公开(公告)号：US20240358855A1

公开(公告)日：2024-10-31

申请号：US18684547

申请日：2022-08-18

Applicant: University of Utah Research Foundation

Inventor： Gregory S. Hageman ,  Burt T. Richards

IPC: A61K48/00 ,  A61K38/17 ,  A61P21/00 ,  C07K16/22 ,  C12N9/22 ,  C12N15/113 ,  C12N15/86

CPC classification number: A61K48/005 ,  A61K38/1725 ,  A61P21/00 ,  C07K16/22 ,  C12N9/22 ,  C12N15/113 ,  C12N15/86 ,  C07K2317/31 ,  C07K2317/622 ,  C12N2310/122 ,  C12N2310/14 ,  C12N2310/20 ,  C12N2750/14143 ,  C12N2830/50 ,  C12N2840/203

Abstract: Gene therapy methods, vectors and cargo described herein can reduce or prevent C3b amplification and/or MAC formation within the neural retina, retinal pigmented epithelium (RPE), choroid, choriocapillaris (CC), Bruch's membrane and other ocular cells and tissues to re-establish appropriate control of the complement system. Gene therapy methods disclosed will benefit patients with complement related diseases such as AMD. Some gene therapy methods use a viral or nonviral vector comprising a cargo encoding two, three, or more than three activities selected from: a) one or more of a complement proteins selected from CFHT, oCFHT, CFH, and CFI; b) one of more binding proteins that specifically binds CFB, CFD, CFP, CFHR-1, CFHR-2, CFHR-3, CFHR-4, CFHR-5, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C8G, or C9; c) HTRA1 protein or a transcriptional activator protein that increases expression of HTRA1; d) a binding protein that specifically binds ApoE2 or VEGFA; e) an inhibitory RNA that targets CFB, CFD, CFP, FHR-1, CFHR-2, CFHR-3, CFHR-4, CFHR-5, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C8G, or C9; and f) an inhibitory RNA that targets ApoE2 or VEGFA. Also disclosed are optimized forms of truncated Complement Factor H (oCFHT) useful for treatment of patients in gene therapy (delivered alone or in combination with other activities).

公开(公告)号：US12123021B2

公开(公告)日：2024-10-22

申请号：US17707725

申请日：2022-03-29

Applicant: KSQ Therapeutics, Inc.

Inventor： Micah Benson ,  Jason J. Merkin ,  Gregory V. Kryukov ,  Solomon Martin Shenker ,  Michael R. Schlabach ,  Noah Jacob Tubo ,  James Martin Kaberna, II

IPC: C12N5/0783 ,  A61K35/17 ,  A61P35/00 ,  A61P35/04 ,  C07K14/705 ,  C07K14/725 ,  C07K16/28 ,  C07K16/32 ,  C12N9/22 ,  C12N15/11 ,  C12N15/113 ,  A61K38/00 ,  A61K39/00

CPC classification number: C12N5/0636 ,  A61K35/17 ,  A61P35/00 ,  A61P35/04 ,  C07K14/7051 ,  C07K14/70517 ,  C07K16/2803 ,  C07K16/2863 ,  C07K16/32 ,  C12N9/22 ,  C12N15/11 ,  C12N15/113 ,  C12N15/1135 ,  A61K38/00 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2319/30 ,  C12N2310/122 ,  C12N2310/14 ,  C12N2310/20 ,  C12N2310/531 ,  C12N2800/80

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

公开(公告)号：US20240316107A1

公开(公告)日：2024-09-26

申请号：US18740688

申请日：2024-06-12

Applicant: The Trustees of the University of Pennsylvania

Inventor： Yangbing Zhao ,  Jiangtao Ren

IPC: A61K35/17 ,  A61K39/00 ,  A61P35/00 ,  A61P37/02 ,  C12N9/22 ,  C12N15/10 ,  C12N15/117 ,  C12N15/90

CPC classification number: A61K35/17 ,  C12N9/22 ,  C12N15/102 ,  C12N15/117 ,  C12N15/90 ,  A61K2039/5158 ,  A61P35/00 ,  A61P37/02 ,  C12N2310/122 ,  C12N2310/20 ,  C12N2310/315

Abstract: The present invention includes compositions and methods for modifying primary T cells. In one aspect, the invention comprises administering to a cell a stem-loop Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) RNA (st-crRNA) and a Cpf1 enzyme.

公开(公告)号：US12037615B2

公开(公告)日：2024-07-16

申请号：US17079097

申请日：2020-10-23

Applicant: INTEGRATED DNA TECHNOLOGIES, INC.

Inventor： Jessica Woodley ,  Bernice Thommandru ,  Joseph Dobosy ,  Mark Behlke ,  Adam Clore ,  Garrett Rettig ,  Beimeng Sun

IPC: C12N15/66 ,  C12N9/22 ,  C12N15/113

CPC classification number: C12N9/22 ,  C12N15/113 ,  C12N15/66 ,  C12N2310/122 ,  C12N2310/20 ,  C12N2310/321 ,  C12N2310/531 ,  C12N2800/80

Abstract: Described herein are compositions and methods for improving homology directed repair (HDR) efficiency and reducing homology-independent integration following introduction of double strand breaks with engineered nucleases. Additionally, modifications to double stranded DNA donors to improve the donor potency and efficiency of homology directed repair following introduction of double stranded breaks with programmable nucleases.

