CA2094512A1 - Fusion polypeptides - Google Patents
Fusion polypeptidesInfo
- Publication number
- CA2094512A1 CA2094512A1 CA002094512A CA2094512A CA2094512A1 CA 2094512 A1 CA2094512 A1 CA 2094512A1 CA 002094512 A CA002094512 A CA 002094512A CA 2094512 A CA2094512 A CA 2094512A CA 2094512 A1 CA2094512 A1 CA 2094512A1
- Authority
- CA
- Canada
- Prior art keywords
- ala
- leu
- tyr
- seq
- pro
- 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.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 186
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 103
- 229920001184 polypeptide Polymers 0.000 title claims description 86
- 230000004927 fusion Effects 0.000 title description 27
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 126
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 102
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims abstract description 77
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 76
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 76
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 claims abstract description 73
- 238000000034 method Methods 0.000 claims abstract description 63
- 102000034288 naturally occurring fusion proteins Human genes 0.000 claims abstract description 16
- 108091006048 naturally occurring fusion proteins Proteins 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 235000018102 proteins Nutrition 0.000 claims description 99
- 101710132601 Capsid protein Proteins 0.000 claims description 48
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 40
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 34
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 18
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 17
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 16
- 229910021645 metal ion Inorganic materials 0.000 claims description 16
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 15
- 125000000539 amino acid group Chemical group 0.000 claims description 15
- 235000004279 alanine Nutrition 0.000 claims description 14
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 13
- 235000014304 histidine Nutrition 0.000 claims description 12
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 11
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 10
- 239000004473 Threonine Substances 0.000 claims description 10
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 10
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 10
- 229960002591 hydroxyproline Drugs 0.000 claims description 10
- 235000008521 threonine Nutrition 0.000 claims description 10
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- 229930182817 methionine Natural products 0.000 claims description 8
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 7
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 claims description 7
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 claims description 7
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 7
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 6
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 6
- 239000000854 Human Growth Hormone Substances 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 6
- 108050009340 Endothelin Proteins 0.000 claims description 5
- 102000002045 Endothelin Human genes 0.000 claims description 5
- 102000051325 Glucagon Human genes 0.000 claims description 5
- 108060003199 Glucagon Proteins 0.000 claims description 5
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 5
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 5
- 229960004666 glucagon Drugs 0.000 claims description 5
- 102000018997 Growth Hormone Human genes 0.000 claims description 4
- 108010051696 Growth Hormone Proteins 0.000 claims description 4
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 4
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 3
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 3
- 102000000589 Interleukin-1 Human genes 0.000 claims description 3
- 108010002352 Interleukin-1 Proteins 0.000 claims description 3
- 102000000588 Interleukin-2 Human genes 0.000 claims description 3
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 108010056088 Somatostatin Proteins 0.000 claims description 3
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 3
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 claims description 3
- 239000000122 growth hormone Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims description 3
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 3
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 2
- HFDKKNHCYWNNNQ-YOGANYHLSA-N 75976-10-2 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 HFDKKNHCYWNNNQ-YOGANYHLSA-N 0.000 claims description 2
- 101800000221 Glucagon-like peptide 2 Proteins 0.000 claims description 2
- 101000983116 Homo sapiens Pancreatic prohormone Proteins 0.000 claims description 2
- 101000585528 Homo sapiens Peptide YY Proteins 0.000 claims description 2
- 101000825742 Homo sapiens Somatoliberin Proteins 0.000 claims description 2
- 101710151321 Melanostatin Proteins 0.000 claims description 2
