	US 12,433,939 B2
	Self-assembling synthetic proteins comprising cholera toxin beta subunit
Keith Alan Charlton, Aberdeen (GB); Erik D'Hondt, Bazel (BE); and Daniel T. Verhamme, Aberdeen (GB)
Assigned to In3Bio Ltd., Hamilton (BM)
Filed by In3Bio Ltd., Hamilton (BM)
Filed on Jul. 12, 2022, as Appl. No. 17/862,952.
Application 17/862,952 is a continuation of application No. 16/843,118, filed on Apr. 8, 2020, granted, now 11,419,923.
Application 16/843,118 is a continuation of application No. 14/854,224, filed on Sep. 15, 2015, granted, now 10,736,948.
Application 14/854,224 is a continuation in part of application No. PCT/IB2014/001125, filed on Mar. 17, 2014.
Claims priority of provisional application 61/791,268, filed on Mar. 15, 2013.
Prior Publication US 2023/0042534 A1, Feb. 9, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); C07K 14/475 (2006.01); C07K 14/485 (2006.01); C07K 14/495 (2006.01); C07K 14/50 (2006.01)

CPC A61K 39/0005 (2013.01) [A61K 39/0011 (2013.01); C07K 14/475 (2013.01); C07K 14/485 (2013.01); C07K 14/495 (2013.01); C07K 14/50 (2013.01); C07K 2319/40 (2013.01)]

9 Claims

1. A recombinant synthetic protein, comprising:

a monomeric sequence that is able to assemble into stable pentamers, including

a Cholera Toxin β (CTB) subunit TPONITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQVEVPGSQ HIDSQKKAIERMKDTLRIAYLTEAKVEKLCVWNNKTPHAIAAISMAN (SEQ ID NO: 18) having mutations TIF, P2T, Q3D, N4I, M37I, A381, 139L, 140V, T41N, T78S, E79N, A80S, A95S, A102V, and N103R;

a peptide spacer; and

a polypeptide including substantially a full-length growth factor selected from the group consisting of IGF-1, IGF-2, FGF1, FGF2, TGF-α, TGF-β, VEGF-A, VEGF-B, VEGF-C, VEGF-D, PDGF, NGF, EGF, HGF, BMP's, PDL1 and IL-1, IL-2, IL-3, IL-4, IL-5, and IL-6, wherein the part thereof includes a neutralizing domain of the growth factor,

wherein the polypeptide is separated from the CTB subunit by the peptide spacer, which prevents the polypeptide from sterically inhibiting assembly of the pentamers by the CTB subunit.

7. A process of preparing a stable homo-pentamer complex comprising assembling monomeric sub-units of claim 1 to form one or more stable homo-pentamer complexes.

8. A process of preparing a multivalent vaccine formulation comprising mixing one or more single monomeric sub-units of claim 1 to form a multivalent vaccine.

9. A process for treating a patient comprising administering an immunogenic dose of the multivalent vaccine formulation of claim 8 to the patient during a treatment period.