Glaxosmithkline Biologicals Sa

Novartis Vaccines & Diagnostics, Gmbh

Novartis Ag

Chiron Corporation

Irm LLC

Seqirus UK Limited

Other

Theraject, Inc.

O'hagan, Derek

Manmohan Singh

Derek T O'Hagan

Gary S Ott

Luis Brito

Andrew John Geall

Siddhartha Jain

Gary Van Nest

Jina Kazzaz

Barbara Baudner

David Skibinski

John J Donnelly

Alex Cortez

Xiaoyue Zhang

John Barackman

Michelle Chan

Padma Malyala

Kathy Yue

Tom Yao-Hsiang Wu

Maninder S Hora

Dennis M Klinman

Christian Walter Mandl

Mario Contorni

Yongkai Li

Mildred Ugozzoli

Simone Bufali

Yefen Zou

Timothy Z Hoffman

Jianfeng Pan

Janet Wendorf

Tom Yao Hsiang Wu

Nicholas M Valiante

Bret A Shirley

Francesco Doro

Sushma Kommareddy

Sung-Yun Kwon

Michelle C Archer

Pranab Mishra

Jia-Hwa Fang

Aravind Chakrapani

Simona Cianetti

David Skibinksi

David A G Skibinksi

Christian Mandi

David A G Skibinski

Amanda Scampini

Derek Thomas O'HAGAN

Derek T O'HAGAN

John Donnelly

Janet R Wendorf

Derek O'hagan

Sun-Yun Kwon

David Ag Skibinski

Nicholas Valiante

Nucleic acid immunisation is achieved by delivering a self-replicating RNA encapsulated within a small particle. The RNA encodes an immunogen of interest, and the particle may deliver this RNA by mimicking the delivery function of a natural RNA virus. Thus the invention provides a non-virion particle for in vivo delivery of RNA to a vertebrate cell, wherein the particle comprises a delivery material encapsulating a self-replicating RNA molecule which encodes an immunogen. These particles are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

Virion-like delivery particles for self-replicating RNA molecules

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

The invention improves TdaP vaccines by including a TLR agonist in them. This agonist can provide stronger protection, longer-lasting protection, and/or can reduce the amount of antigen which is required to achieve a particular immune response.

Adjuvanted formulations of booster vaccines

Combination vaccine compositions as well as methods for their manufacture have a relatively low amount of antigen and/or a relatively low amount of aluminium, but they can nevertheless have immunogenicity which is comparable to combination vaccines with a relatively high amount of antigen and/or a relatively high amount of aluminium. Aluminium-free combination vaccine compositions are also provided e.g. compositions which are adjuvanted with an oil-in-water emulsion adjuvant.

Combination vaccines with lower doses of antigen and/or adjuvant

In one aspect, the present invention provides sterile microparticle compositions comprising biodegradable microparticles, which comprise at least one biodegradable polymer. In other aspects, the present invention provides methods of making and using such compositions as well as articles of manufacture and kits containing the same.

Irradiated biodegradable polymer microparticles

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.

Adjuvant nanoemulsions with crystallisation inhibitors

Cationic oil-in-water emulsions

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.

Immunopotentiators can be adsorbed to insoluble metal salts, such as aluminum salts, to modify their pharmacokinetics, pharmacodynamics, intramuscular retention time, and/or immunostimulatory effect. Immunopotentiators are modified to introduce a moiety, such as a phosphonate group, which can mediate adsorption. These modified compounds can retain or improve their in vivo immunological activity even when delivered in an adsorbed form.

Adsorption of immunopotentiators to insoluble metal salts

The present invention generally relates to homogeneous suspensions of small molecule immune potentiators (SMIPs) that are capable of stimulating or modulating an immune response in a subject in need thereof. The homogeneous suspensions may be used in combinations with various antigens or adjuvants for vaccine therapies.

Homogenous suspension of immunopotentiating compounds and uses thereof

The invention provides a novel class of compounds, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 7. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness of a vaccine.

Compounds and compositions as TLR activity modulators

Growing community of inventors

Cary, NC, United States of America

Manmohan Singh