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US007459539B2 ( 12) United States Patent ( 10 ) Patent No. : US 7 , 459 ,539 B2 Challita - Eid et al. (45 ) Date of Patent: Dec. 2 , 2008 ( 54 ) ANTIBODY THAT BINDS ZINC WO WO 03050236 6 / 2003 TRANSPORTER PROTEIN 108P5H8 ( 75 ) Inventors : Pia M . Challita - Eid , Encino , CA (US ) ; OTHER PUBLICATIONS Mary Faris , Los Angeles , CA (US ) ; Murgia et al . Cloning, expression , and vesicular localization of zinc Daniel E . H . Afar , Brisbane , CA (US ) ; transporter Dri 27 /ZnT4 in intestinal tissue and cells . Am J Physiol Rene S . Hubert , Los Angeles , CA (US ) ; 277 (Gastrointest Liver Physiol 40 ) : G1231 -61239 , 1999 . * Steve Chappell Mitchell, Gurnee , IL Kaufman et al. Blood 9 : 3178 -3184 , 1999 . * (US ) ; Elana Levin , Los Angeles, CA Wang et al . Rapid analysis of gene expression (RAGE ) facilitates (US ) ; Karen Jane Meyrick Morrison , universal expression profiling . Nucleic Acids Res 27 (23 ) : 4609 4618 , 1999 . * Santa Monica , CA (US ) ; Arthur B . Campbell et al. Totipotency of multipotentiality of cultured cells : Raitano , Los Angeles , CA (US ) ; Aya applications and progress . Theriogenology 47 : 63 -72 , 1997 . * Jakobovits , Beverly Hills , CA (US ) Moore , G . Genetically engineered antibodies. Clin Chem 35 ( 9 ) : 1849 - 1853 , 1989 . * (73 ) Assignee : Agensys, Inc ., Santa Monica , CA (US ) Dillman et al .Monoclonal antibodies in the treatment ofmalignancy : basic concepts and recent developments . Cancer Invest 19 ( 8 ) : 833 ( * ) Notice: Subject to any disclaimer, the term of this 841, 2001. * patent is extended or adjusted under 35 Skolnick et al. From genes to protein structure and function : novel U . S . C . 154 ( b ) by 1273 days . applications of computational approaches in the genomic era . Trends in Biotech 18 ( 1 ) : 34 - 39 , 2000 . * ( 21 ) Appl. No. : 10 /024 , 652 Bork, A . Powers and pitfalls in sequence analysis : the 70 % hurdle . Genome Res 10 : 398 - 400 , 2000 . * ( 22 ) Filed : Dec . 17 , 2001 Doerks et al . Protein annotation : detective work for function predic tion . Trends in Genetics 14 ( 6 ) : 248 -250 , 1998 . * Prior Publication Data Smith et al . The challenges of genome sequence annotation or “ The devil is in the details ” . Nature Biotech 15 : 1222 - 1223 , 1997 . * US 2003 /0219738 A1 Nov . 27 , 2003 Brenner, S . E . Errors in genome function . Trends in Genetics 15 ( 4 ) : 132 - 133 , 1999 . * Related U . S . Application Data Bork et al. Go hunting in sequence databases but watch out for the ( 60 ) Provisional application No . 60 / 256 ,210 , filed on Dec. traps. Trends in Genetics. 12 ( 10 ) : 425 -427 , 1996 . * 15 , 2000 . Wells . J . A . Additivity ofmutational effects in proteins . Biochemistry 29 (37 ) : 8509 -8517 , 1990 . * (51 ) Int. Ci. Ngo et al. Computational complexity , protein structure prediction , and the Levinthal paradox . The Protein Folding Problem and Tertiary CO7K 16 / 28 ( 2006 .01 ) Structure Prediction , pp . 492 -495 , 1994. * COZK 16 / 30 ( 2006 .01 ) Daniel et al. Virology 202 :540 - 549 , 1994. * CO7K 16 /46 ( 2006 .01 ) Haynes et al . Proteome analysis : biological assay or data archive. (52 ) U . S . Cl. .. .. .. 530 / 388 . 