Compositions and methods for “resistance-proof” SiRNA therapeutics for influenza
Inventors
Lu, Patrick Y. • Evans, David M. • Xu, John J. • Lu, Alan Y. • Ge, Qing
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9868952-B2
Publication Date
2018-01-16
Expiration Date
Abstract
The present invention relates to compositions and methods for development of resistance-proof siRNA therapeutics for prevention and treatment of influenza viral infections. The compositions include a pharmaceutical composition comprising siRNA molecules that target conserved regions of an influenza virus gene and a pharmaceutically acceptable polymeric carrier. In one embodiment, the polymeric carrier condenses the molecules to form a nanoparticle.
Core Innovation
The invention provides resistance-proof influenza siRNA therapeutics that target conserved influenza gene regions. The approach uses siRNA duplexes directed against conserved regions of influenza A virus genes and is implemented as a pharmaceutical composition that includes siRNA molecules together with a pharmaceutically acceptable polymeric carrier. The formulation is described as being able to condense siRNA into nanoparticles.
The core concept emphasizes multi-targeting by including at least two different siRNA molecules that target conserved regions of different influenza A virus genes. The documented target genes include influenza A genes such as M2, PA, PB, PB1, PB2, and NP. Bioinformatic prediction is described as supporting the selection of siRNAs intended to provide broad coverage across influenza.
The disclosed compositions and siRNAs are exemplified by specific siRNA molecule selections shown in Table 5, including selected molecules such as 89 and 91 for one conserved influenza A gene target and molecules such as 93, 95, 97, 99, 101, 103, and 105 for a different conserved influenza A gene target. The document further describes optional inclusion of potency-enhancing motifs and immune-stimulating motifs in connection with resistance-proof performance, along with reported reporter-based and in vivo validation themes.
Claims Coverage
The partial content includes one independent claim (clm-00001). This claim covers a pharmaceutical composition having at least two different siRNA molecules that target conserved regions of two different influenza A virus genes, together with a pharmaceutically acceptable polymeric carrier, with specific siRNA molecule selections constrained to molecules listed in Table 5.
Two different conserved-region influenza A gene siRNAs
A pharmaceutical composition comprising at least two different siRNA molecules, wherein one targets a conserved region of an influenza A virus gene and is selected from molecules 89 (SEQ ID NOS 14 and 11) or 91 (SEQ ID NOS 61 and 68) as shown in Table 5, and the other targets a conserved region of a different influenza A virus gene and is selected from molecules 93 (SEQ ID NOS 62 and 69), 95 (SEQ ID NOS 63 and 70), 97 (SEQ ID NOS 64 and 71), 99 (SEQ ID NOS 65 and 72), 101 (SEQ ID NOS 66 and 73), 103 (SEQ ID NOS 12 and 13), or 105 (SEQ ID NOS 67 and 74) as shown in Table 5.
Pharmaceutically acceptable polymeric carrier with condensing formulation
The composition further comprises a pharmaceutically acceptable polymeric carrier.
Within the provided independent claim, coverage is anchored on pairing specific Table 5 siRNA molecules that target conserved regions of two different influenza A virus genes, formulated with a pharmaceutically acceptable polymeric carrier.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?