SG10201912368XA - Anti-gprc5d antibody and molecule comprising the antibody - Google Patents
Anti-gprc5d antibody and molecule comprising the antibodyInfo
- Publication number
- SG10201912368XA SG10201912368XA SG10201912368XA SG10201912368XA SG10201912368XA SG 10201912368X A SG10201912368X A SG 10201912368XA SG 10201912368X A SG10201912368X A SG 10201912368XA SG 10201912368X A SG10201912368X A SG 10201912368XA SG 10201912368X A SG10201912368X A SG 10201912368XA
- Authority
- SG
- Singapore
- Prior art keywords
- antibody
- molecule
- gprc5d
- gprc5d antibody
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/2803—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017020220 | 2017-02-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SG10201912368XA true SG10201912368XA (en) | 2020-02-27 |
Family
ID=63108300
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG10201912368XA SG10201912368XA (en) | 2017-02-07 | 2018-02-06 | Anti-gprc5d antibody and molecule comprising the antibody |
| SG11201907321TA SG11201907321TA (en) | 2017-02-07 | 2018-02-06 | Anti-gprc5d antibody and molecule comprising the antibody |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG11201907321TA SG11201907321TA (en) | 2017-02-07 | 2018-02-06 | Anti-gprc5d antibody and molecule comprising the antibody |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20190367612A1 (en) |
| EP (1) | EP3581651A4 (en) |
| JP (1) | JPWO2018147245A1 (en) |
| KR (1) | KR20190133160A (en) |
| CN (1) | CN110462038A (en) |
| AU (1) | AU2018218753A1 (en) |
| BR (1) | BR112019016204A2 (en) |
| CA (1) | CA3052938A1 (en) |
| CO (1) | CO2019009680A2 (en) |
| IL (1) | IL268588A (en) |
| MX (1) | MX2019009358A (en) |
| PH (1) | PH12019501824A1 (en) |
| RU (1) | RU2019128134A (en) |
| SG (2) | SG10201912368XA (en) |
| TW (1) | TW201837174A (en) |
| WO (1) | WO2018147245A1 (en) |
| ZA (1) | ZA201905905B (en) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI781108B (en) | 2016-07-20 | 2022-10-21 | 比利時商健生藥品公司 | Anti- gprc5d antibodies, bispecific antigen binding molecules that bind gprc5d and cd3, and uses thereof |
| WO2018045177A1 (en) | 2016-09-01 | 2018-03-08 | Chimera Bioengineering, Inc. | Gold optimized car t-cells |
| US11110125B2 (en) | 2018-02-13 | 2021-09-07 | Chimera Bioengineering, Inc. | Coordinating gene expression using RNA destabilizing elements |
| CA3100118A1 (en) | 2018-05-16 | 2019-11-21 | Janssen Biotech, Inc. | Bcma/cd3 and gprdc5d/cd3 bispecific antibodies for use in cancer therapy |
| WO2019244107A1 (en) * | 2018-06-21 | 2019-12-26 | Daiichi Sankyo Company, Limited | Compositions including cd3 antigen binding fragments and uses thereof |
| AU2020209257A1 (en) * | 2019-01-18 | 2021-08-05 | Janssen Biotech, Inc. | GPRC5D chimeric antigen receptors and cells expressing the same |
| WO2021018925A1 (en) * | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
| BR112022001460A2 (en) * | 2019-07-31 | 2022-03-22 | Hoffmann La Roche | Bispecific antigen-binding molecules, one or more isolated polynucleotides, host cell, method for producing a bispecific antigen-binding molecule and for treating a disease in an individual, pharmaceutical composition, use of the bispecific antigen-binding molecule and invention |
| CN114786686A (en) | 2019-08-18 | 2022-07-22 | 嵌合体生物工程公司 | Combination therapy of GOLD-controlled transgenes |
| WO2022125392A1 (en) * | 2020-12-09 | 2022-06-16 | Chimera Bioengineering, Inc. | Compositions and methods for activating t-cells |
| WO2022148370A1 (en) * | 2021-01-05 | 2022-07-14 | Lanova Medicines Development Co., Ltd. | Anti-gprc5d monoclonal antibodies and uses thereof |
| AU2022201736B2 (en) | 2021-01-05 | 2023-03-16 | Lanova Medicines Development Co., Ltd. | Anti-GPRC5D monoclonal antibodies and uses thereof |
