RU2018105687A - Иммуноконъюгаты на основе il22 - Google Patents

Иммуноконъюгаты на основе il22 Download PDF

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Publication number
RU2018105687A
RU2018105687A RU2018105687A RU2018105687A RU2018105687A RU 2018105687 A RU2018105687 A RU 2018105687A RU 2018105687 A RU2018105687 A RU 2018105687A RU 2018105687 A RU2018105687 A RU 2018105687A RU 2018105687 A RU2018105687 A RU 2018105687A
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RU
Russia
Prior art keywords
conjugate
paragraphs
conjugate according
patient
antibody molecule
Prior art date
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RU2018105687A
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English (en)
Russian (ru)
Inventor
Франциска Софи БУТЦ
Дарио Нери
Original Assignee
Филоджен С.П.А.
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.)
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Publication date
Priority claimed from GBGB1512486.0A external-priority patent/GB201512486D0/en
Priority claimed from GBGB1517649.8A external-priority patent/GB201517649D0/en
Priority claimed from GBGB1521470.3A external-priority patent/GB201521470D0/en
Application filed by Филоджен С.П.А. filed Critical Филоджен С.П.А.
Publication of RU2018105687A publication Critical patent/RU2018105687A/ru

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/54Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6813Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • 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
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K19/00Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • 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
    • C07K2319/00Fusion polypeptide
    • C07K2319/33Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
RU2018105687A 2015-07-16 2016-07-15 Иммуноконъюгаты на основе il22 RU2018105687A (ru)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
GBGB1512486.0A GB201512486D0 (en) 2015-07-16 2015-07-16 IL22 immunoconjugates
GB1512486.0 2015-07-16
GBGB1517649.8A GB201517649D0 (en) 2015-10-06 2015-10-06 IL22 Immunoconjugates
GB1517649.8 2015-10-06
GBGB1521470.3A GB201521470D0 (en) 2015-12-04 2015-12-04 IL22 immunoconjugates
GB1521470.3 2015-12-04
PCT/EP2016/066979 WO2017009469A1 (en) 2015-07-16 2016-07-15 Il22 immunoconjugates

Publications (1)

Publication Number Publication Date
RU2018105687A true RU2018105687A (ru) 2019-08-16

Family

ID=56413683

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2018105687A RU2018105687A (ru) 2015-07-16 2016-07-15 Иммуноконъюгаты на основе il22

Country Status (21)

Country Link
US (2) US10246502B2 (https=)
EP (1) EP3322719B1 (https=)
JP (1) JP6735822B2 (https=)
KR (1) KR20180030180A (https=)
CN (1) CN108137667A (https=)
AU (1) AU2016293114A1 (https=)
BR (1) BR112018000909A2 (https=)
CA (1) CA2992366A1 (https=)
CL (1) CL2018000131A1 (https=)
CO (1) CO2018000414A2 (https=)
CR (1) CR20180087A (https=)
DO (1) DOP2018000019A (https=)
EC (1) ECSP18010616A (https=)
ES (1) ES2778430T3 (https=)
HK (1) HK1250237A1 (https=)
IL (1) IL256849A (https=)
MX (1) MX2018000687A (https=)
PE (1) PE20180797A1 (https=)
PH (1) PH12018500131A1 (https=)
RU (1) RU2018105687A (https=)
WO (1) WO2017009469A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200123118A (ko) * 2018-02-21 2020-10-28 제넨테크, 인크. IL-22 Fc 융합 단백질로 치료를 위한 투약
WO2020249757A1 (en) 2019-06-14 2020-12-17 Philogen S.P.A Immunoconjugates comprising a single chain diabody and interleukin-15 or interleukin-15 and a sushi domain of interleukin-15 receptor alpha
EP4185615A1 (en) 2020-07-22 2023-05-31 Philogen S.p.A. Treatment of pulmonary hypertension
TW202221019A (zh) * 2020-07-30 2022-06-01 美商安維塔生物科學股份有限公司 介白素-22融合蛋白及其藥物組合物及治療應用
WO2022073038A1 (en) * 2020-10-02 2022-04-07 Abbvie Inc. Interleukin-22 (il-22) fusion proteins and uses thereof
CN115703841A (zh) * 2021-08-10 2023-02-17 复旦大学 白介素17a抗体与白介素22细胞因子融合蛋白及其制备方法与用途
WO2023175077A1 (en) 2022-03-17 2023-09-21 Philogen S.P.A Anti-ed-a antibodies for the treatment of pulmonary hypertension
WO2025101842A1 (en) * 2023-11-09 2025-05-15 Flagship Pioneering Innovations Vii, Llc Compositions and methods for targeted delivery of therapeutic agents
WO2026003203A1 (en) 2024-06-27 2026-01-02 Philogen S.P.A. Combination of an immunocytokine comprising targeted il2 and a jak inhibitor

