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1. 发明申请

WO9617869A3 INTERLEUKIN-6 (IL-6) ANTAGONISTS INTERLEUKIN-6 (IL-6) ANTAGONISTS 审中-公开
标题翻译：白细胞介素-6（IL-6）拮抗剂白细胞介素-6（IL-6）拮抗剂
公开(公告)号：WO9617869A3
公开(公告)日：1996-08-29
申请号：PCT/IT9500208
申请日：1995-12-05
申请人： ANGELETTI P IST RICHERCHE BIO , CILIBERTO GENNARO , TONIATTI CARLO
发明人： CILIBERTO GENNARO , TONIATTI CARLO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P37/00 , C07K7/08 , C07K14/715 , C12P21/02 , C12R1/91
CPC分类号： C07K14/7155 , A61K38/00
摘要： These are antagonists of interleukin-6, characterised in that they consist of soluble forms of the receptor alpha of human IL-6 (shIL-6R alpha ) containing one or more mutation in the gp130 binding interface. In a preferred embodiment, the mutations are present in a position chosen from the group comprising Ala 228, Asn 230, His 280 and Asp 281. These antagonists can be used as agents capable of preventing and treating diseases caused by abnormal IL-6 activity. The figure shows the antagonist activity of the mutant Ala228Asp/Asn 230Asp/His280Ser/Asp281Val in comparison with the agonist properties of wild type shIL-6R alpha . This antagonist can be used for preparation of drugs for the prevention, control and treatment of diseases caused by abnormal IL-6 bioactivity.
摘要翻译：这些是白介素-6的拮抗剂，其特征在于它们由在gp130结合界面中含有一个或多个突变的人IL-6（shIL-6Rα）的受体α的可溶形式组成。在优选的实施方案中，突变存在于选自Ala 228，Asn 230，His 280和Asp 281的位置。这些拮抗剂可用作能够预防和治疗由异常IL-6活性引起的疾病的药剂。该图显示与野生型shIL-6Rα的激动剂性质相比，突变体Ala228Asp / Asn 230Asp / His280Ser / Asp281Val的拮抗剂活性。该拮抗剂可用于制备用于预防，控制和治疗由异常IL-6生物活性引起的疾病的药物。

2. 发明申请

WO2005040212A3 ORTHOGONAL GENE SWITCHES 审中-公开
标题翻译：正交基因切换
公开(公告)号：WO2005040212A3
公开(公告)日：2005-07-28
申请号：PCT/EP2004011683
申请日：2004-10-15
申请人： ANGELETTI P IST RICHERCHE BIO , CILIBERTO GENNARO , DE FRANCESCO RAFFAELE , FATTORI DANIELA , GALLINARI PAOLA , KINZEL OLAF DANIEL , KOCH UWE , MURAGLIA ESTER , TONIATTI CARLO , CORTESE RICCARDO , LAHM ARMIN
发明人： CILIBERTO GENNARO , DE FRANCESCO RAFFAELE , FATTORI DANIELA , GALLINARI PAOLA , KINZEL OLAF DANIEL , KOCH UWE , MURAGLIA ESTER , TONIATTI CARLO , CORTESE RICCARDO , LAHM ARMIN
IPC分类号： C07C45/62 , C07C45/74 , C07C49/747 , C07C49/753 , C07K14/47 , C07K14/705 , C07K14/72 , C12N15/63 , C12N15/10
CPC分类号： C12N15/63 , A61K48/0058 , A61K48/0066 , C07C45/62 , C07C45/74 , C07C49/747 , C07C49/753 , C07K14/4702 , C07K14/4705 , C07K14/70567 , C07K14/72 , C07K2319/715 , C07K2319/80 , C12N15/85 , C12N2830/002 , G01N33/743 , G01N2333/723 , G01N2500/00
摘要： The present invention relates to an orthogonal gene switch for regulating the expression of a desired gene. The gene switch comprises a chimeric transcription factor that does not respond to endogenous ligands, and a ligand that is capable of activating the chimeric transcription factor but not endogenous transcription factors. The present invention also relates to the method of constructing the orthogonal gene switch.
摘要翻译：本发明涉及用于调节所需基因表达的正交基因开关。基因开关包含对内源性配体无反应的嵌合转录因子和能够激活嵌合转录因子而不是内源性转录因子的配体。本发明还涉及构建正交基因开关的方法。

3. 发明专利

JP2001354698A METHOD FOR SELECTING ANTAGONIST AND SUPERANTAGONIST OF HUMAN INTERLEUKIN-6 BASED ON RECEPTOR COMPLEX THREE DIMENSIONAL MODELLING 失效
公开(公告)号：JP2001354698A
公开(公告)日：2001-12-25
申请号：JP2001125516
申请日：2001-04-24
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , SAVINO ROCCO , LAHM ARMIN , TONIATTI CARLO
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
摘要： PROBLEM TO BE SOLVED: To isolate a variety (superagonist or superantagonist) having a large affinity for a specific receptor by forming a filamentous phage library as a wild type hormon. SOLUTION: Provides is 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 the hormone; and on the basis of the above comparison, formulating a three dimensional model of the above 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 invention also provides the use of superantagonists as low dose inhibitors of the growth of human myeloma cells dependent on wild type interleukin-6.

