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1. WO1999009057 - HYBRID TETANUS TOXOID PROTEINS THAT MIGRATE RETROGRADELY AND TRANSYNAPTICALLY INTO THE CNS

Publication Number WO/1999/009057
Publication Date 25.02.1999
International Application No. PCT/EP1998/005113
International Filing Date 12.08.1998
Chapter 2 Demand Filed 08.02.1999
IPC
A61K 38/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
A61K 47/48 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
48the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 14/33 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
195from bacteria
33from Clostridium (G)
CPC
A61K 38/4886
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38Medicinal preparations containing peptides
16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
43Enzymes; Proenzymes; Derivatives thereof
46Hydrolases (3)
48acting on peptide bonds (3.4)
4886Metalloendopeptidases (3.4.24), e.g. collagenase
A61K 47/6415
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
62the modifying agent being a protein, peptide or polyamino acid
64Drug-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
6415Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
A61P 21/02
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
21Drugs for disorders of the muscular or neuromuscular system
02Muscle relaxants, e.g. for tetanus or cramps
C07K 14/33
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
195from bacteria
33from Clostridium (G)
C07K 2319/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
Applicants
  • INSTITUT PASTEUR [FR]/[FR] (AT, BE, CA, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, JP, LU, MC, NL, PT, SE)
  • COEN, Laurent [FR]/[FR] (UsOnly)
  • OSTA PINZOLAS, Rosario [ES]/[ES] (UsOnly)
  • BRULET, Philippe [FR]/[FR] (UsOnly)
Inventors
  • COEN, Laurent
  • OSTA PINZOLAS, Rosario
  • BRULET, Philippe
Agents
  • GUTMANN, Ernest
Priority Data
60/055,61514.08.1997US
60/065,23613.11.1997US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) HYBRID TETANUS TOXOID PROTEINS THAT MIGRATE RETROGRADELY AND TRANSYNAPTICALLY INTO THE CNS
(FR) PROTEINES HYBRIDES D'UNE TOXINE TETANIQUE QUI MIGRENT DE MANIERE RETROGRADE ET TRANSSYNOPTIQUE DANS LE SNC
Abstract
(EN) The non-toxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same ability to bind nerve cells and be retrogradely transported through a synapse as the native toxin. A hybrid protein encoded by the IacZ-TTC gene fusion retains the biological functions of both proteins $i(in vivo), i.e. retrograde transynaptic transport of the TTC fragment and -gal enzymatic activity. After intramuscular injection, enzymatic activity could be detected in motoneurons and connected neurons of the brainstem areas. This strategy is useful for the delivery of a biological activity to neurons from the periphery to the central nervous system. Such a hybrid protein can also be used to map synaptic connections between neural cells.
(FR) Le fragment C protéolitique non toxique d'une toxine tétanique (peptide TTC) a la même aptitude à se lier à des cellules nerveuses et à être transporté de manière rétrograde à travers une synapse que la toxine native. Une protéine hybride codée par la fusion du gène IacZ-TTC conserve les fonctions biologiques des deux protéines $i(in vivo), c'est-à-dire le transport transsynoptique rétrograde du fragment TTC et l'activité enzymatique -gal. Après injection intramusculaire, on peut détecter l'activité enzymatique dans des neurones moteurs et des neurones connectés des régions du transcérébral. Cette stratégie est utilie pour apporter une activité biologique à des neurones depuis la périphérie du système nerveux central. Une telle protéine hybride peut également êre utilisée pour maper des connexions synoptiques entre des cellules neurales
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