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1702069A2 (en) 2004-01-05 2006-09-20 EMD Lexigen Research Center Corp. Interleukin-12 targeted to oncofoetal fibronectin
ES2388068T3 (es) 2004-12-23 2012-10-08 Molmed Spa Producto de conjugación
CA2593648A1 (en) * 2005-01-10 2006-07-13 Research Development Foundation Targeted chimeric molecules for cancer therapy
CA2607954A1 (en) 2005-05-11 2006-11-16 Philogen S.P.A. Conjugate for targeting of drug
WO2008120101A2 (en) 2007-04-02 2008-10-09 Philogen S.P.A. The ed-a antigen of fibrinogen is associated with the neovasculature of tumour metastases
EP2167541B1 (en) 2007-07-25 2012-12-19 Philogen S.p.A. The ed-a antigen of fibronectin is associated with the neovasculature of tumour metastases
DK3281952T3 (da) 2007-10-30 2020-08-03 Philogen Spa Antigen, der er forbundet med reumatoid artritis
AU2011205531B2 (en) 2010-01-13 2013-10-10 Amgen Inc. IL-22-Fc and hepcidin activity
AR081246A1 (es) * 2010-05-14 2012-07-18 Abbott Lab Proteinas de union a il-1
WO2014145016A2 (en) * 2013-03-15 2014-09-18 Genentech, Inc. Il-22 polypeptides and il-22 fc fusion proteins and methods of use
CA2910044A1 (en) * 2013-04-26 2014-10-30 Philogen S.P.A. Il4 conjugated to antibodies against extracellular matrix components
CN104623639A (zh) * 2013-11-07 2015-05-20 健能隆医药技术(上海)有限公司 白介素22二聚体在制备治疗胰腺炎药物中的应用

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Publication number Publication date
PH12018500131A1 (en) 2018-07-23
CO2018000414A2 (es) 2018-04-10
CR20180087A (es) 2018-05-14
US10246502B2 (en) 2019-04-02
MX2018000687A (es) 2018-08-01
US20190169250A1 (en) 2019-06-06
US10858411B2 (en) 2020-12-08
DOP2018000019A (es) 2018-10-15
ECSP18010616A (es) 2018-04-30
BR112018000909A2 (pt) 2018-09-11
US20170305989A1 (en) 2017-10-26
EP3322719A1 (en) 2018-05-23
JP2018525032A (ja) 2018-09-06
EP3322719B1 (en) 2019-12-18
JP6735822B2 (ja) 2020-08-05
CA2992366A1 (en) 2017-01-19
CL2018000131A1 (es) 2018-06-01
HK1250237A1 (zh) 2018-12-07
KR20180030180A (ko) 2018-03-21
PE20180797A1 (es) 2018-05-09
IL256849A (en) 2018-03-29
WO2017009469A1 (en) 2017-01-19
CN108137667A (zh) 2018-06-08
ES2778430T3 (es) 2020-08-10
AU2016293114A1 (en) 2018-02-01

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Effective date: 20190716