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Extract from the Register of European Patents

EP About this file: EP3167888

EP3167888 - TREATMENT OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS BY AN INHIBITOR OF COMPLEMENT [Right-click to bookmark this link]
StatusThe patent has been granted
Status updated on  29.03.2024
Database last updated on 16.04.2026
FormerGrant of patent is intended
Status updated on  03.03.2024
FormerExamination is in progress
Status updated on  17.11.2017
FormerRequest for examination was made
Status updated on  21.07.2017
FormerThe application has been published
Status updated on  18.04.2017
Most recent event   Tooltip11.04.2026New entry: Date of cancellation oral proceedings 
Applicant(s)For all designated states
Alexion Pharmaceuticals, Inc.
100 College Street
New Haven, CT 06510 / US
[2024/18]
Former [2017/20]For all designated states
Alexion Pharmaceuticals, Inc.
100 College Street
New Haven, CT 06510 / US
Inventor(s)01 / BELL, Leonard
59 Tumblebrook Road
Woodbridge, CT Connecticut 06525 / US
02 / ROTHER, Russell P.
10325 Forest Meadow Drive
Oklahoma City, OK Oklahoma 73151 / US
03 / EVANS, Mark J.
Radnor, PA / US
 [2022/52]
Former [2017/20]01 / BELL, Leonard
59 Tumblebrook Road
Woodbridge, CT Connecticut 06525 / US
02 / ROTHER, Russell P.
10325 Forest Meadow Drive
Oklahoma City, OK Oklahoma 73151 / US
Representative(s)J A Kemp LLP
80 Turnmill Street
London EC1M 5QU / GB
[2024/18]
Former [2017/20]Vossius & Partner Patentanwälte Rechtsanwälte mbB
Siebertstrasse 3
81675 München / DE
Application number, filing date16195355.915.03.2007
[2017/20]
Priority number, dateUS20060783070P15.03.2006         Original published format: US 783070 P
[2017/20]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report 
No.:EP3167888
Date:17.05.2017
Language:EN
[2017/20]
Type: B1 Patent specification 
No.:EP3167888
Date:01.05.2024
Language:EN
[2024/18]
Search report(s)(Supplementary) European search report - dispatched on:EP17.03.2017
ClassificationIPC:A61K31/7105, A61K38/00, A61K39/395, A61P7/06, C07K16/18, A61K9/00
[2017/20]
CPC:
C07K16/18 (EP,IL,US); A61K31/7105 (EP,IL,KR,US); A61K38/00 (EP,IL,KR,US);
A61K39/395 (KR); A61K9/0019 (IL,US); A61P1/14 (EP,IL);
A61P13/02 (EP,IL); A61P15/10 (EP,IL); A61P17/00 (EP,IL);
A61P19/00 (EP,IL); A61P21/00 (EP,IL); A61P25/00 (EP,IL);
A61P25/04 (EP,IL); A61P25/18 (EP,IL); A61P25/20 (EP,IL);
A61P25/26 (EP,IL); A61P25/28 (EP,IL); A61P29/02 (EP,IL);
A61P3/00 (EP,IL); A61P3/02 (EP,IL); A61P31/04 (EP,IL);
A61P37/04 (EP,IL); A61P43/00 (EP,IL); A61P7/00 (EP,IL);
A61P7/02 (EP,IL); A61P7/06 (EP,IL); A61P9/12 (EP,IL);
A61K2039/505 (EP,IL,US); C07K2317/24 (IL,US); C07K2317/51 (IL,US);
C07K2317/515 (IL,US); C07K2317/565 (IL,US) (-)
Designated contracting statesAT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MT,   NL,   PL,   PT,   RO,   SE,   SI,   SK,   TR [2017/34]  
Former [2017/20]AT,  BE,  BG,  CH,  CY,  CZ,  DE,  DK,  EE,  ES,  FI,  FR,  GB,  GR,  HU,  IE,  IS,  IT,  LI,  LT,  LU,  LV,  MC,  MT,  NL,  PL,  PT,  RO,  SE,  SI,  SK,  TR 
TitleGerman:BEHANDLUNG VON PATIENTEN MIT PAROXYSMALER NÄCHTLICHER HÄMOGLOBINURIE MIT EINEM KOMPLEMENTINHIBITOR[2017/20]
English:TREATMENT OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS BY AN INHIBITOR OF COMPLEMENT[2017/20]
French:TRAITEMENT DE PATIENTS SOUFFRANT D'HÉMOGLOBINURIE PAROXYSTIQUE NOCTURNE PAR UN INHIBITEUR DE COMPLÉMENT[2017/20]
Examination procedure24.10.2016Date on which the examining division has become responsible
10.07.2017Amendment by applicant (claims and/or description)
10.07.2017Examination requested  [2017/34]
17.11.2017Despatch of a communication from the examining division (Time limit: M04)
12.12.2017Observations by third parties
16.01.2018Reply to a communication from the examining division
19.12.2018Cancellation of oral proceeding that was planned for 05.02.2019
05.02.2019Date of oral proceedings (cancelled)
02.09.2019Observations by third parties
04.09.2019Observations by third parties
05.09.2019Date of oral proceedings
07.02.2020Minutes of oral proceedings despatched
11.02.2020Despatch of communication that the application is refused, reason: substantive examination {1}
04.03.2024Communication of intention to grant the patent
06.03.2024Observations by third parties
08.03.2024Fee for grant paid
08.03.2024Fee for publishing/printing paid
08.03.2024Receipt of the translation of the claim(s)
Appeal following examination24.03.2020Appeal received No.  T1515/20
19.06.2020Statement of grounds filed
21.09.2023Result of appeal procedure: remittal for grant
20.02.2024Despatch of the decision of the Board of Appeal
Parent application(s)   TooltipEP07753249.7  / EP2001490
EP11001632.6  / EP2359834
Divisional application(s)EP23198329.7  / EP4316465
Opposition(s)Opponent(s)01  02.05.2024  28.01.2026  WITHDRAWN
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
 02  28.10.2024  21.11.2025  WITHDRAWN
