ES2623209T3 - Conjugados fármaco-proteína - Google Patents
Conjugados fármaco-proteína Download PDFInfo
- Publication number
- ES2623209T3 ES2623209T3 ES13786530.9T ES13786530T ES2623209T3 ES 2623209 T3 ES2623209 T3 ES 2623209T3 ES 13786530 T ES13786530 T ES 13786530T ES 2623209 T3 ES2623209 T3 ES 2623209T3
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- 230000021615 conjugation Effects 0.000 abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 4
- 102000014914 Carrier Proteins Human genes 0.000 abstract 3
- 108091008324 binding proteins Proteins 0.000 abstract 3
- 125000005647 linker group Chemical group 0.000 abstract 3
- 108010044540 auristatin Proteins 0.000 abstract 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 abstract 1
- 239000005977 Ethylene Substances 0.000 abstract 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 abstract 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 abstract 1
- 125000004450 alkenylene group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 229940009098 aspartate Drugs 0.000 abstract 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 125000004434 sulfur atom Chemical group 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 4
- 238000003514 Retro-Michael reaction Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- A61K47/51—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
- A61K47/68—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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- A61K47/51—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
- A61K47/68—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
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- A61K47/51—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
- A61K47/68—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
- A61K47/6835—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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Molecular Biology (AREA)
Abstract
Un conjugado que contiene auristatina de la fórmula general: (((Dq-Lk1)m-P)p-Lk2-Lk3)n-Ab (I) en la que D representa un resto de auristatina; q representa un número entero de 1 a 10; Lk1 representa un enlazador; m representa un número entero de 1 a 10; P representa un enlace o un grupo valente z -P1-NH- donde z es de 2 a 11 y P1 es un grupo que contiene al menos una unidad de etileno -CH2-CH2- o una unidad de etilenglicol -O-CH2-CH2-; p representa un número entero de 1 a 10; Lk2 representa un enlace o un enlazador valente y donde y es de 2 a 11 y que consiste en 1 a 9 residuos de aspartato y/o glutamato; Lk3 representa un enlazador de la fórmula general: -CO-Ph-X-Y-(II) en la que Ph es un grupo fenilo opcionalmente sustituido; X representa un grupo CO o un grupo CH.OH; e Y representa un grupo de fórmula:**Fórmula** o **Fórmula** en la que cada uno de A y B representa un grupo alquileno o alquenileno C1-4; Ab representa una proteína o péptido de unión capaz de unirse a un compañero de unión en una diana, estando dicha proteína o péptido de unión unido a Lk3 a través de dos átomos de azufre derivados de un enlace disulfuro en la proteína o péptido de unión; y n representa un número entero de 1 a s donde s es el número de enlaces disulfuro presentes en la proteína o péptido de unión antes de la conjugación en Lk3; escogiéndose los significados de m, n, p, c, y y z de tal forma que el conjugado contiene de 1 a 10 grupos D.
Description
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-CO-Ph-Xa-Ya(IX) en la que Ph tiene el significado dado anteriormente, Xa representa un grupo CO, e Ya representa un grupo:
en la que A y B tienen los significados dados anteriormente, cada L representa independientemente un grupo saliente, y x representa un número entero de 1 a 4.
Los grupos de las fórmulas X, XI, XII y XIII anteriores son equivalentes químicos entre sí, con grupos de fórmula X y XI que conducen a un único puente de carbono a través de un enlace disulfuro del anticuerpo, y grupos de fórmula XII y XIII que conducen a puentes de carbono más largos, mostrados a continuación para el caso en el que n = 1:
o
Cuando se hace reaccionar un reactivo de conjugación que contiene un grupo X o XII con un anticuerpo, la etapa inmediato en la vía de reacción es la pérdida de un grupo saliente L que conduce a un reactivo de conjugación que contiene un grupo XI o XIII, respectivamente. Por lo tanto, los reactivos de conjugación de fórmula XI o XIII se preparan in situ o se usan ab initio. Una característica clave del uso de reactivos de conjugación que contienen cualquiera de los grupos X, XI, XII o XIII, es que un grupo saliente α-metileno y un doble enlace están conjugados de forma cruzada con una función aceptora de electrones que actúa como un resto activador de Michael. Si el grupo saliente es propenso a la eliminación en el reactivo multifuncional cruzado en lugar del desplazamiento directo y el grupo aceptor de electrones es un resto de activación adecuado para la reacción de Michael, entonces puede producirse la bis-alquilación intramolecular secuencial mediante reacciones consecutivas de Michael y retro Michael. El resto de salida sirve para enmascarar un doble enlace conjugado latente que no está expuesto hasta después de que se haya producido la primera alquilación y la bis-alquilación resulta de reacciones secuenciales e interactivas de Michael y retro-Michael. El grupo aceptor de electrones y el grupo saliente se seleccionan óptimamente por lo que la bis-alquilación pueda producirse mediante reacciones secuenciales de Michael y retro-Michael. También es posible preparar agentes alquilantes funcionales cruzados con enlaces múltiples adicionales conjugados con el doble enlace
o entre el grupo saliente y el grupo aceptor de electrones.
