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1. 发明申请

WO0047750B1 METALLOPROTEASES OF THE NEPRILYSIN FAMILY 审中-公开
标题翻译： NEPRILYSIN家族的金属蛋白质
公开(公告)号：WO0047750B1
公开(公告)日：2001-05-25
申请号：PCT/CA0000147
申请日：2000-02-11
申请人： UNIVERSTIE DE MONTREAL , DESGROSEILLERS LUC , BOILEAU GUY
发明人： DESGROSEILLERS LUC , BOILEAU GUY
IPC分类号： G01N33/53 , C07K16/40 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12N15/09 , C12N15/57 , C12Q1/68 , G01N33/566 , G01N33/573 , C12N15/62 , C12N15/85
CPC分类号： C12N9/6489 , C07K2319/02
摘要： In this paper, we describe RT-PCR strategies that allowed us to identify and clone members of the NEP-like family. Degenerate oligoncleotide primers corresponding to consensus sequences located on either side of the HEXXH consensus sequence for zincins were designed and used in RT-PCR with mouse and human testis cDNAs. DNA fragments with lengths expected from the sequence of this class of enzympes were obtained. These DNA fragments were cloned and sequenced. Using this PCR strategy and the PCR fragments as probes to screen cDNA libraries, three zincin-like peptidases were identified in addition of known members of the family. The cDNA sequences allowed to derive specific probes for Northern and in situ hybridization, and probe human chromosomes to localize the gene and establish potential links to genetic diseases. Furthermore, these cDNA sequences were used to produce recombinant fusion proteins in Escherichia coli in order to raise specific antibodies. Finally, the cDNA sequences were cloned in mammalian expression vectors and transfected in various mammalian cell lines to produce active recombinant enzymes suitable for testing specific inhibitors.
摘要翻译：在本文中，我们描述了RT-PCR策略，使我们能够识别和克隆NEP样家族的成员。设计了与位于HEXXH共有序列两侧的共有序列相对应的用于锌的简并寡核苷酸引物，并用于小鼠和人睾丸cDNA的RT-PCR。获得了从该类酶的序列预期的长度的DNA片段。克隆并测序这些DNA片段。使用该PCR策略和PCR片段作为筛选cDNA文库的探针，鉴定出已知家族成员的三种类似锌的肽酶。 cDNA序列允许导出用于Northern和原位杂交的特异性探针，并探测人染色体来定位基因并建立与遗传疾病的潜在联系。此外，这些cDNA序列用于在大肠杆菌中产生重组融合蛋白以产生特异性抗体。最后，将cDNA序列克隆到哺乳动物表达载体中并转染到各种哺乳动物细胞系中以产生适于测试特异性抑制剂的活性重组酶。

2. 发明申请

WO0047750A3 METALLOPROTEASES OF THE NEPRILYSIN FAMILY 审中-公开
标题翻译： NEPRILYSIN家族的金属蛋白质
公开(公告)号：WO0047750A3
公开(公告)日：2000-11-30
申请号：PCT/CA0000147
申请日：2000-02-11
申请人： UNIVERSTIE DE MONTREAL , DESGROSEILLERS LUC , BOILEAU GUY
发明人： DESGROSEILLERS LUC , BOILEAU GUY
IPC分类号： G01N33/53 , C07K16/40 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12N15/09 , C12N15/57 , C12Q1/68 , G01N33/566 , G01N33/573 , C12N15/62 , C12N15/85
CPC分类号： C12N9/6489 , C07K2319/02
摘要： In this paper, we describe RT-PCR strategies that allowed us to identify and clone members of the NEP-like family. Degenerate oligoncleotide primers corresponding to consensus sequences located on either side of the HEXXH consensus sequence for zincins were designed and used in RT-PCR with mouse and human testis cDNAs. DNA fragments with lengths expected from the sequence of this class of enzympes were obtained. These DNA fragments were cloned and sequenced. Using this PCR strategy and the PCR fragments as probes to screen cDNA libraries, three zincin-like peptidases were identified in addition of known members of the family. The cDNA sequences allowed to derive specific probes for Northern and in situ hybridization, and probe human chromosomes to localize the gene and establish potential links to genetic diseases. Furthermore, these cDNA sequences were used to produce recombinant fusion proteins in Escherichia coli in order to raise specific antibodies. Finally, the cDNA sequences were cloned in mammalian expression vectors and transfected in various mammalian cell lines to produce active recombinant enzymes suitable for testing specific inhibitors.
摘要翻译：在本文中，我们描述了RT-PCR策略，使我们能够识别和克隆NEP样家族的成员。设计了与位于HEXXH共有序列两侧的共有序列相对应的用于锌的简并寡核苷酸引物，并用于小鼠和人睾丸cDNA的RT-PCR。获得了从该类酶的序列预期的长度的DNA片段。克隆并测序这些DNA片段。使用该PCR策略和PCR片段作为筛选cDNA文库的探针，鉴定出已知家族成员的三种类似锌的肽酶。 cDNA序列允许导出用于Northern和原位杂交的特异性探针，并探测人染色体来定位基因并建立与遗传疾病的潜在联系。此外，这些cDNA序列用于在大肠杆菌中产生重组融合蛋白以产生特异性抗体。最后，将cDNA序列克隆到哺乳动物表达载体中并转染到各种哺乳动物细胞系中以产生适于测试特异性抑制剂的活性重组酶。

3. 发明专利

AU2653400A New metalloproteases of the neprilysin family 未知
公开(公告)号：AU2653400A
公开(公告)日：2000-08-29
申请号：AU2653400
申请日：2000-02-11
申请人： UNIVERSTIE DE MONTREAL
发明人： DESGROSEILLERS LUC , BOILEAU GUY
IPC分类号： G01N33/53 , C07K16/40 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12N15/09 , C12N15/57 , C12Q1/68 , G01N33/566 , G01N33/573 , C12N15/85 , C12N15/62
摘要： In this paper, we describe RT-PCR strategies that allowed us to identify and clone members of the NEP-like family. Degenerate oligoncleotide primers corresponding to consensus sequences located on either side of the HEXXH consensus sequence for zincins were designed and used in RT-PCR with mouse and human testis cDNAs. DNA fragments with lengths expected from the sequence of this class of enzympes were obtained. These DNA fragments were cloned and sequenced. Using this PCR strategy and the PCR fragments as probes to screen cDNA libraries, three zincin-like peptidases were identified in addition of known members of the family. The cDNA sequences allowed to derive specific probes for Northern and in situ hybridization, and probe human chromosomes to localize the gene and establish potential links to genetic diseases. Furthermore, these cDNA sequences were used to produce recombinant fusion proteins in Escherichia coli in order to raise specific antibodies. Finally, the cDNA sequences were cloned in mammalian expression vectors and transfected in various mammalian cell lines to produce active recombinant enzymes suitable for testing specific inhibitors.

4. 发明申请

WO0215918A3 METHOD AND COMPOSITIONS FOR PROMOTING OSTEOGENESIS 审中-公开
标题翻译：促进卵泡发育的方法和组合物
公开(公告)号：WO0215918A3
公开(公告)日：2002-09-26
申请号：PCT/CA0101220
申请日：2001-08-23
申请人： BIOMEP INC , BOILEAU GUY
发明人： BOILEAU GUY
IPC分类号： G01N33/50 , A61C13/00 , A61C13/08 , A61F2/28 , A61K35/76 , A61K38/43 , A61K38/46 , A61K38/48 , A61K39/395 , A61K45/00 , A61K48/00 , A61L27/00 , A61P1/02 , A61P19/00 , A61P19/08 , A61P19/10 , B01J20/281 , C12N9/64 , C12N15/57 , G01N30/88 , G01N33/15 , C07K16/18 , C12N15/62 , G01N33/68
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.
摘要翻译：本发明的目的是增加PHEX活性以改善哺乳动物的成骨过程，其中该过程由于病理学或需要成骨的病症而减少。骨钙素是PHEX活性的内源性抑制剂。因此，通过防止内源性抑制剂的抑制作用，能够增强PHEX活性的物质的鉴定将改善成骨。由于PHEX通常与骨骼或牙齿的生长平面相关，并且不存在骨钙素与增加的骨量相关，PHEX活性的增强可促进骨生长。还可以通过施用酶本身来获得增加的PHEX活性。

5. 发明申请

WO0050580B1 COMPOSITION, METHODS AND REAGENTS FOR THE SYNTHESIS OF A SOLUBLE FORM OF HUMAN PHEX 审中-公开
标题翻译：用于合成可溶形式人PHEX的组合物，方法和试剂
公开(公告)号：WO0050580B1
公开(公告)日：2001-09-07
申请号：PCT/CA0000201
申请日：2000-02-24
申请人： UNIV MONTREAL , CRINE PHILIPPE , BOILEAU GUY
发明人： CRINE PHILIPPE , BOILEAU GUY
IPC分类号： G01N33/53 , A61K38/00 , A61K38/46 , A61K39/395 , A61K48/00 , A61P3/12 , A61P19/08 , C07K16/40 , C12M1/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12N15/02 , C12N15/09 , C12N15/57 , C12P21/08 , C12Q1/37 , G01N33/577 , A61K38/48
CPC分类号： C12N9/6494 , A61K38/00 , A61K48/00 , C12Y304/24011
摘要： This invention relates to a soluble form of PHEX, PHEX being a type II integral membrane glycoprotein. This enzyme is the gene product of a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. To produce a soluble form of PHEX, the transmembrane anchor domain has been modified to encode a signal peptidase coding sequence. The soluble PHEX therefore comprises the active ectodomain. An inactive mutant of PHEX is also an object of this invention. Both soluble and inactive mutant forms of PHEX can be used to screen ligands to PHEX. These ligands can also be used as substrates or inhibitors of PHEX. PHEX being phosphaturic, an inhibitor thereof will be used to treat phosphaturia and/or hypophosphatemia. On the opposite, a substrate for PHEX or PHEX itself can be used to treat hyperphosphatemia.
摘要翻译：本发明涉及可溶形式的PHEX，PHEX是II型整合膜糖蛋白。该酶是与X染色体上的内肽酶具有同源性的磷酸调节基因的基因产物。为了产生可溶形式的PHEX，跨膜锚定域已被修饰以编码信号肽酶编码序列。因此可溶性PHEX包含活性胞外域。 PHEX的失活突变体也是本发明的一个目的。 PHEX的可溶性和无活性突变体形式均可用于筛选PHEX的配体。这些配体也可以用作PHEX的底物或抑制剂。 PHEX为磷酸盐，其抑制剂将用于治疗磷尿和/或低磷酸盐血症。相反，PHEX或PHEX本身的底物可用于治疗高磷酸盐血症。

6. 发明申请

WO0050580A2 COMPOSITION, METHODS AND REAGENTS FOR THE SYNTHESIS OF A SOLUBLE FORM OF HUMAN PHEX 审中-公开
标题翻译：组合物，合成人参皂苷可溶性形式的方法和试剂
公开(公告)号：WO0050580A2
公开(公告)日：2000-08-31
申请号：PCT/CA0000201
申请日：2000-02-24
申请人： UNIV MONTREAL , CRINE PHILIPPE , BOILEAU GUY
发明人： CRINE PHILIPPE , BOILEAU GUY
IPC分类号： G01N33/53 , A61K38/00 , A61K38/46 , A61K39/395 , A61K48/00 , A61P3/12 , A61P19/08 , C07K16/40 , C12M1/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/48 , C12N9/64 , C12N15/02 , C12N15/09 , C12N15/57 , C12P21/08 , C12Q1/37 , G01N33/577 , A61K38/48
CPC分类号： C12N9/6494 , A61K38/00 , A61K48/00 , C12Y304/24011
摘要： This invention relates to a soluble form of PHEX, PHEX being a type II integral membrane glycoprotein. This enzyme is the gene product of a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. To produce a soluble form of PHEX, the transmembrane anchor domain has been modified to encode a signal peptidase coding sequence. The soluble PHEX therefore comprises the active ectodomain. An inactive mutant of PHEX is also an object of this invention. Both soluble and inactive mutant forms of PHEX can be used to screen ligands to PHEX. These ligands can also be used as substrates or inhibitors of PHEX. PHEX being phosphaturic, an inhibitor thereof will be used to treat phosphaturia and/or hypophosphatemia. On the opposite, a substrate for PHEX or PHEX itself can be used to treat hyperphosphatemia.
摘要翻译：本发明涉及可溶形式的PHEX，PHEX是II型整合膜糖蛋白。该酶是与X染色体上的内肽酶同源的磷酸调节基因的基因产物。为了产生可溶形式的PHEX，已经修饰了跨膜锚结构域以编码信号肽酶编码序列。因此，可溶性PHEX包含活性胞外域。 PHEX的无活性突变体也是本发明的目的。 PHEX的可溶性和非活性突变体形式均可用于筛选PHEX的配体。这些配体也可以用作PHEX的底物或抑制剂。 PHEX是磷酸盐，其抑制剂将用于治疗磷酸和/或低磷酸血症。相反，PHEX或PHEX本身的底物可用于治疗高磷血症。

7. 发明专利

CA470433A DISPENSING CONTAINERS FOR TISSUES 未知
公开(公告)号：CA470433A
公开(公告)日：1951-01-02
申请号：CA470433D
申请人： BOILEAU GUY
发明人： BOILEAU GUY

8. 发明申请

WO2008138131A9 BONE TARGETED ALKALINE PHOSPHATASE, KITS AND METHODS OF USE THEREOF 审中-公开
标题翻译：骨靶向碱性磷酸酶，套管及其使用方法
公开(公告)号：WO2008138131A9
公开(公告)日：2009-08-06
申请号：PCT/CA2008000923
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 , C12N5/10 , C12N9/16 , C12N15/85
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.
摘要翻译：包含具有以下结构的多肽的骨靶向碱性磷酸酶：Z-sALP-Y-spacer-X-Wn-V，其中sALP是碱性磷酸酶的细胞外结构域; 其中V不存在或者是至少一个氨基酸的氨基酸序列; X不存在或者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; Wn是n = 10至16的聚天冬氨酸盐或聚谷氨酸盐。组合物及其使用方法。

9. 发明申请

WO2008138131A1 BONE TARGETED ALKALINE PHOSPHATASE, KITS AND METHODS OF USE THEREOF 审中-公开
标题翻译：骨靶向碱性磷酸酶，套管及其使用方法
公开(公告)号：WO2008138131A1
公开(公告)日：2008-11-20
申请号：PCT/CA2008000923
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 , C12N5/10 , C12N9/16 , C12N15/85
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-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.
摘要翻译：一种骨靶向碱性磷酸酶，其包含具有以下结构的多肽：Z-sALP-Y-spacer-X-W-N-N，其中sALP是碱性磷酸酶的细胞外结构域; 其中V不存在或者是至少一个氨基酸的氨基酸序列; 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W n是n = 10至16的聚天冬氨酸盐或聚谷氨酸盐。组合物及其使用方法。

10. 发明申请

WO2005103263B1 BONE DELIVERY CONJUGATES AND METHOD OF USING SAME TO TARGET PROTEINS TO BONE 审中-公开
标题翻译：骨髓移植术和使用相同目标蛋白质的方法
公开(公告)号：WO2005103263B1
公开(公告)日：2005-12-15
申请号：PCT/CA2005000615
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： A61K38/46 , A61K38/48 , A61K47/48 , A61P19/08 , C12N9/14 , C12N9/50 , C12N9/64 , C12N15/55 , C12N15/57 , 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-Dn-Y-protein-Z; and B) Z-protein-Y- Dn-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 Dn 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-Dn-Y-蛋白-Z; 和B）Z-蛋白-Y-Dn-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; Dn是n = 10〜16的天冬氨酸聚天冬氨酸的组合物及其用途。

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