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
A96 F2A8 Dublin / IE
Opponent's representative
Dörries, Hans Ulrich
df-mp Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  31.01.2025  04.02.2025  ADMISSIBLE
Salute HC Ilaç Pazarlama A.S.
Eclipse Ticari Bloklar Maslak Mah.
Sanatkarlar Sok. No:2 D Blok / Kat:2/13
Maslak, Sariyer
34398 Istanbul / TR
Opponent's representative
Grünecker Patent- und Rechtsanwälte PartG mbB
Leopoldstraße 4
80802 München / DE
 [2026/10]
Former [2026/01]
Opponent(s)01  02.05.2024  11.10.2024  ADMISSIBLE
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
 02  28.10.2024  21.11.2025  WITHDRAWN
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
A96 F2A8 Dublin / IE
Opponent's representative
Dörries, Hans Ulrich
df-mp Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  31.01.2025  04.02.2025  ADMISSIBLE
Salute HC Ilaç Pazarlama A.S.
Eclipse Ticari Bloklar Maslak Mah.
Sanatkarlar Sok. No:2 D Blok / Kat:2/13
Maslak, Sariyer
34398 Istanbul / TR
Opponent's representative
Grünecker Patent- und Rechtsanwälte PartG mbB
Leopoldstraße 4
80802 München / DE
Former [2025/13]
Opponent(s)01  02.05.2024  11.10.2024  ADMISSIBLE
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
 02  28.10.2024  29.10.2024  ADMISSIBLE
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
A96 F2A8 Dublin / IE
Opponent's representative
Dörries, Hans Ulrich
df-mp Patentanwälte Rechtsanwälte PartG mbB
Theatinerstraße 16
80333 München / DE
 03  31.01.2025  04.02.2025  ADMISSIBLE
Salute HC Ilaç Pazarlama A.S.
Eclipse Ticari Bloklar Maslak Mah.
Sanatkarlar Sok. No:2 D Blok / Kat:2/13
Maslak, Sariyer
34398 Istanbul / TR
Opponent's representative
Grünecker Patent- und Rechtsanwälte PartG mbB
Leopoldstraße 4
80802 München / DE
Former [2025/11]
Opponent(s)01  02.05.2024  11.10.2024  ADMISSIBLE
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
 02  28.10.2024  29.10.2024  ADMISSIBLE
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
A96 F2A8 Dublin / IE
Opponent's representative
Dörries, Hans Ulrich
df-mp
Fünf Höfe
Theatinerstrasse 16
80333 München / DE
 03  31.01.2025  04.02.2025  ADMISSIBLE
Salute HC Ilaç Pazarlama A.S.
Eclipse Ticari Bloklar Maslak Mah.
Sanatkarlar Sok. No:2 D Blok / Kat:2/13
Maslak, Sariyer
34398 Istanbul / TR
Opponent's representative
Grünecker Patent- und Rechtsanwälte PartG mbB
Leopoldstraße 4
80802 München / DE
Former [2024/49]
Opponent(s)01  02.05.2024  11.10.2024  ADMISSIBLE
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
 02  28.10.2024  29.10.2024  ADMISSIBLE
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
A96 F2A8 Dublin / IE
Opponent's representative
Dörries, Hans Ulrich
df-mp
Fünf Höfe
Theatinerstrasse 16
80333 München / DE
Former [2024/47]
Opponent(s)01  02.05.2024  11.10.2024  ADMISSIBLE
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
Former [2024/46]
Opponent(s)01  02.05.2024   
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Simmons & Simmons LLP (Munich)
Lehel Carré
Gewürzmühlstraße 11
80538 Munich / DE
Former [2024/24]
Opponent(s)01  02.05.2024   
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft / NL
Opponent's representative
Hoffmann Eitle
Patent- und Rechtsanwälte PartmbB
Arabellastraße 30
81925 München / DE
14.02.2025Invitation to proprietor to file observations on the notice of opposition
16.06.2025Reply of patent proprietor to notice(s) of opposition
10.04.2026Cancellation of oral proceeding that was planned for 05.05.2026
05.05.2026Date of oral proceedings
Fees paidRenewal fee
16.02.2017Renewal fee patent year 03
16.02.2017Renewal fee patent year 04
16.02.2017Renewal fee patent year 05
16.02.2017Renewal fee patent year 06
16.02.2017Renewal fee patent year 07
16.02.2017Renewal fee patent year 08
16.02.2017Renewal fee patent year 09
16.02.2017Renewal fee patent year 10
27.03.2017Renewal fee patent year 11
27.03.2018Renewal fee patent year 12
27.03.2019Renewal fee patent year 13
27.03.2020Renewal fee patent year 14
29.03.2021Renewal fee patent year 15
28.03.2022Renewal fee patent year 16
27.03.2023Renewal fee patent year 17
18.03.2024Renewal fee patent year 18
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Documents cited:Search[X] US2005191298  (BELL LEONARD et al.)
 [X]   HILLMEN P ET AL: "Eculizumab, a C5 complement blocking antibody, is the first therapy to reduce transfusion requirements in patients with paroxysmal nocturnal haemoglobinuria (PNH)", BRITISH JOURNAL OF HAEMATOLOGY, WILEY-BLACKWELL PUBLISHING LTD, GB, vol. 121, no. Suppl.1, 1 May 2003 (2003-05-01), pages 87, XP009144758, ISSN: 0007-1048
 [DX]   HILLMEN P ET AL: "EFFECT OF ECULIZUMAB ON HEMOLYSIS AND TRANSFUSION REQUIREMENTS IN PATIENTS WITH PAROXYSMAL NOCTRURNAL HEMAGLOBINURIA", NEW ENGLAND JOURNAL OF MEDICINE, MASSACHUSETTS MEDICAL SOCIETY, BOSTON, MA, US, vol. 350, no. 6, 5 February 2004 (2004-02-05), pages 552 - 559, XP009057948, ISSN: 1533-4406, DOI: 10.1056/NEJMOA031688

