JP2008503216A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2008503216A5 JP2008503216A5 JP2007516800A JP2007516800A JP2008503216A5 JP 2008503216 A5 JP2008503216 A5 JP 2008503216A5 JP 2007516800 A JP2007516800 A JP 2007516800A JP 2007516800 A JP2007516800 A JP 2007516800A JP 2008503216 A5 JP2008503216 A5 JP 2008503216A5
- Authority
- JP
- Japan
- Prior art keywords
- domain
- monomer
- polypeptide
- domains
- sequence
- 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.)
- Pending
Links
- 239000000178 monomer Substances 0.000 claims description 722
- 210000004027 cell Anatomy 0.000 claims description 199
- 238000000034 method Methods 0.000 claims description 183
- 230000027455 binding Effects 0.000 claims description 169
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 166
- 235000001014 amino acid Nutrition 0.000 claims description 156
- 150000001413 amino acids Chemical class 0.000 claims description 156
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 154
- 229920001184 polypeptide Polymers 0.000 claims description 152
- 238000009739 binding Methods 0.000 claims description 150
- 108091033319 polynucleotide Proteins 0.000 claims description 50
- 102000040430 polynucleotide Human genes 0.000 claims description 50
- 239000002157 polynucleotide Substances 0.000 claims description 49
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 claims description 48
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims description 44
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims description 44
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 claims description 44
- 238000012216 screening Methods 0.000 claims description 41
- 235000018417 cysteine Nutrition 0.000 claims description 38
- 108010001831 LDL receptors Proteins 0.000 claims description 37
- 229940027941 immunoglobulin g Drugs 0.000 claims description 35
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 27
- 230000001965 increasing effect Effects 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 17
- 238000002823 phage display Methods 0.000 claims description 17
- 108060003951 Immunoglobulin Proteins 0.000 claims description 16
- 102000018358 immunoglobulin Human genes 0.000 claims description 16
- 210000002966 serum Anatomy 0.000 claims description 13
- 229960000182 blood factors Drugs 0.000 claims description 10
- 210000003743 erythrocyte Anatomy 0.000 claims description 10
- 108010071390 Serum Albumin Proteins 0.000 claims description 9
- 102000007562 Serum Albumin Human genes 0.000 claims description 9
- 230000004663 cell proliferation Effects 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000013508 migration Methods 0.000 claims description 5
- 238000002702 ribosome display Methods 0.000 claims description 4
- 230000012292 cell migration Effects 0.000 claims description 3
- 230000004614 tumor growth Effects 0.000 claims description 2
- 102000000853 LDL receptors Human genes 0.000 claims 8
- 238000001802 infusion Methods 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 191
- 239000003446 ligand Substances 0.000 description 179
- 102000004169 proteins and genes Human genes 0.000 description 172
- 235000018102 proteins Nutrition 0.000 description 155
- 229940024606 amino acid Drugs 0.000 description 130
- 150000007523 nucleic acids Chemical class 0.000 description 85
- 125000005647 linker group Chemical group 0.000 description 80
- 239000000203 mixture Substances 0.000 description 75
- 102000039446 nucleic acids Human genes 0.000 description 68
- 108020004707 nucleic acids Proteins 0.000 description 68
- 210000001519 tissue Anatomy 0.000 description 49
- 239000011324 bead Substances 0.000 description 40
- 238000003752 polymerase chain reaction Methods 0.000 description 38
- 230000006798 recombination Effects 0.000 description 38
- 238000005215 recombination Methods 0.000 description 37
- 230000014509 gene expression Effects 0.000 description 36
- 102000005962 receptors Human genes 0.000 description 35
- 108020003175 receptors Proteins 0.000 description 35
- 239000013598 vector Substances 0.000 description 34
- 108090000144 Human Proteins Proteins 0.000 description 32
- 102000003839 Human Proteins Human genes 0.000 description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
- 241000588724 Escherichia coli Species 0.000 description 30
- 238000003556 assay Methods 0.000 description 30
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- 125000003275 alpha amino acid group Chemical group 0.000 description 26
- 239000000539 dimer Substances 0.000 description 25
- 125000000539 amino acid group Chemical group 0.000 description 23
- 108091028043 Nucleic acid sequence Proteins 0.000 description 22
- 108020001507 fusion proteins Proteins 0.000 description 21
- 102000037865 fusion proteins Human genes 0.000 description 21
- 206010028980 Neoplasm Diseases 0.000 description 20
- 210000004369 blood Anatomy 0.000 description 20
- 239000008280 blood Substances 0.000 description 20
- 239000003795 chemical substances by application Substances 0.000 description 20
- 239000012634 fragment Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 201000010099 disease Diseases 0.000 description 19
- 108091034117 Oligonucleotide Proteins 0.000 description 18
- 239000000872 buffer Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 17
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- 239000003814 drug Substances 0.000 description 16
- 230000001976 improved effect Effects 0.000 description 16
- 239000011347 resin Substances 0.000 description 16
- 229920005989 resin Polymers 0.000 description 16
- -1 sushi domain Proteins 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 15
- 210000000056 organ Anatomy 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 108091035707 Consensus sequence Proteins 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 14
- 238000001514 detection method Methods 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 102000012545 EGF-like domains Human genes 0.000 description 13
- 108050002150 EGF-like domains Proteins 0.000 description 13
- 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 description 13
- 229940079593 drug Drugs 0.000 description 13
- 208000015181 infectious disease Diseases 0.000 description 13
- 150000002500 ions Chemical class 0.000 description 13
