(19)
(11) EP 2 729 496 B8

(12) CORRECTED EUROPEAN PATENT SPECIFICATION
Note: Bibliography reflects the latest situation

(15) Correction information:
Corrected version no 1 (W1 B1)

(48) Corrigendum issued on:
18.10.2017 Bulletin 2017/42

(45) Mention of the grant of the patent:
13.09.2017 Bulletin 2017/37

(21) Application number: 12731507.5

(22) Date of filing: 06.07.2012
(51) International Patent Classification (IPC): 
C07K 16/00(2006.01)
(86) International application number:
PCT/EP2012/063338
(87) International publication number:
WO 2013/004841 (10.01.2013 Gazette 2013/02)

(54)

MODULATION OF COMPLEMENT-DEPENDENT CYTOTOXICITY THROUGH MODIFICATIONS OF THE C-TERMINUS OF ANTIBODY HEAVY CHAINS

MODULATION EINER KOMPLEMENTABHÄNGIGEN-ZYTOTOXIZITÄT DURCH MODIFIKATION DES C-TERMINUS SCHWERER ANTIKÖRPERKETTEN

MODULATION DE LA CYTOTOXICITÉ DÉPENDANTE DU COMPLÉMENT PAR DES MODIFICATIONS DE L'EXTRÉMITÉ C-TERMINALE DES CHAÎNES LOURDES D'ANTICORPS

(84) Designated Contracting States:
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
Designated Extension States:
BA ME

(30) Priority: 06.07.2011 US 201161504987 P
06.07.2011 DK 201100518

(43) Date of publication of application:
14.05.2014 Bulletin 2014/20

(60) Divisional application:
17184944.1

(73) Proprietor: Genmab A/S
1560 Copenhagen V (DK)

(72) Inventors:
  • PARREN, Paul
    3984 PR Odijk (NL)
  • VAN BERKEL, Patrick
    3544 NH Utrecht (NL)
  • VAN DEN BREMER, Ewald
    3584 CM Utrecht (NL)

(74) Representative: Genmab A/S 
Kalvebod Brygge 43
1560 Copenhagen V
1560 Copenhagen V (DK)


(56) References cited: : 
WO-A2-2007/087420
WO-A2-2008/006554
 WO-A2-2007/106707
US-A1- 2010 297 697
   
  • HARRIS R J ET AL: "Identification of multiple sources of charge heterogeneity in a recombinant antibody.", JOURNAL OF CHROMATOGRAPHY. B, BIOMEDICAL SCIENCES AND APPLICATIONS 10 MAR 2001 LNKD- PUBMED:11270864, vol. 752, no. 2, 10 March 2001 (2001-03-10), pages 233-245, XP002682609, ISSN: 1387-2273
  • LINTAO WANG ET AL: "Structural Characterization of a Recombinant Monoclonal Antibody by Electrospray Time-of-Flight Mass Spectrometry", PHARMACEUTICAL RESEARCH, KLUWER ACADEMIC PUBLISHERS-PLENUM PUBLISHERS, NL, vol. 22, no. 8, 1 August 2005 (2005-08-01) , pages 1338-1349, XP019370906, ISSN: 1573-904X, DOI: 10.1007/S11095-005-5267-7
  • STROHL ET AL: "Optimization of Fc-mediated effector functions of monoclonal antibodies", CURRENT OPINION IN BIOTECHNOLOGY, LONDON, GB, vol. 20, no. 6, 1 December 2009 (2009-12-01), pages 685-691, XP026778879, ISSN: 0958-1669, DOI: 10.1016/J.COPBIO.2009.10.011 [retrieved on 2009-11-04]
  • HAMILTON ET AL: "Glycosylation engineering in yeast: the advent of fully humanized yeast", CURRENT OPINION IN BIOTECHNOLOGY, LONDON, GB, vol. 18, no. 5, 24 October 2007 (2007-10-24), pages 387-392, XP022350908, ISSN: 0958-1669, DOI: 10.1016/J.COPBIO.2007.09.001
  • BETENBAUGH M J ET AL: "Biosynthesis of human-type N-glycans in heterologous systems", CURRENT OPINION IN STRUCTURAL BIOLOGY, ELSEVIER LTD, GB, vol. 14, no. 5, 1 October 2004 (2004-10-01), pages 601-606, XP004590073, ISSN: 0959-440X, DOI: 10.1016/J.SBI.2004.09.001
  • JEFFERIS ROY: "Glycosylation as a strategy to improve antibody-based therapeutics", NATURE REVIEWS. DRUG DISCOVERY, NATURE PUBLISHING GROUP, GB, vol. 8, no. 3, 1 March 2009 (2009-03-01), pages 226-234, XP002600969, ISSN: 1474-1784, DOI: 10.1038/NRD2804
  • LIU H ET AL: "Heterogeneity of monoclonal antibodies", JOURNAL OF PHARMACEUTICAL SCIENCES, AMERICAN PHARMACEUTICAL ASSOCIATION, WASHINGTON, US, vol. 97, no. 7, 1 July 2008 (2008-07-01), pages 2426-2447, XP002530921, ISSN: 0022-3549, DOI: 10.1002/JPS.21180
  • MOORE GREGORY L ET AL: "Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions", MABS, LANDES BIOSCIENCE, US, vol. 2, no. 2, 1 March 2010 (2010-03-01), pages 181-189, XP009143498, ISSN: 1942-0862, DOI: 10.4161/MABS.2.2.11158 & G L Moore ET AL: "Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions (Supplementary Information)", mAbs, 1 March 2010 (2010-03-01), pages 1-2, XP055045074, Retrieved from the Internet: URL:http://dx.doi.org/10.4161/mabs.2.2.111 58 [retrieved on 2012-11-21]
  • CHOWDHURY P S ET AL: "Tailor-made antibody therapeutics", METHODS : A COMPANION TO METHODS IN ENZYMOLOGY, ACADEMIC PRESS INC., NEW YORK, NY, US, vol. 36, no. 1, 1 May 2005 (2005-05-01), pages 11-24, XP027216559, ISSN: 1046-2023 [retrieved on 2005-04-19]
  • FILPULA ET AL: "Antibody engineering and modification technologies", BIOMOLECULAR ENGINEERING, ELSEVIER, NEW YORK, NY, US, vol. 24, no. 2, 1 June 2007 (2007-06-01), pages 201-215, XP022081380, ISSN: 1389-0344, DOI: 10.1016/J.BIOENG.2007.03.004
  • ANTES ET AL: "Analysis of lysine clipping of a humanized Lewis-Y specific IgG antibody and its relation to Fc-mediated effector function", JOURNAL OF CHROMATOGRAPHY B: BIOMEDICAL SCIENCES & APPLICATIONS, ELSEVIER, AMSTERDAM, NL, vol. 852, no. 1-2, 31 May 2007 (2007-05-31), pages 250-256, XP022099894, ISSN: 1570-0232, DOI: 10.1016/J.JCHROMB.2007.01.024
  • BRUNHOUSE R ET AL: "Isotypes of IgG: Comparison of the primary structures of three pairs of isotypes which differ in their ability to activate complement", MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 16, no. 11, 1 November 1979 (1979-11-01), pages 907-917, XP023788873, ISSN: 0161-5890, DOI: 10.1016/0161-5890(79)90089-0 [retrieved on 1979-11-01]
   
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