AU776393B2 - Method of enhancing the biological activity of ligands - Google Patents
Method of enhancing the biological activity of ligands Download PDFInfo
- Publication number
- AU776393B2 AU776393B2 AU27147/00A AU2714700A AU776393B2 AU 776393 B2 AU776393 B2 AU 776393B2 AU 27147/00 A AU27147/00 A AU 27147/00A AU 2714700 A AU2714700 A AU 2714700A AU 776393 B2 AU776393 B2 AU 776393B2
- Authority
- AU
- Australia
- Prior art keywords
- nucleic acid
- ang
- cell
- ligand
- fusion polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 113
- 238000000034 method Methods 0.000 title claims abstract description 32
- 230000004071 biological effect Effects 0.000 title claims description 14
- 230000002708 enhancing effect Effects 0.000 title description 5
- 229920001184 polypeptide Polymers 0.000 claims abstract description 101
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 101
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 101
- 230000004927 fusion Effects 0.000 claims abstract description 83
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 74
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 59
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 59
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 210000004027 cell Anatomy 0.000 claims description 153
- 102000005962 receptors Human genes 0.000 claims description 73
- 108020003175 receptors Proteins 0.000 claims description 73
- 108010048154 Angiopoietin-1 Proteins 0.000 claims description 33
- 102000009088 Angiopoietin-1 Human genes 0.000 claims description 33
- 230000014509 gene expression Effects 0.000 claims description 32
- 102000009075 Angiopoietin-2 Human genes 0.000 claims description 30
- 108010048036 Angiopoietin-2 Proteins 0.000 claims description 30
- 239000013598 vector Substances 0.000 claims description 28
- 239000013604 expression vector Substances 0.000 claims description 23
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 16
- 102000008946 Fibrinogen Human genes 0.000 claims description 13
- 108010049003 Fibrinogen Proteins 0.000 claims description 13
- 229940012952 fibrinogen Drugs 0.000 claims description 13
- 239000000539 dimer Substances 0.000 claims description 10
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 9
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 9
- 108060003951 Immunoglobulin Proteins 0.000 claims description 8
- 102000018358 immunoglobulin Human genes 0.000 claims description 8
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 241000588724 Escherichia coli Species 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 241000238631 Hexapoda Species 0.000 claims description 4
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 210000005253 yeast cell Anatomy 0.000 claims description 4
- 108010090091 TIE-2 Receptor Proteins 0.000 abstract description 52
- 102000012753 TIE-2 Receptor Human genes 0.000 abstract description 52
- 230000000694 effects Effects 0.000 abstract description 11
- 108091008815 Eph receptors Proteins 0.000 abstract description 4
- 102000050554 Eph Family Receptors Human genes 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 129
- 102000004169 proteins and genes Human genes 0.000 description 116
- 235000018102 proteins Nutrition 0.000 description 115
- 230000026731 phosphorylation Effects 0.000 description 41
- 238000006366 phosphorylation reaction Methods 0.000 description 41
- 101100323232 Mus musculus Ang3 gene Proteins 0.000 description 34
- 230000001404 mediated effect Effects 0.000 description 28
- 235000001014 amino acid Nutrition 0.000 description 26
- 229940024606 amino acid Drugs 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 26
- 239000006228 supernatant Substances 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 108020004414 DNA Proteins 0.000 description 18
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 16
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 16
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 15
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 15
