EA201100228A1 - Структурные варианты антител для улучшения терапевтических характеристик - Google Patents

Структурные варианты антител для улучшения терапевтических характеристик

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Publication number
EA201100228A1
EA201100228A1 EA201100228A EA201100228A EA201100228A1 EA 201100228 A1 EA201100228 A1 EA 201100228A1 EA 201100228 A EA201100228 A EA 201100228A EA 201100228 A EA201100228 A EA 201100228A EA 201100228 A1 EA201100228 A1 EA 201100228A1
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Eurasian Patent Office
Prior art keywords
antibodies
less
improved
antigen binding
fusion proteins
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EA201100228A
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English (en)
Inventor
Дейвид М. Голденберг
Чиэньсин Чан
Ханс Дж. Хансен
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Иммьюномедикс, Инк.
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Publication of EA201100228A1 publication Critical patent/EA201100228A1/ru

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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • 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
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • A—HUMAN NECESSITIES
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    • C07—ORGANIC CHEMISTRY
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    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]

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Abstract

Настоящее изобретение предлагает замещенные гуманизированные, химерные или человеческие антитела анти-CD20 или их антигенсвязывающие фрагменты и биспецифичные антитела или слитые белки, содержащие замещенные антитела или их антигенсвязывающие фрагменты. Антитела, слитые белки или фрагменты полезны для лечения В-клеточных нарушений, таких как В-клеточные злокачественные опухоли и аутоиммунные заболевания, а также реакции "трансплантат против хозяина", отторжение трансплантата органов и гемолитическая анемия и криоглобулинемия. Аминокислотные замены, в частности замена аспартатного остатка в положении 101 Кабат из VCDR3 (CDRH3), приводят к улучшению терапевтических свойств, таких как снижение скоростей диссоциации, улучшение CDC активности, улучшение апоптоза, уменьшение количеств В-клеток и улучшение терапевтической эффективности при очень низких дозах. Велтузумаб, гуманизированное антитело анти-CD20, которое включает такие изменения последовательности, демонстрирует улучшение терапевтической эффективности по сравнению с аналогичными антителами различных CDRH3 последовательностей, что позволяет достичь терапевтического эффекта при дозах, равных 200 мг или менее, более предпочтительно 100 мг или менее, более предпочтительно 80 мг или менее, более предпочтительно 50 мг или менее, наиболее предпочтительно 30 мг или менее голого антитела при введении внутривенно или подкожно.
EA201100228A 2008-07-21 2009-07-21 Структурные варианты антител для улучшения терапевтических характеристик EA201100228A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US8239908P 2008-07-21 2008-07-21
PCT/US2009/051321 WO2010011697A1 (en) 2008-07-21 2009-07-21 Structural variants of antibodies for improved therapeutic characteristics

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EA201100228A1 true EA201100228A1 (ru) 2011-08-30

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US (2) US7919273B2 (ru)
EP (1) EP2318048B1 (ru)
JP (1) JP6049163B2 (ru)
KR (1) KR20110033233A (ru)
CN (1) CN102159243B (ru)
AU (1) AU2009274129B2 (ru)
BR (1) BRPI0917204A2 (ru)
CA (1) CA2731255C (ru)
EA (1) EA201100228A1 (ru)
HK (1) HK1155388A1 (ru)
IL (1) IL210307B (ru)
MX (1) MX2011000891A (ru)
NZ (1) NZ590330A (ru)
UA (1) UA108735C2 (ru)
WO (1) WO2010011697A1 (ru)
ZA (1) ZA201100013B (ru)

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CA2731255C (en) 2018-06-05
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