoir pour feuilles imprimees par serigraphie
US4200412A (en) * 1978-04-20 1980-04-29 Dynamic Air Incorporated Control for pneumatic conveying system
US4264243A (en) * 1979-01-04 1981-04-28 Dundee Cement Company Constant vacuum barge unloading system
US4515893A (en) 1979-04-26 1985-05-07 Ortho Pharmaceutical Corporation Hybrid cell line for producing complement-fixing monoclonal antibody to human T cells
US4244522A (en) * 1979-08-31 1981-01-13 Deere & Company Liquid storage and distribution apparatus for agricultural implements
CA1126587A (en) * 1980-07-11 1982-06-29 Daniel W. Kelm Seed cup assembly
US4413935A (en) * 1981-06-29 1983-11-08 Combustion Engineering, Inc. Flow splitter for dividing a stream of pulverulent material into multiple streams
GB2112506A (en) * 1981-12-30 1983-07-20 Shell Int Research Distributing valve
US4943529A (en) 1982-05-19 1990-07-24 Gist-Brocades Nv Kluyveromyces as a host strain
DE3239897A1 (de) * 1982-10-28 1984-05-03 Trützschler GmbH & Co KG, 4050 Mönchengladbach Verfahren und vorrichtung zur foerderung von faserfoermigen stoffen, insbesondere von in luft schwebend gefoerderten textilen faserflocken bei spinnereivorbereitungsmaschinen
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4620948A (en) 1982-12-22 1986-11-04 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
AU3145184A (en) 1983-08-16 1985-02-21 Zymogenetics Inc. High expression of foreign genes in schizosaccharomyces pombe
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
US4562779A (en) * 1984-01-26 1986-01-07 Briggs Manufacturing, Inc. Foldable drill implement
DE3420616A1 (de) * 1984-06-02 1985-12-05 Alb. Klein Gmbh & Co Kg, 5241 Niederfischbach Vorrichtung und verfahren zur steuerung eines schleusvorganges fuer ein haufwerk von schuettgutpartikeln
US5672347A (en) 1984-07-05 1997-09-30 Genentech, Inc. Tumor necrosis factor antagonists and their use
US5807715A (en) 1984-08-27 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4572798A (en) 1984-12-06 1986-02-25 Cetus Corporation Method for promoting disulfide bond formation in recombinant proteins
US4652630A (en) 1985-02-22 1987-03-24 Monsanto Company Method of somatotropin naturation
US5523215A (en) 1985-03-28 1996-06-04 Chiron Corporation Enhanced purification and expression of insoluble recombinant proteins
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US4738770A (en) * 1985-11-25 1988-04-19 Cities Service Oil And Gas Corp. Apparatus and method of removal of catalyst blockage from reactor recycle pumps
US5091178A (en) 1986-02-21 1992-02-25 Oncogen Tumor therapy with biologically active anti-tumor antibodies
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
US4779765A (en) * 1987-04-13 1988-10-25 Deere & Company Fertilizer divider for dual air system
US4793743A (en) * 1987-04-29 1988-12-27 Morris Rod-Weeder Company Ltd. Air seeder purging system
IL87737A (en) 1987-09-11 1993-08-18 Genentech Inc Method for culturing polypeptide factor dependent vertebrate recombinant cells
US5091313A (en) 1988-08-05 1992-02-25 Tanox Biosystems, Inc. Antigenic epitopes of IgE present on B cell but not basophil surface
US5720937A (en) 1988-01-12 1998-02-24 Genentech, Inc. In vivo tumor detection assay
US4872785A (en) * 1988-01-22 1989-10-10 Schrage Timothy L Shut-off means for air-actuated planter
US4843983A (en) * 1988-02-02 1989-07-04 Deere & Company Pneumatic manifold quick coupling
US5506126A (en) 1988-02-25 1996-04-09 The General Hospital Corporation Rapid immunoselection cloning method
HUT53672A (en) 1988-02-25 1990-11-28 Gen Hospital Corp Quick immunoselective cloning process
US4861579A (en) 1988-03-17 1989-08-29 American Cyanamid Company Suppression of B-lymphocytes in mammals by administration of anti-B-lymphocyte antibodies
JP2749167B2 (ja) 1988-06-21 1998-05-13 ジェネンテク，インコーポレイテッド 心筋梗塞の処置のための方法および治療用組成物
US6048728A (en) 1988-09-23 2000-04-11 Chiron Corporation Cell culture medium for enhanced cell growth, culture longevity, and product expression
EP0435911B1 (en) 1988-09-23 1996-03-13 Cetus Oncology Corporation Cell culture medium for enhanced cell growth, culture longevity and product expression
US4981952A (en) 1988-10-04 1991-01-01 Eli Lilly And Company Method for the purification of vitamin K-dependent proteins
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
DK167639B1 (da) * 1988-11-16 1993-12-06 Kongskilde Maskinfabrik As Maskine til saaning af granuleret materiale
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
DE394538T1 (de) 1989-04-28 1991-04-11 Rhein Biotech Ges. Fuer Biotechnologische Prozesse Und Produkte Mbh, 4000 Duesseldorf Hefezellen der schwanniomyces-gattung.