DOI:   http://dx.doi.org/10.1056/NEJMoa031688
 [X]   HARDING J: "Eculizumab", DRUGS OF THE FUTURE, PROUS SCIENCE, ES, vol. 29, no. 7, 1 July 2004 (2004-07-01), pages 673 - 676, XP008113000, ISSN: 0377-8282, DOI: 10.1358/DOF.2004.029.07.819330

DOI:   http://dx.doi.org/10.1358/dof.2004.029.07.819330
 [X]   HILL ANITA: "Eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria", CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY, MILLENNIUM MEDICAL PUB., NEW YORK, NY, US, vol. 3, no. 11, 1 November 2005 (2005-11-01), pages 849 - 850, XP001538426, ISSN: 1543-0790
 [X]   DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 14 February 1999 (1999-02-14), XP002767828, retrieved from STN accession no. 219685-50-4 Database accession no. 219685-50-4
ExaminationWO2005074607
 US6355245
 US2005271660
   THOMAS T C ET AL: "Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv", MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 33, no. 17-18, 1 January 1996 (1996-01-01), pages 1389 - 1401, XP002262113, ISSN: 0161-5890, DOI: 10.1016/S0161-5890(96)00078-8

DOI:   http://dx.doi.org/10.1016/S0161-5890(96)00078-8
by applicantWO2005074607
 US6100443
 WO9210205
 US6057131
 US6534058
 US2003129187
 US5660825
 US6355245
 US6180370
 US5693762
 US6407213
 US6548640
 US5565332
 US5225539
 US6103889
 US5260203
 US2005238646
 EP0404097
 WO9311161
 US4816567
 US6331415
 US2005226870
 WO9520401
 US5789208
 US6335163
 WO2004009618
 US4816397
 EP0120694
 WO8601533
 EP0194276
 EP0239400
 US4946778
 US2003202972
 US2004091490
 US2005158316
 WO03106644
 WO2004066957
 WO2004091658
   ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1997, pages 403 - 410
   TOMBAUGH ET AL., J. AM. GERIATR. SOC., vol. 40, 1992, pages 922
   CUMMINGS, JAMA, vol. 269, no. 18, 1993, pages 2420
   CRUM ET AL., JAMA, vol. 269, no. 18, 1993, pages 2386
   FOLSTEIN ET AL., J. PSYCHIAT. RES., vol. 12, 1975, pages 189
   KOKMEN ET AL., MAYO CLIN. PROC., vol. 62, 1987, pages 281
   TANG-WAI ET AL., ARCH. NEUROL., vol. 60, 2003, pages 1777
   TAMBURINI, ANN. ONCOL., vol. 12, no. 3, 2001, pages S7
   WEBSTER ET AL., HEALTH AND QUALITY OF LIFE OUTCOMES., vol. 1, 2003, pages 79, Retrieved from the Internet
   GRANT ET AL., CHEST, vol. 116, 1999, pages 1208, Retrieved from the Internet
   WILKINS, R.; ADAMS, OB., AM J PUBLIC HEALTH, vol. 73, 1983, pages 1073 - 1080
   WEINSTEIN MC; STASON WB, N ENGL J MED, vol. 296, 1977, pages 716 - 721
   WILKINS ET AL., AM J PUBLIC HEALTH, vol. 73, 1983, pages 1073 - 1080
   WEINSTEIN ET AL., N ENGL J MED, vol. 296, 1977, pages 716 - 721
   WARD; ZVAIFLER, J CLIN INVEST., vol. 50, no. 3, March 1971 (1971-03-01), pages 606 - 16
   WURZNER ET AL., COMPLEMENT INFLAMM., vol. 8, 1991, pages 328 - 340
   KABAT AND MAYER: "Experimental Immunochemistry, 2nd ed.", 1961, pages: 135 - 240
   FREI ET AL., MOL. CELL. PROBES, vol. 1, 1987, pages 141 - 149
   JONES ET AL., NATURE, vol. 321, 1986, pages 522 - 5
   ZAPATA ET AL., PROTEIN ENG, vol. 8, 1995, pages 1057 - 1062
   PLUCKTHUN: "The Pharmacology of Monoclonal Antibodies", vol. 113, 1994, SPRINGER-VERLAG, pages: 269 - 315
   HOLLINGER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 6444 - 6448
   C. A. JANEWAY ET AL.: "Immunobiology, 5th ed.", 2001, GARLAND PUBLISHING, pages: 147
   KOHLER ET AL., NATURE, vol. 256, 1975, pages 495 - 497
   CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628
   MARKS ET AL., J. MOL. BIOL., vol. 222, 1991, pages 581 - 597
   NEWMAN ET AL., BIOTECHNOLOGY, vol. 10, 1992, pages 1455 - 1460
   BIRD ET AL., SCIENCE, vol. 242, 1988, pages 423 - 426
   COLIGAN, ET AL.: "Current Protocols In Immunology", 1992, JOHN WILEY & SONS
   HARLOW; LANE: "Antibodies. A Laboratory Manual,", 1988, COLD SPRING HARBOR LABORATORY
   LIDDELL; CRYER: "A Practical Guide To Monoclonal Antibodies.", 1991, JOHN WILEY & SONS
   MONTZ ET AL., CELLULAR IMMUNOL, vol. 127, 1990, pages 337 - 351
   MOLLNES ET AL., SCAND. J. IMMUNOL, vol. 28, 1988, pages 307 - 312
   "Remington's Pharmaceutical Sciences, 17th ed.", 1985, MACK PUBLISHING COMPANY
