RU2014114527A - АНТИТЕЛА ПРОТИВ αβTCR - Google Patents
АНТИТЕЛА ПРОТИВ αβTCR Download PDFInfo
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- 101000998952 Homo sapiens Immunoglobulin heavy variable 1-3 Proteins 0.000 claims abstract 4
- 102100036886 Immunoglobulin heavy variable 1-3 Human genes 0.000 claims abstract 4
- 101001047617 Homo sapiens Immunoglobulin kappa variable 3-11 Proteins 0.000 claims abstract 2
- 102100022955 Immunoglobulin kappa variable 3-11 Human genes 0.000 claims abstract 2
- 230000035772 mutation Effects 0.000 claims 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 102000009490 IgG Receptors Human genes 0.000 claims 2
- 108010073807 IgG Receptors Proteins 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 230000013595 glycosylation Effects 0.000 claims 2
- 238000006206 glycosylation reaction Methods 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000007423 decrease Effects 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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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
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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
- C07K16/2893—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD52
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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- 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
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- C07K2317/71—Decreased effector function due to an Fc-modification
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- 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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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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Abstract
1. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:7, 12 или 13, и каркасную область IGH3-23 человека SEQ ID NO:17, где остатком в положении 6 каркасной области является донорный остаток.2. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:7, 12 или 13, и каркасную область IGH3-23 человека SEQ ID NO:17, где остатком в положении 18 каркасной области является донорный остаток.3. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, по п. 1 или 2, где остатками в положениях 49 и/или 69 каркасной области являются донорные остатки.4. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:15 или 16, и каркасную область IGHV1-3*01 человека SEQ ID NO:18, где одним или более остатков в положениях 38, 44 и/или 48 каркасной области является донорный остаток.5. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:15 или 16, и каркасную область IGHV1-3*01 человека SEQ ID NO:18, где остатками в положениях 44 и 48 каркасной области являются донорные остатки.6. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область легкой цепи, содержащую CDR SEQ ID NO:14, и каркасную область IGKV3-11*01 человека SEQ ID NO:19, где остатками в положени
Claims (20)
1. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:7, 12 или 13, и каркасную область IGH3-23 человека SEQ ID NO:17, где остатком в положении 6 каркасной области является донорный остаток.
2. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:7, 12 или 13, и каркасную область IGH3-23 человека SEQ ID NO:17, где остатком в положении 18 каркасной области является донорный остаток.
3. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, по п. 1 или 2, где остатками в положениях 49 и/или 69 каркасной области являются донорные остатки.
4. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:15 или 16, и каркасную область IGHV1-3*01 человека SEQ ID NO:18, где одним или более остатков в положениях 38, 44 и/или 48 каркасной области является донорный остаток.
5. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, содержащую CDR SEQ ID NO:15 или 16, и каркасную область IGHV1-3*01 человека SEQ ID NO:18, где остатками в положениях 44 и 48 каркасной области являются донорные остатки.
6. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область легкой цепи, содержащую CDR SEQ ID NO:14, и каркасную область IGKV3-11*01 человека SEQ ID NO:19, где остатками в положениях 70 и/или 71 каркасной области являются донорные остатки.
7. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, по п. 6, где остатком в положении 46 каркасной области является донорный остаток.
8. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, выбранную из тяжелых цепей, содержащих аминокислотные последовательности SEQ ID NO:7, SEQ ID NO:12 и SEQ ID NO:13, и последовательность вариабельной области легкой цепи, содержащей аминокислотную последовательность SEQ ID NO:14.
9. Гуманизированное моноклональное антитело, специфическое в отношении комплекса αβTCR/CD3 человека, которое содержит вариабельную область тяжелой цепи, выбранную из тяжелых цепей, содержащих аминокислотные последовательности SEQ ID NO:15 и SEQ ID NO:16, и вариабельную область легкой цепи, содержащей аминокислотную последовательность SEQ ID NO:14.
10. Гуманизированное антитело по любому из пп. 1-9, дополнительно содержащее константную область человеческого происхождения.
11. Гуманизированное антитело по п. 10, дополнительно содержащее модификацию Fc, которая уменьшает связывание с Fcγ-рецептором.
12. Гуманизированное антитело по п. 11, в котором изменен характер гликозилирования.
13. Гуманизированное антитело по п. 12, содержащее одну или более мутаций S298N, T299A и Y300S.
14. Гуманизированное антитело по п. 13, содержащее две или более мутаций N297Q, S298N, T299A и Y300S.
15. Гуманизированное антитело по п. 13, содержащее множественные мутации N297Q/S298N/Y300S, S298N/T299A/Y300S или S298N/Y300S.
16. Нуклеиновая кислота, кодирующая по меньшей мере вариабельную область тяжелой цепи гуманизированного моноклонального антитела по любому из пп. 1-15.
17. Клетка, которая экспрессирует нуклеиновую кислоту по п. 16.
18. Гуманизированное антитело по любому из пп. 1-15 для применения в супрессии T-клеточно-опосредованного ответа у субъекта.
