Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.
Type:
Grant
Filed:
February 9, 2021
Date of Patent:
July 9, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Jared Gollob, Gregory Hinkle, Ivanka Toudjarska, David Bumcrot
Abstract: The disclosure relates to compositions and methods for treating chitinase 3-like protein 1/YKL-40 (CHI3L1/YKL-40)-associated diseases and disorders. More particularly, the disclosure relates to CHI3L1/YKL-40-targeting RNAi agents and methods, as well as methods of inhibiting expression of a CHI3L1/YKL-40 gene and methods of treating subjects having a CHI3L1/YKL-40-associated disease or disorder, such as cerebral amyloid angiopathy (CAA) and early onset familial Alzheimer disease (EOFAD or eFAD), using such dsRNAi agents and compositions.
Type:
Application
Filed:
April 22, 2022
Publication date:
June 27, 2024
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Bret L. Bostwick, Jeffrey Zuber, Mark Schlegel
Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an Elongation of very long chain fatty acids protein 1 (ELOVL1) gene, as well as methods of inhibiting expression of an ELOVL1 gene and methods of treating subjects having an ELOVL1-associated disease or disorder, e.g., X-Linked Adrenoleukodystrophy (X-ALD), using such dsRNAi agents and compositions.
Type:
Application
Filed:
March 24, 2022
Publication date:
June 27, 2024
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
MANGALA MEENAKSHI SOUNDARAPANDIAN, JAMES D. MCININCH, ADAM CASTORENO
Abstract: The disclosure provides systems, compositions, kits, and methods useful for the targeted site-specific modifications of RNA molecules. Generally, the systems, compositions, kits, and methods described herein comprise a polypeptide or a nucleic acid encoding the polypeptide. The polypeptide comprises a first domain comprising a catalytic domain of an RNA modifying enzyme and a second domain comprising a MID domain of an Argonaute (Ago) protein. The systems, compositions, kits, and methods can also comprise an oligonucleotide for targeting the polypeptide to a target RNA. A method for modifying a target RNA, comprises contacting the target RNA with a polypeptide or a nucleic acid encoding the polypeptide and with an oligonucleotide described herein. Some exemplary modifications of the target RNA include, but are not limited to, site-specific deamination of an adenosine, deamination of a cytidine, methylation (e.g., methylation at position 6) of an adenosine, and demethylation of m6-adenosine in the target RNA.
Type:
Application
Filed:
April 29, 2022
Publication date:
June 27, 2024
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Min TAN, Christopher BROWN, Vasant JADHAV
Abstract: 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.
Type:
Grant
Filed:
January 25, 2022
Date of Patent:
June 25, 2024
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Ivan Zlatev, Adam Castoreno, Martin Maier, Vasant Jadhav, Jae Kim, Pushkal Garg
Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Stearoyl-CoA Desaturase 5 (SCD5) gene, as well as methods of inhibiting expression of an SCD5 gene and methods of treating subjects having an SCD5-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.
Type:
Application
Filed:
March 17, 2022
Publication date:
June 20, 2024
Applicant:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
LAN THI HOANG DANG, JAMES D. MCININCH, ADAM CASTORENO
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. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.
Type:
Grant
Filed:
May 3, 2023
Date of Patent:
June 11, 2024
Assignee:
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: One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, which provides for targeting to, and uptake by, tissues and cells of the CNS via administration to a subarachnoid space, e.g., the cisterna magna. Another aspect of the invention relates to a method of gene silencing in tissues and cells of the CNS, that includes administering to the subarachnoid space of a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.
Type:
Application
Filed:
March 4, 2022
Publication date:
May 30, 2024
Applicant:
ALNYLAM PHARMACEUTICALS, INC
Inventors:
Tanya Z. Fischer, Bret L. Bostwick, Christopher S. Thiele, Charalambos Kaittanis, Jeffrey C. Kurz, Jeffrey W. Allen
Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Huntingtin (HTT) gene, as well as methods of inhibiting expression of an HTT gene and methods of treating subjects having an HTT-associated disease or disorder, e.g., Huntington's disease, using such dsRNAi agents and compositions.
