Glaxosmithkline Biologicals Sa

Avidity Biosciences, Inc.

Vical Incorporated

Novartis Ag

Yale University

Andrew John Geall

Venkata Ramana Doppalapudi

Rob Burke

Michael Caramian Cochran

Gillis Otten

Katrin Ramsauer

Christian Walter Mandl

David Sai-Ho Chu

Beatrice Diana Darimont

Luis Brito

Barbora Malecova

Derek T O'Hagan

Gulin Erdogan Marelius

Yunyu Shi

Michael David Hood

Manmohan Singh

Mary Kopke Wloch

Thomas Zabawa

Gabriel Grant Gamber

Palani Balu

Rachel Elizabeth Johns

Kevin Thomas Love

Frederic Zecri

Delai Chen

Hanhua Huang

Gary G Hermanson

Arthur A Levin

Adrian Vilalta

Catherine J Luke

Thomas G Evans

Michelle Chan

Gretchen S Jimenez

Joel Daniel Arias

Philip Kovach

Derek O'hagan

Rohan Eric John Beckwith

Yingxia Wen

Tanzina Fazal

Joel D Enas

Frederick Porter

Ayush Verma

Brian Addison DeChristopher

Michelle C Archer

Jeremy Baryza

Richard J Bucala

Chandra Vargeese

Susan Barnett

Jeremy Lee Baryza

Ethan Settembre

Keith Bowman

Junping Zhao

Francesco Berlanda Scorza

Laura Ellen West

Cameron Lee

Tanzina Labonte

Christian Mandi

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Nucleic acid-polypeptide compositions and uses thereof

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

Compositions and methods of treating muscle atrophy and myotonic dystrophy

RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

Delivery of RNA to trigger multiple immune pathways

Disclosed herein are molecules and pharmaceutical compositions that induce an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion. Also described herein include methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that induces an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion.

Nucleic acid-polypeptide compositions and methods of inducing exon skipping

Methods for purifying RNA from a sample, comprising one or more steps of tangential flow filtration, hydroxyapatite chromatography, core bead flow-through chromatography, or any combinations thereof. These techniques are useful individually, but show very high efficiency when used in combination, or when performed in particular orders. The methods can purify RNA in a highly efficient manner without unduly compromising potency or stability, to provide compositions in which RNA is substantially cleared of contaminants. Moreover, they can be performed without the need for organic solvents.

RNA purification methods

Provided is RNA encoding an immunogen is delivered to a large mammal at a dose of from 5 μg to 100 μg or at a dose between 0.1 μg per kilogram body mass of the large mammal and 1.5 μg per kilogram body mass of the large mammal. Provided is a method of raising an immune response in a large mammal, comprising administering to the large mammal a dose of from 5 μg to 100 μg or a dose of between 0.1 μg of RNA encoding the immunogen per kilogram body mass of the large mammal and 1.5 μg of RNA encoding the immunogen per kilogram body mass of the large mammal. The delivered RNA can elicit an immune response in the large mammal.

Immunisation of large mammals with low doses of RNA

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

This invention generally relates to immunogenic compositions that comprise an RNA component and a polypeptide component. Immunogenic compositions that deliver antigens in two different forms—a first antigen from a pathogen, in RNA-coded form; and a second antigen from a different pathogen, in polypeptide form—are effective in inducing immune response to both pathogens.

Immunogenic combination compositions and uses thereof

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus, the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Immunization of large mammals with low doses of RNA

RNA encoding immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially a neutral surface charge at physiological pH and are effective for immunisation.

Immunisation with lipid formulations with RNA encoding immunogens

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Carlsbad, CA, United States of America

Andrew John Geall