Patents by Inventor LEONARD D. SHULTZ
LEONARD D. SHULTZ 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).
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Publication number: 20240041925Abstract: This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.Type: ApplicationFiled: October 29, 2021Publication date: February 8, 2024Applicant: RIKENInventors: Fumihiko ISHIKAWA, Yoriko SAITO, Ari ITOH, Leonard D. SHULTZ
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Patent number: 11785923Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.Type: GrantFiled: May 28, 2020Date of Patent: October 17, 2023Assignees: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
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Patent number: 11778994Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.Type: GrantFiled: May 14, 2018Date of Patent: October 10, 2023Assignees: The Jackson Laboratory, University of MassachusettsInventors: Michael A. Brehm, Michael V. Wiles, Dale L. Greiner, Leonard D. Shultz
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Publication number: 20230270085Abstract: The present disclosure provides an immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.Type: ApplicationFiled: July 7, 2021Publication date: August 31, 2023Applicant: The Jackson LaboratoryInventors: Anna Karolina Palucka, Chu l. Yu, Jacques Banchereau, Richard Maser, Leonard D. Shultz
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Publication number: 20230255186Abstract: The present disclosure provides a transgenic, immunocompromised mouse engineered to express a human angiotensin converting enzyme 2 (huACE2) sequence. The huACE2 sequence may be operably linked to a human keratin 18 (hKRT18) promoter or the endogenous mouse angiotensin converting enzyme 2 (mACE2) promoter. Transgenic immunocompromised mice of the present disclosure may be utilized in methods of evaluating a test agent for reducing or preventing SARS-CoV-2 infection.Type: ApplicationFiled: July 14, 2021Publication date: August 17, 2023Applicant: The Jackson LaboratoryInventor: Leonard D. Shultz
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Publication number: 20220136002Abstract: Provided herein, in some aspects, is a NOD.Cg-Prkdcscid Il2rgtm1wjl/SzJ (NOD scid gamma or NSG™) mouse comprising a nucleic acid encoding human FLT3L and an inactivated mouse Flt3 allele, methods of producing the mouse, and methods of using the mouse.Type: ApplicationFiled: February 13, 2020Publication date: May 5, 2022Applicant: The Jackson LaboratoryInventor: Leonard D. Shultz
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Publication number: 20200359609Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.Type: ApplicationFiled: May 28, 2020Publication date: November 19, 2020Applicants: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
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Publication number: 20200236916Abstract: An immunodeficient mouse is provided which is useful as a model of functions and regulation of human natural killer (NK) cells and other interleukin 15 (IL-15)-dependent cell populations and processes in studies of human immunity, cancer, infectious diseases, and other areas. According to specific aspects, an immunodeficient mouse is provided which is genetically modified to express human interleukin 15, wherein the mouse does not have or produce functional mouse natural killer cells, and wherein the mouse is modified to include human natural killer cells. Methods of identifying anti-tumor activity of a test substance using a mouse of the present invention are described along with methods of making the mouse.Type: ApplicationFiled: August 9, 2018Publication date: July 30, 2020Applicants: The Jackson Laboratory, University of Massachusetts Medical SchoolInventors: Leonard D. Shultz, Michael A. Brehm, Dale L. Greiner
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Patent number: 10701911Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom IL2rgtm1Wjl/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Sug/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.Type: GrantFiled: June 16, 2016Date of Patent: July 7, 2020Assignees: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
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Publication number: 20200060245Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.Type: ApplicationFiled: May 14, 2018Publication date: February 27, 2020Applicants: The Jackson Laboratory, University of MassachusettsInventors: Michael A. Brehm, Michael V. Wiles, Dale L. Greiner, Leonard D. Shultz
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Publication number: 20190320633Abstract: A genetically-modified, immunodeficient mouse is provided along with methods of use, wherein the mouse includes (a) a nucleotide sequence encoding human stem cell factor (hSCF); (b) a nucleotide sequence encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF); (c) a nucleotide sequence encoding human interleukin-3 (hIL-3); and (d) a nucleotide sequence encoding human colony-stimulating factor 1 (hCSF1), wherein each of the nucleotide sequences is operably linked to a promoter, and wherein the genetically-modified, immunodeficient mouse expresses hSCF, hGM-CSF, hIL-3, and hCSF1, wherein the genetically-modified, immunodeficient mouse allows engraftment of human hematopoietic stem cells along with engraftment of human-patient derived tumor xenografts and/or human tumor cell lines to enable in vivo investigation of the interactions between the human immune system and human cancer.Type: ApplicationFiled: November 30, 2017Publication date: October 24, 2019Applicants: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, James G. Keck, Dale L. Greiner, Michael A. Brehm
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Publication number: 20190274290Abstract: One or more embodiments of the present invention include an immunodeficient mouse genetically modified to include a gene encoding a PiZ variant (Glu342Lys) of human ?-1 antitrypsin (AAT), wherein the mouse expresses the PiZ variant of human ?-1 antitrypsin (Z-AAT), and has a reduced number of mouse hepatocytes compared to an immunodeficient mouse of the same type which does not express Z-AAT. The immunodeficient mouse genetically modified to include a gene encoding a PiZ variant of human AAT can be a genetically modified NSG, NRG or NOG mouse. The immunodeficient mouse may further include xenogeneic hepatocytes, such as human hepatocytes. Putative treatments of human liver disease can be assessed in mice provided according to aspects of the present disclosure.Type: ApplicationFiled: October 27, 2017Publication date: September 12, 2019Applicant: The Jackson LaboratoryInventor: Leonard D. Shultz
