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    MULTIPARAMETRIC NUCLEIC ACID OPTIMIZATION
    13.
    发明申请
    MULTIPARAMETRIC NUCLEIC ACID OPTIMIZATION 审中-公开

    公开(公告)号：US20170362627A1

    公开(公告)日：2017-12-21

    申请号：US15525826

    申请日：2015-11-04

    Applicant: MODERNATX, INC.

    Inventor： John van Wicheren REYNDERS, III ,  Tirtha CHAKRABORTY ,  Stephen HOGE ,  Iain James MCFADYEN

    IPC: C12P21/02 ,  A61K38/02 ,  C07K14/00

    CPC classification number: C12P21/02 ,  A61K38/02 ,  C07K14/00 ,  C07K2319/00

    Abstract: The present disclosure provides multiparametric codon optimization methods to improve at least a property in a candidate nucleic acid sequence. Such parameters include improving nucleic acid stability (e.g., mRNA stability), increasing translation efficacy in the target tissue, reducing the number of truncated proteins expressed, improving the folding or prevent misfolding of the expressed proteins, reducing toxicity of the expressed products, reducing cell death caused by the expressed products, and increasing or decreasing protein aggregation. After such optimization, the resulting optimized nucleic acid sequence has at least one optimized property with respect to the candidate nucleic acid sequence.

    METHODS FOR THERAPEUTIC ADMINISTRATION OF MESSENGER RIBONUCLEIC ACID DRUGS
    18.
    发明申请
    METHODS FOR THERAPEUTIC ADMINISTRATION OF MESSENGER RIBONUCLEIC ACID DRUGS 有权

    公开(公告)号：US20210260097A1

    公开(公告)日：2021-08-26

    申请号：US17036374

    申请日：2020-09-29

    Applicant: ModernaTX, Inc.

    Inventor： Stephen HOGE ,  Tirtha CHAKRABORTY ,  Gilles BESIN ,  Ruchi JAIN

    IPC: A61K31/7115 ,  C12N15/67 ,  A61K9/00 ,  A61K9/127 ,  C12N15/113

    Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

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