PT2835053T - Terapêutica combinada para o tratamento do cancro da mama - Google Patents

Terapêutica combinada para o tratamento do cancro da mama

Info

Publication number
PT2835053T
PT2835053T PT141875070T PT14187507T PT2835053T PT 2835053 T PT2835053 T PT 2835053T PT 141875070 T PT141875070 T PT 141875070T PT 14187507 T PT14187507 T PT 14187507T PT 2835053 T PT2835053 T PT 2835053T
Authority
PT
Portugal
Prior art keywords
breast cancer
combination therapy
treating breast
treating
therapy
Prior art date
Application number
PT141875070T
Other languages
English (en)
Inventor
Harper Jay
Michael Lonning Scott
James Hsu Frank
Original Assignee
Genzyme Corp
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 Genzyme Corp filed Critical Genzyme Corp
Publication of PT2835053T publication Critical patent/PT2835053T/pt

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • 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
    • A61K31/425—Thiazoles
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • 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
    • 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
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1841—Transforming growth factor [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Oncology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
PT141875070T 2010-03-12 2011-03-08 Terapêutica combinada para o tratamento do cancro da mama PT2835053T (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US31351510P 2010-03-12 2010-03-12

Publications (1)

Publication Number Publication Date
PT2835053T true PT2835053T (pt) 2016-07-14

Family

ID=44563812

Family Applications (2)

Application Number Title Priority Date Filing Date
PT141875070T PT2835053T (pt) 2010-03-12 2011-03-08 Terapêutica combinada para o tratamento do cancro da mama
PT16166917T PT3117709T (pt) 2010-03-12 2011-03-08 Terapêutica combinada para o tratamento do cancro da mama

Family Applications After (1)

Application Number Title Priority Date Filing Date
PT16166917T PT3117709T (pt) 2010-03-12 2011-03-08 Terapêutica combinada para o tratamento do cancro da mama

Country Status (18)

Country Link
US (3) US8911736B2 (pt)
EP (4) EP2544541B1 (pt)
JP (2) JP5917418B2 (pt)
CY (1) CY1117831T1 (pt)
DK (2) DK3117709T3 (pt)
ES (2) ES2694288T3 (pt)
HK (1) HK1206936A1 (pt)
HR (2) HRP20160932T1 (pt)
HU (2) HUE040107T2 (pt)
LT (1) LT3117709T (pt)
ME (1) ME02464B (pt)
PL (2) PL2835053T3 (pt)
PT (2) PT2835053T (pt)
RS (2) RS54972B1 (pt)
SI (2) SI2835053T1 (pt)
SM (1) SMT201600253B (pt)
TR (1) TR201816180T4 (pt)
WO (1) WO2011112609A1 (pt)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2835053T (pt) * 2010-03-12 2016-07-14 Genzyme Corp Terapêutica combinada para o tratamento do cancro da mama
US9782452B2 (en) * 2011-11-22 2017-10-10 Cornell University Methods for stimulating hematopoietic recovery by inhibiting TGFβ signaling
PT2971048T (pt) 2013-03-11 2019-02-06 Genzyme Corp Anticorpos anti-tgf-beta manipulados e fragmentos de ligação a antigénios
WO2016094697A2 (en) * 2014-12-10 2016-06-16 The Regents Of The University Of Colorado, A Body Corporate Targeting breast cancer therapy based on stromal subtypes and cd146 composition
GB201503438D0 (en) * 2015-02-27 2015-04-15 Ucl Business Plc Antibodies
CN107427363B (zh) * 2015-03-18 2020-08-28 Med-El电气医疗器械有限公司 骨传导漂浮质量传感器的固定
KR102647231B1 (ko) 2018-08-02 2024-03-13 삼성전자주식회사 반도체 소자 및 이의 제조방법

