公开(公告)号：US12129465B2

公开(公告)日：2024-10-29

申请号：US17563271

申请日：2021-12-28

Applicant: UNIVERSITY OF WASHINGTON ,  FRED HUTCHINSON CANCER RESEARCH CENTER

Inventor： Daniel Ellis ,  Neil King ,  Jesse Bloom ,  Tyler Starr ,  Allison Greaney

IPC: C07K14/165 ,  A61K39/215 ,  C12N15/11 ,  C12N15/64 ,  C12Q1/6811

CPC classification number: C12N15/11 ,  A61K39/215 ,  C07K14/165 ,  C12N15/64 ,  C12Q1/6811

Abstract: Provided herein are compositions and methods comprising mutated coronavirus “S” spike proteins or receptor binding domains thereof that have an increased expression level, yield and stability compared to its corresponding native or wild-type coronavirus spike protein under the same expression, culture or storage conditions. These mutated spike proteins can be used for generating a protein-based vaccine against one or more coronaviruses.

公开(公告)号：US08969521B2

公开(公告)日：2015-03-03

申请号：US13802464

申请日：2013-03-13

Applicant: University of Washington through its Center for Commercialization ,  The Regents of the University of California

Inventor： David Baker ,  Neil King ,  William Sheffler ,  Todd Yeates

IPC: C07K1/00 ,  C07H21/02 ,  C12N1/20 ,  C12N15/00 ,  G06F19/12 ,  G06F19/16

CPC classification number: G06F19/12 ,  G06F19/16

Abstract: Methods and systems for computationally designing self-assembling polypeptides are disclosed. A representation of a docked configuration of a symmetric protein architecture can be determined by a computing device configured to computationally symmetrically dock representations of protein building blocks within a representation of a symmetric protein architecture, where symmetrically docking a representation of a particular protein building block can include determining a configuration of the protein building blocks in three-dimensional space within the symmetric protein architecture configured to generate interfaces between building blocks suitable for computational protein interface design. The amino acid sequence of the docked protein building blocks can be computationally modified to specify protein-protein interfaces between the plurality of protein building blocks that are energetically favorable to drive self-assembly of a protein that includes the modified amino acid sequence.

Abstract translation: 公开了用于计算设计自组装多肽的方法和系统。 对称蛋白质结构的对接配置的表示可以由计算设备确定，该计算设备被配置为计算对称地对接蛋白质构建块在对称蛋白质结构的表示内的表示，其中对称性地对接特定蛋白质构建块的表示可以包括 确定所述对称蛋白质结构内的三维空间中的蛋白质构建块的配置，其被配置为在适于计算蛋白质界面设计的构建块之间产生界面。 对接的蛋白质结构单元的氨基酸序列可以进行计算上的修改，以指定能够有利于驱动包含修饰的氨基酸序列的蛋白质的自组装的多个蛋白质结构单元之间的蛋白质 - 蛋白质界面。

公开(公告)号：US20240165218A1

公开(公告)日：2024-05-23

申请号：US18359154

申请日：2023-07-26

Applicant: University of Washington

Inventor： Neil King ,  David Baker ,  Lance Stewart ,  Brooke Fiala ,  Daniel Ellis ,  Lauren Carter ,  Rashmi Ravichandran ,  George Ueda ,  Jorge Fallas ,  Una Natterman

IPC: A61K39/12 ,  C12N15/86

CPC classification number: A61K39/12 ,  C12N15/86 ,  B82Y5/00

Abstract: The present disclosure provides nanostructures and nanostructure-based vaccines. Some nanostructures of the present disclosure display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens. Some vaccines of the present disclosure are useful for preventing or decreasing the severity of infection with an infectious agent, including. for example and without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus. flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means disclosed herein. Multimeric antigens may optionally be displayed along a symmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins. vaccine compositions, and methods of administration.

公开(公告)号：US11771755B2

公开(公告)日：2023-10-03

申请号：US16971278

申请日：2019-02-28

Applicant: UNIVERSITY OF WASHINGTON

Inventor： Neil King ,  David Baker ,  Lance Stewart ,  Brooke Fiala ,  Daniel Ellis ,  Lauren Carter ,  Rashmi Ravichandran ,  George Ueda ,  Jorge Fallas ,  Una Nattermann

IPC: A61K39/12 ,  C12N15/86 ,  B82Y5/00 ,  B82Y40/00

CPC classification number: A61K39/12 ,  C12N15/86 ,  B82Y5/00 ,  B82Y40/00 ,  C12N2710/16134 ,  C12N2710/16234 ,  C12N2760/00034

Abstract: Nanostructures and nanostructure-based vaccines that display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens are provided. Some vaccines are useful for preventing or decreasing the severity of infection with an infectious agent, including, for example and without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus, flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means. Multimeric antigens may optionally be displayed along a symmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins, vaccine compositions, and methods of administration.