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
DK0479909T3 (da) 1989-06-29 1997-04-07 Medarex Inc Bispecifikke reagenser til AIDS-behandling
FR2649120B1 (fr) 1989-06-30 1994-01-28 Cayla Nouvelle souche et ses mutants de champignons filamenteux, procede de production de proteines recombinantes a l'aide de ladite souche et souches et proteines obtenues selon ce procede
WO1991001367A1 (en) 1989-07-20 1991-02-07 Bioeng, Inc. Supercritical fluid disruption of and extraction from microbial cells
DK0414151T3 (da) 1989-08-21 1995-05-22 Takeda Chemical Industries Ltd Humane nervevæskstfaktorproteiner og fremstilling deraf
US5033914A (en) * 1989-09-29 1991-07-23 Cyclonaire Corporation High efficiency feeder apparatus for pneumatic conveying lines
EP0423980B1 (en) 1989-10-16 2000-07-12 Amgen Inc. Stem cell factor
GB2237288A (en) 1989-10-18 1991-05-01 Celltech Ltd Amplification of a heterologous gene in recombinant eukaryotic host cells
DK0463151T3 (da) 1990-01-12 1996-07-01 Cell Genesys Inc Frembringelse af xenogene antistoffer
JPH06500011A (ja) 1990-06-29 1994-01-06 ラージ　スケール　バイオロジー　コーポレイション 形質転換された微生物によるメラニンの製造
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
DE69127627T2 (de) 1990-08-29 1998-02-19 Genpharm Int Produktion und Nützung nicht-menschliche transgentiere zur Produktion heterologe Antikörper
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
US5069583A (en) * 1990-10-26 1991-12-03 Caldwell Lawrence G Device for changing flow paths in a pneumatic conveying system
ES2107449T3 (es) 1990-11-23 1997-12-01 Roussel Uclaf Procedimiento de preparacion de una proteina elegida entre las citoquinas, que comprende al menos un puente disulfuro intramolecular por oxidacion, a un ph inferior a 5,0 de la proteina recombinante reducida correspondiente.
GB2251249B (en) 1990-12-28 1995-06-21 Mogam Biotech Res Inst High-density medium for animal cell culture
US5494381A (en) * 1991-04-11 1996-02-27 The Young Industries, Inc. Apparatus and method for pneumatically conveying bulk materials
EP0586505A1 (en) 1991-05-14 1994-03-16 Repligen Corporation Heteroconjugate antibodies for treatment of hiv infection
US5161473A (en) * 1991-05-17 1992-11-10 Deere & Company Seed distribution system and method for a seeding implement
DE69233254T2 (de) 1991-06-14 2004-09-16 Genentech, Inc., South San Francisco Humanisierter Heregulin Antikörper
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
DK0602126T3 (da) 1991-08-14 2003-06-16 Genentech Inc Immunoglobulinvarianter til specifikke FC epsilon-receptorer
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
AU3144193A (en) 1991-11-21 1993-06-15 Board Of Trustees Of The Leland Stanford Junior University Controlling degradation of glycoprotein oligosaccharides by extracellular glycosisases
DE69334351D1 (de) 1992-02-06 2011-05-12 Novartis Vaccines & Diagnostic Biosynthetisches Bindeprotein für Tumormarker
US5240355A (en) * 1992-05-22 1993-08-31 Nol-Tec Systems, Inc. Dense phase transporter pneumatic conveying system
AU687346B2 (en) 1992-06-30 1998-02-26 Oncologix, Inc. A combination of anti-erbB-2 monoclonal antibodies and method of using
US5456909A (en) 1992-08-07 1995-10-10 T Cell Sciences, Inc. Glycoform fractions of recombinant soluble complement receptor 1 (sCR1) having extended half-lives in vivo
ATE149570T1 (de) * 1992-08-17 1997-03-15 Genentech Inc Bispezifische immunoadhesine
JPH08500826A (ja) 1992-08-21 1996-01-30 ジェネンテク，インコーポレイテッド Ｌｆａ−１仲介疾患を処置する方法