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US247550A (en) * 1881-09-27 Bakee beos
US5225539A (en) * 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
CA1327358C (en) 1987-11-17 1994-03-01 Morio Fujiu Fluoro cytidine derivatives
US5583103A (en) 1988-06-28 1996-12-10 La Jolla Cancer Research Foundation Inhibition of transforming growth factor beta activity
US5654270A (en) 1988-06-28 1997-08-05 La Jolla Cancer Research Foundation Use of fibromodulin to prevent or reduce dermal scarring
WO1990000194A1 (en) 1988-06-28 1990-01-11 La Jolla Cancer Research Foundation Suppression of cell proliferation by decorin
US5705609A (en) 1988-06-28 1998-01-06 La Jolla Cancer Research Foundation Decorin fragments inhibiting cell regulatory factors
US5571714A (en) 1988-12-22 1996-11-05 Celtrix Pharmaceuticals, Inc. Monoclonal antibodies which bind both transforming growth factors β1 and β2 and methods of use
JPH05503003A (ja) 1989-11-22 1993-05-27 ジェネンテク，インコーポレイテッド 潜在性関与ペプチドおよびその使用
US6008011A (en) 1991-10-31 1999-12-28 Whitehead Institute For Biomedical Research TGF-β type II receptor cDNAs
CA2122491A1 (en) 1991-10-31 1993-05-13 Herbert Y. Lin Tgf-.beta. type receptor cdnas and uses therefor
DK0616536T3 (da) 1991-12-04 1999-10-11 Jolla Cancer Res Found Anvendelse af decorin eller biglycan til fremstilling af et lægemiddel til behandling af diabetesbetingede tilstande
GB9205800D0 (en) 1992-03-17 1992-04-29 British Tech Group Treatment of fibrotic disorders
AU3920693A (en) 1992-03-18 1993-10-21 General Hospital Corporation, The Four novel receptors of the TGF-beta receptor family
AU3943793A (en) 1992-04-01 1993-11-08 Whittier Institute For Diabetes And Endocrinology, The Methods of inhibiting or enhancing scar formation in the CNS
US5869462A (en) 1992-09-10 1999-02-09 The Board Of Trustees Of The Leland Stanford Junior University Inhibition of proliferation of vascular smooth muscle cell
US5821234A (en) 1992-09-10 1998-10-13 The Board Of Trustees Of The Leland Stanford Junior University Inhibition of proliferation of vascular smooth muscle cell
AU5587094A (en) 1992-10-26 1994-05-24 Kirin Brewery Company, Limited Method for producing large latent transforming growth factor-beta complexes and large latency associated peptide
ES2174868T3 (es) 1992-10-29 2002-11-16 Celtrix Pharma Fragmento del receptor de fijacion a tgf-beta tipoii como agente terapeutico.
US5830847A (en) 1992-10-30 1998-11-03 Hsc Research & Development Limited Partnership Soluble TGF-β-binding endoglin polypeptides and homodimers
AU671491B2 (en) 1992-12-18 1996-08-29 F. Hoffmann-La Roche Ag N-oxycarbonyl substituted 5'-deoxy-5-fluorcytidines
DE69429617T2 (de) 1993-04-30 2002-08-22 Biognostik Gesellschaft Fuer Biomolekulare Diagnostik Mbh Antisense-oligonukleotide zur behandlung des immunsuppressiven effektes des transformierenden wachstumsfaktor-beta1(tgf-beta1)
AU6984594A (en) 1993-06-15 1995-01-17 Hun Taeg Chung Anti-sense oligodeoxynucleotide to fibrogenic cytokines and use thereof
US5595756A (en) * 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
DE69523750T2 (de) 1994-05-04 2002-08-01 Mount Sinai Hospital Corp., Toronto Modulatoren der cytokine der tgf-beta überfamilie und verfahren zu ihrer bestimmung
US5772995A (en) 1994-07-18 1998-06-30 Sidney Kimmel Cancer Center Compositions and methods for enhanced tumor cell immunity in vivo
CA2156767A1 (en) 1994-08-25 1996-02-26 Kenichi Matsunaga Binding agent for growth factor
JPH08119984A (ja) 1994-08-31 1996-05-14 Nkk Corp ストレプトミセス属放線菌及びこの菌由来のＴＧＦ−β 阻害剤
US5834248A (en) 1995-02-10 1998-11-10 Millennium Pharmaceuticals Inc. Compositions and methods using rchd534, a gene uregulated by shear stress
US5824655A (en) 1995-02-15 1998-10-20 The University Of Utah Anti-transforming growth factor-β gene therapy
US5824299A (en) 1995-06-22 1998-10-20 President & Fellows Of Harvard College Modulation of endothelial cell proliferation with IP-10
GB9601081D0 (en) 1995-10-06 1996-03-20 Cambridge Antibody Tech Specific binding members for human transforming growth factor beta;materials and methods
AU2749697A (en) 1996-04-30 1997-11-19 Genzyme Corporation Use of prolactin as a tgf-beta antagonist
JPH1067674A (ja) 1996-06-19 1998-03-10 Advanced Sukin Res Kenkyusho:Kk 細胞外マトリツクスの異常蓄積抑制剤
US5807708A (en) 1996-07-30 1998-09-15 Millennium Pharmaceuticals, Inc. Conservin nucleic acid molecules and compositions
AU3215597A (en) 1996-08-30 1998-03-19 Biomeasure Incorporated Method of inhibiting fibrosis with a somatostatin agonist
AU740052B2 (en) 1996-10-25 2001-10-25 Ethicon Inc. Anti-fibrotic agent assay
US5948639A (en) 1997-04-10 1999-09-07 Millennium Pharmaceuticals, Inc. TGF-β pathway genes
US20020102208A1 (en) 1999-03-01 2002-08-01 Paul Chinn Radiolabeling kit and binding assay
HUP0300848A3 (en) * 2000-02-28 2005-03-29 Aventis Pharma Sa A composition comprising camptothecin and a pyrimidine derivative for the treatment of cancer
JP2007515949A (ja) * 2003-11-13 2007-06-21 ジェネンテック・インコーポレーテッド スクリーニングアッセイ及び腫瘍治療の方法
EP1694840A2 (en) * 2003-12-19 2006-08-30 Antisense Pharma GmbH Combination therapy associating a tgf-beta antagonist with a chemotherapeutic agent
BRPI0508761A (pt) * 2004-03-31 2007-08-14 Genentech Inc anticorpo humanizado, composição que compreende um anticorpo humanizado, ácido nucléico isolado, vetor, célula hospedeira, processo de produção de anticorpo humanizado, método de tratamento de disfunção tgf-beta, método de detecção de tgf-beta, artigo industrializado e método de tratamento de cáncer
JP2008520696A (ja) * 2004-11-18 2008-06-19 ブリストル−マイヤーズ スクイブ カンパニー イキサベピロンを含む腸溶性被覆ビーズおよびその製造
CN104177497B (zh) 2005-02-08 2018-01-16 根茨美公司 针对TGFβ的抗体
EP2023923A2 (en) * 2006-05-25 2009-02-18 Bristol-Myers Squibb Company Use of ixabepilone in combination with cyp3a4 inhibitors for pharmaceuticals
WO2008145403A1 (en) 2007-06-01 2008-12-04 Synthon B.V. Processes related to making capecitabine
DE102008002395A1 (de) * 2008-06-12 2009-12-17 Biotronik Vi Patent Ag Wirkstoffbeladenes Implantat
PT2835053T (pt) * 2010-03-12 2016-07-14 Genzyme Corp Terapêutica combinada para o tratamento do cancro da mama

