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Extract from the Register of European Patents

EP About this file: EP3335708

EP3335708 - ADMINISTRATION OF GAMMA HYDROXYBUTYRATE WITH MONOCARBOXYLATE TRANSPORTERS [Right-click to bookmark this link]
StatusPatent revoked
Status updated on  13.12.2024
Database last updated on 31.03.2026
FormerThe patent has been granted
Status updated on  08.11.2019
FormerGrant of patent is intended
Status updated on  18.09.2019
FormerRequest for examination was made
Status updated on  04.01.2019
FormerThe application has been published
Status updated on  18.05.2018
Most recent event   Tooltip13.03.2026Lapse of the patent in a contracting state
New state(s): GR		published on 15.04.2026 [2026/16]
Applicant(s)For all designated states
Jazz Pharmaceuticals Ireland Limited
Waterloo Exchange
Waterloo Road
Dublin 4 / IE
[2019/50]
Former [2018/25]For all designated states
Jazz Pharmaceuticals Ireland Limited
Waterloo Exchange
Waterloo Road
Dublin 4 / IE
Inventor(s)01 / ELLER, Mark
1616 Kentucky Street
Redwood City, CA California 94061 / US
 [2018/25]
Representative(s)Carpmaels & Ransford LLP
One Southampton Row
London WC1B 5HA / GB
[2019/50]
Former [2018/25]Jones Day
Rechtsanwälte, Attorneys-at-Law, Patentanwälte
Prinzregentenstrasse 11
80538 München / DE
Application number, filing date17200764.328.02.2014
[2018/25]
Priority number, dateUS201361771557P01.03.2013         Original published format: US 201361771557 P
US201361777873P12.03.2013         Original published format: US 201361777873 P
US20131383771415.03.2013         Original published format: US201313837714
US20131387300029.04.2013         Original published format: US201313873000
US20131387299729.04.2013         Original published format: US201313872997
[2018/25]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report 
No.:EP3335708
Date:20.06.2018
Language:EN
[2018/25]
Type: B1 Patent specification 
No.:EP3335708
Date:11.12.2019
Language:EN
[2019/50]
Search report(s)(Supplementary) European search report - dispatched on:EP18.05.2018
ClassificationIPC:A61K31/19, A61K31/196, A61P11/00, A61P25/20, A61P43/00, A61K31/00, A61K33/00, A61K31/20, A61K31/33, A61K31/505, A61K31/55, A61K31/616
[2018/25]
CPC:
A61K31/19 (EP,US); A61K31/20 (EP,US); A61K31/33 (EP,US);
A61K31/505 (EP,US); A61K31/55 (EP,US); A61K31/616 (EP,US);
A61P11/00 (EP,US); A61P25/20 (EP,US); A61P43/00 (EP,US);
G16H20/10 (US) (-)
C-Set:
A61K31/196, A61K2300/00 (US,EP);
A61K31/19, A61K2300/00 (EP,US);
A61K31/20, A61K2300/00 (US,EP);
A61K31/616, A61K2300/00 (US,EP)
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 [2019/06]
Former [2018/25]AL,  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 
TitleGerman:VERABREICHUNG VON GAMMA-HYDROXYBUTYRAT MIT MONOCARBOXYLAT-TRANSPORTERN[2018/25]
English:ADMINISTRATION OF GAMMA HYDROXYBUTYRATE WITH MONOCARBOXYLATE TRANSPORTERS[2018/25]
French:ADMINISTRATION D'ACIDE 4-HYDROXYBUTANOÏQUE ET DE TRANSPORTEURS MONOCARBOXYLATE[2018/25]
Examination procedure20.12.2018Examination requested  [2019/06]
20.12.2018Date on which the examining division has become responsible
28.01.2019Despatch of communication that the application is deemed to be withdrawn, reason: reply to the Extended European Search Report/Written Opinion of the International Searching Authority/International Preliminary Examination Report/Supplementary international search report not received in time
04.04.2019Amendment by applicant (claims and/or description)
05.08.2019Observations by third parties
19.09.2019Communication of intention to grant the patent
25.09.2019Observations by third parties
02.10.2019Fee for grant paid
02.10.2019Fee for publishing/printing paid
02.10.2019Receipt of the translation of the claim(s)
Parent application(s)   TooltipEP14709858.6  / EP2961399
Divisional application(s)EP19214483.0  / EP3695833
Opposition(s)Opponent(s)01  16.03.2020  19.03.2020  ADMISSIBLE
Hoffmann Eitle Patent- und Rechtsanwälte Partnerschaftsgesellschaft mbB
Arabellastr. 30
81925 München / DE
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
 02  02.09.2020  08.09.2020  ADMISSIBLE
Zentiva, k.s.
U kabelovny 130
102 37 Praha 10 - Dolni Mecholupy / CZ
Opponent's representative
Greiner, Elisabeth
df-mp Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  10.09.2020  15.09.2020  ADMISSIBLE
Hexal AG
Industriestrasse 25
83607 Holzkirchen / DE
Opponent's representative
Maiwald GmbH
Elisenhof
Elisenstraße 3
80335 München / DE
 04  11.09.2020  15.09.2020  ADMISSIBLE
Ter Meer Steinmeister & Partner Patentanwälte mbB
Nymphenburger Strasse 4
80335 München / DE
Opponent's representative
Ter Meer Steinmeister & Partner
Patentanwälte mbB
Nymphenburger Straße 4
80335 München / DE
 [N/P]
Former [2021/20]
Opponent(s)01  16.03.2020  19.03.2020  ADMISSIBLE
Hoffman Eitle Patent- und Rechtsanwälte Partnerschaftsgesellschaft mbB
Arabellastr. 30
81925 München / DE
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
 02  02.09.2020  08.09.2020  ADMISSIBLE
Zentiva, k.s.
U kabelovny 130
102 37 Praha 10 - Dolni Mecholupy / CZ
Opponent's representative
Greiner, Elisabeth
df-mp Dörries Frank-Molnia & Pohlman
Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  10.09.2020  15.09.2020  ADMISSIBLE
Hexal AG
Industriestrasse 25
83607 Holzkirchen / DE
Opponent's representative
Maiwald Patent- und Rechtsanwaltsgesellschaft mbH
Elisenhof
Elisenstraße 3
80335 München / DE
 04  11.09.2020  15.09.2020  ADMISSIBLE
Ter Meer Steinmeister & Partner Patentanwälte mbB
Nymphenburger Strasse 4