- 102400000064 Neuropeptide Y Human genes 0.000 claims description 2
- 108010084214 Peptide PHI Proteins 0.000 claims description 2
- 239000000132 Peptide PHI Substances 0.000 claims description 2
- 102100040918 Pro-glucagon Human genes 0.000 claims description 2
- 108010057464 Prolactin Proteins 0.000 claims description 2
- 102400000096 Substance P Human genes 0.000 claims description 2
- 101800003906 Substance P Proteins 0.000 claims description 2
- TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 claims description 2
- 102000046327 human PPY Human genes 0.000 claims description 2
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 claims description 2
- 229940097325 prolactin Drugs 0.000 claims description 2
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims 2
- 101710142969 Somatoliberin Proteins 0.000 claims 2
- 102100022831 Somatoliberin Human genes 0.000 claims 2
- 101000825768 Bos taurus Somatoliberin Proteins 0.000 claims 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical group C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims 1
- 102100024819 Prolactin Human genes 0.000 claims 1
- 102400000820 Somatostatin-14 Human genes 0.000 claims 1
- 108010006025 bovine growth hormone Proteins 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 abstract description 24
- 238000002360 preparation method Methods 0.000 abstract description 24
- 230000007017 scission Effects 0.000 abstract description 24
- 235000001014 amino acid Nutrition 0.000 description 74
- 150000001413 amino acids Chemical class 0.000 description 73
- 229940002612 prodrug Drugs 0.000 description 56
- 239000000651 prodrug Substances 0.000 description 56
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 43
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 40
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 25
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- -1 Zn2+ ions Chemical class 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- 229910052751 metal Inorganic materials 0.000 description 20
- 239000002184 metal Substances 0.000 description 20
- 239000002243 precursor Substances 0.000 description 20
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 19
- 241000588724 Escherichia coli Species 0.000 description 18
- DLZBBDSPTJBOOD-BPNCWPANSA-N Pro-Tyr-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O DLZBBDSPTJBOOD-BPNCWPANSA-N 0.000 description 16
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 16
- 235000013930 proline Nutrition 0.000 description 16
- QCTFKEJEIMPOLW-JURCDPSOSA-N Ala-Ile-Phe Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QCTFKEJEIMPOLW-JURCDPSOSA-N 0.000 description 15
- 101710203526 Integrase Proteins 0.000 description 15
- 108020004511 Recombinant DNA Proteins 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 102100034343 Integrase Human genes 0.000 description 14
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 14
- FGBLCMLXHRPVOF-IHRRRGAJSA-N Ser-Tyr-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FGBLCMLXHRPVOF-IHRRRGAJSA-N 0.000 description 14
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- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
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- GGYTXJNZMFRSLX-DFTNLTQTSA-N somatostatin-28 Chemical compound N([C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CSSC1)C(O)=O)[C@@H](C)O)[C@@H](C)O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CO GGYTXJNZMFRSLX-DFTNLTQTSA-N 0.000 description 1
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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
- C07K14/485—Epidermal growth factor [EGF], i.e. urogastrone
-
- 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
- C07K14/575—Hormones
- C07K14/57509—Corticotropin releasing factor [CRF] (Urotensin)
-
- 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
- C07K14/575—Hormones
- C07K14/57536—Endothelin, vasoactive intestinal contractor [VIC]
-
- 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
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- 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
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- 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
- C07K14/575—Hormones
- C07K14/655—Somatostatins
-
- 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
- C07K14/665—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
-
- 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
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
-
- 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
- C07K2319/50—Fusion polypeptide containing protease site
-
- 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62672790A | 1990-12-13 | 1990-12-13 | |
| US626,727 | 1990-12-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2094512A1 true CA2094512A1 (en) | 1992-06-14 |
Family
ID=24511577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002094512A Abandoned CA2094512A1 (en) | 1990-12-13 | 1991-12-12 | Fusion polypeptides |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0561971A1 (ru) |
