Patents by Inventor Irwin D. Bernstein
Irwin D. Bernstein 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: 20240092857Abstract: Delta-like non-canonical Notch ligand 1 (DLK1) inhibitors are disclosed. The DLK1 inhibitors can be used to treat cancers such as myelodysplastic syndrome (MDS), and cancers of the liver, breast, brain, pancreas, colon, lung, kidney, ovary, testes, and/or adrenal gland, among other uses described herein.Type: ApplicationFiled: August 25, 2023Publication date: March 21, 2024Applicant: Fred Hutchinson Cancer CenterInventors: Irwin D. Bernstein, Suzanne Furuyama, Kristen Johnson
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Patent number: 11439667Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.Type: GrantFiled: October 17, 2019Date of Patent: September 13, 2022Assignee: FRED HUTCHINSON CANCER CENTERInventors: Irwin D. Bernstein, Brandon K. Hadland
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Publication number: 20220267437Abstract: The disclosure provides methods for inducing Notch signaling in a targeted manner within aggregations of cells. The methods include contacting the aggregation of cells with a bi-specific molecule that facilitates trans-binding of Notch receptor. The bi-specific molecule comprising a cell-targeting domain that specifically binds to a cell-specific antigen expressed in the aggregation of cells, and a Notch-binding domain that specifically binds to Notch receptor. In some aspects, the disclosed methods and reagents provide methods of promoting pro-inflammatory states in tumor micro-environments.Type: ApplicationFiled: July 28, 2020Publication date: August 25, 2022Applicant: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Suzanne Furuyama
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Patent number: 11359179Abstract: The present disclosure provides methods for immortalizing precursor cells that are non-terminally differentiated cells such as stem cells, the methods comprising culturing the precursor cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist (and, in particular embodiments, one or more growth factors) that support the proliferation but not differentiation of the non-terminally differentiated cells. The present disclosure further provides methods to induce the differentiation of immortalized cells, comprising growing the cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist and at least one growth factor which supports the differentiation of the cell into a more specialized cell type. The immortalized and/or differentiated cells of the disclosure can be used to repopulate cell populations that have been diminished, for example as a result of infection or exposure to certain drugs.Type: GrantFiled: December 20, 2018Date of Patent: June 14, 2022Assignee: FRED HUTCHINSON CANCER CENTERInventor: Irwin D. Bernstein
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Publication number: 20210292711Abstract: The disclosure provides in some aspect methods and compositions related to culturing and engineering T cells that maintain less differentiated state. The T cells are cultured in conditions that induce Notch signaling The resulting T cells exhibit maintenance of a less differentiated state for prolonged periods and have reduced susceptibility to exhaustion. Also provided are the cells produced by the methods, as well as related compositions and methods of use for adoptive therapy.Type: ApplicationFiled: August 28, 2019Publication date: September 23, 2021Applicant: FRED HUTCHINSON CANCER RESEARCH CENTERInventors: Stanley R. Riddell, Irwin D. Bernstein, Margot J. Pont
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Publication number: 20200046775Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.Type: ApplicationFiled: October 17, 2019Publication date: February 13, 2020Applicant: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Brandon K. Hadland
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Publication number: 20200030384Abstract: The present invention relates to methods and compositions for providing hematopoietic function to human patients in need thereof, by selecting a pool of expanded human cord blood stem/progenitor cell samples for administration to the patient, wherein the samples in the pool collectively do not mismatch the patient at more than 2 of the HLA antigens or alleles typed in the patient; and administering the selected pool of expanded human cord blood stem/progenitor cell samples to the patient. Methods for obtaining the pools of expanded human cord blood stem/progenitor cell samples, banks of frozen pools of expanded human umbilical cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.Type: ApplicationFiled: October 1, 2019Publication date: January 30, 2020Applicant: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Colleen Delaney
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Patent number: 10463698Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.Type: GrantFiled: March 28, 2018Date of Patent: November 5, 2019Assignee: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Brandon K. Hadland
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Publication number: 20190330593Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.Type: ApplicationFiled: June 26, 2019Publication date: October 31, 2019Applicants: Fred Hutchinson Cancer Research Center, Board of Regents of the University of Texas SystemInventors: Irwin D. Bernstein, Chengcheng Zhang, Mi Deng, Zhigang Lu, Junke Zheng
