Granted Patent B2

US 12,606,817 · App. 16/906,626 · Granted Apr 21, 2026

Inventor: Richard W. Wagner (Cambridge, MA)

Assignee: X-Chem, Inc.

C12N15/1065C12N15/1068C40B40/08C40B50/06C40B70/00C07H21/00C40B40/04C40B40/06

Abstract

Claims (37)

1 . A library of at least 1,000,000 different complexes, wherein each complex comprises:

(a) a bifunctional linker comprising a first functional group and a second functional group;

(b) a compound comprising at least two chemical building blocks;

(c) a single-stranded initiator oligonucleotide, wherein the initiator oligonucleotide forms a hairpin structure, the hairpin structure having a single-stranded loop comprising at least one natural nucleoside or nucleoside analog; and

(d) an identifier region that encodes the compound, the identifier region comprising at least two oligonucleotide tags, the first oligonucleotide tag encoding the first chemical building block of the compound and the second oligonucleotide tag encoding the second chemical building block of the compound,

wherein the first functional group of the bifunctional linker is covalently bound to the first chemical building block of the compound;

wherein the second functional group of the bifunctional linker is covalently bound to the single-stranded initiator oligonucleotide;

wherein the first oligonucleotide tag of the identifier region is ligated to the initiator oligonucleotide;

wherein the second oligonucleotide tag of the identifier region is ligated to the complex through ligation to the first oligonucleotide tag of the identifier region; and

wherein the second functional group of the bifunctional linker is covalently bound within the initiator oligonucleotide or in the middle of the initiator oligonucleotide;

the complexes comprising different compounds.

2 . A library of complexes, wherein each complex comprises:

(a) a bifunctional linker comprising a first functional group and a second functional group;

(b) a compound comprising at least two chemical building blocks;

(c) a single-stranded initiator oligonucleotide, wherein the initiator oligonucleotide forms a hairpin structure, the hairpin structure having a single-stranded loop comprising at least one natural nucleoside or nucleoside analog; and

(d) an identifier region that encodes the compound, the identifier region comprising at least two oligonucleotide tags, the first oligonucleotide tag encoding the first chemical building block of the compound and the second oligonucleotide tag encoding the second chemical building block of the compound,

wherein the first functional group of the bifunctional linker is covalently bound to the first chemical building block of the compound;

wherein the second functional group of the bifunctional linker is covalently bound to the single-stranded initiator oligonucleotide;

wherein the first oligonucleotide tag of the identifier region is ligated to the initiator oligonucleotide;

wherein the second oligonucleotide tag of the identifier region is ligated to the complex through ligation to the first oligonucleotide tag of the identifier region; and

wherein the initiator oligonucleotide and bifunctional linker combination of the complex have an octanol: water coefficient from 1.0 to 2.5;

the complexes comprising different compounds.

3 . The library of claim 2 , wherein the library comprises at least 1,000,000 different complexes, the complexes comprising different compounds.

4 . The library of claim 1 or 2 , wherein the second functional group of the bifunctional linker of each complex is covalently bound to the single-stranded loop of the hairpin structure of the initiator oligonucleotide of that complex.

5 . The library of claim 1 or 2 , wherein the bifunctional linker of each complex comprises a chemically inert spacer of variable length.

6 . The library of claim 1 or 2 , wherein the bifunctional linker of each complex comprises one or more of a chain of ethylene glycol units, an alkane, an alkene, polyene chain, or peptide chain.

7 . The library of claim 6 , wherein the bifunctional linker of each complex comprises one or more of a chain of ethylene glycol units.

8 . The library of claim 1 or 2 , wherein the first functional group of the bifunctional linker of each complex comprises a carboxylic acid.

9 . The library of claim 1 or 2 , wherein the second functional group of the bifunctional linker of each complex comprises an amine, a thiol, an azide, or an alkyne.

10 . The library of claim 9 , wherein the second functional group of the bifunctional linker of each complex comprises an amine.

11 . The library of claim 1 or 2 , wherein the initiator oligonucleotide of each complex comprises a T or C nucleotide comprising an aliphatic chain at the C5 position.

12 . The library of claim 1 or 2 , wherein the initiator oligonucleotide of each complex comprises a primer-binding region for polymerase amplification.

13 . The library of claim 1 or 2 , wherein the initiator oligonucleotide of each complex comprises an azobenzene.

14 . The library of claim 1 or 2 , wherein the compound of each complex is a small molecule.

15 . The library of claim 1 or 2 , wherein each oligonucleotide tag of each complex is double-stranded.

16 . The library of claim 1 or 2 , wherein each oligonucleotide tag of each complex is ligated to one or two adjacent oligonucleotide tags.

17 . The library of claim 1 or 2 , wherein the hairpin structure of each complex comprises a self-complementary region of 5 to 20 base pairs in length.

Assignments (2)

Continuity (4)

References Cited (400)