NO2424557T3 - - Google Patents
Info
- Publication number
- NO2424557T3 NO2424557T3 NO10718379A NO10718379A NO2424557T3 NO 2424557 T3 NO2424557 T3 NO 2424557T3 NO 10718379 A NO10718379 A NO 10718379A NO 10718379 A NO10718379 A NO 10718379A NO 2424557 T3 NO2424557 T3 NO 2424557T3
- Authority
- NO
- Norway
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
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- 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
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Otolaryngology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17457509P | 2009-05-01 | 2009-05-01 | |
| US33945810P | 2010-03-04 | 2010-03-04 | |
| PCT/US2010/033345 WO2010127336A1 (en) | 2009-05-01 | 2010-05-03 | Modified compstatin with peptide backbone and c-terminal modifications |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO2424557T3 true NO2424557T3 (es) | 2018-03-24 |
Family
ID=42245589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO10718379A NO2424557T3 (es) | 2009-05-01 | 2010-05-03 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8946145B2 (es) |
| EP (1) | EP2424557B1 (es) |
| JP (2) | JP5882890B2 (es) |
| CN (1) | CN102458438A (es) |
| AU (1) | AU2010242739B2 (es) |
| CA (1) | CA2760839C (es) |
| DK (1) | DK2424557T3 (es) |
| ES (1) | ES2655389T3 (es) |
| HU (1) | HUE035378T2 (es) |
| NO (1) | NO2424557T3 (es) |
| PL (1) | PL2424557T3 (es) |
| PT (1) | PT2424557T (es) |
| WO (1) | WO2010127336A1 (es) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| US9358266B2 (en) | 2010-02-25 | 2016-06-07 | The Trustees Of The University Of Pennsylvania | Treatment of sepsis using complement inhibitors |
| US20130324482A1 (en) * | 2010-07-09 | 2013-12-05 | Apellis Pharmaceuticals, Inc. | Compstatin analogs for treatment of rhinosinusitis and nasal polyposis |
| US20140113874A1 (en) | 2010-09-23 | 2014-04-24 | The Trustees Of The University Of Pennsylvania | Modified Compstatin With Improved Stability And Binding Properties |
| WO2012135624A1 (en) | 2011-04-01 | 2012-10-04 | The Trustees Of The University Of Pennsylvania | Treatment of colon cancer using complement inhibitors |
| ES2915265T3 (es) | 2011-05-11 | 2022-06-21 | Apellis Pharmaceuticals Inc | Análogos de compstatina reactivos con células, de acción prolongada o dirigidos y usos de los mismos |
| WO2012162215A1 (en) | 2011-05-20 | 2012-11-29 | The Trustees Of The University Of Pennsylvania | Promotion of fracture healing using complement inhibitors |
| WO2012174055A1 (en) | 2011-06-13 | 2012-12-20 | The Trustees Of The University Of Pennsylvania | Wound healing using complement inhibitors |
| AU2012272706B2 (en) * | 2011-06-22 | 2017-07-06 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
| WO2013036778A2 (en) | 2011-09-07 | 2013-03-14 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved pharmacokinetic properties |
| US9579360B2 (en) * | 2012-06-20 | 2017-02-28 | The Trustees Of The University Of Pennsylvania | Methods of treating or preventing periodontitis and diseases associated with periodontitis |
| RS62243B9 (sr) | 2012-11-15 | 2022-11-30 | Apellis Pharmaceuticals Inc | Analozi kompstatina sa produženim trajanjem dejstva i njihove kompozicije i postupci |
