RU2006103854A - Антитела к рецептору инсулиноподобного фактора роста i и их применение - Google Patents
Антитела к рецептору инсулиноподобного фактора роста i и их применение Download PDFInfo
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- RU2006103854A RU2006103854A RU2006103854/13A RU2006103854A RU2006103854A RU 2006103854 A RU2006103854 A RU 2006103854A RU 2006103854/13 A RU2006103854/13 A RU 2006103854/13A RU 2006103854 A RU2006103854 A RU 2006103854A RU 2006103854 A RU2006103854 A RU 2006103854A
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- Prior art keywords
- igf
- antibody
- antibodies
- cells
- phosphorylation
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Classifications
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- C—CHEMISTRY; METALLURGY
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- 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
- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (18)
1. Антитело, связывающееся с IGF-IR и ингибирующее связывание IGF-I IGF-II с IGF-IR; имеющее следующие свойства:
a) изотип IgGI,
b) соотношение величин IC50 для ингибирования связывания IGF-I с IGF-IR к ингибированию связывания IGF-II с IGF-IR составляет 1:3-3:1;
c) в концентрации 5 нМ ингибирует фосфорилирование IGF-IR по крайней мере на 80%, что определяют с помощью исследования фосфорилирования при использовании клеток НТ29 в среде, содержащей 0,5% инактивированной нагреванием эмбриональной телячьей сыворотки (FCS) при сравнении с результатами такого же исследования, но без указанного антитела,
d) не обладает IGF-IR стимулирующей активностью, которую измеряют по степени фосфорилирования IGF-IR, в концентрации 10 мкМ в исследовании фосфорилирования при использовании ЗТЗ клеток, где на одну клетку в среде, содержащей 0,5% инактивированной нагреванием эмбриональной телячьей сыворотки (FCS), приходится от 400000 до 600000 молекул IGF-IR, при сравнении с результатами такого же исследования, но без указанного антитела;
2. Антитело по п.1, характеризующееся тем, что оно обладает способностью индуцировать гибель 20% клеток и более в культуре, экспрессирующей IGF-IR, через 24 ч в концентрации 100 нМ с помощью ADCC.
3. Антитело по п.1, характеризующееся тем, что оно обладает способностью индуцировать гибель 20% клеток и более в культуре, экспрессирующей IGF-IR через 4 ч в концентрации 100 нМ с помощью CDC.
4. Антитело по п.1, представляющее собой гуманизированное антитело или антитело человека.
5. Антитело по п.1, аффинность которого составляет приблизительно 10-13-10-9 М(КD).
6. Антитело по п.1, имеющее в своем составе участки, определяющие комплементарность (CDRs), имеющие следующие последовательности:
a) тяжелая цепь антитела, включающая CDRs CDR1 (аа 31-35), CDR2 (аа 50-66) и CDR3 (аа 99-107) SEQ ID NO: 1 или 3;
b) легкая цепь антитела, включающая CDRs CDR1 (аа 24-34), CDR2 (аа 50-56) и CDR3 (аа 89-98) SEQ ID NO: 2 или 4;
7. Антитело по п.1, получаемое из клеточной линии гибридомы <IGF-IR>HUMAB Клон 18 (DSM АСС 2587) или <IGF-IR>HUMAB Клон 22 (DSM АСС 2594).
8. Применение антитела по пп.1 и 7 для получения фармацевтической композиции.
9. Фармацевтическая композиция, содержащая антитело по пп.1 и 7 в фармацевтически эффективном количестве.
10. Клеточные линии гибридом <IGF-IR>HUMAB Клон 18 (DSM АСС 2587) и <IGF-IR>HUMAB Клон 22 (DSM АСС 2594).
11. Способ получения фармацевтической композиции, содержащей фармацевтически эффективное количество антитела по пп.1 и 7.
12. Нуклеиновая кислота, кодирующая полипептид, способный объединяться вместе с соответствующей цепью другого антитела, примеры которой приведены ниже
a) тяжелая цепь антитела, включающая CDRs CDR1 (аа 31-35), CDR2 (аа 50-66) и CDR3 (аа 99-107) SEQ ID NO: 1 или 3;
b) легкая цепь антитела, включающая CDRs CDR1 (аа 24-34), CDR2 (аа 50-56) и CDR3 (аа 89-98) SEQ ID NO: 2 или 4;
13. Вектор экспрессии, кодирующий нуклеиновую кислоту по п.12, способный экспрессировать указанную нуклеиновую кислоту в прокариотических и эукариотических клетках-хозяевах.
