Extract from the Register of European Patents

About this file: EP3269736

StatusThe patent has been granted
Status updated on  25.10.2019
Database last updated on 23.01.2020
FormerGrant of patent is intended
Status updated on  12.06.2019
FormerExamination is in progress
Status updated on  16.11.2018
FormerRequest for examination was made
Status updated on  29.06.2018
FormerThe application has been published
Status updated on  15.12.2017
Most recent event   Tooltip25.10.2019(Expected) grantpublished on 27.11.2019  [2019/48]
Applicant(s)For all designated states
Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin
Robert-Koch-Strasse 40
37075 Göttingen / DE
Inventor(s)01 / Bayer, Thomas
Über den Bühwiesen 2d
37083 Göttingen / DE
Representative(s)Wichmann, Hendrik
Wuesthoff & Wuesthoff
Patentanwälte PartG mbB
Schweigerstraße 2
81541 München / DE
Application number, filing date17185247.808.05.2013
Priority number, dateEP2012016756510.05.2012         Original published format: EP 12167565
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report 
Type: B1 Patent specification 
Search report(s)(Supplementary) European search report - dispatched on:EP13.10.2017
ClassificationInternational:C07K16/18, G01N33/68
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 [2018/31]
Former [2018/03]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 
Biological materialThis application mentions deposited biological material, check the file for details
Examination procedure08.08.2017Date on which the examining division has become responsible
22.06.2018Amendment by applicant (claims and/or description)
22.06.2018Examination requested  [2018/31]
19.11.2018Despatch of a communication from the examining division (Time limit: M04)
08.03.2019Reply to a communication from the examining division
20.03.2019Despatch of a communication from the examining division (Time limit: M02)
20.05.2019Reply to a communication from the examining division
21.06.2019Communication of intention to grant the patent
21.10.2019Fee for grant paid
21.10.2019Fee for publishing/printing paid
21.10.2019Receipt of the translation of the claim(s)
Parent application(s)   TooltipEP13724769.8  / EP2847217
Fees paidRenewal fee
08.08.2017Renewal fee patent year 03
08.08.2017Renewal fee patent year 04
08.08.2017Renewal fee patent year 05
28.05.2018Renewal fee patent year 06
30.05.2019Renewal fee patent year 07
Documents cited:Search[XYI]WO2009065054  (UNIV ROCKEFELLER [US], et al) [X] 1,3,6,7,13-15 * examples 3-6 * * figure 5 * * claim - * [Y] 4,5,9,11 [I] 2,8,10,12;
 [Y]  - X. WANG ET AL., "Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers.", FEBS LETTERS, The Netherlands, (20090204), vol. 583, no. 3, pages 579 - 584, XP025923244 [Y] 4,5,9,11 * abstract * * results *

DOI:   http://dx.doi.org/10.1016/j.febslet.2008.12.064
 [A]  - Y. KIM ET AL., "Development of conformation-specific antibodies for neutralization of beta-amyloid oligomers.", NEUROBIOLOGY OF AGING, USA, (20040701), vol. 25, page S145, XP027081976 [A] 1-15 * abstract P1-175 *
 [AD]  - O. WIRTHS ET AL., "Identification of low molecular weight pyroglutamate Abeta oligomers in Alzheimer disease.", JOURNAL OF BIOLOGICAL CHEMISTRY, USA, (20101231), vol. 285, no. 53, pages 41517 - 41524, XP002658320 [AD] 1-15 * abstract * * results *

