DK2827900T3 - Amorf fast dispersion til anvendelse i behandlingen af hjernecancer - Google Patents
Amorf fast dispersion til anvendelse i behandlingen af hjernecancer Download PDFInfo
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- DK2827900T3 DK2827900T3 DK13714497.8T DK13714497T DK2827900T3 DK 2827900 T3 DK2827900 T3 DK 2827900T3 DK 13714497 T DK13714497 T DK 13714497T DK 2827900 T3 DK2827900 T3 DK 2827900T3
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- Prior art keywords
- solid dispersion
- certain embodiments
- yloxy
- triazolo
- methylphenyl
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Classifications
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- 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
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- 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
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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Claims (14)
1. Amorf fast dispersion omfattende amorf/V4-(4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3-methylphenyl)-/V6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazolin-4,6-diamin eller amorf (2-((4-((4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol og en dispersionspolymer, til anvendelse i behandling af lokal eller metastatisk hjernecancer der er forårsaget af ErbB2 over-ekspression eller amplifikation, hvor den amorfe faste dispersion anvendes efter tidligere behandling for hjerne- eller brystcancer.
2. Amorf fast dispersion til anvendelse ifølge krav 1, hvor det administreres som en oral doseringsform.
3. Amorf fast dispersion til anvendelse ifølge kravene 2 eller 3, hvor det er i en tablet.
4. Amorf fast dispersion ifølge et hvilket som helst af kravene 1 til 3, hvor det er i kombination med et andet terapeutisk middel.
5. Amorf fast dispersion til anvendelse ifølge krav 4, hvor det terapeutiske middel er valgt fra trastuzumab, capecitabin, bevacizumab, paclitaxel og docetaxel.
6. Amorf fast dispersion til anvendelse ifølge krav 1, hvor den tidligere behandling for hjernecancer er valgt fra kirurgi, stråleterapi og kemoterapi eller blandinger deraf.
7. Amorf fast dispersion til anvendelse ifølge krav 6, hvor den tidligere behandling for hjernecancer er valgt fra kirurgi, konventionel ekstern stråleterapi, tredimensionel konform stråleterapi, intens moduleret stråleterapi, stereotaktisk strålekirurgi, fraktioneret stereotaktisk stråleterapi, protonstråleterapi, indre- eller implantatstråleterapi, temozolomid, bevacizumab, carmustin, lomustin, procarbazin, vineristin, tumorbehandlingsfeltterapi, everolimus, procarbazin, lomustin, cisplatin, carboplatin og methotrexat eller blandinger deraf.
8. Amorf fast dispersion til anvendelse ifølge krav 1, hvor den tidligere behandling for brystcancer er valgt fra kirurgi, sentinel lymfeknudebiopsi efterfulgt af kirurgi, stråleterapi, kemoterapi, hormonterapi og målrettet terapi.
9. Amorf fast dispersion til anvendelse ifølge krav 1, hvor den tidligere behandling for brystcancer er valgt fra lumpektomi, delvis mastektomi, segmental mastektomi, total mastektomi, modificeret radikal mastektomi, ekstern stråling, indre stråling, methotrexat, paclitaxel albumin-stabiliseret nanopartikelformulering, ado-trastuzumab emtansin, doxorubicin, fluorouracil, everolimus, anastrozol, exemestan, capecitabin, cyclophosphamid, docetaxel, epirubicin, exemestan, toremifen, fulvestrant, letrozol, gemcitabin, trastuzumab, ixabepilon, lapatinib, tamoxifen, pertuzumab og toremifen, eller blandinger deraf.
10. Amorf fast dispersion ifølge et hvilket som helst af kravene 1 til 9, hvor amorf /V4-(4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3-methylphenyl)-/V6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazolin-4,6-diamin anvendes.
11. Amorf fast dispersion til anvendelse ifølge krav 10, hvor det amorfe /V4-(4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3-methylphenyl)-/V6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazolin-4,6-diamin administreres fra 550 til 650 mg to gange om dagen.
