RU2017126476A - Новые модуляторы и способы их применения - Google Patents
Новые модуляторы и способы их применения Download PDFInfo
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- 239000000427 antigen Substances 0.000 claims 16
- 102000036639 antigens Human genes 0.000 claims 16
- 108091007433 antigens Proteins 0.000 claims 16
- 239000012634 fragment Substances 0.000 claims 16
- 206010006187 Breast cancer Diseases 0.000 claims 9
- 208000026310 Breast neoplasm Diseases 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 201000011510 cancer Diseases 0.000 claims 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 6
- 206010033128 Ovarian cancer Diseases 0.000 claims 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 6
- 201000005202 lung cancer Diseases 0.000 claims 6
- 208000020816 lung neoplasm Diseases 0.000 claims 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 3
- 201000000849 skin cancer Diseases 0.000 claims 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 3
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 2
- 101000606465 Homo sapiens Inactive tyrosine-protein kinase 7 Proteins 0.000 claims 1
- 101710099452 Inactive tyrosine-protein kinase 7 Proteins 0.000 claims 1
- 102100039813 Inactive tyrosine-protein kinase 7 Human genes 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 230000000779 depleting effect Effects 0.000 claims 1
- 102000049511 human PTK7 Human genes 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 210000005102 tumor initiating cell Anatomy 0.000 claims 1
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- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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Claims (42)
1. Набор, содержащий один или более контейнеров, содержащих антитело или его антиген-связывающий фрагмент либо конъюгат антитела, содержащий антитело или его антиген-связывающий фрагмент, конъюгированные, связанные или иным образом ассоциированные с цитотоксическим агентом, где антитело или его антиген-связывающий фрагмент связывается с РТК7 (протеинтирозинкиназа 7) человека и содержит:
а) три CDR вариабельной области легкой цепи, представленной в SEQ ID NO: 62, и три CDR вариабельной области тяжелой цепи, представленной в SEQ ID NO: 63; или
б) три CDR вариабельной области легкой цепи, представленной в SEQ ID NO: 64, и три CDR вариабельной области тяжелой цепи, представленной в SEQ ID NO: 65.
2. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 24-34 из SEQ ID NO: 62 для VL CDR1, остатки 50-56 из SEQ ID NO: 62 для VL CDR2, и остатки 89-97 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 31-35 из SEQ ID NO: 63 для VH CDR1, остатки 50-65 из SEQ ID NO: 63 для VH CDR2, и остатки 95-102 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по Kabat.
3. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 23-34 из SEQ ID NO: 62 для VL CDR1, остатки 50-56 из SEQ ID NO: 62 для VL CDR2, и остатки 89-97 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 26-32 из SEQ ID NO: 63 для VH CDR1, остатки 50-58 из SEQ ID NO: 63 для VH CDR2, и остатки 95-102 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по Chothia.
4. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 30-36 из SEQ ID NO: 62 для VL CDR1, остатки 46-55 из SEQ ID NO: 62 для VL CDR2, и остатки 89-96 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 30-35 из SEQ ID NO: 63 для VH CDR1, остатки 47-58 из SEQ ID NO: 63 для VH CDR2, и остатки 93-101 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по MacCallum.
5. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 62, и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 63.
6. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, представленную в SEQ ID NO: 62, и вариабельную область тяжелой цепи, представленную в SEQ ID NO: 63.
7. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 24-34 из SEQ ID NO: 64 для VL CDR1, остатки 50-56 из SEQ ID NO: 64 для VL CDR2 и остатки 89-97 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 31-35 из SEQ ID NO: 65 для VH CDR1, остатки 50-65 из SEQ ID NO: 65 для VH CDR2, и остатки 95-102 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по Kabat.
8. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 23-34 из SEQ ID NO: 64 для VL CDR1, остатки 50-56 из SEQ ID NO: 64 для VL CDR2, и остатки 89-97 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 26-32 из SEQ ID NO: 65 для VH CDR1, остатки 50-58 из SEQ ID NO: 65 для VH CDR2, и остатки 95-102 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по Chothia.
9. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 30-36 из SEQ ID NO: 64 для VL CDR1, остатки 46-55 из SEQ ID NO: 64 для VL CDR2, и остатки 89-96 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 30-35 из SEQ ID NO: 65 для VH CDR1, остатки 47-58 из SEQ ID NO: 65 для VH CDR2, и остатки 93-101 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по MacCallum.
10. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 64, и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 65.
11. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, представленную в SEQ ID NO: 64, и вариабельную область тяжелой цепи, представленную в SEQ ID NO: 65.
12. Набор по любому из пп. 1-11, где антитело или его антиген-связывающий фрагмент представляет собой нейтрализирующее антитело, истощающее антитело и/или интернализованное антитело.
13. Набор по любому из пп. 1-11, где антитело или его антиген-связывающий фрагмент представляет собой моноклональное антитело, химерное антитело, CDR-привитое антитело, гуманизированное антитело или его антиген-связывающий фрагмент.
14. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в обнаружении, диагностике или мониторинге рака.
15. Набор по п. 14, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
16. Набор по п. 15, где рак представляет собой рак яичников.
17. Набор по п. 15, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
18. Набор по п. 15, где рак легкого представляет собой немелкоклеточный рак легкого.
19. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в лечении рака.
20. Набор по п. 19, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
21. Набор по п. 20, где рак представляет собой рак яичников.
22. Набор по п. 20, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
23. Набор по п. 20, где рак легкого представляет собой немелкоклеточный рак легкого.
24. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в снижении частоты появления опухоль-инициирующих клеток у субъекта, имеющего рак.
25. Набор по п. 24, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
26. Набор по п. 25, где рак представляет собой рак яичников.
27. Набор по п. 25, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
28. Набор по п. 25, где рак легкого представляет собой немелкоклеточный рак легкого.
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