ES2572728T3 - Anticuerpos anti-HER biespecíficos - Google Patents
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- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
Un anticuerpo multiespecífico que comprende un dominio variable de cadena pesada (VH) y un dominio de cadena variable ligera (VL), en el que el VH y el VL se emparejan juntos para formar un único dominio de unión a antígeno que se une específicamente al EGFR y al HER3, en donde el anticuerpo comprende: (a) HVR-H1 que comprende la secuencia de aminoácidos de LSGDWIH (SEQ ID NO: 48); (b) HVR-H2 que comprende la secuencia de aminoácidos de VGEISAAGGYTD (SEQ ID NO: 51); y (c) HVR-H3 que comprende la secuencia de aminoácidos de ARESRVSFEAAMDY (SEQ ID NO: 53); y (d) HVR-L1 que comprende la secuencia de aminoácidos de NIATDVA (SEQ ID NO: 55); (e) HVR-L2 que comprende la secuencia de aminoácidos de SASF (SEQ ID NO: 56); y (f) HVR-L3 que comprende la secuencia de aminoácidos de SEPEPYT (SEQ ID NO: 57).
Description
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procedimientos que implican el uso de kits y reactivos disponibles en el mercado se llevan a cabo generalmente de acuerdo con protocolos y/o parámetros definidos por el fabricante salvo que se observe de otra manera.
Antes de que se describan los presentes métodos, kits y usos de los mismos, ha de entenderse que la presente invención no se limita a la metodología, los protocolos, las líneas celulares, las especies o los géneros de animales y los reactivos particulares descritos como tal pueden, por supuesto, variar. También ha de entenderse que la terminología usada en el presente documento es para el fin de describir solamente realizaciones particulares y no está destinada a limitar el alcance de la presente invención que se limitará solamente por las reivindicaciones adjuntas.
Debe observarse que como se usa en el presente documento y en las reivindicaciones adjuntas, las formas singulares “un”, “una” y “el/la” incluyen referentes plurales salvo que el contexto lo dicte claramente de otra manera.
A lo largo de la presente memoria descriptiva y reivindicaciones, la palabra “comprender” o variaciones tales como “comprende” o “que comprende”, se entenderán que implican la inclusión de un número entero o un grupo de números enteros citados pero no la exclusión de cualquier otro número entero o grupo de números enteros.
El término “anticuerpo” en el presente documento se usa en el sentido más amplio y cubre específicamente los anticuerpos monoclonales, los anticuerpos policlonales, los anticuerpos multiespecíficos y los fragmentos de anticuerpos siempre que muestren la actividad biológica deseada. La frase “anticuerpo multiespecífico” se usa en el sentido más amplio y cubre específicamente un anticuerpo que comprende un dominio de unión a antígeno que tiene especificidad poliepitópica (es decir, es capaz de unirse específicamente a dos o más epítopos diferentes en una molécula biológica o es capaz de unirse específicamente a los epítopos en dos o más moléculas biológicas diferentes). Un ejemplo específico de un dominio de unión a antígeno es una unidad VHVL comprendida por un dominio variable de cadena pesada (VH) y un dominio variable de cadena ligera (VL). Tales anticuerpos multiespecíficos incluyen, pero no se limitan a, anticuerpos de longitud completa, anticuerpos que tienen dos o más dominios VL y VH, fragmentos de anticuerpos tales como Fab, Fv, dsFv, scFv, diacuerpos, diacuerpos biespecíficos y triacuerpos, fragmentos de anticuerpos que se han unido covalentemente o no covalentemente. Un “anticuerpo biespecífico” es un anticuerpo multiespecífico que comprende un dominio de unión a antígeno que es capaz de unirse específicamente a dos epítopos diferentes en una molécula biológica o es capaz de unirse específicamente a los epítopos de dos moléculas biológicas diferentes. El anticuerpo biespecífico también se denomina en el presente documento que tiene “especificidad dual” o siendo “específico dual”.
En ciertas realizaciones, un anticuerpo de la invención tiene una constante de disociación (Kd) de ≤ 1 µm, ≤ 100 nM, ≤ 10 nM, ≤ 1 nM, ≤ 0,11 nM, ≤ 0,01 nM o ≤ 0,001 nM (por ejemplo 10-8 M o menos, por ejemplo de 10-8 M a 10-13 M, de 10-9 M a 10-13 M) para su HER o sus HER diana.
La unidad básica del anticuerpo de cuatro cadenas es una glucoproteína heterotetramérica compuesta por dos cadenas ligeras (L) idénticas y dos cadenas pesadas (H) idénticas (un anticuerpo IgM consiste en 5 de las unidades heterotetraméricas básicas junto con un polipéptido adicional llamado cadena J, y por lo tanto contiene 10 sitios de unión a antígenos, mientras que los anticuerpos IgA secretados pueden polimerizar para formar ensamblajes polivalentes que comprenden 2-5 de las unidades básicas de 4 cadenas junto con la cadena J). En el caso de las IgG, la unidad de 4 cadenas tiene en general aproximadamente 150.000 daltons. Cada cadena L se une a una cadena H por un enlace disulfuro covalente, mientras que las dos cadenas H se unen entre sí por uno o más enlaces disulfuro dependiendo del isotipo de la cadena H. Cada cadena H y L también tiene puentes disulfuro intracatenarios espaciados de forma regular. Cada cadena H tiene, en el N-terminal, un dominio variable (VH) seguido de tres dominios constantes (CH) para cada una de las cadenas α y α y cuatro dominios CH para los isotipos µ y α. Cada cadena L tiene, en el N-terminal, un dominio variable (VL) seguido de un dominio constante (CL) en su otro extremo. El VL se alinea con el VH y el CL se alinea con el primer dominio constante de la cadena pesada (CH1). Se cree que los restos de aminoácidos particulares forman una interfaz entre los dominios variables de la cadena ligera y de la cadena pesada. El apareamiento de un VH y un VL juntos forma un único sitio de unión a antígeno. Para la estructura y las propiedades de las diferentes clases de anticuerpos, véase, por ejemplo, Basic and Clinical Immunology, 8ª edición, Daniel P. Stites, Abba I. Terr y Tristam G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, página 71 y Capítulo 6.
La cadena L de cualquier especie de vertebrado puede asignarse a uno de dos tipos claramente distintos, llamados kappa y lambda, basados en las secuencias de aminoácidos de sus dominios constantes. Dependiendo de la secuencia de aminoácidos del dominio constante de sus cadenas pesadas (CH), las inmunoglobulinas pueden asignarse a diferentes clases o isotipos. Hay cinco clases de inmunoglobulinas: IgA, IgD, IgE, IgG e IgM, que tienen cadenas pesadas designadas α, γ, ε y µ, respectivamente. Las clases γ y α se dividen adicionalmente en subclases basándose en diferencias relativamente menores en la secuencia y la función de CH, por ejemplo, los humanos expresan las siguientes subclases: IgG1, IgG2, IgG3, IgG4, IgA1 e IgA2.
El término “variable” se refiere al hecho de que ciertos segmentos de los dominios variables difieren extensivamente en la secuencia entre anticuerpos. El dominio V media la unión a antígeno y define la especificidad de un anticuerpo particular por su antígeno particular. Sin embargo, la variabilidad no se distribuye firmemente a través del intervalo
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variantes delecionales, sustitucionales e insercionales, por ejemplo aquellas descritas en Lynch et al (New England Journal of Medicine 2004, 350:2129), Paez et al (Science 2004, 304:1497) y Pao et al (PNAS 2004, 101:13306).
En el presente documento, “dominio extracelular del EGFR” o “ECD EGFR” se refiere a un dominio del EGFR que está fuera de una célula, bien anclado a una membrana celular o bien en circulación, incluyendo fragmentos del mismo. En una realización, el dominio extracelular del EGFR puede comprender cuatro dominios: “Dominio I” (restos de aminoácido de aproximadamente 1-158), “Dominio II” (restos de aminoácido 159-336), “Dominio III” (restos de aminoácido 337-470) y “Dominio IV” (restos de aminoácido 471-645), donde los límites son aproximados y pueden variar en aproximadamente 1-3 aminoácidos.
Las expresiones “ErbB2” y “HER2” se usan intercambiablemente en el presente documento y se refieren a la proteína HER2 humana descrita, por ejemplo, en Semba et al., PNAS (EE.UU.) 82:6497-6501 (1985) y Yamamoto et al. Nature 319:230-234 (1986) (número de acceso de GenBank X03363). El término “erbB2” se refiere al gen que codifica HER2 humano y “neu” se refiere al gen que codifica p185neu de rata. El HER2 preferido es el HER2 humano de secuencia nativa.
En el presente documento, “dominio extracelular de HER2” o “ECD HER2” se refiere a un dominio de HER2 que está fuera de una célula, bien anclado a una membrana celular o bien en circulación, incluyendo fragmentos del mismo. En una realización, el dominio extracelular de HER2 puede comprender cuatro dominios: “Dominio I” (restos de aminoácido de aproximadamente 1-195), “Dominio II” (restos de aminoácido de aproximadamente 196-319), “Dominio III” (restos de aminoácido de aproximadamente 320-488) y “Dominio IV” (restos de aminoácido de aproximadamente 489-630) (numeración de restos sin péptido señal). Véase Garrett et al. Mol. Cell. 11: 495-505 (2003), Cho et al. Nature 421: 756-760 (2003), Franklin et al. Cancer Cell 5:317-328 (2004), y Plowman et al. Proc. Natl. Acad. Sci. 90:1746-1750 (1993).
