	US 11,746,138 B2
	Artificial synapses
Mickey Pentecost, West Hollywood, CA (US); and Wojciech Bartkowski, La Crescenta, CA (US)
Assigned to DIADEM BIOTHERAPEUTICS INC., Torrance, CA (US)
Filed by DIADEM BIOTHERAPEUTICS INC., Torrance, CA (US)
Filed on Jul. 16, 2021, as Appl. No. 17/377,520.
Application 17/377,520 is a continuation of application No. PCT/US2021/016949, filed on Feb. 5, 2021.
Claims priority of provisional application 62/970,374, filed on Feb. 5, 2020.
Prior Publication US 2021/0371497 A1, Dec. 2, 2021
Int. Cl. C07K 14/705 (2006.01); A61K 47/69 (2017.01); A61K 47/58 (2017.01); A61K 47/62 (2017.01); A61K 47/54 (2017.01); A61P 27/02 (2006.01); A61P 37/06 (2006.01); C12N 9/14 (2006.01); C07K 14/75 (2006.01); A61K 38/00 (2006.01)

CPC C07K 14/70532 (2013.01) [A61K 47/544 (2017.08); A61K 47/605 (2017.08); A61K 47/62 (2017.08); A61K 47/69 (2017.08); A61K 47/6901 (2017.08); A61K 47/6911 (2017.08); A61K 47/6917 (2017.08); A61P 27/02 (2018.01); A61P 37/06 (2018.01); C07K 14/705 (2013.01); C07K 14/7056 (2013.01); C07K 14/70521 (2013.01); C07K 14/70596 (2013.01); C07K 14/75 (2013.01); C12N 9/14 (2013.01); A61K 38/00 (2013.01); C07K 14/70503 (2013.01); C07K 2319/01 (2013.01); C07K 2319/02 (2013.01); C07K 2319/035 (2013.01); C07K 2319/055 (2013.01); C07K 2319/30 (2013.01); C07K 2319/74 (2013.01); C07K 2319/75 (2013.01); C07K 2319/912 (2013.01); C07K 2319/915 (2013.01); C12Y 304/24081 (2013.01)]

25 Claims

1. An engineered extracellular vesicle comprising an engineered fusion protein, the engineered fusion protein comprising:

a signaling domain, selected from the group consisting of (a) either full length or active fragments of IL-10, B7-H7 (HHLA2), VSIG8, VSIG3 (IGSF11), VSIG4, Tim-4 (TIMD4), BTN3A1, BTN2A1, BTN2A2, BTN1A1, and CAS-9, and (b) active fragments of B7-H5 (VISTA), PD-L1, CTLA-4 (CD152), PD-L2, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (CD270), Galectin-9, CEACAM1, OX-2 (CD200), PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoform delta, Fibrinogen like protein 1 (FGL1), Tim-3 (HAVCR2), and TIGIT; and

a vesicle targeting domain linked to the signaling domain,

wherein the vesicle targeting domain includes only one transmembrane domain and the transmembrane domain is CD9 transmembrane domain 2 (CD9tm2),

wherein the N terminus of the vesicle targeting domain is on the exterior of the extracellular vesicle and linked to the C terminal end of the signaling domain,

wherein the vesicle targeting domain spans at least partly through a phospholipid bilayer of the engineered extracellular vesicle, and

wherein the signaling domain is displayed on the exterior of the engineered extracellular vesicle.