80335 München / DE
Opponent's representative
Ter Meer Steinmeister & Partner
Patentanwälte mbB
Nymphenburger Straße 4
80335 München / DE
Former [2020/43]
Opponent(s)01  16.03.2020  19.03.2020  ADMISSIBLE
Hoffman Eitle Patent- und Rechtsanwälte Partnerschaftsgesellschaft mbB
Arabellastr. 30
81925 München / DE
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
 02  02.09.2020  08.09.2020  ADMISSIBLE
Zentiva, k.s.
U kabelovny 130
102 37 Praha 10 - Dolni Mecholupy / CZ
Opponent's representative
Greiner, Elisabeth
df-mp Dörries Frank-Molnia & Pohlman
Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  10.09.2020  15.09.2020  ADMISSIBLE
Hexal AG
Industriestrasse 25
83607 Holzkirchen / DE
Opponent's representative
Maiwald Patent- und Rechtsanwaltsgesellschaft mbH
Elisenhof
Elisenstraße 3
80335 München / DE
 04  11.09.2020  15.09.2020  ADMISSIBLE
Ter Meer Steinmeister & Partner Patentanwälte mbB
Nymphenburger Strasse 4
80335 München / DE
Opponent's representative
Ter Meer Steinmeister & Partner
Patentanwälte mbB
Nymphenburger Straße 4
80335 München / DE
Former [2020/42]
Opponent(s)01  16.03.2020  19.03.2020  ADMISSIBLE
Hoffman Eitle Patent- und Rechtsanwälte Partnerschaftsgesellschaft mbB
Arabellastr. 30
81925 München / DE
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
 02  02.09.2020  08.09.2020  ADMISSIBLE
Zentiva, k.s.
U kabelovny 130
102 37 Praha 10 - Dolni Mecholupy / CZ
Opponent's representative
Greiner, Elisabeth
df-mp Dörries Frank-Molnia & Pohlman
Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  10.09.2020   
Hexal AG
Industriestrasse 25
83607 Holzkirchen / DE
Opponent's representative
Maiwald Patent- und Rechtsanwaltsgesellschaft mbH
Elisenhof
Elisenstraße 3
80335 München / DE
Former [2020/17]
Opponent(s)01  16.03.2020  19.03.2020  ADMISSIBLE
Hoffman Eitle Patent- und Rechtsanwälte Partnerschaftsgesellschaft mbB
Arabellastr. 30
81925 München / DE
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
25.09.2020Invitation to proprietor to file observations on the notice of opposition
06.04.2021Reply of patent proprietor to notice(s) of opposition
01.12.2022Date of oral proceedings
17.01.2023Despatch of interlocutory decision in opposition
17.01.2023Despatch of minutes of oral proceedings
11.12.2024Legal effect of revocation of patent [2025/03]
12.12.2024Despatch of communication that the patent will be revoked
Appeal following opposition24.03.2023Appeal received No.  T0509/23
24.03.2023Payment of appeal fee
26.05.2023Statement of grounds filed
11.12.2024Result of appeal procedure: revocation of the patent
12.12.2024Despatch of the decision of the Board of Appeal
16.03.2023Appeal received No.  T0509/23
16.03.2023Payment of appeal fee
22.05.2023Statement of grounds filed
11.12.2024Result of appeal procedure: revocation of the patent
12.12.2024Despatch of the decision of the Board of Appeal
08.03.2023Appeal received No.  T0509/23
08.03.2023Payment of appeal fee
17.05.2023Statement of grounds filed
11.12.2024Result of appeal procedure: revocation of the patent
12.12.2024Despatch of the decision of the Board of Appeal
Request for further processing for:The application is deemed to be withdrawn due to failure to reply to the Extended European Search Report/Written Opinion of the International Searching Authority/International Preliminary Examination Report/Supplementary international search report/Supplementary European search report
04.04.2019Request for further processing filed
04.04.2019Full payment received (date of receipt of payment)
Request granted
16.04.2019Decision despatched
Fees paidRenewal fee
09.11.2017Renewal fee patent year 03
09.11.2017Renewal fee patent year 04
14.02.2018Renewal fee patent year 05
28.02.2019Renewal 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  TooltipAL11.12.2019
MC11.12.2019
MK11.12.2019
MT11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
LU28.02.2020
IS11.04.2020
GR29.02.2024
[2026/16]
Former [2022/33]AL11.12.2019
MC11.12.2019
MK11.12.2019
MT11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
LU28.02.2020
IS11.04.2020
Former [2022/29]AL11.12.2019
MC11.12.2019
MT11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
LU28.02.2020
IS11.04.2020
Former [2020/50]AL11.12.2019
MC11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
LU28.02.2020
IS11.04.2020
Former [2020/48]AL11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
LU28.02.2020
IS11.04.2020
Former [2020/40]AL11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
IS11.04.2020
Former [2020/38]AL11.12.2019
RO11.12.2019
RS11.12.2019
SM11.12.2019
Former [2020/36]AL11.12.2019
RO11.12.2019
RS11.12.2019
Former [2020/32]AL11.12.2019
RS11.12.2019
Former [2020/27]RS11.12.2019
Documents cited:Search[A]   FULLER D ET AL: "From Club Drug to Orphan Drug: Sodium Oxybate (Xyrem) for the Treatment of Cataplexy", 1 September 2003 (2003-09-01), XP055123175, Retrieved from the Internet [retrieved on 20140613]
 [A]   VIVIANE HECHLER ET AL: "gamma-Hydroxybutyrate Conversion into GABA Induces Displacement of GABA B Binding that is Blocked by Valproate and Ethosuximide 1", 30 January 1997 (1997-01-30), XP055123267, Retrieved from the Internet [retrieved on 20140613]
 [A]   BHATTACHARYA I ET AL: "GHB (GAMMA-HYDROXYBUTYRATE) CARRIER-MEDIATED TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, AMERICAN SOCIETY FOR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, US, vol. 311, no. 1, 1 October 2004 (2004-10-01), pages 92 - 98, XP009049440, ISSN: 0022-3565, DOI: 10.1124/JPET.104.069682

