Patents by Inventor Richard A. Flavell

Richard A. Flavell has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20240099278
    Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
    Type: Application
    Filed: August 21, 2023
    Publication date: March 28, 2024
    Inventors: Richard Flavell, Till Strowig, Markus G. Manz, Chiara Borsotti, Madhav Dhodapkar, Andrew J. Murphy, Sean Stevens, George D. Yancopoulos
  • Publication number: 20240074414
    Abstract: Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.
    Type: Application
    Filed: August 10, 2023
    Publication date: March 7, 2024
    Inventors: Andrew J. Murphy, Sean Stevens, Richard Flavell, Markus Gabriel Manz, Liang Shan
  • Patent number: 11778995
    Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
    Type: Grant
    Filed: August 21, 2020
    Date of Patent: October 10, 2023
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Richard Flavell, Till Strowig, Markus G. Manz, Chiara Borsotti, Madhav Dhodapkar, Andrew J. Murphy, Sean Stevens, George D. Yancopoulos
  • Patent number: 11766032
    Abstract: Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.
    Type: Grant
    Filed: November 1, 2019
    Date of Patent: September 26, 2023
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Andrew J. Murphy, Sean Stevens, Richard Flavell, Markus Gabriel Manz, Liang Shan
  • Publication number: 20230292721
    Abstract: Genetically modified non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.
    Type: Application
    Filed: January 9, 2023
    Publication date: September 21, 2023
    Inventors: Dietmar Herndler-Brandstetter, Richard A. Flavell, Davor Frleta, Cagan Gurer, Markus Gabriel Manz, Andrew J. Murphy, Noah W. Palm, Liang Shan, Sean Stevens, Till Strowig, George D. Yancopoulos, Marcel de Zoete
  • Patent number: 11576356
    Abstract: Genetically modified non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRP? and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.
    Type: Grant
    Filed: February 5, 2020
    Date of Patent: February 14, 2023
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Dietmar Herndler-Brandstetter, Richard A. Flavell, Davor Frleta, Cagan Gurer, Markus Gabriel Manz, Andrew J. Murphy, Noah W. Palm, Liang Shan, Sean Stevens, Till Strowig, George D. Yancopoulos, Marcel de Zoete
  • Publication number: 20220354098
    Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use,
    Type: Application
    Filed: July 17, 2020
    Publication date: November 10, 2022
    Inventors: Richard Flavell, Stephanie Halene, Yuanbin Song
  • Publication number: 20220282274
    Abstract: Methods and materials for modulating biomass composition in plants are disclosed. For example, nucleic acids encoding biomass composition-modulating polypeptides are disclosed as well as methods for using such nucleic acids to transform plant cells. Also disclosed are plants having altered biomass composition and plant products produced from plants having altered biomass composition.
    Type: Application
    Filed: February 23, 2022
    Publication date: September 8, 2022
    Inventors: Joon-Hyun Park, Roger I. Pennell, Richard Flavell, Chuan-Yin Wu
  • Patent number: 11299790
    Abstract: The invention relates to the identification of secretory antibody-bound bacteria in the microbiota in a subject that influence the development and progression of inflammatory diseases and disorders. Thus, the invention relates to compositions and methods for detecting and identifying the constituents of a subject's microbiota, methods of modifying the constituents of the microbiota, and methods for treating inflammatory diseases and disorders in a subject in need thereof.
    Type: Grant
    Filed: August 14, 2020
    Date of Patent: April 12, 2022
    Assignee: Yale University
    Inventors: Richard Flavell, Noah Palm, Marcel de Zoete
  • Patent number: 11299747
    Abstract: Methods and materials for modulating biomass composition in plants are disclosed. For example, nucleic acids encoding biomass composition-modulating polypeptides are disclosed as well as methods for using such nucleic acids to transform plant cells. Also disclosed are plants having altered biomass composition and plant products produced from plants having altered biomass composition.
