US 12,331,076 B2
Alphavirus-based replicons for administration of biotherapeutics
Jason L. Dehart, San Diego, CA (US); Nathaniel Stephen Wang, San Diego, CA (US); Parinaz Aliahmad, San Diego, CA (US); Shigeki Miyake-Stoner, La Jolla, CA (US); and Kurt Iver Kamrud, Olathe, KS (US)
Assigned to Janssen Pharmaceuticals, Inc., Titusville, NJ (US)
Filed by Janssen Pharmaceuticals, Inc., Titusville, NJ (US)
Filed on Oct. 8, 2019, as Appl. No. 16/595,980.
Claims priority of provisional application 62/742,868, filed on Oct. 8, 2018.
Prior Publication US 2020/0109178 A1, Apr. 9, 2020
Int. Cl. C07K 14/005 (2006.01); C12N 7/00 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/005 (2013.01) [C12N 7/00 (2013.01); A61K 38/00 (2013.01); C12N 2770/36122 (2013.01); C12N 2770/36133 (2013.01); C12N 2770/36143 (2013.01)] 20 Claims
 
1. An RNA replicon comprising
(i) an RNA sequence encoding a heterologous protein or peptide;
(ii) 5′ and 3′ alphavirus untranslated regions;
(iii) RNA sequences encoding amino acid sequences derived from New World alphavirus nonstructural proteins nsP1, nsP2, and nsP4; and
(iv) an RNA sequence encoding a nonstructural nsP3, wherein said nsP3 comprises (a) an amino acid sequence derived from an alphavirus nsP3 macro domain;
(b) an RNA sequence encoding an amino acid sequence derived from an alphavirus nsP3 central domain; and
(c) an RNA sequence encoding an amino acid sequence derived from an alphavirus nsP3 hypervariable domain (HVD) comprising at least a portion of an Old World alphavirus nsP3 HVD comprising a FGDF (SEQ ID NO: 18) or a FGSF (SEQ ID NO: 19) motif, wherein said alphavirus nsP3HVD comprises:
an amino acid sequence derived from an Old World alphavirus nsP3 HVD comprising said portion of the Old World alphavirus nsP3 HVD; or
an amino acid sequence comprising a portion derived from a New World alphavirus nsP3 HVD, and said portion derived from the Old World alphavirus nsP3 HVD; and wherein the replicon does not encode at least protein C.