JP2017525336A5 - - Google Patents
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- JP2017525336A5 JP2017525336A5 JP2016572509A JP2016572509A JP2017525336A5 JP 2017525336 A5 JP2017525336 A5 JP 2017525336A5 JP 2016572509 A JP2016572509 A JP 2016572509A JP 2016572509 A JP2016572509 A JP 2016572509A JP 2017525336 A5 JP2017525336 A5 JP 2017525336A5
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- Prior art keywords
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- acid sequence
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- Legal status (The legal status 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 status listed.)
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- 108090000765 processed proteins & peptides Proteins 0.000 claims 39
- 238000000034 method Methods 0.000 claims 23
- 206010028980 Neoplasm Diseases 0.000 claims 19
- 125000003275 alpha amino acid group Chemical group 0.000 claims 13
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims 12
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 12
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims 12
- 108091008874 T cell receptors Proteins 0.000 claims 10
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 10
- 210000004027 cell Anatomy 0.000 claims 10
- 239000000427 antigen Substances 0.000 claims 9
- 108091007433 antigens Proteins 0.000 claims 9
- 102000036639 antigens Human genes 0.000 claims 9
- 108020001507 fusion proteins Proteins 0.000 claims 9
- 102000037865 fusion proteins Human genes 0.000 claims 9
- -1 DMXL0 Proteins 0.000 claims 8
- 108020004707 nucleic acids Proteins 0.000 claims 8
- 102000039446 nucleic acids Human genes 0.000 claims 8
- 150000007523 nucleic acids Chemical class 0.000 claims 8
- 239000013604 expression vector Substances 0.000 claims 7
- 239000003446 ligand Substances 0.000 claims 7
- 150000001413 amino acids Chemical class 0.000 claims 6
- 210000000612 antigen-presenting cell Anatomy 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 4
- 230000005847 immunogenicity Effects 0.000 claims 4
- 238000000338 in vitro Methods 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 2
- 108010058597 HLA-DR Antigens Proteins 0.000 claims 2
- 102000006354 HLA-DR Antigens Human genes 0.000 claims 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 238000003556 assay Methods 0.000 claims 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 108010028930 invariant chain Proteins 0.000 claims 2
- 239000000463 material Substances 0.000 claims 2
- 230000035772 mutation Effects 0.000 claims 2
- 229940023041 peptide vaccine Drugs 0.000 claims 2
- 238000010186 staining Methods 0.000 claims 2
- 229960005486 vaccine Drugs 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 102100035634 B-cell linker protein Human genes 0.000 claims 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims 1
- 102100035671 Cadherin EGF LAG seven-pass G-type receptor 3 Human genes 0.000 claims 1
- 102100038113 Cyclin-dependent kinase 14 Human genes 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 108020004414 DNA Proteins 0.000 claims 1
- 102100024821 Dynamin-binding protein Human genes 0.000 claims 1
- 101150017533 ERP44 gene Proteins 0.000 claims 1
- 238000011510 Elispot assay Methods 0.000 claims 1
- 102100033238 Elongation factor Tu, mitochondrial Human genes 0.000 claims 1
- 102100034241 Elongator complex protein 2 Human genes 0.000 claims 1
- 101710167764 Elongator complex protein 2 Proteins 0.000 claims 1
- 102100031853 Endoplasmic reticulum resident protein 44 Human genes 0.000 claims 1
- 102100020987 Eukaryotic translation initiation factor 5 Human genes 0.000 claims 1
