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1. 发明申请

WO2006091798A3 VACCINES AND METHODS FOR PREVENTION AND TREATMENT OF DRUG-RESISTANT HIV-1 AND HEPATITIS B VIRUS 审中-公开
标题翻译：预防和治疗耐药性HIV-1和乙型肝炎病毒的疫苗和方法
公开(公告)号：WO2006091798A3
公开(公告)日：2007-07-12
申请号：PCT/US2006006563
申请日：2006-02-22
申请人： US GOV HEALTH & HUMAN SERV , CATANZARO ANDREW , YARCHOAN ROBERT , BERZOFSKY JAY A , OKAZAKI TAKAHIRO , SNYDER JAMES T II , BRODER SAMUEL
发明人： CATANZARO ANDREW , YARCHOAN ROBERT , BERZOFSKY JAY A , OKAZAKI TAKAHIRO , SNYDER JAMES T II , BRODER SAMUEL
IPC分类号： A61K39/21 , A61K31/00 , A61K39/12 , A61K39/29 , C07K14/02 , C07K14/16 , C07K14/18
CPC分类号： A61K39/00 , A61K2039/57 , C07K14/005 , C12N2710/16722 , C12N2730/10122 , C12N2740/16222 , C12N2770/24222
摘要： The present invention provides methods for lowering a viral load of a virus resistant to an antiviral drug by inducing cytotoxic T lymphocytes (CTL) to recognize a predetermined mutated epitope within a viral protein of the drug-resistant virus. CTLs are induced by immunizing a host with a peptide comprising the predetermined mutation. The immunostimulating peptide may be further improved by epitope-enhancement for inducing specific CTLs. The antiviral protection against drug-resistant virus shown by compositions of the present invention and mediated by human HLA-restricted CTL has not been previously achieved.
摘要翻译：本发明提供了通过诱导细胞毒性T淋巴细胞（CTL）来识别抗药性病毒的病毒蛋白质内的预定的突变表位来降低对抗病毒药物具有抗性的病毒的病毒载量的方法。通过用包含预定突变的肽免疫宿主诱导CTL。可以通过用于诱导特异性CTL的表位增强来进一步改善免疫刺激肽。由本发明组合物显示并由人HLA限制性CTL介导的抗药性病毒的抗病毒保护尚未获得。

2. 发明申请

WO2005111065A3 EPITOPE-ENHANCEMENT OF A HUMAN CD4 HIV EPITOPE 审中-公开
标题翻译：人类CD4 HIV外显子的抗体增强
公开(公告)号：WO2005111065A3
公开(公告)日：2006-03-30
申请号：PCT/US2005014569
申请日：2005-04-27
申请人： US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , OKAZAKI TAKAHIRO
发明人： BERZOFSKY JAY A , OKAZAKI TAKAHIRO
IPC分类号： C07K14/16 , A61K39/21 , A61P31/18 , C07K14/155
CPC分类号： C07K14/005 , A61K2039/5154 , A61K2039/5158 , A61K2039/57 , C12N2740/16122 , C12N2740/16222 , C12N2740/16322
摘要： Virus-specific CD4 + T cell help and CD8 + cytotoxic T cell responses are critical for the maintenance of effective immunity in chronic viral infections. The importance of the CD4 + T cells has been documented in HIV infection. A T1-specific CD4 + T cell line from a healthy volunteer immunized with a canarypox vector expressing gpl20 has been developed. The cell line was restricted to DR13, which is common in the U.S. in both Caucasians and African-Americans and is one of the major haplotypes in Africans. Amino acid substitutions in the T1 epitope were made to induce a stronger epitope-specific CD4 + T cell response than the original epitope resulting in an improved CD4 epitope. A polypeptide comprising the enhanced CD4 epitope can be used as a component in compositions either alone or in combination with other adjuvants and other immunogenic compositions to induce a more effective immune response to HIV infection.
摘要翻译：病毒特异性CD4 + T细胞帮助和CD8 +细胞毒性T细胞应答对于维持慢性病毒感染中的有效免疫是至关重要的。在HIV感染中已经记录了CD4 + T细胞的重要性。已经开发了用表达gp120的金丝细胞病毒载体免疫的健康志愿者的T1特异性CD4 + T细胞系。细胞系限于DR13，这是美国在高加索人和非洲裔美国人中常见的，是非洲人的主要单倍型之一。使得T1表位中的氨基酸取代引起比原始表位更强的表位特异性CD4 + T细胞应答，导致改善的CD4表位。包含增强的CD4表位的多肽可以单独使用或与其它佐剂和其它免疫原性组合物组合用作组合物，以诱导对HIV感染的更有效的免疫应答。

