EA032203B1 - Производные тубулизина - Google Patents

Производные тубулизина Download PDF

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Publication number
EA032203B1
EA032203B1 EA201691963A EA201691963A EA032203B1 EA 032203 B1 EA032203 B1 EA 032203B1 EA 201691963 A EA201691963 A EA 201691963A EA 201691963 A EA201691963 A EA 201691963A EA 032203 B1 EA032203 B1 EA 032203B1
Authority
EA
Eurasian Patent Office
Prior art keywords
cancer
mmol
resin
antibody
mixture
Prior art date
Application number
EA201691963A
Other languages
English (en)
Russian (ru)
Other versions
EA201691963A1 (ru
Inventor
Лакшмаях Гинджипалли
Дорин Тоадер
Фэнцзян Ван
Original Assignee
МЕДИММЬЮН ЭлЭлСи
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
Application filed by МЕДИММЬЮН ЭлЭлСи filed Critical МЕДИММЬЮН ЭлЭлСи
Publication of EA201691963A1 publication Critical patent/EA201691963A1/ru
Publication of EA032203B1 publication Critical patent/EA032203B1/ru

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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
    • A61K47/6835—Medicinal 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
    • A61K47/6851—Medicinal 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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0212—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -N-C-N-C(=0)-, e.g. retro-inverso peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
EA201691963A 2014-04-11 2015-04-10 Производные тубулизина EA032203B1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461978460P 2014-04-11 2014-04-11
PCT/US2015/025235 WO2015157594A1 (en) 2014-04-11 2015-04-10 Tubulysin derivatives

Publications (2)

Publication Number Publication Date
EA201691963A1 EA201691963A1 (ru) 2017-06-30
EA032203B1 true EA032203B1 (ru) 2019-04-30

Family

ID=54264545

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201691963A EA032203B1 (ru) 2014-04-11 2015-04-10 Производные тубулизина

Country Status (19)

Country Link
US (2) US9427479B2 (enExample)
EP (1) EP3129362A4 (enExample)
JP (1) JP2017510661A (enExample)
KR (1) KR20160142392A (enExample)
CN (1) CN106458942A (enExample)
AR (1) AR100006A1 (enExample)
AU (1) AU2015243379B2 (enExample)
CA (1) CA2945318A1 (enExample)
CL (1) CL2016002548A1 (enExample)
EA (1) EA032203B1 (enExample)
IL (1) IL247822A0 (enExample)
MA (1) MA39862A (enExample)
MX (1) MX2016013373A (enExample)
NZ (1) NZ725131A (enExample)
PH (1) PH12016501995A1 (enExample)
SG (1) SG11201608203RA (enExample)
TW (1) TW201625662A (enExample)
UY (1) UY36075A (enExample)
WO (1) WO2015157594A1 (enExample)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201625662A (zh) * 2014-04-11 2016-07-16 麥迪紐有限責任公司 妥布賴森（ｔｕｂｕｌｙｓｉｎ）衍生物
MX2016012830A (es) 2014-04-11 2017-01-05 Medimmune Llc Anticuerpos contra el receptor 2 del factor de crecimiento epidermico humano (her2) biespecificos.
US10808007B2 (en) * 2015-02-25 2020-10-20 William Marsh Rice University Desacetoxytubulysin H and analogs thereof
KR20180073675A (ko) 2015-11-10 2018-07-02 메디뮨 엘엘씨 Asct2에 특이적인 결합 분자 및 이의 용도
MX2018006218A (es) 2015-12-04 2018-09-05 Seattle Genetics Inc Conjugados de compuestos de tubulisina cuaternizada.
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
US10723727B2 (en) * 2016-02-01 2020-07-28 Pfizer Inc. Tubulysin analogs and methods for their preparation
SG11201808979UA (en) 2016-04-15 2018-11-29 Macrogenics Inc Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof
JP2019534882A (ja) 2016-10-11 2019-12-05 メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ 免疫介在性療法薬を有する抗体−薬物コンジュゲート
AU2018311503C1 (en) 2017-08-01 2023-11-30 Medimmune, Llc BCMA monoclonal antibody-drug conjugate
AU2017445144A1 (en) * 2017-12-31 2020-06-18 Hangzhou Dac Biotech Co. Ltd A conjugate of a tubulysin analog with branched linkers
CN109456212A (zh) * 2018-12-03 2019-03-12 康化（上海）新药研发有限公司 一种沙库比曲中间体的合成方法
WO2020132658A2 (en) 2018-12-21 2020-06-25 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
TWI753252B (zh) * 2019-05-03 2022-01-21 中國大陸商杭州多禧生物科技有限公司 含支鏈連接體的Ｔｕｂｕｌｙｓｉｎ同系物偶聯物
KR20220024914A (ko) * 2019-06-24 2022-03-03 항저우 디에이씨 바이오테크 씨오, 엘티디 분지형 링커를 사용한 세포독성제 대 세포 결합 분자의 접합체
PH12023550032A1 (en) * 2020-06-24 2024-03-18 Regeneron Pharma Tubulysins and protein-tubulysin conjugates
WO2022053650A1 (en) 2020-09-11 2022-03-17 Medimmune Limited Therapeutic b7-h4 binding molecules
KR20240099430A (ko) 2021-11-10 2024-06-28 아스트라제네카 아베 항체 분자 및 접합체
GB202117928D0 (en) 2021-12-11 2022-01-26 Cancer Research Tech Ltd Immunotherapy for cancer
KR20250029133A (ko) 2022-06-27 2025-03-04 아스트라제네카 아베 암 치료를 위한 표피성장인자 수용체 티로신 키나제 억제제를 포함하는 조합물
WO2025078841A2 (en) 2023-10-11 2025-04-17 Antikor Biopharma Limited Antibodies, conjugates, and uses thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060148014A1 (en) * 2004-12-09 2006-07-06 Sergei Agoulnik Tubulin isotype screening in cancer therapy using hemiasterlin analogs
US20080108820A1 (en) * 2002-03-22 2008-05-08 Campagna Silvio A Hemiasterlin Derivatives and Uses Thereof
US20130129753A1 (en) * 2011-11-17 2013-05-23 Pfizer Inc. Cytotoxic peptides and antibody drug conjugates thereof
US20130197259A1 (en) * 2009-08-03 2013-08-01 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof

