SG11201707105TA - scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY - Google Patents

scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY

Info

Publication number
SG11201707105TA
SG11201707105TA SG11201707105TA SG11201707105TA SG11201707105TA SG 11201707105T A SG11201707105T A SG 11201707105TA SG 11201707105T A SG11201707105T A SG 11201707105TA SG 11201707105T A SG11201707105T A SG 11201707105TA SG 11201707105T A SG11201707105T A SG 11201707105TA
Authority
SG
Singapore
Prior art keywords
avidity
scfv
dimers
specificity
growth factor
Prior art date
Application number
SG11201707105TA
Other languages
English (en)
Inventor
Huawei Qiu
Clark Pan
Julie Bird
Original Assignee
Genzyme Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genzyme Corp filed Critical Genzyme Corp
Publication of SG11201707105TA publication Critical patent/SG11201707105TA/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35Valency
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/53Hinge
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/626Diabody or triabody
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72Increased effector function due to an Fc-modification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/23Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a GST-tag
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/73Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Peptides Or Proteins (AREA)
SG11201707105TA 2015-03-04 2016-03-03 scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY SG11201707105TA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562128133P 2015-03-04 2015-03-04
PCT/US2016/020779 WO2016141244A1 (en) 2015-03-04 2016-03-03 scFv-Fc DIMERS THAT BIND TRASFORMING GROWTH FACTOR-β1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY

Publications (1)

Publication Number Publication Date
SG11201707105TA true SG11201707105TA (en) 2017-09-28

Family

ID=55538640

Family Applications (2)

Application Number Title Priority Date Filing Date
SG10201912449UA SG10201912449UA (en) 2015-03-04 2016-03-03 scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY
SG11201707105TA SG11201707105TA (en) 2015-03-04 2016-03-03 scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY

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SG10201912449UA SG10201912449UA (en) 2015-03-04 2016-03-03 scFv-Fc DIMERS THAT BIND TRANSFORMING GROWTH FACTOR-ß1 WITH HIGH AFFINITY, AVIDITY AND SPECIFICITY

Country Status (15)

Country Link
US (3) US10508146B2 (ko)
EP (1) EP3265484A1 (ko)
JP (1) JP6845802B2 (ko)
KR (2) KR102598790B1 (ko)
CN (1) CN107889491B (ko)
AR (1) AR103839A1 (ko)
AU (1) AU2016226097B2 (ko)
BR (1) BR112017018767A2 (ko)
CA (1) CA2978459A1 (ko)
IL (1) IL254238B (ko)
MX (2) MX2017011251A (ko)
RU (1) RU2733286C2 (ko)
SG (2) SG10201912449UA (ko)
TW (1) TWI726870B (ko)
WO (1) WO2016141244A1 (ko)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI733661B (zh) 2015-03-04 2021-07-21 美商健臻公司 以高親合性、結合性及特異性結合轉化生長因子-β1的經修飾IgG抗體
TWI726870B (zh) 2015-03-04 2021-05-11 美商健臻公司 具有高親和性、結合性及專一性之結合轉形生長因子-β1的scFv-Fc二聚體
WO2017189959A1 (en) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions for the treatment of disease
WO2017189964A2 (en) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions for the treatment of disease
CN112500491B (zh) * 2020-12-18 2022-04-08 深圳市迈加瑞生物技术有限公司 一种特异性中和辅助性T细胞TGF-β信号的双特异性抗体、其药物组合及其用途