| JP (1) | JPH06503473A (ru) |
| AU (1) | AU662508B2 (ru) |
| CA (1) | CA2094512A1 (ru) |
| CZ (1) | CZ109393A3 (ru) |
| FI (1) | FI932680A0 (ru) |
| HU (1) | HUT69963A (ru) |
| IE (1) | IE914347A1 (ru) |
| NO (1) | NO932148L (ru) |
| RU (1) | RU2114119C1 (ru) |
| SK (1) | SK60893A3 (ru) |
| TW (1) | TW213923B (ru) |
| WO (1) | WO1992010576A1 (ru) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050272652A1 (en) | 1999-03-29 | 2005-12-08 | Gault Victor A | Peptide analogues of GIP for treatment of diabetes, insulin resistance and obesity |
| US6759393B1 (en) | 1999-04-12 | 2004-07-06 | Pfizer Inc. | Growth hormone and growth hormone releasing hormone compositions |
| EP1052286A3 (en) * | 1999-04-12 | 2001-07-25 | Pfizer Products Inc. | Growth hormone and growth hormone releasing hormone compositions |
| AU784477B2 (en) | 1999-11-19 | 2006-04-13 | Shire Human Genetic Therapies, Inc. | Nucleic acid construct for optimized production of products |
| EP1205551A1 (en) * | 2000-11-09 | 2002-05-15 | Pfizer Products Inc. | Growth hormone and growth hormone releasing hormone compositions |
| EP1694356B1 (en) | 2003-12-09 | 2011-02-16 | Novo Nordisk A/S | Regulation of food preference using glp-1 agonists |
| WO2005120492A1 (en) | 2004-06-11 | 2005-12-22 | Novo Nordisk A/S | Counteracting drug-induced obesity using glp-1 agonists |
| US8404637B2 (en) | 2005-02-11 | 2013-03-26 | Amylin Pharmaceuticals, Llc | GIP analog and hybrid polypeptides with selectable properties |
| US8263545B2 (en) | 2005-02-11 | 2012-09-11 | Amylin Pharmaceuticals, Inc. | GIP analog and hybrid polypeptides with selectable properties |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| WO2007103455A2 (en) † | 2006-03-06 | 2007-09-13 | Amunix, Inc. | Genetic packages and uses thereof |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| MX362028B (es) | 2009-02-03 | 2019-01-04 | Amunix Pharmaceuticals Inc | Polipeptidos recombinantes extendidos y composiciones que comprenden los mismos. |
| AU2010290077C1 (en) | 2009-08-24 | 2015-12-03 | Bioverativ Therapeutics Inc. | Coagulation factor IX compositions and methods of making and using same |
| CN107936092B (zh) | 2010-01-29 | 2022-08-09 | 阿切尔丹尼尔斯密德兰公司 | 结合有工业意义的小分子的肽结构域 |
| ES2771208T3 (es) | 2012-02-15 | 2020-07-06 | Bioverativ Therapeutics Inc | Composiciones de factor VIII y métodos de preparación y uso de las mismas |
| EP3549953A1 (en) | 2012-02-15 | 2019-10-09 | Bioverativ Therapeutics Inc. | Recombinant factor viii proteins |
| WO2015023891A2 (en) | 2013-08-14 | 2015-02-19 | Biogen Idec Ma Inc. | Factor viii-xten fusions and uses thereof |
| EA201890423A1 (ru) | 2015-08-03 | 2018-07-31 | Биовератив Терапьютикс Инк. | Слитые белки фактора ix, способы их получения и применения |
| CA3067674A1 (en) * | 2017-06-29 | 2019-01-03 | Ureka Sarl | Pro-drug peptide with improved pharmaceutical properties |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4703004A (en) * | 1984-01-24 | 1987-10-27 | Immunex Corporation | Synthesis of protein with an identification peptide |
| US4569794A (en) * | 1984-12-05 | 1986-02-11 | Eli Lilly And Company | Process for purifying proteins and compounds useful in such process |
| CA1340522C (en) * | 1987-03-10 | 1999-05-04 | Heinz Dobeli | Fusion proteins containing neighbouring histidines for improved purification |
| WO1990015821A1 (en) * | 1989-06-16 | 1990-12-27 | The Upjohn Company | Stabilized, potent grf analogs |
| AU7685791A (en) * | 1990-04-09 | 1991-10-30 | Upjohn Company, The | Improved process of purifying recombinant proteins and compounds useful in such process |
-
1991
- 1991-12-12 SK SK60893A patent/SK60893A3/sk unknown
- 1991-12-12 WO PCT/US1991/009152 patent/WO1992010576A1/en not_active Application Discontinuation
- 1991-12-12 RU RU93045577A patent/RU2114119C1/ru active
- 1991-12-12 CA CA002094512A patent/CA2094512A1/en not_active Abandoned
- 1991-12-12 HU HU9301705A patent/HUT69963A/hu unknown
- 1991-12-12 AU AU91165/91A patent/AU662508B2/en not_active Ceased
- 1991-12-12 JP JP4501996A patent/JPH06503473A/ja active Pending
- 1991-12-12 EP EP92901817A patent/EP0561971A1/en not_active Withdrawn
- 1991-12-12 CZ CS931093A patent/CZ109393A3/cs unknown
- 1991-12-13 IE IE434791A patent/IE914347A1/en not_active Application Discontinuation
- 1991-12-17 TW TW080109839A patent/TW213923B/zh active
-
1993
- 1993-06-11 NO NO93932148A patent/NO932148L/no unknown
- 1993-06-11 FI FI932680A patent/FI932680A0/fi not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU662508B2 (en) | 1995-09-07 |
| EP0561971A1 (en) | 1993-09-29 |
| NO932148L (no) | 1993-08-09 |
| TW213923B (ru) | 1993-10-01 |
| IE914347A1 (en) | 1992-06-17 |
| RU2114119C1 (ru) | 1998-06-27 |
| HUT69963A (en) | 1995-09-28 |
| AU9116591A (en) | 1992-07-08 |
| NO932148D0 (no) | 1993-06-11 |
| FI932680A (fi) | 1993-06-11 |
| WO1992010576A1 (en) | 1992-06-25 |
| SK60893A3 (en) | 1993-10-06 |
| FI932680A0 (fi) | 1993-06-11 |
| JPH06503473A (ja) | 1994-04-21 |
| HU9301705D0 (en) | 1993-10-28 |
| CZ109393A3 (en) | 1994-01-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |