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    • 41. 发明授权
    • High surface density covalent immobilization of oligonucleotide monolayers using a 1-(thiotrifluoroacetato)-11-(trichlorososilyl)-undecane linker
    • 使用1-(三(三氟乙酰))-11-(三氯硅烷基) - 十一烷接头的高密度共价固定寡核苷酸单层
    • US06169194A
    • 2001-01-02
    • US08951448
    • 1997-10-16
    • Michael ThompsonMark E. McGovern
    • Michael ThompsonMark E. McGovern
    • C07F712
    • B82Y30/00B01J20/3242B32B17/10688B82Y5/00B82Y15/00C03C17/30C03C17/3405C07B2200/11C07H21/00Y10S977/702Y10S977/902Y10S977/92Y10S977/924Y10S977/958
    • Oligonucleotides and other biomolecules are immobilized in high density on solid substrates through covalent forces using either a permanent thioether bond, or a chemoselectively reversible disulfide bond to a surface thiol. Substrates which have hydroxyl groups on their surfaces can be first silanized with a trichlorosilane containing 2-20 carbon atoms in its hydrocarbon backbone, terminating in a protected thiol group. The oligonucleotides or other biomolecules are first connected to a tether consisting of a hydrocarbon or polyether chain of 2-20 units in length which terminates in a thiol group. This thiol may be further modified with a halobenzylic-bifunctional water soluble reagent which allows the conjugate to be immobilized onto the surface thiol group by a permanent thioether bond. Alternatively, the oligonucleotide-tether-thiol group can be converted to a pyridyldisulfide functionality which attaches to the surface thiol by a chemoselectively reversible disulfide bond. The permanently bound oligonucleotides are immobilized in high density compared to other types of thiol functionalized silane surfaces and to the avidin-biotin method.
    • 寡核苷酸和其他生物分子通过共价力使用永久硫醚键或与表面硫醇的化学选择性可逆二硫键以高密度固定在固体基质上。 在其表面上具有羟基的底物可以首先在其烃骨架中用含有2-20个碳原子的三氯硅烷硅烷化,终止于受保护的硫醇基团。 寡核苷酸或其他生物分子首先连接到由长度为2-20单位的烃或聚醚链组成的系链,其终止于硫醇基团。 该硫醇可以用卤代苄基双功能水溶性试剂进一步改性,其允许缀合物通过永久硫醚键固定在表面硫醇基上。 或者,寡核苷酸 - 系链 - 硫醇基团可以转化成通过化学选择性可逆的二硫键附着于表面硫醇的吡啶基二硫键官能团。 与其他类型的硫醇官能化硅烷表面和抗生物素蛋白 - 生物素方法相比,永久结合的寡核苷酸以高密度固定。
    • 49. 发明授权
    • Process for producing thrombin from plasma
    • 从血浆中生产凝血酶的方法
    • US5981254A
    • 1999-11-09
    • US960660
    • 1997-10-30
    • Trung Bui-Khac
    • Trung Bui-Khac
    • C12N9/74A61K35/14A61K38/00A61K38/45A61K38/46A61K38/48A61L2/00A61L24/00A61L24/10C07K1/14C07K14/745C07K14/75C07K14/78
    • C07K14/745A61K38/45A61L2/0017A61L24/106Y10S977/904Y10S977/906Y10S977/908Y10S977/92
    • This invention relates to a process for preparing biological glue components from a plasma pool which combines high recovery, quality product and viral safety. In first instance, a triple viral inactivated product comprising fibrogen, fibronectin and FXIII is obtained by treating a concentrate thereof first with a viricide solvent/detergent solution, second with viral nanofiltration, and third with heat. The recovery of a good quality product is not compromised by the process of the invention. In second instance, the same steps are reproduced for obtaining a triple viral safe thrombin product. In that case, a known proprietary process has been improved to increase the recovery of active thrombin by about two fold. One of the steps which increase the yield of thrombin is the dilution of the prothrombin solution with water 4 volumes to 1 volume prothrombin prior to acid precipitation.