| WO2014152391A1 (en) | 2013-03-15 | 2014-09-25 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| KR20210158880A (ko) | 2013-12-12 | 2021-12-31 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 성분 ｉＲＮＡ 조성물 및 이의 이용 방법 |
| US10213476B2 (en) | 2014-03-17 | 2019-02-26 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with improved potency and pharmacokinetic properties |
| WO2017035405A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amino compounds for treatment of immune and inflammatory disorders |
| WO2017035401A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amide compounds for treatment of immune and inflammatory disorders |
| EP3359555B1 (en) | 2015-10-07 | 2023-12-20 | Apellis Pharmaceuticals, Inc. | Dosing regimens |
| WO2018160891A1 (en) | 2017-03-01 | 2018-09-07 | Achillion Pharmaceutical, Inc. | Pharmaceutical compounds for treatment of medical disorders |
| AU2018227849B2 (en) | 2017-03-01 | 2022-04-28 | Achillion Pharmaceuticals, Inc. | Aryl, heteroary, and heterocyclic pharmaceutical compounds for treatment of medical disorders |
| CN116059313A (zh) | 2017-04-07 | 2023-05-05 | 阿佩利斯制药有限公司 | 给药方案以及相关组合物和方法 |
| SG11202002940QA (en) | 2017-11-01 | 2020-04-29 | Alnylam Pharmaceuticals Inc | Complement component c3 irna compositions and methods of use thereof |
| WO2019166411A1 (en) * | 2018-02-27 | 2019-09-06 | Zealand Pharma A/S | Compstatin analogues and their medical uses |
| EP4011905A3 (en) | 2018-04-06 | 2022-06-29 | The Trustees Of The University Of Pennsylvania | Compstatin analogs with increased solubility and improved pharmacokinetic properties |
| AU2019336238A1 (en) | 2018-09-06 | 2021-04-08 | Achillion Pharmaceuticals, Inc. | Morphic forms of Complement factor D inhibitors |
| US11814391B2 (en) | 2018-09-06 | 2023-11-14 | Achillion Pharmaceuticals, Inc. | Macrocyclic compounds for the treatment of medical disorders |
| AU2019346464A1 (en) | 2018-09-25 | 2021-04-08 | Achillion Pharmaceuticals, Inc. | Morphic forms of complement factor D inhibitors |
| CA3158320A1 (en) | 2019-10-22 | 2021-04-29 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
| JPWO2021177390A1 (es) | 2020-03-04 | 2021-09-10 | ||
| EP4114947A1 (en) | 2020-03-05 | 2023-01-11 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
| IL297680A (en) | 2020-04-30 | 2022-12-01 | Alnylam Pharmaceuticals Inc | IRNA compounds complement factor b (cfb) and methods of using them |
| WO2022150260A1 (en) | 2021-01-05 | 2022-07-14 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| KR20230154183A (ko) | 2021-03-04 | 2023-11-07 | 니혼 메디피직스 가부시키가이샤 | 화합물 및 방사성 표지 화합물 |
| WO2023044370A2 (en) | 2021-09-17 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing complement component 3 (c3) |
| WO2023048151A1 (ja) * | 2021-09-22 | 2023-03-30 | 塩野義製薬株式会社 | ウイルス増殖阻害活性を有する環状ペプチド |
| CA3234636A1 (en) | 2021-10-29 | 2023-05-04 | Alnylam Pharmaceuticals, Inc. | Complement factor b (cfb) irna compositions and methods of use thereof |
| WO2023100852A1 (ja) | 2021-11-30 | 2023-06-08 | 日本メジフィジックス株式会社 | 安定化放射性医薬組成物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2295746A1 (fr) | 1974-12-23 | 1976-07-23 | Francaise Coop Pharma | Nouveaux derives du tryptophane a activite nerveuse centrale renforcee |
