Patents by Inventor Kallanthottathil G. Rajeev
Kallanthottathil G. Rajeev 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).
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SITE-SPECIFIC DELIVERY OF NUCLEIC ACIDS BY COMBINING TARGETING LIGANDS WITH ENDOSOMOLYTIC COMPONENTS
Publication number: 20110123520Abstract: The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components.Type: ApplicationFiled: April 10, 2009Publication date: May 26, 2011Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah Manoharan, Kallanthottathil G. Rajeev, David Butler, Muthusamy Jayaraman -
Patent number: 7947659Abstract: The features of the present invention relate to compounds, compositions and methods useful for modulating the expression of vascular endothelial growth factor (VEGF), such as by the mechanism of RNA interference (RNAi). The compounds and compositions include iRNA agents that can be unmodified or chemically-modified.Type: GrantFiled: March 11, 2005Date of Patent: May 24, 2011Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Antonin de Fougerolles, Maria Frank-Kamenetsky, Muthiah Manoharan, Kallanthottathil G. Rajeev, Philipp Hadwiger
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Publication number: 20110118340Abstract: The invention provides methods for delivering a double-stranded nbonucleic acid (dsRNA) to the central nervous system of a subject, and particularly, to oligodendrocytes of a subject by localized delivery to the brain, e.g., to the corpus caïlosum. For example, the dsRNA molecules can include a first sequence that is selected from the Sroup consisting of the sense sequences of Tables 8, 10, 13-16, and a second sequence selected from the group consisting of the antisense sequences of Tables 8, 10, and 13-16. The dsRNA molecules can include naturally occurring nucleotides or can include at least one modified nucleotide, such as a 2?-O-methyl modified nucleotide, a nucleotide comprising a 5?-phosphorothioate group, or a terminal nucleotide linked to a conjugate group, such as to a cholesteryl derivative or a vitamin E group.Type: ApplicationFiled: February 6, 2009Publication date: May 19, 2011Inventors: Muthiah Manoharan, Kallanthottathil G. Rajeev, Dinah Sah, William Querbes, Pamela Tan, Qingmin Chen
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Publication number: 20110118339Abstract: This invention relates generally to chemically modified oligonuceotides useful for augmenting activity of microRNAs and pre-microRNAs. E.g., the invention relates to single stranded chemically modified oligonuceotides for augmenting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides.Type: ApplicationFiled: January 16, 2009Publication date: May 19, 2011Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah Manoharan, Kallanthottathil G. Rajeev
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Publication number: 20110097707Abstract: One aspect of the present invention relates to an oligonucleotide agent comprising at least one universal nucleobase. In certain embodiments, the universal nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the universal nucleobase is difluorotolyl. In certain embodiments, the oligonucleotide is double-stranded. In certain embodiments, the oligonucleotide is single-stranded. Another aspect of the present invention relates to a method of altering the expression level of a target in the presence of target sequence polymorphism. In a preferred embodiment, the oligonucleotide agent alters the expression of different alleles of a gene. In another preferred embodiment, the oligonucleotide agent alters the expression level of two or more genes. In another embodiment, the oligonucleotide agent alters the expression level of a viral gene from different strains of the virus.Type: ApplicationFiled: October 29, 2010Publication date: April 28, 2011Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah MANOHARAN, Kallanthottathil G. RAJEEV
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Patent number: 7928217Abstract: This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene.Type: GrantFiled: May 27, 2005Date of Patent: April 19, 2011Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Hans-Peter Vornlocher, Ingo Roehl, Philipp Hadwiger, Tracy Stage Zimmermann, Muthiah Manoharan, Kallanthottathil G. Rajeev, Akin Akinc
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Patent number: 7919473Abstract: The features of the present invention relate to compounds, compositions and methods useful for modulating the expression of vascular endothelial growth factor (VEGF), such as by the mechanism of RNA interference (RNAi). The compounds and compositions include iRNA agents that can be unmodified or chemically-modified.Type: GrantFiled: January 25, 2006Date of Patent: April 5, 2011Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Antonin De Fougerolles, Maria Frank-Kamenetsky, Muthiah Manoharan, Kallanthottathil G. Rajeev, Philipp Hadwiger
