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    TOXIC RNA INHIBITORS SELF-ASSEMBLED IN SITU
    1.
    发明申请
    TOXIC RNA INHIBITORS SELF-ASSEMBLED IN SITU 审中-公开

    公开(公告)号：US20190151310A1

    公开(公告)日：2019-05-23

    申请号：US16266832

    申请日：2019-02-04

    申请人： THE SCRIPPS RESEARCH INSTITUTE

    发明人： Matthew D. Disney ,  Suzanne G. Rzuczek

    IPC分类号： A61K31/496 ,  A61K47/54 ,  A61K38/08 ,  A61K31/702 ,  A61K47/55 ,  A61K38/07

    CPC分类号： A61K31/496 ,  A61K31/702 ,  A61K38/07 ,  A61K38/08 ,  A61K47/549 ,  A61K47/55 ,  A61K47/557

    摘要： Potent modulators of RNA function can be assembled in cellulo by using the cell as a reaction vessel and a disease-causing RNA as a catalyst. When designing small molecule effectors of function, a balance between permeability and potency must be struck. Low molecular weight compounds are more permeable while higher molecular weight compounds are more potent. The advantages of both types of compounds could be synergized if low molecular weight molecules could be transformed into potent, multivalent ligands via a reaction catalyzed by binding to a target in cells expressing a genetic defect. We demonstrate that this approach is indeed viable in cellulo. Small molecule modules with precisely positioned alkyne and azide moieties bind adjacent internal loops in r(CCUG)exp, the causative agent of myotonic dystrophy type 2 (DM2), and are transformed into oligomeric, potent inhibitors of DM2 RNA dysfunction via a 1,3 Huisgen dipolar cycloaddition reaction, a variant of click chemistry. Additionally, we show that this approach is applicable to the r(CUG) repeating RNA that causes myotonic dystrophy type 1 (DM1). The click chemistry approach also allows for FRET sensors to be synthesized on-site by using r(CUG) repeats as a catalyst. Furthermore it is shown that small molecule binding sites in patient-derived cells can be identified by using reactive approaches termed Chem-CLIP and Chem-CLIP-Map. Lastly, it is shown that small molecules that target r(CUG) expansions can be designed to cleave this RNA by appending a small molecule with a nucleic acid cleaving module.

    Polyoxazoline antibody drug conjugates
    2.
    发明授权
    Polyoxazoline antibody drug conjugates 有权

    公开(公告)号：US10071168B2

    公开(公告)日：2018-09-11

    申请号：US14815718

    申请日：2015-07-31

    申请人： Serina Therapeutics, Inc.

    发明人： Randall W Moreadith ,  Michael D Bentley ,  Zhihao Fang ,  Tacey Viegas

    IPC分类号： A61K47/64 ,  A61K47/68 ,  A61K47/55 ,  A61K47/48 ,  A61K47/60 ,  A61K47/54 ,  A61K47/59

    CPC分类号： A61K47/6803 ,  A61K47/557 ,  A61K47/59 ,  A61K47/60 ,  A61K47/6849 ,  A61K47/6883 ,  A61K47/6889

    摘要： In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.