RU2016138365A - Pcsk9 вакцины - Google Patents
Pcsk9 вакцины Download PDFInfo
- Publication number
- RU2016138365A RU2016138365A RU2016138365A RU2016138365A RU2016138365A RU 2016138365 A RU2016138365 A RU 2016138365A RU 2016138365 A RU2016138365 A RU 2016138365A RU 2016138365 A RU2016138365 A RU 2016138365A RU 2016138365 A RU2016138365 A RU 2016138365A
- Authority
- RU
- Russia
- Prior art keywords
- seq
- peptide
- amino acid
- peedgtrfhrqask
- vaccine according
- Prior art date
Links
- 229960005486 vaccine Drugs 0.000 title claims 8
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 title claims 2
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 title claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 9
- 125000000539 amino acid group Chemical group 0.000 claims 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 4
- 102000016607 Diphtheria Toxin Human genes 0.000 claims 3
- 108010053187 Diphtheria Toxin Proteins 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- 238000008214 LDL Cholesterol Methods 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 108010055044 Tetanus Toxin Proteins 0.000 claims 2
- 235000012000 cholesterol Nutrition 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 235000018102 proteins Nutrition 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 229940118376 tetanus toxin Drugs 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 102100037840 Dehydrogenase/reductase SDR family member 2, mitochondrial Human genes 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 101710188053 Protein D Proteins 0.000 claims 1
- 101710132893 Resolvase Proteins 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 108060003552 hemocyanin Proteins 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 210000004698 lymphocyte Anatomy 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 210000005259 peripheral blood Anatomy 0.000 claims 1
- 239000011886 peripheral blood Substances 0.000 claims 1
- 125000006850 spacer group Chemical group 0.000 claims 1
Classifications
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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
- A61K39/0005—Vertebrate antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- 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
- A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
- A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
- C07K2319/00—Fusion polypeptide
- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (10)
1. Вакцина, содержащая, по меньшей мере, один пептид, состоящий из 14-25 аминокислотных остатков, который является вариантом пептида PEEDGTRFHRQASK (SEQ. ID. No. 1) с повышенной способностью снижать уровень общего холестерина у млекопитающих, в частности, людей, по сравнению с PEEDGTRFHRQASK (SEQ. ID. No. 1), где указанный вариант выбирают из группы, состоящей из PEEDGTRFHRRASK (SEQ. ID. No. 17), PEEDGTRFHRKASK (SEQ. ID. No. 18), PEEDGTRFHRTASK (SEQ. ID. No. 36), PEEDGSRFHKQASK (SEQ. ID. No. 41) и PEEDGSRFHRQATK (SEQ. ID. No. 44), предпочтительно предназначенная для снижения уровней LDL холестерина в плазме.
2. Вакцина по п. 1, в которой указанный, по меньшей мере, один пептид соединяется или связывается с фармацевтически приемлемым носителем.
3. Вакцина по п. 1 или 2, в которой указанный, по меньшей мере, один пептид содержит на своем N- и/или С-конце, по меньшей мере, один остаток цистеина, соединенный с ним напрямую или через спейсерную последовательность.
4. Вакцина по п. 2 или 3, в которой фармацевтически приемлемый носитель является белковым носителем.
5. Вакцина по п. 4, в которой белковый носитель выбирают из группы, состоящей из гемоцианина лимфы улитки (KLH), столбнячного токсина (ТТ), CRM197, протеина D или дифтерийного токсина (DT), предпочтительно мутированного дифтерийного токсина, CRM197, или KLH, в частности, KLH.
6. Вакцина по любому из пп. 1-5, в состав которой включается адъювант, предпочтительно Al(OH)3 (гидроокись алюминия).
7. Вакцина по любому из пп. 1-6, предназначенная для применения в способе лечения и/или предотвращения заболеваний, вызванных гиперлипидемией, гиперхолестеринемией и/или атеросклерозом, предпочтительно сердечно-сосудистых заболеваний, инсульта или заболеваний периферических кровеносных сосудов, или неопластических болезней, предпочтительно меланомы и метастазов рака печени, связанных с PCSK9.
