Alphavirus-based replicons for administration of biotherapeutics

A technology of alphavirus and replicon, applied in the field of RNA replicon, can solve the problem of reducing the clinical efficacy of biotherapeutics

Pending Publication Date: 2021-08-06
JANSSEN PHARMA NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, delivery of biologics from naturally self-supporting and inflammatory replicons risks promoting ADA responses and reducing the clinical efficacy of the encoded biotherapeutics

Method used

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  • Alphavirus-based replicons for administration of biotherapeutics
  • Alphavirus-based replicons for administration of biotherapeutics
  • Alphavirus-based replicons for administration of biotherapeutics

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0098] Embodiment 1 is an RNA replicon comprising

[0099] RNA sequences encoding heterologous proteins or peptides;

[0100] 5' and 3' alphavirus untranslated regions;

[0101] RNA sequences encoding amino acid sequences derived from the New World alphavirus nonstructural proteins nsP1, nsP2, and nsP4; and

[0102] an RNA sequence encoding an amino acid sequence derived from an alphavirus nsP3 macrodomain;

[0103] an RNA sequence encoding an amino acid sequence derived from the central domain of an alphavirus nsP3; and

[0104] An RNA sequence encoding an amino acid sequence derived from an alphavirus nsP3 hypervariable domain comprising

[0105] a. an amino acid sequence derived from the hypervariable domain of an Old World alphavirus nsP3; or

[0106] b. Amino acid sequence comprising a portion derived from a New World alphavirus nsP3 hypervariable domain and a portion derived from an Old World alphavirus nsP3 hypervariable domain.

Embodiment approach 2

[0107] Embodiment 2 is the RNA replicon of embodiment 1, wherein said alphavirus nsP3 macrodomain and said alphavirus nsP3 central domain are from New World alphaviruses.

Embodiment approach 3

[0108] Embodiment 3 is the RNA replicon of embodiment 1, wherein said alphavirus nsP3 macrodomain and said alphavirus nsP3 central domain are from an Old World alphavirus.

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Abstract

The invention provides RNA replicons useful for administering a heterologous protein or peptide into a mammal and eliciting a reduced immune response or no immune response from the mammal. The RNA replicons have RNA sequences encoding for a heterologous protein or peptide, New World alphavirus nonstructural proteins nsP1, nsP2, and nsP4; and an alphavirus nsP3 protein macro domain, central domain, and hypervariable domain. The encoded hypervariable domain can have an amino acid sequence derived from an Old World alphavirus nsP3 hypervariable domain; or can have an amino acid sequence derived from a portion of a New World alphavirus nsP3 hypervariable domain, and another portion derived from an Old World alphavirus nsP3 hypervariable domain.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 742,868, filed October 8, 2018, the disclosure of which is incorporated herein by reference in its entirety. [0003] References to Electronically Submitted Sequence Listings [0004] This application contains a sequence listing, which is electronically submitted through EFS-Web as a sequence listing in ASCII format, with a file name of "689405.107WO_SL", a creation date of October 7, 2019, and a size of 147KB. The sequence listing submitted via EFS-Web is part of this specification and is hereby incorporated by reference in its entirety. Background technique [0005] Alphavirus-based self-amplifying RNA (replicon) has been used for decades as a general platform for vaccines. Two features that make replicons suitable for such a platform are: 1) high and long-term protein expression; and 2) the self-adjuvanting nature of the platform, whic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/005C12N15/86
CPCC12N15/86C07K14/005C12N2770/36122C12N2770/36143C07K2319/31C07K2319/00C12N2760/16134Y02A50/30A61K38/00C12N7/00C12N2770/36133A61K39/145A61P31/16
Inventor J·L·德哈特N·S·王P·阿里阿赫玛德S·米亚克-斯托纳K·I·卡姆鲁德
Owner JANSSEN PHARMA NV
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