Alnylam Pharmaceuticals, Inc.

Wave Life Sciences Ltd.

Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Alaylam Pharmacueuticals, Inc.

Ivan Zlatev

Muthiah Manoharan

Kallanthottathil G Rajeev

Gregory Lawrence Verdine

Naoki Iwamoto

Nenad Svrzikapa

Martin A Maier

Meena

Vasant R Jadhav

David Butler

Akin Akinc

Jayaprakash K Nair

Eric E Swayze

Thazha P Prakash

Pachamuthu Kandasamy

David Charles Donnell Butler

Marija Prhavc

Punit P Seth

Shigeo Matsuda

Adam Castoreno

Walter F Lima

John M Maraganore

Christopher S Theile

Pushkal Garg

Francois Morvan

Jean-Jacques Vasseur

Francoise Debart

Scott Lentini

Meena Meena

Jae Kim

Muthiah Manorharan

The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.

REVERSIR™ compounds

The present invention relates, in general to, compounds, compositions and methods useful for modulating gene expression of multiple target nucleic acids by a single chemical entity.

Multi-targeted single entity conjugates

The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Chiral design

The present invention relates, in general to agents that modulate the pharmacological activity of siRNAs. In addition, the invention relates generally to methods and systems for use in assessing the efficacy and safety of a pharmaceutical composition for use in the treatment or prophylaxis of a disease.

Tunable Reversir™ compounds

The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Chiral control

The present disclosure relates generally to cleavable linkers and uses thereof.

Endosomal cleavable linkers

The present invention provides nucleosides and oligonucleotides comprising a 5' phosphate mimics of formula (IVc) or (Vc), One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such dinucleotide of formula (Ia). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

5' phosphate mimics

One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene in vivo. The dsRNA duplex comprises one or more 4'-modifications in one or both strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for in vivo therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

RNAi agents modified at the 4'-C position

The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. 

5'-end derivatives

Provided herein are modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom. More particularly, modified 5&#x2032; diphosphate nucleosides are provided that can be further modified at the 2&#x2032; and 5&#x2032; positions. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The oligomeric compounds are also expected to be useful as primers and probes in diagnostic applications.

Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom

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Cambridge, MA, United States of America

Ivan Zlatev