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Extract from the Register of European Patents

EP About this file: EP3302493

EP3302493 - INHIBITORS OF CYSTINE-GLUTAMATE TRANSPORTER FOR USE IN TREATING OR PREVENTING SUBSTANCE-RELATED AND ADDICTIVE DISORDERS [Right-click to bookmark this link]
Former [2018/15]NEW USE OF INHIBITOR OF CYSTINE-GLUTAMATE TRANSPORTER
[2021/08]
StatusNo opposition filed within time limit
Status updated on  13.05.2022
Database last updated on 25.09.2024
FormerThe patent has been granted
Status updated on  12.06.2021
FormerGrant of patent is intended
Status updated on  10.02.2021
FormerExamination is in progress
Status updated on  21.10.2019
FormerRequest for examination was made
Status updated on  09.03.2018
FormerThe international publication has been made
Status updated on  09.12.2016
Most recent event   Tooltip13.09.2024Lapse of the patent in a contracting state
New state(s): MT		published on 16.10.2024 [2024/42]
Applicant(s)For all designated states
China Medical University
No. 91, Hsueh-Shih Road
North District
Taichung 40402 / TW
[2018/15]
Inventor(s)01 / HSIEH, Chia-hung
No.91
Hsueh-shih Road
Taichung 40402 / TW
 [2018/15]
Representative(s)J A Kemp LLP
80 Turnmill Street
London EC1M 5QU / GB
[N/P]
Former [2021/27]J A Kemp LLP
14 South Square
Gray's Inn
London WC1R 5JJ / GB
Former [2018/15]J A Kemp
14 South Square
Gray's Inn
London WC1R 5JJ / GB
Application number, filing date16802610.206.06.2016
[2018/15]
WO2016CN85002
Priority number, dateUS201562171315P05.06.2015         Original published format: US 201562171315 P
[2018/15]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report
No.:WO2016192687
Date:08.12.2016
Language:EN
[2016/49]
Type: A1 Application with search report 
No.:EP3302493
Date:11.04.2018
Language:EN
The application published by WIPO in one of the EPO official languages on 08.12.2016 takes the place of the publication of the European patent application.
[2018/15]
Type: B1 Patent specification 
No.:EP3302493
Date:07.07.2021
Language:EN
[2021/27]
Search report(s)International search report - published on:CN08.12.2016
(Supplementary) European search report - dispatched on:EP04.01.2019
ClassificationIPC:A61K31/44, A61K31/4402, A61K31/655, A61K31/63, A61K45/06, A61P25/36, A61P25/32
[2019/04]
CPC:
A61K31/4402 (EP,US); A61K31/44 (EP,US); A61K31/655 (EP,US);
A61K45/06 (US); A61P25/32 (EP,US); A61P25/36 (EP,US)
Former IPC [2018/15]A61K31/63, A61K31/44, A61P25/36, A61P25/32
Designated contracting statesAL,   AT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MK,   MT,   NL,   NO,   PL,   PT,   RO,   RS,   SE,   SI,   SK,   SM,   TR [2018/15]
Extension statesBANot yet paid
MENot yet paid
Validation statesMANot yet paid
MDNot yet paid
TitleGerman:INHIBITOREN DES CYSTIN-GLUTAMAT-TRANSPORTERS ZUR VERWENDUNG BEI DER BEHANDLUNG ODER VORBEUGUNG VON SUBSTANZBEZOGENEN STÖRUNGEN UND SUCHTERKRANKUNGEN[2021/08]
English:INHIBITORS OF CYSTINE-GLUTAMATE TRANSPORTER FOR USE IN TREATING OR PREVENTING SUBSTANCE-RELATED AND ADDICTIVE DISORDERS[2021/08]
French:INHIBITEURS DU TRANSPORTEUR DE CYSTINE-GLUTAMATE POUR LE TRAITEMENT OU LA PRÉVENTION DE TROUBLES LIÉS AUX SUBSTANCES ET DE TROUBLES DE DÉPENDANCE[2021/08]
Former [2018/15]NEUE VERWENDUNG EINES INHIBITORS DES CYSTIN-GLUTAMAT-TRANSPORTERS
Former [2018/15]NEW USE OF INHIBITOR OF CYSTINE-GLUTAMATE TRANSPORTER
Former [2018/15]NOUVELLE UTILISATION D'UN INHIBITEUR DU TRANSPORTEUR CYSTINE-GLUTAMATE
Entry into regional phase19.12.2017National basic fee paid 
19.12.2017Search fee paid 
19.12.2017Designation fee(s) paid 
19.12.2017Examination fee paid 
Examination procedure19.12.2017Examination requested  [2018/15]
19.12.2017Date on which the examining division has become responsible
