ES2609919T3 - Enzimas conjugados con anticuerpos mediante un conector de PEG heterobifuncional - Google Patents

Enzimas conjugados con anticuerpos mediante un conector de PEG heterobifuncional Download PDF

Info

Publication number
ES2609919T3
ES2609919T3 ES06758689.1T ES06758689T ES2609919T3 ES 2609919 T3 ES2609919 T3 ES 2609919T3 ES 06758689 T ES06758689 T ES 06758689T ES 2609919 T3 ES2609919 T3 ES 2609919T3
Authority
ES
Spain
Prior art keywords
conjugate
scaffolding
antibody
staining
generation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
ES06758689.1T
Other languages
English (en)
Inventor
Christopher Bieniarz
Jennifer Wong
Mark Lefever
Jerome W. Kosmeder
Julia Ashworth-Sharpe
Casey A. Kernag
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ventana Medical Systems Inc
Original Assignee
Ventana Medical Systems Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ventana Medical Systems Inc filed Critical Ventana Medical Systems Inc
Application granted granted Critical
Publication of ES2609919T3 publication Critical patent/ES2609919T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6815—Enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0065—Oxidoreductases (1.) acting on hydrogen peroxide as acceptor (1.11)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/535—Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Conjugado de anticuerpo-resto generador de señal que comprende un anticuerpo unido covalentemente a un resto generador de señal mediante un conector de PEG heterobifuncional, donde el conjugado tiene la fórmula general:**Fórmula** donde Ab es un anticuerpo, SM es un resto generador de señal que lleva un enzima o un punto cuántico, n >= 4 a 12 y s >= 1 hasta 10.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
5
15
25
35
45
55
65
de conejo anti-IgG de ratón con los dos conjugados (“amplificación”), como anticuerpo secundario reactivo para detectar la unión a los antígenos tisulares de los anticuerpos primarios abajo relacionados (que suministra Ventana Medical Systems, Inc, Tucson, AZ). Con estos conjugados se trataron cortes tisulares apropiados de archivo y se desarrollaron siguiendo protocolos estándar para la generación de señales detectables mediante HRP (añadiendo DAB) en un aparato Bench-Mark® XT autostainer (Ventana Medical Systems, Inc, Tucson, AZ). Un típico protocolo automatizado incluye la desparafinación, varias etapas de lavado, la adición de un tampón de reacción, la adición del anticuerpo primario, la adición del anticuerpo secundario, la adición de DAB y peróxido de hidrógeno y una tinción de contraste.
Se tiñeron cortes tisulares comparables (adyacentes) con los conjugados revelados y con conjugados de HRP/ F(ab’)2 con andamiaje de polilisina (en lo sucesivo “conjugados con andamiaje”) usados como anticuerpo secundario reactivo. Los conjugados con andamiaje eran de segunda generación (más pequeños y homogéneos según la determinación por cromatografía de exclusión de tamaños) o de primera generación (más grandes e inhomogéneos según la determinación por cromatografía de exclusión de tamaños). Para una descripción más completa de los conjugados con andamiaje véanse las patentes U.S. nº 6,613,564 y 6,252,053.
Anticuerpos
Anti-bcl-2 (clon 100/D5) Anti-CD15 (clon MMA) Anti-CD20 (clon L26) Anti-PR (clon 16) Anti-EGFR (clon 31G7) Anti-c-erbB-2 (clon CB11)
Anti-CD57 (clon NK-1) Anti-CD23 (clon 1B12) Anti-ER (clon 6F 11) Anti- p53 (clon D07) Anti-ciclina-d1 (clon P2D11F11) Anti-PSA
*nota: todos eran anticuerpos de ratón, excepto el PSA, que es un anticuerpo de conejo.
La FIG. 2 muestra los resultados de tinción para la detección de bcl-2 mediante el conjugado revelado (FIG. 2A) y el conjugado con andamiaje de segunda generación (FIG. 2B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
La FIG. 3 muestra los resultados de tinción para la detección de CD-15 mediante el conjugado revelado (FIG. 3A) y el conjugado con andamiaje de segunda generación (FIG. 3B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
La FIG. 4 muestra los resultados de tinción para la detección de CD-20 mediante el conjugado revelado (usando amplificación, FIG. 4A) y el conjugado con andamiaje de segunda generación (FIG. 4B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
La FIG. 5 muestra los resultados de tinción para la detección de CD-23 mediante el conjugado revelado (FIG. 5A), el conjugado con andamiaje de segunda generación (FIG. 5B) y el conjugado con andamiaje de primera generación (FIG. 5C). Los resultados demuestran que, en cortes tisulares comparables, el conjugado revelado proporciona una intensidad de tinción mayor que la observada para ambos conjugados con andamiaje.
La FIG. 6 muestra los resultados de tinción para la detección de CD57 mediante el conjugado revelado (FIG. 6A) y el conjugado con andamiaje de segunda generación (FIG. 6B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
