AU2010286518C1 - Therapeutic DLL4 binding proteins - Google Patents

Info

Publication number

AU2010286518C1

AU2010286518C1 AU2010286518A AU2010286518A AU2010286518C1 AU 2010286518 C1 AU2010286518 C1 AU 2010286518C1 AU 2010286518 A AU2010286518 A AU 2010286518A AU 2010286518 A AU2010286518 A AU 2010286518A AU 2010286518 C1 AU2010286518 C1 AU 2010286518C1

Authority

AU

Australia

Prior art keywords

ser

gly

thr

val

leu

Prior art date

2009-08-29

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.)

Ceased

Links

• Espacenet
• Global Dossier
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• 101000872077 Homo sapiens Delta-like protein 4 Proteins 0.000 title claims abstract description 304
• 108091008324 binding proteins Proteins 0.000 title claims abstract description 160
• 102100033553 Delta-like protein 4 Human genes 0.000 title claims abstract 274
• 230000001225 therapeutic effect Effects 0.000 title claims description 6
• 102000014914 Carrier Proteins Human genes 0.000 title abstract description 110
• 241000282414 Homo sapiens Species 0.000 claims abstract description 80
• 230000027455 binding Effects 0.000 claims abstract description 55
• 239000012634 fragment Substances 0.000 claims abstract description 29
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
• 230000000694 effects Effects 0.000 claims abstract description 15
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• 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 98
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• 229910052717 sulfur Inorganic materials 0.000 claims description 41
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 38
• 102000036639 antigens Human genes 0.000 claims description 34
• 239000000427 antigen Substances 0.000 claims description 33
• 108091007433 antigens Proteins 0.000 claims description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims description 33
• 102000044457 human DLL4 Human genes 0.000 claims description 30
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 30
• 238000000034 method Methods 0.000 claims description 29
• 229920001184 polypeptide Polymers 0.000 claims description 29
• 150000001413 amino acids Chemical group 0.000 claims description 28
• 108060003951 Immunoglobulin Proteins 0.000 claims description 25
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• 102000018358 immunoglobulin Human genes 0.000 claims description 25
• 239000003814 drug Substances 0.000 claims description 22
• 229910052727 yttrium Inorganic materials 0.000 claims description 20
• 229910052740 iodine Inorganic materials 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
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• 150000007523 nucleic acids Chemical class 0.000 claims description 9
• 102000039446 nucleic acids Human genes 0.000 claims description 9
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• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 7
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• 108010036949 Cyclosporine Proteins 0.000 claims description 5
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 5
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 5
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• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims description 4
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
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• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 4
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
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• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 4
• 229960002930 sirolimus Drugs 0.000 claims description 4
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 4
• 229910052720 vanadium Inorganic materials 0.000 claims description 4
• 241000588724 Escherichia coli Species 0.000 claims description 3
• 241000238631 Hexapoda Species 0.000 claims description 3
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 3
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 3
• 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 3
• 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
• 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 3
• 230000003092 anti-cytokine Effects 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 229960001334 corticosteroids Drugs 0.000 claims description 3
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• 208000011231 Crohn disease Diseases 0.000 claims description 2
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 2
• 201000009273 Endometriosis Diseases 0.000 claims description 2
• 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 2
• 206010020880 Hypertrophy Diseases 0.000 claims description 2
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• 208000008469 Peptic Ulcer Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 206010039491 Sarcoma Diseases 0.000 claims description 2