| US20220267438A1 (en) | 2021-02-16 | 2022-08-25 | Janssen Pharmaceutica Nv | Trispecific antibody targeting bcma, gprc5d, and cd3 |
| EP4317435A1 (en) | 2021-03-29 | 2024-02-07 | Daiichi Sankyo Company, Limited | Stable multispecific molecule and use thereof |
| CN115386010A (en) * | 2021-05-23 | 2022-11-25 | 上海邦耀生物科技有限公司 | Chimeric antigen receptor targeting GPRC5D and application thereof |
| WO2022247804A1 (en) * | 2021-05-23 | 2022-12-01 | 上海祥耀生物科技有限责任公司 | Anti-gprc5d antibody, preparation method therefor, and use thereof |
| WO2022260968A1 (en) * | 2021-06-10 | 2022-12-15 | Chimera Bioengineering, Inc. | Compositions and methods for activating natural killer cells |
| WO2023030272A1 (en) * | 2021-08-30 | 2023-03-09 | 原启生物科技(上海)有限责任公司 | Anti-gprc5d antigen binding protein and use thereof |
| TW202334222A (en) * | 2021-11-05 | 2023-09-01 | 大陸商正大天晴藥業集團股份有限公司 | Antibody binding to GPRC5D and use thereof |
| WO2023115347A1 (en) * | 2021-12-21 | 2023-06-29 | 上海驯鹿生物技术有限公司 | Fully human antibody targeting gprc5d |
| WO2023173272A1 (en) * | 2022-03-15 | 2023-09-21 | 上海驯鹿生物技术有限公司 | Gprc5d-targeting fully humanized chimeric antigen receptor (car) and use thereof |
| WO2023125888A1 (en) * | 2021-12-31 | 2023-07-06 | 山东先声生物制药有限公司 | Gprc5d antibody and application thereof |
| CN116375868A (en) * | 2021-12-31 | 2023-07-04 | 康源博创生物科技(北京)有限公司 | Humanized antibody against CD3 and application thereof in preparation of bispecific antibody |
| WO2023125728A1 (en) * | 2021-12-31 | 2023-07-06 | 康源博创生物科技(北京)有限公司 | Anti-gprc5d antibody and use thereof |
| WO2023143537A1 (en) * | 2022-01-29 | 2023-08-03 | 恺兴生命科技(上海)有限公司 | Gprc5d antibody and use thereof |
| WO2023174238A1 (en) * | 2022-03-14 | 2023-09-21 | 江苏恒瑞医药股份有限公司 | Antigen-binding molecule specifically binding to gprc5d and cd3 and medical use thereof |
| WO2023227062A1 (en) * | 2022-05-27 | 2023-11-30 | Antengene (Hangzhou) Biologics Co., Ltd. | Novel anti-gprc5d antibodies, bispecific antigen binding molecules that bind gprc5d and cd3, and uses thereof |
| WO2024002308A1 (en) * | 2022-06-30 | 2024-01-04 | 康诺亚生物医药科技（成都）有限公司 | Development and use of novel multispecific tumor inhibitor |
| US20240041929A1 (en) | 2022-08-05 | 2024-02-08 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for gprc5d and bcma |
| CN116003598B (en) * | 2022-08-30 | 2024-04-26 | 苏州缔码生物科技有限公司 | Recombinant humanized monoclonal antibody targeting human GPRC5D and application thereof |
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| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| WO1992020791A1 (en) | 1990-07-10 | 1992-11-26 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| DK0605522T3 (en) | 1991-09-23 | 2000-01-17 | Medical Res Council | Process for producing humanized antibodies |
| ES2227512T3 (en) | 1991-12-02 | 2005-04-01 | Medical Research Council | PRODUCTION OF ANTIBODIES AGAINST SELF-ANTIGENS FROM REPERTORIES OF ANTIBODY SEGMENTS FIXED IN A PHOTO. |
| JP3507073B2 (en) | 1992-03-24 | 2004-03-15 | ケンブリッジ アンティボディー テクノロジー リミティド | Methods for producing members of a specific binding pair |
| GB9313509D0 (en) | 1993-06-30 | 1993-08-11 | Medical Res Council | Chemisynthetic libraries |
| EP0731842A1 (en) | 1993-12-03 | 1996-09-18 | Medical Research Council | Recombinant binding proteins and peptides |
| US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
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| DE19819846B4 (en) | 1998-05-05 | 2016-11-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Multivalent antibody constructs |
| PT1914244E (en) | 1999-04-09 | 2013-07-26 | Kyowa Hakko Kirin Co Ltd | Method of modulating the activity of functional immune molecules |
| CA2785941C (en) | 2000-10-06 | 2017-01-10 | Kyowa Hakko Kirin Co., Ltd. | Antibody composition-producing cell |
| PT1583830E (en) | 2003-01-07 | 2006-11-30 | Symphogen As | Method for manufacturing recombinant polyclonal proteins |
