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    • 2. 发明申请
    • Generation and affinity maturation of antibody library in silico
    • 抗体库的生成和亲和力成熟
    • US20110124528A1
    • 2011-05-26
    • US12916077
    • 2010-10-29
    • Peizhi LuoMark HsiehPingyu ZhongCaili WangYicheng CaoShengjiang Liu
    • Peizhi LuoMark HsiehPingyu ZhongCaili WangYicheng CaoShengjiang Liu
    • C40B50/02
    • C07K16/22B01J2219/00689B01J2219/00695B01J2219/007B01J2219/00725C07K16/00C07K2299/00C07K2317/21C07K2317/24C07K2317/565C07K2317/567C07K2317/622C07K2317/92C07K2319/00C40B40/10G16B35/00G16C20/60
    • The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
    • 本发明提供了一种用于有效地产生和筛选具有所需生物学功能的优化蛋白质的蛋白质文库的方法,例如改善对生物和/或治疗重要的靶分子的结合亲和力。 该过程以高通量方式通过开发不断扩大的所有生物体,特别是人的蛋白质序列数据库进行。 在一个实施方案中,构建设计蛋白质文库的方法,包括以下步骤:提供衍生自铅蛋白的氨基酸序列,所述氨基酸序列指定为引导序列; 将引导序列与多个测试蛋白序列进行比较; 以及从所述多个测试蛋白序列中选择与所述引物序列具有至少15%序列同一性的至少两个肽片段,所选择的肽片段形成命中文库; 并通过用命中库替换引导序列形成设计蛋白质的文库。 设计的蛋白质文库可以在体外或体内表达,以产生重组蛋白文库,该文库可以筛选出超过铅蛋白质的新的或改进的功能,例如针对治疗重要靶标的抗体。
    • 3. 发明申请
    • Generation and selection of protein library in silico
    • 蛋白质库的生成和选择
    • US20070037214A1
    • 2007-02-15
    • US11502838
    • 2006-08-10
    • Peizhi LuoMark HsiehPingyu ZhongCaili WangYicheng CaoShengjiang Liu
    • Peizhi LuoMark HsiehPingyu ZhongCaili WangYicheng CaoShengjiang Liu
    • C40B30/06C40B40/10
    • C07K16/22B01J2219/00689B01J2219/00695B01J2219/007B01J2219/00725C07K16/00C07K2299/00C07K2317/21C07K2317/24C07K2317/565C07K2317/567C07K2317/622C07K2317/92C07K2319/00C40B40/10G16B35/00G16C20/60
    • The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
    • 本发明提供了一种用于有效地产生和筛选具有所需生物学功能的优化蛋白质的蛋白质文库的方法,例如改善对生物和/或治疗重要的靶分子的结合亲和力。 该过程以高通量方式通过开发不断扩大的所有生物体,特别是人的蛋白质序列数据库进行。 在一个实施方案中,构建设计蛋白质文库的方法,包括以下步骤:提供衍生自铅蛋白的氨基酸序列,所述氨基酸序列指定为引导序列; 将引导序列与多个测试蛋白序列进行比较; 以及从所述多个测试蛋白序列中选择与所述引物序列具有至少15%序列同一性的至少两个肽片段,所选择的肽片段形成命中文库; 并通过用命中库替换引导序列形成设计蛋白质的文库。 设计的蛋白质文库可以在体外或体内表达,以产生重组蛋白文库,该文库可以筛选出超过铅蛋白质的新的或改进的功能,例如针对治疗重要靶标的抗体。