CA2808432C - Tricyclic proteasome activity enhancing compounds with thieno[2,3-d]pyrimidine core - Google Patents
Tricyclic proteasome activity enhancing compounds with thieno[2,3-d]pyrimidine core Download PDFInfo
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- CA2808432C CA2808432C CA2808432A CA2808432A CA2808432C CA 2808432 C CA2808432 C CA 2808432C CA 2808432 A CA2808432 A CA 2808432A CA 2808432 A CA2808432 A CA 2808432A CA 2808432 C CA2808432 C CA 2808432C
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- amyloidosis
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- 235000005713 safflower oil Nutrition 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
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- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
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- 239000003549 soybean oil Substances 0.000 description 1
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- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005888 tetrahydroindolyl group Chemical group 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 238000011144 upstream manufacturing Methods 0.000 description 1
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- 239000002076 α-tocopherol Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- A61P27/12—Ophthalmic agents for cataracts
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- 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
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
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- Neurology (AREA)
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- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36717310P | 2010-07-23 | 2010-07-23 | |
| US61/367,173 | 2010-07-23 | ||
| PCT/US2011/044999 WO2012012712A2 (en) | 2010-07-23 | 2011-07-22 | Tricyclic proteasome activity enhancing compounds |
Publications (2)
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| CA2808432A1 CA2808432A1 (en) | 2012-01-26 |
| CA2808432C true CA2808432C (en) | 2019-06-04 |
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|---|---|
| US (3) | US8933087B2 (enExample) |
| EP (1) | EP2595993B1 (enExample) |
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| AU (1) | AU2011281015B2 (enExample) |
| CA (1) | CA2808432C (enExample) |
| WO (1) | WO2012012712A2 (enExample) |
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| KR20120117905A (ko) * | 2010-01-28 | 2012-10-24 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 프로테아좀 활성을 향상시키는 조성물 및 방법 |
| CN103119047B (zh) | 2010-07-23 | 2016-06-15 | 哈佛大学校长及研究员协会 | 三环类蛋白酶体活性增强化合物 |
| EP3239154A1 (en) | 2011-01-10 | 2017-11-01 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| TR201906779T4 (tr) | 2011-05-12 | 2019-05-21 | Proteostasis Therapeutics Inc | Proteostaz regülatörleri. |
| TW201728592A (zh) | 2012-01-10 | 2017-08-16 | 林伯士艾瑞斯公司 | Ｉｒａｋ抑制劑及其用途 |
| WO2013112706A1 (en) | 2012-01-25 | 2013-08-01 | Proteostasis Therapeutics, Inc. | Proteasome activity modulating compounds |
| HK1210732A1 (en) | 2012-07-11 | 2016-05-06 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| EP2872144A4 (en) | 2012-07-11 | 2015-12-02 | Nimbus Iris Inc | IRAQ INHIBITOR AND USES THEREOF |
| EP2938610A2 (en) | 2012-12-28 | 2015-11-04 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Inhibitors of the usp1/uaf1 deubiquitinase complex and uses thereof |
| WO2014110114A1 (en) | 2013-01-10 | 2014-07-17 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| WO2014116228A1 (en) | 2013-01-25 | 2014-07-31 | President And Fellows Of Harvard College | Usp14 inhibitors for treating or preventing viral infections |
| WO2014145576A2 (en) | 2013-03-15 | 2014-09-18 | Northwestern University | Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer |
| EP3049086A4 (en) | 2013-09-27 | 2017-02-22 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| WO2015073528A1 (en) | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| CA3231484A1 (en) | 2021-10-01 | 2023-04-06 | Qinwen Mao | Pathologic tdp-43 as a biomarker for the diagnosis of tdp-43 proteinopathy |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3577420A (en) | 1968-01-05 | 1971-05-04 | Pfizer | Certain 4-aminofuro(2,3-d)pyrimidines |
| GB1570494A (en) * | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| DD245666A1 (de) | 1985-09-20 | 1987-05-13 | Univ Halle Wittenberg | Verfahren zur herstellung von 4-aminosubstituierten thieno 2,3-d-pyrimidin-2-ylessigsaeureestern |
