公开(公告)号：US09549976B1

公开(公告)日：2017-01-24

申请号：US14081629

申请日：2013-11-15

Applicant: David S. Peabody ,  Bryce Chackerian ,  Carlee Ashley ,  Eric Carnes ,  Oscar Negrete

Inventor： David S. Peabody ,  Bryce Chackerian ,  Carlee Ashley ,  Eric Carnes ,  Oscar Negrete

IPC: A61K39/00 ,  A61K39/155 ,  A61K49/00 ,  A61K39/385 ,  C12Q1/70 ,  C12N7/00 ,  G01N33/569

CPC classification number: A61K39/155 ,  A61K39/12 ,  A61K2039/5256 ,  A61K2039/5258 ,  C12N2760/18234 ,  G01N33/56983

Abstract: The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.

Abstract translation: 本发明涉及噬菌体MS2（MS2 VLP）的病毒样颗粒，其显示了尼泊尔病毒包膜糖蛋白的表位的肽表位或肽模拟物，其在接种人或动物时引起针对尼帕病毒的免疫应答。 在Nipah病毒中和单克隆抗体上的亲和力选择，使用MS2 VLP上的随机序列肽文库，选择与Nipah本身的包膜糖蛋白内发现的肽序列具有序列相似性的肽，从而鉴定抗体识别的表位。 所选择的肽序列本身在所有方面不一定与尼帕病毒糖蛋白内的序列相同，因此可以称为表位模拟物，显示这些表位模拟物的VLP可以用作疫苗。 另一方面，从Nipah Virus得到的相应野生型序列的显示与通过亲和力选择映射的表位对应，也可以用作疫苗。

公开(公告)号：US08992984B1

公开(公告)日：2015-03-31

申请号：US12909572

申请日：2010-10-21

Applicant: C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/14 ,  A61K9/51

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

Abstract translation: 各种实施方案提供用于合成原细胞以用于向癌细胞靶向递送货物组分的材料和方法。 在一个实施方案中，脂质双层可以与多孔颗粒核心融合以形成原细胞。 脂质双层可以用靶向配体或其他配体进行修饰，以实现载体在原细胞内的货物组分的靶向递送到靶细胞，例如一种类型的癌症。 屏蔽材料可以结合到脂质双层的表面以减少不期望的非特异性结合。

公开(公告)号：US20130149336A1

公开(公告)日：2013-06-13

申请号：US13662060

申请日：2012-10-26

Applicant: Brian L. Hjelle ,  David S. Peabody ,  Bryce Chackerian

Inventor： Brian L. Hjelle ,  David S. Peabody ,  Bryce Chackerian

IPC: G01N33/68

CPC classification number: G01N33/6878 ,  G01N33/56983 ,  G01N33/6845 ,  Y02A50/51 ,  Y02A50/53 ,  Y02A50/58 ,  Y02A50/60

Abstract: The invention is directed to methods of screening immunogenic viral like particles and related immunogenic compositions and diagnostic techniques. In one embodiment, the invention provides methods of screening immunogenic viral like particles containing peptides corresponding to epitope regions of a wide variety of pathogens, including viruses, bacteria, parasites, and microbes. Non-infectious antigens and allergens of interest can also be screened as described herein. Immunization, therapeutic and diagnostic applications are also described for the compositions and methods according to the invention.In another embodiment, the invention provides novel methods of identifying a cryptic neutralizing epitope and related vaccines, constructs, and libraries. In some embodiments, these methods use high-throughput formats that are facilitated by in silica or in vitro steps.

Abstract translation: 本发明涉及筛选免疫原性病毒样颗粒和相关的免疫原性组合物和诊断技术的方法。 在一个实施方案中，本发明提供筛选含有对应于多种病原体（包括病毒，细菌，寄生虫和微生物）的表位区域的肽的免疫原性病毒样颗粒的方法。 还可以如本文所述筛选感兴趣的非传染性抗原和过敏原。 还描述了根据本发明的组合物和方法的免疫，治疗和诊断应用。 在另一个实施方案中，本发明提供鉴定隐性中和表位和相关疫苗，构建体和文库的新方法。 在一些实施方案中，这些方法使用通过二氧化硅或体外步骤促进的高通量形式。

公开(公告)号：US20120295813A1

公开(公告)日：2012-11-22

申请号：US13520057

申请日：2010-12-31

Applicant: David S. Peabody ,  Bryce Chackerian

Inventor： David S. Peabody ,  Bryce Chackerian

IPC: C12N15/70 ,  C12N7/00 ,  C40B40/02 ,  C40B30/04 ,  C40B30/00 ,  C07K2/00 ,  C07K1/14 ,  C12N1/21 ,  C40B50/06

CPC classification number: A61K39/12 ,  A61K39/07 ,  A61K2039/5256 ,  A61K2039/5258 ,  C12N7/00 ,  C12N15/1037 ,  C12N2710/20022 ,  C12N2710/20034 ,  C12N2740/16034 ,  C12N2740/16134 ,  C12N2795/16021 ,  C12N2795/16022 ,  C12N2795/16023 ,  C12N2795/16042 ,  C12N2795/18023 ,  C40B40/08

