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1. 发明授权

US5679352A Synthetic Haemophilus influenzae conjugate vaccine 失效
标题翻译：合成型流感嗜血杆菌结合疫苗
公开(公告)号：US5679352A
公开(公告)日：1997-10-21
申请号：US475989
申请日：1995-06-07
申请人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
发明人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
IPC分类号： G01N33/53 , A61K31/00 , A61K39/00 , A61K39/102 , A61K39/21 , A61K39/385 , A61K39/39 , A61K39/395 , A61K47/48 , A61P31/00 , A61P31/04 , A61P37/04 , C07H15/04 , C07H15/08 , C07H15/18 , C07H21/04 , C07K7/08 , C07K14/11 , C07K14/16 , C07K14/195 , C07K14/285 , C07K16/00 , C12N15/09 , C12N15/31 , G01N33/569 , C07K16/12 , C12Q1/04
CPC分类号： C07H15/04 , A61K47/48215 , A61K47/4833 , C07H15/08 , C07H15/18 , C07K14/285 , A61K39/00 , Y02P20/55 , Y10S435/851
摘要： Synthetic peptides have an amino acid sequence corresponding to at least one antigenic determinant of at least one protein, usually a structural protein, particularly the P1, P2 and P6 protein, of Haemophilus influenzae (Hi), particularly type b, and are used as is, in chimeric T-B form, in lipidated form, linked to a carrier molecule, particularly a synthetic PRP molecule and/or polymerized to form molecular aggregates, in vaccines against Hi.
摘要翻译：合成肽具有对应于至少一种蛋白质，通常是流感嗜血杆菌（Hi）的结构蛋白，特别是P1，P2和P6蛋白，特别是b型的抗原决定簇的氨基酸序列，并且按原样使用以与脂质化形式的嵌合TB形式连接到抗体的疫苗中，与载体分子特别是合成的PRP分子连接和/或聚合以形成分子聚集体。

2. 发明授权

US6018019A Synthetic Haemophilus influenzae conjugate vaccine 失效
标题翻译：合成型流感嗜血杆菌结合疫苗
公开(公告)号：US6018019A
公开(公告)日：2000-01-25
申请号：US256839
申请日：1994-10-03
申请人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
发明人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
IPC分类号： G01N33/53 , A61K31/00 , A61K39/00 , A61K39/102 , A61K39/21 , A61K39/385 , A61K39/39 , A61K39/395 , A61K47/48 , A61P31/00 , A61P31/04 , A61P37/04 , C07H15/04 , C07H15/08 , C07H15/18 , C07H21/04 , C07K7/08 , C07K14/11 , C07K14/16 , C07K14/195 , C07K14/285 , C07K16/00 , C12N15/09 , C12N15/31 , G01N33/569 , A61K38/12
CPC分类号： C07H15/04 , A61K47/48215 , A61K47/4833 , C07H15/08 , C07H15/18 , C07K14/285 , A61K39/00 , Y02P20/55 , Y10S435/851
摘要： The present invention provides immunogenic synthetic peptides which are useful alone or in PRP-conjugates in vaccines against Hemophilus influenza infection. Modifications are possible within the scope of the invention.
摘要翻译： PCT No.PCT / CA93 / 00041 Sec。 371日期：1994年10月3日 102（e）日期1994年10月3日PCT提交1993年2月3日PCT公布。公开号WO93 / 15205 日期1993年8月5日本发明提供了免疫原性合成肽，其在抗血友病流感感染的疫苗中可单独使用或用于PRP缀合物。在本发明的范围内可以进行修改。

3. 发明授权

US06290971B1 Adjuvant compositions comprising a mineral salt and another immunostimulating compound 失效
标题翻译：包含矿物盐和另一种免疫刺激化合物的佐剂组合物
公开(公告)号：US06290971B1
公开(公告)日：2001-09-18
申请号：US08750624
申请日：1997-02-26
申请人： Ali Kandil , Olive A. James , Pele Chong , Michel H. Klein
发明人： Ali Kandil , Olive A. James , Pele Chong , Michel H. Klein
IPC分类号： A61K4500
CPC分类号： A61K39/39 , A61K2039/55505 , A61K2039/55511
摘要： Adjuvant compositions for modulating an immune response to an antigen administered to a host comprise a mineral salt adjuvant and at least one other adjuvant. The compositions provide an adjuvanting effect on an antigen which is greater than the adjuvanting effect attainable by one of the adjuvants alone. An antigen is covalently bonded to a glycolipid analog to provide a discrete molecule which exhibits an enhanced adjuvanting effect on the antigen which is greater than the adjuvanting effect attainable in the absence of such covalent bonding.
摘要翻译：用于调节对宿主施用的抗原的免疫应答的佐剂组合物包含矿物盐佐剂和至少一种其他佐剂。所述组合物对抗原提供佐剂效应，其大于单独一种佐剂可获得的佐剂效应。抗原与糖脂类似物共价键合以提供对抗原具有增强的佐剂效应的离散分子，其大于在不存在这种共价键的情况下可获得的佐剂效应。

