WO2001004311A1 - Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides - Google Patents

Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides Download PDF

Info

Publication number
WO2001004311A1
WO2001004311A1 PCT/US2000/004414 US0004414W WO0104311A1 WO 2001004311 A1 WO2001004311 A1 WO 2001004311A1 US 0004414 W US0004414 W US 0004414W WO 0104311 A1 WO0104311 A1 WO 0104311A1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
atcc
polypeptide
amino acid
acid sequence
Prior art date
Application number
PCT/US2000/004414
Other languages
English (en)
Inventor
Avi J. Ashkenazi
David Botstein
Luc Desnoyers
Dan L. Eaton
Napoleone Ferrara
Ellen Filvaroff
Sherman Fong
Wei-Qiang Gao
Hanspeter Gerber
Mary E. Gerritsen
Audrey Goddard
Paul J. Godowski
Christopher J. Grimaldi
Austin L. Gurney
Kenneth J. Hillan
Ivar J. Kljavin
Jennie P. Mather
James Pan
Nicholas F. Paoni
Margaret Ann Roy
Timothy A. Stewart
Daniel Tumas
P. Mickey Williams
William I. Wood
Original Assignee
Genentech, Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from PCT/US1999/020594 external-priority patent/WO2000015666A2/fr
Priority claimed from PCT/US1999/020944 external-priority patent/WO2000015792A2/fr
Priority claimed from PCT/US1999/021090 external-priority patent/WO2000015796A2/fr
Priority claimed from PCT/US1999/021547 external-priority patent/WO2000015797A2/fr
Priority claimed from PCT/US1999/023089 external-priority patent/WO2000021996A2/fr
Priority claimed from PCT/US1999/028214 external-priority patent/WO2001019987A1/fr
Priority claimed from PCT/US1999/028313 external-priority patent/WO2000032221A2/fr
Priority claimed from PCT/US1999/028564 external-priority patent/WO2000055319A1/fr
Priority claimed from PCT/US1999/028565 external-priority patent/WO2000037638A2/fr
Priority claimed from PCT/US1999/030095 external-priority patent/WO2000037640A2/fr
Priority claimed from PCT/US1999/030911 external-priority patent/WO2000075316A1/fr
Priority claimed from PCT/US1999/030999 external-priority patent/WO2001005836A1/fr
Priority claimed from PCT/US2000/000219 external-priority patent/WO2000053753A2/fr
Priority to AU28839/00A priority Critical patent/AU2883900A/en
Application filed by Genentech, Inc. filed Critical Genentech, Inc.
Priority to AU33816/00A priority patent/AU768694B2/en
Priority to PCT/US2000/005004 priority patent/WO2000053757A2/fr
Priority to KR1020017011378A priority patent/KR100553300B1/ko
Priority to EP00912015A priority patent/EP1159419A1/fr
Priority to CA002361849A priority patent/CA2361849A1/fr
Priority to KR1020017011378D priority patent/KR20010104373A/ko
Priority to JP2000603378A priority patent/JP2003531811A/ja
Priority to JP2000603379A priority patent/JP2004516227A/ja
Priority to EP00913764A priority patent/EP1220905A2/fr
Priority to AU35144/00A priority patent/AU3514400A/en
Priority to PCT/US2000/005841 priority patent/WO2000053758A2/fr
Priority to KR1020017011406A priority patent/KR20010103046A/ko
Priority to CA002362427A priority patent/CA2362427A1/fr
Priority to EP00917878A priority patent/EP1214409B1/fr
Priority to CNA2004100465359A priority patent/CN1560249A/zh
Priority to KR1020027003131A priority patent/KR20020059591A/ko
Priority to DK00917878T priority patent/DK1214409T3/da
Priority to CA002384089A priority patent/CA2384089A1/fr
Priority to SI200030879T priority patent/SI1214409T1/sl
Priority to MXPA02002491A priority patent/MXPA02002491A/es
Priority to PCT/US2000/006471 priority patent/WO2001018210A1/fr
Priority to PT00917878T priority patent/PT1214409E/pt
Priority to DE60028054T priority patent/DE60028054T2/de
Priority to CN00815274A priority patent/CN1387570A/zh
Priority to AU38784/00A priority patent/AU783117B2/en
Priority to AT00917878T priority patent/ATE326532T1/de
Priority to JP2001521746A priority patent/JP2004500037A/ja
Priority to ES00917878T priority patent/ES2264929T3/es
Priority to IL14818800A priority patent/IL148188A0/xx
Priority to JP2001500766A priority patent/JP2004522402A/ja
Priority to AU37743/00A priority patent/AU3774300A/en
Priority to CA002383254A priority patent/CA2383254A1/fr
Priority to AT00916675T priority patent/ATE478145T1/de
Priority to EP00916675A priority patent/EP1210418B1/fr
Priority to PCT/US2000/008439 priority patent/WO2000073454A1/fr
Priority to EP07025117A priority patent/EP1978029A3/fr
Priority to JP2001503894A priority patent/JP2003529324A/ja
Priority to AU51527/00A priority patent/AU5152700A/en
Priority to EP00936172A priority patent/EP1208195A2/fr
Priority to EP07025116A priority patent/EP1953173B1/fr
Priority to PCT/US2000/014042 priority patent/WO2000077037A2/fr
Priority to EP07025118A priority patent/EP1956030B1/fr
Priority to AT07025118T priority patent/ATE448246T1/de
Priority to AT07025116T priority patent/ATE449109T1/de
Priority to CA2372511A priority patent/CA2372511C/fr
Priority to PCT/US2000/015264 priority patent/WO2000073452A2/fr
Priority to AU63910/00A priority patent/AU6391000A/en
Priority to PCT/US2000/020710 priority patent/WO2001009327A2/fr
Priority to EP05019538A priority patent/EP1623992A3/fr
Priority to EP07019808A priority patent/EP1892249A1/fr
Priority to JP2001520864A priority patent/JP3951035B2/ja
Priority to EP05019537A priority patent/EP1637541B1/fr
Priority to AT05019537T priority patent/ATE459645T1/de
Priority to EP05019536A priority patent/EP1623991A3/fr
Priority to ES05019537T priority patent/ES2341257T3/es
Priority to AU75730/00A priority patent/AU7573000A/en
Priority to CA002645727A priority patent/CA2645727A1/fr
Priority to EP05019540A priority patent/EP1621620A3/fr
Priority to CA002380355A priority patent/CA2380355A1/fr
Priority to DE60043951T priority patent/DE60043951D1/de
Priority to EP05019539A priority patent/EP1623993A3/fr
Priority to EP00964919A priority patent/EP1208202A2/fr
Priority to PCT/US2000/023328 priority patent/WO2001016318A2/fr
Priority to EP06000582A priority patent/EP1666495A1/fr
Priority to EP06000585A priority patent/EP1661996A1/fr
Priority to EP06000583A priority patent/EP1686134A3/fr
Priority to CA002491610A priority patent/CA2491610A1/fr
Priority to EP06000586A priority patent/EP1688497A1/fr
Priority to EP05025102A priority patent/EP1672070A3/fr
Priority to EP06000589A priority patent/EP1661997A1/fr
Priority to CA002491433A priority patent/CA2491433A1/fr
Priority to CA2709291A priority patent/CA2709291A1/fr
Priority to EP10005292A priority patent/EP2228446A1/fr
Priority to EP00983846A priority patent/EP1250426A2/fr
Priority to CA002491258A priority patent/CA2491258A1/fr
Priority to CA002391455A priority patent/CA2391455A1/fr
Priority to EP06000584A priority patent/EP1669371A3/fr
Priority to AU20554/01A priority patent/AU2055401A/en
Priority to JP2001542531A priority patent/JP2004522404A/ja
Priority to EP06000587A priority patent/EP1690872A3/fr
Priority to CA002492049A priority patent/CA2492049A1/fr
Priority to CA002492070A priority patent/CA2492070A1/fr
Priority to EP06000581A priority patent/EP1666494A1/fr
Priority to CA002490909A priority patent/CA2490909A1/fr
Priority to PCT/US2000/032678 priority patent/WO2001040466A2/fr
Priority to CA002494705A priority patent/CA2494705A1/fr
Priority to CA002496312A priority patent/CA2496312A1/fr
Priority to EP06000588A priority patent/EP1690873A3/fr
Priority to CA002490853A priority patent/CA2490853A1/fr
Publication of WO2001004311A1 publication Critical patent/WO2001004311A1/fr
Priority to US09/767,609 priority patent/US20020042367A1/en
Priority to US09/828,366 priority patent/US20020010137A1/en
Priority to US09/866,028 priority patent/US6642360B2/en
Priority to US09/902,903 priority patent/US20030044839A1/en
Priority to US09/902,736 priority patent/US20030049676A1/en
Priority to US09/902,713 priority patent/US20030082541A1/en
Priority to US09/902,979 priority patent/US20030113718A1/en
Priority to US09/902,853 priority patent/US20020192659A1/en
Priority to US09/902,634 priority patent/US20030082540A1/en
Priority to US09/902,759 priority patent/US20030077654A1/en
Priority to US09/902,736 priority patent/US6894148B2/en
Priority to US09/902,692 priority patent/US20030054400A1/en
Priority to US09/902,615 priority patent/US20030092002A1/en
Priority to US09/902,572 priority patent/US20030108983A1/en
Priority to US09/902,775 priority patent/US6686451B1/en
Priority to US09/903,786 priority patent/US20030044793A1/en
Priority to US09/904,011 priority patent/US20030003530A1/en
Priority to US09/903,562 priority patent/US6965015B2/en
Priority to US09/903,603 priority patent/US6767995B2/en
Priority to US09/903,823 priority patent/US20030104381A1/en
Priority to US09/903,806 priority patent/US20030130489A1/en
Priority to US09/903,520 priority patent/US20030054401A1/en
Priority to US09/903,603 priority patent/US20030148419A1/en
Priority to US09/903,943 priority patent/US20030054349A1/en
Priority to US09/903,925 priority patent/US20030096233A1/en
Priority to US09/904,119 priority patent/US20030049621A1/en
Priority to US09/903,640 priority patent/US7208308B2/en
Priority to US09/903,749 priority patent/US7147853B2/en
Priority to US09/904,992 priority patent/US20030135025A1/en
Priority to US09/905,088 priority patent/US20030073077A1/en
Priority to US09/904,938 priority patent/US20030211569A1/en
Priority to US09/905,056 priority patent/US20030054441A1/en
Priority to US09/905,291 priority patent/US20020160374A1/en
Priority to US09/904,805 priority patent/US20030211568A1/en
Priority to US09/904,859 priority patent/US20030036060A1/en
Priority to US09/905,125 priority patent/US6664376B2/en
Priority to US09/904,766 priority patent/US20030152999A1/en
Priority to US09/904,786 priority patent/US7557192B2/en
Priority to US09/904,877 priority patent/US20030186358A1/en
Priority to US09/904,485 priority patent/US20030064367A1/en
Priority to US09/905,075 priority patent/US7169906B2/en
Priority to US09/905,449 priority patent/US6965011B2/en
Priority to US09/904,838 priority patent/US20030148370A1/en
Priority to US09/904,920 priority patent/US6806352B2/en
Priority to US09/904,820 priority patent/US20030036094A1/en
Priority to US09/904,532 priority patent/US7151160B2/en
Priority to US09/904,462 priority patent/US6878807B2/en
Priority to US09/905,381 priority patent/US6818746B2/en
Priority to US09/905,348 priority patent/US20030064923A1/en
Priority to US09/904,553 priority patent/US20030059828A1/en
Priority to US09/904,956 priority patent/US20030049622A1/en
Priority to US09/906,742 priority patent/US20030023054A1/en
Priority to US09/906,815 priority patent/US7094567B2/en
Priority to US09/906,838 priority patent/US7070979B2/en
Priority to US09/906,760 priority patent/US20030096340A1/en
Priority to US09/906,679 priority patent/US6974689B1/en
Priority to US09/906,646 priority patent/US6852848B2/en
Priority to US09/906,618 priority patent/US6828146B2/en
Priority to US09/906,700 priority patent/US6723535B2/en
Priority to US09/906,777 priority patent/US20030148371A1/en
Priority to US09/906,722 priority patent/US6946262B2/en
Priority to US09/907,942 priority patent/US7087738B2/en
Priority to US09/908,093 priority patent/US20030017498A1/en
Priority to US09/907,575 priority patent/US20030073079A1/en
Priority to US09/907,794 priority patent/US6635468B2/en
Priority to US09/907,925 priority patent/US20030054352A1/en
Priority to US09/907,824 priority patent/US20020197671A1/en
Priority to US09/907,652 priority patent/US20030104469A1/en
Priority to US09/907,841 priority patent/US7033825B2/en
Priority to US09/907,613 priority patent/US20030027145A1/en
Priority to US09/907,728 priority patent/US20030190611A1/en
Priority to US09/907,979 priority patent/US20030082542A1/en
Priority to US09/909,204 priority patent/US20030036061A1/en
Priority to US09/909,064 priority patent/US6818449B2/en
Priority to US09/908,576 priority patent/US20040005553A1/en
Priority to US09/909,088 priority patent/US20020146709A1/en
Priority to US09/909,320 priority patent/US7074592B2/en
Priority to US09/924,647 priority patent/US20020155543A1/en
Priority to US09/941,992 priority patent/US20030082546A1/en
Priority to US09/943,762 priority patent/US20020142958A1/en
Priority to US09/944,449 priority patent/US20020102647A1/en
Priority to US09/943,851 priority patent/US20020150976A1/en
Priority to US09/943,664 priority patent/US20040091972A1/en
Priority to US09/944,403 priority patent/US20020165143A1/en
Priority to US09/944,432 priority patent/US20020142419A1/en
Priority to US09/943,780 priority patent/US20030096742A1/en
Priority to US09/944,396 priority patent/US20020132981A1/en
Priority to US09/944,413 priority patent/US20020156004A1/en
Priority to US09/944,457 priority patent/US6734288B2/en
Priority to US09/944,929 priority patent/US7550573B2/en
Priority to US09/944,896 priority patent/US7189566B2/en
Priority to US09/945,587 priority patent/US6936254B2/en
Priority to US09/944,654 priority patent/US20020142959A1/en
Priority to US09/944,852 priority patent/US20030083479A1/en
Priority to US09/944,862 priority patent/US20020115145A1/en
Priority to US09/945,584 priority patent/US6908993B2/en
Priority to US09/944,944 priority patent/US6929947B2/en
Priority to US09/945,015 priority patent/US20020132768A1/en
Priority to US09/944,884 priority patent/US7018837B2/en
Priority to US09/944,907 priority patent/US20020198147A1/en
Priority to US09/991,163 priority patent/US20020132253A1/en
Priority to US09/990,427 priority patent/US20030073809A1/en
Priority to US09/990,442 priority patent/US20020132252A1/en
Priority to US09/991,854 priority patent/US20030059780A1/en
Priority to US09/990,444 priority patent/US6930170B2/en
Priority to US09/991,073 priority patent/US20020127576A1/en
Priority to US09/990,443 priority patent/US20030054987A1/en
Priority to US09/993,687 priority patent/US20020198149A1/en
Priority to US09/990,711 priority patent/US20030032023A1/en
Priority to US09/992,521 priority patent/US20030083461A1/en
Priority to US09/990,440 priority patent/US20030060407A1/en
Priority to US09/993,748 priority patent/US20030069403A1/en
Priority to US09/992,598 priority patent/US6956108B2/en
Priority to US09/993,469 priority patent/US20030068623A1/en
Priority to US09/990,456 priority patent/US20020137890A1/en
Priority to US09/990,562 priority patent/US20030027985A1/en
Priority to US09/990,726 priority patent/US20030054359A1/en
Priority to US09/990,438 priority patent/US20030027754A1/en
Priority to US09/990,436 priority patent/US20020198148A1/en
Priority to US09/993,583 priority patent/US7074897B2/en
Priority to US09/993,667 priority patent/US20030022187A1/en
Priority to US09/997,573 priority patent/US20030049682A1/en
Priority to US09/997,653 priority patent/US7034122B2/en
Priority to US09/997,641 priority patent/US20030224358A1/en
Priority to US09/997,683 priority patent/US20030059783A1/en
Priority to US09/997,666 priority patent/US20030027163A1/en
Priority to US09/997,857 priority patent/US20030064375A1/en
Priority to US09/997,585 priority patent/US20030119055A1/en
Priority to US10/002,796 priority patent/US20030032057A1/en
Priority to US09/997,641 priority patent/US7112656B2/en
Priority to US09/997,542 priority patent/US20030068647A1/en
Priority to US09/997,440 priority patent/US20030059833A1/en
Priority to US09/997,628 priority patent/US20030059782A1/en
Priority to US09/997,601 priority patent/US7189814B2/en
Priority to US09/998,041 priority patent/US7309775B2/en
Priority to US09/997,529 priority patent/US20030134284A1/en
Priority to US09/997,529 priority patent/US7309761B2/en
Priority to US09/997,428 priority patent/US20030027162A1/en
Priority to US09/998,156 priority patent/US20030044806A1/en
Priority to US09/997,585 priority patent/US7166282B2/en
Priority to US09/997,559 priority patent/US20030054403A1/en
Priority to US09/997,349 priority patent/US7034106B2/en
Priority to US09/997,384 priority patent/US7119177B2/en
Priority to US09/997,614 priority patent/US20030124531A1/en
Priority to US09/998,041 priority patent/US20030119001A1/en
Priority to US09/997,333 priority patent/US6953836B2/en
Priority to US09/997,666 priority patent/US7244816B2/en
Priority to US09/997,601 priority patent/US20030054404A1/en
Priority to US09/997,514 priority patent/US7019116B2/en
Priority to US09/997,384 priority patent/US20030087305A1/en
Priority to US09/991,172 priority patent/US20030050457A1/en
Priority to US09/990,437 priority patent/US20030045463A1/en
Priority to US09/991,150 priority patent/US20030194760A1/en
Priority to US09/991,181 priority patent/US6913919B2/en
Priority to US09/990,441 priority patent/US7041804B2/en
Priority to US09/991,157 priority patent/US7101687B2/en
Priority to US09/989,862 priority patent/US20030130182A1/en
Priority to US09/989,723 priority patent/US20020072092A1/en
Priority to US09/989,328 priority patent/US7056736B2/en
Priority to US09/989,729 priority patent/US20030059831A1/en
Priority to US09/989,734 priority patent/US7491529B2/en
Priority to US09/989,726 priority patent/US7018811B2/en
Priority to US09/989,279 priority patent/US7083978B2/en
Priority to US09/989,732 priority patent/US7037679B2/en
Priority to US09/989,735 priority patent/US6972185B2/en
Priority to US09/989,721 priority patent/US20020142961A1/en
Priority to US09/989,727 priority patent/US20020072497A1/en
Priority to US09/989,722 priority patent/US20020072067A1/en
Priority to US09/989,293 priority patent/US7034136B2/en
Priority to US09/989,725 priority patent/US20030139329A1/en
Priority to US09/989,728 priority patent/US7029873B2/en
Priority to US09/989,731 priority patent/US20020103125A1/en
Priority to US09/989,730 priority patent/US7157247B2/en
Priority to US10/006,867 priority patent/US7160985B2/en
Priority to US10/028,072 priority patent/US20030004311A1/en
Priority to US10/033,244 priority patent/US20020192668A1/en
Priority to US10/032,996 priority patent/US20030054447A1/en
Priority to US10/032,990 priority patent/US20030032060A1/en
Priority to US10/033,301 priority patent/US20020098506A1/en
Priority to US10/033,245 priority patent/US20020160392A1/en
Priority to US10/033,223 priority patent/US20020164646A1/en
Priority to US10/033,167 priority patent/US20020182618A1/en
Priority to US10/033,326 priority patent/US20020098507A1/en
Priority to US10/033,435 priority patent/US20030027256A1/en
Priority to US10/033,396 priority patent/US20030077657A1/en
Priority to US10/033,246 priority patent/US20020098505A1/en
Priority to US10/052,586 priority patent/US20020127584A1/en
Priority to US10/066,500 priority patent/US20020177165A1/en
Priority to US10/066,198 priority patent/US20030170721A1/en
Priority to US10/066,273 priority patent/US7317092B2/en
Priority to US10/066,269 priority patent/US20030040014A1/en
Priority to US10/066,203 priority patent/US20030180796A1/en
Priority to US10/066,211 priority patent/US20030044844A1/en
Priority to US10/066,494 priority patent/US20030032063A1/en
Priority to US10/066,193 priority patent/US20030044902A1/en
Priority to US10/081,056 priority patent/US20040043927A1/en
Priority to US10/119,480 priority patent/US20040087769A1/en
Priority to US10/121,041 priority patent/US20030077776A1/en
Priority to US10/121,046 priority patent/US20030194791A1/en
Priority to US10/121,059 priority patent/US20030190721A1/en
Priority to US10/121,040 priority patent/US20030082759A1/en
Priority to US10/121,047 priority patent/US20030077778A1/en
Priority to US10/121,042 priority patent/US20030096386A1/en
Priority to US10/121,051 priority patent/US20030092147A1/en
Priority to US10/121,045 priority patent/US20030073210A1/en
Priority to US10/121,044 priority patent/US20030190717A1/en
Priority to US10/121,062 priority patent/US20030077779A1/en
Priority to US10/121,050 priority patent/US20030054516A1/en
Priority to US10/121,048 priority patent/US20030199051A1/en
Priority to US10/121,055 priority patent/US20030190718A1/en
Priority to US10/121,056 priority patent/US20030082760A1/en
Priority to US10/121,052 priority patent/US20030199052A1/en
Priority to US10/121,054 priority patent/US20030199054A1/en
Priority to US10/121,058 priority patent/US20030190720A1/en
Priority to US10/121,057 priority patent/US20030190719A1/en
Priority to US10/121,060 priority patent/US20030190722A1/en
Priority to US10/121,063 priority patent/US20030199055A1/en
Priority to US10/121,053 priority patent/US20030199053A1/en
Priority to US10/121,061 priority patent/US20030082761A1/en
Priority to US10/121,043 priority patent/US7220831B2/en
Priority to US10/121,049 priority patent/US20030022239A1/en
Priority to US10/123,109 priority patent/US20030190723A1/en
Priority to US10/123,214 priority patent/US7343721B2/en
Priority to US10/123,154 priority patent/US20030190724A1/en
Priority to US10/123,292 priority patent/US20030073211A1/en
Priority to US10/123,156 priority patent/US20030194792A1/en
Priority to US10/123,212 priority patent/US7276577B2/en
Priority to US10/123,215 priority patent/US7291329B2/en
Priority to US10/123,108 priority patent/US7635478B2/en
Priority to US10/123,155 priority patent/US20030068794A1/en
Priority to US10/123,235 priority patent/US20030082762A1/en
Priority to US10/123,262 priority patent/US20030049816A1/en
Priority to US10/123,213 priority patent/US20030199057A1/en
Priority to US10/123,291 priority patent/US20030199058A1/en
Priority to US10/123,157 priority patent/US20030190725A1/en
Priority to US10/123,292 priority patent/US7045603B2/en
Priority to US10/123,771 priority patent/US20030199060A1/en
Priority to US10/123,213 priority patent/US7193048B2/en
Priority to US10/123,261 priority patent/US20030068796A1/en
Priority to US10/123,322 priority patent/US20030199059A1/en
Priority to US10/123,236 priority patent/US20030068795A1/en