DOI:   http://dx.doi.org/10.1124/jpet.104.069682
 [A]   PETRINE WELLENDORPH ET AL: "Phenylacetic acids and the structurally related non-steroidal anti-inflammatory drug diclofenac bind to specific [gamma]-hydroxybutyric acid sites in rat brain", FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol. 23, no. 2, 1 April 2009 (2009-04-01), pages 207 - 213, XP055123069, ISSN: 0767-3981, DOI: 10.1111/j.1472-8206.2008.00664.x

DOI:   http://dx.doi.org/10.1111/j.1472-8206.2008.00664.x
by applicantUS6472431
 US6780889
 US7262219
 US7851506
 US8263650
 US8324275
 US7895059
 US7797171
 US7668730
 US7765106
 US7765107
 US201113071369
 US201313739886
 US26470908
 US2010033572
 US2009061312
 US2009137565
 US2012076865
 US5380937
 US4393236
 DD237309
 GB922029
 US5758095
 US5833599
 US5845255
 US6014631
 US6067524
 US6112182
 US6317719
 US6356873
 US7072840
 US3325361
 US4155929
 GB980279
 GB1522450
 US3385886
   ARENA ET AL.: "Absorption of Sodium y-Hydroxybutyrate and Its Prodrug y-Butyrolactone: Relationship between In Vitro Transport and In Vivo Absorption", J. PHARMACEUTICAL SCIENCES, vol. 69, no. 3, 1980, pages 356 - 358
   BANERJEE ET AL.: "Presynaptic Gamma-Hydroxybutyric Acid (GHB) and Gamma-Aminobutyric Acids (GABA ) Receptor-Mediated Release of GABA and glutamate (GLU) in Rat Thalamic Ventrobasal Nucleus (VB): A Possible Mechanism for the Generation of Absence-Like Seizures Induced by GHB", J. PHARMACOL. EXP. THER., vol. 273, no. 3, 1995, pages 1534 - 1543
   BEDARD ET AL.: "Nocturnal -Hydroxybutyrate. Effect on Periodic Leg Movements and Sleep Organization of Narcoleptic Patients", CLIN. NEUROPHARMACOL., vol. 12, no. 1, 1989, pages 29 - 36
   BROUGHTON ET AL.: "The Treatment of Narcolepsy-Cataplexy with Nocturnal Gamma-Hydroxybutyrate", LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES, vol. 6, no. 1, 1979, pages 1 - 6, XP002083192
   CASH ET AL.: "y-Hydroxybutyrate Receptor Function Studied by the Modulation of Nitric Oxide Synthase Activity in Rat Frontal Cortex Punches", BIOCHEMICAL PHARMACOLOGY, vol. 58, no. 11, 1999, pages 1815 - 1819, XP000876980, DOI: doi:10.1016/S0006-2952(99)00265-8

DOI:   http://dx.doi.org/10.1016/S0006-2952(99)00265-8
   DIMITRIJEVIC ET AL.: "Drosophila GABA Receptors are Involved in Behavioral Effects of y-Hydroxybutyric Acid (GHB", EUR. J. PHARMACOL., vol. 519, no. 3, 2005, pages 246 - 252, XP005071265, DOI: doi:10.1016/j.ejphar.2005.07.016

DOI:   http://dx.doi.org/10.1016/j.ejphar.2005.07.016
   GALLIMBERTI ET AL.: "Gamma-Hydroxybutyric Acid for Treatment of Alcohol Withdrawal Syndrome", THE LANCET, vol. 30, September 1989 (1989-09-01), pages 787 - 789
   GALLIMBERTI ET AL.: "Gamma-Hydroxybutyric Acid in the Treatment of Alcohol Dependence: A Double-Blind Study", ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH, vol. 16, no. 4, 1992, pages 673 - 676
   GALLIMBERTI ET AL.: "Gamma-Hydroxybutyric Acid for Treatment of Opiate Withdrawal Syndrome", NEUROPSYCHOPHARMACOLOGY, vol. 9, no. 1, 1993, pages 77 - 81
   GALLIMBERTI ET AL.: "Clinical Efficacy of Gamma-Hydroxybutyric Acid in Treatment of Opiate Withdrawal", EUR ARCH PSYCHIATRY CLIN NEUROSCI, vol. 244, 1994, pages 113 - 114
   GESSA ET AL.: "Gamma-Hydroxybutyric Acid in the Treatment of Alcohol Dependence", CLIN. NEUROPHARM.--SUPPLEMENT, vol. 15, no. 1, 1992, pages 303A - 304A
   GERRA ET AL.: "Flumazenil Effects on Growth Hormone Response to Gamma-Hydroxybutyric Acid", INTERNAT. CLIN. PSYCHOPHARM., vol. 9, 1994, pages 211 - 215
   HASENBOS ET AL.: "Anaesthesia for bullectomy", ANAESTHESIA, vol. 40, 1985, pages 977 - 980
   HECHLER ET AL.: "Extracellular Events Induced by y-Hydroxybutyrate in Striatum: A Microdialysis Study", J. NEUROCHEM., vol. 56, no. 3, 1991, pages 938 - 944
   KURIYAMA ET AL.: "Blood-Brain Barrier to H3--Aminobutyric Acid in Normal and Amino Oxyacetic Acid-Treated Animals", NEUROPHARMACOLOGY, vol. 10, 1971, pages 103 - 108, XP025490209, DOI: doi:10.1016/0028-3908(71)90013-X

