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    • 65. 发明授权
    • Modified factor VIII
    • 修改因子VIII
    • US06180371B2
    • 2001-01-30
    • US09037601
    • 1998-03-10
    • John S. Lollar
    • John S. Lollar
    • C12P2104
    • C07K14/755A61K38/00C07K2319/00
    • Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients who have developed such antibodies after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is not inhibited by inhibitory antibodies against the A2 or C2 domain epitopes. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.
    • 人因子VIII的特异性氨基酸位点与用因子VIII处理后发展了这种抗体的血友病患者的抑制性抗体相互作用。 公开了修饰因子VIII,其中通过在一个或多个特定基因座处的取代改变氨基酸序列。 修饰因子VIII不受针对A2或C2结构域表位的抑制性抗体的抑制。 修饰的因子VIII可用于血友病患者,以避免或预防抑制性抗体的作用。
    • 66. 发明授权
    • Interferon tau mutants and methods for making them
    • 干扰素tau突变体及其制备方法
    • US06833256B1
    • 2004-12-21
    • US09599413
    • 2000-06-22
    • Carol H. PontzerLynnette H. ShortsChristina Dancz Clark
    • Carol H. PontzerLynnette H. ShortsChristina Dancz Clark
    • C12P2104
    • C07K14/555A61K38/00
    • The present invention is directed to the field of animal and human health, and more particularly to pharmacological uses of analogs or mutants of interferon-tau (IFN-&tgr;) that differ from native IFN-&tgr; because of substitutions of amino acids near the amino terminus of the IFN-&tgr; molecule that impart improved biological activity. The IFN-&tgr; mutants described in this disclosure have low toxicity, retain the same or slightly reduced antiviral activity compared with highly effective IFN-alpha, and have enhanced antiproliferative activity compared to native IFN-tau, making them useful in treating viral infections, cancer, and immune system diseases including autoimmune diseases. The present invention is also directed to a method for making novel recombinant proteins, especially interferons, interleukins, and cytokines, polypeptide hormones and other biopharmaceuticals that have improved biological activity over known proteins and/or lower toxicity and/or increased stability.
    • 本发明涉及动物和人类健康领域,更具体地涉及由于氨基末端附近的氨基酸取代而与天然IFN-τ不同的干扰素-τ(IFN-τ)的类似物或突变体的药理学用途 的IFN-τ分子,其赋予改善的生物活性。 在本公开中描述的IFN-τ突变体具有低毒性,与高效IFN-α相比保持相同或略微降低的抗病毒活性,并且与天然IFN-τ相比具有增强的抗增殖活性,使其可用于治疗病毒感染,癌症 和免疫系统疾病,包括自身免疫性疾病。 本发明还涉及一种制备新型重组蛋白质,特别是干扰素,白细胞介素和细胞因子,多肽激素和其它生物活性比已知蛋白质改善和/或降低毒性和/或增加的稳定性的生物药物的方法。
    • 69. 发明授权
    • Secretion of T cell receptor fragments from recombinant host cells
    • 从重组宿主细胞分泌T细胞受体片段
    • US06623957B2
    • 2003-09-23
    • US10162127
    • 2002-06-04
    • Elizabeth S. Ward
    • Elizabeth S. Ward
    • C12P2104
    • C07K16/00A61K47/6827A61K47/6849C07K14/70503C07K14/7051C07K14/70514C07K14/70535C07K14/70539C07K2317/52C07K2317/53C07K2319/00
    • Variable domain murine T-cell receptor genes have been isolated and used to construct cloning and expression vectors. V&agr;, V&bgr;, and single chain V&agr;-V&bgr; fragments have been expressed as secreted domains in Escherichia coli using the vectors. The domains are secreted into the culture supernatant in milligram quantities. The single domains and the single chain T-cell receptors are folded into &bgr;-pleated sheet structures similar to those of immunoglobulin variable domains. The secreted fragments may be useful for immunization to generate anti-clonotypic antibodies, in vaccination or for high resolution structural studies. The genes encoding these domains may also serve as templates for in vitro mutagenesis and improvement of affinities of the TCR fragments for their interaction with cognate peptide-MHC complexes.
    • 已经分离了可变结构域鼠T细胞受体基因,并用于构建克隆和表达载体。 Valpha,Vbeta和单链Valpha-Vbeta片段已经使用载体在大肠杆菌中表达为分泌结构域。 以毫克量将结构域分泌到培养上清液中。 单结构域和单链T细胞受体被折叠成类似于免疫球蛋白可变结构域的β-折叠片结构。 分泌的片段可用于免疫以产生抗克隆型抗体,在疫苗接种或高分辨率结构研究中。 编码这些结构域的基因也可以用作体外诱变和提高TCR片段与同源肽-MHC复合物相互作用的亲和力的模板。