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    REDUCTION OF ENDOTOXIN IN POLYSIALIC ACIDS
    1.
    发明申请
    REDUCTION OF ENDOTOXIN IN POLYSIALIC ACIDS 审中-公开
    减少多糖中的内毒素

    公开(公告)号：WO2008104811A1

    公开(公告)日：2008-09-04

    申请号：PCT/GB2008/050138

    申请日：2008-02-28

    Applicant: LIPOXEN TECHNOLOGIES LIMITED ,  JAIN, Sanjay ,  LAING, Peter ,  GREGORIADIS, Gregory

    Inventor： JAIN, Sanjay ,  LAING, Peter ,  GREGORIADIS, Gregory

    IPC: C08B37/00

    CPC classification number: C08B37/0006 ,  B01D15/363 ,  C08B37/0003

    Abstract: The present invention relates to process for reducing the endotoxin content of a sample of fermentation broth containing polysialic acid and endotoxin comprising the sequential steps: (i) adding to the sample a base having a pKa of at least 12 to form a basic solution having a pH of at least 12, incubating the solution for a pre - determined time at a pre - determined temperature; and (ii) recovery of PSA, suitably by (iii) passing the sample through an anion - exchange column whereby polysialic acid is absorbed on the ion exchange resin; (iv) washing the column with one washing buffer, whereby polysialic acid remains absorbed on the ion exchange resin; and (v) eluting the polysialic acid from the column using an elution buffer to provide a product solution of polysialic acid having reduced endoto xin content.

    Abstract translation: 本发明涉及降低含有唾液酸和内毒素的发酵肉汤样品的内毒素含量的方法，其包括以下顺序步骤：（i）向样品中加入pKa至少为12的碱，以形成具有 pH至少为12，在预定温度下将溶液温育预定时间; 和（ii）PSA的回收，适当地通过（iii）使样品通过阴离子交换柱，由此唾液酸被吸收在离子交换树脂上; （iv）用一个洗涤缓冲液洗涤该柱，由此聚唾液酸保持吸收在离子交换树脂上; 和（v）使用洗​​脱缓冲液从柱中洗脱聚唾液酸，以提供具有降低的内毒素含量的聚唾液酸的产物溶液。

    PHARMACEUTICAL COMPOSITIONS
    4.
    发明申请
    PHARMACEUTICAL COMPOSITIONS 审中-公开
    药物组合物

    公开(公告)号：WO1992022331A1

    公开(公告)日：1992-12-23

    申请号：PCT/GB1992001022

    申请日：1992-06-08

    Applicant: THE SCHOOL OF PHARMACY ,  GREGORIADIS, Gregory

    Inventor： THE SCHOOL OF PHARMACY

    IPC: A61K47/48

    CPC classification number: A61K9/1271 ,  A61K47/61 ,  A61K47/6911 ,  Y02A50/473

    Abstract: Polysaccharides comprising at least 5 sialic acid residues per molecule and used to increase the circulation time, decrease the immunogenicity and/or increase the stability in vivo of pharmaceutically active compounds. The pharmaceutically active compound may be a foreign protein which is covalently bound to the polysaccharide. Alternatively the active compound may be associated with a drug delivery system (DDS), for instance a macro-molecular DDS or a particulate DDS, such as liposomes. The polysaccharide is usually a bacterial polysaccharide, e.g. a glycolipid or a derivative thereof, for instance polysaccharide B or E. Coli K1, N. meningitidis, Moraxella liquifaciens or Pasteurella aeroginosis, or K92 of E. Coli K92 strain.

    Abstract translation: 每分子含有至少5个唾液酸残基并用于增加循环时间，降低免疫原性和/或增加药物活性化合物体内稳定性的多糖。 药物活性化合物可以是与多糖共价结合的外来蛋白质。 或者，活性化合物可以与药物递送系统（DDS）相关联，例如大分子DDS或颗粒DDS，例如脂质体。 多糖通常是细菌多糖，例如 糖脂或其衍生物，例如多糖B或大肠杆菌K1，脑膜炎奈瑟氏球菌，流感病酒石杆菌或嗜碱性乳杆菌病，或大肠杆菌K92菌株的K92。

    DERIVATISATION OF PROTEINS IN AQUEOUS SOLUTION
    8.
    发明申请
    DERIVATISATION OF PROTEINS IN AQUEOUS SOLUTION 审中-公开
    蛋白质在水溶液中的衍生

