WO2007138336A3 - Treatment of pain by single chain, polypeptide fusion protein - Google Patents

Treatment of pain by single chain, polypeptide fusion protein Download PDF

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Publication number
WO2007138336A3
WO2007138336A3 PCT/GB2007/002042 GB2007002042W WO2007138336A3 WO 2007138336 A3 WO2007138336 A3 WO 2007138336A3 GB 2007002042 W GB2007002042 W GB 2007002042W WO 2007138336 A3 WO2007138336 A3 WO 2007138336A3
Authority
WO
WIPO (PCT)
Prior art keywords
protease
sensory afferent
nociceptive sensory
afferent cell
pain
Prior art date
Application number
PCT/GB2007/002042
Other languages
French (fr)
Other versions
WO2007138336A2 (en
Inventor
Keith Foster
John Chaddock
Charles Penn
Roger K Aoki
Joseph Francis
Lance Steward
Original Assignee
Syntaxin Ltd
Allergan Inc
Keith Foster
John Chaddock
Charles Penn
Roger K Aoki
Joseph Francis
Lance Steward
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 Syntaxin Ltd, Allergan Inc, Keith Foster, John Chaddock, Charles Penn, Roger K Aoki, Joseph Francis, Lance Steward filed Critical Syntaxin Ltd
Publication of WO2007138336A2 publication Critical patent/WO2007138336A2/en
Publication of WO2007138336A3 publication Critical patent/WO2007138336A3/en

Links

Classifications

    • 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
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
    • 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
    • A61K47/6425—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 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
    • 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
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Abstract

Use of a therapeutic molecule for the manufacture of a medicament for the treatment of a particular type of pain, wherein the therapeutic molecule comprises a non-cytotoxic protein conjugate that binds to a nociceptive sensory afferent cell, and comprises: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of said nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell.
PCT/GB2007/002042 2006-06-01 2007-06-01 Treatment of pain by single chain, polypeptide fusion protein WO2007138336A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0610868.2 2006-06-01
GBGB0610868.2A GB0610868D0 (en) 2006-06-01 2006-06-01 Treatment of pain

Publications (2)

Publication Number Publication Date
WO2007138336A2 WO2007138336A2 (en) 2007-12-06
WO2007138336A3 true WO2007138336A3 (en) 2008-12-11

Family

ID=36694796

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2007/002042 WO2007138336A2 (en) 2006-06-01 2007-06-01 Treatment of pain by single chain, polypeptide fusion protein

Country Status (2)

Country Link
GB (1) GB0610868D0 (en)
WO (1) WO2007138336A2 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9617671D0 (en) * 1996-08-23 1996-10-02 Microbiological Res Authority Recombinant toxin fragments
US7192596B2 (en) 1996-08-23 2007-03-20 The Health Protection Agency Ipsen Limited Recombinant toxin fragments
JP2011514308A (en) 2007-10-23 2011-05-06 アラーガン、インコーポレイテッド Method for the treatment of genitourinary neurological disorders using modified Clostridial toxins
CN102202677A (en) 2008-09-03 2011-09-28 阿尔伯维塔公司 Agents and methods for treatment of pain
US9005628B2 (en) 2012-10-04 2015-04-14 Dublin City University Biotherapy for pain
US9216210B2 (en) 2013-12-23 2015-12-22 Dublin City University Multiprotease therapeutics for chronic pain

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998007864A1 (en) * 1996-08-23 1998-02-26 Microbiological Research Authority Camr (Centre For Applied Microbiology & Research) Recombinant toxin fragments
WO2005023309A2 (en) * 2003-09-11 2005-03-17 Health Protection Agency Design of re-targeted toxin conjugates
WO2006059105A2 (en) * 2004-12-01 2006-06-08 Health Protection Agency Non-cytotoxic Protein Conjugates

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998007864A1 (en) * 1996-08-23 1998-02-26 Microbiological Research Authority Camr (Centre For Applied Microbiology & Research) Recombinant toxin fragments
WO2005023309A2 (en) * 2003-09-11 2005-03-17 Health Protection Agency Design of re-targeted toxin conjugates
WO2006059105A2 (en) * 2004-12-01 2006-06-08 Health Protection Agency Non-cytotoxic Protein Conjugates

