Patents by Inventor Irving L. Weissman

Irving L. Weissman 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).

  • Patent number: 10406179
    Abstract: The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.
    Type: Grant
    Filed: August 26, 2015
    Date of Patent: September 10, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Judith A. Shizuru, Irving L. Weissman, Kipp Andrew Weiskopf, Aaron Michael Ring, Akanksha Chhabra, Peter Schnorr
  • Patent number: 10386361
    Abstract: Hoxb5 identifies long-term hematopoietic stem cells. Expression of Hoxb5 distinguishes between LT-HSCs and non-LT-HSCs, and the marker identifies substantially all LT-HSC in the bone marrow. By utilizing fluorescent proteins under the endogenous expression control of Hoxb5, LT-HSC can be monitored and isolated, including without limitation detection and monitoring of HSC in bone morrow; production of LT-HSC from pluripotent stem cells such as iPS cells; for analysis of early stage LT-HSC; in screening methods for expansion and manipulation of LT-HSC, and the like.
    Type: Grant
    Filed: June 7, 2017
    Date of Patent: August 20, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: James Y. Chen, Masanori Miyanishi, Irving L. Weissman
  • Publication number: 20190241664
    Abstract: Methods and compositions are provided for inducing phagocytosis of a target cell, treating an individual having cancer, treating an individual having an intracellular pathogen infection (e.g., a chronic infection), and/or reducing the number of inflicted cells (e.g., cancer cells, cells infected with an intracellular pathogen, etc.) in an individual. Methods and compositions are also provided for predicting whether an individual is resistant (or susceptible) to treatment with an anti-CD47/SIRPA agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent (e.g., co-administration of an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent). Kits are also provided for practicing the methods of the disclosure.
    Type: Application
    Filed: April 25, 2019
    Publication date: August 8, 2019
    Inventors: Roy Louis Maute, Kipp Andrew Weiskopf, Aaron Michael Ring, Irving L. Weissman
  • Publication number: 20190233515
    Abstract: Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, acute leukemia cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.
    Type: Application
    Filed: March 22, 2019
    Publication date: August 1, 2019
    Inventors: Siddhartha Jaiswal, Irving L. Weissman, Ravindra Majeti, Mark P. Chao
  • Patent number: 10358472
    Abstract: High affinity CD47 reagents are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for a SIRP? relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity CD47 reagent, which blocks the physiological binding interaction between SIRP? and a ligand, e.g., native CD47.
    Type: Grant
    Filed: May 5, 2016
    Date of Patent: July 23, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Chia Chi Ho, Kenan Christopher Garcia, Aaron Michael Ring, Kipp Andrew Weiskopf, Irving L. Weissman, Nan Guo Ring
  • Publication number: 20190218260
    Abstract: Cell loss by apoptosis is a common feature in certain conditions, including cancer. Dying tumor cells induce immune tolerance within the tumor microenvironment largely through highly conserved homeostatic clearance programs that are designed to restore tissue homeostasis and contribute to the formation of an immunosuppressive niche. The translocation of phosphatidylserine (PS) on cellular membranes, during the initial phases of apoptosis, functions as a recognition and removal signal that limits the immunogenicity of cell death. To remove inhibitory signals in the homeostatic clearance pathway a fusion protein comprising a phosphatidylserine binding domain and an immunostimulatory domain can restore immune responses to dead tumor cells in antigen cross presentation assays and promotes recruitment and retention of tumor antigen specific immune effector cells into tumors.
    Type: Application
    Filed: August 4, 2017
    Publication date: July 18, 2019
    Inventors: Daniel Mark Corey, Aaron Michael Ring, Melissa N. McCracken, Irving L. Weissman
  • Publication number: 20190218289
    Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.
    Type: Application
    Filed: April 4, 2019
    Publication date: July 18, 2019
    Inventors: Stephen Willingham, Maureen Howard, Jie Liu, Ravindra Majeti, Susan Sweeney Prohaska, Anne Kathrin Volkmer, Jens-Peter Volkmer, Irving L. Weissman
  • Patent number: 10344094
    Abstract: Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS or BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.
    Type: Grant
    Filed: December 8, 2016
    Date of Patent: July 9, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Irving L. Weissman, Stephen Willingham, Doris Po Yi Ho, Piero D. Dalerba, Kelly Marie McKenna, Jens-Peter Volkmer
  • Patent number: 10329354
    Abstract: Smooth muscle cells (SMC) from subjects carrying at least one 9p21 risk factor, can be resistant to efferocytosis, leading to the retention of such cells in the necrotic core of atherosclerotic plaque. In the methods of the invention, an agent that increases efferocytosis of cellular components of coronary plaque, including efferocytosis of apoptotic smooth muscle cells, is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce atherosclerotic plaque in the individual.
    Type: Grant
    Filed: September 15, 2014
    Date of Patent: June 25, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Nicholas J. Leeper, Irving L. Weissman
  • Publication number: 20190183940
    Abstract: Methods, compositions, and kits for producing functional blood vessels, and progenitors thereof are provided. Human disorders of the vascular system are treated by reconstitution of functional vessels in vivo through co-transplantation with supporting niche stromal cells for treatment of ischemic injury in the peripheral limbs and heart. The cell populations of the invention, when engrafted into a recipient, anastomose with host vasculature and regenerate functional blood vessels.
