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1. 发明授权

US5204096A Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers 失效
标题翻译：前S基因编码肽乙型肝炎免疫原，疫苗，诊断和合成脂质囊泡载体
公开(公告)号：US5204096A
公开(公告)日：1993-04-20
申请号：US338028
申请日：1989-04-14
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： A61K9/127 , A61K39/00 , A61K47/48 , C07K14/02 , C07K16/08 , G01N33/576
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K47/48876 , A61K9/1271 , C07K16/082 , G01N33/5764 , A61K39/00 , C12N2730/10122 , Y10S530/81
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen or hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.
摘要翻译：一种乙型肝炎疫苗，其含有乙型肝炎病毒包膜前S基因编码区内具有至少六个连续氨基酸的氨基酸链的肽。该疫苗不含对应于乙型肝炎病毒的天然存在的包膜蛋白的氨基酸序列和生理上可接受的稀释剂。肽与载体无关或连接。载体是常规载体或包含通过交联稳定并在其外表面上具有共价键合的活性位点的脂质囊泡的新型载体。这种新型载体不仅用于将含有氨基酸链的新肽与表面抗原或乙型肝炎病毒的S前编码区之前的氨基酸连接，还可用于结合其他病毒的合成肽类似物蛋白质，以及人和动物的细菌，变应原和寄生蛋白。本发明的肽可用于诊断抗原和抗体的检测。

2. 发明授权

US4861588A Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers 失效
标题翻译：前S基因编码肽乙型肝炎免疫原，疫苗，诊断和合成脂质囊泡载体
公开(公告)号：US4861588A
公开(公告)日：1989-08-29
申请号：US856522
申请日：1986-04-28
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： C12P21/00 , A61K9/127 , A61K39/00 , A61K39/29 , A61K47/48 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/02 , C07K14/10 , C07K14/18 , C07K14/705 , C07K16/08 , C12Q1/16 , G01N33/53 , G01N33/576
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K9/1271 , C07K16/082 , G01N33/5761 , A61K39/00 , C12N2730/10122 , Y10S930/223
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.
摘要翻译：一种乙型肝炎疫苗，其含有乙型肝炎病毒包膜前S基因编码区内具有至少六个连续氨基酸的氨基酸链的肽。该疫苗不含对应于乙型肝炎病毒的天然存在的包膜蛋白的氨基酸序列和生理上可接受的稀释剂。肽与载体无关或连接。载体是常规载体或包含通过交联稳定并在其外表面上具有共价键合的活性位点的脂质囊泡的新型载体。这种新型载体不仅可用于将含有氨基酸链的新肽与乙型肝炎病毒表面抗原前S基因编码区内的氨基酸连接，还可用于结合其他病毒的合成肽类似物蛋白质，以及人和动物的细菌，变应原和寄生蛋白。本发明的肽可用于诊断抗原和抗体的检测。

3. 发明授权

US4847080A Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipide vesicle carriers 失效
标题翻译：前S基因编码肽乙型肝炎免疫原，疫苗，诊断和合成脂质囊泡载体
公开(公告)号：US4847080A
公开(公告)日：1989-07-11
申请号：US698499
申请日：1985-02-05
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： G01N33/576 , A61K9/127 , A61K39/00 , A61K39/29 , A61K39/385 , A61K47/48 , C07K7/04 , C07K14/00 , C07K14/02 , C07K14/10 , C07K14/18 , C07K14/435 , C07K16/08 , C07K19/00 , C12N15/00 , C12N15/09 , C12P21/00 , C12P21/08 , G01N33/543 , G01N33/577
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K9/1271 , C07K16/082 , G01N33/5764 , A61K39/00 , C12N2730/10122 , Y10S930/221 , Y10S930/222 , Y10S930/223 , Y10S930/26 , Y10S930/27
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.V

4. 发明授权

US4803156A Peptide-beta-lactamase conjugates for enzyme-linked immunoassays 失效
标题翻译：用于酶联免疫测定的肽-β-内酰胺酶缀合物
公开(公告)号：US4803156A
公开(公告)日：1989-02-07
申请号：US774829
申请日：1985-09-11
申请人： Alexander R. Neurath , Stephen B. H. Kent , Nathan Strick
发明人： Alexander R. Neurath , Stephen B. H. Kent , Nathan Strick
IPC分类号： C07K14/02 , C07K14/16 , G01N33/535 , G01N33/576 , G01N33/53
CPC分类号： C07K14/005 , G01N33/535 , G01N33/5761 , C12N2730/10122 , C12N2740/16222 , Y10S436/82 , Y10S436/828 , Y10S930/142 , Y10S930/221 , Y10S930/222 , Y10S930/223 , Y10S930/26 , Y10S930/31
摘要： A reagent for an ELISA determination of an antibody, the reagent comprising a peptide covalently linked to beta-lactamase. The reagent can be used in the following method to detect antibodies in a sample which involvesa. contacting the sample with protein A linked to a solid support,b. incubating the sample-protein A linked to the solid support,c. washing the incubated sample-protein A linked to the solid support,d. contacting the washed sample-protein A with the reagent,e. incubating the sample-protein A and reagent,f. washing the incubated sample-protein A-reagent, andg. determining the enzymatic activity of the resultant mass.
摘要翻译：用于ELISA测定抗体的试剂，所述试剂包含与β-内酰胺酶共价连接的肽。试剂可以按照以下方法用于检测涉及a的样品中的抗体。使样品与连接到固体支持物的蛋白A接触，b。孵育与固体支持物连接的样品蛋白A，c。洗涤与固体支持物连接的温育样品 - 蛋白A，d。将洗涤过的样品蛋白A与试剂接触，孵育样品蛋白A和试剂，f。洗涤孵育的样品蛋白A试剂，g。测定所得物质的酶活性。

5. 发明授权

US5565548A Pre-S gene coded peptide hepatitis B immunogens and synthetic lipid vesicle carriers 失效
标题翻译：前S基因编码肽乙型肝炎免疫原和合成脂质囊泡载体
公开(公告)号：US5565548A
公开(公告)日：1996-10-15
申请号：US31735
申请日：1993-03-15
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： A61K9/127 , A61K39/00 , A61K47/48 , C07K14/02 , C07K16/08 , G01N33/576 , A61K38/00 , A61K45/00 , C17K5/00
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K47/48876 , A61K9/1271 , C07K16/082 , G01N33/5764 , A61K39/00 , C12N2730/10122 , Y10S530/81
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.
摘要翻译：一种乙型肝炎疫苗，其含有乙型肝炎病毒包膜前S基因编码区内具有至少六个连续氨基酸的氨基酸链的肽。该疫苗不含对应于乙型肝炎病毒的天然存在的包膜蛋白的氨基酸序列和生理上可接受的稀释剂。肽与载体无关或连接。载体是常规载体或包含通过交联稳定并在其外表面上具有共价键合的活性位点的脂质囊泡的新型载体。这种新型载体不仅可用于将含有氨基酸链的新肽与乙型肝炎病毒表面抗原前S基因编码区内的氨基酸连接，还可用于结合其他病毒的合成肽类似物蛋白质，以及人和动物的细菌，变应原和寄生蛋白。本发明的肽可用于诊断抗原和抗体的检测。

6. 发明授权

US5158769A Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers 失效
标题翻译：前S基因编码肽乙型肝炎免疫原，疫苗，诊断和合成脂质囊泡载体
公开(公告)号：US5158769A
公开(公告)日：1992-10-27
申请号：US337784
申请日：1989-04-13
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： A61K9/127 , A61K39/00 , A61K47/48 , C07K14/02 , C07K16/08 , G01N33/576
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K9/1271 , B82Y5/00 , C07K16/082 , G01N33/5761 , G01N33/5764 , A61K39/00 , C12N2730/10122
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.
摘要翻译：一种乙型肝炎疫苗，其含有乙型肝炎病毒包膜前S基因编码区内具有至少六个连续氨基酸的氨基酸链的肽。该疫苗不含对应于乙型肝炎病毒的天然存在的包膜蛋白的氨基酸序列和生理上可接受的稀释剂。肽与载体无关或连接。载体是常规载体或包含通过交联稳定并在其外表面上具有共价键合的活性位点的脂质囊泡的新型载体。这种新型载体不仅可用于将含有氨基酸链的新肽与乙型肝炎病毒表面抗原前S基因编码区内的氨基酸连接，还可用于结合其他病毒的合成肽类似物蛋白质，以及人和动物的细菌，变应原和寄生蛋白。本发明的肽可用于诊断抗原和抗体的检测。

7. 发明授权

US5620844A Assays for detecting hepatitis B virus envelope antigens or antibodies thereto and diagnostic test kits for use in performing the assays 失效
标题翻译：用于检测乙型肝炎病毒包膜抗原或其抗体的检测方法以及用于进行检测的诊断检测试剂盒
公开(公告)号：US5620844A
公开(公告)日：1997-04-15
申请号：US57200
申请日：1993-05-03
申请人： Alexander R. Neurath , Stephen B. H. Kent
发明人： Alexander R. Neurath , Stephen B. H. Kent
IPC分类号： A61K9/127 , A61K39/00 , A61K47/48 , C07K14/02 , C07K16/08 , G01N33/576 , C12Q1/70 , A61K38/08 , G01N33/53 , G01N33/537
CPC分类号： C07K14/005 , A61K47/48176 , A61K47/48315 , A61K47/48815 , A61K9/1271 , B82Y5/00 , C07K16/082 , G01N33/5761 , G01N33/5764 , A61K39/00 , C12N2730/10122
摘要： A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.
摘要翻译：一种乙型肝炎疫苗，其含有乙型肝炎病毒包膜前S基因编码区内具有至少六个连续氨基酸的氨基酸链的肽。该疫苗不含对应于乙型肝炎病毒的天然存在的包膜蛋白的氨基酸序列和生理上可接受的稀释剂。肽与载体无关或连接。载体是常规载体或包含通过交联稳定并在其外表面上具有共价键合的活性位点的脂质囊泡的新型载体。这种新型载体不仅可用于将含有氨基酸链的新肽与乙型肝炎病毒表面抗原前S基因编码区内的氨基酸连接，还可用于结合其他病毒的合成肽类似物蛋白质，以及人和动物的细菌，变应原和寄生蛋白。本发明的肽可用于诊断抗原和抗体的检测。