US7744877B2 (en) 1992-11-13 2010-06-29 Biogen Idec Inc. Expression and use of anti-CD20 Antibodies
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
EP0752248B1 (en) 1992-11-13 2000-09-27 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5581476A (en) 1993-01-28 1996-12-03 Amgen Inc. Computer-based methods and articles of manufacture for preparing G-CSF analogs
US5379706A (en) * 1993-04-07 1995-01-10 Agco Corporation Seed distribution system for planters and drills
AU5752594A (en) * 1993-04-20 1994-11-03 Deere & Company Air separation tube for a pneumatic delivery system
US5407305A (en) * 1993-04-29 1995-04-18 Semco, Inc. Continuous dense phase conveying method utilizing high pressure gas at predetermined gas pressures within a conveying pipe
US5417972A (en) 1993-08-02 1995-05-23 The Board Of Trustees Of The Leland Stanford Junior University Method of killing B-cells in a complement independent and an ADCC independent manner using antibodies which specifically bind CDIM
US5663304A (en) 1993-08-20 1997-09-02 Genentech, Inc. Refolding of misfolded insulin-like growth factor-I
US5595721A (en) 1993-09-16 1997-01-21 Coulter Pharmaceutical, Inc. Radioimmunotherapy of lymphoma using anti-CD20
ES2108566T3 (es) 1993-12-10 1997-12-16 Genentech Inc Procedimientos para diagnosticar alergias y para seleccionar agentes terapeuticos antialergicos.
AP660A (en) 1994-01-18 1998-08-18 Genentech Inc A method of treatment of parasitic infection using IgE antagonists.
JP3780315B2 (ja) 1994-03-03 2006-05-31 ジェネンテク・インコーポレイテッド 炎症性疾患の処置のための抗ｉｌ−８モノクローナル抗体
GB9413127D0 (en) 1994-06-30 1994-08-24 Philips Electronics Uk Ltd Data processing apparatus
US5639635A (en) 1994-11-03 1997-06-17 Genentech, Inc. Process for bacterial production of polypeptides
US5575225A (en) * 1995-02-27 1996-11-19 Unverferth Manufacturing Company, Inc. Air-powered apparatus for filling grain drills and method of using same
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
IL117645A (en) 1995-03-30 2005-08-31 Genentech Inc Vascular endothelial cell growth factor antagonists for use as medicaments in the treatment of age-related macular degeneration
DE19513676A1 (de) 1995-04-11 1996-10-17 Behringwerke Ag Cytoplasmatische Expression von Antikörpern, Antikörperfragmenten und Antikörperfragmentfusionsmolekülen in E.coli
KR100654645B1 (ko) 1995-04-27 2007-04-04 아브게닉스, 인크. 면역화된 제노마우스 유래의 인간 항체
AU2466895A (en) 1995-04-28 1996-11-18 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP0827409A1 (en) * 1995-05-15 1998-03-11 Cedars-Sinai Medical Center Compositions and methods for inhibiting xenograft rejection
US5721121A (en) 1995-06-06 1998-02-24 Genentech, Inc. Mammalian cell culture process for producing a tumor necrosis factor receptor immunoglobulin chimeric protein
JPH11507535A (ja) 1995-06-07 1999-07-06 イムクローン システムズ インコーポレイテッド 腫瘍の成長を抑制する抗体および抗体フラグメント類
US5830761A (en) 1995-06-07 1998-11-03 Genetics Institute, Inc. Medium and methods for culturing mammalian cho cells
US5783186A (en) 1995-12-05 1998-07-21 Amgen Inc. Antibody-induced apoptosis
US5854067A (en) 1996-01-19 1998-12-29 Board Of Regents, The University Of Texas System Hexokinase inhibitors
CA2242414C (en) 1996-01-23 2012-01-03 Genentech, Inc. Anti-cd18 antibodies for use against stroke
US5813801A (en) * 1996-06-28 1998-09-29 Mac Equipment, Inc. Dense phase particulate conveying system and method with continuous air leakage management