Un grupo saliente L puede representar, por ejemplo, -SR4, -SO2R4, -OSO2R4, -N+R43, -N+HR42, -N+H2R4, halógeno, o -O∅, en los que R4 tiene el significado dado anteriormente, y 0 representa un grupo arilo sustituido, especialmente fenilo, que contiene al menos un sustituyente aceptor de electrones, por ejemplo -CN, -NO2, -CO2R4, -COH, -CH2OH, -COR4, -OR4, -OCOR4, -OCO2R4, -SR4,-SOR4, -SO2R4, -NHCOR4, -NR4COR4, -NHCO2R4, -NR4CO2R4, -NO, -NHOH, -NR4OH, -C=N-NHCOR4, -C=N-NR4COR4, -N+R43, -N+HR42, -N+H2R4, halógeno, especialmente cloro o, especialmente, flúor, -CCR4, -C=CR42 y -C=CHR4, en los que cada R4 independientemente tiene uno de los significados dados anteriormente. Un grupo saliente especialmente preferido L es -SR4 o -SO2R4, especialmente -SO2R4, donde R4 representa un grupo fenilo o, especialmente, tosilo. Por lo tanto, un grupo particularmente preferido
Ya es:
17
Claims (1)
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imagen1 imagen2 imagen3 imagen4
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261717743P | 2012-10-24 | 2012-10-24 | |
| US201261717710P | 2012-10-24 | 2012-10-24 | |
| US201261717743P | 2012-10-24 | ||
| US201261717710P | 2012-10-24 | ||
| US201361811285P | 2013-04-12 | 2013-04-12 | |
| US201361811285P | 2013-04-12 | ||
| PCT/GB2013/051593 WO2013190292A2 (en) | 2012-06-19 | 2013-06-19 | Novel process for preparation of antibody conjugates and novel antibody conjugates |
| WOPCT/GB2013/051593 | 2013-06-19 | ||
| PCT/GB2013/052661 WO2014064423A1 (en) | 2012-10-24 | 2013-10-11 | Drug-protein conjugates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2623209T3 true ES2623209T3 (es) | 2017-07-10 |
Family
ID=50544085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13786530.9T Active ES2623209T3 (es) | 2012-10-24 | 2013-10-11 | Conjugados fármaco-proteína |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US20150290342A1 (es) |
| EP (2) | EP3159013A1 (es) |
| JP (1) | JP6328648B2 (es) |
| KR (1) | KR102209395B1 (es) |
| CN (1) | CN104870021B (es) |
| AU (1) | AU2013336409B2 (es) |
| BR (1) | BR112015008376A2 (es) |
| CA (1) | CA2884299A1 (es) |
| DK (1) | DK2911700T5 (es) |
| ES (1) | ES2623209T3 (es) |
| HK (1) | HK1208187A1 (es) |
| IL (1) | IL237672B (es) |
| IN (1) | IN2015DN02349A (es) |
| MX (1) | MX2015005122A (es) |
| MY (1) | MY169147A (es) |
| RU (1) | RU2015119561A (es) |
| SG (1) | SG11201501618WA (es) |
| WO (1) | WO2014064423A1 (es) |
| ZA (1) | ZA201501642B (es) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105658240A (zh) * | 2013-06-04 | 2016-06-08 | 西托姆克斯治疗公司 | 用于缀合可活化抗体的组合物和方法 |
| CA2921707C (en) | 2013-10-15 | 2023-03-28 | Seattle Genetics, Inc. | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
| JP6721572B2 (ja) * | 2014-05-23 | 2020-07-15 | ノバルティス アーゲー | ジスルフィド含有タンパク質からコンジュゲートを作製するための方法 |
| MY177148A (en) * | 2014-06-12 | 2020-09-08 | Cspc Megalith Biopharmaceutical Co Ltd | Homogenous antibody drug conjugates via enzymatic methods |