DOI:   http://dx.doi.org/10.1074/JBC.M110.178707
by applicantWO2011151076
    - KANG et al., Nature, (19870000), vol. 325, pages 733 - 736
    - TANZI et al., Science, (19870000), vol. 235, pages 880 - 884
    - HAASS; SELKOE, Nat Rev Mol Cell Biol, (20070000), vol. 8, pages 101 - 112
    - ONO et al., Proc. Natl. Acad. Sci., (20090000), vol. 106, pages 14745 - 14750
    - WIRTHS et al., J Neurochem, (20040000), vol. 91, pages 513 - 520
    - KAYED et al., Science, (20030000), vol. 300, pages 486 - 489
    - KLYUBIN et al., Nat Med, (20050000), vol. 11, pages 556 - 561
    - WALSHET, Biochemistry, (20000000), vol. 39, pages 10831 - 10839
    - WALSH et al., Nature, (20020000), vol. 416, pages 535 - 539
    - KLYUBIN et al., J. Neurosci., (20080000), vol. 28, pages 4231 - 4237
    - HAMPEL et al., Nat Rev Drug Discov, (20100000), vol. 9, pages 560 - 574
    - FUKUMOTO et al., Faseb J, (20100000), vol. 24, pages 2716 - 2726
    - WITTNAM et al., Journal of Biological Chemistry, (20120000), vol. 287, pages 8154 - 8162
    - WIRTHS et al., J. Biol. Chem., (20100000), vol. 285, pages 41517 - 41524
    - WANG et al., FEBS Letters, (20090000), vol. 583, pages 579 - 584
    - KIM et al., Neurobiology of Aging, (20040000), vol. 25, page S145
    - KOHLER, G. et al., Nature, (19750000), vol. 256, page 495
    - BITTER et al., Methods in Enzymology, (19870000), vol. 153, pages 516 - 544
    - SAWERS et al., Applied Microbiology and Biotechnology, (19960000), vol. 46, pages 1 - 9
    - BILLMAN-JACOBE, Current Opinion in Biotechnology, (19960000), vol. 7, pages 500 - 4
    - HOCKNEY, Trends in Biotechnology, (19940000), vol. 12, pages 456 - 463
    - GRIFFITHS et al., Methods in Molecular Biology, (19970000), vol. 75, pages 427 - 440
    - COLOMA et al., J. Imm. Methods, (19920000), vol. 152, pages 89 - 104
    - GURTU et al., Biochem. Biophys. Res. Comm., (19960000), vol. 229, pages 295 - 298
    - WIRTHS et al., J. Neural Transm., (20100000), vol. 117, pages 85 - 96
    - CASAS et al., Am. J. Pathol., (20040000), vol. 165, pages 1289 - 1300
    - JAWHAR et al., Neurobiol. Aging, (20120000), vol. 33
    - BUCHHAVE, P.; MINTHON, L.; ZETTERBERG, H.; WALLIN, A. K.; BLENNOW, K.; HANSSON, O., Cerebrospinal Fluid Levels of {beta}-Amyloid, (20120000), pages 1 - 42
    - TAU, "Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer's Dementia", Arch Gen Psychiatry, vol. 69, pages 98 - 106
    - CASAS, C.; SERGEANT, N.; ITIER, J. M.; BLANCHARD, V.; WIRTHS, O.; VAN DER KOLK, N.; VINGTDEUX, V.; VAN DE STEEG, E.; RET, G.; CANT, "Massive CA1/2 Neuronal Loss with Intraneuronal and N-Terminal Truncated A{beta}42 Accumulation in a Novel Alzheimer's Transgenic Model", Am. J. Pathol., (20040000), vol. 165, pages 1289 - 1300
    - FUKUMOTO, H.; TOKUDA, T.; KASAI, T.; ISHIGAMI, N.; HIDAKA, H.; KONDO, M.; ALLSOP, D.; NAKAGAWA, M., "High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer's patients", Faseb, (20100000), vol. 24, doi:doi:10.1096/fj.09-150359, pages 2716 - 2726, XP002664693

DOI:   http://dx.doi.org/10.1096/fj.09-150359
    - HAASS, C.; SELKOE, D. J., "Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid [beta]-peptide", Nat Rev Mol Cell Biol, (20070000), vol. 8, doi:doi:10.1038/NRM2101, pages 101 - 112, XP002545389

