Polymeric micelles for polynucleotide encapsulation

• US 8,287,910 B2
• Filed: 04/29/2010
• Issued: 10/16/2012
• Est. Priority Date: 04/30/2009
• Status: Expired due to Fees

• Current Assignee: Intezyne Technologies
• Original Assignee: Intezyne Technologies
• Inventors: Mirosevich, Janni, Cardoen, Gregoire, Sill, Kevin N., Skaff, Habib
• Primary Examiner(s): Sajjadi, Fereydoun G
• Assistant Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US12/770,331
• Publication Number:
  US 20100278927A1
• Time in Patent Office: 901 Days
• Field of Search: 424/497
• US Class Current: 424/497
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides micelles having a polynucleotide encapsulated therein, the micelle comprising copolymers comprising hydrophobic moieties in a cationic complexing block. The invention further provides methods of preparing and using said micelles, and compositions thereof.

Claims

1. A micelle having a polynucleotide encapsulated therein, comprising a multiblock copolymer of formula III-a:

2. The micelle of claim 1, wherein R^x is an amino acid side-chain group corresponding to that of leucine, norleucine, or phenylalanine.

3. The micelle of claim 1, wherein R² is methyl.

4. The micelle of claim 1, wherein Q is —

CH₂—

.

5. The micelle of claim 1, wherein R¹ is N₃.

6. The micelle of claim 1, wherein R^z is selected from the group consisting of:

7. The micelle of claim 1, wherein R³ is a targeting group selected from the group consisting of folate, a Her-2 binding peptide, a urokinase-type plasminogen activator receptor (uPAR) antagonist, a CXCR4 chemokine receptor antagonist, a GRP78 peptide antagonist, an RGD peptide, an RGD cyclic peptide, a luteinizing hormone-releasing hormone (LHRH) antagonist peptide, an aminopeptidase targeting peptide, a brain homing peptide, a kidney homing peptide, a heart homing peptide, a gut homing peptide, an integrin homing peptide, an angiogencid tumor endothelium homing peptide, an ovary homing peptide, a uterus homing peptide, a sperm homing peptide, a microglia homing peptide, a synovium homing peptide, a urothelium homing peptide, a prostate homing peptide, a lung homing peptide, a skin homing peptide, a retina homing peptide, a pancreas homing peptide, a liver homing peptide, a lymph node homing peptide, an adrenal gland homing peptide, a thyroid homing peptide, a bladder homing peptide, a breast homing peptide, a neuroblastoma homing peptide, a lymphoma homing peptide, a muscle homing peptide, a wound vasculature homing peptide, an adipose tissue homing peptide, a virus binding peptide, and a fusogenic peptide.

8. The micelle of claim 1, wherein the polynucleotide is combined with a metal ion.

9. The micelle of claim 8, wherein the metal ion is Mg, Ca, Cu, Mn, Zn, Ni, Fe, or combinations thereof.