8 ; 530 / 388 . 1 ; 530 / 388 . 15 ; Electrophoresis 19 : 1862 - 1871 , 1998 . * 530 /388 . 2 ; 530 / 387 . 3 ; 530 /391 . 1 ; 530 /391 . 3 ; Hu et al . Analysis of genomic and proteomic data using advanced 530 / 391. 7 ; 530 /809 literature mining . J Proteome Res 2 : 405 -412 , 2003 . * (58 ) Field of Classification Search .. .. 503 / 387 . 1 , Chen et al . Discordant protein and mRNA expression in lung 503 /387 . 3 , 387 . 9 , 388 . 1 , 389 . 1 , 391 . 1 , 391 . 3 , adenocarcinomas. Molec Cellular Proteomics 1 : 304 - 313 , 2002 . * 503 / 391. 7 ; 514 / 2 ; 424 / 130 . 1 , 133 . 1 , 134 . 1 , Huang et al . , Nature Genetics ( 1997 ) 17 ( 3 ) : 292 - 297 . 424 / 135 . 1 , 141 . 1 , 178 . 1 , 181. 1 , 183 . 1 Hwang et al. , Seminars in Oncology ( 1999 ) 26 ( 2 ): 192 - 201. See application file for complete search history . Southwood et al ., Journal of Immunology ( 1998 ) 160 ( 7 ): 3363 - 3373 . ( 56 ) References Cited * cited by examiner U . S . PATENT DOCUMENTS Primary ExaminerDavid S Romeo 5 , 869 ,045 A * 2 / 1999 Hellstrom et al. .. .. 424 / 130 . 1 ( 74 ) Attorney , Agent, or Firm — Morrison & Foerster LLP (57 ) ABSTRACT FOREIGN PATENT DOCUMENTS EP 1033401 A2 9 / 2000 A novel gene (designated 108P5H8) and its encoded protein , WO WO 9733605 9 / 1997 and variants thereof, are described wherein 108P5H8 exhibits WO WO0055174 Al 9 / 2000 tissue specific expression in normal adult tissue, and is aber wo W00159063 A2 8 /2001 rantly expressed in the cancers listed in Table I. Consequently , WO W00160860 A2 8 /2001 108P5H8 provides a diagnostic , prognostic , prophylactic WO W00210449 A2 2 / 2002 and /or therapeutic target for cancer. The 108P5H8 gene or WO WO0218632 A2 3 / 2002 fragment thereof, or its encoded protein , or variants thereof , WO WO 0224718 3 / 2002 or a fragment thereof, can be used to elicit a humoral or WO W00224718 A1 3 / 2002 cellular immune response ; antibodies or T cells reactive with Wo W00230268 A2 4 / 2002 191P1E1B can be used in active or passive immunization . WO WO02055700 A2 7 / 2002 WO WO 02060953 8 /2002 12 Claims, 38 Drawing Sheets U . S . Patent Dec . 2 , 2008 Sheet 1 of 38 US 7 ,459 , 539 B2 Figure 1 : 108P5H8 SSH sequence of 448 nucleotides (SEQ ID : 2568 ) 1 GATCCAGATT TCTCTGCACA CTGGACTTCG TAGAGTAAGT GTGGTAGACA AAGAGACTAC 61 ACTGCACAAC CACCAGTGAA TATCATTGCT AAGAAGACTT TGGGTCGTGT TTCTCAGCCA 121 CTCTCACAGC TTTTGTAGAC TTATTTGATT TTGAAACAAG CAGTTAGCTA AATCTATTTT 181 CCTTTTATGC ATATATGTTA ATTGGCTCAA CTTAATATGG TGTTCTTACA GAATATGAGC 241 CCATTTGAAA TAAGGTTTTA GGCAATTTTG CTGTTGGCTC TGATTTGTAT ATAGCAAATT 301 TAAAGGTACA GAGTGTTTCC TAGATAGAAG ATTAGTTCAT TTGGTTCATT TTGTCTTTGA 361 AGCAAGCCAA GCTCATGAGC CAGTTGGTTA TTTGTCATAA ATGAACACCC ATCACTATAT 421 GCTATGTTGA GGGGAGGCAA GGCTGATC Figure 2A . The cDNA ( SEQ ID . NO . :2569 ) and amino acid sequence (SEQ ID . NO . :2570 ) of 108P5H8 v . 