Priority to US10/123,904 priority patent/US20030022328A1/en
Priority to US10/123,902 priority patent/US20030077781A1/en
Priority to US10/123,911 priority patent/US7408032B2/en
Priority to US10/123,905 priority patent/US7285625B2/en
Priority to US10/123,905 priority patent/US20030087344A1/en
Priority to US10/123,903 priority patent/US20030073212A1/en
Priority to US10/123,908 priority patent/US7335728B2/en
Priority to US10/123,907 priority patent/US7084258B2/en
Priority to US10/123,912 priority patent/US20030100087A1/en
Priority to US10/123,910 priority patent/US7329404B2/en
Priority to US10/123,909 priority patent/US7193049B2/en
Priority to US10/123,913 priority patent/US20030203462A1/en
Priority to US10/123,906 priority patent/US20030190726A1/en
Priority to US10/124,823 priority patent/US20030199062A1/en
Priority to US10/124,822 priority patent/US7109305B2/en
Priority to US10/125,166 priority patent/US20030039648A1/en
Priority to US10/124,816 priority patent/US20030190728A1/en
Priority to US10/124,818 priority patent/US20030082763A1/en
Priority to US10/124,813 priority patent/US7312307B2/en
Priority to US10/125,795 priority patent/US7304131B2/en
Priority to US10/124,819 priority patent/US7285626B2/en
Priority to US10/125,805 priority patent/US20030194794A1/en
Priority to US10/124,820 priority patent/US20030190729A1/en
Priority to US10/125,704 priority patent/US7357926B2/en
Priority to US10/124,821 priority patent/US20030199023A1/en
Priority to US10/124,824 priority patent/US20030077659A1/en
Priority to US10/124,817 priority patent/US20030077786A1/en
Priority to US10/124,814 priority patent/US7105335B2/en
Priority to US10/125,932 priority patent/US7317079B2/en
Priority to US10/125,927 priority patent/US20030190731A1/en
Priority to US10/125,924 priority patent/US7342097B2/en
Priority to US10/125,922 priority patent/US7309762B2/en
Priority to US10/125,931 priority patent/US20030199063A1/en
Priority to US10/127,831 priority patent/US20030082689A1/en
Priority to US10/128,689 priority patent/US20030087365A1/en
Priority to US10/131,823 priority patent/US7304132B2/en
Priority to US10/131,817 priority patent/US7291701B2/en
Priority to US10/131,825 priority patent/US7282566B2/en
Priority to US10/131,815 priority patent/US20030092103A1/en
Priority to US10/137,867 priority patent/US20030207349A1/en
Priority to US10/137,865 priority patent/US20030032155A1/en
Priority to US10/137,868 priority patent/US20030082764A1/en
Priority to US10/139,980 priority patent/US7247710B2/en
Priority to US10/140,020 priority patent/US20030207415A1/en
Priority to US10/140,470 priority patent/US20030022331A1/en
Priority to US10/140,024 priority patent/US20040058424A1/en
Priority to US10/139,963 priority patent/US7288625B2/en
Priority to US10/140,474 priority patent/US20030032156A1/en
Priority to US10/140,023 priority patent/US20030207416A1/en
Priority to US10/140,805 priority patent/US20030207417A1/en
Priority to US10/140,925 priority patent/US20030073215A1/en
Priority to US10/063,651 priority patent/US7193057B2/en
Priority to US10/140,808 priority patent/US7425621B2/en
Priority to US10/140,928 priority patent/US20030068798A1/en
Priority to US10/140,865 priority patent/US20030207420A1/en
Priority to US10/140,860 priority patent/US7307151B2/en
Priority to US10/140,921 priority patent/US7317080B2/en
Priority to US10/140,864 priority patent/US20030207419A1/en
Priority to US10/140,809 priority patent/US20030207418A1/en
Priority to US10/141,754 priority patent/US7361732B2/en
Priority to US10/141,756 priority patent/US7488586B2/en
Priority to US10/141,701 priority patent/US20030207421A1/en
Priority to US10/141,760 priority patent/US7342104B2/en
Priority to US10/141,755 priority patent/US7297764B2/en
Priority to US10/142,417 priority patent/US7304133B2/en
Priority to US10/142,430 priority patent/US7309766B2/en
Priority to US10/142,425 priority patent/US20030207424A1/en
Priority to US10/143,114 priority patent/US20030036180A1/en
Priority to US10/143,113 priority patent/US7329730B2/en
Priority to US10/143,032 priority patent/US7408033B2/en
Priority to US10/142,419 priority patent/US7153941B2/en
Priority to US10/142,431 priority patent/US7285629B2/en
Priority to US10/142,423 priority patent/US20030049817A1/en
Priority to US10/145,627 priority patent/US20030180869A1/en
Priority to US10/145,753 priority patent/US20030207372A1/en
Priority to US10/145,876 priority patent/US20030134371A1/en
Priority to US10/145,875 priority patent/US20030166079A1/en
Priority to US10/146,792 priority patent/US20030207428A1/en
Priority to US10/146,789 priority patent/US20030180872A1/en
Priority to US10/146,730 priority patent/US20030207427A1/en
Priority to US10/146,786 priority patent/US20030203438A1/en
Priority to US10/146,794 priority patent/US20030207375A1/en
Priority to US10/147,528 priority patent/US20030219885A1/en
Priority to US10/147,536 priority patent/US20040077064A1/en
Priority to US10/147,492 priority patent/US20030082765A1/en
Priority to US10/147,519 priority patent/US20030077791A1/en
Priority to US10/152,373 priority patent/US20030186367A1/en
Priority to US10/152,395 priority patent/US7189534B2/en
Priority to US10/153,934 priority patent/US20030129695A1/en
Priority to US10/156,843 priority patent/US20030207805A1/en
Priority to US10/157,786 priority patent/US20030208055A1/en
Priority to US10/157,782 priority patent/US20030077792A1/en
Priority to US10/158,782 priority patent/US20030082766A1/en
Priority to US10/160,498 priority patent/US20030073216A1/en
Priority to US10/158,791 priority patent/US20030207429A1/en
Priority to US10/173,701 priority patent/US20030104538A1/en
Priority to US10/173,707 priority patent/US20030166110A1/en
Priority to US10/173,690 priority patent/US20030166105A1/en
Priority to US10/173,695 priority patent/US20030032101A1/en
Priority to US10/173,703 priority patent/US20030170794A1/en
Priority to US10/173,706 priority patent/US20030022293A1/en
Priority to US10/173,699 priority patent/US20030166109A1/en
Priority to US10/173,704 priority patent/US20030170795A1/en
Priority to US10/173,696 priority patent/US20030082767A1/en
Priority to US10/173,702 priority patent/US20030170793A1/en
Priority to US10/173,708 priority patent/US20030040053A1/en
Priority to US10/173,698 priority patent/US20030166108A1/en
Priority to US10/173,689 priority patent/US20030166104A1/en
Priority to US10/173,691 priority patent/US20030166106A1/en
Priority to US10/173,694 priority patent/US20030166107A1/en
Priority to US10/173,700 priority patent/US20030027262A1/en
Priority to US10/173,693 priority patent/US20030073169A1/en
Priority to US10/173,697 priority patent/US20030032102A1/en
Priority to US10/173,705 priority patent/US20030032103A1/en
Priority to US10/173,692 priority patent/US20030166188A1/en
Priority to US10/174,582 priority patent/US20030027265A1/en
Priority to US10/175,740 priority patent/US20030027268A1/en
Priority to US10/174,588 priority patent/US20030027266A1/en
Priority to US10/174,583 priority patent/US7211645B2/en
Priority to US10/174,574 priority patent/US20030170796A1/en
Priority to US10/174,587 priority patent/US20030166113A1/en
Priority to US10/174,589 priority patent/US20030166114A1/en
Priority to US10/174,590 priority patent/US20030008352A1/en
Priority to US10/174,591 priority patent/US20030166115A1/en
Priority to US10/174,572 priority patent/US20030027263A1/en
Priority to US10/174,579 priority patent/US20030027264A1/en
Priority to US10/174,570 priority patent/US20030211572A1/en
Priority to US10/174,578 priority patent/US20030073170A1/en
Priority to US10/174,569 priority patent/US20030166111A1/en
Priority to US10/174,585 priority patent/US20030032105A1/en
Priority to US10/174,586 priority patent/US20030032106A1/en
Priority to US10/174,581 priority patent/US7153939B2/en
Priority to US10/174,576 priority patent/US7125962B2/en
Priority to US10/175,750 priority patent/US20030073172A1/en
Priority to US10/175,749 priority patent/US20050196832A1/en
Priority to US10/175,747 priority patent/US20030032107A1/en
Priority to US10/175,743 priority patent/US20030027269A1/en
Priority to US10/175,748 priority patent/US20030166121A1/en
Priority to US10/175,741 priority patent/US20030073171A1/en
Priority to US10/175,739 priority patent/US20030027267A1/en
Priority to US10/175,738 priority patent/US20030022294A1/en
Priority to US10/175,735 priority patent/US20030082715A1/en
Priority to US10/175,751 priority patent/US20030166122A1/en
Priority to US10/175,746 priority patent/US20030027270A1/en
Priority to US10/175,754 priority patent/US20030166123A1/en
Priority to US10/175,752 priority patent/US20030022295A1/en
Priority to US10/175,744 priority patent/US20030166119A1/en
Priority to US10/175,753 priority patent/US20030077732A1/en
Priority to US10/175,742 priority patent/US20030166118A1/en
Priority to US10/175,737 priority patent/US20030013153A1/en
Priority to US10/175,736 priority patent/US20030166117A1/en
Priority to US10/175,745 priority patent/US20030166120A1/en
Priority to US10/176,746 priority patent/US20030068680A1/en
Priority to US10/176,989 priority patent/US20030170803A1/en
Priority to US10/176,747 priority patent/US20030027273A1/en
Priority to US10/176,479 priority patent/US20030040054A1/en
Priority to US10/176,757 priority patent/US7317082B2/en
Priority to US10/176,981 priority patent/US20030170800A1/en
Priority to US10/176,749 priority patent/US20030017542A1/en
Priority to US10/176,754 priority patent/US7709602B2/en
Priority to US10/176,921 priority patent/US20030027276A1/en
Priority to US10/176,482 priority patent/US20030022296A1/en
Priority to US10/176,911 priority patent/US20030032113A1/en
Priority to US10/176,484 priority patent/US20030059876A9/en
Priority to US10/176,919 priority patent/US20030032114A1/en
Priority to US10/176,483 priority patent/US20030017541A1/en
Priority to US10/176,485 priority patent/US20030032109A1/en
Priority to US10/176,990 priority patent/US20030036119A1/en
Priority to US10/176,487 priority patent/US20030032110A1/en
Priority to US10/176,918 priority patent/US7495083B2/en
Priority to US10/176,988 priority patent/US20030170802A1/en
Priority to US10/176,759 priority patent/US20030166128A1/en
Priority to US10/176,917 priority patent/US20030044918A1/en
Priority to US10/176,491 priority patent/US20030087373A1/en
Priority to US10/176,753 priority patent/US20030044917A1/en
Priority to US10/176,493 priority patent/US20030032111A1/en
Priority to US10/176,993 priority patent/US20030027280A1/en
Priority to US10/176,913 priority patent/US20030022298A1/en
Priority to US10/176,914 priority patent/US20030017543A1/en
Priority to US10/176,920 priority patent/US20030166129A1/en
Priority to US10/176,490 priority patent/US20030170798A1/en
Priority to US10/176,481 priority patent/US20030032108A1/en
Priority to US10/176,982 priority patent/US20030044919A1/en
Priority to US10/176,991 priority patent/US20030027324A1/en
Priority to US10/176,492 priority patent/US20030027272A1/en
Priority to US10/176,488 priority patent/US20030027271A1/en
Priority to US10/176,915 priority patent/US20030017544A1/en
Priority to US10/176,985 priority patent/US20030027277A1/en
Priority to US10/176,992 priority patent/US20030027279A1/en
Priority to US10/176,748 priority patent/US20030040055A1/en
Priority to US10/176,489 priority patent/US20030166125A1/en
Priority to US10/176,979 priority patent/US20030087374A1/en
Priority to US10/176,750 priority patent/US20030027274A1/en
Priority to US10/176,758 priority patent/US20030008353A1/en
Priority to US10/176,983 priority patent/US20030170801A1/en
Priority to US10/176,924 priority patent/US20030166131A1/en
Priority to US10/176,756 priority patent/US20030032112A1/en
Priority to US10/176,916 priority patent/US20030040056A1/en
Priority to US10/176,978 priority patent/US20030032116A1/en
Priority to US10/176,760 priority patent/US7339033B2/en
Priority to US10/176,923 priority patent/US20030068681A1/en
Priority to US10/176,925 priority patent/US20030032115A1/en
Priority to US10/176,986 priority patent/US20030073173A1/en
Priority to US10/176,751 priority patent/US20030036117A1/en
Priority to US10/176,755 priority patent/US20030166127A1/en
Priority to US10/176,922 priority patent/US20030166130A1/en
Priority to US10/176,987 priority patent/US20030027278A1/en
Priority to US10/176,486 priority patent/US7354999B2/en
Priority to US10/176,480 priority patent/US20030166124A1/en
Priority to US10/176,752 priority patent/US20030170799A1/en
Priority to US10/179,515 priority patent/US20030166135A1/en
Priority to US10/179,508 priority patent/US20030166133A1/en
Priority to US10/179,511 priority patent/US20030104539A1/en
Priority to US10/179,522 priority patent/US20030044923A1/en
Priority to US10/179,506 priority patent/US20030044920A1/en
Priority to US10/179,523 priority patent/US20030215909A1/en
Priority to US10/179,512 priority patent/US20030166134A1/en
Priority to US10/179,507 priority patent/US20030040057A1/en
Priority to US10/179,525 priority patent/US20030040060A1/en
Priority to US10/179,516 priority patent/US20030040058A1/en
Priority to US10/179,520 priority patent/US20030096353A1/en
Priority to US10/179,514 priority patent/US20030044922A1/en
Priority to US10/179,521 priority patent/US20030170806A1/en
Priority to US10/179,518 priority patent/US20030104540A1/en
Priority to US10/179,519 priority patent/US7339024B2/en
Priority to US10/179,509 priority patent/US20030207392A1/en
Priority to US10/179,510 priority patent/US20030032117A1/en
Priority to US10/179,513 priority patent/US20030044921A1/en
Priority to US10/179,517 priority patent/US20030170805A1/en
Priority to US10/179,526 priority patent/US20030100061A1/en
Priority to US10/180,555 priority patent/US20030032123A1/en
Priority to US10/180,549 priority patent/US20030032122A1/en
Priority to US10/180,541 priority patent/US20030036120A1/en
Priority to US10/180,550 priority patent/US20030064440A1/en
Priority to US10/180,544 priority patent/US20030032119A1/en
Priority to US10/180,560 priority patent/US20030044925A1/en
Priority to US10/180,548 priority patent/US7696319B2/en
Priority to US10/180,556 priority patent/US7355000B2/en
Priority to US10/180,542 priority patent/US20030036121A1/en
Priority to US10/180,546 priority patent/US20030032120A1/en
Priority to US10/180,559 priority patent/US20030032124A1/en
Priority to US10/180,557 priority patent/US20030022301A1/en
Priority to US10/180,552 priority patent/US7348415B2/en
Priority to US10/180,554 priority patent/US20050202526A1/en
Priority to US10/180,547 priority patent/US20030032121A1/en
Priority to US10/180,540 priority patent/US20030040061A1/en
Priority to US10/180,553 priority patent/US7365156B2/en
Priority to US10/180,545 priority patent/US20030040062A1/en
Priority to US10/180,551 priority patent/US20030036123A1/en
Priority to US10/180,543 priority patent/US20030032118A1/en
Priority to US10/183,001 priority patent/US7084255B2/en
Priority to US10/180,998 priority patent/US7087421B2/en
Priority to US10/183,002 priority patent/US20030054454A1/en
Priority to US10/183,015 priority patent/US20030044926A1/en
Priority to US10/183,006 priority patent/US7297776B2/en
Priority to US10/181,000 priority patent/US7319137B2/en
Priority to US10/183,016 priority patent/US20030082717A1/en
Priority to US10/183,014 priority patent/US20030064441A1/en
Priority to US10/183,012 priority patent/US7718770B2/en
Priority to US10/183,013 priority patent/US7309769B2/en
Priority to US10/183,003 priority patent/US20030082716A1/en
Priority to US10/183,008 priority patent/US20030040064A1/en
Priority to US10/183,009 priority patent/US7339034B2/en
Priority to US10/183,005 priority patent/US7317093B2/en
Priority to US10/183,019 priority patent/US7425605B2/en
Priority to US10/183,017 priority patent/US20030040065A1/en
Priority to US10/183,018 priority patent/US20030104541A1/en
Priority to US10/180,999 priority patent/US7297767B2/en
Priority to US10/183,010 priority patent/US20030032126A1/en
Priority to US10/183,011 priority patent/US20030068682A1/en
Priority to US10/184,627 priority patent/US20030040070A1/en
Priority to US10/184,651 priority patent/US7291704B2/en
Priority to US10/184,612 priority patent/US20030036127A1/en
Priority to US10/184,618 priority patent/US7393917B2/en
Priority to US10/184,628 priority patent/US7309770B2/en
Priority to US10/184,641 priority patent/US20030073174A1/en
Priority to US10/184,631 priority patent/US20030036134A1/en
Priority to US10/184,613 priority patent/US20030119105A1/en
Priority to US10/184,652 priority patent/US20030032134A1/en
Priority to US10/184,630 priority patent/US20030036133A1/en
Priority to US10/184,627 priority patent/US7282569B2/en
Priority to US10/184,638 priority patent/US20030054456A1/en
Priority to US10/184,630 priority patent/US7304143B2/en
Priority to US10/184,615 priority patent/US20030044927A1/en
Priority to US10/184,616 priority patent/US20030036128A1/en
Priority to US10/184,619 priority patent/US20030049738A1/en
Priority to US10/184,642 priority patent/US7332573B2/en
Priority to US10/184,654 priority patent/US7378486B2/en
Priority to US10/184,614 priority patent/US20030032128A1/en
Priority to US10/184,640 priority patent/US7271250B2/en
Priority to US10/184,633 priority patent/US20030068683A1/en
Priority to US10/184,646 priority patent/US20030032132A1/en
Priority to US10/184,632 priority patent/US20030036135A1/en
Priority to US10/184,626 priority patent/US20030040069A1/en
Priority to US10/184,636 priority patent/US20030036136A1/en
Priority to US10/184,647 priority patent/US20030032133A1/en
Priority to US10/184,658 priority patent/US20030027281A1/en
Priority to US10/184,617 priority patent/US20030036129A1/en
Priority to US10/184,656 priority patent/US20030044931A1/en
Priority to US10/184,645 priority patent/US7291718B2/en
Priority to US10/184,637 priority patent/US20030032131A1/en
Priority to US10/184,635 priority patent/US20030032130A1/en
Priority to US10/184,650 priority patent/US20030036138A1/en
Priority to US10/184,625 priority patent/US20030040068A1/en
Priority to US10/184,657 priority patent/US20030104543A1/en
Priority to US10/184,624 priority patent/US20030104542A1/en
Priority to US10/184,643 priority patent/US20030044929A1/en
Priority to US10/184,655 priority patent/US20030040073A1/en
Priority to US10/184,629 priority patent/US20030036132A1/en
Priority to US10/184,634 priority patent/US20030068684A1/en
Priority to US10/184,621 priority patent/US20030054455A1/en
Priority to US10/184,623 priority patent/US20030032129A1/en
Priority to US10/184,644 priority patent/US20030044930A1/en
Priority to US10/184,620 priority patent/US20030044928A1/en
Priority to US10/184,622 priority patent/US20030036130A1/en
Priority to US10/187,594 priority patent/US7294335B2/en
Priority to US10/187,598 priority patent/US20030036142A1/en
Priority to US10/187,739 priority patent/US7291706B2/en
Priority to US10/187,588 priority patent/US7351795B2/en
Priority to US10/187,887 priority patent/US7285645B2/en
Priority to US10/187,747 priority patent/US7291707B2/en
Priority to US10/187,597 priority patent/US20030036141A1/en
Priority to US10/187,886 priority patent/US7291708B2/en
Priority to US10/187,884 priority patent/US20030036155A1/en
Priority to US10/187,601 priority patent/US7291705B2/en
Priority to US10/187,754 priority patent/US20030036153A1/en
Priority to US10/188,770 priority patent/US7358340B2/en
Priority to US10/187,596 priority patent/US20030032136A1/en
Priority to US10/187,600 priority patent/US20030036143A1/en
Priority to US10/187,603 priority patent/US20030036146A1/en
Priority to US10/187,746 priority patent/US20030036149A1/en
Priority to US10/187,743 priority patent/US20030036148A1/en
Priority to US10/187,747 priority patent/US20030036150A1/en
Priority to US10/187,751 priority patent/US20030036151A1/en
Priority to US10/188,780 priority patent/US7268217B2/en
Priority to US10/188,773 priority patent/US20030036159A1/en
Priority to US10/188,775 priority patent/US20030040075A1/en
Priority to US10/187,602 priority patent/US20030036145A1/en
Priority to US10/188,767 priority patent/US7312310B2/en
Priority to US10/188,774 priority patent/US20030040074A1/en
Priority to US10/188,769 priority patent/US20030036157A1/en
Priority to US10/187,885 priority patent/US20030032138A1/en
Priority to US10/187,757 priority patent/US7276578B2/en
Priority to US10/187,753 priority patent/US20030036152A1/en
Priority to US10/188,781 priority patent/US20030036160A1/en
Priority to US10/187,741 priority patent/US20030036147A1/en
Priority to US10/188,766 priority patent/US7351804B2/en
Priority to US10/187,745 priority patent/US7250490B2/en
Priority to US10/192,010 priority patent/US20030044932A1/en
Priority to US10/194,462 priority patent/US7388073B2/en
Priority to US10/194,365 priority patent/US7381791B2/en
Priority to US10/194,423 priority patent/US7339025B2/en
Priority to US10/194,361 priority patent/US20030036161A1/en
Priority to US10/194,461 priority patent/US20030054459A1/en
Priority to US10/195,883 priority patent/US20060073544A1/en
Priority to US10/195,892 priority patent/US7385033B2/en
Priority to US10/195,889 priority patent/US7534856B2/en
Priority to US10/195,888 priority patent/US20060073545A1/en
Priority to US10/195,901 priority patent/US20030036165A1/en
Priority to US10/195,894 priority patent/US20030043176A1/en
Priority to US10/195,902 priority patent/US20030038826A1/en
Priority to US10/195,897 priority patent/US20030036164A1/en
Priority to US10/195,893 priority patent/US20030206188A1/en
Priority to US10/196,762 priority patent/US20030040078A1/en
Priority to US10/196,760 priority patent/US7408034B2/en
Priority to US10/196,756 priority patent/US7304145B2/en
