RU2007116973A - Терапевтические средства с пониженной токсичностью - Google Patents
Терапевтические средства с пониженной токсичностью Download PDFInfo
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- RU2007116973A RU2007116973A RU2007116973/13A RU2007116973A RU2007116973A RU 2007116973 A RU2007116973 A RU 2007116973A RU 2007116973/13 A RU2007116973/13 A RU 2007116973/13A RU 2007116973 A RU2007116973 A RU 2007116973A RU 2007116973 A RU2007116973 A RU 2007116973A
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- conjugate molecule
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
-
- 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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
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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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2318/00—Antibody mimetics or scaffolds
- C07K2318/10—Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Transplantation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (27)
1. Молекула конъюгата, содержащая по меньшей мере один связывающий сывороточный альбумин домен (SABM), по меньшей мере одно направляющее к мишени средство (TA) и по меньшей мере одно цитотоксическое средство (CA).
2. Молекула конъюгата по п.1, в котором SABM содержит аминокислотную последовательность, которая по меньшей мере на 50% идентична последовательности DICLPRWGCLW (SEQ ID NO: 8), и в котором аминокислотная последовательность имеет два остатка Cys с пятью аминокислотными остатками между остатками Cys.
3. Молекула конъюгата по п.1, в котором SABM содержит вариант аминокислотной последовательности DICLPRWGCLW (SEQ ID NO: 8), в котором от 1 до 5 любых остатков последовательности SEQ ID NO: 8, за исключением остатков Cys, заменены другим аминокислотным остатком.
5. Молекула конъюгата по п.1, в котором SABM содержит любую одну из аминокислотных последовательностей, выбранных из группы, состоящей из SEQ ID NO: 7-20, 27-154 и 157-421.
6. Молекула конъюгата по п.1, в котором SABM содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 и 20.
7. Молекула конъюгата по п.1, в котором SABM содержит любую одну из последовательностей пептидов, описанных в таблицах 1-9.
8. Молекула конъюгата по п.1, в котором SABM связывается с сывороточным альбумином с Kd, которая составляет примерно 100 мкМ или меньше.
9. Молекула конъюгата по п. 1, в котором TA является антителом.
10. Молекула конъюгата по п.9, в котором антитело представляет собой Fab, F(ab)2, scFv или диантитело.
11. Молекула конъюгата по п.1, в котором TA связывается с белком клеточной поверхности, уровень которого повышен в злокачественной опухоли.
12. Молекула конъюгата по п.11, в котором белком клеточной поверхности является HER2, PSMA, PCMA, KDR и Flt-1.
13. Молекула конъюгата по п.11, в котором белок клеточной поверхности является поверхностным маркером B-клеток.
14. Молекула конъюгата по п.11, в котором белок поверхности клеток является поверхностным маркером B-клеток CD20 или BR3.
15. Молекула конъюгата по п.1, в котором TA представляет собой анти-HER2-антитело.
16. Молекула конъюгата по п.15, в котором TA представляет собой антитело, имеющее последовательности VH и VL SEQ ID NO: 428 и 429.
17. Молекула конъюгата по п.l5, в котором TA содержит вариант последовательности анти-HER2-антитела, который содержит последовательности SEQ ID NO: 428 и SEQ ID NO: 429.
18. Молекула конъюгата по п.1, в котором цитотоксическим средством является монометилауристатин (MMAE).
19. Молекула конъюгата по п.1, в котором линкерным компонентом, расположенным между указанным SABM и направляющим к мишени средством или цитотоксическим средством, является GGGS.
20. Молекула конъюгата по п.1, в котором SABM связывается с альбумином человека.
21. Композиция, содержащая молекулу конъюгата по п.1 в смеси с фармацевтическим носителем для терапевтического применения.
22. Способ снижения токсичности терапевтического средства, включающий в себя стадию получения терапевтического средства со связывающим сывороточный альбумин компонентом (SABM), конъюгированным с терапевтическим средством.
23. Способ снижения токсичности терапевтического средства у млекопитающего, включающий в себя введение млекопитающему терапевтически эффективного количества молекулы конъюгата по п.1.
