CA2850763A1 - Novel quinoxaline inhibitors of pi3k - Google Patents
Novel quinoxaline inhibitors of pi3k Download PDFInfo
- Publication number
- CA2850763A1 CA2850763A1 CA2850763A CA2850763A CA2850763A1 CA 2850763 A1 CA2850763 A1 CA 2850763A1 CA 2850763 A CA2850763 A CA 2850763A CA 2850763 A CA2850763 A CA 2850763A CA 2850763 A1 CA2850763 A1 CA 2850763A1
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- CA
- Canada
- Prior art keywords
- group
- optionally substituted
- nhc
- 3alkylenen
- 4alkylenec
- Prior art date
- 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.)
- Abandoned
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Classifications
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Landscapes
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| US201161543176P | 2011-10-04 | 2011-10-04 | |
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| PCT/US2012/058800 WO2013052699A2 (en) | 2011-10-04 | 2012-10-04 | Novel quinoxaline inhibitors of pi3k |
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Families Citing this family (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102076865B (zh) | 2008-05-02 | 2016-03-16 | 西雅图基因公司 | 用于制造核心岩藻糖基化降低的抗体和抗体衍生物的方法和组合物 |
| EP2845856A1 (en) | 2009-06-29 | 2015-03-11 | Incyte Corporation | Pyrimidinones as PI3K inhibitors |
| GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
| GB201020179D0 (en) | 2010-11-29 | 2011-01-12 | Astex Therapeutics Ltd | New compounds |
| TW201249844A (en) | 2010-12-20 | 2012-12-16 | Incyte Corp | N-(1-(substituted-phenyl)ethyl)-9H-purin-6-amines as PI3K inhibitors |
| UA121539C2 (uk) | 2011-09-02 | 2020-06-25 | Інсайт Холдинґс Корпорейшн | Гетероцикліламіни як інгібітори рі3к |
| GB201118654D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118675D0 (en) | 2011-10-28 | 2011-12-14 | Astex Therapeutics Ltd | New compounds |
| GB201118656D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118652D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| WO2013090725A1 (en) * | 2011-12-15 | 2013-06-20 | Philadelphia Health & Education Corporation | NOVEL PI3K p110 INHIBITORS AND METHODS OF USE THEREOF |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| GB201209609D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| WO2014072937A1 (en) | 2012-11-08 | 2014-05-15 | Rhizen Pharmaceuticals Sa | Pharmaceutical compositions containing a pde4 inhibitor and a pi3 delta or dual pi3 delta-gamma kinase inhibitor |
| GB201307577D0 (en) | 2013-04-26 | 2013-06-12 | Astex Therapeutics Ltd | New compounds |
| US10612095B2 (en) | 2013-12-06 | 2020-04-07 | Dana-Farber Cancer Institute, Inc. | Methods to distinguish Waldenström's Macroglobulinemia from IgM monoclonal gammopathy of undetermined significance |
| JP6878004B2 (ja) | 2013-12-13 | 2021-05-26 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | リンパ形質細胞性リンパ腫を処置する方法 |
| JP6879740B2 (ja) | 2013-12-13 | 2021-06-02 | ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド | リンパ形質細胞性リンパ腫を処置する方法 |
| CA2939219C (en) * | 2014-02-11 | 2023-02-28 | Mitokinin Llc | Compositions and methods using the same for treatment of neurodegenerative and mitochondrial disease |
| AU2015238305B2 (en) | 2014-03-26 | 2020-06-18 | Astex Therapeutics Ltd | Combinations of an FGFR inhibitor and an IGF1R inhibitor |
| MA39784B1 (fr) | 2014-03-26 | 2021-03-31 | Astex Therapeutics Ltd | Combinaisons des inhibiteurs du fgfr et du cmet destinées au traitement du cancer |
| JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
| CN104003982A (zh) * | 2014-05-05 | 2014-08-27 | 成都尔珏科技有限公司 | 一种可用于制备肺癌的化合物 |
| US10077277B2 (en) | 2014-06-11 | 2018-09-18 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors |
| SG11201610770PA (en) | 2014-07-04 | 2017-01-27 | Lupin Ltd | Quinolizinone derivatives as pi3k inhibitors |
| CN105503877A (zh) * | 2014-09-24 | 2016-04-20 | 和记黄埔医药（上海）有限公司 | 咪唑并哒嗪类化合物及其用途 |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| US10112957B2 (en) | 2014-10-22 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
| US9637488B2 (en) | 2015-01-29 | 2017-05-02 | Fuqiang Ruan | Heterocyclic compounds as inhibitors of class I PI3KS |
| TW201639573A (zh) | 2015-02-03 | 2016-11-16 | 吉李德科學股份有限公司 | 有關治療癌症之合併治療 |
| JO3695B1 (ar) | 2015-02-10 | 2020-08-27 | Astex Therapeutics Ltd | تركيبات صيدلانية تشتمل على n- (3.5- ثنائي ميثوكسي فينيل)-n-(1-ميثيل إيثيل)-n- 3-( ميثيل-h1-بيرازول-4-يل) كينوكسالين-6-يل) إيثان- 1.2-ثنائي الأمين) |
| UA122332C2 (uk) | 2015-02-27 | 2020-10-26 | Інсайт Корпорейшн | Солі інгібітора pi3k і способи їх отримання |
| US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
| WO2016183063A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Crystalline forms of a pi3k inhibitor |
| WO2016183060A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
| CN107922396B (zh) | 2015-07-20 | 2022-08-05 | 建新公司 | 集落刺激因子-1受体(csf-1r)抑制剂 |
| KR102703498B1 (ko) | 2015-09-23 | 2024-09-04 | 얀센 파마슈티카 엔브이 | 신규 화합물 |
| CN108137546B (zh) | 2015-09-23 | 2021-07-27 | 詹森药业有限公司 | 双杂芳基取代的1,4-苯并二氮杂卓化合物及其用于治疗癌症的用途 |
| EP3355875B1 (en) | 2015-10-01 | 2021-09-29 | Gilead Sciences, Inc. | Combination of a btk inhibitor and a checkpoint inhibitor for treating cancers |
| EP3394044A1 (en) | 2015-12-17 | 2018-10-31 | Gilead Sciences, Inc. | Tank-binding kinase inhibitor compounds |
| AU2017228371A1 (en) | 2016-03-04 | 2018-09-13 | Gilead Sciences, Inc. | Compositions and combinations of autotaxin inhibitors |
| WO2017177179A1 (en) | 2016-04-08 | 2017-10-12 | Gilead Sciences, Inc. | Compositions and methods for treating cancer, inflammatory diseases and autoimmune diseases |
| US10919914B2 (en) | 2016-06-08 | 2021-02-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US10059769B2 (en) | 2016-06-13 | 2018-08-28 | I-Mab | Anti-PD-L1 antibodies and uses thereof |
| JP6764017B2 (ja) | 2016-08-04 | 2020-09-30 | ギリアード サイエンシーズ， インコーポレイテッド | がんの処置での使用のためのコビシスタット |
| UA123558C2 (uk) | 2016-09-22 | 2021-04-21 | Астразенека Аб | Похідні 5-[2-(піридин-2-іламіно)-1,3-тіазол-5-іл]-2,3-дигідро-1h-ізоіндол-1-ону та їх застосування як подвійних інгібіторів фосфатидилінозитол-3-кіназ дельта і гамма |
| WO2018085069A1 (en) | 2016-11-03 | 2018-05-11 | Gilead Sciences, Inc. | Combination of a bcl-2 inhibitor and a bromodomain inhibitor for treating cancer |
| US20180141939A1 (en) | 2016-11-22 | 2018-05-24 | Gilead Sciences, Inc. | Solid forms of a bet inhibitor |
| UA126571C2 (uk) | 2017-01-24 | 2022-11-02 | Ай-Маб Байофарма Юес Лімітед | Антитіло до cd73 та його застосування |
| AR110998A1 (es) | 2017-02-24 | 2019-05-22 | Gilead Sciences Inc | Inhibidores de la tirosina cinasa de bruton |
| WO2018156901A1 (en) | 2017-02-24 | 2018-08-30 | Gilead Sciences, Inc. | Inhibitors of bruton's tyrosine kinase |
| BR102018007822A2 (pt) | 2017-04-20 | 2018-11-06 | Gilead Sciences, Inc. | composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição |
| KR20200019228A (ko) | 2017-06-21 | 2020-02-21 | 미토키닌, 인크. | 신경퇴행성 및 미토콘드리아 질환의 치료를 위한 조성물 및 이를 사용하는 방법 |
| JP7098748B2 (ja) | 2017-12-20 | 2022-07-11 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール，ヴイ．ヴイ．アイ． | Ｓｔｉｎｇアダプタータンパク質を活性化するホスホン酸結合を有する２’３’環状ジヌクレオチド |
| KR102492187B1 (ko) | 2017-12-20 | 2023-01-27 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | Sting 어댑터 단백질을 활성화하는 포스포네이트 결합을 가진 3'3' 사이클릭 다이뉴클레오티드 |
| KR102708681B1 (ko) | 2018-02-13 | 2024-09-26 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| EP4600247A3 (en) | 2018-04-19 | 2025-11-19 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic nucleotide |
