Patents Assigned to Institute for Research in Biomedicine
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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: 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: 10730933Abstract: This disclosure relates to binding agents with specificity for HIV and to methods for using the same to treat, prevent and/or ameliorate HIV infection and/or AIDS.Type: GrantFiled: December 5, 2016Date of Patent: August 4, 2020Assignees: Centre Hospitalier Universitaire Vaudois, Institute For Research In BiomedicineInventors: Giuseppe Pantaleo, Antonio Lanzavecchia
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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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Publication number: 20200048311Abstract: Embodiments of a recombinant human Parainfluenza Virus (hPIV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the hPIV F ectodomain trimer and methods of producing the hPIV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or inhibiting a hPIV infection in a subject by administering a effective amount of the recombinant hPIV F ectodomain trimer to the subject.Type: ApplicationFiled: October 25, 2017Publication date: February 13, 2020Applicants: The United States of America, as represented by the Secretary, Dept. of Health and Human Services, Institute for Research in BiomedicineInventors: Baoshan Zhang, Guillaume Stewart-Jones, Tongqing Zhou, John Mascola, Kai Xu, Yongping Yang, Paul Thomas, Gwo-Yu Chuang, Li Ou, Peter Kwong, Yaroslav Tsybovsky, Wing-Pui Kong, Aliaksandr Druz, Davide Corti, Antonio Lanzavecchia
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Publication number: 20200009243Abstract: Metapneumovirus (MPV) F proteins stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.Type: ApplicationFiled: September 23, 2019Publication date: January 9, 2020Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Servic, Institute for Research in BiomedicineInventors: Peter Kwong, Michael Gordon Joyce, Baoshan Zhang, Yongping Yang, Peter Collins, Ursula Buchholz, Davide Corti, Antonio Lanzavecchia, Guillaume Stewart-Jones
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Patent number: 10526404Abstract: The present invention provides multispecific antibodies, and antigen binding fragments thereof, that potently neutralize a cytokine and that may thus be useful in the prevention and/or treatment of inflammatory and/or autoimmune diseases. In particular, the present invention provides a multispecific antibody, or an antigen binding fragment thereof, comprising at least two different domains specifically binding to at least two different, non-overlapping sites in a cytokine and an Fc moiety. The invention also relates to nucleic acids that encode such antibodies and antibody fragments and immortalized B cells and cultured plasma cells that produce such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies and antibody fragments of the invention in screening methods as well as in the diagnosis, prophylaxis and treatment of inflammatory and/or autoimmune diseases.Type: GrantFiled: April 29, 2015Date of Patent: January 7, 2020Assignee: INSTITUTE FOR RESEARCH IN BIOMEDICINEInventors: Davide Corti, Antonio Lanzavecchia, Luca Piccoli
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Publication number: 20190345234Abstract: This disclosure relates to binding agents with specificity for HIV and to methods for using the same to treat, prevent and/or ameliorate HIV infection and/or AIDS.Type: ApplicationFiled: December 5, 2016Publication date: November 14, 2019Applicants: Centre Hospitalier Universitaire Vaudois, Institute for Research in BiomedicineInventors: Giuseppe Pantaleo, Antonio Lanzavecchia
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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: 10420834Abstract: Metapneumovirus (MPV) F proteins stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the MPV F proteins and/or nucleic acid molecules can be used to generate an immune response to MPV in a subject. In additional embodiments, the therapeutically effective amount of the MPV F ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing MPV infection.Type: GrantFiled: December 24, 2015Date of Patent: September 24, 2019Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, Institute for Research in BiomedicineInventors: Peter Kwong, Michael Gordon Joyce, Baoshan Zhang, Yongping Yang, Peter Collins, Ursula Buchholz, Davide Corti, Antonio Lanzavecchia, Guillaume Stewart-Jones
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Patent number: 10414817Abstract: The invention relates to neutralizing antibodies, and antibody fragments thereof, having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for one, or a combination of two or more, hCMV gene UL products. The invention also relates to immortalized B cells that produce, and to epitopes that bind to, such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and epitopes in screening methods as well as in the diagnosis, prevention, and therapy of disease.Type: GrantFiled: July 2, 2018Date of Patent: September 17, 2019Assignee: Institute for Research in BiomedicineInventors: Antonio Lanzavecchia, Annalisa Macagno