DOI:   http://dx.doi.org/10.1016/0028-3908(71)90013-X
   LABORIT, H.: "Gamma-Hydroxybutyrate, Succinic Semialdehyde and Sleep", LABORATOIRE D'EUTONOLOGIE, HOPITAL BOUCICAUT, 1973, pages 257 - 274
   LADINSKY ET AL.: "Mode of Action of Gamma-Butyrolactone on the Central Cholinergic System", NAUNYN-SCHMIEDEBERG'S ARCH. PHARMACAL., vol. 322, 1983, pages 42 - 48
   LAMMERS ET AL.: "Gammahydroxybutyrate and Narcolepsy: A Double-Blind Placebo-Controlled Study", SLEEP, vol. 16, no. 3, 1993, pages 216 - 220
   LAPIERRE ET AL.: "The Effect of Gamma-Hydroxybutyrate: A Double-Blind Study of Normal Subjects", SLEEP RESEARCH, vol. 17, 1988, pages 99
   LAPIERRE ET AL.: "The Effect of Gamma-Hydroxybutyrate on Nocturnal and Diurnal Sleep of Normal Subjects: Further Considerations on REM Sleep-Triggering Mechanisms", SLEEP, vol. 13, no. 1, 1990, pages 24 - 30
   LEE, C.R.: "Evidence for the -Oxidation of Orally Administered 4-Hydroxybutyrate in Humans", BIOCHEM. MED., vol. 17, 1977, pages 284 - 291, XP026177020, DOI: doi:10.1016/0006-2944(77)90034-5

DOI:   http://dx.doi.org/10.1016/0006-2944(77)90034-5
   LETTIERI ET AL.: "Improved Pharmacological Activity via Pro-Drug Modification: Comparative Pharmacokinetics of Sodium -Hydroxybutyrate and y-Butyrolactone", RESEARCH COMMUNICATIONS IN CHEMICAL PATHOLOGY AND PHARMACOLOGY, vol. 22, no. 1, 1978, pages 107 - 118
   MAITRE ET AL.: "A Specific y-Hydroxybutyrate Receptor Ligand Possesses both Antagonistic and Anticonvulsant Properties", J. PHARMACOL. EXP. THER., vol. 255, no. 2, 1990, pages 657 - 663
   MAITRE ET AL.: "Mecanismes d'action d'un medicament detourne: le -hydroxybutyrate'' ('A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse", MED SCI (PARIS), vol. 21, no. 3, 2005, pages 284 - 9
   MAMELAK ET AL.: "Sleep-Inducing Effects of Gammahydroxybutyrate", THE LANCET, vol. 302, no. 7824, 1973, pages 328 - 329
   MAMELAK ET AL.: "The Effects of y-Hydroxybutyrate on Sleep", BIOL. PSYCHIATRY, vol. 12, no. 2, 1977, pages 273 - 288, XP000600034
   MAMELAK ET AL.: "Treatment of Narcolepsy and Sleep Apnea with Gammahydroxybutyrate: A Clinical and Polysomnographic Case Study", SLEEP, vol. 4, no. 1, 1981, pages 105 - 111
   MAMELAK: "Gammahydroxybutyrate: An Endogenous Regulator of Energy Metabolism", NEUROSCIENCE AND BIOBEHAV. REVIEWS, vol. 13, 1989, pages 187 - 198
   NEMA ET AL.: "Excipients and Their Use in Injectable Products", PDA J. PHARM. SCI. TECHNOL., vol. 51, no. 4, 1997, pages 166 - 171
   PALATINI ET AL.: "Dose-Dependent Absorption and Elimination of Gamma-Hydroxybutyric Acid in Healthy Volunteers", EUR. J. CLIN. PHARMACOL., vol. 45, 1993, pages 353 - 356
   ROTH ET AL.: "y-Butyrolactone and -Hydroxybutyric Acid-I Distribution and Metabolism", BIOCHEMICAL PHARMACOLOGY, vol. 15, 1966, pages 1333 - 1348, XP023727801, DOI: doi:10.1016/0006-2952(66)90045-1

DOI:   http://dx.doi.org/10.1016/0006-2952(66)90045-1
   ROTH ET AL.: "y-Butyrolactone and y-Hydroxybutyric AcidII The Pharmacologically Active Form", INT. J. NEROPHARMACOL., vol. 5, 1966, pages 421 - 428, XP023763604, DOI: doi:10.1016/0028-3908(66)90007-4

DOI:   http://dx.doi.org/10.1016/0028-3908(66)90007-4
   SCHARF ET AL.: "The Effects and Effectiveness of y-Hydroxybutyrate in Patients with Narcolepsy", J. CLIN. PSYCHIATRY, vol. 46, no. 6, 1985, pages 222 - 225
   SCRIMA ET AL.: "Gamma-Hydroxybutyrate Effects on Cataplexy and Sleep Attacks in Narcoleptics", SLEEP RES., vol. 16, 1987, pages 134
   SCRIMA ET AL.: "Efficacy of Gamma-Hydroxybutyrate versus Placebo in Treating NarcolepsyCataplexy: Double-Blind Subjective Measured", BIOL. PSYCHIATRY, vol. 26, 1989, pages 331 - 343, XP025418901, DOI: doi:10.1016/0006-3223(89)90048-6

DOI:   http://dx.doi.org/10.1016/0006-3223(89)90048-6
   SCRIMA ET AL.: "The Effects of y-Hydroxybutyrate on the Sleep of Narcolepsy Patients: A Double-Blind Study", SLEEP, vol. 13, no. 6, 1990, pages 479 - 490
   SERIES ET AL.: "Effects of Enhancing Slow-Wave Sleep by Gamma-Hydroxybutyrate on Obstructive Sleep Apnea", AM. REV. RESPIR. DIS., 1992, pages 1378 - 1383
   SMOLDERS ET AL.: "Tonic GABA-ergic Modulation of Striatal Dopamine Release Studied by In Vivo Microdialysis in the Freely Moving Rat", EUR. J. PHARMACOL., vol. 284, no. 1-2, 1995, pages 83 - 91
   STRONG: "y-Hydroxybutyric Acid and Intracranial Pressure", THE LANCET, vol. 1, no. 8389, 1984
   VAN DEN BOGERT ET AL.: "Placentatransfer of 4-Hydroxybutyric Acid in Man", ANESTHESIOLOGY AND INTENSIVE CARE MEDICINE, vol. 110, 1978, pages 55 - 64
   VICKERS, M.D.: "Gammahydroxybutyric Acid", INT. ANESTH. CLINIC, vol. 7, 1969, pages 75 - 89
   WASZKIELEWICZ ET AL.: "y-Hydrobutyric Acid (GHB) and its Chemical Modifications: A Review of the GHBergic System", POL J PHARMACOL., vol. 56, no. 1, 2004, pages 43 - 49
   WU ET AL.: "-Hydroxybutyric acid (GHB) and y-aminobutyric acids receptor (GABA R) binding sites are distinctive from one another: molecular evidence", NEUROPHARMACOLOGY, vol. 47, no. 8, 2004, pages 1146 - 56, XP004655801, DOI: doi:10.1016/j.neuropharm.2004.08.019

DOI:   http://dx.doi.org/10.1016/j.neuropharm.2004.08.019
   YAMADA ET AL.: "Effect of Butyrolactone and Gamma-Hydroxybutyrate on the EEG and Sleep Cycle in Man", ELECTROENCEPH. CLIN. NEUROPHYSIOL., vol. 22, 1967, pages 558 - 562, XP024292630, DOI: doi:10.1016/0013-4694(67)90064-8

DOI:   http://dx.doi.org/10.1016/0013-4694(67)90064-8
   FERRARA ET AL.: "Pharmacokinetics of Gamma-hydroxybutyric Acid in Alcohol Dependent Patients after Single and Repeated Oral Doses", BR. J. CLIN. PHARMACOL., vol. 34, no. 3, 1992, pages 231 - 5
   ROSENBERG, G.: "The Mechanisms of Action of Valproate in Neuropsychiatric Disorders: Can We See the Forest for the Trees?", CEL. MOL. LIFE SCI., vol. 64, no. 16, 2007, pages 2090 - 2103, XP019536863, DOI: doi:10.1007/s00018-007-7079-x

DOI:   http://dx.doi.org/10.1007/s00018-007-7079-x
   GONZALEZ ET AL.: "Goodman & Gilman's The Pharmacological Basis of Therapeutics", 2006, MCGRAW-HILL, article "Drug Metabolism", pages: 71 - 91
   HENRY, T.R.: "The History of Divalproex in Clinical Neuroscience", PSYCHOPHARMACOLOGY BULLETIN, vol. 37, no. 2, 2003, pages 5 - 16
   AULER ET AL.: "Diclofenac Plasma Protein Binding: PK-PD Modelling in Cardiac Patients Submitted to Cardiopulmonary Bypass", BRAZ. J. MED. BIO. RES., vol. 30, 1997, pages 369 - 374
   HASAN ET AL.: "Pharmacokinetics of Diclofenac Sodium in Normal Man", PAKISTAN JOUR. PHARMACEUTICAL SCIENCES, vol. 18, no. 1, 2005, pages 18 - 24
   HALESTRAP ET AL.: "The SLC16 Gene Family-From Monocarboxylate Transporters (MCTs) to Aromatic Amino Acid Transporters and Beyond", PFLUGERS ARCH., vol. 447, no. 5, 2004, pages 619 - 628
otherUS201313739886
 EP14709858
   ANONYMOUS: "Possible Xyrem side effects in 53 year old male", DRUGLIB.COM, Retrieved from the Internet
   ANONYMOUS: "Lithium Carbonate Tablets USP, Lithium Carbonate Capsules USP, Lithium Oral Solution USP", ROXANE LABORATORIES, INC., October 2011 (2011-10-01)
   ANNA WASZKIELEWICZ, JACEK BOJARSKI: "Gamma-Hydroxybutyric Acid (GHB) and Its Chemical Mdoficiations: A Review of the GHBergic System", POL J PHARMACOL., vol. 56, no. 1, 2004, pages 43 - 49, XP008091834
   INDRANIL BHATTACHARYA, KATHLEEN M.K. BOJE: "Potential -Hydroxybutyric acid (GHB) Drug Interactions Through Blood-Brain Barrier Transport Inhibition: A Pharmacokinetic Simulation-Based Evaluation", J PHARMACOKINET PHARMACODYN., vol. 33, no. 5, 2006, pages 657 - 681, XP019401210

