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1. 发明申请

US20100278853A1 CONSTRAINED HIV V3 LOOP PEPTIDES AS NOVEL IMMUNOGENS AND RECEPTOR ANTAGONISTS 审中-公开
标题翻译：受约束的HIV V3环肽作为免疫调节剂和受体拮抗剂
公开(公告)号：US20100278853A1
公开(公告)日：2010-11-04
申请号：US12579938
申请日：2009-10-15
申请人： Jacob Anglister , Michal Sharon , Matthieu Schapira , Susan Zolla-Pazner , Osnat Rosen
发明人： Jacob Anglister , Michal Sharon , Matthieu Schapira , Susan Zolla-Pazner , Osnat Rosen
IPC分类号： A61K39/21 , C07K7/08 , C07K7/64 , C07K14/00 , A61P31/18 , C07K16/10
CPC分类号： G01N33/56988 , A61K39/00 , C07K14/005 , C12N2740/16122 , G01N2333/16 , G01N2333/715 , G01N2500/02
摘要： The present invention provides constrained peptides and other organic molecules, that mimic the three dimensional characteristics of the HIV-1 V3 loop peptide when bound by a highly potent human neutralizing monoclonal antibody specific for a V3 conformational epitope, which structure is determined by NMR. Methods for screening for, and designing such molecules are disclosed. These molecules are useful as immunogens for inducing broadly-neutralizing antibodies against HIV-1 as well as antagonists for inhibiting the binding of HIV-1 to the relevant co-receptors, and may therefore be used in method of preventing or treating HIV-1 infection and disease.
摘要翻译：本发明提供受约束的肽和其它有机分子，当通过对V3构象表位特异性的高效人中和单克隆抗体结合时，模拟HIV-1 V3环肽的三维特征，该结构通过NMR测定。公开了筛选和设计这些分子的方法。这些分子可用作诱导针对HIV-1的广泛中和抗体的免疫原，以及用于抑制HIV-1与相关辅助受体结合的拮抗剂，因此可用于预防或治疗HIV-1感染的方法和疾病。

2. 发明申请

US20080206264A1 Constrained Hiv V3 Loop Peptides as Novel Immunogens and Receptor Antagonists 审中-公开
标题翻译：约束Hiv V3环肽作为新型免疫原和受体拮抗剂
公开(公告)号：US20080206264A1
公开(公告)日：2008-08-28
申请号：US10544399
申请日：2004-02-04
申请人： Jacob Anglister , Michal Sharon , Matthieu Schapira , Susan Zolla-Pazner , Osnat Rosen
发明人： Jacob Anglister , Michal Sharon , Matthieu Schapira , Susan Zolla-Pazner , Osnat Rosen
IPC分类号： A61K39/00 , C07K2/00 , C07K16/46 , A61P31/18 , G06F17/50 , C12N5/06 , G01N33/68
CPC分类号： G01N33/56988 , A61K39/00 , C07K14/005 , C12N2740/16122 , G01N2333/16 , G01N2333/715 , G01N2500/02
摘要： The present invention provides constrained peptides and other organic molecules, that mimic the three dimensional characteristics of the HIV-1 V3 loop peptide when bound by a highly potent human neutralizing monoclonal antibody specific for a V3 conformational epitope, which structure is determined by NMR. Methods for screening for, and designing such molecules are disclosed. These molecules are useful as immunogens for inducing broadly-neutralizing antibodies against HIV-1 as well as antagonists for inhibiting the binding of HIV-1 to the relevant co-receptors, and may therefore be used in method of preventing or treating HIV-1 infection and disease.
摘要翻译：本发明提供受约束的肽和其它有机分子，当通过对V3构象表位特异性的高效人中和单克隆抗体结合时，模拟HIV-1 V3环肽的三维特征，该结构通过NMR测定。公开了筛选和设计这些分子的方法。这些分子可用作诱导针对HIV-1的广泛中和抗体的免疫原，以及用于抑制HIV-1与相关辅助受体结合的拮抗剂，因此可用于预防或治疗HIV-1感染的方法和疾病。