1 . The start methionine is underlined . The open reading frame extends from nucleic acid 253 - 1542 including the stop codon . i gccggcctccagcagcgggcgcggcgggcgcgagcacgaccccactctcctgcggccgcg 61 ggtggagcagcgcgagcccgcctcgctgagccggccgggggcggggagatgagttgcggc 121 cccgcggcagcgccccaggatggggagggacgcgcggcactgccctcgagaactggcgct 181 ccggegaagtaggcgccgccggccgtccgcctcccccaagccgttccgcaccgcggccgc MAGS GA W KRL K S M L R K 241 tcagcctctgCCATGGCCGGCTCTGGCGCGTGGAAGCGCCTCAAATCTATGCTAAGGAAG 17 DD A PL FIND T S A F D F S D E A G 301 GATGATGCGCCGCTGTTTTTAPATGACACCAGCGCCTTTGACTTCTCGGATGAGGCGGGG 37 D E GLS RF N K L R V V V A DDGS E 361 GACGAGGGGCTTTCTCGGTTCAACAAACTTCGAGTTGTGGTGGCCGATGACGGTTCCGAA 57 APE RP VNG A H P T L QADD DSL 421 GCCCCGGAAAGGCCTGTTAACGGGGCGCACCCGACCCTCCAGGCCGACGATGATTCCTTA 77 L DOD L P L T N SQL K v Ds CD 481 CTGGACCAAGACTTACCTTTGACCAACAGTCAGCTGAGTTTGAAGGTGGACTCCTGTGAC 97 N C S K Q R E I L K Q R K V K A R L T I 541 AACTGCAGCAAACAGAGAGAGATACTGAAGCAGAGAAAGGTGAAAGCCAGGTTGACCATT 117 A AV LY L L MI GE IV G GYI AN 601 GCTGCCGTTCTGTACTTGCTTTTCATGATTGGAGAACTTGTAGGTGGATACATTGCAAAT 137 S L A I MI DA L H M L T D L SA II L 661 AGCCTAGCAATCATGACAGATGCACTTCATATGTTAACTGACCTAAGCGCCATCATACTC 157 TL L AL WLS S K S P T K RF TF GF 721 ACCCTGCTTGCTTTGTGGCTATCATCAAAATCACCAACCAAAAGATTCACCTTTGGATTT 177 H R LE V SAM I SV V YILM G 781 CATCGCTTAGAGGTTTTGTCAGCTATGATTAGTGTGCTGTTGGTGTATATACTTATGGGA U . S . Patent Dec . 2 , 2008 Sheet 2 of 38 US 7 ,459 , 539 B2 Figure 2A continued 197 F 1 ? ? ? ? ? Q R ? ? ? ? ? ? ? ? ? G D 841 TTCCTCTTATATGAAGCTGTGCAAAGAACTATCCATATGAACTATGAAATAAATGGAGAT 217 I M L IT AA v G v Av NV IMG FLL 901 ATAATGCTCATCACCGCAGCTGTTGGAGTTGCAGTTAATGTAATAATGGGGTTTCTGTTG 237 N e S G H RHS S S L P S N S P I R 961 AACCAGTCTGGTCACCGTCACTCCCATTCCCACTCCCTGCCTTCAAATTCCCCTACCAGA 257 G S G C E R N G e DSL A RA A EV 1021 GGTTCTGGGTGTGAACGTAACCATGGGCAGGATAGCCTGGCAGTGAGAGCTGCATTTGTA 277 H A L G D L V OS v G v L I AAYI I R 1081 CATGCTTTGGGAGATTTGGTACAGAGTGTTGGTGTGCTAATAGCTGCATACATCATACGA 297 F KPE Y KI A DPI c I Y v F S L L v 1141 TTCAAGCCAGAATACAAGATTGCTGACCCCATCTGTACATACGTATTTTCATTACTTGTG 317 A E T T E R I I W D T V VI I L E G v P 1201 GCTTTTACAACATTTCGAATCATATGGGATACAGTAGTTATAATACTAGAAGGTGTGCCA 337 S H L N V DY I K E AL MK I E D V Y S 1261 AGCCATTTGAATGTAGACTATATCAAAGAAGCCTTGATGAAAATAGAAGATGTATATTCA 357 V E D L N I W S L I S G K S T A I v H I 1321 GTCGAAGATTTAAATATCTGGTCTCTCACTTCAGGAAAATCTACTGCCATAGTTCACATA 377 Q I P G S S S K W E E ve S K A NHL 1381 CAGCTAATTCCTGGAAGTTCATCTAAATGGGAGGAAGTACAGTCCAAAGCAAACCATTTA 397 L L W T F G M Y R c T I Q L 2 s Y R E 1441 TTATTGAACACATTTGGCATGTATAGATGTACTATTCAGCTTCAGAGTTACAGGCAAGAA 417 v D R T C A N C Q S S S P + 1501 GTGGACAGAACTTGTGCAAATTGTCAGAGTTCTAGTCCCTAAttttatgtattttgggaa 1561 ctcctgccttatttatcctgcagtcacagacttgagagcaataaatgcaaacctaaatga 1621 gaaaatggaatccctgacagctgtgtccgtatcaagcatcagtctctcaaacagttgccc 1681 cagcctgacagtgctagtctctgtttaatggtaaaaggagactttgccataattttcaga 1741 tgaagatgtttcccaaacactgtttacagaatgagatgtgactctacagatacctcatag 1801 aagacaatccaagatcatacttcattaacttgacagagtacgtgtcttaaaggaagcatc 1861 aagaattcaatatttgcatttaaaaatactttttaaggccattttatattaagccagtgc 1921 tggaaaactgaattttttttattatgtataataatctcgacacccagcttctggaattge 1981 tgctttctttttacagaaattactacccaacagatttcaggaagtactagtagttatccc 2041 aaaagtggaataagcatgtattcctaagtgtttcagaaatgttttatttcacacataagt 2101 cttaatgttattgttatgactatactttataaacaaccttttccagatgctacagggttt 2161 tgaatctcaaagttaacatttttcattatttgtaatcttagaaccaaatctttatttatt 2221 gtggtcactgttattaaatgatttaggaaatactttcaatattattctgaatggctgaag 2281 ttagtcttaaactcaaattactatatgatgatttaaaacaaaataaaagagcgaggatgg