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Extract from the Register of European Patents

EP About this file: EP2297207

EP2297207 - USE OF ANTI-FACTOR XI ANTIBODIES FOR PREVENTION OR TREATMENT OF THROMBUS FORMATION [Right-click to bookmark this link]
Former [2011/12]USE OF ANTI-FACTORS XI ANTIBODIES FOR PREVENTION OF THROMBUS FORMATION
[2018/15]
StatusPatent revoked
Status updated on  27.07.2024
Database last updated on 20.12.2024
FormerThe patent has been granted
Status updated on  31.08.2018
FormerGrant of patent is intended
Status updated on  25.04.2018
FormerExamination is in progress
Status updated on  17.02.2017
Most recent event   Tooltip02.08.2024Revocation of patentpublished on 04.09.2024  [2024/36]
Applicant(s)For all designated states
Prothix BV
Warmonderweg 23
2334 AB Leiden / NL
[2011/12]
Inventor(s)01 / Hack, Erik
Paulus Emtinckweg 40
NL-1111 BV Diemen / NL
 [2011/12]
Representative(s)Nederlandsch Octrooibureau
P.O. Box 29720
2502 LS The Hague / NL
[2013/28]
Former [2011/12]van Westenbrugge, Andries
Nederlandsch Octrooibureau J.W. Frisolaan 13
2517 JS Den Haag / NL
Application number, filing date09766879.219.06.2009
[2011/12]
WO2009NL50361
Priority number, dateUS20080073882P19.06.2008         Original published format: US 73882 P
[2011/12]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report
No.:WO2009154461
Date:23.12.2009
Language:EN
[2009/52]
Type: A1 Application with search report 
No.:EP2297207
Date:23.03.2011
Language:EN
The application published by WIPO in one of the EPO official languages on 23.12.2009 takes the place of the publication of the European patent application.
[2011/12]
Type: B1 Patent specification 
No.:EP2297207
Date:03.10.2018
Language:EN
[2018/40]
Search report(s)International search report - published on:EP23.12.2009
ClassificationIPC:A61K39/395, C07K14/745, C07K16/36
[2018/15]
CPC:
C07K16/36 (EP,US); A61P7/02 (EP); A61P9/10 (EP);
A61K2039/505 (EP,US); C07K2317/76 (EP,US)
Former IPC [2011/12]C07K16/36
Designated contracting statesAT,   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,   SE,   SI,   SK,   TR [2018/40]
Former [2011/12]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,  SE,  SI,  SK,  TR 
TitleGerman:VERWENDUNG VON ANTIKÖRPERN GEGEN GERINNUNGSFAKTOR XI ZUR VORBEUGUNG ODER BEHANDLUNG VON THROMBOSEN[2018/15]
English:USE OF ANTI-FACTOR XI ANTIBODIES FOR PREVENTION OR TREATMENT OF THROMBUS FORMATION[2018/15]
French:UTILISATION D ANTICORPS ANTI-FACTEURS XI POUR PRÉVENIR LA FORMATION DE THROMBUS[2011/12]
Former [2011/12]VERWENDUNG VON ANTIKÖRPERN GEGEN ANTIFAKTOREN XI ZUR PRÄVENTION EINER THROMBUSBILDUNG
Former [2011/12]USE OF ANTI-FACTORS XI ANTIBODIES FOR PREVENTION OF THROMBUS FORMATION
Entry into regional phase15.12.2010National basic fee paid 
15.12.2010Designation fee(s) paid 
15.12.2010Examination fee paid 
Examination procedure15.12.2010Examination requested  [2011/12]
04.03.2011Amendment by applicant (claims and/or description)
23.07.2015Despatch of a communication from the examining division (Time limit: M06)
20.01.2016Reply to a communication from the examining division
18.05.2016Despatch of a communication from the examining division (Time limit: M04)
21.09.2016Reply to a communication from the examining division
08.02.2017Despatch of a communication from the examining division (Time limit: M04)
08.06.2017Reply to a communication from the examining division
29.06.2017Despatch of a communication from the examining division (Time limit: M02)
31.07.2017Observations by third parties
24.08.2017Reply to a communication from the examining division
31.08.2017Observations by third parties
15.09.2017Despatch of a communication from the examining division (Time limit: M02)
24.11.2017Reply to a communication from the examining division
21.12.2017Observations by third parties
26.04.2018Communication of intention to grant the patent
20.08.2018Fee for grant paid
20.08.2018Fee for publishing/printing paid
