OA12282A - Antibody molecules having specificity for human tumor necrosis factor alpha, and use thereof. - Google Patents

Info

Publication number

OA12282A

OA12282A OA1200200368A OA1200200368A OA12282A OA 12282 A OA12282 A OA 12282A OA 1200200368 A OA1200200368 A OA 1200200368A OA 1200200368 A OA1200200368 A OA 1200200368A OA 12282 A OA12282 A OA 12282A

Authority

OA

OAPI

Prior art keywords

ser

artificial sequence

gly

thr

val

Prior art date

2000-06-06

Links

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• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 title abstract description 8
• 102000057041 human TNF Human genes 0.000 title abstract description 5
• 239000013598 vector Substances 0.000 claims abstract description 41
• 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 27
• 238000011282 treatment Methods 0.000 claims abstract description 22
• 230000001404 mediated effect Effects 0.000 claims abstract description 6
• 108020004414 DNA Proteins 0.000 claims description 110
• 241000282414 Homo sapiens Species 0.000 claims description 86
• 229960003115 certolizumab pegol Drugs 0.000 claims description 40
• 239000000203 mixture Substances 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 28
• 210000004027 cell Anatomy 0.000 claims description 27
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 27
• 108091034117 Oligonucleotide Proteins 0.000 claims description 25
• 235000001014 amino acid Nutrition 0.000 claims description 23
• 150000001413 amino acids Chemical class 0.000 claims description 22
• 150000001875 compounds Chemical class 0.000 claims description 22
• 229920000642 polymer Polymers 0.000 claims description 21
• 241000588724 Escherichia coli Species 0.000 claims description 20
• 230000014509 gene expression Effects 0.000 claims description 19
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 17
• 239000012636 effector Substances 0.000 claims description 17
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 15
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 15
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 13
• 230000001225 therapeutic effect Effects 0.000 claims description 13
• 210000004899 c-terminal region Anatomy 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 239000013604 expression vector Substances 0.000 claims description 11
• 229920001223 polyethylene glycol Polymers 0.000 claims description 11
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
• 241001529936 Murinae Species 0.000 claims description 10
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 10
• 125000003277 amino group Chemical group 0.000 claims description 9
• 238000010367 cloning Methods 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 229920001184 polypeptide Polymers 0.000 claims description 8
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
• 108091035707 Consensus sequence Proteins 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 238000012258 culturing Methods 0.000 claims description 5
• 229920001427 mPEG Polymers 0.000 claims description 5
• 229920001282 polysaccharide Polymers 0.000 claims description 4
• 239000005017 polysaccharide Substances 0.000 claims description 4
• 102100033400 4F2 cell-surface antigen heavy chain Human genes 0.000 claims description 3
• 101710114762 50S ribosomal protein L11, chloroplastic Proteins 0.000 claims description 3
• 101710164994 50S ribosomal protein L13, chloroplastic Proteins 0.000 claims description 3
• 101710177347 50S ribosomal protein L15, chloroplastic Proteins 0.000 claims description 3
• 101000800023 Homo sapiens 4F2 cell-surface antigen heavy chain Proteins 0.000 claims description 3
• 230000009824 affinity maturation Effects 0.000 claims description 3
• 229940093476 ethylene glycol Drugs 0.000 claims description 3
• 210000004602 germ cell Anatomy 0.000 claims description 3
• 150000004676 glycans Chemical class 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• 230000007170 pathology Effects 0.000 claims description 3
• 210000001322 periplasm Anatomy 0.000 claims description 3
• 229920001281 polyalkylene Polymers 0.000 claims description 3
• 101710083129 50S ribosomal protein L10, chloroplastic Proteins 0.000 claims description 2
• 101710082414 50S ribosomal protein L12, chloroplastic Proteins 0.000 claims description 2
• 239000013599 cloning vector Substances 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 229920002859 polyalkenylene Polymers 0.000 claims description 2
• 108700012920 TNF Proteins 0.000 claims 21
• 108010089804 glycyl-threonine Proteins 0.000 claims 10
• UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 claims 8
• PDIDTSZKKFEDMB-UWVGGRQHSA-N Lys-Pro-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O PDIDTSZKKFEDMB-UWVGGRQHSA-N 0.000 claims 8
• 108010069020 alanyl-prolyl-glycine Proteins 0.000 claims 8
