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1. 发明申请

WO2005027835A3 THERAPEUTIC IMMUNIZATION OF HIV-INFECTED INDIVIDUALS 审中-公开
标题翻译：艾滋病毒感染个体的治疗性免疫
公开(公告)号：WO2005027835A3
公开(公告)日：2007-08-16
申请号：PCT/US2004029844
申请日：2004-09-14
申请人： MERCK & CO INC , EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , HAZUDA DARIA , SCHLEIF WILLIAM A
发明人： EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , HAZUDA DARIA , SCHLEIF WILLIAM A
IPC分类号： A01N43/04 , A01N63/00 , A01N65/00 , A61K20060101 , A61K31/70
CPC分类号： A61K39/21 , A61K39/12 , A61K2039/53 , A61K2039/545 , A61K2039/55 , C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10343 , C12N2740/15022 , C12N2740/15034 , C12N2740/15071 , C12N2740/16134 , C12N2740/16222
摘要： The present invention provides an improved method for eliciting a therapeutic immune response in an individual infected with human immunodeficiency virus ("HIV"). The method comprises administering an adenoviral vaccine composition expressing an HIV antigen to an individual with controlled viremia. Immunization of infected individuals in this manner elicits a cellular-mediated immune response against the virus that is significant both in the level of the response and the breadth of the response. The therapeutic immune response that ensues is capable of effectively maintaining low titers of virus and, thus, offers the prospect of reducing individual dependency on antiviral therapy.
摘要翻译：本发明提供了在感染人类免疫缺陷病毒（“HIV”）的个体中引发治疗性免疫应答的改进方法。该方法包括向具有受控制的病毒血症的个体施用表达HIV抗原的腺病毒疫苗组合物。以这种方式免疫感染的个体引起针对病毒的细胞介导的免疫应答，其在反应水平和反应的广度方面是显着的。随后的治疗性免疫应答能够有效地维持低滴度的病毒，从而提供减少个体对抗病毒治疗依赖性的前景。

2. 发明申请

WO2008121282A3 BROADLY REPRESENTATIVE ANTIGEN SEQUENCES AND METHOD FOR SELECTION 审中-公开
标题翻译：广泛代表性的抗原序列和选择方法
公开(公告)号：WO2008121282A3
公开(公告)日：2008-11-20
申请号：PCT/US2008003947
申请日：2008-03-26
申请人： MERCK & CO INC , FINNEFROCK ADAM C , CASIMIRO DANILO R , BETT ANDREW J , CONDRA JON H , SHIVER JOHN W
发明人： FINNEFROCK ADAM C , CASIMIRO DANILO R , BETT ANDREW J , CONDRA JON H , SHIVER JOHN W
IPC分类号： G06G7/48 , C12Q1/00 , C12Q1/68 , G06F19/22
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/21 , A61K2039/5256 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K16/1045 , C12N2710/10343 , C12N2740/16222 , C12N2740/16234 , C12N2740/16322 , C12N2740/16334 , G06F19/22
摘要： A novel method for generating vaccine sequences is disclosed herein that preserves contiguous epitope length stretches of amino acids or nucleotides from an input pool of sequences. The method generates continuous, stepwise epitope consensus that together provides for a single globally optimized sequence. The end sequences are designed to maximize overlap between any potential epitope length sequence extract from a natural antigen sequence. The disclosed method, thus, allows one to maximize the number of potential natural epitopes that are mimicked in a resultant vaccine sequence. Various representative HIV vaccine sequences have been generated and are disclosed herein.
摘要翻译：本文公开了产生疫苗序列的新方法，其保留来自输入序列库的氨基酸或核苷酸的连续表位长度延伸。该方法产生连续的逐步表位共有，其一起提供单个全局优化的序列。设计末端序列以使来自天然抗原序列的任何潜在表位长度序列提取物之间的重叠最大化。因此，所公开的方法允许最大化在所得疫苗序列中模拟的潜在天然表位的数量。已经产生了各种代表性的HIV疫苗序列并且在本文中公开。

