DE69933550T2 - Modifizierte adenoviren welche ein faserersatzprotein enthalten - Google Patents

Modifizierte adenoviren welche ein faserersatzprotein enthalten Download PDF

Info

Publication number
DE69933550T2
DE69933550T2 DE69933550T DE69933550T DE69933550T2 DE 69933550 T2 DE69933550 T2 DE 69933550T2 DE 69933550 T DE69933550 T DE 69933550T DE 69933550 T DE69933550 T DE 69933550T DE 69933550 T2 DE69933550 T2 DE 69933550T2
Authority
DE
Germany
Prior art keywords
fiber
adenovirus
protein
fibritin
gene
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.)
Expired - Lifetime
Application number
DE69933550T
Other languages
German (de)
English (en)
Other versions
DE69933550D1 (de
Inventor
T. David Birmingham CURIEL
N. Victor Birmingham KRASNYKH
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
UAB Research Foundation
Original Assignee
UAB Research Foundation
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 UAB Research Foundation filed Critical UAB Research Foundation
Publication of DE69933550D1 publication Critical patent/DE69933550D1/de
Application granted granted Critical
Publication of DE69933550T2 publication Critical patent/DE69933550T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A61K35/761—Adenovirus
    • 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
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/45—Transferases (2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10321—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10332—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10345—Special targeting system for viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/40—Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00—Vectors comprising a targeting moiety
    • C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
    • C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
    • C12N2810/85—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian
    • C12N2810/859—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian from immunoglobulins

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Plant Pathology (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
DE69933550T 1998-02-17 1999-02-16 Modifizierte adenoviren welche ein faserersatzprotein enthalten Expired - Lifetime DE69933550T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US7484498P 1998-02-17 1998-02-17
US74844P 1998-02-17
PCT/US1999/003233 WO1999041359A1 (en) 1998-02-17 1999-02-16 Modified adenovirus containing a fiber replacement protein

Publications (2)

Publication Number Publication Date
DE69933550D1 DE69933550D1 (de) 2006-11-23
DE69933550T2 true DE69933550T2 (de) 2007-06-28

Family

ID=22122019

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69933550T Expired - Lifetime DE69933550T2 (de) 1998-02-17 1999-02-16 Modifizierte adenoviren welche ein faserersatzprotein enthalten

Country Status (15)

