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1. 发明申请

WO2008138131A4 BONE TARGETED ALKALINE PHOSPHATASE, KITS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2008138131A4
公开(公告)日：2008-11-20
申请号：PCT/CA2008/000923
申请日：2008-05-12
申请人： ENOBIA PHARMA INC. , CRINE, Philippe , BOILEAU, Guy , LOISEL, Thomas, P. , LEMIRE, Isabelle , LEONARD, Pierre , HEFT, Robert , LANDY, Hal
发明人： CRINE, Philippe , BOILEAU, Guy , LOISEL, Thomas, P. , LEMIRE, Isabelle , LEONARD, Pierre , HEFT, Robert , LANDY, Hal
IPC分类号： C12N15/55 , A61K38/46 , A61P19/08 , C12N15/85 , C12N5/10 , C12N9/16
摘要： A bone targeted alkaline phosphatase comprising a polypeptide having the structure : Z-sALP-Y-spacer-X-W n -V, wherein sALP is the extracellular domain of the alkaline phosphatase; wherein V is absent or is an amino acid sequence of at least one amino acid; X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and W n is a polyaspartate or a polyglutamate wherein n = 10 to 16. Kits and methods of use thereof.

2. 发明申请

WO2005103263A1 BONE DELIVERY CONJUGATES AND METHOD OF USING SAME TO TARGET PROTEINS TO BONE 审中-公开
标题翻译：骨递送缀合物及使用该方法将蛋白质靶向骨骼的方法
公开(公告)号：WO2005103263A1
公开(公告)日：2005-11-03
申请号：PCT/CA2005/000615
申请日：2005-04-21
申请人： ENOBIA PHARMA INC. , CRINE, Philippe , BOILEAU, Guy , LEMIRE, Isabelle , LOISEL, Thomas, P.
发明人： CRINE, Philippe , BOILEAU, Guy , LEMIRE, Isabelle , LOISEL, Thomas, P.
IPC分类号： C12N15/57
CPC分类号： C07K7/06 , A61K38/00 , A61K47/645 , C07K14/51 , C07K2319/01 , C07K2319/23 , C12N9/16 , C12N9/6421 , C12N9/6494 , C12Y301/03001 , C12Y304/24011
摘要： A bone delivery conjugate having a structure selected from the group consisting of :A) X-D n -Y-protein-Z; and B) Z-protein-Y- D n -X, wherein X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and D n is a poly aspartate wherein n = 10 to 16. Compositions comprising same and uses thereof.
摘要翻译：具有选自以下的结构的骨递送缀合物：A）X-D n -Y蛋白-Z; 和B）Z-蛋白-Y-D n -X，其中X不存在或是至少一个氨基酸的氨基酸序列; Y不存在或是至少一个氨基酸的氨基酸序列; Z不存在或是至少一个氨基酸的氨基酸序列; 并且D n是聚天冬氨酸，其中n = 10至16.包含其的组合物及其用途。

3. 发明申请

WO2004050620A2 DERIVATIVES OF SUCCINIC AND GLUTARIC ACIDS AND ANALOGS THEREOF USEFUL AS INHIBITORS OF PHEX 审中-公开
标题翻译：化合物和葡萄糖的衍生物及其类似物作为PHEX的抑制剂有用
公开(公告)号：WO2004050620A2
公开(公告)日：2004-06-17
申请号：PCT/CA2003/001893
申请日：2003-12-03
申请人： BIOMEP INC. , GRAVEL, Denis , RATEMI, Elaref, S. , HATAM, Mostafa , BOILEAU, Guy , CRINE, Philippe , LEMIRE, Isabelle
发明人： GRAVEL, Denis , RATEMI, Elaref, S. , HATAM, Mostafa , BOILEAU, Guy , CRINE, Philippe , LEMIRE, Isabelle
IPC分类号： C07D209/00
CPC分类号： C07K5/0819 , C07C233/05 , C07C259/06 , C07D209/16 , C07D209/20 , C07D213/40 , C07F9/4006 , C07F9/5728 , C07F9/653 , C07K5/06104 , C07K5/06113 , C07K5/06191
摘要： The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula (I), useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.
摘要翻译：本发明涉及具有以下通式（I）的琥珀酸和戊二酸及其类似物的衍生物，其可用作PHEX的抑制剂。这些衍生物可用于促进骨量的产生和治疗或预防与磷酸盐代谢缺陷相关的疾病或病症。还公开了制备方法和中间体。

4. 发明授权

EP1311691B1 METHOD AND COMPOSITIONS FOR PROMOTING OSTEOGENESIS 有权
标题翻译：方法和组合物中促进骨生成
公开(公告)号：EP1311691B1
公开(公告)日：2006-10-04
申请号：EP01966885.4
申请日：2001-08-23
申请人： Enobia Pharma Inc.
发明人： BOILEAU, Guy
IPC分类号： C12N15/57 , C12N15/62 , C12N9/64 , C07K16/18 , G01N33/68 , A61K38/48 , A61P19/10
CPC分类号： C12Y304/24011 , A61K38/00 , C12N9/6494 , G01N33/6893 , G01N2800/10 , G01N2800/108
摘要： The object of the present invention is to increase PHEX activity to improve the osteogenic process in a mammal where this process has been diminished due to pathology or a condition that require osteogenesis. Osteocalcin is an endogenous inhibitor of the PHEX activity. Therefore, the identification of a substance capable of potentiating PHEX activity by preventing the inhibitory action of endogenous inhibitors will improve osteogenesis. Since PHEX is generally associated with the growth plane of bone or teeth and the absence of osteocalcin is associated with increased bone mass, potentiation of PHEX activity can promote bone growth. Increased PHEX activity can also be obtained by administration of the enzyme itself.