DOI:   http://dx.doi.org/10.1038/NRM2101
    - HAMPEL, H.; FRANK, R.; BROICH, K.; TEIPEL, S. J.; KATZ, R. G.; HARDY, J.; HERHOLZ, K.; BOKDE, A. L. W.; JESSEN, F.; HOESSLER, Y. C, "Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives", Nat Rev Drug Discov, (20100000), vol. 9, pages 560 - 574
    - JAGER, S.; LEUCHTENBERGER, S.; MARTIN, A.; CZIRR, E.; WESSELOWSKI, J.; DIECKMANN, M.; WALDRON, E.; KORTH, C.; KOO, E. H.; HENEKA,, "alpha-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Abeta generation", J Neurochem, (20090000), vol. 111, pages 1369 - 1382
    - JAWHAR, S.; TRAWICKA, A.; JENNECKENS, C.; BAYER, T. A.; WIRTHS, O., "Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Abeta aggregation in the 5XFAD mouse model of Alzheimer's disease", Neurobiol. Aging, (20120000), vol. 33
    - KANG, J.; LEMAIRE, H. G.; UNTERBECK, A.; SALBAUM, J. M.; MASTERS, C. L.; GRZESCHIK, K. H.; MULTHAUP, G.; BEYREUTHER, K.; MUELLER-H, "The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor", Nature, (19870000), vol. 325, pages 733 - 736
    - KAYED, R.; HEAD, E.; THOMPSON, J. L.; MCINTIRE, T. M.; MILTON, S. C.; COTMAN, C. W.; GLABE, C. G., "Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis", Science, (20030000), vol. 300, pages 486 - 489
    - KIM, Y. S.; MOSS, J. A.; JANDA, K. D., "Development of Conformation-specific Antibodies for Neutralization of (B-Amyloid Oligomers", Neurobiology of Aging, (20040000), vol. 25, doi:doi:10.1016/S0197-4580(04)80488-3, page S145, XP004625102

DOI:   http://dx.doi.org/10.1016/S0197-4580(04)80488-3
    - KLYUBIN, I.; BETTS, V.; WELZEL, A. T.; BLENNOW, K.; ZETTERBERG, H.; WALLIN, A.; LEMERE, C. A.; CULLEN, W. K.; PENG, Y.; WISNIEWSKI, "Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization", J. Neurosci., (20080000), vol. 28, doi:doi:10.1523/JNEUROSCI.5161-07.2008, pages 4231 - 4237, XP055231488

DOI:   http://dx.doi.org/10.1523/JNEUROSCI.5161-07.2008
    - KLYUBIN, I.; WALSH, D. M.; LEMERE, C. A.; CULLEN, W. K.; SHANKAR, G. M.; BETTS, V.; SPOONER, E. T.; JIANG, L.; ANWYL, R.; SELKOE,, "Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo", Nat Med, (20050000), vol. 11, doi:doi:10.1038/NM1234, pages 556 - 561, XP002545388

DOI:   http://dx.doi.org/10.1038/NM1234
    - A Laboratory Course Manual, Cold Spring Harbor Laboratory Press, (19900000), vol. Methods
    - MORRIS, R., "Developments of a water-maze procedure for studying spatial learning in the rat", J. Neurosci. Methods, (19840000), vol. 11, doi:doi:10.1016/0165-0270(84)90007-4, pages 47 - 60, XP024322669

DOI:   http://dx.doi.org/10.1016/0165-0270(84)90007-4
    - OAKLEY, H.; COLE, S.L.; LOGAN, S.; MAUS, E.; SHAO, P.; CRAFT, J.; GUILLOZET-BONGAARTS, A.; OHNO, M.; DISTERHOFT, J.; VAN ELDIK, L., "Intraneuronal beta-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation", J. Neurosci., (20060000), vol. 26, doi:doi:10.1523/JNEUROSCI.1202-06.2006, pages 10129 - 10140, XP002688009

DOI:   http://dx.doi.org/10.1523/​JNEUROSCI.1202-06.2006
    - ONO, K.; CONDRON, M. M.; TEPLOW, D. B., "Structure-neurotoxicity relationships of amyloid β-protein oligomers", Proc. Natl. Acad. Sci., (20090000), vol. 106, doi:doi:10.1073/PNAS.0905127106, pages 14745 - 14750, XP002657969

