US 2010O221257A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0221257 A1 Campbell et al. (43) Pub. Date: Sep. 2, 2010 (54) BINDING MEMBERS-513 Publication Classification (75) Inventors: Jamie Iain Campbell, (51) Int. Cl. Cambridgeshire (GB); Duncan A 6LX 39/395 (2006.01) James Cochrane, Cambridgeshire C07K 6/00 (2006.01) (GB); Donna Kirsty Finch, CI2N 5/3 (2006.01) Cambridgeshire (GB); Maria A6IP 9/02 (2006.01) Anastasia Teresa Groves, A6IP 9/10 (2006.01) Cambridgeshire (GB); David A6IP II/00 (2006.01) Christopher Lowe, A6IP 25/28 (2006.01) A6IP 9/10 (2006.01) Cambridgeshire (GB); Simon A6IP3/10 (2006.01) Charles Cruwys, Leicestershire A6IP35/00 (2006.01) (GB) A6IP3 L/18 (2006.01) Correspondence Address: CI2N I/00 (2006.01) Medimmune, Limited CI2P 2L/00 (2006.01) One Medimmune Way (52) U.S. Cl. ................ 424/143.1; 530/389.1536/23.53; Gaithersburg, MD 20878 (US) 424/172.1; 530/388.22; 435/243; 435/69.6 (73) Assignee: MEDIMMUNE LIMITED, (57) ABSTRACT CAMBRIDGESHIRE (GB) This invention relates to binding members, especially anti body molecules, specific for interleukin 1 receptor 1 (IL (21) Appl. No.: 12/612,781 1R1). For example, isolated binding members specific for IL-1R1 which competes with IL-1 and IL-1Ra for binding to (22) Filed: Nov. 5, 2009 IL-1R1 and binds Il-1R1 with a K, of 10 pM or less when measured by KinexatM. The binding members are useful for, Related U.S. Application Data interalia, treatment of disorders mediated by IL-1R1 includ (60) Provisional application No. 61/112,381, filed on Nov. ing rheumatoid arthritis, athma and chronic obstructive pull 7, 2008. monary disease (COPD). Patent Application Publication Sep. 2, 2010 Sheet 1 of 14 US 2010/0221257 A1 Figure 1 Cynomolgus Monkey IL-1R1 extracellular domain cDNA ATGAAAGTGTTACTCCGACTTATTTGTTTCATTGCTCTACTGATTTCTTTTCTGGAGG CTGATAAATGCAATGAACGTGAAGAAAAAATAATTTTAGTGTCATCTGCAAATGAA ATTGATGTTCGTCCCTGTCCTCTTAACCCAAATGAATACAAAGGCACTATAACATGG TATAAAAATGACAGCAAGACACCTATATCTACAGAACAAGCCTCCAGGATTCATCA GCACAAAAAGAAACTTTGGTTTGTTCCTGCTAAGGTAGAAGATTCAGGACATTACTA CTGTGTGGTAAGAAATTCATCTTACTGCCTCAGAATTAAAATAACTGCAAAATTTGT GGAGAATGAGCCTAACTTGTGTTATAATGCAGAAGCCATATTTAAGCAGAGACTAC CCGTTGCAGGAGATGGAGGACTTGTGTGCCCTTATATGGAGTTTTTTAAAGACGAAA ATAATGAGTTACCTAAATTACTGTGGTATAAGGATTGCAAACCTCTACTTCTTGACA ATATAAACTTTAGTGGAGTCAA AGATAGGCTCATCGTGATGAATGTGGCTGAAAAG CATAGAGGGAACTATACTTGTCATGCATCCTACACATACTTGGGCAAGCAATATCCT