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1. 发明授权

US06475755B2 Adenoviral vectors for mutants of human interleukin 6 (hIL-6) with hIL-6 antagonist activity, pharmaceutical compositions therewith and their uses 失效
标题翻译：具有hIL-6拮抗剂活性的人白介素6（hIL-6）突变体的腺病毒载体及其用途及其用途
公开(公告)号：US06475755B2
公开(公告)日：2002-11-05
申请号：US09147948
申请日：1999-06-30
申请人： Gennaro Ciliberto , Isabella Saggio , Rocco Savino , Michel Perricaudet
发明人： Gennaro Ciliberto , Isabella Saggio , Rocco Savino , Michel Perricaudet
IPC分类号： C12P2106
CPC分类号： A61K38/204 , C07K14/5412 , C12N2799/022
摘要： The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.
摘要翻译：本发明的主题是重组缺陷性腺病毒，其包含编码具有人白细胞介素6（hIL-6）拮抗剂或超吸附剂活性的突变蛋白的异源DNA序列。此外，本发明涉及其治疗用途，特别是用于制备用于治疗和/或预防由hIL-6过量产生引起的病理学的药物组合物。

2. 发明授权

US06641807B1 Adenoviral vectors encoding erythropoietin and their use in gene therapy 失效
标题翻译：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
申请人： Rocco Savino , Gennaro Ciliberto , Nicola La Monica
发明人： Rocco Savino , Gennaro Ciliberto , Nicola La Monica
IPC分类号： A01N6300
CPC分类号： A61K38/1816 , A61K48/00 , C07K14/505 , C12N2799/022
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）。

3. 发明授权

US06706261B1 Compositions and methods comprising immunogenic muteins of interleukin-6 失效
标题翻译：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
申请人： Gennaro Ciliberto , Rocco Savino , Riccardo Cortese
发明人： Gennaro Ciliberto , Rocco Savino , Riccardo Cortese
IPC分类号： C07K1454
CPC分类号： A61K39/0008 , A61K2039/55505
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。

4. 发明授权

US5891998A Interleukin-6 receptor agonists 失效
标题翻译：白细胞介素-6受体激动剂
公开(公告)号：US5891998A
公开(公告)日：1999-04-06
申请号：US567048
申请日：1995-12-04
申请人： Rocco Savino , Armin Lahm , Gennaro Ciliberto
发明人： Rocco Savino , Armin Lahm , Gennaro Ciliberto
IPC分类号： C07K14/475 , C07K14/52 , C07K14/54 , C12N15/24 , G01N33/68 , G01N33/74 , C12N5/10 , C12N15/63
CPC分类号： C07K14/52 , C07K14/475 , C07K14/5412 , G01N33/6863 , G01N33/6869 , G01N33/6872 , G01N33/74 , C07K2319/00 , G01N2500/00 , Y10S930/14
摘要： Disclosed are interleukin-6 receptor agonists. These receptor agonists wereenerated by mutating amino acid positions 175, 176, 177, 181, and/or 183 of human interleukin-6.
摘要翻译：公开了白细胞介素-6受体激动剂。这些受体激动剂是通过突变人白细胞介素-6的氨基酸位置175,176,177,181和/或183产生的。

5. 发明授权

US5914106A Interleukin-6 receptor agonists 失效
标题翻译：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
申请人： Gennaro Ciliberto , Rocco Savino , Armin Lahm , Carlo Toniatti
发明人： Gennaro Ciliberto , Rocco Savino , Armin Lahm , Carlo Toniatti
IPC分类号： C12N15/00 , A61K38/00 , A61K38/16 , A61K48/00 , A61P3/02 , A61P7/06 , A61P19/02 , A61P19/10 , A61P29/00 , A61P35/00 , A61P37/02 , A61P43/00 , C07K14/54 , C12N15/09 , C12N15/24 , C12P21/02 , C12R1/19 , G01N33/68 , A61K38/20 , C12N15/63
CPC分类号： C07K14/5412 , G01N33/6869 , A61K38/00 , Y10S930/141
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。

6. 发明授权

US5681723A Mutant interleukin 6 with improved biological activity over wild interleukin 6 失效
标题翻译：具有改善生物活性的野生型白细胞介素6的突变白细胞介素6
公开(公告)号：US5681723A
公开(公告)日：1997-10-28
申请号：US437680
申请日：1995-05-05
申请人： Gennaro Ciliberto , Rocco Savino
发明人： Gennaro Ciliberto , Rocco Savino
IPC分类号： C12N15/09 , A61K38/00 , C07K14/52 , C07K14/54 , C12N1/21 , C12N15/00 , C12N15/24 , C12P21/02 , C12R1/19 , C12R1/91 , A61K38/20 , C07H21/04
CPC分类号： C07K14/5412 , A61K38/00 , Y10S930/14 , Y10S930/141 , Y10S930/142
摘要： The present invention is drawn to mutant interleukin 6, which has the amino acid arginine in position 176, replacing serine in position 176 with wild-type interleukin 6. The mutant interleukin 6 of the present invention has greater biological activity than the wild-type protein. The present invention is further drawn to methods of making mutant interleukin 6, having arginine at position 176 and methods of using the same.
摘要翻译：本发明涉及突变白细胞介素6，其具有位置176的氨基酸精氨酸，用野生型白介素6代替位置176处的丝氨酸。本发明的突变白细胞介素6具有比野生型蛋白更大的生物活性。本发明还涉及制备在176位具有精氨酸的突变白细胞介素6及其使用方法。