Priority to US10/196,743 priority patent/US20030038827A1/en
Priority to US10/196,745 priority patent/US7423120B2/en
Priority to US10/196,759 priority patent/US20030071835A1/en
Priority to US10/199,316 priority patent/US20030068726A1/en
Priority to US10/199,464 priority patent/US20030032140A1/en
Priority to US10/198,768 priority patent/US20030049756A1/en
Priority to US10/199,462 priority patent/US20030054468A1/en
Priority to US10/202,938 priority patent/US20030104551A1/en
Priority to US10/205,904 priority patent/US20030073813A1/en
Priority to US10/215,371 priority patent/US20040137561A1/en
Priority to US10/226,739 priority patent/US7390879B2/en
Priority to JP2002341509A priority patent/JP4017507B2/ja
Priority to US10/265,542 priority patent/US20030171568A1/en
Priority to US10/299,937 priority patent/US20030185846A1/en
Priority to US10/298,993 priority patent/US20030211576A1/en
Priority to US10/299,976 priority patent/US20030180312A1/en
Priority to US10/336,979 priority patent/US20050026243A1/en
Priority to US10/425,447 priority patent/US20040023331A1/en
Priority to US10/429,667 priority patent/US20030207401A1/en
Priority to US10/439,249 priority patent/US20030228664A1/en
Priority to US10/449,656 priority patent/US20040005665A1/en
Priority to US10/448,580 priority patent/US7208312B1/en
Priority to US10/448,923 priority patent/US7241865B2/en
Priority to US10/448,713 priority patent/US20040006211A1/en
Priority to US10/633,008 priority patent/US7192589B2/en
Priority to US10/712,560 priority patent/US20040146908A1/en
Priority to US10/735,014 priority patent/US7442772B2/en
Priority to JP2003420475A priority patent/JP2004154140A/ja
Priority to US10/771,187 priority patent/US7355002B2/en
Priority to US10/797,366 priority patent/US7378507B2/en
Priority to US10/855,211 priority patent/US20050026832A1/en
Priority to US10/916,250 priority patent/US7368250B2/en
Priority to US10/943,353 priority patent/US20050059115A1/en
Priority to US10/955,952 priority patent/US20050153396A1/en
Priority to US10/963,467 priority patent/US7223586B2/en
Priority to US10/964,241 priority patent/US20070026487A1/en
Priority to US10/970,823 priority patent/US7307152B2/en
Priority to US10/972,317 priority patent/US7208321B2/en
Priority to US11/050,559 priority patent/US7157267B2/en
Priority to US11/050,154 priority patent/US7122631B2/en
Priority to US11/057,268 priority patent/US20060084144A1/en
Priority to US11/057,966 priority patent/US20050187379A1/en
Priority to JP2005054646A priority patent/JP2005224245A/ja
Priority to US11/080,062 priority patent/US7619062B2/en
Priority to US11/081,485 priority patent/US20050170465A1/en
Priority to US11/100,159 priority patent/US7425613B2/en
Priority to JP2005118701A priority patent/JP2005253469A/ja
Priority to JP2005119030A priority patent/JP2005261437A/ja
Priority to JP2005118968A priority patent/JP2005270107A/ja
Priority to JP2005118817A priority patent/JP2005245460A/ja
Priority to JP2005118579A priority patent/JP2005253468A/ja
Priority to US11/110,133 priority patent/US20050181445A1/en
Priority to US11/176,863 priority patent/US20050266490A1/en
Priority to US11/189,442 priority patent/US20060246465A1/en
Priority to JP2005235120A priority patent/JP2006068006A/ja
Priority to JP2005264293A priority patent/JP2006068016A/ja
Priority to JP2005238217A priority patent/JP2006051031A/ja
Priority to JP2005238274A priority patent/JP2006051032A/ja
Priority to JP2005238266A priority patent/JP2006025795A/ja
Priority to JP2005238244A priority patent/JP2006061156A/ja
Priority to US11/240,891 priority patent/US20060246540A1/en
Priority to US11/283,473 priority patent/US20090142800A1/en
Priority to US11/296,155 priority patent/US20060127983A1/en
Priority to US11/323,117 priority patent/US20070092941A1/en
Priority to US11/341,175 priority patent/US7468427B2/en
Priority to US11/353,554 priority patent/US7417126B2/en
Priority to US11/355,441 priority patent/US7449551B2/en
Priority to US11/471,396 priority patent/US20060233803A1/en
Priority to US11/518,609 priority patent/US20070077623A1/en
Priority to US11/542,578 priority patent/US20070031405A1/en
Priority to US11/642,816 priority patent/US20070088151A1/en
Priority to US11/725,027 priority patent/US20080312421A1/en
Priority to US11/725,063 priority patent/US7741056B2/en
Priority to US11/725,076 priority patent/US20070190049A1/en
Priority to JP2007172879A priority patent/JP5512073B2/ja
Priority to JP2007326609A priority patent/JP2008148701A/ja
Priority to JP2007326424A priority patent/JP2008167749A/ja
Priority to JP2007326613A priority patent/JP2008161190A/ja
Priority to JP2007325484A priority patent/JP2008148699A/ja
Priority to US12/031,612 priority patent/US7514538B2/en
Priority to US12/079,178 priority patent/US20090170158A1/en
Priority to JP2008256822A priority patent/JP2009095345A/ja
Priority to US12/393,224 priority patent/US20090227776A1/en
Priority to JP2011138276A priority patent/JP2011236224A/ja

Links

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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Definitions

  • the present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.
  • Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms.
  • secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment.
  • Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors.
  • Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins.
  • Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents.
  • Efforts are being undertaken by both industry and proficient to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)].
  • Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms.
  • membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
  • Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
  • EGF Epidermal growth factor
  • EGFR EGF receptor
  • CNS central nervous system
  • EGF acts directly on cultured cerebral cortical and cerebellar neurons, enhancing neurite outgrowth and survival.
  • EGF also acts on other cell types, including septal cholinergic and mesencephalic dopaminergic neurons, indirectly through glial cells.
  • Evidence of the effects of EGF on neurons in the CNS is accumulating, but the mechanisms of action remain essentially unknown.
  • EGF-induced signaling in mitotic cells is better understood than in postmitotic neurons.
  • Studies of cloned pheochromocytoma PC 12 cells and cultured cerebral cortical neurons have suggested that the EGF-induced neurotrophic actions are mediated by sustained activation of the EGFR and mitogen-activated protein kinase (MAPK) in response to EGF.
  • MAPK mitogen-activated protein kinase
  • EGF is a multi-potent growth factor that acts upon various types of cells including mitotic cells and postmitotic neurons.
  • EGF is produced by the salivary and Brunner's glands of the gastrointestinal system, kidney, pancreas, thyroid gland, pituitary gland, and the nervous system, and is found in body fluids such as saliva, blood, cerebrospinal fluid (CSF), urine, amniotic fluid, prostatic fluid, pancreatic juice, and breast milk, Plata-Salaman, Peptides 12: 653-663 (1991).
  • EGF is mediated by its membrane specific receptor, which contains an intrinsic tyrosine kinase.
  • EGF is believed to function by binding to the extracellular portion of its receptor which induces a transmembrane signal that activates the intrinsic tyrosine kinase.
  • Non isolated peptides having this motif include TGF- ⁇ , amphiregulin, schwannoma-derived growth factor (SDGF), heparin-binding EGF-like growth factors and certain virally encoded peptides (e.g., Vaccinia virus, Reisner, Nature 313: 801-803 (1985), Shope fibroma virus, Chang et al., Mol Cell Biol. 7: 535-540 (1987), Molluscum contagiosum, Porter and Archard, J. Gen. Virol. 68: 673-682 (1987), and Myxoma virus, Upton et al., J. Virol. 6J.: 1271-1275 (1987), Prigent and Lemoine, Prog. Growth Factor Res. 4: 1-24 (1992).
  • EGF-like domains are not confined to growth factors but have been observed in a variety of cell-surface and extracellular proteins which have interesting properties in cell adhesion, protein-protein interaction and development, Laurence and Gusterson, Tumor Biol. IT : 229-261 (1990). These proteins include blood coagulation factors (factors VI, IX, X, XII, protein C, protein S, protein Z, tissue plasminogen activator, urokinase), extracellular matrix components (laminin, cytotactin, entactin), cell surface receptors (LDL receptor, thrombomodulin receptor) and immunity-related proteins (complement Clr, uromodulin).
  • blood coagulation factors factors VI, IX, X, XII, protein C, protein S, protein Z, tissue plasminogen activator, urokinase
  • extracellular matrix components laminin, cytotactin, entactin
  • LDL receptor thrombomodulin receptor
  • immunity-related proteins complement
  • EGF-like precursors are preserved through lower organisms as well as in mammalian cells.
  • a number of genes with developmental significance have been identified in invertebrates with EGF-like repeats.
  • the notch gene of Drosophila encodes 36 tandemly arranged 40 amino acid repeats which show homology to EGF, Wharton et al., Cell 43: 557-581 (1985).
  • Hydropathy plots indicate a putative membrane spanning domain, with the EGF-related sequences being located on the extracellular side of the membrane.
  • EGF EGF-like repeats
  • Delta Delta
  • 95F 5ZD
  • Lin-12 nematode gene Lin-12 which encodes a putative receptor for a developmental signal transmitted between two specified cells.
  • EGF has been shown to have potential in the preservation and maintenance of gastrointestinal mucosa and the repair of acute and chronic mucosal lesions, Konturek et al, Eur. J. Gastroenterol Hepatol. 7 (10), 933-37 (1995), including the treatment of necrotizing enterocolitis, Zollinger- Ellison syndrome, gastrointestinal ulceration gastrointestinal ulcerations and congenital microvillus atrophy, Guglietta and Sullivan, Eur. J.
  • EGF is also implicated various skin disease characterized by abnormal keratinocyte differentiation, e.g. , psoriasis, epithelial cancers such as squamous cell carcinomas of the lung, epidermoid carcinoma of the vulva and gliomas. King et al, Am. J. Med. Sci. 296: 154-158 (1988).
  • Nephritis is a condition characterized by inflammation of the kidney affecting the structure and normal function of the kidney. This condition can be chronic or acute and is generally caused by infection, degenerative process or vascular disease. In all cases, early detection is desirable so that the patient with nephritis can begin treatment of the condition.
  • TIN-ag tubulointerstitial nephritis antigen
  • the rabbit TIN-ag has a domain in the amino-terminal region containing an epidermal growth factor-like motif that shares homology with laminin A and S chains, alpha 1 chain of type I collagen, von Willebrand's factor and mucin, indicating structural and functional similarities. Studies have also been conducted in mice. However, it is desirable to identify tubulointerstitial nephritis antigens in humans to aid in the development of early detection methods and treatment of nephritis.
  • Proteins which have homology to tubulointerstitial nephritis antigens are of particular interest to the medical and industrial communities. Often, proteins having homology to each other have similar function. It is also of interest when proteins having homology do not have similar functions, indicating that certain structural motifs identify information other than function, such as locality of function.
  • hgerein a novel polypeptide, designated hgerein as PRO230, which has homology to tubulointerstitial nephritis antigens.
  • Stem cells are undifferentiated cells capable of (a) proliferation, (b) self maintenance, (c) the production of a large number of differentiated functional progeny, (d) regeneration of tissue after injury and/or (e) a flexibility in the use of these options.
  • Stem cells often express cell surface antigens which are capable of serving as cell specific markers that can be exploited to identify stem cells, thereby providing a means for identifying and isolating specific stem cell populations.
  • stem cell populations Having possession of different stem cell populations will allow for a number of important applications. For example, possessing a specific stem cell population will allow for the identification of growth factors and other proteins which are involved in their proliferation and differentiation. In addition, there may be as yet undiscovered proteins which are associated with (1) the early steps of dedication of the stem cell to a particular lineage, (2) prevention of such dedication, and (3) negative control of stem cell proliferation, all of which may be identified if one has possession of the stem cell population. Moreover, stem cells are important and ideal targets for gene therapy where the inserted genes promote the health of the individual into whom the stem cells are transplanted. Finally, stem cells may play important roles in transplantation of organs or tissues, for example liver regeneration and skin grafting.
  • PRQ187 Growth factors are molecular signals or mediators that enhance cell growth or proliferation, alone or in concert, by binding to specific cell surface receptors. However, there are other cellular reactions than only growth upon expression to growth factors. As a result, growth factors are better characterized as multifunctional and potent cellular regulators. Their biological effects include proliferation, chemotaxis and stimulation of extracellular matrix production. Growth factors can have both stimulatory and inhibitory effects. For example, transforming growth factor (TGF- ⁇ ) is highly pleiotropic and can stimulate proliferation in some cells, especially connective tissue, while being a potent inhibitor of proliferation in others, such as lymphocytes and epithelial cells.
  • TGF- ⁇ transforming growth factor
  • Peptide growth factors are elements of a complex biological language, providing the basis for intercellular communication. They permit cells to convey information between each other, mediate interaction between cells and change gene expression. The effect of these multifunctional and pluripotent factors is dependent on the presence or absence of other peptides.
  • FGF-8 is a member of the fibroblast growth factors (FGFs) which are a family of heparin-binding, potent mitogens for both normal diploid fibroblasts and established cell lines, Gospodarowicz et al. ( 1984), Proc. Natl. Acad. Sci. USA 81:6963.
  • the FGF family comprises acidic FGF (FGF-1), basic FGF (FGF-2), INT-2 (FGF-3), K-FGF/HST (FGF-4), FGF-5, FGF-6, KGF (FGF-7), AIGF (FGF-8) among others. All FGFs have two conserved cysteine residues and share 30-50% sequence homology at the amino acid level.
  • Fibroblast growth factors can also stimulate a large number of cell types in a non-mitogenic manner. These activities include promotion of cell migration into wound area (chemotaxis), initiation of new blood vessel formulation (angiogenesis), modulation of nerve regeneration and survival (neurotrophism), modulation of endocrine functions, and stimulation or suppression of specific cellular protein expression, extracellular matrix production and cell survival. Baird & Bohlen, Handbook of Exp. Pharmacol. 95(1): 369-418, Springer, (1990). These properties provide a basis for using fibroblast growth factors in therapeutic approaches to accelerate wound healing, nerve repair, collateral blood vessel formation, and the like. For example, fibroblast growth factors have been suggested to minimize myocardium damage in heart disease and surgery (U.S. P.
  • FGF-8 also known as androgen-induced growth factor (AIGF)
  • AIGF androgen-induced growth factor
  • FGF-8 has been proposed to be under androgenic regulation and induction in the mouse mammary carcinoma cell line SC3. Tanaka et al., Proc. Natl. Acad. Sci. USA 89: .8928-8932 (1992); Sato et al, J. Steroid Biochem. Molec. Biol. £7: 91-98 (1993).
  • FGF-8 may have a local role in the prostate, which is known to be an androgen-responsive organ.
  • FGF-8 can also be oncogenic, as it displays transforming activity when transfected into NIH-3T3 fibroblasts. Kouhara et al., Oncogene 9455-462 (1994). While FGF-8 has been detected in heart, brain, lung, kidney, testis, prostate and ovary, expression was also detected in the absence of exogenous androgens. Schmitt et al., J. Steroid Biochem. Mol. Biol. 57 (3-4): 173-78 (1996).
  • FGF-8 shares the property with several other FGFs of being expressed at a variety of stages of murine embryogenesis, which supports the theory that the various FGFs have multiple and perhaps coordinated roles in differentiation and embryogenesis. Moreover, FGF-8 has also been identified as a protooncogene that cooperates with Wnt-1 in the process of mammary tumorigenesis (Shackleford et ⁇ /., Proc. Natl. Acad. Sci. USA 90, 740-744 (1993); Heikinheimo et al, Mech. Dev. 48: 129-138 (1994)).
  • FGF-8 exists as three protein isoforms, as a result of alternative splicing of the primary transcript. Tanaka et al., supra. Normal adult expression of FGF-8 is weak and confined to gonadal tissue, however northern blot analysis has indicated that FGF-8 mRNA is present from day 10 through day 12 or murine gestation, which suggests that FGF-8 is important to normal development. Heikinheimo et al., Mech Dev. 48(2): 129-38 (1994).
  • FGF-8 has a unique temporal and spatial pattern in embryogenesis and suggests a role for this growth factor in multiple regions of ectodermal differentiation in the post-gastrulation embryo.
  • novel poypeptides having homology to FGF-8 wherein those polypeptides are heein designated PRO 187 polypeptides.
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • von Willebrand factor is a protein which plays an important role in the maintenence of hemostasis. More specifically, von Willebrand factor is a protein which is known to participate in platelet-vessel wall interactions at the site of vascular injury via its ability to interact and form a complex with Factor VIII. The absence of von Willebrand factor in the blood causes an abnormality with the blood platelets that prevents platelet adhesion to the vascular wall at the site of the vascular injury. The result is the propensity for brusing, nose bleeds, intestinal bleeding, and the like comprising von Willebrand's disease.
  • the cell surface protein HCAR is a membrane-bound protein that acts as a receptor for subgroup C of the adenoviruses and subgroup B of the coxsackieviruses.
  • HCAR may provide a means for mediating viral infection of cells in that the presence of the HCAR receptor on the cellular surface provides a binding site for viral particles, thereby facilitating viral infection.
  • CD97 is a seven-span transmembrane receptor which has a cellular ligand, CD55, DAF. Hamann, et al., J. Exp. Med. (U.S.), 184(3): 1189 (1996). Additionally, CD97 has been reported as being a dedifferentiation marker in human thyroid carcinomas and as associated with inflammation. Aust, et al. , Cancer Res. (U.S.), 57(9): 1798 (1997); Gray, et al., J. Immunol. (U.S.), 157(12):5438 (1996).
  • CD97 has also been reported as being related to the secretin receptor superfamily, but unlike known members of that family, CD97 and EMRl have extended extracellular regions that possess several EGF domains at the N-terminus.
  • EMRl is further described in Lin, et al., Genomics. 41(3):301 (1997) and Baud, et al., Genomics. 26(2):334 (1995).
  • CD97 and EMRl appear to be related to the secretin receptors
  • a known member of the secretin family of G protein-coupled receptors includes the alpha-latroxin receptor, latrophilin, which has been described as calcium independent and abundant among neuronal tissues.
  • latrophilin alpha-latroxin receptor
  • Both members of the secretin receptor superfamily and non-members which are related to the secretin receptor superfamily, or CRF and calcitonin receptors are of interest. In particular, new members of these families, identified by their homology to known proteins, are of interest.
  • Growth factors are molecular signals or mediators that enhance cell growth or proliferation, alone or in concert, by binding to specific cell surface receptors, however, there are other cellular reactions than only growth upon expression to growth factors. As a result, growth factors are better characterized as multifunctional and potent cellular regulators. Their biological effects include proliferation, chemotaxis and stimulation of extracellular matrix production. Growth factors can have both stimulatory and inhibitory effects.
  • TGF- ⁇ transforming growth factors
  • TGF- ⁇ is highly pleiotropic and can stimulate proliferation in some cells, especially connective tissues, while being a potent inhibitor of proliferation in others, such as lymphocytes and epithelial cells.
  • Peptide growth factors are elements of a complex biological language, providing the basis for intercellular communication. They permit cells to convey information between each other, mediate interaction between cells and change gene expression, the effect of these multifunctional and pluripotent factors is dependent on the presence or absence of other peptides.
  • Fibroblast growth factors are a family of heparin-binding, potent mitogens for both normal diploid fibroblasts and established cell lines, Godpodarowicz, D. et al. (1984), Proc. Natl. Acad. Sci. USA 81: 6983.
