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    • 1. 发明申请
    • ANTI - TGF - BETA RECEPTOR TYPE II SINGLE DOMAIN ANTIBODIES
    • 抗TGF - β受体II型单个抗体
    • WO2011012609A3
    • 2011-09-15
    • PCT/EP2010060867
    • 2010-07-27
    • GLAXO GROUP LTDDE WILDT RUDOLF MARIADIMECH CAROLINE JHOLMES STEVESTOOP ADRIAAN ALLART
    • DE WILDT RUDOLF MARIADIMECH CAROLINE JHOLMES STEVESTOOP ADRIAAN ALLART
    • C07K16/28A61P27/02A61P43/00C07K16/40
    • C07K16/2863C07K16/40C07K2317/21C07K2317/56C07K2317/565C07K2317/567C07K2317/569C07K2317/76C07K2317/92
    • The invention provides an anti-TGFbetaRII immunoglobulin single variable domain. Suitably, an anti-TGFbetaRII immunoglobulin single variable domain in accordance with the invention is one which binds to TGFbetaRII with a dissociation constant (Kd) in the range of 10pM to 50nM, preferably 10pM to 10nM, preferably 250pM to 10nM. Isolated polypeptides comprising an amino acid sequence that is at least 70% identical to at least one amino acid sequence selected from the group of: SEQ ID NOs: 1 to 23, wherein said isolated polypeptide binds to TGFbetaRII are also provided. The invention also provides a polypeptide, ligand or pharmaceutical composition for treating a disease associated with TGFbeta signalling and suitably a disease selected from the group of: tissue fibrosis, such as pulmonary fibrosis, including idiopathic pulmonary fibrosis, liver fibrosis, including cirrhosis and chronic hepatitis, rheumatoid arthritis, ocular disorders, or fibrosis of the skin, including keloid of skin, and kidney such as nephritis, kidney fibrosis and nephrosclerosis, and a vascular condition, such as restenosis.
    • 本发明提供抗TGFbetaRII免疫球蛋白单可变结构域。 适当地,根据本发明的抗TGFbetaRII免疫球蛋白单可变结构域是以解离常数(Kd)在10pM至50nM,优选10pM至10nM,优选250pM至10nM范围内结合TGFbetaRII的结合。 分离的多肽包含与选自SEQ ID NO:1至23的至少一个氨基酸序列至少70%相同的氨基酸序列,其中所述分离的多肽与TGFbetaRII结合。 本发明还提供了用于治疗与TGFbeta信号传导相关疾病的合适的多肽,配体或药物组合物,适当地选自以下组中的疾病:组织纤维化,例如肺纤维化,包括特发性肺纤维化,肝纤维化,包括肝硬化和慢性肝炎 ,类风湿性关节炎,眼部疾病或皮肤纤维化,包括皮肤瘢痕疙瘩,肾脏如肾炎,肾纤维化和肾硬化,以及血管病变,如再狭窄。
    • 7. 发明申请
    • COMPOSITIONS MONOVALENT FOR CD28 BINDING AND METHODS OF USE
    • CD28结合的组合物单一使用方法和使用方法
    • WO2010007376A3
    • 2010-05-27
    • PCT/GB2009001762
    • 2009-07-17
    • DOMANTIS LTDENEVER CAROLYNGRANT STEVENSANSOM DAVIDHOLMES STEVE
    • ENEVER CAROLYNGRANT STEVENSANSOM DAVIDHOLMES STEVE
    • C07K16/28A61K39/395A61P37/06
    • C07K16/2818C07K2317/21C07K2317/565C07K2317/567C07K2317/569C07K2317/76
    • The disclosure relates to a monovalent polypeptide domain which specifically binds CD28, as well as to an antagonist of CD28, where the antagonist comprises a monovalent polypeptide domain which specifically binds CD28. This disclosure encompasses monovalent polypeptide domains comprising an antibody single variable domain that monovalently binds CD28. An antibody single variable domain that is monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a monovalent anti-CD28 antibody single variable domain consists of or comprises an antibody single variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the monovalent anti-CD28 antibody single variable domain is a human antibody single variable domain. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a monovalent anti-CD28 antibody single variable domain to the individual.
    • 本公开涉及特异性结合CD28的单价多肽结构域以及CD28拮抗剂,其中拮抗剂包含特异性结合CD28的单价多肽结构域。 本公开内容涵盖包含单价结合CD28的抗体单可变结构域的单价多肽结构域。 用于结合CD28的单价抗体单可变区可抑制CD28活性。 在一个方面,单价抗CD28抗体单可变结构域由一个方面组成或包含特异性结合和拮抗CD28的活性的抗体单可变结构域,而不具有实质上激动的CD28活性。 另一方面,单价抗CD28抗体单可变结构域是人抗体单可变结构域。 本公开还包括在个体中拮抗CD80和/或CD86相互作用的方法以及涉及CD80和/或CD86与CD28相互作用的疾病或病症的方法,涉及向单克隆抗CD28抗体单可变结构域施用的方法 个人。