BRPI0508970A - método combinatórios e composições para o tratamento de melanoma - Google Patents

método combinatórios e composições para o tratamento de melanoma

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Publication number
BRPI0508970A
BRPI0508970A BRPI0508970-0A BRPI0508970A BRPI0508970A BR PI0508970 A BRPI0508970 A BR PI0508970A BR PI0508970 A BRPI0508970 A BR PI0508970A BR PI0508970 A BRPI0508970 A BR PI0508970A
Authority
BR
Brazil
Prior art keywords
melanoma
agent
melanoma tumor
tumor
mammal
Prior art date
Application number
BRPI0508970-0A
Other languages
English (en)
Inventor
Gavin P Robertson
Mark Kester
Lakshman Sandirasegarane
Arati Sharma
Original Assignee
Penn State Res Found
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Penn State Res Found filed Critical Penn State Res Found
Publication of BRPI0508970A publication Critical patent/BRPI0508970A/pt

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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • 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
    • 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
    • A61K31/435—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/14—Type of nucleic acid interfering N.A.
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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications

Abstract

MéTODOS COMBINATóRIOS E COMPOSIçõES PARA O TRATAMENTO DE MELANOMA A presente invenção propõe uma base racional para se combinar terapia dercionada juntamente com quimioterápicos selecionados que não existe ataulmente para o tratamento de melanoma. A presente invenção é baseada na descoberta dos inventores da presente invenção de que AKt3 regula a apoptose e que V599E B-Raf regula o crescimento e o desenvolvimento vascular em melanoma. Os inventores são os primeiros a reconhecer uma terapia direcionada combinada efetiva para o tratamento de melanoma. Em uma modalidade,a invenção propõe um método para a indução de apoptose em uma célula tumoral de melanoma por redução da atividade de AKt3. Em outra modalidade, a invenção um método para a indução de apoptose em uma célula tumoral de melanoma que compreende colacar-se uma célula melanoma em contato com um agente que reduz a atividade de AKt3.Consequentemente, o método proposto restaura uma sensibilidade apoptótica normal a uma célula tumoral de melanoma, permitindo assim a administração de uma concentração mais baixa de agentes quimioterápicos resultando em uma toxicidade reduzida um paciente. Os inventores da presente invenção comtemplam um método para o tratamento de um tumor de melnoma em um mamífero que compreende: a administração a um tumor de melanoma de uma quantidade efetiva de um agente para induzir apoptose; e administração a um tumo de melanoma de uma quantidade efetiva de um agente para reduzir a angiogênese e a proliferação celular. Também é descrito na presente invenção um método para tratamento de um melanoma em um mamífero, que compreende : a administração, a um tumor de melanoma em um mamífero,de uma quantidade efetiva de um agente que reduz atividade de AKt3, a administração, a um tumor de melanoma em um mamífero,de uma quantidade efetiva de um agente que reduz a atividade de V599E B-Raf, tratando assim um tumor de melanoma. Em um outro aspecto, a invenção propõe uma composição fermacêutica para o tratamento de um tumor de melanoma que compreende: um agente que reduz a atividade de AKt3; e um veículo.
BRPI0508970-0A 2004-03-19 2005-03-18 método combinatórios e composições para o tratamento de melanoma BRPI0508970A (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US55450904P 2004-03-19 2004-03-19
PCT/US2005/008950 WO2005089443A2 (en) 2004-03-19 2005-03-18 Combinatorial methods and compositions for treatment of melanoma

Publications (1)

Publication Number Publication Date
BRPI0508970A true BRPI0508970A (pt) 2007-08-21

Family

ID=34994352

Family Applications (1)

Application Number Title Priority Date Filing Date
BRPI0508970-0A BRPI0508970A (pt) 2004-03-19 2005-03-18 método combinatórios e composições para o tratamento de melanoma

Country Status (9)

