IP Library › Granted Patent US 9,796,756
Granted Patent B2
US 9,796,756 · App. 14/972,385 · Granted Oct 24, 2017

Galactose cluster-pharmacokinetic modulator targeting moiety for siRNA

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Quick Facts
Patent No.
US 9,796,756
App. No.
14/972,385
Granted
Oct 24, 2017
Kind
B2
Abstract

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.

Claims (21)

1. A composition for delivering an RNA interference polynucleotide to a liver cell in vivo comprising the structure represented by:

wherein R 1 comprises a hydrophobic group having 16 or more carbon atoms, R 2 comprises the RNA interference polynucleotide, and R 3 comprises a galactose or galactose derivative having affinity for the asialoglycoprotein receptor equal to or greater than that of galactose.

2. The composition of claim 1 wherein R 1 comprises cholesterol.

3. The composition of claim 1 wherein R 1 comprises hexadec-8-enoyl.

4. The composition of claim 1 wherein R 1 comprises oleyl.

5. The composition of claim 1 wherein R 1 comprises (9E,12E)-octadeca-9,12-dienoyl.

6. The composition of claim 1 wherein R 1 comprises dioctanoyl.

7. The composition of claim 1 wherein R 1 comprises C16-C20 acyl.

8. The composition of claim 7 wherein R 1 comprises C16 acyl.

9. The composition of claim 7 wherein R 1 comprises C18 acyl.

10. The composition of claim 7 wherein R 1 comprises C80 acyl.

11. The composition of claim 1 wherein R 3 comprises: galactosamine, N-formyl-galactosamine, N-acetylgalactosamine, N-propionyl-galactosamine, N-n-butanoyl-galactosamine, or N-iso-butanoylgalactosamine.

12. The composition of claim 1 wherein R 3 comprises N-formyl-galactosamine.

13. The composition of claim 1 wherein R 3 comprises N-acetylgalactosamine.

14. The composition of claim 1 wherein R 3 comprises N-propionyl-galactosamine.

15. The composition of claim 1 wherein R 3 comprises N-n-butanoyl-galactosamine.

16. The composition of claim 1 wherein R 3 comprises N-iso-butanoylgalactosamine.

17. The composition of claim 1 wherein the composition further comprises a polynucleotide delivery polymer.

18. The composition of claim 17 wherein the polynucleotide delivery polymer comprises a reversibly modified membrane active polyamine.

19. The composition of claim 1 wherein R 2 comprises: DNA, RNA, dsRNA, siRNA, or miRNA.

20. The composition of claim 1 wherein R 2 comprises siRNA.

Assignments (3)
SECURITY INTEREST Recorded Aug 7, 2024
From: ARROWHEAD PHARMACEUTICALS, INC.
To: SIXTH STREETLENDING PARTNERS, AS THE ADMINISTRATIVE AGENT
Reel/Frame 068510/0363 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2016
From: ARROWHEAD MADISON INC.
To: ARROWHEAD PHARMACEUTICALS, INC.
Reel/Frame 039254/0108 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 27, 2016
From: ROZEMA, DAVID B.; LEWIS, DAVID L.; WAKEFIELD, DARREN H.; HOFFMANN, TORSTEN; KITAS, ERIC A.; MOHR, PETER; HADWIGER, PHILIPP; ROEHL, INGO; VALIS, LINDA
To: ARROWHEAD MADISON INC.
Reel/Frame 039018/0971 →