“ErbB3” y “HER3” se refiere al polipéptido receptor como se desvela, por ejemplo, en las Patente de EE.UU. N.º
5.183.884 y N.º 5.480.968 así como Kraus et al. PNAS (EE.UU.) 86:9193:9197 (1989).
En el presente documento, “dominio extracelular de HER3” o “ECD HER3” se refiere a un dominio de HER3 que está fuera de una célula, bien anclado a una membrana celular o bien en circulación, incluyendo fragmentos del mismo. En una realización, el dominio extracelular de HER3 puede comprender cuatro dominios: Dominio I, Dominio II, Dominio III y Dominio IV. En una realización, el ECD HER3 comprende los aminoácidos 1-636 (numeración incluyendo el péptido señal). En una realización, el dominio III del HER3 comprende los aminoácidos 328-532 (numeración incluyendo el péptido señal).
Los términos “ErbB4” y “HER4” en el presente documento se refieren al polipéptido receptor como se desvela, por ejemplo, en la Solicitud de Patente EP N.º 599.274; Plowman et al., Proc. Natl. Acad. Sci. EE.UU., 90:1746-1750 (1993); y Plowman et al., Nature, 366:473-475 (1993), incluyendo las isoformas del mismo, por ejemplo, como se desvela en el documento WO99/19488, publicado el 22 de abril, 1999.
Por “ligando HER” se entiende un polipéptido que se une a y/o activa un receptor HER. El ligando HER de interés particular en el presente documento es un ligando HER humano de secuencia nativa tal como el factor de crecimiento epidérmico (EGF) (Savage et al., J. Biol. Chem. 247:7612-7621 (1972)); el factor transformante del crecimiento alfa (TGF-α) (Marquardt et al., Science 223:1079-1082 (1984)); la anfirregulina también conocida como factor de crecimiento autocrino del schwanoma o del queratinocito (Shoyab et al. Science 243:1074-1076 (1989); Kimura et al. Nature 348:257-260 (1990); y Cook et al. Mol. Cell. Biol. 11:2547-2557 (1991)); la betacelulina (Shing et al., Science 259:1604-1607 (1993); y Sasada et al. Biochem. Biophys. Res. Commun. 190:1173 (1993)); el factor de crecimiento epidérmico de unión a heparina (HB-EGF) (Higashiyama et al., Science 251:936-939 (1991)); la epirregulina (Toyoda et al., J. Biol. Chem. 270:7495-7500 (1995); y Komurasaki et al. Oncogene 15:2841-2848 (1997)); una herregulina (véase a continuación); la neurregulina-2 (NRG-2) (Carraway et al., Nature 387:512-516 (1997)); la neurregulina-3 (NRG-3) (Zhang et al., Proc. Natl. Acad. Sci. 94:9562-9567 (1997)); la neurregulina-4 (NRG-4) (Harari et al. Oncogene 18:2681-89 (1999)); y cripto (CRL-1) (Kannan et al. J. Biol. Chem. 272(6):33303335 (1997)). Los ligandos HER que unen EGFR incluyen EGF, TGF-α, anfirregulina, betacelulina, HB-EGF y epirregulina. Los ligandos HER que unen HER3 incluyen herregulinas y NRG-2. Los ligandos HER capaces de unir HER4 incluyen betacelulina, epirregulina, HB-EGF, NRG-2, NRG-3, NRG-4 y herregulinas.
“Herregulina” (HRG) cuando se usa en el presente documento se refiere a un polipéptido codificado por el producto génico de la herregulina como se desvela en la Patente de EE.UU. N.º 5.641.869 o Marchionni et al., Nature, 362:312-318 (1993). Los ejemplos de las herregulinas incluyen herregulina-α, herregulina-β1, herregulina-β2y herregulina-β3 (Holmes et al., Science, 256:1205-1210 (1992); y Patente de EE.UU. N.º 5.641.869); factor de diferenciación neu (NDF) (Peles et al. Cell 69: 205-216 (1992)); actividad inductora del receptor de acetilcolina (ARIA) (Falls et al. Cell 72:801-815 (1993)); factores de crecimiento glial (GGF) (Marchionni et al., Nature, 362:312318 (1993)); factor derivado de neuronas sensoriales y motoneuronas (SMDF) (Ho et al. J. Biol. Chem. 270:1452314532 (1995)); γ-herregulina (Schaefer et al. Oncogene 15:1385-1394 (1997)).
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citoplasmático (véase la revisión M. en Daëron, Annu. Rev. Immunol. 15:203-234 (1997)). Los FcR se revisan en Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991); Capel et al., Immunomethods 4:25-34 (1994); y de Haas e tal., J. Lab. Clin. Med. 126:330-41 (1995). Otros FcR, incluyendo aquellos a identificarse en el futuro, se abarcan por el término “FcR” del presente documento. El término también incluye el receptor neonatal, FcRn, que es responsable de la transferencia de las IgG maternas al feto (Guyer et al., J. Immunol. 117:587 (1976) y Kim et al., J. Immunol. 24:249 (1994)).
Las “células efectoras humanas” son leucocitos que expresan uno o más FcR y realizan funciones efectoras. Preferentemente, las células expresan al menos FcγRIII y realizan una función efectora ADCC. Los ejemplos de los leucocitos humanos que median la ADCC incluyen células mononucleares de sangre periférica (PBCM), linfocitos citolíticos naturales (NK), monocitos, linfocitos T citotóxicos y neutrófilos; siendo preferidas las PBMC y las células NK. Las células efectoras pueden aislarse de una fuente nativa, por ejemplo, de sangre.
“Citotoxicidad dependiente del complemento” o “CDC” se refiere a la lisis de una célula diana en presencia del complemento. La activación de la ruta clásica del complemento se inicia por la unión del primer componente del sistema del complemento (C1q) a los anticuerpos (de la subclase apropiada) que se unen a su antígeno cognado. Para evaluar la activación del complemento, puede realizarse un ensayo de CDC, por ejemplo, como se describe en Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996).
Como se usa en el presente documento, “tratamiento” (y las variaciones gramaticales del mismo tales como “tratar” o “tratando”) se refiere a la intervención clínica en un intento de alterar el transcurso natural del individuo a tratarse, y puede realizarse bien por profilaxis o bien durante el transcurso de la patología clínica. Los efectos deseables del tratamiento incluyen, pero no se limitan a, la prevenir la aparición o la reaparición de la enfermedad, el alivio de los síntomas, la disminución de cualquier consecuencia patológica directa o indirecta de la enfermedad, prevenir la metástasis, disminuir la velocidad del avance de la enfermedad, aliviar o paliar el estado de la enfermedad y la remisión o la prognosis mejorada. En algunas realizaciones, los anticuerpos de la invención se usan para retrasar el desarrollo o para ralentizar el avance de una enfermedad.
La frase “cantidad terapéuticamente eficaz” se refiere a una cantidad de un anticuerpo o de un fragmento de anticuerpo para tratar una enfermedad o un trastorno en un sujeto. En el caso de un tumor (por ejemplo, un tumor canceroso), la cantidad terapéuticamente eficaz del anticuerpo o del fragmento de anticuerpo puede reducir el número de células cancerígenas, reducir el tamaño primario del tumor; inhibir (es decir, ralentizar en algún grado y preferentemente parar) la infiltración de las células cancerígenas en órganos periféricos; inhibir (es decir, ralentizar en algún grado y preferentemente parar) la metástasis del tumor; inhibir, en algún grado, el crecimiento tumoral; y/o aliviar en algún grado uno o más de los síntomas asociados al trastorno. Hasta el grado de que el anticuerpo o el fragmento de anticuerpo puedan prevenir el crecimiento y/o matar las células cancerígenas existentes, puede ser citostático y/o citotóxico. Para la terapia del cáncer, la eficiencia in vivo puede, por ejemplo, medirse evaluando la duración de la supervivencia, el tiempo del avance de la enfermedad (TTP), las tasas de respuesta (RR), la duración de la respuesta y/o la calidad de vida.
Por “reducir o inhibir” se entiende la capacidad de provocar una disminución global preferentemente del 20 % o mayor, más preferentemente del 50 % o mayor y más preferentemente del 75 %, del 85 %, del 90 %, del 95 % o mayor. Reducir o inhibir puede referirse a los síntomas del trastorno a tratarse, la presencia o el tamaño de la metástasis, el tamaño del tumor primario o el tamaño o el número de los vasos sanguíneos en trastornos angiogénicos.
Los términos “cáncer” y “canceroso” ser refieren a o describen la afección fisiológica en los mamíferos que se caracteriza normalmente por el crecimiento celular sin regular. En esta definición se incluyen los cánceres benignos y malignos. Por “cáncer en fase temprana” se entiende un cáncer que no es invasivo o metastásico o se clasifica como un Cáncer de Fase 0, I, o II.