Abstract: The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on VLPs, especially MS2 VLPS over a wide range, from few than one-on average—to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency. Nucleic acid constructs useful in the expression of virus-like particles are disclosed, comprised of a coat polypeptide of MS2 modified by insertion of a heterologous peptide, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates MS2 niRNA. Nucleic acid constructs are also disclosed which are useful in the expression of virus-like particles comprised of a coat polypeptide of PP7 modified by insertion of a heterologous peptide, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates PP7 mRNA.

Abstract translation: 本发明涉及一种用于控制病毒样颗粒（VLPs），特别是包括MS2 VLP的肽显示效价的系统和方法。 在该方法中，可以从单个RNA产生大量野生型和低量的单链二聚体外壳蛋白。 通过提供允许从单个RNA产生大量野生型和少量单链二聚体包被蛋白质的系统，允许轻度调整VLP上的显示剂价位水平，特别是 MS2 VLPS在广泛的范围内，从一个平均至少一个到每个粒子多达九十个。 这有助于免疫原和疫苗的生产，包括显示低效价的VLP。 公开了可用于病毒样颗粒表达的核酸构建物，其由通过插入异源肽修饰的MS2的外壳多肽组成，其中异源肽显示在病毒样颗粒上并包裹MS2nRNA。 还公开了核酸构建体，其可用于由通过插入异源肽修饰的PP7的外壳多肽组成的病毒样颗粒的表达，其中异源肽显示在病毒样颗粒上并包裹PP7 mRNA。

公开(公告)号：US20090054246A1

公开(公告)日：2009-02-26

申请号：US11895198

申请日：2007-08-23

Applicant: David S. Peabody ,  Bryce Chackerian

Inventor： David S. Peabody ,  Bryce Chackerian

IPC: C40B30/00 ,  C40B40/10 ,  C07H21/04 ,  C07K1/00 ,  C40B50/06

CPC classification number: C12N15/1037 ,  A61K2039/5256 ,  A61K2039/5258 ,  C07K14/005 ,  C12N2740/16122 ,  C12N2795/18123 ,  C40B40/02

Abstract: The invention is directed to virus-like particles (VLPs) of an RNA bacteriophage that (a) comprises a coat polypeptide of said phage modified by insertion of a heterologous peptide that is displayed on said VLP and (b) encapsidates said bacteriophage mRNA as well as populations of these VLPs, and their uses. The invention is further directed to VLPs that encapsidate heterologous substances, as well as populations of these VLPs and their uses.

Abstract translation: 本发明涉及RNA噬菌体的病毒样颗粒（VLP），其（a）包含通过插入在所述VLP上显示的异源肽修饰的所述噬菌体的外壳多肽，和（b）还包封所述噬菌体mRNA 作为这些VLP的群体及其用途。 本发明还涉及包裹异源物质的VLP以及这些VLP的群体及其用途。

公开(公告)号：US07479280B2

公开(公告)日：2009-01-20

申请号：US11415611

申请日：2006-05-01

Applicant: John T. Schiller ,  Bryce Chackerian ,  Douglas R. Lowy

Inventor： John T. Schiller ,  Bryce Chackerian ,  Douglas R. Lowy

IPC: A61A39/00 ,  A61A39/12 ,  A61A47/48 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18

CPC classification number: C12N7/00 ,  A61K38/00 ,  A61K39/00 ,  A61K47/6901 ,  A61K2039/5258 ,  C07K14/005 ,  C07K14/525 ,  C07K14/7158 ,  C07K16/084 ,  C07K16/241 ,  C07K16/2866 ,  C07K17/00 ,  C07K2317/34 ,  C07K2319/20 ,  C07K2319/40 ,  C07K2319/74 ,  C12N2710/14143 ,  C12N2710/20022 ,  C12N2710/20023 ,  C12N2710/22022 ,  C12N2710/22023

Abstract: The invention described herein relates to compositions and methods for stimulating immune responses in vivo against a tolerogen. Novel biotechnological tools, pharmaceuticals, therapeutics and prophylactics, which concern chimeric or conjugated virus-like particles, and methods of use of the foregoing are provided for the study of B cell tolerance and the treatment or prevention of human diseases, which involve the onset of B cell tolerance, such as chronic viral infection, chronic inflammatory disease, and neoplasia.