5. 发明授权

EP2158319B1 BONE TARGETED ALKALINE PHOSPHATASE, KITS AND METHODS OF USE THEREOF 有权转让
标题翻译：对骨有针对性的碱性磷酸酶试剂盒和其使用方法
公开(公告)号：EP2158319B1
公开(公告)日：2011-12-07
申请号：EP08757088.3
申请日：2008-05-12
申请人： Enobia Pharma Inc.
发明人： CRINE, Philippe , BOILEAU, Guy , LOISEL, Thomas, P. , LEMIRE, Isabelle , LEONARD, Pierre , HEFT, Robert , LANDY, Hal
IPC分类号： C12N15/55 , A61K38/46 , A61P19/08 , C12N15/85 , C12N5/10 , C12N9/16
CPC分类号： C12N9/16 , A61K38/00 , C07K2319/33 , C12N2799/025 , C12Y301/03001
摘要： A bone targeted alkaline phosphatase comprising a polypeptide having the structure : Z-sALP-Y-spacer-X-Wn-V, wherein sALP is the extracellular domain of the alkaline phosphatase; wherein V is absent or is an amino acid sequence of at least one amino acid; X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and Wn is a polyaspartate or a polyglutamate wherein n = 10 to 16. Kits and methods of use thereof.

6. 发明申请

WO2004085465A1 PHEX SUBSTRATES AND METHODS USING SAME 审中-公开
标题翻译： PHEX基板及其使用方法
公开(公告)号：WO2004085465A1
公开(公告)日：2004-10-07
申请号：PCT/CA2004/000453
申请日：2004-03-25
申请人： BIOMEP INC. , BOILEAU, Guy , CARMONA, Adriana, Karaoglanovic , CAMPOS, Marcelo , JULIANO, Maria, Aparecida , JULIANO, Luiz
发明人： BOILEAU, Guy , CARMONA, Adriana, Karaoglanovic , CAMPOS, Marcelo , JULIANO, Maria, Aparecida , JULIANO, Luiz
IPC分类号： C07K7/00
CPC分类号： C07K7/06 , C07K5/1016 , C07K5/1019 , C07K7/08 , C07K2319/60 , C12Q1/37 , G01N33/542 , G01N2500/00
摘要： A fluorogenic PHEX substrate comprising a peptide unit; a fluorophore unit capable of conferring fluorescence on said substrate attached to an amino acid residue at a first end of the peptide unit; and a quencher unit capable of providing intramolecular quenching of said fluorescence attached to an amino acid residue at a second end of the peptide unit; the peptide unit having at least 6 amino acids residues including a sequence P 2 -P l -P 1' -P 2' of 4 amino acid residues at positions P 2 , P 1 , P l' and P 2' of the peptide unit, respectively; the amino acid residue at position P 2 being any amino acid residue; the amino acid residue at position P, being any amino acid residue except an isoleucine, a valine, or a histidine residue; the amino acid residue at position P 1' being an acidic amino acid residue selected from the group consisting of a glutamic acid residue and an aspartic acid residue, and being located at least 2 amino acid residues distal to both the fluorophore and the quencher units; the amino acid residue at position P 2' being any amino acid residue except a leucine, a proline or a glycine residue, with the proviso that said peptide unit does not have the sequence as set forth in SEQ ID NO:1. Methods of using the peptide sequence unit to identify PHEX modulators and for detecting PHEX in a sample.
摘要翻译：含有肽单元的含氟PHEX底物; 能够赋予附着在肽单元的第一末端的氨基酸残基的所述底物上的荧光的荧光团单元; 以及猝灭单元，其能够提供附着于所述肽单元的第二末端的氨基酸残基的所述荧光的分子内猝灭; 肽单元具有至少6个氨基酸残基，分别包含肽单元的P2，P1，P1'和P2'的4个氨基酸残基的序列P2-P1-P1'-P2'; 位置P2处的氨基酸残基是任何氨基酸残基; 位置P处的氨基酸残基是除异亮氨酸，缬氨酸或组氨酸残基之外的任何氨基酸残基; 位置P1'处的氨基酸残基是选自谷氨酸残基和天冬氨酸残基的酸性氨基酸残基，并且位于远离荧光团和猝灭单元的至少2个氨基酸残基; 该位置P2'处的氨基酸残基是除亮氨酸，脯氨酸或甘氨酸残基之外的任何氨基酸残基，条件是所述肽单元不具有如SEQ ID NO：1所示的序列。使用肽序列单元识别PHEX调节剂并检测样品中的PHEX的方法。

7. 发明公开

EP2158319A1 BONE TARGETED ALKALINE PHOSPHATASE, KITS AND METHODS OF USE THEREOF 有权转让
标题翻译：对骨有针对性的碱性磷酸酶试剂盒和其使用方法
公开(公告)号：EP2158319A1
公开(公告)日：2010-03-03
申请号：EP08757088.3
申请日：2008-05-12
申请人： Enobia Pharma Inc.
发明人： CRINE, Philippe , BOILEAU, Guy , LOISEL, Thomas, P. , LEMIRE, Isabelle , LEONARD, Pierre , HEFT, Robert , LANDY, Hal
IPC分类号： C12N15/55 , A61K38/46 , A61P19/08 , C12N15/85 , C12N5/10 , C12N9/16
CPC分类号： C12N9/16 , A61K38/00 , C07K2319/33 , C12N2799/025 , C12Y301/03001
摘要： A bone targeted alkaline phosphatase comprising a polypeptide having the structure : Z-sALP-Y-spacer-X-Wn-V, wherein sALP is the extracellular domain of the alkaline phosphatase; wherein V is absent or is an amino acid sequence of at least one amino acid; X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and Wn is a polyaspartate or a polyglutamate wherein n = 10 to 16. Kits and methods of use thereof.

8. 发明公开

EP1572645A2 DERIVATIVES OF SUCCINIC AND GLUTARIC ACIDS AND ANALOGS THEREOF USEFUL AS INHIBITORS OF PHEX 审中-公开
标题翻译：琥珀酸酐和戊二衍生物和模拟AS PHEX抑制剂
公开(公告)号：EP1572645A2
公开(公告)日：2005-09-14
申请号：EP03767325.8
申请日：2003-12-03
申请人： Enobia Pharma Inc.
发明人： GRAVEL, Denis , RATEMI, Elaref, S. , HATAM, Mostafa , BOILEAU, Guy , CRINE, Philippe , LEMIRE, Isabelle
IPC分类号： C07D209/00
CPC分类号： C07K5/0819 , C07C233/05 , C07C259/06 , C07D209/16 , C07D209/20 , C07D213/40 , C07F9/4006 , C07F9/5728 , C07F9/653 , C07K5/06104 , C07K5/06113 , C07K5/06191
摘要： The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula (I), useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.

9. 发明授权

EP1759001B1 BONE DELIVERY CONJUGATES AND METHOD OF USING SAME TO TARGET PROTEINS TO BONE 有权转让
标题翻译：共轭物喂养骨和方法中所使用的铅蛋白在骨
公开(公告)号：EP1759001B1
公开(公告)日：2011-04-13
申请号：EP05739065.0
申请日：2005-04-21
申请人： Enobia Pharma Inc.
发明人： CRINE, Philippe , BOILEAU, Guy , LEMIRE, Isabelle , LOISEL, Thomas, P.
IPC分类号： C12N15/62 , A61K38/46 , A61K47/48 , A61P19/08 , C12N9/16
CPC分类号： C07K7/06 , A61K38/00 , A61K47/645 , C07K14/51 , C07K2319/01 , C07K2319/23 , C12N9/16 , C12N9/6421 , C12N9/6494 , C12Y301/03001 , C12Y304/24011
摘要： A bone delivery conjugate having a structure selected from the group consisting of :A) X-D n -Y-protein-Z; and B) Z-protein-Y- D n -X, wherein X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and D n is a poly aspartate wherein n = 10 to 16. Compositions comprising same and uses thereof.

10. 发明公开

EP1759001A1 BONE DELIVERY CONJUGATES AND METHOD OF USING SAME TO TARGET PROTEINS TO BONE 有权转让
标题翻译：共轭物喂养骨和方法中所使用的铅蛋白在骨
公开(公告)号：EP1759001A1
公开(公告)日：2007-03-07
申请号：EP05739065.0
申请日：2005-04-21
申请人： Enobia Pharma Inc.
发明人： CRINE, Philippe , BOILEAU, Guy , LEMIRE, Isabelle , LOISEL, Thomas, P.
IPC分类号： C12N15/57 , A61K38/46 , A61K38/48 , A61K47/48 , C12N15/55 , C12N9/50 , C12N9/14 , A61P19/08 , G01N33/68
CPC分类号： C07K7/06 , A61K38/00 , A61K47/645 , C07K14/51 , C07K2319/01 , C07K2319/23 , C12N9/16 , C12N9/6421 , C12N9/6494 , C12Y301/03001 , C12Y304/24011
摘要： A bone delivery conjugate having a structure selected from the group consisting of :A) X-D n -Y-protein-Z; and B) Z-protein-Y- D n -X, wherein X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and D n is a poly aspartate wherein n = 10 to 16. Compositions comprising same and uses thereof.

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