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    • 2. 发明申请
    • METHODS AND COMPOSITIONS FOR MODULATING IL-17F/IL-17A BIOLOGICAL ACTIVITY
    • 用于调节IL-17F / IL-17A生物活性的方法和组合物
    • WO2008121865A1
    • 2008-10-09
    • PCT/US2008/058735
    • 2008-03-28
    • WYETHWRIGHT, Jill, F.LIANG, Spencer, C.BENNETT, Frances, K.COLLINS, MaryCARRENO, Beatriz, M.
    • WRIGHT, Jill, F.LIANG, Spencer, C.BENNETT, Frances, K.COLLINS, MaryCARRENO, Beatriz, M.
    • G01N33/68
    • G01N33/6869G01N2333/54G01N2500/02
    • The invention provides a novel mouse IL-17F/IL-17A, and further provides uses of such mouse IL-17F/IL-17A in the characterization of the IL-17F/IL-17A heterodimer. The present invention is also related to polynucleotides and polypeptides of the IL-17F/IL-17A signaling pathway, and targeting of the IL-17F/IL-17A signaling pathway in methods of treating IL-17F/IL-17A- associated disorders. The invention thus provides methods of using isolated IL-17F/IL-17A heterodimer, e.g., in a mouse model of airway inflammation, and specific or selective IL-17F/IL-17A modulators (e.g., signaling agonists or signaling antagonists (e.g., specific or selective antagonistic antibodies, specific or selective antagonistic small molecules, etc.)). The invention also provides methods of screening for compounds capable of modulating IL-17F/IL-17A biological activity, e.g., IL-17F/IL-17A signaling antagonists (e.g., using the mouse model of airway inflammation), as well as methods of identifying whether the IL-17F/IL-17A modulator is a specific IL-17F/IL-17A modulator. The invention is also directed to novel methods for diagnosing, prognosing, monitoring, preventing, and/or treating IL-17F/IL-17A-associated disorders, including, but not limited to, inflammatory disorders (e.g., arthritis (including rheumatoid arthritis), psoriasis, systemic lupus erythematosus, and multiple sclerosis), respiratory diseases (e.g., airway inflammation, chronic obstructive pulmonary disease, cystic fibrosis, asthma, allergy), transplant rejection (including solid organ transplant rejection), and inflammatory bowel diseases or disorders (e.g., ulcerative colitis, Crohn's disease). The present invention is further directed to novel therapeutics and therapeutic targets identified by methods of screening of the invention, and uses of such identified therapeutics in methods of treatment and prevention of IL- 17F/IL- 17A-associated disorders.
    • 本发明提供了一种新型小鼠IL-17F / IL-17A,并且还提供了这种小鼠IL-17F / IL-17A在IL-17F / IL-17A异二聚体表征中的用途。 本发明还涉及IL-17F / IL-17A信号通路的多核苷酸和多肽,以及IL-17F / IL-17A信号通路在治疗IL-17F / IL-17A-相关疾病的方法中的靶向。 因此,本发明提供了使用分离的IL-17F / IL-17A异二聚体的方法,例如在气道炎症的小鼠模型中,以及特异性或选择性IL-17F / IL-17A调节剂(例如,信号传导激动剂或信号传导拮抗剂 特异性或选择性拮抗性抗体,特异性或选择性拮抗性小分子等))。 本发明还提供筛选能够调节IL-17F / IL-17A生物活性的化合物的方法,例如IL-17F / IL-17A信号传导拮抗剂(例如,使用气道炎症的小鼠模型),以及 识别IL-17F / IL-17A调节剂是否是特异性IL-17F / IL-17A调节剂。 本发明还涉及用于诊断,预后,监测,预防和/或治疗IL-17F / IL-17A相关疾病的新方法,包括但不限于炎症性疾病(例如关节炎(包括类风湿性关节炎) ,牛皮癣,系统性红斑狼疮和多发性硬化症),呼吸系统疾病(例如气道炎症,慢性阻塞性肺病,囊性纤维化,哮喘,过敏),移植排斥(包括实体器官移植排斥)和炎性肠病或疾病 例如溃疡性结肠炎,克罗恩病)。 本发明还涉及通过筛选本发明的方法鉴定的新型治疗学和治疗靶标,以及这些鉴定的治疗剂在治疗和预防IL-17F / IL-17A相关疾病的方法中的用途。