RU2013113933A - Антитело к cd38 и леналтдомид или бортезомиб для лечения множественной миеломы и nhl - Google Patents
Антитело к cd38 и леналтдомид или бортезомиб для лечения множественной миеломы и nhl Download PDFInfo
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- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 title claims abstract 14
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 title claims abstract 14
- 229960001467 bortezomib Drugs 0.000 title claims abstract 6
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 title claims abstract 6
- 208000034578 Multiple myelomas Diseases 0.000 title claims abstract 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 title claims abstract 5
- 206010035226 Plasma cell myeloma Diseases 0.000 title claims abstract 5
- 229960004942 lenalidomide Drugs 0.000 claims abstract 10
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims abstract 10
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims abstract 9
- 229940079156 Proteasome inhibitor Drugs 0.000 claims abstract 7
- 239000003207 proteasome inhibitor Substances 0.000 claims abstract 7
- 229960003433 thalidomide Drugs 0.000 claims abstract 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims abstract 4
- 239000011885 synergistic combination Substances 0.000 claims abstract 4
- 210000000988 bone and bone Anatomy 0.000 claims abstract 2
- 230000006378 damage Effects 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims abstract 2
- 230000004048 modification Effects 0.000 claims abstract 2
- 238000012986 modification Methods 0.000 claims abstract 2
- 206010057248 Cell death Diseases 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 230000009089 cytolysis Effects 0.000 claims 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims 2
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Abstract
1. Синергическая комбинация антитела, специфичного к CD38, содержащего HCDR1 участок с последовательностью GFTFSSYYMN (SEQ ID NO: 1) или SYYMN (SEQ ID NO: 14), HCDR2 участок с последовательностью GISGDPSNTYYADSVKG (SEQ ID NO: 2), HCDR3 с последовательностью DLPLVYTGFAY (SEQ ID NO: 3), LCDR1 участок с последовательностью SGDNLRHYYVY (SEQ ID NO: 4), LCDR2 участок с последовательностью GDSKRPS (SEQ ID NO: 5) и LCDR3 участок с последовательностью QTYTGGASL (SEQ ID NO: 6), и(a) талидомида или его аналога или(b) ингибитора протеасомдля применения при лечении множественной миеломы и/или неходжкинской лимфомы.2. Комбинация по п.1, где антитело содержит вариабельный участок тяжелой цепи с последовательностьюQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS (SEQ ID NO: 10) и вариабельный участок легкой цепи с последовательностьюDIELTQPPSVSVAPGQTARISCSGDNLRHYYVYWYQQKPGQAPVLVIYGDSKRPSGIPERFSGSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ (SEQ ID NO: 11).3. Комбинация по п.1 или 2, где антитело содержит Fc-участок IgG1.4. Комбинация по п.1, где антитело содержит модифицированный Fc-участок, где указанная модификация усиливает активность ADCC.5. Комбинация по п.1, где указанное антитело, специфичное к CD38, и указанный талидомид или его аналог или ингибитор протеасом вводятся раздельно.6. Комбинация по п.1, которая способна снижать разрушение кости с эффективностью по меньшей мере в два раза лучшей, чем леналидомид и/или бортезомиб сами по себе.7. Комбинация по п.1, где указанное антитело, специфичное к CD38, объединено с талидомидом или его аналогом.8. Комбинация по п.7, где аналог талидомида включает леналидомид.9. Комбинация по п.1, где леналидомид вводится до введения антитела, специфичного к CD38.10. Комбинация по п.1, где леналидомид вводится по меньшей мере за 72 ч до введения антитела, спец�
Claims (16)
1. Синергическая комбинация антитела, специфичного к CD38, содержащего HCDR1 участок с последовательностью GFTFSSYYMN (SEQ ID NO: 1) или SYYMN (SEQ ID NO: 14), HCDR2 участок с последовательностью GISGDPSNTYYADSVKG (SEQ ID NO: 2), HCDR3 с последовательностью DLPLVYTGFAY (SEQ ID NO: 3), LCDR1 участок с последовательностью SGDNLRHYYVY (SEQ ID NO: 4), LCDR2 участок с последовательностью GDSKRPS (SEQ ID NO: 5) и LCDR3 участок с последовательностью QTYTGGASL (SEQ ID NO: 6), и
(a) талидомида или его аналога или
(b) ингибитора протеасом
для применения при лечении множественной миеломы и/или неходжкинской лимфомы.
