RU2015119165A - Клеточно-реактивные аналоги компстатина, аналоги компстатина длительного действия или аналоги компстатина нацеленного действия, и связанные с ними композиции и способы - Google Patents
Клеточно-реактивные аналоги компстатина, аналоги компстатина длительного действия или аналоги компстатина нацеленного действия, и связанные с ними композиции и способы Download PDFInfo
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- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- A61K38/00—Medicinal preparations containing peptides
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- A61K38/10—Peptides having 12 to 20 amino acids
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- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
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- A—HUMAN NECESSITIES
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- 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
- A61K47/54—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 organic compound
- A61K47/55—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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
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- A—HUMAN NECESSITIES
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- 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
- A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
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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
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- Transplantation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Claims (28)
1. Аналог компстатина, содержащий клик-химическую группу, причем указанный аналог компстатина содержит соединение, содержащее любую из последовательностей SEQ ID NO: 3-36, 37, 71, 72, 73, 74 или 75.
2. Аналог компстатина длительного действия, содержащий снижающий клиренс фрагмент, присоединенный к двум фрагментам аналога компстатина, причем
каждый фрагмент аналога компстатина содержит циклический пептид, удлиненный на одну или более аминокислот на N-конце, С-конце или на обоих концах, причем одна или более аминокислот отделена от циклической части указанного пептида жестким или гибким спейсером, содержащим фрагмент олиго(этиленгликоля); и
указанный снижающий клиренс фрагмент содержит линейный полимер, причем каждый конец указанного линейного полимера связан с одним из фрагментов аналога компстатина посредством карбамата или амида.
3. Аналог компстатина длительного действия, содержащий снижающий клиренс фрагмент, присоединенный к двум фрагментам аналога компстатина, причем
каждый фрагмент аналога компстатина содержит циклический пептид, содержащий аминокислотную последовательность, представленную в любой из SEQ ID NO: 71, 72, 73, 74 или 75, удлиненный на одну или более аминокислот на N-конце, С-конце или на обоих концах, причем одна или более аминокислот отделена от циклической части указанного пептида жестким или гибким спейсером, содержащим фрагмент олиго(этиленгликоля); и
указанный снижающий клиренс фрагмент содержит линейный полимер, причем каждый конец указанного линейного полимера связан с одним из фрагментов аналога компстатина посредством линкерной группировки, содержащей карбонильную группу.
4. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный циклический пептид содержит аминокислотную последовательность, представленную в любой из SEQ ID NO: 3-36, 71, 72, 73, 74 или 75.
5. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный циклический пептид удлинен на аминокислотную последовательность, которая содержит по меньшей мере одну аминокислоту с боковой цепью, содержащей первичный или вторичный амин.
6. Аналог компстатина длительного действия по п. 5, отличающийся тем, что указанная по меньшей мере одна аминокислота с боковой цепью, содержащей первичный или вторичный амин, представляет собой лизин на С-конце указанного циклического пептида.
7. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный фрагмент олиго(этиленгликоля) представляет собой (-(O-СН2-СН2-)n, где n составляет от 1 до 10.
8. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный спейсер содержит ковалентно связанные -(СН2)m- и -(O-CH2-CH2-)n, где m составляет от 1 до 10, и n составляет от 1 до 10.
9. Аналог компстатина длительного действия по п. 8, отличающийся тем, что m составляет 1 и n составляет 2.
10. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный спейсер содержит 8-амино-3,6-диоксаоктановую кислоту (АЕЕАс) или 11-амино-3,6,9-триоксаундекановую кислоту.
11. Аналог компстатина длительного действия по п. 2, отличающийся тем, что указанный линейный полимер представляет собой полиэтиленгликоль (ПЭГ) или полиоксазолин (ПОЗ).
12. Аналог компстатина длительного действия по п. 11, отличающийся тем, что указанный линейный полимер представляет собой ПЭГ.
13. Аналог компстатина длительного действия по п. 12, отличающийся тем, что указанный ПЭГ имеет среднюю молекулярную массу примерно от 30 кДа до примерно 50 кДа.
14. Аналог компстатина длительного действия по п. 13, отличающийся тем, что указанный ПЭГ имеет среднюю молекулярную массу примерно от 35 кДа до примерно 45 кДа.
15. Аналог компстатина длительного действия по п. 14, отличающийся тем, что указанный ПЭГ имеет среднюю молекулярную массу примерно от 37,5 кДа до примерно 42,5 кДа.
