HRP20171315T1 - Optimizacija humanih antitijela koja vezuju limfocitni aktivacijski gen-3 (lag-3), i njihove primjene - Google Patents
Optimizacija humanih antitijela koja vezuju limfocitni aktivacijski gen-3 (lag-3), i njihove primjene Download PDFInfo
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- HRP20171315T1 HRP20171315T1 HRP20171315TT HRP20171315T HRP20171315T1 HR P20171315 T1 HRP20171315 T1 HR P20171315T1 HR P20171315T T HRP20171315T T HR P20171315TT HR P20171315 T HRP20171315 T HR P20171315T HR P20171315 T1 HRP20171315 T1 HR P20171315T1
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- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 title claims 4
- 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 title 1
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 title 1
- 238000005457 optimization Methods 0.000 title 1
- 239000000427 antigen Substances 0.000 claims 31
- 108091007433 antigens Proteins 0.000 claims 31
- 102000036639 antigens Human genes 0.000 claims 31
- 229940127121 immunoconjugate Drugs 0.000 claims 15
- 230000028993 immune response Effects 0.000 claims 6
- 102000017578 LAG3 Human genes 0.000 claims 4
- 101150030213 Lag3 gene Proteins 0.000 claims 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims 4
- 230000005867 T cell response Effects 0.000 claims 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 230000003308 immunostimulating effect Effects 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims 4
- 102000000588 Interleukin-2 Human genes 0.000 claims 3
- 108010002350 Interleukin-2 Proteins 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 230000004936 stimulating effect Effects 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 210000004881 tumor cell Anatomy 0.000 claims 2
- 230000004614 tumor growth Effects 0.000 claims 2
- 230000009385 viral infection Effects 0.000 claims 2
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 1
- 241000282693 Cercopithecidae Species 0.000 claims 1
- 101710112752 Cytotoxin Proteins 0.000 claims 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 241001529936 Murinae Species 0.000 claims 1
- 210000001744 T-lymphocyte Anatomy 0.000 claims 1
- 230000005975 antitumor immune response Effects 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 239000002619 cytotoxin Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002285 radioactive effect Effects 0.000 claims 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims 1
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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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- 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
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- 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
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- 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
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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- 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
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- 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
- C07K16/3061—Blood cells
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/00—Immunoglobulins specific features
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Claims (35)
1. Izolirano monoklonsko antitijelo, ili njegov antigen-vezujući dio, koji vezuje humani LAG-3, gdje CDR1, CDR2, i CDR3 regije teškog lanca sadrže aminokiselinske sekvence sa identifikacijskim brojevima sekvenci - SEQ ID NOs: 15, 16, i 17, redom, i gdje CDR1, CDR2, i CDR3 regije lakog lanca sadrže aminokiselinske sekvence sa SEQ ID NOs: 18, 19, i 20, redom.
2. Antitijelo, ili njegov antigen-vezujući dio, patentnog zahtjeva 1, gdje varijabilna regija teškog lanca sadrži aminokiselinsku sekvencu sa SEQ ID NO: 12, i varijabilnu regiju lakog lanca sadrži aminokiselinsku sekvencu sa SEQ ID NO: 14.
3. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koji pokazuje jednu ili kombinaciju sljedećih svojstava:
(a) vezivanje za majmunski LAG-3;
(b) nedostatak vezivanja za mišji LAG-3;
(c) vezivanje za LAG-3 molekule glavnog kompleksa histokompatibilnosti (MHC) klase II;
(d) inhibira vezivanje LAG-3 za molekule glavnog kompleksa histokompatibilnosti (MHC) klase II; ili
(e) stimulira imunološki odgovor.
4. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koji stimulira proizvodnju interleukina-2 (IL-2) u odgovoru antigen-specifične T stanice i/ili stimulira anti-tumorski imunološki odgovor.
5. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koji se vezuje za humani LAG-3 sa KD od 0.27 x 10-9 M ili manje kao što je određeno površinskom plazmonskom rezonancom.
6. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koje je humano antitijelo.
7. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koje je IgG1, IgG2 ili IgG4 izotip.
8. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koje je IgG4 izotip.
9. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, koje je fragment antitijela ili antitijelo sa jednim lancem.
10. Antitijelo bilo kojeg od patentnih zahtjeva 1-8, koje je antitijelo u punoj dužini.
11. Antitijelo bilo kojeg od patentnih zahtjeva 1-8 ili 10, gdje antitijelo je izolirano IgG4 humano monoklonsko antitijelo u punoj dužini koje se vezuje za humani LAG-3 sa KD od 0.27 x 10-9 M ili manje kao što je određeno površinskom plazmonskom rezonancom.
12. Bispecifična molekula koja sadrži antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od prethodnih patentnih zahtjeva, i drugo antitijelo ili njegov antigen-vezujući dio.
13. Imunokonjugat koji sadrži antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, vezan za terapijski agens.
14. Imunokonjugat patentnog zahtjeva 13, gdje terapijski agens je citotoksin ili radioaktivni izotop.
15. Kompozicija koji sadrži antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, bispecifična molekula patentnog zahtjeva 12, ili imunokonjugat patentnog zahtjeva 13 ili 14, i farmaceutski prihvatljiv nosač.