El término “precanceroso” se refiere a una afección o a un crecimiento que precede normalmente o se desarrolla en un cáncer.
Por “no metastásico” se entiende un cáncer que es benigno o que se mantiene en el sitio primario y no ha penetrado en el sistema de vasos linfáticos o sanguíneos o a los tejidos distintos del sitio primario. Generalmente, un cáncer no metastásico es cualquier cáncer que está en un Cáncer en fase 0, I o II, y ocasionalmente un Cáncer en fase III.
Un “vehículo farmacéuticamente aceptable” se refiere a un ingrediente en una formulación farmacéutica, distinto a un ingrediente activo, que no es tóxico para un sujeto. Un vehículo farmacéuticamente aceptable incluye, pero no se limita a, un tampón, un excipiente, un estabilizante o un conservante.
La frase “terapia anti-cáncer” se refiere a una terapia útil tratando el cáncer. Los ejemplos de agentes terapéuticos anti-cáncer incluyen, pero se limitan a, por ejemplo, agentes quimioterapéuticos, agentes inhibidores del crecimiento, agentes citotóxicos, agentes usados en terapia de radiación, agentes anti-angiogénesis, agentes apoptóticos, agentes anti-tubulina y otros agentes para tratar el cáncer, anticuerpos anti-CD20, inhibidores del factor
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Families Citing this family (129)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2471816A1 (en) | 2006-08-30 | 2012-07-04 | Genentech, Inc. | Multispecific antibodies |
JP5779350B2 (ja) | 2007-03-27 | 2015-09-16 | シー レーン バイオテクノロジーズ, エルエルシー | 抗体代替軽鎖配列を含む構築物およびライブラリー |
US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
US20090226443A1 (en) * | 2008-03-06 | 2009-09-10 | Genentech, Inc. | Combination therapy with c-met and egfr antagonists |
ES2572728T3 (es) | 2009-03-20 | 2016-06-02 | F. Hoffmann-La Roche Ag | Anticuerpos anti-HER biespecíficos |
US20120128671A1 (en) | 2009-05-13 | 2012-05-24 | Lawrence Horowitz | Neutralizing molecules to influenza viruses |
US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
EP2507381A4 (en) | 2009-12-04 | 2016-07-20 | Hoffmann La Roche | PLURISPECIFIC ANTIBODIES, ANTIBODY ANALOGUES, COMPOSITIONS AND METHODS |
DK2516469T3 (en) | 2009-12-22 | 2016-05-02 | Roche Glycart Ag | ANTI-HER3 antibodies and uses thereof |
JP5981853B2 (ja) | 2010-02-18 | 2016-08-31 | ジェネンテック, インコーポレイテッド | ニューレグリンアンタゴニスト及び癌の治療におけるそれらの使用 |
ES2617777T5 (es) | 2010-04-23 | 2022-10-13 | Hoffmann La Roche | Producción de proteínas heteromultiméricas |
TW201302793A (zh) | 2010-09-03 | 2013-01-16 | Glaxo Group Ltd | 新穎之抗原結合蛋白 |
US9217039B2 (en) * | 2010-11-01 | 2015-12-22 | Symphogen A/S | Anti-HER3 antibodies and compositions |
US9155802B2 (en) | 2010-11-01 | 2015-10-13 | Symphogen A/S | Pan-HER antibody composition |
US20130230581A1 (en) * | 2010-11-30 | 2013-09-05 | Qingping Feng | Egfr antagonist for the treatment of heart disease |
CN103403025B (zh) | 2011-02-28 | 2016-10-12 | 弗·哈夫曼-拉罗切有限公司 | 单价抗原结合蛋白 |
ES2549638T3 (es) | 2011-02-28 | 2015-10-30 | F. Hoffmann-La Roche Ag | Proteínas de unión a antígeno |
EA201300996A1 (ru) | 2011-03-11 | 2014-01-30 | Мерримак Фармасьютикалс, Инк. | Использование ингибиторов рецепторов семейства egfr в лечении гормонорезистентного рака молочной железы |
SG192775A1 (en) | 2011-03-15 | 2013-09-30 | Merrimack Pharmaceuticals Inc | Overcoming resistance to erbb pathway inhibitors |
US9127065B2 (en) | 2011-05-19 | 2015-09-08 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Anti-human HER3 antibodies and uses thereof |
EP2736928B1 (en) * | 2011-07-28 | 2019-01-09 | i2 Pharmaceuticals, Inc. | Sur-binding proteins against erbb3 |
MX2014001766A (es) | 2011-08-17 | 2014-05-01 | Genentech Inc | Anticuerpos de neuregulina y sus usos. |
JP6297490B2 (ja) | 2011-08-31 | 2018-03-20 | ジェネンテック, インコーポレイテッド | 診断マーカー |
US20130058947A1 (en) | 2011-09-02 | 2013-03-07 | Stem Centrx, Inc | Novel Modulators and Methods of Use |
US9273143B2 (en) | 2011-09-30 | 2016-03-01 | Regeneron Pharmaceuticals, Inc. | Methods and compositions comprising a combination of an anti-ErbB3 antibody and an anti-EGFR antibody |
WO2013055530A1 (en) | 2011-09-30 | 2013-04-18 | Genentech, Inc. | Diagnostic methylation markers of epithelial or mesenchymal phenotype and response to egfr kinase inhibitor in tumours or tumour cells |
JP6271432B2 (ja) | 2011-09-30 | 2018-01-31 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 抗ErbB3抗体およびその使用 |
US9220775B2 (en) | 2011-11-23 | 2015-12-29 | Medimmune Llc | Binding molecules specific for HER3 and uses thereof |
CA2857114A1 (en) | 2011-11-30 | 2013-06-06 | Genentech, Inc. | Erbb3 mutations in cancer |
CN104159924B (zh) * | 2011-12-05 | 2018-03-16 | 诺华股份有限公司 | 表皮生长因子受体3(her3)的抗体 |
EP2793940B1 (en) | 2011-12-22 | 2018-11-14 | i2 Pharmaceuticals, Inc. | Surrogate binding proteins |
JP2015514710A (ja) * | 2012-03-27 | 2015-05-21 | ジェネンテック, インコーポレイテッド | Her3阻害剤に関する診断及び治療 |
MX360109B (es) | 2012-04-20 | 2018-10-23 | Merus Nv | Metodos y medios para la produccion de moleculas de tipo ig. |
BR112014027291A2 (pt) * | 2012-05-02 | 2017-08-08 | Symphogen As | composições de anticorpos pan-her humanizados |
JP6267689B2 (ja) | 2012-05-10 | 2018-01-24 | バイオアトラ、エルエルシー | 多重特異性モノクローナル抗体 |
BR112014028600B1 (pt) | 2012-05-18 | 2022-11-22 | Genentech, Inc | Formulações de suspensão compreendendo anticorpo monoclonal de alta concentração, seu método de preparação, seu uso e dispositivo para sua administração subcutânea, e método para produção de um artigo de fabricação |
MX2014014162A (es) | 2012-05-24 | 2015-02-04 | Hoffmann La Roche | Anticuerpos multiespecificos. |
TW201843172A (zh) * | 2012-06-25 | 2018-12-16 | 美商再生元醫藥公司 | 抗-egfr抗體及其用途 |
AU2013322710A1 (en) | 2012-09-25 | 2015-04-16 | Glenmark Pharmaceuticals S.A. | Purification of hetero-dimeric immunoglobulins |
SI2900694T1 (sl) | 2012-09-27 | 2018-12-31 | Merus N.V. | Bispecifična IGG protitelesa kot vključitelji T-celic |
EP2727941A1 (en) | 2012-11-05 | 2014-05-07 | MAB Discovery GmbH | Method for the production of multispecific antibodies |
EP2914629A1 (en) | 2012-11-05 | 2015-09-09 | MAB Discovery GmbH | Method for the production of multispecific antibodies |
EP2727943A1 (en) | 2012-11-05 | 2014-05-07 | MAB Discovery GmbH | Trispecific antibodies against human EGFR, HER2 and HER3 |
EP2727942A1 (en) | 2012-11-05 | 2014-05-07 | MAB Discovery GmbH | Bispecific antibodies against human EGFR, HER2, and HER3 |
PE20150955A1 (es) | 2012-11-08 | 2015-06-20 | Hoffmann La Roche | Proteinas ligantes de antigeno anti-her3/her4 de union a la horquilla beta de her3 y a la horquilla beta de her4 |
WO2014089570A1 (en) | 2012-12-07 | 2014-06-12 | The General Hospital Corporation | Combinations of a pi3k/akt inhibitor compound with an her3/egfr inhibitor compound and use thereof in the treatment of a hyperproliferative disorder |
AR094403A1 (es) | 2013-01-11 | 2015-07-29 | Hoffmann La Roche | Terapia de combinación de anticuerpos anti-her3 |
WO2014124326A1 (en) | 2013-02-08 | 2014-08-14 | Stem Centrx, Inc. | Novel multispecific constructs |
EP2968540A2 (en) * | 2013-03-14 | 2016-01-20 | Genentech, Inc. | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
KR102238226B1 (ko) | 2013-05-14 | 2021-04-09 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 가공된 키메라 항원 수용체 (car) t-세포의 인간 적용 |
EP3004168A4 (en) | 2013-05-24 | 2017-03-01 | Board of Regents, The University of Texas System | Chimeric antigen receptor-targeting monoclonal antibodies |
KR102190220B1 (ko) * | 2013-05-29 | 2020-12-14 | 삼성전자주식회사 | 타겟 특이적 세포막 단백질 제거용 조성물 |
EP2821071A1 (en) | 2013-07-04 | 2015-01-07 | Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) | Compounds for breast cancer treatment |