ATTACCCGGGTAATAGAATTTATTACTCTAGAGGAAAACAAACCCACAAGGCCTGT GATTGTGAGCCCAGCTAATGAGACAATAGAAGTAGACTTGGGATCCCAGATACAAT TGATCTGTAATGTCACTGGCCAGTTGAGTGATACTGCCTACTGGAAGTGGAATGGGT CCTTCATTGATGAACATGACCCAGTGCTAGGGGAAG ACTATTACAGTGTGGAAAAT CCTGCAAACAAAAGAAGGAGTACCCTCATCACAGTGCTTAATATATCAGAAACTGA AAGTAGATTTTATAAACATCCATTTACCTGTTTAGCCAGGAATACACATGGTATGGA TGCAGCATATGTCCAGTTAATATATCCAGTCACTAAATTCCAGAAG Patent Application Publication Sep. 2, 2010 Sheet 2 of 14 US 2010/0221257 A1 Figure 2 Cynomolgus Monkey IL-1R1 extracellular domain amino acid sequence MKVLLRLICFIALLISFLEADKCNEREEKIILVSSANEIDVRPCPLNPNEYKGTITWYKNDS KTPISTEQASRIHQHKKKLWFVPAKVEDSGHYYCVVRNSSYCLRIKITAKFVENEPNLCY NAEAIFKQRLPVAGDGGLVCPYMEFFKDENNELPKLLWYKDCKPLLLDNINFSGVKDR LIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEENKPTRPVIVSPANETIEVDLG SQIQLICNVTGQLSDTAYWKWNGSFIDEDDPVLGEDYYSVENPANKRRSTLITVLNISET ESRFYKHPFTCLARNTHGMDAAYVQLIYPVTKFQK Patent Application Publication Sep. 2, 2010 Sheet 3 of 14 US 2010/0221257 A1 Figure 3 Human IL1R1 Fc cDNA nucleotide ATGAAAGTGTTACTCAGACTTATTTGTTTCATAGCTCTACTGATTTCTTCTCTGGAGG CTGATAAATGCAAGGAACGTGAAGAAAAAATAATTTTAGTGTCATCTGCAAATGAA ATTGATGTTCGTCCCTGTCCTCTTAACCCAAATGAACACAAAGGCACTATAACTTGG TATAAAGATGACAGCAAGACACCTGTATCTACAGAACAAGCCTCCAGGATTCATCA ACACAAAGAGAAACTTTGGTTTGTTCCTGCTAAGGTGGAGGATTCAGGACATTACTA TTGCGTGGTAAGAAATTCATCTTACTGCCTCAGAATTAAAATAAGTGCAAAATTTGT GGAGAATGAGCCTAACTTATGTTATAATGCACAAGCCATATTTAAGCAGAAACTAC CCGTTGCAGGAGACGGAGGACTTGTGTGCCCTTATATGGAGTTTTTTAAAAATGAAA ATAATGAGTTACCTA AATTACAGTGGTATAAGGATTGCAA ACCTCTACTTCTTGACA ATATACACTTTAGTGGAGTCAAAGATAGGCTCATCGTGATGAATGTGGCTGAAAAG CATAGAGGGAACTATACTTGTCATGCATCCTACACATACTTGGGCAAGCAATATCCT ATTACCCGGGTAATAGAATTTATTACTCTAGAGGAAAACAAACCCACAAGGCCTGT GATTGTGAGCCCAGCTAATGAGACAATGGAAGTAGACTTGGGATCCCAGATACAAT TGATCTGTAATGTCACCGGCCAGTTGAGTGACATTGCTTACTGGAAGTGGAATGGGT CAGTAATTGATGAAGATGACCCAGTGCTAGGGGAAGACTATTACAGTGTGGAAAAT CCTGCAAACAAAAGAAGGAGTACCCTCATCACAGTGCTTAATATATCGGAAATTGA AAGTAGATTTTATAAACATCCATTTACCTGTTTTGCCAAGAATACACATGGTATAGA TGCAGCATATATCCAGTTAATATATCCAGTCACTAATTTCCAGAAGAAGGGTGGGCG CGCCGACCCAGCTTTCTTGTACAAAGTGGTGGGGGCCGCCCCCAAATCTTGTGACAA AACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTT CCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCAC ATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCA ACTGGTACG TGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAA CAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGG CAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAA CCATCTCCAAAGCCAAAGGGCAGCCCCGAGA ACCACAGGTGTACACCCTGCCCCCA TCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA AAGGCTT CTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACT ACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGC TCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATG CATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA CATCATCATCACCACCATTAA Patent Application Publication Sep. 2, 2010 Sheet 5 of 14 US 2010/0221257 A1 Figure S Cynomolgus Monkey ILIRIFc cDNA nucleotide ATGAAAGTGTTACTCCGACTTATTTGTTTCATTGCTCTACTGATTTCTTTTCTGGAGG CTGATAAATGCAATGAACGTGAAGAAAAAATAATTTTAGTGTCATCTGCAAATGAA ATTGATGTTCGTCCCTGTCCTCTTAACCCAAATGAATACAAAGGCACTATAACATGG TATAAAAATGACAGCAAGACACCTATATCTACAGAACAAGCCTCCAGGATTCATCA GCACAAAAAGAAACTTTGGTTTGTTCCTGCTAAGGTAGAAGATTCAGGACATTACTA CTGTGTGGTAAGAAATTCATCTTACTGCCTCAGAATTAAAATAACTGCAAAATTTGT GGAGAATGAGCCTAACTTGTGTTATAATGCAGAAGCCATATTTAAGCAGAGACTAC CCGTTGCAGGAGATGGAGGACTTGTGTGCCCTTATATGGAGTTTTTTAAAGACGAAA ATAATGAGTTACCTAAATTACTGTGGTATAAGGATTGCAAACCTCTACTTCTTGACA ATATAAACTTTAGTGGAGTCAA AGATAGGCTCATCGTGATGAATGTGGCTGAAAAG CATAGAGGGAACTATACTTGTCATGCATCCTACACATACTTGGGCAAGCAATATCCT ATTACCCGGGTAATAGAATTTATTACTCTAGAGGAAAACAA ACCCACAAGGCCTGT GATTGTGAGCCCAGCTAATGAGACAATAGAAGTAGACTTGGGATCCCAGATACAAT TGATCTGTAATGTCACTGGCCAGTTGAGTGATACTGCCTACTGGAAGTGGAATGGGT CCTTCATTGATGAAGATGACCCAGTGCTAGGGGAAGACTATTACAGTGTGGAAAAT CCTGCAAACAAAAGAAGGAGTACCCTCATCACAGTGCTTAATATATCAGAAACTGA AAGTAGATTTTATAAACATCCATTTACCTGTTTAGCCAGGAATACACATGGTATGGA TGCAGCATATGTCCAGTTAATATATCCAGTCACTAAATTCCAGAAGAAGGGTGGGC GCGCCGACCCAGCTTTCTTGTACAAAGTGGTGGGGGCCGCCCCCAAATCTTGTGACA AAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCT TCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCA CATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACA ACAGCACGTACCGTGTGGTCAGCCTCCTCACCGTCCTGCACCAGGACTGGCTGAATG GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAA ACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCC ATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA AGGCT TCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAAC TACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAG CTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGAT GCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA ACATCATCATCACCACCATTAA Patent Application Publication Sep. 2, 2010 Sheet 7 of 14 US 2010/0221257 