Stereochemically enriched compositions for delivery of nucleic acids

• US 10,138,213 B2
• Filed: 06/24/2015
• Issued: 11/27/2018
• Est. Priority Date: 06/24/2014
• Status: Active Grant

• Current Assignee: Translate Bio, Inc. (Sanofi )
• Original Assignee: Translate Bio, Inc. (Sanofi )
• Inventors: DeRosa, Frank, Karve, Shrirang, Heartlein, Michael
• Primary Examiner(s): Popa, Ileana
• Application Number:
  US14/749,027
• Publication Number:
  US 20150376144A1
• Time in Patent Office: 1,252 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 241/08 with oxygen atoms directly attached to ring carbon atoms

Abstract

Provided, in part, is a composition comprising one or more chemical entities of formula I, each of which is a compound of formula I:

a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, the composition characterized in that greater than a first threshold amount of the total amount of chemical entities of formula I in the composition: are chemical entities of formula I.a, wherein the first threshold amount is 50%; or are chemical entities of formula I.b.1, wherein the first threshold amount is 25%; or are chemical entities of formula I.b.2, wherein the first threshold amount is 25%, wherein the chemical entities of formula I.a, I.b.1, and I.b.2, are described herein, and methods of using such compositions, for example, for the delivery of a polynucleotide in vivo.

Claims

1. A composition comprising one or more chemical entities of formula I, each of which is a compound of formula I:

2. The composition of claim 1, wherein 80% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.

3. The composition of claim 2, wherein 90% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.

4. A lipid nanoparticle comprising the composition of claim 1 and a polynucleotide.

5. The lipid nanoparticle of claim 4, wherein 80% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.

6. The lipid nanoparticle of claim 4, wherein said polynucleotide is mRNA.

7. The lipid nanoparticle of claim 4, further comprising one or more cationic lipids, non-cationic lipids, cholesterol-based lipids, PEG-modified lipids, and/or polymers.

8. The lipid nanoparticle of claim 4, wherein 90% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.