Country Link
US (1) US6210946B1 (enExample)
EP (1) EP1070118B1 (enExample)
JP (1) JP2002503459A (enExample)
KR (1) KR20010074429A (enExample)
CN (1) CN1297479A (enExample)
AT (1) ATE342350T1 (enExample)
AU (1) AU751542B2 (enExample)
BR (1) BR9908018A (enExample)
CA (1) CA2321135A1 (enExample)
DE (1) DE69933550T2 (enExample)
IL (1) IL137730A0 (enExample)
NO (1) NO20004563D0 (enExample)
NZ (1) NZ506451A (enExample)
WO (1) WO1999041359A1 (enExample)
ZA (1) ZA200004208B (enExample)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6815200B1 (en) * 1998-02-17 2004-11-09 The Uab Research Foundation Modified adenovirus containing a fiber replacement protein
US20050095231A1 (en) * 1998-02-17 2005-05-05 Curiel David T. Modified adenovirus containing a fiber replacement protein
WO1999055365A1 (en) 1998-04-30 1999-11-04 Cornell Research Foundation, Inc. Adenoviral vectors with tandem fiber proteins
AU767975B2 (en) 1998-09-11 2003-11-27 Genvec, Inc. Alternatively targeted adenovirus
WO2000046364A1 (en) * 1999-02-05 2000-08-10 The Uab Research Foundation Fiber receptor-independent system for the propagation of adenoviral vectors
EP1196435A1 (en) * 1999-07-06 2002-04-17 Got-A-Gene AB Recombinant adenovirus
WO2001081607A2 (en) * 2000-04-26 2001-11-01 Crucell Holland B.V. Adenovirus vectors with knobless fibers, and their uses
US7332337B2 (en) * 2000-05-16 2008-02-19 Galapagos Nv Viral vectors having tissue tropism for T-lymphocytes, B- and mast cells
US6849446B2 (en) 2000-05-31 2005-02-01 University Of Saskatchewan Modified bovine adenovirus having altered tropism
JP3635462B2 (ja) * 2000-05-31 2005-04-06 国立医薬品食品衛生研究所長 アデノウイルスベクター
GB0017720D0 (en) * 2000-07-19 2000-09-06 Got A Gene Ab Modified virus
CA2450470C (en) 2001-06-22 2012-08-28 The Trustees Of The University Of Pennsylvania Method for rapid screening of bacterial transformants and novel simian adenovirus proteins
US6905678B2 (en) 2001-07-07 2005-06-14 Crucell Holland B.V. Gene delivery vectors with cell type specificity for mesenchymal stem cells
EP1516055A4 (en) * 2002-01-24 2007-08-08 Scripps Research Inst FIBER OPERATING MODIFICATIONS FOR EFFICIENT TARGETS
US20040147025A1 (en) * 2002-07-22 2004-07-29 Nikolay Korokhov Targeted adenoviral vector displaying immunoglobulin-binding domain and uses thereof
AU2003259199A1 (en) * 2002-07-22 2004-02-09 Vectorlogics, Inc. Adenoviral vector incorporating zipper peptide-modified fiber protein and uses thereof
US20050003548A1 (en) * 2002-07-22 2005-01-06 Nikolay Korokhov Targeted adenoviral vector displaying immunoglobulin-binding domain and uses thereof
CA2524499A1 (en) 2003-05-14 2004-11-25 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa Broadening adenovirus tropism
JP2007531507A (ja) * 2003-06-11 2007-11-08 ザ スクリップス リサーチ インスティテュート 効率的な受容体結合のための修飾型線維タンパク質
US7291498B2 (en) 2003-06-20 2007-11-06 The Trustees Of The University Of Pennsylvania Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses
EP2580234B1 (en) 2010-06-10 2017-03-08 University Of Washington Through Its Center For Commercialization Methods and systems for adenovirus interaction with desmoglein 2 (dsg2)
KR102089121B1 (ko) 2013-03-14 2020-03-13 더 솔크 인스티튜트 포 바이올로지칼 스터디즈 종양살상형 아데노바이러스 조성물
EP3132038A4 (en) 2014-04-18 2017-11-29 Washington University Adenoviral targeting, compositions and methods therefor
WO2016123142A1 (en) * 2015-01-26 2016-08-04 The University Of Chicago IL13RAα2 BINDING AGENTS AND USE THEREOF IN CANCER TREATMENT
CA3013637A1 (en) 2016-02-23 2017-08-31 Salk Institute For Biological Studies High throughput assay for measuring adenovirus replication kinetics
KR20180112024A (ko) 2016-02-23 2018-10-11 더 솔크 인스티튜트 포 바이올로지칼 스터디즈 바이러스 동역학에 미치는 영향 최소화를 위한 치료용 아데노바이러스의 외인성 유전자 발현
AU2017375633C1 (en) 2016-12-12 2023-04-27 Salk Institute For Biological Studies Tumor-targeting synthetic adenoviruses and uses thereof
CN110650745A (zh) 2016-12-21 2020-01-03 曼珍有限责任公司 武装复制型溶瘤腺病毒
AU2019251356B2 (en) 2018-04-09 2025-06-12 Salk Institute For Biological Studies Oncolytic adenovirus compositions with enhanced replication properties

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9223084D0 (en) * 1992-11-04 1992-12-16 Imp Cancer Res Tech Compounds to target cells
US5543328A (en) * 1993-08-13 1996-08-06 Genetic Therapy, Inc. Adenoviruses having modified fiber proteins
US5846782A (en) * 1995-11-28 1998-12-08 Genvec, Inc. Targeting adenovirus with use of constrained peptide motifs
US5559099A (en) * 1994-09-08 1996-09-24 Genvec, Inc. Penton base protein and methods of using same
US5770442A (en) * 1995-02-21 1998-06-23 Cornell Research Foundation, Inc. Chimeric adenoviral fiber protein and methods of using same
EP0866721A4 (en) * 1995-12-08 2003-06-04 Univ Alabama Birmingham Res Fo TARGET ADENOVIRAL VECTORS
US5877011A (en) * 1996-11-20 1999-03-02 Genzyme Corporation Chimeric adenoviral vectors

