MX2016006674A - Metodos para la conjugacion de oxima con polipeptidos modificados con cetona. - Google Patents
Metodos para la conjugacion de oxima con polipeptidos modificados con cetona.Info
- Publication number
- MX2016006674A MX2016006674A MX2016006674A MX2016006674A MX2016006674A MX 2016006674 A MX2016006674 A MX 2016006674A MX 2016006674 A MX2016006674 A MX 2016006674A MX 2016006674 A MX2016006674 A MX 2016006674A MX 2016006674 A MX2016006674 A MX 2016006674A
- Authority
- MX
- Mexico
- Prior art keywords
- ketone
- protein
- oxime
- payload
- methods
- Prior art date
Links
- 150000002923 oximes Chemical class 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 3
- 230000021615 conjugation Effects 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 title 1
- 102000004196 processed proteins & peptides Human genes 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 title 1
- 235000018102 proteins Nutrition 0.000 abstract 5
- 102000004169 proteins and genes Human genes 0.000 abstract 5
- 108090000623 proteins and genes Proteins 0.000 abstract 5
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 abstract 3
- 150000002576 ketones Chemical class 0.000 abstract 3
- 230000001268 conjugating effect Effects 0.000 abstract 2
- 235000018417 cysteine Nutrition 0.000 abstract 2
- 239000000376 reactant Substances 0.000 abstract 2
- 125000004434 sulfur atom Chemical group 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
-
- 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
- A61K47/54—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 organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- 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
-
- 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
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
-
- 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
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- 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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361909236P | 2013-11-26 | 2013-11-26 | |
| US201462002614P | 2014-05-23 | 2014-05-23 | |
| PCT/IB2014/066300 WO2015079376A1 (en) | 2013-11-26 | 2014-11-24 | Methods for oxime conjugation to ketone-modified polypeptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2016006674A true MX2016006674A (es) | 2016-12-09 |
Family
ID=52117931
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2016006674A MX2016006674A (es) | 2013-11-26 | 2014-11-24 | Metodos para la conjugacion de oxima con polipeptidos modificados con cetona. |
Country Status (15)
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2013350802B2 (en) | 2012-11-30 | 2016-07-14 | Novartis Ag | Methods for making conjugates from disulfide-containing proteins |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| SG11201701565PA (en) | 2014-09-03 | 2017-03-30 | Immunogen Inc | Conjugates comprising cell-binding agents and cytotoxic agents |
| US20190194315A1 (en) | 2015-06-17 | 2019-06-27 | Novartis Ag | Antibody drug conjugates |
| WO2017051254A1 (en) * | 2015-09-25 | 2017-03-30 | Legochem Biosciences, Inc. | Compositions and methods related to anti-egfr antibody drug conjugates |
| WO2017055582A1 (en) | 2015-10-01 | 2017-04-06 | Novo Nordisk A/S | Protein conjugates |
| CR20180229A (es) | 2015-10-29 | 2018-08-24 | Novartis Ag | Conjugados de anticuerpos que comprenden un agonista del receptor tipo toll |
| HUE067016T2 (hu) | 2015-11-25 | 2024-09-28 | Ligachem Biosciences Inc | Önfeláldozó csoportokat tartalmazó konjugátumok és ezekkel kapcsolos eljárások |
| CN107847605B (zh) | 2015-11-25 | 2021-12-24 | 乐高化学生物科学股份有限公司 | 包含分支接头的抗体-药物缀合物及其相关方法 |
| KR102468989B1 (ko) * | 2016-11-18 | 2022-11-22 | 가고시마 유니버시티 | IgG 결합 펩타이드를 포함하는 고상 담체 및 IgG의 분리 방법 |
| JP7664680B2 (ja) | 2017-03-29 | 2025-04-18 | リガケム バイオサイエンシズ， インク． | ピロロベンゾジアゼピン二量体前駆体及びそのリガンド－リンカーコンジュゲート化合物 |
| AR111651A1 (es) | 2017-04-28 | 2019-08-07 | Novartis Ag | Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación |
| US11827703B2 (en) | 2018-05-09 | 2023-11-28 | Legochem Biosciences, Inc. | Compositions and methods related to anti-CD19 antibody drug conjugates |
| US12391939B2 (en) | 2018-07-23 | 2025-08-19 | The Governors Of The University Of Alberta | Genetically-encoded bicyclic peptide libraries |
| KR20210096115A (ko) * | 2018-11-28 | 2021-08-04 | 더 거버너스 오브 더 유니버시티 오브 알버타 | 약물작용 발생단이 내재된 유전자-암호화된 거대고리형 펩타이드 라이브러리 |
| KR20210028544A (ko) | 2019-09-04 | 2021-03-12 | 주식회사 레고켐 바이오사이언스 | 인간 ror1에 대한 항체를 포함하는 항체 약물 접합체 및 이의 용도 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6239110B1 (en) | 1990-02-22 | 2001-05-29 | W.R. Grace & Co. -Conn. | Synthetic analogs of thrombospondin and therapeutic use thereof |
| WO1999013062A1 (en) | 1997-09-09 | 1999-03-18 | Nycomed Imaging As | Factors vii fragments and analogs thereof and their use in the treatment of blood clotting disorders |
| WO1999013063A1 (en) | 1997-09-09 | 1999-03-18 | Nycomed Imaging As | Factor vii fragments and analogs thereof and their use in the treatment of blood clottng disorders |
| GB0316294D0 (en) * | 2003-07-11 | 2003-08-13 | Polytherics Ltd | Conjugated biological molecules and their preparation |
| US8673848B2 (en) | 2012-01-27 | 2014-03-18 | Novartis Ag | Synthetic apelin mimetics for the treatment of heart failure |
| WO2008157380A2 (en) | 2007-06-15 | 2008-12-24 | Adherex Technologies Inc. | Chemically modified cyclic peptides containing cell adhesion recognition (car) sequences and uses therefor |
| US20110172126A1 (en) | 2008-09-03 | 2011-07-14 | Xenome Ltd | Libraries of peptide conjugates and methods for making them |
| DK2889624T3 (en) | 2009-08-10 | 2018-12-10 | Ucl Business Plc | Reversible covalent bonding of functional molecules |
| SG11201502757QA (en) | 2012-10-09 | 2015-05-28 | Igenica Biotherapeutics Inc | Anti-c16orf54 antibodies and methods of use thereof |
| WO2014078623A2 (en) | 2012-11-15 | 2014-05-22 | Brandeis University | Tethering cysteine residues using cyclic disulfides |
| AU2013350802B2 (en) * | 2012-11-30 | 2016-07-14 | Novartis Ag | Methods for making conjugates from disulfide-containing proteins |
-
2014
- 2014-11-24 ES ES14815051T patent/ES2729643T3/es active Active
- 2014-11-24 EA EA201691075A patent/EA201691075A1/ru unknown
- 2014-11-24 EP EP14815051.9A patent/EP3074048B1/en not_active Not-in-force
- 2014-11-24 AU AU2014356126A patent/AU2014356126B2/en not_active Ceased
- 2014-11-24 CN CN201480064270.7A patent/CN105764530B/zh not_active Expired - Fee Related
- 2014-11-24 US US14/551,187 patent/US10172948B2/en active Active
- 2014-11-24 JP JP2016554939A patent/JP6609563B2/ja not_active Expired - Fee Related
- 2014-11-24 CA CA2928087A patent/CA2928087A1/en not_active Abandoned
- 2014-11-24 WO PCT/IB2014/066300 patent/WO2015079376A1/en not_active Ceased
- 2014-11-24 MX MX2016006674A patent/MX2016006674A/es unknown
- 2014-11-24 KR KR1020167016645A patent/KR20160088429A/ko not_active Withdrawn
- 2014-11-25 UY UY0001035854A patent/UY35854A/es not_active Application Discontinuation
- 2014-11-25 TW TW103140861A patent/TWI572361B/zh not_active IP Right Cessation
-
2016
- 2016-04-15 ZA ZA2016/02603A patent/ZA201602603B/en unknown
- 2016-04-20 IL IL245244A patent/IL245244A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20150150998A1 (en) | 2015-06-04 |
| ZA201602603B (en) | 2017-06-28 |
| TWI572361B (zh) | 2017-03-01 |
| AU2014356126A1 (en) | 2016-05-19 |
| CN105764530B (zh) | 2019-09-13 |
| UY35854A (es) | 2015-06-30 |
| JP6609563B2 (ja) | 2019-11-20 |
| AU2014356126B2 (en) | 2017-01-05 |
| EP3074048A1 (en) | 2016-10-05 |
| JP2016539190A (ja) | 2016-12-15 |
| IL245244A0 (en) | 2016-06-30 |
| CA2928087A1 (en) | 2015-06-04 |
| CN105764530A (zh) | 2016-07-13 |
| KR20160088429A (ko) | 2016-07-25 |
| WO2015079376A1 (en) | 2015-06-04 |
| ES2729643T3 (es) | 2019-11-05 |
| US10172948B2 (en) | 2019-01-08 |
| EP3074048B1 (en) | 2019-03-06 |
| TW201524520A (zh) | 2015-07-01 |
| EA201691075A1 (ru) | 2016-09-30 |
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