Abstract: The invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided.
Type:
Grant
Filed:
May 13, 2019
Date of Patent:
January 4, 2022
Assignee:
President and Fellows of Harvard College
Inventors:
David R. Liu, Kevin Michael Esvelt, Jacob Charles Carlson
Abstract: A binding agent to a target molecule, or method or kit where the binding agent is selected from a library where each variant has a circular permutation of the FHA domain where the rearrange does not substantially disrupt the FHA domain's beta-sheet scaffold or increase the stability of the beta-sheet scaffold. The randomized regions of the FHA domain include the endogenous binding interface the FHA domain, the region opposite of the endogenous binding interface, and the circular permutation region.
Abstract: The present invention relates to methods of selecting, screening, engineering, making and modifying antibodies that have improved bioavailability upon subcutaneous administration to a human. Antibodies and variant antibodies with improved bioavailability upon subcutaneous administration to a human are also described.
Type:
Grant
Filed:
July 29, 2016
Date of Patent:
December 21, 2021
Assignee:
GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Inventors:
Valeriu Damian, Austin Keith Doyle, Laura Maria Halo, Emma R. Harding, Xuan Hong, Alan Peter Lewis, Mark Uden
Abstract: The present invention relates to a process for determining in vitro the immune status of an individual according to which: (a) a blood sample from the individual is provided, (b) at least two reagents specific to at least two products of expression of at least two target genes are provided; (c) the expression of said at least two target genes is determined, and (d) the expression of said at least two target genes respectively is compared with a reference expression, with a change in the expression of said at least two target genes relative to their reference expression indicating that the individual's immune status has changed, and a correlation between the expression of said at least two target genes with their reference expression indicating that the individual's immune status is normal; as well as a kit for determining said immune status of the individual.
Type:
Grant
Filed:
April 24, 2018
Date of Patent:
November 23, 2021
Assignees:
BIOMERIEUX, HOSPICES CIVILS DE LYON (HCL)
Abstract: The present invention relates to a polypeptide comprising an antigen binding domain and a carrying moiety having an inhibiting domain that inhibits the antigen binding activity of the antigen binding domain, and having a longer half-life than that of the antigen binding domain existing alone, methods for producing and screening for the polypeptide, a pharmaceutical composition comprising the polypeptide, methods for producing and screening for a single-domain antibody whose antigen binding activity is inhibited by associating with particular VL, VH or VHH, and a fusion polypeptide library including a single-domain antibody whose antigen binding activity is inhibited by associating with particular VL, VH or VHH.
Abstract: The present invention relates to certain new methods to select epitopes for antibodies. The present invention also provides a method of generating an antibody (e.g. a functional antibody) to a protein, said method comprising (i) identifying an antigenic epitope in said protein by exposing the protein to limited or restricted proteolysis by contacting the protein with at least one protease to form at least one digested, deconstructed or truncated version of the protein and at least one surface-exposed peptide that is cleaved off from the protein by the action of said protease and generating an antigenic epitope based on said surface-exposed peptide; and (ii) raising an antibody against the antigenic epitope. The present invention also provides antigenic epitopes and antibodies against such epitopes.
Abstract: The present inventors have successfully prepared a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, the antigen-binding molecules each comprising an antibody variable region that has binding activity against a first antigen and a second antigen different from the first antigen, but does not bind to the first antigen and the second antigen at the same time. Use of the library of the present invention allows the obtainment of a variable region having enhanced ability to bind to the first antigen and the production of a bispecific antibody against the first antigen and a cancer antigen. Moreover, the present inventors have also successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against three different antigens, but does not bind to these antigens at the same time.
Type:
Grant
Filed:
November 11, 2015
Date of Patent:
October 26, 2021
Assignee:
Chugai Seiyaku Kabushiki Kaisha
Inventors:
Tomoyuki Igawa, Shojiro Kadono, Naoka Hironiwa, Mika Sakurai
Abstract: Platforms, systems and methods are provided for identifying engineered lanthipeptide display peptides expressed in vivo from biological organisms.
Type:
Grant
Filed:
September 28, 2015
Date of Patent:
October 19, 2021
Assignee:
The Board of Trustees of the University of Illinois
Inventors:
Wilfred A. van der Donk, Ayse Okesli, Xiao Yang, Mark Walker, Kenton J. Hetrick
Abstract: The present invention relates to a method for preparing a library of template polynucleotides and use thereof in methods of solid-phase nucleic acid amplification. More specifically, the invention relates to a method for preparing a library of template polynucleotides that have common sequences at their 5? ends and at their 3? ends.