20.08.2018Receipt of the translation of the claim(s)
Divisional application(s)The date of the Examining Division's first communication in respect of the earliest application for which a communication has been issued is  23.07.2015
Opposition(s)Opponent(s)01  02.07.2019  05.07.2019  ADMISSIBLE
Mathys & Squire LLP
The Shard
32 London Bridge Street
London SE1 9SG / GB
Opponent's representative
Ford, Hazel
Mathys & Squire The Shard
32 London Bridge Street
London SE1 9SG / GB
 [2021/10]
Former [2019/32]
Opponent(s)01  02.07.2019    ADMISSIBLE
Mathys & Squire
The Shard
32 London Bridge Street
London SE1 9SG / GB
Opponent's representative
Ford, Hazel
Mathys & Squire LLP The Shard
32 London Bridge Street
London SE1 9SG / GB
17.07.2019Invitation to proprietor to file observations on the notice of opposition
27.11.2019Reply of patent proprietor to notice(s) of opposition
15.05.2020Despatch of a communication from the opposition division (Time limit: M04)
25.09.2020Reply to a communication from the opposition division
03.02.2022Date of oral proceedings
03.03.2022Despatch of interlocutory decision in opposition
03.03.2022Despatch of minutes of oral proceedings
25.07.2024Legal effect of revocation of patent [2024/36]
25.07.2024Despatch of communication that the patent will be revoked
Appeal following opposition05.05.2022Appeal received No.  T1103/22
05.05.2022Payment of appeal fee
13.07.2022Statement of grounds filed
20.06.2024Result of appeal procedure: revocation of the patent
25.07.2024Despatch of the decision of the Board of Appeal
Fees paidRenewal fee
31.05.2011Renewal fee patent year 03
31.05.2012Renewal fee patent year 04
31.05.2013Renewal fee patent year 05
02.06.2014Renewal fee patent year 06
29.05.2015Renewal fee patent year 07
31.05.2016Renewal fee patent year 08
31.05.2017Renewal fee patent year 09
06.06.2018Renewal fee patent year 10
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  TooltipAT03.10.2018
CY03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
MC03.10.2018
MK03.10.2018
MT03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
LU19.06.2019
[2022/31]
Former [2021/34]AT03.10.2018
CY03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
MC03.10.2018
MT03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
LU19.06.2019
Former [2021/26]AT03.10.2018
CY03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
MC03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
LU19.06.2019
Former [2020/27]AT03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
MC03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
LU19.06.2019
Former [2020/08]AT03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
MC03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
Former [2019/50]AT03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
SI03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
Former [2019/40]AT03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
SK03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
Former [2019/37]AT03.10.2018
CZ03.10.2018
EE03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
Former [2019/26]AT03.10.2018
CZ03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
PT03.02.2019
Former [2019/24]AT03.10.2018
CZ03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
BG03.01.2019
NO03.01.2019
GR04.01.2019
IS03.02.2019
Former [2019/23]AT03.10.2018
CZ03.10.2018
FI03.10.2018
LT03.10.2018
LV03.10.2018
BG03.01.2019
NO03.01.2019
IS03.02.2019
Former [2019/22]CZ03.10.2018
FI03.10.2018
LT03.10.2018
BG03.01.2019
NO03.01.2019
IS03.02.2019
Former [2019/21]FI03.10.2018
LT03.10.2018
NO03.01.2019
IS03.02.2019
Former [2019/20]LT03.10.2018
NO03.01.2019
Cited inInternational search[PX]WO2009067660  (UNIV OREGON HEALTH & SCIENCE [US], et al) [PX] 1-14 * the whole document *;
 [X]  - GRUBER ANDRAS ET AL, "Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, (20030801), vol. 102, no. 3, ISSN 0006-4971, pages 953 - 955, XP002526372 [X] 1-14 * the whole document *

