Detoxified mutants of escherichia coli heat-labile enterotoxin
    1.
    发明授权
    Detoxified mutants of escherichia coli heat-labile enterotoxin 有权
    大肠杆菌热不稳定肠毒素的解毒突变体

    公开(公告)号:US07722887B1

    公开(公告)日:2010-05-25

    申请号:US10088202

    申请日:1999-09-15

    CPC分类号: C07K14/245 A61K39/00

    摘要: The present invention relates to detoxified and immunologically active proteins (“mutant LTs”) having mutated amino acid sequences of heat-labile enterotoxin of E. coli, DNA sequences encoding the mutant LTs, recombinant expression vectors comprising the DNAs, recombinant microorganisms transformed with the recombinant expression vectors, process for preparing the mutant LTs and pharmaceutical application of the said protein as immunogenic antigens for vaccination and as adjuvants for anti-body production. In contrast to wild-type LT, the mutant LTs did not induce any toxic activities. The mutant LTs elicited high and comparable levels of anti-LT antibodies when delivered either intragastrically or intranasally, inducing systemic and local responses in serum and fecal extracts. Thus, they might be useful for the development of a novel diarrheal vaccine in humans and animals. In addition, the antibody production ability using mutant LTs as an adjuvant may be effective for prevention and treatment of various diseases.

    摘要翻译: 本发明涉及具有大肠杆菌热不稳定肠毒素突变氨基酸序列的解毒和免疫活性蛋白(“突变LT”),编码突变LT的DNA序列,包含DNA的重组表达载体,用 重组表达载体,用于制备突变LT的方法和所述蛋白质的药物应用作为用于疫苗接种的免疫原性抗原以及用于抗体产生的佐剂。 与野生型LT相比,突变LT不诱导任何毒性活性。 突变LTs在胃内或鼻内递送时引起高水平和相当水平的抗LT抗体,在血清和粪便提取物中诱导全身和局部反应。 因此,它们可能对于在人和动物中发展新的腹泻疫苗是有用的。 此外,使用突变型LTs作为佐剂的抗体生产能力可有效预防和治疗各种疾病。

    Angiogenesis inhibitor
    6.
    发明授权
    Angiogenesis inhibitor 失效
    血管生成抑制剂

    公开(公告)号:US06743428B1

    公开(公告)日:2004-06-01

    申请号:US10088548

    申请日:2002-03-15

    IPC分类号: A61K3900

    CPC分类号: C07K14/4703 A61K38/00

    摘要: The present invention provides a novel angiogenesis inhibitor, LK68 whose amino acid sequence is identical with the human apolipoprotein (a) kringle domains IV36, IV37 and V38, a cDNA sequence encoding the LK68, a recombinant expression vector comprising the cDNA, a recombinant microorganism transformed with the recombinant expression vector and a novel use of the LK68 as an anticancer agent and a method for treating angiogenesis-mediated disease. LK68, LK6, LK7 and LK8 exhibit inhibitory activities on the cultured endothelial cell proliferation as well as on the endothelial cell migration. LK68 and its single kringles also inhibit the normal development of capillaries in the chick embryo chorioallantoic membrane (CAM). It was also showed that systemic administration of LK68 causes the inhibition of primary tumor growth, which is correlated with a suppression of tumor-induced angiogenesis. Accordingly, LK68 protein, its single kringles or their functional equivalents may be applied for the development of a potent anti-cancer agent, which is highly effective for angiogenesis-mediated diseases covering cancer, rheumatoid arthritis, psoriasis, ocular angiogenic disease, etc.

    摘要翻译: 本发明提供了一种新型的血管生成抑制剂LK68,其氨基酸序列与人载脂蛋白(a)三环结构域IV36,IV37和V38相同,编码LK68的cDNA序列,包含cDNA的重组表达载体,转化的重组微生物 用重组表达载体和LK68作为抗癌剂的新用途和治疗血管生成介导的疾病的方法。 LK68,LK6,LK7和LK8表现出对培养的内皮细胞增殖以及内皮细胞迁移的抑制活性。 LK68及其单克隆也抑制鸡胚绒毛尿囊膜(CAM)毛细血管的正常发育。 还表明,LK68的全身给药导致原发性肿瘤生长的抑制,其与抑制肿瘤诱导的血管发生相关。 因此,LK68蛋白,其单克隆或其功能等同物可用于开发有效的抗癌剂,其对于涵盖癌症,类风湿性关节炎,牛皮癣,眼血管生成疾病等的血管生成介导的疾病是非常有效的。

    DNA and peptides of a diabetes-specific endogenous retrovirus
    7.
    发明授权
    DNA and peptides of a diabetes-specific endogenous retrovirus 失效
    糖尿病特异性内源性逆转录病毒的DNA和肽

    公开(公告)号:US06365727B1

    公开(公告)日:2002-04-02

    申请号:US09120653

    申请日:1998-07-22

    IPC分类号: C07H2104

    CPC分类号: C12Q1/702

    摘要: The present invention relates to gene and peptide sequences of a diabetes-specific endogenous retrovirus which is derived from type 1 diabetes patients. In particular, the present invention relates to a whole genome of the diabetes-specific variant of endogenous retrovirus (ERV-9) purified from pancreatic tissues of type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) patients and its genes and peptide and their sequences, which can be used as a diagnosing reagent for type 1 diabetes and as an immunogen. The diabetes-specific retrovirus expressed exclusively in pancreatic beta cells was purified from deceased type 1 diabetes patients. Subsequently, the retroviral gene sequences were determined, and by analyzing the amino acid sequence of the peptide deduced from the gene, 21 domains of the peptide having hydrophilicity and immuno-dominancy were identified. Therefore, the variant gene of the endogenous retrovirus and the peptide deduced from the gene can be effectively used as a diagnosing reagent of autoimmune-antibody for type 1 diabetes and as a vaccine for the variant ERV-9 related diseases.