14. Прокариотическая или эукариотическая клетка-хозяин, содержащая вектор по п.13.
15. Способ получения полипептида, связывающегося с IGF-IR и ингибирующего связывание IGF-I и IGF-II с IGF-IR, заключающийся в экспрессии нуклеиновой кислоты, кодирующей тяжелую цепь, и нуклеиновой кислоты, кодирующей легкую цепь, по п.11 в прокариотических и эукариотических клетках-хозяевах и выделении указанного полипептида их этих клеток.
16. Способ лечения пациентов, нуждающихся в противоопухолевой терапии, заключающийся во введении указанным пациентам терапевтически эффективного количества антитела по пп.1 и 7.
17. Способ по п.16, заключающийся во введении анитела в комбинации с цитотоксическим агентом, его пролекарством или совместном применении его с цитотоксической радиотерапией.
18. Способ получения фармацевтической композиции, который заключается в выборе антитела к IGF-IR из множества других антител к IGF-IR, что осуществляют с помощью исследования клеточного фосфорилирования с указанными антителами с использованием клеток ЗТЗ, причем на одну клетку в среде, содержащей 0,5% инактивированной нагреванием эмбриональной телячьей сыворотки (FCS), приходится от 400000 до 600000 молекул IGF-IR, и при этом отбирается антитело, не обладающее IGF-стимулирующей активностью, которая измеряется как РКВ фосфорилирование в концентрации 10 мкМ, при сравнении с результатами аналогичного исследования, но без указанного антитела; получении указанного антитела с помощью рекомбинантной экспрессии; выделении указанного антитела и объединении его с фармацевтически приемлемым буфером и/или адъювантом.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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EP03015526 | 2003-07-10 | ||
EP03015526.1 | 2003-07-10 |
Related Child Applications (1)
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RU2008126743/13A Division RU2008126743A (ru) | 2003-07-10 | 2008-07-02 | Способ получения фармацевтической композиции |
Publications (2)
Publication Number | Publication Date |
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RU2006103854A true RU2006103854A (ru) | 2007-08-20 |
RU2363706C2 RU2363706C2 (ru) | 2009-08-10 |
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Application Number | Title | Priority Date | Filing Date |
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RU2006103854/13A RU2363706C2 (ru) | 2003-07-10 | 2004-07-09 | Антитела к рецептору инсулиноподобного фактора роста i и их применение |
RU2008126743/13A RU2008126743A (ru) | 2003-07-10 | 2008-07-02 | Способ получения фармацевтической композиции |
Family Applications After (1)
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RU2008126743/13A RU2008126743A (ru) | 2003-07-10 | 2008-07-02 | Способ получения фармацевтической композиции |
Country Status (29)
Country | Link |
---|---|
US (3) | US7579157B2 (ru) |
EP (4) | EP1959014B9 (ru) |
JP (2) | JP4276262B2 (ru) |
KR (1) | KR100795745B1 (ru) |
CN (1) | CN100453645C (ru) |
AR (1) | AR046071A1 (ru) |
AT (2) | ATE413454T1 (ru) |
AU (3) | AU2004256215B2 (ru) |
BR (1) | BRPI0412478B8 (ru) |
CA (1) | CA2532173C (ru) |
CO (1) | CO5640053A1 (ru) |
CY (1) | CY1116227T1 (ru) |
DE (2) | DE602004017614D1 (ru) |
DK (3) | DK1959014T5 (ru) |
ES (3) | ES2534638T3 (ru) |
HK (1) | HK1094713A1 (ru) |
IL (1) | IL172925A (ru) |
MX (1) | MXPA06000270A (ru) |
MY (1) | MY140209A (ru) |
NO (2) | NO339935B1 (ru) |
NZ (1) | NZ544455A (ru) |
PL (3) | PL2272873T3 (ru) |
PT (3) | PT1646720E (ru) |
RU (2) | RU2363706C2 (ru) |
SG (1) | SG129437A1 (ru) |
SI (1) | SI2272873T1 (ru) |
TW (1) | TWI290147B (ru) |
WO (1) | WO2005005635A2 (ru) |
ZA (1) | ZA200600181B (ru) |
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2009
- 2009-07-17 US US12/504,717 patent/US20090275126A1/en not_active Abandoned
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2015
- 2015-04-27 CY CY20151100386T patent/CY1116227T1/el unknown
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2016
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