- 102100033079 HLA class II histocompatibility antigen, DM alpha chain Human genes 0.000 claims 1
- 108010050568 HLA-DM antigens Proteins 0.000 claims 1
- 101000803266 Homo sapiens B-cell linker protein Proteins 0.000 claims 1
- 101000715671 Homo sapiens Cadherin EGF LAG seven-pass G-type receptor 3 Proteins 0.000 claims 1
- 101000884374 Homo sapiens Cyclin-dependent kinase 14 Proteins 0.000 claims 1
- 101000909230 Homo sapiens Dynamin-binding protein Proteins 0.000 claims 1
- 101001002481 Homo sapiens Eukaryotic translation initiation factor 5 Proteins 0.000 claims 1
- 101001011446 Homo sapiens Interferon regulatory factor 6 Proteins 0.000 claims 1
- 101000613960 Homo sapiens Lysine-specific histone demethylase 1B Proteins 0.000 claims 1
- 101001109463 Homo sapiens NACHT, LRR and PYD domains-containing protein 1 Proteins 0.000 claims 1
- 101000979288 Homo sapiens Negative elongation factor E Proteins 0.000 claims 1
- 101000801640 Homo sapiens Phospholipid-transporting ATPase ABCA3 Proteins 0.000 claims 1
- 101001113440 Homo sapiens Poly [ADP-ribose] polymerase 2 Proteins 0.000 claims 1
- 101000874142 Homo sapiens Probable ATP-dependent RNA helicase DDX46 Proteins 0.000 claims 1
- 101000891084 Homo sapiens T-cell activation Rho GTPase-activating protein Proteins 0.000 claims 1
- 101000987017 Homo sapiens Tumor protein p53-inducible protein 11 Proteins 0.000 claims 1
- 101000723904 Homo sapiens Zinc finger protein 296 Proteins 0.000 claims 1
- 101000782294 Homo sapiens Zinc finger protein 638 Proteins 0.000 claims 1
- 102100030130 Interferon regulatory factor 6 Human genes 0.000 claims 1
- 102100040596 Lysine-specific histone demethylase 1B Human genes 0.000 claims 1
- 102100022698 NACHT, LRR and PYD domains-containing protein 1 Human genes 0.000 claims 1
- 102100023070 Negative elongation factor E Human genes 0.000 claims 1
- 102100033623 Phospholipid-transporting ATPase ABCA3 Human genes 0.000 claims 1
- 102100023652 Poly [ADP-ribose] polymerase 2 Human genes 0.000 claims 1
- 102100035725 Probable ATP-dependent RNA helicase DDX46 Human genes 0.000 claims 1
- 102100027551 Ras-specific guanine nucleotide-releasing factor 1 Human genes 0.000 claims 1
- 101100501116 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) TUF1 gene Proteins 0.000 claims 1
- 230000005867 T cell response Effects 0.000 claims 1
- 102100040346 T-cell activation Rho GTPase-activating protein Human genes 0.000 claims 1
- 101150026786 TUFM gene Proteins 0.000 claims 1
- 102100027873 Tumor protein p53-inducible protein 11 Human genes 0.000 claims 1
- 102100028430 Zinc finger protein 296 Human genes 0.000 claims 1
- 102100035806 Zinc finger protein 638 Human genes 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 239000002299 complementary DNA Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000003013 cytotoxicity Effects 0.000 claims 1
- 231100000135 cytotoxicity Toxicity 0.000 claims 1
- 210000004443 dendritic cell Anatomy 0.000 claims 1
- 238000005538 encapsulation Methods 0.000 claims 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 238000010195 expression analysis Methods 0.000 claims 1
- 230000014509 gene expression Effects 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 238000011502 immune monitoring Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 230000006698 induction Effects 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 238000004949 mass spectrometry Methods 0.000 claims 1
- 238000002493 microarray Methods 0.000 claims 1
- 230000002018 overexpression Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 229920002477 rna polymer Polymers 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000012163 sequencing technique Methods 0.000 claims 1
