WO2000033880A2 - Conjugue pour l'administration dans des cellules neuronales - Google Patents

Conjugue pour l'administration dans des cellules neuronales Download PDF

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Publication number
WO2000033880A2
WO2000033880A2 PCT/DE1999/003924 DE9903924W WO0033880A2 WO 2000033880 A2 WO2000033880 A2 WO 2000033880A2 DE 9903924 W DE9903924 W DE 9903924W WO 0033880 A2 WO0033880 A2 WO 0033880A2
Authority
WO
WIPO (PCT)
Prior art keywords
toxin
heavy chain
conjugate according
protein
conjugate
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.)
Ceased
Application number
PCT/DE1999/003924
Other languages
German (de)
English (en)
Other versions
WO2000033880A3 (fr
Inventor
Achim LÖHR
Manfred Schwab
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.)
Deutsches Krebsforschungszentrum DKFZ
Original Assignee
Deutsches Krebsforschungszentrum DKFZ
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 Deutsches Krebsforschungszentrum DKFZ filed Critical Deutsches Krebsforschungszentrum DKFZ
Publication of WO2000033880A2 publication Critical patent/WO2000033880A2/fr
Publication of WO2000033880A3 publication Critical patent/WO2000033880A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • This construct was called pCYB4-HIS-HCH.
  • a purification of the recombinant heavy chain via the His tag was also possible with this plasmid.
  • this protein had 18 amino acids at the N-terminus (6xHis-Leu-Glu-Gly-Gly-Tyr-Val-Lys-Ser-Ala-Pro-Ser-Gly).
  • the reaction mixture was purified by gel filtration over a G-25 desalination column (FPLC) in 50 mM MOPS pH 7.4; 80 mM NaCl transferred and the excess crosslinker removed.
  • FPLC G-25 desalination column
  • the protein concentration of the column fractions was determined with the Bio-Rad Protein Assay Kit I (Bio-Rad, Kunststoff) and subsequently, by reducing part of the modified protein, the number of coupled linkers per molecule is determined photometrically according to standard methods. There was a number of 1.9 linkers per avidin molecule.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Toxicology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un conjugué utilisé pour introduire des principes actifs dans des cellules neuronales. Ce conjugué comprend la chaîne lourde d'une toxine de l'espèce Clostridium et au moins un principe actif, la chaîne légère de la toxine étant absente. L'invention concerne en outre un procédé de production d'un tel conjugué, une trousse associée et l'utilisation dudit conjugué.
PCT/DE1999/003924 1998-12-04 1999-12-03 Conjugue pour l'administration dans des cellules neuronales Ceased WO2000033880A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19856052A DE19856052A1 (de) 1998-12-04 1998-12-04 Konjugat zur Anreicherung in neuronalen Zellen
DE19856052.4 1998-12-04

Publications (2)

Publication Number Publication Date
WO2000033880A2 true WO2000033880A2 (fr) 2000-06-15
WO2000033880A3 WO2000033880A3 (fr) 2000-10-12

Family

ID=7890019

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1999/003924 Ceased WO2000033880A2 (fr) 1998-12-04 1999-12-03 Conjugue pour l'administration dans des cellules neuronales

Country Status (2)

Country Link
DE (1) DE19856052A1 (fr)
WO (1) WO2000033880A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004071525A1 (fr) * 2002-02-08 2004-08-26 Allergan, Inc. Methodes de traitement de troubles des glandes mammaires
WO2006010360A3 (fr) * 2004-07-22 2007-12-27 Biotecon Therapeutics Gmbh Vehicule permettant d'obtenir des medicaments a biodisponibilite orale
WO2009083738A3 (fr) * 2007-12-31 2009-08-27 Syntaxin Limited Véhicules de délivrance d'arn
US7628992B1 (en) 1994-05-31 2009-12-08 Invent Dcu Limited Modification of clostridial toxins for use as transport proteins
US7838008B2 (en) 1999-12-07 2010-11-23 Allergan, Inc. Methods for treating diverse cancers

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8507277B2 (en) 2003-10-24 2013-08-13 Gencia Corporation Nonviral vectors for delivering polynucleotides
US8133733B2 (en) 2003-10-24 2012-03-13 Gencia Corporation Nonviral vectors for delivering polynucleotides to target tissues
US8062891B2 (en) 2003-10-24 2011-11-22 Gencia Corporation Nonviral vectors for delivering polynucleotides to plants
US20090123468A1 (en) 2003-10-24 2009-05-14 Gencia Corporation Transducible polypeptides for modifying metabolism
CA2543257C (fr) 2003-10-24 2013-12-31 Gencia Corporation Procedes et compositions permettant de distribuer des polynucleotides

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4594336A (en) * 1982-09-28 1986-06-10 Institut Pasteur Thiolated polypeptide compound derived from a tetanus toxin fragment, the process for obtaining and its application
EP0399001B1 (fr) * 1988-02-01 1994-07-27 Praxis Biologics, Inc. Epitopes de cellules t a titre de molecules porteuses pour vaccins conjugues
JP3523879B2 (ja) * 1994-05-31 2004-04-26 アレルガン インコーポレイテッド 輸送タンパク質用クロストリジウム属細菌毒素の修飾
GB9524807D0 (en) * 1995-12-05 1996-02-07 Smithkline Beecham Plc Novel compounds
GB9824282D0 (en) * 1998-11-05 1998-12-30 Microbiological Research Agenc Delivery of superoxide dismutase to neuronal cells

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7628992B1 (en) 1994-05-31 2009-12-08 Invent Dcu Limited Modification of clostridial toxins for use as transport proteins
US7838008B2 (en) 1999-12-07 2010-11-23 Allergan, Inc. Methods for treating diverse cancers
US7838007B2 (en) 1999-12-07 2010-11-23 Allergan, Inc. Methods for treating mammary gland disorders
US7846456B2 (en) 1999-12-07 2010-12-07 Allergan, Inc. Methods for breast treatment
WO2004071525A1 (fr) * 2002-02-08 2004-08-26 Allergan, Inc. Methodes de traitement de troubles des glandes mammaires
JP2006510723A (ja) * 2002-02-08 2006-03-30 アラーガン、インコーポレイテッド 乳腺障害の処置方法
EP2204183A1 (fr) * 2002-02-08 2010-07-07 Allergan, Inc. Traitement du neuroblastome
WO2006010360A3 (fr) * 2004-07-22 2007-12-27 Biotecon Therapeutics Gmbh Vehicule permettant d'obtenir des medicaments a biodisponibilite orale
WO2009083738A3 (fr) * 2007-12-31 2009-08-27 Syntaxin Limited Véhicules de délivrance d'arn

Also Published As

Publication number Publication date
DE19856052A1 (de) 2000-06-08
WO2000033880A3 (fr) 2000-10-12

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