Type:
Grant
Filed:
April 2, 2019
Date of Patent:
October 12, 2021
Assignee:
Illumina Cambridge Limited
Inventors:
Niall Anthony Gormley, Geoffrey Paul Smith, David Bentley, Roberto Rigatti, Shujun Luo
Abstract: Disclosed are methods, components, compositions, and kits for preparing and identifying engineered E. coli ribosomes. The E. coli ribosomes may be prepared and identified under a set of defined conditions, such as in the presences of antibiotics, in order to obtain an engineered ribosome that is resistant to the antibiotic.
Type:
Grant
Filed:
October 7, 2019
Date of Patent:
October 5, 2021
Assignee:
Northwestern University
Inventors:
Michael Christopher Jewett, Brian R. Fritz
Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain comprising an alpha chain variable domain and a beta chain comprising a beta chain variable domain and the library comprises more than one TRAV gene product and/or more than one TRBV gene product, wherein the beta chain variable domain does not comprise one or more of a TRBV5-1, 5-3, 5-4, 5-5, 5-6, 5-7 or 5-8 gene product and wherein the plurality of TCRs do not consist essentially of TCRs comprising a TRAV12-2 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire and TCRs comprising a TRAV21 gene product from a natural repertoire and a TRBV6 gene product from a natural repertoire.
Type:
Grant
Filed:
September 15, 2016
Date of Patent:
October 5, 2021
Assignee:
Immunocore Limited
Inventors:
Peter Eamon Molloy, Arsen Valeryevich Volkov, Dhaval Jaykant Sangani, Graham Anthony Hood, Chandramouli Reddy Chillakuri
Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from one or more cells. Such polynucleotide processing may be useful for a variety of applications, including generation of labeled macromolecules, including major mistocompatability complex (MHC) molecules, dextramers, etc. Labeled macromolecules may be generated using an in vitro transcription reaction. Labeled macromolecules may be generated in one or more partitions.
Type:
Grant
Filed:
April 4, 2019
Date of Patent:
September 28, 2021
Assignee:
10X GENOMICS, INC.
Inventors:
Katherine Pfeiffer, Sarah Taylor, Michael Stubbington
Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV12-2 gene product and the beta chain variable domain comprises a TRBV gene product.
Abstract: Methods for screening of affinity reagents for many target proteins of interest simultaneously. Arrayed targets (e.g., peptide, protein, RNA, cell, etc.) are used in affinity selection experiments to reduce the amount of target needed and to improve the throughput of discovering recombinant affinity reagents to a large collection of targets.
Type:
Grant
Filed:
September 13, 2016
Date of Patent:
September 21, 2021
Assignees:
ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY, THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Inventors:
Joshua Labaer, Kevin Gorman, Brian Kay, Jie Wang, Ji Qiu
Abstract: Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.
Type:
Grant
Filed:
June 17, 2019
Date of Patent:
September 7, 2021
Assignee:
GigaGen, Inc.
Inventors:
David Scott Johnson, Adam Shultz Adler, Matthew James Spindler, Rena Aviva Mizrahi
Abstract: The present invention provides, in part, an antibody display system that simultaneously uses a secretion and a display mode. A bait complexed with a monovalent antibody fragment can be expressed on the surface of the host cell wherein the fragment may be assayed for antigen binding while full antibody is simultaneously secreted from the host cell. Methods of using the system for identifying antibodies that bind specifically to an antigen of interest are also provided. Polypeptides, polynucleotides and host cells useful for making the antibody display system are also provided along with methods of use thereof.
Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.
Type:
Grant
Filed:
July 24, 2019
Date of Patent:
August 31, 2021
Assignee:
President and Fellows of Harvard College
Inventors:
David R. Liu, David B. Thompson, Jeffrey L. Bessen
Abstract: The invention features compositions and methods that are useful for identifying allele variants that modulate gene expression. Compositions and articles defined by the invention were isolated or otherwise manufactured.
Type:
Grant
Filed:
March 24, 2017
Date of Patent:
August 31, 2021
Assignee:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Abstract: The present invention relates generally to the field of making novel antigen binding domains against infectious diseases. The present invention also relates to novel CARs that utilize the novel antigen binding domains as an extracellular element. The present invention also relates to use of the novel antigen binding domains as therapeutic agents.