DOI:   http://dx.doi.org/10.1007/s10928-006-9029-x
OppositionUS201361771557
 US201361777873
 US201313837714
 US201313873000
 US201313872997
 WO2014134380
 WO2014134380
 US6780889
   FDA APPROVED LABELING TEXT FOR XYREM ORAL SOLUTION, 18 November 2005 (2005-11-18)
   GEORGE, C.F.P. ; FELDMAN, N. ; INHABER, N. ; STEININGER, T.L. ; GRZESCHIK, S.M. ; LAI, C. ; ZHENG, Y.: "A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing", SLEEP MEDICINE, ELSEVIER, AMSTERDAM, NL, vol. 11, no. 1, 1 January 2010 (2010-01-01), AMSTERDAM, NL, pages 38 - 42, XP026823110, ISSN: 1389-9457
   TOMI SARKANEN, VALTER NIEMEL, ANNE-MARIE LANDTBLOM, MARKKU PARTINEN: "Psychosis in Patients with Narcolepsy as an Adverse Effect of Sodium Oxybate", FRONTIERS IN NEUROLOGY, vol. 5, XP055713476, DOI: 10.3389/fneur.2014.00136

DOI:   http://dx.doi.org/10.3389/fneur.2014.00136
   GOSWAMY: "Sodium Oxybate", NARCOLEPSY A CLINICAL GUIDE, 1 January 2016 (2016-01-01), pages 89, XP055713479
   DANIEL PARDI, BLACK JED: "-Hydroxybutyrate/Sodium Oxybate Neurobiology, and Impact on Sleep and Wakefulness", CNS DRUGS, ADIS INTERNATIONAL, AUCKLAND, NZ, vol. 20, no. 12, 1 December 2006 (2006-12-01), AUCKLAND, NZ, pages 993 - 1018, XP055516866, ISSN: 1172-7047, DOI: 10.2165/00023210-200620120-00004

DOI:   http://dx.doi.org/10.2165/00023210-200620120-00004
   XYREM PACKAGE INSERT IN THE UNITED STATES (CITED BY PATENTEE DURING PROSECUTION
   BOJARSKI J, WASZKIELEWICZ A: "Gamma-Hydroxybutyric Acid (GHB) and Its Chemical Mdoficiations: A Review of the GHBergic System", POLISH JOURNAL OF PHARMACOLOGY, vol. 56, no. 1, 1 January 2004 (2004-01-01), pages 43 - 49, XP008091834, ISSN: 1230-6002
   EMA: "Guideline on the Investigation of Drug Interactions", CPMP/EWP/560/95/REV. 1 CORR., 22 April 2010 (2010-04-22), pages 1 - 38, XP055509801, Retrieved from the Internet [retrieved on 20180925]
   MARILYN E MORRIS: "Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases -Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study", JOURNAL OF CLINICAL TOXICOLOGY, vol. 01, no. 02, XP055713482, DOI: 10.4172/2161-0495.1000105

DOI:   http://dx.doi.org/10.4172/2161-0495.1000105
   SAMUEL A. ROIKO, NISHA VIJAY, MELANIE A. FELMLEE, MARILYN E. MORRIS: "Brain Extracellular -hydroxybutyrate Concentrations are Decreased by L-lactate in Rats: Role in the Treatment of Overdoses", PHARMACEUTICAL RESEARCH, SPRINGER NEW YORK LLC, US, vol. 30, no. 5, 1 May 2013 (2013-05-01), US, pages 1338 - 1348, XP055713484, ISSN: 0724-8741, DOI: 10.1007/s11095-013-0973-z

DOI:   http://dx.doi.org/10.1007/s11095-013-0973-z
   INDRANIL BHATTACHARYA ; KATHLEEN M. K. BOJE: "Potential -Hydroxybutyric acid (GHB) Drug Interactions Through BloodBrain Barrier Transport Inhibition: A Pharmacokinetic Simulation-Based Evaluation", JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS, KLUWER ACADEMIC PUBLISHERS-PLENUM PUBLISHERS, NE, vol. 33, no. 5, 29 August 2006 (2006-08-29), Ne, pages 657 - 681, XP019401210, ISSN: 1573-8744, DOI: 10.1007/s10928-006-9029-x

DOI:   http://dx.doi.org/10.1007/s10928-006-9029-x
   "Xyrem", HIGHLIGHTS OF PRESCRIBING INFORMATION, December 2012 (2012-12-01), XP055744989
   "Highlights of Prescribing Information - Stavzor", NDA 22-152/STAVZOR, July 2008 (2008-07-01), XP055744372
   "Depakene", HIGHLIGHTS OF PRESCRIBING INFORMATION -, February 2013 (2013-02-01), XP055744992
   "Lithium Carbonate Tablets USP", ROXANE LABORATORIES, October 2011 (2011-10-01), XP055516882
   "xyrem 500", PRODUCT INFORMATION
   VAYER, P. ET AL.: "Is the anticonvulsant mechanism of valproate linked to its interaction with the cerebral @c-hydroxybutyrate system", TRENDS IN PHARMACOLOGICAL SCI., vol. 9, no. 4, 1988, pages 127 - 129, XP023855737

DOI:   http://dx.doi.org/10.1016/0165-6147(88)90193-9
   SNEAD, O. C. ET AL.: "Effect of acute and chronic anticonvulsant administration on endogenous -hydroxybutyrate in rat brain", NEUROPHARMACOLOGY, vol. 19, no. 1, 1980, pages 47 - 52, XP055517010