31.07.2019Amendment by applicant (claims and/or description)
24.10.2019Despatch of a communication from the examining division (Time limit: M06)
23.04.2020Reply to a communication from the examining division
24.07.2020Despatch of a communication from the examining division (Time limit: M02)
24.09.2020Reply to a communication from the examining division
11.02.2021Communication of intention to grant the patent
28.05.2021Fee for grant paid
28.05.2021Fee for publishing/printing paid
28.05.2021Receipt of the translation of the claim(s)
Opposition(s)08.04.2022No opposition filed within time limit [2022/24]
Fees paidRenewal fee
12.06.2018Renewal fee patent year 03
07.05.2019Renewal fee patent year 04
31.03.2020Renewal fee patent year 05
12.05.2021Renewal fee patent year 06
Opt-out from the exclusive  Tooltip
competence of the Unified
Patent Court		 See the Register of the Unified Patent Court for opt-out data
Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court.
Lapses during opposition  TooltipHU06.06.2016
AL07.07.2021
AT07.07.2021
CY07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
MC07.07.2021
MK07.07.2021
MT07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
[2024/42]
Former [2024/22]HU06.06.2016
AL07.07.2021
AT07.07.2021
CY07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
MC07.07.2021
MK07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2024/20]HU06.06.2016
AL07.07.2021
AT07.07.2021
CY07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
MC07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2024/18]HU06.06.2016
AL07.07.2021
AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
MC07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2023/08]AL07.07.2021
AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
MC07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/36]AL07.07.2021
AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
IT07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/29]AL07.07.2021
AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SI07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/25]AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SK07.07.2021
SM07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/24]AT07.07.2021
CZ07.07.2021
DK07.07.2021
EE07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RO07.07.2021
RS07.07.2021
SE07.07.2021
SK07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/21]AT07.07.2021
DK07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RS07.07.2021
SE07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/11]AT07.07.2021
ES07.07.2021
FI07.07.2021
HR07.07.2021
LT07.07.2021
LV07.07.2021
NL07.07.2021
PL07.07.2021
RS07.07.2021
SE07.07.2021
BG07.10.2021
NO07.10.2021
GR08.10.2021
IS07.11.2021
PT08.11.2021
Former [2022/09]AT07.07.2021
ES07.07.2021
FI07.07.2021
LT07.07.2021
NL07.07.2021
RS07.07.2021
SE07.07.2021
BG07.10.2021
NO07.10.2021
PT08.11.2021
Former [2022/08]AT07.07.2021
ES07.07.2021
FI07.07.2021
LT07.07.2021
NL07.07.2021
SE07.07.2021
BG07.10.2021
NO07.10.2021
Former [2022/07]AT07.07.2021
LT07.07.2021
NL07.07.2021
NO07.10.2021
Documents cited:Search[X]WO2007084541  (UNIV COLORADO [US], et al) [X] 1-5,7,8 * page 15 *;
 [X]WO2008042795  (UNIV ILLINOIS [US], et al) [X] 1-7,9,11,14,15 * page 7, lines 25-26 * * page 14, lines 2-4, 22-25 * * examples 2, 3, 5 * * claims 1, 2, 10, 12-16, 23, 24, 26 *;
 [XI]  - DAVID A BAKER ET AL, "Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse", NATURE NEUROSCI, NATURE AMERICA, INC, US, (20030601), vol. 6, doi:10.1038/NN1069, ISSN 1097-6256, pages 743 - 749, XP008132286 [X] 1-7,11,14,15 * abstract * * page 745, column 1, paragraph 2 * * figures 3, 5 * * page 746, column 2, paragraph 2 - page 747, column 1, paragraph 1 * [I] 8-10,12,13