La FIG. 7 muestra los resultados de tinción para la detección de cerb-B2/CB11 mediante el conjugado revelado (FIG. 7A), el conjugado con andamiaje de segunda generación (FIG. 7B) y el conjugado con andamiaje de primera generación (FIG. 7C). Los resultados demuestran que, en cortes tisulares comparables, el conjugado revelado proporciona una intensidad de tinción mayor que la observada para ambos conjugados con andamiaje.
La FIG. 8 muestra los resultados de tinción para la detección de ciclina-D1 mediante el conjugado revelado (FIG. 8A) y el conjugado con andamiaje de segunda generación (FIG. 8B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
La FIG. 9 muestra los resultados de tinción para la detección de EGFR mediante el conjugado revelado (FIG. 9A), el conjugado con andamiaje de segunda generación (FIG. 9B) y el conjugado con andamiaje de primera generación (FIG. 9C). Los resultados demuestran que, en cortes tisulares comparables, el conjugado revelado proporciona una intensidad de tinción mayor que la observada para ambos conjugados con andamiaje.
La FIG. 10 muestra los resultados de tinción para la detección de ER mediante el conjugado revelado (FIG. 10A) y el conjugado con andamiaje de segunda generación (FIG. 10B). Los resultados demuestran que la mayor intensidad de tinción se consigue con el conjugado revelado en cortes tisulares comparables.
14
imagen13
imagen14
5
10
15
20
25
30
35
40
45
I. Preparación de un conjugado de anticuerpo de conejo anti-biotina-HRP-PEG12 y su uso para la hibridación metalográfica enzimática in situ
HRP-PEG12-maleimida (4): en un vial ámbar de 4 ml se introdujeron 18,4 mg (100 eq.) de éster MAL-dPEG12® NHS (Quanta Biodesign, Powell, OH, peso fórmula = 865,92) y luego 341 ul (8,52 mg, 0,213 mM) de HRP (peroxidasa de rábano picante, Pierce, Rockford, IL) en forma de una solución de 25 mg / ml de fosfato sódico 0,1 M, pH 7,5. Luego el vial se puso en un girador automático, en la oscuridad, a la temperatura ambiente (23 – 25ºC) y la reacción de formación del enlace amida se dejo proceder durante 1 hora. Después se tomó un alícuota de 340 µl para purificar. (La capacidad del bucle de inyección del aparato Akta Purifier empleado fue de 500 µl). Luego se obtuvo HRPPEG12-maleimida pura fraccionando la muestra en un aparato Akta Purifier equipado con una columna Superdex 10/300 eluida con 1,0 ml / min de fosfato sódico 0,1 M, pH 7,5. Las fracciones que contenían HRP (F15-17) se reunieron para dar 1,5 ml de una solución de 4,75 mg / ml de HRP-PEG12-maleimida (83,6% de recuperación) según la medición en un espectrofotómetro UV/VIS, usando el coeficiente de extinción a 280 nm de una solución al 1% de pH 7,5, igual a 6,52.
Anticuerpo de conejo anti-biotina tiol (5): en un vial ámbar de 4 ml se introdujeron 2,0 ml de una solución de 1,0 mg/ml de anticuerpo de conejo anti-biotina (Bethyl, Montgomery, TX). A esta solución se le añadieron luego 105,2 µl de una solución 500 mM del agente reductor DTT (1,4-ditiotreitol) recién preparada. El vial se puso en un girador automático en la oscuridad y la reacción de reducción del disulfuro se dejo proceder durante 25 minutos. La solución se dividió en dos volúmenes iguales (debido a la limitada capacidad de las columnas de desalinización) y el exceso de DTT se eliminó pasando cada una de las fracciones a través de una columna de desalinización PD-10 eluida con fosfato sódico 0,1 M, EDTA 1,0 mM, pH 6,5. Las fracciones que contenían anticuerpo (F4-5) se reunieron para obtener 4,0 ml de una solución de 0,436 mg / ml de anticuerpo de conejo anti-biotina-SH libre de DTT (87,5% de recuperación) según la medición en un espectrofotómetro UV/VIS de Agilent, usando un coeficiente de extinción a 280 nm de una solución al 1% de pH 6,5, igual a 14.
Conjugación HRP-anticuerpo (6): al anticuerpo de conejo anti-biotina-IgG-tiol (5) se le añadió un exceso tres veces molar de HRP-PEG12-maleimida (4). Luego la reacción se incubó a temperatura ambiente (23 – 25ºC) por la noche. Después de purificarlo a través de una columna Superdex 200 10/300 GL SE se obtuvieron 875 mg de conjugado con un PM medio de 359 kD.
El procedimiento metalográfico enzimático descrito en el ejemplo G se repitió usando el conjugado de PEG12 antibiotina como anticuerpo primario (es decir sin amplificación) y sorprendentemente se obtuvo una tinción intensa, aunque no se empleó ninguna amplificación. Estos resultados demuestran que el empleo de conectores largos de PEG heterobifuncionales (PEG8 o superior, por ejemplo PEG12 o superior) para preparar los conjugados revelados elimina sorprendentemente la necesidad de esquemas de amplificación para las aplicaciones de IHC y ISH en los cortes tisulares.
J. Síntesis del conector de maleimida/hidrazida PEG (ejemplo de referencia)
El esquema 6 muestra un método general de preparación de conectores heterobifuncionales de maleimida/hidrazida PEG. En resumen, un conector de maleimida/éster activo de PEG (como el adquirido de Quanta Biodesign) se hace reaccionar con un derivado de hidrazina protegido y después con ácido, para dar el conector de maleimida/hidrazida PEG.
ácido
Esquema 6 17
imagen15

Claims (1)

  1. imagen1
    imagen2
ES06758689.1T 2005-04-28 2006-04-27 Enzimas conjugados con anticuerpos mediante un conector de PEG heterobifuncional Expired - Lifetime ES2609919T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US67575905P 2005-04-28 2005-04-28
US675759P 2005-04-28
PCT/US2006/016087 WO2006116628A2 (en) 2005-04-28 2006-04-27 Enzymes conjugated to antiobodies via a peg heterobifuctional linker

Publications (1)

Publication Number Publication Date
ES2609919T3 true ES2609919T3 (es) 2017-04-25

Family

ID=37027498

Family Applications (1)

Application Number Title Priority Date Filing Date
ES06758689.1T Expired - Lifetime ES2609919T3 (es) 2005-04-28 2006-04-27 Enzimas conjugados con anticuerpos mediante un conector de PEG heterobifuncional

Country Status (8)

Country Link
US (4) US20060246523A1 (es)
EP (2) EP1877101B1 (es)
JP (1) JP5628476B2 (es)
AU (1) AU2006239315B2 (es)
CA (1) CA2609702C (es)
DK (1) DK1877101T3 (es)
ES (1) ES2609919T3 (es)
WO (1) WO2006116628A2 (es)

Families Citing this family (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2606018A1 (en) * 2005-04-28 2006-11-02 Ventana Medical Systems, Inc. Nanoparticle conjugates
JP5628476B2 (ja) * 2005-04-28 2014-11-19 ベンタナ・メデイカル・システムズ・インコーポレーテツド 抗体コンジュゲート
ES2548518T3 (es) * 2005-11-23 2015-10-19 Ventana Medical Systems, Inc. Conjugado molecular
US20090163698A1 (en) * 2007-05-11 2009-06-25 John Joseph Grigsby Method for Preparing Antibody Conjugates
ES2613963T3 (es) * 2008-01-18 2017-05-29 Medimmune, Llc Anticuerpos manipulados con cisteína para conjugación específica de sitio
US20100136584A1 (en) * 2008-09-22 2010-06-03 Icb International, Inc. Methods for using antibodies and analogs thereof
WO2010078376A2 (en) 2008-12-30 2010-07-08 Ventana Medical Systems, Inc. Fc-specific polymer-conjugated antibodies and their diagnostic use
SG182303A1 (en) 2009-12-31 2012-08-30 Ventana Med Syst Inc Methods for producing uniquely specific nucleic acid probes
EP2531569B1 (en) 2010-02-02 2017-01-25 Ventana Medical Systems, Inc. Composition and method for stabilizing fluorescent particles
ES2606012T3 (es) 2010-02-26 2017-03-17 Ventana Medical Systems, Inc. Hibridación in situ con sondas PolyTag
CA2786853A1 (en) 2010-02-26 2011-09-01 Ventana Medical Systems, Inc. Cytogenic analysis of metaphase chromosomes
JP5822913B2 (ja) 2010-04-20 2015-11-25 ヴェンタナ メディカル システムズ， インク． ２色発色性インサイツハイブリダイゼーション
EP2380909A1 (en) 2010-04-26 2011-10-26 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. PTK-7 protein involved in breast cancer
WO2012003478A2 (en) 2010-07-02 2012-01-05 Ventana Medical Systems, Inc. Detecting targets using mass tags and mass spectrometry
WO2012012759A2 (en) * 2010-07-22 2012-01-26 The Regents Of The University Of California Anti-tumor antigen antibodies and methods of use
WO2012024185A1 (en) 2010-08-16 2012-02-23 Ventana Medical Systems, Inc. Substrates for chromogenic detection and methods of use in detection assays and kits
CA2816472A1 (en) 2010-11-08 2012-05-18 Dako Denmark A/S Quantification of single target molecules in histological samples
WO2012076010A1 (en) 2010-12-06 2012-06-14 Dako Denmark A/S Combined histological stain
CN103534359B (zh) 2011-03-14 2016-07-06 文塔纳医疗系统公司 分析染色体易位的方法及其系统
US8609355B2 (en) 2011-07-26 2013-12-17 Indicator Systems International, Inc. Assays for the detection of microbes
WO2013167387A1 (en) 2012-05-10 2013-11-14 Ventana Medical Systems, Inc. Uniquely specific probes for pten, pik3ca, met, top2a, and mdm2
KR20220051197A (ko) 2012-05-17 2022-04-26 익스텐드 바이오사이언시즈, 인크. 개선된 약물 전달용 캐리어
WO2014009535A2 (en) 2012-07-12 2014-01-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time and treatment responsiveness of a patient suffering from a solid cancer with a signature of at least 7 genes
DK2880180T3 (en) 2012-08-06 2019-01-14 Inst Nat Sante Rech Med METHODS AND KITS TO SCREEN PATIENTS WITH CANCER
WO2014048942A1 (en) 2012-09-25 2014-04-03 Ventana Medical Systems, Inc. Probes for pten, pik3ca, met, and top2a, and method for using the probes
US20140134651A1 (en) * 2012-11-07 2014-05-15 Quanta Eqip, Llc Stable Discrete PEG Based Peroxidase Biological Conjugates
AU2012395148B2 (en) 2012-11-24 2016-10-27 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
JP6576835B2 (ja) 2013-03-12 2019-09-18 ヴェンタナ メディカル システムズ， インク． 標的物をｉｎｓｉｔｕ検出するための近接アッセイ
ES2804594T3 (es) * 2013-03-15 2021-02-08 Amicus Therapeutics Inc Reticuladores químicos
EP3016973A1 (en) 2013-07-05 2016-05-11 INSERM - Institut National de la Santé et de la Recherche Médicale Novel alternative splice transcripts for mhc class i related chain alpha (mica) and uses thereof
WO2015036405A1 (en) 2013-09-10 2015-03-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing and treating basal cell carcinoma
FI3122757T3 (fi) 2014-02-28 2023-10-10 Hangzhou Dac Biotech Co Ltd Varautuneita linkkereitä ja niiden konjugointikäyttötapoja
CN106415269B (zh) * 2014-05-08 2020-11-27 贵州美鑫达医疗科技有限公司 直接免疫组织化学测定
EP3009147A1 (en) 2014-10-16 2016-04-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for treating resistant glioblastoma
US9585934B2 (en) 2014-10-22 2017-03-07 Extend Biosciences, Inc. Therapeutic vitamin D conjugates
WO2016065052A1 (en) 2014-10-22 2016-04-28 Extend Biosciences, Inc. Insulin vitamin d conjugates
US9789197B2 (en) 2014-10-22 2017-10-17 Extend Biosciences, Inc. RNAi vitamin D conjugates
AU2015352625B2 (en) 2014-11-25 2019-07-25 Ventana Medical Systems, Inc. Proximity assays using chemical ligation and hapten transfer
BR112017017719A2 (pt) 2015-02-20 2018-04-10 Idexx Lab Inc imunoensaio homogêneo com compensação para sinal antecedente
KR20170007181A (ko) 2015-07-10 2017-01-18 3스캔 인크. 조직학적 염색제의 공간 다중화
CN108369229A (zh) * 2015-07-17 2018-08-03 奥菲迪亚有限公司 用于处理基底表面的连接分子
JP6675165B2 (ja) * 2015-07-31 2020-04-01 シスメックス株式会社 被検物質の検出方法、検出用試薬キットおよび検出用試薬
WO2017029391A1 (en) 2015-08-20 2017-02-23 INSERM (Institut National de la Santé et de la Recherche Médicale) New method for treating cancer
WO2017040349A1 (en) 2015-08-28 2017-03-09 Ventana Medical Systems, Inc. Protein proximity assay in formalin fixed paffafin embedded tissue using caged haptens
WO2017055326A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of myeloid dendritic cells in a tissue sample
WO2017055327A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of endothelial cells in a tissue sample
WO2017055319A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of b cells in a tissue sample
WO2017055322A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of neutrophils in a tissue sample
WO2017055321A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of fibroblasts in a tissue sample
WO2017055320A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of cytotoxic lymphocytes in a tissue sample
WO2017055324A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of cells of monocytic origin in a tissue sample
WO2017055325A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of nk cells in a tissue sample
WO2017060397A1 (en) 2015-10-09 2017-04-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time of subjects suffering from melanoma metastases
WO2017067944A1 (en) 2015-10-19 2017-04-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time of subjects suffering from triple negative breast cancer
WO2017087879A2 (en) * 2015-11-18 2017-05-26 Synergy Pharmaceuticals, Inc. Compositions and method for the treatment and detection of colon cancer
AU2017229370B2 (en) 2016-03-08 2021-03-11 Ventana Medical Systems, Inc. Multiplexed immunohistochemistry using recombinant antibodies with epitope tags
US10900069B2 (en) 2016-03-10 2021-01-26 Emory University Devices and methods useful for detecting mechanical forces of ligand receptor interactions
WO2017182834A1 (en) 2016-04-19 2017-10-26 INSERM (Institut National de la Santé et de la Recherche Médicale) New method for treating resistant glioblastoma
EP3463452A1 (en) 2016-05-24 2019-04-10 Institut National de la Sante et de la Recherche Medicale (INSERM) Methods and pharmaceutical compositions for the treatment of non small cell lung cancer (nsclc) that coexists with chronic obstructive pulmonary disease (copd)
CN121021395A (zh) 2016-06-28 2025-11-28 文塔纳医疗系统公司 点击化学用于ihc和ish测定中的信号扩增的应用
EP3475701B1 (en) 2016-06-28 2023-02-22 Ventana Medical Systems, Inc. New colors for chromogenic ihc and ish staining with multi-dye quinone methide and tyramide conjugates
WO2018011107A1 (en) 2016-07-11 2018-01-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of er-alpha 46 in methods and kits for assessing the status of breast cancer
WO2018011166A2 (en) 2016-07-12 2018-01-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of myeloid dendritic cells in a tissue sample
CN106405087A (zh) * 2016-08-31 2017-02-15 上海科华生物工程股份有限公司 羊抗HBsAg多克隆抗体‑碱性磷酸酶交联物及其制备方法和检测试剂盒
WO2018046736A1 (en) 2016-09-12 2018-03-15 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time of patients suffering from cancer
WO2018055080A1 (en) 2016-09-22 2018-03-29 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for reprograming immune environment in a subject in need thereof
EP3516071B1 (en) 2016-09-22 2021-02-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of lung cancer
WO2018122249A1 (en) 2016-12-28 2018-07-05 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time of patients suffering from a microsatellite stable colorectal cancer
WO2018122245A1 (en) 2016-12-28 2018-07-05 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of predicting the survival time of patients suffering from cms3 colorectal cancer
WO2018146239A1 (en) 2017-02-10 2018-08-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Biomarker for outcome in aml patients
WO2018162404A1 (en) 2017-03-06 2018-09-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Biomarker for outcome in aml patients
WO2018172540A1 (en) 2017-03-24 2018-09-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Method to predict the progression of alzheimer's disease
