Patents by Inventor Muthiah Manoharan

Muthiah Manoharan has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 12290573
    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: June 24, 2022
    Date of Patent: May 6, 2025
    Assignee: Alnylam Pharmaceuticals, Inc.
    Inventors: Kallanthottathil G. Rajeev, Tracy Zimmermann, Muthiah Manoharan, Martin Maier, Satyanarayana Kuchimanchi, Klaus Charisse
  • Patent number: 12275938
    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: Grant
    Filed: May 13, 2022
    Date of Patent: April 15, 2025
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Shigeo Matsuda, Mark K. Schlegel, Maja Janas, Vasant R. Jadhav, Martin Maier, Klaus Charisse, Muthiah Manoharan, Kallanthottathil Rajeev, Jayaprakash K. Nair
  • Patent number: 12247203
    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: Grant
    Filed: May 16, 2019
    Date of Patent: March 11, 2025
    Inventors: Shigeo Matsuda, Mark K. Schlegel, Maja Janas, Vasant R. Jadhav, Martin Maier, Klaus Charisse, Muthiah Manoharan, Kallanthottathil Rajeev, Jayaprakash K. Nair
  • Publication number: 20250075208
    Abstract: The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.
    Type: Application
    Filed: January 30, 2024
    Publication date: March 6, 2025
    Inventors: Muthiah MANOHARAN, Jayaprakash K. NAIR, Pachamuthu KANDASAMY, Shigeo MATSUDA, Alexander V. KELIN, Muthusamy JAYARAMAN, Kallanthottathil G. RAJEEV
  • Patent number: 12239709
    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: February 28, 2024
    Date of Patent: March 4, 2025
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Martin Maier, Muthusamy Jayaraman, Akin Akinc, Shigeo Matsuda, Pachamuthu Kandasamy, Kallanthottathil G. Rajeev, Muthiah Manoharan, Jayaprakash K. Nair, Thomas A. Baillie
  • Patent number: 12241064
    Abstract: The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.
    Type: Grant
    Filed: August 10, 2021
    Date of Patent: March 4, 2025
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Vasant Jadhav, John Maraganore, Martin Maier, Kallanthottathil G. Rajeev, Muthiah Manoharan, Akin Akinc, Ivan Zlatev
  • Publication number: 20250051765
    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: Application
    Filed: April 29, 2024
    Publication date: February 13, 2025
    Inventors: Kevin Fitzgerald, William Querbes, James Butler, Stephanie Williams, Abigail Liebow, Gregory Hinkle, Martin A. Maier, Stuart Milstein, Satyanarayana Kuchimanchi, Muthiah Manoharan
  • Patent number: 12221607
    Abstract: 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.
    Type: Grant
    Filed: February 22, 2021
    Date of Patent: February 11, 2025
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Vasant Jadhav, Martin Maier, Ivan Zlatev, Akin Akinc, Kallanthottathil G. Rajeev, Jayaprakash K. Nair, Pachamuthu Kandasamy, Muthiah Manoharan
  • Publication number: 20250043279
    Abstract: The invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.
    Type: Application
    Filed: April 24, 2024
    Publication date: February 6, 2025
    Inventors: Mark K. Schlegel, Maja Janas, Vasant R. Jadhav, Donald Foster, Muthiah Manoharan, Kallanthottathil G. Rajeev, Alexander V. Kel'in, Klaus Charisse, Jayaprakash K. Nair, Martin A. Maier, Shigeo Matsuda, Muthusamy Jayaraman, Alfica Sehgal, Christopher Brown, Kevin Fitzgerald, Stuart Milstein
  • Publication number: 20250034572
    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: Application
    Filed: October 8, 2024
    Publication date: January 30, 2025
    Inventors: Martin Maier, Don Foster, Stuart Milstein, Satya Kuchimanchi, Vasant Jadhav, Kallanthottathil Rajeev, Muthiah Manoharan, Rubina Parmar
  • Publication number: 20250025564
    Abstract: The present disclosure relates monomers and methods for synthesizing oligonucleotides comprising 2,6-diaminopurine (DAP) and 2-aminoadenine conjugates. The methodology employs simple aromatic nucleophilic substitution of halogen atom at the 2-position in 2-haloadenosine derivatives with amines or alkali earth hydroxides obviating the need for any protecting group on adenine.
    Type: Application
    Filed: July 15, 2022
    Publication date: January 23, 2025
    Applicant: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Muthiah MANOHARAN, Dhrubajyoti DATTA, Mimouna MADAOUI
  • Publication number: 20240424105
    Abstract: The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).
    Type: Application
    Filed: June 6, 2024
    Publication date: December 26, 2024
    Applicant: ARBUTUS BIOPHARMA CORPORATION
    Inventors: Muthiah Manoharan, Muthusamy Jayaraman, Kallanthottathil G. Rajeev, Laxman Eltepu, Steven Ansell, Jianxin Chen
  • Patent number: 12173288
    Abstract: The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.
    Type: Grant
    Filed: October 2, 2020
    Date of Patent: December 24, 2024
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Muthiah Manoharan, Jayaprakash K. Nair, Pachamuthu Kandasamy, Shigeo Matsuda, Alexander V. Kelin, Muthusamy Jayaraman, Kallanthottathil G. Rajeev
  • Patent number: 12173287
    Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent 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.
    Type: Grant
    Filed: May 7, 2019
    Date of Patent: December 24, 2024
    Assignee: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Rubina G. Parmar, Pawan Kumar, Masaaki Akabane-Nakata, Shigeo Matsuda, Muthiah Manoharan
  • Patent number: 12168767
    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: December 22, 2022
    Date of Patent: December 17, 2024
    Assignee: Alnylam Pharmaceuticals, Inc.
    Inventors: Martin Maier, Don Foster, Stuart Milstein, Satya Kuchimanchi, Vasant Jadhav, Kallanthottathil Rajeev, Muthiah Manoharan, Rubina Parmar
  • Publication number: 20240409942
    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: Application
    Filed: August 23, 2024
    Publication date: December 12, 2024
    Inventors: Martin MAIER, Don FOSTER, Stuart MILSTEIN, Satya KUCHIMANCHI, Vasant JADHAV, Kallanthottathil RAJEEV, Muthiah MANOHARAN, Rubina PARMAR
  • Publication number: 20240398956
    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: Application
    Filed: December 15, 2023
    Publication date: December 5, 2024
    Inventors: Martin MAIER, Muthusamy JAYARAMAN, Akin AKINC, Shigeo MATSUDA, Pachamuthu KANDASAMY, Kallanthottathil G. RAJEEV, Muthiah MANOHARAN
  • Publication number: 20240358738
    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: Application
    Filed: April 30, 2024
    Publication date: October 31, 2024
    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
  • Publication number: 20240285768
    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: Application
    Filed: March 4, 2024
    Publication date: August 29, 2024
    Inventors: Martin MAIER, Muthusamy JAYARAMAN, Akin AKINC, Shigeo MATSUDA, Pachamuthu KANDASAMY, Kallanthottathil G. RAJEEV, Muthiah MANOHARAN, Jayaprakash K. NAIR, Thomas A. BAILLIE
  • Publication number: 20240285767
    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: Application
    Filed: February 28, 2024
    Publication date: August 29, 2024
    Inventors: Martin MAIER, Muthusamy JAYARAMAN, Akin AKINC, Shigeo MATSUDA, Pachamuthu KANDASAMY, Kallanthottathil G. RAJEEV, Muthiah MANOHARAN, Jayaprakash K. NAIR, Thomas A. BAILLIE