AR116718A1 - Proteínas de unión triespecíficas anti-cd38, anti-cd28 y anti-cd3 y métodos de uso para tratar infección vírica - Google Patents
Proteínas de unión triespecíficas anti-cd38, anti-cd28 y anti-cd3 y métodos de uso para tratar infección víricaInfo
- Publication number
- AR116718A1 AR116718A1 ARP190102858A ARP190102858A AR116718A1 AR 116718 A1 AR116718 A1 AR 116718A1 AR P190102858 A ARP190102858 A AR P190102858A AR P190102858 A ARP190102858 A AR P190102858A AR 116718 A1 AR116718 A1 AR 116718A1
- Authority
- AR
- Argentina
- Prior art keywords
- viral infection
- binding proteins
- methods
- treat viral
- polypeptide
- Prior art date
Links
Classifications
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- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
-
- 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
- C07K16/2818—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 CD28 or CD152
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- 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
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- 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
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- 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
- C07K2317/524—CH2 domain
-
- 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
- C07K2317/526—CH3 domain
-
- 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
- C07K2317/567—Framework region [FR]
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- General Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
La descripción proporciona métodos para tratar la infección viral usando proteínas de unión triespecíficas que comprenden cuatro cadenas de polipéptidos que forman tres sitios de unión a antígeno a los que se unen específicamente un polipéptido CD38 (p.ej., polipéptidos CD38 humano y/o mono de cinomolgo), un polipéptido CD28, y un polipéptido CD3.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762570655P | 2017-10-10 | 2017-10-10 | |
US201762570660P | 2017-10-11 | 2017-10-11 | |
US201862676221P | 2018-05-24 | 2018-05-24 | |
EP18187186 | 2018-08-03 | ||
PCT/US2018/055084 WO2019074973A2 (en) | 2017-10-10 | 2018-10-09 | ANTI-CD38 ANTIBODIES AND METHODS OF USE |
Publications (1)
Publication Number | Publication Date |
---|---|
AR116718A1 true AR116718A1 (es) | 2021-06-09 |
Family
ID=63963620
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP190102858A AR116718A1 (es) | 2017-10-10 | 2019-10-08 | Proteínas de unión triespecíficas anti-cd38, anti-cd28 y anti-cd3 y métodos de uso para tratar infección vírica |
Country Status (17)
Country | Link |
---|---|
US (3) | US11186649B2 (es) |
EP (2) | EP4249068A3 (es) |
JP (3) | JP7036909B2 (es) |
KR (1) | KR20200061402A (es) |
CN (2) | CN111788225A (es) |
AR (1) | AR116718A1 (es) |
AU (1) | AU2018348093A1 (es) |
BR (1) | BR112020007002A2 (es) |
CA (1) | CA3078800A1 (es) |
IL (1) | IL273871A (es) |
MA (1) | MA50359A (es) |
MX (1) | MX2020004129A (es) |
PH (1) | PH12020550408A1 (es) |
SG (1) | SG11202003212PA (es) |
TW (2) | TW202342544A (es) |
UY (1) | UY37928A (es) |
WO (1) | WO2019074973A2 (es) |
Families Citing this family (30)
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EP1914242A1 (en) * | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
TWI622597B (zh) * | 2011-03-28 | 2018-05-01 | 賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
DK2943511T3 (da) | 2013-01-14 | 2019-10-21 | Xencor Inc | Nye heterodimeriske proteiner |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
IL252480B2 (en) | 2014-11-26 | 2023-12-01 | Xencor Inc | Heterodimeric antibodies that bind CD3 and tumor antigens |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
RS62437B1 (sr) | 2015-10-25 | 2021-11-30 | Sanofi Sa | Trispecifični i/ili trivalentni vezujući proteini za prevenciju ili lečenje hiv infekcije |
BR112018070998A2 (pt) | 2016-04-13 | 2019-02-26 | Sanofi | proteínas de ligação triespecíficas e/ou trivalentes |
SI3443006T1 (sl) | 2016-04-13 | 2024-01-31 | Sanofi | Trispecifični in/ali trivalentni vezni proteini |