    • 本发明涉及一种从血浆池制备生物胶组分的方法,其结合了高回收率,优质产品和病毒安全性。 首先,通过首先用杀病毒剂溶剂/洗涤剂溶液处理浓缩物,然后用病毒纳滤过滤,然后加热加热,获得包含纤维素,纤连蛋白和FXIII的三重病毒灭活产物。 本发明的方法不会损害高质量产品的回收。 在第二种情况下,为了获得三重病毒安全性凝血酶产物,再现相同的步骤。 在这种情况下,已经改进了已知的专利方法,以将活性凝血酶的回收率增加约2倍。 提高凝血酶产量的步骤之一是在酸沉淀之前用水4体积至1体积的凝血酶原将凝血酶原溶液稀释。
    • 50. 发明授权
    • Inducing cytotoxic T lymphocyte responses
    • 诱导细胞毒性T淋巴细胞反应
    • US5928647A
    • 1999-07-27
    • US481327
    • 1995-09-15
    • Kenneth Rock
    • Kenneth Rock
    • A61K47/48A61K9/16A61K9/18A61K39/00A61K39/385A61K39/39A61P31/00A61P35/00A61P37/04
    • A61K9/167A61K39/00A61K2039/60Y10S977/802Y10S977/803Y10S977/915Y10S977/917Y10S977/918Y10S977/92
    • The invention provides compositions and methods for inducing MHC class I-restricted cytotoxic T lymphocyte responses in a mammalian host by immunization with non-replicating protein antigens. The compositions of the invention comprise a particulate-protein complex capable of inducing a class I-restricted CTL response to a protein antigen in a mammal, in which the particulate protein complex comprises a particulate component having an average diameter ranging in size from about 0.5 .mu.m to about 6 .mu.m, linked to a non-replicating protein antigen derived from a tumor cell or from pathogenic organism where CTL response is likely to play an important role in conferring protective immunity in a mammal, with the proviso that the particulate component is not a prokaryotic or eukaryotic cell or a micellar multimicellar, or liposome vesicle composed of detergents or lipids. The non-replicating protein antigen is attached to the particle component through a covalent or non-covalent association to form particulate protein antigen complexes and the complexes are administered to a mammalian host in conjunction with a pharmaceutically acceptable excipient, in a CTL-stimulatory amount. The invention also provides non-replicating vaccines and methods of vaccinating a mammalian host against pathogenic diseases or tumors for CTL immunity.
    • PCT No.PCT / US94 / 00362 Sec。 371 1995年9月15日第 102(e)1995年9月15日PCT PCT 1994年1月10日PCT公布。 第WO94 / 15635号公报 日期1994年7月21日本发明提供了通过用非复制蛋白抗原免疫在哺乳动物宿主中诱导MHC I类限制性细胞毒性T淋巴细胞应答的组合物和方法。 本发明的组合物包含能够在哺乳动物中诱导对蛋白质抗原的I类限制性CTL应答的颗粒蛋白复合物,其中所述颗粒蛋白质复合物包含平均直径范围为约0.5μm的颗粒组分 与衍生自肿瘤细胞的非复制蛋白质抗原或来自致病生物体的CTL复合蛋白抗原连接,其中CTL应答可能在哺乳动物赋予保护性免疫中起重要作用,条件是颗粒组分为 不是原核或真核细胞或胶束多片剂,或由洗涤剂或脂质组成的脂质体囊泡。 非复制蛋白质抗原通过共价或非共价缔合连接到颗粒组分上以形成颗粒蛋白抗原复合物,并且将复合物以CTL刺激量与药学上可接受的赋形剂联合施用于哺乳动物宿主。 本发明还提供了非复制性疫苗和将哺乳动物宿主接种抗病原性疾病或肿瘤用于CTL免疫的方法。