Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.
Type:
Grant
Filed:
November 22, 2017
Date of Patent:
November 22, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Mark K. Schlegel, Maja Janas, Vasant R. Jadhav, Donald Foster, Muthiah Manoharan, Kallanthottathil G. Rajeev, Muthusamy Jayaraman, Alexander V. Kel'in, Shigeo Matsuda, Klaus Charisse, Jayaprakash K. Nair, Martin A. Maier, Alfica Sehgal, Christopher Brown, Christopher Theile, Stuart Milstein
Abstract: The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.
Type:
Grant
Filed:
August 12, 2019
Date of Patent:
November 8, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Vasant R. Jadhav, Martin A. Maier, Stuart Milstein, Mark K. Schlegel
Abstract: One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier, which provides for targeting to, and uptake by, tissues and cells of the CNS, and in particular the striatum. Another aspect of the invention relates to a method of gene silencing in tissues and cells of the CNS, and in particular the striatum, that includes administering to a tissue/cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.
Type:
Application
Filed:
June 16, 2020
Publication date:
September 29, 2022
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Jayaprakash K. Nair, Martin Maier, Vasant Jadhav, Stuart Milstein, Kirk Brown, Rubina G. Parmar, Kallanthottathil G. Rajeev, Muthiah Manoharan, Alexander V. Kel'in, Muthusamy Jayaraman, Klaus Charisse, Adam Castoreno, Christopher S. Theile, Kevin Fitzgerald
Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the HAO1 gene, and methods of using such RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.
Type:
Grant
Filed:
November 4, 2019
Date of Patent:
September 20, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
William Querbes, Kevin Fitzgerald, Brian Bettencourt, Abigail Liebow, David V. Erbe
Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.
Type:
Application
Filed:
May 13, 2022
Publication date:
September 15, 2022
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Shigeo MATSUDA, Mark K. SCHLEGEL, Maja JANAS, Vasant R. JADHAV, Martin MAIER, Klaus CHARISSE, Muthiah MANOHARAN, Kallathotathil G. RAJEEV, Jayaprakash K. NAIR
Abstract: The disclosure relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the LECT2 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of LECT2.
Abstract: The invention relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the SCAP gene, as well as methods of inhibiting expression of a SCAP gene and methods of treating subjects having a SCAP-associated disorder, such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), using such dsRNAi agents and compositions.
Type:
Grant
Filed:
July 27, 2020
Date of Patent:
September 6, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Kevin Fitzgerald, Huilei Xu, Gregory Hinkle
Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2?-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for 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.
Type:
Grant
Filed:
November 10, 2021
Date of Patent:
August 30, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Martin Maier, Don Foster, Stuart Milstein, Satya Kuchimanchi, Vasant Jadhav, Kallanthottathil Rajeev, Muthiah Manoharan, Rubina Parmar
Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the angiotensinogen (AGT) gene, and methods of using such RNAi agents to inhibit expression of AGT and methods of treating subjects having an AGT-associated disorder, e.g., hypertension.
Type:
Grant
Filed:
September 15, 2020
Date of Patent:
August 23, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Donald Foster, Brian Bettencourt, Klaus Charisse, Gregory Hinkle, Satyanarayana Kuchimanchi, Martin A. Maier, Stuart Milstein
Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the apolipoprotein C3 (APOC3) gene, and methods of using such RNAi agents to inhibit expression of APOC3 and methods of treating subjects having an APOC3 associated disorder, e.g., hypertriglyceridemia.
Type:
Grant
Filed:
June 15, 2021
Date of Patent:
August 9, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Kevin Fitzgerald, William Querbes, James Butler, Stephanie Williams, Abigail Liebow, Gregory Hinkle, Martin A. Maier, Stuart Milstein, Satyanarayana Kuchimanchi, Muthiah Manoharan
Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for 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.
Type:
Grant
Filed:
April 16, 2020
Date of Patent:
August 9, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Kallanthottathil G. Rajeev, Tracy Zimmermann, Muthiah Manoharan, Martin Maier, Satyanarayana Kuchimanchi, Klaus Charisse
Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2?-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for 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.
Type:
Grant
Filed:
November 25, 2019
Date of Patent:
August 2, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Martin Maier, Don Foster, Stuart Milstein, Satya Kuchimanchi, Vasant Jadhav, Kallanthottathil Rajeev, Muthiah Manoharan, Rubina Parmar
Abstract: The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.
Type:
Grant
Filed:
January 12, 2022
Date of Patent:
August 2, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Martin Maier, Muthusamy Jayaraman, Akin Akinc, Shigeo Matsuda, Pachamuthu Kandasamy, Kallanthottathil G. Rajeev, Muthiah Manoharan
Abstract: The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.
Type:
Grant
Filed:
December 17, 2021
Date of Patent:
July 12, 2022
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Martin Maier, Muthusamy Jayaraman, Akin Akinc, Shigeo Matsuda, Pachamuthu Kandasamy, Kallanthottathil G. Rajeev, Muthiah Manoharan
Abstract: The invention relates to dual targeting siRNA agents targeting a PCSK9 gene and a second gene, and methods of using dual targeting siRNA agents to inhibit expression of PCSK9 and to treat PCSK9 related disorders, e.g., hyperlipidemia.
Type:
Application
Filed:
August 13, 2021
Publication date:
July 7, 2022
Applicant:
Alnylam Pharmaceuticals, Inc.
Inventors:
Kevin Fitzgerald, Maria Frank-Kamenetsky, Klaus Charisse
Abstract: The invention relates to double stranded ribonucleic acid (dsRNA) agents and compositions targeting a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, as well as methods of inhibiting expression of Hdlbp/Vigilin and methods of treating subjects having a disorder of lipid metabolism, such as mixed hyperlipidemia, hypertriglyceridemia or hypercholesterolemia, using such dsRNA agents and compositions.
Type:
Application
Filed:
November 17, 2021
Publication date:
June 30, 2022
Applicants:
Alnylam Pharmaceuticals, Inc., ETH Zurich
Inventors:
Muthiah Manoharan, Markus Stoffel, Mehrpouya Balaghy Mobin
Abstract: The technology described herein relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the Serpina1 gene, and methods of using such dsRNA compositions to inhibit expression of Serpina1.
Type:
Application
Filed:
October 5, 2021
Publication date:
May 19, 2022
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Alfica SEHGAL, David BUMCROT, Brian BETTENCOURT
Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.
Type:
Grant
Filed:
November 5, 2020
Date of Patent:
May 17, 2022
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Brian Bettencourt, William Querbes, Kevin Fitzgerald, Maria Frank-Kamenetsky, Stuart Milstein, Svetlana Shulga Morskaya