Type:
Grant
Filed:
June 1, 2023
Date of Patent:
May 28, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Mangala Meenakshi Soundarapandian, James D. McIninch, Mark K. Schlegel, Adam Castoreno
Abstract: The invention 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 disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.
Type:
Application
Filed:
April 7, 2023
Publication date:
May 9, 2024
Applicant:
Alnylam Pharmaceuticals, Inc.
Inventors:
Adam Castoreno, Jason Gilbert, Charalambos Kaittanis, James D. McIninch, Stuart Milstein, Mark K. Schlegel
Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the complement factor B (CFB) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a CFB gene and to methods of treating or preventing a CFB-associated disease in a subject.
Type:
Grant
Filed:
March 22, 2023
Date of Patent:
April 23, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
James D. McIninch, Mark K. Schlegel, Adam Castoreno, Elane Fishilevich, Kristina Yucius
Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the transthyretin (TTR) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an TTR gene and to methods of preventing and treating an TTR-associated disorder, e.g., senile systemic amyloidosis (SSA), systemic familial amyloidosis, familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy (FAC), leptomeningeal/Central Nervous System (CNS) amyloidosis, and hyperthyroxinemia.
Type:
Grant
Filed:
September 28, 2022
Date of Patent:
April 16, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Mark K. Schlegel, Adam Castoreno, James D. McIninch
Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) molecules comprising a 6-methyladenine nucleobase and capable of inhibiting the expression of a target gene. 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.
Abstract: This disclosure relates to an improved process for the preparation of carbohydrate conjugates. The disclosure also relates to carbohydrate conjugated iRNA agents comprising these carbohydrate conjugates, which have improved purity and are advantageous for the in vivo delivery of the iRNA agents.
Type:
Grant
Filed:
July 5, 2022
Date of Patent:
April 2, 2024
Assignee:
ALNYLAM PHARMACEUTICALS, INC.
Inventors:
Jayaprakash K. Nair, Alexander V Kel'in, Pachamuthu Kandasamy, Kallanthottathil G Rajeev, Muthiah Manoharan
Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the ketohexokinase (KHK) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KHK gene and to methods of treating or preventing a KHK-associated disorder in a subject.
Type:
Grant
Filed:
December 2, 2022
Date of Patent:
March 12, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Leila Noetzli, James D. McIninch, Frederic Tremblay, Mark K. Schlegel, Adam Castoreno
Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA.
Type:
Grant
Filed:
September 14, 2021
Date of Patent:
January 30, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Antonin de Fougerolles, Tatiana Novobrantseva, Gregory Hinkle
Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.
Type:
Grant
Filed:
July 12, 2021
Date of Patent:
January 16, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Kevin Fitzgerald, James Butler, Brian Bettencourt, Anna Borodovsky, Satyanarayana Kuchimanchi, Klaus Charisse, Muthiah Manoharan, Martin A. Maier, Kallanthottathil G. Rajeev, Donald Foster
Abstract: The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement factor C3 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of a C3 gene and to treat subjects having a complement component C3-associated disease, e.g., paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), atypical hemolytic uremic syndrome (aHUS), neuromyelitis optica (NMO), multifocal motor neuropathy (MMN), myasthenia gravis (MG), and C3 glomerulonephritis.
Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Transmembrane protease, serine 6 (TMPRSS6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a TMPRSS6 gene and to methods of preventing and treating a TMPRSS6-associated disorder, e.g., a disorder associated with iron overload and/or a disorder of ineffective erythropoiesis, e.g., hereditary hemochromatosis, ?-thalassemia (e.g., ?-thalassemia major and ?-thalassemia intermedia), polycythemia vera, myelodysplastic syndrome, congenital dyserythropoietic anemias, pyruvate kinase deficiency, erythropoietic porphyria, Parkinson's Disease, Alzheimer's Disease or Friedreich's Ataxia.
Type:
Grant
Filed:
January 6, 2023
Date of Patent:
January 9, 2024
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Aimee M. Deaton, John Michael Gansner, James D. McIninch, Mark K. Schlegel, Benjamin P. Garfinkel