3. 发明申请

WO2004092201A3 ENHANCED HIV-1 VACCINES AND METHODS FOR THEIR USE 审中-公开
标题翻译：增强的HIV-1疫苗及其使用方法
公开(公告)号：WO2004092201A3
公开(公告)日：2004-12-02
申请号：PCT/US2004009617
申请日：2004-03-29
申请人： US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , OKAZAKI TAKAHIRO
发明人： BERZOFSKY JAY A , OKAZAKI TAKAHIRO
IPC分类号： A61K39/21 , A61K39/385 , C07K20060101 , C07K14/16
CPC分类号： C12N9/1276 , A61K39/00 , A61K39/12 , A61K39/21 , A61K39/385 , A61K2039/5158 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/55522 , A61K2039/55566 , A61K2039/57 , A61K2039/6018 , A61K2039/645 , C07K14/005 , C12N7/00 , C12N2740/16222 , C12N2740/16234
摘要： ENHANCED HIV-1 VACCINES AND METHODS FOR THEIR USE ABSTRACT The present invention provides peptides and proteins for use in second generation HIV vaccines and as diagnostic tools in the treatment and control of HIV infection. The antiviral protection shown by compositions of the present invention has not been previously achieved with an HLA epitope-enhanced vaccine. These findings define a critical balance between MHC affinity and receptor crossreactivity required for effective epitope enhancement and also demonstrate construction and efficacy of such a component of a new generation vaccine.
摘要翻译：增强的HIV-1疫苗及其使用方法摘要本发明提供了用于第二代HIV疫苗的肽和蛋白质，并作为治疗和控制HIV感染的诊断工具。用本发明的组合物显示的抗病毒保护以前没有用HLA表位增强的疫苗实现。这些发现确定了有效表位增强所需的MHC亲和力与受体交叉反应性之间的关键平衡，并且还证明了新一代疫苗的这种组分的构建和功效。

4. 发明申请

WO2009088401A3 IMMUNOSTIMULATORY COMBINATIONS OF TLR3 LIGANDS WITH TLR2 AND/OR TLR9 AGONISTS AND METHODS OF USE 审中-公开
标题翻译： TLR3配体与TLR2和/或TLR9激动剂的免疫组化联合及其使用方法
公开(公告)号：WO2009088401A3
公开(公告)日：2009-10-15
申请号：PCT/US2008011236
申请日：2008-09-24
申请人： US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , ZHU QING
发明人： BERZOFSKY JAY A , ZHU QING
IPC分类号： A61K39/00
CPC分类号： A61K39/39 , A61K39/21 , A61K2039/55516 , A61K2039/55561 , A61K2039/57 , C12N7/00 , C12N2740/16034
摘要： The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.
摘要翻译：本发明提供了TLR配体的免疫刺激组合以及治疗和/或预防方法，其包括对受试者施用免疫刺激组合。通常，与其它免疫刺激组合和/或组合物相比，本文所述的免疫刺激组合可以提供增加的免疫应答。