- 238000012070 whole genome sequencing analysis Methods 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462014849P | 2014-06-20 | 2014-06-20 | |
| GBGB1411037.3A GB201411037D0 (en) | 2014-06-20 | 2014-06-20 | Novel immunotherapy against several tumors of the blood, in particular chronic lymphoid leukemai (CLL) |
| US62/014,849 | 2014-06-20 | ||
| GB1411037.3 | 2014-06-20 | ||
| PCT/EP2015/063566 WO2015193359A2 (en) | 2014-06-20 | 2015-06-17 | Novel immunotherapy against several tumors of the blood, in particular chronic lymphoid leukemia (cll) |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019132609A Division JP2020014460A (ja) | 2014-06-20 | 2019-07-18 | 数種の血液腫瘍、特に慢性リンパ性白血病(cll)に対する新規免疫療法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017525336A JP2017525336A (ja) | 2017-09-07 |
| JP2017525336A5 true JP2017525336A5 (enExample) | 2017-10-26 |
| JP6560261B2 JP6560261B2 (ja) | 2019-08-14 |
Family
ID=51409910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016572509A Expired - Fee Related JP6560261B2 (ja) | 2014-06-20 | 2015-06-17 | 数種の血液腫瘍、特に慢性リンパ性白血病(cll)に対する新規免疫療法 |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP3708185A3 (enExample) |
| JP (1) | JP6560261B2 (enExample) |
| CA (1) | CA2950827A1 (enExample) |
| DK (1) | DK3157549T3 (enExample) |
| ES (1) | ES2802155T3 (enExample) |
| GB (1) | GB201411037D0 (enExample) |
| HU (1) | HUE050070T2 (enExample) |
| LT (1) | LT3157549T (enExample) |
| PL (1) | PL3157549T3 (enExample) |
| PT (1) | PT3157549T (enExample) |
| RS (1) | RS60592B1 (enExample) |
| SI (1) | SI3157549T1 (enExample) |
| TW (3) | TW202024125A (enExample) |
| WO (1) | WO2015193359A2 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201408255D0 (en) * | 2014-05-09 | 2014-06-25 | Immatics Biotechnologies Gmbh | Novel immunotherapy against several tumours of the blood, such as acute myeloid leukemia (AML) |
| JP7174627B2 (ja) | 2015-10-23 | 2022-11-17 | ウニフェルシタイト・トゥヴェンテ | インテグリン結合ペプチド及びその使用 |
| CN108601731A (zh) | 2015-12-16 | 2018-09-28 | 磨石肿瘤生物技术公司 | 新抗原的鉴别、制造及使用 |
| CN114028549A (zh) | 2016-02-19 | 2022-02-11 | 伊玛提克斯生物技术有限公司 | 用于nhl和其他癌症免疫治疗的新型肽和肽组合物 |
| GB201602918D0 (en) | 2016-02-19 | 2016-04-06 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against NHL and other cancers |
| MA54832A (fr) | 2016-03-01 | 2021-12-01 | Immatics Biotechnologies Gmbh | Peptides, combinaison de peptides et médicaments à base de cellules destinés à être utilisés en immunothérapie contre le cancer de la vessie et d'autres cancers |
| GB201603987D0 (en) * | 2016-03-08 | 2016-04-20 | Immatics Biotechnologies Gmbh | Uterine cancer treatments |
| CR20200608A (es) | 2016-04-21 | 2021-01-20 | Immatics Biotechnologies Gmbh | INMUNOTERAPIA CONTRA EL MELANOMA Y OTROS TIPOS DE CÁNCER (Divisional 2018-0551) |
| SG11201808629UA (en) | 2016-04-21 | 2018-11-29 | Immatics Biotechnologies Gmbh | Immunotherapy against melanoma and other cancers |
| DE102016005550B4 (de) | 2016-05-09 | 2024-09-26 | Hans-Georg Rammensee | Adjuvans zur lnduzierung einer zellulären lmmunantwort |
| GB201609193D0 (en) | 2016-05-25 | 2016-07-06 | Immatics Biotechnologies Gmbh | Novel peptides, combination of peptides as targets for use in immunotherapy against gallbladder cancer and cholangiocarcinoma and other cancers |
| JP7075125B2 (ja) | 2016-05-25 | 2022-05-25 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 標的としてのおよび胆嚢がんおよび胆管がんおよびその他のがんに対する免疫療法で使用するための新規ペプチド、ペプチド組み合わせ |
| CN106046130B (zh) * | 2016-07-07 | 2017-12-12 | 胡国田 | 一种多肽及其应用 |