Country Link
US (4) US20050267060A1 (pt)
EP (1) EP1744788A4 (pt)
JP (1) JP2007530453A (pt)
CN (1) CN101389345A (pt)
AU (1) AU2005223649A1 (pt)
BR (1) BRPI0508970A (pt)
CA (1) CA2560269A1 (pt)
MX (1) MXPA06010667A (pt)
WO (1) WO2005089443A2 (pt)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2359244C (en) 1999-01-13 2013-10-08 Bayer Corporation .omega.-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
MXPA04007832A (es) 2002-02-11 2005-09-08 Bayer Pharmaceuticals Corp Aril-ureas con actividad inhibitoria de angiogenesis.
DE602004007382T2 (de) 2003-05-20 2008-04-17 Bayer Pharmaceuticals Corp., West Haven Diaryl-harnstoffe für durch pdgfr vermittelte krankheiten
CL2004001834A1 (es) 2003-07-23 2005-06-03 Bayer Pharmaceuticals Corp Compuesto 4-{4-[3-(4-cloro-3-trifluorometilfenil)-ureido]-3-fluorofenoxi}-piridin-2-metilamida, inhibidor de la raf, vegfr, p38 y pdgfr quinasas, sus sales; composiicon farmaceutica; combinacion farmaceutica; y su uso para tratar trastornos hiperprol
JP4931823B2 (ja) 2004-10-18 2012-05-16 アムジエン・インコーポレーテツド チアジアゾール化合物及び使用方法
US20090306020A1 (en) * 2005-05-27 2009-12-10 Bayer Healthcare Ag Combination therapy comprising diaryl ureas for treating diseases
MX2008006239A (es) * 2005-11-14 2008-12-12 Bayer Healthcare Llc Metodos para prediccion y pronostico de cancer y monitoreo de terapia contra el cancer.
WO2008128189A1 (en) 2007-04-13 2008-10-23 The Penn State Research Foundation Anti-cancer compositions and methods
AU2008276521B2 (en) 2007-07-17 2011-11-03 Amgen Inc. Heterocyclic modulators of PKB
WO2009011871A2 (en) 2007-07-17 2009-01-22 Amgen Inc. Thiadiazole modulators of pkb
WO2009015368A2 (en) 2007-07-25 2009-01-29 Eisai R & D Management Co., Ltd. Multikinase inhibitors for use in the treatment of cancer
ATE545023T1 (de) * 2007-10-29 2012-02-15 Eisai R&D Man Co Ltd Verfahren zur vorhersage der fähigkeit einer zearalenon-analogverbindung für die krebsbehandlung
US20100029657A1 (en) * 2008-02-29 2010-02-04 Wyeth Bridged, Bicyclic Heterocyclic or Spiro Bicyclic Heterocyclic Derivatives of Pyrazolo[1, 5-A]Pyrimidines, Methods for Preparation and Uses Thereof
UA103319C2 (en) 2008-05-06 2013-10-10 Глаксосмитклайн Ллк Thiazole- and oxazole-benzene sulfonamide compounds
EP2409156A4 (en) 2009-02-06 2013-07-17 H Lee Moffitt Cancer Ct & Res AKT TYROSINE 176 PHOSPHORYLATION BIOMARKER FOR CANCER
JP5641232B2 (ja) * 2010-11-24 2014-12-17 石川県公立大学法人 オゴノリ由来のシクロオキシゲナーゼの遺伝子及び該遺伝子を利用するプロスタグランジン類生産方法
US8747891B2 (en) 2011-05-10 2014-06-10 The Penn State Research Foundation Ceramide anionic liposome compositions
WO2013109142A1 (en) 2012-01-16 2013-07-25 Stichting Het Nederlands Kanker Instituut Combined pdk and mapk/erk pathway inhibition in neoplasia
WO2015041533A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut Rock in combination with mapk-pathway
WO2015041534A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut P90rsk in combination with raf/erk/mek
CN110088136A (zh) * 2016-10-13 2019-08-02 达纳-法伯癌症研究所有限公司 使用基因表达签名预测黑素瘤中对于ctla4封锁的应答和耐药性的组合物和方法
CN110476953B (zh) * 2019-09-09 2021-11-12 广州中鑫基因医学科技有限公司 一种细胞活性保存液以及疾病检测试剂盒
CN111759794B (zh) * 2020-07-14 2023-07-21 中山大学 一种治疗黑色素瘤的微针及其制备方法

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5843974A (en) * 1995-06-06 1998-12-01 Eli Lilly And Company Methods of inhibiting melanoma using Benzothiophenes as cytotoxic agents per se
US6506559B1 (en) * 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
US20030035790A1 (en) * 1999-01-15 2003-02-20 Shu-Hsia Chen Combination therapy for the prevention or treatment of cancer, inflammatory disorders or infectious diseases in a subject
SK3812002A3 (en) * 1999-09-17 2003-09-11 Abbott Gmbh & Co Kg Pyrazolopyrimidines as therapeutic agents
US6187586B1 (en) * 1999-12-29 2001-02-13 Isis Pharmaceuticals, Inc. Antisense modulation of AKT-3 expression
CA2400447C (en) * 2000-02-17 2008-04-22 Amgen Inc. Kinase inhibitors
US6809194B1 (en) * 2000-05-10 2004-10-26 Chiron Corporation Akt3 inhibitors
US20040106540A1 (en) * 2001-04-10 2004-06-03 Barnett Stanley F Method of treating cancer
PT1381384E (pt) * 2001-04-24 2011-09-01 Merck Patent Gmbh Terapia de combinação usando agentes anti-angiogénicos e tnfa
WO2003047523A2 (en) * 2001-12-04 2003-06-12 Onyx Pharmaceuticals, Inc. Raf-mek-erk pathway inhibitors to treat cancer
US6998391B2 (en) * 2002-02-07 2006-02-14 Supergen.Inc. Method for treating diseases associated with abnormal kinase activity
AU2003237121A1 (en) * 2002-04-26 2003-11-10 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
US7556944B2 (en) * 2002-05-03 2009-07-07 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for use in preparing siRNAs
SI1530636T1 (sl) * 2002-08-21 2010-12-31 Stry Liaison Ofiice The University Of British Columbia Umiversity Indu Zdravljenje melanoma z zniĹľanjem nivojev klusterina
KR101238701B1 (ko) * 2002-08-21 2013-03-05 더 유니버시티 오브 브리티쉬 콜롬비아 암-관련 단백질을 표적으로 하는 알엔에이아이 프로브
EP2305813A3 (en) * 2002-11-14 2012-03-28 Dharmacon, Inc. Fuctional and hyperfunctional sirna
US20080161547A1 (en) * 2002-11-14 2008-07-03 Dharmacon, Inc. siRNA targeting serine/threonine protein kinase AKT
US20050221354A1 (en) * 2004-02-18 2005-10-06 Wyeth Nucleic acid arrays for monitoring expression profiles of drug target genes

Also Published As

Publication number Publication date
US20130217949A1 (en) 2013-08-22
US20050267060A1 (en) 2005-12-01
MXPA06010667A (es) 2007-07-04
EP1744788A2 (en) 2007-01-24
EP1744788A4 (en) 2010-08-18
CN101389345A (zh) 2009-03-18
CA2560269A1 (en) 2005-09-29
WO2005089443A2 (en) 2005-09-29
JP2007530453A (ja) 2007-11-01
US20140348901A1 (en) 2014-11-27
US20130209546A1 (en) 2013-08-15
AU2005223649A1 (en) 2005-09-29
WO2005089443A3 (en) 2009-04-23

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B08K Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]

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