3. 发明申请

WO2006086357A3 ADENOVIRUS SEROTYPE 36 VECTORS, NUCLEIC ACID AND VIRUSES PRODUCED THEREBY 审中-公开
标题翻译： ADENOVIRUS SEROTYPE 36载体，生产的核酸和病毒
公开(公告)号：WO2006086357A3
公开(公告)日：2007-02-01
申请号：PCT/US2006004213
申请日：2006-02-06
申请人： MERCK & CO INC , BETT ANDREW J , CASIMIRO DANILO R , SHIVER JOHN W , EMINI EMILIO A , CHASTAIN MICHAEL , KASLOW DAVID C
发明人： BETT ANDREW J , CASIMIRO DANILO R , SHIVER JOHN W , EMINI EMILIO A , CHASTAIN MICHAEL , KASLOW DAVID C
IPC分类号： C12N15/09 , C12N15/63
CPC分类号： A61K39/21 , A61K39/12 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N15/86 , C12N2710/10321 , C12N2710/10343 , C12N2740/16134 , C12N2740/16234 , C12N2740/16334
摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g, fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication-defective adenovirus of serotype 36, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for delivery and expression of heterologous genes are provided.
摘要翻译：腺病毒血清型的自然向性不同。已经发现各种各样的腺病毒血清型至少在其衣壳蛋白（例如五邻体和六邻体蛋白质），负责细胞结合的蛋白质（例如纤维蛋白质）和参与腺病毒复制的蛋白质方面不同。血清型中的向性和衣壳蛋白的这种差异导致了许多研究工作，旨在通过修饰衣壳蛋白来重新定向腺病毒向性。本发明绕过这样的衣壳蛋白修饰的要求，因为它呈现血清型36的重组，复制缺陷型腺病毒，罕见的腺病毒血清型，以及用于产生替代重组腺病毒的方法。另外，提供了使用重组腺病毒递送和表达异源基因的方法。

4. 发明申请

WO2006086284A9 ADENOVIRUS SEROTYPE 26 VECTORS, NUCLEIC ACID AND VIRUSES PRODUCED THEREBY 审中-公开
标题翻译： ADENOVIRUS SEROTYPE 26载体，生产的核酸和病毒
公开(公告)号：WO2006086284A9
公开(公告)日：2011-12-29
申请号：PCT/US2006004060
申请日：2006-02-07
申请人： MERCK & CO INC , BETT ANDREW J , CASIMIRO DANILO R , SHIVER JOHN W , EMINI EMILIO A , CHASTAIN MICHAEL , KASLOW DAVID C
发明人： BETT ANDREW J , CASIMIRO DANILO R , SHIVER JOHN W , EMINI EMILIO A , CHASTAIN MICHAEL , KASLOW DAVID C
IPC分类号： C12Q1/70
CPC分类号： C12N15/86 , A61K39/12 , A61K39/21 , A61K2039/5256 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N7/00 , C12N2710/10321 , C12N2710/10343 , C12N2740/16134 , C12N2740/16234 , C12N2740/16334
摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g., fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication-defective adenovirus of serotype 26, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for delivery and expression of heterologous genes are provided.

