DE69431832D1 - Mittel für die steuerung von der zellaktivität - Google Patents

Mittel für die steuerung von der zellaktivität

Info

Publication number
DE69431832D1
DE69431832D1 DE69431832T DE69431832T DE69431832D1 DE 69431832 D1 DE69431832 D1 DE 69431832D1 DE 69431832 T DE69431832 T DE 69431832T DE 69431832 T DE69431832 T DE 69431832T DE 69431832 D1 DE69431832 D1 DE 69431832D1
Authority
DE
Germany
Prior art keywords
domain
agent
cell
endosome
cell activity
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
DE69431832T
Other languages
English (en)
Other versions
DE69431832T2 (de
Inventor
John Robert North
Keith Alan Foster
Conrad Padraig Quinn
Clifford Charles Shone
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.)
Syntaxin Ltd
Original Assignee
Microbiological Research Authority
Speywood Laboratory Ltd
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 Microbiological Research Authority, Speywood Laboratory Ltd filed Critical Microbiological Research Authority
Priority claimed from PCT/GB1994/000558 external-priority patent/WO1994021300A1/en
Application granted granted Critical
Publication of DE69431832D1 publication Critical patent/DE69431832D1/de
Publication of DE69431832T2 publication Critical patent/DE69431832T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • 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
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
DE69431832T 1993-03-19 1994-03-18 Mittel für die steuerung von der zellaktivität Expired - Lifetime DE69431832T2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB939305735A GB9305735D0 (en) 1993-03-19 1993-03-19 Novel agent for controlling cell activity
PCT/GB1994/000558 WO1994021300A1 (en) 1993-03-19 1994-03-18 Novel agent for controlling cell activity

Publications (2)

Publication Number Publication Date
DE69431832D1 true DE69431832D1 (de) 2003-01-16
DE69431832T2 DE69431832T2 (de) 2003-04-10

Family

ID=10732382

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69431832T Expired - Lifetime DE69431832T2 (de) 1993-03-19 1994-03-18 Mittel für die steuerung von der zellaktivität

Country Status (24)