KR102089591B1 (ko) | 2013-07-29 | 2020-03-18 | 삼성전자주식회사 | 항 EGFR scFv 단편 및 이를 포함하는 항 c-Met/항 EGFR 이중 특이 항체 |
WO2015048008A2 (en) | 2013-09-24 | 2015-04-02 | Medimmune, Llc | Binding molecules specific for her3 and uses thereof |
MX2016003593A (es) | 2013-10-11 | 2016-06-02 | Hoffmann La Roche | Anticuerpos de cadena ligera variable comun intercambiada de dominio multiespecifico. |
PE20160724A1 (es) | 2013-11-04 | 2016-08-04 | Glenmark Pharmaceuticals Sa | Produccion de inmunoglobulinas heterodimericas de redireccionamiento de celulas t |
CN105849125B (zh) | 2013-11-07 | 2020-05-15 | 国家医疗保健研究所 | 神经调节蛋白变构抗her3抗体 |
CN105849124B (zh) | 2013-12-20 | 2022-04-12 | 豪夫迈·罗氏有限公司 | 双重特异性抗体 |
NZ724013A (en) * | 2014-02-28 | 2019-11-29 | Merus Nv | Antibodies that bind egfr and erbb3 |
IL301147A (en) | 2014-02-28 | 2023-05-01 | Merus Nv | An antibody that binds to ErbB-2 and ErbB-3 |
PL3126388T3 (pl) | 2014-03-11 | 2019-10-31 | Regeneron Pharma | Przeciwciała anty-egfrviii i ich zastosowania |
BR112016021383A2 (pt) | 2014-03-24 | 2017-10-03 | Genentech Inc | Método para identificar um paciente com câncer que é susceptível ou menos susceptível a responder ao tratamento com um antagonista de cmet, método para identificar um paciente apresentando câncer previamente tratado, método para determinar a expressão do biomarcador hgf, antagonista anti-c-met e seu uso, kit de diagnóstico e seu método de preparo |
DK3126384T3 (da) * | 2014-04-01 | 2021-01-18 | Adimab Llc | Multispecifikke antistofanaloger omfattende en fælles letkæde, og fremgangsmåder til deres fremstilling og anvendelse |
WO2015157634A1 (en) | 2014-04-11 | 2015-10-15 | Kolltan Pharmaceuticals, Inc. | Anti-erbb antibodies and methods of use thereof |
FR3020063A1 (fr) | 2014-04-16 | 2015-10-23 | Gamamabs Pharma | Anticorps humain anti-her4 |
KR102223502B1 (ko) * | 2014-05-09 | 2021-03-05 | 삼성전자주식회사 | 항 c-Met/항 EGFR/항 Her3 다중 특이 항체 및 이의 이용 |
BR112016025056A2 (pt) | 2014-05-14 | 2018-02-20 | F. Hoffmann-La Roche Ag | uso de pelo menos um polipeptídeo, anticorpo biespecífico, anticorpo biespecífico isolado, anticorpo her3/her2 biespecífico, célula hospedeira, método de produção do anticorpo biespecífico her3/her2, imunoconjugado e formulação farmacêutica |
CN113549153A (zh) | 2014-05-29 | 2021-10-26 | 宏观基因有限公司 | 三特异性结合分子和其使用方法 |
TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
MX2017000821A (es) * | 2014-07-21 | 2017-08-18 | Delinia Inc | Moleculas que activan selectivamente celulas t reguladoras para el tratamiento de enfermedades autoinmunes. |
KR102259232B1 (ko) * | 2014-08-25 | 2021-05-31 | 삼성전자주식회사 | 항 c-Met/항 Ang2 이중 특이 항체 |
NZ730348A (en) | 2014-09-26 | 2024-03-22 | Macrogenics Inc | Bi-specific monovalent diabodies that are capable of binding cd19 and cd3, and uses thereof |
US11773166B2 (en) | 2014-11-04 | 2023-10-03 | Ichnos Sciences SA | CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production |
CA2964785A1 (en) | 2014-11-05 | 2016-05-12 | Board Of Regents, The University Of Texas System | Gene modified immune effector cells and engineered cells for expansion of immune effector cells |
WO2016073629A1 (en) | 2014-11-05 | 2016-05-12 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors (car) to selectively target protein complexes |
CN113150165A (zh) * | 2014-12-22 | 2021-07-23 | 西雅图免疫公司 | 双特异性四价抗体及其制造和使用方法 |
AU2015380455A1 (en) | 2015-01-26 | 2017-08-03 | Macrogenics, Inc. | Multivalent molecules comprising DR5-binding domains |
TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
CN115505042A (zh) | 2015-06-26 | 2022-12-23 | 赛诺菲生物技术公司 | 单克隆抗il-1racp抗体 |
CN108026174B (zh) | 2015-07-10 | 2023-02-17 | 美勒斯公司 | 人cd3结合抗体 |
TW201716439A (zh) | 2015-07-20 | 2017-05-16 | 美國禮來大藥廠 | Her3抗體 |
KR20180034588A (ko) | 2015-07-30 | 2018-04-04 | 마크로제닉스, 인크. | Pd-1-결합 분자 및 그것의 사용 방법 |
WO2017062619A2 (en) | 2015-10-08 | 2017-04-13 | Macrogenics, Inc. | Combination therapy for the treatment of cancer |
AU2016340764B2 (en) | 2015-10-23 | 2023-06-01 | Fundació lnstitut de Recerca Biomèdica (IRB Barcelona) | Binding molecules that inhibit cancer growth |
CN106729743B (zh) | 2015-11-23 | 2021-09-21 | 四川科伦博泰生物医药股份有限公司 | 抗ErbB2抗体-药物偶联物及其组合物、制备方法和应用 |
WO2017100642A1 (en) | 2015-12-11 | 2017-06-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or preventing growth of tumors resistant to egfr and/or erbb3 blockade |
CR20180318A (es) | 2015-12-14 | 2018-09-19 | Macrogenics Inc | Moléculas biespecíficas que tienen inmunorreactividad con pd-1 y ctla-4, y métodos de uso de las mismas |
US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
UY37127A (es) | 2016-02-17 | 2017-08-31 | Macrogenics Inc | Moléculas de unión a ror1, y métodos de uso de las mismas |
JP2019508428A (ja) | 2016-03-15 | 2019-03-28 | メリマック ファーマシューティカルズ インコーポレーティッド | 抗erbb3抗体を含む組み合わせ療法を用いて、er+、her2−、hrg+乳癌を治療するための方法 |
MY198114A (en) | 2016-04-15 | 2023-08-04 | Macrogenics Inc | Novel b7-h3-binding molecules, antibody drug conjugates thereof and methods of use thereof |
EP3241845A1 (en) | 2016-05-06 | 2017-11-08 | MAB Discovery GmbH | Humanized anti-il-1r3 antibodies |
US10167342B2 (en) | 2016-08-29 | 2019-01-01 | Fazel Shokri | Production of hersintuzumab: a new humanized antibody against HER2 for cancer treatment |
BR112019005895A2 (pt) | 2016-09-23 | 2019-06-11 | Merus N.V. | moléculas de ligação que modulam uma atividade biológica expressa por uma célula |
CA3084459A1 (en) * | 2016-10-16 | 2018-04-19 | Cellerant Therapeutics, Inc. | Anti-il1-rap antibodies |
EA201991142A1 (ru) | 2016-11-08 | 2019-10-31 | Варианты il-2 для лечения аутоиммунных заболеваний | |
EP3558368A4 (en) | 2016-12-23 | 2020-12-30 | MacroGenics, Inc. | ADAM9 BINDING MOLECULES AND THEIR METHODS FOR USE |
US11459394B2 (en) | 2017-02-24 | 2022-10-04 | Macrogenics, Inc. | Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof |
EP3590534A4 (en) | 2017-02-28 | 2020-12-23 | Kinki University | METHOD OF TREATMENT OF EGFR-TKI RESISTANT NON-SMALL CELL LUNG CANCER BY ADMINISTRATION OF ANTI-3-ANTIBODY ACTIVE CONJUGATE |
EP3600413A1 (en) | 2017-03-31 | 2020-02-05 | Merus N.V. | Erbb-2 and erbb3 binding bispecific antibodies for use in the treatment f cells that have an nrg1 fusion gene |
KR20190140944A (ko) | 2017-03-31 | 2019-12-20 | 메뤼스 엔.페. | ErbB-2, ErbB-2/ErbB-3 양성 종양을 가진 개체의 치료를 위한, ErbB-2 및 ErbB-3의 세포외 부분 상의 에피토프에 결합하는 항원-결합 부위를 가진 이중특이적 항체 및 ErbB-2 표적화제 |
EP3401332A1 (en) | 2017-05-08 | 2018-11-14 | MAB Discovery GmbH | Anti-il-1r3 antibodies for use in inflammatory conditions |
CN111148764A (zh) | 2017-05-17 | 2020-05-12 | 美勒斯公司 | 用于乳腺癌的ErbB-2/ErbB-3双特异性抗体与内分泌治疗的组合 |
MX2020001432A (es) | 2017-08-09 | 2020-03-20 | Merus Nv | Anticuerpos que se unen al receptor del factor de crecimiento epidermico (egfr) y tirosina-proteina cinasa met (cmet). |
WO2019057792A1 (en) | 2017-09-19 | 2019-03-28 | Mab Discovery Gmbh | CD40 ANTIBODY AGONISTS |
WO2019108065A1 (en) | 2017-12-01 | 2019-06-06 | Merus N.V. | Use of bispecific antibody and il-15 for combination therapy |
RU2020122822A (ru) | 2017-12-12 | 2022-01-13 | Макродженикс, Инк. | Биспецифичные связывающие cd16 молекулы и их применение при лечении заболеваний |
US11685781B2 (en) | 2018-02-15 | 2023-06-27 | Macrogenics, Inc. | Variant CD3-binding domains and their use in combination therapies for the treatment of disease |
US20220072144A1 (en) | 2018-09-20 | 2022-03-10 | Daiichi Sankyo Company, Limited | Treatment of her3-mutated cancer by administration of anti-her3 antibody-drug conjugate |
TW202034952A (zh) | 2018-12-20 | 2020-10-01 | 荷蘭商美勒斯公司 | 用於治療疾病之CLEC12AxCD3雙特異性抗體及方法 |
AU2019406712A1 (en) | 2018-12-21 | 2021-06-17 | F. Hoffmann-La Roche Ag | Antibody that binds to VEGF and IL-1beta and methods of use |