US5714388A (en) 1996-08-14 1998-02-03 Bayer Corporation Apparatus and method for detecting chemiluminescent light
US7147851B1 (en) 1996-08-15 2006-12-12 Millennium Pharmaceuticals, Inc. Humanized immunoglobulin reactive with α4β7 integrin
US5749682A (en) * 1996-09-10 1998-05-12 Renfro Corporation Article collection and distribution system
US5912327A (en) 1996-09-30 1999-06-15 Human Genome Sciences, Inc. Method of purifying chemokines from inclusion bodies
JP2001503401A (ja) 1996-10-24 2001-03-13 ヴァンダービルト・ユニバーシティ 直接タンパク質送達することが困難な領域での遺伝子送達及び発現
CN1268639C (zh) 1996-11-15 2006-08-09 基因技术股份有限公司 神经营养蛋白的纯化
ES2293661T3 (es) * 1996-11-27 2008-03-16 Genentech, Inc. Purificacion por afinidad de polipeptido en una matriz de proteinas a.
KR100532178B1 (ko) 1996-11-27 2005-12-01 제넨테크, 인크. 인간화 항-ＣＤ11ａ 항체
US6037454A (en) 1996-11-27 2000-03-14 Genentech, Inc. Humanized anti-CD11a antibodies
JP4215172B2 (ja) 1996-12-03 2009-01-28 アムジェン フレモント インク． 複数のＶ▲下Ｈ▼およびＶ▲下κ▼領域を含むヒトＩｇ遺伝子座を有するトランスジェニック哺乳動物、ならびにそれから産生される抗体
US6306393B1 (en) 1997-03-24 2001-10-23 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
CN100480269C (zh) 1997-04-07 2009-04-22 基因技术股份有限公司 抗-血管内皮生长因子的抗体
US20020032315A1 (en) * 1997-08-06 2002-03-14 Manuel Baca Anti-vegf antibodies
JP2001511653A (ja) 1997-05-15 2001-08-14 ジェネンテク，インコーポレイテッド Ａｐｏ−２レセプター
ES2190087T3 (es) 1997-06-13 2003-07-16 Genentech Inc Formulacion estabilizada de un anticuerpo.
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
US5927217A (en) * 1997-06-16 1999-07-27 Conserva Pak Seeding Systems Metering particulate material
US6955917B2 (en) 1997-06-20 2005-10-18 Bayer Healthcare Llc Chromatographic method for high yield purification and viral inactivation of antibodies
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
US5994511A (en) 1997-07-02 1999-11-30 Genentech, Inc. Anti-IgE antibodies and methods of improving polypeptides
WO1999002567A2 (en) 1997-07-08 1999-01-21 Board Of Regents, The University Of Texas System Compositions and methods for producing homoconjugates of antibodies which induce growth arrest or apoptosis of tumor cells
US5878679A (en) * 1997-08-18 1999-03-09 Deere & Company Product disconnect for metering device
AU759779B2 (en) 1997-10-31 2003-05-01 Genentech Inc. Methods and compositions comprising glycoprotein glycoforms
KR100253916B1 (ko) 1997-12-29 2000-05-01 김충환 사람 인슐린 전구체의 제조방법
EP1049772A1 (en) 1998-01-30 2000-11-08 Genesense Technologies, Inc. Oligonucleotide sequences complementary to thioredoxin or thioredoxin reductase genes and methods of using same to modulate cell growth
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US6242195B1 (en) 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
DK1068241T3 (da) 1998-04-02 2008-02-04 Genentech Inc Antistofvarianter og fragmenter deraf
DK2180007T4 (da) 1998-04-20 2017-11-27 Roche Glycart Ag Glycosyleringsteknik for antistoffer til forbedring af antistofafhængig cellecytotoxicitet
TR200003087T2 (tr) * 1998-04-21 2001-02-21 Micromet Ag Yeni CD19 X CD3 Spesifik polipeptidler ve kullanımları
US6047652A (en) * 1998-05-12 2000-04-11 Case Corporation Seed planter distribution system
EP1241250A3 (en) 1998-05-15 2003-03-19 Genentech, Inc. Human dehydrogenase-like protein and nucleic acid encoding it
CN1320044A (zh) 1998-08-11 2001-10-31 Idec药物公司 包括施用抗－cd20抗体的b－细胞淋巴瘤联合疗法
BRPI9913018B8 (pt) 1998-08-27 2021-07-06 Lg Chemical Ltd processo para a preparaÇço de somatotropina ativa a partir de corpésculos de inclusço.
