US009890216B2 ( 12 ) United States Patent Georgiou et al . ( 10 ) Patent No . : US 9 , 890 , 216 B2 ( 45 ) Date of Patent : Feb . 13 , 2018 ( 54 ) ANTIBODIES WITH ENGINEERED IGG FC DOMAINS A61K 47 / 6801 ; A61K 47 / 6815 ; A61K 47 / 6813 ; A61K 47 / 6875 ; A61K 47 / 6879 ; A61K 47 / 6851 ; A61K 47 / 6849 ; A61K 51 / 10 See application file for complete search history . ( 71 ) Applicant : THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM , Austin , TX ( US ) ( 56 ) References Cited U . S . PATENT DOCUMENTS ( 72 ) Inventors : George Georgiou , Austin , TX ( US ); William Kelton , Austin , TX ( US ); Nishant Mehta , Basel ( CH ) @ ( 73 ) Assignee : Board of Regents , The University of Texas System , Austin , TX ( US ) . . . . . . . . . . . . .. . 8, 871 , 912 B2 10 / 2014 Davis 2005 / 0249723 A1 * 11 / 2005 Lazar .. . .. . ... .. . .. . . .. . .. C07K 16 / 00 424 / 133 . 1 2010 / 0093979 A1 * 4 / 2010 Lazar CO7K 16 / 00 530 / 387 . 3 2011 / 0097323 A1 * 4/ 2011 Johnson .. . . . ... . . . . .. CO7K 16 / 32 424 / 133 . 1 2012 / 0142593 Al * 6/ 2012 Zhao . . . CO7K 14 / 755 514 / 14 . 1 2012 / 0237506 A1 * 9 / 2012 Bossenmaier .. . . . . . . CO7K 16 / 00 424 / 133 . 1 ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 U . S .C . 154 (b ) by 59 days . ( 21 ) Appl . No .: 14 / 437 , 544 FOREIGN PATENT DOCUMENTS ( 22 ) PCT Filed : ( 86 ) PCT No . : $ 371 (c )( 1 ), ( 2 ) Date : Aug . 30 , 2013 PCT / US2013 / 057605 WO WO WO 1998 / 023646 WO2010 / 111414 6 / 1998 9 / 2010 * OTHER PUBLICATIONS Apr . 22 , 2015 ( 87 ) PCT Pub . No .: W02014 / 065945 PCT Pub . Date : May 1, 2014 ( 65 ) Prior Publication Data US 2015 / 0266960 A1 Sep . 24 , 2015 Related U .S . Application Data ( 60 ) Provisional application No . 61 / 717 , 568 , filed on Oct . 23 , 2012 . Yu et al . , Investigative Ophthalmology & Visual Science 49 (2 ): 522 - 527 , Feb . 2008 .* Stancovski et al . , PNAS , 88 : 8691 - 8695 , 1991 .* Herr et al ., “ Insights into IgA - mediated immune responses from the crystal structures of human FcaRI and its complex with IgAl - Fc ” , Nature , 423 ( 6940 ): 614 - 620 , 2003 , 2003 . International Preliminary Report on Patentability issued in Interna tional Application No . PCT / US2013 / 057605 , dated May 7 , 2015 . International Search Report and Written Opinion issued in Interna tional Application No . PCT / US2013 / 057605 , dated Nov . 28 , 2013 . Pleass et al . , “ Identification of residues in the CH2 / CH3 domain interface of IgA essential for interaction with the human Fca receptor ( FcaR ) CD89 ” , Journal of Biological Chemistry , 274 ( 33 ): 23508 - 23514 , 1999 . Van Egmond et al ., “ Enhancement of Polymorphonuclear Cell mediated Tumor Cell Killing on Simultaneous Engagement of FcyRI ( CD64 ) and FcaRI ( CD89 )" , Cancer Research , 61 ( 10 ): 4055 , 2001 . Woof et al . , “ Localisation of the monocyte - binding region on human immunoglobulin G ” , Molecular Immunology , 23 ( 3 ): 319 - 330 , 1986 . Woof et al ., " Structure and function relationships in IgA " , Mucosal Immunology , 4 (6 ): 590 - 597 , 2011 . Woof et al . , “ The human IgA - Fca receptor interaction and its blockade by Streptococcal IgA - binding proteins ” , Biochemical Society Transactions , 30 : 491 - 494 , 2002 . * cited by examiner ( 51 ) Int . CI . CO7K 16 / 30 ( 2006 . 01 ) CO7K 16 / 32 ( 2006 . 01 ) COZK 16 / 28 ( 2006 . 01 ) A61K 4748 ( 2006 . 01 ) CO7K 16 / 00 ( 2006 . 01 ) A61K 47 / 68 ( 2017 . 01 ) ( 52 ) U . S . Cl . CPC . COOK 16 / 2863 ( 2013 . 01 ) ; A61K 47 / 48561 ( 2013 . 01 ); A61K 47 / 6849 ( 2017 . 08 ); COOK 16 / 00 ( 2013 . 01 ); CO7K 16 / 30 ( 2013 . 01 ); COOK 16 / 32 ( 2013 . 01 ); CO7K 2317 / 52 ( 2013 . 01 ); CO7K 2317 / 524 ( 2013 . 01 ); CO7K 2317 / 56 ( 2013 . 01 ) ; COZK 2317 / 66 ( 2013 . 01 ); COOK 2317 / 71 ( 2013 . 01 ) ; C07K 2317 / 72 ( 2013 . 01 ) ; CO7K 2317 / 732 ( 2013 . 01 ); C07K 2317 / 92 ( 2013 . 01 ) ( 58 ) Field of Classification Search CPC . . . CO7K 16 / 00 , CO7K 16 / 2863 ; CO7K 16 / 30 ; CO7K 16 / 32 ; CO7K 2317 / 41 ; COOK 2317 / 52 ; CO7K 2317 / 524 ; CO7K 2317 / 56 ; CO7K 2317 / 526 ; CO7K 2317 / 71 ; CO7K 2317 / 72 ; CO7K 2317 / 732 ; COOK 2317 / 734 ; CO7K 2317 / 92 ; CO7K 2319 / 30 ; Primary Examiner – Phuong Huynh ( 74 ) Attorney , Agent , or Firm — Parker Highlander PLLC ( 57 ) ABSTRACT Antibody Fc polypeptides are provided that efficiently bind to both Fcy and Fca receptors . In certain aspects , a Fc polypeptide comprises a chimeric IgG CH2 domain having a al loop from IgA and an IgA CH3 domain . Recombinant antibodies comprising Fc polypeptides of the embodiments and methods for making and using such antibodies are likewise provided . 20 Claims , 16 Drawing Sheets