Glaxosmithkline Biologicals Sa

Novartis Ag

Modernatx, Inc.

Luis Brito

Andrew John Geall

Derek T O'Hagan

Manmohan Singh

Thomas Zabawa

Gabriel Grant Gamber

Kevin Thomas Love

Frederic Zecri

Delai Chen

Michelle Chan

Rohan Eric John Beckwith

Orn Almarsson

Kimberly Hassett

Joseph Schariter

Michelle C Archer

Mike Smith

Brian Addison DeChristopher

Gilles Besin

Silvia Vendetti

Ugo D'Oro

The disclosure features novel methods of producing nucleic acid lipid nanoparticle (LNP) compositions employing a modifying agent after formation of a precursor nucleic acid lipid nanoparticle, the produced compositions thereof, and methods involving the nucleic acid lipid nanoparticles useful in the delivery of therapeutics and/or prophylactics, such as a nucleic acid, to mammalian cells or organs to, for example, to regulate polypeptide, protein, or gene expression.

Methods of making lipid nanoparticles

This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering nucleic acids in vivo. These compositions have reduced immune activation resulting in accelerated blood clearance and/or anti-drug antibodies and they have an improved toxicity profile and therapeutic index in vivo.

Reduction of elimination of immune responses to non-intravenous, e.g., subcutaneously administered therapeutic proteins

This invention provides for a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R-R, L, n and p are defined herein. The compounds of formula (X) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

Lipids and lipid compositions for the delivery of active agents

Retinoic acid, or an analogue thereof, is delivered within an oil-in-water emulsion to provide an improved immunological adjuvant.

Oil-in-water emulsions including retinoic acid

This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

Cationic oil-in-water emulsions

This invention generally relates to cationic oil-in-water emulsions that can be used to deliver negatively charged molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are particularly suitable for delivering nucleic acid molecules (such as an RNA molecule encoding an antigen) to cells and formulating nucleic acid-based vaccines.

Method for preparing composition comprising a cationic oil-in-water emulsion

This invention generally relates to cationic oil-in-water emulsions that can be used to deliver nucleic acid molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The emulsion particles have an average diameter of about 80 nm to about 180 nm, and the emulsion have an N/P ratio of at least 1.1:1.

Oil-in-water emulsions that contain nucleic acids

This invention provides for a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R-R, n, p, Land Lare defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

This invention provides for a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R, R, Rand Rare defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

This invention provides for a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R-R, n, p, Land Lare defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues. 

To formulate amphiphilic pharmacological agents (in particular, amphiphilic immunopotentiators) in oil-in-water emulsions the invention provides an oil-in-water emulsion comprising an aqueous phase, an oil phase, a surfactant, and a phospholipid.

Adjuvant nanoemulsions with phospholipids

High loading of lipophilic pharmacological agents (in particular, lipophilic immunopotentiators) in oil-in-water emulsions can result in crystallisation of the lipophilic agent. To overcome this problem the invention uses an oil-in-water emulsion in combination with a crystallisation inhibitor, and this combination provides emulsions which can be loaded with high levels of lipophilic pharmacological agents.

Growing community of inventors

Cambridge, MA, United States of America

Luis Brito