3. 发明授权

US07638319B2 Method for determining co-receptor selectivity of Human Immunodeficiency Virus-1 有权
标题翻译：测定人类免疫缺陷病毒-1的共受体选择性的方法
公开(公告)号：US07638319B2
公开(公告)日：2009-12-29
申请号：US11369010
申请日：2006-03-07
申请人： Timothy Cardozo , Susan Zolla-Pazner
发明人： Timothy Cardozo , Susan Zolla-Pazner
IPC分类号： C12N7/00 , C12Q1/00
CPC分类号： C12Q1/703 , G06F19/16
摘要： Newly discovered structural characteristic of the gp120 V3 loop have resulted in a “rule” or algorithm, that is used in a method for determining whether a subject is infected with HIV-1 virus that expresses selectivity for CXCR4 or CCR5 chemokine receptors. A positively charged surface patch defined by V3 loop residues 11 and 24 or 25 at the base of the β-strands in the V3 loop and the homologous β2-β3 chemokine hairpin is responsible for CXCR4 receptor selection. Thus a method for detecting the presence of HIV-1 virus that is selective for X4-co-receptors in a subject infected with HIV-1 or suspected of being infected, from the amino acid sequence of at least a part of the HIV-1 gp120 V3 region peptide that includes residues 11, 24 and 25, or from the nucleotide sequence of a nucleic acid encoding said V3 region peptide, is disclosed.
摘要翻译：新发现的gp120 V3环的结构特征已经导致了一种“规则”或算法，用于确定受试者是否感染HIV-1病毒的方法，该HIV-1病毒表达对CXCR4或CCR5趋化因子受体的选择性。由V3环中的β链的碱基和同源的β2-β3趋化因子发夹的V3环残基11和24或25定义的带正电荷的表面贴片负责CXCR4受体选择。因此，从HIV-1的至少一部分的氨基酸序列中检测HIV-1感染HIV或HIV或被怀疑被感染的受试者中对X4-共受体有选择性的HIV-1病毒的存在的方法公开了包括残基11,24和25或来自编码所述V3区肽的核酸的核苷酸序列的gp120 V3区肽。

4. 发明授权

US08961987B2 Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies 有权
标题翻译：包含诱导广泛中和抗体的构象的HIV GP120 V3环的免疫原
公开(公告)号：US08961987B2
公开(公告)日：2015-02-24
申请号：US12195318
申请日：2008-08-20
申请人： Susan Zolla-Pazner , Miroslaw K. Gorny , Timothy J. Cardozo , Xiang-peng Kong , Ruben Abagyan , Maxim Totrov , Shan Lu , Abraham Pinter
发明人： Susan Zolla-Pazner , Miroslaw K. Gorny , Timothy J. Cardozo , Xiang-peng Kong , Ruben Abagyan , Maxim Totrov , Shan Lu , Abraham Pinter
IPC分类号： A61K39/21 , A61K39/00 , A61K38/00 , C07K14/005 , A61K38/03 , A61K38/16
CPC分类号： C07K14/005 , A61K38/03 , A61K38/16 , A61K39/00 , A61K39/12 , A61K39/21 , A61K2039/53 , A61K2039/545 , A61K2039/55555 , C07K2319/35 , C07K2319/55 , C12N2740/16122 , C12N2740/16134 , Y02A50/472
摘要： Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely related E. coli enterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.
摘要翻译：将HIV-1 V3环肽从病毒糖蛋白gp120插入到选定的免疫原性支架蛋白中导致重组多肽，其是有效的V3免疫原。 V3免疫原包括天然和共有的V3序列和环状和反向肽。优选的支架蛋白是霍乱毒素亚基B及其同系物，包括密切相关的大肠杆菌肠毒素。这样的免疫原性多肽诱导可以中和异源HIV-1亚型和菌株的V3表位特异性的广泛反应性抗gp120抗体。公开了这些多肽，其制备方法和诱导抗gp120（V3特异性）抗体的方法）。

