CA2827052C - Anti-alpha-v integrin antibody for the treatment of prostate cancer - Google Patents

Anti-alpha-v integrin antibody for the treatment of prostate cancer Download PDF

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Publication number
CA2827052C
CA2827052C CA2827052A CA2827052A CA2827052C CA 2827052 C CA2827052 C CA 2827052C CA 2827052 A CA2827052 A CA 2827052A CA 2827052 A CA2827052 A CA 2827052A CA 2827052 C CA2827052 C CA 2827052C
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Canada
Prior art keywords
use according
administration
antibody
patients
di17e6
Prior art date
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Application number
CA2827052A
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English (en)
French (fr)
Other versions
CA2827052A1 (en
Inventor
Axel Hoffmann
Heinrich LANNERT
Klaus Brischwein
Frederic Christian PIPP
Juergen REINDL
Karin GROLL
Michael ZUEHLSDORF
Otmar PFAFF
Sabine RAAB
Ulrike DAU
Benoit Destenaves
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Merck Patent GmbH
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Merck Patent GmbH
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.)
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Publication of CA2827052A1 publication Critical patent/CA2827052A1/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2839Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/28Antiandrogens
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2839Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
    • C07K16/2848Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069Reproductive system, e.g. ovaria, uterus, testes, prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/53Hinge
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567Framework region [FR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Endocrinology (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)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CA2827052A 2011-02-11 2012-02-07 Anti-alpha-v integrin antibody for the treatment of prostate cancer Active CA2827052C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11001135 2011-02-11
EP11001135.0 2011-02-11
PCT/EP2012/000548 WO2012107211A1 (en) 2011-02-11 2012-02-07 Anti-alpha-v integrin antibody for the treatment of prostate cancer

Publications (2)

Publication Number Publication Date
CA2827052A1 CA2827052A1 (en) 2012-08-16
CA2827052C true CA2827052C (en) 2022-08-16

Family

ID=45569571

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2827052A Active CA2827052C (en) 2011-02-11 2012-02-07 Anti-alpha-v integrin antibody for the treatment of prostate cancer

Country Status (23)

Country Link
US (3) US9555110B2 (enExample)
EP (2) EP3415162A1 (enExample)
JP (2) JP6320042B2 (enExample)
KR (2) KR101972533B1 (enExample)
CN (1) CN103347540B (enExample)
AU (2) AU2012216145B2 (enExample)
CA (1) CA2827052C (enExample)
DK (1) DK2672994T3 (enExample)
EA (1) EA032117B1 (enExample)
ES (1) ES2683347T3 (enExample)
HR (1) HRP20181212T1 (enExample)
HU (1) HUE037212T2 (enExample)
IL (1) IL227687B (enExample)
LT (1) LT2672994T (enExample)
MX (2) MX352025B (enExample)
PL (1) PL2672994T3 (enExample)
PT (1) PT2672994T (enExample)
RS (1) RS57524B1 (enExample)
SG (1) SG192667A1 (enExample)
SI (1) SI2672994T1 (enExample)
TR (1) TR201810294T4 (enExample)
WO (1) WO2012107211A1 (enExample)
ZA (1) ZA201306807B (enExample)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012107211A1 (en) 2011-02-11 2012-08-16 Merck Patent Gmbh Anti-alpha-v integrin antibody for the treatment of prostate cancer
ES2897782T3 (es) * 2014-09-17 2022-03-02 Merck Patent Gmbh Método de tratamiento de las enfermedades de la metástasis ósea, medicamentos para el tratamiento y método para predecir el resultado clínico del tratamiento de las enfermedades causadas por metástasis ósea
WO2016041614A1 (en) 2014-09-17 2016-03-24 Merck Patent Gmbh A method of treating solid cancers and/or metastases thereof, medicaments therefore, and a method of predicting the clinical outcome of treating solid cancers and/or metastases thereof
HK1254295A1 (zh) 2015-11-23 2019-07-19 默克专利股份有限公司 用於治疗纤维化和/或纤维化病症的抗-αV整合素抗体
WO2017088974A2 (en) * 2015-11-23 2017-06-01 Merck Patent Gmbh Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders
EP4637731A1 (en) 2022-12-21 2025-10-29 Gilead Sciences, Inc. Combination therapy for treating cancer