16. Аналог компстатина длительного действия по п. 15, отличающийся тем, что указанный ПЭГ имеет среднюю молекулярную массу примерно 40 кДа.
17. Аналог компстатина длительного действия по п. 2, у которого конечное время полужизни составляет по меньшей мере примерно 3 дня при введении примату.
18. Аналог компстатина длительного действия по п. 17, у которого конечное время полужизни составляет по меньшей мере примерно 5 дней при введении примату.
19. Аналог компстатина длительного действия по п. 2, у которого активность в молярном выражении составляет по меньшей мере 90% от активности аналога компстатина, содержащего ту же последовательность аналога компстатина, что и указанный фрагмент аналога компстатина, но не связанного с указанным снижающим клиренс фрагментом.
20. Способ лечения субъекта, страдающего от или подверженного риску комплемент-опосредованного расстройства, включающий введение субъекту эффективного количества аналога компстатина по п. 2.
21. Композиция фармацевтического класса, содержащая аналог компстатина длительного действия по п. 2.
22. Способ получения аналога компстатина длительного действия, включающий реакцию соединения Формулы В
с фрагментом аналога компстатина.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201261727094P | 2012-11-15 | 2012-11-15 | |
US61/727,094 | 2012-11-15 | ||
PCT/US2013/070417 WO2014078731A2 (en) | 2012-11-15 | 2013-11-15 | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
Publications (2)
Publication Number | Publication Date |
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RU2015119165A true RU2015119165A (ru) | 2017-01-10 |
RU2705215C2 RU2705215C2 (ru) | 2019-11-06 |
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RU2015119165A RU2705215C2 (ru) | 2012-11-15 | 2013-11-15 | Клеточно-реактивные аналоги компстатина, аналоги компстатина длительного действия или аналоги компстатина нацеленного действия и связанные с ними композиции и способы |
Country Status (25)
Country | Link |
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US (4) | US10035822B2 (ru) |
EP (3) | EP3929206A1 (ru) |
JP (5) | JP2016505527A (ru) |
CN (2) | CN105051057B (ru) |
AU (4) | AU2013344462B2 (ru) |
BR (1) | BR112015011244B1 (ru) |
CA (1) | CA2891673A1 (ru) |
CY (1) | CY1124474T1 (ru) |
DK (2) | DK3660033T5 (ru) |
ES (2) | ES2780674T3 (ru) |
FR (1) | FR22C1025I2 (ru) |
HK (2) | HK1215445A1 (ru) |
HR (1) | HRP20211342T2 (ru) |
HU (2) | HUE055564T2 (ru) |
IL (2) | IL238852A0 (ru) |
LT (2) | LT3660033T (ru) |
MX (2) | MX366404B (ru) |
NL (1) | NL301178I2 (ru) |
NO (1) | NO2022017I1 (ru) |
PL (2) | PL2920201T3 (ru) |
PT (2) | PT3660033T (ru) |
RS (1) | RS62243B9 (ru) |
RU (1) | RU2705215C2 (ru) |
SI (1) | SI3660033T1 (ru) |
WO (1) | WO2014078731A2 (ru) |
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CN105051057B (zh) * | 2012-11-15 | 2019-11-19 | 阿佩利斯制药公司 | 细胞反应性的、长效的或靶向的坎普他汀类似物及相关组合物和方法 |
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WO2017035405A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amino compounds for treatment of immune and inflammatory disorders |
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EP3846803A4 (en) | 2018-09-06 | 2022-08-10 | Achillion Pharmaceuticals, Inc. | MACROCYCLIC COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS |
AU2019346464A1 (en) | 2018-09-25 | 2021-04-08 | Achillion Pharmaceuticals, Inc. | Morphic forms of complement factor D inhibitors |
WO2020109343A1 (en) | 2018-11-29 | 2020-06-04 | F. Hoffmann-La Roche Ag | Combination therapy for treatment of macular degeneration |
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CN110244053B (zh) * | 2019-05-09 | 2022-03-11 | 北京大学第三医院(北京大学第三临床医学院) | 用于诊断狼疮肾炎并肺动脉高压疾病的分子标志物及其用途 |
JP2022539238A (ja) * | 2019-07-05 | 2022-09-07 | アペリス・ファーマシューティカルズ・インコーポレイテッド | ウイルスベクター療法 |
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CN111235264B (zh) * | 2020-02-20 | 2023-05-16 | 圣湘生物科技股份有限公司 | 检测人tpmt基因和nudt15基因多态性的组合物、试剂盒及方法 |
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