5. 发明申请

US20110104194A1 IMMUNODOMINANT MYCOBACTERIUM TUBERCULOSIS PEPTIDES FROM CELL WALL PROTEINS FOR EARLY DIAGNOSIS AND IMMUNIZATION 有权
标题翻译：从细胞壁蛋白中免疫组织化学检测细胞膜蛋白，用于早期诊断和免疫
公开(公告)号：US20110104194A1
公开(公告)日：2011-05-05
申请号：US12988595
申请日：2009-04-20
申请人： Suman Laal , Susan Zolla-Pazner
发明人： Suman Laal , Susan Zolla-Pazner
IPC分类号： A61K39/04 , C07K7/08 , C07K7/06 , C07K19/00 , C07K14/35 , G01N33/68 , C12Q1/02 , A61P31/06 , A61P37/04
CPC分类号： G01N33/5695 , C07K14/35 , G01N2333/35 , G01N2469/20
摘要： A number of peptide epitopes and fragments from three Mycobacterium tuberculosis (Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.
摘要翻译：已经将来自三种结核分枝杆菌（Mtb）细胞壁蛋白质的许多肽表位和片段鉴定为在人类Mtb感染期间早期诱导抗体的早期抗原。蛋白质是脯氨酸 - 苏氨酸重复蛋白（PTRP），PE-PGRS51和LipC。这些肽单独或混合，或作为融合多肽或肽多聚体的部分，可用作抗原，用于通过检测针对这些蛋白质的早期抗体的存在来检测早期感染的血清学检测，从而允许早期诊断Mtb感染比以前可能通过常规手段。上述肽和其它基于肽的组合物也被用作包含在结核病疫苗中的免疫原。还提供了早期诊断Mtb感染和免疫受试者以预防或治疗Mtb感染和结核病的方法。

6. 发明申请

US20080279879A1 INDUCTION OF BROADLY REACTIVE NEUTRALIZING ANTIBODIES BY FOCUSING THE IMMUNE RESPONSE ON V3 EPITOPES OF THE HIV-1 gp120 ENVELOPE 审中-公开
标题翻译：通过对HIV-1 gp120环境V3病毒抗体的免疫反应诱导广泛的反应性中和抗体
公开(公告)号：US20080279879A1
公开(公告)日：2008-11-13
申请号：US11942634
申请日：2007-11-19
申请人： Susan Zolla-Pazner
发明人： Susan Zolla-Pazner
IPC分类号： A61K39/21 , A61P31/18
CPC分类号： A61K39/21 , A61K39/12 , A61K2039/53 , A61K2039/545 , A61K2039/55566 , A61K2039/575 , A61K2039/70 , C07K14/005 , C07K2319/00 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134
摘要： Compositions, kits and methods for boosting, or for priming and boosting, high titer broadly neutralizing cross-clade antibody responses focused on single HIV-1 neutralizing epitopes are disclosed. gp120 DNA plasmids comprising HIV env genes are used to prime the antibody response. Primed subjects are immunized with recombinant fusion proteins that comprise a “carrier” protein fusion partner, preferably a truncated form of the MuLV gp70 Env protein, and a desired HIV neutralizing epitopes. Preferred epitopes are epitopes of V3 from one or more HIV clades. Immune sera from such immunized subjects neutralized primary isolates from virus strains heterologous to those from which the immunogens were constructed. Neutralizing activity was primarily due to V3-specific antibodies and cross-clade neutralizing Abs were present. This approach results in more potent and broader neutralizing antibody levels, a result of “immunofocusing” the humoral immune response on neutralizing epitopes such as V3.
摘要翻译：公开了用于增强或用于引发和增强高滴度广泛中和的交叉进化枝抗体反应的组合物，试剂盒和方法，其集中在单个HIV-1中和表位上。使用包含HIV env基因的gp120 DNA质粒来引发抗体应答。用包含“载体”蛋白质融合配偶体，优选截短形式的MuLV gp70Env蛋白质和所需的HIV中和表位的重组融合蛋白免疫引导的受试者。优选的表位是来自一个或多个HIV进化枝的V3的表位。来自这些免疫受试者的免疫血清将来自与构建免疫原的病毒株异源的病原菌中和的初级分离物中和。中和活性主要是由于V3特异性抗体而存在交叉进化枝中和抗体。这种方法导致更有效和更广泛的中和抗体水平，这是中和表位如V3的“免疫聚焦”体液免疫应答的结果。