AU771239C (en) * 1998-09-14 2004-10-14 Soren Buus A method of producing a functional immunoglobulin superfamily protein
US6224866B1 (en) 1998-10-07 2001-05-01 Biocrystal Ltd. Immunotherapy of B cell involvement in progression of solid, nonlymphoid tumors
US6298797B1 (en) * 1998-11-05 2001-10-09 Flexi-Coil Ltd. Nurse inductor apparatus for air seeders
KR20010099788A (ko) 1998-11-09 2001-11-09 케네쓰 제이. 울코트 Ｂｍｔ 또는 ｐｂｓｃ 이식을 받은 환자의 키메라항-ｃｄ２０ 항체 치료법
EP1131093A4 (en) 1998-11-09 2002-05-02 Idec Pharma Corp TREATMENT OF HEMATOLOGICAL VILTIES ASSOCIATED WITH CIRCULATING TUMOR CELLS USING CHIMERIC ANTI-CD20 ANTIBODIES
MX353234B (es) 1999-01-15 2018-01-08 Genentech Inc Variantes de polipeptidos con función efectora alterada.
US6897044B1 (en) 1999-01-28 2005-05-24 Biogen Idec, Inc. Production of tetravalent antibodies
US6383276B1 (en) 1999-03-12 2002-05-07 Fuji Photo Film Co., Ltd. Azomethine compound and oily magenta ink
EP1048732A1 (de) 1999-04-26 2000-11-02 F. Hoffmann-La Roche Ag Verfahren zur Herstellung von natürlich gefalteten und sekretierten Proteinen
EP1176981B1 (en) 1999-05-07 2005-11-30 Genentech, Inc. Treatment of autoimmune diseases with antagonists which bind to b cell surface markers
US6946129B1 (en) 1999-06-08 2005-09-20 Seattle Genetics, Inc. Recombinant anti-CD40 antibody and uses thereof
DE05075555T1 (de) 1999-06-09 2007-02-08 Immunomedics, Inc. Immuntherapie von Autoimmunerkrankungen durch die Verwendung von B-Zell-spezifischen Antikörpern
ITMI991299A1 (it) 1999-06-11 2000-12-11 Consiglio Nazionale Ricerche Uso di anticorpi contro antigeni di superficie per il trattamento della malattia trapianto contro ospite
DE19930748C2 (de) 1999-07-02 2001-05-17 Infineon Technologies Ag Verfahren zur Herstellung von EEPROM- und DRAM-Grabenspeicherzellbereichen auf einem Chip
JP2003528805A (ja) 1999-07-12 2003-09-30 ジェネンテック・インコーポレーテッド Ｃｄ２０に結合するアンタゴニストを用いた異種抗原に対する免疫応答のブロッキング
AU778022B2 (en) 1999-07-30 2004-11-11 Genentech Inc. Charged filtration membranes and uses therefor
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
AU784971B2 (en) 1999-08-11 2006-08-10 Biogen Inc. Treatment of patients having non-Hodgkins lymphoma with bone marrow involvement with anti-CD20 antibodies
US6451284B1 (en) 1999-08-11 2002-09-17 Idec Pharmaceuticals Corporation Clinical parameters for determining hematologic toxicity prior to radioimmunotheraphy
AU6929100A (en) 1999-08-23 2001-03-19 Biocrystal Limited Methods and compositions for immunotherapy of b cell involvement in promotion ofa disease condition comprising multiple sclerosis
AUPQ296799A0 (en) 1999-09-20 1999-10-14 Unisearch Limited A cell-membrane impermeable trivalent organoarsenical derivative and use thereof
US6872563B1 (en) * 1999-10-05 2005-03-29 President And Fellows Of Harvard College Compositions and methods for production of disulfide bond containing proteins in host cells
NZ518477A (en) 1999-10-29 2004-10-29 Genentech Inc Isolated anti-prostate stem cell antigen (PSCA) antibodies that internalise upon binding to PSCA on a mammalian cell, including a PSCA-expressing tumour cell, in vivo