   "The United States Pharmacopeial Convention", PHARMACOPEIAL FORUM, vol. 26, no. 1, 2000, pages 223
   TAKEDA J; MIYATA T; KAWAGOE K ET AL.: "Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.", CELL, vol. 73, 1993, pages 703 - 11
   BESSLER M; MASON PJ; HILLMEN P ET AL.: "Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene", EMBO J, vol. 13, 1994, pages 110 - 7
   YAMASHINA M; UEDA E; KINOSHITA T ET AL.: "Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria.", N ENGL J MED, vol. 323, 1990, pages 1184 - 9
   MOTOYAMA N; OKADA N; YAMASHINA M; OKADA H.: "Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene.", EUR J IMMUNOL, vol. 22, 1992, pages 2669 - 73
   HOLGUIN MH; FREDRICK LR; BEMSHAW ' NJ; WILCOX LA; PARKER CJ.: "Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria.", J CLIN INVEST, vol. 84, 1989, pages 7 - 17
   ROLLINS SA; SIMS PJ.: "The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9.", J IMMUNOL, vol. 144, 1990, pages 3478 - 83
   SIMS PJ; ROLLINS SA; WIEDMER T.: "Regulatory control of complement on blood platelets. Modulation of platelet procoagulant responses by a membrane inhibitor of the C5b-9 complex", J BIOL CHEM, vol. 264, 1989, pages 19228 - 35
   WIEDMER T; HALL SE; ORTEL TL; KANE WH; ROSSE WF; SIMS PJ.: "Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria.", BLOOD, vol. 82, 1993, pages 1192 - 6
   ROTHER RP; BELL L; HILLMEN P; GLADWIN MT.: "The clinical sequelae of intravascular hemolysis and extravascular plasma hemoglobin: a novel mechanism of human disease", JAMA, vol. 293, 2005, pages 1653 - 62
   ROSSE WF.: "Paroxysmal nocturnal hemoglobinuria.", HOFFINAN. NEW YORK: CHURCHILL LIVINGSTONE, 2000, pages 331 - 342
   THOMAS TC; ROLLINS SA; ROTHER RP ET AL.: "Inhibition of complement activity by humanized antibody that binds C5 and single-chain Fv.", MOL IMMUNOL, vol. 33, 1996, pages 1389 - 401
   HILLRRIEN P; HALL C; MARSH JC ET AL.: "Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria.", N ENGL J MED, vol. 350, 2004, pages 552 - 9
   YELLEN SB; CELLA DF; WEBSTER K; BLENDOWSKI C; KAPLAN E.: "Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system.", J PAIN SYMPTOM MANAGE, vol. 13, 1997, pages 63 - 74
   AARONSON NK; AHMEDZAI S; BERGMAN B ET AL.: "The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.", J NATL CANCER INST, vol. 85, 1993, pages 365 - 76
   CELLA D.: "Manual of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System", vol. 4, 1997, CENTER ON OUTCOMES RESEARCH AND EDUCATION
   FAYERS PM; AARONSON NK; BJORDAL K ET AL.: "The EORTC QLQ-C30 Scoring Manual, 3rd ed.", 2001, EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER
   JASINSKI M; PANTAZOPOULOS P; ROTHER RP ET AL.: "A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol-linked proteins.", BLOOD, vol. 103, 2004, pages 2827 - 34
   HILL A; WANG X; SAPSFORD RJ ET AL.: "Nitric oxide Consumption and Pulmonary Hypertension in Patients with Paroxysmal Nocturnal Hemoglobinuria.", BLOOD, vol. 106, no. 11, 2005
   CELLA D; ETON DT; LAI JS; PETERMAN AH; MERKEL DE.: "Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales.", J PAIN SYMPTOM MANAGE, vol. 24, 2002, pages 547 - 61
   HILL A; ROTHER RP; HILLMEN P.: "Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria.", HAEMATOLOGICA, vol. 90, 2005, pages ECR40
   PARKER C; OMINE M; RICHARDS S ET AL.: "Diagnosis and management of paroxysmal nocturnal hemoglobinuria.", BLOOD, vol. 106, 2005, pages 3699 - 709
   HILL A; WANG X; SAPSFORD RJ ET AL.: "Nitric oxide Consumption and Pulmonary Hypertension in Patients, with Paroxysmal Nocturnal Hemoglobinuria.", BLOOD, vol. 106, 2005, pages A1046
otherEP2380907
 EP1988882
 EP1755674
 EP2061810
 EP1720571
 EP1720571
 EP1720571
 EP1720571
 EP2359834
 WO2007092772
 US2005271660
   MUELLER ET AL.: "Humanized porcine VCAM-specific monoclonal antibodies with chimeric IgG2/G4 constant regions block human leukocyte binding to porcine endothelial cells", MOL IMMUNOL, vol. 34, no. 6, 1997, pages 441 - 452, XP055166865