| CA3098873A1 (en) | 2018-05-11 | 2019-11-14 | Phosphorex, Inc. | Microparticles and nanoparticles having negative surface charges |
| CN112118845B (zh) | 2018-05-14 | 2023-06-13 | 吉利德科学公司 | Mcl-1抑制剂 |
| MX2020012826A (es) | 2018-06-01 | 2021-03-09 | Incyte Corp | Regimen de dosificacion para el tratamiento de trastornos relacionados con fosfatidilinositol 3-cinasas (pi3k). |
| UA126421C2 (uk) | 2018-07-13 | 2022-09-28 | Гіліад Сайєнсіз, Інк. | Інгібітори pd-1/pd-l1 |
| EP3860717A1 (en) | 2018-10-03 | 2021-08-11 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| US11236085B2 (en) | 2018-10-24 | 2022-02-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| WO2020092528A1 (en) | 2018-10-31 | 2020-05-07 | Gilead Sciences, Inc. | Substituted 6-azabenzimidazole compounds having hpk1 inhibitory activity |
| PE20211655A1 (es) | 2018-10-31 | 2021-08-24 | Gilead Sciences Inc | Compuestos de 6-azabencimidazol sustituidos como inhibidores de hpk1 |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| WO2020178770A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| CN113543851B (zh) | 2019-03-07 | 2025-03-18 | 捷克共和国有机化学与生物化学研究所 | 2’3’-环二核苷酸及其前药 |
| TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI826690B (zh) | 2019-05-23 | 2023-12-21 | 美商基利科學股份有限公司 | 經取代之烯吲哚酮化物及其用途 |
| AU2020301161B2 (en) | 2019-06-25 | 2023-10-26 | Gilead Sciences, Inc. | FLT3L-Fc fusion proteins and methods of use |
| AU2020315598B2 (en) | 2019-07-16 | 2024-12-12 | Gilead Sciences, Inc. | HIV vaccines and methods of making and using |
| EP4458975A3 (en) | 2019-09-30 | 2025-02-12 | Gilead Sciences, Inc. | Hbv vaccines and methods treating hbv |
| KR102902719B1 (ko) | 2019-10-18 | 2025-12-24 | 포티 세븐, 엘엘씨 | 골수이형성 증후군 및 급성 골수성 백혈병을 치료하기 위한 조합 치료 |
| CA3153636A1 (en) | 2019-10-31 | 2021-05-06 | Forty Seven, Inc. | Anti-cd47 and anti-cd20 based treatment of blood cancer |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| EP4445902A3 (en) | 2019-12-24 | 2024-12-18 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
| CN117964757A (zh) | 2020-02-14 | 2024-05-03 | 吉利德科学公司 | 与ccr8结合的抗体和融合蛋白及其用途 |
| US12110294B2 (en) | 2020-05-01 | 2024-10-08 | Gilead Sciences, Inc. | CD73 compounds |
| WO2022017371A1 (zh) * | 2020-07-21 | 2022-01-27 | 中国医药研究开发中心有限公司 | 具有磷脂酰肌醇3-激酶δ和γ的双重抑制剂活性的杂环化合物及其医药用途 |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | ＣＤ４７／ＳＩＲＰα結合及ＮＥＤＤ８活化酶Ｅ１調節次單元之共抑制以用於治療癌症 |
| TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用ＦＬＴ３Ｌ—Ｆｃ融合蛋白之方法 |
| EP4359415A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271650A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| US11932634B2 (en) | 2021-06-23 | 2024-03-19 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| AU2022375782B2 (en) | 2021-10-28 | 2026-02-26 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
| AU2022376954B2 (en) | 2021-10-29 | 2026-04-23 | Gilead Sciences, Inc. | Cd73 compounds |
| WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| AU2022419982B2 (en) | 2021-12-22 | 2026-04-16 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| CA3237577A1 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Ｐａｒｐ７抑制劑 |
| EP4493554A1 (en) | 2022-03-17 | 2025-01-22 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| WO2023183817A1 (en) | 2022-03-24 | 2023-09-28 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
| TWI876305B (zh) | 2022-04-05 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| CR20240451A (es) | 2022-04-21 | 2024-12-04 | Gilead Sciences Inc | Compuestos de modulación de kras g12d |
| PE20250758A1 (es) | 2022-07-01 | 2025-03-13 | Gilead Sciences Inc | Compuestos de cd73 |
| KR20250036855A (ko) | 2022-07-12 | 2025-03-14 | 길리애드 사이언시즈, 인코포레이티드 | Hiv 면역원성 폴리펩타이드 및 백신, 및 이들의 용도 |
