AU2013203637B2 - Combination therapy for proliferative disorders - Google Patents
Combination therapy for proliferative disorders Download PDFInfo
- Publication number
- AU2013203637B2 AU2013203637B2 AU2013203637A AU2013203637A AU2013203637B2 AU 2013203637 B2 AU2013203637 B2 AU 2013203637B2 AU 2013203637 A AU2013203637 A AU 2013203637A AU 2013203637 A AU2013203637 A AU 2013203637A AU 2013203637 B2 AU2013203637 B2 AU 2013203637B2
- Authority
- AU
- Australia
- Prior art keywords
- day
- acceptable salt
- pharmaceutically
- administered
- vemurafenib
- 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.)
- Ceased
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/402—1-aryl substituted, e.g. piretanide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261612441P | 2012-03-19 | 2012-03-19 | |
| US61/612,441 | 2012-03-19 | ||
| PCT/EP2013/055522 WO2013139724A1 (en) | 2012-03-19 | 2013-03-18 | Combination therapy (vemrufenib and a mdm2 inhibitor) for the treatment proliferative disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2013203637A1 AU2013203637A1 (en) | 2013-10-03 |
| AU2013203637B2 true AU2013203637B2 (en) | 2016-07-07 |
Family
ID=47884369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013203637A Ceased AU2013203637B2 (en) | 2012-03-19 | 2013-03-18 | Combination therapy for proliferative disorders |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US9216170B2 (enExample) |
| EP (1) | EP2827859B1 (enExample) |
| JP (1) | JP6141958B2 (enExample) |
| KR (1) | KR101673731B1 (enExample) |
| CN (2) | CN108295063A (enExample) |
| AR (1) | AR090349A1 (enExample) |
| AU (1) | AU2013203637B2 (enExample) |
| BR (1) | BR112014018910A8 (enExample) |
| CA (1) | CA2861056A1 (enExample) |
| HK (1) | HK1201198A1 (enExample) |
| MX (1) | MX2014010590A (enExample) |
| NZ (1) | NZ626985A (enExample) |
| RU (1) | RU2014141362A (enExample) |
| SG (1) | SG11201404418QA (enExample) |
| WO (1) | WO2013139724A1 (enExample) |
| ZA (1) | ZA201405411B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| PL2603600T3 (pl) | 2010-08-13 | 2019-06-28 | Aileron Therapeutics, Inc. | Makrocykle peptidomometyczne |
| US8709419B2 (en) | 2010-08-17 | 2014-04-29 | Hoffmann-La Roche, Inc. | Combination therapy |
| US9295669B2 (en) | 2010-12-14 | 2016-03-29 | Hoffman La-Roche Inc. | Combination therapy for proliferative disorders |
| CA2852468A1 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocyles |
| US9216170B2 (en) | 2012-03-19 | 2015-12-22 | Hoffmann-La Roche Inc. | Combination therapy for proliferative disorders |
| US20130245089A1 (en) | 2012-03-19 | 2013-09-19 | Hoffmann-La Roche Inc. | Method for administration |
| US20140200255A1 (en) | 2012-03-19 | 2014-07-17 | Brian Higgins | Method for administration |
| RS59113B1 (sr) | 2012-08-17 | 2019-09-30 | Hoffmann La Roche | Kombinovane terapije za melanom koje uključuju davanje kobimetiniba i vemurafiniba |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| PT3068393T (pt) * | 2013-11-11 | 2022-06-14 | Amgen Inc | Terapia de combinação, incluindo um inibidor de mdm2 e um ou mais agentes farmaceuticamente ativos adicionais para o tratamento de cancros |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| CA2926307C (en) * | 2013-12-05 | 2021-11-16 | F. Hoffmann-La Roche Ag | Novel combination treatment for acute myeloid leukemia (aml) |
| RU2016144187A (ru) * | 2014-04-15 | 2018-05-16 | Ф. Хоффманн-Ля Рош Аг | Твердые формы фармацевтически активного соединения |
| TW201613576A (en) * | 2014-06-26 | 2016-04-16 | Novartis Ag | Intermittent dosing of MDM2 inhibitor |