DOI:   http://dx.doi.org/10.1016/S0161-5890(97)00042-4
OppositionUS2003232972
 US6355245
 US2005191298
 WO9711971
 WO2005074607
 WO2004050017
 WO2005007809
 WO2004108158
   D01: The Final Order of the Hamburg Local Division of June 26, 2024 in case UPC_CFI_124/2024, ORD_38032/2024
   D02: Overview over claims sought by Alexion and discussed in TBA decisions
   D03: INN Publication for eculizumab
   D04: Decision of the CoA of the UPC dated December 20, 2024
   D05: Proprietors submissions in relation to EP 1 720 571
   D06: Proprietors submission of 2 August 2011 in relation to US 11/127,438
   D07: Proprietors Submission at the EPO of 15 November 2012
   D08: Declaration of Prof. Kontermann
   D09: CV of Professor Roland Kontermann
   CHEN H, KIM J, KENDALL D A: "Competition between functional signal peptides demonstrates variation in affinity for the secretion pathway", JOURNAL OF BACTERIOLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 178, no. 23, 1 December 1996 (1996-12-01), US , pages 6658 - 6664, XP093260223, ISSN: 0021-9193, DOI: 10.1128/jb.178.23.6658-6664.1996
   CROMWELL MARY E M , HILARIO E, JACOBSON F: "Protein aggregation and bioprocessing.", AAPS JOURNAL, AMERICAN ASSOCIATION OF PHARMACEUTICAL SCIENTISTS, US, vol. 8, no. 3, 1 September 2006 (2006-09-01), US , pages E572 - E579, XP002557046, ISSN: 1550-7416, DOI: 10.1208/aapsj080366

DOI:   http://dx.doi.org/10.1208/aapsj080366
   WANG, W.: "Protein aggregation and its inhibition in biopharmaceutics", INTERNATIONAL JOURNAL OF PHARMACEUTICS, ELSEVIER, AMSTERDAM, NL, vol. 289, no. 1-2, 31 January 2005 (2005-01-31), AMSTERDAM, NL, pages 1 - 30, XP004706998, ISSN: 0378-5173, DOI: 10.1016/j.ijpharm.2004.11.014