Country Link
US (1) US20080070278A1 (de)
EP (1) EP0689459B1 (de)
JP (2) JP4300265B2 (de)
KR (1) KR960700756A (de)
CN (1) CN1195551C (de)
AT (1) ATE228856T1 (de)
AU (1) AU671203C (de)
BR (1) BR9406232A (de)
CA (1) CA2158647A1 (de)
CZ (1) CZ242695A3 (de)
DE (1) DE69431832T2 (de)
DK (1) DK0689459T3 (de)
ES (1) ES2183836T3 (de)
FI (1) FI954390A (de)
GB (1) GB9305735D0 (de)
HU (1) HU217220B (de)
IL (1) IL109045A0 (de)
IN (1) IN178499B (de)
NO (1) NO953643L (de)
NZ (1) NZ262484A (de)
PL (1) PL178895B1 (de)
PT (1) PT689459E (de)
SG (1) SG73411A1 (de)
SK (1) SK115595A3 (de)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9305735D0 (en) * 1993-03-19 1993-05-05 North John R Novel agent for controlling cell activity
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
PL201879B1 (pl) * 1998-05-13 2009-05-29 Biotecon Ges Fuer Biotechnologische Entwicklung & Consulting Mbh Białko hybrydowe i jego zastosowanie
GB9922554D0 (en) * 1999-09-23 1999-11-24 Microbiological Res Authority Inhibition of secretion from non-neuronal cells
GB9926875D0 (en) * 1999-11-12 2000-01-12 Microbiological Research Agenc Use of lytic toxins and toxin conjugates
GB0321344D0 (en) * 2003-09-11 2003-10-15 Health Prot Agency Re-targeted toxin conjugates
ES2340850T3 (es) * 2003-11-14 2010-06-10 Starhome Gmbh Control de llamada terminada para itinerancia de suscriptores de telefonia movil.
US8512984B2 (en) 2004-12-01 2013-08-20 Syntaxin, Ltd. Non-cytotoxic protein conjugates
US7659092B2 (en) * 2004-12-01 2010-02-09 Syntaxin, Ltd. Fusion proteins
US8603779B2 (en) 2004-12-01 2013-12-10 Syntaxin, Ltd. Non-cytotoxic protein conjugates
US8778634B2 (en) 2004-12-01 2014-07-15 Syntaxin, Ltd. Non-cytotoxic protein conjugates
GB0426394D0 (en) * 2004-12-01 2005-01-05 Health Prot Agency Fusion proteins
US8399400B2 (en) * 2004-12-01 2013-03-19 Syntaxin, Ltd. Fusion proteins
US8796216B2 (en) 2008-06-12 2014-08-05 Syntaxin Limited Suppression of neuroendocrine diseases
KR101642363B1 (ko) * 2008-06-12 2016-07-25 입센 바이오이노베이션 리미티드 신경내분비계 질환의 억제
US9623117B2 (en) * 2011-04-04 2017-04-18 Wisconsin Alumni Research Foundation Method for selective targeting and entry of bacterial toxins to cells
GB201312317D0 (en) 2013-07-09 2013-08-21 Syntaxin Ltd Cationic neurotoxins
EP3822286A1 (de) 2015-01-09 2021-05-19 Ipsen Bioinnovation Limited Kationische neurotoxine
GB201517450D0 (en) 2015-10-02 2015-11-18 Ipsen Biopharm Ltd Method
EP3263710A1 (de) 2016-07-01 2018-01-03 Ipsen Biopharm Limited Herstellung von aktivierten clostridien-neurotoxinen
US20210187194A1 (en) 2018-02-26 2021-06-24 Ipsen Biopharm Limited Use of Ultrasound to Guide Injection of Non-cytotoxic Protease
GB201815817D0 (en) 2018-09-28 2018-11-14 Ispen Biopharm Ltd Clostridial neurotoxins comprising and exogenous activation loop
GB201900621D0 (en) 2019-01-16 2019-03-06 Ipsen Biopharm Ltd Labelled polypeptides
GB201914034D0 (en) 2019-09-30 2019-11-13 Ipsen Biopharm Ltd Treatment of neurological disorders
GB202100566D0 (en) 2021-01-15 2021-03-03 Ipsen Biopharm Ltd Treatment of brain damage
GB202104294D0 (en) 2021-03-26 2021-05-12 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an exogenous activation loop
JP2024513191A (ja) 2021-03-30 2024-03-22 イプセン バイオファーム リミテッド 疼痛及び炎症性障害の処置
WO2022208039A1 (en) 2021-03-30 2022-10-06 Ipsen Biopharm Limited Catalytically inactive clostridial neurotoxins for the treatment of pain & inflammatory disorders
GB202116795D0 (en) 2021-11-22 2022-01-05 Ipsen Biopharm Ltd Treatment of visceral pain
GB202214232D0 (en) 2022-09-28 2022-11-09 Ispen Biopharm Ltd Clostridial neurotoxins comprising an activating exogenous protease cleavage site
GB202214229D0 (en) 2022-09-28 2022-11-09 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an activating endosomal protease cleavage site

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4664911A (en) * 1983-06-21 1987-05-12 Board Of Regents, University Of Texas System Immunotoxin conjugates employing toxin B chain moieties
US5668255A (en) * 1984-06-07 1997-09-16 Seragen, Inc. Hybrid molecules having translocation region and cell-binding region
EP0329184A3 (de) * 1988-02-19 1990-05-23 Neorx Corporation Antimere und antimere Konjugation
US5045451A (en) * 1988-10-26 1991-09-03 Board Of Regents Methods for screening antibodies for use as immunotoxins
WO1990010692A1 (en) * 1989-03-15 1990-09-20 University Of Florida Monoclonal antibody for use in detection and treatment of childhood leukemia
US5300496A (en) * 1991-09-30 1994-04-05 The University Of British Columbia Complexed vanadium for the treatment of diabetes mellitus
US5877295A (en) * 1992-09-30 1999-03-02 The Center For Blood Research Antibodies which bind a subpopulation of Mac-1 (CD11b/CD18) molecules which mediate neutrophil adhesion to ICAM-1 and fibrinogen
GB9305735D0 (en) * 1993-03-19 1993-05-05 North John R Novel agent for controlling cell activity