US20020006404A1 (en) 1999-11-08 2002-01-17 Idec Pharmaceuticals Corporation Treatment of cell malignancies using combination of B cell depleting antibody and immune modulating antibody related applications
US6426208B1 (en) 1999-11-12 2002-07-30 Harbor-Ucla Research And Education Institute Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof
US6808902B1 (en) 1999-11-12 2004-10-26 Amgen Inc. Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules
WO2001046453A1 (en) 1999-12-22 2001-06-28 Novo Nordisk A/S Method for extractive refolding of scrambled single-chain polypeptides
US20020009427A1 (en) 2000-03-24 2002-01-24 Wolin Maurice J. Methods of therapy for non-hodgkin's lymphoma
US20030185796A1 (en) 2000-03-24 2003-10-02 Chiron Corporation Methods of therapy for non-hodgkin's lymphoma
MXPA02009626A (es) 2000-03-31 2003-05-14 Idec Pharma Corp Uso combinado de anticuerpos anti-citocina o antagonistas y anti-cd20 para el tratamiento de linfoma de celulas b.
PL357939A1 (en) 2000-04-11 2004-08-09 Genentech, Inc. Multivalent antibodies and uses therefor
EP1286692A4 (en) 2000-04-25 2004-11-17 Idec Pharma Corp INTRATHECAL ADMINISTRATION OF RITUXIMAB FOR THE TREATMENT OF LYMPHOMAS OF THE CENTRAL NERVOUS SYSTEM
US20030009301A1 (en) 2000-05-30 2003-01-09 M.B. Anand Integrated utility meter-reading, billing, payment and usage management system
EP1299128A2 (en) 2000-06-20 2003-04-09 Idec Pharmaceuticals Corporation Cold anti-cd20 antibody/radiolabeled anti-cd22 antibody combination
SI1296714T1 (sl) 2000-06-22 2010-01-29 S For Entpr University Of Iowa Kombinacija CpG-ja in protiteles, usmerjenih proti CD19, CD20, CD22 ali CD40 za zdravljenje ali preprečevanje raka
JP2004502742A (ja) 2000-07-12 2004-01-29 アイデック　ファーマスーティカルズ　コーポレイション Ｂ細胞を消滅させる抗体及び免疫調節抗体を併用するｂ細胞悪性疾患の治療関連出願
US6548276B2 (en) 2000-09-06 2003-04-15 The Board Of Trustees Of The Leland Stanford Junior University Enhanced in vitro synthesis of active proteins containing disulfide bonds
US7041479B2 (en) * 2000-09-06 2006-05-09 The Board Of Trustess Of The Leland Stanford Junior University Enhanced in vitro synthesis of active proteins containing disulfide bonds
US20020058029A1 (en) 2000-09-18 2002-05-16 Nabil Hanna Combination therapy for treatment of autoimmune diseases using B cell depleting/immunoregulatory antibody combination
US20040185535A1 (en) 2003-03-21 2004-09-23 Giles Wilson Industrial-scale serum-free production of recombinant FVII in mammalian cells
US20020128448A1 (en) 2000-10-20 2002-09-12 Idec Pharmaceuticals Corporation Variant IgG3 Rituxan and therapeutic use thereof
US20070292411A1 (en) 2000-11-08 2007-12-20 Human Genome Sciences, Inc. Antibodies That Immunospecifically Bind to TRAIL Receptors
CN1494553A (zh) 2001-01-29 2004-05-05 IDECҩ�﹫˾ 改变的抗体及其使用方法
AU2002327164A1 (en) 2001-01-29 2002-12-09 Idec Pharmaceuticals Corporation Engineered tetravalent antibodies and methods of use
US20030103971A1 (en) 2001-11-09 2003-06-05 Kandasamy Hariharan Immunoregulatory antibodies and uses thereof
CZ20032208A3 (cs) 2001-02-23 2004-01-14 Immunex Corporation Zvýšený výtěžek aktivních proteinů
EP3088412B1 (en) * 2001-03-09 2021-05-05 Chugai Seiyaku Kabushiki Kaisha Protein purification method