公开(公告)号：US12031137B2

公开(公告)日：2024-07-09

申请号：US17302113

申请日：2021-04-23

Applicant: RSEM, LIMITED PARTNERSHIP

Inventor： Przemyslaw Sapieha ,  Frédérick Antoine Mallette ,  Malika Oubaha ,  Normand Beaulieu ,  Ariel Wilson

IPC: A61K47/68 ,  A61K31/155 ,  A61K31/7088 ,  A61K38/17 ,  A61P3/04 ,  C07K16/28 ,  C12N15/113 ,  C12N15/62

CPC classification number: C12N15/1138 ,  A61K31/155 ,  A61K31/7088 ,  A61K38/179 ,  A61P3/04 ,  C07K16/2863 ,  C07K2319/30 ,  C12N2310/111 ,  C12N2310/122 ,  C12N2310/531

Abstract: Described herein are compositions and methods for modulating cellular senescence of a cell or induction of the senescence-associated secretory phenotype (SASP) in a cell. The methods generally comprise modulating the level or activity of IRE1a as a mean to control cellular senescence and induction of the SASP. Also described are methods for treating and preventing ocular vascular diseases comprising contacting cells in an eye of a subject with a biguanide compound and ophthalmic compositions comprising a biguanide compound.

公开(公告)号：US12012599B2

公开(公告)日：2024-06-18

申请号：US17046276

申请日：2019-04-15

Applicant: CZ Biohub SF LLC ,  The Board of Trustees of the Leland Stanford Junior University

Inventor： Michael F. Clarke ,  Neethan A. Lobo ,  Maider Zabala Ugalde ,  Jane Antony

IPC: A61P35/00 ,  A61K38/18 ,  C07K16/22 ,  C12N15/113 ,  C12Q1/6886 ,  G01N33/574 ,  G01N33/74 ,  A61K39/00

CPC classification number: C12N15/1136 ,  A61K38/1808 ,  A61K38/1841 ,  A61K38/1875 ,  A61P35/00 ,  C07K16/22 ,  C12Q1/6886 ,  G01N33/57484 ,  G01N33/74 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/76 ,  C12N2310/122 ,  C12N2310/14 ,  C12Q2600/158 ,  G01N2333/495 ,  G01N2333/51 ,  G01N2500/02

Abstract: This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

公开(公告)号：US20240150763A1

公开(公告)日：2024-05-09

申请号：US18275591

申请日：2022-02-02

Applicant: SPARTINA BIOTECHNOLOGIES, INC.

Inventor： Richard Sayre ,  Tatiana Vinogradova-Shah ,  Alexander Pertzev

IPC: C12N15/113 ,  A61K9/50 ,  A61P31/14 ,  C07K14/515 ,  C07K14/705 ,  C12N1/18 ,  C12R1/865

CPC classification number: C12N15/1131 ,  A61K9/5068 ,  A61P31/14 ,  C07K14/515 ,  C07K14/705 ,  C12N1/185 ,  C12N2310/122 ,  C12R2001/865

Abstract: The present invention is directed to Saccharomyces-generated extracellular vesicles (EVs) comprising a foreign RNA molecule or protein and at least one foreign membrane surface exposed ligand that specifically binds to a target receptor displayed on a target cell. The present invention also relates to methods of making and using these Saccharomyces-generated EVs for targeted gene silencing. The present invention also relates to fusion proteins comprising a Saccharomyces extracellular vesicle anchor protein and a second peptide designed to bind to cell-specific receptors.

公开(公告)号：US20240110164A1

公开(公告)日：2024-04-04

申请号：US18375415

申请日：2023-09-29

Applicant: VedaBio, Inc.

Inventor： Anurup Ganguli ,  Joshua Miller ,  Andrew Garst ,  Robert Plasschaert ,  Swetha Murali

IPC: C12N9/22

CPC classification number: C12N9/22 ,  C12N2310/122 ,  C12N2310/20

Abstract: The present disclosure relates to compositions of matter and methods used to activate effector nucleic acids and effector targets in vivo via a CRISPR-based cascade system. The compositions and methods achieve non-specific delivery of cascade system components to cells yet the cascade system works in a cell-specific manner.

公开(公告)号：US11898144B2

公开(公告)日：2024-02-13

申请号：US17155387

申请日：2021-01-22

Applicant: Arizona Board of Regents on behalf of Arizona State University

Inventor： Alexander Green ,  Yu Zhou

IPC: C12N15/113 ,  C12N15/67 ,  H03K19/20

CPC classification number: C12N15/113 ,  C12N15/67 ,  H03K19/20 ,  C12N2310/122 ,  C12N2310/531

Abstract: Provided herein are synthetic nucleic acid molecules and methods of using such synthetic nucleic acid molecules for strong repression of target gene expression. In particular, provided herein are methods for altering expression of a protein in a cell, where the method comprises introducing into a cell a protein coding sequence operably linked to a near-threshold translational repressor having first and second trigger recognition sequences that are fully or partially complementary to a repressing trigger RNA; and introducing into a cell the repressing trigger RNA.

公开(公告)号：US11840563B2

公开(公告)日：2023-12-12

申请号：US16496142

申请日：2018-03-22

Applicant: Children's Medical Center Corporation

Inventor： Randolph S. Watnick

IPC: C07K14/81 ,  A61K31/7088 ,  A61P35/04 ,  A61K38/00 ,  A61K39/395 ,  C07K16/38 ,  C12N15/113 ,  A61K39/00

CPC classification number: C07K14/811 ,  A61K31/7088 ,  A61K38/005 ,  A61K39/3955 ,  A61P35/04 ,  C07K16/38 ,  C12N15/1137 ,  A61K2039/545 ,  C07K2317/32 ,  C07K2317/76 ,  C12N2310/122 ,  C12N2310/14 ,  C12N2310/531

Abstract: Provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Further provided herein are agents that bind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1 Methods of using these agents in treating cancer are also provided.