IP Library › Granted Patent US 12,435,338
Granted Patent B2
US 12,435,338 · App. 18/518,177 · Granted Oct 7, 2025

Composition for regulating production of interfering ribonucleic acid

Inventors: Bradley G. Thompson (Calgary, CA); Jillian Thompson (Calgary, CA)
Assignee: Wyvern Pharmaceuticals Inc.
C12N15/117C12N15/86C12N2310/141C12N2750/14143
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Quick Facts
Patent No.
US 12,435,338
App. No.
18/518,177
Granted
Oct 7, 2025
Kind
B2
Abstract

Embodiments of the present disclosure relate to a composition that comprises a recombinant plasmid (RP) with a sequence of nucleic acids. The sequence comprise a start region, an end region and an insert positioned between the start region and the end region. The insert encodes for a sequence of micro interfering ribonucleic acid (miRNA) that may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is an immune checkpoint protein.

Claims (2)

1. A composition that comprises a recombinant plasmid (RP) with a sequence of nucleotides that is 100% identical to SEQ ID NO: 2.

2. The composition of claim 1 , wherein the RP is encased in a protein coat, a lipid vesicle, or any combination thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 6, 2025
From: THOMPSON, BRADLEY G.; THOMPSON, JILL
To: WYVERN PHARMACEUTICALS INC.
Reel/Frame 071951/0283 →
Continuity (1)
Related Publication 20250163432A1 · May 22, 2025
References Cited (54)
US 11085055B2 · Mallol et al. · 2021 [cited by applicant]
US 11162102B2 · Minshull · 2021 [cited by examiner]
US 11530423B1 · Thompson · 2022 [cited by applicant]
US 11873505B2 · Thompson · 2024 [cited by applicant]
US 12018274B2 · Thompson · 2024 [cited by applicant]
US 12134770B1 · Thompson · 2024 [cited by applicant]
US 20220220187A1 · Sabzevari · 2022 [cited by examiner]
US 20220356489A1 · Thompson · 2022 [cited by applicant]
US 20240026377A1 · Thompson · 2024 [cited by applicant]
CA 2721333A1 · 2009 [cited by applicant]
Barnum KJ, O'Connell MJ. Cell cycle regulation by checkpoints. Methods Mol Biol. 2014;1170:29-40. doi: 10. 1007/978-1-4939-0888-2_2. PMID: 24906307; PMCID: PMC4990352. (Year: 2014). [cited by examiner]
O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). Aug. 3, 2018;9:402. doi: 10.3389/fendo.2018.00402. PMID: 30123182; PMCID: PMC60… [cited by examiner]
Zhang S, Cheng Z, Wang Y, Han T. The Risks of miRNA Therapeutics: In a Drug Target Perspective. Drug Des Devel Ther. Feb. 22, 2021;15:721-733. doi: 10.2147/DDDT.S288859. Erratum in: Drug Des Devel Ther. Mar. 30, 2021;15… [cited by examiner]
Defining checkpoint molecules: Zhang, Y., Zheng, J. (2020). Functions of Immune Checkpoint Molecules Beyond Immune Evasion. In: Xu, J. (eds) Regulation of Cancer Immune Checkpoints. Advances in Experimental Medicine and… [cited by examiner]
Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. Jan. 8, 2019;47(D1):D155-D162. doi: 10.1093/nar/gky1141. PMID: 30423142; PMCID: PMC6323917. (Year: 2018). [cited by examiner]
Juppner H. Functional properties of the PTH/PTHrP receptor. Bone. Aug. 1995;17(2 Suppl):39S-42S. doi: 10.1016/8756-3282(95)00206-s. PMID: 8579896. (Year: 1995). [cited by examiner]
Ha M, Pang M, Agarwal V, Chen ZJ. Interspecies regulation of microRNAs and their targets. Biochim Biophys Acta. Nov. 2008;1779(11):735-42. doi: 10.1016/j.bbagrm.2008.03.004. Epub Mar. 25, 2008. PMID: 18407843; PMCID: PM… [cited by examiner]
Ahmad et al .Adaptive selection in the evolution of programmed cell death-1 and its ligands in vertebrates. Aging (Albany NY). Feb. 11, 2020;12(4):3516-3557. (Year: 2020). [cited by examiner]
Lam et al. 2015. siRNA Versus miRNA as Therapeutics for Gene Silencing. Molec. Ther. Nuc. Ac. 4:e252. doi: 10.1038/mtna.2015.23. (Year: 2015). [cited by examiner]
Ying et al. 2008. The MicroRNA (miRNA): Overview of the RNA Genes that Modulate Gene Function. Mol. Biotechnol. 38:257-268. doi: 10.1007/s12033-007-9013-8 (Year: 2008). [cited by examiner]
Gorski, S., Vogel, J. & Doudna, J. RNA-based recognition and targeting: sowing the seeds of specificity. Nat Rev Mol Cell Biol 18, 215-228 (2017). (Year: 2017). [cited by examiner]
Denzler R et al. Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression. Mol Cell. Nov. 3, 2016;64(3):565-579. doi: 10.1016/j.molcel.2016.09.027 (… [cited by examiner]
NCBI Reference Sequence: NG_012110.1. Homo sapiens programmed cell death 1 (PDCD1), RefSeqGene on chromosome 2. Aug. 31, 2020. (Year: 2020). [cited by examiner]
O'Brien et al. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation, Frontiers in Endocrinology, vol. 9, Article 402: 1-12 (2018). (Year: 2018). [cited by examiner]
Zhang et al. The Risks of miRNA Therapeutics: In a Drug Target Perspective, Drug Design, Development and Therapy 15: 721-733 (2021). (Year: 2021). [cited by examiner]
Ha et al. Interspecies Regulation of MicroRNAs and Their Targets, Biochim Biophys Acta. Nov. 2008 ; 1779(11): 735-74. (Year: 2008). [cited by examiner]
Van den Berg, et al., pp. 1-12, Molecular Therapy—Nucleic Acids, vol. 5, 2016 (Year: 2016). [cited by examiner]
Wang et al. “Adeno-associated virus vector as a platform for gene therapy delivery”. Nat Rev Drug Discov. May 2019; 18(5):358-378. (Year: 2019). [cited by applicant]
NCBI Reference Sequence: NC_000009.12. Homo sapiens chromosome 9, GRCh38.p14 Primary Assembly. (gene=“CD274”, gene_synonym=B7-H; B7H1; hPD-L1; PD-L1; PDCD1L1; PDCD1LG1; PDL1). Oct. 7, 2023. (Year: 2023). [cited by applicant]
Qiniou et al. Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates. Front. Immunol., Nov. 12, 2024. Sec. Comparative Immunology. vol. 15—2024. (Year: 2024). [cited by applicant]
NCBI Reference Sequence: NG_011502.1. Homo sapiens cytotoxic T-lymphocyte-associated protein 4 (CTLA4) on chromosome 2. Mar. 11, 2009. (Year: 2009). [cited by applicant]
NCBI Reference Sequence: NR_030784.1. Homo sapiens microRNA 155 (MIR155), microRNA. Nov. 24, 2009. (Year: 2009). [cited by applicant]
Vaddi et al. CTLA4 mRNA is downregulatA4 mRNA is downregulated by miR-155 in regulatory T cells, and reduced blood CTLA4 levels are associated with poor prognosis in metastatic melanoma patients. Front. Immunol. Apr. 30… [cited by applicant]
Yuasa et al. Low efficiency ID02 enzymes are conserved in lower vertebrates, whereas higher efficiency ID01 enzymes are dispensable. FEBS Journal 282 (2015) 2735-2745. (Year: 2015). [cited by applicant]
GenBank: LM608503.1. TPA: Homo sapiens microRNA hsa-mir-153-1 precursor. Mar. 3, 2015. (Year: 2015). [cited by applicant]
GenBank: LM608504.1. Tpa: Homo sapiens microRNA hsa-mir-153-2 precursor. Mar. 3, 2015. (Year: 2015). [cited by applicant]
NCBI Reference Sequence: NG_028155.1. Homo sapiens indoleamine 2,3-dioxygenase 1 (IDO1), RefSeqGene on chromosome 8. May 18, 2020. (Year: 2020). [cited by applicant]
Bottoni et al. “Targeting BTK through microRNA in chronic lymphocytic leukemia.” Blood, The Journal of the American. [cited by applicant]
Christensen et al. “Recombinant adeno-associated virus-mediated microRNA delivery into the postnatal mouse brain reveals a role for miR-134 in dendritogenesis in vivo.” Frontiers in neural circuits 3 (2010): 848. [cited by applicant]
Bofill-De Ros et al. “Guidelines for the optimal design of miRNA-based shRNAs.” Methods 103 (2016): 157-166. [cited by applicant]
Tritschler et al. “Concepts and limitations for learning developmental trajectories from single cell genomics.” Development 146.12 (2019): dev170506. [cited by applicant]
Ahmadzadeh et al. “BRAF mutation in hairy cell leukemia.” Oncology reviews 8.2 (2014): 253. [cited by applicant]
Patton et al. “Biogenesis, delivery, and function of extracellular RNA.” Journal of extracellular vesicles 4.1 (2015): 27494. [cited by applicant]
Clark et al. “Detection of BRAF splicing variants in plasma-derived cell-free nucleic acids and extracellular vesicles of melanoma patients failing targeted therapy therapies.” Oncotarget 11.44 (2020): 4016. [cited by applicant]
Kondratov et al. “Direct head-to-head evaluation of recombinant adeno-associated viral vectors manufactured in human versus insect cells.” Molecular Therapy 25.12 (2017): 2661-2675. [cited by applicant]
Nature (2010. Gene Expression. Scitable. Available online at Nature.com) <https://www.nature.com/scitable/topicpage/gene-expression-14121669> (2010). [cited by applicant]
Brutons Tyrosine Kinase Genbank Sequence (2023). [cited by applicant]
GenBank EGFR Sequence (2023). [cited by applicant]
GenBank EGF Sequence (2023). [cited by applicant]
NCBI search results for SEQ ID No. 5 (2024). [cited by applicant]
NCBI Nucleotide Sequence ALK Lingand, search performed Dec. 26, 2024 (2023). [cited by applicant]
NCBI Nucleotide Sequence ALK Receptor, search performed Dec. 26, 2024 (2023). [cited by applicant]
NCBI Nucleotide Sequence for PARP, search performed Dec. 26, 2024 (2024). [cited by applicant]
GenBank FLT3 Sequence (2024). [cited by applicant]
Cited By (1)
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