| IT1179866B (it) | 1984-12-12 | 1987-09-16 | Rotta Research Lab | Derivati del triptofano farmaceuticamente attivi e composizioni farmaceutiche che li contengono |
| US4576750A (en) | 1985-04-22 | 1986-03-18 | Merck & Co., Inc. | Tryptophan derivative |
| US5776970A (en) | 1994-04-28 | 1998-07-07 | Yeda Research And Development Co. Ltd. | Tryptophan derivatives as protein tyrosine kinase blockers and their use in the treatment of neoplastic diseases |
| US6319897B1 (en) | 1996-03-13 | 2001-11-20 | John D. Lambris | Peptides which inhibit complement activation |
| US6169057B1 (en) | 1997-09-04 | 2001-01-02 | The Regents Of The University Of California | Use of tryptophan and analogs as plant growth regulators |
| AU4648197A (en) * | 1997-09-17 | 1999-04-05 | Burnham Institute, The | Peptides and peptidomimetics for inhibiting complement activation |
| US6214790B1 (en) | 1998-04-10 | 2001-04-10 | Mayo Foundation For Medical Education And Research | Neo-tryptophan |
| PT1549333E (pt) * | 2002-09-20 | 2012-01-03 | Univ Pennsylvania | Análogos de compstatina com actividade melhorada |
| US8168584B2 (en) * | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| CN105582523B (zh) * | 2005-10-08 | 2022-04-15 | 阿佩利斯制药公司 | 用于眼部病症的补体抑制素和其类似物 |
| DK1960422T3 (da) * | 2005-11-28 | 2012-08-13 | Univ Pennsylvania | Meget virksomme compstatin-analoger |
| WO2008153963A1 (en) | 2007-06-08 | 2008-12-18 | The Trustees Of The University Of Pennsylvania | Structure of compstatin-c3 complex and use for rational drug design |
-
2010
- 2010-05-03 AU AU2010242739A patent/AU2010242739B2/en active Active
- 2010-05-03 DK DK10718379.0T patent/DK2424557T3/en active
- 2010-05-03 CN CN2010800262930A patent/CN102458438A/zh active Pending
- 2010-05-03 NO NO10718379A patent/NO2424557T3/no unknown
- 2010-05-03 PL PL10718379T patent/PL2424557T3/pl unknown
- 2010-05-03 EP EP10718379.0A patent/EP2424557B1/en active Active
- 2010-05-03 WO PCT/US2010/033345 patent/WO2010127336A1/en active Application Filing
- 2010-05-03 JP JP2012508814A patent/JP5882890B2/ja active Active
- 2010-05-03 US US13/318,272 patent/US8946145B2/en active Active
- 2010-05-03 HU HUE10718379A patent/HUE035378T2/en unknown
- 2010-05-03 PT PT107183790T patent/PT2424557T/pt unknown
- 2010-05-03 CA CA2760839A patent/CA2760839C/en active Active
- 2010-05-03 ES ES10718379.0T patent/ES2655389T3/es active Active
-
2015
- 2015-02-02 US US14/611,742 patent/US9371365B2/en active Active
- 2015-10-06 JP JP2015198674A patent/JP6106731B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010242739B2 (en) | 2016-08-25 |
| DK2424557T3 (en) | 2018-01-22 |
| EP2424557A1 (en) | 2012-03-07 |
| PT2424557T (pt) | 2018-02-05 |
| US20150203539A1 (en) | 2015-07-23 |
| US9371365B2 (en) | 2016-06-21 |
| CA2760839A1 (en) | 2010-11-04 |
| JP2012525443A (ja) | 2012-10-22 |
| JP6106731B2 (ja) | 2017-04-05 |
| CA2760839C (en) | 2019-02-12 |
| JP2016041711A (ja) | 2016-03-31 |
| PL2424557T3 (pl) | 2018-04-30 |
| HUE035378T2 (en) | 2018-05-02 |
| JP5882890B2 (ja) | 2016-03-09 |
| EP2424557B1 (en) | 2017-10-25 |
| WO2010127336A1 (en) | 2010-11-04 |
| US8946145B2 (en) | 2015-02-03 |
| AU2010242739A1 (en) | 2011-12-08 |
| CN102458438A (zh) | 2012-05-16 |
| US20120178694A1 (en) | 2012-07-12 |
| ES2655389T3 (es) | 2018-02-19 |