EP3924377A1 (en) | 2019-02-14 | 2021-12-22 | Merus N.V. | Producing compositions comprising two or more antibodies |
MA54944A (fr) | 2019-02-14 | 2021-12-22 | Merus Nv | Combinaisons de fractions de liaison se liant à egfr, her2 et her3 |
TW202039578A (zh) | 2019-03-29 | 2020-11-01 | 荷蘭商美勒斯公司 | Cd3結合分子 |
MX2021013646A (es) | 2019-05-09 | 2022-01-31 | Merus Nv | Dominios variantes para las proteínas multimerizantes y su separación. |
JP2022545457A (ja) | 2019-08-19 | 2022-10-27 | メルス ナムローゼ フェンノートシャップ | Lgr5及びegfrに結合する抗体とトポイソメラーゼi阻害剤との組合せを用いる癌の治療 |
GB201913079D0 (en) * | 2019-09-11 | 2019-10-23 | Hummingbird Bioscience Holdings Pte Ltd | Treatment and prevention of cancer using her3 antigen-binding molecules |
US20220057383A1 (en) * | 2019-12-19 | 2022-02-24 | Johnson & Johnson Consumer Inc. | Use of biomarkers to evaluate the efficacy of a composition in reducing the effects of cancer therapeutics on skin |
CA3166407A1 (en) | 2020-01-29 | 2021-08-05 | Merus N.V. | Means and method for modulating fimmune cell engaging effects |
CN115397850A (zh) | 2020-03-30 | 2022-11-25 | 豪夫迈·罗氏有限公司 | 与vegf和pdgf-b结合的抗体及其使用方法 |
MX2022013182A (es) | 2020-04-24 | 2023-01-16 | Merus Nv | Tratamiento de cánceres con un anticuerpo que se une a lgr5 y egfr. |
EP4175650A1 (en) | 2020-07-06 | 2023-05-10 | Kiromic BioPharma, Inc. | Mesothelin isoform binding molecules and chimeric pd1 receptor molecules, cells containing the same and uses thereof |
KR20230061458A (ko) | 2020-09-04 | 2023-05-08 | 에프. 호프만-라 로슈 아게 | Vegf-a 및 ang2에 결합하는 항체 및 사용 방법 |
WO2022108627A1 (en) | 2020-11-18 | 2022-05-27 | Kiromic Biopharma, Inc.Kiromic Biopharma, Inc. | Gamma-delta t cell manufacturing processes and chimeric pd1 receptor molecules |
CN116710472A (zh) | 2020-12-15 | 2023-09-05 | 美勒斯公司 | 利用结合lgr5和egfr的抗体治疗癌症 |
US20240058444A1 (en) | 2020-12-18 | 2024-02-22 | Merus N.V. | Antibody composition |
WO2022255871A2 (en) | 2021-06-03 | 2022-12-08 | Merus N.V. | New nrg1 fusions, fusion junctions and methods for detecting them |
AU2022359551A1 (en) | 2021-10-06 | 2024-04-11 | Merus N.V. | Treatment of immune checkpoint inhibitor-treated cancers with high egfr expression using an antibody that binds at least egfr |
Family Cites Families (280)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
CU22545A1 (es) | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
US3896111A (en) | 1973-02-20 | 1975-07-22 | Research Corp | Ansa macrolides |
US4151042A (en) | 1977-03-31 | 1979-04-24 | Takeda Chemical Industries, Ltd. | Method for producing maytansinol and its derivatives |
US4137230A (en) | 1977-11-14 | 1979-01-30 | Takeda Chemical Industries, Ltd. | Method for the production of maytansinoids |
US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
US4265814A (en) | 1978-03-24 | 1981-05-05 | Takeda Chemical Industries | Matansinol 3-n-hexadecanoate |
JPS5562090A (en) | 1978-10-27 | 1980-05-10 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
JPS55164687A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS5566585A (en) | 1978-11-14 | 1980-05-20 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
JPS55164685A (en) | 1979-06-08 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55164686A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4309428A (en) | 1979-07-30 | 1982-01-05 | Takeda Chemical Industries, Ltd. | Maytansinoids |
JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
US4935341A (en) | 1986-06-04 | 1990-06-19 | Whitehead Institute For Biomedical Research | Detection of point mutations in neu genes |
WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US6054561A (en) | 1984-02-08 | 2000-04-25 | Chiron Corporation | Antigen-binding sites of antibody molecules specific for cancer antigens |
US4943533A (en) | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
US7838216B1 (en) | 1986-03-05 | 2010-11-23 | The United States Of America, As Represented By The Department Of Health And Human Services | Human gene related to but distinct from EGF receptor gene |
US5401638A (en) | 1986-06-04 | 1995-03-28 | Oncogene Science, Inc. | Detection and quantification of neu related proteins in the biological fluids of humans |
US4968603A (en) | 1986-12-31 | 1990-11-06 | The Regents Of The University Of California | Determination of status in neoplastic disease |
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 |
US5079233A (en) | 1987-01-30 | 1992-01-07 | American Cyanamid Company | N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same |
EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5824311A (en) | 1987-11-30 | 1998-10-20 | Trustees Of The University Of Pennsylvania | Treatment of tumors with monoclonal antibodies against oncogene antigens |
US5720937A (en) | 1988-01-12 | 1998-02-24 | Genentech, Inc. | In vivo tumor detection assay |
WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
JPH03505964A (ja) | 1988-04-18 | 1991-12-26 | アプライド・バイオテクノロジー・インコーポレーテッド | neu遺伝子の発現及び遺伝子産物の検出 |
AU4128089A (en) | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
DK0474727T3 (da) | 1989-05-19 | 1998-01-12 | Genentech Inc | HER2 ekstracellulært domæne |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5705157A (en) | 1989-07-27 | 1998-01-06 | The Trustees Of The University Of Pennsylvania | Methods of treating cancerous cells with anti-receptor antibodies |
US6884418B1 (en) | 1989-08-04 | 2005-04-26 | Berlex Laboratories, Inc. | Use of ligand-mimicking agents and anti-neoplastic drugs in cancer therapy |
EP0444181B2 (en) | 1989-08-04 | 2010-11-24 | Bayer Schering Pharma Aktiengesellschaft | C-erbb-2 external domain: gp75 |
CA2066428C (en) | 1989-09-08 | 2000-11-28 | Bert Vogelstein | Structural alterations of the egf receptor gene in human gliomas |
DE68926248T2 (de) | 1989-09-29 | 1996-12-19 | Oncogene Science Inc | p100 "neu" menschlisches Protein and Verwendung dieses Proteins zum Nachweis von preneoplasmatischen- oder neoplasmatischen beim Menschen |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5959177A (en) | 1989-10-27 | 1999-09-28 | The Scripps Research Institute | Transgenic plants expressing assembled secretory antibodies |
US5183884A (en) | 1989-12-01 | 1993-02-02 | United States Of America | Dna segment encoding a gene for a receptor related to the epidermal growth factor receptor |
DE69120146T2 (de) | 1990-01-12 | 1996-12-12 | Cell Genesys Inc | Erzeugung xenogener antikörper |
ES2246502T3 (es) | 1990-08-29 | 2006-02-16 | Genpharm International, Inc. | Animales no humanos transgenicos capaces de producir anticuerpos heterologos. |
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 |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
AU662311B2 (en) | 1991-02-05 | 1995-08-31 | Novartis Ag | Recombinant antibodies specific for a growth factor receptor |
IL101943A0 (en) | 1991-05-24 | 1992-12-30 | Genentech Inc | Structure,production and use of heregulin |
ES2206447T3 (es) | 1991-06-14 | 2004-05-16 | Genentech, Inc. | Anticuerpo humanizado para heregulina. |
US6800738B1 (en) | 1991-06-14 | 2004-10-05 | Genentech, Inc. | Method for making humanized antibodies |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
US5939531A (en) | 1991-07-15 | 1999-08-17 | Novartis Corp. | Recombinant antibodies specific for a growth factor receptor |
EP0656367A1 (en) | 1991-08-22 | 1995-06-07 | Becton, Dickinson and Company | Method and composition for cancer therapy and for prognosticating responses to cancer theraphy |
US7018809B1 (en) | 1991-09-19 | 2006-03-28 | Genentech, Inc. | Expression of functional antibody fragments |
