Arcturus Therapeutics, Inc.

Nitto-denko Corporation

Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Arcturus, Inc.

Joseph E Payne

Padmanabh Chivukula

Mohammad Ahmadian

Richard P Witte

Victor Knopov

Violetta Akopian

Priya Prakash Karmali

Yoshiro Niitsu

Yasunobu Tanaka

Loren A Perelman

John Gaudette

Zheng Hou

Steven Paul Tanis

Wenbin Ying

Kiyoshi Tachikawa

Sridhar C Nagarajan

Elena Feinstein

Igor Mett

Hagar Kalinski

Kenjiro Minomi

Yun Liu

Sharon Avkin-Nahum

Nicholas D Smith

Jun Zhang

Jean-Michel Andre Vernier

Dehua Huang

Lei Yu

Brian Walter Eastman

Thomas Jon Seiders

Jeffrey Roger Roppe

Jeannie M Arruda

Bowei Wang

Nicholas David Cosford

Steve Fong Poon

Xiumin Zhao

Neda Safarzadeh

Chris King

Yanjie Bao

David Webb

Benito Munoz

Thomas S Reger

Michael Figa

Luigi Warren

Scott A Roberts

Andreas Wagner

Nicholas D Cosford

Yun Lui

C Nagarajan Sridhar

Padmanabh Chivikula

Priya Karmali

John A Gaudette

Sharon Avkin-nachum

What is described is a compound of formula (1) wherein

Ionizable cationic lipid for RNA delivery

What is described is a method of synthesis of the compound of formula 1A, or a salt thereof, wherein

Method of synthesis of an ionizable cationic lipid

A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1tube having an inner diameter (ID) of between about 0.1″ and 0.132″; b) flowing an ethanol solution comprising lipids through a 2tube having an ID of between about 0.005″ and 0.02″ at one third the flow rate of the aqueous solution through the 1tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2tube perpendicularly joined to the 1tube; wherein the mixing produces an output solution flowing in the 1tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.

Method of making lipid-encapsulated RNA nanoparticles

A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1tube having an inner diameter (ID) of between about 0.1&#x2033; and 0.132&#x2033;; b) flowing an ethanol solution comprising lipids through a 2tube having an ID of between about 0.005&#x2033; and 0.02&#x2033; at one third the flow rate of the aqueous solution through the 1tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2tube perpendicularly joined to the 1tube; wherein the mixing produces an output solution flowing in the 1tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

Lipids for therapeutic agent delivery formulations

Here described is a composition comprising a compound of formula I: wherein Rand Ris independently selected from a group consisting of Cto Calkyl, Cto Calkenyl, and oleoyl group; Rand Rare independently selected from a group consisting of Cto Calkyl, and Cto Calkanol; X is selected from a group consisting of &#x2014;CH&#x2014;, &#x2014;S&#x2014;, and &#x2014;O&#x2014; or absent; Y is selected from &#x2014;(CH), &#x2014;S(CH), &#x2014;O(CH)&#x2014;, thiophene, &#x2014;SO(CH)&#x2014;, and ester; n=1-4; a=1-4; b=1-4; c=1-4; and Zis a counterion.

Cationic lipids for therapeutic agent delivery formulations

What is described is a compound of formula I consisting of a compound in which Ris a branched chain alkyl consisting of 10 to 31 carbons; Ris a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; Land Lare the same or different, each a linear alkylene or alkenylene consisting of 2 to 20 carbons; Xis S or O; Ris a linear or branched alkylene consisting of 1 to 6 carbons; and Rand Rare the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

What is described is a trinucleotide cap analog comprising mG(5')p-NpNfor increased efficiency of in vitro transcription of m7G(5&#x2032;)p-RNA, wherein mG is N-methylguanosine or analog, (5&#x2032;)pis a 5&#x2032;,5&#x2032;-triphosphate bridge, and Nor Nor both ribonucleotide analogs linked to each other by a phosphate, p, and wherein the trinucleotide cap analog increases the efficiency of in vitro transcription.

Trinucleotide mRNA cap analogs

Disclosed herein is a compound of Formula I, wherein Ris a branched chain alkyl consisting of 10 to 31 carbons; Ris a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; Land Lare the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; Xis S or O; Ris a linear or branched alkylene consisting of 1 to 6 carbons; and Rand Rare the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt or solvate thereof. 

This invention provides a range of translatable messenger UNA (mUNA) molecules. The mUNA molecules can be translated in vitro and in vivo to provide an active polypeptide or protein, or to provide an immunization agent or vaccine component. The mUNA molecules can be used as an active agent to express an active polypeptide or protein in cells or subjects. Among other things, the mUNA molecules are useful in methods for treating rare diseases.

Messenger UNA molecules and uses thereof

Disclosed herein is a lipid composition comprising a compound having the formula IA, or a pharmaceutically acceptable salt thereof, wherein

This invention provides UNA oligomers for gene silencing with reduced off-target effects. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and various nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis with reduced off-target effects by administering a UNA oligomer to a subject.

UNA oligomers having reduced off-target effects in gene silencing

Here described are compounds consisting of the structure(targeting molecule)-linker-(targeting molecule),wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including these compounds which are useful for the targeting and delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.

Compounds for targeting drug delivery and enhancing siRNA activity

This invention provides pharmaceutical compositions containing a UNA oligomer targeted to TTR and a pharmaceutically acceptable carrier. The compositions can be used in methods for treating or preventing TTR-related amyloidosis in a primate. The compositions, upon administering a single dose to the primate, can reduce TTR protein in the primate for a period of days to weeks.

Therapeutic oligomers for treating amyloidosis

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San Diego, CA, United States of America

Joseph E Payne