DOI:   http://dx.doi.org/10.1038/nn1069
 [I]  - Anonymous, "Effects of Sulfasalazine on BOLD Response to Alcohol Cues", (20140922), GlinicalTrials.gov, URL: https://clinicaltrials.gov/ct2/show/record/NCT01312129, (20181207), XP002787247 [I] 1-15 * Current primary outcome measures; page 1 * * Brief summary; pages 2-3 * * page 5, paragraph 2 * * Intervention; page 6 *
 [A]  - ALESSANDRA T. PEANA ET AL, "Change of cystine/glutamate antiporter expression in ethanol-dependent rats", FRONTIERS IN NEUROSCIENCE, (20141006), vol. 8, doi:10.3389/fnins.2014.00311, XP055531895 [A] 1-15 * abstract * * page 5, column 1, paragraph 3 - column 2, paragraph 1 * * page 6, column 1, paragraph 1 - column 2, paragraph 1 * * page 7, column 2, paragraph 1 * * figure 2 *

DOI:   http://dx.doi.org/10.3389/fnins.2014.00311
 [XPI]  - DHAVAL PATEL ET AL, "Emerging roles of system antiporter and its inhibition in CNS disorders", MOLECULAR MEMBRANE BIOLOGY., GB, (20151027), vol. 32, no. 4, doi:10.3109/09687688.2015.1096972, ISSN 0968-7688, pages 89 - 116, XP055531897 [XP] 1-7,11,14,15 * page 95, column 1, paragraph 3 - column 2, paragraph 1 * * page 99, column 1, paragraph 4 * * page 99, column 2, paragraphs 1, 4 * * pages 100-102; table 2 * * page 104; table 2 * * page 110; table 2 * [I] 8,12,13

DOI:   http://dx.doi.org/10.3109/09687688.2015.1096972
International search[X]WO2007084541  (UNIV COLORADO [US], et al) [X] 1-18 * see description, page 15 *;
 [A]WO2014197536  (UNIV TEMPLE [US]) [A] 1-18* see description, paragraph [032] *;
 [A]WO2015070034  (PROMENTIS PHARM INC [US]) [A] 1-18 * see description, paragraph [008] *
Examination   - BRIDGES RICHARD J ET AL, "System xc- cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS", BRITISH JOURNAL OF PHARMACOLOGY, (201201), vol. 165, no. 1, ISSN 0007-1188, pages 20 - 34
    - Statistical Analysis of the results presented in "Effects of Sulfasalazine on BOLD Response to Alcohol Cues"
    - EVANS SUZETTE M ET AL, "A pilot double-blind treatment trial of memantine for alcohol dependence", ALCOHOLISM CLINICAL AND EXPERIMENTAL RESEARCH, (200705), vol. 31, no. 5, ISSN 0145-6008, pages 775 - 782
    - MUIR ALEXANDER ET AL, "Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition", ELIFE, (20170815), vol. 6, ISSN 2050-084X
    - TOMI MASATOSHI ET AL, "Induction of xCT gene expression and L-cystine transport activity by diethyl maleate at the inner blood-retinal barrier", IOVS, (200203), vol. 43, no. 3, pages 774 - 779
    - Anonymous, "Azulfidine EN-tabs", (20121201), pages 1 - 21, URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/007073s125lbl.pdf, (20200721), XP055716661
    - Anonymous, "Sulfasalazine", NCBI Bookshelf, (20170925), pages 1 - 2, URL: https://www.ncbi.nlm.nih.gov/books/NBK548792/, (20200721), XP055716660
    - SABHA MUSHTAQ ET AL, "Sulfasalazine in dermatology: A lesser explored drug with broad therapeutic potential", INTERNATIONAL JOURNAL OF WOMEN'S DERMATOLOGY, (20200601), vol. 6, no. 3, doi:10.1016/j.ijwd.2020.01.009, ISSN 2352-6475, pages 191 - 198, XP055716667

