Patents Assigned to Seattle Children's Hospital
-
Patent number: 10865242Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. In some alternatives, the ligand binding domains binds to CD171.Type: GrantFiled: April 8, 2015Date of Patent: December 15, 2020Assignee: Seattle Children's HospitalInventor: Michael C. Jensen
-
Patent number: 10829556Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.Type: GrantFiled: January 4, 2019Date of Patent: November 10, 2020Assignee: SEATTLE CHILDREN'S HOSPITALInventor: Michael Jensen
-
Patent number: 10780118Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.Type: GrantFiled: August 20, 2013Date of Patent: September 22, 2020Assignees: Fred Hutchinson Cancer Research Center, Seattle Children's HospitalInventors: Michael C. Jensen, Stanley R. Riddell, Michael Hudecek
-
Patent number: 10745690Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.Type: GrantFiled: May 25, 2018Date of Patent: August 18, 2020Assignee: SEATTLE CHILDREN'S HOSPITALInventors: Andrew M. Scharenberg, Michael T. Certo, Kamila Sabina Gwiazda, David J. Rawlings
-
Patent number: 10736918Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.Type: GrantFiled: November 17, 2017Date of Patent: August 11, 2020Assignees: Fred Hutchinson Cancer Research Center, Seattle Children's HospitalInventors: Michael C. Jensen, Stanley R. Riddell, Michael Hudecek
-
Publication number: 20200209237Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.Type: ApplicationFiled: August 5, 2019Publication date: July 2, 2020Applicant: Seattle Children's HospitalInventors: Neelufar Mozaffarian, Anne M. Stevens
-
Patent number: 10610247Abstract: A spring-biased nasal molding device for presurgical molding of cleft lip deformities, the device having a pair of intra-nasal shaping members for insertion into the nostrils and having an extra-nasal shaping member to be positioned external to the nostrils connected to each intra-nasal shaping member, wherein the intra-nasal and extra-nasal shaping members are brought together by the spring member to mold the nasal anatomy into the desired shape.Type: GrantFiled: November 15, 2016Date of Patent: April 7, 2020Assignee: SEATTLE CHILDREN'S HOSPITALInventors: Richard A. Hopper, Thomas S. Johnston, Jr.
-
Patent number: 10611837Abstract: The present invention provides genetic tags operably linked to transgenes. The expression of the genetic tag allows identification, detection, selection, and ablation of cells expressing the transgene and the genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag.Type: GrantFiled: April 8, 2015Date of Patent: April 7, 2020Assignee: Seattle Children's HospitalInventors: Michael C. Jensen, Adam Johnson
-
Patent number: 10563226Abstract: Disclosed herein are nuclease-based systems for genome editing and methods of using the system for genome editing. Also, disclosed are approaches to enhance Cas9-mediated gene editing efficiency in primary human cells with minimal toxicity when using adeno-associated virus vectors (AAV) to express the guide RNAs necessary for CRISPR/Cas9-based genome editing in the presence of helper proteins.Type: GrantFiled: May 12, 2016Date of Patent: February 18, 2020Assignee: Seattle Children's HospitalInventors: Andrew Scharenberg, David Rawlings, Michael C. Jensen, Kamila Gwiazda, Alexandra Grier
-
Publication number: 20200009266Abstract: In vivo gene therapies for immune deficiencies are described. The in vivo gene therapies utilize a foamy viral vector including a PGK promoter with a therapeutic gene. The foamy viral vector can be beneficially administered with cell mobilization into the peripheral blood.Type: ApplicationFiled: February 15, 2018Publication date: January 9, 2020Applicants: Fred Hutchinson Cancer Research Center, Seattle Children's Hospital d/b/a Seattle Children's Research InstituteInventors: Frieda Chan, Olivier Humbert, Hans-Peter Kiem, Jennifer E. Adair, David Rawlings, Andrew Scharenberg, Troy Torgerson
-
Patent number: 10525082Abstract: Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.Type: GrantFiled: September 7, 2016Date of Patent: January 7, 2020Assignee: Seattle Children's HospitalInventors: Courtney Crane, Michael Jensen, Kara White Moyes, Nicole Lieberman
-