US20030040095A1 (en) 2001-03-16 2003-02-27 Achille Arini Method for the production of pharmaceutically active recombinant proteins
AU2002307037B2 (en) 2001-04-02 2008-08-07 Biogen Idec Inc. Recombinant antibodies coexpressed with GnTIII
JP4679035B2 (ja) 2001-04-02 2011-04-27 ジェネンテック， インコーポレイテッド 併用療法
WO2003061694A1 (en) 2001-05-10 2003-07-31 Seattle Genetics, Inc. Immunosuppression of the humoral immune response by anti-cd20 antibodies
EP1404813A4 (en) 2001-06-13 2004-11-24 Genentech Inc METHOD FOR CULTIVATING ANIMAL CELLS AND POLYPEPTIDE PRODUCTION IN ANIMAL CELLS
AU2002315168A1 (en) 2001-06-14 2003-01-02 Intermune, Inc. Combination therapy of gamma-interferon and b cell specific antibodies
US7321026B2 (en) 2001-06-27 2008-01-22 Skytech Technology Limited Framework-patched immunoglobulins
WO2003011878A2 (en) 2001-08-03 2003-02-13 Glycart Biotechnology Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
EP2131198B1 (en) 2001-09-20 2013-03-27 Board of Regents, The University of Texas System Measuring circulating therapeutic antibody, antigen and antigen/antibody complexes using ELISA assays
DE60221553T2 (de) 2001-10-02 2008-04-10 Novo Nordisk Health Care Ag Verfahren zur herstelllung rekombinanter proteine in eukaryontischen zellen
CA2463879C (en) 2001-10-25 2012-12-04 Genentech, Inc. Glycoprotein compositions
US6852680B2 (en) 2001-10-26 2005-02-08 Ethyl Corporation Dithiocarbamates containing alkylthio and hydroxy substituents
US20060040348A1 (en) 2001-11-13 2006-02-23 Minmin Qin Methods for producing and purifying recombinant alpha-L-iduronidase
WO2003049694A2 (en) 2001-12-07 2003-06-19 Chiron Corporation Methods of therapy for non-hodgkin's lymphoma
GB0130955D0 (en) 2001-12-24 2002-02-13 Cancer Res Ventures Expression system
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
EP1572902B1 (en) 2002-02-01 2014-06-11 Life Technologies Corporation HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES
WO2003068821A2 (en) 2002-02-14 2003-08-21 Immunomedics, Inc. Anti-cd20 antibodies and fusion proteins thereof and methods of use
US20030219870A1 (en) 2002-03-23 2003-11-27 George Georgiou Secretion of proteins with multiple disulfide bonds in bacteria and uses thereof
WO2003085118A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Process for producing antibody composition
BR0309145A (pt) 2002-04-09 2005-02-01 Kyowa Hakko Kogyo Kk Células das quais o genoma é modificado
DK1501369T3 (en) 2002-04-26 2015-09-28 Genentech Inc Non-affinity purification of proteins
US20030219818A1 (en) 2002-05-10 2003-11-27 Bohen Sean P. Methods and compositions for determining neoplastic disease responsiveness to antibody therapy
US20040029229A1 (en) 2002-05-20 2004-02-12 Reeves Philip J. High level protein expression system
AU2002345829A1 (en) 2002-06-24 2004-01-06 Dr. Reddy's Laboratories Ltd. Process for preparing g-csf
GB0216648D0 (en) 2002-07-18 2002-08-28 Lonza Biologics Plc Method of expressing recombinant protein in CHO cells
US7189811B2 (en) 2002-09-06 2007-03-13 National Institute Of Immunology Process for solubilization of recombinant proteins expressed as inclusion body
DK1561756T3 (en) * 2002-09-11 2016-02-15 Chugai Pharmaceutical Co Ltd PROCEDURE FOR CLEANING PROTEIN.
