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New antibodies that bind to human insulin-like growth factor receptor, useful for treatment, prevention and diagnosis of cancers

机译:与人胰岛素样生长因子受体结合的新抗体,可用于治疗,预防和诊断癌症

摘要

An isolated antibody (Ab), and its functional fragments, that bind to human insulin-like growth factor-1 receptor (IGF-1R) and optionally: (i) inhibit natural binding of insulin-like growth factors (IGF)-1 and/or -2; and/or (ii) inhibit specifically tyrosine kinase activity of IGF-1R. An isolated antibody (Ab), and its functional fragments, that bind to human insulin-like growth factor-1 receptor (IGF-1R) and optionally inhibit natural binding of insulin-like growth factors (IGF)-1 and/or -2 and/or inhibit specifically tyrosine kinase activity of IGF-1R, is new. Ab comprises: (a) a light chain containing at least one complementarity-determining region (CDR) of one of 3 fully defined sequences comprising 16, 7 or 9 amino acids as given in the specification; or (b) a heavy chain containing at least one of the CDRs of one of 3 fully defined sequences comprising 6, 16 or 8 amino acids as given in the specification or sequences with 80% identity after optimal alignment. Independent claims are also included for the following: (1) murine hybridomas that secrete Ab; (2) an isolated nucleic acid (I) that: (a) is RNA or DNA and encodes Ab or its fragments; (b) is the complement of (a); or (c) has at least 18 nucleotides that can hybridize under stringent conditions with any of six sequences fully defined in the specification that encode the specified CDR, or with sequences having 80% identity after optimal alignment; (3) a vector containing (I); (4) a host cell containing the vector of (3); (5) a non-human transgenic animal containing at least one cell transfected with the vector of (3); (6) producing Ab or its fragments; (7) in vitro diagnosis of diseases induced by over- or under-expression of IGF-1R and or EGFR (epidermal growth factor receptor) by reaction with optionally labeled Ab; and (8) kit for performing method (7).
机译:一种分离的抗体(Ab)及其功能片段,与人胰岛素样生长因子-1受体(IGF-1R)结合,并可选地:(i)抑制胰岛素样生长因子(IGF)-1的自然结合,并且/或-2;和/或(ii)特异性抑制IGF-1R的酪氨酸激酶活性。与人胰岛素样生长因子-1受体(IGF-1R)结合并任选抑制胰岛素样生长因子(IGF)-1和/或-2的天然结合的分离的抗体(Ab)及其功能片段和/或特异性抑制IGF-1R的酪氨酸激酶活性是新的。 Ab包括:(a)轻链,其包含说明书中给出的包含16、7或9个氨基酸的3个完全限定序列之一的至少一个互补决定区(CDR); (b)重链,其包含在说明书中给定的包含6,16或8个氨基酸的3个完整定义序列之一的CDR中的至少一个,或在最佳比对后具有80%的同一性的序列。还包括以下方面的独立权利要求:(1)分泌Ab的鼠杂交瘤; (2)一种分离的核酸(I),其:(a)是RNA或DNA并且编码Ab或其片段; (b)是(a)的补语; (c)具有至少18个核苷酸,它们可以在严格条件下与说明书中完全定义的编码指定CDR的六个序列中的任何一个杂交,或与在最佳比对后具有80%同一性的序列杂交;或(3)含有(I)的载体; (4)含有(3)的载体的宿主细胞。 (5)一种非人转基因动物,其含有至少一种用(3)的载体转染的细胞。 (六)产生抗体或其片段; (7)通过与任选标记的Ab反应体外诊断由IGF-1R和/或EGFR(表皮生长因子受体)过表达或过表达诱导的疾病; (8)用于执行方法(7)的套件。

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