Compositions and methods comprising immunogenic muteins of interleukin-6
    1.
    发明授权
    Compositions and methods comprising immunogenic muteins of interleukin-6 失效
    包含白介素-6的免疫原性突变蛋白的组合物和方法

    公开(公告)号:US06706261B1

    公开(公告)日:2004-03-16

    申请号:US09559950

    申请日:2000-04-27

    IPC分类号: C07K1454

    摘要: Cytokines, including muteins thereof, which are biologically inactive in humans but remain immunogenic, are used in pharmaceutical compositions to promote a neutralizing immune response against native cytokines when administered to a subject in need thereof to treat homeostatic disorders and disorders associated with an overproduction of cytokines.

    摘要翻译: 在药物组合物中使用细胞因子,包括其在人体中具有生物学活性但保持免疫原性的突变蛋白,以在施用于有需要的受试者时治疗对于天然细胞因子的中和免疫应答,以治疗与细胞因子过量产生相关的体内平衡疾病和病症 。

    Adenoviral vectors encoding erythropoietin and their use in gene therapy
    2.
    发明授权
    Adenoviral vectors encoding erythropoietin and their use in gene therapy 失效
    编码促红细胞生成素的腺病毒载体及其在基因治疗中的应用

    公开(公告)号:US06641807B1

    公开(公告)日:2003-11-04

    申请号:US09762668

    申请日:2001-04-23

    IPC分类号: A01N6300

    摘要: Helper dependent adenoviral vectors encoding erythropoietin (epo) provide high levels of epo to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients with disorders such as anaemia of Chronic Renal Failure (CFR), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA).

    摘要翻译: 编码促红细胞生成素(epo)的辅助依赖性腺病毒载体提供高水平的epo以实现长期治疗有效剂量,并且允许对患有慢性肾功能衰竭(CFR)的贫血,由于β-地中海贫血造成的贫血的疾病患者重复施用 ,和镰状细胞性贫血(SCA)。

    Interleukin-6 receptor agonists
    5.
    发明授权
    Interleukin-6 receptor agonists 失效
    白细胞介素-6受体激动剂

    公开(公告)号:US5914106A

    公开(公告)日:1999-06-22

    申请号:US8482

    申请日:1998-01-16

    摘要: It is known that the ligands of the group of cytokines similar to Interleuk 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce the formation of a receptor complex of which the membrane molecule gp 130 is a part. The present invention refers to a methodology for selecting superagonists, antagonists and superantagonists of human interleukin-6 comprising the following operations: comparing the amino acid sequence of bovine granulocyte colony stimulating factor (bG-CSF) with the sequence of said hormone; and on the basis of the above comparison, formulating a three dimensional model of said hormone, which allows the identification of residues that form the site of interaction with the specific receptor (Site 1) and those that constitute the site of interaction with gp 130 (Site 2) respectively. The invention allows the identification of these sites in human interleukin-6 and the isolation of variants having, with respect to the wild type hormone, a greater affinity for the specific receptor (superagonists and superantagonists) or affinity for gp 130 reduced or abolished (antagonists and superantagonists). A scheme illustrating the methodology applied to identify site 1 and site 2 in the case of human interleukin-6 is disclosed. The invention also describes the obtaining of specific superagonists and superantagonists of interleukin-6 and the use of superantagonists as low dose inhibitors of the growth of human myeloma cells dependent on wild type interleukin-6.

    摘要翻译: 众所周知,与Interleuk 6(IL-6)相似的细胞因子组,即制瘤素M(OSM),白血病抑制因子(LIF),睫状神经营养因子(CNTF)和白介素11(IL-11) 诱导膜分子gp 130为其一部分的受体复合物的形成。 本发明涉及一种用于选择人白细胞介素-6的超级拮抗剂,拮抗剂和超吸收剂的方法,包括以下操作:将牛粒细胞集落刺激因子(bG-CSF)的氨基酸序列与所述激素的序列进行比较; 并且基于上述比较,制定所述激素的三维模型,其允许鉴定形成与特异性受体(位点1)相互作用的位点的残基和构成与gp 130相互作用的位点( 站点2)。 本发明允许在人白细胞介素-6中鉴定这些位点,并且相对于野生型激素的变体的分离对特异性受体(超级拮抗剂和超吸收剂)具有更大的亲和力或对gp 130的亲和力降低或消除(拮抗剂 和超级玩家)。 公开了在人白细胞介素-6的情况下应用于鉴定位点1和位点2的方法的方案。 本发明还描述了获得白细胞介素-6的特定的超级拮抗剂和超吸收剂以及使用超吸收剂作为依赖于野生型白细胞介素-6的人骨髓瘤细胞生长的低剂量抑制剂。

    Human interleukin-6 receptor antagonists
    9.
    发明授权
    Human interleukin-6 receptor antagonists 失效
    人白细胞介素-6受体拮抗剂

    公开(公告)号:US5849283A

    公开(公告)日:1998-12-15

    申请号:US693182

    申请日:1996-08-14

    摘要: It is known that the ligands of the group of cytokines similar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce the formation of a receptor complex of which the membrane molecule gp 130 is a part. The present invention refers to a methodology for selecting superagonists, antagonists and superantagonists of human interleukin-6 comprising the following operations: comparing the amino acid sequence of bovine granulocyte colony stimulating factor (bG-CSF) with the sequence of said hormone; and on the basis of the above comparison, formulating a three dimensional model of said hormone, which allows the identification of residues that form the site of interaction with the specific receptor (Site 1) and those that constitute the site of interaction with gp 130 (Site 2) respectively. The invention allows the identification of these sites in human interleukin-6 and the isolation of variants having, with respect to the wild type hormone, a greater affinity for the specific receptor (superagonists and superantagonists) or affinity for gp 130 reduced or abolished (antagonists and superantagonists). The figure shows a scheme illustrating the methodology applied to identify site 1 and site 2 in the case of human interleukin-6. The invention also describes the obtaining of specific superagonists and superantagonists of interleukin-6 and the use of superantagonists as low dose inhibitors of the growth of human myeloma cells dependent on wild type interleukin-6. (FIG. 1)

    摘要翻译: PCT No.PCT / IT95 / 00216 Sec。 371日期:1996年8月14日 102(e)日期1996年8月14日PCT提交1995年12月13日PCT公布。 公开号WO96 / 18648 日期:1996年6月20日已知与制巢碱M(OSM),白血病抑制因子(LIF),睫状神经营养因子(CNTF)和白介素11(IL-6)相似的细胞因子组的配体是已知的 (IL-11)诱导膜分子gp 130为其一部分的受体复合物的形成。 本发明涉及一种用于选择人白细胞介素-6的超级拮抗剂,拮抗剂和超吸收剂的方法,包括以下操作:将牛粒细胞集落刺激因子(bG-CSF)的氨基酸序列与所述激素的序列进行比较; 并且基于上述比较,制定所述激素的三维模型,其允许鉴定形成与特异性受体(位点1)相互作用的位点的残基和构成与gp 130相互作用的位点( 站点2)。 本发明允许在人白细胞介素-6中鉴定这些位点,并且相对于野生型激素的变体的分离对特异性受体(超级拮抗剂和超吸收剂)具有更大的亲和力或对gp 130的亲和力降低或消除(拮抗剂 和超级玩家)。 该图示出了说明在人白细胞介素-6的情况下应用于鉴定位点1和位点2的方法的方案。 本发明还描述了获得白细胞介素-6的特定的超级拮抗剂和超吸收剂以及使用超吸收剂作为依赖于野生型白细胞介素-6的人骨髓瘤细胞生长的低剂量抑制剂。 (图。1)