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    FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATIONG PAIN
    11.
    发明申请
    FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATIONG PAIN 审中-公开
    融合蛋白和治疗，预防或改善疼痛的方法

    公开(公告)号：US20150197739A1

    公开(公告)日：2015-07-16

    申请号：US14422574

    申请日：2013-08-27

    Applicant: Syntaxin Limited ,  Allergan, Inc.

    Inventor： Peter James ,  Keith Foster ,  John Chaddock ,  Roger Kei Aoki ,  Lance Steward ,  Joseph Francis

    IPC: C12N9/52 ,  C07K14/575

    Abstract: A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which protease is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease and the galanin Targeting Moiety; a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; a first spacer located between the non-cytotoxic protease and the protease cleavage site, wherein said first spacer comprises an amino acid sequence of from 4 to 25 amino acid residues; and a second spacer located between the galanin Targeting Moiety and the translocation domain, wherein said second spacer comprises an amino acid sequence of from 4 to 35 amino acid residues. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

    Abstract translation: 一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶，该蛋白酶能够切割伤害性感觉传入的胞外融合装置的蛋白质; 能够结合伤害性感觉传入物的结合位点的甘丙肽靶向部位，该结合位点能够经受内吞作用以掺入伤害性感觉传入内的内体; 蛋白酶切割位点，其中融合蛋白可被蛋白酶切割，其中蛋白酶切割位点位于非细胞毒性蛋白酶和甘丙肽靶向部位之间; 能够将位于内体内的蛋白酶从内体膜转移到伤害性感觉传入体的胞质溶胶中的易位结构域; 位于所述非细胞毒性蛋白酶和所述蛋白酶切割位点之间的第一间隔物，其中所述第一间隔物包含4至25个氨基酸残基的氨基酸序列; 和位于甘丙肽靶向部位和易位结构域之间的第二间隔物，其中所述第二间隔物包含4至35个氨基酸残基的氨基酸序列。 还描述了编码多肽融合蛋白的核酸序列，其制备方法及其用途。

    CARRIER FOR TARGETING NERVE CELLS
    12.
    发明申请
    CARRIER FOR TARGETING NERVE CELLS 有权
    携带神经细胞

    公开(公告)号：US20150038401A1

    公开(公告)日：2015-02-05

    申请号：US14451984

    申请日：2014-08-05

    Applicant: SYNTAXIN LIMITED

    Inventor： Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

    IPC: C12N9/52 ,  C07K14/33

    CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K14/33 ,  C12Y304/24069 ,  Y02A50/469 ,  Y02A50/473

    Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

    Abstract translation: 本发明涉及通过改变由肉毒梭菌形成的神经毒素的重链而获得的转运蛋白，其中（i）所述蛋白质以与天然神经毒素更高或更低的亲和力的神经细胞特异性结合; （ii）与天然神经毒素相比，蛋白质具有增加或减少的神经毒性，神经毒性优选在膈膜测定中确定; 和/或（iii）与天然神经毒素相比，蛋白质包含对中和抗体的较低亲和力。 本发明还涉及其制备方法及其在化妆品和药物组合物中的用途。

    SUPPRESSION OF NEUROENDOCRINE DISEASES
    13.
    发明申请
    SUPPRESSION OF NEUROENDOCRINE DISEASES 审中-公开
    抑制神经退行性疾病

    公开(公告)号：US20140302006A1

    公开(公告)日：2014-10-09

    申请号：US14250959

    申请日：2014-04-11

    Applicant: Syntaxin Limited

    Inventor： Steven JOHNSTONE ,  Philip MARKS ,  Keith FOSTER

    IPC: C12N9/52

    CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12P21/06

    Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumour cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalised and inhibits secretion from said tumour cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

    Abstract translation: 本发明涉及抑制神经内分泌疾病的方法。 该疗法使用非细胞毒性蛋白酶，其优选靶向神经内分泌肿瘤细胞，优选经由生长抑素或皮质抑素受体，GHRH受体，生长素释放肽受体，铃蟾肽受体，泌尿生素受体，黑色素浓缩激素受体1 ; KiSS-1受体或催乳素释放肽受体。 当这样传递时，蛋白酶被内化并且抑制来自所述肿瘤细胞的分泌。 本发明还涉及用于所述方法的多肽和核酸。

    SUPPRESSION OF CANCERS
    14.
    发明申请
    SUPPRESSION OF CANCERS 审中-公开
    抑制癌症

    公开(公告)号：US20140219983A1

    公开(公告)日：2014-08-07

    申请号：US14250954

    申请日：2014-04-11

    Applicant: Syntaxin Limited

    Inventor： Frederic MADEC ,  Phil LECANE ,  Philip MARKS ,  Keith FOSTER

    IPC: C12N9/50 ,  C07K14/60 ,  C07K14/33 ,  C07K14/82 ,  C07K7/08 ,  C07K14/48 ,  C07K14/575 ,  C07K14/65

    Abstract: The present invention relates to a method for suppressing or treating cancer, in particular to a method for suppressing or treating one or more of colorectal cancer, breast cancer, prostate cancer and/or lung cancer. The therapy employs use of a non-cytotoxic protease, which is targeted to a growth hormone-secreting cell such as to a pituitary cell. When so delivered, the protease is internalised and inhibits secretion/transmission of growth hormone from said cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

    Abstract translation: 本发明涉及抑制或治疗癌症的方法，特别涉及抑制或治疗结肠直肠癌，乳腺癌，前列腺癌和/或肺癌中的一种或多种的方法。 该疗法使用非细胞毒性蛋白酶，其靶向生长激素分泌细胞，例如垂体细胞。 当这样传递时，蛋白酶被内化并且抑制生长激素从所述细胞的分泌/传递。 本发明还涉及用于所述方法的多肽和核酸。

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