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RU2430927C2 - Atomic compound capable of specifically identifying and cross linkinking cell surface molecule or intracellular molecule - Google Patents

Atomic compound capable of specifically identifying and cross linkinking cell surface molecule or intracellular molecule Download PDF

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Publication number
RU2430927C2
RU2430927C2 RU2006127049/10A RU2006127049A RU2430927C2 RU 2430927 C2 RU2430927 C2 RU 2430927C2 RU 2006127049/10 A RU2006127049/10 A RU 2006127049/10A RU 2006127049 A RU2006127049 A RU 2006127049A RU 2430927 C2 RU2430927 C2 RU 2430927C2
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compound
molecule
cell surface
intracellular
compound according
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RU2006127049/10A
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Russian (ru)
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RU2006127049A (en
Inventor
Наоси ФУКУСИМА (JP)
Наоси ФУКУСИМА
Масаюки ЦУТИЯ (JP)
Масаюки ЦУТИЯ
Синсуке УНО (JP)
Синсуке УНО
Тосихико ОХТОМО (JP)
Тосихико ОХТОМО
Наохиро ЯБУТА (JP)
Наохиро ЯБУТА
Хироюки ЦУНОДА (JP)
Хироюки ЦУНОДА
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Тугаи Сейяку Кабусики Кайся
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Priority claimed from PCT/JP2001/003288 external-priority patent/WO2001079494A1/en
Application filed by Тугаи Сейяку Кабусики Кайся filed Critical Тугаи Сейяку Кабусики Кайся
Publication of RU2006127049A publication Critical patent/RU2006127049A/en
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Abstract

FIELD: chemistry.
SUBSTANCE: invention relates to a compound which contains two or more V-regions of an H-chain and two or more V-regions of an L-chain of a monoclonal antibody, joined directly or through a linker by a covalent or noncovalent bond. The compound is a whole antibody or F(ab')2 and has two or more antigen-binding sites. The compound is capable of transducing a signal to cells by forming cell surface molecule cross links, thus playing the role of an agonist. The compound can be used as a signal transduction agonist and can therefore be used as a prophylactic and/or therapeutic agent for different diseases such as cancer, inflammation, hormonal disorders and blood disorders.
EFFECT: disclosed compound exhibits higher agonistic activity compared to a natural ligand such as TPO.
7 cl, 61 dwg, 3 tbl, 1 ex

Description

Текст описания приведен в факсимильном виде.

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The text of the description is given in facsimile form.
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Claims (6)

1. Соединение, содержащее две или более V-областей Н-цепи и две или более V-областей L-цепи моноклонального антитела, объединенных непосредственно или через линкер ковалентной или нековалентной связью, где указанное исходное моноклональное антитело узнает рецепторы и поперечно сшивает их межклеточно, причем указанное соединение обнаруживает эквивалентное или лучшее агонистическое действие (ED50) в сравнении с природным лигандом, который связывается с молекулой (молекулами) клеточной поверхности или с внутриклеточной молекулой (молекулами), где указанное соединение представляет собой целое антитело или F(ab')2, причем указанное соединение имеет два или более антигенсвязывающих участков, и где указанное соединение способно специфически узнавать и внутриклеточно поперечно сшивать молекулу (молекулы) клеточной поверхности или внутриклеточную молекулу (внутриклеточные молекулы).1. A compound containing two or more V-regions of the H chain and two or more V-regions of the L chain of a monoclonal antibody, linked directly or via a linker with a covalent or non-covalent bond, wherein said parent monoclonal antibody recognizes the receptors and cross-links them intercellularly, wherein said compound exhibits an equivalent or better agonistic effect (ED50) compared to a natural ligand that binds to a cell surface molecule (s) or to an intracellular molecule (s) ), wherein said compound is a whole antibody or F (ab ') 2, wherein said compound has two or more antigen binding sites, and where said compound is capable of specifically recognizing and intracellularly crosslinking a cell surface molecule (s) or an intracellular molecule (intracellular molecules ) 2. Соединение по п.1, которое обнаруживает по меньшей мере в 2 раза большее агонистическое действие (ED50) в сравнении с природным лигандом, который связывается с молекулой (молекулами) клеточной поверхности или с внутриклеточной молекулой (внутриклеточными молекулами).2. The compound according to claim 1, which exhibits at least a 2-fold greater agonistic effect (ED50) compared to a natural ligand that binds to a cell surface molecule (s) or an intracellular molecule (intracellular molecules). 3. Соединение по п.2, которое обнаруживает по меньшей мере в 10 раз большее агонистическое действие (ED50) в сравнении с природным лигандом, который связывается с молекулой (молекулами) клеточной поверхности или с внутриклеточной молекулой (внутриклеточными молекулами).
4 Соединение по любому из пп.1-3, которое, по существу, не имеет межклеточного адгезионного действия.3. The compound according to claim 2, which exhibits at least 10 times greater agonistic action (ED50) compared to a natural ligand that binds to a cell surface molecule (s) or an intracellular molecule (intracellular molecules).
4 A compound according to any one of claims 1 to 3, which essentially has no intercellular adhesive action. 5. Соединение по любому из пп.1-3, которое имеет межклеточное адгезионное действие (ED50), составляющее не более чем 1/10 в сравнении с исходным антителом.5. The compound according to any one of claims 1 to 3, which has an intercellular adhesive action (ED50) of not more than 1/10 in comparison with the original antibody. 6. Соединение по любому из пп.1-5, которое имеет от двух до шести антигенсвязывающих участков.6. The compound according to any one of claims 1 to 5, which has from two to six antigen binding sites. 7. Соединение по любому из пп.1-5, которое имеет два антигенсвязывающих участка. 7. The compound according to any one of claims 1 to 5, which has two antigen-binding sites.
RU2006127049/10A 2000-10-20 2001-10-22 Atomic compound capable of specifically identifying and cross linkinking cell surface molecule or intracellular molecule RU2430927C2 (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
JP2000-321821 2000-10-20
JP2000321821 2000-10-20
JP2000321822 2000-10-20
JP2000-321822 2000-10-20
JPPCT/JP01/01912 2001-03-12
JPPCT/JP01/03288 2001-04-17
PCT/JP2001/003288 WO2001079494A1 (en) 2000-04-17 2001-04-17 Agonist antibodies
JP2001-277314 2001-09-12