Also Published As

Publication number Publication date
PT3117709T (pt) 2018-11-15
HUE040107T2 (hu) 2019-02-28
EP2544541B1 (en) 2014-10-08
ES2584433T3 (es) 2016-09-27
US8911736B2 (en) 2014-12-16
DK3117709T3 (en) 2018-11-26
JP2016164174A (ja) 2016-09-08
RS57942B1 (sr) 2019-01-31
RS54972B1 (sr) 2016-11-30
EP3117709B1 (en) 2018-08-01
US9539325B2 (en) 2017-01-10
LT3117709T (lt) 2018-11-26
ES2694288T3 (es) 2018-12-19
SMT201600253B (it) 2016-08-31
EP3406141A1 (en) 2018-11-28
EP2835053A1 (en) 2015-02-11
US20130034549A1 (en) 2013-02-07
HK1206936A1 (zh) 2016-01-22
US20170319691A1 (en) 2017-11-09
PL3117709T3 (pl) 2019-01-31
JP2013522210A (ja) 2013-06-13
US20150086547A1 (en) 2015-03-26
US10507242B2 (en) 2019-12-17
EP2544541A1 (en) 2013-01-16
HRP20181757T1 (hr) 2019-01-25
CY1117831T1 (el) 2017-05-17
JP6289528B2 (ja) 2018-03-07
PL2835053T3 (pl) 2016-12-30
ME02464B (me) 2017-02-20
HUE027831T2 (en) 2016-11-28
JP5917418B2 (ja) 2016-05-11
EP3406141B1 (en) 2020-10-14
DK2835053T3 (en) 2016-08-15
EP3117709A1 (en) 2017-01-18
WO2011112609A1 (en) 2011-09-15
SI3117709T1 (sl) 2018-12-31
EP2544541A4 (en) 2013-07-31
SI2835053T1 (sl) 2016-09-30
EP2835053B1 (en) 2016-04-27
HRP20160932T1 (hr) 2016-10-07
TR201816180T4 (tr) 2018-11-21

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