Also Published As

Publication number Publication date
HUT76556A (en) 1997-09-29
KR960700756A (ko) 1996-02-24
IN178499B (de) 1997-05-03
ATE228856T1 (de) 2002-12-15
AU6217594A (en) 1994-10-11
JP4740206B2 (ja) 2011-08-03
SG73411A1 (en) 2000-06-20
HU217220B (hu) 1999-12-28
CA2158647A1 (en) 1994-09-29
NZ262484A (en) 1996-08-27
FI954390A0 (fi) 1995-09-18
DE69431832T2 (de) 2003-04-10
GB9305735D0 (en) 1993-05-05
WO1994021300A2 (en) 1994-09-29
CN1195551C (zh) 2005-04-06
NO953643L (no) 1995-11-16
AU671203B2 (en) 1996-08-15
SK115595A3 (en) 1997-02-05
FI954390A (fi) 1995-11-17
PT689459E (pt) 2003-04-30
JPH09500867A (ja) 1997-01-28
PL310698A1 (en) 1995-12-27
CN1124929A (zh) 1996-06-19
ES2183836T3 (es) 2003-04-01
CZ242695A3 (en) 1996-04-17
EP0689459A1 (de) 1996-01-03
BR9406232A (pt) 1996-01-09
JP2007302696A (ja) 2007-11-22
JP4300265B2 (ja) 2009-07-22
DK0689459T3 (da) 2003-03-24
PL178895B1 (pl) 2000-06-30
AU671203C (en) 2003-02-27
IL109045A0 (en) 1994-06-24
US20080070278A1 (en) 2008-03-20
NO953643D0 (no) 1995-09-15
EP0689459B1 (de) 2002-12-04
HU9502673D0 (en) 1995-11-28

Similar Documents

Publication Publication Date Title
DE69431832D1 (de) Mittel für die steuerung von der zellaktivität
PT826051E (pt) Derivados de toxina botulinica capazes de modificar funcoes aferentes sensoriaisperifericas
DE69435307D1 (de) Bazillus Thuringiensis und dessen insektizide Proteine
PT1200105E (pt) Factor viii modificado
BR9815518A (pt) Agentes antibacterianos de oxazolidinona tendo funcionalidade de tiocarbonila
DE69416824T2 (de) Polypeptide und daraus hergestellte, gegen hiv wirksame substanzen
ES2139740T3 (es) Cola de fibrina de dos componentes.
MX9304070A (es) Piperidilamidas, piperidilsulfonamidas y piperidilsulfoxamidas novedosas como inhibidores de la biosintesis del colesterol.
ATE91689T1 (de) Geminale bisphosphonsaeuren und deren derivate als antiarthritische mittel.
KR910700067A (ko) 항 hiv제
DK0633928T3 (da) Mikroorganismer, deres fremstilling og anvendelse
DE69838615D1 (de) ppGpp-SYNTHETASE UND EXPRESSIONSSYSTEME ZUR VERBESSERTEN HERSTELLUNG VON PROTEINEN
NO960710D0 (no) Nye tripeptider nyttige i immun- og CNS-terapi
ATE171072T1 (de) Rezeptor-konjugate zum targeting von arzneiwirkstoffen und anderen wirksubstanzen
MXPA02012299A (es) Inhibicion zeolitica del grupo bacillus anthracis y sus toxinas.

Legal Events

Date Code Title Description
8364 No opposition during term of opposition
8327 Change in the person/name/address of the patent owner

Owner name: IPSEN LTD., BERKSHIRE, GB

Owner name: HEALTH PROTECTION AGENCY, SALISBURY, WILTSHIRE, GB

8327 Change in the person/name/address of the patent owner

Owner name: SYNTAXIN LTD., ABINGDON, OXFORDSHIRE, GB