2. Комбинация по п.1, где антитело содержит вариабельный участок тяжелой цепи с последовательностью
QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS (SEQ ID NO: 10) и вариабельный участок легкой цепи с последовательностью
DIELTQPPSVSVAPGQTARISCSGDNLRHYYVYWYQQKPGQAPVLVIYGDSKRPSGIPERFSGSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ (SEQ ID NO: 11).
3. Комбинация по п.1 или 2, где антитело содержит Fc-участок IgG1.
4. Комбинация по п.1, где антитело содержит модифицированный Fc-участок, где указанная модификация усиливает активность ADCC.
5. Комбинация по п.1, где указанное антитело, специфичное к CD38, и указанный талидомид или его аналог или ингибитор протеасом вводятся раздельно.
6. Комбинация по п.1, которая способна снижать разрушение кости с эффективностью по меньшей мере в два раза лучшей, чем леналидомид и/или бортезомиб сами по себе.
7. Комбинация по п.1, где указанное антитело, специфичное к CD38, объединено с талидомидом или его аналогом.
8. Комбинация по п.7, где аналог талидомида включает леналидомид.
9. Комбинация по п.1, где леналидомид вводится до введения антитела, специфичного к CD38.
10. Комбинация по п.1, где леналидомид вводится по меньшей мере за 72 ч до введения антитела, специфичного к CD38.
11. Комбинация по любому из пп.7-10, которая способна опосредовать цитолиз экспрессирующих CD38 клеток АМО-1 и/или NCI-H929 посредством ADCC в присутствии выделенных РВМС человека с эффективностью, по меньшей мере в два раза лучшей, чем леналидомид сам по себе.
12. Комбинация по п.1, содержащая указанное антитело, специфичное к CD38, и ингибитор протеасом.
13. Комбинация по п.12, где указанный ингибитор протеасом представляет собой бортезомиб.
14. Комбинация по п.12 или 13, которая способна опосредовать цитолиз экспрессирующих CD38 клеток LP-1 и/или NCI-H929 посредством ADCC в присутствии выделенных РВМС человека с эффективностью по меньшей мере в два раза лучшей, чем бортезомиб сам по себе.
15. Синергическая комбинация антитела, специфичного к CD38, содержащего HCDR1 участок с последовательностью GFTFSSYYMN (SEQ ID NO: 1), HCDR2 участок с последовательностью GISGDPSNTYYADSVKG (SEQ ID NO: 2), HCDR3 участок с последовательностью DLPLVYTGFAY (SEQ ID NO: 3), LCDR1 участок с последовательностью SGDNLRHYYVY (SEQ ID NO: 4), LCDR2 участок с последовательностью GDSKRPS (SEQ ID NO: 5) и LCDR3 участок с последовательностью QTYTGGASL (SEQ ID NO: 6), и леналидомида или другого аналога талидомида для применения при лечении множественной миеломы и/или неходжкинской лимфомы.