DOI:   http://dx.doi.org/10.1182/blood-2003-01-0324
 [X]  - TUCKER ERIK I ET AL, "Inhibition of factor XI decreases thrombin production and prevents vascular occlusion in experimental thrombosis in primates", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, (20071211), vol. 110, no. 11, Part 1, ISSN 0006-4971, page 235A, XP009116108 [X] 1-14 * the whole document *
 [X]  - GRUBER ANDRAS ET AL, "Antithrombotic factor XI antibody inhibition of the intrinsic pathway", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, (20011211), vol. 98, no. 11 Part 1, ISSN 0006-4971, page 42a, XP009116110 [X] 1-14 * the whole document *
 [A]  - SUN YUEHUI ET AL, "Identification of a factor IX binding site on the third apple domain of activated factor XI", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOCHEMICAL BIOLOGISTS, BIRMINGHAM, US, (19960101), vol. 271, no. 46, ISSN 0021-9258, pages 29023 - 29028, XP002435764 [A] 1-14 * the whole document *

DOI:   http://dx.doi.org/10.1074/jbc.271.46.29023
ExaminationWO2017162791
 WO2016207858
    - Sinha ET AL, "Functional characterization of human blood coagulation factor XIa using hybridoma antibodies.", Journal of Biological Chemistry, (19850901), vol. 260, no. 19, ISSN 0021-9258, pages 10714 - 10719, XP055072113
    - BAGLIA F A ET AL, "A binding site for thrombin in the apple 1 domain of factor XI", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, (19960216), vol. 271, no. 7, doi:10.1074/JBC.271.7.3652, ISSN 0021-9258, pages 3652 - 3658, XP002368765

DOI:   http://dx.doi.org/10.1074/jbc.271.7.3652
    - Dipali Sinha ET AL, "Macromolecular Substrate-Binding Exosites on Both the Heavy and Light Chains of Factor XIa Mediate the Formation of the Michaelis Complex Required for Factor IX-Activation +", Biochemistry, (20070801), vol. 46, no. 34, doi:10.1021/bi062296c, ISSN 0006-2960, pages 9830 - 9839, XP055202101

DOI:   http://dx.doi.org/10.1021/bi062296c
    - T. RENNE ET AL, "Characterization of the H-kininogen-binding Site on Factor XI: A COMPARISON OF FACTOR XI AND PLASMA PREKALLIKREIN", JOURNAL OF BIOLOGICAL CHEMISTRY, (20011130), vol. 277, no. 7, doi:10.1074/jbc.M105221200, ISSN 0021-9258, pages 4892 - 4899, XP055202244

DOI:   http://dx.doi.org/10.1074/jbc.M105221200
    - HIDEKI AKIYAMA ET AL, "Mechanism of Activation of Coagulation Factor Xi by Factor Xlla Studied with Monoclonal Antibodies", J. CLIN. INVEST., (19861201), vol. 78, pages 1631 - 1637, XP055267640
    - A. Yamashita ET AL, "Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery", Journal of Thrombosis and Haemostasis, (20060701), vol. 4, no. 7, doi:10.1111/j.1538-7836.2006.01973.x, ISSN 1538-7933, pages 1496 - 1501, XP055025684

DOI:   http://dx.doi.org/10.1111/j.1538-7836.2006.01973.x
other   - White Book, vol. II
OppositionWO2017162791
 US4963657
    - GOLDSMITH et al., "Inhibitors of plasma thromboplastin antecedent (factor XI): studies on mechanism of inhibition", J Lab Clin Med, (19850100), vol. 106, no. 3, pages 279 - 285, XP009509394
    - MINNEMA et al., "ENHANCEMENT OF RABBIT JUGULAR VEIN THROMBOLYSIS BY NEUTRALIZATION OF FACOR XI IN VIVO EVIDENCE FOR A ROLE OF FACTOR XI AS AN ANTI-FIBRINOLYTIC FACTOR", Journal of Clinical Investigation, (19980100), vol. 101, no. 1, pages 10 - 14, XP001018094

DOI:   http://dx.doi.org/10.1172/JCI781
    - YAMASHITA et al., "Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery", Journal of Thrombosis and Haemostasis, (20060700), vol. 4, no. 7, pages 1496 - 1501, XP055025684

DOI:   http://dx.doi.org/10.1111/j.1538-7836.2006.01973.x
    - SINHA et al., "Functional characterization of human blood coagulation factor XIa using hybridoma antibodies", The Journal of Biological Chemistry, (19850900), vol. 260, no. 19, pages 10714 - 10719, XP055072113
    - PAPAGRIGORIOU et al., "Crystal structure of the factor XI zymogen reveals a pathway for transactivation", Nature Structural & Molecular Biology, (20060600), vol. 13, no. 6, pages 557 - 558, XP055621547

DOI:   http://dx.doi.org/10.1038/nsmb1095
    - WONG et al., "A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain", Blood, (20160000), vol. 127, pages 2915 - 2923, XP055621544

DOI:   http://dx.doi.org/10.1182/blood-2015-10-
    - EMSLEY et al., "Structure and function of factor XI", Blood, (20100401), vol. 115, no. 13, pages 2569 - 2577, XP055121321

DOI:   http://dx.doi.org/10.1182/blood-2009-09-199182
    - FUJIKAWA et al., "Amino Acid Sequence of Human Factor XI, a Blood Coagulation Factor with Four Tandem Repeats That Are Highly Homologous with Plasma Prekallikrein", Biochemistry, (19860501), vol. 25, no. 9, pages 2417 - 2424, XP001317126
    - JIN et al., "Crystal Structures of the FXIa Catalytic Domain in Complex with Ecotin Mutants Reveal Substrate-like Interactions*", J Biol Chem, (20050211), vol. 280, no. 6, pages 4704 - 4712, XP055121414

DOI:   http://dx.doi.org/10.1074/jbc.M411309200
    - NAVANEETHAM et al., "Structural and Mutational Analyses of the Molecular Interactions between the Catalytic Domain of Factor Xia and the Kunitz Protease Inhibitor Domain of Protease Nexin 2", J Biol Chem, (20050866), vol. 280, no. 43, pages 36165 - 36175, XP055521676