5. 发明申请

WO2006020480A3 ADENOVIRAL VECTOR COMPOSITIONS 审中-公开
标题翻译：腺病毒载体组合物
公开(公告)号：WO2006020480A3
公开(公告)日：2006-11-23
申请号：PCT/US2005027658
申请日：2005-08-05
申请人： MERCK & CO INC , EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , BETT ANDREW J
发明人： EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , BETT ANDREW J
IPC分类号： C12N15/00 , A61K39/12 , A61K49/00 , C12N7/00
CPC分类号： C12N15/86 , A61K39/12 , A61K39/21 , A61K48/00 , A61K48/0083 , A61K2039/53 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N7/00 , C12N2710/10343 , C12N2740/16134 , C12N2740/16334
摘要： Applicants disclose herein novel methods, vectors, and vector compositions for improving the efficiency of adenoviral vectors in the delivery and expression of heterologous nucleic acid encoding a polypeptide(s) (e.g, a protein or antigen) of interest. Adenoviral infection is quite common in the general population, and a large percentage of people have neutralizing antibodies to the more prevalent adenoviral serotypes. Such pre-existing anti-adenoviral immunity can dampen or possibly abrogate the effectiveness of this virus for the delivery and expression of heterologous proteins or antigens. The method taught herein functions to offset pre-existing immunity through the delivery of the protein or antigen by a cocktail of at least two adenoviral serotypes. Utilizing a composition of at least two adenoviral serotypes in this manner has been found to increase the effectiveness of adenoviral administration. Adenoviral vectors of utility in the elicitation of an immune response against Human Immunodeficiency Virus ("HIV") are also disclosed.
摘要翻译：申请人在此公开用于提高腺病毒载体在递送和表达编码感兴趣的多肽（例如，蛋白质或抗原）的异源核酸的表达中的效率的新颖方法，载体和载体组合物。腺病毒感染在普通人群中相当常见，并且大部分人具有针对更普遍的腺病毒血清型的中和抗体。这种预先存在的抗腺病毒免疫力可抑制或可能消除该病毒对异源蛋白质或抗原递送和表达的有效性。本文教导的方法用于通过由至少两种腺病毒血清型的混合物递送蛋白质或抗原来抵消预先存在的免疫性。已经发现以这种方式利用至少两种腺病毒血清型的组合物可以增加腺病毒给药的有效性。也公开了用于引发针对人类免疫缺陷病毒（“HIV”）的免疫应答的腺病毒载体。

6. 发明申请

WO2004018627A3 METHODS FOR PROPAGATING ADENOVIRUS AND VIRUS PRODUCED THEREBY 审中-公开
标题翻译：传播由其产生的腺病毒和病毒的方法
公开(公告)号：WO2004018627A3
公开(公告)日：2004-09-02
申请号：PCT/US0326145
申请日：2003-08-21
申请人： MERCK & CO INC , BETT ANDREW J , CHASTAIN MICHAEL , SANDIG VOLKER , EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , KASLOW DAVID C , MORSY MANAL
发明人： BETT ANDREW J , CHASTAIN MICHAEL , SANDIG VOLKER , EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , KASLOW DAVID C , MORSY MANAL
IPC分类号： A61K39/21 , A61K48/00 , C07K14/16 , C12N7/00 , C12N7/01 , C12N15/00 , C12N15/09 , C12N15/63 , C12N15/70 , C12N15/74 , C12N15/861 , C12Q1/68
CPC分类号： C12N15/86 , A61K39/12 , A61K39/21 , A61K48/00 , A61K2039/5256 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/57 , C07K14/005 , C12N7/00 , C12N2710/10343 , C12N2740/16122 , C12N2740/16134 , C12N2740/16234 , C12N2810/6018
摘要： Various methods for propagating and rescuing multiple serotypes of replication-defective adenovirus in a single adenoviral E1-complementing cell line are disclosed. Typically, replication-defective adenovirus vectors propagate only in cell lines which express E1 proteins of the same serotype or subgroup as the vector. The disclosed methods offer the ability to propagate vectors derived from multiple adenoviral serotypes in a single production cell line which expresses E1 proteins from a single serotype. Propagation in this manner is accomplished by providing all or a portion of an E4 region in cis within the genome of the replication-defective adenovirus. The added E4 region or portion thereof is cloned from a virus of the same or highly similar serotype as that of the E1 gene product(s) of the complementing cell line. Interaction between the expressed E1 of the cell line and the heterologous E4 of the replication-defective adenoviral vectors enables their propagation and rescue. The invention bypasses a need in the art to customize specific cell lines to the serotype or subgroup of the adenoviral vector being propagated and enables one to easily and rapidly develop alternative adenoviral serotypes as gene delivery vectors for use as vaccines or as a critical component in gene therapy.
摘要翻译：公开了在单一腺病毒E1补体细胞系中繁殖和拯救复制缺陷型腺病毒的多种血清型的各种方法。通常，复制缺陷型腺病毒载体仅在表达与载体相同的血清型或亚组的E1蛋白的细胞系中增殖。所公开的方法提供了在表达来自单一血清型的E1蛋白的单一生产细胞系中繁殖衍生自多种腺病毒血清型的载体的能力。以这种方式繁殖是通过在复制缺陷型腺病毒的基因组中提供全部或部分顺式E4区域来完成的。添加的E4区或其部分从与补体细胞系的E1基因产物相同或高度相似的血清型的病毒克隆。细胞系的表达E1与复制缺陷型腺病毒载体的异源E4之间的相互作用使得它们能够繁殖和拯救。本发明绕过了本领域的需要，以定制正在繁殖的腺病毒载体的血清型或亚型的特定细胞系，并且使人们能够容易且快速地开发替代的腺病毒血清型作为基因递送载体用作疫苗或作为基因中的关键组分治疗。