- 238000000149 argon plasma sintering Methods 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- 102000009840 Angiopoietins Human genes 0.000 description 13
- 108010009906 Angiopoietins Proteins 0.000 description 13
- 239000000556 agonist Substances 0.000 description 13
- 108010055334 EphB2 Receptor Proteins 0.000 description 12
- 102000000075 EphB2 Receptor Human genes 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 12
- 102000012803 ephrin Human genes 0.000 description 12
- 108060002566 ephrin Proteins 0.000 description 12
- 238000003566 phosphorylation assay Methods 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 10
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 230000000903 blocking effect Effects 0.000 description 10
- 230000003993 interaction Effects 0.000 description 10
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 102100023721 Ephrin-B2 Human genes 0.000 description 9
- 108010044090 Ephrin-B2 Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000012091 fetal bovine serum Substances 0.000 description 9
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 9
- 230000004988 N-glycosylation Effects 0.000 description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 102100033946 Ephrin-B1 Human genes 0.000 description 7
- 108010044099 Ephrin-B1 Proteins 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 238000010276 construction Methods 0.000 description 7
- 210000002889 endothelial cell Anatomy 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000002523 gelfiltration Methods 0.000 description 7
- 230000003394 haemopoietic effect Effects 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-N 0.000 description 6
- 239000007943 implant Substances 0.000 description 6
- 238000013365 molecular weight analysis method Methods 0.000 description 6
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 229960005322 streptomycin Drugs 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 101100445383 Rattus norvegicus Ephb1 gene Proteins 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 238000012300 Sequence Analysis Methods 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 239000012460 protein solution Substances 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 238000001542 size-exclusion chromatography Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 102100030322 Ephrin type-A receptor 1 Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000007747 plating Methods 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
- 238000007900 DNA-DNA hybridization Methods 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000016978 Orphan receptors Human genes 0.000 description 2
- 108070000031 Orphan receptors Proteins 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- -1 for example Chemical class 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000002356 laser light scattering Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 108010079892 phosphoglycerol kinase Proteins 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 206010002961 Aplasia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010001515 Galectin 4 Proteins 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 206010018687 Granulocytopenia Diseases 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-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
- 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 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 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
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101100065491 Rattus norvegicus Epha5 gene Proteins 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 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
- 208000005485 Thrombocytosis Diseases 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 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
- 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
- 230000008512 biological response Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 230000001456 gonadotroph Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000002607 hemopoietic effect Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000009120 phenotypic response Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/515—Angiogenesic factors; Angiogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Physics & Mathematics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11338798P | 1998-12-23 | 1998-12-23 | |