WO2018189215A1 (en) 2017-04-12 2018-10-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for predicting the survival time of a patient suffering from hepatocellular carcinoma
GB201709503D0 (en) * 2017-06-15 2017-08-02 Method and device for assay improvement
EP3638699A1 (en) * 2017-06-16 2020-04-22 Eli Lilly and Company Engineered antibody compounds and conjugates thereof
WO2019038219A1 (en) 2017-08-21 2019-02-28 INSERM (Institut National de la Santé et de la Recherche Médicale) New prognostic method of pancreatic cancer
WO2019043138A1 (en) 2017-09-01 2019-03-07 INSERM (Institut National de la Santé et de la Recherche Médicale) METHOD FOR PREDICTING OUTCOME OF CANCER
US11422136B2 (en) * 2017-10-19 2022-08-23 Idexx Laboratories, Inc. Detection of symmetrical dimethylarginine
EP3710820B1 (en) 2017-11-13 2025-06-11 F. Hoffmann-La Roche AG Devices for sample analysis using epitachophoresis
CA3130653A1 (en) 2018-03-09 2019-09-12 Valitor, Inc. Multivalent peptide conjugates for sustained intra-articular treatment of joint inflammation
WO2019207030A1 (en) 2018-04-26 2019-10-31 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting a response with an immune checkpoint inhibitor in a patient suffering from a lung cancer
WO2020074742A1 (en) 2018-10-12 2020-04-16 F. Hoffmann-La Roche Ag Detection methods for epitachophoresis workflow automation
WO2020089428A1 (en) 2018-11-02 2020-05-07 INSERM (Institut National de la Santé et de la Recherche Médicale) New prognostic method of pancreatic cancer
WO2020089432A1 (en) 2018-11-02 2020-05-07 INSERM (Institut National de la Santé et de la Recherche Médicale) New prognostic method of pancreatic cancer
WO2020141199A1 (en) 2019-01-03 2020-07-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for enhancing cd8+ t cell-dependent immune responses in subjects suffering from cancer
JP2022522265A (ja) 2019-01-16 2022-04-15 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル エリスロフェロンの変異体及びその使用
US20220098674A1 (en) 2019-02-13 2022-03-31 Inserm (Institut National De La Santé Et Dr La Recherch Médicale) Methods and compositions for selecting a cancer treatment in a subject suffering from cancer
WO2020182932A1 (en) 2019-03-13 2020-09-17 INSERM (Institut National de la Santé et de la Recherche Médicale) New gene signatures for predicting survival time in patients suffering from renal cell carcinoma
WO2020193740A1 (en) 2019-03-28 2020-10-01 INSERM (Institut National de la Santé et de la Recherche Médicale) New strategy for treating pancreatic cancer
US20220177978A1 (en) 2019-04-02 2022-06-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of predicting and preventing cancer in patients having premalignant lesions
JP2022530390A (ja) 2019-04-24 2022-06-29 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 抗精神病剤の応答を予測するための方法
WO2020229521A1 (en) 2019-05-14 2020-11-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for inhibiting or reducing bacterial biofilms on a surface
CN113785184B (zh) 2019-05-14 2025-02-28 文塔纳医疗系统公司 包括生物学样品处理腔室的系统
WO2020229437A1 (en) 2019-05-14 2020-11-19 F. Hoffmann-La Roche Ag Devices and methods for sample analysis
CN114222802B (zh) * 2019-05-20 2025-07-11 尼尔瓦纳科学股份有限公司 窄发射染料、包含其的组合物以及制备和使用其的方法
SG11202112712RA (en) 2019-06-03 2021-12-30 Inst Nat Sante Rech Med Methods for modulating a treatment regimen
KR20220027215A (ko) * 2019-07-01 2022-03-07 발리터 인코포레이티드 다가 펩티드 컨쥬게이트를 위한 친수성 링커
WO2021001539A1 (en) 2019-07-04 2021-01-07 INSERM (Institut National de la Santé et de la Recherche Médicale) New strategy to detect and treat eosinophilic fasciitis
US20220340975A1 (en) 2019-09-05 2022-10-27 INSERM (Institute National de la Santé et de la Recherche Médicale) Method of treatment and pronostic of acute myeloid leukemia
US20240301497A1 (en) 2019-10-17 2024-09-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing nasal intestinal type adenocarcinomas
WO2021170777A1 (en) 2020-02-28 2021-09-02 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing, prognosing and managing treatment of breast cancer
EP4121768A1 (en) 2020-03-20 2023-01-25 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for predicting the survival time of a patient suffering from a cancer
JP7515855B2 (ja) * 2020-04-13 2024-07-16 国立研究開発法人産業技術総合研究所 非特異的吸着抑制効果の高い糖鎖リガンド、および該糖鎖リガンドを固定化した毒素検知チップ
JP2023528978A (ja) 2020-06-10 2023-07-06 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 悪性膠芽腫のような癌の治療及び予防方法
US20230218608A1 (en) 2020-06-18 2023-07-13 INSERM (Institut National de la Santé et de la Recherche Médicale) New strategy for treating pancreatic cancer
WO2022002874A1 (en) 2020-06-30 2022-01-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapy and radical surgery
EP4172621A1 (en) 2020-06-30 2023-05-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapies
WO2022018163A1 (en) 2020-07-22 2022-01-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for predicting survival time in patients suffering from cancer
WO2022064049A1 (en) 2020-09-28 2022-03-31 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for diagnosing brucella infection
