公开(公告)号：US20110020342A1

公开(公告)日：2011-01-27

申请号：US12894278

申请日：2010-09-30

申请人： DAVID J. GLASS ,  GEORGE D. YANCOPOULOS ,  THOMAS J. DALY ,  NICHOLAS J. PAPADOPOULOS

发明人： DAVID J. GLASS ,  GEORGE D. YANCOPOULOS ,  THOMAS J. DALY ,  NICHOLAS J. PAPADOPOULOS

IPC分类号： A61K39/395 ,  C07K19/00 ,  C07H21/04 ,  C12N15/63 ,  C12N1/21 ,  C12N1/19 ,  C12N5/10 ,  C12P21/00 ,  A61P21/00 ,  A61P3/10

CPC分类号： C07K14/65 ,  A61K38/30 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/75

摘要： A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibits improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, such as an immunoglobulin domain, in particular, the Fc domain of IgG or a heavy chain of IgG. IGF1 variants were shown to have improved ability to increase muscle mass in a subject suffering from muscle atrophy caused by cachexia, immobilization, aging, chronic disease, cancer, hereditary condition, an atrophy-causing agent, and the like. IGF1 variants are also effective in decreasing blood glucose in a subject suffering from diabetes or hyperglycemia.

摘要翻译： 包含至少一种IGF1变体组分和融合组分（F）以及任选的信号序列的融合蛋白相对于天然IGF1或IGF2多肽表现出改进的稳定性。 融合组分（F）可以是多聚化组分，例如免疫球蛋白结构域，特别是IgG的Fc结构域或IgG的重链。 IGF1变体显示具有改善的能力，以增加受到恶病质，固定化，老化，慢性疾病，癌症，遗传性疾病，引起萎缩症等引起的肌肉萎缩的受试者的肌肉质量的增加。 IGF1变体在降低患有糖尿病或高血糖症的受试者中的血糖中也是有效的。