DOI:   http://dx.doi.org/10.1016/j.ijpharm.2004.11.014
   ANONYMOUS: "GUIDELINE ON IMMUNOGENICITY ASSESSMENT OF BIOTECHNOLOGY-DERIVED THERAPEUTIC PROTEINS ", EMEA, COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP), 1 December 2007 (2007-12-01), pages 1 - 18, XP093260233
   ALLEN DEBORAH: "PROPERTIES AND BIOLOGICAL ACTIVITIES* OF CLASSES AND SUBCLASSES OF HUMAN SERUM IMMUNOGLOBULINS", IMMUNOLOGY, THIRD EDITION, 1 January 1997 (1997-01-01), pages 125, XP093260238
   FRANK MICHAEL M, MILETIC VOJISLAV D, JIANG HAIXIANG: "Immunoglobulin in the Control of Complement Action", IMMUNOLOGIC RESEARCH, vol. 22, no. 2, 1 January 2000 (2000-01-01), pages 137 - 146, XP093260241
   THOMAS THOMAS C. ET AL: "Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv", MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 33, no. 17-18, 1 December 1996 (1996-12-01), GB , pages 1389 - 1401, XP093260245, ISSN: 0161-5890, DOI: 10.1016/S0161-5890(96)00078-8
   MUELLER J.P. ET AL: "Humanized porcine VCAM-specific monoclonal antibidies with chimeric igG2/G4 constant regions block human leukocyte binding to porcine endothelial cells.", MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 34, no. 6, 1 January 1997 (1997-01-01), GB , pages 441 - 452, XP002988985, ISSN: 0161-5890, DOI: 10.1016/S0161-5890(97)00042-4

DOI:   http://dx.doi.org/10.1016/S0161-5890(97)00042-4
   HARDING J: "Eculizumab", DRUGS OF THE FUTURE, PROUS SCIENCE, ES, vol. 29, no. 7, 1 July 2004 (2004-07-01), ES , pages 673 - 676, XP008113000, ISSN: 0377-8282, DOI: 10.1358/dof.2004.029.07.819330

DOI:   http://dx.doi.org/10.1358/dof.2004.029.07.819330
   RUSSO NOONAN: "Alexion Pharmaceuticals Reports Positive Phase III Results for Eculizumab From Pivotal TRIUMPH Efficacy Trial in Paroxysmal Nocturnal Hemoglobinuria Patients", PRESS RELEASE, 26 January 2006 (2006-01-26), pages 1 - 4, XP093260307
   ANONYMOUS: "ALEXION Completes Enrollment in Phase II Membranous Nephritis Clinical Trial with 5G1.1", PRESS RELEASE, 20 February 2002 (2002-02-20), pages 1 - 2, XP093260315
   TACKEN PAUL J ET AL: "Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody.", BLOOD, W.B. SAUNDERS, AMSTERDAM, NL, vol. 106, no. 4, 15 August 2005 (2005-08-15), AMSTERDAM, NL, pages 1278 - 1285, XP002449006, ISSN: 0006-4971, DOI: 10.1182/blood-2005-01-0318

DOI:   http://dx.doi.org/10.1182/blood-2005-01-0318
   PRESTA, L.G.: "Engineering of therapeutic antibodies to minimize immunogenicity and optimize function", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER, AMSTERDAM , NL, vol. 58, no. 5-6, 7 August 2006 (2006-08-07), Amsterdam , NL , pages 640 - 656, XP005611419, ISSN: 0169-409X, DOI: 10.1016/j.addr.2006.01.026

DOI:   http://dx.doi.org/10.1016/j.addr.2006.01.026
   D23: Sequence alignment with D11 and D12
   D26: Grounds for the decision to refuse the patent application, dated February 11, 2020
   D27: T 1515/20
   D28: Final Order UPC LD Hamburg (UPC_CFI_123/2004)
   D29: Final Order UPC Court of Appeal (UPC_CFI_123/2004)
   D30: Final Order UPC Court of Appeal (UPC_CFI_124/2004)
   D31: Case Law of the BoA, 10th edition, p. 122 124; I.C.4.2
   D32: T 0153/85
   D33: CAS Database Registry for Eculizumab (RN 219685-50-4, 14 February 1999)
   HILLMEN P C ET AL: "Eculizumab, a C5 complement blocking antibody, is the first therapy to reduce transfusion requirements in patients with paroxysmal nocturnal haemoglobinuria (PNH)", BRITISH JOURNAL OF HAEMATOLOG, BLACKWELL PUBLISHING, vol. 121, no. Suppl. 1, 1 January 2003 (2003-01-01), pages 87 - 95, XP093260326
   HILLMEN P, ET AL.: "EFFECT OF ECULIZUMAB ON HEMOLYSIS AND TRANSFUSION REQUIREMENTS IN PATIENTS WITH PAROXYSMAL NOCTRURNAL HEMAGLOBINURIA", NEW ENGLAND JOURNAL OF MEDICINE, THE - NEJM, MASSACHUSETTS MEDICAL SOCIETY, US, vol. 350, no. 06, 5 February 2004 (2004-02-05), US , pages 552 - 559, XP009057948, ISSN: 1533-4406, DOI: 10.1056/NEJMoa031688