| US60/113387 | 1998-12-23 | ||
| PCT/US1999/030900 WO2000037642A1 (en) | 1998-12-23 | 1999-12-23 | Method of enhancing the biological activity of ligands |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2714700A AU2714700A (en) | 2000-07-12 |
| AU776393B2 true AU776393B2 (en) | 2004-09-09 |
Family
ID=22349103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU27147/00A Expired AU776393B2 (en) | 1998-12-23 | 1999-12-23 | Method of enhancing the biological activity of ligands |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7008781B1 (https=) |
| EP (1) | EP1141294B1 (https=) |
| JP (1) | JP4493854B2 (https=) |
| AT (1) | ATE290089T1 (https=) |
| AU (1) | AU776393B2 (https=) |
| CA (1) | CA2354846A1 (https=) |
| DE (1) | DE69924009T2 (https=) |
| HK (1) | HK1040093B (https=) |
| IL (1) | IL143558A0 (https=) |
| NZ (1) | NZ512326A (https=) |
| PL (1) | PL199645B1 (https=) |
| WO (1) | WO2000037642A1 (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9901428D0 (sv) * | 1999-04-21 | 1999-04-21 | Karolinska Innovations Ab | Amphibodies |
| WO2001047951A2 (en) * | 1999-12-23 | 2001-07-05 | An-Go-Gen Inc. | Angiopoietin analogs |
| PL366000A1 (en) | 2000-08-08 | 2005-01-24 | M.G.V.S.Ltd. | Nucleic acid constructs, vascular cells transformed therewith, pharmaceutical compositions and methods utilizing same for inducing angiogenesis |
| US20030027751A1 (en) * | 2001-04-10 | 2003-02-06 | Genvec, Inc. | VEGF fusion proteins |
| WO2003034990A2 (en) | 2001-10-25 | 2003-05-01 | Regeneron Pharmaceuticals, Inc. | Angiopoietins and methods of use thereof |
| GB0201679D0 (en) * | 2002-01-25 | 2002-03-13 | Asterion Ltd | Polypeptide variants |
| US7081443B2 (en) * | 2002-05-21 | 2006-07-25 | Korea Advanced Institutes Of Science And Technology (Kaist) | Chimeric comp-ang1 molecule |
| US8298532B2 (en) | 2004-01-16 | 2012-10-30 | Regeneron Pharmaceuticals, Inc. | Fusion polypeptides capable of activating receptors |
| WO2008100288A2 (en) * | 2006-09-15 | 2008-08-21 | The Burnham Institute | High affinity ephb receptor binding compounds and methods of use thereof |
| ES2612258T3 (es) | 2006-10-27 | 2017-05-16 | Sunnybrook Health Sciences Center | Agonistas multiméricos de Tie 2 y usos de los mismos en la estimulación de la angiogénesis |
| EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| EP2714738B1 (en) | 2011-05-24 | 2018-10-10 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
| US10150800B2 (en) | 2013-03-15 | 2018-12-11 | Zyngenia, Inc. | EGFR-binding modular recognition domains |
| CA2909080C (en) | 2013-04-11 | 2022-07-26 | Sunnybrook Research Institute | Methods, uses and compositions of tie2 agonists |
| CA2928852A1 (en) | 2013-11-01 | 2015-05-07 | Regeneron Pharmaceuticals, Inc. | Angiopoietin-based interventions for treating cerebral malaria |
| ES2867249T3 (es) | 2015-11-06 | 2021-10-20 | Regeneron Pharma | Angiopoyetinas para usar en la promoción de la coagulación sanguínea y en el tratamiento de trastornos de la coagulación sanguínea |
| KR101685532B1 (ko) * | 2016-04-26 | 2016-12-13 | 한국프라임제약주식회사 | 혈관내피성장인자 수용체 융합단백질 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995027060A2 (en) * | 1994-04-04 | 1995-10-12 | Regeneron Pharma | Biologically active eph family ligands |
| WO1996037621A2 (en) * | 1995-05-23 | 1996-11-28 | Morphosys Gesellschaft Für Proteinoptimierung Mbh | Multimeric proteins |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0547163B1 (en) * | 1990-08-29 | 2002-02-06 | Centre Hospitalier Regional De Nantes | Protein polyligands joined to a stable protein core |
| US5401650A (en) * | 1990-10-24 | 1995-03-28 | The Mount Sinai School Of Medicine Of The City University Of New York | Cloning and expression of biologically active α-galactosidase A |
| JPH08505765A (ja) | 1992-11-13 | 1996-06-25 | アムジエン・インコーポレーテツド | Ｅｃｋ受容体リガンド |