7. 发明授权

US5972902A DNA encoding human IL-6 receptor antagonist and protein encoded thereby 失效
标题翻译：编码人IL-6受体拮抗剂的DNA和由此编码的蛋白质
公开(公告)号：US5972902A
公开(公告)日：1999-10-26
申请号：US945529
申请日：1997-10-28
申请人： Gennaro Ciliberto , Rocco Savino , Giacomo Paonessa
发明人： Gennaro Ciliberto , Rocco Savino , Giacomo Paonessa
IPC分类号： C12N15/02 , A61K38/00 , A61K48/00 , A61P3/02 , A61P19/10 , A61P29/00 , A61P35/00 , A61P37/00 , A61P37/02 , A61P43/00 , C07K14/54 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/24 , C12P21/02 , A61K38/20
CPC分类号： C07K14/5412 , A61K38/00
摘要： The present invention relates to human interleukin-6 receptor antagonists which are incapable of binding to the receptor chain responsible for transduction of the signal associated with interleukin-6, namely, gp130. The present invention also relates to DNA encoding human interleukin-6 receptor antagonists.
摘要翻译： PCT No.PCT / IT96 / 00084 Sec。 371日期1997年10月28日第 102（e）1997年10月28日PCT PCT 1996年4月26日PCT公布。第WO96 / 34104号公报日期：1996年10月31日本发明涉及不能与负责转导与白细胞介素-6相关信号（即gp130）的受体链结合的人白细胞介素-6受体拮抗剂。本发明还涉及编码人白细胞介素-6受体拮抗剂的DNA。

8. 发明授权

US5849283A Human interleukin-6 receptor antagonists 失效
标题翻译：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
申请人： Gennaro Ciliberto , Rocco Savino , Armin Lahm , Carlo Toniatti
发明人： Gennaro Ciliberto , Rocco Savino , Armin Lahm , Carlo Toniatti
IPC分类号： C12N15/00 , A61K38/00 , A61K38/16 , A61K48/00 , A61P3/02 , A61P7/06 , A61P19/02 , A61P19/10 , A61P29/00 , A61P35/00 , A61P37/02 , A61P43/00 , C07K14/54 , C12N15/09 , C12N15/24 , C12P21/02 , C12R1/19 , G01N33/68 , A61K38/19
CPC分类号： C07K14/5412 , G01N33/6869 , A61K38/00 , Y10S930/141
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）

9. 发明授权

US5789552A Interleukin-6 receptor antagonists 失效
标题翻译：白细胞介素-6受体拮抗剂
公开(公告)号：US5789552A
公开(公告)日：1998-08-04
申请号：US567047
申请日：1995-12-04
申请人： Rocco Savino , Armin Lahm , Gennaro Cillberto
发明人： Rocco Savino , Armin Lahm , Gennaro Cillberto
IPC分类号： C07K14/475 , C07K14/52 , C07K14/54 , C12N15/24 , G01N33/68 , G01N33/74 , C12N5/10 , C12N15/63
CPC分类号： C07K14/52 , C07K14/475 , C07K14/5412 , G01N33/6863 , G01N33/6869 , G01N33/6872 , G01N33/74 , C07K2319/00 , G01N2500/00 , Y10S930/14
摘要： Disclosed are interleukin-6 receptor antagonists. These receptor antagonists are generated by mutating amino acid positions 31, 35, 118, 121, 175, 176 and/or 183 of human interleukin-6.
摘要翻译：公开了白细胞介素-6受体拮抗剂。这些受体拮抗剂是通过突变人白介素-6的氨基酸位置31,35,118,121,175,176和/或183产生的。

10. 发明申请

US20070104685A1 Synthetic gene encoding human carcinoembryonic antigen and uses thereof 审中-公开
标题翻译：编码人癌胚抗原的合成基因及其用途
公开(公告)号：US20070104685A1
公开(公告)日：2007-05-10
申请号：US10555744
申请日：2004-05-03
申请人： Nicola La Monica , Armin Lahm , Carmela Mennuni , Rocco Savino
发明人： Nicola La Monica , Armin Lahm , Carmela Mennuni , Rocco Savino
IPC分类号： A61K48/00 , C12Q1/68 , C07H21/04 , C12P21/06 , C12N15/861 , C07K14/82
CPC分类号： C07K14/4748 , A61K39/00 , A61K2039/53 , C07K14/70503 , C12N2799/022
摘要： Synthetic polynucleotides encoding human carcinoembryonic antigen (CEA) are provided, the synthetic polynucleotides being codon-optimized for expression in a human cellular environment. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying codon-optimed human CEA and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：提供了编码人癌胚抗原（CEA）的合成多核苷酸，所述合成多核苷酸被密码子优化用于在人细胞环境中表达。编码CEA的基因通常与人类癌的发展有关。本发明提供了引发或增强由CEA肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常CEA表达与癌症或其发展相关。本发明具体提供携带密码子优化的人CEA的腺病毒载体和质粒构建体，并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。

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