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    MODIFIED TOXINS
    3.
    发明申请
    MODIFIED TOXINS 有权
    改性毒素

    公开(公告)号：US20090221500A1

    公开(公告)日：2009-09-03

    申请号：US12335297

    申请日：2008-12-15

    申请人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    发明人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    IPC分类号： A61K38/16 ,  C07K14/00

    CPC分类号： C07K14/34 ,  A61K38/00 ,  C07K2319/035

    摘要： The present application relates to compositions of modified toxins exhibiting reduced immunogenicity and reduced binding to vascular endothelium or vascular endothelial cells, thereby reducing the incidence of Vascular Leak Syndrome. Also provided are polypeptide toxophores from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope. Another aspect relates to a polypeptide toxophore from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope and at least one amino acid residue of at least one VLS motif of an unmodified native diphtheria toxin. Another aspect relates to a fusion protein which comprises a modified diphtheria toxin and a non-diphtheria toxin fragment that is a cell binding portion. Another aspect relates to the use of a modified diphtheria toxin for the treatment of a malignant disease or a non-malignant disease.

    摘要翻译： 本申请涉及具有降低的免疫原性并降低与血管内皮细胞或血管内皮细胞结合的修饰毒素的组合物，从而降低血管渗漏综合征的发生率。 还提供了来自修饰的白喉毒素的多肽毒素体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基中。 另一方面涉及来自修饰的白喉毒素的多肽毒候球体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基和未修饰的天然白喉毒素的至少一个VLS基序的至少一个氨基酸残基 。 另一方面涉及融合蛋白，其包含修饰的白喉毒素和作为细胞结合部分的非白喉毒素片段。 另一方面涉及使用修饰的白喉毒素治疗恶性疾病或非恶性疾病。

    Modified toxins
    5.
    发明授权
    Modified toxins 有权
    改良毒素

    公开(公告)号：US08252897B2

    公开(公告)日：2012-08-28

    申请号：US12143469

    申请日：2008-06-20

    申请人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    发明人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    IPC分类号： A61K39/02 ,  C07K16/46

    CPC分类号： C07K14/34 ,  A61K38/16 ,  A61K39/0011 ,  A61K39/39 ,  A61K47/6415 ,  A61K47/642 ,  A61K2039/5156 ,  A61K2039/55533 ,  A61K2039/55544

    摘要： The present application relates to compositions of modified toxins exhibiting reduced immunogenicity and reduced binding to vascular endothelium or vascular endothelial cells, thereby reducing the incidence of Vascular Leak Syndrome. Also provided are polypeptide toxophores from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope. Another aspect relates to a polypeptide toxophore from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope and at least one amino acid residue of at least one VLS motif of an unmodified native diphtheria toxin. Another aspect relates to a fusion protein which comprises a modified diphtheria toxin and a non-diphtheria toxin fragment that is a cell binding portion. Another aspect relates to the use of a modified diphtheria toxin for the treatment of a malignant disease or a non-malignant disease.

    摘要翻译： 本申请涉及具有降低的免疫原性并降低与血管内皮细胞或血管内皮细胞结合的修饰毒素的组合物，从而降低血管渗漏综合征的发生率。 还提供了来自修饰的白喉毒素的多肽毒素体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基中。 另一方面涉及来自修饰的白喉毒素的多肽毒候球体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基和未修饰的天然白喉毒素的至少一个VLS基序的至少一个氨基酸残基 。 另一方面涉及融合蛋白，其包含修饰的白喉毒素和作为细胞结合部分的非白喉毒素片段。 另一方面涉及使用修饰的白喉毒素治疗恶性疾病或非恶性疾病。

    MODIFIED DIPHTHERIA TOXINS
    7.
    发明申请
    MODIFIED DIPHTHERIA TOXINS 审中-公开
    改性DIPHTHERIA毒素

    公开(公告)号：US20090010966A1

    公开(公告)日：2009-01-08

    申请号：US12143581

    申请日：2008-06-20

    申请人： Claude Geoffrey Davis ,  Deepshikha Datta

    发明人： Claude Geoffrey Davis ,  Deepshikha Datta

    IPC分类号： A61K39/05 ,  C07K14/195 ,  A61P35/04

    CPC分类号： C07K14/34 ,  A61K38/16 ,  A61K39/0011 ,  A61K39/39 ,  A61K47/6415 ,  A61K47/642 ,  A61K2039/5156 ,  A61K2039/55533 ,  A61K2039/55544

    摘要： The present application relates to compositions of modified diphtheria toxin and fusion proteins containing modified diphtheria toxin that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome, as well as methods of making the compositions. The present application also relates to a polypeptide toxophore from a modified diphtheria toxin, where the modification is at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of an unmodified native diphtheria toxin. Also described are fusion proteins which contain a modified diphtheria toxin and a non-diphtheria toxin fragment which contains a cell binding portion. The modified diphtheria toxins described can be used for the treatment of a malignant disease or a non-malignant disease.

