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序号	专利名	申请号	申请日	公开（公告）号	公开（公告）日	发明人
21	Rationally-designed single-chain meganucleases with non-palindromic recognition sequences	EP13165733.0	2008-10-31	EP2660317B1	2016-04-06	Smith, James, Jefferson; Jantz, Derek

22	METHODS AND PRODUCTS FOR PRODUCING ENGINEERED MAMMALIAN CELL LINES WITH AMPLIFIED TRANSGENES	EP12792301	2012-06-01	EP2714936A4	2015-07-29	JANTZ DEREK; SMITH JAMES JEFFERSON; NICHOLSON MICHAEL G
Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.
23	RATIONALLY-DESIGNED SINGLE-CHAIN MEGANUCLEASES WITH NON-PALINDROMIC RECOGNITION SEQUENCES	EP08845549	2008-10-31	EP2215223A4	2011-01-05	SMITH JAMES JEFFERSON; JANTZ DEREK

24	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US16201855	2018-11-27	US20190106713A1	2019-04-11	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
25	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US16201853	2018-11-27	US20190106712A1	2019-04-11	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
26	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15959715	2018-04-23	US20180298406A1	2018-10-18	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
27	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15803424	2017-11-03	US20180282764A1	2018-10-04	Martin Jinek; Emmanuelle Charpentier; Krzysztof Chylinski; James Harrison Doudna Cate; Wendell Lim; Lei Qi; Jennifer A. Doudna
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
28	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15981809	2018-05-16	US20180251795A1	2018-09-06	Emmanuelle Charpentier; Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
29	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15965598	2018-04-27	US20180245101A1	2018-08-30	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
30	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15959782	2018-04-23	US20180245100A1	2018-08-30	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
31	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15959762	2018-04-23	US20180237801A1	2018-08-23	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
32	METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION	US15947680	2018-04-06	US20180230495A1	2018-08-16	Jennifer A. Doudna; Martin Jinek; Krzysztof Chylinski; Emmanuelle Charpentier
The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.
33	NOVEL BACTERIAL ENDOPHYTE WITH ANTIFUNGAL ACTIVITY	US15514241	2015-09-28	US20170273308A1	2017-09-28	Manish N. Raizada; Walaa Mousa; Charles Schearer
An Enterobacter species isolated from finger millet, characterized by 16S rRNA gene analysis and the identification of genes that prevent or inhibit the growth of fungal plant pathogens, is disclosed for use with agricultural plants.
34	Rationally-designed single-chain meganucleases with non-palindromic recognition sequences	US14858989	2015-09-18	US09434931B2	2016-09-06	James Jefferson Smith; Derek Jantz
Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.
35	METHODS AND PRODUCTS FOR PRODUCING ENGINEERED MAMMALIAN CELL LINES WITH AMPLIFIED TRANSGENES	US14806175	2015-07-22	US20160017372A1	2016-01-21	Derek JANTZ; James Jefferson SMITH; Michael G. NICHOLSON
Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.
36	RATIONALLY-DESIGNED SINGLE-CHAIN MEGANUCLEASES WITH NON-PALINDROMIC RECOGNITION SEQUENCES	US14858989	2015-09-18	US20160002615A1	2016-01-07	James Jefferson SMITH; Derek JANTZ
Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.
37	Optimization of Expression and Purification of Recombinant Human MxA Protein in E. Coli	US13788716	2013-03-07	US20130344565A1	2013-12-26	Robert W. VanDine; Robert P. Sambursky; Uma Mahesh Babu; Kyosuke Nagata
Full length MxA constructs and truncated MxA constructs produce human MxA protein in E. coli. The full length MxA and truncated MxA constructs are preferably E. coli codon-optimized to optimize the amount of protein made using the constructs. T5 or T7 promoters can each be used in combination with either the full length MxA or the truncated MxA constructs. In one preferred embodiment, the MxA protein produced by the full length MxA or truncated MxA constructs is used in a control prep or external control. In other preferred embodiments, the MxA protein is used as a therapeutic.
38	Process For Producing a Baked Product Having Increased Flavor Stability with Catalase and Phospholipase	US13810272	2011-07-19	US20130216651A1	2013-08-22	Sidsel Langballe Bennedbæk-Jensen; Henrik Østdal
The present invention relates to a process for producing a baked product having increased flavor stability comprising the steps of: (a) preparing a dough comprising flour, water, an enzyme preparation having catalase activity and an enzyme preparation having phospholipase activity; and (b) baking the dough to obtain the baked product.
39	FLUOROQUINOLONE DERIVATIVES OR SULFONAMIDE MOIETY-CONTAINING COMPOUNDS AS INHIBITORS OF TYROSYL-DNAPHOSPHODIESTERASE (TDP1)	US13283282	2011-10-27	US20120172371A1	2012-07-05	Yves Pommier; Christophe Marchand; Periyasamy Selvam; Thomas Dexheimer; Kasthuraiah Maddali
A method for treating cancer in a subject, comprising administering to a subject having cancer a therapeutically effective amount of (i) a fluoroquinolone derivative that inhibits tyrosyl-DNA-phosphodiesterase 1 (Tdp1) activity or (ii) a sulfonamide moiety-containing compound that inhibits tyrosyl-DNA-phosphodiesterase 1 (Tdp1) activity, thereby treating the cancer in the subject. In certain embodiments, the fluoroquinolone derivative or sulfonamide moiety-containing compound is co-administered with a topoisomerase I (TopI) inhibitor.
40	METHODS AND PRODUCTS FOR PRODUCING ENGINEERED MAMMALIAN CELL LINES WITH AMPLIFIED TRANSGENES	US16258207	2019-01-25	US20190249199A1	2019-08-15	Derek Jantz; James Jefferson Smith; Michael G. Nicholson
Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.

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