| SG11201702223UA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| CA2972076A1 (en) * | 2014-12-23 | 2016-06-30 | Millennium Pharmaceuticals, Inc. | Combination of raf inhibitors and aurora kinase inhibitors |
| CN107427501B (zh) | 2015-02-20 | 2023-12-01 | 第一三共株式会社 | 通过联合使用治疗癌症的方法 |
| AU2016235424A1 (en) | 2015-03-20 | 2017-10-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| EP3347372A4 (en) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
| WO2017066193A1 (en) * | 2015-10-15 | 2017-04-20 | Princeton Drug Discovery, Llc | Novel inhibitors of protein kinases |
| RU2018120366A (ru) | 2015-12-14 | 2020-01-16 | Рэд.Ком, Ллс | Модульные цифровая камера и сотовый телефон |
| AU2018209164B2 (en) | 2017-01-17 | 2021-11-04 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| US11091522B2 (en) | 2018-07-23 | 2021-08-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN110585433A (zh) * | 2019-09-27 | 2019-12-20 | 青岛大学 | Braf-v600e的抑制剂的应用及用于治疗甲状腺癌的药物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100152190A1 (en) * | 2008-09-18 | 2010-06-17 | David Joseph Bartkovitz | Substituted Pyrrolidine-2-Carboxamides |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1925855B (zh) | 2003-12-19 | 2010-06-16 | 普莱希科公司 | 开发Ret调节剂的化合物和方法 |
| DK2395004T3 (en) | 2005-06-22 | 2016-03-21 | Plexxikon Inc | Pyrrolo [2,3-b] pyridine derivatives as protein kinase inhibitors |
| EP2130822A1 (en) | 2005-12-01 | 2009-12-09 | F. Hoffmann-La Roche AG | 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between p53 and mdm2 proteins for use as anticancer agents |
| KR20170058465A (ko) | 2009-04-03 | 2017-05-26 | 에프. 호프만-라 로슈 아게 | 프로판-１-술폰산 ｛３-［５-（４-클로로-페닐）-１Ｈ-피롤로［２，３-ｂ］피리딘-３-카르보닐］-２，４-디플루오로-페닐｝-아미드 조성물 및 그의 용도 |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| US20120214828A1 (en) | 2009-08-24 | 2012-08-23 | Georgia Hatzivassiliou | Determining sensitivity of cells to b-raf inhibitor treatment by detecting kras mutation and rtk expression levels |
| US8779150B2 (en) | 2010-07-21 | 2014-07-15 | Hoffmann-La Roche Inc. | Processes for the manufacture of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1 H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide |
| US8709419B2 (en) | 2010-08-17 | 2014-04-29 | Hoffmann-La Roche, Inc. | Combination therapy |
| US20120045433A1 (en) | 2010-08-17 | 2012-02-23 | Kapil Dhingra | Combination therapy |
| US9295669B2 (en) | 2010-12-14 | 2016-03-29 | Hoffman La-Roche Inc. | Combination therapy for proliferative disorders |
| TWI558702B (zh) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | 醫藥活性物質的固態形式 |
| WO2012135759A1 (en) | 2011-04-01 | 2012-10-04 | Genentech, Inc. | Combinations of akt inhibitor compounds and abiraterone, and methods of use |
| EP2776051A4 (en) | 2011-10-28 | 2015-06-17 | Hoffmann La Roche | THERAPEUTIC COMBINATIONS AND METHOD FOR THE TREATMENT OF MELANOMA |
| US20130172375A1 (en) | 2011-12-13 | 2013-07-04 | Hoffmann-La Roche Inc. | Pharmaceutical composition |
| US9216170B2 (en) | 2012-03-19 | 2015-12-22 | Hoffmann-La Roche Inc. | Combination therapy for proliferative disorders |
-
2013
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- 2015-07-22 US US14/806,427 patent/US9486445B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100152190A1 (en) * | 2008-09-18 | 2010-06-17 | David Joseph Bartkovitz | Substituted Pyrrolidine-2-Carboxamides |
Non-Patent Citations (3)
| Title |
|---|
| LEE J. et al.,Journal of Investigative Dermatology, 2012, vol. 132, pages 263-265 * |
| PARAISO K.H. ey al., Clinical Cancer Research, February 2012, vol. 18, no. 9, pages 2502-2514 * |
| SHI H. et al., Cancer Research, 2011, vol 71, pages 5067-5074 * |
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