5. 发明申请

WO02055100A2 METHOD AND COMPOSITION FOR ENHANCING AN IMMUNE RESPONSE 审中-公开
标题翻译：增强免疫反应的方法和组合
公开(公告)号：WO02055100A2
公开(公告)日：2002-07-18
申请号：PCT/US0151339
申请日：2001-10-22
申请人： INST GENETICS LLC , US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , TERABE MASAKI , DONALDSON DEBRA D , MATSUI SO , NOBEN-TRAUTH NANCY , PAUL WILLIAM E
发明人： BERZOFSKY JAY A , TERABE MASAKI , DONALDSON DEBRA D , MATSUI SO , NOBEN-TRAUTH NANCY , PAUL WILLIAM E
IPC分类号： A61K47/34 , A61K38/00 , A61K38/17 , A61K39/00 , A61K39/39 , A61K39/395 , A61K45/00 , A61K48/00 , A61P31/12 , A61P31/14 , A61P31/18 , A61P31/20 , A61P35/00 , A61P35/02 , A61P37/04 , C07K14/54 , C07K16/24 , C07K16/28
CPC分类号： C07K16/244 , A61K38/1793 , A61K38/208 , A61K39/39 , A61K2039/505 , A61K2039/55516 , A61K2039/55538 , C07K16/2812 , C07K2319/30 , A61K2300/00
摘要： Provided is a method and composition for enhancing an immune response in a subject by administering to the subject an inhibitor of IL-13 or an inhibitor of an NK-T cell to the subject. The method can be used to prevent growth of a tumor in the subject, e.g., to inhibit tumor recurrence or metastasis. The method can also be used to enhance a response to a vaccine in a subject.
摘要翻译：本发明提供了一种通过向受试者施用IL-13抑制剂或NK-T细胞抑制剂来对受试者增强受试者的免疫应答的方法和组合物。该方法可用于预防受试者中肿瘤的生长，例如抑制肿瘤复发或转移。该方法还可用于增强对受试者中疫苗的反应。

6. 发明申请

WO2004037209A3 METHODS TO PREVENT TUMOR RECURRENCE BY BLOCKADE OF TGF-beta 审中-公开
标题翻译：通过阻断TGF-β预防肿瘤复发的方法
公开(公告)号：WO2004037209A3
公开(公告)日：2004-11-25
申请号：PCT/US0334023
申请日：2003-10-24
申请人： US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , TERABE MASAKI , MATSUI SO
发明人： BERZOFSKY JAY A , TERABE MASAKI , MATSUI SO
IPC分类号： A61K38/00 , C07K16/22 , A61K39/395
CPC分类号： G01N33/74 , A61K2039/505 , C07K16/22 , C07K2317/76 , G01N33/5011 , G01N33/5041 , G01N33/5047 , G01N2333/495
摘要： Methods are provided herein to prevent a tumor recurrence in a subject, involving administering to the subject an agent that blocks the TGF-beta signaling pathway. In one embodiment, the agent inhibits the immunosuppressive effects of TGF-beta. Also provided is a method of enhancing an immune respond in a subject to inhibit recurrence of a tumor by administering an agent which blocks the TGF-beta signaling pathway. A method of enhancing the activity of an immune cell to inhibit recurrence of a tumor by contacting a TGF-beta receptor-expressing cell with an agent which blocks the TGF-beta signaling pathway is also provided, as are methods of screening for an agent that inhibits or measurably reduces the recurrence of a tumor.
摘要翻译：本文提供了用于预防受试者肿瘤复发的方法，涉及给受试者施用阻断TGF-β信号传导途径的药剂。在一个实施方案中，所述药剂抑制TGF-β的免疫抑制作用。还提供了通过施用阻断TGF-β信号传导途径的试剂来增强受试者中的免疫应答以抑制肿瘤复发的方法。还提供了通过使TGF-β受体表达细胞与阻断TGF-β信号传导途径的试剂接触来增强免疫细胞活性以抑制肿瘤复发的方法，如筛选抑制或可测量地减少肿瘤的复发。