- 238000004091 panning Methods 0.000 description 13
- 230000036961 partial effect Effects 0.000 description 13
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 13
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 12
- 102000007641 Trefoil Factors Human genes 0.000 description 12
- 108010007389 Trefoil Factors Proteins 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 238000010790 dilution Methods 0.000 description 12
- 239000012895 dilution Substances 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 235000004035 Cryptotaenia japonica Nutrition 0.000 description 11
- 239000004098 Tetracycline Substances 0.000 description 11
- 102000002938 Thrombospondin Human genes 0.000 description 11
- 108060008245 Thrombospondin Proteins 0.000 description 11
- 108010034949 Thyroglobulin Proteins 0.000 description 11
- 102000009843 Thyroglobulin Human genes 0.000 description 11
- 235000015724 Trifolium pratense Nutrition 0.000 description 11
- 150000001945 cysteines Chemical class 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 229960002180 tetracycline Drugs 0.000 description 11
- 229930101283 tetracycline Natural products 0.000 description 11
- 235000019364 tetracycline Nutrition 0.000 description 11
- 150000003522 tetracyclines Chemical class 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 229960002175 thyroglobulin Drugs 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 229920001213 Polysorbate 20 Polymers 0.000 description 10
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 230000001186 cumulative effect Effects 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 210000004324 lymphatic system Anatomy 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 108010067306 Fibronectins Proteins 0.000 description 9
- 102000016359 Fibronectins Human genes 0.000 description 9
- 239000004606 Fillers/Extenders Substances 0.000 description 9
- 238000010171 animal model Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000010367 cloning Methods 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 230000002163 immunogen Effects 0.000 description 9
- 230000005847 immunogenicity Effects 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 238000002703 mutagenesis Methods 0.000 description 9
- 231100000350 mutagenesis Toxicity 0.000 description 9
- 238000005457 optimization Methods 0.000 description 9
- 239000008188 pellet Substances 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 108020004705 Codon Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 8
- 230000003321 amplification Effects 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 238000005755 formation reaction Methods 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 7
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 7
- 102000007547 Laminin Human genes 0.000 description 7
- 108010085895 Laminin Proteins 0.000 description 7
- 238000012408 PCR amplification Methods 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 238000003016 alphascreen Methods 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 229930027917 kanamycin Natural products 0.000 description 7
- 229960000318 kanamycin Drugs 0.000 description 7
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 7
- 229930182823 kanamycin A Natural products 0.000 description 7
- 239000011159 matrix material Substances 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 239000013638 trimer Substances 0.000 description 7
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 6
- 108010039627 Aprotinin Proteins 0.000 description 6
- 102000002110 C2 domains Human genes 0.000 description 6
- 108050009459 C2 domains Proteins 0.000 description 6
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 102000002090 Fibronectin type III Human genes 0.000 description 6
- 108050009401 Fibronectin type III Proteins 0.000 description 6
- 108010001515 Galectin 4 Proteins 0.000 description 6
- 102100039556 Galectin-4 Human genes 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 108010090804 Streptavidin Proteins 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 101150036876 cre gene Proteins 0.000 description 6
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 201000005249 lung adenocarcinoma Diseases 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000009870 specific binding Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 108010047303 von Willebrand Factor Proteins 0.000 description 6
- 102100036537 von Willebrand factor Human genes 0.000 description 6
- 229960001134 von willebrand factor Drugs 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000000601 blood cell Anatomy 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 229940072221 immunoglobulins Drugs 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 102000006495 integrins Human genes 0.000 description 5
- 108010044426 integrins Proteins 0.000 description 5
- 235000013336 milk Nutrition 0.000 description 5
- 239000008267 milk Substances 0.000 description 5
- 210000004080 milk Anatomy 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 229920001155 polypropylene Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108020001580 protein domains Proteins 0.000 description 5
- 238000002864 sequence alignment Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 102000003930 C-Type Lectins Human genes 0.000 description 4
- 108090000342 C-Type Lectins Proteins 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 4
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 4
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 4
- 108090000056 Complement factor B Proteins 0.000 description 4
- 102000003712 Complement factor B Human genes 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 108050001049 Extracellular proteins Proteins 0.000 description 4
- 102000013271 Hemopexin Human genes 0.000 description 4
- 108010026027 Hemopexin Proteins 0.000 description 4
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 4
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 4
- 102000010954 Link domains Human genes 0.000 description 4
- 108050001157 Link domains Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 108700008625 Reporter Genes Proteins 0.000 description 4
- 102000014400 SH2 domains Human genes 0.000 description 4
- 108050003452 SH2 domains Proteins 0.000 description 4
- 108050008568 SRCR domains Proteins 0.000 description 4