  • the FGF family comprises acidic FGF (FGF-1), basic FGF (FGF-2), INT-2 (FGF-3), K-FGF/HST (FGF- ' 4), FGF-5, FGF-6, KGF (FGF-7), AIGF (FGF-8) among others. All FGFs have two conserved cysteine residues and share 30-50% sequence homology at the amino acid level.
  • Fibroblast growth factors can also stimulate a large number of cell types in a non-mitogenic manner. These activities include promotion of cell migration into a wound area (chemotaxis), initiation of new blood vessel formulation (angiogenesis), modulation of nerve regeneration and survival (neurotrophism), modulation of endocrine functions, and stimulation or suppression of specific cellular protein expression, extracellular matrix production and cell survival. Baird, A. & Bohlen, P., Handbook of Exp. Phrmacol. 95(1): 369-418 (1990). These properties provide a basis for using fibroblast growth factors in therapeutic approaches to accelerate wound healing, nerve repair, collateral blood vessel formation, and the like.
  • fibroblast growth factors have been suggested to minimize myocardium damage in heart disease and surgery (U.S. P. 4,378,437).
  • PR0533 polypeptides have been suggested to minimize myocardium damage in heart disease and surgery.
  • Some of the most important proteins involved in the above described regulation and modulation of cellular processes are the enzymes which regulate levels of protein phosphorylation in the cell.
  • the enzymes that catalyze these processes include the protein kinases, which function to phosphorylate various cellular proteins, and the protein phosphatases, which function to remove phosphate residues from various cellular proteins. The balance of the level of protein phosphorylation in the cell is thus mediated by the relative activities of these two types of enzymes.
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • Immunoglobulins are antibody molecules, the proteins that function both as receptors for antigen on the B-cell membrane and as the secreted products of the plasma cell. Like all antibody molecules, immunoglobulins perform two major functions: they bind specifically to an antigen and they participate in a limited number of biological effector functions. Therefore, new members of the Ig superfamily are always of interest. Molecules which act as receptors by various viruses and those which act to regulate immune function are of particular interest. Also of particular interest are those molecules which have homology to known Ig family members which act as virus receptors or regulate immune function. Thus, molecules having homology to poliovirus receptors, CRTAM and CD166 (a ligand for lymphocyte antigen CD6) are of particular interest.
  • Extracellular and membrane-bound proteins play important roles in the formation, differentiation and maintenance of multicellular organisms.
  • secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment, usually at a membrane-bound receptor protein.
  • PR0258 polypeptides have homology to CRT AM, designated herein as PR0258 polypeptides.
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape.
  • Thrombomodulin binds to and regulates the activity of thrombin. It is important in the control of blood coagulation. Thrombomodulin functions as a natural anticoagulant by accelerating the activation of protein C by thrombin. Soluble thrombomodulin may have therapeutic use as an antithrombotic agent with reduced risk for hemorrhage as compared with heparin. Thrombomodulin is a cell surface trans-membrane glycoprotein, present on endothelial cells and platelets. A smaller, functionally active form of thrombomodulin circulates in the plasma and is also found in urine. (In Haeberli, A., Human Protein Data, VCH Oub., N.Y., 1992). Peptides having homology to thrombomodulin are particularly desirable.
  • PR0269 polypeptides having homology to thrombomodulin, designated herein as PR0269 polypeptides.
  • PRQ287 Procollagen C-proteinase enhancer protein binds to and enhances the activity of bone morphogenic protein "BMP1 "/procollagen C-proteinase (PCP). It plays a role in extracellular matrix deposition. BMP1 proteins may be used to induce bone and/or cartilage formation and in wound healing and tissue repair. Therefore, procollagen C-proteinase enhancer protein, BMP1 and proteins having homology thereto, are of interest to the scientific and medical communities. We herein describe the identification and characterization of novel polypeptides having homology to procollagen C-proteinase enhancer protein precursor and procollagen C-proteinase enhancer protein, designated herein as PR0287 polypeptides.
  • PRQ214 Growth factors are molecular signals or mediators that enhances cell growth or proliferation, alone or in concert, by binding to specific cell surface receptors. However, there are other cellular reactions than only growth upon expression to growth factors. As a result, growth factors are better characterized as multifunctional and potent cellular regulators. Their biological effects include proliferation, chemotaxis and stimulation of extracellular matrix production. Growth factors can have both stimulatory and inhibitory effects. For example, transforming growth factor ⁇ (TGF- ⁇ ) is highly pleiotropic and can stimulate proliferation in some cells, especially connective tissue, while being a potent inhibitor of proliferation in others, such as lymphocytes and epithelial cells.
  • TGF- ⁇ transforming growth factor ⁇
  • Peptide growth factors are elements of a complex biological language, providing the basis for intercellular communication. They permit cells to convey information between each other, mediate interaction between cells and change gene expression. The effect of these multifunctional and pluripotent factors is dependent on the presence or absence of other peptides.
  • Epidermal growth factor is a conventional mitogenic factor that stimulates the proliferation of various types of cells including epithelial cells and fibroblasts. EGF binds to and activates the EGF receptor (EGFR), which initiates intracellular signaling and subsequent effects.
  • EGFR EGF receptor
  • the EGFR is expressed in neurons of the cerebral cortex, cerebellum, and hippocampus in addition to other regions of the central nervous system (CNS). In addition, EGF is also expressed in various regions of the CNS. Therefore, EGF acts not only on mitotic cells, but also on postmitotic neurons. In fact, many studies have indicated that EGF has neurotrophic or neuromodulatory effects on various types of neurons in the CNS.
  • EGF acts directly on cultured cerebral cortical and cerebellar neurons, enhancing neurite outgrowth and survival.
  • EGF also acts on other cell types, including septal cholinergic and mesencephalic dopaminergic neurons, indirectly through glial cells.
  • Evidence of the effects of EGF on neurons in the CNS is accumulating, but the mechanisms of action remain essentially unknown.
  • EGF-induced signaling in mitotic cells is better understood than in postmitotic neurons.
  • Studies of cloned pheochromocytoma PC12 cells and cultured cerebral cortical neurons have suggested that the EGF-induced neurotrophic actions are mediated by sustained activation of the EGFR and mitogen-activated protein kinase (MAPK) in response to EGF.
  • MAPK mitogen-activated protein kinase
  • EGF is a multi-potent growth factor that acts upon various types of cells including mitotic cells and postmitotic neurons.
  • EGF is produced by the salivary and Brunner's glands of the gastrointestinal system, kidney, pancreas, thyroid gland, pituitary gland, and the nervous system, and is found in body fluids such as saliva, blood, cerebrospinal fluid (CSF), urine, amniotic fluid, prostatic fluid, pancreatic juice, and breast milk, Plata-Salaman, CR Peptides 12: 653-663 (1991).
  • body fluids such as saliva, blood, cerebrospinal fluid (CSF), urine, amniotic fluid, prostatic fluid, pancreatic juice, and breast milk, Plata-Salaman, CR Peptides 12: 653-663 (1991).
  • EGF is mediated by its membrane specific receptor, which contains an intrinsic tyrosine kinase. Stoscheck CM et al., J. Cell Biochem. 31: 135-152 (1986). EGF is believed to function by binding to the extracellular portion of its receptor which induces a transmembrane signal that activates the intrinsic tyrosine kinase.
  • Non isolated peptides having this motif include TGF-a, amphiregulin, schwannoma-derived growth factor (SDGF), heparin-binding EGF-like growth factors and certain virally encoded peptides (e.g., Vaccinia virus, Reisner AH, Nature 313: 801-803 (1985), Shope fibroma virus, Chang W. , et al. , Mol Cell Biol. 7: 535-540 (1987), Molluscum contagiosum, Porter CD & Archard LC, /. Gen. Virol. 68: 673-682 (1987), and Myxoma virus, Upton C e/ ⁇ /., . Virol. 61 : 1271-1275 (1987).
  • EGF-like domains are not confined to growth factors but have been observed in a variety of cell-surface and extracellular proteins which have interesting properties in cell adhesion, protein-protein interaction and development, Laurence DJR & Gusterson BA, Tumor Biol. 11 : 229-261 (1990).
  • proteins include blood coagulation factors (factors VI, IX, X, XII, protein C, protein S, protein Z, tissue plasminogen activator, urokinase), extracellular matrix components (laminin, cytotactin, entactin), cell surface receptors (LDL receptor, thrombomodulin receptor) and immunity-related proteins (complement Clr, uromodulin).
  • EGF-like precursors are preserved through lower organisms as well as in mammalian cells.
  • a number of genes with developmental significance have been identified in invertebrates with EGF-like repeats.
  • the notch gene of Drosophila encodes 36 tandemly arranged 40 amino acid repeats which show homology to EGF, Wharton W et al., Cell 43: 557-581 (1985).
  • Hydropathy plots indicate a putative membrane spanning domain, with the EGF-related sequences being located on the extracellular side of the membrane.
  • Other homeotic genes with EGF-like repeats include Delta, 95F and 5ZD which were identified using probes based on Notch, and the nematode gene Lin-12 which encodes a putative receptor for a developmental signal transmitted between two specified cells.
  • EGF has been shown to have potential in the preservation and maintenance of gastrointestinal mucosa and the repair of acute and chronic mucosal lesions, Konturek, PC et al, Eur. J. Gastroenterol Hepatol. 7 (10), 933-37 (1995), including the treatment of necrotizing enterocolitis, Zollinger- Ellison syndrome, gastrointestinal ulceration gastrointestinal ulcerations and congenital microvillus atrophy, A. Guglietta & PB Sullivan, Eur. J. Gastroenterol Hepatol, 7(10), 945-50 (1995). Additionally, EGF has been implicated in hair follicle differentiation; CL. du Cros, . Invest. Dermatol.
  • EGF is also implicated various skin disease characterized by abnormal keratinocyte differentiation, e.g., psoriasis, epithelial cancers such as squamous cell carcinomas of the lung, epidermoid carcinoma of the vulva and gliomas. King, LE et al., Am. J. Med. Sci. 296: 154-158 (1988).
  • TGF- ⁇ supergene family or simply TGF- ⁇ superfamily, a group of secreted proteins, includes a large number of related growth and differentiation factors expressed in virtually all phyla.
  • Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their multifunctional cytokine effects. Kolodziejczyk and Hall, Biochem. Cell. Biol.. 74: 299-314 (1996); Attisano and Wrana, Cytokine Growth Factor Rev.. 7: 327-339 (1996); and Hill, Cellular Signaling. 8: 533-544 (1996).
  • Members of this family include five distinct forms of TGF- ⁇ (Sporn and Roberts, in Peptide Growth Factors and Their Receptors.
  • the proteins of the TGF- ⁇ superfamily are disulfide-linked homo- or heterodimers encoded by larger precursor polypeptide chains containing a hydrophobic signal sequence, a long and relatively poorly conserved N-terminal pro region of several hundred amino acids, a cleavage site (usually polybasic), and a shorter and more highly conserved C-terminal region.
  • This C-terminal region corresponds to the processed mature protein and contains approximately 100 amino acids with a characteristic cysteine motif, i. e. , the conservation of seven of the nine cysteine residues of TGF- ⁇ among all known family members.
  • TGF- ⁇ Although the position of the cleavage site between the mature and pro regions varies among the family members, the C-terminus of all of the proteins is in the identical position, ending in the sequence Cys-X-Cys-X, but differing in every case from the TGF- ⁇ consensus C-terminus of Cys-Lys-Cys-Ser. Sporn and Roberts, 1990, supra.
  • TGF- ⁇ l There are at least five forms of TGF- ⁇ currently identified, TGF- ⁇ l, TGF- ⁇ 2, TGF- ⁇ 3, TGF- ⁇ 4, and
  • the activated form of TGF- ⁇ l is a homodimer formed by dimerization of the carboxy-terminal 112 amino acids of a 390 amino acid precursor.
  • Recombinant TGF- ⁇ l has been cloned (Derynck et al, Nature. 316:701-705 (1985)) and expressed in Chinese hamster ovary cells (Gentry etal., Mol. Cell. Biol..7: 3418-3427 (1987)). Additionally, recombinant human TGF- ⁇ 2 (deMartin et al , EMBO J.. 6: 3673 (1987)), as well as human and porcine TGF- ⁇ 3 (Derynck etal. , EMBOJ..
  • TGF- ⁇ 2 has a precursor form of 414 amino acids and is also processed to a homodimer from the carboxy-terminal 112 amino acids that shares approximately 70% homology with the active form of TGF- ⁇ l (Marquardt et al. , J. Biol. Chem.. 262: 12127 (1987)). See also EP 200,341; 169,016; 268,561; and 267,463; U.S. Pat. No. 4,774,322; Cheifetz etal.
  • TGF- ⁇ 4 and TGF- ⁇ 5 were cloned from a chicken chondrocyte cDNA library (Jakowlew et al. , Molec. Endocrinol.. 2: 1186-1195 (1988)) and from a frog oocyte cDNA library, respectively.
  • the pro region of TGF- ⁇ associates non-covalently with the mature TGF- ⁇ dimer (Wakefield et al. , J. Biol. Chem.. 263: 7646-7654 (1988); Wakefield et al , Growth Factors. 1: 203-218 (1989)), and the pro regions are found to be necessary for proper folding and secretion of the active mature dimers of both TGF- ⁇ and activin (Gray and Mason, Science. 247: 1328-1330 (1990)).
  • the association between the mature and pro regions of TGF- ⁇ masks the biological activity of the mature dimer, resulting in formation of an inactive latent form.
  • Latency is not a constant of the TGF- ⁇ superfamily, since the presence of the pro region has no effect on activin or inhibin biological activity.
  • a unifying feature of the biology of the proteins from the TGF- ⁇ superfamily is their ability to regulate developmental processes.
  • TGF- ⁇ has been shown to have numerous regulatory actions on a wide variety of both normal and neoplastic cells. TGF- ⁇ is multifunctional, as it can either stimulate or inhibit cell proliferation, differentiation, and other critical processes in cell function (Sporn and Roberts, supra).
  • EBAF TGF- ⁇ superfamily
  • the predicted protein sequence of EBAF showed a strong homology to the protein encoded by mouse lefty IstraS of the TGF- ⁇ superfamily.
  • a motif search revealed that the predicted EBAF protein contains most of the cysteine residues which are conserved among the TGF- ⁇ -related proteins and which are necessary for the formation of the cysteine knot structure.
  • the EBAF sequence contains an additional cysteine residue, 12 amino acids upstream from the first conserved cysteine residue.
  • the only other family members known to contain an additional cysteine residue are TGF- ⁇ s, inhibins, and GDF-3.
  • EBAF similar to LEFTY, GDF-3/Vgr2, and GDF-9, lacks the cysteine residue that is known to form the intermolecular disulfide bond.
  • EBAF appears to be an additional member of the TGF- ⁇ superfamily with an unpaired cysteine residue that may not exist as a dimer.
  • hydrophobic contacts between the two monomer subunits may promote dimer formation.
  • Fluorescence in situ hybridization showed that the ebaf gene is located on human chromosome 1 at band q42.1.
  • TGF- ⁇ superfamily such as those related to EBAF
  • PR0317 polypeptides Additional members of the TGF- ⁇ superfamily, such as those related to EBAF, are being searched for by industry and academics.
  • PR0317 polypeptides novel polypeptides having homology to EBAF, designated herein as PR0317 polypeptides.
  • mAbs cancer specific monoclonal antibodies
  • Such mAbs which can distinguish between normal and cancerous cells are useful in the diagnosis, prognosis and treatment of the disease.
  • antigens are known to be associated with neoplastic diseases, such as colorectal cancer.
  • the A33 antigen is expressed in more than 90% of primary or metastatic colon cancers as well as normal colon epithelium. Since colon cancer is a widespread disease, early diagnosis and treatment is an important medical goal. Diagnosis and treatment of colon cancer can be implemented using monoclonal antibodies (mAbs) specific therefore having fluorescent, nuclear magnetic or radioactive tags. Radioactive gene, toxins and/or drug tagged mAbs can be used for treatment in situ with minimal patient description. mAbs can also be used to diagnose during the diagnosis and treatment of colon cancers. For example, when the serum levels of the A33 antigen are elevated in a patient, a drop of the levels after surgery would indicate the mmor resection was successful.
  • mAbs monoclonal antibodies
  • adenovirus-derived vectors have been proposed as a means of inserting antisense nucleic acids into tumors (U.S. P. 5,518,885).
  • antisense nucleic acids U.S. P. 5,518,885
  • PRO301 polypeptides having homology to certain cancer-associated antigens, designated herein as PRO301 polypeptides.
  • Cholesterol uptake can have serious implications on one's health. Cholesterol uptake provides cells with most of the cholesterol they require for membrane synthesis. If this uptake is blocked, cholesterol accumulates in the blood and can contribute to the formation of atherosclerotic plaques in blood vessel walls. Most cholesterol is transported in the blood bound to protein in the form of complexes known as low-density lipoproteins (LDLs). LDLs are endocytosed into cells via LDL receptor proteins. Therefore, LDL receptor proteins, and proteins having homology thereto, are of interest to the scientific and medical communities.
  • LDLs low-density lipoproteins
  • Membrane-bound proteins and receptors can play an important role in the formation, differentiation and maintenance of multicellular organisms.
  • the LDL receptors are an example of membrane-bound proteins which are involved in the synthesis and formation of cell membranes, wherein the health of an individual is affected directly and indirectly by its function.
  • Many membrane-bound proteins act as receptors such as the LDL receptor. These receptors can function to endocytose substrates or they can function as a receptor for a channel.
  • Other membrane-bound proteins function as signals or antigens.
  • Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents.
  • the membrane-bound proteins can also be employed for screening of potential peptide or small molecule regulators of the relevant receptor/ligand interaction.
  • LDL receptor In the case of the LDL receptor, it is desirable to find molecules which enhance endocytosis so as to lower blood cholesterol levels and plaque formation. It is also desirable to identify molecules which inhibit endocytosis so that these molecules can be avoided or regulated by individuals having high blood cholesterol.
  • Polypeptides which are homologous to lipoprotein receptors but which do not function as lipoprotein receptors are also of interest in the determination of the function of the fragments which show homology.
  • Complement is a group of proteins found in the blood that are important in humoral immunity and inflammation. Complement proteins are sequentially activated by antigen-antibody complexes or by proteolytic enzymes. When activated, complement proteins kill bacteria and other microorganisms, affect vascular permeability, release histamine and attract white blood cells. Complement also enhances phagocytosis when bound to target cells. In order to prevent harm to autologous cells, the complement activation pathway is tightly regulated.
  • Deficiencies in the regulation of complement activation or in the complement proteins themselves may lead to immune-complex diseases, such as systemic lupus erythematosus, and may result in increased susceptibility to bacterial infection. In all cases, early detection of complement deficiency is desirable so that the patient can begin treatment. Thus, research efforts are currently directed toward identification of soluble and membrane proteins that regulate complement activation.
  • Factor H is a 150 kD soluble serum protein that interacts with complement protein C3b to accelerate the decay of C3 convertase and acts as a cofactor for Factor I-mediated cleavage of complement protein C4b.
  • Complement receptor type 1 is a 190-280 kD membrane bound protein found in mast cells and most blood cells.
  • CRl interacts with complement proteins C3b, C4b, and iC3b to accelerate dissociation of C3 convertases, acts as a cofactor for Factor I-mediated cleavage of C3b and C4b, and binds immune complexes and promotes their dissolution and phagocytosis.
  • Proteins which have homology to complement proteins are of particular interest to the medical and industrial communities. Often, proteins having homology to each other have similar function. It is also of interest when proteins having homology do not have similar functions, indicating that certain structural motifs identify information other than function, such as locality of function.
  • PR0222 polypeptides having homology to complement receptors, designated herein as PR0222 polypeptides.
  • oligosaccharide structures can be created through the differential activities of a smaller number of glycosyltransferases.
  • the diverse structures of oligosaccharides can be generated by transcription of relatively few gene products, which suggests that the oligosaccharides are a plausible mechanism by which is directed a wide range of cell-cell interactions. Examples of differential expression of cell surface carbohydrates and putative carbohydrate binding proteins (lectins) on interacting cells have been described (J. Dodd & T.M. Jessel, /. Neurosci. 5: 3278 (1985); L.J. Regan et al, Proc. Natl. Acad. Sci. USA 83: 2248 (1986); M.
  • cell adhesion molecules that are involved in the interaction between leukocytes and the endothelium during an inflammatory response currently stands at four: (1) selectins; (2) (carbohydrate and glycoprotein) ligands for selectins; (3) integrins; and (4) integrin ligands, which are members of the immunoglobulin gene superfamily.
  • selectins are cell adhesion molecules that are unified both structurally and functionally. Structurally, selectins are characterized by the inclusion of a domain with homology to a calcium-dependent lectin (C -lectins), an epidermal growth factor (egf)-like domain and several complement binding-like domains, Bevilacqua, M.P. et al, Science 243: 1160-1165 (1989); Johnston et al., Cell 56: 1033-1044 (1989); Lasky et al, Cell 56: 1045-1055 (1989); Siegalman, M. et al, Science 243: 1165-1172 (1989); Stoolman, L.M., Ce// 56: 907-910 (1989).
  • C -lectins calcium-dependent lectin
  • egf epidermal growth factor
  • selectins share the common property of their ability to mediate cell binding through interactions between their lectin domains and cell surface carbohydrate ligands (Brandley , B, et al. , Cell 63, 861-863 (1990); Springer, T. and Lasky, L.A. , Nature 349. 19-197 (1991); Bevilacqua, M.P. and Nelson, R.M., /. Clin. Invest. 91 379-387 (1993) and Tedder et al, J. Exp. Med. 170: 123-133 (1989).
  • L-selectin also called peripheral lymph node homing receptor (pnHR), LEC-CAM-1 , LAM-1, gp90 MEL , gpl00 MEL , gpl 10 MEL , MEL-14 antigen, Leu-8 antigen, TQ-1 antigen, DREG antigen
  • E-selectin LEC-CAM-2, LECAM-2, ELAM-1
  • P-selectin LEC-CAM-3, LECAM-3, GMP-140, PADGEM
  • E-selectin is believed to recognize the carbohydrate sequence NeuNAc 2-3Gal ⁇ l-4(Fuc ⁇ l-3)GlcNAc (sialyl-Lewis x, or sLe x ) and related oligosaccharides, Berg et al, J. Biol. Chem. 265: 14869-14872 (1991); Lowe etal, Cell ⁇ : 475-484 (1990); Phillips etal, Science 250: 1130- 1132 (1990); Tiemeyer et al, Proc. Natl. Acad. Sci. USA SS: 1138-1142 (1991).
