US 12,331,125 B2
Anti-cMet antibody-drug conjugates and uses thereof
Brian P. Fiske, Waltham, MA (US); Nimish Gera, Waltham, MA (US); and Alexander J. Nichols, Lincoln, MA (US)
Assigned to Mythic Therapeutics, Inc., Waltham, MA (US)
Filed by Mythic Therapeutics, Inc., Waltham, MA (US)
Filed on Nov. 15, 2023, as Appl. No. 18/510,256.
Application 18/510,256 is a continuation of application No. 18/273,078, previously published as PCT/US2022/015116, filed on Feb. 3, 2022.
Claims priority of provisional application 63/145,348, filed on Feb. 3, 2021.
Prior Publication US 2024/0101688 A1, Mar. 28, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); C07K 16/32 (2006.01)
CPC C07K 16/2863 (2013.01) [A61K 47/68031 (2023.08); A61K 47/68035 (2023.08); A61K 47/6849 (2017.08); A61P 35/00 (2018.01); C07K 16/32 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/52 (2013.01); C07K 2317/73 (2013.01); C07K 2317/77 (2013.01); C07K 2317/94 (2013.01)] 10 Claims
OG exemplary drawing
 
1. An antibody-drug conjugate, wherein the antibody-drug conjugate comprises:
(a) a heavy chain variable domain and a light chain variable domain selected from the group of:
(i) SEQ ID NO: 5 and SEQ ID NO: 6, respectively;
(ii) SEQ ID NO: 11 and SEQ ID NO: 12, respectively;
(iii) SEQ ID NO: 13 and SEQ ID NO: 14, respectively;
(iv) SEQ ID NO: 15 and SEQ ID NO: 16, respectively;
(v) SEQ ID NO: 17 and SEQ ID NO: 18, respectively; and
(vi) SEQ ID NO: 21 and SEQ ID NO: 22, respectively;
(b) a light chain constant region sequence of SEQ ID NO: 157 comprising a valine to cysteine substitution at amino acid position 98, wherein the drug is monomethyl auristatin E (MMAE) and the MMAE is conjugated to the cysteine at amino acid position 98 via a valine-citrulline (vc) linker; and
(c) a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 155 or SEQ ID NO: 189 optionally comprising one or more of (A) through (C):
(A) a lysine to cysteine substitution at amino acid position 105 and deletion of a threonine at amino acid positions 106 and 108;
(B) a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; and
(C) a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317.