- 102000000185 SRCR domains Human genes 0.000 description 4
- 229940122055 Serine protease inhibitor Drugs 0.000 description 4
- 101710102218 Serine protease inhibitor Proteins 0.000 description 4
- 102000000890 Somatomedin B domains Human genes 0.000 description 4
- 108050007913 Somatomedin B domains Proteins 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 210000003679 cervix uteri Anatomy 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 239000007857 degradation product Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 102000057308 human HGF Human genes 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 210000002307 prostate Anatomy 0.000 description 4
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- 239000003001 serine protease inhibitor Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 210000002105 tongue Anatomy 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 108700012359 toxins Proteins 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 210000001215 vagina Anatomy 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 101100447914 Caenorhabditis elegans gab-1 gene Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000012410 DNA Ligases Human genes 0.000 description 3
- 108010061982 DNA Ligases Proteins 0.000 description 3
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 3
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 108091005461 Nucleic proteins Proteins 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- 239000012614 Q-Sepharose Substances 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 102000018120 Recombinases Human genes 0.000 description 3
- 108010091086 Recombinases Proteins 0.000 description 3
- 102000000395 SH3 domains Human genes 0.000 description 3
- 108050008861 SH3 domains Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000011543 agarose gel Substances 0.000 description 3
- 238000013357 binding ELISA Methods 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 210000002729 polyribosome Anatomy 0.000 description 3
- 238000010837 poor prognosis Methods 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 241001515965 unidentified phage Species 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 238000011179 visual inspection Methods 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 238000012270 DNA recombination Methods 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 2
- 101700012268 Holin Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000659879 Homo sapiens Thrombospondin-1 Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 102000003960 Ligases Human genes 0.000 description 2
- 108090000364 Ligases Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101100042271 Mus musculus Sema3b gene Proteins 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 102000016978 Orphan receptors Human genes 0.000 description 2
- 108070000031 Orphan receptors Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 2
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 102000009203 Sema domains Human genes 0.000 description 2
- 108050000099 Sema domains Proteins 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- 102100036034 Thrombospondin-1 Human genes 0.000 description 2
- 108010088412 Trefoil Factor-1 Proteins 0.000 description 2
- 102100039175 Trefoil factor 1 Human genes 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 238000000333 X-ray scattering Methods 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000003314 affinity selection Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 238000005349 anion exchange Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000009087 cell motility Effects 0.000 description 2
- 229960005091 chloramphenicol Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001841 cholesterols Chemical class 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 235000013861 fat-free Nutrition 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 101150098203 grb2 gene Proteins 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002898 library design Methods 0.000 description 2
- 108020001756 ligand binding domains Proteins 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 230000009149 molecular binding Effects 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 108010008217 nidogen Proteins 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000002818 protein evolution Methods 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- JCVDICFLPGDHAT-DJLDLDEBSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3,5-dimethylpyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 JCVDICFLPGDHAT-DJLDLDEBSA-N 0.000 description 1
- KYNFOMQIXZUKRK-UHFFFAOYSA-N 2,2'-dithiodiethanol Chemical compound OCCSSCCO KYNFOMQIXZUKRK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241001504639 Alcedo atthis Species 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 241000272517 Anseriformes Species 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- NTTIDCCSYIDANP-UHFFFAOYSA-N BCCP Chemical compound BCCP NTTIDCCSYIDANP-UHFFFAOYSA-N 0.000 description 1
- 101710201279 Biotin carboxyl carrier protein Proteins 0.000 description 1
- 101710180532 Biotin carboxyl carrier protein of acetyl-CoA carboxylase Proteins 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 241001429175 Colitis phage Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 101100181494 Cricetulus griseus LDLR gene Proteins 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 102100031096 Cubilin Human genes 0.000 description 1
- 229920002271 DEAE-Sepharose Polymers 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 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
- 101150039808 Egfr gene Proteins 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000033121 FYVE zinc finger Human genes 0.000 description 1
- 108091009544 FYVE zinc finger Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150108358 GLAA gene Proteins 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101150014526 Gla gene Proteins 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101710184069 Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101000984626 Homo sapiens Low-density lipoprotein receptor-related protein 12 Proteins 0.000 description 1
- 101001043562 Homo sapiens Low-density lipoprotein receptor-related protein 2 Proteins 0.000 description 1