    Type: Grant
    Filed: August 13, 2020
    Date of Patent: April 12, 2022
    Assignee: Ceres, Inc.
    Inventors: Joon-Huyn Park, Roger I. Pennell, Richard Flavell, Chuan-Yin Wu
  • Publication number: 20220031617
    Abstract: A “nanolipogel” is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.
    Type: Application
    Filed: August 11, 2021
    Publication date: February 3, 2022
    Inventors: Tarek M. Fahmy, Eric Stern, Richard A. Flavell, Jason Park, Alyssa Siefert, Stephen H. Wrzesinski
  • Publication number: 20220000084
    Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.
    Type: Application
    Filed: June 9, 2021
    Publication date: January 6, 2022
    Inventors: Sean Stevens, Andrew J. Murphy, Richard Flavell, Elizabeth Eynon, Jorge Galan, Tim Willinger, Markus Manz, Anthony Rongvaux, George D. Yancopoulos
  • Publication number: 20210368752
    Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.
    Type: Application
    Filed: May 10, 2021
    Publication date: December 2, 2021
    Inventors: Richard Flavell, Markus Manz, Anthony Rongvaux, Till Strowig, Tim Willinger, Andrew J. Murphy, Sean Stevens, George Yancopoulos
  • Patent number: 11173119
    Abstract: A “nanolipogel” is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.
    Type: Grant
    Filed: December 12, 2019
    Date of Patent: November 16, 2021
    Assignee: Yale University
    Inventors: Tarek M. Fahmy, Eric Stern, Richard A. Flavell, Jason Park, Alyssa Siefert, Stephen H. Wrzesinski
  • Patent number: 11051499
    Abstract: A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.
    Type: Grant
    Filed: March 13, 2019
    Date of Patent: July 6, 2021
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Sean Stevens, Andrew J. Murphy, Richard Flavell, Elizabeth Eynon, Jorge Galan, Tim Willinger, Markus Manz, Anthony Rongvaux, George D. Yancopoulos
  • Publication number: 20210170014
    Abstract: The invention relates to compositions and methods for treating inflammatory diseases and disorders in a subject in need thereof. In certain aspects, the invention relates to immunogenic compositions (e.g., vaccines) to diminish the number or pathogenic effects of one or more bacteria associated with the development or progression of an inflammatory disease or disorder.
    Type: Application
    Filed: February 18, 2021
    Publication date: June 10, 2021
    Inventors: Richard Flavell, Noah Palm, Marcel De Zoete
  • Patent number: 11026408
    Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.
    Type: Grant
    Filed: September 27, 2019
    Date of Patent: June 8, 2021
    Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)
    Inventors: Richard Flavell, Markus Manz, Anthony Rongvaux, Till Strowig, Tim Willinger, Andrew J. Murphy, Sean Stevens, George Yancopoulos
  • Publication number: 20210112791
    Abstract: Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.
    Type: Application
    Filed: August 21, 2020
    Publication date: April 22, 2021
    Inventors: Andrew J. Murphy, Sean Stevens, Chozhavendan Rathinam, Elizabeth Eynon, Markus Manz, Richard Flavell, George D. Yancopoulos
  • Publication number: 20210100228
    Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
    Type: Application
    Filed: August 21, 2020
    Publication date: April 8, 2021
    Inventors: Richard Flavell, Till Strowig, Markus G. Manz, Chiara Borsotti, Madhav Dhodapkar, Andrew J. Murphy, Sean Stevens, George D. Yancopoulos
  • Publication number: 20210079420
    Abstract: Methods and materials for modulating biomass composition in plants are disclosed. For example, nucleic acids encoding biomass composition-modulating polypeptides are disclosed as well as methods for using such nucleic acids to transform plant cells. Also disclosed are plants having altered biomass composition and plant products produced from plants having altered biomass composition.
    Type: Application
    Filed: August 13, 2020
    Publication date: March 18, 2021
    Inventors: Joon-Huyn Park, Roger I. Pennell, Richard Flavell, Chuan-Yin Wu