4. 发明申请

WO0198506A3 Methods and means for regulation of gene expression 审中-公开
标题翻译：调控基因表达的方法和手段
公开(公告)号：WO0198506A3
公开(公告)日：2002-04-25
申请号：PCT/EP0106792
申请日：2001-06-15
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： TONIATTI CARLO , CILIBERTO GENNARO , CORTESE RICCARDO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P35/00 , C07K14/47 , C07K14/72 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/85 , C12P21/02 , C12N15/62 , C12N15/67
CPC分类号： A61K48/00 , C07K14/4702 , C12N15/85 , C12N2830/001 , C12N2830/15 , C12N2830/85
摘要： A transcription factor, which is a transcriptional activator or a transcriptional repressor, comprising a DNA-binding domain and a transcriptional activator or repressor domain, and optionally a regulatory domain for ligand-dependent DNA binding and/or transcriptional activation or repression by the transcription factor, wherein the transcription factor is chimeric, comprising a HNF1 polypeptide DNA-binding domain and a transcriptional activator or repressor domain of a different polypeptide, with the proviso that where the transcription factor is a transcriptional activator comprising a transcriptional activator domain the transcription factor does not comprise a regulatory domain which binds AcylHSL or an analogue thereof whereby upon AcylHSL binding DNA binding function of the DNA-binding domain is activated. A transcriptional activator comprises a human HNF1 polypeptide DNA-binding domain, a human estrogen receptor alpha regulatory domain containing a G521R mutation, and a human p65 activation domain.

5. 发明专利

CA2413468A1 METHODS AND MEANS FOR REGULATION OF GENE EXPRESSION 未知
公开(公告)号：CA2413468A1
公开(公告)日：2001-12-27
申请号：CA2413468
申请日：2001-06-15
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CORTESE RICCARDO , TONIATTI CARLO , CILIBERTO GENNARO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P35/00 , C07K14/47 , C07K14/72 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/85 , C12P21/02 , C12N15/62 , C12N15/67
摘要： A transcription factor, which is a transcriptional activator or a transcriptional repressor, comprising a DNA-binding domain and a transcriptional activator or repressor domain, and optionally a regulatory domain for ligand-dependent DNA binding and/or transcriptional activation or repression by the transcription factor, wherein the transcription factor is chimeric, comprising a HNF1 polypeptide DNA-binding domain and a transcriptional activator or repressor domain of a different polypeptide, wi th the proviso that where the transcription factor is a transcriptional activat or comprising a transcriptional activator domain the transcription factor does not comprise a regulatory domain which binds AcylHSL or an analogue thereof whereby upon AcylHSL binding DNA binding function of the DNA-binding domain is activated. A transcriptional activator comprises a human HNF1 polypeptide DN A- binding domain, a human estrogen receptor alpha regulatory domain containing a G521R mutation, and a human p65 activation domain.

6. 发明专利

CA2177838A1 A METHODOLOGY FOR SELECTING SUPERAGONISTS, ANTAGONISTS AND SUPERANTAGONISTS OF HUMAN INTERLEUKIN-6 BASED ON RECEPTOR COMPLEX THREE DIMENSIONAL MODELLING 未知
公开(公告)号：CA2177838A1
公开(公告)日：1996-06-15
申请号：CA2177838
申请日：1995-12-13
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , SAVINO ROCCO , LAHM ARMIN , TONIATTI CARLO
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 , C12N5/08 , A61K38/20
摘要： It is known that the ligands of the group of cytokincs 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. (Figure 1)

7. 发明专利

ITRM940794D0 未知
公开(公告)号：ITRM940794D0
公开(公告)日：1994-12-06
申请号：ITRM940794
申请日：1994-12-06
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , TONIATTI CARLO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P37/00 , C07K7/08 , C07K14/715 , C12P21/02 , C12R1/91

8. 发明专利

IT1274350B 未知
公开(公告)号：IT1274350B
公开(公告)日：1997-07-17
申请号：ITRM940794
申请日：1994-12-06
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , TONIATTI CARLO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P37/00 , C07K7/08 , C07K14/715 , C12P21/02 , C12R1/91 , C12K

9. 发明专利

AU4186696A Interleukin-6 (il-6) antagonists 未知
公开(公告)号：AU4186696A
公开(公告)日：1996-06-26
申请号：AU4186696
申请日：1995-12-05
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , TONIATTI CARLO
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , A61P37/00 , C07K7/08 , C07K14/715 , C12P21/02 , C12R1/91

10. 发明专利

ITRM940805A1 未知
公开(公告)号：ITRM940805A1
公开(公告)日：1996-06-14
申请号：ITRM940805
申请日：1994-12-14
申请人： ANGELETTI P IST RICHERCHE BIO
发明人： CILIBERTO GENNARO , SAVINO ROCCO , LAHM ARMIN , TONIATTI CARLO
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
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.

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