| WO2009048072A1 (en) | 2007-10-11 | 2009-04-16 | Daiichi Sankyo Company, Limited | ANTIBODY TARGETING OSTEOCLAST-RELATED PROTEIN Siglec-15 |
| WO2009089004A1 (en) | 2008-01-07 | 2009-07-16 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| EP2285969B1 (en) | 2008-05-15 | 2013-01-16 | National Research Council Of Canada | Use of protein kinase b and valproic acid to increase heterologous gene expression in mammalian cells |
| PL2975051T3 (en) | 2009-06-26 | 2021-09-20 | Regeneron Pharmaceuticals, Inc. | Readily isolated bispecific antibodies with native immunoglobulin format |
| PL2773671T3 (en) | 2011-11-04 | 2022-01-24 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| EP2832856A4 (en) | 2012-03-29 | 2016-01-27 | Chugai Pharmaceutical Co Ltd | Anti-lamp5 antibody and utilization thereof |
| CN110981964B (en) | 2013-01-14 | 2023-09-15 | Xencor股份有限公司 | Novel heterodimeric proteins |
| AU2014273817B2 (en) | 2013-05-31 | 2019-03-14 | Zymeworks Bc Inc. | Heteromultimers with reduced or silenced effector function |
| EP3593812A3 (en) * | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
| RU2725819C2 (en) | 2014-12-05 | 2020-07-06 | Мемориал Слоан-Кеттеринг Кэнсер Сентер | Antibodies targeting a receptor bound to g-proteins, and methods for use thereof |
| AU2015357518B2 (en) * | 2014-12-05 | 2021-10-07 | Eureka Therapeutics, Inc. | Chimeric antigen receptors targeting G-protein coupled receptor and uses thereof |
| EP4039710A3 (en) * | 2015-01-23 | 2022-10-19 | Sanofi | Anti-cd3 antibodies, anti-cd123 antibodies and bispecific antibodies specifically binding to cd3 and/or cd123 |
| TWI781108B (en) * | 2016-07-20 | 2022-10-21 | 比利時商健生藥品公司 | Anti- gprc5d antibodies, bispecific antigen binding molecules that bind gprc5d and cd3, and uses thereof |
-
2018
- 2018-02-06 KR KR1020197026251A patent/KR20190133160A/en unknown
- 2018-02-06 CA CA3052938A patent/CA3052938A1/en not_active Abandoned
- 2018-02-06 JP JP2018567427A patent/JPWO2018147245A1/en active Pending
- 2018-02-06 EP EP18750649.8A patent/EP3581651A4/en not_active Withdrawn
- 2018-02-06 BR BR112019016204-6A patent/BR112019016204A2/en not_active IP Right Cessation
- 2018-02-06 CN CN201880021882.6A patent/CN110462038A/en active Pending
- 2018-02-06 TW TW107104091A patent/TW201837174A/en unknown
- 2018-02-06 RU RU2019128134A patent/RU2019128134A/en not_active Application Discontinuation
- 2018-02-06 AU AU2018218753A patent/AU2018218753A1/en not_active Abandoned
- 2018-02-06 SG SG10201912368XA patent/SG10201912368XA/en unknown
- 2018-02-06 SG SG11201907321TA patent/SG11201907321TA/en unknown
- 2018-02-06 MX MX2019009358A patent/MX2019009358A/en unknown
- 2018-02-06 WO PCT/JP2018/003888 patent/WO2018147245A1/en unknown
- 2018-06-02 US US16/483,211 patent/US20190367612A1/en not_active Abandoned
-
2019
- 2019-08-07 IL IL268588A patent/IL268588A/en unknown
- 2019-08-07 PH PH12019501824A patent/PH12019501824A1/en unknown
- 2019-09-06 CO CONC2019/0009680A patent/CO2019009680A2/en unknown
- 2019-09-06 ZA ZA2019/05905A patent/ZA201905905B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20190133160A (en) | 2019-12-02 |
| PH12019501824A1 (en) | 2020-09-14 |
| WO2018147245A1 (en) | 2018-08-16 |
| BR112019016204A2 (en) | 2020-07-07 |
| US20190367612A1 (en) | 2019-12-05 |
| EP3581651A1 (en) | 2019-12-18 |
| AU2018218753A1 (en) | 2019-09-26 |
| CN110462038A (en) | 2019-11-15 |
| ZA201905905B (en) | 2022-05-25 |
| JPWO2018147245A1 (en) | 2019-11-21 |
| RU2019128134A3 (en) | 2021-12-27 |
| RU2019128134A (en) | 2021-03-09 |
| EP3581651A4 (en) | 2021-05-12 |
| SG11201907321TA (en) | 2019-09-27 |
| CA3052938A1 (en) | 2018-08-16 |
| CO2019009680A2 (en) | 2020-02-07 |
| MX2019009358A (en) | 2019-12-02 |
| IL268588A (en) | 2019-09-26 |
| TW201837174A (en) | 2018-10-16 |
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