Compositions and methods for inducing ESR1, PI3K, HER2, and HER3 immune responses
Inventors
Wang, Nathaniel Stephen • Miyake-Stoner, Shigeki Joseph • Aliahmad, Parinaz
Assignees
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Publication Number
US-11510975-B1
Publication Date
2022-11-29
Expiration Date
Abstract
The present disclosure relates to the field of molecular virology, and particularly relates to nucleic acid molecules encoding a modified equine encephalitis virus viral genome or self-replicating RNA (srRNA) construct, pharmaceutical compositions containing the same, and the use of such nucleic acid molecules and compositions for production of desired products in cell cultures or in a living body. Also provided are methods for eliciting an immune response in a subject in need thereof, as well as methods for preventing and/or treating cancer.
Core Innovation
The invention provides a nucleic acid construct comprising a nucleic acid sequence encoding a modified Eastern Equine Encephalitis virus (EEEV) genome or self-replicating RNA (srRNA), in which at least a portion of the nucleic acid sequence encoding the viral structural proteins is replaced with a coding sequence for a polypeptide construct comprising estrogen receptor 1 (ESR1), PI3K, HER2, and HER3, each with variants. The disclosure specifies activating variants for ESR1 and PI3K and a kinase-inactive HER3 variant.
The described constructs further include molecular architecture options for expressing multiple polypeptides. These architectures include a single ORF polycistronic arrangement with a subgenomic promoter and/or separate promoters, and connector/linker elements including autoproteolytic peptides and/or IRES elements.
The disclosure further specifies sequence constraints for the nucleic acid sequences, including sequence identity thresholds relative to sequences selected from SEQ ID NOS: 7-10. The construct is defined by the replacement of viral structural-protein coding region with the multi-antigen polypeptide construct and the specified variant features.
Claims Coverage
The independent claim provides one inventive feature centered on replacing a portion of the modified EEEV genome or srRNA structural-protein coding region with a polypeptide construct encoding ESR1, PI3K, HER2, and HER3. Dependent claims further specify activating ESR1 and PI3K mutations, a kinase-inactive HER3 form, sequence-identity thresholds, and molecular architecture features.
Modified EEEV or srRNA structural-protein replacement with multi-antigen polypeptide construct
A nucleic acid construct encoding a modified Eastern Equine Encephalitis virus (EEEV) genome or self-replicating RNA (srRNA), wherein at least a portion of the nucleic acid sequence encoding the viral structural proteins is replaced by a coding sequence for a polypeptide construct comprising ESR1, PI3K, HER2, and HER3, each with variants.
Activating ESR1 variant mutations
The nucleic acid construct includes activating mutations chosen from K303R, E380Q, Y537C, Y537S, Y537N, and D538G.
Activating PI3K variant mutations
The nucleic acid construct includes activating mutations chosen from E542K, E545K, H1047L, and H1047R.
Kinase-inactive HER3 variant
The HER3 variant includes a coding sequence for a kinase-inactive HER3.
Nucleic acid sequence identity thresholds to specified SEQ ID NOS
The nucleic acid sequence has at least the indicated sequence-identity percentage (80% to 100%) to a nucleic acid sequence selected from SEQ ID NOS: 7-10.
Overall, the claims center on replacing modified EEEV or srRNA structural-protein coding with a multi-antigen polypeptide construct encoding ESR1, PI3K, HER2, and HER3, with dependent refinements specifying named activating ESR1 and PI3K mutations, a kinase-inactive HER3 form, and nucleic acid sequence identity thresholds relative to SEQ ID NOS: 7-10.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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