	US 11,987,622 B2
	Drug-conjugates with a targeting molecule and two different drugs
Zhenwei Miao, San Diego, CA (US); Gang Chen, San Diego, CA (US); Tong Zhu, San Diego, CA (US); Alisher B. Khasanov, San Diego, CA (US); Yufeng Hong, San Diego, CA (US); Hong D. Zhang, San Diego, CA (US); and Alexander Chucholowski, San Diego, CA (US)
Assigned to Vivasor, Inc., San Diego, CA (US)
Filed by Sorrento Therapeutics, Inc., San Diego, CA (US)
Filed on Sep. 29, 2020, as Appl. No. 17/037,370.
Application 17/037,370 is a division of application No. 14/515,352, filed on Oct. 15, 2014, granted, now 10,836,821.
Claims priority of provisional application 61/891,310, filed on Oct. 15, 2013.
Prior Publication US 2021/0017274 A1, Jan. 21, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 47/55 (2017.01); A61K 47/65 (2017.01); A61K 47/68 (2017.01); C07K 16/18 (2006.01)

CPC C07K 16/28 (2013.01) [A61K 47/55 (2017.08); A61K 47/65 (2017.08); A61K 47/6801 (2017.08); C07K 16/18 (2013.01)]

21 Claims

1. A method of preparing a dual-drug conjugate, the method comprising conjugating a first moiety comprising D¹to a lysine side chain of A and conjugating a second moiety comprising D²to cysteine side chains of A, thereby producing a dual-drug conjugate which is a compound of Formula I

or a pharmaceutically acceptable salt thereof,

wherein:

A is an antibody or antigen-binding antibody fragment;

D¹is an active agent;

each L¹is independently a linker comprising at least one N (nitrogen) atom;

the nitrogen between the antibody or antigen-binding antibody fragment and the carbonyl of C(O)-L¹-D¹is the nitrogen of a Lys side chain of the antibody or antigen-binding antibody fragment;

D²an active agent, wherein D¹and D²are different active agents;

each L²is independently a linker;

the E-component is selected from the group consisting of

L³is —(CH₂)—;

L⁴is —(CH₂)—;

m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.