US5362852A (en) | 1991-09-27 | 1994-11-08 | Pfizer Inc. | Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties |
US5288477A (en) | 1991-09-27 | 1994-02-22 | Becton, Dickinson And Company | Method for prognosticating response to cancer therapy |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
JPH07501451A (ja) | 1991-11-25 | 1995-02-16 | エンゾン・インコーポレイテッド | 多価抗原結合タンパク質 |
AU3236793A (en) | 1991-12-12 | 1993-07-19 | Berlex Laboratories, Inc. | Recombinant and chimeric antibodies to c-erbB-2 |
AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
AU675929B2 (en) | 1992-02-06 | 1997-02-27 | Curis, Inc. | Biosynthetic binding protein for cancer marker |
AU4025193A (en) | 1992-04-08 | 1993-11-18 | Cetus Oncology Corporation | Humanized C-erbB-2 specific antibodies |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
AU687346B2 (en) | 1992-06-30 | 1998-02-26 | Oncologix, Inc. | A combination of anti-erbB-2 monoclonal antibodies and method of using |
WO1994009022A1 (en) | 1992-10-09 | 1994-04-28 | Oncor, Inc. | Methods for the detection of chromosome structural abnormalities by in situ hybridization to fixed tissue |
CA2149329C (en) | 1992-11-13 | 2008-07-15 | Darrell R. Anderson | Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma |
CA2103323A1 (en) | 1992-11-24 | 1994-05-25 | Gregory D. Plowman | Her4 human receptor tyrosine kinase |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
ATE186219T1 (de) | 1993-03-24 | 1999-11-15 | Berlex Biosciences | Kombination von antihormonale und bindende moleküle zur krebsbehandlung |
AU6527894A (en) | 1993-03-30 | 1994-10-24 | Trustees Of The University Of Pennsylvania, The | Prevention of tumors with monoclonal antibodies against (neu) |
JPH08511420A (ja) | 1993-06-16 | 1996-12-03 | セルテック・セラピューテイクス・リミテッド | 抗 体 |
GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
ATE207366T1 (de) | 1993-12-24 | 2001-11-15 | Merck Patent Gmbh | Immunokonjugate |
US5654307A (en) | 1994-01-25 | 1997-08-05 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
US6524832B1 (en) | 1994-02-04 | 2003-02-25 | Arch Development Corporation | DNA damaging agents in combination with tyrosine kinase inhibitors |
US6811779B2 (en) | 1994-02-10 | 2004-11-02 | Imclone Systems Incorporated | Methods for reducing tumor growth with VEGF receptor antibody combined with radiation and chemotherapy |
US20030108545A1 (en) | 1994-02-10 | 2003-06-12 | Patricia Rockwell | Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5910486A (en) | 1994-09-06 | 1999-06-08 | Uab Research Foundation | Methods for modulating protein function in cells using, intracellular antibody homologues |
US5846749A (en) | 1994-10-12 | 1998-12-08 | The Regents Of The University Of California | Quantitative measurement of tissue protein identified by immunohistochemistry and standardized protein determination |
US5804396A (en) | 1994-10-12 | 1998-09-08 | Sugen, Inc. | Assay for agents active in proliferative disorders |
US5789199A (en) | 1994-11-03 | 1998-08-04 | Genentech, Inc. | Process for bacterial production of polypeptides |
US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
EP0711565B1 (en) | 1994-11-10 | 1998-08-26 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Inhibiting growth of leukemic cells by targeting HER-2 protein |
AU4289496A (en) | 1994-12-02 | 1996-06-19 | Chiron Corporation | Method of promoting an immune response with a bispecific antibody |
US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5783404A (en) | 1995-04-13 | 1998-07-21 | Amgen Inc. | Methods and compositions for determining HER-2/neu expression using monoclonal antibodies |
GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
ES2304786T3 (es) | 1995-04-27 | 2008-10-16 | Amgen Fremont Inc. | Anticuerpos anti-il-8 humanos, derivados a partir de xenoratones inmunizados. |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US6410690B1 (en) | 1995-06-07 | 2002-06-25 | Medarex, Inc. | Therapeutic compounds comprised of anti-Fc receptor antibodies |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
CA2222231A1 (en) | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
US5977322A (en) | 1995-06-14 | 1999-11-02 | The Regents Of The University Of California | High affinity human antibodies to tumor antigens |
SI9620103A (sl) | 1995-07-06 | 1998-10-31 | Novartis Ag | Pirolopirimidini in postopki za njihovo pripravo |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
DE19544393A1 (de) | 1995-11-15 | 1997-05-22 | Hoechst Schering Agrevo Gmbh | Synergistische herbizide Mischungen |
US5783186A (en) | 1995-12-05 | 1998-07-21 | Amgen Inc. | Antibody-induced apoptosis |
US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
US5968511A (en) | 1996-03-27 | 1999-10-19 | Genentech, Inc. | ErbB3 antibodies |
TW517061B (en) * | 1996-03-29 | 2003-01-11 | Pharmacia & Amp Upjohn Ab | Modified/chimeric superantigens and their use |
PL190489B1 (pl) | 1996-04-12 | 2005-12-30 | Warner Lambert Co | Nieodwracalne inhibitory kinaz tyrozyny, kompozycja farmaceutyczna je zawierająca i ich zastosowanie |
US5925519A (en) | 1996-06-03 | 1999-07-20 | The Regents Of The University Of California | Genetic alterations associated with prostate cancer |
US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
ES2186908T3 (es) | 1996-07-13 | 2003-05-16 | Glaxo Group Ltd | Compuestos heterociciclos condensados como inhibidores de pproteina-tirosina-quinasas. |
ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
NZ519191A (en) | 1996-10-18 | 2005-04-29 | Univ Texas | Antibodies that bind to domain 1 of ErbB2 useful for inducing cell death via apoptosis, and nucleic acids encoding such antibodies |
WO1998018489A1 (en) | 1996-10-30 | 1998-05-07 | The Uab Research Foundation | Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain intracellular antibodies |
US6468547B1 (en) | 1996-10-30 | 2002-10-22 | Uab Research Foundation | Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain secretory antibodies |
EP1864999B1 (en) | 1996-11-27 | 2009-03-18 | Genentech, Inc. | Affinity purification of polypeptide on protein a matrix |
DK1500329T3 (da) | 1996-12-03 | 2012-07-09 | Amgen Fremont Inc | Humane antistoffer, der specifikt binder TNF-alfa |
CA2279547A1 (en) | 1997-01-31 | 1998-08-06 | University Of Rochester | Chimeric antibody fusion proteins for the recruitment and stimulation of an antitumor immune response |
US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
US20020076695A1 (en) | 1997-04-04 | 2002-06-20 | Jeffrey S. Ross | Methods for treating prostate cancer |
US5994071A (en) | 1997-04-04 | 1999-11-30 | Albany Medical College | Assessment of prostate cancer |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
WO1998050038A1 (en) | 1997-05-06 | 1998-11-12 | American Cyanamid Company | Use of quinazoline compounds for the treatment of polycystic kidney disease |
DE69830315T2 (de) | 1997-06-24 | 2006-02-02 | Genentech Inc., San Francisco | Galactosylierte glykoproteine enthaltende zusammensetzungen und verfahren zur deren herstellung |
TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
US6040498A (en) | 1998-08-11 | 2000-03-21 | North Caroline State University | Genetically engineered duckweed |
AU9805398A (en) | 1997-10-15 | 1999-05-03 | Children's Medical Center Corporation | Novel human egf receptors and use thereof |
ATE419009T1 (de) | 1997-10-31 | 2009-01-15 | Genentech Inc | Methoden und zusammensetzungen bestehend aus glykoprotein-glykoformen |
KR20010031813A (ko) | 1997-11-06 | 2001-04-16 | 윌리암 에이취 캘넌, 에곤 이 버그 | 결장 폴립 치료용 티로신 키나제 억제제로서의 퀴나졸린유도체의 용도 |
ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
GB9800569D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