- 101001043596 Homo sapiens Low-density lipoprotein receptor-related protein 3 Proteins 0.000 description 1
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 description 1
- 101001039199 Homo sapiens Low-density lipoprotein receptor-related protein 6 Proteins 0.000 description 1
- 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 description 1
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 1
- 101000701411 Homo sapiens Suppressor of tumorigenicity 7 protein Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000666934 Homo sapiens Very low-density lipoprotein receptor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100027120 Low-density lipoprotein receptor-related protein 12 Human genes 0.000 description 1
- 102100021922 Low-density lipoprotein receptor-related protein 2 Human genes 0.000 description 1
- 102100021917 Low-density lipoprotein receptor-related protein 3 Human genes 0.000 description 1
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 description 1
- 102100040704 Low-density lipoprotein receptor-related protein 6 Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 108010091175 Matriptase Proteins 0.000 description 1
- 241000579835 Merops Species 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 102100037369 Nidogen-1 Human genes 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 101000882917 Penaeus paulensis Hemolymph clottable protein Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 102000004422 Phospholipase C gamma Human genes 0.000 description 1
- 108010056751 Phospholipase C gamma Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 1
- 102100038567 Properdin Human genes 0.000 description 1
- 108010005642 Properdin Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101710200251 Recombinase cre Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 102100027296 SCO-spondin Human genes 0.000 description 1
- 108010010180 SCO-spondin Proteins 0.000 description 1
- 241000724762 Salmonella phage 5 Species 0.000 description 1
- 101100477512 Schizosaccharomyces pombe (strain 972 / ATCC 24843) shf1 gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 102100025639 Sortilin-related receptor Human genes 0.000 description 1
- 101710126735 Sortilin-related receptor Proteins 0.000 description 1
- 102100036428 Spondin-1 Human genes 0.000 description 1
- 101710092167 Spondin-1 Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 102100037942 Suppressor of tumorigenicity 14 protein Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102000008816 Trefoil Factor-2 Human genes 0.000 description 1
- 108010088411 Trefoil Factor-2 Proteins 0.000 description 1
- 102000014456 Trefoil Factor-3 Human genes 0.000 description 1
- 108010078184 Trefoil Factor-3 Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102100039066 Very low-density lipoprotein receptor Human genes 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 108700041800 Xenopus TFF1 Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 238000007845 assembly PCR Methods 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000032341 cell morphogenesis Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 210000000448 cultured tumor cell Anatomy 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 108010062797 equistatin Proteins 0.000 description 1
- 108700021358 erbB-1 Genes Proteins 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000008902 immunological benefit Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 108010003082 intrinsic factor-cobalamin receptor Proteins 0.000 description 1
- 108010028930 invariant chain Proteins 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- PWPJGUXAGUPAHP-UHFFFAOYSA-N lufenuron Chemical compound C1=C(Cl)C(OC(F)(F)C(C(F)(F)F)F)=CC(Cl)=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F PWPJGUXAGUPAHP-UHFFFAOYSA-N 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000007392 microtiter assay Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- YDBYJHTYSHBBAU-UHFFFAOYSA-O s-methylmethionine Chemical compound C[S+](C)CCC(N)C(O)=O YDBYJHTYSHBBAU-UHFFFAOYSA-O 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012106 screening analysis Methods 0.000 description 1
- 239000013606 secretion vector Substances 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 210000003046 sporozoite Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 230000004572 zinc-binding Effects 0.000 description 1
Images
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/871,602 US20050089932A1 (en) | 2001-04-26 | 2004-06-17 | Novel proteins with targeted binding |
| US10/957,351 US20060008844A1 (en) | 2004-06-17 | 2004-09-30 | c-Met kinase binding proteins |
| PCT/US2005/021558 WO2006009888A2 (en) | 2004-06-17 | 2005-06-17 | C-met kinase binding proteins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008503216A JP2008503216A (ja) | 2008-02-07 |
| JP2008503216A5 true JP2008503216A5 (https=) | 2008-08-21 |
Family
ID=35785714
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007516800A Pending JP2008503216A (ja) | 2004-06-17 | 2005-06-17 | ｃ−ＭＥＴキナーゼ結合タンパク質 |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US20060008844A1 (https=) |
| EP (2) | EP1776134A4 (https=) |
| JP (1) | JP2008503216A (https=) |
| KR (1) | KR101238074B1 (https=) |
| AU (1) | AU2005265150B2 (https=) |
| CA (1) | CA2569191C (https=) |
| MX (1) | MXPA06014796A (https=) |
| WO (1) | WO2006009888A2 (https=) |
Families Citing this family (186)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040005673A1 (en) * | 2001-06-29 | 2004-01-08 | Kevin Jarrell | System for manipulating nucleic acids |
| CA2360011A1 (en) * | 1999-01-05 | 2000-07-13 | Trustees Of Boston University | Ordered gene assembly |
| US7435562B2 (en) * | 2000-07-21 | 2008-10-14 | Modular Genetics, Inc. | Modular vector systems |
| US20050053973A1 (en) * | 2001-04-26 | 2005-03-10 | Avidia Research Institute | Novel proteins with targeted binding |
| US20040175756A1 (en) * | 2001-04-26 | 2004-09-09 | Avidia Research Institute | Methods for using combinatorial libraries of monomer domains |
| US20050048512A1 (en) * | 2001-04-26 | 2005-03-03 | Avidia Research Institute | Combinatorial libraries of monomer domains |
| US20050089932A1 (en) * | 2001-04-26 | 2005-04-28 | Avidia Research Institute | Novel proteins with targeted binding |
