公开(公告)号：WO2019133842A1

公开(公告)日：2019-07-04

申请号：PCT/US2018/067913

申请日：2018-12-28

Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  JONES, Jennifer C. ,  WELSH, Joshua A. ,  MCKINNON, Katherine M. ,  BERZOFSKY, Jay A.

Inventor： JONES, Jennifer C. ,  WELSH, Joshua A. ,  MCKINNON, Katherine M. ,  BERZOFSKY, Jay A.

IPC: B01D15/38 ,  B01D15/34 ,  G01N33/533 ,  G01N33/538 ,  G01N33/545

CPC classification number: G01N33/545 ,  B01D15/34 ,  B01D15/3804 ,  B01D15/3847 ,  G01N33/533 ,  G01N33/538

Abstract: Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

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

Applicant: US GOV HEALTH & HUMAN SERV ,  BERZOFSKY JAY A ,  ZHU QING

Inventor： BERZOFSKY JAY A ,  ZHU QING

IPC: A61K39/00

CPC classification number: A61K39/39 ,  A61K39/21 ,  A61K2039/55516 ,  A61K2039/55561 ,  A61K2039/57 ,  C12N7/00 ,  C12N2740/16034

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2005111065A2

公开(公告)日：2005-11-24

申请号：PCT/US2005/014569

申请日：2005-04-27

Applicant: THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  BERZOFSKY, Jay, A. ,  OKAZAKI, Takahiro

Inventor： BERZOFSKY, Jay, A. ,  OKAZAKI, Takahiro

IPC: C07K14/155

CPC classification number: C07K14/005 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/57 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2740/16322

Abstract: 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.

Abstract translation: 病毒特异性CD4 + T细胞帮助和CD8 +细胞毒性T细胞反应对于维持慢性病毒感染的有效免疫是至关重要的。 HIV感染中CD4 + T细胞的重要性已有记载。 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，从而导致改善的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。

公开(公告)号：WO2002055100A3

公开(公告)日：2002-07-18

申请号：PCT/US2001/051339

申请日：2001-10-22

Applicant: GENETICS INSTITUTE, LLC ,  THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  BERZOFSKY, Jay, A. ,  TERABE, Masaki ,  DONALDSON, Debra, D. ,  MATSUI, So ,  NOBEN-TRAUTH, Nancy ,  PAUL, William, E.

Inventor： BERZOFSKY, Jay, A. ,  TERABE, Masaki ,  DONALDSON, Debra, D. ,  MATSUI, So ,  NOBEN-TRAUTH, Nancy ,  PAUL, William, E.

IPC: A61K38/00

Abstract: 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.

公开(公告)号：WO2019190986A1

公开(公告)日：2019-10-03

申请号：PCT/US2019/023890

申请日：2019-03-25

Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  UNIVERSITY OF CONNECTICUT ,  PASQUET, Lise H. ,  BERZOFSKY, Jay A. ,  HOWELL, Amy R. ,  TERABE, Masaki ,  CAMARA, Kaddy ,  RICHARDSON, Stewart K.

Inventor： PASQUET, Lise H. ,  BERZOFSKY, Jay A. ,  HOWELL, Amy R. ,  TERABE, Masaki ,  CAMARA, Kaddy ,  RICHARDSON, Stewart K.

IPC: C07H15/06 ,  C07H15/10 ,  A61K31/7028 ,  A61P35/00 ,  A61P37/00

Abstract: Disclosed is a compound of the formula (I) or (II): wherein a f are as described herein. The compounds are useful in the activation of Type II NKT cells and in treating cancer.