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SK281143B6 (sk) 1991-03-06 2000-12-11 Merck Patent Gesellschaft Mit Beschr�Nkter Haftung Chimérická monoklonálna protilátka, expresné vektory a farmaceutický prostriedok
US5753230A (en) 1994-03-18 1998-05-19 The Scripps Research Institute Methods and compositions useful for inhibition of angiogenesis
DE69531187T2 (de) 1994-12-20 2004-04-22 Merck Patent Gmbh Monoklonaler Antikörper gegen das Alpha-V-Integrin
DE19534177A1 (de) 1995-09-15 1997-03-20 Merck Patent Gmbh Cyclische Adhäsionsinhibitoren
WO1998052976A1 (en) 1997-05-21 1998-11-26 Biovation Limited Method for the production of non-immunogenic proteins
DE19842415A1 (de) 1998-09-16 2000-03-23 Merck Patent Gmbh Pharmazeutische Zubereitung
EP1051432B1 (en) 1998-12-08 2007-01-24 Biovation Limited Method for reducing immunogenicity of proteins
US7163681B2 (en) * 2000-08-07 2007-01-16 Centocor, Inc. Anti-integrin antibodies, compositions, methods and uses
AU2002256624B2 (en) 2001-02-19 2007-12-06 Merck Patent Gmbh Method for identification of T-cell epitopes and use for preparing molecules with reduced immunogenicity
DE10163459A1 (de) 2001-12-21 2003-07-03 Merck Patent Gmbh Lyophilisierte Zubereitung enthaltend Antikörper gegen EGF-Rezeptor
EP1575516B1 (en) 2002-11-26 2012-05-30 Abbott Biotherapeutics Corp. Chimeric and humanized antibodies to alpha5 beta1 integrin that modulate angiogenesis
US8147832B2 (en) 2003-08-14 2012-04-03 Merck Patent Gmbh CD20-binding polypeptide compositions and methods
RU2390353C2 (ru) 2004-02-12 2010-05-27 Мерк Патент Гмбх Высококонцентрированные жидкие композиции анти-egfr антител
KR20060002667A (ko) 2004-07-03 2006-01-09 삼성전자주식회사 디스크 댐퍼와 디스크 프로텍터를 구비한 하드 디스크드라이브
US8202465B2 (en) 2004-11-03 2012-06-19 Honeywell International Inc. Preferential curing technique in compression molding of fiber reinforced composites
US20070025889A1 (en) 2005-07-28 2007-02-01 Pcbu Business Services, Inc. Reactors, reactor assemblies and production processes
DE102005062440B4 (de) 2005-12-27 2011-02-24 Lts Lohmann Therapie-Systeme Ag Proteinbasiertes Trägersystem zur Resistenzüberwindung von Tumorzellen
EP2270050B1 (en) 2005-12-30 2013-06-05 Merck Patent GmbH Anti-CD19 antibodies with reduced immunogenicity
AU2007207465B2 (en) 2006-01-18 2012-12-06 Merck Patent Gmbh Specific therapy using integrin ligands for treating cancer
US8715718B2 (en) 2006-07-14 2014-05-06 Rutgers, The State University Of New Jersey Extracellular matrix production from nanoscale substrate
EP2526967A1 (en) * 2007-07-17 2012-11-28 Merck Patent GmbH Engineered anti-alpha v-integrin hybrid antibodies
US20110177155A1 (en) 2007-08-21 2011-07-21 Immune Disease Institute, Inc. Methods of delivery of agents to leukocytes and endothelial cells
CA2747937C (en) 2008-12-23 2019-02-26 Merck Patent Gmbh Biomarkers for inhibitors with anti-angiogenic activity
EA032728B1 (ru) 2009-08-19 2019-07-31 Мерк Патент Гмбх Антитела для выявления комплексов интегрина в ffpe материале
AU2010318323A1 (en) 2009-11-13 2012-06-28 Merck Patent Gmbh Anti integrin antibodies linked to nanoparticles loaded with chemotherapeutic agents
WO2011162933A1 (en) * 2010-06-04 2011-12-29 Immunogen, Inc. Anti-integrin immunoconjugate dosing regimens
WO2012107211A1 (en) 2011-02-11 2012-08-16 Merck Patent Gmbh Anti-alpha-v integrin antibody for the treatment of prostate cancer
JP6035716B2 (ja) 2011-08-26 2016-11-30 ソニー株式会社 情報処理システム及び情報処理方法
WO2014143383A1 (en) 2013-03-13 2014-09-18 Agilent Technologies, Inc. Transposome tethered to a gene delivery vehicle
CA2923145C (en) 2013-09-05 2025-09-16 Amgen Inc. MOLECULES CONTAINING FCS AND EXHIBITING PREDICTABLE, UNIFORM AND REPRODUCIBLE GLYCOFORM PROFILES

Also Published As

Publication number Publication date
JP2017066156A (ja) 2017-04-06
WO2012107211A1 (en) 2012-08-16
IL227687B (en) 2019-02-28
EP2672994A1 (en) 2013-12-18
CN103347540B (zh) 2016-05-25
IL227687A0 (en) 2013-09-30
US9555110B2 (en) 2017-01-31
SG192667A1 (en) 2013-09-30
HRP20181212T1 (hr) 2018-10-05
US20140086908A1 (en) 2014-03-27
MX352025B (es) 2017-11-07
MX2013009062A (es) 2013-10-01
EP3415162A1 (en) 2018-12-19
ZA201306807B (en) 2014-05-28
KR20190044696A (ko) 2019-04-30
PT2672994T (pt) 2018-10-22
ES2683347T3 (es) 2018-09-26
AU2012216145B2 (en) 2016-11-17
CA2827052A1 (en) 2012-08-16
KR20140012087A (ko) 2014-01-29
AU2017200998B2 (en) 2018-08-09
RS57524B1 (sr) 2018-10-31
JP6488273B2 (ja) 2019-03-20
US20170218070A1 (en) 2017-08-03
EA201391147A1 (ru) 2014-01-30
MX385144B (es) 2025-03-14
EP2672994B1 (en) 2018-05-09
TR201810294T4 (tr) 2018-08-27
HUE037212T2 (hu) 2018-08-28
KR101972533B1 (ko) 2019-08-26
JP2014510047A (ja) 2014-04-24
AU2012216145A1 (en) 2013-09-26
SI2672994T1 (sl) 2018-09-28
US20190263913A1 (en) 2019-08-29
DK2672994T3 (en) 2018-07-16
CN103347540A (zh) 2013-10-09
LT2672994T (lt) 2018-07-25
JP6320042B2 (ja) 2018-05-09
KR102103701B1 (ko) 2020-04-23
EA032117B1 (ru) 2019-04-30
HK1190094A1 (zh) 2014-06-27
AU2017200998A1 (en) 2017-03-09
PL2672994T3 (pl) 2018-11-30

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