| US20060008844A1 (en) * | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
| WO2006053131A1 (en) * | 2004-11-11 | 2006-05-18 | Modular Genetics, Inc. | Ladder assembly and system for generating diversity |
| AU2006268111A1 (en) * | 2005-07-13 | 2007-01-18 | Amgen Mountain View Inc. | Il-6 binding proteins |
| WO2007111714A2 (en) | 2005-11-28 | 2007-10-04 | Zymogenetics, Inc. | Il-21 antagonists |
| GB2433505A (en) * | 2005-12-20 | 2007-06-27 | Sharp Kk | Capture agents for binding a ligand |
| GB2433506A (en) * | 2005-12-20 | 2007-06-27 | Sharp Kk | A method of producing a multimeric capture agent |
| GB2433591A (en) * | 2005-12-20 | 2007-06-27 | Sharp Kk | Method for functionalising a hydrophobic substrate |
| CN101454339A (zh) * | 2006-05-05 | 2009-06-10 | 马斯特里赫特大学/马斯特里赫特心血管研究院 | 用于诊断个体中破裂的动脉粥样硬化损伤的存在的肽 |
| CA2662350A1 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
| MX2009003306A (es) | 2006-10-02 | 2009-04-23 | Medarex Inc | Anticuerpos humanos que se unen a cxcr4 y sus usos. |
| US8481683B2 (en) | 2006-12-01 | 2013-07-09 | Medarex, Inc. | Human antibodies that bind CD22 and uses thereof |
| CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
| EP2474556A3 (en) | 2007-03-14 | 2012-10-17 | Novartis AG | APCDD1 inhibitors for treating, diagnosing or detecting cancer |
| CA2687896A1 (en) | 2007-06-05 | 2008-12-18 | Yale University | Antibody directed against the d4 ig-like domain of the kit receptor |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| US7883700B2 (en) | 2007-12-07 | 2011-02-08 | Zymogenetics, Inc. | Anti-human IL-21 monoclonal antibodies |
| US8937047B2 (en) | 2007-12-19 | 2015-01-20 | General Electric Company | Biokinetics of fast-clearing polypeptides |
| US8124725B2 (en) * | 2007-12-19 | 2012-02-28 | General Electric Company | PDGF-Rβ binders |
| IL198545A0 (en) * | 2008-05-14 | 2011-07-31 | Metheresis Translational Res Sa | High affinity binding site of hgfr and methods for identification of antagonists thereof |
| EP2316030B1 (en) | 2008-07-25 | 2019-08-21 | Wagner, Richard W. | Protein screeing methods |
| PY09026846A (es) | 2008-08-05 | 2015-09-01 | Novartis Ag | Composiciones y métodos para anticuerpos que se dirigen a la proteína de complemento c5 |
| ES2410579T5 (es) | 2008-12-16 | 2021-10-04 | Novartis Ag | Sistemas de despliegue de levaduras |
| AU2010207552A1 (en) | 2009-01-21 | 2011-09-01 | Oxford Biotherapeutics Ltd. | PTA089 protein |
| CN102341412B (zh) | 2009-03-05 | 2018-01-05 | 梅达雷克斯有限责任公司 | 特异于cadm1 的全人抗体 |
| DK2421898T3 (en) | 2009-04-20 | 2016-05-30 | Oxford Biotherapeutics Ltd | Cadherin-17 SPECIFIC ANTIBODIES |
| PE20120532A1 (es) | 2009-04-27 | 2012-05-18 | Novartis Ag | ANTICUERPOS ANTI-ActRIIB |
| US9133500B2 (en) | 2009-08-10 | 2015-09-15 | MorphoSys A6 | Screening strategies for the identification of binders |
| EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
| WO2011054007A1 (en) | 2009-11-02 | 2011-05-05 | Oxford Biotherapeutics Ltd. | Ror1 as therapeutic and diagnostic target |
| US20120282276A1 (en) | 2009-11-05 | 2012-11-08 | The Regents Of The University Of Michigan | Biomarkers predictive of progression of fibrosis |
| WO2011080050A2 (en) | 2009-12-11 | 2011-07-07 | Novartis Ag | Binding molecules |
| US20120296403A1 (en) | 2010-02-10 | 2012-11-22 | Novartis Ag | Methods and compounds for muscle growth |
| EP2566892B1 (en) | 2010-05-06 | 2017-12-20 | Novartis AG | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies |
| PH12012502193A1 (en) | 2010-05-06 | 2021-08-09 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
| AU2011290672B2 (en) | 2010-08-20 | 2015-07-09 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (HER3) |
| EP2625203A1 (en) | 2010-10-05 | 2013-08-14 | Novartis AG | Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders |
| WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
| WO2012178038A1 (en) | 2011-06-24 | 2012-12-27 | The Broad Institute, Inc. | Methods of treating cancer |
| PL2726094T3 (pl) | 2011-06-28 | 2017-06-30 | Oxford Biotherapeutics Ltd | Cel terapeutyczny i diagnostyczny |
| PL2726508T3 (pl) | 2011-06-28 | 2017-12-29 | Oxford Biotherapeutics Ltd | Przeciwciała przeciwko cyklazie ADP-rybozylowej 2 |
| JP6472999B2 (ja) | 2011-07-01 | 2019-02-20 | ノバルティス アーゲー | 代謝障害を治療するための方法 |
| WO2013010955A1 (en) | 2011-07-15 | 2013-01-24 | Morphosys Ag | Antibodies that are cross-reactive for macrophage migration inhibitory factor (mif) and d-dopachrome tautomerase (d-dt) |
| WO2013054307A2 (en) | 2011-10-14 | 2013-04-18 | Novartis Ag | Antibodies and methods for wnt pathway-related diseases |
| WO2013074840A1 (en) | 2011-11-15 | 2013-05-23 | Allergan, Inc. | Treatment of dry age related macular degeneration |
| EP3590538A1 (en) | 2011-12-05 | 2020-01-08 | Novartis AG | Antibodies for epidermal growth factor receptor 3 (her3) |
| CN104105709A (zh) | 2011-12-05 | 2014-10-15 | 诺华股份有限公司 | 抗her3的结构域ii的表皮生长因子受体3(her3)抗体 |
| ES2728278T3 (es) | 2011-12-21 | 2019-10-23 | Novartis Ag | Composiciones que comprenden anticuerpos dirigidos al factor P y C5 |
| GB201213652D0 (en) | 2012-08-01 | 2012-09-12 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
| US9376489B2 (en) | 2012-09-07 | 2016-06-28 | Novartis Ag | IL-18 binding molecules |
| WO2014084859A1 (en) | 2012-11-30 | 2014-06-05 | Novartis Ag | Molecules and methods for modulating tmem16a activities |
| DK2928921T3 (da) | 2012-12-05 | 2021-04-19 | Novartis Ag | Sammensætninger og fremgangsmåder til antistoffer målrettet epo |
| LT2953969T (lt) | 2013-02-08 | 2019-12-10 | Novartis Ag | Anti-il-17a antikūnai ir jų panaudojimas autoimuninių ir uždegiminių ligų gydymui |
| GB201302447D0 (en) | 2013-02-12 | 2013-03-27 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
| CA2902068C (en) | 2013-02-28 | 2023-10-03 | Caprion Proteomics Inc. | Tuberculosis biomarkers and uses thereof |
| EP2970468B1 (en) | 2013-03-13 | 2021-07-07 | Novartis AG | Notch2 binding molecules for treating respiratory diseases |
| EP3611189A1 (en) | 2013-03-14 | 2020-02-19 | Novartis AG | Antibodies against notch 3 |
| WO2014145252A2 (en) | 2013-03-15 | 2014-09-18 | Milone Michael C | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
| UY35620A (es) | 2013-06-21 | 2015-01-30 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| AR096601A1 (es) | 2013-06-21 | 2016-01-20 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