WO2022084327A1 (en) 2020-10-20 2022-04-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for predicting the response to tnf inhibitors
CN112305222A (zh) * 2020-11-05 2021-02-02 东莞市医本生物科技有限公司 一种小多聚体酶-抗体片段及其制备与应用
WO2022096633A1 (en) 2020-11-06 2022-05-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosis and treating polycystic ovary syndrome (pcos)
WO2022135753A1 (en) 2020-12-21 2022-06-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for prognosis the humoral response of a subject prior to vaccination
WO2022136252A1 (en) 2020-12-21 2022-06-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for prognosis the humoral response of a subject prior to vaccination
WO2022152698A1 (en) 2021-01-12 2022-07-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of npdk-d to evaluate cancer prognosis
EP4278181A1 (en) 2021-01-15 2023-11-22 Ventana Medical Systems, Inc. Storage stable caged haptens
KR20230133289A (ko) * 2021-01-18 2023-09-19 아지노모토 가부시키가이샤 화합물 또는 이의 염, 및 이들에 의해 얻어지는 항체
CN116868054A (zh) 2021-01-25 2023-10-10 文塔纳医疗系统公司 包括用一个或多个可检测部分标记的一种或多种生物标志物的染色生物学样本
US20240044901A1 (en) 2021-02-09 2024-02-08 Institut National de la Santé et de la Recherche Médicale New method to pronostic lung cancer
EP4308934A1 (en) 2021-03-17 2024-01-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for diagnosing pancreatic cancer
WO2022207566A1 (en) 2021-03-29 2022-10-06 INSERM (Institut National de la Santé et de la Recherche Médicale) New method to evaluate pancreatic cancer prognosis
EP4326903A1 (en) 2021-04-23 2024-02-28 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating cell senescence accumulation related disease
EP4367269A1 (en) 2021-07-05 2024-05-15 Inserm (Institut National De La Sante Et De La Recherche Medicale) Gene signatures for predicting survival time in patients suffering from renal cell carcinoma
WO2023089159A1 (en) 2021-11-22 2023-05-25 INSERM (Institut National de la Santé et de la Recherche Médicale) New strategy targeting stroma/tumor cell crosstalk to treat a cancer
EP4472740A1 (en) 2022-01-31 2024-12-11 INSERM (Institut National de la Santé et de la Recherche Médicale) Cd38 as a biomarker and biotarget in t-cell lymphomas
WO2023152133A1 (en) 2022-02-08 2023-08-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for diagnosing colorectal cancer
WO2023175366A1 (en) 2022-03-17 2023-09-21 Veracyte Methods for predicting response to an immunotherapeutic treatment in a patient with a cancer
US20230408497A1 (en) * 2022-06-20 2023-12-21 Sysmex Corporation Labeled polypeptide, modified polypeptide, production method for these polypeptides, reagent containing these polypeptides, and measurement method for target substance
WO2024061930A1 (en) 2022-09-22 2024-03-28 Institut National de la Santé et de la Recherche Médicale New method to treat and diagnose peripheral t-cell lymphoma (ptcl)
EP4593867A2 (en) 2022-09-30 2025-08-06 Extend Biosciences, Inc. Long-acting parathyroid hormone
WO2024115935A1 (en) 2022-11-29 2024-06-06 Inserm Methods for the treatment of b-cell lymphoma using cd39 inhibitors
WO2024236131A1 (en) 2023-05-17 2024-11-21 Institut National de la Santé et de la Recherche Médicale Stratificate and method to treat a patient suffering from a cancer
WO2024245951A1 (en) 2023-05-26 2024-12-05 Institut National de la Santé et de la Recherche Médicale Combination of slc8a1 inhibitor and mitochondria-targeted antioxidant for treating melanoma
WO2025027127A1 (en) 2023-08-02 2025-02-06 Institut National de la Santé et de la Recherche Médicale New prognostic method of kidney failure
WO2025068340A1 (en) 2023-09-27 2025-04-03 Institut National de la Santé et de la Recherche Médicale Method to predict aml outcome
WO2025073765A1 (en) 2023-10-03 2025-04-10 Institut National de la Santé et de la Recherche Médicale Methods of prognosis and treatment of patients suffering from melanoma
WO2025078632A1 (en) 2023-10-12 2025-04-17 Institut National de la Santé et de la Recherche Médicale Methods of prognosis and treatment of patients suffering from cancer
WO2025109147A1 (en) 2023-11-24 2025-05-30 Institut National de la Santé et de la Recherche Médicale Method to predict the risk of a cardiovascular event in a patient with type 2 diabetes
WO2025114473A1 (en) 2023-11-29 2025-06-05 Institut National de la Santé et de la Recherche Médicale Method for assessing diseases associated with a loss of p53 function in subjects in need thereof
KR20240123233A (ko) * 2023-12-06 2024-08-13 순천향대학교 산학협력단 캄토테신-iRGD 접합체를 포함하는 암세포 표적화 약물전달체 및 이의 제조방법
CN118373870B (zh) * 2024-05-10 2024-11-26 中汉生物医学技术研究(昆山)有限公司 一种基于醛基巯基反应的蛋白偶联方法
WO2026013153A1 (en) 2024-07-10 2026-01-15 Institut National de la Santé et de la Recherche Médicale Methods of prognosis and treatment of patients suffering from myc-high tumors
WO2026070901A1 (ja) * 2024-09-25 2026-04-02 積水メディカル株式会社 標識抗体及びその製造方法、並びに免疫学的測定試薬及び免疫学的測定方法
WO2026093526A1 (en) 2024-10-31 2026-05-07 Institut National de la Santé et de la Recherche Médicale Methods of predicting cancer in patients having premalignant lesions