12. Amorf fast dispersion ifølge et hvilket som helst af kravene 1 til 9, hvor amorf (2-((4-((4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3- methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol anvendes.
13. Amorf fast dispersion til anvendelse ifølge krav 12, hvor det amorfe (2-((4-((4-([l,2,4]triazolo[l,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol administreres fra ca. 25 til ca. 1800 mg pr. dag.
14. Amorf fast dispersion til anvendelse ifølge et hvilket som helst af kravene 1 til 13, hvor dispersionspolymeren er valgt fra vinylpolymerer og copolymerer, vinylpyrrolidinvinylacetatcopolymer ("PVP-VA"), polyvinylalkoholer, polyvinylalkoholpolyvinylacetatcopolymerer, polyvinylpyrrolidin("PVP"), acrylat- og methacrylatcopolymerer, methacrylsyremethylmethacrylatcopolymer (såsom Eudragit®), polyethylenpolyvinylalkoholcopolymerer, polyoxyethylen-polyoxypropylen-blokcopolymerer (også henvist til som poloxamerer), graft-copolymer bestående af polyethylenglycol, polyvinylcaprolactam- og polyvinylacetat (såsom Soluplus®), cellulosepolymerer, såsom hydroxypropylmethylcelluloseacetat ("HPMCA"), hydroxypropylmethylcellulose ("HPMC"), hydroxypropylcellulose ("HPC"), methylcellulose, hydroxyethylmethyl cellulose, hydroxyethylcellulose, hydroxyethylcelluloseacetat, og hydroxyethylethylcellulose, hydroxypropylmethylcelluloseacetatsuccinat ("HPMCAS"), hydroxypropylmethylcellulosephthalat ("HPMCP"), carboxymethylethylcellulose ("CMEC"), celluloseacetatphthalat ("CAP"), celluloseacetatsuccinat ("CAS"), hydroxypropylmethylcelluloseacetatphthalat ("HPMCAP"), celluloseacetattrimellitat ("CAT"), hydroxypropylmethylcellulose cetattrimellitat ("HPMCAT"), og carboxymethylcelluloseacetatbutyrat ("CMCAB"), og blandinger af to eller flere sådanne polymerer.
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| US201261615082P | 2012-03-23 | 2012-03-23 | |
| PCT/US2013/033751 WO2013142875A1 (en) | 2012-03-23 | 2013-03-25 | Treatment of brain cancer |
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| DK18162971.8T DK3400943T3 (da) | 2012-03-23 | 2013-03-25 | Forbindelser til anvendelse til behandling af hjernemetastaser hos en patient med erbb2+ brystkræft |
| DK13714497.8T DK2827900T3 (da) | 2012-03-23 | 2013-03-25 | Amorf fast dispersion til anvendelse i behandlingen af hjernecancer |
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| UA116875C2 (uk) | 2011-10-14 | 2018-05-25 | Еррей Біофарма Інк. | Поліморфи arry-380 селективного інгібітору erbb2 і фармацевтичні композиції, що їх містять |
| RU2018138976A (ru) | 2012-03-23 | 2018-12-06 | Эррэй Биофарма Инк. | Лечение рака головного мозга |
| EP3592387A4 (en) * | 2017-03-09 | 2021-03-31 | The Board of Trustees of the Leland Stanford Junior University | TREATMENT OF PEDIATRIC BRAIN TUMORS WITH TARGETING THE CD47 SIGNAL PATH |
| JP7328151B2 (ja) | 2017-04-28 | 2023-08-16 | シージェン インコーポレイテッド | Ｈｅｒ２陽性がんの処置 |