DOI:   http://dx.doi.org/10.1074/jbc.M504990200
    - JIN et al., "Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors", Acta Crystallogr D Biol Crystallogr, (20051000), vol. 61, no. Pt 10, pages 1418 - 1425, XP055621602

DOI:   http://dx.doi.org/10.1107/S0907444905024340
    - MOHAMMED et al., "An Update on Factor XI Structure and Function", Thromb Res, (20180100), vol. 161, pages 94 - 105, XP085320857

DOI:   http://dx.doi.org/10.1016/j.thromres.2017.10.008
    - Anonymous, "2F83 structure", RCSB Protein Data Bank, (20060516), URL: http://www.rcsb.orq/structure/2F83, XP055621609
    - Anonymous, "1ZHR structure", RCSB Protein Data Bank, (20050920), URL: http://www.rcsb.orq/structure/1ZHR, XP055621611
    - WU et al., "Structural insight into distinct mechanisms of protease inhibition by antibodies", Proc Natl Acad Sci USA, (20071211), vol. 104, no. 50, pages 19784 - 19789, XP009141928

DOI:   http://dx.doi.org/10.1073/pnas.0708251104
    - AL-HORANI et al., "Designing Allosteric Inhibitors of Factor Xia. Lessons from the Interactions of Sulfated Pentagalloylglucopyranosides", Journal of Medicinal Chemistry, (20140529), vol. 57, no. 111, pages 4805 - 4818, XP055521602

DOI:   http://dx.doi.org/10.1021/jm500311e
    - ARGADE et al., "Allosteric Inhibition of Human Factor Xia: Discovery of Monosulfated Benzofurans as a Class of Promising Inhibitors", Journal of Medicinal Chemistry, (20140424), vol. 57, no. 8, pages 3559 - 3569, XP055621615

DOI:   http://dx.doi.org/10.1021/jm5002698
    - SU et al., "The Role of Factor Xia (FXla) Catalytic Domain Exosite Residues in Substrate Catalysis and Inhibition by the Kunitz Protease Inhibitor Domain of Protease Nexin 2*[", The Journal of Biological Chemistry, (20110909), vol. 286, no. 36, pages 31904 - 31914, XP055621617

DOI:   http://dx.doi.org/10.1074/jbc.M111.257527
    - SCOTT et al., "Amidolytic Assay of Human Factor XI in Plasma: Comparison With a Coagulant Assay and a New Rapid Radioimmunoassay", Blood, (19840100), vol. 63, no. 1, pages 42 - 50, XP000999510
    - SUN et al., The Journal of Biological Chemistry, (19960100), vol. 271, no. 46, pages 29023 - 29028, XP002435764

DOI:   http://dx.doi.org/10.1074/jbc.271.46.29023
    - BAGLIA et al., "A binding site for thrombin in the apple 1 domain of factor XI", The Journal of Biological Chemistry, (19960216), vol. 271, no. 7, pages 3652 - 3658, XP002368765

DOI:   http://dx.doi.org/10.1074/jbc.271.7.3652
    - GAILANI et al., "The intrinsic pathway of coagulation: a target for treating thromboembolic disease?", J Thrombosis & Haemostatis, (20070601), vol. 5, no. 6, pages 1106 - 1112, XP055025685

DOI:   http://dx.doi.org/10.1111/j.1538-7836.2007.02446.x
    - OGAWA et al., "Exosite-mediated Substrate Recognition of Factor IX by Factor XIa", The Journal of Biological Chemistry, (20050624), vol. 280, no. 25, pages 23523 - 23530, XP055331637

DOI:   http://dx.doi.org/10.1074/jbc.M500894200
    - VAN DER GRAAF et al., "Isolation and Functional Characterization of the Active Light Chain of Activated Human Blood Coagulation Factor XI", The Journal of Biological Chemistry, (19830825), vol. 258, no. 16, pages 9669 - 9675, XP055621628
    - OHKUBO et al., "Characterization of a Panel of Monoclonal Antibody to Human Coagulation Factor XI and detection of Factor XI in Hep G2 Cell Conditioned Medium", Thrombosis & Haemostasis, (19900600), vol. 63, no. 3, pages 417 - 423, XP055621632

DOI:   http://dx.doi.org/10.1055/s-0038-1645058
    - MORGAN et al., "Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency", Thrombosis & Haemostasis, (19840700), vol. 51, no. 3, pages 371 - 375, XP055621634

DOI:   http://dx.doi.org/10.1055/s-0038-1661104
    - TANS et al., Eur. J. Biochem., (19870500), vol. 164, no. 3, pages 637 - 642, XP055621637
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.