| WO2016059377A1 (en) * | 2014-10-14 | 2016-04-21 | Polytherics Limited | Process for the conjugation of a peptide or protein with a reagent comprising a leaving group including a portion of peg |
| MX2017005199A (es) * | 2014-10-24 | 2017-07-26 | Polytherics Ltd | Conjugados y reactivos de conjugacion. |
| GB201419108D0 (en) | 2014-10-27 | 2014-12-10 | Glythera Ltd | Materials and methods relating to linkers for use in antibody drug conjugates |
| EP3165532B1 (en) | 2015-11-03 | 2018-12-19 | Industrial Technology Research Institute | Auristatin derivatives, linker-drugs and ligand-drug conjugates |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| AU2016363013B2 (en) | 2015-12-04 | 2022-03-10 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
| SG11201807827VA (en) | 2016-03-25 | 2018-10-30 | Seattle Genetics Inc | Process for the preparation of pegylated drug-linkers and intermediates thereof |
| CN109152845B (zh) | 2016-04-14 | 2022-07-12 | 宝力泰锐克斯有限公司 | 含有在环内包含至少两个(-ch2-ch2-o-)单元的接头的缀合物和缀合试剂 |
| GB201608936D0 (en) * | 2016-05-20 | 2016-07-06 | Polytherics Ltd | Novel conjugates and novel conjugating reagents |
| WO2017212250A1 (en) * | 2016-06-06 | 2017-12-14 | Polytherics Limited | Antibodies, uses thereof and conjugates thereof |
| GB201614162D0 (en) * | 2016-08-18 | 2016-10-05 | Polytherics Ltd | Antibodies, uses thereof and conjugates thereof |
| IL269398B2 (en) | 2017-03-24 | 2024-05-01 | Seagen Inc | A process for the preparation of glucuronide-drug binders and their intermediates |
| GB201820864D0 (en) * | 2018-12-20 | 2019-02-06 | J A Kemp | Antibody-drug conjugates |
| JP2023521920A (ja) * | 2020-04-15 | 2023-05-25 | シェンチェン・エンデュアリング・バイオテック・リミテッド | 抗体－薬物コンジュゲート |
| EP4308163A1 (en) * | 2021-03-19 | 2024-01-24 | Shenzhen Enduring Biotech, Ltd. | Pegylated t cell engager with dual specificities to cd3 and cd19 |
| WO2023141855A1 (en) * | 2022-01-27 | 2023-08-03 | Glyco-Therapy Biotechnology Co., Ltd. | Protein conjugates with multiple payloads and methods for making the same |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0316294D0 (en) | 2003-07-11 | 2003-08-13 | Polytherics Ltd | Conjugated biological molecules and their preparation |
| BR122018071808B8 (pt) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugado |
| BRPI0617546A2 (pt) * | 2005-09-26 | 2011-07-26 | Medarex Inc | conjugado de fÁrmaco-anticorpo, formulaÇço farmacÊutica, mÉtodo para matar uma cÉlula de tumor, mÉtodo para retardar ou interromper o crescimento de um tumor em um sujeito mamÍfero e composto |
| US7968687B2 (en) * | 2007-10-19 | 2011-06-28 | Seattle Genetics, Inc. | CD19 binding agents and uses thereof |
| PL2842575T3 (pl) | 2008-03-18 | 2018-02-28 | Seattle Genetics, Inc. | Koniugaty aurystatyny lek łącznik |
| BRPI0911442A2 (pt) * | 2008-04-30 | 2019-03-12 | Immunogen, Inc. | conjugados potentes e ligantes hidrofílicos |
| EP2403538B1 (en) | 2009-03-04 | 2017-10-04 | Polytherics Limited | Conjugated proteins and peptides |
| WO2010120561A1 (en) * | 2009-04-01 | 2010-10-21 | Genentech, Inc. | Anti-fcrh5 antibodies and immunoconjugates and methods of use |