DOI:   http://dx.doi.org/10.1073/PNAS.0905127106
    - PILLOT T et al., "The Nonfibrillar Amyloid β-Peptide Induces Apoptotic Neuronal Cell Death", J. Neurochem., (19990000), vol. 73, no. 4, pages 1626 - 1634, XP009151628
    - PORTELIUS, E.; BOGDANOVIC, N.; GUSTAVSSON, M. K.; VOLKMANN, I.; BRINKMALM, G.; ZETTERBERG, H.; WINBLAD, B.; BLENNOW, K., "Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer's disease", Acta Neuropathol, (20100000), vol. 120, pages 185 - 193, XP019847010
    - TANZI, R. E.; GUSELLA, J. F.; WATKINS, P. C.; BRUNS, G. A. P.; ST.GEORGE-HYSLOP, P. H.; VAN KEUREN, M. L.; PATTERSON, D.; PAGAN, S, "The amyloid 6 protein gene: cDNA cloning, mRNA distribution, and genetic linkage near the Alzheimer's locus", Science, (19870000), vol. 235, pages 880 - 884
    - VORHEES, C.V.; WILLIAMS, M.T., "Morris water maze: procedures for assessing spatial and related forms of learning and memory", Nat. Protoc., (20060000), vol. 1, pages 848 - 858
    - WALSH, D. M.; KLYUBIN, I.; FADEEVA, J. V.; CULLEN, W. K.; ANWYL, R.; WOLFE, M. S.; ROWAN, M. J.; SELKOE, D. J., "Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo", Nature, (20020000), vol. 416, doi:doi:10.1038/416535a, pages 535 - 539, XP002348771

DOI:   http://dx.doi.org/10.1038/416535a
    - WALSH, D. M.; TSENG, B. P.; RYDEL, R. E.; PODLISNY, M. B.; SELKOE, D. J., "The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain", Biochemistry, (20000000), vol. 39, pages 10831 - 10839
    - WANG, X.; ZHANG, J.; WANG, Y.; FENG, Y.; ZHANG, X.; SUN, X.; LI, J.; DU, X.; LAMBERT, M. P.; YANG, S., "Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers", FEBS Letters, (20090000), vol. 583, doi:doi:10.1016/j.febslet.2008.12.064, pages 579 - 584, XP025923244

DOI:   http://dx.doi.org/10.1016/j.febslet.2008.12.064
    - WIRTHS, 0.; BETHGE, T.; MARCELLO, A.; HARMEIER, A.; JAWHAR, S.; LUCASSEN, P. J.; MULTHAUP, G.; BRODY, D. L.; ESPARZA, T.; INGELSSO, "Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases", J. Neural Transm., (20100000), vol. 117, pages 85 - 96, XP019783126
    - WIRTHS, 0.; ERCK, C.; MARTENS, H.; HARMEIER, A.; GEUMANN, C.; JAWHAR, S.; KUMAR, S.; MULTHAUP, G.; WALTER, J.; INGELSSON, M., "Identification of low molecular weight pyroglutamate Abeta oligomers in Alzheimer's disease: a novel tool for therapy and diagnosis", J. Biol. Chem., (20100000), vol. 285, doi:doi:10.1074/JBC.M110.178707, pages 41517 - 41524, XP002658320

DOI:   http://dx.doi.org/10.1074/JBC.M110.178707
    - WIRTHS, 0.; MULTHAUP, G.; BAYER, T. A., "A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide - the first step of a fatal cascade", J Neurochem, (20040000), vol. 91, pages 513 - 520
    - WITTNAM, J. L.; PORTELIUS, E.; ZETTERBERG, H.; GUSTAVSSON, M. K.; SCHILLING, S.; KOCH, B.; DE-MUTH, H.-U.; BLENNOW, K.; WIRTHS, O., "Pyroglutamate Amyloid β (Aβ) Aggravates Behavioral Deficits in Transgenic Amyloid Mouse Model for Alzheimer's Disease", Journal of Biological Chemistry, (20120000), vol. 287, doi:doi:10.1074/jbc.M111.308601, pages 8154 - 8162, XP055210664

DOI:   http://dx.doi.org/10.1074/jbc.M111.308601
    - YOUSSEF I et al., "N-truncated amy oid-β oligomers induce learning impairment and neuronal apoptosis", Neurobiof. Aging, (20080000), vol. 29, no. 9, pages 1319 - 1333