8. 发明授权

US07030218B2 Pseudo native chemical ligation 失效
标题翻译：伪天然化学结扎
公开(公告)号：US07030218B2
公开(公告)日：2006-04-18
申请号：US10332386
申请日：2001-07-12
申请人： Christie L. Hunter , Paolo Botti , James A. Bradburne , Shiah-yun Chen , Sonya Cressman , Stephen B. H. Kent , Gerd G. Kochendoerfer , Donald W. Low
发明人： Christie L. Hunter , Paolo Botti , James A. Bradburne , Shiah-yun Chen , Sonya Cressman , Stephen B. H. Kent , Gerd G. Kochendoerfer , Donald W. Low
IPC分类号： C07K1/02 , C07K1/07
CPC分类号： C07K14/505 , A61K38/00
摘要： The present invention concerns methods and compositions for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond (see FIG. 1). The invention further provides methods and uses for such proteins and derivatized proteins. The invention is particularly suitable for use in the synthesis of optionally polymer-modified, synthetic bioactive proteins, and of pharmaceutical compositions that contain such proteins.
摘要翻译：本发明涉及通过酰胺键扩展更宽范围的肽，多肽，其它聚合物和其它分子的天然化学连接技术的方法和组合物（参见图1）。本发明还提供了这些蛋白质和衍生化蛋白质的方法和用途。本发明特别适用于合成任选的聚合物改性的合成生物活性蛋白质和含有这种蛋白质的药物组合物。

9. 发明授权

US06271037B1 Method and product for the sequence determination of peptides using a mass spectrometer 失效
标题翻译：使用质谱仪对肽进行序列测定的方法和产品
公开(公告)号：US06271037B1
公开(公告)日：2001-08-07
申请号：US08341555
申请日：1996-06-24
申请人： Brian T. Chait , Ronald Beavis , Rong Wang , Stephen B. H. Kent
发明人： Brian T. Chait , Ronald Beavis , Rong Wang , Stephen B. H. Kent
IPC分类号： G01N3300
CPC分类号： G01N33/6842 , C07K1/107 , C07K1/128 , G01N33/6824 , Y10T436/24 , Y10T436/25 , Y10T436/255
摘要： Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.
摘要翻译：描述了通过形成包含一系列多肽的肽梯级来测序多肽的方法，其中该序列的相邻成员变化一个氨基酸残基，并通过质谱确定多肽中每个氨基酸的同一性和位置。

10. 发明授权

US5831005A Synthesis of N-substituted oligomers 失效
标题翻译： N-取代的低聚物的合成
公开(公告)号：US5831005A
公开(公告)日：1998-11-03
申请号：US441826
申请日：1995-05-16
申请人： Ronald N. Zuckerman , Janice M. Kerr , Stephen B. H. Kent , Walter H. Moos , Reyna J. Simon , Dane A. Goff
发明人： Ronald N. Zuckerman , Janice M. Kerr , Stephen B. H. Kent , Walter H. Moos , Reyna J. Simon , Dane A. Goff
IPC分类号： A61K38/00 , C07B61/00 , C07K1/04 , C07K7/06 , C07K7/08 , C07K14/00 , C08G69/10
CPC分类号： C40B50/14 , C07K1/04 , C07K1/047 , C07K14/001 , C07K7/06 , C07K7/08 , C08G69/10 , A61K38/00 , B01J2219/00497 , B01J2219/00596 , B01J2219/0072 , C07B2200/11 , C40B40/10
摘要： A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic is displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology of the present method makes these oligomers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of the invention, such as N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of peptide-like compounds not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability.
摘要翻译：用于合成N-取代的低聚物（例如聚（N-取代的甘氨酸）（本文称为多聚NSG））的固相方法用于获得低聚物，例如聚NSG可具有的潜在治疗兴趣的聚NSG 各种各样的侧链取代基。每个N-取代的甘氨酸单体直接在固体支持物上由两个“亚单体”组装。单体添加的每个循环由两个步骤组成：（1）用包含能够亲核的离去基团的酰化剂与载体结合的仲胺的酰化被-NH 2取代，例如卤代乙酸，和（2）引入的侧链通过亲核取代离去基团，例如卤素（作为树脂结合的α-卤代乙酰胺）与足够量的包含-NH 2基团的第二亚单体如伯胺，烷氧基胺，氨基脲，酰肼，卡巴肼等。重复酰化和置换的两个步骤循环，得到所需的低聚物。使用本发明方法的自动化合成技术有效合成各种各样的低聚NSG使得这些寡聚物成为用于不同肽模拟文库的产生和快速筛选的有吸引力的候选者。本文公开的本发明的低聚物，例如N-取代的甘氨酸（即多聚NSG）提供了一类新型的肽样化合物，它们在自然界中没有发现，但是它们是合成可及的，并且已被证明具有显着的生物活性和蛋白水解稳定性。

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