Patents by Inventor Peter M. Glazer
Peter M. Glazer 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).
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Publication number: 20220017609Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.Type: ApplicationFiled: March 5, 2021Publication date: January 20, 2022Inventors: James E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
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Publication number: 20210189431Abstract: Methods for gene editing of embryos in vitro are provided. The methods typically include contacting an embryo in vitro with an effective amount of non-enzymatic (e.g., non-nuclease) gene editing active agent(s) optionally encapsulated, entrapped, complexed to or dispersed in polymeric particles to induce at least one alteration in the genome of the embryo. The embryo can be a single cell zygote, however, treatment of male and female gametes prior to fertilization, and embryos having 2, 4, 8, or 16 cells, and including not only zygotes, but also morulas and blastocysts are also provided. Typically, the embryo is contacted with the particles on culture days 0-6 during or following in vitro fertilization.Type: ApplicationFiled: August 12, 2019Publication date: June 24, 2021Inventors: Rachael Putman, Adele S. Ricciardi, Peter M. Glazer, W. Mark Saltzman
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Patent number: 10961301Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.Type: GrantFiled: June 6, 2017Date of Patent: March 30, 2021Assignees: Yale University, The Regents of the University of California, The United States Government Represented by the Department of Veterans AffairsInventors: James E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
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Publication number: 20200308590Abstract: Compositions and methods of genome engineering in vitro and in vivo are provided. In some embodiments, the compositions are triplex forming molecules that bind or hybridize to a target region sequence in the human cystic fibrosis transmembrane conductance regulator (CFTR) gene. Preferably the triplex forming molecules are peptide nucleic acids that include a Hoogsteen binding peptide nucleic acid (PNA) segment and a Watson-Crick binding PNA segment collectively totaling no more than 50 nucleobases in length, wherein the two segments can binid or hybridize to a target region in the CFTR gene having a polypurine sequences and induce strand invasion, displacement, and formation of a triple-stranded molecule among the two PNA segments and the target region's sequence. Methods of using the triplex forming molecules to treat cystic fibrosis are also provided.Type: ApplicationFiled: February 16, 2017Publication date: October 1, 2020Inventors: Peter M. Glazer, W. Mark Saltzman, Marie Egan, Nicole Ali McNeer
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Publication number: 20200113821Abstract: Compositions and methods for fetal or in utero delivery of active agents are provided. The compositions are most typically administered intravenously via the vitelline vein, umbilical vein, or directly into the amniotic cavity of a pregnant mother. Growth factors can be delivered to correct structural defects. Gene editing can be carried out utilizing a gene editing composition such as triplex-forming molecules, CRISPR, zinc finger nucleases, TALENS, or others. The methods can include administration of a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particularly preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the ? position for increased DNA binding affinity. Polymeric particle compositions for extracellular and intracellular delivery of the active agents are also provided.Type: ApplicationFiled: April 4, 2018Publication date: April 16, 2020Inventors: W. Mark Saltzman, Peter M. Glazer, Adele S. Ricciardi, David H. Stitelman, James Farrelly, Anthony Bianchi, Alexandra S. Piotrowski-Daspit, Amy Kauffman
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Publication number: 20170334981Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.Type: ApplicationFiled: June 6, 2017Publication date: November 23, 2017Inventors: James E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
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Patent number: 9701740Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.Type: GrantFiled: April 2, 2012Date of Patent: July 11, 2017Assignees: YALE UNIVERSITY, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, The United States of America represented by the Department of Veterans AffairsInventors: James E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
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Publication number: 20160271156Abstract: The present invention is directed to novel anti-cancer compounds and methods of treating and/or inhibiting cancer in patients, including metastatic cancer, recurrent cancer and drug resistant cancers, including multiple drug resistant cancers. Compounds according to the present invention provide anti-cancer activity, at least in part, by virtue of their nucleotide intercalating activity through the use of analogs of (?)lomaiviticin A, a potent anticancer agent which exhibits cytotoxicity through its principal mechanism of cleavage and to a lesser extent, its intercalation of cellular polynucleotides, especially DNA. In additional embodiments, compounds according to the present invention are also conjugated and/or linked to other bioactive agents, especially agents which selectively target cancer cells (cancer cell targeting moiety or CCTM) to target and increase the delivery of the anticancer agent to the cancer cell.Type: ApplicationFiled: April 29, 2016Publication date: September 22, 2016Inventors: SETH HERZON, Christina Woo, Peter M. Glazer
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Patent number: 9346846Abstract: The present invention is directed to novel anti-cancer compounds and methods of treating and/or inhibiting cancer in patients, including metastatic cancer, recurrent cancer and drug resistant cancers, including multiple drug resistant cancers. Compounds according to the present invention provide anti-cancer activity, at least in part, by virtue of their nucleotide intercalating activity through the use of analogs of (?)lomaiviticin A, a potent anticancer agent which exhibits cytotoxicity through its principal mechanism of cleavage and to a lesser extent, its intercalation of cellular polynucleotides, especially DNA. In additional embodiments, compounds according to the present invention are also conjugated and/or linked to other bioactive agents, especially agents which selectively target cancer cells (cancer cell targeting moiety or CCTM) to target and increase the delivery of the anticancer agent to the cancer cell.Type: GrantFiled: December 2, 2014Date of Patent: May 24, 2016Assignee: YALE UNIVERSITYInventors: Seth Herzon, Christina Woo, Peter M. Glazer
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Patent number: 8658608Abstract: High affinity, chemically modified triplex-forming oligonucleotides (TFOs) and methods for use thereof are disclosed. TFOs are defined as triplex-forming oligonucleotides which bind as third strands to duplex DNA in a sequence specific manner. Triplex-forming oligonucleotides may be comprised of any possible combination of nucleotides and modified nucleotides. Modified nucleotides may contain chemical modifications of the heterocyclic base, sugar moiety or phosphate moiety. A high affinity oligonucleotide (Kd?2×10?8) which forms a triple strand with a specific DNA segment of a target gene DNA is generated. It is preferable that the Kd for the high affinity oligonucleotide is below 2×10?10. The nucleotide binds or hybridizes to a target sequence within a target gene or target region of a chromosome, forming a triplex region. The binding of the oligonucleotide to the target region stimulates mutations within or adjacent to the target region using cellular DNA synthesis, recombination, and repair mechanisms.Type: GrantFiled: November 22, 2006Date of Patent: February 25, 2014Assignees: Yale University, Department of Health and Human ServicesInventors: Peter M. Glazer, Michael M. Siedman
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Publication number: 20140050723Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.Type: ApplicationFiled: April 2, 2012Publication date: February 20, 2014Applicants: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, YALE UNIVERSITYInventors: James E. Hansen, Peter M. Glazer, Richard H. Weisbart, Robert N. Nishimura, Grace Chan
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Patent number: 8309356Abstract: Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.Type: GrantFiled: April 1, 2010Date of Patent: November 13, 2012Assignee: Yale UniversityInventor: Peter M. Glazer
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Publication number: 20110293585Abstract: Compositions and methods for treating lysosomal storage diseases are disclosed. Lysosomal dysfunction is usually the result of deficiency of a single enzyme necessary for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides which are fated for breakdown or recycling. The compositions contain triplex-forming molecules which can be used to induce site-specific homologous recombination in mammalian cells when combined with donor DNA molecules, by stimulating cellular DNA synthesis, recombination, and repair mechanisms. The methods are particular useful for correcting point mutations in genes associated with lysosomal storage diseases such as Gaucher's disease, Fabry disease, and Hurler syndrome. Methods for determining the frequency of target gene repair and assessing the restoration of the enzymatic activity of corrected polypeptides are also disclosed. Ex vivo and in vivo methods of gene correction in patients are also provided.Type: ApplicationFiled: April 21, 2011Publication date: December 1, 2011Inventors: Jacob del Campo, Ranjit S. Bindra, Peter M. Glazer
