US 12,227,550 B2
Targeted modified TNF family members
Jan Tavernier, Balegem (BE); Jennyfer Bultinck, Ledeberg (BE); Frank Peelman, Gentbrugge (BE); and Gilles Uze, Montpellier (FR)
Assigned to VIB VZW, Ghent (BE); UNIVERSITEIT GENT, Ghent (BE); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); UNIVERSITÉ DE MONTPELLIER, Montpellier (FR); and CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE MONTPELLIER, Montpellier (FR)
Filed by VIB VZW, Ghent (BE); UNIVERSITEIT GENT, Ghent (BE); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); UNIVERSITÉ DE MONTPELLIER, Montpellier (FR); and CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE MONTPELLIER, Montpellier (FR)
Filed on Jun. 23, 2022, as Appl. No. 17/847,380.
Application 17/847,380 is a continuation of application No. 16/865,833, filed on May 4, 2020, granted, now 11,396,532.
Application 16/865,833 is a continuation of application No. 16/441,324, filed on Jun. 14, 2019, granted, now 10,787,493, issued on Sep. 29, 2020.
Application 16/441,324 is a continuation of application No. 16/020,469, filed on Jun. 27, 2018, granted, now 10,407,480, issued on Sep. 10, 2019.
Application 16/020,469 is a continuation of application No. 15/883,925, filed on Jan. 30, 2018, granted, now 10,035,835, issued on Jul. 31, 2018.
Application 15/883,925 is a continuation of application No. 14/905,354, granted, now 9,914,759, issued on Mar. 13, 2018, previously published as PCT/EP2014/065554, filed on Jul. 18, 2014.
Claims priority of application No. 13306046 (EP), filed on Jul. 19, 2013.
Prior Publication US 2022/0324929 A1, Oct. 13, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/525 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); C07K 16/28 (2006.01); C07K 16/32 (2006.01)
CPC C07K 14/525 (2013.01) [C07K 16/2869 (2013.01); C07K 16/32 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/569 (2013.01); C07K 2319/00 (2013.01); C07K 2319/74 (2013.01)] 7 Claims
 
1. A composition comprising a proteinaceous construct, comprising:
(i) a single chain polypeptide comprising three human TNFs, wherein:
at least one human TNF is modified, wherein the at least one modified human TNF comprises a modified amino acid residue by substitution at the same position selected from Y87, I97, or Y115 relative to wild type human TNF (SEQ ID NO: 14),
and wherein the at least one modified human TNF has reduced affinity towards its receptor as compared to wild type human TNF;
(ii) a targeting moiety that is a single domain antibody (sdAb) directed to a neo-vasculature tissue or cancer tissue specific marker,
wherein the composition has significant biological activity towards cells that are targeted by the targeting moiety.