Family Cites Families (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB782420A (en) 1954-08-23 1957-09-04 Ici Ltd New hydrazides
US3654090A (en) * 1968-09-24 1972-04-04 Organon Method for the determination of antigens and antibodies
NL154599B (nl) * 1970-12-28 1977-09-15 Organon Nv Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen, alsmede testverpakking.
US4002532A (en) * 1974-10-21 1977-01-11 Weltman Joel K Enzyme conjugates
IL47468A (en) * 1975-06-12 1979-05-31 Rehovot Res Prod Process for the cross-linking of proteins using water soluble cross-linking agents
US4016043A (en) * 1975-09-04 1977-04-05 Akzona Incorporated Enzymatic immunological method for the determination of antigens and antibodies
JPS5344622A (en) * 1976-09-30 1978-04-21 Mochida Pharm Co Ltd Immunologically measuring method
DE2708018A1 (de) * 1977-02-24 1978-09-07 Boehringer Mannheim Gmbh An polyamid fixiertes biologisch aktives protein und verfahren zu seiner herstellung
SE427505B (sv) * 1977-03-04 1983-04-11 Pharmacia Diagnostics Ab Reagens till anvendning vid immunkemiska bestemningsmetoder
US4235960A (en) * 1977-07-29 1980-11-25 The Medical College Of Wisconsin, Inc. Competitive enzyme-linked immunoassay
US4218539A (en) * 1978-03-24 1980-08-19 Weltman Joel K Enzyme conjugates and method of preparation and use
US4433059A (en) * 1981-09-08 1984-02-21 Ortho Diagnostic Systems Inc. Double antibody conjugate
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4454226A (en) * 1982-03-17 1984-06-12 Majid Ali Enzymatic immunoassay
US4657863A (en) 1982-07-02 1987-04-14 Celanese Corporation Stabilization of a mutant microorganism population
US4657853A (en) * 1984-09-14 1987-04-14 E. I. Du Pont De Nemours And Company Immunoassays utilizing covalent conjugates of polymerized enzyme and antibody
US4732863A (en) 1984-12-31 1988-03-22 University Of New Mexico PEG-modified antibody with reduced affinity for cell surface Fc receptors
US5057313A (en) * 1986-02-25 1991-10-15 The Center For Molecular Medicine And Immunology Diagnostic and therapeutic antibody conjugates
US4810638A (en) * 1986-07-24 1989-03-07 Miles Inc. Enzyme-labeled antibody reagent with polyalkyleneglycol linking group
US4994385A (en) * 1987-10-30 1991-02-19 Abbott Laboratories Heterobifunctional coupling agents
US5002883A (en) * 1987-10-30 1991-03-26 Abbott Laboratories Covalent attachment of antibodies and antigens to solid phases using extended length heterobifunctional coupling agents
US5053520A (en) 1988-09-22 1991-10-01 Abbott Laboratories Heterobifunctional maleimido containing coupling agents
US5063109A (en) * 1988-10-11 1991-11-05 Abbott Laboratories Covalent attachment of antibodies and antigens to solid phases using extended length heterobifunctional coupling agents
US5157123A (en) 1989-03-13 1992-10-20 Georgetown University S-(2-thiopyridyl)-l-cysteine, a heterobifunctional crosslinking reagent
ATE140795T1 (de) 1990-10-22 1996-08-15 Abbott Lab Homobifunktionelle agenzien zur kupplung von enzymen un deren analogen an antikörper und deren analoge
US5191066A (en) * 1990-12-07 1993-03-02 Abbott Laboratories Site-specific conjugation of immunoglobulins and detectable labels
US6787153B1 (en) 1991-06-28 2004-09-07 Mitsubishi Chemical Corporation Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane
JP3236667B2 (ja) * 1991-06-28 2001-12-10 三菱化学株式会社 ヒト型モノクローナル抗体およびそれをコードする遺伝子、ハイブリドーマ並びに抗腫瘍剤
US5329028A (en) * 1992-08-05 1994-07-12 Genentech, Inc. Carbohydrate-directed cross-linking reagents
US6005079A (en) 1992-08-21 1999-12-21 Vrije Universiteit Brussels Immunoglobulins devoid of light chains
PT1621554E (pt) 1992-08-21 2009-07-13 Univ Bruxelles Imunoglobtainas desprovidas de cadeias leves
US5648218A (en) * 1993-02-12 1997-07-15 Sealite Sciences, Inc. Preparation of photoprotein conjugates and methods of use thereof
US5736624A (en) * 1994-12-02 1998-04-07 Abbott Laboratories Phosphatase activated crosslinking, conjugating and reducing agents; methods of using such agents; and reagents comprising phosphatase activated crosslinking and conjugating agents
DE19654823A1 (de) * 1995-12-29 1997-07-03 Biotez Berlin Buch Gmbh Verfahren zur Markierung von Biomolekülen mit Meerrettichperoxidase
KR19990029749A (ko) * 1997-09-17 1999-04-26 미우라 아끼라 2가 반응성 수용성 고분자 유도체 및 이들을 함유하는 복합체
JP4385152B2 (ja) * 1997-09-17 2009-12-16 三菱化学株式会社 ２価反応性水溶性高分子誘導体及びそれを含有する複合体
US6218160B1 (en) * 1997-10-31 2001-04-17 Roche Diagnostics Corporation Site-specific conjugation of glycoproteins
JP3524401B2 (ja) 1998-09-16 2004-05-10 株式会社ニチレイ 酵素抗体複合体およびその製造方法
EP2306195A3 (en) 1998-09-18 2012-04-25 Massachusetts Institute of Technology Biological applications of semiconductor nanocrystals
US6576746B2 (en) * 1998-10-13 2003-06-10 Immunomedics, Inc. Site-specific labeling of disulfide-containing targeting vectors
WO2000054807A1 (en) * 1999-03-17 2000-09-21 Mitsubishi Chemical Corporation Ligand-bonded complex
US20050074499A1 (en) 1999-03-17 2005-04-07 Mitsubishi Chemical Corporation Ligand-bonded complex
US6274323B1 (en) * 1999-05-07 2001-08-14 Quantum Dot Corporation Method of detecting an analyte in a sample using semiconductor nanocrystals as a detectable label
GB9919338D0 (en) * 1999-08-16 1999-10-20 Celltech Therapeutics Ltd Biological products
JP3781934B2 (ja) * 1999-12-22 2006-06-07 株式会社ニチレイバイオサイエンス 酵素−タンパク質複合体
EP1118334A1 (en) * 2000-01-11 2001-07-25 Aventis Behring Gesellschaft mit beschränkter Haftung Method for the production of conjugates and uses thereof for the prevention and treatment of allergic reactions and autoimmune diseases
EP1118335A1 (en) * 2000-01-11 2001-07-25 Aventis Behring GmbH Method for the production of conjugates for the treatment of allergic reactions and autoimmune diseases
US6800728B2 (en) * 2000-03-22 2004-10-05 Solulink Biosciences, Inc. Hydrazine-based and carbonyl-based bifunctional crosslinking reagents
US6649138B2 (en) * 2000-10-13 2003-11-18 Quantum Dot Corporation Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media
US20020083888A1 (en) * 2000-12-28 2002-07-04 Zehnder Donald A. Flow synthesis of quantum dot nanocrystals
US6670113B2 (en) * 2001-03-30 2003-12-30 Nanoprobes Enzymatic deposition and alteration of metals
WO2003092043A2 (en) * 2001-07-20 2003-11-06 Quantum Dot Corporation Luminescent nanoparticles and methods for their preparation
EP2042196B1 (en) 2001-10-10 2016-07-13 ratiopharm GmbH Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF)
US20030149246A1 (en) * 2002-02-01 2003-08-07 Russell John C. Macromolecular conjugates and processes for preparing the same
CA2499075A1 (en) * 2002-09-16 2004-03-25 Elusys Therapeutics, Inc. Production of bispecific molecules using polyethylene glycol linkers
US7217845B2 (en) * 2002-11-25 2007-05-15 Sun Bio, Inc. Bifunctional polyethylene glycol derivatives
US7888536B2 (en) * 2004-02-13 2011-02-15 Quanta Biodesign, Ltd. Selective and specific preparation of discrete PEG compounds
US20050176108A1 (en) * 2003-03-13 2005-08-11 Young-Min Kim Physiologically active polypeptide conjugate having prolonged in vivo half-life
EP1627420B1 (en) 2003-05-07 2020-07-15 Indiana University Research and Technology Corporation Alloyed semiconductor quantum dots and concentration-gradient alloyed quantum dots, series comprising the same and methods related thereto
CA2773566C (en) * 2003-06-24 2015-09-15 Ventana Medical Systems, Inc. Enzyme-catalyzed metal deposition for the enhanced in situ detection of immunohistochemical epitopes and nucleic acid sequences
US7642064B2 (en) * 2003-06-24 2010-01-05 Ventana Medical Systems, Inc. Enzyme-catalyzed metal deposition for the enhanced detection of analytes of interest
KR100657891B1 (ko) * 2003-07-19 2006-12-14 삼성전자주식회사 반도체 나노결정 및 그 제조방법
US7541455B2 (en) * 2003-12-22 2009-06-02 Ventana Medical Systems, Inc. Microwave mediated synthesis of nucleic acid probes
US20050186642A1 (en) * 2004-02-24 2005-08-25 Biocare Medical, Inc. Immunoassay reagents and methods of use thereof
GB0412181D0 (en) * 2004-06-01 2004-06-30 Celltech R&D Ltd Biological products
US7361516B2 (en) 2004-09-24 2008-04-22 The United States Of America As Represented By The Secretary Of The Navy Field of modular multifunctional ligands
CA2606018A1 (en) * 2005-04-28 2006-11-02 Ventana Medical Systems, Inc. Nanoparticle conjugates
JP5628476B2 (ja) * 2005-04-28 2014-11-19 ベンタナ・メデイカル・システムズ・インコーポレーテツド 抗体コンジュゲート
WO2007048127A2 (en) 2005-10-20 2007-04-26 The Scripps Research Institute Fc labeling for immunostaining and immunotargeting
ES2548518T3 (es) * 2005-11-23 2015-10-19 Ventana Medical Systems, Inc. Conjugado molecular

