CA2331926C - Methods for generating highly diverse libraries - Google Patents
Methods for generating highly diverse libraries Download PDFInfo
- Publication number
- CA2331926C CA2331926C CA2331926A CA2331926A CA2331926C CA 2331926 C CA2331926 C CA 2331926C CA 2331926 A CA2331926 A CA 2331926A CA 2331926 A CA2331926 A CA 2331926A CA 2331926 C CA2331926 C CA 2331926C
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- population
- stranded nucleic
- templates
- fragments
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 107
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 174
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 141
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 141
- 239000012634 fragment Substances 0.000 claims abstract description 64
- 230000000295 complement effect Effects 0.000 claims abstract description 43
- 108091026890 Coding region Proteins 0.000 claims abstract description 31
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims abstract description 22
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims abstract description 22
- 238000009396 hybridization Methods 0.000 claims abstract description 18
- 102000012410 DNA Ligases Human genes 0.000 claims abstract description 16
- 108010061982 DNA Ligases Proteins 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 238000006073 displacement reaction Methods 0.000 claims abstract description 12
- 230000000694 effects Effects 0.000 claims abstract description 12
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 claims abstract description 10
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 claims abstract description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 38
- 230000035772 mutation Effects 0.000 claims description 33
- 108090000623 proteins and genes Proteins 0.000 claims description 23
- 102000004190 Enzymes Human genes 0.000 claims description 21
- 108090000790 Enzymes Proteins 0.000 claims description 21
- 108091034117 Oligonucleotide Proteins 0.000 claims description 21
- 230000008439 repair process Effects 0.000 claims description 20
- 150000001413 amino acids Chemical class 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 18
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 13
- 230000004927 fusion Effects 0.000 claims description 12
- 238000000338 in vitro Methods 0.000 claims description 11
- 108060002716 Exonuclease Proteins 0.000 claims description 10
- 102000013165 exonuclease Human genes 0.000 claims description 10
- 241001524679 Escherichia virus M13 Species 0.000 claims description 5
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- 108020004414 DNA Proteins 0.000 description 38
- 102000053602 DNA Human genes 0.000 description 24
- 239000002773 nucleotide Substances 0.000 description 18
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- 238000013459 approach Methods 0.000 description 14
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- 238000005215 recombination Methods 0.000 description 7
- 230000006798 recombination Effects 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
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- 150000001875 compounds Chemical class 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 108091033380 Coding strand Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- 108091027305 Heteroduplex Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- AXEOMQHKTSGLGS-VIFPVBQESA-N (2s)-2-amino-3-(4-hydroxy-2-methylphenyl)propanoic acid Chemical compound CC1=CC(O)=CC=C1C[C@H](N)C(O)=O AXEOMQHKTSGLGS-VIFPVBQESA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000212384 Bifora Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 108010063113 DNA Polymerase II Proteins 0.000 description 1
- 102000010567 DNA Polymerase II Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 108010059724 Micrococcal Nuclease Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000006846 excision repair Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
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- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- -1 therapeutics Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biochemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Compounds Of Unknown Constitution (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9097098P | 1998-06-29 | 1998-06-29 | |
| US60/090,970 | 1998-06-29 | ||
| PCT/US1999/014776 WO2000000632A1 (en) | 1998-06-29 | 1999-06-29 | Methods for generating highly diverse libraries |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2331926A1 CA2331926A1 (en) | 2000-01-06 |
| CA2331926C true CA2331926C (en) | 2013-09-10 |
Family
ID=22225171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2331926A Expired - Lifetime CA2331926C (en) | 1998-06-29 | 1999-06-29 | Methods for generating highly diverse libraries |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1092039B1 (https=) |
| JP (1) | JP4700805B2 (https=) |
| KR (1) | KR20010071613A (https=) |
| CN (1) | CN1308683A (https=) |
| AT (1) | ATE547532T1 (https=) |
| AU (1) | AU761570B2 (https=) |
| CA (1) | CA2331926C (https=) |
| ES (1) | ES2381824T3 (https=) |
| IL (1) | IL140100A0 (https=) |
| NO (1) | NO20006675D0 (https=) |
| NZ (1) | NZ508287A (https=) |
| WO (1) | WO2000000632A1 (https=) |
| ZA (1) | ZA200007261B (https=) |
Families Citing this family (103)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7883872B2 (en) | 1996-10-10 | 2011-02-08 | Dyadic International (Usa), Inc. | Construction of highly efficient cellulase compositions for enzymatic hydrolysis of cellulose |