公开(公告)号：US20130274441A1

公开(公告)日：2013-10-17

申请号：US13802464

申请日：2013-03-13

Applicant: University of Washington through its Center for Commercialization ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： David Baker ,  Neil King ,  William Sheffler ,  Todd Yeates

IPC: G06F19/12

CPC classification number: G06F19/12 ,  G06F19/16

Abstract: Methods and systems for computationally designing self-assembling polypeptides are disclosed. A representation of a docked configuration of a symmetric protein architecture can be determined by a computing device configured to computationally symmetrically dock representations of protein building blocks within a representation of a symmetric protein architecture, where symmetrically docking a representation of a particular protein building block can include determining a configuration of the protein building blocks in three-dimensional space within the symmetric protein architecture configured to generate interfaces between building blocks suitable for computational protein interface design. The amino acid sequence of the docked protein building blocks can be computationally modified to specify protein-protein interfaces between the plurality of protein building blocks that are energetically favorable to drive self-assembly of a protein that includes the modified amino acid sequence.

Abstract translation: 公开了用于计算设计自组装多肽的方法和系统。 对称蛋白质结构的对接配置的表示可以由计算设备确定，该计算设备被配置为计算对称地对接蛋白质构建块在对称蛋白质结构的表示内的表示，其中对称性地对接特定蛋白质构建块的表示可以包括 确定所述对称蛋白质结构内的三维空间中的蛋白质构建块的配置，其被配置为在适于计算蛋白质界面设计的构建块之间产生界面。 对接的蛋白质结构单元的氨基酸序列可以进行计算上的修改，以指定能够有利于驱动包含修饰的氨基酸序列的蛋白质的自组装的多个蛋白质结构单元之间的蛋白质 - 蛋白质界面。

公开(公告)号：US20230313167A1

公开(公告)日：2023-10-05

申请号：US18174041

申请日：2023-02-24

Applicant: University of Washington ,  University of Utah Research Foundation

Inventor： Neil King ,  Wesley Sundquist ,  Joerg Votteler ,  Yang Hsia ,  David Baker ,  Jacob Bale ,  Marc Lajoie ,  Gabriel Butterfield ,  Elizabeth Gray ,  Daniel Stetson

IPC: C12N9/88 ,  C07K14/00 ,  C07K14/435

CPC classification number: C12N9/88 ,  C07K14/00 ,  C07K14/435 ,  C12Y401/02014 ,  C07K2319/03 ,  C07K2319/06 ,  C07K2319/735

Abstract: The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

公开(公告)号：US11028383B2

公开(公告)日：2021-06-08

申请号：US16676253

申请日：2019-11-06

Applicant: UNIVERSITY OF WASHINGTON ,  UNIVERSITY OF UTAH

Inventor： Neil King ,  Wesley Sundquist ,  Joerg Votteler ,  Yang Hsia ,  David Baker ,  Jacob Bale ,  Marc Lajoie ,  Gabriel Butterfield ,  Elizabeth Gray ,  Daniel Stetson

IPC: C12N9/88 ,  C07K14/00 ,  C07K14/435

Abstract: The application discloses multimeric assemblies including multiple oligomeric substructures, where each oligomeric substructure includes multiple proteins that self-interact around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface (“O interface”); and one or more polypeptide domain that is capable of effecting membrane scission and release of an enveloped multimeric assembly from a cell by recruiting the ESCRT machinery to the site of budding by binding to one or more proteins in the eukaryotic ESCRT complex (“L domain”); and where the multimeric assembly includes one or more subunits comprising one or more polypeptide domain that is capable of interacting with a lipid bilayer (“M domain”), as well as membrane-enveloped versions of the multimeric assemblies.

公开(公告)号：US10248758B2

公开(公告)日：2019-04-02

申请号：US14759308

申请日：2014-02-07

Applicant: UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

Inventor： David Baker ,  Neil King ,  Jacob Bale ,  William Sheffler

IPC: G06F19/18 ,  C07K14/00 ,  G01N33/68 ,  G06F19/16 ,  G06F19/12 ,  C07K14/195 ,  B82Y5/00

Abstract: Synthetic nanostructures, proteins that are useful, for example, in making synthetic nanostructures, and methods for designing such synthetic nanostructures are disclosed herein.