Patents Assigned to Institute for Research in Biomedicine (IRB)
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Patent number: 11778995Abstract: 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: GrantFiled: August 21, 2020Date of Patent: October 10, 2023Assignees: 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
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Patent number: 11766032Abstract: 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: GrantFiled: November 1, 2019Date of Patent: September 26, 2023Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)Inventors: Andrew J. Murphy, Sean Stevens, Richard Flavell, Markus Gabriel Manz, Liang Shan
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Patent number: 11576356Abstract: 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: GrantFiled: February 5, 2020Date of Patent: February 14, 2023Assignees: 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
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Patent number: 11051499Abstract: 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: GrantFiled: March 13, 2019Date of Patent: July 6, 2021Assignees: 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
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Patent number: 11026408Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.Type: GrantFiled: September 27, 2019Date of Patent: June 8, 2021Assignees: 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
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Patent number: 10785966Abstract: 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: GrantFiled: April 14, 2017Date of Patent: September 29, 2020Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)Inventors: Andrew J. Murphy, Sean Stevens, Chozhavendan Rathinam, Elizabeth Eynon, Markus Manz, Richard Flavell, George D. Yancopoulos
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Patent number: 10785968Abstract: 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: GrantFiled: November 6, 2017Date of Patent: September 29, 2020Assignees: 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
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Patent number: 10561126Abstract: 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: GrantFiled: April 16, 2018Date of Patent: February 18, 2020Assignees: 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
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Patent number: 10463028Abstract: 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: GrantFiled: May 18, 2015Date of Patent: November 5, 2019Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)Inventors: Andrew J. Murphy, Sean Stevens, Richard Flavell, Markus Gabriel Manz, Liang Shan
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Patent number: 10433527Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.Type: GrantFiled: May 15, 2018Date of Patent: October 8, 2019Assignees: 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
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Patent number: 10278374Abstract: 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 mll2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/ll2rg 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: GrantFiled: January 3, 2017Date of Patent: May 7, 2019Assignees: 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
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Patent number: 10123518Abstract: 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: GrantFiled: April 12, 2016Date of Patent: November 13, 2018Assignees: 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
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Patent number: 9986724Abstract: 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: GrantFiled: June 24, 2016Date of Patent: June 5, 2018Assignees: 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
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Patent number: 9901082Abstract: 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: GrantFiled: November 5, 2013Date of Patent: February 27, 2018Assignees: 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
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Patent number: 9820476Abstract: The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.Type: GrantFiled: September 6, 2013Date of Patent: November 21, 2017Assignees: 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
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Patent number: 9655352Abstract: 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: GrantFiled: August 26, 2014Date of Patent: May 23, 2017Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)Inventors: Andrew J. Murphy, Sean Stevens, Chozhavendan Rathinam, Elizabeth Eynon, Markus Manz, Richard Flavell, George D. Yancopoulos
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Patent number: 9554563Abstract: 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: GrantFiled: October 14, 2013Date of Patent: January 31, 2017Assignees: 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
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Patent number: 9301509Abstract: 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: GrantFiled: September 14, 2012Date of Patent: April 5, 2016Assignees: 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
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Patent number: 8847004Abstract: 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: GrantFiled: February 14, 2012Date of Patent: September 30, 2014Assignees: Regeneron Pharmaceuticals, Inc., Yale University, Institute for Research in Biomedicine (IRB)Inventors: Andrew J. Murphy, Sean Stevens, Chozhavendan Rathinam, Elizabeth Eynon, Markus Manz, Richard Flavell, George D. Yancopoulos
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Patent number: 8692052Abstract: 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: GrantFiled: September 14, 2012Date of Patent: April 8, 2014Assignees: Regeneron Pharmaceuticals, 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