Composition and methods of RNAi prophylactics and therapeutics for treatment of severe acute respiratory infection caused by 2019 novel coronavirus (2019-nCoV)
Inventors
TANG, DANNY • CHEN, XUEPING • Lu, Patrick Y. • Simonenko, Vera • Evans, David • Xu, John • WANG, Deling • Lu, Alan
Assignees
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Publication Number
US-12006500-B2
Publication Date
2024-06-11
Expiration Date
Abstract
Compositions and methods for development of potent siRNA therapeutics for prevention and treatment of Corona Virus (2019-nCoV; COVID-19) infections are provided. The compositions include a pharmaceutical composition comprising siRNA cocktails that target critical viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers. Administration methods for prevention and treatment are provided, including airway instillation, subcutaneous injections and nebulizer aerosolization.
Core Innovation
The disclosed invention relates to a pharmaceutical composition for targeting 2019-nCoV using RNA interference. The composition includes at least a first siRNA molecule targeting a conserved region of an ORF1AB gene and at least a second siRNA targeting a conserved region of an N-protein gene, thereby addressing conserved viral genomic regions.
The composition further comprises a pharmaceutically acceptable carrier in which the siRNA is formulated with polymeric nanoparticle and/or liposomal nanoparticle carriers. The polymeric carrier is described as comprising a histidine-lysine co-polymer (HKP), and the liposomal carrier is described as comprising spermine–lipid conjugate (SLiC) in formulation with cholesterol, where the carrier components are part of the claimed nanoparticle formulation.
In one claimed embodiment, the composition comprises a combination of two sense strands selected from defined sense-strand pairs (CoV3 and CoV18; CoV3 and CoV14; CoV4 and CoV14; CoV4 and CoV18) with specified nucleotide sequences and SEQ ID numbers. This sense-strand combination is presented as part of the siRNA-containing nanoparticle pharmaceutical composition directed to conserved ORF1AB and N-protein gene regions.
Claims Coverage
The partial content includes two independent claims. Across these, the claims share a core structure: two siRNA molecules targeting conserved ORF1AB and conserved N-protein gene regions of 2019-nCoV, formulated with a pharmaceutically acceptable nanoparticle and/or liposomal carrier, with additional specificity in the second independent claim via defined combinations of sense strands and sequences.
Two-siRNA composition against conserved ORF1AB and N-protein regions
A pharmaceutical composition comprising at least a first siRNA molecule that targets a conserved region of an ORF1AB gene of the Wuhan seafood market novel pneumonia 2019-nCoV genome, and at least a second siRNA that targets a conserved region of an N-protein gene of said 2019-nCoV genome.
Nanoparticle or liposomal pharmaceutically acceptable carrier
The composition comprises a pharmaceutically acceptable carrier, wherein said carrier comprises a polymeric nanoparticle and/or a liposomal nanoparticle carrier.
Defined first and second siRNA sequence selections
The first siRNA molecule is selected from the group consisting of SEQ ID NO:401-403 and 414-418, and the second siRNA molecule is selected from the group consisting of SEQ ID NO:404-406 and 425-431.
Two sense-strand combinations with specified CoV sense sequences
The composition further comprises a combination of two sense strands, one from each of said first and second siRNA molecules, and said combination is selected from the group consisting of CoV3 and CoV18, CoV3 and CoV14, CoV4 and CoV14, and CoV4 and CoV18, with CoV3, CoV4, CoV-14, and CoV18 defined by the provided nucleotide sequences and SEQ ID numbers (SEQ ID NO:401-406).
Overall, claim coverage centers on a 2019-nCoV-directed pharmaceutical composition containing two siRNA molecules against conserved ORF1AB and N-protein gene regions, formulated in polymeric and/or liposomal nanoparticle carriers, with the second independent claim further restricting the composition to specific two-sense-strand pair combinations (CoV3/CoV18, CoV3/CoV14, CoV4/CoV14, or CoV4/CoV18) using defined sequences.
Stated Advantages
Documented Applications
No documented applications found
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