7. 发明授权

US06241986B1 Human monoclonal antibodies to the CD4-binding domain of HIV, uses thereof and synergistic neutralization of HIV 失效
标题翻译：针对HIV的CD4结合域的人单克隆抗体，其使用和HIV的协同中和
公开(公告)号：US06241986B1
公开(公告)日：2001-06-05
申请号：US08215395
申请日：1994-03-21
申请人： Susan Zolla-Pazner , Miroslaw K. Gorny , Sylwia Karwowska , Aby Buchbinder
发明人： Susan Zolla-Pazner , Miroslaw K. Gorny , Sylwia Karwowska , Aby Buchbinder
IPC分类号： A61K3942
CPC分类号： C07K16/1063 , A61K38/00 , C07K2317/34
摘要： Human monoclonal antibodies specific for the CD4-binding domain of HIV gp120 are useful in the neutralization of HIV and in the prevention of HIV infection and the treatment of a subject infected with HIV. Such antibodies and heterohybridomas producing them are disclosed. Synergistic mixtures of at least two human monoclonal antibodies specific for two different epitopes of gp120 are used to neutralize HIV, to prevent HIV infection and to treat a subject infected with HIV. In this synergistic mixture, one antibody has broad HIV group specificity, and is preferably specific for the CD4-binding domain. The other antibody is preferably specific for the V3 loop and has a range of neutralizing activity such that it neutralizes virus of the MN strain, MN-like families, and widely divergent HIV-1 isolates which are members of various V3 lop classes.
摘要翻译：对HIV gp120的CD4结合结构域特异的人单克隆抗体可用于HIV的中和和HIV感染的预防以及感染HIV的受试者的治疗。公开了这样的抗体和产生它们的异源杂交瘤。使用对gp120的两个不同表位特异的至少两种人单克隆抗体的协同混合物来中和HIV，以防止HIV感染并治疗感染HIV的受试者。在该协同混合物中，一种抗体具有广泛的HIV组特异性，并且优选对CD4结合结构域是特异性的。其它抗体优选对V3环具有特异性，并且具有一定范围的中和活性，使得其中和MN菌株，MN样家族的病毒和广泛分散的HIV-1分离物，其是各种V3 lop等级的成员。

8. 发明授权

US09611294B2 Peptides mimicking HIV-1 viral epitopes in the V2 loop for the GP120 surface envelope glycoprotein 有权
公开(公告)号：US09611294B2
公开(公告)日：2017-04-04
申请号：US13612300
申请日：2012-09-12
申请人： Timothy Cardozo , Xiangpeng Kong , Susan Zolla-Pazner
发明人： Timothy Cardozo , Xiangpeng Kong , Susan Zolla-Pazner
IPC分类号： C07K7/64 , A61K38/19 , A61K39/21 , A61K39/12 , C07K7/08 , C07K14/005 , C07K14/245 , C07K16/10 , C07K14/28 , G01N33/68 , G01N33/569 , A61K39/00
CPC分类号： C07K16/1063 , A61K38/19 , A61K39/12 , A61K39/21 , A61K2039/545 , A61K2039/6037 , A61K2039/64 , C07K7/08 , C07K7/64 , C07K14/005 , C07K14/245 , C07K14/28 , C07K2317/34 , C07K2317/76 , C07K2319/55 , C12N7/00 , C12N2740/16122 , C12N2740/16134 , C12N2799/023 , G01N33/56988 , G01N33/6854 , G01N2333/162 , G01N2469/20
摘要： The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