19. Гуманизированное антитело по п. 18, где T-клеточно-опосредованный ответ вовлечен в ситуацию, выбранную из трансплантации ткани, включая трансплантат цельного органа и смешанный тканевый трансплантат, пересадки ткани, рассеянного склероза и сахарного диабета типа 1.
20. Антитело, содержащее модифицированную Fc-область, в котором указанная модифицированная Fc включает в себя модифицированный характер гликозилирования, который уменьшает связывание с Fcγ-рецептором, включая одну или более мутаций S298N, T299A и Y300S.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161533510P | 2011-09-12 | 2011-09-12 | |
| US61/533,510 | 2011-09-12 | ||
| PCT/EP2012/003819 WO2013037484A2 (en) | 2011-09-12 | 2012-09-12 | Anti-aplhabetatcr antibody |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017129721A Division RU2017129721A (ru) | 2011-09-12 | 2012-09-12 | АНТИТЕЛА ПРОТИВ αβTCR |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2014114527A true RU2014114527A (ru) | 2015-10-20 |
| RU2630656C2 RU2630656C2 (ru) | 2017-09-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2014114527A RU2630656C2 (ru) | 2011-09-12 | 2012-09-12 | АНТИТЕЛА ПРОТИВ αβTCR |
| RU2017129721A RU2017129721A (ru) | 2011-09-12 | 2012-09-12 | АНТИТЕЛА ПРОТИВ αβTCR |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2017129721A RU2017129721A (ru) | 2011-09-12 | 2012-09-12 | АНТИТЕЛА ПРОТИВ αβTCR |
Country Status (34)
| Country | Link |
|---|---|
| US (3) | US10017573B2 (ru) |
| EP (1) | EP2755999B1 (ru) |
| JP (2) | JP6096196B2 (ru) |
| KR (1) | KR20140072092A (ru) |
| CN (3) | CN119119269A (ru) |
| AU (2) | AU2012307816C1 (ru) |
| BR (2) | BR112014005644A2 (ru) |
| CA (1) | CA2847949C (ru) |
| CL (2) | CL2014000574A1 (ru) |
| CO (1) | CO6930307A2 (ru) |
| CR (1) | CR20140127A (ru) |
| DK (1) | DK2755999T3 (ru) |
| DO (1) | DOP2014000052A (ru) |
| EC (1) | ECSP14013307A (ru) |
| ES (1) | ES2667893T3 (ru) |
| GT (1) | GT201400045A (ru) |
| HU (1) | HUE037470T2 (ru) |
| IL (2) | IL231304B (ru) |
| LT (1) | LT2755999T (ru) |
| MA (1) | MA35711B1 (ru) |
| MX (2) | MX355735B (ru) |
| MY (1) | MY173924A (ru) |
| NI (1) | NI201400019A (ru) |
| PE (1) | PE20141548A1 (ru) |
| PH (1) | PH12014500408A1 (ru) |
| PL (1) | PL2755999T3 (ru) |
| PT (1) | PT2755999T (ru) |
| RU (2) | RU2630656C2 (ru) |
| SG (2) | SG10201601738UA (ru) |
| TN (1) | TN2014000107A1 (ru) |
| TW (1) | TWI593706B (ru) |
| UA (1) | UA115533C2 (ru) |
| UY (1) | UY34317A (ru) |
| WO (1) | WO2013037484A2 (ru) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UY34317A (es) | 2011-09-12 | 2013-02-28 | Genzyme Corp | Anticuerpo antireceptor de célula T (alfa)/ß |
| PL3366705T3 (pl) * | 2012-09-12 | 2023-09-18 | Genzyme Corporation | FC zawierające polipeptydy o zmienionej glikozylacji i zmniejszonej funkcji efektorowej |
| US9790268B2 (en) | 2012-09-12 | 2017-10-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
| IL275376B2 (en) | 2013-03-11 | 2024-01-01 | Genzyme Corp | Hyperglycosylated binding polypeptides |
| SG10201803473WA (en) | 2013-10-30 | 2018-06-28 | Genzyme Corp | Methods for enhancing immunosuppressive therapy by multiple administration of alpha beta tcr-binding polypeptide |
| SG11201607198WA (en) | 2014-03-19 | 2016-09-29 | Genzyme Corp | Site-specific glycoengineering of targeting moieties |
| SG11201702786RA (en) | 2014-10-09 | 2017-05-30 | Genzyme Corp | Glycoengineered antibody drug conjugates |
| WO2016059220A1 (en) | 2014-10-16 | 2016-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Tcr-activating agents for use in the treatment of t-all |
| MX2017015619A (es) * | 2015-06-01 | 2018-08-15 | Medigene Immunotherapies Gmbh | Anticuerpos especificos de receptor de celulas t. |
| CN107614519B (zh) * | 2015-10-23 | 2022-08-05 | 优瑞科生物技术公司 | 抗体/t细胞受体嵌合构建体及其用途 |
| LT3652215T (lt) | 2017-07-14 | 2021-05-25 | Immatics Biotechnologies Gmbh | Pagerinta dvejopo savitumo polipeptido molekulė |
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