8. Пептид, содержащий от 14 до 25 аминокислотных остатков, который является вариантом пептида PEEDGTRFHRQASK (SEQ. ID. No. 1) с повышенной способностью снижать уровень общего холестерина у млекопитающих, в частности, людей, по сравнению с PEEDGTRFHRQASK (SEQ. ID. No. 1), где указанный вариант характеризуется, по меньшей мере, одной или самое большее четырьмя заменами аминокислот по сравнению с PEEDGTRFHRQASK (SEQ. ID. No. 1), и при этом пептид состоит из или содержит аминокислотную последовательность, выбранную из группы, состоящей из PEEDGTRFHRRASK (SEQ. ID. No. 17), PEEDGTRFHRKASK (SEQ. ID. No. 18), PEEDGTRFHRTASK (SEQ. ID. No. 36), PEEDGSRFHKQASK (SEQ. ID. No. 41) и PEEDGSRFHRQATK (SEQ. ID. No. 44), предпочтительно предназначенный для снижения уровней LDL холестерина в плазме.
9. Пептид по п. 8, который состоит из 9-20 аминокислотных остатков, в частности 9-15 аминокислотных остатков.
10. Пептид по п. 8 или 9, предназначенный для использования при лечении пациентов, имеющих или подвергающихся риску развития заболеваний, вызванных гиперлипидемией, гиперхолестеринемией и/или атеросклерозом.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14157221 | 2014-02-28 | ||
| EP14157221.4 | 2014-02-28 | ||
| PCT/EP2015/053725 WO2015128287A1 (en) | 2014-02-28 | 2015-02-23 | Pcsk9 vaccines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2016138365A true RU2016138365A (ru) | 2018-03-29 |
| RU2016138365A3 RU2016138365A3 (ru) | 2018-08-20 |
| RU2698971C2 RU2698971C2 (ru) | 2019-09-02 |
Family
ID=50179534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016138365A RU2698971C2 (ru) | 2014-02-28 | 2015-02-23 | Pcsk9 вакцины |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US10004791B2 (ru) |
| EP (1) | EP3110439B1 (ru) |
| JP (1) | JP6494667B2 (ru) |
| KR (1) | KR102360250B1 (ru) |
| CN (1) | CN106459209B (ru) |
| AU (1) | AU2015222283B2 (ru) |
| BR (1) | BR112016019389A8 (ru) |
| CA (1) | CA2940315C (ru) |
| DK (1) | DK3110439T3 (ru) |
| ES (1) | ES2732741T3 (ru) |
| IL (1) | IL247159B (ru) |
| MX (1) | MX2016010838A (ru) |
| PL (1) | PL3110439T3 (ru) |
| RU (1) | RU2698971C2 (ru) |
| SG (1) | SG11201606685XA (ru) |
| WO (1) | WO2015128287A1 (ru) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112018008697A2 (pt) | 2015-11-03 | 2018-10-30 | Affiris Ag | método e kit para vacinação contra um auto-antígeno, uso de um kit, e, vacina para uso em vacinação. |
| CN107531795B (zh) * | 2016-01-05 | 2021-01-19 | 江苏恒瑞医药股份有限公司 | Pcsk9抗体、其抗原结合片段及其医药用途 |
| ES2571055B1 (es) * | 2016-02-15 | 2016-12-28 | Araclon Biotech, S.L. | Conjugado amiloide y usos y procedimientos del mismo |
| CN106822881A (zh) * | 2016-12-09 | 2017-06-13 | 四川大学 | 一种针对pcsk9的抗高血脂蛋白疫苗 |
| KR102401796B1 (ko) | 2017-04-13 | 2022-05-25 | 카딜라 핼쓰캐어 리미티드 | 신규의 펩타이드 기재 pcsk9 백신 |
| WO2022147373A1 (en) * | 2020-12-31 | 2022-07-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins |
| WO2023161526A1 (en) | 2022-02-28 | 2023-08-31 | Tridem Bioscience Gmbh & Co Kg | A CONJUGATE CONSISTING OF OR COMPRISING AT LEAST A ß-GLUCAN OR A MANNAN |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101660577B1 (ko) | 2009-09-03 | 2016-09-27 | 화이자 백신스 엘엘씨 | Ｐｃｓｋ９ 백신 |
| AU2010313381A1 (en) | 2009-10-30 | 2012-04-12 | Merck Sharp & Dohme Corp. | AX1 and AX189 PCSK9 antagonists and variants |
| JP2013509194A (ja) | 2009-10-30 | 2013-03-14 | メルク・シャープ・エンド・ドーム・コーポレイション | Ａｘ２１３およびａｘ１３２ｐｃｓｋ９アンタゴニストおよびバリアント |
| GB201005005D0 (en) * | 2010-03-25 | 2010-05-12 | Angeletti P Ist Richerche Bio | New vaccine |
| SI2570135T1 (sl) | 2011-09-13 | 2016-05-31 | Affiris Ag | PCSK9 cepivo |
| WO2013148284A1 (en) | 2012-03-29 | 2013-10-03 | Genentech, Inc. | Antibodies that bind to a pcsk9 cleavage site and methods of use |
-
2015
- 2015-02-23 JP JP2016571473A patent/JP6494667B2/ja active Active
- 2015-02-23 CN CN201580015813.0A patent/CN106459209B/zh active Active
- 2015-02-23 ES ES15714770T patent/ES2732741T3/es active Active
- 2015-02-23 AU AU2015222283A patent/AU2015222283B2/en active Active
- 2015-02-23 DK DK15714770.3T patent/DK3110439T3/da active
- 2015-02-23 KR KR1020167026735A patent/KR102360250B1/ko active IP Right Grant
- 2015-02-23 EP EP15714770.3A patent/EP3110439B1/en active Active
- 2015-02-23 MX MX2016010838A patent/MX2016010838A/es active IP Right Grant
- 2015-02-23 SG SG11201606685XA patent/SG11201606685XA/en unknown
- 2015-02-23 PL PL15714770T patent/PL3110439T3/pl unknown
- 2015-02-23 RU RU2016138365A patent/RU2698971C2/ru active
- 2015-02-23 BR BR112016019389A patent/BR112016019389A8/pt not_active Application Discontinuation
- 2015-02-23 WO PCT/EP2015/053725 patent/WO2015128287A1/en active Application Filing
- 2015-02-23 US US15/122,316 patent/US10004791B2/en active Active
- 2015-02-23 CA CA2940315A patent/CA2940315C/en active Active
-
2016
- 2016-08-08 IL IL247159A patent/IL247159B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP3110439A1 (en) | 2017-01-04 |
| ES2732741T3 (es) | 2019-11-25 |
| CN106459209A (zh) | 2017-02-22 |
| WO2015128287A1 (en) | 2015-09-03 |
| MX2016010838A (es) | 2016-11-17 |
| RU2016138365A3 (ru) | 2018-08-20 |
| EP3110439B1 (en) | 2019-03-27 |
| US10004791B2 (en) | 2018-06-26 |
| SG11201606685XA (en) | 2016-09-29 |
| KR20160124901A (ko) | 2016-10-28 |
| CA2940315A1 (en) | 2015-09-03 |
| JP2017508006A (ja) | 2017-03-23 |
| RU2698971C2 (ru) | 2019-09-02 |
| KR102360250B1 (ko) | 2022-02-07 |
| US20170065689A1 (en) | 2017-03-09 |
| CA2940315C (en) | 2022-08-23 |
| JP6494667B2 (ja) | 2019-04-03 |
| AU2015222283A1 (en) | 2016-09-08 |
| DK3110439T3 (da) | 2019-05-13 |
| CN106459209B (zh) | 2019-10-11 |
| BR112016019389A8 (pt) | 2022-11-08 |
| AU2015222283B2 (en) | 2019-11-21 |
| IL247159B (en) | 2018-01-31 |
| PL3110439T3 (pl) | 2019-09-30 |
| NZ722918A (en) | 2022-03-25 |
| BR112016019389A2 (pt) | 2017-10-24 |
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