US6358682B1 (en) | 1998-01-26 | 2002-03-19 | Ventana Medical Systems, Inc. | Method and kit for the prognostication of breast cancer |
US6417168B1 (en) | 1998-03-04 | 2002-07-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
US20020192211A1 (en) | 1998-03-17 | 2002-12-19 | Hudziak Robert M. | Method of treating tumor cells by inhibiting growth factor receptor function |
WO1999048527A1 (en) | 1998-03-27 | 1999-09-30 | Genentech, Inc. | Apo-2 ligand-anti-her-2 antibody synergism |
ATE375365T1 (de) | 1998-04-02 | 2007-10-15 | Genentech Inc | Antikörper varianten und fragmente davon |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
AU3657899A (en) | 1998-04-20 | 1999-11-08 | James E. Bailey | Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity |
US7244826B1 (en) | 1998-04-24 | 2007-07-17 | The Regents Of The University Of California | Internalizing ERB2 antibodies |
ATE321066T1 (de) | 1998-05-06 | 2006-04-15 | Genentech Inc | Anti-her2 antikörperzusammensetzung |
MXPA00011248A (es) | 1998-05-15 | 2004-09-06 | Imclone Systems Inc | Tratamientos de tumores humanos con radiacion e inhibidores de tirosina cinasas de recptor de factor de crecimiento. |
US6573043B1 (en) | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
ES2188254T3 (es) | 1998-11-19 | 2003-06-16 | Warner Lambert Co | N-(4-(3-chloro-4-fluoro-fenilamino)-7-(3-morfolin-4-il-propoxi)-quin azolin-6-il)-acrilamada, un inhibidor irreversible de tirosina quinasas. |
HUP0104865A3 (en) | 1999-01-15 | 2004-07-28 | Genentech Inc | Polypeptide variants with altered effector function |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
DE60041808D1 (de) | 1999-01-27 | 2009-04-30 | Cornell Res Foundation Inc | Behandlung von mit her-2/neu-überexprimierung einhergehendem krebs |
US6333348B1 (en) | 1999-04-09 | 2001-12-25 | Aventis Pharma S.A. | Use of docetaxel for treating cancers |
EP2275540B1 (en) | 1999-04-09 | 2016-03-23 | Kyowa Hakko Kirin Co., Ltd. | Method for controlling the activity of immunologically functional molecule |
US6316462B1 (en) | 1999-04-09 | 2001-11-13 | Schering Corporation | Methods of inducing cancer cell death and tumor regression |
ES2320311T3 (es) | 1999-05-14 | 2009-05-21 | Genentech, Inc. | Tratamiento con anticuerpos anti-erbb2. |
BR0010524A (pt) | 1999-05-14 | 2002-05-28 | Imclone Systems Inc | Tratamento de tumores humanos refratários com antagonistas de receptor de fator de crescimento epidérmico |
AUPQ105799A0 (en) | 1999-06-18 | 1999-07-08 | Victor Chang Cardiac Research Institute, The | Cell growth inhibition |
JP4579471B2 (ja) | 1999-06-25 | 2010-11-10 | ジェネンテック, インコーポレイテッド | 抗ErbB2抗体を用いる前立腺癌の処置 |
DK2283866T3 (en) | 1999-06-25 | 2015-05-18 | Genentech Inc | METHODS OF TREATMENT USING ANTI-ERBB ANTIBODY-MAYTANSINOID CONJUGATES |
US6949245B1 (en) | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
EP1189641B1 (en) | 1999-06-25 | 2009-07-29 | Genentech, Inc. | HUMANIZED ANTI-ErbB2 ANTIBODIES AND TREATMENT WITH ANTI-ErbB2 ANTIBODIES |
US20030086924A1 (en) | 1999-06-25 | 2003-05-08 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
US20040013667A1 (en) | 1999-06-25 | 2004-01-22 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
GB9917012D0 (en) | 1999-07-20 | 1999-09-22 | Pharmacia & Upjohn Spa | Combined preparations comprising antitumor agents |
MXPA02000962A (es) | 1999-07-29 | 2002-07-02 | Medarex Inc | Anticuerpos monoclonales humanos para her2/neu. |
ES2330301T3 (es) | 1999-08-27 | 2009-12-09 | Genentech, Inc. | Dosificaciones para tratamiento con anticuerpos anti-erbb2. |
WO2001021192A2 (en) | 1999-09-22 | 2001-03-29 | Corixa Corporation | Methods for diagnosis and therapy of hematological and virus-associated malignancies |
AU782626B2 (en) | 1999-10-04 | 2005-08-18 | Medicago Inc. | Method for regulating transcription of foreign genes |
US7125978B1 (en) | 1999-10-04 | 2006-10-24 | Medicago Inc. | Promoter for regulating expression of foreign genes |
EP1229125A4 (en) | 1999-10-19 | 2005-06-01 | Kyowa Hakko Kogyo Kk | PROCESS FOR PRODUCING A POLYPEPTIDE |
GB9925958D0 (en) | 1999-11-02 | 1999-12-29 | Bundred Nigel J | Therapeutic use |
AU2001227966A1 (en) | 2000-01-20 | 2001-07-31 | Chiron Corporation | Methods for treating tumors |
US20030022918A1 (en) | 2000-02-29 | 2003-01-30 | Horak Ivan David | Farnesyl protein transferase inhibitor combinations with an her2 antibody |
US7097840B2 (en) | 2000-03-16 | 2006-08-29 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
US6632979B2 (en) | 2000-03-16 | 2003-10-14 | Genentech, Inc. | Rodent HER2 tumor model |
US6767541B2 (en) | 2000-03-20 | 2004-07-27 | The Regents Of The University Of California | HER-2/neu overexpression abrogates growth inhibitory pathways |
GB0008368D0 (en) | 2000-04-06 | 2000-05-24 | Astrazeneca Ab | Combination product |
WO2001076630A1 (fr) | 2000-04-06 | 2001-10-18 | Kyowa Hakko Kogyo Co., Ltd. | Diagnostics et remedes contre la polyarthrite rhumatoide |
ES2528794T3 (es) | 2000-04-11 | 2015-02-12 | Genentech, Inc. | Anticuerpos multivalentes y usos de los mismos |
US7306801B2 (en) | 2000-05-15 | 2007-12-11 | Health Research, Inc. | Methods of therapy for cancers characterized by overexpression of the HER2 receptor protein |
CZ20023748A3 (cs) | 2000-05-15 | 2003-04-16 | Pharmacia Italia S.P.A. | Inhibitory aromatasy a monoklonální anti-HER2 protilátky jako protitumorová činidla |
CN102698265A (zh) | 2000-05-19 | 2012-10-03 | 杰南技术公司 | 用于提高对ErbB 拮抗剂癌症治疗的有效应答可能性的基因检测试验 |
GB0017635D0 (en) | 2000-07-18 | 2000-09-06 | Pharmacia & Upjohn Spa | Antitumor combined therapy |
TWI317285B (en) | 2000-07-28 | 2009-11-21 | Dainippon Sumitomo Pharma Co | New use and kit for remedies for cancer |
JP2004527456A (ja) | 2000-08-09 | 2004-09-09 | イムクローン システムズ インコーポレイティド | Egf受容体拮抗剤による過増殖性の疾患の治療 |
US6984494B2 (en) | 2000-08-15 | 2006-01-10 | Genentech, Inc. | Analytical method |
US20020119148A1 (en) | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
CA2424602C (en) | 2000-10-06 | 2012-09-18 | Kyowa Hakko Kogyo Co., Ltd. | Antibody composition-producing cell |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
CA2436910C (en) | 2000-12-01 | 2014-06-17 | Response Genetics, Inc. | Method of determining epidermal growth factor receptor and her2-neu gene expression and correlation of levels thereof with survival rates |
US6582919B2 (en) | 2001-06-11 | 2003-06-24 | Response Genetics, Inc. | Method of determining epidermal growth factor receptor and HER2-neu gene expression and correlation of levels thereof with survival rates |
US6602670B2 (en) | 2000-12-01 | 2003-08-05 | Response Genetics, Inc. | Method of determining a chemotherapeutic regimen based on ERCC1 expression |
US20020142328A1 (en) | 2000-12-01 | 2002-10-03 | Danenberg Kathleen D. | Method of determining a chemotherapeutic regimen by assaying gene expression in primary tumors |
US7005278B2 (en) | 2001-03-02 | 2006-02-28 | Danenberg Kathleen D | Method of determining dihydropyrimidine dehydrogenase gene expression |
WO2002045653A2 (en) | 2000-12-08 | 2002-06-13 | Uab Research Foundation | Combination radiation therapy and chemotherapy in conjuction with administration of growth factor receptor antibody |
EP1349574A2 (en) | 2001-01-09 | 2003-10-08 | MERCK PATENT GmbH | Combination therapy using receptor tyrosine kinase inhibitors and angiogenesis inhibitors |
EP1228766A1 (en) | 2001-01-31 | 2002-08-07 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | PYK2 phosphorylation by HER3 induces tumor invasion |
JP4398644B2 (ja) * | 2001-04-06 | 2010-01-13 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルベニア | ErbB界面ペプチド擬態およびその使用方法 |