16. Kompozicija patentnog zahtjeva 15, koja dalje sadrži antikancerogeni agens.
17. Kompozicija patentnog zahtjeva 16, gdje antikancerogeni agens je antitijelo ili kemoterapijski agens.
18. Kompozicija patentnog zahtjeva 17, gdje antitijelo je antitijelo u punoj dužini.
19. Kompozicija patentnog zahtjeva 17 ili 18, gdje antitijelo je IgG4 izotip.
20. Izolirana nukleinska kiselina koja kodira varijabilnu regiju teškog i lakog lanca antitijela, ili njegov antigen-vezujući dio, patentnog zahtjeva 1 ili 2.
21. Ekspresivni vektor koji sadrži nukleinsku kiselinu patentnog zahtjeva 20.
22. Stanica domaćina koja sadrži ekspresivni vektor patentnog zahtjeva 21.
23. Metoda za pripremanje anti-LAG-3 antitijela koja sadrži eksprimiranje antitijela u stanici domaćina patentnog zahtjeva 22 i izoliranje antitijela iz stanice domaćina.
24. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, ili bispecifična molekula patentnog zahtjeva 12, ili imunokonjugat patentnog zahtjeva 13 ili 14 za primjenu u metodi stimulacije imunološkog odgovora kod subjekta.
25. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 24, gdje subjekt je subjekt koji ima tumor i imunološki odgovor na tumor je stimuliran.
26. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 24, gdje subjekt je subjekt koji ima virus i imunološki odgovor na virus je stimuliran.
27. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 24, gdje imunološki odgovor je odgovor antigen-specifične T stanice, tako da je odgovor antigen-specifične T stanice stimuliran.
28. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 27, gdje je proizvodnja interleukina-2 pomoću antigen-specifične T stanice stimulirana.
29. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa bilo kojim od patentnih zahtjeva 24-26, koji dalje sadrži administraciju najmanje jednog dodatnog imunostimulirajućeg antitijela.
30. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 29, gdje najmanje jedno imunostimulirajuće dodatno antitijelo je anti-PD-1 antitijelo.
31. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 29, gdje najmanje jedno dodatno imunostimulirajuće antitijelo je anti-PD-L1 antitijelo.
32. Antitijelo, antigen-vezujući dio, bispecifična molekula, ili imunokonjugat za primjenu u skladu sa patentnim zahtjevom 29, gdje najmanje jedno dodatno imunostimulirajuće antitijelo je anti-CTLA-4 antitijelo.
33. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, bispecifična molekula patentnog zahtjeva 12, ili imunokonjugat patentnog zahtjeva 13 ili 14 za primjenu u metodi za inhibiranje rasta tumorskih stanica kod subjekta.
34. Antitijelo, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, bispecifična molekula patentnog zahtjeva 12, ili imunokonjugat patentnog zahtjeva 13 ili 14 za primjenu u metodi za liječenje virusne infekcije kod subjekta.
35. Primjena antitijela, ili njegov antigen-vezujući dio, bilo kojeg od patentnih zahtjeva 1-11, bispecifična molekula patentnog zahtjeva 12, ili imunokonjugat patentnog zahtjeva 13 ili 14, u proizvodnji lijeka za stimuliranje imunološkog odgovora, opcionalno odgovor antigen specifične T stanice, ili inhibiranje rasta tumorskih stanica, ili liječenje virusne infekcije kod subjekta.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261667058P | 2012-07-02 | 2012-07-02 | |
EP13737946.7A EP2867258B1 (en) | 2012-07-02 | 2013-07-02 | Optimization of human antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
PCT/US2013/048999 WO2014008218A1 (en) | 2012-07-02 | 2013-07-02 | Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
Publications (1)
Publication Number | Publication Date |
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HRP20171315T1 true HRP20171315T1 (hr) | 2017-10-20 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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HRP20171315TT HRP20171315T1 (hr) | 2012-07-02 | 2017-08-31 | Optimizacija humanih antitijela koja vezuju limfocitni aktivacijski gen-3 (lag-3), i njihove primjene |
HRP20201852TT HRP20201852T8 (hr) | 2012-07-02 | 2020-11-20 | Optimizacija antitijela koja vezuju limfocitni aktivacijski gen-3 (lag-3), i njihove primjene |
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Application Number | Title | Priority Date | Filing Date |
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HRP20201852TT HRP20201852T8 (hr) | 2012-07-02 | 2020-11-20 | Optimizacija antitijela koja vezuju limfocitni aktivacijski gen-3 (lag-3), i njihove primjene |
Country Status (38)
Country | Link |
---|---|
US (6) | US9505839B2 (hr) |
EP (3) | EP3275899B1 (hr) |
JP (5) | JP6320376B2 (hr) |
KR (5) | KR102461102B1 (hr) |
CN (2) | CN108101991B (hr) |
AR (2) | AR091649A1 (hr) |
AU (4) | AU2013286914B2 (hr) |
BR (1) | BR112014032999B1 (hr) |
CA (2) | CA2877746C (hr) |
CL (1) | CL2014003637A1 (hr) |
CO (1) | CO7170127A2 (hr) |
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