公开(公告)号：US11136597B2

公开(公告)日：2021-10-05

申请号：US15434978

申请日：2017-02-16

申请人： Yale University ,  Carnegie Mellon University

发明人： W. Mark Saltzman ,  Peter Glazer ,  Raman Bahal ,  Nicole Ali McNeer ,  Danith H. Ly ,  Elias Quijano

IPC分类号： C07H21/04 ,  C12N15/90 ,  C07K14/00 ,  C12N15/10 ,  C12N15/11 ,  A61K9/16 ,  A61K48/00 ,  C12N15/113

摘要： Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

公开(公告)号：US20170283830A1

公开(公告)日：2017-10-05

申请号：US15434978

申请日：2017-02-16

申请人： Yale University ,  Carnegie Mellon University

发明人： W. Mark Saltzman ,  Peter Glazer ,  Raman Bahal ,  Nicole Ali McNeer ,  Danith H. Ly ,  Elias Quijano

IPC分类号： C12N15/90 ,  A61K48/00 ,  A61K9/16 ,  C12N15/11

CPC分类号： C12N15/907 ,  A61K9/1647 ,  A61K48/005 ,  C07K14/003 ,  C12N15/102 ,  C12N15/11 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/15 ,  C12N2310/152 ,  C12N2310/318 ,  C12N2310/3181 ,  C12N2310/334 ,  C12N2310/351 ,  C12N2310/3519

摘要： Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

公开(公告)号：US12005121B2

公开(公告)日：2024-06-11

申请号：US17823492

申请日：2022-08-30

申请人： Yale University

发明人： Elias Quijano ,  Peter Glazer

IPC分类号： A61K47/54 ,  A61K39/00 ,  A61K47/68 ,  A61K48/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/52 ,  C07K16/44 ,  C12N15/11 ,  C12N15/113 ,  C12N15/87

CPC分类号： A61K47/549 ,  A61K47/6807 ,  A61K47/6851 ,  A61K48/0025 ,  A61K48/005 ,  A61P35/00 ,  C07K14/4747 ,  C07K14/52 ,  C07K16/44 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1135 ,  C12N15/87 ,  A61K2039/505 ,  A61K48/00 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/77 ,  C07K2319/33 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/3181 ,  C12N2310/3513 ,  C12N2320/32

摘要： Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

公开(公告)号：US20230265214A1

公开(公告)日：2023-08-24

申请号：US18043534

申请日：2021-08-31

申请人： YALE UNIVERSITY ,  GENNAO BIO, INC.

发明人： Elias Quijano ,  Peter Glazer ,  Bruce C. Turner ,  Audrey Turchick ,  W. Mark Saltzman

IPC分类号： C07K16/40 ,  C12N15/117 ,  A61P35/00

CPC分类号： C07K16/40 ,  C12N15/117 ,  A61P35/00 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/24

摘要： Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

公开(公告)号：US20220280656A1

公开(公告)日：2022-09-08

申请号：US17631661

申请日：2020-07-31

申请人： Yale University

发明人： Peter Glazer ,  Elias Quijano ,  W. Mark Saltzman ,  Hee Won Suh

IPC分类号： A61K48/00 ,  A61K9/51 ,  C12N15/113

摘要： Peptide nucleic acid (PNA) oligomers that target the β-globin gene and can increase the frequency of recombination of donor oligonucleotide at the site of a Sickle Cell Disease mutation are provided. Nanoparticle formulations for delivering the PNA oligomers and donor oligonucleotides, and potentiating agents for increase the frequency of recombination of the donor oligonucleotide are also provided. Methods of using the PNA oligomers, donor oligonucleotides, nanoparticles, and potentiating agents for treating Sickle Cell Disease are also provided.

公开(公告)号：US20210340279A1

公开(公告)日：2021-11-04

申请号：US17272124

申请日：2019-08-30

申请人： Yale University

发明人： Peter Glazer ,  Audrey Turchick

IPC分类号： C07K16/44 ,  A61K45/06

摘要： Combination therapies including administering a subject in need thereof a cell-penetrating binding protein, such as an antibody, and an immune checkpoint modulator are provided. Typically, the cell-penetrating binding protein can induce DNA damage or reduce DNA damage repair in an effective amount to activate the innate immunity inflammatory pathway in target cells such as cancer cells or infected cells. For example, in some embodiments, the cell-penetrating binding protein increases induced p21 and/or p27 protein expression, increases accumulation of single-strand DNA in the cytosol, increases phosphorylation of STAT1, or a combination thereof in target cells. The subject can have cancer or an infection and the combination of the cell-penetrating binding protein and the immune checkpoint modulator reduce one or more symptoms of cancer or infection, preferably to a greater degree than administering the subject the same amount of cell-penetrating binding protein alone or the same amount of immune checkpoint modulator alone.