24. Способ по п.22 или 23, дополнительно включающий в себя стадию измерения токсичности конъюгата терапевтическое средство:SABM in vivo.
25. Способ лечения злокачественной опухоли у млекопитающего, включающий в себя стадию лечения млекопитающего, имеющего злокачественную опухоль, терапевтически эффективным количеством молекулы конъюгата по п.1.
26. Способ лечения аутоиммунного расстройства у млекопитающего, включающий в себя стадию лечения млекопитающего, имеющего аутоиммунное расстройство, терапевтически эффективным количеством молекулы конъюгата по п.1, которая связывается с B-клетками, которые вносят вклад или вызывают аутоиммунное расстройство.
27. Предмет производства, содержащий емкость, композицию в емкости, содержащую молекулу конъюгата по п.1, вкладыш в упаковку, содержащий инструкции по введению терапевтически эффективной дозы.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61650704P | 2004-10-05 | 2004-10-05 | |
US60/616,507 | 2004-10-05 | ||
US64153405P | 2005-01-05 | 2005-01-05 | |
US60/641,534 | 2005-01-05 |
Publications (1)
Publication Number | Publication Date |
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RU2007116973A true RU2007116973A (ru) | 2008-11-20 |
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RU2007116973/13A RU2007116973A (ru) | 2004-10-05 | 2005-09-22 | Терапевтические средства с пониженной токсичностью |
Country Status (11)
Country | Link |
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US (2) | US20060073152A1 (ru) |
EP (1) | EP1796718A2 (ru) |
JP (1) | JP2008515889A (ru) |
KR (1) | KR20070073886A (ru) |
AU (1) | AU2005294723A1 (ru) |
BR (1) | BRPI0516577A (ru) |
CA (1) | CA2583137A1 (ru) |
IL (1) | IL182261A0 (ru) |
MX (1) | MX2007003907A (ru) |
RU (1) | RU2007116973A (ru) |
WO (1) | WO2006041641A2 (ru) |
Families Citing this family (23)
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KR101520209B1 (ko) * | 2003-11-06 | 2015-05-13 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
-
2005
- 2005-09-22 WO PCT/US2005/033952 patent/WO2006041641A2/en active Application Filing
- 2005-09-22 EP EP05810079A patent/EP1796718A2/en not_active Withdrawn
- 2005-09-22 CA CA002583137A patent/CA2583137A1/en not_active Abandoned
- 2005-09-22 AU AU2005294723A patent/AU2005294723A1/en not_active Abandoned
- 2005-09-22 RU RU2007116973/13A patent/RU2007116973A/ru not_active Application Discontinuation
- 2005-09-22 MX MX2007003907A patent/MX2007003907A/es not_active Application Discontinuation
- 2005-09-22 US US11/233,256 patent/US20060073152A1/en not_active Abandoned
- 2005-09-22 BR BRPI0516577-6A patent/BRPI0516577A/pt not_active Application Discontinuation
- 2005-09-22 KR KR1020077010255A patent/KR20070073886A/ko not_active Application Discontinuation
- 2005-09-22 JP JP2007535700A patent/JP2008515889A/ja not_active Withdrawn
-
2006
- 2006-09-25 US US11/535,027 patent/US20090123376A1/en not_active Abandoned
-
2007
- 2007-03-28 IL IL182261A patent/IL182261A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
JP2008515889A (ja) | 2008-05-15 |
CA2583137A1 (en) | 2006-04-20 |
US20060073152A1 (en) | 2006-04-06 |
AU2005294723A1 (en) | 2006-04-20 |
EP1796718A2 (en) | 2007-06-20 |
MX2007003907A (es) | 2007-05-21 |
WO2006041641A2 (en) | 2006-04-20 |
KR20070073886A (ko) | 2007-07-10 |
BRPI0516577A (pt) | 2008-09-16 |
WO2006041641A3 (en) | 2006-06-29 |
US20090123376A1 (en) | 2009-05-14 |
IL182261A0 (en) | 2007-07-24 |
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