7. 发明申请

WO2006089251A3 SYNERGISTIC EFFECT OF TGF-ß BLOCKADE AND IMMUNOGENIC AGENTS ON TUMORS 审中-公开
标题翻译： TGF-β片段和免疫原性对肿瘤的协同作用
公开(公告)号：WO2006089251A3
公开(公告)日：2006-12-28
申请号：PCT/US2006005888
申请日：2006-02-16
申请人： US GOV HEALTH & HUMAN SERV , TERABE MASAKI , TAKAKU SHUN , BERZOFSKY JAY A
发明人： TERABE MASAKI , TAKAKU SHUN , BERZOFSKY JAY A
IPC分类号： A61K39/395 , A61K39/00 , A61K39/12 , A61K41/00 , A61P35/00 , A61P35/02 , A61P35/04 , A61P37/04 , C07K14/025 , C07K16/22
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/12 , A61K39/3955 , A61K39/39558 , A61K2039/5152 , A61K2039/55516 , A61K2039/55522 , A61K2039/55566 , A61K2039/585 , C07K16/22 , C12N2710/20022 , C12N2710/20034 , A61K2300/00
摘要： Methods are provided herein for synergistically affecting tumor growth in a subject, involving the administration to the subject of an agent that blocks the TGF- ß signaling pathway in combination with an immunogenic agent. The agent that blocks the TGF-ß signaling pathway is believed to inhibit the immunosuppressive effects of TGF-ß, while the immunogenic agent is believed to enhance an immune response. Surprisingly, the combination of such elements produces a synergistic effect. In one embodiment, the administration of the IDl 1.16 anti-TGF-ß antibody in combination with the human papilloma virus E7(49-57) peptide enhances tumor regression and tumor-specific CTL response in the subject. In another embodiment, the administration of the IDl 1.16 anti-TGF-ß antibody in combination with irradiated CT26 cells enhances tumor regression in the subject. The method of administering the combination of agents to the subject is more effective than the administration of each agent individually, or the sum of their individual effects.
摘要翻译：本文提供了协同地影响受试者的肿瘤生长的方法，涉及向受试者施用阻断TGF-β信号通路的试剂与免疫原性试剂的组合。认为阻断TGF-β信号通路的药物可以抑制TGF-β的免疫抑制作用，而免疫原性药物被认为可增强免疫反应。令人惊讶的是，这些元素的组合产生协同效应。在一个实施方案中，ID11.16抗TGF-β抗体与人乳头状瘤病毒E7（49-57）组合的施用增强受试者的肿瘤消退和肿瘤特异性CTL应答。在另一个实施方案中，ID11.16抗TGF-β抗体与照射的CT26细胞的组合的施用增强了受试者的肿瘤消退。给予受试者的药物组合的方法比单独施用每种药剂或其各自作用的总和更有效。

8. 发明申请

WO02055100A9 Method and composition for inhibition of tumor growth and enhancing an immune response 审中-公开
标题翻译：用于抑制肿瘤生长和增强免疫应答的方法和组合物
公开(公告)号：WO02055100A9
公开(公告)日：2006-05-11
申请号：PCT/US0151339
申请日：2001-10-22
申请人： BERZOFSKY JAY A , TERABE MASAKI , DONALDSON DEBRA D , MATSUI SO , NOBEN-TRAUTH NANCY , PAUL WILLIAM E , INST GENETICS LLC , US GOV HEALTH & HUMAN SERV
发明人： BERZOFSKY JAY A , TERABE MASAKI , DONALDSON DEBRA D , MATSUI SO , NOBEN-TRAUTH NANCY , PAUL WILLIAM E
IPC分类号： A61K47/34 , A61K38/00 , A61K38/17 , A61K39/00 , A61K39/39 , A61K39/395 , A61K45/00 , A61K48/00 , A61P31/12 , A61P31/14 , A61P31/18 , A61P31/20 , A61P35/00 , A61P35/02 , A61P37/04 , C07K14/54 , C07K16/24 , C07K16/28
CPC分类号： C07K16/244 , A61K38/1793 , A61K38/208 , A61K39/39 , A61K2039/505 , A61K2039/55516 , A61K2039/55538 , C07K16/2812 , C07K2319/30 , A61K2300/00
摘要： Provided is a method and composition for enhancing an immune response in a subject by administering to the subject an inhibitor of IL-13 or an inhibitor of an NK-T cell to the subject. The method can be used to prevent growth of a tumor in the subject, e.g., to inhibit tumor recurrence or metastasis. The method can also be used to enhance a response to a vaccine in a subject.
摘要翻译：本发明提供了一种通过向受试者施用IL-13抑制剂或NK-T细胞抑制剂来增强受试者的免疫应答的方法和组合物。该方法可用于预防受试者中肿瘤的生长，例如抑制肿瘤复发或转移。该方法还可用于增强对受试者中疫苗的反应。