9. 发明授权

US07847085B2 Recombinant HIV-1 gp120 immunogen with three different V3 loops from viruses of different clades 有权
标题翻译：重组HIV-1 gp120免疫原与不同进化枝病毒的三个不同的V3环
公开(公告)号：US07847085B2
公开(公告)日：2010-12-07
申请号：US11772760
申请日：2007-07-02
申请人： Susan Zolla-Pazner , Shan Lu , Shixia Wang
发明人： Susan Zolla-Pazner , Shan Lu , Shixia Wang
IPC分类号： C07H21/04 , A61K39/21
CPC分类号： C07K14/005 , A61K39/12 , A61K39/21 , A61K2039/53 , A61K2039/545 , C07K2319/00 , C12N2740/16122 , C12N2740/16134
摘要： A novel immunogenic HIV-1 Env, particularly gp120, DNA construct is disclosed in which either the V1/V2 loop and the V4 loop, or all three variable loops, including V3, are replaced with a V3 sequence each of which is from a different viral isolate. Preferably, each replacement V3 loop is a consensus sequence of V3 of a different clade. Such constructs are useful as immunogens as each presents three independent V3 epitopes, so that the immunized subject generates a more broadly reactive neutralizing antibody response than with conventional gp120 or V3 DNA or polypeptide immunogens. Also disclosed are methods of using the DNA construct to immunize a mammal, preferably a human, particularly in a priming regiment in which the DNA immunogen is followed by administration of a V3 fusion protein boosting immunogen.
摘要翻译：公开了一种新型免疫原性HIV-1Env，特别是gp120，DNA构建体，其中V1 / V2环和V4环或所有三个可变环（包括V3）被V3序列替代，每个V3序列来自不同的病毒分离株。优选地，每个替换V3环是不同进化枝的V3的共有序列。这样的构建体可用作免疫原，因为每个呈现三个独立的V3表位，使得免疫受试者比常规gp120或V3 DNA或多肽免疫原产生更广泛的反应性中和抗体应答。还公开了使用DNA构建体免疫哺乳动物，优选人的方法，特别是在其中DNA免疫原之后是施用V3融合蛋白增强免疫原的引发团中。

10. 发明授权

US06245331B1 Early detection of mycobacterial disease 失效
标题翻译：早期发现分枝杆菌病
公开(公告)号：US06245331B1
公开(公告)日：2001-06-12
申请号：US09001984
申请日：1997-12-31
申请人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
发明人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
IPC分类号： A61K3940
CPC分类号： G01N33/5695 , C07K16/1289
摘要： A number of protein and glycoprotein antigens secreted by Mycobacterium. tuberculosis (Mt) have been identified as “early” Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof. For the first time, a surrogate marker is available for inexpensive screening of individuals at heightened risk for developing TB, in particular HIV-1 infected subjects and other immunocompromised individuals.
摘要翻译：许多由分枝杆菌分泌的蛋白质和糖蛋白抗原。在发现可检测的临床疾病之前，基于在感染Mt的受试者中存在的早期抗体，已经将结核病（Mt）鉴定为“早期”Mt抗原。这些早期的Mt抗原，特别是一种具有约5.2的pI约为5.2的88kDa分泌蛋白，存在于无脂质阿拉伯聚糖的培养滤液中，以Mt抗原85C为特征的蛋白质; 特征为Mt抗原MPT51的蛋白质，以Mt抗原MPT32为特征的糖蛋白; 和具有约5.1的pI的49kDa蛋白质可用于在受试者中早期，快速检测TB的免疫测定方法。还提供了用于检测早期Mt抗原，早期Mt抗体及其免疫复合物的抗原组合物，试剂盒和方法。第一次，替代标记可用于廉价筛选个体，发展结核病风险增加，特别是HIV-1感染的受试者和其他免疫受损的个体。

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