Improved Therapeutic Control of Proteolytically Sensitive, Destabilized Forms of Interleukin-12

    公开(公告)号:US20190062394A1

    公开(公告)日:2019-02-28

    申请号:US15767298

    申请日:2016-10-10

    Abstract: The present invention relates to modified forms of IL-12. These modified forms of IL-12 may be engineered to have a shortened in vivo half-life compared and/or enhanced localization of biological effects compared to that of corresponding non-modified form of IL-12. Short half-life and membrane bound forms of IL-12 may provide greater therapeutic control for in vivo therapeutic delivery, in particular when used in combination with ligand inducible delivery of IL-12. Modified forms of IL-12 engineered to have shortened in vivo half-life and/or enhanced localization of biological effects include heterodimeric p35/p40, single chain and membrane bound forms of IL-12 wherein a naturally occurring IL-12 amino acid sequence is genetically modified to destabilize IL-12 tertiary structure/polypeptide folding and enhance susceptibility of the IL-12 molecule to in vivo proteolytic degradation.

    INTERCALATED SINGLE-CHAIN VARIABLE FRAGMENTS
    2.
    发明申请
    INTERCALATED SINGLE-CHAIN VARIABLE FRAGMENTS 审中-公开
    单相单链可变片

    公开(公告)号:US20160176983A1

    公开(公告)日:2016-06-23

    申请号:US14971502

    申请日:2015-12-16

    Abstract: Single chain antibody polypeptides with engineered peptide bond crossovers in the light chain and/or heavy chain variable domains, compositions comprising the same, and methods of making and using the same are provided. The antibody polypeptides can be intercalated (crossover) single chain variable fragments (scFvs) or any antibody frameworks which comprise such scFvs, such as diabodies, bispecific antibodies or bssFvs. The single chain antibody polypeptides may or may not contain a linker. The single chain antibody polypeptides are useful in applications where standard (conventional) scFvs are useful, such as in the development of scFv libraries for screening, as therapeutic antibodies, or in in vitro and in vivo targeting applications.

    Abstract translation: 提供了在轻链和/或重链可变结构域中具有工程肽键交叉的单链抗体多肽,包含其的组合物及其制备和使用方法。 抗体多肽可插入(交叉)单链可变片段(scFv)或包含这种scFv的任何抗体框架,例如双抗体,双特异性抗体或bssFv。 单链抗体多肽可以含有或可以不含有接头。 单链抗体多肽可用于标准(常规)scFv有用的应用中,例如用于筛选scFv文库,作为治疗性抗体或体外和体内靶向应用。

    INTERCALATED SINGLE-CHAIN VARIABLE FRAGMENTS

    公开(公告)号:US20190031770A1

    公开(公告)日:2019-01-31

    申请号:US16158053

    申请日:2018-10-11

    Abstract: Single chain antibody polypeptides with engineered peptide bond crossovers in the light chain and/or heavy chain variable domains, compositions comprising the same, and methods of making and using the same are provided. The antibody polypeptides can be intercalated (crossover) single chain variable fragments (scFvs) or any antibody frameworks which comprise such scFvs, such as diabodies, bispecific antibodies or bssFvs. The single chain antibody polypeptides may or may not contain a linker. The single chain antibody polypeptides are useful in applications where standard (conventional) scFvs are useful, such as in the development of scFv libraries for screening, as therapeutic antibodies, or in in vitro and in vivo targeting applications.

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