    Type: Application
    Filed: August 25, 2017
    Publication date: June 20, 2019
    Inventors: Charles K.F. Chan, Andrew Stephen Lee, Michael T. Longaker, Irving L. Weissman, Joseph Wu, Divya Nag, Eun Young Seo
  • Patent number: 10316094
    Abstract: Methods and compositions are provided for inducing phagocytosis of a target cell, treating an individual having cancer, treating an individual having an intracellular pathogen infection (e.g., a chronic infection), and/or reducing the number of inflicted cells (e.g., cancer cells, cells infected with an intracellular pathogen, etc.) in an individual. Methods and compositions are also provided for predicting whether an individual is resistant (or susceptible) to treatment with an anti-CD47/SIRPA agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent (e.g., co-administration of an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent). Kits are also provided for practicing the methods of the disclosure.
    Type: Grant
    Filed: October 23, 2015
    Date of Patent: June 11, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Roy Louis Maute, Kipp Andrew Weiskopf, Aaron Michael Ring, Irving L. Weissman
  • Patent number: 10301387
    Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.
    Type: Grant
    Filed: February 2, 2017
    Date of Patent: May 28, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Stephen Willingham, Maureen Howard, Jie Liu, Ravindra Majeti, Susan Sweeney Prohaska, Anne Kathrin Volkmer, Jens-Peter Volkmer, Irving L. Weissman
  • Publication number: 20190112374
    Abstract: Humanized or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to and neutralize human CD47, and find use in various therapeutic methods. Preferred are non-activating antibodies. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid sequences of the antibodies.
    Type: Application
    Filed: December 19, 2018
    Publication date: April 18, 2019
    Inventors: Jie Liu, Irving L. Weissman, Ravindra Majeti
  • Publication number: 20190106491
    Abstract: Methods are provided for treating a subject with an anti-CD47 agent.
    Type: Application
    Filed: April 14, 2017
    Publication date: April 11, 2019
    Inventors: Irving L. Weissman, Mark P. Chao, Ravindra Majeti, Jie Liu, Jens-Peter Volkmer
  • Publication number: 20190092873
    Abstract: Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRP? on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.
    Type: Application
    Filed: December 10, 2018
    Publication date: March 28, 2019
    Inventors: Kipp Andrew Weiskopf, Kim J. Hasenkrug, Cheryl A. Stoddart, Joseph McCrary McCune, Irving L. Weissman
  • Publication number: 20190048077
    Abstract: Aspects of the present disclosure include methods of treating a subject to reduce adhesion formation, the method comprising administering to a subject in need of thereof an agent that that targets adhesion-formation by injured mesothelial cells. The agent can act at a variety of checkpoints in the development of adhesions by injured mesothelial cells, including: targeting the injured mesothelial cells for destruction, recruiting inflammatory macrophages to the site of adhesion, preventing neutrophil recruitment to the site of adhesion, and/or inhibiting the expression or activity of a gene product whose expression is induced in the injured mesothelial cells. Compositions and kits for performing the methods are also provided.
    Type: Application
    Filed: May 1, 2017
    Publication date: February 14, 2019
    Inventors: Jonathan Tsai, Nathaniel Fernhoff, Rahul Sinha, Yuval Rinkevich, Irving L. Weissman
  • Publication number: 20190048075
    Abstract: Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.
    Type: Application
    Filed: April 3, 2018
    Publication date: February 14, 2019
    Inventors: Irving L. Weissman, Ravindra Majeti, Arash Ash Alizadeh, Mark P. Chao
  • Patent number: 10184004
    Abstract: Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRP? on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.
    Type: Grant
    Filed: August 14, 2017
    Date of Patent: January 22, 2019
    Assignees: The Board of Trustees of the Leland Stanford Junior University, The Regents of the University of California, The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Kipp Andrew Weiskopf, Kim J. Hasenkrug, Cheryl A. Stoddart, Joseph McCrary McCune, Irving L. Weissman
  • Publication number: 20180353582
    Abstract: Methods are provided for enhancing immunization strategies by manipulation, e.g. in vitro manipulation, of phagocytic antigen presenting cells. In the methods of the invention, phagocytic antigen presenting cells (phAPC) are incubated with a particulate antigen in the presence of an anti-CD47 agent in a dose and for a period of time sufficient to allow the phAPC to phagocytose the particulate antigen, which process generates a “loaded” phAPC. The loaded phAPC is contacted with a population of T cells matched for at least one major histocompatibility locus with the phAPC, where the T cells are stimulated after contacting to generate an effector response against an epitope or epitopes present on the particulate antigen.
    Type: Application
    Filed: July 30, 2018
    Publication date: December 13, 2018
    Inventors: Diane Tseng, Jens-Peter Volkmer, Kipp Andrew Weiskopf, Stephen Willingham, Irving L. Weissman
  • Publication number: 20180327507
    Abstract: The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment and tolerance.
    Type: Application
    Filed: July 13, 2018
    Publication date: November 15, 2018
    Inventors: Irving L. Weissman, Agnieszka Czechowicz, Deepta Bhattacharya, Daniel Kraft