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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: 10273288Abstract: Neutralizing antibodies and antigen binding fragments that specifically bind to Ebola virus glycoprotein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting Ebola virus using the antibodies and antigen binding fragments are disclosed. The antibodies, antigen binding fragments, nucleic acids, and vectors, can be used, for example, to prevent and/or treat Ebola virus infection in a subject.Type: GrantFiled: November 14, 2018Date of Patent: April 30, 2019Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, Institute for Research in Biomedicine, The United States of America, as represented by the Secretary of the Army, Humabs Biomed SAInventors: Nancy Sullivan, Sabue Mulangu, Davide Corti, Antonio Lanzavecchia, Barney Graham, Jean-Jacques Muyembe-Tamfun, John Trefry, Julie Ledgerwood, Daphne Stanley
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Publication number: 20190071489Abstract: Neutralizing antibodies and antigen binding fragments that specifically bind to Ebola virus glycoprotein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting Ebola virus using the antibodies and antigen binding fragments are disclosed. The antibodies, antigen binding fragments, nucleic acids, and vectors, can be used, for example, to prevent and/or treat Ebola virus infection in a subject.Type: ApplicationFiled: November 14, 2018Publication date: March 7, 2019Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services, Institute for Research in Biomedicine, The Government of the United States, as represented by the Secretary of the Army, Humabs BioMed SAInventors: Nancy Sullivan, Sabue Malangu, Davide Corti, Antonio Lanzavecchia, Barney Graham, Jean-Jacques Muyembe-Tamfun, John Trefry, Julie Ledgerwood, Daphne Stanley
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Patent number: 10160795Abstract: Neutralizing antibodies and antigen binding fragments that specifically bind to Ebola virus glycoprotein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting Ebola virus using the antibodies and antigen binding fragments are disclosed. The antibodies, antigen binding fragments, nucleic acids, and vectors, can be used, for example, to prevent and/or treat Ebola virus infection in a subject.Type: GrantFiled: November 13, 2015Date of Patent: December 25, 2018Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, Institute for Research in Biomedicine, The United States of America as represented by the Secretary of the Army, Humabs BioMed SAInventors: Nancy Sullivan, Sabue Mulangu, Davide Corti, Antonio Lanzavecchia, Barney Graham, Jean-Jacques Muyembe-Tamfun, John Trefry, Julie Ledgerwood, Daphne Stanley
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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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Publication number: 20180291088Abstract: Neutralizing antibodies and antigen binding fragments that specifically bind to Ebola virus glycoprotein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting Ebola virususing the antibodies and antigen binding fragments are disclosed. The antibodies, antigen binding fragments, nucleic acids, and vectors, can be used, for example, to prevent and/or treat Ebola virusinfection in a subject.Type: ApplicationFiled: November 13, 2015Publication date: October 11, 2018Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services, Institute for Research in Biomedicine, The Government of the United States as represented by the Secretary of the Army, Humabs BioMed SAInventors: Nancy Sullivan, Sabue Mulangu, Davide Corti, Antonio Lanzavecchia, Barney Graham, Jean-Jacques Muyembe-Tamfun, John Trefry, Julie Ledgerwood, Daphne Stanley
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Patent number: 10040845Abstract: The invention relates to neutralizing antibodies, and antibody fragments thereof, having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for one, or a combination of two or more, hCMV gene UL products. The invention also relates to immortalized B cells that produce, and to epitopes that bind to, such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and epitopes in screening methods as well as in the diagnosis, prevention, and therapy of disease.Type: GrantFiled: September 27, 2017Date of Patent: August 7, 2018Assignee: Institute for Research in BiomedicineInventors: Antonio Lanzavecchia, Annalisa Macagno
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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