Sirna/nanoparticle formulations for treatment of middle-east respiratory syndrome coronaviral infection
Inventors
Lu, Patrick Y. • Simonenko, Vera • Cai, Yibin • Xu, John • Evans, David
Assignees
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Publication Number
US-11058779-B2
Publication Date
2021-07-13
Expiration Date
Abstract
The present invention relates to compositions and methods for siRNA therapeutics for prevention and treatment of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infections. The compositions include a pharmaceutical composition comprising siRNA cocktails that target viral genes and pharmaceutically acceptable polymeric nanoparticle carriers and liposomal nanoparticle carriers.
Core Innovation
The invention relates to siRNA therapeutics for Middle East Respiratory Syndrome coronavirus (MERS-CoV) that target conserved viral genes and conserved genomic regions. The compositions include at least two different siRNA molecules and siRNA cocktails directed to MERS-CoV sequences, including Spike protein targeting and genome targeting, with pharmaceutically acceptable carriers.
A central aspect of the invention is formulation of the siRNA molecules as pharmaceutical compositions with a carrier comprising polymeric nanoparticle or liposomal nanoparticle components. The disclosed carrier options include a polymeric nanoparticle comprising a Histidine-Lysine co-polymer (HKP) and liposomal nanoparticles comprising a Spermine-Lipid Conjugate (SLiC) and cholesterol. This enables siRNA cocktails together with the selected nanoparticle carriers.
The disclosed use addresses both therapeutic and preventive applications in mammals infected with MERS-CoV. The invention further includes administration of a therapeutically effective amount of the siRNA/nanoparticle composition for treating a mammal with MERS infection, with mammalian use including human.
Claims Coverage
The independent claims cover siRNA molecules and siRNA cocktails for MERS-CoV, including Spike-targeting combinations and conserved-region genome targeting defined by specific SEQ ID NO selections, optionally formulated with polymeric or liposomal nanoparticle carriers.
Nanoparticle-formulated Spike-targeting siRNA pair
A pharmaceutical composition comprising at least two different siRNA molecules that target the MERS-CoV Spike protein, and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
Defined genome-targeting siRNA pair in a pharmaceutical composition
A pharmaceutical composition comprising at least two different siRNA molecules that target the genome of a MERS-CoV, wherein a first siRNA molecule comprises MRR2: GGGAUUUCAUGCUUAAAACAUUGUA (SEQ ID NO: 20) and a second siRNA molecule comprises MSP2: GCCGUACAUAUUCUAACAUAACUAU (SEQ ID NO: 700).
Cocktail composition MSTRS1 with specified siRNA molecules and nanoparticle carrier
A pharmaceutical composition comprising a siRNA cocktail, MSTRS1, wherein a first siRNA molecule comprises MRR1: CCCAGUGUUAUUGGUGUUUAUCAUA (SEQ ID NO: 21) and a second siRNA molecule comprises MSP1: GGCCGUACAUAUUCUAACAUAACUA (SEQ ID NO: 12) and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
Cocktail composition MSTPRS1 with specified siRNA molecules and nanoparticle carrier
A pharmaceutical composition comprising a siRNA cocktail, MSTPRS1, wherein a first siRNA molecule comprises MPL1: CGCAAUACGUAAAGCUAAAGAUAU (SEQ ID NO: 22), a second siRNA molecule comprises MRR1: CCCAGUGUUAUUGGUGUUUAUCAUA (SEQ ID NO: 7), and a third siRNA molecule comprises MSP1: GGCCGUACAUAUUCUAACAUAACUA (SEQ ID NO: 12) and a pharmaceutically acceptable carrier comprising a polymeric nanoparticle or a liposomal nanoparticle.
Conserved-region MERS-CoV genome-targeting siRNA selected from enumerated SEQ ID NOs
An siRNA molecule that targets a conserved region of the genome of a MERS-CoV wherein the molecule is selected from the group consisting of the molecules of SEQ ID NOs 12, 1031, 700, 1032, 703, 1033, 717, 1034, 13, 1035, 741, 1036, 14, 1037, 765, 1038, 770, 1039, 771, 1040, 774, 1041, 15, 1042, 16, 1043, 17, 1044, 813, 1045, 18, and 1046.
Conserved-region MERS-CoV genome-targeting siRNA selected from MSP1–MSP8 SEQ ID NOs
An siRNA molecule that targets a conserved region of the genome of a MERS-CoV selected from the group consisting of (SEQ ID NO: 12) MSP1: GGCCGUACAUAUUCUAACAUAACUA, (SEQ ID NO: 700) MSP2: GCCGUACAUAUUCUAACAUAACUAU, (SEQ ID NO: 13) MSP3: CCGAAGAUGAGAUUUUAGAGUGGUU, (SEQ ID NO: 14) MSP4: CCCAGUUUAAUUAUAAACAGUCCUU, (SEQ ID NO: 15) MSP5: GGCUUCACUACAACUAAUGAAGCUU, (SEQ ID NO: 16) MSP6: CCCCUGUUAAUGGCUACUUUAUUAA, (SEQ ID NO: 17) MSP7: CCCUGUUAAUGGCUACUUUAUUAAA, and (SEQ ID NO: 18) MSP8: GCCGCAUAAGGUUCAUGUUCACUAA.
The claims cover siRNA molecules and siRNA cocktails for MERS-CoV, including Spike-targeting combinations and conserved-region genome targeting defined by specific SEQ ID NO selections, optionally formulated with polymeric or liposomal nanoparticle carriers.
Stated Advantages
Documented Applications
No documented applications found
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