| CA2919790C (en) | 2013-08-02 | 2018-06-19 | Pfizer Inc. | Anti-cxcr4 antibodies and antibody-drug conjugates |
| HK1219280A1 (zh) | 2013-08-14 | 2017-03-31 | Novartis Ag | 治疗偶发性包涵体肌炎之方法 |
| WO2015069459A1 (en) | 2013-11-05 | 2015-05-14 | Novartis Ag | Organic compounds |
| EP3087101B1 (en) | 2013-12-20 | 2024-06-05 | Novartis AG | Regulatable chimeric antigen receptor |
| KR102291465B1 (ko) * | 2014-01-24 | 2021-08-18 | 삼성전자주식회사 | c-Met 저해제의 효능 예측을 위한 바이오마커 TFF1 |
| ES2857226T3 (es) | 2014-03-15 | 2021-09-28 | Novartis Ag | Receptor de antígeno quimérico regulable |
| TW201622746A (zh) | 2014-04-24 | 2016-07-01 | 諾華公司 | 改善或加速髖部骨折術後身體復原之方法 |
| EP3161001A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
| US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
| EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
| WO2016020882A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoetin-like 4 (angptl4) antibodies and methods of use |
| WO2016020880A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
| JP6839074B2 (ja) | 2014-09-17 | 2021-03-03 | ノバルティス アーゲー | 養子免疫療法のためのキメラ受容体での細胞毒性細胞のターゲティング |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| UY36449A (es) | 2014-12-19 | 2016-07-29 | Novartis Ag | Composiciones y métodos para anticuerpos dirigidos a bmp6 |
| WO2016105542A2 (en) | 2014-12-24 | 2016-06-30 | Neximmune, Inc | Nanoparticle compositions and methods for immunotherapy |
| JP6961490B2 (ja) | 2015-04-08 | 2021-11-05 | ノバルティス アーゲー | Ｃｄ２０療法、ｃｄ２２療法、およびｃｄ１９キメラ抗原受容体（ｃａｒ）発現細胞との併用療法 |
| EP3303387A2 (en) | 2015-06-05 | 2018-04-11 | Novartis AG | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
| UY36751A (es) | 2015-06-26 | 2017-01-31 | Novartis Ag | Anticuerpos de factor xi y métodos de uso |
| US11236159B2 (en) | 2015-08-03 | 2022-02-01 | Novartis Ag | Methods of treating FGF21-associated disorders |
| EA038332B1 (ru) | 2015-09-09 | 2021-08-10 | Новартис Аг | Молекулы, связывающиеся с тимусным стромальным лимфопоэтином (tslp), и способы применения таких молекул |
| HRP20210650T1 (hr) | 2015-09-09 | 2021-05-28 | Novartis Ag | Protutijela koja vežu timusni stromalni limfopoetin (tslp) i postupci uporabe protutijela |
| WO2017077382A1 (en) | 2015-11-06 | 2017-05-11 | Orionis Biosciences Nv | Bi-functional chimeric proteins and uses thereof |
| CN108883150A (zh) | 2015-11-19 | 2018-11-23 | 阿斯克雷佩西治疗公司 | 具有抗血管生成、抗淋巴管生成以及消水肿性质的肽和纳米粒子制剂 |
| GB201521894D0 (en) | 2015-12-11 | 2016-01-27 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various cancers |
| PE20230343A1 (es) | 2015-12-11 | 2023-03-01 | Immatics Biotechnologies Gmbh | Peptidos que estimulan respuestas inmunitarias antitumorales |
| RU2018126297A (ru) | 2015-12-18 | 2020-01-22 | Новартис Аг | Антитела, нацеленные на cd32b, и способы их применения |
| CN116769054A (zh) | 2016-02-05 | 2023-09-19 | 奥里尼斯生物科学私人有限公司 | 双特异性信号传导剂及其用途 |
| EP3426278B1 (en) | 2016-03-07 | 2024-01-03 | Vib Vzw | Cd20 binding single domain antibodies |
| WO2017189724A1 (en) | 2016-04-27 | 2017-11-02 | Novartis Ag | Antibodies against growth differentiation factor 15 and uses thereof |
| WO2017194783A1 (en) | 2016-05-13 | 2017-11-16 | Orionis Biosciences Nv | Targeted mutant interferon-beta and uses thereof |
| EP3455245A2 (en) | 2016-05-13 | 2019-03-20 | Orionis Biosciences NV | Therapeutic targeting of non-cellular structures |
| TW201802121A (zh) | 2016-05-25 | 2018-01-16 | 諾華公司 | 抗因子XI/XIa抗體之逆轉結合劑及其用途 |
| AU2017283787B2 (en) | 2016-06-15 | 2020-09-17 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (BMP6) |
| WO2018022917A1 (en) * | 2016-07-27 | 2018-02-01 | Protagonist Therapeutics, Inc. | Disulfide-rich peptide libraries and methods of use thereof |
| MX2019003895A (es) | 2016-10-04 | 2019-10-07 | Asclepix Therapeutics Inc | Compuestos y metodos para activar la señalizacion tie2. |
| WO2018077893A1 (en) | 2016-10-24 | 2018-05-03 | Orionis Biosciences Nv | Targeted mutant interferon-gamma and uses thereof |
| AU2017383232B2 (en) | 2016-12-23 | 2024-09-12 | Novartis Ag | Factor XI antibodies and methods of use |
| KR102642385B1 (ko) | 2017-02-06 | 2024-03-04 | 오리오니스 바이오사이언시스 엔브이 | 표적화된 키메라 단백질 및 이의 용도 |
| CN110573172A (zh) | 2017-02-06 | 2019-12-13 | 奥里尼斯生物科学有限公司 | 靶向的工程化干扰素及其用途 |
| WO2018146074A1 (en) | 2017-02-07 | 2018-08-16 | Vib Vzw | Immune-cell targeted bispecific chimeric proteins and uses thereof |
| KR102572663B1 (ko) | 2017-02-08 | 2023-09-01 | 노파르티스 아게 | Fgf21 모방 항체 및 이의 용도 |
| CN110392697A (zh) | 2017-03-02 | 2019-10-29 | 国家医疗保健研究所 | 对nectin-4具有特异性的抗体及其用途 |
| LT3600415T (lt) | 2017-03-24 | 2025-12-29 | Novartis Ag | Antikūnas prieš ii tipo aktivino receptorių, skirtas naudoti širdies nepakankamumo gydymui |
| WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
| CA3063659A1 (en) | 2017-06-28 | 2019-01-03 | Novartis Ag | Methods for preventing and treating urinary incontinence |
| EP3661536A4 (en) | 2017-08-03 | 2021-07-21 | Asclepix Therapeutics, Inc. | PROCESS FOR IDENTIFICATION AND MANUFACTURING OF PHARMACEUTICAL INGREDIENTS FOR ACTIVATING A TIE2 RECEPTOR |
| WO2019075056A1 (en) | 2017-10-10 | 2019-04-18 | The Johns Hopkins University | BIODEGRADABLE BIOMIMETIC PARTICLES |
| WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | CD32B TARGETING ANTIBODIES AND METHODS OF USE |
| ES3062820T3 (en) | 2017-11-08 | 2026-04-14 | L E A F Holdings Group Llc | Platinum complexes and uses thereof |
| KR20250070609A (ko) | 2017-11-14 | 2025-05-20 | 아르셀엑스, 인크. | 다기능성 면역 세포 요법 |
| EP3713965A1 (en) | 2017-11-22 | 2020-09-30 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
| US12247060B2 (en) | 2018-01-09 | 2025-03-11 | Marengo Therapeutics, Inc. | Calreticulin binding constructs and engineered T cells for the treatment of diseases |
| EP3743448A4 (en) | 2018-01-26 | 2021-11-03 | Orionis Biosciences, Inc. | XCR1 BINDING AGENTS AND USES THEREOF |
| KR102877915B1 (ko) | 2018-02-05 | 2025-10-29 | 오리오니스 바이오사이언시즈 인코포레이티드 | 섬유아세포 결합제 및 이의 용도 |
| CA3090389A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated raltitrexed and uses thereof |
| WO2019157129A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated pralatrexate and uses thereof |
| EP3749314A4 (en) | 2018-02-07 | 2022-02-23 | L.E.A.F Holdings Group LLC | ALPHA-POLYGLUTAMATE METHOTREXATE AND ITS USES |
| US12310966B2 (en) | 2018-02-07 | 2025-05-27 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated aminopterin and uses thereof |
