RU2019124332A - Комбинированная терапия с использованием антител против клаудина 18.2 для лечения рака - Google Patents
Комбинированная терапия с использованием антител против клаудина 18.2 для лечения рака Download PDFInfo
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- RU2019124332A RU2019124332A RU2019124332A RU2019124332A RU2019124332A RU 2019124332 A RU2019124332 A RU 2019124332A RU 2019124332 A RU2019124332 A RU 2019124332A RU 2019124332 A RU2019124332 A RU 2019124332A RU 2019124332 A RU2019124332 A RU 2019124332A
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- Prior art keywords
- antibody
- gemcitabine
- acid
- bisphosphonate
- combination
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims 2
- 201000011510 cancer Diseases 0.000 title claims 2
- 102000002029 Claudin Human genes 0.000 title 1
- 108050009302 Claudin Proteins 0.000 title 1
- 238000002648 combination therapy Methods 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims 6
- 229960005277 gemcitabine Drugs 0.000 claims 6
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 6
- 229940122361 Bisphosphonate Drugs 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 150000004663 bisphosphonates Chemical class 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 claims 2
- 229930012538 Paclitaxel Natural products 0.000 claims 2
- 230000003902 lesion Effects 0.000 claims 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims 2
- 229960001756 oxaliplatin Drugs 0.000 claims 2
- 229960001592 paclitaxel Drugs 0.000 claims 2
- 210000000496 pancreas Anatomy 0.000 claims 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 1
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims 1
- 102000000588 Interleukin-2 Human genes 0.000 claims 1
- 108010002350 Interleukin-2 Proteins 0.000 claims 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims 1
- 229940123237 Taxane Drugs 0.000 claims 1
- UGEPSJNLORCRBO-UHFFFAOYSA-N [3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O UGEPSJNLORCRBO-UHFFFAOYSA-N 0.000 claims 1
- 229960004343 alendronic acid Drugs 0.000 claims 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 claims 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims 1
- 229960004562 carboplatin Drugs 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 1
- 229960002286 clodronic acid Drugs 0.000 claims 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229960002949 fluorouracil Drugs 0.000 claims 1
- 229960005236 ibandronic acid Drugs 0.000 claims 1
- 229950006971 incadronic acid Drugs 0.000 claims 1
- LWRDQHOZTAOILO-UHFFFAOYSA-N incadronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCCCCC1 LWRDQHOZTAOILO-UHFFFAOYSA-N 0.000 claims 1
- 229960004768 irinotecan Drugs 0.000 claims 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 1
- 229950011129 minodronic acid Drugs 0.000 claims 1
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 claims 1
- -1 nitrogen-containing bisphosphonate Chemical class 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 125000003835 nucleoside group Chemical class 0.000 claims 1
- 229950004969 olpadronic acid Drugs 0.000 claims 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims 1
- 229960003978 pamidronic acid Drugs 0.000 claims 1
- 150000003058 platinum compounds Chemical class 0.000 claims 1
- 229960000759 risedronic acid Drugs 0.000 claims 1
- 229960004276 zoledronic acid Drugs 0.000 claims 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims 1
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Claims (18)
1. Способ лечения предракового поражения поджелудочной железы, характеризующегося клетками поджелудочной железы, экспрессирующими сплайсинг вариант 2 клаудина 18 (CLDN18.2), включающий введение пациенту
(i) антитела, обладающего способностью связываться с CLDN18.2; а также
(ii) агента, стабилизирующего или увеличивающего экспрессию CLDN18.2, где
(а) антитело связывается с CLDN18.2 и обеспечивает уничтожение клеток, экспрессирующих CLDN18.2, где антитело содержит тяжелую цепь антитела, содержащую аминокислотную последовательность, представленную SEQ ID NO: 32, и легкую цепь антитела, содержащую аминокислотную последовательность представлен SEQ ID NO: 39, и
(б) агент представляет собой нуклеозидный аналог, выбранный из группы, состоящей из гемцитабина и его сложного эфира или соли.
2. Способ по п. 1, где экспрессия CLDN18.2 происходит на клеточной поверхности раковых клеток.
3. Способ по п. 1 или 2, отличающийся тем, что включает введение агента, выбранного из группы, состоящей из соединений платины, таксанов, их солей и их комбинаций.
4. Способ по п.1 или 2, который включает введение агента, выбранного из группы, состоящей из 5-фторурацила, оксалиплатина, иринотекана, паклитаксела, альбумин-связанного паклитаксела, их солей и их комбинаций.
5. Способ по п.1 или 2, который включает введение комбинации гемцитабина и оксалиплатина, комбинации гемцитабина и цисплатина, комбинации гемцитабина и карбоплатина или комбинации паклитаксела или альбумин-связанного паклитаксела и гемцитабина.
6. Способ лечения предракового поражения поджелудочной железы, характеризующегося клетками поджелудочной железы, экспрессирующими CLDN18.2, включающий введение пациенту
(i) антитела, обладающего способностью связываться с CLDN18.2; и
(ii) гемцитабина,
где антитело опосредует уничтожение клеток, экспрессирующих CLDN18.2, где антитело содержит тяжелую цепь антитела, содержащую аминокислотную последовательность, представленную SEQ ID NO: 32, и легкую цепь антитела, содержащую аминокислотную последовательность, представленную SEQ ID NO: 39, и где способ включает введение бисфосфоната пациенту.
7. Способ по п.6, в котором бисфосфонат представляет собой азотсодержащий бисфосфонат (аминобисфосфонат).
8. Способ по п.6, в котором бисфосфонат выбирают из группы, состоящей из золедроновой кислоты, клодроновой кислоты, ибандроновой кислоты, памидроновой кислоты, ризедроновой кислоты, минодроновой кислоты, олпадроновой кислоты, алендроновой кислоты, инкадроновой кислоты и их солей.
9. Способ по п.6, в котором бисфосфонат вводят в комбинации с интерлейкином-2.
10. Способ по любому из пп.1-9, в котором способ включает введение антитела, обладающего способностью связываться с CLDN18.2, в дозе до 1000 мг/м2.
11. Способ по любому из пп.1-9, в котором способ включает введение антитела, обладающего способностью связываться с CLDN18.2, повторно в дозе от 300 до 600 мг/м2.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2013/000505 WO2014127785A1 (en) | 2013-02-20 | 2013-02-20 | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
| EPPCT/EP2013/000505 | 2013-02-20 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015139901A Division RU2699549C2 (ru) | 2013-02-20 | 2014-02-18 | Комбинированная терапия с использованием антител против клаудина 18.2 для лечения рака |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2019124332A true RU2019124332A (ru) | 2019-10-04 |
| RU2792932C2 RU2792932C2 (ru) | 2023-03-28 |
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