DOI:   http://dx.doi.org/10.1016/0028-3908(80)90165-3
   ELI, M. ET AL.: "Endogenous gamma-Hydroxybutyrate in Rat Brain Areas: Postmortem Changes and Effects of Drugs Interfering with gamma-Aminobutyric Acid Metabolism", J. NEUROCHEM., vol. 41, no. 2, 1983, pages 524 - 530, XP055517246

DOI:   http://dx.doi.org/10.1111/j.1471-4159.1983.tb04770.x
   CASH, C. D.: "Gammahydroxybutyrate: An Overview of the Pros and Cons for it Being a Neurotransmitter And/Or a Useful Therapeutic Agent", NEUROSCI. BEHAV. REV., vol. 18, no. 2, 1994, pages 291 - 304, XP055517014
   LOSCHER, W.: "Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action", PROGRESS NEUROBIOL., vol. 58, 1999, pages 31 - 59, XP055517204

DOI:   http://dx.doi.org/10.1016/S0301-0082(98)00075-6
   EXCERPT FROM KEGG DATABASE (KYOTO ENCYCLOPEDIA OF GENES AND GENOMES, 12 July 2018 (2018-07-12), XP055745021, Retrieved from the Internet
   KAUFMAN, E. E. ET AL.: "An overview of y-hydroxybutyrate catabolism: The role of the cytosolic NADP+-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxiacid transhydrogenase in the initial, rate-limiting step in this pathway", NEUROCHEM. RES., vol. 16, no. 9, 1991, pages 965 - 974, XP008082252

DOI:   http://dx.doi.org/10.1007/BF00965839
   HECHLER, V. ET AL.: "y- Hydroxy butyrate Conversion into GABA InducesDisplacement of GABAb Binding that is Blocked by Valproate and Ethosuximide1", J. PHARMACOL. EXP. THERAP., vol. 281, no. 2, 1997, pages 753 - 760, XP055745030
   WASZKIELEWICZ, A. ET AL.: "Gamma-Hydroxybutyric Acid (GHB) and Its Chemical Mdoficiations: A Review of the GHBergic System", POL. J. PHARMACOL., vol. 56, no. 1, 2004, pages 43 - 49, XP008091834
   KAUFMAN, E.E. ET AL.: "EVIDENCE FOR THE PARTICIPATION OF A CYTOSOLIC NADP-DEPENDENT OXIDOREDUCTASE IN THE CATABOLISM OF GAMMA HYDROXYBUTYRATE IN-VIVO", JOURNAL OF NEUROCHEMISTRY, vol. 48, no. 6, 1987, pages 1935 - 1941, XP002607528
   "Metabolism and distribution of gamma hydroxybutyrate in the brain", GAMMA-HYDROXYBUTYRATE: MOLECULAR, FUNCTIONAL AND CLINICAL ASPECTS, 2002, London, XP055745044
   SHINKA, T. ET AL.: "Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency", J. CHROMATOGR. B., vol. 792, no. 1, 2003, pages 99 - 106, XP004431819

DOI:   http://dx.doi.org/10.1016/S1570-0232(03)00276-9
   MAITRE, M.: "THE GAMMA-HYDROXYBUTYRATE SIGNALLING SYSTEM IN BRAIN: ORGANIZATION AND FUNCTIONAL IMPLICATIONS TI - THE GAMMA-HYDROXYBUTYRATE SIGNALLING SYSTEM IN BRAIN: ORGANIZATION AND FUNCTIONAL IMPLICATIONS", PROG. NEUROBIOL., vol. 51, no. 3, 1997, pages 337 - 361, XP000877100

DOI:   http://dx.doi.org/10.1016/S0301-0082(96)00064-0
   PARDI, D. ET AL.: "-Hydroxybutyrate/Sodium Oxybate Neurobiology, and Impact on Sleep and Wakefulness", CNS DRUGS, vol. 20, no. 12, 2006, pages 993 - 1018, XP055516866

DOI:   http://dx.doi.org/10.2165/00023210-200620120-00004
   ELLER, M. ET AL.: "Evaluation of drug-drug interactions of sodium oxybate with divalproex: Results from a pharmacokinetic/pharmacodynamic study", SLEEP MEDICINE, vol. 14, no. 1, 2013, pages e302 - e303, XP055517276
   ANONYMOUS: "XYREM is an FDA-approved treatment for both cataplexy and EDS in narcolepsy", XYREM, 28 November 2011 (2011-11-28), XP055765881, Retrieved from the Internet
   ANONYMOUS: "XYREM is an FDA-approved treatment for both cataplexy and EDS in narcolepsy", XYREM, 15 December 2012 (2012-12-15), XP055765880, Retrieved from the Internet
   FDA: "Xyrem (sodium oxybate) oral solution CIII", FDA - HIGHLIGHTS OF PRESCRIBING INFORMATION, December 2012 (2012-12-01), pages 1 - 30, XP055765878, Retrieved from the Internet
   MICHEL BILLIARD: "Narcolepsy: Current treatment options and future approaches, Neuropsychiatric Disease and Treatment", NEUROPSYCHIATR DIS TREAT ., vol. 4, no. 3, 6 June 2008 (2008-06-06), pages 557 - 566, XP055765874
   FDA: "Depakote (divalproex sodium) Tablets for Oral use", FDA - HIGHLIGHTS OF PRESCRIBING INFORMATION, February 2013 (2013-02-01), pages 1 - 51, XP055765877
   PARDI, D. ET AL.: "y-Hydroxybutyrate/Sodium Oxybate Neurobiology, and Impact on Sleep and Wakefulness", CNS DRUGS, vol. 20, 2006, pages 993 - 1018, XP055516866, DOI: 10.2165/00023210-200620120-00004