| KR20240140193A (ko) | 2018-01-31 | 2024-09-24 | 데시페라 파마슈티칼스, 엘엘씨. | 위장관 기질 종양의 치료를 위한 병용 요법 |
| SG11202007287XA (en) | 2018-01-31 | 2020-08-28 | Deciphera Pharmaceuticals Llc | Combination therapy for the treatment of mastocytosis |
| JP7139448B2 (ja) * | 2018-04-09 | 2022-09-20 | ノボキュア ゲーエムベーハー | ＴＴＦｉｅｌｄｓ及びオーロラキナーゼ阻害剤による腫瘍の治療 |
| CN109942576B (zh) * | 2019-03-07 | 2020-09-11 | 上海工程技术大学 | Irbinitinib及中间体的制备方法 |
| CN111825604A (zh) * | 2019-04-16 | 2020-10-27 | 宁波药腾医药科技有限公司 | 一种图卡替尼及其中间产物的合成方法 |
| CA3150433A1 (en) | 2019-08-12 | 2021-02-18 | Deciphera Pharmaceuticals, Llc | Ripretinib for treating gastrointestinal stromal tumors |
| KR20220123058A (ko) | 2019-12-30 | 2022-09-05 | 데시페라 파마슈티칼스, 엘엘씨. | 1-(4-브로모-5-(1-에틸-7-(메틸아미노)-2-옥소-1,2-디히드로-1,6-나프티리딘-3-일)-2-플루오로페닐)-3-페닐우레아의 조성물 |
| AU2020419197B2 (en) * | 2019-12-30 | 2023-08-31 | Deciphera Pharmaceuticals, Llc | Amorphous kinase inhibitor formulations and methods of use thereof |
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| RU2255765C2 (ru) * | 2000-01-21 | 2005-07-10 | Чилдренз Хоспитал Лос-Анджелес | Способ ингибирования роста опухолей головного мозга с помощью отобранных антагонистов интегринов |
| US20020137731A1 (en) | 2000-05-30 | 2002-09-26 | Gewirtz David A. | Combination of radiation and vitamin D3 analogs for the treatment of cancer |
| AU2004264937B2 (en) | 2003-08-14 | 2010-04-29 | Array Biopharma Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
| WO2005120504A2 (en) | 2004-06-03 | 2005-12-22 | Smithkline Beecham (Cork) Limited | Cancer treatment method |
| CN1989112A (zh) * | 2004-06-03 | 2007-06-27 | 史密丝克莱恩比彻姆（科克）有限公司 | 癌症治疗方法 |
| SI2090575T1 (sl) | 2005-11-15 | 2011-08-31 | Array Biopharma Inc | Postopki in intermediati za pripravo N4-fenil-kinazolin-4-aminskih derivatov |
| US8012477B2 (en) | 2006-01-31 | 2011-09-06 | Novartis Ag | Methods of treating multiple myeloma using IL-17 binding molecules |
| CA2700673A1 (en) * | 2007-09-24 | 2009-04-02 | Tragara Pharmaceuticals, Inc. | Therapies for treating cancer using combinations of cox-2 inhibitors and anti-her2(erbb2) antibodies or combinations of cox-2 inhibitors and her2(erbb2) receptor tyrosine kinase inhibitors |
| MY188477A (en) | 2008-03-18 | 2021-12-13 | Genentech Inc | Combinations of an anti-her2 antibody-drug conjugate and chemotherapeutic agents, and methods of use |
| BR122020010643B1 (pt) | 2011-10-14 | 2022-05-17 | Array Biopharma Inc | Dispersão sólida, composições farmacêuticas compreendendo a referida dispersão, usos das composições farmacêuticas e processo de preparação de uma dispersão sólida |
| UA116875C2 (uk) * | 2011-10-14 | 2018-05-25 | Еррей Біофарма Інк. | Поліморфи arry-380 селективного інгібітору erbb2 і фармацевтичні композиції, що їх містять |
| RU2018138976A (ru) | 2012-03-23 | 2018-12-06 | Эррэй Биофарма Инк. | Лечение рака головного мозга |
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