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US 10,894,091 B2Granted
Linker units and molecular constructs comprising the same
AssigneeImmunwork Inc.
InventorsTse-Wen Chang, Hsing-Mao Chu
Life of this patent
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Abstract
The present disclosure provides various linker units and molecular constructs, each of which has a targeting element and an effector element linked therewith. Methods for treating various diseases using such linker units and molecular constructs are also disclosed.
Claims23
A linker unit comprising,
- a core, which comprises, a plurality of lysine (K) residues, one or more spacers, and a first conjugating moiety, wherein,
- any two of the K residues are adjacent to each other or are separated by one of the spacers,
- each of the spacers comprises, independently, (1) one or more non-K amino acid residues, or (2) a PEGylated amino acid having 2 to 12 repeats of ethylene glycol (EG) unit,
- at least one of the spacers is linked to the N-terminus of the first K residue starting from the N-terminus or the C-terminus of the last K residue starting from the N-terminus, and
- the first conjugating moiety has either a carboxyl group or an amine group, and a conjugating group selected from the group consisting of, azide, alkyne, tetrazine, cyclooctene and cyclooctyne groups, wherein,
- when the spacer is linked to the N-terminus of the first K residue, the first conjugating moiety has the carboxyl group and is bonded to the spacer via forming an amide bond with the alpha-amine group of the spacer;
- or
- when the spacer is linked to the C-terminus of the last K residue, the first conjugating moiety has the amine group and is bonded to the spacer via forming an amide bond with the carboxyl group of the spacer;
- and
- a plurality of linking arms, wherein,
- each of the linking arms has a reactive group at one terminus thereof and a functional group at the other terminus thereof, and is linked to the K residues of the core via forming an amide bond between the reactive group of the linking arm and the amine group of the K reside of the core, and
- the functional group is selected from the group consisting of amine, carboxyl, hydroxyl, tert-Butyldimethylsilyl (TBDMS), N-hydroxysuccinimidyl (NHS), maleimide, vinyl sulfone, mono-sulfone, methylsulfonyl benzothiazole, iodo, iodoacetamide, azide, alkyne, cyclooctyne, tetrazine, and cyclooctene groups, with the proviso that when the conjugating group is the azide, alkyne, or cyclooctyne group, then the functional group is the tetrazine or cyclooctene group, and when the conjugating group is the tetrazine or the cyclooctene group, then the functional group is the azide, alkyne, or cyclooctyne group.
9 more elements
Dependencies are inferred from the claim text.