    摘要翻译: 本发明涉及衍生自1型糖尿病患者的糖尿病特异性内源性逆转录病毒的基因和肽序列。 特别地,本发明涉及从1型糖尿病(胰岛素依赖性糖尿病[IDDM])患者的胰组织纯化的内源性逆转录病毒(ERV-9)的糖尿病特异性变体及其基因和肽的全基因组, 它们的序列可用作1型糖尿病的诊断试剂和免疫原。仅在死亡的1型糖尿病患者中纯化了在胰腺β细胞中表达的糖尿病特异性逆转录病毒。 随后,测定逆转录病毒基因序列,通过分析从该基因推定的肽的氨基酸序列,鉴定出具有亲水性和免疫多肽的21个结构域。因此,内源性逆转录病毒和肽的变体基因 从该基因推测可以有效地用作1型糖尿病的自身免疫抗体的诊断试剂和用于变异型ERV-9相关疾病的疫苗。

    Nucleic acid encoding angiogenesis inhibitor
    9.
    发明授权
    Nucleic acid encoding angiogenesis inhibitor 有权
    核酸编码血管生成抑制剂

    公开(公告)号:US07118905B2

    公开(公告)日:2006-10-10

    申请号:US10849961

    申请日:2004-05-19

    CPC分类号: C07K14/4703 A61K38/00

    摘要: The present invention provides a novel angiogenesis inhibitor, LK68 whose amino acid sequence is identical with the human apolipoprotein (a) kringle domains IV36, IV37 and V38, a cDNA sequence encoding the LK68, a recombinant expression vector comprising the cDNA, a recombinant microorganism transformed with the recombinant expression vector and a novel use of the LK68 as an anticancer agent and a method for treating angiogenesis-mediated disease. LK68, LK6, LK7 and LK8 exhibit inhibitory activities on the cultured endothelial cell proliferation as well as on the endothelial cell migration. LK68 and its single kringles also inhibit the normal development of capillaries in the chick embryo chorioallantoic membrane (CAM). It was also showed that systemic administration of LK68 causes the inhibition of primary tumor growth, which is correlated with a suppression of tumor-induced angiogenesis. Accordingly, LK68 protein, its single kringles or their functional equivalents may be applied for the development of a potent anti-cancer agent, which is highly effective for angiogenesis-mediated diseases covering cancer, rheumatoid arthritis, psoriasis, ocular angiogenic disease, etc.

    摘要翻译: 本发明提供了一种新型的血管生成抑制剂LK68,其氨基酸序列与人载脂蛋白(a)三环结构域IV36,IV37和V38相同,编码LK68的cDNA序列,包含cDNA的重组表达载体,转化的重组微生物 用重组表达载体和LK68作为抗癌剂的新用途和治疗血管生成介导的疾病的方法。 LK68,LK6,LK7和LK8表现出对培养的内皮细胞增殖以及内皮细胞迁移的抑制活性。 LK68及其单克隆也抑制鸡胚绒毛尿囊膜(CAM)毛细血管的正常发育。 还表明,LK68的全身给药导致原发性肿瘤生长的抑制,其与抑制肿瘤诱导的血管发生相关。 因此,LK68蛋白,其单克隆或其功能等同物可用于开发有效的抗癌剂,其对于涵盖癌症,类风湿性关节炎,牛皮癣,眼血管生成疾病等的血管生成介导的疾病是非常有效的。

    Variant of C6 &bgr;-chemokine leukotactin-1(shLkn-1) with enhanced biological activity
    10.
    发明授权
    Variant of C6 &bgr;-chemokine leukotactin-1(shLkn-1) with enhanced biological activity 失效
    具有增强的生物活性的C6β趋化因子白细胞生成素-1(shLkn-1)的变体

    公开(公告)号:US06692735B1

    公开(公告)日:2004-02-17

    申请号:US09355193

    申请日:1999-07-21

    IPC分类号: C07K1452

    CPC分类号: C07K14/523 A61K38/00

    摘要: The present invention relates to a variant of Lkn-1(shLkn-1) with enhanced biological activity, which is a truncated form of Lkn-1, a process for preparing a recombinant shLkn-1 by employing expression vector therefor and pharmaceutical application of the said protein. shLkn-1 is generated by missing 26 amino acid residues from the amino terminus of Lkn-1 to contain 66 amino acids. Recombinant shLkn-1 inhibits colony formation and cell proliferation in vivo, which suggests that it can be used as a potential drug for the antibody production, the treatment during HIV-1 infection, the protection of bone marrow stem cells during chemotherapy or radiotherapy, and the inhibition of leukemia.

    摘要翻译: 本发明涉及具有增强的生物活性的Lkn-1(shLkn-1)的变体,其是截短形式的Lkn-1,通过使用其表达载体制备重组shLkn-1的方法和药物应用 说蛋白质。 通过从Lkn-1的氨基末端缺失26个氨基酸残基来产生shLkn-1,以含有66个氨基酸。 重组shLkn-1在体内抑制集落形成和细胞增殖,这表明它可以用作抗体生产的潜在药物,HIV-1感染期间的治疗,化疗或放疗期间对骨髓干细胞的保护,以及 抑制白血病。