Patents Assigned to The Trustees of the University of Pennsylvania
  • Publication number: 20240117378
    Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.
    Type: Application
    Filed: June 30, 2023
    Publication date: April 11, 2024
    Applicant: The Trustees of the University of Pennsylvania
    Inventors: Luk VANDENBERGHE, Guangping GAO, James M. WILSON
  • Publication number: 20240115740
    Abstract: This invention relates to the compositions and methods for labeling antibodies and other proteins and targeting agents with a helical bundle protein that is functionalized with cargo. Cargos can include but are not limited to fluorescent dyes, haptens (e.g. biotin), contrast agents (e.g. gadolinium, radionuclides), chelated metals, therapeutic agents, sensitizers, or other small molecules. Specifically, provided herein are compositions having a helical bundle, that has been labeled at precisely defined locations with cargo, and that can be conjugated, attached or fused to an antibody or other targeting agent.
    Type: Application
    Filed: November 30, 2021
    Publication date: April 11, 2024
    Applicants: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, AlphaThera LLC
    Inventors: Andrew TSOURKAS, Feifan YU
  • Publication number: 20240117322
    Abstract: A recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid produced in a production system comprising a nucleotide sequence of SEQ ID NO: 1, or a sequence at least 75% identical thereto which encodes SEQ ID NO:2. The AAVhu68 capsid comprises subpopulations of highly deamidated asparagine residues in asparagine-glycine pairs in the amino acid sequence of SEQ ID NO: 2. Also provided are compositions containing the rAAV and uses thereof. Additionally, rAAV having an engineered AAV capsid comprising at least one subpopulation of vp1 or vp2 proteins having a Val at amino acid position 157 with reference to the AAVhu68 vp1 numbering are provided.
    Type: Application
    Filed: October 11, 2023
    Publication date: April 11, 2024
    Applicant: The Trustees of the University of Pennsylvania
    Inventors: James M. Wilson, Qiang Wang, April Tepe, Kevin Turner
  • Patent number: 11950805
    Abstract: Disclosed are steerable needles having a shaft that can be controllably buckled, a steering head positioned at a distal end of the shaft, a transmission for controlling the orientation of the steering head, and a base at the end of the shaft, the base optionally comprising a controller for controlling the transmission. Also disclosed are methods of using the disclosed steerable needles.
    Type: Grant
    Filed: March 28, 2023
    Date of Patent: April 9, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventor: Mark Yim
  • Publication number: 20240110190
    Abstract: Compositions and methods for treating fibrosis using oligonucleotide-based therapies are provided. These therapies can be used to increase expression of Bone morphogenetic protein receptor type II (BMPR2) via inhibition of upstream Open Reading Frames, thereby reducing vasoconstriction, vascular remodeling, and formation of fibrosis, particularly pulmonary arterial fibrosis related in patients in need thereof.
    Type: Application
    Filed: February 28, 2022
    Publication date: April 4, 2024
    Applicant: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: Yoseph BARASH, David Sheng Ming LEE, Louis R. GHANEM, Nicholas J. HAND
  • Patent number: 11946028
    Abstract: The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five-layer model including a first and second microchannel with a membrane-gel layer-membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.
    Type: Grant
    Filed: July 26, 2022
    Date of Patent: April 2, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Dongeun Huh, Mark Mondrinos
  • Patent number: 11939672
    Abstract: A nanoscale plate structure includes base plates and rib plates with nanoscale thickness and macroscopic lateral dimensions. The base plate resides in the first plane, the ribs can reside out-of-plane and form at least one strengthening rib, and additional base plates can reside in planes parallel to the first plane. The strengthening rib can be patterned such that there is no straight line path extending through a lateral dimension of the plate structure that does not intersect the at least one base plate and the at least one strengthening rib. The plates and ribs used in the structure have a thickness between about 1 nm and about 100 nm. The plate structures can be fabricated using a conformal deposition method including atomic layer deposition.
    Type: Grant
    Filed: December 3, 2021
    Date of Patent: March 26, 2024
    Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: Igor Bargatin, Keivan Davami
  • Patent number: 11938200
    Abstract: The present disclosure relates to magnetic resonance imaging (MRI) methods comprising (i) obtaining a baseline chemical exchange saturation transfer (CEST) MRI image of a patient, (ii) administering an effective amount of a non-nutritive sweetener to the patient, and (iii) obtaining one or more test CEST MRI image of the patient subsequent to the administering step (ii); wherein the step (i) and (iii) acquisition parameters are substantially the same. The non-nutritive sweetener may include a natural or artificial sugar alcohol, polyol, or combinations or derivatives thereof.
    Type: Grant
    Filed: February 3, 2017
    Date of Patent: March 26, 2024
    Assignees: The Trustees of the University of Pennsylvania, Sidra Medicine
    Inventors: Ravinder Reddy, Mohammad Haris, Hari Hariharan, Puneet Bagga, Francesco M. Marincola, Mitchell D. Schnall
  • Patent number: 11931380
    Abstract: The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DGK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DGK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.
    Type: Grant
    Filed: April 14, 2021
    Date of Patent: March 19, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Steven M. Albelda, Liang-Chuan Wang, Gary Koretzky, Matthew Riese
  • Publication number: 20240082361
    Abstract: This invention relates to methods of treating and ameliorating congenital and neonatal hyperinsulinism and post-prandial hypoglycemia, comprising the step of administering an antagonist of the Glucagon-Like Peptide-1 (GLP-1) receptor, e.g. a GLP-1 fragment or analogue thereof.
    Type: Application
    Filed: February 14, 2023
    Publication date: March 14, 2024
    Applicants: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, The Children's Hospital of Philadelphia
    Inventors: Doris STOFFERS, Diva D. DE LEON, Charles STANLEY
  • Patent number: 11925466
    Abstract: An electrode, the electrode including an exposed contact surface, the exposed surface comprising a contact material, the contact material comprising a MXene. A device, the device including a plurality of electrodes, each of the plurality of electrodes comprising an exposed contact surface, the exposed surface comprising a contact material, the contact material comprising a MXene. A method, the method including delivering electrical stimulation to a subject with an electrode that comprises an exposed contact surface, the exposed contact surface comprising a contact material that includes a MXene.
    Type: Grant
    Filed: September 14, 2018
    Date of Patent: March 12, 2024
    Assignees: The Trustees of the University of Pennsylvania, Drexel University
    Inventors: Flavia Vitale, Brian Litt, Nicolette Driscoll, Yury Gogotsi, Babak Anasori, Kathleen Maleski
  • Patent number: 11925685
    Abstract: Disclosed herein is a composition comprising a recombinant nucleic acid sequence that encodes an antibody to a Zika viral antigen, and functional fragments thereof. The invention also relates to a composition comprising the combination of a first composition that elicits an immune response in a mammal against zika virus and a second composition comprising a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof. In some instances, the nucleic acid molecule comprises a nucleotide sequence encoding an anti-ZIKV-Envelope (anti-ZIKV E) Protein antibody.
    Type: Grant
    Filed: September 19, 2017
    Date of Patent: March 12, 2024
    Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc., The Wistar Institute of Anatomy and Biology
    Inventors: David Weiner, Karuppiah Muthumani, Jian Yan
  • Patent number: 11925662
    Abstract: The present invention relates to compositions and methods that provide novel anti-tumor therapies in cancer. In one aspect, the present invention features a hybrid neutrophil in a non-naturally occurring container, wherein the hybrid neutrophil expresses at least one neutrophil associated molecule selected from the group consisting of: Arg1, MPO, CD66b, and CD15, and at least one antigen-presenting cell (APC) associated molecule selected from the group consisting of: CD14, HLA-DR, CD32, CD64, and CD89. In another aspect, the present invention features methods of generating a hybrid neutrophil. In still another aspect, the present invention features methods of inhibiting tumor growth in a subject, treating a tumor in a subject, and increasing efficacy of an antibody against a tumor in a subject. The methods comprise (a) administering to the subject an effective amount of an anti-tumor antibody and (b) administering to or generating in the subject an effective amount of a hybrid neutrophil.