9. 发明申请

WO2009018429A2 TREATMENT OF CANCER VIA TARGETING OF IL-13 RECEPTOR-a2 审中-公开
标题翻译：通过IL-13受体-a2的靶向治疗癌症
公开(公告)号：WO2009018429A2
公开(公告)日：2009-02-05
申请号：PCT/US2008071736
申请日：2008-07-31
申请人： US GOV HEALTH & HUMAN SERV , STROBER WARREN , BERZOFSKY JAY A , FICHTNER-FEIGL STEFAN , KITANI ATSUSHI , FUSS IVAN J , TERABE MASAKI , MANNON PETER
发明人： STROBER WARREN , BERZOFSKY JAY A , FICHTNER-FEIGL STEFAN , KITANI ATSUSHI , FUSS IVAN J , TERABE MASAKI , MANNON PETER
IPC分类号： A61K39/395 , A61K38/17 , A61P35/00
CPC分类号： A61K31/00 , A61K38/1793 , A61K2039/505 , C07K16/241 , C12N15/1138 , C12N2310/13 , C12N2310/14
摘要： Disclsoed herein are compositions and methods for treating or preventing cancer involving the use of a TNF-alpha antagonist, an IL- 13Ra2 antagonist, and/or a AP-I antagonist.
摘要翻译：本文中所述的是用于治疗或预防涉及使用TNF-α拮抗剂，IL-13Ra2拮抗剂和/或AP-1拮抗剂的癌症的组合物和方法。

10. 发明申请

WO2005058944A3 IMMUNOGENIC PEPTIDES FRAGMENTS OF XAGE-1 审中-公开
标题翻译： XAGE-1免疫原性片段
公开(公告)号：WO2005058944A3
公开(公告)日：2006-01-05
申请号：PCT/US2004041639
申请日：2004-12-13
申请人： US GOV HEALTH & HUMAN SERV , BERZOFSKY JAY A , PASTAN IRA H , TERABE MASAKI
发明人： BERZOFSKY JAY A , PASTAN IRA H , TERABE MASAKI
IPC分类号： C07K14/47 , A61K38/17 , A61P35/00
CPC分类号： C07K7/06 , A61K39/0011 , A61K45/06 , C07K14/4748
摘要： XAGE-1 is a gene expressed in a number of important human cancers, including prostate cancer, lung cancer, breast cancer, ovarian cancer, glioblastoma, pancreatic cancer, and melanoma. It has now been discovered that peptides of fifty or fewer amino acids comprising the sequence X 1 X 2 X 3 PSAPSPX 4 (SEQ ID NO:5), where X 1 is any amino acid and is preferably G or Y; X 2 is selected from the group consisting of L, M, A, I, V, and T, with L and M being preferred; X 3 is a hydrophobic residue, M or A; and X 4 is V, M, L, A, I, or T, and is preferably V, bind to the HLA-A2 MHC class I molecule, and can be used to raise immune responses to XAGE-1-expressing cancers. In some embodiments, the P at position 7, the S at position 8, or the P at position 9, can be omitted to create a 9 amino acid peptide. The invention provides immunogenic peptides, nucleic acids encoding them, vectors comprising the nucleic acids, uses of the peptides and nucleic acids for manufacture of medicaments, methods of using the peptides and nucleic acids, and compositions of the peptides or nucleic acids in pharmaceutically acceptable carriers.
摘要翻译： XAGE-1是在许多重要的人类癌症中表达的基因，包括前列腺癌，肺癌，乳腺癌，卵巢癌，胶质母细胞瘤，胰腺癌和黑素瘤。现在已经发现，包含序列X 1，X 2，X 3，CPSPSPX 4的五十个或更少的氨基酸的肽， SUB（SEQ ID NO：5），其中X 1是任何氨基酸，优选为G或Y; X 2选自L，M，A，I，V和T，其中L和M是优选的; X 3是疏水残基M或A; 并且X 4是V，M，L，A，I或T，并且优选为V，结合HLA-A2 MHC I类分子，并且可用于提高对XAGE的免疫应答 -1表达的癌症。在一些实施方案中，可以省略位置7处的P，位置8处的S或位置9处的P，以产生9个氨基酸的肽。本发明提供免疫原性肽，编码它们的核酸，包含核酸的载体，肽和核酸用于制备药物的用途，使用肽和核酸的方法，以及肽或核酸在药学上可接受的载体中的组合物。

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