| UY32913A (es) * | 2009-10-02 | 2011-04-29 | Sanofi Aventis | Nuevos maitansinoides y el uso de dichos maitansinoides para preparar conjugados con un anticuero |
| US9995804B2 (en) * | 2012-04-25 | 2018-06-12 | Koninklijke Philips N.V. | System and method for locating a gradient coil |
| KR20150023027A (ko) * | 2012-06-19 | 2015-03-04 | 폴리테릭스 리미티드 | 항체 접합체의 제조를 위한 신규한 공정 및 신규한 항체 접합체 |
-
2013
- 2013-10-11 IN IN2349DEN2015 patent/IN2015DN02349A/en unknown
- 2013-10-11 JP JP2015538560A patent/JP6328648B2/ja active Active
- 2013-10-11 BR BR112015008376A patent/BR112015008376A2/pt not_active Application Discontinuation
- 2013-10-11 MY MYPI2015701285A patent/MY169147A/en unknown
- 2013-10-11 US US14/437,537 patent/US20150290342A1/en not_active Abandoned
- 2013-10-11 AU AU2013336409A patent/AU2013336409B2/en active Active
- 2013-10-11 WO PCT/GB2013/052661 patent/WO2014064423A1/en active Application Filing
- 2013-10-11 KR KR1020157011427A patent/KR102209395B1/ko active IP Right Grant
- 2013-10-11 MX MX2015005122A patent/MX2015005122A/es unknown
- 2013-10-11 DK DK13786530.9T patent/DK2911700T5/en active
- 2013-10-11 EP EP16203350.0A patent/EP3159013A1/en not_active Withdrawn
- 2013-10-11 ES ES13786530.9T patent/ES2623209T3/es active Active
- 2013-10-11 CA CA2884299A patent/CA2884299A1/en not_active Abandoned
- 2013-10-11 CN CN201380055880.6A patent/CN104870021B/zh active Active
- 2013-10-11 SG SG11201501618WA patent/SG11201501618WA/en unknown
- 2013-10-11 EP EP13786530.9A patent/EP2911700B1/en active Active
- 2013-10-11 RU RU2015119561A patent/RU2015119561A/ru unknown
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2015
- 2015-03-10 ZA ZA2015/01642A patent/ZA201501642B/en unknown
- 2015-03-11 IL IL237672A patent/IL237672B/en active IP Right Grant
- 2015-09-11 HK HK15108932.7A patent/HK1208187A1/xx unknown
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2021
- 2021-09-17 US US17/477,565 patent/US20220062436A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014064423A1 (en) | 2014-05-01 |
| BR112015008376A2 (pt) | 2017-09-26 |
| JP6328648B2 (ja) | 2018-05-23 |
| AU2013336409A1 (en) | 2015-04-02 |
| EP3159013A1 (en) | 2017-04-26 |
| ZA201501642B (en) | 2016-01-27 |
| EP2911700B1 (en) | 2017-02-08 |
| CA2884299A1 (en) | 2014-05-01 |
| CN104870021A (zh) | 2015-08-26 |
| RU2015119561A (ru) | 2016-12-20 |
| DK2911700T5 (en) | 2017-05-22 |
| CN104870021B (zh) | 2018-03-13 |
| HK1208187A1 (en) | 2016-02-26 |
| KR20150103656A (ko) | 2015-09-11 |
| JP2015533847A (ja) | 2015-11-26 |
| US20220062436A1 (en) | 2022-03-03 |
| AU2013336409B2 (en) | 2017-08-03 |
| MY169147A (en) | 2019-02-18 |
| KR102209395B1 (ko) | 2021-01-28 |
| US20150290342A1 (en) | 2015-10-15 |
| EP2911700A1 (en) | 2015-09-02 |
| IL237672A0 (en) | 2015-04-30 |
| DK2911700T3 (en) | 2017-05-15 |
| MX2015005122A (es) | 2015-10-29 |
| IL237672B (en) | 2018-02-28 |
| IN2015DN02349A (es) | 2015-08-28 |
| SG11201501618WA (en) | 2015-04-29 |
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