| US5747033A (en) | 1993-10-28 | 1998-05-05 | Regeneron Pharmaceuticals, Inc. | Method of enhancing the biological activity of Eph family ligands |
| US5643755A (en) | 1994-10-07 | 1997-07-01 | Regeneron Pharmaceuticals Inc. | Nucleic acid encoding tie-2 ligand |
| US5879672A (en) | 1994-10-07 | 1999-03-09 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand 1 |
| US5650490A (en) | 1994-10-07 | 1997-07-22 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand 2 |
| US5814464A (en) | 1994-10-07 | 1998-09-29 | Regeneron Pharma | Nucleic acids encoding TIE-2 ligand-2 |
| JP4122056B2 (ja) | 1995-04-06 | 2008-07-23 | リジエネロン ファーマシューティカルズ，インコーポレイテッド | Ｔｉｅ−２リガンド、その作製方法および使用方法 |
| WO1997015667A1 (en) | 1995-10-25 | 1997-05-01 | Regeneron Pharmaceuticals, Inc. | Biologically active eph family ligands |
| US6337387B1 (en) * | 1995-11-17 | 2002-01-08 | Asahi Kasei Kabushiki Kaisha | Differentiation-suppressive polypeptide |
| US5814478A (en) | 1995-12-15 | 1998-09-29 | Regeneron Pharmaceuticals, Inc. | Tyrosine kinase receptors and ligands |
| WO1997023639A1 (en) * | 1995-12-22 | 1997-07-03 | Toray Industries, Inc. | Process for producing biologically active fused proteins |
| US5851797A (en) | 1996-06-19 | 1998-12-22 | Regeneron Pharmaceuticals, Inc. | Tie ligand-3, methods of making and uses thereof |
| IL127623A0 (en) | 1996-06-19 | 1999-10-28 | Regeneron Pharma | Tie-2 receptor ligands (tie ligand-3; tie ligand-4) and their uses |
| US6265564B1 (en) * | 1996-08-02 | 2001-07-24 | Regeneron Pharmaceuticals, Inc. | Expressed ligand-vascular intercellular signalling molecule |
-
1999
- 1999-12-23 IL IL14355899A patent/IL143558A0/xx not_active IP Right Cessation
- 1999-12-23 JP JP2000589696A patent/JP4493854B2/ja not_active Expired - Lifetime
- 1999-12-23 HK HK02101186.0A patent/HK1040093B/en not_active IP Right Cessation
- 1999-12-23 PL PL349158A patent/PL199645B1/pl unknown
- 1999-12-23 CA CA002354846A patent/CA2354846A1/en not_active Abandoned
- 1999-12-23 WO PCT/US1999/030900 patent/WO2000037642A1/en not_active Ceased
- 1999-12-23 US US09/868,677 patent/US7008781B1/en not_active Expired - Lifetime
- 1999-12-23 EP EP99968956A patent/EP1141294B1/en not_active Expired - Lifetime
- 1999-12-23 DE DE69924009T patent/DE69924009T2/de not_active Expired - Lifetime
- 1999-12-23 NZ NZ512326A patent/NZ512326A/en not_active IP Right Cessation
- 1999-12-23 AT AT99968956T patent/ATE290089T1/de active
- 1999-12-23 AU AU27147/00A patent/AU776393B2/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995027060A2 (en) * | 1994-04-04 | 1995-10-12 | Regeneron Pharma | Biologically active eph family ligands |
| WO1996037621A2 (en) * | 1995-05-23 | 1996-11-28 | Morphosys Gesellschaft Für Proteinoptimierung Mbh | Multimeric proteins |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2354846A1 (en) | 2000-06-29 |
| PL199645B1 (pl) | 2008-10-31 |
| DE69924009D1 (de) | 2005-04-07 |
| HK1040093A1 (en) | 2002-05-24 |
| ATE290089T1 (de) | 2005-03-15 |
| JP4493854B2 (ja) | 2010-06-30 |
| NZ512326A (en) | 2003-11-28 |
| JP2003506008A (ja) | 2003-02-18 |
| WO2000037642A9 (en) | 2000-11-02 |
| HK1040093B (en) | 2005-05-06 |
| AU2714700A (en) | 2000-07-12 |
| PL349158A1 (en) | 2002-07-01 |
| WO2000037642A1 (en) | 2000-06-29 |
| US7008781B1 (en) | 2006-03-07 |
| IL143558A0 (en) | 2002-04-21 |
| DE69924009T2 (de) | 2006-04-13 |
| EP1141294A1 (en) | 2001-10-10 |
| EP1141294B1 (en) | 2005-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4723140B2 (ja) | 改善された薬物動態特性を有する改変キメラポリペプチド | |
| AU776393B2 (en) | Method of enhancing the biological activity of ligands | |
| US8343737B2 (en) | Cell culture compositions capable of producing a VEGF-binding fusion polypeptide | |
| EP2126092B1 (en) | Fusion proteins binding to growth factors | |
| US20060074230A1 (en) | Chimeric coiled coil molecules | |
| AU712737B2 (en) | Biologically active EPH family ligands | |
| CA2588221C (en) | Modified chimeric polypeptides with improved pharmacokinetic properties | |
| HK1043388B (en) | Modified chimeric polypeptides with improved pharmacokinetic properties |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |