Patents by Inventor David B. Thompson
David B. Thompson 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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Patent number: 9737604Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: GrantFiled: August 18, 2014Date of Patent: August 22, 2017Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20170044520Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.Type: ApplicationFiled: July 22, 2016Publication date: February 16, 2017Inventors: David R. Liu, David B. Thompson, Jeffrey L. Bessen
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Patent number: 9526784Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of funcational effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: GrantFiled: August 18, 2014Date of Patent: December 27, 2016Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20160280748Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.Type: ApplicationFiled: December 29, 2015Publication date: September 29, 2016Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
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Publication number: 20160215276Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: September 5, 2014Publication date: July 28, 2016Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20160200779Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: ApplicationFiled: September 5, 2014Publication date: July 14, 2016Applicant: President and Fellows of Harvard CollegeInventors: David R. LIU, John Anthony ZURIS, David B. THOMPSON
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Patent number: 9388430Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: GrantFiled: June 30, 2014Date of Patent: July 12, 2016Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Patent number: 9322037Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: GrantFiled: June 30, 2014Date of Patent: April 26, 2016Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Patent number: 9221886Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.Type: GrantFiled: April 28, 2010Date of Patent: December 29, 2015Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
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Publication number: 20150118216Abstract: Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.Type: ApplicationFiled: October 30, 2014Publication date: April 30, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, David B. Thompson, John Anthony Zuris
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Publication number: 20150071903Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: ApplicationFiled: August 18, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20150071898Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: June 30, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20150071899Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: June 30, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20150071906Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of funcational effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.Type: ApplicationFiled: August 18, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Anthony Zuris, David B. Thompson
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Publication number: 20120100569Abstract: Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof.Type: ApplicationFiled: April 28, 2010Publication date: April 26, 2012Inventors: David R. Liu, Brian R. McNaughton, James Joseph Cronican, David B. Thompson
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Publication number: 20110112040Abstract: Compositions, systems and related methods for delivering a supercharged protein or a complex of a supercharged protein and therapeutic agent (e g, nucleic acid, peptide, small molecule) to cells are disclosed. Superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. The systems and methods may involve altering the primary sequence of a protein in order to “supercharge” the protein (e g, to generate a superpositively-charged protein). The compositions may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.Type: ApplicationFiled: April 28, 2009Publication date: May 12, 2011Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Brian R. Mcnaughton, James Joseph Cronican, David B. Thompson
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Publication number: 20080023604Abstract: A bracket for engaging one or more struts and a method of engaging the bracket and strut. The bracket comprises a body portion and one or more arm portions extending from the body portion. The arm portions include at least one pair of grooves that are adapted to releaseably engage complementary lips of the strut and at least one recessed region that is adapted to securely engage one or more crimped portions of the strut. A plurality of brackets and struts may be engaged to construct a frame.Type: ApplicationFiled: July 5, 2005Publication date: January 31, 2008Applicant: N. G. Bailey & Company LimitedInventors: David Bottomley, David B. Thompson
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Patent number: 6802484Abstract: An accessory holder designed to attach to a stand. The stand has a lower tube, a locking collet on the top of the lower tube, and a mast extending upward from the locking collet. The accessory holder has a top mount with a mast receiver that slips around the mast just over the top of the locking collet. The accessory holder also has a clip designed to slip around and engage the mast below the locking collet in the order to lock the holder to the stand. A variety of holding devices can be affixed to the accessory holder, including devices configured to hold an ashtray, a beverage, and a pick.Type: GrantFiled: August 5, 2003Date of Patent: October 12, 2004Inventors: Kevin J. Kiley, Danny Joe Crutchfield, David B. Thompson, Johnny W Mills
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Patent number: 6632377Abstract: Copper or a copper alloy is removed by chemical-mechanical planarization (CMP) in a slurry of an oxidizer, an oxidation inhibitor, and an additive that appreciably regulates copper complexing with the oxidation inhibitor.Type: GrantFiled: September 30, 1999Date of Patent: October 14, 2003Assignee: International Business Machines CorporationInventors: Vlasta Brusic, Daniel C. Edelstein, Paul M. Feeney, William Guthrie, Mark Jaso, Frank B. Kaufman, Naftali Lustig, Peter Roper, Kenneth Rodbell, David B. Thompson
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Patent number: D375711Type: GrantFiled: September 12, 1995Date of Patent: November 19, 1996Inventors: David B. Thompson, David C. Moore, Dusty R. Pace, Michael E. Gannon