IP Library › Granted Patent US 12,697,307
Granted Patent B2
US 12,697,307 · App. 17/924,758 · Granted Aug 4, 2026

Compositions and methods related to megakaryocyte-derived extracellular vesicles

Inventor: Jonathan Thon (Cambridge, MA)
Assignee: STRM.bio Incorporated
A61K9/5068A61K9/127A61K35/19A61K48/0033C12N5/0644C12N13/00C12N2506/03C12N2506/11
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Quick Facts
Patent No.
US 12,697,307
App. No.
17/924,758
Granted
Aug 4, 2026
Kind
B2
Abstract

Disclosed herein are compositions and methods related to megakaryocyte-derived extracellular vesicles derived from human pluripotent stem cells, where the megakaryocyte-derived extracellular vesicles may be utilized for drug delivery and treating various diseases.

Claims (20)

1 . A composition comprising:

a plurality of megakaryocyte-generated extracellular vesicles (MkEVs) comprising a lipid bilayer membrane surrounding a lumen, wherein:

a. the MkEV lumen comprises one or more nucleic acid molecules from the megakaryocytes selected from mRNA, tRNA, rRNA, siRNA, microRNA, regulating RNA, and non-coding and coding RNA; and,

b. the lipid bilayer membrane comprises one or more proteins associated with or embedded within, wherein the one or more proteins are selected from CD21 and GPVI; and,

C. the MkEVs are isolated from megakaryocytes derived from a human pluripotent stem cell (HPSC).

2 . The composition of claim 1 , wherein the lipid bilayer membrane further comprises one or more of CD9, CD63, CD47, CD43, CD54, and CD18.

3 . The composition of claim 1 , wherein the lipid bilayer membrane further comprises one or more of CD41, CD61, CD11b, LAMP-1 (CD107a), CD51, CD31, CD147, phosphatidylserine, CLEC-2, CD62, CD42b, and CD32a.

4 . The composition of claim 1 , wherein the MkEVs are of a diameter in the range between 100 nm to 300 nm.

5 . The composition of claim 1 , wherein the MkEVs are essentially free of:

a. megakaryocytes, and/or

b. platelets

C. organelles, and/or

d. mitochondria or nuclei.

6 . The composition of claim 1 , wherein the MkEVs are suitable for homing to a hematopoietic stem cell, a bone marrow, a lymphatic cell, or a regulatory T cell in vivo and/or in vitro.

7 . The composition of claim 1 , wherein the MkEVs are suitable for loading with cargo into the lumen and/or loading with cargo associated with the surface of the MkEVs.

8 . The composition of claim 7 , wherein the cargo is selected from one or more of a RNA, DNA, protein, carbohydrate, lipid, biomolecule, and small molecule.

9 . The composition of claim 8 , wherein the cargo is one or more therapeutic agents.

10 . The composition of claim 9 , wherein the therapeutic agent is selected from one or more of an antibody or an antibody fragment, recombinant protein, fusion protein, gene-editing protein, cytokine, antigen, and peptide.

11 . The composition of claim 9 , wherein the therapeutic agent is a nucleic acid therapeutic agent selected from one or more non-autologous and/or recombinant nucleic acid constructs selected from mRNA, tRNA, rRNA, siRNA, microRNA, regulating RNA, non-coding and coding RNA, linear DNA, DNA fragments, and DNA plasmids.