Also Published As

Publication number Publication date
EP1877101A2 (en) 2008-01-16
CA2609702C (en) 2013-05-28
US20090176253A1 (en) 2009-07-09
WO2006116628A2 (en) 2006-11-02
US20060246523A1 (en) 2006-11-02
JP2008539270A (ja) 2008-11-13
US8658389B2 (en) 2014-02-25
DK1877101T3 (en) 2017-01-09
US11359185B2 (en) 2022-06-14
US20160187324A1 (en) 2016-06-30
CA2609702A1 (en) 2006-11-02
WO2006116628A3 (en) 2007-12-13
EP3144675A1 (en) 2017-03-22
US20140147906A1 (en) 2014-05-29
AU2006239315A1 (en) 2006-11-02
US9315789B2 (en) 2016-04-19
AU2006239315B2 (en) 2012-03-01
EP1877101B1 (en) 2016-11-16
JP5628476B2 (ja) 2014-11-19

Similar Documents

Publication Publication Date Title
Shabat Self‐immolative dendrimers as novel drug delivery platforms
JP5628476B2 (ja) 抗体コンジュゲート
Versteegen et al. Click to release: instantaneous doxorubicin elimination upon tetrazine ligation
de Groot et al. “Cascade‐release dendrimers” liberate all end groups upon a single triggering event in the dendritic core
WO2005037992A3 (en) Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
EP0539477B1 (fr) Procede d'amplification du signal d'emission d'un compose luminescent
James et al. Catalytic and binding poly‐reactivities shared by two unrelated proteins: The potential role of promiscuity in enzyme evolution
Lerchen et al. Antibody–drug conjugates with pyrrole‐based KSP inhibitors as the payload class
Jbara et al. Oligonucleotide bioconjugation with bifunctional palladium reagents
Schneider et al. Dextramabs: a novel format of antibody‐drug conjugates featuring a multivalent polysaccharide scaffold
Fontaine et al. Drug delivery to the malaria parasite using an arterolane‐like scaffold
JP2021521202A (ja) 固形腫瘍の治療のための標的化されたアマトキシン複合体
PE20211473A1 (es) Conjugados de anticuerpo-farmaco de herboxidieno y metodos de uso
Shabat et al. Chemical adaptor systems
Lai et al. Enhanced cytotoxicity of saporin by polyamidoamine dendrimer conjugation and photochemical internalization
Refsnes et al. Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells
Park et al. Excited-state tautomerization dynamics of 7-hydroxyquinoline in β-cyclodextrin
Guo et al. RNA Control via Redox‐Responsive Acylation
Singh et al. Antibody–drug conjugates with indolinobenzodiazepine dimer payloads: DNA-binding mechanism of indolinobenzodiazepine dimer catabolites in target cancer cells
JP2011173960A (ja) 高分子ミセル型光刺激応答性一酸化窒素供与体
Zhang et al. Switchable Enzymatic Accessibility for Precision Cell‐Selective Surface Glycan Remodeling
EP0454783A1 (en) IN VIVO ACTIVATION SPECIFIC TO A SITE OF THERAPEUTIC DRUGS.
Reille‐Seroussi et al. Genetic encoding and enzymatic deprotection of a latent thiol side chain to enable new protein bioconjugation applications
Chen et al. Nanoalbumin–prodrug conjugates prepared via a thiolation‐and‐conjugation method improve cancer chemotherapy and immune checkpoint blockade therapy by promoting CD8+ T‐cell infiltration
EP1161685B1 (fr) Reduction de l'extinction de fluorescence lors d'un dosage