16. Синергическая комбинация антитела, специфичного к CD38, содержащего HCDR1 участок с последовательностью GFTFSSYYMN (SEQ ID NO: 1), HCDR2 участок с последовательностью GISGDPSNTYYADSVKG (SEQ ID NO: 2), HCDR3 участок с последовательностью DLPLVYTGFAY (SEQ ID NO: 3), LCDR1 участок с последовательностью SGDNLRHYYVY (SEQ ID NO: 4), LCDR2 участок с последовательностью GDSKRPS (SEQ ID NO: 5) и LCDR3 участок с последовательностью QTYTGGASL (SEQ ID NO: 6), и бортезомиба или другого ингибитора протеасом для применения при лечении множественной миеломы и/или неходжкинской лимфомы.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38661910P | 2010-09-27 | 2010-09-27 | |
| US61/386,619 | 2010-09-27 | ||
| EP10180485 | 2010-09-27 | ||
| EP10180485.4 | 2010-09-27 | ||
| US201161437696P | 2011-01-31 | 2011-01-31 | |
| US61/437,696 | 2011-01-31 | ||
| US201161468607P | 2011-03-29 | 2011-03-29 | |
| US61/468,607 | 2011-03-29 | ||
| US201161486814P | 2011-05-17 | 2011-05-17 | |
| US61/486,814 | 2011-05-17 | ||
| PCT/EP2011/066648 WO2012041800A1 (en) | 2010-09-27 | 2011-09-26 | Anti-cd38 antibody and lenalidomide or bortezomib for the treatment of multiple myeloma and nhl |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2013113933A true RU2013113933A (ru) | 2014-11-10 |
| RU2595839C2 RU2595839C2 (ru) | 2016-08-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2013113933/15A RU2595839C2 (ru) | 2010-09-27 | 2011-09-26 | Антитело к cd38 и леналидомид или бортезомиб для лечения множественной миеломы и nhl |
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| CN (1) | CN103118706B (ru) |
| AU (1) | AU2011310696B2 (ru) |
| BR (1) | BR112013006769B1 (ru) |
| CA (1) | CA2812631C (ru) |
| DK (1) | DK2621531T3 (ru) |
| ES (1) | ES2617446T3 (ru) |
| HU (1) | HUE031956T2 (ru) |
| IL (1) | IL224915A (ru) |
| LT (1) | LT2621531T (ru) |
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| NZ (1) | NZ607473A (ru) |
| PL (1) | PL2621531T3 (ru) |
| PT (1) | PT2621531T (ru) |
| RU (1) | RU2595839C2 (ru) |
| SG (1) | SG188345A1 (ru) |
| SI (1) | SI2621531T1 (ru) |
| WO (1) | WO2012041800A1 (ru) |
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| UA118255C2 (uk) * | 2012-12-07 | 2018-12-26 | Санофі | Композиція, яка містить антитіло до cd38 і леналідомід |
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| SMT202100202T1 (it) * | 2015-05-13 | 2021-05-07 | Morphosys Ag | Trattamento per il mieloma multiplo |
| WO2016187546A1 (en) | 2015-05-20 | 2016-11-24 | Janssen Biotech, Inc. | Anti-cd38 antibodies for treatment of light chain amyloidosis and other cd38-positive hematological malignancies |
| US10668149B2 (en) | 2015-06-22 | 2020-06-02 | Janssen Biotech, Inc. | Combination therapies for heme malignancies with anti-CD38 antibodies and survivin inhibitors |
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| SG10201400973XA (en) | 2005-10-12 | 2014-08-28 | Morphosys Ag | Generation and profiling of fully human hucal gold-derived therapeutic antibodies specific for human cd38 |
| PT2081595T (pt) * | 2006-09-26 | 2019-07-16 | Genmab As | Anti-cd38 mais corticosteroides mais um quimioterápico não corticosteroide para tratar tumores |
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| AU2009271401A1 (en) * | 2008-06-16 | 2010-01-21 | Immunogen Inc. | Novel synergistic effects |
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| EP2191843A1 (en) * | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and cyclophosphamide |
| EP2191842A1 (en) | 2008-11-28 | 2010-06-02 | Sanofi-Aventis | Antitumor combinations containing antibodies recognizing specifically CD38 and cytarabine |
| ES2617446T3 (es) | 2010-09-27 | 2017-06-19 | Morphosys Ag | Anticuerpo anti-cd38 y lenalidomida o bortezomib para el tratamiento del mieloma múltiple y nhl |
| UA112170C2 (uk) | 2010-12-10 | 2016-08-10 | Санофі | Протипухлинна комбінація, що містить антитіло, яке специфічно розпізнає cd38, і бортезоміб |
| JOP20210044A1 (ar) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
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