DOI:   http://dx.doi.org/10.2165/00023210-200620120-00004
   ELLER, M. ET AL.: "Evaluation of drug-drug interactions of sodium oxybate with divalproex: Results from a pharmacokinetic/pharmacodynamics study", SLEEP MEDICINE, vol. 14, 2013, pages e302 - e303, XP055517276
   WASZKIELEWICZ, A. ET AL.: "y-Hydroxybutyric Acid (GHB) and its Chemical modifications: A Review of the GHBergic System", POL. J. PHARMACOL., vol. 56, 2004, pages 43 - 49, XP008091834
   VAYER, P. ET AL.: "Is the Anticonvulsant Mechanism of Valproate Linked to its Interaction with the Cerebral gamma-Hydroxybutyrate System?", TRENDS IN PHARMACOL. SCI., vol. 9, no. 4, 1 April 1988 (1988-04-01), pages 127 - 129, XP025843177

DOI:   http://dx.doi.org/10.1016/0165-6147(88)90193-9
   DATABASE KEGG ENZYME 12 July 2018 (2018-07-12), "glucuronate reductase", XP055765873, retrieved from genome Database accession no. 1.1.1.19
   KAUFMAN, E.-E. ET AL.: "An Overview of gamma-Hydroxybutyrate Catabolism: The Role of the Cytosolic NADP+-Dependent Oxidoreductase EC 1.1.1.19 and of a Mitochondrial Hydroxyacid-Oxoacid Transhydrogenase in the Initial, Rate-Limiting Step in This Pathway", NEUROCHEM. RES., vol. 16, no. 9, 1 January 1991 (1991-01-01), pages 965 - 974, XP008082252

DOI:   http://dx.doi.org/10.1007/BF00965839
   ELI, M. ET AL.: "Endogenous gamma-Hydroxybutyrate in Rat Brain Areas: Postmortem Changes and Effects of Drugs Interfering with gamma-Aminobutyric Acid Metabolism", J. NEUROCHEM., vol. 41, 1983, pages 524 - 530, XP055517246, DOI: 10.1111/j.1471-4159.1983.tb04770.x

DOI:   http://dx.doi.org/10.1111/j.1471-4159.1983.tb04770.x
   SNEAD, O.-D. ET AL.: "Effect of Acute and Chronic Anticonvulsant Administration on Endogenous gamma-Hydroxybutyrate in Rat Brain", NEUROPHARMACOLOGY, vol. 19, 1979, pages 47 - 52, XP055517010, DOI: 10.1016/0028-3908(80)90165-3

DOI:   http://dx.doi.org/10.1016/0028-3908(80)90165-3
   CASH, C.-D.: "Gammahydroxybutyrate: An Overview of the Pros and Cons for it being a Neurotransmitter and/or a Useful Therapeutic Agent", NEUROSCI. BEHAV. REV., vol. 18, 1994, pages 291 - 304, XP055517014
   "Xyrem (sodium oxybate) oral solution CIII", FDA - HIGHLIGHTS OF PRESCRIBING INFORMATION, December 2012 (2012-12-01), XP055765878
   KOTHARE ET AL.: "Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate", CLINICAL MEDICINE INSIGHTS, THERAPEUTICS, vol. 2, 2010, pages 37 - 52, XP055516920
   "XYREM (sodium oxybate) oral solution", September 2016 (2016-09-01), XP055770970
   "Xyrem (sodium oxybate) oral solution", FDA APPROVED LABELING, November 2005 (2005-11-01), XP055770975
   GEORGE ET AL.: "A safety trial of sodium oxybate in patients with obstructive sleep apnea: acute effect on sleep-disordered breathing", SLEEP MEDICINE, vol. 11, 2010, pages 38 - 42, XP026823110
   SARKANEN ET AL.: "Psychosis in patients with narcolepsy as an adverse effect of sodium oxybate", FRONTIERS IN NEUROLOGY, vol. 5, 2014, XP055713476

DOI:   http://dx.doi.org/10.3389/fneur.2014.00136
   FULLER ET AL.: "From Club Drug to Orphan Drug: Sodium Oxybate Xyrem for the Treatment of Cataplexy", PHARMACOTHERAPY, vol. 23, no. 9, 2003, pages 1205 - 1209, XP055123175
   PARDI ET AL.: "y-Hydroxybutyrate/Sodium Oxybate", CNS DRUGS, vol. 20, no. 12, 2006, pages 993 - 1018, XP055516866, DOI: 10.2165/00023210-200620120-00004

DOI:   http://dx.doi.org/10.2165/00023210-200620120-00004
   "Xyrem 500 mg/mL oral solution", SUMMARY OF PRODUCT CHARACTERISTICS
   WASZKIELEWISCZ ET AL.: "y-Hydroxybutyric acid (GHb) and its chemical modifications: a review of the GHBergic system", POLISH JOURNAL OF PHARMACOLOGY, vol. 56, 2004, pages 43 - 49, XP008091834
   MAITRE: "The y-Hydroxybutyrate signaling system in brain: organization and functional implications", PROGRESS IN NEUROBIOLOGY, vol. 51, 1997, pages 337 - 361, XP000877100

DOI:   http://dx.doi.org/10.1016/S0301-0082(96)00064-0
   "Guidelines on the investigation of drug interactions", EUROPEAN MEDICINES AGENCY EMA,, 2012, XP055770989
   ANONYMOUS: "Important safety information Xyrem", XYREM.COM, 19 February 2013 (2013-02-19), XP055970231, Retrieved from the Internet [retrieved on 20221012]
   ANONYMOUS: "Information about Xyrem.com", WHOIS LOOKUP, 9 November 2000 (2000-11-09), XP055970235, [retrieved on 20221012]
   ANONYMOUS: "PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION FOR XYREM", XYREM, 11 June 2018 (2018-06-11), XP055970240, [retrieved on 20221012]
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.