US 12,084,510 B2
Antibodies selective for cells presenting EGFR at high density
Ilia Alexandre Tikhomirov, Toronto (CA); Maria L. Jaramillo, Beaconsfield (CA); Maureen D. O'Connor-McCourt, Beaconsfield (CA); Traian Sulea, Kirkland (CA); Renald Gilbert, Montreal (CA); Bruno Gaillet, Sainte Julienne (CA); Jason Baardsnes, Montreal (CA); Myriam Banville, Laval (CA); and Suzanne Grothe, Montreal (CA)
Assigned to Gilead Sciences, Inc., Foster City, CA (US); and National Research Council of Canada, Ottawa (CA)
Filed by GILEAD SCIENCES, INC., Foster City, CA (US); and NATIONAL RESEARCH COUNCIL OF CANADA, Ottawa (CA)
Filed on Feb. 21, 2020, as Appl. No. 16/797,364.
Application 16/797,364 is a continuation of application No. 13/821,832, granted, now 10,570,211, previously published as PCT/CA2012/050034, filed on Jan. 20, 2012.
Claims priority of provisional application 61/435,510, filed on Jan. 24, 2011.
Prior Publication US 2020/0325243 A1, Oct. 15, 2020
Int. Cl. C07K 16/30 (2006.01); C07K 16/28 (2006.01)
CPC C07K 16/30 (2013.01) [C07K 16/2863 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01)] 25 Claims
 
1. An epidermal growth factor receptor (EGFR) antibody that binds preferentially to disease cells having an EGFR density greater than a normal EGFR density as compared to cells comprising the normal EGFR density, wherein the normal EGFR density is less than 10,000 EGFR molecules per cell, the EGFR antibody comprising a heavy chain and a light chain, each chain having a constant region and a variable region, each variable region comprising framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below:
For the heavy chain:
 
 For the heavy chain:
 
 CDR1
 
 (SEQ ID No. 1)
 
 NYGVH
 
 
 
 CDR2
 
 (SEQ ID No. 2)
 
 VIWSGGNTD58YNTPFTS
 
 
 
 CDR3
 
 (SEQ ID No. 3)
 
 ALTY101Y102D103YE105FAY
 
 
 
 For the light chain:
 
 CDR1
 
 (SEQ ID No. 4)
 
 RASQSIGTNIH
 
 
 
 CDR2
 
 (SEQ ID No. 5)
 
 ASE53SIS
 
 
 
 CDR3
 
 (SEQ ID No. 6)
 
 QQNNNW94PTT
wherein Y101, Y102 or D103 is/are substituted with at least one of A101, A102 or N103, and D58, Y101, Y102, D103, or E105 is/are substituted with up to three of N58, A101, A102, N103 and/or Q105, and/or wherein E53 or W94 is/are wild type or substituted with at least one of K53 or A94, wherein the substituted amino acid(s) confer(s) on said antibody a reduced EGFR binding affinity (Kd) that is 1.0 nM or weaker.