WO2002087619A1 (fr) | 2001-04-27 | 2002-11-07 | Takeda Chemical Industries, Ltd. | Methode de prevention et de traitement du cancer |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
CA2449166A1 (en) | 2001-05-08 | 2002-11-14 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Combination therapy using anti-egfr antibodies and anti-hormonal agents |
ITRM20010408A1 (it) | 2001-07-10 | 2003-01-10 | Univ Napoli Federico Ii | Mini-anticorpo umano citotossico per cellule tumorali che esprimono il recettore erbb2. |
NZ592087A (en) | 2001-08-03 | 2012-11-30 | Roche Glycart Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
WO2003012072A2 (en) | 2001-08-03 | 2003-02-13 | The Trustees Of The University Of Pennsylvania | Monoclonal antibodies to activated erbb family members and methods of use thereof |
EP1283053A1 (en) | 2001-08-09 | 2003-02-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibitors of HER3 activity |
US20030068318A1 (en) | 2001-09-28 | 2003-04-10 | O'brien Timothy | Treatment of uterine serous papillary cancer |
ES2326964T3 (es) | 2001-10-25 | 2009-10-22 | Genentech, Inc. | Composiciones de glicoproteina. |
US20030096823A1 (en) | 2001-11-16 | 2003-05-22 | Beryl Asp | Method for the treatment of cardiotoxicity induced by antitumor compounds |
US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
US20030175845A1 (en) | 2002-03-13 | 2003-09-18 | Kalbag Suresh M. | Use of sulfitolysis in high performance peptide mapping |
US7332585B2 (en) * | 2002-04-05 | 2008-02-19 | The Regents Of The California University | Bispecific single chain Fv antibody molecules and methods of use thereof |
US7332580B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The University Of California | Bispecific single chain Fv antibody molecules and methods of use thereof |
JP2005534623A (ja) | 2002-04-08 | 2005-11-17 | スミスクライン ビーチャム コーポレーション | Erbファミリーの阻害剤並びにraf及び/又はras阻害剤を投与することを含む癌の治療法 |
CA2481837A1 (en) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Production process for antibody composition |
ATE503829T1 (de) | 2002-04-09 | 2011-04-15 | Kyowa Hakko Kirin Co Ltd | Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins |
AU2003236019A1 (en) | 2002-04-09 | 2003-10-20 | Kyowa Hakko Kirin Co., Ltd. | Drug containing antibody composition appropriate for patient suffering from Fc Gamma RIIIa polymorphism |
US20040110704A1 (en) | 2002-04-09 | 2004-06-10 | Kyowa Hakko Kogyo Co., Ltd. | Cells of which genome is modified |
US7691568B2 (en) | 2002-04-09 | 2010-04-06 | Kyowa Hakko Kirin Co., Ltd | Antibody composition-containing medicament |
AU2003236018A1 (en) | 2002-04-09 | 2003-10-20 | Kyowa Hakko Kirin Co., Ltd. | METHOD OF ENHANCING ACTIVITY OF ANTIBODY COMPOSITION OF BINDING TO FcGamma RECEPTOR IIIa |
CA2481515C (en) | 2002-04-10 | 2013-10-01 | Genentech, Inc. | Anti-her2 antibody variants |
ITTO20020340A1 (it) | 2002-04-19 | 2003-10-20 | Biother Di Contardi Gabriella | Localizzazione del recettore her2 mediante anticorpo umanizzato biotinilato. |
US20030202973A1 (en) | 2002-04-29 | 2003-10-30 | Dr. George Pieczenik | Treatment of refractory human tumors with epidermal growth factor receptor and HER1 mitogenic ligand (EGFRML) antagonists |
EP1513879B1 (en) | 2002-06-03 | 2018-08-22 | Genentech, Inc. | Synthetic antibody phage libraries |
PT1517921E (pt) * | 2002-06-28 | 2006-09-29 | Domantis Ltd | Ligandos duplamente especificos com semi-vida no soro aumentada |
PT1585966E (pt) | 2002-07-15 | 2012-02-20 | Hoffmann La Roche | Tratamento de cancro com o anticorpo anti-erbb2 rhumab 2c4 |
EP1391213A1 (en) | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
ES2629602T5 (es) | 2002-09-11 | 2021-06-08 | Genentech Inc | Purificación de proteínas |
EP1549345A1 (en) | 2002-10-10 | 2005-07-06 | MERCK PATENT GmbH | Bispecific anti-erb-b antibodies and their use in tumor therapy |
US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
WO2004048525A2 (en) | 2002-11-21 | 2004-06-10 | Genentech, Inc. | Therapy of non-malignant diseases or disorders with anti-erbb2 antibodies |
DE60332957D1 (de) | 2002-12-16 | 2010-07-22 | Genentech Inc | Immunoglobulinvarianten und deren verwendungen |
WO2004087207A2 (en) | 2003-03-27 | 2004-10-14 | Georgetown University | Method for inducing apoptosis and aneuploidy regression in cancer cells |
MXPA05012723A (es) | 2003-05-30 | 2006-02-08 | Genentech Inc | Tratamiento con anticuerpos anti-vgf. |
KR20060037447A (ko) | 2003-08-18 | 2006-05-03 | 화이자 프로덕츠 인크. | erbB2 항암제에 대한 투약 스케쥴 |
US20080241884A1 (en) | 2003-10-08 | 2008-10-02 | Kenya Shitara | Fused Protein Composition |
AU2004280065A1 (en) | 2003-10-09 | 2005-04-21 | Kyowa Hakko Kirin Co., Ltd. | Process for producing antibody composition by using RNA inhibiting the function of alpha1,6-fucosyltransferase |
EA036531B1 (ru) | 2003-11-05 | 2020-11-19 | Роше Гликарт Аг | Гуманизированное антитело типа ii к cd20 (варианты), фармацевтическая композиция, содержащая эти варианты антитела, и их применение |
JPWO2005053742A1 (ja) | 2003-12-04 | 2007-06-28 | 協和醗酵工業株式会社 | 抗体組成物を含有する医薬 |
CA2885854C (en) | 2004-04-13 | 2017-02-21 | F. Hoffmann-La Roche Ag | Anti-p-selectin antibodies |
BRPI0510716A (pt) | 2004-05-05 | 2007-11-20 | Merrimack Pharmaceuticals Inc | uso de um agente de ligação bi-especìfico, agente de ligação bi-especìfico, composição de um agente de ligação bi-especìfico, e, kit |
TWI380996B (zh) | 2004-09-17 | 2013-01-01 | Hoffmann La Roche | 抗ox40l抗體 |
EP1791565B1 (en) | 2004-09-23 | 2016-04-20 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
JP2008526205A (ja) | 2004-12-31 | 2008-07-24 | ジェネンテック・インコーポレーテッド | Br3に結合するポリペプチド及びその使用 |
EP3698807A1 (en) | 2005-01-21 | 2020-08-26 | Genentech, Inc. | Fixed dosing of her antibodies |
WO2006091209A2 (en) | 2005-02-23 | 2006-08-31 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents for modulating biological activity |
PE20070207A1 (es) | 2005-07-22 | 2007-03-09 | Genentech Inc | Tratamiento combinado de los tumores que expresan el her |
JP2009511032A (ja) * | 2005-10-11 | 2009-03-19 | アブリンクス エン.ヴェー. | Egfrおよびigf−irに対するナノボディおよびポリペプチド |
AR056857A1 (es) | 2005-12-30 | 2007-10-24 | U3 Pharma Ag | Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos |
EP2471816A1 (en) | 2006-08-30 | 2012-07-04 | Genentech, Inc. | Multispecific antibodies |
CA2670315A1 (en) | 2006-11-21 | 2008-11-20 | The Regents Of The University Of California | Anti-egfr family antibodies, bispecific anti-egfr family antibodies and methods of use thereof |
US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
PL2716301T3 (pl) | 2007-02-16 | 2017-10-31 | Merrimack Pharmaceuticals Inc | Przeciwciała przeciw ERBB3 i ich zastosowania |
GB0807018D0 (en) | 2008-04-17 | 2008-05-21 | Fusion Antibodies Ltd | Antibodies and treatment |
EP2138511A1 (en) | 2008-06-27 | 2009-12-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | HER3 as a determinant for the prognosis of melanoma |
ES2572728T3 (es) * | 2009-03-20 | 2016-06-02 | F. Hoffmann-La Roche Ag | Anticuerpos anti-HER biespecíficos |
MX2011010166A (es) | 2009-04-07 | 2011-10-11 | Roche Glycart Ag | Anticuerpos biespecificos anti-erbb-3/anti-c-met. |
HUE035605T2 (en) | 2009-11-13 | 2018-05-28 | Daiichi Sankyo Europe Gmbh | Materials and Methods for the Treatment or Prevention of HER-3-Related Diseases |
DK2516469T3 (en) | 2009-12-22 | 2016-05-02 | Roche Glycart Ag | ANTI-HER3 antibodies and uses thereof |
JP2012016491A (ja) | 2010-07-08 | 2012-01-26 | Panasonic Electric Works Co Ltd | 往復式電気かみそり |
JP2015514710A (ja) * | 2012-03-27 | 2015-05-21 | ジェネンテック, インコーポレイテッド | Her3阻害剤に関する診断及び治療 |
CN105074006A (zh) * | 2013-03-14 | 2015-11-18 | 豪夫迈·罗氏有限公司 | 预测对egfr抑制剂的响应 |
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