| EP3749318A4 (en) | 2018-02-07 | 2022-07-06 | L.E.A.F Holdings Group LLC | GAMMA-POLYGLUTAMATED RALTITREXED AND ITS USES |
| WO2019160734A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated lometrexol and uses thereof |
| JP7462950B2 (ja) | 2018-02-14 | 2024-04-08 | エル．イー．エー．エフ． ホールディングス グループ エルエルシー | ガンマポリグルタミン酸化メトトレキセートおよびその使用 |
| CA3090753A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated pralatrexate and uses thereof |
| US12350271B2 (en) | 2018-02-14 | 2025-07-08 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated aminopterin and uses thereof |
| EP3765517A1 (en) | 2018-03-14 | 2021-01-20 | Elstar Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
| TWI869346B (zh) | 2018-05-30 | 2025-01-11 | 瑞士商諾華公司 | Ｅｎｔｐｄ２抗體、組合療法、及使用該等抗體和組合療法之方法 |
| CA3105448A1 (en) | 2018-07-03 | 2020-01-09 | Elstar Therapeutics, Inc. | Anti-tcr antibody molecules and uses thereof |
| WO2020069405A1 (en) | 2018-09-28 | 2020-04-02 | Novartis Ag | Cd22 chimeric antigen receptor (car) therapies |
| WO2020069409A1 (en) | 2018-09-28 | 2020-04-02 | Novartis Ag | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies |
| US12410225B2 (en) | 2018-11-08 | 2025-09-09 | Orionis Biosciences, Inc | Modulation of dendritic cell lineages |
| JP2020080784A (ja) * | 2018-11-29 | 2020-06-04 | シスメックス株式会社 | 融合ポリペプチド、融合ポリペプチドの製造方法、及び融合ポリペプチドをコードするｄｎａ |
| EP3898700A1 (en) | 2018-12-18 | 2021-10-27 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
| JP2022520632A (ja) | 2019-02-15 | 2022-03-31 | インテグラル・モレキュラー・インコーポレイテッド | 共通軽鎖を含む抗体及びその使用 |
| MA54955A (fr) | 2019-02-15 | 2021-12-22 | Integral Molecular Inc | Anticorps anti-claudine 6 et leurs utilisations |
| CN119039441A (zh) | 2019-02-21 | 2024-11-29 | 马伦戈治疗公司 | 与nkp30结合的抗体分子及其用途 |
| GB2599228B (en) | 2019-02-21 | 2024-02-07 | Marengo Therapeutics Inc | Multifunctional molecules that bind to T cell related cancer cells and uses thereof |
| CN113544509A (zh) | 2019-03-08 | 2021-10-22 | 牛津遗传学有限公司 | 选择抗体的方法 |
| GB201903233D0 (en) | 2019-03-08 | 2019-04-24 | Oxford Genetics Ltd | Method of selecting for antibodies |
| JP7773372B2 (ja) | 2019-03-28 | 2025-11-19 | オリオニス バイオサイエンシズ，インコーポレイテッド | 線維芽細胞活性化タンパク質結合物質およびその使用 |
| WO2020232243A2 (en) * | 2019-05-14 | 2020-11-19 | Froude Jeffrey W | Antibodies to sudan and ebola virus |
| US20230000997A1 (en) | 2019-08-06 | 2023-01-05 | L.E.A.F. Holdings Group Llc | Processes of preparing polyglutamated antifolates and uses of their compositions |
| TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與ｅｎｔｐｄ２抗體之組合療法 |
| CN114502590A (zh) | 2019-09-18 | 2022-05-13 | 诺华股份有限公司 | Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法 |
| EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
| AU2020416273A1 (en) | 2020-01-03 | 2022-07-28 | Marengo Therapeutics, Inc. | Anti-TCR antibody molecules and uses thereof |
| GB202004514D0 (en) | 2020-03-27 | 2020-05-13 | Inst De Medicina Molecular Joaeo Lobo Antunes | Treatment of Immunosuppressive Cancer |
| CA3180683A1 (en) | 2020-05-12 | 2021-11-18 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
| US20220267450A1 (en) | 2020-10-14 | 2022-08-25 | Viridian Therapeutics, Inc. | Compositions and methods for treatment of thyroid eye disease |
| CA3211368A1 (en) | 2021-03-09 | 2022-09-15 | Molecular Partners Ag | Novel darpin based cd123 engagers |
| US20240317852A1 (en) | 2021-03-09 | 2024-09-26 | Molecular Partners Ag | Novel darpin based cd33 engagers |
| MX2023011110A (es) | 2021-03-26 | 2023-11-23 | Arcellx Inc | Terapias de celulas inmunitarias multifuncionales. |
| WO2022216993A2 (en) | 2021-04-08 | 2022-10-13 | Marengo Therapeutics, Inc. | Multifuntional molecules binding to tcr and uses thereof |
| EP4384219A4 (en) | 2021-08-10 | 2025-06-18 | Viridian Therapeutics, Inc. | COMPOSITIONS, DOSAGES AND METHODS FOR THE TREATMENT OF THYROID EYE DISEASE |
| EP4490172A1 (en) | 2022-03-11 | 2025-01-15 | Institut National De La Sante Et De La Recherche Medicale - Inserm | Nucleic acid system to specifically reprogram b and t cells and uses thereof |
| US20250223326A1 (en) | 2022-05-10 | 2025-07-10 | Institut National de la Santé et de la Recherche Médicale | Syncitin-1 fusion proteins and uses thereof for cargo delivery into target cells |
| JP2025523630A (ja) | 2022-07-04 | 2025-07-23 | ブイアイビー ブイゼットダブリュ | 血液－脳脊髄液関門通過抗体 |
| WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
| US20240228620A1 (en) | 2022-10-06 | 2024-07-11 | Bicara Therapeutics Inc. | Multispecific proteins and related methods |
| TW202430574A (zh) | 2022-11-30 | 2024-08-01 | 美商積分分子股份有限公司 | 針對密連蛋白６之抗體，包括其雙特異性格式 |
| EP4673159A1 (en) | 2023-02-27 | 2026-01-07 | Molecular Partners AG | Darpins for use in reducing renal accumulation of drugs |
| AU2024243709A1 (en) | 2023-04-03 | 2025-11-06 | Katholieke Universiteit Leuven | Blood-brain barrier crossing antibodies |
| AU2024287547A1 (en) | 2023-07-07 | 2026-01-22 | Viridian Therapeutics, Inc. | Methods of treating chronic thyroid eye disease |
| AU2024299328A1 (en) | 2023-07-21 | 2026-01-22 | Marrow Therapeutics, Inc. | Hematopoietic cell targeting conjugates and related methods |
| WO2025093683A1 (en) | 2023-11-03 | 2025-05-08 | Neuvasq Biotechnologies Sa | Wnt7 signaling agonists |
| WO2025136985A1 (en) | 2023-12-17 | 2025-06-26 | Viridian Therapeutics, Inc. | Compositions, doses, and methods for treatment of thyroid eye disease |
| WO2025151492A1 (en) | 2024-01-09 | 2025-07-17 | Viridian Therapeutics, Inc. | Compositions and methods for treatment of thyroid eye disease |
| WO2025151502A1 (en) | 2024-01-09 | 2025-07-17 | Viridian Therapeutics, Inc. | Modified antibodies |
| WO2025151496A1 (en) | 2024-01-09 | 2025-07-17 | Viridian Therapeutics, Inc. | Compositions and methods for treatment of thyroid eye disease |
| TW202545974A (zh) | 2024-01-26 | 2025-12-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 免疫受體抑制蛋白及相關方法 |
| WO2025224297A1 (en) | 2024-04-26 | 2025-10-30 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to tgfbi and uses thereof |
| US20250353881A1 (en) | 2024-05-16 | 2025-11-20 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor inhibitory proteins and related methods |
| WO2025242732A1 (en) | 2024-05-21 | 2025-11-27 | Institut National de la Santé et de la Recherche Médicale | Pan antibodies against sars-cov-2 spike protein and uses thereof for therapeutical purposes |
