IP Library › Granted Patent US 12,364,771
Granted Patent B2
US 12,364,771 · App. 17/601,575 · Granted Jul 22, 2025

Conjugation linkers

Inventors: Gary W. Ashley (Alameda, CA); Brian Hearn (Moraga, CA); Shaun Fontaine (Concord, CA); Eric L. Schneider (Oakland, CA)
Assignee: PROLYNX LLC
A61K47/6903A61K38/12A61K38/26A61K38/28A61K47/542A61K47/60
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Quick Facts
Patent No.
US 12,364,771
App. No.
17/601,575
Granted
Jul 22, 2025
Kind
B2
Abstract

Provided are β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

Claims (18)

1. A linker of formula (I),

wherein:

n is an integer from 0 to 6;

R 1 is —CN or —SO 2 R 3 , wherein R 3 is optionally substituted alkyl, optionally substituted aryl, or —N(R 8 ) 2 , wherein each R 8 is independently optionally substituted alkyl, or both R 8 groups are taken together with the nitrogen to which they are attached to form an optionally substituted heterocyclic ring;

R 2 is H;

each R 4 is independently C 1 -C 3 alkyl or the two R 4 are taken together with the carbon atom to which they attach to form a 3-6 member ring;

X is halogen, N-succinimidyloxy, nitrophenoxy, pentahalophenoxy, imidazolyl, triazolyl, tetrazolyl, or N(R 6 )CH 2 Cl, wherein R 6 is optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; and

Z is N 3 , —NHC(O)C(OEt) 2 CH 3 , NH-pyruvoyl, maleimidyl, 1,2,4,6-tetrazinyl, trans-cyclooctenyl, bicyclononynyl, or cyclooctynyl.

2. The linker of claim 1 , wherein Z is N 3 , maleimidyl, 1,2,4,6-tetrazinyl, trans-cyclooctenyl, bicyclononynyl, or cyclooctynyl.

3. The linker of claim 1 , wherein each R 4 is independently C 1 -C 3 alkyl.

4. The linker of claim 1 , where both R 4 are methyl.

5. The linker of claim 1 , wherein R 1 is —CN.

6. The linker of claim 1 , wherein and R 1 is SO 2 R 3 .

7. The linker of claim 6 , where R 3 is methyl, isopropyl, phenyl, p-chlorophenyl, p-tolyl, dimethylamino, ethylmethylamino, 4-methylpiperidinyl, 4-morpholino, or bis(2-methoxyethyl)amino.

8. The linker of claim 1 , wherein n is 1.

9. The linker of claim 1 , wherein Z is N3.

10. The linker of claim 1 , wherein Z is —NHC(O)C(OEt) 2 CH 3 .

11. The linker of claim 1 , wherein Z is NH-pyruvoyl.

Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME FROM "LLC, PROLYNX" TO PROLYNX LLC. PREVIOUSLY RECORDED ON REEL 64440 FRAME 689. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Mar 12, 2025
From: ASHLEY, GARY W.; HEARN, BRIAN; FONTAINE, SHAUN; SCHNEIDER, ERIC L.
To: PROLYNX LLC
Reel/Frame 070494/0758 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2023
From: ASHLEY, GARY W.; HEARN, BRIAN; FONTAINE, SHAUN; SCHNEIDER, ERIC L.
To: LLC, PROLYNX
Reel/Frame 064440/0689 →
Continuity (2)
Provisional Application 62830280 · Apr 5, 2019
Related Publication 20220280654A1 · Sep 8, 2022
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