| US6902918B1 (en) | 1998-05-21 | 2005-06-07 | California Institute Of Technology | Oxygenase enzymes and screening method |
| ES2237159T3 (es) | 1998-10-06 | 2005-07-16 | Mark Aaron Emalfarb | Sistema de transformacion en el campo de los hongos micoticos filamentosos en chrysosporium. |
| US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6917882B2 (en) | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
| EP1130093A1 (en) | 1999-01-19 | 2001-09-05 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US7873477B1 (en) | 2001-08-21 | 2011-01-18 | Codexis Mayflower Holdings, Llc | Method and system using systematically varied data libraries |
| US7702464B1 (en) | 2001-08-21 | 2010-04-20 | Maxygen, Inc. | Method and apparatus for codon determining |
| US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US8457903B1 (en) | 1999-01-19 | 2013-06-04 | Codexis Mayflower Holdings, Llc | Method and/or apparatus for determining codons |
| US7430477B2 (en) | 1999-10-12 | 2008-09-30 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
| EP1230269A2 (en) | 1999-11-03 | 2002-08-14 | Maxygen, Inc. | Antibody diversity generation |
| US7115403B1 (en) | 2000-05-16 | 2006-10-03 | The California Institute Of Technology | Directed evolution of galactose oxidase enzymes |
| US6539102B1 (en) | 2000-09-01 | 2003-03-25 | Large Scale Proteomics | Reference database |
| US6980674B2 (en) | 2000-09-01 | 2005-12-27 | Large Scale Proteomics Corp. | Reference database |
| EP1341911A1 (en) * | 2000-12-06 | 2003-09-10 | Novozymes A/S | Method for producing a polynucleotide library |
| US6783941B2 (en) | 2000-12-06 | 2004-08-31 | Novozymes A/S | Method for producing a polynucleotide library in vitro by mismatch repair of heteroduplexes |
| US6689568B2 (en) | 2001-02-01 | 2004-02-10 | Agilent Technologies, Inc. | Capture arrays using polypeptide capture agents |
| EP1358322B1 (en) * | 2001-02-02 | 2009-10-28 | Large Scale Biology Corporation | A method of increasing complementarity in a heteroduplex polynucleotide |
| AU2002307340A1 (en) | 2001-04-16 | 2002-10-28 | California Institute Of Technology | Peroxide-driven cytochrome p450 oxygenase variants |
| US20030032028A1 (en) * | 2001-06-12 | 2003-02-13 | Gayle Dace | In vitro capture of nucleic acids via modified oligonucleotides and magnetic beads |
| US7226768B2 (en) | 2001-07-20 | 2007-06-05 | The California Institute Of Technology | Cytochrome P450 oxygenases |
| WO2003062417A1 (fr) * | 2002-01-22 | 2003-07-31 | Mitsubishi Chemical Corporation | Produit de ligation arn-adn, et utilisation correspondante |
| EP1493027B1 (en) | 2002-03-01 | 2014-10-15 | Codexis Mayflower Holdings, LLC | Methods, systems, and software for identifying functional bio-molecules |
| US7620500B2 (en) | 2002-03-09 | 2009-11-17 | Maxygen, Inc. | Optimization of crossover points for directed evolution |
| US7226771B2 (en) | 2002-04-19 | 2007-06-05 | Diversa Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
| AU2003243157C1 (en) | 2002-04-19 | 2008-09-04 | Verenium Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
| US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| WO2005003289A2 (en) | 2002-08-06 | 2005-01-13 | Verdia, Inc. | Ap1 amine oxidase variants |
| DK2194133T3 (en) | 2003-03-06 | 2016-02-29 | Basf Enzymes Llc | Amylases, nucleic acids encoding them, and methods of making and using the same |
| EP2853593B1 (en) | 2003-03-07 | 2017-10-04 | DSM IP Assets B.V. | Hydrolases, nucleic acids encoding them and mehods for making and using them |
| US7592434B2 (en) | 2003-04-04 | 2009-09-22 | Verenium Corporation | Pectate lyases, nucleic encoding them and methods for making and using them |
| CN1863914B (zh) | 2003-04-29 | 2011-03-09 | 先锋高级育种国际公司 | 新的草甘膦-n-乙酰转移酶(gat)基因 |
| WO2005017105A2 (en) | 2003-06-17 | 2005-02-24 | California University Of Technology | Regio- and enantioselective alkane hydroxylation with modified cytochrome p450 |
| CN103484486B (zh) | 2003-07-02 | 2018-04-24 | 维莱尼姆公司 | 葡聚糖酶，编码它们的核酸以及制备和使用它们的方法 |
| WO2005017116A2 (en) | 2003-08-11 | 2005-02-24 | California Institute Of Technology | Thermostable peroxide-driven cytochrome p450 oxygenase variants and methods of use |
| EP1668113B1 (en) | 2003-08-11 | 2013-06-19 | Verenium Corporation | Laccases, nucleic acids encoding them and methods for making and using them |
| JP2005065575A (ja) * | 2003-08-22 | 2005-03-17 | Japan Science & Technology Agency | フレームシャッフリングによるタンパク質分子多様性集団の作製 |
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1999
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- 1999-06-29 IL IL14010099A patent/IL140100A0/xx unknown
- 1999-06-29 JP JP2000557385A patent/JP4700805B2/ja not_active Expired - Lifetime
- 1999-06-29 CA CA2331926A patent/CA2331926C/en not_active Expired - Lifetime
- 1999-06-29 NZ NZ508287A patent/NZ508287A/en not_active IP Right Cessation
- 1999-06-29 CN CN99807977A patent/CN1308683A/zh active Pending
- 1999-06-29 KR KR1020007014838A patent/KR20010071613A/ko not_active Withdrawn
- 1999-06-29 WO PCT/US1999/014776 patent/WO2000000632A1/en not_active Ceased
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| IL140100A0 (en) | 2002-02-10 |
| ATE547532T1 (de) | 2012-03-15 |
| JP2002519038A (ja) | 2002-07-02 |
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| CA2331926A1 (en) | 2000-01-06 |
| WO2000000632A9 (en) | 2000-10-26 |
| JP4700805B2 (ja) | 2011-06-15 |
| NO20006675D0 (no) | 2000-12-28 |
| AU761570B2 (en) | 2003-06-05 |
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