4. 发明授权

US06177085B1 Generation of immune response using immunogenic conjugate of molecules 失效
标题翻译：使用分子的免疫原性缀合物产生免疫应答
公开(公告)号：US06177085B1
公开(公告)日：2001-01-23
申请号：US08467884
申请日：1995-06-06
申请人： Yan-ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
发明人： Yan-ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
IPC分类号： A61K3909
CPC分类号： C07K17/10 , A61K39/092 , A61K2039/55505 , A61K2039/6068 , C07K14/285 , Y10S424/831
摘要： Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from Streptococcus pneumoniae are linked to an outer membrane protein of a Haemophilus influenzae strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.
摘要翻译：提供包含与嗜血杆菌菌株的外膜蛋白的至少一部分连接的链球菌菌株的至少一部分荚膜多糖的免疫原性缀合物分子，其中荚膜多糖的免疫原性增加。特别是来自肺炎链球菌的荚膜多糖与流感嗜血杆菌菌株的外膜蛋白连接，该蛋白质可以是P1，P2或特别是P6外膜蛋白。还描述了包含与除链球菌以外的包囊病原体的荚膜多糖连接的P6蛋白的缀合物分子，其中荚膜多糖的免疫原性增强。这样的缀合物分子可以并入免疫原性组合物中，用于保护宿主免受由链球菌菌株引起的疾病，优选还有嗜血杆菌属菌株。对于荚膜多糖或对外膜蛋白特异的缀合物分子和抗体可用于诊断程序和试剂盒。还提供了从嗜血杆菌菌株单独分离P1，P2和P6外膜蛋白的方法。

5. 发明授权

US5780606A Neisseria meningitidis capsular polysaccharide conjugates 失效
标题翻译：脑膜炎奈瑟氏球菌荚膜多糖共轭物
公开(公告)号：US5780606A
公开(公告)日：1998-07-14
申请号：US474392
申请日：1995-06-07
申请人： Ali Kandil , Pele Chong , Michel H. Klein
发明人： Ali Kandil , Pele Chong , Michel H. Klein
IPC分类号： A61K39/095 , A61K47/48 , C07K16/12 , C12P21/08 , C08B37/00 , A61K31/715
CPC分类号： A61K39/095 , A61K47/4823 , C07K16/1217 , A61K2039/6037
摘要： Capsular polysaccharides containing multiple sialic acid residues, particularly the Group B polysaccharide of Neisseria meningitidis, are modified by chemical reaction to randomly introduce pendant reactive residues of heterobifunctional linker molecules to the polysaccharide backbone. The capsular polysaccharide is deacetylated and the heterobifunctional linker molecule is reacted with the deacetylated material and any residual amino groups are blocked by reaction with alkyl acid anhydride. The introduction of the linker molecules to the polysaccharide chain between the termini enables the polysaccharide to be linked to a carrier molecule, such as a protein, to enhance the immunogenicity of the polysaccharide. The conjugate molecule may be formulated as an immunogenic composition for raising antibodies in a host to the polysaccharide.
摘要翻译：含有多种唾液酸残基的荚膜多糖，特别是脑膜炎奈瑟球菌B组多糖，通过化学反应进行修饰，随机引入异双功能连接分子的侧链反应性残基至多糖主链。荚膜多糖脱乙酰化，异双功能连接分子与脱乙酰化物反应，任何残留氨基均与烷基酸酐反应而被阻断。将连接体分子引入末端之间的多糖链可使多糖与载体分子如蛋白质连接，以增强多糖的免疫原性。缀合物分子可以配制成用于在多糖的宿主中产生抗体的免疫原性组合物。

