US 11,753,463 B2
Therapeutic targeting of non-cellular structures
Nikolai Kley, Newton, MA (US); Jan Tavernier, Balegem (BE); Leander Huyghe, Beernem (BE); and Anje Cauwels, Merelbeke (BE)
Assigned to Orionis Biosciences BV, Ghent (BE)
Appl. No. 16/301,299
Filed by Orionis Biosciences BV, Ghent (BE); VIB VZW, Ghent (BE); and Universiteit Gent, Ghent (BE)
PCT Filed May 12, 2017, PCT No. PCT/EP2017/061543
§ 371(c)(1), (2) Date Nov. 13, 2018,
PCT Pub. No. WO2017/194782, PCT Pub. Date Nov. 16, 2017.
Claims priority of provisional application 62/335,990, filed on May 13, 2016.
Prior Publication US 2021/0238264 A1, Aug. 5, 2021
Int. Cl. C07K 16/28 (2006.01); C07K 14/56 (2006.01); A61K 39/395 (2006.01); A61K 38/21 (2006.01); A61P 35/00 (2006.01); C07K 16/18 (2006.01); A61K 31/704 (2006.01); A61K 38/19 (2006.01); C07K 14/525 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/18 (2013.01) [A61K 31/704 (2013.01); A61K 38/191 (2013.01); A61K 38/212 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07K 14/525 (2013.01); C07K 14/56 (2013.01); C07K 16/2815 (2013.01); C07K 16/2818 (2013.01); C07K 16/2827 (2013.01); A61K 2039/505 (2013.01); C07K 2317/22 (2013.01); C07K 2317/24 (2013.01); C07K 2317/569 (2013.01); C07K 2317/73 (2013.01); C07K 2317/75 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/30 (2013.01)] 13 Claims
 
1. A composition comprising a chimeric protein consisting of:
(a) one or more modified signaling agents, wherein at least one signaling agent is a human interferon alpha 2 (IFNα2) comprising an amino acid sequence having at least 98% identity with a sequence selected from SEQ ID NO: 1 or 2 and having one or more mutations at one or more amino acid positions 144-154;
(b) one or more targeting moieties, wherein at least one targeting moiety comprises a single-domain antibody recognition domain which specifically binds to non-cellular tenascin-CA1 and,
wherein the one or more mutations confer reduced affinity or activity to IFNα2 that is restorable by attachment to the one or more targeting moieties,
wherein at least one targeting moiety and signaling agent are connected with one or more flexible linkers.