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1.发明申请IMMUNOGENIC POLYPEPTIDES HAVING AN IMMUNOGENIC SCAFFOLD PROTEIN AND A LOOP PEPTIDE, PRESENTING A 3074- OR 2219/2557- MONOCLONAL ANTIBODY-TARGETED EPITOPE, WHICH IS PRESENT IN THE HIV GP120 PROTEIN 有权具有免疫原性SCAFFOLD蛋白和环腺苷的免疫多肽具有存在于HIV GP120蛋白中的3074-或2219 / 2557-单克隆抗体靶向抗原决定簇公开(公告)号：US20130287804A1
公开(公告)日：2013-10-31
申请号：US13876918
申请日：2011-09-28
申请人： Timothy Cardozo , Xian-peng Kong , Susan Zolla-Pazner , Abraham Pinter , Chavdar Krachmarov , Shan Lu , Shixia Wang , Maxim Totrov
发明人： Timothy Cardozo , Xian-peng Kong , Susan Zolla-Pazner , Abraham Pinter , Chavdar Krachmarov , Shan Lu , Shixia Wang , Maxim Totrov
IPC分类号： C07K14/00
CPC分类号： C07K14/001 , A61K39/12 , A61K39/21 , A61K2039/53 , A61K2039/55555 , A61K2039/6037 , C07K7/08 , C07K14/005 , C07K14/245 , C07K14/28 , C12N2740/16034
摘要： The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.
摘要翻译： 本发明涉及重组免疫原性多肽。 多肽包括插入免疫原性支架蛋白的环肽。 环多肽具有呈现HIV gp120蛋白的3074 mAb或2219/2557 mAb靶向表位的氨基酸序列，而不是HIV gp120蛋白的其他已知表位。 当用作免疫原时，多肽诱导抗体应答，其分别以与针对3074mAb-或2219 / 2557mAb靶向表位观察到的模式相似的方式中和异源HIV-1病毒。 还公开了含有免疫原性多肽的药物组合物及其制备和使用方法。
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2.发明授权Immunogenic polypeptides comprising a modified loop peptide presenting the HIV-1 GP120 3074 mAb epitope and scaffold proteins containing said peptide 有权包含呈递HIV-1 GP120 3074mAb表位的修饰环肽和含有所述肽的支架蛋白的免疫原性多肽公开(公告)号：US09534020B2
公开(公告)日：2017-01-03
申请号：US13876918
申请日：2011-09-28
申请人： Timothy Cardozo , Xiang-peng Kong , Susan Zolla-Pazner , Shan Lu , Shixia Wang , Maxim Totrov
发明人： Timothy Cardozo , Xiang-peng Kong , Susan Zolla-Pazner , Shan Lu , Shixia Wang , Maxim Totrov
IPC分类号： C07K14/005 , C07K7/08 , A61K39/21 , C07K14/00 , C07K14/245 , C07K14/28 , A61K39/12 , A61K39/00
CPC分类号： C07K14/001 , A61K39/12 , A61K39/21 , A61K2039/53 , A61K2039/55555 , A61K2039/6037 , C07K7/08 , C07K14/005 , C07K14/245 , C07K14/28 , C12N2740/16034
摘要： The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.
摘要翻译： 本发明涉及重组免疫原性多肽。 多肽包括插入免疫原性支架蛋白的环肽。 环多肽具有呈现HIV gp120蛋白的3074 mAb或2219/2557 mAb靶向表位的氨基酸序列，而不是HIV gp120蛋白的其他已知表位。 当用作免疫原时，多肽诱导抗体应答，其分别以与针对3074mAb-或2219 / 2557mAb靶向表位观察到的模式相似的方式中和异源HIV-1病毒。 还公开了含有免疫原性多肽的药物组合物及其制备和使用方法。
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3.发明授权Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies 有权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
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）。
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4.发明授权Recombinant HIV-1 gp120 immunogen with three different V3 loops from viruses of different clades 有权重组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
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。
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5.发明申请Recombinant HIV-1 gp120 Immunogen with Three Different V3 Loops from Viruses of Different Clades 有权重组HIV-1 gp120免疫原与不同来源的病毒的三个不同的V3环公开(公告)号：US20080095791A1
公开(公告)日：2008-04-24
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
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。
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6.发明授权Method for determining co-receptor selectivity of Human Immunodeficiency Virus-1 有权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
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。
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7.发明授权公开(公告)号：US09611294B2
公开(公告)日：2017-04-04
申请号：US13612300
申请日：2012-09-12
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.
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8.发明申请Method for determining co-receptor selectivity of human immunodeficiency virus-1 有权确定人类免疫缺陷病毒-1的共受体选择性的方法1公开(公告)号：US20070072200A1
公开(公告)日：2007-03-29
申请号：US11369010
申请日：2006-03-07
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。
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9.发明申请CONSTRAINED HIV V3 LOOP PEPTIDES AS NOVEL IMMUNOGENS AND RECEPTOR ANTAGONISTS 审中-公开受约束的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
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。
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10.发明申请IMMUNODOMINANT MYCOBACTERIUM TUBERCULOSIS PEPTIDES FROM CELL WALL PROTEINS FOR EARLY DIAGNOSIS AND IMMUNIZATION 有权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。
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