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Publication number: 20190183101Abstract: A genetically modified immunodeficient non-human animal whose genome includes a genetic modification that renders the non-human animal deficient in macrophages and/or macrophage anti-human red blood cell activity so as to prolong the survival of human red blood cells when administered into said non-human animal is provided according to aspects of the present invention. Methods of assaying effects of putative therapeutic agents in such a genetically modified immunodeficient non-human animal are provided by the present invention.Type: ApplicationFiled: August 11, 2017Publication date: June 20, 2019Applicant: The Jackson LaboratoryInventors: Leonard D. Shultz, Michael V. Wiles
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Publication number: 20180325085Abstract: A genetically modified NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mouse is provided by the present invention wherein the genome of the mouse includes a mutated Rhbdf2 gene such that the mouse expresses a mutant iRhom2 protein, wherein the mutant iRhom2 protein differs from wild-type iRhom2 protein due to one or more mutations selected from p.I156T, p.D158N and p.P159L, and wherein the mouse is characterized by hairless phenotype and increased growth of an exogenous tumor compared to a mouse of the same genetic background which express wild-type iRhom2 protein.Type: ApplicationFiled: October 31, 2016Publication date: November 15, 2018Inventors: Michael V. Wiles, Vishnu Hosur, Leonard D. Shultz
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Patent number: 10021861Abstract: Described herein are immunodeficient non-human animals lacking expression of toll-like receptor 4 (TLR4) by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient non-human animal lacking expression of toll-like receptor 4 (TLR4), thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells. Further described are immunodeficient mice lacking expression of toll-like receptor 4 by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient mouse lacking expression of toll-like receptor 4, thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells.Type: GrantFiled: August 15, 2016Date of Patent: July 17, 2018Assignees: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Dale L. Greiner, Michael A. Brehm
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Publication number: 20180184629Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wj1/SzJ (NSG), NOD. Cg-Rag1tm1Mom IL2rgtm1Wj1/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Wj1/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.Type: ApplicationFiled: June 16, 2016Publication date: July 5, 2018Inventors: Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
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Publication number: 20170241986Abstract: Methods for identifying a compound that modulates activity of an iRhom polypeptide according to aspects of the present invention are described herein which include contacting a cell expressing an iRhom polypeptide with a test compound; and determining the effect of the compound on activity of the iRhom polypeptide. Detection of a decrease in proteolytic activity of the iRhom polypeptide indicates that the compound is capable of one or more of: reducing tumor growth, reducing tumor progression, treatment of cancer and promoting hair growth in a subject, and detecting an increase in proteolytic activity of the iRhom polypeptide indicates that the compound is capable of accelerating wound healing in a subject.Type: ApplicationFiled: May 11, 2015Publication date: August 24, 2017Inventors: Vishnu Hosur, Leonard D. Shultz
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Publication number: 20160345548Abstract: Described herein are immunodeficient non-human animals lacking expression of toll-like receptor 4 (TLR4) by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient non-human animal lacking expression of toll-like receptor 4 (TLR4), thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells. Further described are immunodeficient mice lacking expression of toll-like receptor 4 by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient mouse lacking expression of toll-like receptor 4, thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells.Type: ApplicationFiled: August 15, 2016Publication date: December 1, 2016Inventors: Leonard D. Shultz, Dale L. Greiner, Michael A. Brehm
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Patent number: 9414576Abstract: Described herein are immunodeficient non-human animals lacking expression of toll-like receptor 4 (TLR4) by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient non-human animal lacking expression of toll-like receptor 4 (TLR4), thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells. Further described are immunodeficient mice lacking expression of toll-like receptor 4 by endogenous autogeneic innate immune cells, as well as methods and compositions for engraftment of xenogeneic hematopoietic stem cells in the immunodeficient mouse lacking expression of toll-like receptor 4, thereby creating an innate immune system in the animal derived from the xenogeneic hematopoietic stem cells.Type: GrantFiled: October 10, 2014Date of Patent: August 16, 2016Assignees: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Dale L. Greiner, Michael A. Brehm
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Patent number: 9125384Abstract: The invention relates to a method of selectively expanding human leukemic cells in a non-adult NOD/SCID/IL2rgnull mouse by transplanting a substance containing a leukemic stem cell derived from a human acute myelogenous leukemia patient to the mouse. In addition, the invention relates to screening for a medicament capable of eradicating leukemic stem cell (LSC), consideration of treatment methods suitable for individual patients, identification of a differentially expressed gene and the like, using a mouse with expanded human leukemic cells.Type: GrantFiled: October 17, 2008Date of Patent: September 8, 2015Assignees: RIKEN, The Jackson LaboratoryInventors: Fumihiko Ishikawa, Yoriko Saito, Osamu Ohara, Leonard D. Shultz