Family Cites Families (6)

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Publication number Priority date Publication date Assignee Title
IT1394860B1 (it) * 2009-07-22 2012-07-20 Kemotech S R L Composti farmaceutici
US20130224228A1 (en) * 2011-12-05 2013-08-29 Igenica, Inc. Antibody-Drug Conjugates and Related Compounds, Compositions, and Methods
KR102215954B1 (ko) * 2013-02-14 2021-02-15 브리스톨-마이어스 스큅 컴퍼니 튜부리신 화합물, 그의 제조 및 사용 방법
TW201625662A (zh) * 2014-04-11 2016-07-16 麥迪紐有限責任公司 妥布賴森（ｔｕｂｕｌｙｓｉｎ）衍生物
WO2015155345A1 (en) * 2014-04-11 2015-10-15 Medimmune Limited Antibodies and antibody-drug conjugates
MX2016012830A (es) 2014-04-11 2017-01-05 Medimmune Llc Anticuerpos contra el receptor 2 del factor de crecimiento epidermico humano (her2) biespecificos.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080108820A1 (en) * 2002-03-22 2008-05-08 Campagna Silvio A Hemiasterlin Derivatives and Uses Thereof
US20060148014A1 (en) * 2004-12-09 2006-07-06 Sergei Agoulnik Tubulin isotype screening in cancer therapy using hemiasterlin analogs
US20130197259A1 (en) * 2009-08-03 2013-08-01 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
US20130129753A1 (en) * 2011-11-17 2013-05-23 Pfizer Inc. Cytotoxic peptides and antibody drug conjugates thereof

Also Published As

Publication number Publication date
AU2015243379B2 (en) 2018-02-01
US10159745B2 (en) 2018-12-25
TW201625662A (zh) 2016-07-16
WO2015157594A1 (en) 2015-10-15
CL2016002548A1 (es) 2017-02-24
AR100006A1 (es) 2016-08-31
CN106458942A (zh) 2017-02-22
IL247822A0 (en) 2016-11-30
JP2017510661A (ja) 2017-04-13
US9427479B2 (en) 2016-08-30
EP3129362A4 (en) 2017-08-23
UY36075A (es) 2015-10-30
AU2015243379A1 (en) 2016-11-03
US20160339114A1 (en) 2016-11-24
NZ725131A (en) 2018-03-23
KR20160142392A (ko) 2016-12-12
SG11201608203RA (en) 2016-10-28
US20150291657A1 (en) 2015-10-15
PH12016501995A1 (en) 2017-01-09
EP3129362A1 (en) 2017-02-15
MX2016013373A (es) 2017-05-02
MA39862A (fr) 2017-02-15
EA201691963A1 (ru) 2017-06-30
CA2945318A1 (en) 2015-10-15

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