  • L-selectin which comprises a lectin domain, performs its adhesive function by recognizing carbohydrate-containing ligands on endothelial cells. L-selectin is expressed on the surface of leukocytes, such as lymphocytes, neutrophils, monocytes and eosinophils, and is involved with the trafficking of lymphocytes to peripheral lymphoid tissues (Gallatin et al, Nature 303: 30-34 (1983)) and with acute neutrophil-medicated inflammatory responses (Watson, S.R., Nature 349: 164-167 (1991)).
  • leukocytes such as lymphocytes, neutrophils, monocytes and eosinophils
  • the amino acid sequence of L-selectin and the encoding nucleic acid sequence are, for example, disclosed in U.S. patent No. 5,098,833 issued 24 March 1992.
  • L-selectin (LECAM-1) is particularly interesting because of its ability to block neutrophil influx (Watson et al, Nature 349: 164-167 (1991). It is expressed in chronic lymphocytic leukemia cells which bind to HEV (Spertini et al, Nature 349: 691-694 (1991). It is also believed that HEV structures at sites of chronic inflammation are associated with the symptoms of diseases such as rheumatoid arthritis, psoriasis and multiple sclerosis.
  • E-selectin is particularly interesting because of its transient expression on endothelial cells in response to IL-1 or TNF. Bevilacqua et al., Science 243: 1160 (1989). The time course of this induced expression (2-8 h) suggests a role for this receptor in initial neutrophil induced extravasation in response to infection and injury. It has further been reported that anti-ELAM-1 antibody blocks the influx of neutrophils in a primate asthma model and thus is beneficial for preventing airway obstruction resulting from the inflammatory response. Gundel et al, J. Clin. Invest. 88: 1407 (1991). The adhesion of circulating neutrophils to stimulated vascular endothelium is a primary event of the inflammatory response.
  • P-selectin has been reported to recognize the Lewis x structure (Gal ⁇ l-4(Fuc ⁇ l-3) GlcNAc), Larsen et al, Cell 63: 467-474(1990). Others report that an additional terminal linked sialic acid is required for high affinity binding, Moore et al, J. Cell. Biol. ⁇ 2: 491-499 (1991). P-selectin has been shown to be significant in acute lung injury. Anti-P-selectin antibody has been shown to have strong protective effects in a rodent lung injury model. M.S. Mulligan et al, J. Clin. Invest. 90: 1600 (1991).
  • PR0234 polypeptides having homology to lectin proteins, herein designated as PR0234 polypeptides. 22. PRQ231
  • Some of the most important proteins involved in the above described regulation and modulation of cellular processes are the enzymes which regulate levels of protein phosphorylation in the cell.
  • the enzymes that catalyze these processes include the protein kinases, which function to phosphorylate various cellular proteins, and the protein phosphatases, which function to remove phosphate residues from various cellular proteins. The balance of the level of protein phosphorylation in the cell is thus mediated by the relative activities of these two types of enzymes.
  • Protein phosphatases represent a growing family of enzymes that are found in many diverse forms, including both membrane-bound and soluble forms. While many protein phosphatases have been described, the functions of only a very few are beginning to be understood (Tonks, Semin. Cell Biol. 4:373-453 (1993) and Dixon, Recent Prog. Horm. Res. 51 :405-414 (1996)). However, in general, it appears that many of the protein phosphatases function to modulate the positive or negative signals induced by various protein kinases. Therefore, it is likely that protein phosphatases play critical roles in numerous and diverse cellular processes. Given the physiological importance of the protein phosphatases, efforts are being undertaken by both industry and academia to identify new, native phosphatase proteins.
  • Scavenger receptors are known to protect IgG molecules from catabolic degradation. Riechmann and Hollinger, Nature Biotechnology. 15:617 (1997). In particular, studies of the CH2 and CH3 domains have shown that specific sequences of these domains are important in determining the half-lives of antibodies. Ellerson, et al., J. Immunol.. 116: 510 (1976); Yasmeen, et al., J. Immunol. 116: 518 (1976; Pollock, et al., Eur. J. Immunol .. 20: 2021 (1990). Scavenger receptor proteins and antibodies thereto are further reported in U.S. Patent No. 5,510,466 to Krieger, et al. Due to the ability of scavenger receptors to increase the half-life of polypeptides and their involvement in immune function, molecules having homology to scavenger receptors are of importance to the scientific and medical community.
  • Oxygen free radicals and antioxidants appear to play an important role in the central nervous system after cerebral ischemia and reperfusion. Moreover, cardiac injury, related to ischaemia and reperfusion has been reported to be caused by the action of free radicals. Additionally, studies have reported that the redox state of the cell is a pivotal determinant of the fate of the cells. Furthermore, reactive oxygen species have been reported to be cytotoxic, causing inflammatory disease, including tissue necrosis, organ failure, atherosclerosis, infertility, birth defects, premature aging, mutations and malignancy. Thus, the control of oxidation and reduction is important for a number of reasons including for control and prevention of strokes, heart attacks, oxidative stress and hypertension.
  • reductases and particularly, oxidoreductases, are of interest.
  • Publications further describing this subject matter include Kelsey, et al., Br. J. Cancer. 76(7):852-4 (1997); Friedrich and Weiss, J. Theor. Biol.. 187(4):529-40 (1997) and Pieulle, et al., J. Bacteriol.. 179(18):5684-92 (1997).
  • Oxygen free radicals and antioxidants appear to play an important role in the central nervous system after cerebral ischemia and reperfusion. Moreover, cardiac injury, related to ischaemia and reperfusion has been reported to be caused by the action of free radicals.
  • reductases and particularly, oxidoreductases
  • the transcription factors, NF-kappa B and AP-1 are known to be regulated by redox state and to affect the expression of a large variety of genes thought to be involved in the pathogenesis of AIDS, cancer, atherosclerosis and diabetic complications. Publications further describing this subject matter include Kelsey, et al. , Br. J. Cancer. 76(7):852-4 (1997); Friedrich and Weiss, J. Theor. Biol.. 187(4):529-40 (1997) and Pieulle, et al., J. Bacteriol.. 179(18): 5684-92 (1997).
  • PR0233 polypeptides which have homology to reductase
  • the carboxypeptidase family of exopeptidases constitutes a diverse group of enzymes that hydrolyze carboxyl-terminal amide bonds in polypeptides, wherein a large number of mammalian tissues produce these enzymes.
  • Many of the carboxypeptidase enzymes that have been identified to date exhibit rather strong cleavage specificities for certain amino acids in polypeptides.
  • carboxypeptidase enzymes have been identified which prefer lysine, arginine, serine or amino acids with either aromatic or branched aliphatic side chains as substrates at the carboxyl terminus of the polypeptide.
  • serine carboxypeptidases such amino acid specific enzymes have been identified from a variety of different mammalian and non-mammalian organisms.
  • the mammalian serine carboxypeptidase enzymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • efforts are being undertaken by both industry and proficient to identify new, native secreted and membrane-bound receptor proteins and specifically novel carboxypeptidases. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted and membrane-bound receptor proteins.
  • novel polypeptides having homology to one or more serine carboxypeptidase polypeptides, designated herein as PR0223 polypeptides.
  • Plexin was first identified in Xenopus tadpole nervous system as a membrane glycoprotein which was shown to mediate cell adhesion via a homophilic binding mechanism in the presence of calcium ions. Strong evolutionary conservation between Xenopus, mouse and human homologs of plexin has been observed. [Kaneyama et al., Biochem. And Biophys. Res. Comm. 226: 524-529 (1996)]. Given the physiological importance of cell adhesion mechanisms in vivo, efforts are currently being under taken to identify new, native proteins which are involved in cell adhesion. We describe herein the identification of a novel polypeptide which has homology to plexin, designated herein as PR0235.
  • PRQ236 and PRQ262 ⁇ -galactosidase is a well known enzymatic protein which functions to hydrolyze ⁇ -galactoside molecules
  • ⁇ -galactosidase has been employed for a variety of different applications, both in vitro and in vivo and has proven to be an extremely useful research tool. As such, there is an interest in obtaining novel polypeptides which exhibit homology to the ⁇ -galactosidase polypeptide.
  • Densin is a glycoprotein which has been isolated from the brain which has all the hallmarks of an adhesion molecule. It is highly concentrated at synaptic sites in the brain and is expressed prominently in dendritic processes in developing neurons. Densin has been characterized as a member of the O-linked sialoglycoproteins. Densin has relevance to medically important processes such as regeneration. Given the physiological importance of synaptic processes and cell adhesion mechanisms in vivo, efforts are currently being under taken to identify new, native proteins which are involved in synaptic machinery and cell adhesion. We describe herein the identification of novel polypeptides which have homology to densin, designated herein as PR0239 polypeptides.
  • Ebnerin is a cell surface protein associated with von Ebner glands in mammals. Efforts are being undertaken by both industry and proficient to identify new, native cell surface receptor proteins and specifically those which possess sequence homology to cell surface proteins such as ebnerin. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins. We herein describe the identification of novel polypeptides having significant homology to the von Ebner's gland-associated protein ebnerin, designated herein as PR0257 polypeptides.
  • PRO260 Fucosidases are enzymes that remove fucose residues from fucose containing proteoglycans. In some pathological conditions, such as cancer, rheumatoid arthritis, and diabetes, there is an abnormal fucosylation of serum proteins. Therefore, fucosidases, and proteins having homology to fucosidase, are of importance to the study and abrogation of these conditions. In particular, proteins having homology to the al ⁇ ha-1-fucosidase precursor are of interest. Fucosidases and fucosidase inhibitors are further described in U.S. Patent Nos.
  • PRO260 polypeptides having homology to fucosidases
  • PRQ263 CD44 is a cell surface adhesion molecule involved in cell-cell and cell-matrix interactions.
  • Hyaluronic acid a component of the extracellular matrix is a major ligand.
  • Other ligands include collagen, fibronectin, laminin, chrondroitin sulfate, mucosal addressin, serglycin and osteoponin.
  • CD44 is also important in regulating cell traffic, lymph node homing, transmission of growth signals, and presentation of chemokines and growth factors to traveling cells.
  • CD44 surface proteins are associated with metastatic tumors and CD44 has been used as a marker for HIV infection. Certain splice variants are associated with metastasis and poor prognosis of cancer patients.
  • CD44 molecules having homology with CD44 are of particular interest, as their homology indicates that they may have functions related to those functions of CD44.
  • CD44 is further described in U.S. Patent Nos. 5,506, 119, 5,504,194 and 5, 108,904; Gerberick, et al. , Toxicol. Appl. Pharmacol.. 146(1): 1 (1997); Wittig, et al.. Immunol. Letters (Netherlands), 57(1-3):217 (1997); and Oliveira and Odell, Oral Oncol. (England), 33(4):260 (1997).
  • PR0263 polypeptides having homology to CD44 antigen, designated herein as PR0263 polypeptides.
  • Thioredoxins effect reduction-oxidation (redox) state. Many diseases are potentially related to redox state and reactive oxygen species may play a role in many important biological processes.
  • the transcription factors, NF-kappa B and AP-1 are regulated by redox state and are known to affect the expression of a large variety of genes thought to be involved in the pathogenesis of AIDS, cancer, atherosclerosis and diabetic complications.
  • Such proteins may also play a role in cellular antioxidant defense, and in pathological conditions involving oxidative stress such as stroke and inflammation in addition to having a role in apoptosis. Therefore, thioredoxins, and proteins having homology thereto, are of interest to the scientific and medical communities. We herein describe the identification and characterization of novel polypeptides having homology to thioredoxin, designated herein as PRO270 polypeptides.
  • the proteoglycan link protein is a protein which is intimately associated with various extracellular matrix proteins and more specifically with proteins such as collagen.
  • one primary component of collagen is a large proteoglycan called aggrecan.
  • aggrecan a large proteoglycan called aggrecan.
  • This molecule is retained by binding to the glycosaminoglycan hyaluronan through the amino terminal Gl globular domain of the core protein. This binding is stabilized by the proteoglycan link protein which is a protein that is also associated with other tissues containing hyaluronan binding proteoglycans such as versican.
  • Link protein has been identified as a potential target for autoimmune antibodies in individuals who suffer from juvenile rheumatoid arthritis (see Guerassimov et al., J. Rheumatology 24(5):959-964 (1997)). As such, there is strong interest in identifying novel proteins having homology to link protein. We herein describe the identification and characterization of novel polypeptides having such homology, designated herein as PR0271 polypeptides.
  • Reticulocalbin is an endoplasmic reticular protein which may be involved in protein transport and luminal protein processing. Reticulocalbin resides in the lumen of the endopladsmic rerticulum, is known to bind calcium, and may be involved in a luminal retention mechanism of the endoplasmic reticulum. It contains six domains of the EF-hand motif associated with high affinity calcium binding. We describe herein the identification and characterization of a novel polypeptide which has homology to the reticulocalbin protein, designated herein as PR0272.
  • PRQ294 Collagen, a naturally occurring protein, finds wide application in industry. Chemically hydrolyzed natural collagen can be denatured and renatured by heating and cooling to produce gelatin, which is used in photographic and medical, among other applications. Collagen has important properties such as the ability to form interchain aggregates having a conformation designated as a triple helix. We herein describe the identification and characterization of a novel polypeptide which has homology to portions of the collagen molecule, designated herein as PR0294.
  • the integrins comprise a supergene family of cell-surface glycoprotein receptors that promote cellular adhesion. Each cell has numerous receptors that define its cell adhesive capabilities. Integrins are involved in a wide variety of interaction between cells and other cells or matrix components . The integrins are of particular importance in regulating movement and function of immune system cells The platelet Hb/IIIA integrin complex is of particular importance in regulating platelet aggregation. A member of the integrin family, integrin ⁇ -6, is expressed on epithelial cells and modulates epithelial inflammation. Another integrin, leucocyte-associated antigen- 1 (LFA-1) is important in the adhesion of lymphocytes during an immune response.
  • LFA-1 leucocyte-associated antigen- 1
  • integrins are expressed as heterodimers of non-covalently associated alpha and beta subunits.
  • PR0295 The integrins are expressed as heterodimers of non-covalently associated alpha and beta subunits.
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • PR0293 leucine rich repeat proteins
  • Protein-protein interactions include receptor and antigen complexes and signaling mechanisms . As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community. All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • Densin is a glycoprotein which has been isolated from the brain which has all the hallmarks of an adhesion molecule. It is highly concentrated at synaptic sites in the brain and is expressed prominently in dendritic processes in developing neurons. Densin has been characterized as a member of the O-linked sialoglycoproteins. Densin has relevance to medically important processes such as regeneration. Given the physiological importance of synaptic processes and cell adhesion mechanisms in vivo, efforts are currently being under taken to identify new, native proteins which are involved in synaptic machinery and cell adhesion. Densin is further described in Kennedy, M.B, Trends Neurosci. (England), 20(6):264 (1997) and Apperson, et al., L Neurosci.. 16(21):6839 (1996).
  • PR0247 leucine rich repeat proteins
  • Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized. The mammalian protease enzymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
  • the GLIP protein family has been characterized as comprising zinc-finger proteins which play important roles in embryogenesis. These proteins may function as transcriptional regulatory proteins and are known to be amplified in a subset of human tumors.
  • Glioma pathogenesis protein is structurally related to a group of plant pathogenesis-related proteins. It is highly expressed in glioblastoma. See US Pat. Nos. 5,582,981 (issued Dec. 10, 1996) and 5,322,801 (issued June 21 , 1996), Ellington, A.D. et al., Nature. 346:818 (1990), Grindley, J.C. et al., Dev. Biol..
  • CRISP or cysteine rich secretory protein family are a group of proteins which are also structurally related to a group of plant pathogenesis proteins. [Schwidetzky, U., Biochem. J.. 321:325 (1997), Pfisterer, P., Mol. Cell Biol.. 16(11):6160 (1996), Kratzschmar, J., Eur. J. Biochem.. 236(3): 827 (1996)].
  • PR0328 polypeptides a novel polypeptide which has homology to GLIP and CRISP
  • Protein-protein interactions include receptor and antigen complexes and signal ing mechanisms . As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction. Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community. All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
  • Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations.
  • the crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape.
  • IGF insulin like growth factor
  • the acid labile subunit of IGF is also of interest in that it increases the half-life of IGF and is part of the IGF complex in vivo.
  • Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518- A 1 by Yale University .
  • LIG- 1 a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains. Suzuki, et al., J.
  • proteoglycans comprising a repeat characterized by an arrangement of conserved leucine residues (leucine-rich repeat motif) have diverse biological roles.
  • Certain proteoglycans such as biglycan, fibromodulin and decorin, are, for example, characterized by the presence of a leucine-rich repeat of about 24 amino acids [Ruoslahti, Ann. Rev. Cell. Biol. 4 229-255 (1988); Oldberg et al , EMBO J. 8, 2601-2604 (1989)].
  • proteoglycans are believed to play a role in regulating extracellular matrix, cartilage or bone function.
  • the proteoglycan decorin binds to collagen type I and II and affects the rate of fibril formation.
  • Fibromodulin also binds collagen and delays fibril formation. Both fibromodulin and decorin inhibit the activity of transforming growth factor beta (TGF- ⁇ ) (U.S. Patent No. 5,583, 103 issued December 10, 1996). TGF- ⁇ is known to play a key role in the induction of extracellular matrix and has been implicated in the development of fibrotic diseases, such as cancer and glomerulonephritis. Accordingly, proteoglycans have been proposed for the treatment of fibrotic cancer, based upon their ability to inhibit TGF- ⁇ 's growth stimulating activity on the cancer cell.
  • TGF- ⁇ transforming growth factor beta
  • Proteoglycans have also been described as potentially useful in the treatment of other proliferative pathologies, including rheumatoid arthritis, arteriosclerosis, adult respiratory distress syndrome, cirrhosis of the liver, fibrosis of the lungs, post-myocardial infarction, cardiac fibrosis, post-angioplasty restenosis, renal interstitial fibrosis and certain dermal fibrotic conditions, such as keloids and scarring, which might result from burn injuries, other invasive skin injuries, or cosmetic or reconstructive surgery (U.S. Patent No. 5,654,270, issued August 5, 1997).
  • PR0332 polypeptides which have homology to proteins of the leucine rich repeat superfamily, designated herein as PR0332 polypeptides.
  • Fibrillin microfibrils define the continuous elastic network of skin, and are present in dermis as microfibril bundles devoid of measurable elastin extending from the dermal-epithelial junction and as components of the thick elastic fibres present in the deep reticular dermis.
  • Marfan syndrome has been linked to mutations which interfere with multimerization of fibrillin monomers or other connective tissue elements.
  • Fibulin-1 is a modular glycoprotein with amino-terminal anaphlatoxin-like modules followed by nine epidermal growth factor (EGF)-like modules and, depending on alternative splicing, four possible carboxyl termini.
  • Fibulin-2 is a novel extracellular matrix protein frequently found in close association with microfibrils containing either fibronectin or fibrillin.
  • fibrillin, fibulin, and molecules related thereto are of interest, particularly for the use of preventing skin from being damaged from aging, injuries or the sun, or for restoring skin damaged from same.
  • these molecules are generally of interest in the study of connective tissue and attachment molecules and related mechanisms. Fibrillin, fibulin and related molecules are further described in Adams, et al.. J.
  • PR0334 polypeptides having homology to fibulin and fibrillin, designated herein as PR0334 polypeptides.
  • mAbs tumor or cancer specific monoclonal antibodies
  • Such mAbs which can distinguish between normal and cancerous cells are useful in the diagnosis, prognosis and treatment of the disease.
  • Particular antigens are known to be associated with neoplastic diseases, such as colorectal and breast cancer. Since colon cancer is a widespread disease, early diagnosis and treatment is an important medical goal.
  • Diagnosis and treatment of cancer can be implemented using monoclonal antibodies (mAbs) specific therefore having fluorescent, nuclear magnetic or radioactive tags. Radioactive genes, toxins and/or drug tagged mAbs can be used for treatment in situ with minimal patient description.
  • CEA Carcinoembryonic antigen
  • CEA is a glycoprotein found in human colon cancer and the digestive organs of a 2-6 month human embryos.
  • CEA is a known human mmor marker and is widely used in the diagnosis of neoplastic diseases, such as colon cancer. For example, when the serum levels of CEA are elevated in a patient, a drop of CEA levels after surgery would indicate the mmor resection was successful. On the other hand, a subsequent rise in serum CEA levels after surgery would indicate that metastases of the original mmor may have formed or that new primary tumors may have appeared.
  • CEA may also be a target for mAb, antisense nucleotides
  • Protein disulfide isomerase is an enzymatic protein which is involved in the promotion of correct refolding of proteins through the establishment of correct disulfide bond formation. Protein disulfide isomerase was initially identified based upon its ability to catalyze the renaturation of reduced denatured RNAse (Goldberger et al., J. Biol. Chem. 239: 1406-1410 (1964) and Epstein et al. , Cold Spring Harbor Symp. Quant. Biol. 28:439-449 (1963)).
  • Protein disulfide isomerase has been shown to be a resident enzyme of the endoplasmic reticulum which is retained in the endoplasmic reticulum via a -KDEL or -HDEL amino acid sequence at its C-terminus.
  • disulfide bond-forming enzymes and their potential uses in a number of different applications, for example in increasing the yield of correct refolding of recombinantly produced proteins, efforts are currently being undertaken by both industry and proficient to identify new, native proteins having homology to protein disulfide isomerase. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel protein disulfide isomerase homologs.