    摘要翻译： 本申请涉及修饰的白喉毒素和含有修饰的白喉毒素的融合蛋白的组合物，其减少与血管内皮细胞或血管内皮细胞的结合，并因此降低血管渗漏综合征的发生率，以及制备组合物的方法。 本申请还涉及来自修饰的白喉毒素的多肽毒株，其中所述修饰是未修饰的天然白喉毒素的氨基酸残基6-8,28-30或289-291处的至少一个氨基酸残基。 还描述了含有修饰的白喉毒素和含有细胞结合部分的非白喉毒素片段的融合蛋白。 所述的改良的白喉毒素可用于治疗恶性疾病或非恶性疾病。

    Modified toxins
    9.
    发明授权
    Modified toxins 有权
    改良毒素

    公开(公告)号：US08470314B2

    公开(公告)日：2013-06-25

    申请号：US12335297

    申请日：2008-12-15

    申请人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    发明人： Claude Geoffrey Davis ,  Deepshikha Datta ,  Matthew Paul Baker ,  Alyson Jane Rust ,  Simon Keen

    IPC分类号： A61K39/00

    CPC分类号： C07K14/34 ,  A61K38/00 ,  C07K2319/035

    摘要： The present application relates to compositions of modified toxins exhibiting reduced immunogenicity and reduced binding to vascular endothelium or vascular endothelial cells, thereby reducing the incidence of Vascular Leak Syndrome. Also provided are polypeptide toxophores from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope. Another aspect relates to a polypeptide toxophore from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope and at least one amino acid residue of at least one VLS motif of an unmodified native diphtheria toxin. Another aspect relates to a fusion protein which comprises a modified diphtheria toxin and a non-diphtheria toxin fragment that is a cell binding portion. Another aspect relates to the use of a modified diphtheria toxin for the treatment of a malignant disease or a non-malignant disease.

    摘要翻译： 本申请涉及具有降低的免疫原性并降低与血管内皮细胞或血管内皮细胞结合的修饰毒素的组合物，从而降低血管渗漏综合征的发生率。 还提供了来自修饰的白喉毒素的多肽毒素体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基中。 另一方面涉及来自修饰的白喉毒素的多肽毒候球体，其中修饰在至少一个T细胞表位的至少一个氨基酸残基和未修饰的天然白喉毒素的至少一个VLS基序的至少一个氨基酸残基 。 另一方面涉及融合蛋白，其包含修饰的白喉毒素和作为细胞结合部分的非白喉毒素片段。 另一方面涉及使用修饰的白喉毒素治疗恶性疾病或非恶性疾病。

    Modulating pH-sensitive binding using non-natural amino acids
    10.
    发明申请
    Modulating pH-sensitive binding using non-natural amino acids 审中-公开
    使用非天然氨基酸调节pH敏感结合

    公开(公告)号：US20050260711A1

    公开(公告)日：2005-11-24

    申请号：US11094625

    申请日：2005-03-30

    申请人： Deepshikha Datta ,  William Goddard ,  David Tirrell ,  Joyce Peng

    发明人： Deepshikha Datta ,  William Goddard ,  David Tirrell ,  Joyce Peng

    IPC分类号： C07H21/04 ,  C07K16/32 ,  C07K16/44 ,  C12N5/06 ,  C12P21/06

    CPC分类号： C07K16/32

    摘要： The invention provides methods, systems and reagents for regulating pH-sensitive protein interaction by incorporating non-natural amino acids into the protein (e.g. an antibody, or its functional fragment, derivative, etc.). The invention also relates to specific uses in regulating pH-sensitive binding of antibodies to tumor site, by conferring enhanced tumor-specificity/selectivity. In that embodiment, the non-natural amino acids preferably have desirable side-chain pKa's, such that at below physiological pH (e.g. about pH 6.3-6.5) the non-natural amino acid confer enhanced binding to tumor antigens in acidic environments. Such non-natural amino acids can be incorporated by any suitable means, such as by utilizing a modified aminoacyl-tRNA synthetase to charge the nonstandard amino acid to a modified tRNA, which forms strict Watson-Crick base-pairing with a codon that normally forms wobble base-pairing with natural tRNAs (e.g. the degenerate codon orthogonal system.

    摘要翻译： 本发明提供了通过将非天然氨基酸掺入蛋白质（例如抗体或其功能片段，衍生物等）来调节pH敏感蛋白质相互作用的方法，系统和试剂。 本发明还涉及通过赋予增强的肿瘤特异性/选择性来调节抗体对肿瘤部位的pH敏感结合的具体用途。 在该实施方案中，非天然氨基酸优选具有所需的侧链pKa，使得在低于生理pH（例如约pH 6.3-6.5）下，非天然氨基酸在酸性环境中赋予增强的与肿瘤抗原的结合。 这样的非天然氨基酸可以通过任何合适的方式并入，例如通过利用修饰的氨酰-tRNA合成酶将非标准氨基酸装入修饰的tRNA，其与通常形成的密码子形成严格的沃森 - 克里克碱基配对 与天然tRNA的摆动碱基配对（如简并密码子正交系统）。