| TWI796299B (zh) | 2016-08-26 | 2023-03-21 | 德商英麥提克生物技術股份有限公司 | 用於頭頸鱗狀細胞癌和其他癌症免疫治療的新型肽和支架 |
| EP4317432A3 (en) | 2016-12-08 | 2024-04-17 | Immatics Biotechnologies GmbH | T cell receptors with improved pairing |
| DE102016123893A1 (de) | 2016-12-08 | 2018-06-14 | Immatics Biotechnologies Gmbh | T-Zellrezeptoren mit verbesserter Bindung |
| EA201992416A1 (ru) | 2017-04-10 | 2020-02-25 | Имматикс Байотекнолоджиз Гмбх | Пептиды и комбинации пептидов для применения в иммунотерапии лейкозов и других видов рака |
| CN111533799A (zh) | 2017-04-10 | 2020-08-14 | 伊玛提克斯生物技术有限公司 | 用于白血病和其他癌症免疫治疗的肽和肽组合物 |
| EP4576103A3 (en) | 2017-10-10 | 2025-08-27 | Gritstone bio, Inc. | Neoantigen identification using hotspots |
| EP3714275A4 (en) | 2017-11-22 | 2021-10-27 | Gritstone bio, Inc. | REDUCTION OF JUNCTION EPITOPIC PRESENTATION FOR NEOANTIGENS |
| DE102018107224A1 (de) | 2018-02-21 | 2019-08-22 | Immatics Biotechnologies Gmbh | Peptide und Kombinationen von Peptiden nicht-kanonischen Ursprungs zur Verwendung in der Immuntherapie gegen verschiedene Krebsarten |
| US10925947B2 (en) * | 2018-06-29 | 2021-02-23 | Immatics Biotechnologies Gmbh | A*03 restricted peptides for use in immunotherapy against cancers and related methods |
| TW202019955A (zh) | 2018-07-31 | 2020-06-01 | 德商英麥提克生物技術股份有限公司 | B*07 限制肽和肽組合的抗癌免疫治療和相關方法 |
| WO2020035123A1 (en) * | 2018-08-11 | 2020-02-20 | Baerlecken Niklas | Autoantibodies binding to negative elongation factor e (nelf-e) for diagnosing sarcoidosis |
| CN109593125A (zh) * | 2018-12-12 | 2019-04-09 | 深圳市龙华区人民医院 | 基于前列腺癌干细胞标志物cd44的抗原表位多肽cd44-p1及其应用 |
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| US4440859A (en) | 1977-05-27 | 1984-04-03 | The Regents Of The University Of California | Method for producing recombinant bacterial plasmids containing the coding sequences of higher organisms |
| US4704362A (en) | 1977-11-08 | 1987-11-03 | Genentech, Inc. | Recombinant cloning vehicle microbial polypeptide expression |
| IN151589B (enExample) | 1978-12-22 | 1983-05-28 | Biogen Nv | |
| US4530901A (en) | 1980-01-08 | 1985-07-23 | Biogen N.V. | Recombinant DNA molecules and their use in producing human interferon-like polypeptides |
| US4342566A (en) | 1980-02-22 | 1982-08-03 | Scripps Clinic & Research Foundation | Solid phase anti-C3 assay for detection of immune complexes |
| US4678751A (en) | 1981-09-25 | 1987-07-07 | Genentech, Inc. | Hybrid human leukocyte interferons |
| US4766075A (en) | 1982-07-14 | 1988-08-23 | Genentech, Inc. | Human tissue plasminogen activator |
| US4582800A (en) | 1982-07-12 | 1986-04-15 | Hoffmann-La Roche Inc. | Novel vectors and method for controlling interferon expression |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| US4677063A (en) | 1985-05-02 | 1987-06-30 | Cetus Corporation | Human tumor necrosis factor |
| US4810648A (en) | 1986-01-08 | 1989-03-07 | Rhone Poulenc Agrochimie | Haloarylnitrile degrading gene, its use, and cells containing the gene |
| US4897445A (en) | 1986-06-27 | 1990-01-30 | The Administrators Of The Tulane Educational Fund | Method for synthesizing a peptide containing a non-peptide bond |
| AU6852594A (en) | 1993-06-03 | 1995-01-03 | Therapeutic Antibodies Inc. | Production of antibody fragments |
| AUPM322393A0 (en) | 1993-12-24 | 1994-01-27 | Austin Research Institute, The | Mucin carbohydrate compounds and their use in immunotherapy |
| CA2243235C (en) | 1996-01-17 | 2010-08-10 | Imperial College Innovations Limited | Immunotherapy using cytotoxic t lymphocytes (ctl) |