DOI:   http://dx.doi.org/10.1016/j.ijwd.2020.01.009
by applicant   - TZSCHENTKE, T.M.W.J. SCHMIDT, "Glutamatergic mechanisms in addiction", Mol Psychiatry, (20030000), vol. 8, no. 4, pages 373 - 82
    - DING, Z.M. et al., "Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats", Addict Biol, (20130000), vol. 18, no. 2, pages 297 - 306
    - WILLIAMS, J.M., J.D. STEKETEE, "Steketee, Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study", Eur J Neurosci, (20040000), vol. 20, no. 6, pages 1639 - 46
    - SAELLSTROEM BAUM, S. et al., "Nicotine stimulation on extracellular glutamate levels in the nucleus accumbens of ethanol-withdrawn rats in vivo", Alcohol Clin Exp Res, (20060000), vol. 30, no. 8, pages 1414 - 21
    - MOGHADDAM, B. et al., "Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex", J Neurosci, (19970000), vol. 17, no. 8, pages 2921 - 7
    - DEL ARCO, A. et al., "Amphetamine increases the extracellular concentration of glutamate in striatum of the awake rat: involvement of high affinity transporter mechanisms", Neuropharmacology, (19990000), vol. 38, no. 7, pages 943 - 54
    - PETERS, J.T.J. DE VRIES, "Glutamate mechanisms underlying opiate memories", Cold Spring Harb Perspect Med, (20120000), vol. 2, no. 9, page a012088
    - GONZALES, R.A.J.N. JAWORSKI, "Alcohol and glutamate", Alcohol Health Res World, (19970000), vol. 21, no. 2, pages 120 - 7
    - BRIDGES, R.J.N.R. NATALES.A. PATEL, "System xc(-) cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS", Br JPharmacol, (20120000), vol. 165, no. 1, doi:10.1111/j.1476-5381.2011.01480.x, pages 20 - 34, XP055247839

DOI:   http://dx.doi.org/10.1111/j.1476-5381.2011.01480.x
    - SATO, H. et al., "Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins.", J Biol Chem, (19990000), vol. 274, no. 17, doi:10.1074/jbc.274.17.11455, pages 11455 - 8, XP002941607

DOI:   http://dx.doi.org/10.1074/jbc.274.17.11455
    - BUCKINGHAM, S.C. et al., "Glutamate release by primary brain tumors induces epileptic activity", Nat Med, (20110000), vol. 17, no. 10, pages 1269 - 74
    - ALBRECHT, P. et al., "Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter system xc- as a neuroprotective drug target", CNS Neurol Disord Drug Targets, (20100000), vol. 9, no. 3, pages 373 - 82
    - DE BUNDEL, D. et al., "Loss of system x(c)- does not induce oxidative stress but decreases extracellular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility", J Neurosci, (20110000), vol. 31, no. 15, pages 5792 - 803
    - BAKER, D.A., et al., "Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse", Nat Neurosci, (20030000), vol. 6, no. 7, doi:10.1038/nn1069, pages 743 - 9, XP008132286

DOI:   http://dx.doi.org/10.1038/nn1069
    - KNACKSTEDT, L.A., et al., "The role of cystine-glutamate exchange in nicotine dependence in rats and humans", Biol Psychiatry, (20090000), vol. 65, no. 10, doi:10.1016/j.biopsych.2008.10.040, pages 841 - 5, XP026056813

DOI:   http://dx.doi.org/10.1016/j.biopsych.2008.10.040
    - PEANA, A. T.G. MUGGIRONIF. BENNARDINI, "Change of cystine/glutamate antiporter expression in ethanol-dependent rats", Front Neurosci, (20140000), vol. 8, page 311
    - LEWERENZ, J. et al., "The cystine/glutamate antiporter system x(c)(~) in health and disease: from molecular mechanisms to novel therapeutic opportunities", Antioxid Redox Signal, (20130000), vol. 18, no. 5, doi:10.1089/ars.2011.4391, pages 522 - 55, XP055592843

DOI:   http://dx.doi.org/10.1089/ars.2011.4391
    - BAKER et al., Nature Neuroscience, (20030000), vol. 6, no. 7, pages 743 - 749
    - PEANA et al., Frontiers In Neuroscience, (20140000), vol. 8, no. 311
    - PATEL et al., Moi. Membr. Biol., (20150000), vol. 32, no. 4, pages 89 - 116
    - SHYU, W.C., et al., "Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke", J Clin Invest, (20080000), vol. 118, no. 1, pages 133 - 48
    - CHUNG, W.J. et al., "Inhibition of cystine uptake disrupts the growth of primary brain tumors", J Neurosci, (20050000), vol. 25, no. 31, pages 7101 - 10
The EPO accepts no responsibility for the accuracy of data originating from other authorities; in particular, it does not guarantee that it is complete, up to date or fit for specific purposes.