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US20020099179A1 (en) 1989-12-21 2002-07-25 Linda K. Jolliffe Cdr-grafted antibodies
US5616561A (en) 1995-03-31 1997-04-01 Regents Of The University Of California TGF-β antagonists as mitigators of radiation-induced tissue damage
ES2146552B1 (es) * 1998-11-24 2001-04-16 Inst Cientifico Tecnol Navarra Peptidos inhibidores de tgf/31
EP1486560A3 (en) 1999-04-30 2005-02-09 Cambridge Antibody Technology LTD Specific antibodies and antibody fragments for TGFBETA1
US6492497B1 (en) 1999-04-30 2002-12-10 Cambridge Antibody Technology Limited Specific binding members for TGFbeta1
WO2004098637A1 (en) 2003-04-30 2004-11-18 Genzyme Corporation Tgf-beta antagonists combined with renin-angiotensin-aldosteron-system antagonists for treating renal insufficiency
ZA200608130B (en) 2004-03-31 2008-12-31 Genentech Inc Humanized anti-TGF-beta antibodies
WO2006036729A2 (en) 2004-09-22 2006-04-06 Genzyme Corporation USE OF TGF-β ANTAGONISTS TO LIMIT NEPHROTOXICITY OF IMMUNOSUPPRESSIVE AGENTS
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WO2006116002A2 (en) * 2005-04-22 2006-11-02 Eli Lilly And Company Tgf beta 1 specific antibodies
AU2006330542B2 (en) 2005-12-23 2012-05-24 Eli Lilly And Company TGF-beta binding compositions
AU2007227292B2 (en) 2006-03-17 2012-04-12 Biogen Ma Inc. Stabilized polypeptide compositions
EP2006380A4 (en) 2006-03-23 2010-08-11 Kyowa Hakko Kirin Co Ltd AGONIST ANTIBODY AGAINST THE HUMAN THROMBOPOIETINE RECEPTOR
EP2083863B1 (en) 2006-10-03 2015-03-18 Genzyme Corporation Antibodies to tgf-beta for use in the treatment of infants at risk of developing bronchopulmonary dysplasia
JP2012531885A (ja) 2008-07-02 2012-12-13 エマージェント プロダクト デベロップメント シアトル, エルエルシー Il6免疫治療剤
WO2012088461A2 (en) * 2010-12-23 2012-06-28 Biogen Idec Inc. Linker peptides and polypeptides comprising same
TWI588156B (zh) 2011-03-28 2017-06-21 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
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IN2015DN01299A (ko) 2012-07-23 2015-07-03 Zymeworks Inc
ES2713505T3 (es) * 2013-03-11 2019-05-22 Genzyme Corp Anticuerpos anti-TGF-beta modificados genéticamente y fragmentos de unión a antígeno
TWI733661B (zh) 2015-03-04 2021-07-21 美商健臻公司 以高親合性、結合性及特異性結合轉化生長因子-β1的經修飾IgG抗體
TWI726870B (zh) 2015-03-04 2021-05-11 美商健臻公司 具有高親和性、結合性及專一性之結合轉形生長因子-β1的scFv-Fc二聚體

Also Published As

Publication number Publication date
WO2016141244A1 (en) 2016-09-09
AU2016226097B2 (en) 2022-01-13
KR20170120173A (ko) 2017-10-30
US20180222970A1 (en) 2018-08-09
SG10201912449UA (en) 2020-02-27
KR102598790B1 (ko) 2023-11-07
CN107889491A (zh) 2018-04-06
MX2022007456A (es) 2022-06-27
AU2016226097A1 (en) 2017-10-26
US20220363740A1 (en) 2022-11-17
JP6845802B2 (ja) 2021-03-24
RU2017134042A3 (ko) 2019-10-08
KR20230156798A (ko) 2023-11-14
AR103839A1 (es) 2017-06-07
RU2017134042A (ru) 2019-04-05
CA2978459A1 (en) 2016-09-09
EP3265484A1 (en) 2018-01-10
US11325971B2 (en) 2022-05-10
AU2016226097A8 (en) 2017-11-09
IL254238B (en) 2022-01-01
US20200131258A1 (en) 2020-04-30
WO2016141244A8 (en) 2016-10-20
JP2018508218A (ja) 2018-03-29
IL254238A0 (en) 2017-10-31
US10508146B2 (en) 2019-12-17
TW201706303A (zh) 2017-02-16
BR112017018767A2 (pt) 2018-04-17
RU2733286C2 (ru) 2020-10-01
CN107889491B (zh) 2022-01-07
MX2017011251A (es) 2018-02-19
TWI726870B (zh) 2021-05-11
US11976112B2 (en) 2024-05-07

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