| US5849589A (en) | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| US20040191260A1 (en) | 2003-03-26 | 2004-09-30 | Technion Research & Development Foundation Ltd. | Compositions capable of specifically binding particular human antigen presenting molecule/pathogen-derived antigen complexes and uses thereof |
| DE60142475D1 (de) | 2000-03-27 | 2010-08-12 | Technion Res And Dev Of Founda | Einkettige haupthistokompatibilitätskomplexe der klasse i (mhc-i), kodierende konstrukte und methoden ihrer erzeugung |
| US20030144474A1 (en) | 2000-06-05 | 2003-07-31 | Sunol Molecular Corporation | T cell receptor fusions and conjugates and methods of use thereof |
| US20040053292A1 (en) * | 2000-11-15 | 2004-03-18 | Jurg Tschopp | Proteins and dna sequences underlying these proteins used for treating inflammations |
| US7919467B2 (en) * | 2000-12-04 | 2011-04-05 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
| US6992176B2 (en) | 2002-02-13 | 2006-01-31 | Technion Research & Development Foundation Ltd. | Antibody having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease |
| CA2476625A1 (en) | 2002-02-20 | 2003-08-28 | Dyax Corp. | Mhc-peptide complex binding ligands |
| US7569664B2 (en) | 2002-10-09 | 2009-08-04 | Immunocore Limited | Single chain recombinant T cell receptors |
| PT1558643E (pt) | 2002-11-09 | 2009-08-24 | Immunocore Ltd | Apresentação de um receptor das células t |
| GB0304068D0 (en) | 2003-02-22 | 2003-03-26 | Avidex Ltd | Substances |
| WO2005114221A2 (en) * | 2004-05-21 | 2005-12-01 | The Institute For Systems Biology | Compositions and methods for quantification of serum glycoproteins |
| PL1760088T3 (pl) | 2005-09-05 | 2008-10-31 | Immatics Biotechnologies Gmbh | Związane z nowotworem peptydy wiążące się w sposób niedyskryminujący z cząsteczkami antygenu ludzkiego leukocytu klasy II (HLA) |
| US20070248628A1 (en) * | 2005-12-06 | 2007-10-25 | Keller Lorraine H | Immunogens in cancer stem cells |
| US20090263574A1 (en) | 2008-04-21 | 2009-10-22 | Quinn Daniel E | Method of restoring an article |
| GB201006360D0 (en) | 2010-04-16 | 2010-06-02 | Immatics Biotechnologies Gmbh | Method for differentially quantifying naturally processed HLA-restricted peptides for cancer, autoimmune and infectious diseases immunotherapy development |
| WO2012056407A1 (en) | 2010-10-26 | 2012-05-03 | Technion Research & Development Foundation Ltd. | Antibodies which bind soluble t-cell receptor ligands |
| WO2013057586A1 (en) | 2011-10-19 | 2013-04-25 | Oslo Universitetssykehus Hf | Compositions and methods for producing soluble t - cell receptors |
-
2014
- 2014-06-20 GB GBGB1411037.3A patent/GB201411037D0/en not_active Ceased
-
2015
- 2015-06-17 LT LTEP15730135.9T patent/LT3157549T/lt unknown
- 2015-06-17 JP JP2016572509A patent/JP6560261B2/ja not_active Expired - Fee Related
- 2015-06-17 EP EP20170980.5A patent/EP3708185A3/en not_active Withdrawn
- 2015-06-17 PL PL15730135T patent/PL3157549T3/pl unknown
- 2015-06-17 CA CA2950827A patent/CA2950827A1/en not_active Abandoned
- 2015-06-17 RS RS20200910A patent/RS60592B1/sr unknown
- 2015-06-17 EP EP15730135.9A patent/EP3157549B1/en active Active
- 2015-06-17 SI SI201531301T patent/SI3157549T1/sl unknown
- 2015-06-17 PT PT157301359T patent/PT3157549T/pt unknown
- 2015-06-17 ES ES15730135T patent/ES2802155T3/es active Active
- 2015-06-17 HU HUE15730135A patent/HUE050070T2/hu unknown
- 2015-06-17 WO PCT/EP2015/063566 patent/WO2015193359A2/en not_active Ceased
- 2015-06-17 DK DK15730135.9T patent/DK3157549T3/da active
- 2015-06-18 TW TW109104580A patent/TW202024125A/zh unknown
- 2015-06-18 TW TW104119833A patent/TWI670282B/zh not_active IP Right Cessation
- 2015-06-18 TW TW108109176A patent/TW201930347A/zh unknown
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