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

Applicant: US GOV HEALTH & HUMAN SERV ,  BERZOFSKY JAY A ,  OKAZAKI TAKAHIRO

Inventor： BERZOFSKY JAY A ,  OKAZAKI TAKAHIRO

IPC: C07K14/16 ,  A61K39/21 ,  A61P31/18 ,  C07K14/155

CPC classification number: C07K14/005 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/57 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2740/16322

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2004041065A3

公开(公告)日：2005-03-24

申请号：PCT/US0334362

申请日：2003-10-29

Applicant: US HEALTH ,  MORRIS JOHN J ,  BERZOFSKY JAY A ,  SAKAI YOSHIO ,  PARK JONG-MYUN ,  TERABE MASAKE

Inventor： MORRIS JOHN J ,  BERZOFSKY JAY A ,  SAKAI YOSHIO ,  PARK JONG-MYUN ,  TERABE MASAKE

IPC: A01N37/18 ,  A61B20060101 ,  A61K38/00 ,  A61K48/00 ,  C12N15/00 ,  C12N15/09 ,  C12N15/63 ,  C12N15/70 ,  C12N15/74 ,  C12N15/85

CPC classification number: A61K48/005 ,  C12N2799/022

Abstract: The invention provides for methods for vaccination of dendritic cells, modified by recombinant adenoviral vectors (rAds) expressing truncated HER2/neu genes. Infection of dendritic cells with recombinant adenoviral vectors increases the expression of the DC surface maturation markers CD80, CD86, MHC-class I, II; and CD40 and spontaneous breast cancers were delayed or prevented by vaccination with dendritic cells genetically modified by recombinant adenoviruses expressing a non-signaling HER2/neu antigen.

Abstract translation: 本发明提供了通过表达截短的HER2 / neu基因的重组腺病毒载体（rAd）修饰的树突细胞疫苗接种方法。 用重组腺病毒载体感染树突状细胞增加DC表面成熟标志物CD80，CD86，MHC-I，II型的表达; 并通过用表达非信号转导HER2 / neu抗原的重组腺病毒遗传修饰的树突状细胞进行接种来延缓或预防CD40和自发性乳腺癌。

公开(公告)号：WO2005000889A1

公开(公告)日：2005-01-06

申请号：PCT/US2004/017574

申请日：2004-06-02

Applicant: THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  BERZOFSKY, Jay, A. ,  OH, SangKon ,  PASTAN, Ira

Inventor： BERZOFSKY, Jay, A. ,  OH, SangKon ,  PASTAN, Ira

IPC: C07K14/47

CPC classification number: C07K14/4748 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5158 ,  A61K2039/53 ,  A61K2039/57

Abstract: Immunogenic T-cell receptor gamma Alternate Reading frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.

Abstract translation: 本文公开了免疫原性T细胞受体γ替代阅读框架蛋白（TARP）多肽。 这些免疫原性TARP多肽包括SEQ ID NO：9所示的氨基酸序列的9个连续氨基酸，并且不包含SEQ ID NO：1的氨基酸1-26或氨基酸38-58。几个具体的，非限制性的 这些多肽的实例如SEQ ID NO：3-7所示。 还公开了编码这些多肽的核酸和用这些核酸转染的宿主细胞。 还公开了使用这些多肽的方法和编码这些多肽的多核苷酸用于治疗乳腺癌和前列腺癌。

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

Applicant: US GOV HEALTH & HUMAN SERV ,  BERZOFSKY JAY A ,  OKAZAKI TAKAHIRO

Inventor： BERZOFSKY JAY A ,  OKAZAKI TAKAHIRO

IPC: A61K39/21 ,  A61K39/385 ,  C07K20060101 ,  C07K14/16

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

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

Applicant: US GOV HEALTH & HUMAN SERV ,  BERZOFSKY JAY A ,  TERABE MASAKI ,  MATSUI SO

Inventor： BERZOFSKY JAY A ,  TERABE MASAKI ,  MATSUI SO

IPC: A61K38/00 ,  C07K16/22 ,  A61K39/395

CPC classification number: G01N33/74 ,  A61K2039/505 ,  C07K16/22 ,  C07K2317/76 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/5047 ,  G01N2333/495

Abstract: 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.

Abstract translation: 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。