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Patent number: 7893224Abstract: One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase.Type: GrantFiled: July 31, 2009Date of Patent: February 22, 2011Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Kallanthottathil G. Rajeev, Jie Xia
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Publication number: 20100324120Abstract: The invention features a cationic lipid of formula I, an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.Type: ApplicationFiled: June 10, 2010Publication date: December 23, 2010Inventors: Jianxin Chen, Steven Ansell, Akin Akinc, Joseph Robert Dorkin, Xiaojun Qin, William Cantley, Muthiah Manoharan, Kallanthottathil G. Rajeev, Jayaprakash K. Narayanannair, Muthusamy Jayaraman
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Publication number: 20100292455Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.Type: ApplicationFiled: February 26, 2010Publication date: November 18, 2010Applicant: ALNYLAM PHARMACEUTICALSInventors: Muthiah MANOHARAN, Venkitasamy KESAVAN, Kallanthottathil G. RAJEEV
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Publication number: 20100267941Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.Type: ApplicationFiled: March 15, 2010Publication date: October 21, 2010Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah MANOHARAN, Kallanthottathil G. RAJEEV
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Publication number: 20100240881Abstract: This application relates to therapeutic siRNA agents and methods of making and using the agents.Type: ApplicationFiled: March 10, 2010Publication date: September 23, 2010Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah MANOHARAN, Kallanthottathil G. RAJEEV, David BUMCROT
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Publication number: 20100222413Abstract: This invention relates generally to chemically modified oligonuceotides useful for modulating expression of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonuceotides for inhibiting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. Also included in the invention are compositions and methods for silencing microRNAs in the central nervous system.Type: ApplicationFiled: March 1, 2010Publication date: September 2, 2010Applicants: The Rockefeller University, Alnylam Pharmaceuticals, Inc.Inventors: Markus Stoffel, Muthiah Manoharan, Kallanthottathil G. Rajeev
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Patent number: 7772387Abstract: One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl.Type: GrantFiled: July 1, 2009Date of Patent: August 10, 2010Assignee: Alnylam PharmaceuticalsInventors: Muthiah Manoharan, Jie Xia, Kallanthottathil G. Rajeev
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Publication number: 20100197899Abstract: The present invention provides single-stranded and double-stranded oligonucleotides comprising at least one aralkyl ligand that improvise the pharmacokinetic properties of the oligonucleotide. The aralkyl ligands of the present invention include naproxen, ibuprofen, and derivatives thereof. The present invention also provides method for modulating gene expression using the modified oligonucleotide compounds and compositions comprising those modified oligonucleotides.Type: ApplicationFiled: October 23, 2009Publication date: August 5, 2010Applicant: Alnylam Pharmaceuticals, Inc.Inventors: Muthiah MANOHARAN, Kallanthottathil G. Rajeev, Vekitasamy Kesavan
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Publication number: 20100179309Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a carbohydrate; or a steroid, e.g., cholesterol, which is optionally substituted with at least one carbohydrate. is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.Type: ApplicationFiled: November 16, 2009Publication date: July 15, 2010Applicant: Alnylam PharmaceuticalsInventors: Muthiah MANOHARAN, Kallanthottathil G. Rajeev
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Patent number: 7745608Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.Type: GrantFiled: August 10, 2004Date of Patent: June 29, 2010Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Venkitasamy Kesavan, Kallanthottathil G. Rajeev
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Patent number: 7723509Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.Type: GrantFiled: November 9, 2004Date of Patent: May 25, 2010Assignee: Alnylam PharmaceuticalsInventors: Muthiah Manoharan, Kallanthottathil G. Rajeev
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Patent number: 7723512Abstract: One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3?-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide.Type: GrantFiled: July 1, 2009Date of Patent: May 25, 2010Assignee: Alnylam PharmaceuticalsInventors: Muthiah Manoharan, Kallanthottathil G. Rajeev
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Publication number: 20100076056Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g.Type: ApplicationFiled: July 27, 2009Publication date: March 25, 2010Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah MANOHARAN, Kallanthottathil G. RAJEEV, MEENA