  • PR0268 a novel polypeptide having homology to protein disulfide isomerase
  • Prolyl 4-hydroxylase is an enzyme which functions to post-translationally hydroxylate proline residues at the Y position of the amino acid sequence Gly-X-Y, which is a repeating three amino acid sequence found in both collagen and procollagen. Hydroxylation of proline residues at the Y position of the Gly-X-Y amino acid triplet to form 4-hydroxyproline residues at those positions is required before newly synthesized collagen polypeptide chains may fold into their proper three-dimensional triple-helical conformation. If hydroxylation does not occur, synthesized collagen polypeptides remain non-helical, are poorly secreted by cells and cannot assemble into stable functional collagen fibrils. Vuorio et al. , Proc. Natl. Acad. Sci. USA 89:7467-7470 (1992). Prolyl 4-hydroxylase is comprised of at least two different polypeptide subunits, alpha and beta.
  • Fringe is a protein which specifically blocks serrate-mediated activation of notch in the dorsal compartment of the Drosophila wing imaginal disc.
  • novel polypeptides which may have a role in development and/or the regulation of serrate-like molecules.
  • novel polypeptides having homology to fringe as identified and described herein, designated herein as PR0339 and PRO310 polypeptides.
  • Lectins are a class of proteins comprising a region that binds carbohydrates specifically and non- covalently. Numerous lectins have been identified in higher animals, both membrane-bound and soluble, and have been implicated in a variety of cell-recognition phenomena and mmor metastasis.
  • lectins can be classified as either C-type (calcium-dependent) or S-type (thiol -dependent).
  • Lectins are thought to play a role in regulating cellular events that are initiated at the level of the plasma membrane.
  • plasma membrane associated molecules are involved in the activation of various subsets of lymphoid cells, e.g. T-lymphocytes, and it is known that cell surface molecules are responsible for activation of these cells and consequently their response during an immune reaction.
  • a particular group of cell adhesion molecules, selectins belong in the superfamily of C-type lectins.
  • This group includes L-selectin (peripheral lymph node homing receptor (pnHR), LEC-CAM-1 , LAM-1, gp90 MEL , gpl00 MEL , gpl lO ME , MEL-14 antigen, Leu-8 antigen, TQ-1 antigen, DREG antigen), E-selectin (LEC-CAM-2, LECAM-2, ELAM-1), and P-selectin (LEC-CAM-3, LECAM-3, GMP-140, PADGEM).
  • pnHR peripheral lymph node homing receptor
  • LEC-CAM-1 peripheral lymph node homing receptor (pnHR)
  • LAM-1 LAM-1
  • gp90 MEL gpl00 MEL
  • gpl lO ME MEL-14 antigen
  • Leu-8 antigen Leu-8 antigen
  • selectins consist of a C-type lectin (carbohydrate binding) domain, an epidermal growth factor-like (EGF-like) motif, and variable numbers of complement regulatory (CR) motifs.
  • Selectins are associated with leukocyte adhesion, e.g. the attachment of neutrophils to venular endothelial cells adjacent to inflammation (E- selectin), or with the trafficking of lymphocytes from blood to secondary lymphoid organs, e.g. lymph nodes and Peyer's patches (L-selectin).
  • Mac-2 Another exemplary lectin is the cell-associated macrophage antigen, Mac-2 that is believed to be involved in cell adhesion and immune responses. Macrophages also express a lectin that recognizes Tn Ag, a human carcinoma-associated epitope.
  • CD95 Fluorescence-activated protein
  • Apoptosis is a non-necrotic cell death that takes place in metazoan animal cells following activation of an intrinsic cell suicide program.
  • the cloning of Fas antigen is described in PCT publication WO 91/10448, and European patent application EP510691.
  • the mature Fas molecule consists of 319 amino acids of which 157 are extracellular, 17 constimte the transmembrane domain, and 145 are intracellular. Increased levels of Fas expression at T cell surface have been associated with mmor cells and HIV-infected cells. Ligation of CD95 triggers apoptosis in the presence of interleukin-1 (IL-2).
  • IL-1 interleukin-1
  • C-type lectins also include receptors for oxidized low-density lipoprotein (LDL). This suggests a possible role in the pathogenesis of atherosclerosis.
  • LDL low-density lipoprotein
  • Applicants have identified cDNA clones that encode novel polypeptides having homology to EGF, designated in the present application as "PR021 1 " and "PR0217” polypeptides.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0211 or PR0217 polypeptide.
  • the isolated nucleic acid comprises DNA encoding EGF-like homologue PR0211 and PR0217 polypeptides of Fig. 2 (SEQ ID NO:2) and/or 4 (SEQ ID NO:4) indicated in Fig. 1 (SEQ ID NOl) and/or Fig. 3 (SEQ ID NO:3), respectively, or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0211 and PR0217 EGF-like homologue
  • PR0211 and PR0217 polypeptides are isolated native sequence PR0211 and PR0217 EGF-like homologue polypeptides, which in one embodiment, includes an amino acid sequence comprising residues: 1 to 353 of Fig. 2 (SEQ ID NO:2) or (2) 1 to 379 of Fig. 4 (SEQ ID NO: 4).
  • PRO230 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PRO230".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO230 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO230 polypeptide having amino acid residues 1 through 467 of Figure 6 (SEQ ID NO : 12) , or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO230 polypeptide.
  • the invention provides isolated native sequence PRO230 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 467 of Figure 6 (SEQ ID NO: 12).
  • the invention provides an expressed sequence tag (EST) comprising the nucleotide sequence of SEQ ID NO: 13 ( Figure 7) which is herein designated as DNA20088.
  • EST expressed sequence tag
  • PRQ232 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0232" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0232 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0232 polypeptide having amino acid residues 1 to 114 of Figure 9 (SEQ ID NO: 18), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0232 polypeptide.
  • the invention provides isolated native sequence PR0232 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 114 of Figure 9 (SEQ ID NO: 18).
  • PRQ187 Applicants have identified a cDNA clone that encodes a novel polypeptide, designated in the present application as "PRO 187".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0187 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0187 polypeptide of Figure 11 (SEQ ID NO:23), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides a nucleic acid comprising the coding sequence of Figure 10 (SEQ ID NO: 22) or its complement.
  • the invention provides a nucleic acid of the full length protein of clone DNA27864-1155, deposited with the ATCC under accession number ATCC 209375, alternatively the coding sequence of clone DNA27864-1155, deposited under accession number ATCC 209375.
  • the invention provides isolated PR0187 polypeptide.
  • the invention provides isolated native sequence PRO 187 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 205 of Figure 11 (SEQ ID NO:23).
  • the invention provides a polypeptide encoded by the nucleic acid deposited under accession number ATCC 209375.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0265 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0265 polypeptide having amino acid residues 1 to 660 of Figure 13 (SEQ ID NO: 28), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0265 polypeptide.
  • the invention provides isolated native sequence PR0265 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 660 of Figure 13 (SEQ ID NO:28).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0265 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0219 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0219 polypeptide having amino acid residues 1 to 915 of Figure 15 (SEQ ID NO:34), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0219 polypeptide.
  • the invention provides isolated native sequence PR0219 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 915 of Figure 15 (SEQ ID NO:34).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0246 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0246 polypeptide having amino acid residues 1 to 390 of Figure 17 (SEQ ID NO:39), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0246 polypeptide.
  • the invention provides isolated native sequence PR0246 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 390 of Figure 17 (SEQ ID NO: 39).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0246 polypeptide.
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to CD97, EMRl and latrophilin, wherein the polypeptide is designated in the present application as "PR0228" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0228 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0228 polypeptide having amino acid residues 1 to 690 of Figure 19 (SEQ ID NO:49), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0228 polypeptide.
  • the invention provides isolated native sequence PR0228 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 690 of Figure 19 (SEQ ID NO: 49).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0228 polypeptide.
  • the invention provides an expressed sequence tag (EST) comprising the nucleotide sequence of SEQ ID NO:50, designated herein as DNA21951.
  • EST expressed sequence tag
  • the invention provides an isolated nucleic acid molecule having at least about 80% sequence identity to (a) a DNA molecule encoding a PR0533 polypeptide comprising the sequence of amino acids 23 to 216 of Figure 22 (SEQ ID NO:59), or (b) the complement of the DNA molecule of (a).
  • the sequence identity preferably is about 85 % , more preferably about 90% , most preferably about 95 % .
  • the isolated nucleic acid has at least about 80%, preferably at least about 85 % , more preferably at least about 90% , and most preferably at least about 95% sequence identity with a polypeptide having amino acid residues 23 to 216 of Figure 22 (SEQ ID NO:59).
  • the highest degree of sequence identity occurs within the secreted portion (amino acids 23 to 216 of Figure 22, SEQ ID NO:59).
  • the isolated nucleic acid molecule comprises DNA encoding a PR0533 polypeptide having amino acid residues 1 to 216 of Figure 22 (SEQ ID NO:59), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides a nucleic acid of the full length protein of clone DNA49435-1219, deposited with the ATCC under accession number ATCC 209480.
  • the invention provides isolated PR0533 polypeptide.
  • the invention provides isolated native sequence PR0533 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 216 of Figure 22 (SEQ ID NO:59).
  • Native PR0533 polypeptides with or without the native signal sequence (amino acids 1 to 22 in Figure 22 (SEQ ID NO:59)), and with or without the initiating methionine are specifically included.
  • the invention provides a PR0533 polypeptide encoded by the nucleic acid deposited under accession number ATCC 209480.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0245 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0245 polypeptide having amino acid residues 1 to 312 of Fig. 24 (SEQ ID NO:64), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0245 polypeptide.
  • the invention provides isolated native sequence PR0245 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 312 of Figure 24 (SEQ ID NO:64).
  • an isolated nucleic acid comprises DNA encoding the PRO220 polypeptide having amino acid residues 1 through 708 of Figure 26 (SEQ ID NO: 69), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • an isolated nucleic acid comprises DNA encoding the PR0221 polypeptide having amino acid residues 1 through 259 of Figure 28 (SEQ ID NO:71), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • an isolated nucleic acid comprises DNA encoding the PR0227 polypeptide having amino acid residues 1 through 620 of Figure 30 (SEQ ID NO:73), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO220, PR0221 and PR0227 polypeptides.
  • the isolated native sequence for the PRO220 polypeptide which in one embodiment, includes an amino acid sequence comprising residues 1 to 708 of Figure 26 (SEQ ID NO:69).
  • the isolated native sequence for the PR0221 polypeptide which in one embodiment, includes an amino acid sequence comprising residues 1 to 259 of Figure 28 (SEQ ID NO:71).
  • the isolated native sequence for the PR0227 polypeptide which in one embodiment, includes an amino acid sequence comprising residues 1 to 620 of Figure 30 (SEQ ID NO:73).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0258 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0258 polypeptide having amino acid residues 1 to 398 of Figure 32 (SEQ ID NO:84), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0258 polypeptide.
  • the invention provides isolated native sequence PR0258 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 398 of Figure 32 (SEQ ID N0:84).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0258 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0266 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0266 polypeptide having amino acid residues 1 to 696 of Figure 34 (SEQ ID NO:91), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0266 polypeptide.
  • the invention provides isolated native sequence PR0266 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 696 of Figure 34 (SEQ ID NO:91).
  • PRQ269 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as PR0269.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0269 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0269 polypeptide having amino acid residues 1 to 490 of Fig. 36 (SEQ ID NO:96), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0269 polypeptide.
  • the invention provides isolated native sequence PR0269 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 490 of Figure 36 (SEQ ID NO:96).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0269 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0287 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0287 polypeptide having amino acid residues 1 to 415 of Fig. 38 (SEQ ID NO: 104), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0287 polypeptide.
  • the invention provides isolated native sequence PR0287 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 415 of Figure 38 (SEQ ID NO: 104).
  • PRQ214 Applicants have identified a cDNA clone that encodes a novel polypeptide, designated in the present application as "PR0214" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0214 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0214 polypeptide of Fig. 40 (SEQ ID NO: 109), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides a nucleic acid comprising the coding sequence of Fig. 39 (SEQ ID NO: 108) or its complement.
  • the invention provides a nucleic acid of the full length protein of clone DNA32286-1191 , deposited with ATCC under accession number ATCC 209385.
  • the invention provides isolated PR0214 polypeptide.
  • the invention provides isolated native sequence PR0214 polypeptide, which in one embodiment, includes an amino acid sequence comprising the residues of Figure 40 (SEQ ID NO: 109).
  • the invention provides a polypeptide encoded by the nucleic acid deposited under accession number ATCC 209385.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding PR0317 polypeptide.
  • the isolated nucleic acid comprises DNA (SEQ ID NO: 113) encoding
  • the invention provides isolated PR0317 polypeptide.
  • the invention provides isolated native-sequence PR0317 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 366 of Figure 42 (SEQ ID NO: 114).
  • the invention supplies a method of detecting the presence of PR0317 in a sample, the method comprising: a) contacting a detectable anti-PR0317 antibody with a sample suspected of containing PR0317; and b) detecting binding of the antibody to the sample; wherein the sample is selected from the group consisting of a body fluid, a tissue sample, a cell extract, and a cell culture medium.
  • a method for determining the presence of PR0317 mRNA in a sample comprising: a) contacting a sample suspected of containing PR0317 mRNA with a detectable nucleic acid probe that hybridizes under moderate to stringent conditions to PR0317 mRNA; and b) detecting hybridization of the probe to the sample.
  • the sample is a tissue sample and the detecting step is by in situ hybridization, or the sample is a cell extract and detection is by Northern analysis.
  • the invention provides a method for treating a PR0317-associated disorder comprising administering to a mammal an effective amount of the PR0317 polypeptide or a composition thereof containing a carrier, or with an effective amount of a PR0317 agonist or PR0317 antagonist, such as an antibody which binds specifically to PR0317.
  • PRQ301 Applicants have identified a cDNA clone (DNA40628-1216) that encodes a novel polypeptide, designated in the present application as "PRO301 ".
  • the invention provides an isolated nucleic acid molecule having at least about 80% sequence identity to (a) a DNA molecule encoding a PRO301 polypeptide comprising the sequence of amino acids 28 to 258 of Fig. 44 (SEQ ID NO: 119), or (b) the complement of the DNA molecule of (a).
  • the sequence identity preferably is about 85% , more preferably about 90% , most preferably about 95 % .
  • the isolated nucleic acid has at least about 80 % , preferably at least about 85 % , more preferably at least about 90 % , and most preferably at least about 95 % sequence identity with a polypeptide having amino acid residues 28 to 258 of Fig. 44 (SEQ ID NO: 119).
  • the highest degree of sequence identity occurs within the extracellular domains (amino acids 28 to 258 of Fig. 44, SEQ ID NO: 119).
  • the isolated nucleic acid molecule comprises DNA encoding a PRO301 polypeptide having amino acid residues 28 to 299 of Fig.
  • the invention provides a nucleic acid of the full length protein of clone DNA40628-1216, deposited with the ATCC under accession number ATCC 209432, alternatively the coding sequence of clone DNA40628-1216, deposited under accession number ATCC 209432.
  • the invention provides isolated PRO301 polypeptide.
  • the invention provides isolated native sequence PRO301 polypeptide, which in one embodiment, includes an amino acid sequence comprising the extracellular domain residues 28 to 258 of Figure 44 (SEQ ID NO: 119).
  • Native PRO301 polypeptides with or without the native signal sequence amino acids 1 to 27 in Figure 44 (SEQ ID NO: 119), and with or without the initiating methionine are specifically included.
  • the sequences of the invention may also comprise the transmembrane domain (residues 236 to about 258 in Figure 44; SEQ ID NO: 119) and/or the intracellular domain (about residue 259 to 299 in Figure 44; SEQ ID NO: 119).
  • the invention provides a PRO301 polypeptide encoded by the nucleic acid deposited under accession number ATCC 209432.
  • PRQ224 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0224" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0224 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0224 polypeptide having amino acid residues 1 to 282 of Figure 46 (SEQ ID NO: 127), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0224 polypeptide.
  • the invention provides isolated native sequence PR0224 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 282 of Figure 46 (SEQ ID NO: 127). 20. PRQ222
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0222 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0222 polypeptide having amino acid residues 1 to 490 of Fig. 48 (SEQ ID NO: 132), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0222 polypeptide.
  • the invention provides isolated native sequence PR0222 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 490 of Figure 48 (SEQ ID NO: 132).
  • the invention provides an isolated nucleic acid encoding a novel lectin comprising
  • the isolated nucleic acid comprises the DNA encoding PR0234 polypeptides having amino acid residues 1 to 382 of Fig. 50 (SEQ ID NO: 137), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising the nucleotide sequence of Fig. 49 (SEQ ID NO: 136).
  • the invention provides isolated novel PR0234 polypeptides.
  • the invention provides isolated native sequence PR0234 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 382 of Figure 50 (SEQ ID NO: 137).
  • the invention provides oligonucleotide probes useful for isolating genomic and cDNA nucleotide sequences.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0231 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0231 polypeptide having amino acid residues 1 to 428 of Fig. 52 (SEQ ID NO: 142), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0231 polypeptide.
  • the invention provides isolated native sequence PR0231 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 428 of Figure 52 (SEQ ID NO: 142). 23. PRQ229
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to scavenger receptors wherein the polypeptide is designated in the present application as "PR0229".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0229 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0229 polypeptide having amino acid residues 1 to 347 of Figure 54 (SEQ ID NO: 148), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0229 polypeptide.
  • the invention provides isolated native sequence PR0229 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 347 of Figure 54 (SEQ ID NO: 148).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0238 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0238 polypeptide having amino acid residues 1 to 310 of Figure 56 (SEQ ID NO: 153), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0238 polypeptide.
  • the invention provides isolated native sequence PR0238 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 310 of Figure 56 (SEQ ID NO: 153).
  • PRQ233 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0233".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0233 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0233 polypeptide having amino acid residues 1 to 300 of Figure 58 (SEQ ID NO: 159), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0233 polypeptide.
  • the invention provides isolated native sequence PR0233 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 300 of Figure 58 (SEQ ID NO: 159). 26. PRQ223
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to serine carboxypeptidase polypeptides, wherein the polypeptide is designated in the present application as "PR0223".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0223 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0223 polypeptide having amino acid residues 1 to 476 of Figure 60 (SEQ ID NO: 164), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0223 polypeptide.
  • the invention provides isolated native sequence PR0223 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 476 of Figure 60 (SEQ ID NO: 164).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0235 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0235 polypeptide having amino acid residues 1 to 552 of Figure 62 (SEQ ID NO: 170), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0235 polypeptide.
  • the invention provides isolated native sequence PR0235 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 552 of Figure 62 (SEQ ID NO: 170).
  • PRQ236 and PRQ262 Applicants have identified cDNA clones that encode novel polypeptides having homology to ⁇ - galactosidase, wherein those polypeptides are designated in the present application as "PR0236" and "PR0262”.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0236 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0236 polypeptide having amino acid residues 1 to 636 of Figure 64 (SEQ ID NO: 175), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0262 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0262 polypeptide having amino acid residues 1 to 654 of Figure 66 (SEQ ID NO: 177), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0236 polypeptide.
  • the invention provides isolated native sequence PR0236 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 636 of Figure 64 (SEQ ID NO: 175).
  • the invention provides isolated PR0262 polypeptide.
  • the invention provides isolated native sequence PR0262 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 654 of Figure 66 (SEQ ID NO: 177).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0239 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0239 polypeptide having amino acid residues 1 to 501 of Figure 68 (SEQ ID NO: 185), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0239 polypeptide.
  • the invention provides isolated native sequence PR0239 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 501 of Figure 68 (SEQ ID NO: 185).
  • PRQ257 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0257”.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0257 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0257 polypeptide having amino acid residues 1 to 607 of Figure 70 (SEQ ID NO: 190), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0257 polypeptide.
  • the invention provides isolated native sequence PR0257 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 607 of Figure 70 (SEQ ID NO: 190).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0257 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO260 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO260 polypeptide having amino acid residues 1 to 467 of Figure 72 (SEQ ID NO: 195), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO260 polypeptide.
  • the invention provides isolated native sequence PRO260 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 467 of Figure 72 (SEQ ID NO: 195).
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to CD44 antigen, wherein the polypeptide is designated in the present application as "PR0263".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0263 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0263 polypeptide having amino acid residues 1 to 322 of Figure 74 (SEQ ID NO:201), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0263 polypeptide.
  • the invention provides isolated native sequence PR0263 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 322 of Figure 74 (SEQ ID NO: 201).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0263 polypeptide.
  • PRO270 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PRO270".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO270 polypeptide.
  • the isolated nucleic acid comprises DNA whivch includes the sequence encoding the PRO270 polypeptide having amino acid residues 1 to 296 of Fig. 76 (SEQ ID NO: 207), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO270 polypeptide.
  • the invention provides isolated native sequence PRO270 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 296 of Figure 76 (SEQ ID NO: 207).
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to the proteoglycan link protein, wherein the polypeptide is designated in the present application as "PR0271".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0271 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0271 polypeptide having amino acid residues 1 to 360 of Figure 78 (SEQ ID N0:213), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0271 polypeptide.
  • the invention provides isolated native sequence PR0271 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 360 of Figure 78 (SEQ ID NO:213).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0272 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0272 polypeptide having amino acid residues 1 to 328 of Figure 80 (SEQ ID NO:221), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0272 polypeptide.
  • the invention provides isolated native sequence PR0272 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 328 of Figure 80 (SEQ ID NO:211).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0294 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0294 polypeptide having amino acid residues 1 to 550 of Figure 82 (SEQ ID NO:227), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0294 polypeptide.
  • the invention provides isolated native sequence PR0294 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 550 of Figure 82 (SEQ ID NO: 227).
  • PRQ295 Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0295" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0295 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0295 polypeptide having amino acid residues 1 to 350 of Figure 84 (SEQ ID NO:236), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0295 polypeptide.
  • the invention provides isolated native sequence PR0295 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 350 of Figure 84 (SEQ ID NO: 236).
  • PRQ293 Applicants have identified a cDNA clone that encodes a novel human neuronal leucine rich repeat polypeptide, wherein the polypeptide is designated in the present application as "PR0293" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0293 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0293 polypeptide having amino acid residues 1 to 713 of Figure 86 (SEQ ID NO: 245), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0293 polypeptide.