A1 Figure 7 Human IL-1R1 extracellular sequence MKVLLRLICFALLISSLEADKCKEREEKI ILVSSANEIDVRPCPLNPNEHKGTITWYKDDS KTPVSTEQASRIHQHKEK LWFVPAKVEDSGHYYCVVRNSSYCLRIKISAKFVENEPNLCYNAQAIFKQKLPVAGDGG LVCPYMEFFKNENNELPKLQW YKDCKPLLLDNIHFSGVKDRLIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEE NKPTRPVIVSPANETMEVDL GSQIQLICNVTGQLSDIAYWKWNGSVIDEDDPVLGEDYYSVENPANKRRSTLITVLNISEI ESRFYKHPFTCFAKNTHG DAAYIQLIYPVTNFQK Patent Application Publication Sep. 2, 2010 Sheet 8 of 14 US 2010/0221257 A1 Figure 8 Human IL-1R1 cDNA sequence CACCATGAAAGTGTTACTCAGACTTATTTGTTTCATAGCTCTACTGATTTCTTCTCTG GAGGCTGATAAATGCAAGGAAC GTGAAGAAAAAATAATTTTAGTGTCATCTGCAAATGAAATTGATGTTCGTCCCTGTC CTCTTA ACCCAAATGAACACAAA GGCACTATAACTTGGTATAAAGATGACAGCAAGACACCTGTATCTACAGAACAAGC CTCCAGGATTCATCA ACACAAAGA GAAACTTTGGTTTGTTCCTGCTAAGGTGGAGGATTCAGGACATTACTATTGCGTGGT AAGAAATTCATCTTACTGCCTCA GAATTAAAATAAGTGCAAAATTTGTGGAGAATGAGCCTAACTTATGTTATAATGCAC AAGCCATATTTAAGCAGAAACTA CCCGTTGCAGGAGACGGAGGACTTGTGTGCCCTTATATGGAGTTTTTTAAAAATGAA AATAATGAGTTACCTAAATTACA GTGGTATAAGGATTGCAAACCTCTACTTCTTGACAATATACACTTTAGTGGAGTCAA AGATAGGCTCATCGTGATGAATG TGGCTGAAAAGCATAGAGGGAACTATACTTGTCATGCATCCTACACATACTTGGGCA AGCAATATCCTATTACCCGGGTA ATAGAATTTATTACTCTAGAGGAAAACAAACCCACAAGGCCTGTGATTGTGAGCCC AGCTAATGAGACAATGGAAGTAGA CTTGGGATCCCAGATACAATTGATCTGTAATGTCACCGGCCAGTTGAGTGACATTGC TTACTGGAAGTGGAATGGGTCAG TAATTGATGAAGATGACCCAGTGCTAGGGGAAGACTATTACAGTGTGGAAAATCCT GCAAACAAAAGAAGGAGTACCCTC ATCACAGTGCTTAATATATCGGAAATTGAAAGTAGATTTTATAAACATCCATTTACC TGTTTTGCCAAGAATACACATGG TATAGATGCAGCATATATCCAGTTAATATATCCAGTCACTAATTTCCAGAAG Patent Application Publication Sep. 2, 2010 Sheet 9 of 14 US 2010/0221257 A1 Figure 9 Cyno IL-1R1 Extracellular sequence (residues 1 to 337) MKVLLRLICFIALLISFLEADKCNEREEKIILVSSANEIDVRPCPLNPNEYKGTITWYKNDS KTPISTEQASRI HQHKKK LWFVPAKVEDSGHYYCVVRNSSYCLRIKITAKFVENEPNLCYNAEAIFKQRLPVAGDGG LVCPYMEFFKDENNELPKLLW YKDCKPLLLDNINFSGVKDRLIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEE NKPTRPVVSPANETIEVDL GSQIQLICNVTGQLSDTAYWKWNGSFIDEDDPVLGEDYYSVENPANKRRSTLITVLNISE TESRFYKHPFTCLARNTHGM DAAYVOLIYPVTKFQK Patent Application Publication Sep. 2, 2010 Sheet 10 of 14 US 2010/0221257 A1 Figure 10 Cyno cDNA extracellular IL-1R1 sequence CACCATGAAAGTGTTACTCCGACTTATTTGTTTCATTGCTCTACTGATTTCTTTTCTG GAGGCTGATAAATGCAATGAAC GTGAAGAAAAAATAATTTTAGTGTCATCTGCAAATGAAATTGATGTTCGTCCCTGTC CTCTTAACCCAAATGAATACAAA GGCACTATA ACATGGTATAAAAATGACAGCAAGACACCTATATCTACAGAACAAGC