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RU2003114746/13A Division RU2295537C2 (en) 2000-10-20 2001-10-22 Modified antagonistic antibody

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WO2008076960A2 (en) * 2006-12-18 2008-06-26 Genentech, Inc. Antagonist anti-notch3 antibodies and their use in the prevention and treatment of notch3-related diseases
EP2050764A1 (en) 2007-10-15 2009-04-22 sanofi-aventis Novel polyvalent bispecific antibody format and uses thereof
US20090162359A1 (en) 2007-12-21 2009-06-25 Christian Klein Bivalent, bispecific antibodies
US8268314B2 (en) * 2008-10-08 2012-09-18 Hoffmann-La Roche Inc. Bispecific anti-VEGF/anti-ANG-2 antibodies
DK2417156T3 (en) 2009-04-07 2015-03-02 Roche Glycart Ag Trivalent, bispecific antibodies
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
US8703132B2 (en) * 2009-06-18 2014-04-22 Hoffmann-La Roche, Inc. Bispecific, tetravalent antigen binding proteins
CA2781519A1 (en) 2009-09-16 2011-03-24 Genentech, Inc. Coiled coil and/or tether containing protein complexes and uses thereof
US8298535B2 (en) * 2010-02-24 2012-10-30 Rinat Neuroscience Corp. Anti-IL-7 receptor antibodies
TW201138821A (en) 2010-03-26 2011-11-16 Roche Glycart Ag Bispecific antibodies
CA2807278A1 (en) 2010-08-24 2012-03-01 F. Hoffmann - La Roche Ag Bispecific antibodies comprising a disulfide stabilized - fv fragment
RU2440142C1 (en) * 2011-02-07 2012-01-20 Общество С Ограниченной Ответственностью "Онкомакс" Antibody, stopping or retarding tumour growth (versions), method of suppressing tumour growth, method of diagnosing malignant lesions
CN103403025B (en) 2011-02-28 2016-10-12 弗·哈夫曼-拉罗切有限公司 Monovalent antigen binding protein
JP5764677B2 (en) * 2011-02-28 2015-08-19 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト Antigen binding protein
KR101886983B1 (en) * 2011-08-23 2018-08-08 로슈 글리카트 아게 Fc-free antibodies comprising two fab fragments and methods of use
RU2016115866A (en) 2013-10-11 2017-11-16 Ф. Хоффманн-Ля Рош Аг MULTI-SPECIFIC ANTIBODIES WITH EXCHANGED DOMAINS AND SAME VARIABLE DOMAINS OF EASY CHAIN
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