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Publication number: 20110268810Abstract: Polymeric microparticles are used to deliver recombinagenic or mutagenic nucleic acid molecules such as donor nucleic acid alone, or in combination with triplex-forming molecules, to induce a site-specific mutation in the target DNA. Target cells endocytose the particles, releasing the nucleic acid molecules inside of the cell, where they induce mutagenesis or recombination at a target site. The examples demonstrate that triplex forming oligonucleotides, preferably PNAs, preferably in combination with a donor nucleotide molecule, can be encapsulated into polymeric microparticles, which are delivered into cells. Results demonstrate significantly greatly levels of uptake and expression, and less cytotoxicity, as compared to direct transfer of the nucleic acid molecules into the cell by nucleofection.Type: ApplicationFiled: November 2, 2010Publication date: November 3, 2011Inventors: William Mark Saltzman, Peter M. Glazer, Joanna Chin, Nicole McNeer
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Publication number: 20110262406Abstract: Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that displace the polypyrimidine strand of target duplex and form a triple-stranded structure and hybrid duplex in a sequence specific manner with the polypurine strand of the target duplex. The triplex-forming molecules include a mixed-sequence “tail” which increases the stringency of binding to the target duplex, improves the frequency of modification at the target site, and reduces the requirement for a polypurine:polypyrimidine stretch. Methods for using the triplex-forming molecules in combination with one or more donor oligonucleotides for targeted modification of sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV) are also disclosed. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.Type: ApplicationFiled: April 21, 2011Publication date: October 27, 2011Inventors: Jacob del Campo, Erica Beth Schleifman, Ranjit S. Bindra, Peter M. Glazer
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Publication number: 20110086905Abstract: Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.Type: ApplicationFiled: April 1, 2010Publication date: April 14, 2011Inventor: Peter M. Glazer
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Publication number: 20100172882Abstract: Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that bind to duplex DNA in a sequence specific manner at target sites to form triple-stranded structures. The triplex-forming molecules can be triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs). The triplex-forming molecules are useful to induce site-specific homologous recombination in mammalian cells when used in combination with donor oligonucleotides. The triplex-forming molecules target sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV). This binding stimulates homologous recombination of a donor oligonucleotide to cause mutations in HIV cell surface receptor genes that result in one or more deficiencies in the ability of the encoded receptor to bind to HIV and allow its transport into the cell.Type: ApplicationFiled: January 11, 2008Publication date: July 8, 2010Inventors: Peter M. Glazer, Ranjit Bindra, Erica B. Schleifman
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Patent number: 7407752Abstract: The methods disclosed herein are of use for the treatment of a wide variety of diseases. In particular, the methods provide for the targeting of a transcription altering agent to a specific target site of a viral genome in order to inactivate the virus. In addition, the methods provide for a triplex-forming oligonucleotide capable of interacting with a target site in a viral genome in order to alter transcription. The methods of the present invention may be used against viral pathogens or agents of bioterrorism.Type: GrantFiled: April 21, 2004Date of Patent: August 5, 2008Assignees: University of Utah Research Foundation, Yale UniversityInventors: John D. Kriesel, Brandt B. Jones, Charles B. Grissom, Geoff Herpin, Peter M. Glazer
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Patent number: 7279463Abstract: A high affinity, triplex-forming oligonucleotide and methods for use thereof wherein an oligonucleotide is used to form a triple-stranded nucleic acid molecule with a specific DNA segment of a target DNA molecule. Upon formation of the triplex, the binding of the oligonucleotide stimulates mutagenesis within or adjacent to the target sequence using cellular DNA synthesis or repair mechanisms thereby producing heritable changes in a human or animal. The mutation activates, inactivates or alters the activity and function of the target molecule. This mutation may be the result of a recombinagenic mechanism induced by the oligonucleotide.Type: GrantFiled: October 15, 2001Date of Patent: October 9, 2007Assignee: Yale UniversityInventor: Peter M. Glazer
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Patent number: 7078389Abstract: A mutagenic, triplex-forming oligonucleotide and methods for use thereof wherein the oligonucleotide is chemically modified to incorporate a mutagen and forms a triple-stranded nucleic acid molecule with a specific DNA segment of a target DNA molecule. Upon formation of the triplex, the mutagen is brought into proximity with the target molecule and causes a mutation at a specific site therein. The mutation activates, inactivates or alters the activity and function of the target molecule.Type: GrantFiled: February 14, 2001Date of Patent: July 18, 2006Assignee: Yale UniversityInventors: Peter M. Glazer, Pamela A. Havre