DOI:   http://dx.doi.org/10.1056/NEJMoa031688
   HILL ANITA: "Eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria.", CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY, MILLENIUM MEDICAL PUB , NEW YORK , NY, US, vol. 3, no. 11, 1 November 2005 (2005-11-01), US , pages 849 - 850, XP001538426, ISSN: 1543-0790
   MARINA NORIS, FEDERICA MESCIA, GIUSEPPE REMUZZI: "STEC-HUS, atypical HUS and TTP are all diseases of complement activation", NATURE REVIEWS. NEPHROLOGY, NATURE PUBLISHING GROUP, GB, vol. 8, no. 11, GB , pages 622 - 633, XP055259427, ISSN: 1759-5061, DOI: 10.1038/nrneph.2012.195

DOI:   http://dx.doi.org/10.1038/nrneph.2012.195
   TAKAHIKO HORIUCHI, TSUKAMOTO HIROSHI: "Complement-targeted therapy: development of C5- and C5a-targeted inhibition", INFLAMMATION AND REGENERATION, vol. 36, no. 1, 1 December 2016 (2016-12-01), pages 1 - 5, XP055644542, DOI: 10.1186/s41232-016-0013-6

DOI:   http://dx.doi.org/10.1186/s41232-016-0013-6
   HAMILTON RG, ABMLI D, MOHAN CHANDRA: "Human IgG subclass measurements in the clinical laboratory", CLINICAL CHEMISTRY, OXFORD UNIVERSITY PRESS, US, vol. 33, no. 10, 1 October 1987 (1987-10-01), US , pages 1707 - 1725, XP093260502, ISSN: 0009-9147, DOI: 10.1093/clinchem/33.10.1707

DOI:   http://dx.doi.org/10.1093/clinchem/33.10.1707
   DAUGHERTY, A.L. MRSNY, R.J.: "Formulation and delivery issues for monoclonal antibody therapeutics", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER, AMSTERDAM , NL, vol. 58, no. 5-6, 7 August 2006 (2006-08-07), Amsterdam , NL , pages 686 - 706, XP005611422, ISSN: 0169-409X, DOI: 10.1016/j.addr.2006.03.011

DOI:   http://dx.doi.org/10.1016/j.addr.2006.03.011
   WANG W; SINGH S; ZENG D L; KING K; NEMA S: "ANTIBODY STRUCTURE, INSTABILITY, AND FORMULATION", JOURNAL OF PHARMACEUTICAL SCIENCES, ELSEVIER INC, HOBOKEN, vol. 96, no. 1, 1 January 2007 (2007-01-01), Hoboken, pages 1 - 26, XP009084505, ISSN: 0022-3549, DOI: 10.1002/jps.20727

DOI:   http://dx.doi.org/10.1002/jps.20727
   PAUL R HINTON, JOANNA M XOING, MARY G JOHLFS, ET AL: "An engineered human IgG1 antibody with longer serum half-life.", JOURNAL OF IMMUNOLOGY, WILLIAMS & WILKINS, vol. 176, no. 1, 1 January 2006 (2006-01-01), pages 346 - 356, XP002484005, ISSN: 0022-1767, DOI: 10.4049/jimmunol.176.1.346

DOI:   http://dx.doi.org/10.4049/jimmunol.176.1.346
   FEINSTEIN, A. ; RICHARDSON, N. ; TAUSSIG, M.I.: "Immunoglobulin flexibility in complement activation", IMMUNOLOGY TODAY, ELSEVIER PUBLICATIONS, CAMBRIDGE., GB, vol. 7, no. 6, 1 June 1986 (1986-06-01), GB , pages 169 - 174, XP023943155, ISSN: 0167-5699, DOI: 10.1016/0167-5699(86)90168-4

DOI:   http://dx.doi.org/10.1016/0167-5699(86)90168-4
   D47: Application US 08/487283
   KAPLAN MARIANA: "Eculizumab (Alexion).", CURRENT OPINION IN INVESTIGATIONAL DRUGS, PHARMAPRESS, US, vol. 3, no. 7, 1 July 2002 (2002-07-01), US , pages 1017 - 1023, XP009506295, ISSN: 1472-4472
   D50: EP 11 001 632.6 Decision revoking the European patent
   D51: EP 16 172 335.8 Decision to refuse a European patent application (28.01.2020)
   D52: EP 16 172 335.8 Decision to refuse a European patent application (11.02.2020)
   ROSSE WENDELL F , HILLMEN P, SCHREIBER A D: "Immune-mediated hemolytic anemia.", AMERICAN SOCIETY OF HEMATOLOGY, AMERICAN SOCIETY OF HEMATOLOGY, WASHINGTON, DC, US, 1 January 2004 (2004-01-01), US , pages 48 - 62, XP002497825, ISSN: 1520-4391, DOI: 10.1182/asheducation-2004.1.48

