	US 12,257,281 B2
	Hydrophilic antibody-drug conjugates
Svetlana Doronina, Snohomish, WA (US); Robert Lyon, Sammamish, WA (US); and Peter Senter, Seattle, WA (US)
Assigned to Seagen Inc., Bothell, WA (US)
Filed by Seagen Inc., Bothell, WA (US)
Filed on Jul. 28, 2023, as Appl. No. 18/361,558.
Application 18/361,558 is a division of application No. 17/963,939, filed on Oct. 11, 2022, abandoned.
Application 17/963,939 is a division of application No. 17/160,225, filed on Jan. 27, 2021, granted, now 11,510,959, issued on Nov. 29, 2022.
Application 17/160,225 is a division of application No. 15/118,031, granted, now 10,933,112, issued on Mar. 2, 2021, previously published as PCT/US2015/016185, filed on Feb. 17, 2015.
Claims priority of provisional application 61/947,368, filed on Mar. 3, 2014.
Claims priority of provisional application 61/940,759, filed on Feb. 17, 2014.
Prior Publication US 2024/0115648 A1, Apr. 11, 2024
Int. Cl. A61K 38/05 (2006.01); A61K 9/00 (2006.01); A61K 47/68 (2017.01)

CPC A61K 38/05 (2013.01) [A61K 9/0019 (2013.01); A61K 47/68031 (2023.08); A61K 47/6861 (2017.08); A61K 47/6867 (2017.08); A61K 47/6889 (2017.08)]

6 Claims

1. A Compound having the formula:

(a) (L^H)_p′-L^A

or a pharmaceutically acceptable salt or solvate thereof, wherein:

L^His an optionally branched hydrophilic linker, each branch of L^Hhaving the formula:

-AA₁—R^L1—R^L2—R^L3—;

L^Ais a Ligand Attachment component; and

p′ is an integer from 1 to 4; and

wherein the left and right lines of L^Hindicate attachment sites for a D_Eunit and L^A, respectively; or

(b) ([L^H]_p′-L^A)_p-L

or a pharmaceutically acceptable salt or solvate thereof; wherein:

L is a Ligand that specifically binds to a target;

L^His an optionally branched hydrophilic linker, each branch of L^Hhaving the formula:

-AA₁—R^L1—R^L2—R^L3—;

L^Ais a Ligand Attachment component;

the subscript p is an integer from about 4 to 20; and

the subscript p′ is an integer from 1 to 4;

wherein the left and right lines of L^Hindicate attachment sites to the D_EUnit and L^A, respectively;

wherein in (a) or (b):

AA₁is a hydrophilic amino acid that can form a cleavable bond with a D_Eunit when it is attached;

R^L1is a hydrophilic amino acid or an optionally substituted alkylene, which may share an atom with L^Awhen R^L2and R^L3are not present;

R^L2is optional and is selected from a hydrophilic amino acid and an optionally substituted alkylene, which may share an atom with L^Awhen R^L2is present and R^L3is not present; and

R^L3is optional and is selected from a hydrophilic amino acid and an optionally substituted alkylene, which may share an atom with L^Awhen R^L3is present,

wherein at least one of R^L1, R^L2, and R^L3is an amino acid that is covalently linked by a reactive group in its side chain to an adjacent group.