In vivo stimulation of peripheral blood progenitor cells by granulocyte-macrophage colony stimulating factor (GM-CSF) cysteine muteins and their PEGylated variants
    11.
    发明授权
    In vivo stimulation of peripheral blood progenitor cells by granulocyte-macrophage colony stimulating factor (GM-CSF) cysteine muteins and their PEGylated variants 有权
    粒细胞 - 巨噬细胞集落刺激因子(GM-CSF)半胱氨酸突变蛋白及其聚乙二醇化变体体外刺激外周血祖细胞

    公开(公告)号:US07824669B2

    公开(公告)日:2010-11-02

    申请号:US12502839

    申请日:2009-07-14

    摘要: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby. Also disclosed are therapeutic methods for using the cysteine variants of the invention.

    摘要翻译: 生长激素超基因家族包含大于20个结构相关的细胞因子和生长因子。 提供了一种用于产生这些蛋白质的位点特异性,生物活性缀合物的通用方法。 该方法包括将半胱氨酸残基添加到蛋白质的非必需区域中,或者使用定点突变将蛋白质中的非必需氨基酸取代半胱氨酸残基,然后将半胱氨酸反应性聚合物或其它类型的半胱氨酸反应性部分共价偶联到 通过添加的半胱氨酸残基的蛋白质。 本文公开了用于添加半胱氨酸残基或将半胱氨酸取代引入蛋白质的优选位点,以及由此产生的蛋白质和蛋白质衍生物。 还公开了使用本发明的半胱氨酸变体的治疗方法。

    Preparation of water-soluble non-acetylated polysaccharide polymer
having repeating pentamer units with xanthomonas
    13.
    发明授权
    Preparation of water-soluble non-acetylated polysaccharide polymer having repeating pentamer units with xanthomonas 失效
    制备具有黄色单生型重复五聚体单元的水溶性非乙酰化多糖聚合物

    公开(公告)号:US5948651A

    公开(公告)日:1999-09-07

    申请号:US406804

    申请日:1995-03-20

    摘要: Water-soluble polysaccharide polymers are provided including a polymer composed of repeating pentamer units having a D-glucose:D-mannose:D-glucuronic acid ratio of about 2:2:1, and a polymer composed of repeating tetramer units having a D-glucose:D-mannose:D-glucuronic acid ratio of about 2:1:1. The D-glucose moieties are linked in a beta-�1,4! configuration. The inner D-mannose moieties are linked in an alpha-�1,3! configuration, generally to alternate glucose moieties. The D-glucuronic acid moieties are linked in a beta-�1,2! configuration to the inner mannose moieties. The outer mannose moieties are linked to the glucuronic acid moieties in a beta-�1,4! configuration. Also an isolated acetylase deficient mutant of Xanthomonas is used in a process to produce the polysaccharide.

    摘要翻译: 提供水溶性多糖聚合物,其包含由D-葡萄糖:D-甘露糖:D-葡萄糖醛酸比例为约2:2:1的重复五聚体单元组成的聚合物,以及由具有D-葡萄糖的D重复四聚体单元组成的聚合物, 葡萄糖:D-甘露糖:D-葡萄糖醛酸比约为2:1:1。 D-葡萄糖部分以β-(1,4)构型连接。 内部D-甘露糖部分以α-[1,3]构型连接,通常为交替的葡萄糖部分。 D-葡萄糖醛酸部分以β-(1,2)构型连接到内部甘露糖部分。 外部甘露糖部分以β-(1,4)构型与葡萄糖醛酸部分连接。 在产生多糖的过程中也使用黄单胞菌属的分离的乙酰酶缺陷型突变体。

    Process for the synthesis of sugar nucleotides using recombinant-DNA
methods
    15.
    发明授权
    Process for the synthesis of sugar nucleotides using recombinant-DNA methods 失效
    使用重组DNA方法合成糖核苷酸的方法

    公开(公告)号:US5824472A

    公开(公告)日:1998-10-20

    申请号:US467145

    申请日:1995-06-06

    CPC分类号: C12N15/52 C12P19/305

    摘要: A recombinant-DNA mediated method for the synthesis of sugar nucleotides is disclosed. This method utilizes portable DNA sequences capable of directing the microbial synthesis of various enzymes that catalyze the synthesis of sugar nucleotides, including UDP-glucose, UDP-glucuronic acid and GDP-mannose. The sugar moieties of these sugar nucleotides may subsequently be incorporated into industrially-useful polysaccharides such as xanthan gum. It has been found that vectors containing the portable DNA sequences described herein are capable both of causing sugar nucleotide production in microorganisms previously incapable of such synthesis and of causing increased sugar nucleotide production in organisms capable of synthesizing small quantities of these compounds. In particular, plasmids pAS7, pAS9 and pTS13 are disclosed. These plasmids are capable of directing sugar nucleotide synthesis in various hosts, including Xanthomonas sp. such as X. campestris and other organisms such as E. coli and various Pseudomonas sp.

    摘要翻译: 公开了用于合成糖核苷酸的重组DNA介导的方法。 该方法利用能够引导微生物合成催化合成糖核苷酸的各种酶的便携式DNA序列,包括UDP-葡萄糖,UDP-葡糖醛酸和GDP-甘露糖。 这些糖核苷酸的糖部分可以随后掺入工业上有用的多糖如黄原胶中。 已经发现,含有本文所述的便携式DNA序列的载体能够在先前不能进行这种合成的微生物中产生糖核苷酸并且能够在能够合成少量这些化合物的生物体中引起增加的糖核苷酸产生。 特别地,公开了质粒pAS7,pAS9和pTS13。 这些质粒能够引导各种宿主中的糖核苷酸合成,包括黄单胞菌属 如野菜和其他生物如大肠杆菌和各种假单胞菌属。