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    • 88. 发明授权
    • Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease
    • 用于选择性还原循环生物活性可溶性TNF的组合物和治疗TNF介导的疾病的方法
    • US09580502B2
    • 2017-02-28
    • US15176503
    • 2016-06-08
    • Thymon, LLC
    • Gideon Goldstein
    • A61K39/395C07K16/24C07K14/525
    • C07K16/241C07K14/525C07K2317/34C07K2317/565C07K2317/76
    • An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF. These methods and compositions disrupt or reduce the in vivo assembly or reassembly of dissociated monomers of TNF into bioactive trimeric human sTNF.
    • 提供分离或合成的抗体或配体,其特异性结合人TNF的解离单体的表位。 这种结合破坏单体组装成生物活性三聚人sTNF。 药物组合物含有一种或多种抗体或配体:(a)特异性结合SEQ ID NO:1具有序列PSDKPVAH或PSDKPVAHV,氨基酸8-15或8-16的TNF单体特异性表位的抗体或配体; 和(b)特异性结合SEQ ID NO:1的序列EPIYLGGVF的氨基酸116至124的TNF单体特异性表位的抗体或配体。结合或与(a)和 /或(b))可用于治疗由人TNF介导的疾病(例如类风湿性关节炎,强直性脊柱炎,幼年类风湿性关节炎,银屑病关节炎,动脉粥样硬化,代谢综合征,阿尔茨海默病,HIV,II型糖尿病)的受试者的方法 。 这些方法和组合物将TNF的解离的单体的体内装配或重新组装破坏或减少为生物活性三聚人sTNF。