• 206010040047 Sepsis Diseases 0.000 claims description 2
• 206010046798 Uterine leiomyoma Diseases 0.000 claims description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 210000005002 female reproductive tract Anatomy 0.000 claims description 2
• 201000011066 hemangioma Diseases 0.000 claims description 2
• 230000009033 hematopoietic malignancy Effects 0.000 claims description 2
• 102000055590 human KDR Human genes 0.000 claims description 2
• 102000057041 human TNF Human genes 0.000 claims description 2
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• 241000880493 Leptailurus serval Species 0.000 claims 112
• XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 claims 84
• 108010003137 tyrosyltyrosine Proteins 0.000 claims 74
• VTFWAGGJDRSQFG-MELADBBJSA-N Tyr-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O VTFWAGGJDRSQFG-MELADBBJSA-N 0.000 claims 65
• MNQMTYSEKZHIDF-GCJQMDKQSA-N Asp-Thr-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O MNQMTYSEKZHIDF-GCJQMDKQSA-N 0.000 claims 64
• YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 claims 62
• ZKOKTQPHFMRSJP-YJRXYDGGSA-N Ser-Thr-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZKOKTQPHFMRSJP-YJRXYDGGSA-N 0.000 claims 61
• 108010010147 glycylglutamine Proteins 0.000 claims 61
• RXBGWGRSWXOBGK-KKUMJFAQSA-N Asp-Lys-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RXBGWGRSWXOBGK-KKUMJFAQSA-N 0.000 claims 60
• LCNASHSOFMRYFO-WDCWCFNPSA-N Leu-Thr-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O LCNASHSOFMRYFO-WDCWCFNPSA-N 0.000 claims 60
• UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 claims 60
• YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 claims 59
• HPBNLFLSSQDFQW-WHFBIAKZSA-N Asn-Ser-Gly Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O HPBNLFLSSQDFQW-WHFBIAKZSA-N 0.000 claims 54
• JRCUFCXYZLPSDZ-ACZMJKKPSA-N Glu-Asp-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O JRCUFCXYZLPSDZ-ACZMJKKPSA-N 0.000 claims 54
• 108010041407 alanylaspartic acid Proteins 0.000 claims 54
• FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 claims 53
• MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 claims 53
• GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 claims 53
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• VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 claims 50
• NZYNRRGJJVSSTJ-GUBZILKMSA-N Val-Ser-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NZYNRRGJJVSSTJ-GUBZILKMSA-N 0.000 claims 50
• 102000023732 binding proteins Human genes 0.000 claims 50
• RTXQQDVBACBSCW-CFMVVWHZSA-N Asp-Ile-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RTXQQDVBACBSCW-CFMVVWHZSA-N 0.000 claims 49
• GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 claims 49
• RKQAYOWLSFLJEE-SVSWQMSJSA-N Ile-Thr-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)O)N RKQAYOWLSFLJEE-SVSWQMSJSA-N 0.000 claims 49
• DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 claims 49
• ZZDYJFVIKVSUFA-WLTAIBSBSA-N Tyr-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ZZDYJFVIKVSUFA-WLTAIBSBSA-N 0.000 claims 49
• 108010043240 arginyl-leucyl-glycine Proteins 0.000 claims 49
• 108010038745 tryptophylglycine Proteins 0.000 claims 49
• VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 claims 48
• 108010089804 glycyl-threonine Proteins 0.000 claims 48
• MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 claims 47
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• QYBRQMLZDDJBSW-AVGNSLFASA-N Ser-Tyr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYBRQMLZDDJBSW-AVGNSLFASA-N 0.000 claims 47
• QLSRIZIDQXDQHK-RCWTZXSCSA-N Arg-Val-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QLSRIZIDQXDQHK-RCWTZXSCSA-N 0.000 claims 46
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• HXIDVIFHRYRXLZ-NAKRPEOUSA-N Ile-Ser-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)O)N HXIDVIFHRYRXLZ-NAKRPEOUSA-N 0.000 claims 46
• JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 claims 46
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• MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 claims 44
• ZLFNNVATRMCAKN-ZKWXMUAHSA-N Ile-Ser-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZLFNNVATRMCAKN-ZKWXMUAHSA-N 0.000 claims 44
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• CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 claims 44
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• YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 claims 44
• 108010044374 isoleucyl-tyrosine Proteins 0.000 claims 44
• IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 claims 43
• ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 claims 42
• BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 claims 42
• LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 claims 42
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