| WO2024064668A1 (en) | 2022-09-21 | 2024-03-28 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPα DISRUPTION ANTICANCER COMBINATION THERAPY |
| CN120225509A (zh) | 2022-12-22 | 2025-06-27 | 吉利德科学公司 | Prmt5抑制剂及其用途 |
| AU2024252725A1 (en) | 2023-04-11 | 2025-11-06 | Gilead Sciences, Inc. | Kras modulating compounds |
| PE20260121A1 (es) | 2023-04-21 | 2026-01-16 | Gilead Sciences Inc | Inhibidores de prmt5 y usos de los mismos |
| AU2024306338A1 (en) | 2023-06-30 | 2026-01-08 | Gilead Sciences, Inc. | Kras modulating compounds |
| KR20260046403A (ko) | 2023-07-26 | 2026-04-07 | 길리애드 사이언시즈, 인코포레이티드 | Parp7 저해제 |
| WO2025024811A1 (en) | 2023-07-26 | 2025-01-30 | Gilead Sciences, Inc. | Parp7 inhibitors |
| US20250101042A1 (en) | 2023-09-08 | 2025-03-27 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| AU2024337913A1 (en) | 2023-09-08 | 2026-03-26 | Gilead Sciences, Inc. | Pyrimidine-containing polycyclic derivatives as kras g12d modulating compounds |
| US20250154172A1 (en) | 2023-11-03 | 2025-05-15 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2025137640A1 (en) | 2023-12-22 | 2025-06-26 | Gilead Sciences, Inc. | Azaspiro wrn inhibitors |
| WO2025245003A1 (en) | 2024-05-21 | 2025-11-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2026039365A1 (en) | 2024-08-12 | 2026-02-19 | Gilead Sciences, Inc. | Kras modulating compounds |
| WO2026089992A1 (en) | 2024-10-21 | 2026-04-30 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100354309B1 (ko) * | 1993-11-12 | 2003-01-06 | 파마시아 앤드 업존 캄파니 | 피리미딘-티오알킬및알킬에테르화합물 |
| JP2002534512A (ja) * | 1999-01-15 | 2002-10-15 | ノボ ノルディスク アクティーゼルスカブ | 非ペプチドｇｌｐ−１アゴニスト |
| US6927214B1 (en) * | 1999-01-15 | 2005-08-09 | Novo Nordisk A/S | Non-peptide GLP-1 agonists |
| MX2009010050A (es) * | 2007-03-23 | 2009-10-12 | Amgen Inc | Derivados de quinolina o quinoxalina 3-sustituidos y su uso como inhibidores de fosfotidilinositol 3-cinasa (p13k). |
| AU2008231384B2 (en) * | 2007-03-23 | 2011-09-15 | Amgen Inc. | Heterocyclic compounds and their use |
| RS54706B1 (sr) * | 2007-03-23 | 2016-08-31 | Amgen Inc. | Heterociklična jedinjenja i njihove upotrebe |
| EA019064B1 (ru) * | 2007-04-11 | 2013-12-30 | Экселиксис, Инк. | Способы лечения рака с применением хинаксолинового ингибитора pi3k-альфа |
| EP2231641B1 (en) * | 2007-12-21 | 2016-06-01 | UCB Biopharma SPRL | Quinoxaline and quinoline derivatives as kinase inhibitors |
| JP5731978B2 (ja) * | 2008-09-26 | 2015-06-10 | インテリカイン， エルエルシー | 複素環キナーゼ阻害剤 |
| CA2784710A1 (en) * | 2009-12-15 | 2011-06-23 | Shionogi & Co., Ltd. | Oxadiazole derivative having endothelial lipase inhibitory activity |
| WO2012037204A1 (en) * | 2010-09-14 | 2012-03-22 | Exelixis, Inc. | Inhibitors of pi3k-delta and methods of their use and manufacture |
-
2012
- 2012-10-04 AU AU2012318580A patent/AU2012318580A1/en not_active Abandoned
- 2012-10-04 HK HK15101538.0A patent/HK1201065A1/xx unknown
- 2012-10-04 CN CN201280049200.5A patent/CN104024257A/zh active Pending
- 2012-10-04 EP EP12838127.4A patent/EP2763994A4/en not_active Withdrawn
- 2012-10-04 WO PCT/US2012/058800 patent/WO2013052699A2/en not_active Ceased
- 2012-10-04 JP JP2014534732A patent/JP2014528451A/ja active Pending
- 2012-10-04 US US14/350,039 patent/US20140235643A1/en not_active Abandoned
- 2012-10-04 CA CA2850763A patent/CA2850763A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014528451A (ja) | 2014-10-27 |
| AU2012318580A1 (en) | 2014-05-22 |
| HK1201065A1 (en) | 2015-08-21 |
| EP2763994A4 (en) | 2015-08-26 |
| US20140235643A1 (en) | 2014-08-21 |
| WO2013052699A3 (en) | 2013-06-06 |
| EP2763994A2 (en) | 2014-08-13 |
| CN104024257A (zh) | 2014-09-03 |
| WO2013052699A2 (en) | 2013-04-11 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20171004 |