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
CHADDOCK J A ET AL: "A CONJUGATE COMPOSED OF NERVE GROWTH FACTOR COUPLED TO A NON-TOXIC DERIVATIVE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A CAN INHIBIT NEUROTRANSMITTER RELEASE IN VITRO", GROWTH FACTORS, HARWOOD ACADEMIC PUBLISHERS GMBH, XX, vol. 18, no. 2, 1 January 2000 (2000-01-01), pages 147 - 155, XP001064444, ISSN: 0897-7194 *
CHADDOCK J A ET AL: "Expression and purification of catalytically active, non-toxic endopeptidase derivatives of Clostridium botulinum toxin type A", PROTEIN EXPRESSION AND PURIFICATION, ACADEMIC PRESS, SAN DIEGO, CA, vol. 25, no. 2, 1 July 2002 (2002-07-01), pages 219 - 228, XP002266556, ISSN: 1046-5928 *
CHADDOCK J A ET AL: "INHIBITION OF VESICULAR SECRETION IN BOTH NEURONAL AND NONNEURONAL CELLS BY A RETARGETED ENDOPEPTIDASE DERIVATIVE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A", INFECTION AND IMMUNITY, AMERICAN SOCIETY FOR MICROBIOLOGY. WASHINGTON, vol. 68, no. 5, 1 May 2000 (2000-05-01), pages 2587 - 2593, XP001010268, ISSN: 0019-9567 *
CHADDOCK J A ET AL: "Manipulation of signal transduction by botulinum neurotoxins and their derivatives", CURRENT SIGNAL TRANSDUCTION THERAPY,, vol. 2, no. 3, 1 January 2007 (2007-01-01), pages 221 - 225, XP001538465, ISSN: 1574-3624 *
CHADDOCK J A ET AL: "Retargeted clostridial endopeptidases: Inhibition of nociceptive neurotransmitter release in vitro, and antinociceptive activity in in vivo models of pain", NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, SPRINGER, BERLIN, DE, vol. 365, no. Suppl 2, 1 June 2002 (2002-06-01), pages R15, XP009101762, ISSN: 0028-1298 *
CHADDOCK JOHN A ET AL: "Retargeted clostridial endopeptidases: inhibition of nociceptive neurotransmitter release in vitro, and antinociceptive activity in in vivo models of pain.", MOVEMENT DISORDERS : OFFICIAL JOURNAL OF THE MOVEMENT DISORDER SOCIETY MAR 2004, vol. 19 Suppl 8, March 2004 (2004-03-01), pages S42 - S47, XP002497764, ISSN: 0885-3185 *
FOSTER K A ET AL: "Re-engineering the target specificity of Clostridial neurotoxins - a route to novel therapeutics", NEUROTOXICITY RESEARCH, HARWOOD ACADEMIC PUBLISHERS, LAUSANNE, vol. 9, no. 2-3, 1 April 2006 (2006-04-01), pages 101 - 107, XP009089826, ISSN: 1029-8428 *
INOUE M ET AL: "Nociceptin/orphanin FQ-induced nociceptive responses through substance P release from peripheral nerve endings in mice.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1 SEP 1998, vol. 95, no. 18, 1 September 1998 (1998-09-01), pages 10949 - 10953, XP002497765, ISSN: 0027-8424 *
KEITH FOSTER: "Harnessing toxins", MANUFACTURING CHEMIST, 1 October 2006 (2006-10-01), pages 23 - 24, AND 26, XP002497767, Retrieved from the Internet <URL:http://www.syntaxin.com/media/Manufacturing-Chemist-article.pdf> [retrieved on 20080929] *
MOULSDALE H J ET AL: "Retargeted endopeptidase-dependent inhibition of neurotransmitters from neurons involved in nociception", NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, SPRINGER, BERLIN, DE, vol. Suppl 2, 1 June 2002 (2002-06-01), pages R30 - 365, XP009101752, ISSN: 0028-1298 *
SUTTON J MARK ET AL: "Preparation of specifically activatable endopeptidase derivatives of Clostridium botulinum toxins type A, B, and C and their applications.", PROTEIN EXPRESSION AND PURIFICATION MAR 2005, vol. 40, no. 1, March 2005 (2005-03-01), pages 31 - 41, XP004753559, ISSN: 1046-5928 *

Also Published As

Publication number Publication date
GB0610868D0 (en) 2006-07-12
WO2007138336A2 (en) 2007-12-06

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