US 10,376,549 B2
Detargeted adenovirus variants and related methods
Dmitry M. Shayakhmetov, Snellville, GA (US); and Nelson C. Di Paolo, Avondale Estates, GA (US)
Assigned to ADCURE BIOTECHNOLOGIES, LLC., Snellville, GA (US)
Appl. No. 15/537,392
Filed by Dmitry M. Shayakhmetov, Snellville, GA (US); Nelson C. Di Paolo, Avondale Estates, GA (US); and ADCURE BIOTECHNOLOGIES, LLC., Snellville, GA (US)
PCT Filed Jan. 17, 2016, PCT No. PCT/US2016/013765
§ 371(c)(1), (2) Date Jun. 16, 2017,
PCT Pub. No. WO2016/118433, PCT Pub. Date Jul. 28, 2016.
Claims priority of provisional application 62/105,284, filed on Jan. 20, 2015.
Prior Publication US 2018/0099015 A1, Apr. 12, 2018
Int. Cl. A61K 35/00 (2006.01); A61K 35/761 (2015.01); A61K 35/76 (2015.01); C07K 14/005 (2006.01); C12N 15/86 (2006.01); C12N 7/00 (2006.01); A61P 43/00 (2006.01); A61K 48/00 (2006.01); C07K 14/075 (2006.01); C12N 7/06 (2006.01); C12N 15/861 (2006.01)
CPC A61K 35/761 (2013.01) [A61K 35/76 (2013.01); A61K 48/00 (2013.01); A61P 43/00 (2018.01); C07K 14/005 (2013.01); C07K 14/075 (2013.01); C12N 7/00 (2013.01); C12N 7/06 (2013.01); C12N 15/86 (2013.01); C12N 15/8616 (2013.01); C12N 2710/00043 (2013.01); C12N 2710/00061 (2013.01); C12N 2710/10021 (2013.01); C12N 2710/10322 (2013.01); C12N 2710/10332 (2013.01); C12N 2710/10333 (2013.01); C12N 2710/10334 (2013.01); C12N 2710/10345 (2013.01); C12N 2810/405 (2013.01)] 21 Claims
 
1. An isolated adenovirus with a mutation in the RGD motif of the penton protein, wherein the mutation causes reduced binding of β3 integrins of a host cell, and two mutations in the hexon hypervariable loops, wherein said mutations in the hexon hypervariable loops comprise a mutation in the HVR1 loop and a mutation in the HVR7 loop,
wherein the mutation in the HVR1 loop of the hexon protein causes reduced virus trapping in Kupffer cells, and
wherein the combination of the mutation in the RGD motif, the mutation in the HVR1 loop and the mutation in the HVR7 loop causes reduced liver sequestration of the adenovirus.