Also Published As

Publication number Publication date
NZ506451A (en) 2003-06-30
IL137730A0 (en) 2001-10-31
DE69933550D1 (de) 2006-11-23
NO20004563L (no) 2000-09-13
US6210946B1 (en) 2001-04-03
EP1070118A1 (en) 2001-01-24
NO20004563D0 (no) 2000-09-13
CA2321135A1 (en) 1999-08-19
AU3294099A (en) 1999-08-30
AU751542B2 (en) 2002-08-22
ATE342350T1 (de) 2006-11-15
EP1070118B1 (en) 2006-10-11
JP2002503459A (ja) 2002-02-05
ZA200004208B (en) 2002-01-30
BR9908018A (pt) 2000-10-24
EP1070118A4 (en) 2003-05-02
KR20010074429A (ko) 2001-08-04
CN1297479A (zh) 2001-05-30
WO1999041359A1 (en) 1999-08-19

Similar Documents

Publication Publication Date Title
DE69933550T2 (de) Modifizierte adenoviren welche ein faserersatzprotein enthalten
DE69534591T2 (de) Adenovirusfaser mit hinzugefügten liganden
DE60116513T2 (de) Adenovirenvektoren zur transduktion der chondrozyten
DE69931112T2 (de) Chimäre Adenoviren
DE69931391T2 (de) Trans-aktivierung und cis-aktivierung um die dauer der expression eines transgens zu modulieren
DE69634300T2 (de) Gentherapie mit hilfe von schaf-adenoviralen vektoren
DE69831741T2 (de) Modifizierte adenovirale fiber und sie enthaltende adenoviren
DE69518910T3 (de) Verfahren zur herstellung von viralen vektoren von mindestens 20kb durch intermolekulare homologe rekombination in einer prokaryotischen zelle
DE69637393T2 (de) Vektoren und methoden zum gentransfer in zellen
DE60014489T3 (de) Von Adenovirus abgeleitete Gentransfervehikel, die zumindest ein Element des Adenovirus Typ 35 enthalten
DE69637432T2 (de) Adenovirale vektoren für die gentherapie
DE69633565T2 (de) Verpackungssysteme für humane rekombinante adenoviren, zur vewendung in der ge ntherapie
AU684278B2 (en) DNA encoding a growth factor specific for epithelial cells
DE69430071T2 (de) Herstellung von rekombinanten proteinen in einem rinderadenovirus-expressionsvektorsystem
DE69333886T2 (de) Adenovirus-gelenkter Gen-Transfer zum Herz-und glattem vaskulären Muskel
DE69429260T2 (de) Adenovirale vektoren tierischen ursprungs und ihre verwendung bei der gentherapie
EP0724643B1 (de) Endosomolytisch wirksame partikel
DE60018920T2 (de) Rekombinante adenovirale vektoren, die chimäre fiberproteine exprimieren, für die zellspezifische infektion und genomische integration
DE60023600T2 (de) Replizierende retrovirale Konstrukte, ihre Herstellung und Verwendungen für den Gentransfer
DE69839403T2 (de) Adenovirale vektoren und eine methode zur reduktion von homologer rekombination
JP2002503459A5 (enExample)
DE19735593A1 (de) Hüllprotein-modifizierter Baculovirus-Vektor für die Gentherapie
DE69934421T2 (de) Selektiv-replizierende virale vectoren
DE69535093T2 (de) Defektive rekombinante adenoviren mit einem inaktivierten gen iv a 2
DE69925567T2 (de) Genverabreichende Vektoren mit Gewebetropismus für glatte Muskelzellen und/oder Endothelzellen

Legal Events

Date Code Title Description
8364 No opposition during term of opposition