    公开(公告)号：WO0187922A3

    公开(公告)日：2003-05-30

    申请号：PCT/GB0102115

    申请日：2001-05-14

    Applicant: LIPOXEN TECHNOLOGIES LTD ,  GREGORIADIS GREGORY

    Inventor： GREGORIADIS GREGORY

    IPC: A61K38/00 ,  A61P37/00 ,  C07K1/107 ,  C07K1/113 ,  C07K14/62 ,  C07K14/81 ,  C07K16/00 ,  C07K16/18 ,  C12N9/08

    CPC classification number: C12N9/0065 ,  C07K1/1077 ,  C07K14/62 ,  C07K14/8117 ,  C07K16/00 ,  C12Y111/01006

    Abstract: Proteins are derivatised by reaction of pendant groups, usually groups which are side chains in non-terminal amino acyl units of the protein, in aqueous reactions in the presence of a denaturant. The denaturant is preferably an amphiphilic compound, most preferably an anionic amphiphilic compound such as a long chain alkyl sulphate mono ester, preferably an alkaline metal salt, for instance sodium dodecyl sulphate. The degree of derivatisation is increased, whilst the protein retains activity, such as enzyme activity. The increase in the degree of derivatisation enhances the increase in circulation time in vivo and stability on storage and in vivo. Preferably the derivatising reagent is an aldehyde compound which reacts with primary amine groups, generally the epsilon-amino group of lysyl units. Derivatisation is conducted under reducing conditions to generate a secondary amine derivative.

    Abstract translation: 蛋白质通过在变性剂存在下的水性反应中的侧基（通常是蛋白质的非末端氨基酰基单元侧链的基团）的反应衍生化。 变性剂优选为两亲性化合物，最优选阴离子两亲化合物，例如长链烷基硫酸酯单酯，优选碱金属盐，例如十二烷基硫酸钠。 衍生化程度增加，而蛋白质保留活性，如酶活性。 衍生化程度的增加增加了体内循环时间的增加和储存和体内的稳定性。 优选地，衍生试剂是与伯胺基团（通常是赖氨酰单元的ε-氨基）反应的醛化合物。 衍生化在还原条件下进行以产生仲胺衍生物。

    GLYCOPOLYSIALYLATION OF NON-BLOOD COAGULATION PROTEINS
    9.
    发明申请
    GLYCOPOLYSIALYLATION OF NON-BLOOD COAGULATION PROTEINS 审中-公开
    非凝血蛋白的糖肽聚糖化

    公开(公告)号：WO2011012850A3

    公开(公告)日：2011-04-14

    申请号：PCT/GB2010001422

    申请日：2010-07-26

    Applicant: LIPOXEN TECHNOLOGIES LTD ,  JAIN SANJAY ,  GREGORIADIS GREGORY ,  DWIVEDI ARCHANA ,  NATH SRIJIT ,  SIEKMANN JUERGEN ,  HAIDER STEFAN ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER ,  BAXTER INT ,  BAXTER HEALTHCARE SA

    Inventor： JAIN SANJAY ,  GREGORIADIS GREGORY ,  DWIVEDI ARCHANA ,  NATH SRIJIT ,  SIEKMANN JUERGEN ,  HAIDER STEFAN ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER

    IPC: A61K47/48

    CPC classification number: A61K47/6455 ,  A61K47/4823 ,  A61K47/60 ,  A61K47/61 ,  A61K47/65

    Abstract: A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety.

    Abstract translation: 水溶性聚合物，特别是聚唾液酸（PSA）或改性PSA（mPSA），通过使氧化碳水化合物部分与血液凝固蛋白以外的糖蛋白的氧化碳水化合物部分或神经节苷脂或药物递送系统偶联 与水溶性聚合物接触，其中所述水溶性聚合物含有氨氧基，并且在氧化碳水化合物部分和水溶性聚合物上的氨氧基之间形成肟键，或者其中所述水溶性聚合物含有酰肼基，腙键为 在氧化碳水化合物部分和水溶性聚合物上的酰肼基团之间形成。 因此获得氨氧基或酰肼 - 水溶性聚合物如PSA和mPSA的偶联物，其中PSA或mPSA通过碳水化合物部分连接。

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