公开(公告)号：US20240216530A1

公开(公告)日：2024-07-04

申请号：US18548823

申请日：2022-03-03

申请人： Yale University ,  Gennao Bio, Inc.

发明人： Elias Quijano ,  Peter Glazer ,  Bruce C. Turner ,  Stephen Squinto

IPC分类号： A61K48/00 ,  A61K38/17 ,  A61K47/68 ,  A61P21/00 ,  C07K16/44

CPC分类号： A61K48/0025 ,  A61K38/1719 ,  A61K47/6807 ,  A61P21/00 ,  C07K16/44

摘要： Compositions and methods are provided for treating myopathies by administering a complex formed between a therapeutic mRNA polynucleotide and a 3E10 antibody or variant thereof, or antigen-binding fragment thereof. In some instances, the complexes are stabilized through a molar ratio of 3E10 antibody or variant thereof, or antigen-binding fragment thereof to therapeutic polynucleotide of at least about 2:1.

公开(公告)号：US11311538B2

公开(公告)日：2022-04-26

申请号：US16510122

申请日：2019-07-12

申请人： YALE UNIVERSITY

发明人： Ranjit Bindra ,  Peter Glazer ,  Parker Sulkowski ,  Brian Shuch

IPC分类号： A61K31/55 ,  A61K31/498 ,  A61K31/445 ,  A61K31/4196 ,  A61K31/4164 ,  A61P35/00 ,  A61K31/502 ,  A61K31/166 ,  A61K31/454 ,  A61K31/4184 ,  A61K31/215 ,  A61K31/04 ,  A61K31/47 ,  A61K31/145 ,  A61K31/5025 ,  A61K45/06

摘要： In various aspects and embodiments the invention provides a method of treating or preventing a cancer in a mammalian subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one compound selected from the group consisting of a DNA repair inhibitor, a DNA strand break repair inhibitor, and a homologous recombination (HR) repair inhibitor, wherein cells in the cancer comprise a fumarate hydratase (FH) and/or succinate dehydrogenase (SDH) mutation.

公开(公告)号：US20240190998A1

公开(公告)日：2024-06-13

申请号：US18255753

申请日：2021-12-06

申请人： YALE UNIVERSITY ,  GENNAO BIO, INC.

发明人： Elias Quijano ,  Peter Glazer ,  Bruce Turner ,  Stephen Squinto

IPC分类号： C07K16/40 ,  A61K31/7105 ,  A61K31/713 ,  A61K39/00 ,  A61K47/68 ,  A61P35/00

CPC分类号： C07K16/40 ,  A61K31/7105 ,  A61K31/713 ,  A61K47/6807 ,  A61K47/6879 ,  A61P35/00 ,  A61K2039/505 ,  C07K2317/31 ,  C07K2317/565

摘要： Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

公开(公告)号：US20240181086A1

公开(公告)日：2024-06-06

申请号：US18548827

申请日：2022-03-03

申请人： Yale University ,  Gennao Bio, Inc.

发明人： Elias Quijano ,  Peter Glazer ,  Bruce C. Turner ,  Stephen Squinto

IPC分类号： A61K48/00 ,  A61K39/00 ,  C07K16/44 ,  C12N15/87

CPC分类号： A61K48/0066 ,  C07K16/44 ,  C12N15/87 ,  A61K2039/505 ,  C07K2317/565 ,  C07K2317/77

摘要： Compositions and methods are provided for delivering therapeutic polynucleotides by administering a complex formed between a therapeutic polynucleotide having a 3E10 or 3E10 variant binding domain and a 3E10 antibody or variant thereof, or antigen-binding fragment thereof. In some instances, the complexes are stabilized through a molar ratio of 3E10 antibody or variant thereof, or antigen-binding fragment thereof to therapeutic polynucleotide of at least about 2:1.