Publication number: 20190381159Abstract: The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP 2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.Type: ApplicationFiled: January 24, 2018Publication date: December 19, 2019Applicant: Seattle Children's Hospital d/b/a Seattle Children's Research InstituteInventors: Ashley M. Vaughan, Stefan H.I. Kappe, Dorender A. Dankwa
-
Patent number: 10494422Abstract: The present application generally relates to methods of genetically modifying a T-cell comprising a chimeric antigen receptor wherein the T-cell lacks a co-receptor for HIV. The application further relates to methods of making a nucleic acid encoding a chimeric antigen receptor, nucleic acids encoding a chimeric antigen receptor, and genetically modified T-cells comprising a chimeric antigen receptor disclosed herein. The application further relates to methods of treating, inhibiting, or ameliorating HIV in a subject including administering to the subject a cell disclosed herein.Type: GrantFiled: April 8, 2015Date of Patent: December 3, 2019Assignee: Seattle Children's HospitalInventors: Thor Wagner, Andrew M. Scharenberg, David J. Rawlings, Blythe Sather, Jaya Sahni
-
Patent number: 10407672Abstract: According to particular exemplary aspects, DNA target site binding and cleavage properties of native, variant or modified homing endonucleases (HE) (e.g., LAGLIDAG (LHE), HNH, His-Cys Box, GIY-YIG, I-SspI-type, and fusions, muteins or variants thereof) in solution are recapitulated on the cell surface (e.g., as assessed by flow cytometric analysis) to provide for novel cells expressing one or more cell surface HEs (e.g., expressing one or more HE binding and/or cleavage specificities), novel cell libraries, and high-throughput methods for assessing target site binding, target site cleavage. The rapid analysis of HE and LHE-DNA interactions on the cell surface with concurrent sorting options provides for high-throughput library screening affording rapid identification, analysis and isolation of novel HEs or LHEs having novel sequence specificities.Type: GrantFiled: March 27, 2007Date of Patent: September 10, 2019Assignee: Seattle Children's HospitalInventor: Andrew M. Scharenberg
-
Patent number: 10371702Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.Type: GrantFiled: October 5, 2015Date of Patent: August 6, 2019Assignee: SEATTLE CHILDREN'S HOSPITALInventors: Neelufar Mozaffarian, Anne M. Stevens
-
Publication number: 20190183997Abstract: Provided herein are methods of sorting antigen-specific IgM memory B cells (MBCs), compositions and methods comprising such antigen-specific IgM MBCs, and recombinant antibody or antigen-binding fragments isolated from such antigen-specific IgM MBCs. As demonstrated herein, IgM and IgD MBCs are unique populations of cells with distinct phenotypic, functional and survival properties. Accordingly, the antigen-specific IgM MBCs and antibodies and antigen-binding fragments derived from these cells described herein are useful in therapeutic applications in vaccine strategies and treatment of infectious diseases.Type: ApplicationFiled: July 21, 2017Publication date: June 20, 2019Applicants: UNIVERSITY OF WASHINGTON, SEATTLE CHILDREN'S HOSPITAL D/B/A SEATTLE CHILDREN'S RESEARCH INSTITUTEInventors: Marion PEPPER, Akshay KRISHNAMURTY, David J. RAWLINGS, Christopher THOUVENEL
-
Publication number: 20190119382Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.Type: ApplicationFiled: January 4, 2019Publication date: April 25, 2019Applicant: Seattle Children's Hospital d/b/a Seattle Children's Research InstituteInventor: Michael Jensen
-
Patent number: 10266592Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient.Type: GrantFiled: April 8, 2015Date of Patent: April 23, 2019Assignee: Seattle Children's HospitalInventor: Michael C. Jensen
-
Publication number: 20190112379Abstract: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.Type: ApplicationFiled: March 22, 2017Publication date: April 18, 2019Applicant: SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE)Inventors: Michael JENSEN, Rebecca GARDNER
-
Patent number: 10189903Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.Type: GrantFiled: August 10, 2016Date of Patent: January 29, 2019Assignee: Seattle Children's HospitalInventor: Michael Jensen