Compounds for targeting drug delivery and enhancing siRNA activity

Patent metadata

Field	Value
Publication number	US-10100004-B2
Application number	US-201615177284-A
Country	US
Kind code	B2
Filing date	Jun 8, 2016
Priority date	Jun 8, 2011
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

Here described are compounds consisting of the structure
(targeting molecule) m -linker-(targeting molecule) n ,

wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including these compounds which are useful for the targeting and delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.

First claim

What is claimed:

1. A composition, consisting of a compound of the structure (retinoid) m -linker-(retinoid) n , wherein m and n are independently 1, 2, or 3; wherein m+n=4-6; and wherein the linker comprises one or more elements selected from a polyethylene glycol (PEG), glutarate (Glu), hexyl, Gly 3 , and 4-aminobutanoate (GluNH).

2. The composition of claim 1 , wherein the retinoid is selected from vitamin A, retinoic acid, tretinoin, adapalene, 4-hydroxy(phenyl)retinamide (4-HPR), retinyl palmitate, retinal, saturated retinoic acid, and saturated, demethylated retinoic acid.

3. The composition of claim 1 , wherein the compound is selected from (retinoid) 2 -PEG-(retinoid) 2 , (retinoid) 2 -bis-amido-PEG-(retinoid) 2 , and (retinoid) 2 -Lys-bis-amido-PEG-Lys-(retinoid) 2 .

4. The composition of claim 3 , wherein the retinoid is selected from vitamin A, retinoic acid, tretinoin, adapalene, 4-hydroxy(phenyl)retinamide (4-HPR), retinyl palmitate, retinal, saturated retinoic acid, and saturated, demethylated retinoic acid.

5. The composition of claim 4 , wherein the compound has the structure of formula I

wherein q, r, and s are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

6. The composition of claim 4 , wherein the compound has the structure of formula II

7. The composition of claim 1 , wherein the PEG is mono disperse.

8. The composition of claim 1 , wherein the PEG has a molecular weight of about 550 to about 2000 g/mole.

9. The composition of claim 1 , wherein the linker comprises one or more elements selected from bis-amido-PEG, tris-amido-PEG, tetra-amido-PEG, Lys-bis-amido-PEG Lys, Lys-tris-amido-PEG-Lys, Lys-tetra-amido-PEG-Lys, Lys-PEG-Lys, PEG2000, PEG1250, PEG1000, PEG750, PEG550, PEG-Glu, glutarate (Glu), hexyl, Gly 3 , and 4-aminobutanoate (GluNH).

10. A composition, consisting of a compound of the structure (retinoid) m -linker-(retinoid) n , wherein m and n are 1 or 2; wherein m+n=3; and wherein the linker comprises one or more elements selected from bis-amido-polyethylene glycol (PEG), tris-amido-PEG, tetra-amido-PEG, Lys-bis-amido-PEG Lys, Lys-tris-amido-PEG-Lys, Lys-tetra-amido-PEG-Lys, Lys-PEG-Lys, PEG2000, PEG1250, PEG1000, PEG750, PEG550, PEG-Glu, glutarate (Glu), hexyl, Gly 3 , and 4-aminobutanoate (GluNH).

Assignees

• Nitto Denko Corp

Inventors

• Niitsu Yoshiro
• Payne Joseph E
• Gaudette John A
• Hou Zheng
• Knopov Victor
• Witte Richard P
• Ahmadian Mohammad
• Perelman Loren A
• Tanaka Yasunobu
• Akopian Violetta

Classifications

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61P11/04

  for throat disorders · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title