US 11,890,354 B2
Activatable antibodies that bind epidermal growth factor receptor and methods thereof
Henry Bernard Lowman, El Granada, CA (US); Luc Roland Desnoyers, San Francisco, CA (US); Shouchun Liu, Burlingame, CA (US); James William West, Bend, OR (US); Jason Gary Sagert, San Mateo, CA (US); Olga Vasiljeva, Cupertino, CA (US); and Elizabeth-Edna Mary Menendez, San Mateo, CA (US)
Assigned to CYTOMX THERAPEUTICS, INC., South San Francisco, CA (US)
Filed by CytomX Therapeutics, Inc., South San Francisco, CA (US)
Filed on Jun. 4, 2020, as Appl. No. 16/892,973.
Application 16/892,973 is a division of application No. 15/875,947, filed on Jan. 19, 2018, granted, now 10,709,799.
Application 15/875,947 is a division of application No. 15/381,972, filed on Dec. 16, 2016, granted, now 9,889,211, issued on Feb. 13, 2018.
Application 15/381,972 is a division of application No. 14/815,111, filed on Jul. 31, 2015, granted, now 9,545,442, issued on Jan. 17, 2017.
Application 14/815,111 is a division of application No. 13/872,052, filed on Apr. 26, 2013, granted, now 9,120,853, issued on Sep. 1, 2015.
Claims priority of provisional application 61/639,796, filed on Apr. 27, 2012.
Claims priority of provisional application 61/662,204, filed on Jun. 20, 2012.
Claims priority of provisional application 61/749,220, filed on Jan. 4, 2013.
Claims priority of provisional application 61/749,529, filed on Jan. 7, 2013.
Claims priority of provisional application 61/763,237, filed on Feb. 11, 2013.
Prior Publication US 2021/0023243 A1, Jan. 28, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); C07K 16/00 (2006.01); A61K 49/00 (2006.01); C07K 16/28 (2006.01); A61K 47/68 (2017.01); A61K 39/395 (2006.01); C07K 16/30 (2006.01); G01N 33/574 (2006.01); G01N 33/58 (2006.01); G01N 33/68 (2006.01)
CPC A61K 49/0058 (2013.01) [A61K 39/3955 (2013.01); A61K 47/6803 (2017.08); A61K 47/6849 (2017.08); C07K 16/2863 (2013.01); C07K 16/2866 (2013.01); C07K 16/30 (2013.01); G01N 33/57492 (2013.01); G01N 33/58 (2013.01); G01N 33/6872 (2013.01); A61K 2039/505 (2013.01); C07K 2317/14 (2013.01); C07K 2317/24 (2013.01); C07K 2317/56 (2013.01); C07K 2317/90 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01); G01N 2333/71 (2013.01)] 16 Claims
 
1. A method of treating or delaying the progression of a cancer associated with aberrant expression or activity of Epidermal Growth Factor Receptor (EGFR) in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an activatable antibody that in an activated state binds EGFR, wherein said activatable antibody comprises:
(a) an antibody or an antigen binding fragment thereof (AB) that specifically binds to EGFR, wherein the AB comprises:
(i) a heavy chain comprising:
(1) an amino acid sequence with at least one of the following amino acid sequence features: (1) a glutamine residue at the position corresponding to position 88 of SEQ ID NO: 26, SEQ ID NO: 30, and SEQ ID NO: 34, and (2) an alanine residue at the position corresponding to position 299 of SEQ ID NO: 26, SEQ ID NO: 30, and SEQ ID NO: 34, and
(2) heavy chain complementarity determining regions (HCDRs), wherein the HCDRs are the HCDRs of a heavy chain amino acid sequence selected from the group consisting of: SEQ ID NO: 26, SEQ ID NO: 30, and SEQ ID NO: 34, and
(ii) a light chain comprising light chain complementarity determining regions (LCDRs), wherein the LCDRs are the LCDRs of light chain amino acid sequence SEQ ID NO: 68;
(b) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB of the activatable antibody in an uncleaved state to EGFR, wherein the MM comprises the amino acid sequence CISPRGCPDGPYVMY (SEQ ID NO:14); and
(c) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease and wherein the CM comprises the amino acid sequence LSGRSDNH (SEQ ID NO: 13),
wherein the activatable antibody in the uncleaved state has the structural arrangement from N-terminus to C-terminus as follows: MM-CM-AB or AB-CM-MM.