• 108010086434 alanyl-seryl-glycine Proteins 0.000 claims 8
• 108010038745 tryptophylglycine Proteins 0.000 claims 8
• 241000880493 Leptailurus serval Species 0.000 claims 7
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• MBLJBGZWLHTJBH-SZMVWBNQSA-N Trp-Val-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 MBLJBGZWLHTJBH-SZMVWBNQSA-N 0.000 claims 6
• 108010069205 aspartyl-phenylalanine Proteins 0.000 claims 6
• 108010044292 tryptophyltyrosine Proteins 0.000 claims 6
• CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 claims 5
• AUFHLLPVPSMEOG-YUMQZZPRSA-N Arg-Gly-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AUFHLLPVPSMEOG-YUMQZZPRSA-N 0.000 claims 5
• KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 claims 5
• ZAESWDKAMDVHLL-RCOVLWMOSA-N Asn-Val-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O ZAESWDKAMDVHLL-RCOVLWMOSA-N 0.000 claims 5
• XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 claims 5
• ICUTTWWCDIIIEE-BQBZGAKWSA-N Gly-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN ICUTTWWCDIIIEE-BQBZGAKWSA-N 0.000 claims 5
• XHVONGZZVUUORG-WEDXCCLWSA-N Gly-Thr-Lys Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN XHVONGZZVUUORG-WEDXCCLWSA-N 0.000 claims 5
• WTUSRDZLLWGYAT-KCTSRDHCSA-N Gly-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN WTUSRDZLLWGYAT-KCTSRDHCSA-N 0.000 claims 5
• DUAWRXXTOQOECJ-JSGCOSHPSA-N Gly-Tyr-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O DUAWRXXTOQOECJ-JSGCOSHPSA-N 0.000 claims 5
• LPFBXFILACZHIB-LAEOZQHASA-N Ile-Gly-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)O)N LPFBXFILACZHIB-LAEOZQHASA-N 0.000 claims 5
• UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 claims 5
• RYJRPPUATSKNAY-STECZYCISA-N Pro-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@@H]2CCCN2 RYJRPPUATSKNAY-STECZYCISA-N 0.000 claims 5
• SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 5
• MTEQZJFSEMXXRK-CFMVVWHZSA-N Tyr-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N MTEQZJFSEMXXRK-CFMVVWHZSA-N 0.000 claims 5
• BIWVVOHTKDLRMP-ULQDDVLXSA-N Tyr-Pro-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O BIWVVOHTKDLRMP-ULQDDVLXSA-N 0.000 claims 5
• 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 claims 5
• 108010044374 isoleucyl-tyrosine Proteins 0.000 claims 5
• 108010051242 phenylalanylserine Proteins 0.000 claims 5
• 108010033670 threonyl-aspartyl-tyrosine Proteins 0.000 claims 5
• VKKYFICVTYKFIO-CIUDSAMLSA-N Arg-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N VKKYFICVTYKFIO-CIUDSAMLSA-N 0.000 claims 4
• 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 4
• OZHXXYOHPLLLMI-CIUDSAMLSA-N Cys-Lys-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OZHXXYOHPLLLMI-CIUDSAMLSA-N 0.000 claims 4
• NVTPVQLIZCOJFK-FOHZUACHSA-N Gly-Thr-Asp Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O NVTPVQLIZCOJFK-FOHZUACHSA-N 0.000 claims 4
• KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 claims 4
• AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 claims 4
• IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 claims 4
• GQFDWEDHOQRNLC-QWRGUYRKSA-N Lys-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN GQFDWEDHOQRNLC-QWRGUYRKSA-N 0.000 claims 4
• CAODKDAPYGUMLK-FXQIFTODSA-N Met-Asn-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CAODKDAPYGUMLK-FXQIFTODSA-N 0.000 claims 4
• KAKJTZWHIUWTTD-VQVTYTSYSA-N Met-Thr Chemical compound CSCC[C@H]([NH3+])C(=O)N[C@@H]([C@@H](C)O)C([O-])=O KAKJTZWHIUWTTD-VQVTYTSYSA-N 0.000 claims 4
• RAGOJJCBGXARPO-XVSYOHENSA-N Phe-Thr-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 RAGOJJCBGXARPO-XVSYOHENSA-N 0.000 claims 4
• KLYYKKGCPOGDPE-OEAJRASXSA-N Phe-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O KLYYKKGCPOGDPE-OEAJRASXSA-N 0.000 claims 4
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• QWCZXKIFPWPQHR-JYJNAYRXSA-N Val-Pro-Tyr Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QWCZXKIFPWPQHR-JYJNAYRXSA-N 0.000 claims 4
• PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 claims 4
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• OWFGFHQMSBTKLX-UFYCRDLUSA-N Val-Tyr-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N OWFGFHQMSBTKLX-UFYCRDLUSA-N 0.000 claims 4
• 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 claims 4
• XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 claims 4
• 108010015792 glycyllysine Proteins 0.000 claims 4
• 108010037850 glycylvaline Proteins 0.000 claims 4
• YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 claims 3
• BUDNAJYVCUHLSV-ZLUOBGJFSA-N Ala-Asp-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O BUDNAJYVCUHLSV-ZLUOBGJFSA-N 0.000 claims 3
• ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 claims 3
• AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 claims 3
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