6. 发明授权

US5972349A Synthesis of polyribosylribitol phosphate oligosaccharides 失效
标题翻译：多糖基核糖醇磷酸寡糖的合成
公开(公告)号：US5972349A
公开(公告)日：1999-10-26
申请号：US475985
申请日：1995-06-07
申请人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
发明人： Pele Chong , Ali Kandil , Charles Sia , Michel Klein
IPC分类号： G01N33/53 , A61K31/00 , A61K39/00 , A61K39/102 , A61K39/21 , A61K39/385 , A61K39/39 , A61K39/395 , A61K47/48 , A61P31/00 , A61P31/04 , A61P37/04 , C07H15/04 , C07H15/08 , C07H15/18 , C07H21/04 , C07K7/08 , C07K14/11 , C07K14/16 , C07K14/195 , C07K14/285 , C07K16/00 , C12N15/09 , C12N15/31 , G01N33/569
CPC分类号： C07H15/04 , A61K47/48215 , A61K47/4833 , C07H15/08 , C07H15/18 , C07K14/285 , A61K39/00 , Y02P20/55 , Y10S435/851
摘要： Polyribosylribitol phosphate oligosaccharides are produced in a multistep process. The compound of the formula: ##STR1## wherein R.sub.1 is a first protecting group and R.sub.2 is a second protecting group, is coupled to a solid polyethylene glycol monomethyl ether (PEG) support. Following removal of the first protecting group, the resulting compound is coupled with a repeating unit for chain elongation of the formula: ##STR2## The protecting group is removed from the phosphorus atom and the steps of removing the first protecting group, coupling with the repeating unit is repeated until the desired number of repeating units in the oligomer has been terminated. The oligomer then is terminated with a chain terminating molecule of the formula: ##STR3## wherein m is an integer and R.sub.3 is a third protecting group. The resulting PEG-bound protected oligomer is a new product and the oligomer may be cleaved from the support and processed to provide a chemically-reactive functional group for binding the polysaccharide oligomer to a carrier molecule.
摘要翻译：多核糖核糖醇磷酸寡糖以多步法生产。下式的化合物：其中R 1是第一保护基，R 2是第二保护基，与固体聚乙二醇单甲醚（PEG）载体偶合。除去第一保护基后，所得化合物与下式的链延长的重复单元偶联：保护基团从磷原子上除去，除去第一保护基的步骤，重复与重复单元的偶合直到所述低聚物中所需的重复单元数目已经终止。然后用下式的链终止分子终止寡聚体：其中m是整数，R 3是第三保护基。得到的PEG结合的被保护的低聚物是新产物，并且寡聚体可以从载体上裂解并进行处理以提供用于将多糖低聚物结合到载体分子的化学反应性官能团。

7. 发明授权

US5681570A Immunogenic conjugate molecules 失效
标题翻译：免疫原性共轭分子
公开(公告)号：US5681570A
公开(公告)日：1997-10-28
申请号：US371965
申请日：1995-01-12
申请人： Yan-ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
发明人： Yan-ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
IPC分类号： A61P31/04 , C07K14/285 , C07K17/10 , A61K39/385 , A61K39/02 , A61K39/09 , A61K39/116
CPC分类号： C07K17/10 , A61K39/092 , C07K14/285 , A61K2039/55505 , A61K2039/6068 , Y10S424/831
摘要： Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from Streptococcus pneumoniae are linked to an outer membrane protein of a Haemophilus influenzae strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.
摘要翻译：提供包含与嗜血杆菌菌株的外膜蛋白的至少一部分连接的链球菌菌株的至少一部分荚膜多糖的免疫原性缀合物分子，其中荚膜多糖的免疫原性增加。特别是来自肺炎链球菌的荚膜多糖与流感嗜血杆菌菌株的外膜蛋白连接，该蛋白质可以是P1，P2或特别是P6外膜蛋白。还描述了包含与除链球菌以外的包囊病原体的荚膜多糖连接的P6蛋白的缀合物分子，其中荚膜多糖的免疫原性增强。这样的缀合物分子可以并入免疫原性组合物中，用于保护宿主免受由链球菌菌株引起的疾病，优选还有嗜血杆菌属菌株。对于荚膜多糖或对外膜蛋白特异的缀合物分子和抗体可用于诊断程序和试剂盒。还提供了从嗜血杆菌菌株单独分离P1，P2和P6外膜蛋白的方法。

8. 发明授权

US06764682B1 Adjuvant compositions containing more than one adjuvant 失效
标题翻译：含有多于一种佐剂的佐剂组合物
公开(公告)号：US06764682B1
公开(公告)日：2004-07-20
申请号：US08261194
申请日：1994-06-16
申请人： Ali Kandil , Olive A. James , Michel H. Klein , Pele Chong
发明人： Ali Kandil , Olive A. James , Michel H. Klein , Pele Chong
IPC分类号： A61K3938
CPC分类号： C07H15/12 , A61K31/351 , A61K33/06 , A61K33/08 , A61K33/30 , A61K33/42 , A61K39/092 , A61K39/099 , A61K39/102 , A61K39/12 , A61K39/145 , A61K39/385 , A61K39/39 , A61K45/06 , A61K47/549 , A61K2039/55505 , A61K2039/55516 , A61K2039/60 , A61K2039/6018 , C12N2740/16234 , C12N2760/16134 , C12N2760/18534 , C12N2760/18634 , C12N2770/36234 , A61K2300/00
摘要： Adjuvant compositions for modulating an immune response to an antigen administered to a host comprise a mineral salt adjuvant and at least one other adjuvant. The compositions provide an adjuvanting effect on an antigen which is greater than the adjuvanting effect attainable by one of the adjuvants alone. An antigen is covalently bonded to a glycolipid analog to provide a discrete molecule which exhibits an enhanced adjuvanting effect on the antigen which is greater than the adjuvanting effect attainable in the absence of such covalent bonding.
摘要翻译：用于调节对宿主施用的抗原的免疫应答的佐剂组合物包含矿物盐佐剂和至少一种其他佐剂。所述组合物对抗原提供佐剂效应，其大于单独一种佐剂可获得的佐剂效应。抗原与糖脂类似物共价键合以提供对抗原具有增强的佐剂效应的离散分子，其大于在不存在这种共价键的情况下可获得的佐剂效应。

9. 发明授权

US06329512B1 Immunogenic conjugate molecules 失效
标题翻译：免疫原性共轭分子
公开(公告)号：US06329512B1
公开(公告)日：2001-12-11
申请号：US08467883
申请日：1995-06-06
申请人： Yan-Ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
发明人： Yan-Ping Yang , Ali Kandil , Lucy Gisonni , Raafat Emil Fahmy Fahim , Michel Henri Klein
IPC分类号： A23J100
CPC分类号： C07K17/10 , A61K39/092 , A61K2039/55505 , A61K2039/6068 , C07K14/285 , Y10S424/831
摘要： Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from Streptococcus pneumoniae are linked to an outer membrane protein of a Haemophilus influenzae strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.
摘要翻译：提供包含与嗜血杆菌菌株的外膜蛋白的至少一部分连接的链球菌菌株的至少一部分荚膜多糖的免疫原性缀合物分子，其中荚膜多糖的免疫原性增加。特别是来自肺炎链球菌的荚膜多糖与流感嗜血杆菌菌株的外膜蛋白连接，该蛋白质可以是P1，P2或特别是P6外膜蛋白。还描述了包含与除链球菌以外的包囊病原体的荚膜多糖连接的P6蛋白的缀合物分子，其中荚膜多糖的免疫原性增强。这样的缀合物分子可以并入免疫原性组合物中，用于保护宿主免受由链球菌菌株引起的疾病，优选还有嗜血杆菌属菌株。对于荚膜多糖或对外膜蛋白特异的缀合物分子和抗体可用于诊断程序和试剂盒。还提供了从嗜血杆菌菌株单独分离P1，P2和P6外膜蛋白的方法。

10. 发明授权

US6080589A Neisseria meningitidis capsular polysacchride conjugates 失效
标题翻译：脑膜炎奈瑟氏球菌荚膜多糖缀合物
公开(公告)号：US6080589A
公开(公告)日：2000-06-27
申请号：US61189
申请日：1998-04-17
申请人： Ali Kandil , Pele Chong , Michel H. Klein
发明人： Ali Kandil , Pele Chong , Michel H. Klein
IPC分类号： A61K39/095 , A61K47/48 , C07K16/12 , C12P21/08 , G01N33/563 , A61K38/16 , C07K1/00
CPC分类号： A61K39/095 , A61K47/4823 , C07K16/1217 , A61K2039/6037
摘要： Capsular polysaccharides containing multiple sialic acid residues, particularly the Group B polysaccharide of Neisseria meningitidis, are modified by chemical reaction to randomly introduce pendant reactive residues of heterobifunctional linker molecules to the polysaccharide backbone. The capsular polysaccharide is deacetylated and the heterobifunctional linker molecule is reacted with the deacetylated material and any residual amino groups are blocked by reaction with alkyl acid anhydride. The introduction of the linker molecules to the polysaccharide chain between the termini enables the polysaccharide to be linked to a carrier molecule, such as a protein, to enhance the immunogenicity of the polysaccharide. The conjugate molecule may be formulated as an immunogenic composition for raising antibodies in a host to the polysaccharide.
摘要翻译：含有多种唾液酸残基的荚膜多糖，特别是脑膜炎奈瑟球菌B组多糖，通过化学反应进行修饰，随机引入异双功能连接分子的侧链反应性残基至多糖主链。荚膜多糖脱乙酰化，异双功能连接分子与脱乙酰化物反应，任何残留氨基均与烷基酸酐反应而被阻断。将连接体分子引入末端之间的多糖链可使多糖与载体分子如蛋白质连接，以增强多糖的免疫原性。缀合物分子可以配制成用于在多糖的宿主中产生抗体的免疫原性组合物。

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