| JPH01313480A (ja) | 1988-06-14 | 1989-12-18 | Nippon Soda Co Ltd | ピリミジン誘導体、その製造方法及び農園芸用殺菌剤 |
| AU7890598A (en) | 1996-12-27 | 1998-07-31 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused pyrimidine compounds and medicinal use thereof |
| CA2365578A1 (en) | 1999-03-30 | 2000-10-12 | Seiichi Uchida | Thienopyrimidine compounds and salts thereof and process for the preparation of the same |
| JP2002543200A (ja) | 1999-04-30 | 2002-12-17 | ニューロゲン コーポレイション | ９Ｈ−ピリミド［４、５−ｂ］インドール誘導体：ＣＲＦ１特異性リガンド |
| JP2002105082A (ja) | 2000-09-29 | 2002-04-10 | Nippon Soda Co Ltd | 縮合チエノピリミジン化合物、その塩及び製造法 |
| DE10064994A1 (de) | 2000-12-23 | 2002-07-04 | Merck Patent Gmbh | Sulfamidothienopyrimidine |
| WO2002060449A2 (de) | 2001-01-31 | 2002-08-08 | Merck Patent Gmbh | Pharmazeutische formulierung enthaltend pyrazolo[4,3-d]pyrimidine und nitrate oder thienopyrimidine und nitrate |
| CN101100472A (zh) | 2001-04-30 | 2008-01-09 | 美国拜尔公司 | 4-氨基-5,6-取代的噻吩并[2,3-d]嘧啶化合物及其应用 |
| DE10148883A1 (de) | 2001-10-04 | 2003-04-10 | Merck Patent Gmbh | Pyrimidinderivate |
| JP2003137886A (ja) * | 2001-10-31 | 2003-05-14 | Bayer Ag | ピリミド［４，５−ｂ］インドール |
| CA2464934A1 (en) * | 2001-10-31 | 2003-05-08 | Bayer Healthcare Ag | Pyrimido [4,5-b] indole derivatives |
| EP1556053A4 (en) | 2002-10-31 | 2006-04-19 | Amgen Inc | ANTI-INFLAMMATORY AGENTS |
| ES2217956B1 (es) | 2003-01-23 | 2006-04-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de 4-aminotieno(2,3-d)pirimidin-6-carbonitrilo. |
| BRPI0408988A (pt) * | 2003-03-31 | 2006-03-28 | Predix Pharmaceuticals Holding | composto de piperidinilamino-tieno[2,3-d]pirimidina |
| US7612078B2 (en) | 2003-03-31 | 2009-11-03 | Epix Delaware, Inc. | Piperidinylamino-thieno[2,3-D] pyrimidine compounds |
| EP1954290B1 (en) * | 2005-11-22 | 2012-07-25 | Merck Sharp & Dohme Corp. | Tricyclic compounds useful as inhibitors of kinases |
| US7960400B2 (en) | 2007-08-27 | 2011-06-14 | Duquesne University Of The Holy Ghost | Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof |
| US7982035B2 (en) * | 2007-08-27 | 2011-07-19 | Duquesne University Of The Holy Spirit | Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof |
| CA2699349C (en) | 2007-09-14 | 2016-04-19 | Bayer Schering Pharma Aktiengesellschaft | Substituted tricyclic heterocyclic compounds for use as egfr inhibitors |
| US20100227853A1 (en) | 2008-04-18 | 2010-09-09 | Trustees Of Boston College | Inhibitors of cyclic amp phosphodiesterases |
| WO2010054285A2 (en) | 2008-11-10 | 2010-05-14 | National Health Research Institutes | Fused bicyclic and tricyclic pyrimidine compounds as tyrosine kinase inhibitors |
| WO2010099166A1 (en) | 2009-02-27 | 2010-09-02 | Siga Technologies, Inc. | Thienopyridine derivatives for the treatment and prevention of dengue virus infections |
| KR20120117905A (ko) | 2010-01-28 | 2012-10-24 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 프로테아좀 활성을 향상시키는 조성물 및 방법 |
| CN103119047B (zh) | 2010-07-23 | 2016-06-15 | 哈佛大学校长及研究员协会 | 三环类蛋白酶体活性增强化合物 |
| TW201219401A (en) | 2010-09-14 | 2012-05-16 | Lexicon Pharmaceuticals Inc | Bicyclic inhibitors of Notum Pectinacetylesterase and methods of their use |
| WO2012062044A1 (zh) | 2010-11-12 | 2012-05-18 | Yao Xuebiao | 动点马达蛋白cenp-e小分子抑制剂syntelin及其应用 |
| EP3239154A1 (en) | 2011-01-10 | 2017-11-01 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| TW201728592A (zh) | 2012-01-10 | 2017-08-16 | 林伯士艾瑞斯公司 | Ｉｒａｋ抑制劑及其用途 |
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2011
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- 2011-07-22 US US13/811,129 patent/US8933087B2/en active Active
- 2011-07-22 EP EP11810459.5A patent/EP2595993B1/en not_active Not-in-force
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2014
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|---|---|
| EP2595993A2 (en) | 2013-05-29 |
| WO2012012712A3 (en) | 2012-05-31 |
| CA2808432A1 (en) | 2012-01-26 |
| JP6042331B2 (ja) | 2016-12-14 |
| CN103119047A (zh) | 2013-05-22 |
| JP2013532662A (ja) | 2013-08-19 |
| US20180265519A1 (en) | 2018-09-20 |
| EP2595993B1 (en) | 2018-04-18 |
| US9981981B2 (en) | 2018-05-29 |
| US20130210845A1 (en) | 2013-08-15 |
| US20160039839A1 (en) | 2016-02-11 |
| CN103119047B (zh) | 2016-06-15 |
| US8933087B2 (en) | 2015-01-13 |
| AU2011281015B2 (en) | 2015-09-24 |
| AU2011281015A1 (en) | 2013-03-07 |
| WO2012012712A2 (en) | 2012-01-26 |
| EP2595993A4 (en) | 2014-01-08 |
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