DOI:   http://dx.doi.org/10.1182/asheducation-2004.1.48
   GOGESCH PATRICIA ET AL: "The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 22, no. 16, pages 8947, XP093069323, DOI: 10.3390/ijms22168947

DOI:   http://dx.doi.org/10.3390/ijms22168947
   D57: Sequence listing for EP - Counterpart of Rother WO
   D58: EP 11 001 632.6_Applicants submission of 15.11.2012
   BINDON C I, HALE G, BRGGEMANN M, WALDMANN H: "Human monoclonal IgG isotypes differ in complement activating function at the level of C4 as well as C1q.", JOURNAL OF EXPERIMENTAL MEDICINE, ROCKEFELLER UNIVERSITY PRESS, US, vol. 168, no. 1, 1 July 1988 (1988-07-01), US , pages 127 - 142, XP093138374, ISSN: 0022-1007, DOI: 10.1084/jem.168.1.127

DOI:   http://dx.doi.org/10.1084/jem.168.1.127
   D60: Affidavit of F. Bertelli (30.04.2024)
   D61: F. Bertellis CV
   D62: Sequence overview_F. Bertelli
   NEZU JUN-ICHI ET AL: "Identification of CDCP1 as a novel molecular target of anti-cancer therapeutic antibody targeting prostate cancer", AMERICAN ASSOCIATION FOR CANCER RESEARCH. PROCEEDINGS OF THE ANNUAL MEETING, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 48, 1 April 2007 (2007-04-01) - 18 April 2007 (2007-04-18), US , pages 153, XP008115766, ISSN: 0197-016X
   D64: Affidavit of F. Bertelli (14.06.2024)
   D66: Alexion Press Release
   BREKKE O H, SANDLIE I: "THERAPEUTIC ANTIBODIES FOR HUMAN DISEASES AT THE DAWN OF THE TWENTY-FIRST CENTURY.", NATURE REVIEWS. DRUG DISCOVERY, NATURE PUBLISHING GROUP, GB, vol. 2, 1 January 2003 (2003-01-01), GB , pages 52 - 62, XP003009494, ISSN: 1474-1784, DOI: 10.1038/nrd984

DOI:   http://dx.doi.org/10.1038/nrd984
   PIERANGELI SILVIA S. ET AL: "Requirement of activation of complement C3 and C5 for antiphospholipid antibodymediated thrombophilia", ARTHRITIS & RHEUMATISM, WILEY INTERSCIENCE, US, vol. 52, no. 7, 1 July 2005 (2005-07-01), US , pages 2120 - 2124, XP093260537, ISSN: 0004-3591, DOI: 10.1002/art.21157
   ANONYMOUS: "Eculizumab: 5G1.1, h5G1.1, long-acting anti-C5 monoclonal antibody 5G1-1, long-acting anti-C5 monoclonal antibody 5G1.1", DRUGS IN R&D, ADIS INTERNATIONAL LTD , NZL, vol. 8, no. 1, 1 January 2007 (2007-01-01), pages 61 - 68, XP009161624, ISSN: 1174-5886, DOI: 10.2165/00126839-200708010-00006

DOI:   http://dx.doi.org/10.2165/00126839-200708010-00006
   D70: EP 11 001 632.6_Proprietors statement of ground of appeal
   D71: EP 2 359 834_Second declaration of Dino Miano (14.01.2019)
   D72: Prof. Dr. Arne Skerra_Witness declaration
   ANONYMOUS: "GUIDELINES ON THE USE OF INTERNATIONAL NONPROPRIETARY NAMES (INNs) FOR PHARMACEUTICAL SUBSTANCES", HO/PHARM S/MON 1570:, WORLD HEALTH ORGANIZATION, 1 January 1997 (1997-01-01), pages 1 - 40, XP093260540
   CANFIELD S M, MORRISON S L: "THE BINDING AFFINITY OF HUMAN IGG FOR ITS HIGH AFFINITY FC RECEPTOR IS DETERMINED BY MULTIPLE AMINO ACIDS IN THE CH2 DOMAIN AND IS MODULATED BY THE HINGE REGION", JOURNAL OF EXPERIMENTAL MEDICINE, ROCKEFELLER UNIVERSITY PRESS, US, vol. 173, no. 06, 1 June 1991 (1991-06-01), US , pages 1483 - 1491, XP001181027, ISSN: 0022-1007, DOI: 10.1084/jem.173.6.1483

DOI:   http://dx.doi.org/10.1084/jem.173.6.1483
   RAVETCH J V, BOLLAND S: "IGG FC RECEPTORS", ANNUAL REVIEW OF IMMUNOLOGY, ANNUAL REVIEWS INC., vol. 19, 1 January 2001 (2001-01-01), pages 275 - 290, XP008008612, ISSN: 0732-0582, DOI: 10.1146/annurev.immunol.19.1.275

DOI:   http://dx.doi.org/10.1146/annurev.immunol.19.1.275
   D129 - UPC FINAL ORDER
   D130 - DECISION UK COURT
   D131 - PRELIMINARY OPINION BOA T1087_19
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