| WO2025245111A1 (en) | 2024-05-22 | 2025-11-27 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor targeting proteins and related methods |
| WO2025257181A1 (en) | 2024-06-11 | 2025-12-18 | Institut National de la Santé et de la Recherche Médicale | Antibodies targeting trans-active response dna-binding protein-43 (tdp-43) |
| WO2026011013A1 (en) | 2024-07-02 | 2026-01-08 | Epibiologics, Inc. | Binding agents and uses thereof |
| WO2026019692A2 (en) | 2024-07-15 | 2026-01-22 | Flagship Pioneering Innovations Vii, Llc | Immunomodulatory fusion proteins and related methods |
| WO2026050572A2 (en) | 2024-08-29 | 2026-03-05 | Marengo Therapeutics, Inc. | Multifunctional molecules binding to tcr and uses thereof |
| WO2026052839A1 (en) | 2024-09-06 | 2026-03-12 | Hone Bio Limited | Targeting fusion proteins |
| WO2026068504A2 (en) | 2024-09-24 | 2026-04-02 | The University Of Bristol | Novel protein conjugates |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US6673559B1 (en) | 1989-12-27 | 2004-01-06 | The Government Of The United States Of America As Represented By The Department Of Health And Human Services | Met proto-oncogene and a method for predicting breast cancer progression |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| DK0600866T3 (da) | 1990-06-01 | 1998-03-09 | Chiron Corp | Præparater og fremgangsmåder til identifikation af biologisk aktive molekyler |
| US5723286A (en) | 1990-06-20 | 1998-03-03 | Affymax Technologies N.V. | Peptide library and screening systems |
| US5843701A (en) | 1990-08-02 | 1998-12-01 | Nexstar Pharmaceticals, Inc. | Systematic polypeptide evolution by reverse translation |
| US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| US5426039A (en) | 1993-09-08 | 1995-06-20 | Bio-Rad Laboratories, Inc. | Direct molecular cloning of primer extended DNA containing an alkane diol |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| ATE332368T1 (de) | 1997-01-21 | 2006-07-15 | Gen Hospital Corp | Selektion von proteinen mittels rns-protein fusionen |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| US6818418B1 (en) | 1998-12-10 | 2004-11-16 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
| US6703491B1 (en) * | 1999-03-17 | 2004-03-09 | Exelixis, Inc. | Drosophila sequences |
| WO2000060070A1 (en) | 1999-04-01 | 2000-10-12 | Innogenetics N.V. | A polypeptide structure for use as a scaffold |
| AU2001277854B2 (en) * | 2000-06-29 | 2007-03-01 | North Shore-Long Island Jewish Health System | Modulators of cellular proliferation and angiogenesis, methods for use and identification thereof |
| WO2002016600A2 (en) * | 2000-08-25 | 2002-02-28 | Curagen Corporation | Novel proteins and nucleic acids encoding same |
| WO2002068649A2 (en) * | 2001-01-31 | 2002-09-06 | Curagen Corporation | Proteins and nucleic acids encoding same |
| WO2002085923A2 (en) | 2001-04-19 | 2002-10-31 | The Scripps Research Institute | In vivo incorporation of unnatural amino acids |
| US20050089932A1 (en) * | 2001-04-26 | 2005-04-28 | Avidia Research Institute | Novel proteins with targeted binding |
| US20040175756A1 (en) * | 2001-04-26 | 2004-09-09 | Avidia Research Institute | Methods for using combinatorial libraries of monomer domains |
| US20030082630A1 (en) * | 2001-04-26 | 2003-05-01 | Maxygen, Inc. | Combinatorial libraries of monomer domains |
| US20050048512A1 (en) * | 2001-04-26 | 2005-03-03 | Avidia Research Institute | Combinatorial libraries of monomer domains |
| US20030157561A1 (en) * | 2001-11-19 | 2003-08-21 | Kolkman Joost A. | Combinatorial libraries of monomer domains |
| US20050053973A1 (en) * | 2001-04-26 | 2005-03-10 | Avidia Research Institute | Novel proteins with targeted binding |
| US6867005B2 (en) | 2001-10-24 | 2005-03-15 | Beckman Coulter, Inc. | Method and apparatus for increasing the dynamic range and accuracy of binding assays |
| ES2396368T3 (es) | 2003-03-03 | 2013-02-21 | Dyax Corporation | Péptidos que se unen específicamente al receptor del HGF (CMET) y usos de los mismos |
| US20050164301A1 (en) * | 2003-10-24 | 2005-07-28 | Avidia Research Institute | LDL receptor class A and EGF domain monomers and multimers |
| US20060008844A1 (en) * | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
| US11624505B2 (en) | 2020-03-17 | 2023-04-11 | Weber-Stephen Products Llc | Ignition-based protocols for pellet grills |
-
2004
- 2004-09-30 US US10/957,351 patent/US20060008844A1/en not_active Abandoned
-
2005
- 2005-06-17 JP JP2007516800A patent/JP2008503216A/ja active Pending
- 2005-06-17 EP EP05787547A patent/EP1776134A4/en not_active Withdrawn
- 2005-06-17 AU AU2005265150A patent/AU2005265150B2/en not_active Ceased
- 2005-06-17 US US11/155,989 patent/US7803907B2/en not_active Expired - Fee Related
- 2005-06-17 KR KR1020077001057A patent/KR101238074B1/ko not_active Expired - Fee Related
- 2005-06-17 WO PCT/US2005/021558 patent/WO2006009888A2/en not_active Ceased
- 2005-06-17 CA CA2569191A patent/CA2569191C/en not_active Expired - Fee Related
- 2005-06-17 EP EP09176476A patent/EP2151453A1/en not_active Withdrawn
- 2005-06-17 MX MXPA06014796A patent/MXPA06014796A/es active IP Right Grant
-
2010
- 2010-04-15 US US12/761,346 patent/US7968681B2/en not_active Expired - Fee Related
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008503216A5 (https=) | ||
| JP2008503216A (ja) | ｃ−ＭＥＴキナーゼ結合タンパク質 | |
| JP4369662B2 (ja) | 単量体ドメインのコンビナトリアルライブラリー | |
| US20100204052A1 (en) | Protein scaffolds and uses thereof | |
| US20050164301A1 (en) | LDL receptor class A and EGF domain monomers and multimers | |
| JP2013512672A (ja) | ヒトＦＧＦＲ１ｃ、ヒトβ−クロト−、ならびにヒトＦＧＦＲ１ｃおよびヒトβ−クロト−の両方に結合する結合タンパク質 | |
| JP2007524341A (ja) | 単量体ドメインの組み合わせライブラリー | |
| US20060234299A1 (en) | Protein scaffolds and uses thereof | |
| US20050053973A1 (en) | Novel proteins with targeted binding | |
| US7820790B2 (en) | IL-6 binding proteins | |
| JP2007531503A (ja) | 涙リポカリンの突然変異タンパク質 | |
| US7786262B2 (en) | IL-6 binding proteins | |
| JP2008520208A (ja) | タンパク質骨格およびその使用 | |
| JP2003531635A (ja) | ヒト・ウィングレス（ｗｉｎｇｌｅｓｓ）様遺伝子 | |
| CN101018559A (zh) | c－MET激酶结合蛋白 | |
| HK1140213A (en) | C-met kinase binding proteins | |
| Apone | Muscle gene E-box control elements: evidence for quantitatively different transcriptional activities and the binding of distinct regulatory factors |