Novartis Ag

Arrowhead Pharmaceuticals, Inc.

Dieter Huesken

Jan Weiler

Jean-Michel Rene Rondeau

Juerg Hunziker

Francois Jean-Charles Natt

Andrew William Patterson

Jeremy Lee Baryza

Erin Geno

Marcel Blommers

Cesar Fernandez

Alvar Gossert

Paulette Greenidge

Meicheng Zhu

Anup Patnaik

Stuart Milstein

Brian R Bettencourt

Ivanka Toudjarska

Frank Peter Stegmeier

Shanthi Ganesh

Elizabeth George

Jonathan Solomon

Emily Thomas

Jennifer Tullai

Chandra Vargeese

David A Bumcrot

Satyanarayana Kuchimanchi

Markus Warmuth

Wenlai Zhou

Meghan Marie Holdorf

William Chutkow

Jinyun Chen

Michael Ray Schlabach, Jr

Zainab Jagani

Mark Stump

Kalyani Gampa

Michael Jr Schlabach

Earl Mcdonald

Andrew Patterson

Brian Bettencourt

Jan Wieler

The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preeclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

Organic compositions to treat EPAS1-related diseases

The disclosure relates to novel compounds and compositions comprising a RNAi agent comprising a novel compound as a 3' end cap. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.

3' end caps for RNAi agents for use in RNA interference

The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preemclampsia, inflammation, chronic imflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3' end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5&#x2032; to 3&#x2032; order: a spacer; a second phosphate or modified internucleoside linker; and a 3&#x2032; end cap. In some embodiments, the 3&#x2032; end of both the sense and anti-sense strand further comprise, in 5&#x2032; to 3&#x2032; order: a spacer; a second phosphate or modified internucleoside linker; and a 3&#x2032; end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3&#x2032; end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5&#x2032; end. Optionally, the sense strand can comprise a 5&#x2032; end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.

Organic compounds to treat hepatitis B virus

The present disclosure relates to methods of treating heat stock factor 1 (HSF1)-related diseases such as cancer, autoimmune and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

Organic compositions to treat HSF1-related diseases

3'end caps for RNAi agents for use in RNA interference

The present disclosure relates to RNAi agents useful in methods of treating Beta-Catenin-related diseases such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to Beta-Catenin.

Organic compositions to treat beta-catenin-related diseases

The disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand; the two strands form a duplex with at least one blunt end; and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker; and a 3 end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3 end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optionally, the first or second strand is the sense strand, and the sense strand can comprise a 5 end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.

Formats for organic compounds for use in RNA interference

Growing community of inventors

Basel, Switzerland

Dieter Huesken