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Publication number: 20190298777Abstract: The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.Type: ApplicationFiled: April 8, 2019Publication date: October 3, 2019Applicant: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Colleen Delaney
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Publication number: 20190298778Abstract: The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.Type: ApplicationFiled: April 8, 2019Publication date: October 3, 2019Applicant: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Colleen Delaney
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Patent number: 10370643Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.Type: GrantFiled: May 21, 2015Date of Patent: August 6, 2019Assignees: Fred Hutchinson Cancer Research Center, Board of Regents of the University of Texas SystemInventors: Irwin D. Bernstein, Chengcheng Zhang, Mi Deng, Zhigang Lu, Junke Zheng
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Publication number: 20190127698Abstract: The present disclosure provides methods for immortalizing precursor cells that are non-terminally differentiated cells such as stem cells, the methods comprising culturing the precursor cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist (and, in particular embodiments, one or more growth factors) that support the proliferation but not differentiation of the non-terminally differentiated cells. The present disclosure further provides methods to induce the differentiation of immortalized cells, comprising growing the cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist and at least one growth factor which supports the differentiation of the cell into a more specialized cell type. The immortalized and/or differentiated cells of the disclosure can be used to repopulate cell populations that have been diminished, for example as a result of infection or exposure to certain drugs.Type: ApplicationFiled: December 20, 2018Publication date: May 2, 2019Applicant: Fred Hutchinson Cancer Research CenterInventor: Irwin D. Bernstein
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Patent number: 10208286Abstract: The present disclosure provides methods for immortalizing precursor cells that are non-terminally differentiated cells such as stem cells, the methods comprising culturing the precursor cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist (and, in particular embodiments, one or more growth factors) that support the proliferation but not differentiation of the non-terminally differentiated cells. The present disclosure further provides methods to induce the differentiation of immortalized cells, comprising growing the cells in the presence of a Notch 1 agonist, Notch 2 agonist or Notch 1 agonist and Notch 2 agonist and at least one growth factor which supports the differentiation of the cell into a more specialized cell type. The immortalized and/or differentiated cells of the disclosure can be used to repopulate cell populations that have been diminished, for example as a result of infection or exposure to certain drugs.Type: GrantFiled: June 3, 2015Date of Patent: February 19, 2019Assignee: Fred Hutchinson Cancer Research CenterInventor: Irwin D. Bernstein
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Publication number: 20180214491Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.Type: ApplicationFiled: March 28, 2018Publication date: August 2, 2018Inventors: Irwin D. Bernstein, Brandon K. Hadland
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Publication number: 20180142212Abstract: The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.Type: ApplicationFiled: November 6, 2017Publication date: May 24, 2018Inventors: Irwin D. Bernstein, Anthony E. Boitano, Michael Cooke, Colleen Delaney
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Patent number: 9956249Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFp pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TOP? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.Type: GrantFiled: January 7, 2014Date of Patent: May 1, 2018Assignee: Fred Hutchinson Cancer Research CenterInventors: Irwin D. Bernstein, Brandon K. Hadland
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Publication number: 20180085406Abstract: The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.Type: ApplicationFiled: November 10, 2017Publication date: March 29, 2018Inventors: Irwin D. Bernstein, Colleen Delaney
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Patent number: 9834755Abstract: The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.Type: GrantFiled: December 7, 2012Date of Patent: December 5, 2017Assignees: Fred Hutchinson Cancer Research Center, Novartis AGInventors: Irwin D. Bernstein, Anthony E. Boitano, Michael Cooke, Colleen Delaney
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Publication number: 20170260508Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.Type: ApplicationFiled: May 21, 2015Publication date: September 14, 2017Inventors: Irwin D. Bernstein, Chengcheng Zhang, Mi Deng, Zhigang Lu, Junke Zheng