12 . The composition of claim 11 , wherein the nucleic acid therapeutic agent encodes a functional protein or a gene-editing protein.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 8, 2023
From: THON, JONATHAN
To: STRM.BIO INCORPORATED
Reel/Frame 062631/0476 →
Continuity (7)
Provisional Application 63173725 · Apr 12, 2021
Provisional Application 63173731 · Apr 12, 2021
Provisional Application 63173732 · Apr 12, 2021
Provisional Application 63022888 · May 11, 2020
Provisional Application 63022883 · May 11, 2020
Provisional Application 63022884 · May 11, 2020
Related Publication 20230190815A1 · Jun 22, 2023
References Cited (62)
US 9085778B2 · Lötvall et al. · 2015 [cited by applicant]
US 9629929B2 · Lötvall et al. · 2017 [cited by applicant]
US 9856477B2 · Lötvall et al. · 2018 [cited by applicant]
US 9889210B2 · Lötvall et al. · 2018 [cited by applicant]
US 10195290B1 · Dooley et al. · 2019 [cited by applicant]
US 10370663B2 · Lötvall et al. · 2019 [cited by applicant]
US 10538738B2 · Papoutsakis et al. · 2020 [cited by applicant]
US 10561740B2 · Dooley et al. · 2020 [cited by applicant]
US 10695443B2 · Lötvall et al. · 2020 [cited by applicant]
US 10723782B2 · Lewis et al. · 2020 [cited by applicant]
US 11512315B2 · Sathyanarayanan et al. · 2022 [cited by applicant]
US 20010005591A1 · Qasba et al. · 2001 [cited by applicant]
US 20040152628A9 · Tandon et al. · 2004 [cited by applicant]
US 20080069807A1 · Jy et al. · 2008 [cited by applicant]
US 20080213377A1 · Bhatia et al. · 2008 [cited by applicant]
US 20120238020A1 · Mitchell et al. · 2012 [cited by applicant]
US 20120315338A1 · Li et al. · 2012 [cited by applicant]
US 20120321723A1 · Bruno et al. · 2012 [cited by applicant]
US 20160324897A1 · Ingber · 2016 [cited by examiner]
US 20170058262A1 · Papoutsakis · 2017 [cited by examiner]
US 20180055891A1 · Zhao · 2018 [cited by applicant]
US 20180328940A1 · Goetzl · 2018 [cited by examiner]
US 20190202892A1 · Lewis et al. · 2019 [cited by applicant]
US 20200115681A1 · Papoutsakis et al. · 2020 [cited by applicant]
US 20220143095A1 · Hett et al. · 2022 [cited by applicant]
WO WO2015179301A1 · 2015 [cited by applicant]
WO WO2017044149A1 · 2017 [cited by applicant]
WO WO2018165308A1 · 2018 [cited by applicant]
WO WO2019136318A2 · 2019 [cited by applicant]
WO WO2020006539A1 · 2020 [cited by applicant]
WO WO2020018950A1 · 2020 [cited by applicant]
WO WO2020113059A1 · 2020 [cited by applicant]
WO WO2021123775A2 · 2021 [cited by examiner]
WO WO2021138332A1 · 2021 [cited by applicant]
WO WO2021173828A1 · 2021 [cited by applicant]
WO WO2022081836A1 · 2022 [cited by applicant]
Kao, Chen-Yuan, and Eleftherios T. Papoutsakis. “Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications.” Current opinion in biotechno… [cited by examiner]
Aoyama, Keisuke, et al. “Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cells.” Blood, The Journal of the American Society of Hematology 93.8 (1999): 2586-2594. (Year: 1999). [cited by examiner]
Kao, Chen-Yuan, and Eleftherios T. Papoutsakis. “Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications.” Current opinion in biotechno… [cited by examiner]
Lagrue-Lak-Hal, Anne-Hélène, et al. “Expression and function of the collagen receptor GPVI during megakaryocyte maturation.” Journal of Biological Chemistry 276.18 (2001): 15316-15325. (Year: 2001). [cited by examiner]
Flaumenhaft, Robert, et al. “Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles.” Blood, The Journal of the American Society of Hematology 113.5 (2009): 1112-… [cited by examiner]
Gilligan, Cells 2020, 9, 224; doi:10.3390/cells9010224. [cited by applicant]
Kamerkar, Nature. Jun. 22, 2017; 546(7659): 498-503. doi:10.1038/nature22341. [cited by applicant]
Schlinker, Biotechnol Bioeng. Apr. 2015; 112(4): 788-800. [cited by applicant]
Kotmakç, J Pharm Pharm Sci 18(3) 396-413, 2015. [cited by applicant]
Arraud, et al., “Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration,” Journal of Thrombosis and Haemostasis, vol. 12, pp. 614-217, 2014. [cited by applicant]
Berge, et al., “Pharmaceutical Salts,” Pharmaceutical Sciences, vol. 66, No. 1, 19, pages, 1977. [cited by applicant]
Brisson, et al., “Extracellular vesicles from activated platelets: a semiquantitative cryo-electron microscopy and immuno-gold labeling study,” Platelets, vol. 28, No. 3, pp. 263-271, 2017. [cited by applicant]
Bulcha, et al., “Viral vector platforms within the gene therapy landscape,” Signal Transduction and Targeted Therapy, vol. 6, No. 53, 24 pages, 2021. [cited by applicant]
Epstein, “Cosmeceutical vehicles,” Clinics in Dermatology, vol. 27, pp. 453-460, 2009. [cited by applicant]
Escobar, et al., “Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model,” Blood Advances, vol. 4, No. 5, pp. 804-814, 2020. [cited by applicant]
Flaumenhaft, et al., “Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles,” Blood, vol. 113, No. 5, pp. 1112-1121, 2009. [cited by applicant]
French, et al., “Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation,” Blood Advances, vol. 4, No. 13, pp. 3011-3023, 2020. [cited by applicant]
Jiang, et al., “How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?” J Control Release, vol. 247, pp. 1-18, 2017. [cited by applicant]
Jiang, et al., “Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells,” Blood, vol. 124, No. 13, pp. 2094-2103, 2014. [cited by applicant]
Kao, et al., “Engineering human megakaryocytic microparticles for targeted delivery of nucleic acids to hematopoietic stem and progenitor cells,” Sci. Adv., vol. 4, 11 pages, 2018. [cited by applicant]
Kao, et al., “Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications,” Current Opinion in Biotechnology, vol. 60, pp. 89-98, 2019. [cited by applicant]
Stahl, et al., “Handbook of Pharmaceutical Salts: Properties, Selection, and Use,” Journal of Medicinal Chemistry, vol. 46, No. 7, pp. 1277-1278, 2003. [cited by applicant]
Zeltner, et al., “Near-perfect infectivity of wild-type AAV as benchmark for infectivity of recombinant AAV vectors,” Gene Ther., vol. 17, No. 7, pp. 872-879, 2010. [cited by applicant]
Zhou, et al., “A pneumonia outbreak associated with a new coronavirus of probable bat origin,” Nature, vol. 579, 20 pages, 2020. [cited by applicant]
International Search Report & Written Opinion PCT Application No. PCT/US21/31778, dated Sep. 14, 2021, 9 pages. [cited by applicant]
Kanada, et al., “Differential fates of biomolecules delivered to target cells via extracellular vesicles,” PNAS, vol. 112, No. 12, pp. E1433-E1442, Feb. 23, 2015. [cited by applicant]