RU2014143531A - Вакцина против PCSK9 - Google Patents
Вакцина против PCSK9 Download PDFInfo
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- RU2014143531A RU2014143531A RU2014143531A RU2014143531A RU2014143531A RU 2014143531 A RU2014143531 A RU 2014143531A RU 2014143531 A RU2014143531 A RU 2014143531A RU 2014143531 A RU2014143531 A RU 2014143531A RU 2014143531 A RU2014143531 A RU 2014143531A
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- antigenic peptide
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- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 title claims abstract 29
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 title claims abstract 29
- 229960005486 vaccine Drugs 0.000 title 1
- 230000002163 immunogen Effects 0.000 claims abstract 40
- 230000000890 antigenic effect Effects 0.000 claims abstract 21
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 21
- 230000028993 immune response Effects 0.000 claims abstract 6
- 230000001939 inductive effect Effects 0.000 claims abstract 6
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims abstract 2
- 239000002245 particle Substances 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 12
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 claims 5
- 239000002671 adjuvant Substances 0.000 claims 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 4
- 235000018417 cysteine Nutrition 0.000 claims 4
- 229940037003 alum Drugs 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 2
- QMDCLAZNUPXSOJ-UHFFFAOYSA-N odn 10103 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(O)=O)C(O)C1 QMDCLAZNUPXSOJ-UHFFFAOYSA-N 0.000 claims 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
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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
- A61K38/08—Peptides having 5 to 11 amino acids
-
- 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
- A61K39/0005—Vertebrate antigens
-
- 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
- A61K38/10—Peptides having 12 to 20 amino acids
-
- 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
- A61K39/002—Protozoa antigens
- A61K39/005—Trypanosoma antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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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
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- 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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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
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- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
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Abstract
1. Иммуноген для индуцирования иммунного ответа против белка PCSK9, содержащий антигенный пептид PCSK9, выбранный из группы, состоящей из SEQ ID NO: 191-226, конъюгированный с иммуногенным носителем.2. Иммуноген по п. 1, где антигенный пептид PCSK9 конъюгирован с иммуногенным носителем, выбранным из CRM 197 или Qbeta вирусоподобной частицы (VLP).3. Иммуноген по п. 2, где антигенный пептид PCSK9 выбран из группы, состоящей из SEQ ID NO: 191-198.4. Иммуноген по п. 2, где антигенный пептид PCSK9 выбран из группы, состоящей из SEQ ID NO: 199-205.5. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит любой из следующих:- на своем С-конце линкер, имеющий формулу (G)C, (G)SC или (G)K, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10,- на своем N-конце линкер, имеющий формулу C(G), CS(G)или K(G), где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10, или- на своем С-конце линкер, имеющий формулу (G)C, (G)SC или (G)K, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10, и на своем N-конце линкер, имеющий формулу C(G), CS(G)или K(G), где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10.6. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит любой из следующих:- на своем С-конце линкер, имеющий формулу (G)C, (G)SC или (G)K, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2,- на своем N-конце линкер, имеющий формулу C(G), CS(G)или K(G), где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2, или- на своем С-конце линкер, имеющий формулу (G)C, (G)SC или (G)K, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2, и на своем N-конце линкер, имеющий формулу C(G), CS(G)или K(G), где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2.7. Иммуноген по п. 3 или 4, где указанный анти
Claims (24)
1. Иммуноген для индуцирования иммунного ответа против белка PCSK9, содержащий антигенный пептид PCSK9, выбранный из группы, состоящей из SEQ ID NO: 191-226, конъюгированный с иммуногенным носителем.
2. Иммуноген по п. 1, где антигенный пептид PCSK9 конъюгирован с иммуногенным носителем, выбранным из CRM 197 или Qbeta вирусоподобной частицы (VLP).
3. Иммуноген по п. 2, где антигенный пептид PCSK9 выбран из группы, состоящей из SEQ ID NO: 191-198.
4. Иммуноген по п. 2, где антигенный пептид PCSK9 выбран из группы, состоящей из SEQ ID NO: 199-205.
5. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит любой из следующих:
- на своем С-конце линкер, имеющий формулу (G)nC, (G)nSC или (G)nK, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10,
- на своем N-конце линкер, имеющий формулу C(G)n, CS(G)n или K(G)n, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10, или
- на своем С-конце линкер, имеющий формулу (G)nC, (G)nSC или (G)nK, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10, и на своем N-конце линкер, имеющий формулу C(G)n, CS(G)n или K(G)n, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10.
6. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит любой из следующих:
- на своем С-конце линкер, имеющий формулу (G)nC, (G)nSC или (G)nK, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2,
- на своем N-конце линкер, имеющий формулу C(G)n, CS(G)n или K(G)n, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2, или
- на своем С-конце линкер, имеющий формулу (G)nC, (G)nSC или (G)nK, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2, и на своем N-конце линкер, имеющий формулу C(G)n, CS(G)n или K(G)n, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1 или 2.
7. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит цистеин на своем С-конце.
8. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит группу CG или цистеин на своем N-конце.
9. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит CGG на своем N-конце.
10. Иммуноген по п. 3 или 4, где указанный антигенный пептид PCSK9 дополнительно содержит GGC на своем С-конце.
11. Иммуноген по п. 1 или 2, где указанный антигенный пептид PCSK9 циклизован и содержит цистеин, (G)nC- или С(G)n-фрагмент, где n представляет собой целое число, выбранное из группы, состоящей из 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 и 10.
12. Иммуноген по п. 1 или 2, где указанный антигенный пептид PCSK9 циклизован и содержит цистеин, GC- или CG-фрагмент.
13. Иммуноген по п. 1 или 2, где указанный антигенный пептид PCSK9 дополнительно содержит KG или KGG на своем N-конце.
14. Иммуноген по п. 1 или 2, где антигенный пептид PCSK9 конформационно ограничен.
15. Композиция для индуцирования иммунного ответа против белка PCSK9, содержащая по меньшей мере два иммуногена в иммунологически эффективных количествах, где первый иммуноген представляет собой иммуноген по п. 1.
16. Композиция для индуцирования иммунного ответа против белка PCSK9, содержащая по меньшей мере два иммуногена в иммунологически эффективных количествах, где первый иммуноген представляет собой иммуноген по п. 2.
17. Композиция для индуцирования иммунного ответа против белка PCSK9, содержащая по меньшей мере два иммуногена в иммунологически
эффективных количествах, где первый иммуноген представляет собой иммуноген по п.
18. Композиция по п. 17, где антигенный пептид PCSK9 во втором иммуногене выбран из группы, состоящей из SEQ ID NO: 67, 68, 69, 70, 71, 72, 73, 182, 183, 184, 185, 186, 187 и 188.
19. Иммуногенная композиция для индуцирования иммунного ответа против белка PCSK9, содержащая композицию иммуногенов в иммунологически эффективных количествах по п. 17, дополнительно содержащая по меньшей мере один адъювант.
20. Иммуногенная композиция по п. 19, где указанный адъювант выбран из квасцов, CpG ODN (олигодезоксинуклеотид), QS21 и Iscomatrix.
21. Иммуногенная композиция по п. 19, где указанный адъювант выбран из QS21, квасцов в комбинации с CpG ODN или Iscomatrix в комбинации с CpG ODN.
22. Иммуногенная композиция по п. 19, где указанный адъювант выбран из квасцов в комбинации с CpG ODN.
23. Иммуногенная композиция по п. 19, где CpG ODN выбран из:
5′ TCGTCGTTTTTCGGTGCTTTT 3′, или
5′ TCGTCGTTTTTCGGTCGTTTT 3′, или
5′ TCGTCGTTTTGTCGTTTTGTCGTT 3′.
24. Фармацевтическая композиция, предназначенная для предупреждения, лечения или облегчения PCSK9-связанных расстройств, содержащая:
(1) в терапевтически эффективном количестве иммуноген по п. 1 или 2, композицию по п. 17 или иммуногенную композицию по п. 19; и
(2) фармацевтически приемлемый эксципиент.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23954109P | 2009-09-03 | 2009-09-03 | |
| US61/239,541 | 2009-09-03 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012107657/10A Division RU2538162C2 (ru) | 2009-09-03 | 2010-08-23 | Вакцина против pcsk9 |
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| Publication Number | Publication Date |
|---|---|
| RU2014143531A true RU2014143531A (ru) | 2016-05-20 |
| RU2014143531A3 RU2014143531A3 (ru) | 2018-06-22 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2012107657/10A RU2538162C2 (ru) | 2009-09-03 | 2010-08-23 | Вакцина против pcsk9 |
| RU2014143531A RU2014143531A (ru) | 2009-09-03 | 2014-10-29 | Вакцина против PCSK9 |
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| RU2012107657/10A RU2538162C2 (ru) | 2009-09-03 | 2010-08-23 | Вакцина против pcsk9 |
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| Country | Link |
|---|---|
| US (4) | US8889144B2 (ru) |
| EP (3) | EP2865752A1 (ru) |
| JP (5) | JP2013503623A (ru) |
| KR (3) | KR101660578B1 (ru) |
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