AU2003286493A1 (en) 2002-10-18 2004-05-04 Abgenix, Inc. System and method for cleaving antibodies
ATE364092T1 (de) 2003-01-09 2007-06-15 Genentech Inc Reinigung von polypeptiden
PL212317B1 (pl) 2003-01-31 2012-09-28 Organon Nv Sposób izolacji bialka zawierajacego wiazania disulfidowe w natywnej konformacji
RU2005127664A (ru) * 2003-02-06 2006-09-10 Микромет Аг (De) Тримерная полипептидная конструкция, индуцирующая пролонгированный т-клеточный ответ
LT3095793T (lt) 2003-07-28 2020-07-10 Genentech, Inc. Baltymo a išplovimo sumažinimas afininės baltymo a chromatografijos metu
ES2565077T3 (es) 2003-10-10 2016-03-31 Novo Nordisk Health Care Ag Método para producción en gran escala de un polipéptido en células eucariotas
ATE375385T1 (de) 2004-03-01 2007-10-15 Ares Trading Sa Verwendung eines serumfreien zellkulturmediums zur produktion von il-18bp in säugerzellen
BRPI0516284A (pt) 2004-09-23 2008-09-02 Genentech Inc anticorpo construìdo com cisteìna, método de selecionar anticorpos, compostos conjugados de droga-anticorpo, composição farmacêutica, método para matar ou inibir a proliferação de células de tumor, métodos de inibir a proliferação celular e o crescimento de células de tumor, artigo manufaturado e método para produzir um composto
US7435804B2 (en) 2004-10-19 2008-10-14 Phage Biotechnology, Inc. Method for obtaining single chain antibodies to human interferon α2b
EP1805205A1 (en) 2004-10-22 2007-07-11 Amgen Inc. Methods for refolding polypeptides
WO2006047340A2 (en) 2004-10-22 2006-05-04 Amgen Inc. Methods for refolding of recombinant antibodies
GB0425534D0 (en) 2004-11-19 2004-12-22 Celltech R&D Ltd Process for obtaining antibodies
JP2006186521A (ja) 2004-12-27 2006-07-13 Leader Electronics Corp チューナのビットエラーレート（ｂｅｒ）測定の方法および装置
US8029783B2 (en) 2005-02-02 2011-10-04 Genentech, Inc. DR5 antibodies and articles of manufacture containing same
DOP2006000029A (es) 2005-02-07 2006-08-15 Genentech Inc Antibody variants and uses thereof. (variantes de un anticuerpo y usos de las mismas)
WO2007062090A2 (en) 2005-11-23 2007-05-31 Genentech, Inc. Methods and compositions related to b cell assays
EP1996697A2 (en) 2006-03-07 2008-12-03 Novartis AG Preventing norvaline and norleucine misincorporation in recombinant proteins
CA2842964A1 (en) 2006-09-13 2008-03-20 Abbvie Inc. Cell culture improvements
TWI442965B (zh) 2006-11-01 2014-07-01 Biogen Idec Inc 使用低ｐＨ及二價陽離子分離生物巨分子的方法
MX2009006969A (es) 2006-12-29 2010-04-07 Gloucester Pharmaceuticals Purificacion de romidepsina.
US8467449B2 (en) * 2007-01-08 2013-06-18 Qualcomm Incorporated CAVLC enhancements for SVC CGS enhancement layer coding
US20100209434A1 (en) 2007-03-30 2010-08-19 Medimmune, Llc Antibody formulation
WO2008135498A2 (en) 2007-05-04 2008-11-13 Novo Nordisk A/S Prevention of protein degradation in mammalian cell cultures
EP2188302B1 (en) 2007-07-09 2017-11-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
AU2007356356A1 (en) 2007-07-12 2009-01-15 Lorcan Michael Murphy A hydroalcoholic fat emulsion and emulsifier for use therein
WO2011009625A1 (en) 2009-07-24 2011-01-27 F. Hoffmann-La Roche Ag Stirrer system
KR20160088930A (ko) 2013-12-04 2016-07-26 이뮤노젠 아이엔씨 항체 생산용 조성물 및 항체 생성 방법
WO2015198451A1 (ja) 2014-06-26 2015-12-30 楽天株式会社 情報処理装置、情報処理方法及び情報処理プログラム
CA3118488A1 (en) 2018-11-05 2020-05-14 Avista Pharma Solutions, Inc. Chemical compounds
IT201900007998A1 (it) 2019-06-04 2020-12-04 Benelli Armi Spa Calcio per arma

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