WO2018237037A2 (en) | 2017-06-20 | 2018-12-27 | Teneobio, Inc. | HEAVY CHAIN ANTIBODY ONLY ANTI-BCMA |
KR20200061402A (ko) | 2017-10-10 | 2020-06-02 | 사노피 | 항-cd38 항체 및 항-cd3 및 항-cd28 항체와의 조합 |
EP3784699A4 (en) | 2018-04-25 | 2022-04-13 | Prometheus Biosciences, Inc. | OPTIMIZED ANTI-TL1A ANTIBODIES |
KR20210075129A (ko) | 2018-10-09 | 2021-06-22 | 사노피 | 삼중특이적 항-cd38, 항-cd28, 및 항-cd3 결합 단백질 및 바이러스 감염을 치료하기 위한 사용 방법 |
BR112021019915A2 (pt) * | 2019-04-09 | 2021-12-07 | Sanofi Sa | Proteínas de ligação triespecíficas, métodos e usos dos mesmos |
US11613576B2 (en) | 2019-04-09 | 2023-03-28 | Sanofi | Trispecific binding proteins, methods, and uses thereof |
AU2020299600A1 (en) * | 2019-07-03 | 2022-01-06 | Crystal Bioscience Inc. | Anti-CD38 antibody and methods of use thereof |
KR20220103721A (ko) | 2019-10-24 | 2022-07-22 | 프로메테우스 바이오사이언시즈, 인크. | Tnf 유사 리간드 1a(tl1a)에 대한 인간화 항체 및 그의 용도 |
US20210123926A1 (en) | 2019-10-25 | 2021-04-29 | Sanofi | Methods for analyzing chain mispairing in multispecific binding proteins |
CN112876563B (zh) * | 2019-11-29 | 2022-08-16 | 康诺亚生物医药科技(成都)有限公司 | 药物组合物及其制备方法和应用 |
UY39191A (es) * | 2020-04-29 | 2021-11-30 | Teneobio Inc | Anticuerpos de cadena pesada multiespecíficos con regiones constantes de cadena pesada modificadas |
CA3176792A1 (en) * | 2020-04-29 | 2021-11-04 | Katherine HARRIS | Anti-cd3 and anti-bcma bispecific antibodies wth modified heavy chain constant regions |
US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
MX2023001962A (es) | 2020-08-19 | 2023-04-26 | Xencor Inc | Composiciones anti-cd28. |
AU2021345262A1 (en) * | 2020-09-18 | 2023-05-11 | Regeneron Pharmaceuticals, Inc. | Antigen-binding molecules that bind cd38 and/or cd28, and uses thereof |
WO2022192403A1 (en) | 2021-03-09 | 2022-09-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cldn6 |
EP4305065A1 (en) | 2021-03-10 | 2024-01-17 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and gpc3 |
WO2023284806A1 (zh) * | 2021-07-14 | 2023-01-19 | 江苏恒瑞医药股份有限公司 | 特异性结合cd38、bcma和cd3的抗原结合分子及其医药用途 |
CA3226428A1 (en) * | 2021-08-02 | 2023-02-09 | Hangzhou Unogen Biotech, Ltd | Anti-cd38 antibodies, anti-cd3 antibodies, and bispecific antibodies, and uses thereof |
AR126838A1 (es) * | 2021-08-20 | 2023-11-22 | Novartis Ag | Métodos para preparar células que expresan receptores de antígeno quiméricos |
WO2023246911A1 (zh) * | 2022-06-24 | 2023-12-28 | 北京可瑞生物科技有限公司 | 基于t细胞受体的双特异性多肽分子及其用途 |
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BR112018070998A2 (pt) | 2016-04-13 | 2019-02-26 | Sanofi | proteínas de ligação triespecíficas e/ou trivalentes |
WO2018120842A1 (zh) | 2016-12-30 | 2018-07-05 | 上海欣百诺生物科技有限公司 | 一种双功能分子及其应用 |
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KR20200061402A (ko) | 2017-10-10 | 2020-06-02 | 사노피 | 항-cd38 항체 및 항-cd3 및 항-cd28 항체와의 조합 |
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- 2018-10-09 JP JP2020519704A patent/JP7036909B2/ja active Active
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IL273871A (en) | 2020-05-31 |
WO2019074973A2 (en) | 2019-04-18 |
CN111788225A (zh) | 2020-10-16 |
JP7036909B2 (ja) | 2022-03-15 |
JP2024020377A (ja) | 2024-02-14 |
SG11202003212PA (en) | 2020-05-28 |
EP3694882A2 (en) | 2020-08-19 |
JP2020536543A (ja) | 2020-12-17 |
US20220275102A1 (en) | 2022-09-01 |
TWI821202B (zh) | 2023-11-11 |
UY37928A (es) | 2019-05-31 |
US11186649B2 (en) | 2021-11-30 |
PH12020550408A1 (en) | 2021-04-12 |
TW202342544A (zh) | 2023-11-01 |
CA3078800A1 (en) | 2019-04-18 |
RU2020115450A (ru) | 2021-11-15 |
EP4249068A3 (en) | 2023-11-22 |
WO2019074973A3 (en) | 2019-06-13 |
BR112020007002A2 (pt) | 2020-11-17 |
US20190106504A1 (en) | 2019-04-11 |
CN117964758A (zh) | 2024-05-03 |
KR20200061402A (ko) | 2020-06-02 |
JP7387780B2 (ja) | 2023-11-28 |
US20220041746A1 (en) | 2022-02-10 |
TW201930338A (zh) | 2019-08-01 |
MA50359A (fr) | 2020-08-19 |
MX2020004129A (es) | 2020-08-20 |
US11365261B2 (en) | 2022-06-21 |
JP2022071087A (ja) | 2022-05-13 |
AU2018348093A1 (en) | 2020-05-28 |
EP4249068A2 (en) | 2023-09-27 |
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