    Type: Grant
    Filed: December 15, 2020
    Date of Patent: March 12, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Evgeniy Eruslanov, Steven Albelda
  • Patent number: 11919946
    Abstract: The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).
    Type: Grant
    Filed: April 1, 2020
    Date of Patent: March 5, 2024
    Assignees: Novartis AG, The Trustees of the University of Pennsylvania
    Inventors: Michael C. Milone, Enxiu Wang
  • Patent number: 11920116
    Abstract: The presently disclosed subject matter provides systems and methods for producing a three-dimensional model of a human cervix. A microdevice is provided for culturing human cervical cells. The microdevice can include an upper microchannel including live ectocervical epithelial cells. The microdevice can include a lower microchannel including a first parallel lane and a second parallel lane including stromal media. The first and the second parallel lanes can be lined with live vascular endothelial cells. The lower microchannel can include a third parallel lane including uterine fibroblasts and live smooth muscle cells embedded in hydrogel. The first, second, and third lanes of the lower microchannel can be separated by protrusion structures. The third parallel lane can be positioned in the lower microchannel in between the first and the second parallel lanes. The microdevice can further include a porous membrane positioned in between the upper microchannel and the lower microchannel.
    Type: Grant
    Filed: June 18, 2021
    Date of Patent: March 5, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Dongeun Huh, Jeongyun Seo
  • Patent number: 11918586
    Abstract: The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O—C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2—O—CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substitu
    Type: Grant
    Filed: March 26, 2021
    Date of Patent: March 5, 2024
    Assignees: TORQUR AG, THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: Doriano Fabbro, Paul Hebeisen, Petra Hillmann-Wuellner, Anton Stuetz, John T. Seykora, Florent Beaufils
  • Patent number: 11920130
    Abstract: The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).
    Type: Grant
    Filed: May 12, 2022
    Date of Patent: March 5, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Yangbing Zhao, Jiangtao Ren
  • Patent number: 11923908
    Abstract: Provided are methods for optical communication, comprising: generating a phase difference signal with heterodyne or homodyne phase-locked-loop (PLL) from between an optical input signal and a local laser source; controlling the local laser source with the phase difference signal; demodulating the optical input signal using the local laser source as a carrier signal to generate a baseband output signal; and controlling the heterodyne or homodyne PLL and the demodulation with an electrical oscillator signal. Also provided are related methods.
    Type: Grant
    Filed: March 18, 2022
    Date of Patent: March 5, 2024
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Firooz Aflatouni, Zhe Xuan
  • Publication number: 20240067948
    Abstract: The present invention includes mutant AID, APOBEC, and Tet enzymes with improved functions. In one aspect the invention provides APOBEC fusion proteins comprising hyperactive deamination activity. In another aspect, the invention provides AID mutant proteins comprising hyperactive deamination activity. In yet another aspect, the invention provides mutant Tet proteins capable of stalling oxidation at a 5-hydroxymethylcytosine (hmC).
    Type: Application
    Filed: April 5, 2023
    Publication date: February 29, 2024
    Applicant: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
    Inventors: Rahul Kohli, Emily Schutsky, Monica Yun Liu
  • Patent number: RE49847
    Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.
    Type: Grant
    Filed: January 5, 2022
    Date of Patent: February 27, 2024
    Assignees: Novartis AG, The Trustees of the University of Pennsylvania
    Inventors: Barbara Brannetti, Jennifer Brogdon, Boris Engels, Brian Granda, Lu Huang, Ming Lei, Na Li, Jimin Zhang, Carla Guimaraes, Saar Gill, Marco Ruella, Regina M. Young