7. 发明专利

CA2681579A1 BROADLY REPRESENTATIVE ANTIGEN SEQUENCES AND METHOD FOR SELECTION 未知
公开(公告)号：CA2681579A1
公开(公告)日：2008-10-09
申请号：CA2681579
申请日：2008-03-26
申请人： MERCK & CO INC
发明人： SHIVER JOHN W , CONDRA JON H , FINNEFROCK ADAM C , CASIMIRO DANILO R , BETT ANDREW J
IPC分类号： G06G7/48 , C12Q1/00 , C12Q1/68 , G06F19/22
摘要： A novel method for generating vaccine sequences is disclosed herein that preserves contiguous epitope length stretches of amino acids or nucleotides from an input pool of sequences. The method generates continuous, stepwise e pitope consensus that together provides for a single globally optimized sequ ence. The end sequences are designed to maximize overlap between any potenti al epitope length sequence extract from a natural antigen sequence. The disc losed method, thus, allows one to maximize the number of potential natural e pitopes that are mimicked in a resultant vaccine sequence. Various represent ative HIV vaccine sequences have been generated and are disclosed herein.

8. 发明专利

CA2518926A1 ADENOVIRUS SEROTYPE 24 VECTORS, NUCLEIC ACIDS AND VIRUS PRODUCED THEREBY 未知
公开(公告)号：CA2518926A1
公开(公告)日：2004-09-30
申请号：CA2518926
申请日：2003-08-21
申请人： MERCK & CO INC
发明人： SHIVER JOHN W , MORSY MANAL A , EMINI EMILIO A , BETT ANDREW J , CASIMIRO DANILO R , CHASTAIN MICHAEL , KASLOW DAVID C
IPC分类号： A61K39/00 , C07K14/16 , C12N7/01 , C12N15/861 , C12N7/00
摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g. , penton-base and hexon proteins), proteins responsible for cell binding (e.g. , fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to the man y research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication- defective adenovirus of serotype 24, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for the delivery and expression of exogenous genes are provided.

9. 发明专利

AU779951B2 Polynucleotide vaccines expressing codon optimized HIV-1 pol and modified HIV-1 pol 未知
公开(公告)号：AU779951B2
公开(公告)日：2005-02-24
申请号：AU2585801
申请日：2000-12-21
申请人： MERCK & CO INC
发明人： SHIVER JOHN W , PERRY HELEN C , CASIMIRO DANILO R , FU TONG-MING
IPC分类号： C12N15/09 , A61K39/00 , A61K48/00 , A61P31/18 , C07K14/16 , C12Q1/70

10. 发明专利

AU2003268145A1 METHODS FOR PROPAGATING ADENOVIRUS AND VIRUS PRODUCED THEREBY 未知
公开(公告)号：AU2003268145A1
公开(公告)日：2004-03-11
申请号：AU2003268145
申请日：2003-08-21
申请人： MERCK & CO INC
发明人： BETT ANDREW J , CHASTAIN MICHAEL , SANDIG VOLKER , EMINI EMILIO A , SHIVER JOHN W , CASIMIRO DANILO R , KASLOW DAVID C , MORSY MANAL
IPC分类号： A61K39/21 , A61K48/00 , C07K14/16 , C12N7/00 , C12N7/01 , C12N15/00 , C12N15/09 , C12N15/63 , C12N15/70 , C12N15/74 , C12N15/861 , C12Q1/68

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