  • the invention provides isolated native sequence PR0293 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 713 of Figure 86 (SEQ ID NO: 245).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0293 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0247 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0247 polypeptide having amino acid residues 1 to 546 of Figure 88 (SEQ ID NO:250), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0247 polypeptide.
  • the invention provides isolated native sequence PR0247 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 546 of Figure 88 (SEQ ID NO:250).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0247 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO302 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO302 polypeptide having amino acid residues 1 to 452 of Figure 90 (SEQ ID NO:255), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO303 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO303 polypeptide having amino acid residues 1 to 314 of Figure 92 (SEQ ID NO:257), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO304 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO304 polypeptide having amino acid residues 1 to 556 of Figure 94 (SEQ ID NO:259), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO307 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO307 polypeptide having amino acid residues 1 to 383 of Figure 96 (SEQ ID NO:261), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0343 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0343 polypeptide having amino acid residues 1 to 317 of Figure 98 (SEQ ID NO:263), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO302 polypeptide.
  • the invention provides isolated native sequence PRO302 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 452 of Figure 90 (SEQ ID NO:255).
  • the invention provides isolated PRO303 polypeptide.
  • the invention provides isolated native sequence PRO303 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 314 of Figure 92 (SEQ ID NO:257).
  • the invention provides isolated PRO304 polypeptide.
  • the invention provides isolated native sequence PRO304 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 556 of Figure 94 (SEQ ID NO:259).
  • the invention provides isolated PRO307 polypeptide.
  • the invention provides isolated native sequence PRO307 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 383 of Figure 96 (SEQ ID NO:261).
  • the invention provides isolated PR0343 polypeptide.
  • the invention provides isolated native sequence PR0343 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 317 of Figure 98 (SEQ ID NO: 263). 41. PRQ328
  • Applicants have identified a cDNA clone that encodes a novel polypeptide, wherein the polypeptide is designated in the present application as "PR0328" .
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0328 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0328 polypeptide having amino acid residues 1 to 463 of Figure 100 (SEQ ID NO: 285), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0328 polypeptide.
  • the invention provides isolated native sequence PR0328 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 463 of Figure 100 (SEQ ID NO:285).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PRO306 polypeptide.
  • Applicants have identified three cDNA clones that respectively encode three novel polypeptides, each having leucine rich repeats and homology to LIG-1 and ALS. These polypeptides are designated in the present application as PR0335, PR0331 and PR0326, respectively.
  • the invention provides three isolated nucleic acid molecules comprising DNA respectively encoding PR0335, PR0331 and PR0326, respectively.
  • an isolated nucleic acid comprising DNA encoding the PR0335 polypeptide having amino acid residues 1 through 1059 of Figure 102 (SEQ ID NO:290), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate , and optionally , under high stringency conditions .
  • an isolated nucleic acid comprises DNA encoding the PR0331 polypeptide having amino acid residues 1 through 640 of Figure 104 (SEQ ID NO:292), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. Additionally provided herein is an isolated nucleic acid comprises DNA encoding the PR0326 polypeptide having amino acid residues 1 through 1119 of Figure 106 (SEQ ID NO:294), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0335, PR0331 and PR0326 polypeptides or extracellular domains thereof.
  • the invention provides isolated native sequence for the PR0335 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 1059 of Figure 102 (SEQ ID NO:290).
  • the isolated native sequence for the PR0331 polypeptide which in one embodiment, includes an amino acid sequence comprising residues 1 through 640 of Figure 104 (SEQ ID NO:292).
  • the isolated native sequence for the PR0326 polypeptide which in one embodiment, includes an amino acid sequence comprising residues 1 through 1119 of Figure 106 (SEQ ID NO:294).
  • the invention provides an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity to (a) a DNA molecule encoding a PR0358 polypeptide comprising the sequence of amino acids 49 to 642 of Fig. 108 (SEQ ID NO:310), or (b) the complement of the DNA molecule of (a).
  • the sequence identity preferably is about 85 % , more preferably about 90% , most preferably about 95 % .
  • the isolated nucleic acid has at least about 80%, preferably at least about 85% , more preferably at least about 90% , and most preferably at least about 95% sequence identity with a polypeptide having amino acid residues 1 to 642 of Fig. 108 (SEQ ID NO: 310).
  • the highest degree of sequence identity occurs within the leucine-rich repeat domains (amino acids 116 to 624 of Fig. 108, SEQ ID NO:310).
  • the isolated nucleic acid molecule comprises DNA encoding a PR0332 polypeptide having amino acid residues 49 to 642 of Fig. 108 (SEQ ID NO:310), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0332 polypeptides.
  • the invention provides isolated native sequence PR0332 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 49 to 624 of Figure 108 (SEQ ID NO:310).
  • Native PR0332 polypeptides with or without the native signal sequence amino acids 1 to 48 in Figure 108, SEQ ID NO:310, and with or without the initiating methionine are specifically included.
  • Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to fibulin and fibrillin, wherein the polypeptide is designated in the present application as "PR0334".
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0334 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0334 polypeptide having amino acid residues 1 to 509 of Figure 110 (SEQ ID NO:315), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0334 polypeptide.
  • the invention provides isolated native sequence PR0334 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 509 of Figure 110 (SEQ ID NO:315).
  • the invention provides an isolated nucleic acid molecule having at least about 80% sequence identity to (a) a DNA molecule encoding a PR0346 polypeptide comprising the sequence of amino acids 19 to 339 of Fig. 112 (SEQ ID NO: 320), or (b) the complement of the DNA molecule of (a).
  • the sequence identity preferably is about 85%, more preferably about 90%, most preferably about 95 % .
  • the isolated nucleic acid has at least about 80% , preferably at least about 85% , more preferably at least about 90% , and most preferably at least about 95% sequence identity with a polypeptide having amino acid residues 19 to 339 of Fig. 112 (SEQ ID NO:320).
  • the highest degree of sequence identity occurs within the extracellular domains (amino acids 19 to 339 of Fig. 112, SEQ IP NO:320).
  • the polypeptide by which the homology is measured comprises the residues 1-339, 19-360 or 19- 450 of Fig. 112, SEQ IP NO:320).
  • the isolated nucleic acid molecule comprises PNA encoding a PR0346 polypeptide having amino acid residues 19 to 339 of Fig. 112 (SEQ IP NO:320), alternatively residues 1-339, 19-360 or 19-450 of Fig.
  • the invention provides a nucleic acid of the full length protein of clone PNA44167-1243, deposited with the ATCC under accession number ATCC 209434, alternatively the coding sequence of clone DNA44167- 1243, deposited under accession number ATCC 209434.
  • the invention provides isolated PR0346 polypeptide.
  • the invention provides isolated native sequence PR0346 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 339 of Figure 112 (SEQ ID NO:320).
  • Native PR0346 polypeptides with or without the native signal sequence (residues 1 to 18 in Figure 112 (SEQ ID NO:320), with or without the initiating methionine, with or without the transmembrane domain (residues 340 to 360) and with or without the intracellular domain (residues 361 to 450) are specifically included.
  • the invention provides a PR0346 polypeptide encoded by the nucleic acid deposited under accession number ATCC 209434.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0268 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0268 polypeptide having amino acid residues 1 to 280 of Figure 114 (SEQ ID NO:325), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0268 polypeptide.
  • the invention provides isolated native sequence PR0268 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 280 of Figure 114 (SEQ ID NO:325).
  • An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR0268 polypeptide.
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO330 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PRO330 polypeptide having amino acid residues 1 to 533 of Figure 116 (SEQ ID NO:332), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PRO330 polypeptide.
  • the invention provides isolated native sequence PRO330 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 533 of Figure 116 (SEQ ID NO:332).
  • PRQ339 and PRO310 Applicants have identified two cDNA clones wherein each clone encodes a novel polypeptide having homology to fringe, wherein the polypeptides are designated in the present application as "PR0339” and "PRO310" .
  • the invention provides isolated nucleic acid molecules comprising DNA encoding a PR0339 and/or a PR0310 polypeptide.
  • the isolated nucleic acid comprises DNA encoding the PR0339 polypeptide having amino acid residues 1 to 772 of Figure 118 (SEQ ID NO:339), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the isolated nucleic acid comprises DNA encoding the PR0310 polypeptide having amino acid residues 1 to 318 of Figure 120 (SEQ ID NO : 341 ) , or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0339 as well as isolated PRO310 polypeptides.
  • the invention provides isolated native sequence PR0339 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 772 of Figure 118 (SEQ ID NO:339).
  • the invention further provides isolated native sequence PR0310 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 318 of Figure 120 (SEQ ID NO:341).
  • the invention provides an isolated nucleic acid molecule comprising DNA encoding
  • the isolated nucleic acid comprises DNA encoding PR0244 polypeptide having amino acid residues 1 to 219 of Fig. 122 (SEQ ID NO:377), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions.
  • the invention provides isolated PR0244 polypeptide.
  • the invention provides isolated native sequence PR0244 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 219 of Figure 122 (SEQ ID NO: 377). 50. Additional Embodiments
  • the invention provides vectors comprising DNA encoding any of the herein described polypeptides.
  • Host cell comprising any such vector are also provided.
  • the host cells may be CHO cells, E. coli, or yeast.
  • a process for producing any of the herein described polypeptides is further provided and comprises culturing host cells under conditions suitable for expression of the desired polypeptide and recovering the desired polypeptide from the cell culture.
  • the invention provides chimeric molecules comprising any of the herein described polypeptides fused to a heterologous polypeptide or amino acid sequence.
  • Example of such chimeric molecules comprise any of the herein described polypeptides fused to an epitope tag sequence or a Fc region of an immunoglobulin.
  • the invention provides an antibody which specifically binds to any of the above or below described polypeptides.
  • the antibody is a monoclonal antibody, humanized antibody, antibody fragment or single-chain antibody.
  • the invention provides oligonucleotide probes useful for isolating genomic and cDNA nucleotide sequences, wherein those probes may be derived from any of the above or below described nucleotide sequences.
  • the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a PRO polypeptide.
  • the isolated nucleic acid molecule comprises a nucleotide sequence having at least about
  • sequence identity preferably at least about 81 % sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about
  • sequence identity yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88 % sequence identity, yet more preferably at least about 89 % sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94 % sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule encoding a PRO polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein or an extracellular domain of a transmembrane protein, with or
  • the isolated nucleic acid molecule comprises a nucleotide sequence having at least about
  • sequence identity preferably at least about 81 % sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about
  • sequence identity yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93 % sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95% sequence identity, yet more preferably at least about 96% sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet more preferably at least about 99% sequence identity to (a) a DNA molecule comprising the coding sequence of a full-length PRO polypeptide cDNA as disclosed herein, the coding sequence of a PRO polypeptide lacking the signal peptide as disclosed herein or the coding sequence of an extracellular domain of a trans
  • the invention concerns an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81 % sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83 % sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85 % sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96 % sequence identity, yet more preferably at least about 97% sequence identity, yet more preferably at least about 98%
  • Another aspect the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding a PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain- inactivated, or is complementary to such encoding nucleotide sequence, wherein the transmembrane domain(s) of such polypeptide are disclosed herein. Therefore, soluble extracellular domains of the herein described PRO polypeptides are contemplated.
  • Another embodiment is directed to fragments of a PRO polypeptide coding sequence, or the complement thereof, that may find use as, for example, hybridization probes or for encoding fragments of a PRO polypeptide that may optionally encode a polypeptide comprising a binding site for an anti-PRO antibody.
  • nucleic acid fragments are usually at least about 20 nucleotides in length, preferably at least about 30 nucleotides in length, more preferably at least about 40 nucleotides in length, yet more preferably at least about 50 nucleotides in length, yet more preferably at least about 60 nucleotides in length, yet more preferably at least about 70 nucleotides in length, yet more preferably at least about 80 nucleotides in length, yet more preferably at least about 90 nucleotides in length, yet more preferably at least about 100 nucleotides in length, yet more preferably at least about 110 nucleotides in length, yet more preferably at least about 120 nucleotides in length, yet more preferably at least about 130 nucleotides in length, yet more preferably at least about 140 nucleotides in length, yet more preferably at least about 150 nucleotides in length, yet more preferably at least about 160 nucleotides in length, yet more preferably at least about 170 nucleot
  • novel fragments of a PRO polypeptide-encoding nucleotide sequence may be determined in a routine manner by aligning the PRO polypeptide-encoding nucleotide sequence with other known nucleotide sequences using any of a number of well known sequence alignment programs and determining which PRO polypeptide-encoding nucleotide sequence fragment(s) are novel. All of such PRO polypeptide-encoding nucleotide sequences are contemplated herein. Also contemplated are the PRO polypeptide fragments encoded by these nucleotide molecule fragments, preferably those PRO polypeptide fragments that comprise a binding site for an anti-PRO antibody.
  • the invention provides isolated PRO polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
  • the invention concerns an isolated PRO polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 81 % sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84% sequence identity, yet more preferably at least about 85% sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity, yet more preferably at least about 96 % sequence
  • the invention concerns an isolated PRO polypeptide comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 81 % sequence identity, more preferably at least about 82% sequence identity, yet more preferably at least about 83% sequence identity, yet more preferably at least about 84 % sequence identity, yet more preferably at least about 85 % sequence identity, yet more preferably at least about 86% sequence identity, yet more preferably at least about 87% sequence identity, yet more preferably at least about 88% sequence identity, yet more preferably at least about 89% sequence identity, yet more preferably at least about 90% sequence identity, yet more preferably at least about 91 % sequence identity, yet more preferably at least about 92% sequence identity, yet more preferably at least about 93% sequence identity, yet more preferably at least about 94% sequence identity, yet more preferably at least about 95 % sequence identity , yet more preferably at least about 96 % sequence identity , yet more preferably at least about 97% sequence identity, yet more preferably at least about 98% sequence identity and yet
  • the invention concerns an isolated PRO polypeptide comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 81 % positives, more preferably at least about 82% positives, yet more preferably at least about 83% positives, yet more preferably at least about 84% positives, yet more preferably at least about 85% positives, yet more preferably at least about 86% positives, yet more preferably at least about 87% positives, yet more preferably at least about 88% positives, yet more preferably at least about 89% positives, yet more preferably at least about 90% positives, yet more preferably at least about 91 % positives, yet more preferably at least about 92% positives, yet more preferably at least about 93% positives, yet more preferably at least about 94% positives, yet more preferably at least about 95% positives, yet more preferably at least about 96% positives, yet more preferably at least about 97% positives, yet more preferably at least about 98% positives and yet more preferably at least about 99%
  • the invention provides an isolated PRO polypeptide without the N-terminal signal sequence and/or the initiating methionine and is encoded by a nucleotide sequence that encodes such an amino acid sequence as hereinbefore described.
  • Processes for producing the same are also herein described, wherein those processes comprise culmring a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.
  • Another aspect the invention provides an isolated PRO polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated.
  • Processes for producing the same are also herein described, wherein those processes comprise culmring a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the PRO polypeptide and recovering the PRO polypeptide from the cell culture.
  • the invention concerns agonists and antagonists of a native PRO polypeptide as defined herein.
  • the agonist or antagonist is an anti-PRO antibody or a small molecule.
  • the invention concerns a method of identifying agonists or antagonists to a PRO polypeptide which comprise contacting the PRO polypeptide with a candidate molecule and monitoring a biological activity mediated by said PRO polypeptide.
  • the PRO polypeptide is a native PRO polypeptide.
  • the invention concerns a composition of matter comprising a PRO polypeptide, or an agonist or antagonist of a PRO polypeptide as herein described, or an anti-PRO antibody, in combination with a carrier.
  • the carrier is a pharmaceutically acceptable carrier.
  • Another embodiment of the present invention is directed to the use of a PRO polypeptide, or an agonist or antagonist thereof as hereinbefore described, or an anti-PRO antibody, for the preparation of a medicament useful in the treatment of a condition which is responsive to the PRO polypeptide, an agonist or antagonist thereof or an anti-PRO antibody.
  • Figure 1 shows a nucleotide sequence (SEQ ID NO: l) of a native sequence PR0211 cDNA, wherein SEQ ID NO: l is a clone designated herein as "DNA32292-1131 ".
  • Figure 2 shows the amino acid sequence (SEQ ID NO: 2) derived from the coding sequence of SEQ ID NO: l shown in Figure 1.
  • Figure 3 shows a nucleotide sequence (SEQ ID NO:3) of a native sequence PR0217 cDNA, wherein
  • SEQ ID NO:3 is a clone designated herein as "DNA33094-1131 ".
  • Figure 4 shows the amino acid sequence (SEQ ID NO: 4) derived from the coding sequence of SEQ ID NO: 3 shown in Figure 3.
  • Figure 5 shows a nucleotide sequence (SEQ ID NO: 11) of a native sequence PRO230 cDNA, wherein SEQ ID NO: 11 is a clone designated herein as "DNA33223-1136" .
  • Figure 6 shows the amino acid sequence (SEQ ID NO: 12) derived from the coding sequence of SEQ ID NO: 11 shown in Figure 5.
  • Figure 7 shows a nucleotide sequence designated herein as DNA20088 (SEQ ID NO: 13).
  • Figure 8 shows a nucleotide sequence (SEQ ID NO: 17) of a native sequence PR0232 cDNA, wherein SEQ ID NO: 17 is a clone designated herein as "PNA34435-1140" .
  • Figure 9 shows the amino acid sequence (SEQ IP NO: 18) derived from the coding sequence of SEQ ID NO: 17 shown in Figure 8.
  • Figure 10 shows a nucleotide sequence (SEQ ID NO: 22) of a native sequence PRO 187 cDNA, wherein SEQ ID NO:22 is a clone designated herein as "DNA27864-1155" .
  • Figure 11 shows the amino acid sequence (SEQ ID NO:23) derived from the coding sequence of SEQ
  • Figure 12 shows a nucleotide sequence (SEQ ID NO: 27) of a native sequence PR0265 cDNA, wherein SEQ ID NO:27 is a clone designated herein as "DNA36350-1158" .
  • Figure 13 shows the amino acid sequence (SEQ ID NO: 28) derived from the coding sequence of SEQ ID NO:27 shown in Figure 12.
  • Figure 14 shows a nucleotide sequence (SEQ ID NO:33) of a native sequence PR0219 cDNA, wherein SEQ ID NO:33 is a clone designated herein as "DNA32290-1164" .
  • Figure 15 shows the amino acid sequence (SEQ ID NO: 34) derived from the coding sequence of SEQ ID NO: 33 shown in Figure 14.
  • Figure 16 shows a nucleotide sequence (SEQ ID NO:38) of a native sequence PR0246 cDNA, wherein SEQ ID NO:38 is a clone designated herein as "DNA35639-1172".
  • Figure 17 shows the amino acid sequence (SEQ ID NO:39) derived from the coding sequence of SEQ ID NO:38 shown in Figure 16.
  • Figure 18 shows a nucleotide sequence (SEQ ID NO:48) of a native sequence PR0228 cDNA, wherein SEQ ID NO:48 is a clone designated herein as "DNA33092-1202".
  • Figure 19 shows the amino acid sequence (SEQ ID NO:49) derived from the coding sequence of SEQ ID NO:48 shown in Figure 18.
  • Figure 20 shows a nucleotide sequence designated herein as DNA21951 (SEQ ID NO:50).
  • Figure 21 shows a nucleotide sequence (SEQ ID NO:58) of a native sequence PR0533 cDNA, wherein SEQ ID N0:58 is a clone designated herein as "DNA49435-1219".
  • Figure 22 shows the amino acid sequence (SEQ ID NO:59) derived from the coding sequence of SEQ ID NO:58 shown in Figure 21.
  • Figure 23 shows a nucleotide sequence (SEQ ID NO:63) of a native sequence PR0245 cDNA, wherein
  • SEQ ID NO:63 is a clone designated herein as "DNA35638-1141".
  • Figure 24 shows the amino acid sequence (SEQ ID NO: 64) derived from the coding sequence of SEQ ID NO:63 shown in Figure 23.
  • Figure 25 shows a nucleotide sequence (SEQ ID NO:68) of a native sequence PRO220 cDNA, wherein SEQ ID NO:68 is a clone designated herein as "DNA32298-1132" .
  • Figure 26 shows the amino acid sequence (SEQ ID NO: 69) derived from the coding sequence of SEQ ID NO:68 shown in Figure 25.
  • Figure 27 shows a nucleotide sequence (SEQ ID NO:70) of a native sequence PR0221 cDNA, wherein SEQ ID NO:70 is a clone designated herein as "DNA33089-1132".
  • Figure 28 shows the amino acid sequence (SEQ ID NO:71) derived from the coding sequence of SEQ
  • Figure 29 shows a nucleotide sequence (SEQ ID NO:72) of a native sequence PR0227 cDNA, wherein SEQ ID NO:72 is a clone designated herein as "DNA33786-1132".
  • Figure 30 shows the amino acid sequence (SEQ ID NO:73) derived from the coding sequence of SEQ ID NO:72 shown in Figure 29.
  • Figure 31 shows a nucleotide sequence (SEQ ID NO:83) of a native sequence PR0258 cDNA, wherein SEQ ID NO:83 is a clone designated herein as "DNA35918-1174".
  • Figure 32 shows the amino acid sequence (SEQ ID NO: 84) derived from the coding sequence of SEQ ID NO:83 shown in Figure 31.
  • Figure 33 shows a nucleotide sequence (SEQ ID NO:90) of a native sequence PR0266 cDNA, wherein
  • SEQ ID NO:90 is a clone designated herein as "DNA37150-1178".
  • Figure 34 shows the amino acid sequence (SEQ ID NO:91) derived from the coding sequence of SEQ ID NO: 90 shown in Figure 33.
  • Figure 35 shows a nucleotide sequence (SEQ ID NO:95) of a native sequence PR0269 cDNA, wherein SEQ ID NO:95 is a clone designated herein as "DNA38260-1180".
  • Figure 36 shows the amino acid sequence (SEQ ID NO:96) derived from the coding sequence of SEQ ID NO:95 shown in Figure 35.
  • Figure 37 shows a nucleotide sequence (SEQ ID NO: 103) of a native sequence PR0287 cDNA, wherein SEQ ID NO: 103 is a clone designated herein as "DNA39969-1185".
  • Figure 38 shows the amino acid sequence (SEQ ID NO: 104) derived from the coding sequence of SEQ ID NO: 103 shown in Figure 37.
  • Figure 39 shows a nucleotide sequence (SEQ ID NO: 108) of a native sequence PR0214 cDNA, wherein
  • SEQ ID NO: 108 is a clone designated herein as "DNA32286-1191".
  • Figure 40 shows the amino acid sequence (SEQ ID NO: 109) derived from the coding sequence of SEQ ID NO: 108 shown in Figure 39.
  • Figure 41 shows a nucleotide sequence (SEQ ID NO: 113) of a native sequence PR0317 cDNA, wherein SEQ ID NO: 113 is a clone designated herein as "DNA33461-1199" .
  • Figure 42 shows the amino acid sequence (SEQ ID NO: 114) derived from the coding sequence of SEQ ID NO: 113 shown in Figure 41.
  • Figure 43 shows a nucleotide sequence (SEQ ID NO: 118) of a native sequence PRO301 cDNA, wherein SEQ ID NO: 118 is a clone designated herein as "DNA40628-1216".
  • Figure 44 shows the amino acid sequence (SEQ ID NO: 119) derived from the coding sequence of SEQ ID NO: 118
  • Figure 45 shows a nucleotide sequence (SEQ ID NO: 126) of a native sequence PR0224 cDNA, wherein SEQ ID NO: 126 is a clone designated herein as "DNA33221-1133".
  • Figure 46 shows the amino acid sequence (SEQ ID NO: 127) derived from the coding sequence of SEQ ID NO : 126 shown in Figure 45.
  • Figure 47 shows a nucleotide sequence (SEQ ID NO: 131) of a native sequence PR0222 cDNA, wherein SEQ ID NO:131 is a clone designated herein as "DNA33107-1135".
  • Figure 48 shows the amino acid sequence (SEQ ID NO: 132) derived from the coding sequence of SEQ ID NO: 131 shown in Figure 47.
  • Figure 49 shows a nucleotide sequence (SEQ ID NO: 136) of a native sequence PR0234 cDNA, wherein
  • SEQ ID NO:136 is a clone designated herein as "DNA35557-1137".
  • Figure 50 shows the amino acid sequence (SEQ ID NO: 137) derived from the coding sequence of SEQ ID NO: 136 shown in Figure 49.
  • Figure 51 shows a nucleotide sequence (SEQID NO: 141) of a native sequence PR0231 cDN A , wherein SEQ ID NO: 141 is a clone designated herein as "DNA34434-1139" .
  • Figure 52 shows the amino acid sequence (SEQ ID NO: 142) derived from the coding sequence of SEQ ID NO: 141 shown in Figure 51.
  • Figure 53 shows a nucleotide sequence (SEQ ID NO: 147) of a native sequence PR0229 cDNA, wherein SEQ ID NO:147 is a clone designated herein as "DNA33100-1159".
  • Figure 54 shows the amino acid sequence (SEQ ID NO: 148) derived from the coding sequence of SEQ ID NO: 147 shown in Figure 53.
  • Figure 55 shows a nucleotide sequence (SEQ ID NO: 152) of a native sequence PR0238 cDNA, wherein SEQ ID NO:152 is a clone designated herein as "DNA35600-1162".
  • Figure 56 shows the amino acid sequence (SEQ ID NO: 153) derived from the coding sequence of SEQ ID NO: 152 shown in Figure 55.
  • Figure 57 shows a nucleotide sequence (SEQ ID NO: 158) of a native sequence PR0233 cDNA, wherein SEQ ID NO: 158 is a clone designated herein as "DNA34436-1238".
  • Figure 58 shows the amino acid sequence (SEQ ID NO: 159) derived from the coding sequence of SEQ
  • Figure 59 shows a nucleotide sequence (SEQ ID NO: 163) of a native sequence PR0223 cDNA, wherein SEQ ID NO:163 is a clone designated herein as "DNA33206-1165".
  • Figure 60 shows the amino acid sequence (SEQ ID NO: 164) derived from the coding sequence of SEQ ID NO: 163 shown in Figure 59.
  • Figure 61 shows a nucleotide sequence (SEQ ID NO: 169) of a native sequence PR0235 cDNA, wherein SEQ ID NO:169 is a clone designated herein as "DNA35558-1167".
  • Figure 62 shows the amino acid sequence (SEQ ID NO: 170) derived from the coding sequence of SEQ ID NO: 169 shown in Figure 61.
  • Figure 63 shows a nucleotide sequence (SEQ ID NO: 174) of a native sequence PR0236 cDNA, wherein
  • SEQ ID NO: 174 is a clone designated herein as "DNA35599-1168".
  • Figure 64 shows the amino acid sequence (SEQ ID NO: 175) derived from the coding sequence of SEQ ID NO: 174 shown in Figure 63.
  • Figure 65 shows a nucleotide sequence (SEQ ID NO: 176) of a native sequence PR0262 cDNA, wherein SEQ ID NO: 176 is a clone designated herein as "DNA36992-1168" .
  • Figure 66 shows the amino acid sequence (SEQ ID NO: 177) derived from the coding sequence of SEQ ID NO: 176 shown in Figure 65.
  • Figure 67 shows a nucleotide sequence (SEQ ID NO: 184) of a native sequence PR0239 cDNA, wherein SEQ ID NO: 184 is a clone designated herein as "DNA34407-1169".
  • Figure 68 shows the amino acid sequence (SEQ ID NO: 185) derived from the coding sequence of SEQ
  • Figure 69 shows a nucleotide sequence (SEQ ID NO: 189) of a native sequence PR0257 cDNA, wherein SEQ ID NO: 189 is a clone designated herein as "DNA35841-1173".
  • Figure 70 shows the amino acid sequence (SEQ ID NO: 190) derived from the coding sequence of SEQ ID NO: 189 shown in Figure 69.
  • Figure 71 shows a nucleotide sequence (SEQ ID NO: 194) of a native sequence PRO260 cDNA, wherein SEQ ID NO: 194 is a clone designated herein as "DNA33470-1175".
  • Figure 72 shows the amino acid sequence (SEQ ID NO: 195) derived from the coding sequence of SEQ ID NO: 194 shown in Figure 71.
  • Figure 73 shows a nucleotide sequence (SEQ ID NO: 200) of a native sequence PR0263 cDNA, wherein SEQ ID NO:200 is a clone designated herein as "DNA34431-1177".
  • Figure 74 shows the amino acid sequence (SEQ ID NO:201) derived from the coding sequence of SEQ ID NO:200 shown in Figure 73.
  • Figure 75 shows a nucleotide sequence (SEQ ID NO:206) of a native sequence PRO270 cDNA, wherein SEQ ID NO:206 is a clone designated herein as "DNA39510-1181 " .
  • Figure 76 shows the amino acid sequence (SEQ ID NO:207) derived from the coding sequence of SEQ ID NO: 206 shown in Figure 75.
  • Figure 77 shows a nucleotide sequence (SEQ ID NO : 212) of a native sequence PR0271 cDN A , wherein
  • SEQ ID NO:212 is a clone designated herein as "DNA39423-1182".
  • Figure 78 shows the amino acid sequence (SEQ ID NO:213) derived from the coding sequence of SEQ ID NO:212 shown in Figure 77.
  • Figure 79 shows a nucleotide sequence (SEQ ID NO : 220) of a native sequence PR0272 cDN A , wherein SEQ ID NO:220 is a clone designated herein as "DNA40620-1183".
  • Figure 80 shows the amino acid sequence (SEQ ID NO: 221) derived from the coding sequence of SEQ ID NO:220 shown in Figure 79.
  • Figure 81 shows a nucleotide sequence (SEQ ID NO : 226) of a native sequence PR0294 cDN A , wherein SEQ ID NO:226 is a clone designated herein as "DNA40604-1187".
  • Figure 82 shows the amino acid sequence (SEQ ID NO:227) derived from the coding sequence of SEQ
  • Figure 83 shows a nucleotide sequence (SEQ ID NO:235) of a native sequence PR0295 cDNA, wherein SEQ ID NO:235 is a clone designated herein as "DN A38268- 1188".
  • Figure 84 shows the amino acid sequence (SEQ ID NO: 236) derived from the coding sequence of SEQ ID NO: 235 shown in Figure 83.
  • Figure 85 shows a nucleotide sequence (SEQ ID NO:244) of a native sequence PR0293 cDNA, wherein SEQ ID NO:244 is a clone designated herein as "DNA37151-1193".
  • Figure 86 shows the amino acid sequence (SEQ ID NO:245) derived from the coding sequence of SEQ ID NO:244 shown in Figure 85.
  • Figure 87 shows a nucleotide sequence (SEQ ID NO : 249) of a native sequence PR0247 cDN A , wherein
  • SEQ ID NO:249 is a clone designated herein as "DNA35673-1201 ".
  • Figure 88 shows the amino acid sequence (SEQ ID NO:250) derived from the coding sequence of SEQ ID NO:249 shown in Figure 87.
  • Figure 89 shows a nucleotide sequence (SEQ ID NO:254) of a native sequence PRO302 cDNA, wherein SEQ ID NO:254 is a clone designated herein as "DNA40370-1217".
  • Figure 90 shows the amino acid sequence (SEQ ID NO:255) derived from the coding sequence of SEQ ID NO:254 shown in Figure 89.
  • Figure 91 shows a nucleotide sequence (SEQ IP NO:256) of a native sequence PRO303 cPNA, wherein SEQ IP NO:256 is a clone designated herein as "PNA42551-1217".
  • Figure 92 shows the amino acid sequence (SEQ IP NO:257) derived from the coding sequence of SEQ IP NO:256 shown in Figure 91.
  • Figure 93 shows a nucleotide sequence (SEQ ID NO: 258) of a native sequence PRO304 cDNA, wherein SEQ ID NO:258 is a clone designated herein as "DNA39520-1217" .
  • Figure 94 shows the amino acid sequence (SEQ ID NO:259) derived from the coding sequence of SEQ ID NO:258 shown in Figure 93.
  • Figure 95 shows a nucleotide sequence (SEQ ID NO:260) of a native sequence PRO307 cDNA, wherein SEQ ID NO:260 is a clone designated herein as "DNA41225-1217".
  • Figure 96 shows the amino acid sequence (SEQ ID NO: 261) derived from the coding sequence of SEQ
  • Figure 97 shows a nucleotide sequence (SEQ ID NO:262) of a native sequence PR0343 cDNA, wherein SEQ ID NO:262 is a clone designated herein as "DNA43318-1217".
  • Figure 98 shows the amino acid sequence (SEQ ID NO: 263) derived from the coding sequence of SEQ ID NO : 262 shown in Figure 97.
  • Figure 99 shows a nucleotide sequence (SEQ ID NO:284) of a native sequence PR0328 cDNA, wherein SEQ IP NO:284 is a clone designated herein as "PNA40587-1231 " .
  • Figure 100 shows the amino acid sequence (SEQ ID NO:285) derived from the coding sequence of SEQ ID NO: 284 shown in Figure 99.
  • Figure 101 shows a nucleotide sequence (SEQ ID NO:289) of a native sequence PR0335 cDNA, wherein SEQ ID NO:289 is a clone designated herein as "DNA41388-1234" .
  • Figure 102 shows the amino acid sequence (SEQ ID NO: 290) derived from the coding sequence of SEQ ID NO:289 shown in Figure 101.
  • Figure 103 shows a nucleotide sequence (SEQ ID NO:291) of a native sequence PR0331 cDNA, wherein SEQ ID NO:291 is a clone designated herein as "DNA40981-1234" .
  • Figure 104 shows the amino acid sequence (SEQ ID NO:292) derived from the coding sequence of SEQ ID NO:291 shown in Figure 103.
  • Figure 105 shows a nucleotide sequence (SEQ ID NO:293) of a native sequence PR0326 cDNA, wherein SEQ ID NO:293 is a clone designated herein as "DNA37140-1234".
  • Figure 106 shows the amino acid sequence (SEQ ID NO:294) derived from the coding sequence of SEQ
  • Figure 107 shows a nucleotide sequence (SEQ ID NO:309) of a native sequence PR0332 cDNA, wherein SEQ ID NO:309 is a clone designated herein as "DNA40982-1235".
  • Figure 108 shows the amino acid sequence (SEQ ID NO:310) derived from the coding sequence of SEQ ID NO:309 shown in Figure 107.
  • Figure 109 shows a nucleotide sequence (SEQ ID NO:314) of a native sequence PR0334 cDNA, wherein SEQ ID NO:314 is a clone designated herein as "DNA41379-1236".
  • Figure 110 shows the amino acid sequence (SEQ ID NO: 315) derived from the coding sequence of SEQ ID NO:314 shown in Figure 109.
  • Figure 111 shows a nucleotide sequence (SEQ ID NO:319) of a native sequence PR0346 cDNA, wherein SEQ ID NO:319 is a clone designated herein as "DNA44167- 1243".
  • Figure 112 shows the amino acid sequence (SEQ ID NO:320) derived from the coding sequence of SEQ ID NO:319 shown in Figure 111.
  • Figure 113 shows a nucleotide sequence (SEQ ID NO:324) of a native sequence PR0268 cDNA, wherein SEQ ID NO:324 is a clone designated herein as "DNA39427-1179".
  • Figure 114 shows the amino acid sequence (SEQ ID NO:325) derived from the coding sequence of SEQ ID NO:324 shown in Figure 113.
  • Figure 115 shows a nucleotide sequence (SEQ ID NO:331) of a native sequence PRO330 cDNA, wherein SEQ ID NO:331 is a clone designated herein as "DNA40603-1232".
  • Figure 116 shows the amino acid sequence (SEQ ID NO:332) derived from the coding sequence of SEQ ID NO: 331 shown in Figure 115.
  • Figure 117 shows a nucleotide sequence (SEQ ID NO:338) of a native sequence PR0339 cDNA, wherein SEQ ID NO:338 is a clone designated herein as "DNA43466-1225".
  • Figure 118 shows the amino acid sequence (SEQ ID NO:339) derived from the coding sequence of SEQ ID NO:338 shown in Figure 117.
  • Figure 119 shows a nucleotide sequence (SEQ ID NO: 340) of a native sequence PRO310 cDNA, wherein SEQ ID NO:340 is a clone designated herein as "DNA43046-1225".
  • Figure 120 shows the amino acid sequence (SEQ ID NO:341) derived from the coding sequence of SEQ
  • Figure 121 shows a nucleotide sequence (SEQ ID NO:376) of a native sequence PR0244 cDNA, wherein SEQ ID NO:376 is a clone designated herein as "DNA35668-1171".
  • Figure 122 shows the amino acid sequence (SEQ ID NO:377) derived from the coding sequence of SEQ ID NO : 376 shown in Figure 121.
  • Figure 123 shows a nucleotide sequence (SEQ ID NO:422) of a native sequence PR01868 cDNA, wherein SEQ ID NO:422 is a clone designated herein as "DNA77624-2515".
  • Figure 124 shows the amino acid sequence (SEQ ID NO:423) derived from the coding sequence of SEQ ID NO:422 shown in Figure 123.
  • PRO polypeptide and "PRO” as used herein and when immediately followed by a numerical designation refer to various polypeptides, wherein the complete designation (i.e. , PRO/number) refers to specific polypeptide sequences as described herein.
  • PRO/number polypeptide and “PRO/number” wherein the term “number” is provided as an actual numerical designation as used herein encompass native sequence polypeptides and polypeptide variants (which are further defined herein).
  • the PRO polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods.
  • a “native sequence PRO polypeptide” comprises a polypeptide having the same amino acid sequence as the corresponding PRO polypeptide derived from nature. Such native sequence PRO polypeptides can be isolated from nature or can be produced by recombinant or synthetic means.
  • the term "native sequence PRO polypeptide” specifically encompasses naturally-occurring truncated or secreted forms of the specific PRO polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide.
  • the native sequence PRO polypeptides disclosed herein are mature or full-length native sequence polypeptides comprising the full-length amino acids sequences shown in the accompanying figures. Start and stop codons are shown in bold font and underlined in the figures. However, while the PRO polypeptide disclosed in the accompanying figures are shown to begin with methionine residues designated herein as amino acid position 1 in the figures, it is conceivable and possible that other methionine residues located either upstream or downstream from the amino acid position 1 in the figures may be employed as the starting amino acid residue for the PRO polypeptides.
  • the PRO polypeptide "extracellular domain” or “ECD” refers to a form of the PRO polypeptide which is essentially free of the transmembrane and cytoplasmic domains. Ordinarily, a PRO polypeptide ECD will have less than 1 % of such transmembrane and/or cytoplasmic domains and preferably, will have less than 0.5% of such domains. It will be understood that any transmembrane domains identified for the PRO polypeptides of the present invention are identified pursuant to criteria routinely employed in the art for identifying that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain as initially identified herein.
  • an extracellular domain of a PRO polypeptide may contain from about 5 or fewer amino acids on either side of the transmembrane domain/extracellular domain boundary as identified in the Examples or specification and such polypeptides, with or without the associated signal peptide, and nucleic acid encoding them, are comtemplated by the present invention.
  • cleavage of a signal sequence from a secreted polypeptide is not entirely uniform, resulting in more than one secreted species.
  • These mature polypeptides, where the signal peptide is cleaved within no more than about 5 amino acids on either side of the C-terminal boundary of the signal peptide as identified herein, and the polynucleotides encoding them, are contemplated by the present invention.
  • PRO polypeptide variant means an active PRO polypeptide as defined above or below having at least about 80% amino acid sequence identity with a full-length native sequence PRO polypeptide sequence as disclosed herein, a PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein.
  • Such PRO polypeptide variants include, for instance, PRO polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C- terminus of the full-length native amino acid sequence.
  • a PRO polypeptide variant will have at least about 80% amino acid sequence identity, preferably at least about 81 % amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, more preferably at least about 83% amino acid sequence identity, more preferably at least about 84% amino acid sequence identity, more preferably at least about 85 % amino acid sequence identity, more preferably at least about 86% amino acid sequence identity, more preferably at least about 87% amino acid sequence identity, more preferably at least about 88% amino acid sequence identity, more preferably at least about 89% amino acid sequence identity, more preferably at least about 90% amino acid sequence identity, more preferably at least about 91 % amino acid sequence identity, more preferably at least about 92% amino acid sequence identity, more preferably at least about 93% amino acid sequence identity, more preferably at least about 94% amino acid sequence identity, more preferably at least about 95 % amino acid sequence identity, more preferably at least about 96 % amino acid sequence identity, more preferably at least about 97% amino acid sequence identity, more preferably at least at least
  • PRO variant polypeptides are at least about 10 amino acids in length, often at least about 20 amino acids in length, more often at least about 30 amino acids in length, more often at least about 40 amino acids in length, more often at least about 50 amino acids in length, more often at least about 60 amino acids in length, more often at least about 70 amino acids in length, more often at least about 80 amino acids in length, more often at least about 90 amino acids in length, more often at least about 100 amino acids in length, more often at least about 150 amino acids in length, more often at least about 200 amino acids in length, more often at least about 300 amino acids in length, or more.
  • Percent (%) amino acid sequence identity with respect to the PRO polypeptide sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific PRO polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.
  • % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below.
  • the ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C. , 20559, where it is registered under U.S. Copyright Registration No. TXU510087.
  • the ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Table 1 below.
  • the ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D.
  • % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B is calculated as follows:
  • Tables 2 and 3 demonstrate how to calculate the % amino acid sequence identity of the amino acid sequence designated "Comparison Protein” to the amino acid sequence designated "PRO” , wherein “PRO” represents the amino acid sequence of a hypothetical PRO polypeptide of interest, “Comparison Protein” represents the amino acid sequence of a polypeptide against which the "PRO” polypeptide of interest is being compared, and "X, "Y” and “Z” each represent different hypothetical amino acid residues.
  • a % amino acid sequence identity value is determined by dividing (a) the number of matching identical amino acid residues between the amino acid sequence of the PRO polypeptide of interest having a sequence derived from the native PRO polypeptide and the comparison amino acid sequence of interest (i . e . , the sequence against which the PRO polypeptide of interest is being compared which may be a PRO variant polypeptide) as determined by WU-BLAST-2 by (b) the total number of amino acid residues of the PRO polypeptide of interest.
  • amino acid sequence A is the comparison amino acid sequence of interest and the amino acid sequence B is the amino acid sequence of the PRO polypeptide of interest.
  • Percent amino acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)).
  • NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov.
  • % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B is calculated as follows:
  • PRO variant polynucleotide or "PRO variant nucleic acid sequence” means a nucleic acid molecule which encodes an active PRO polypeptide as defined below and which has at least about 80% nucleic acid sequence identity with a nucleotide acid sequence encoding a full-length native sequence PRO polypeptide sequence as disclosed herein, a full-length native sequence PRO polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a PRO polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length PRO polypeptide sequence as disclosed herein.
  • a PRO variant polynucleotide will have at least about 80% nucleic acid sequence identity, more preferably at least about 81 % nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91 % nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence
  • PRO variant polynucleotides are at least about 30 nucleotides in length, often at least about 60 nucleotides in length, more often at least about 90 nucleotides in length, more often at least about 120 nucleotides in length, more often at least about 150 nucleotides in length, more often at least about 180 nucleotides in length, more often at least about 210 nucleotides in length, more often at least about 240 nucleotides in length, more often at least about 270 nucleotides in length, more often at least about 300 nucleotides in length, more often at least about 450 nucleotides in length, more often at least about 600 nucleotides in length, more often at least about 900 nucleotides in length, or more.
  • Percent (%) nucleic acid sequence identity with respect to PRO-encoding nucleic acid sequences identified herein is defined as the percentage of nucleotides in a candidate sequence that are identical with the nucleotides in the PRO nucleic acid sequence of interest, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software.
  • % nucleic acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below.
  • the ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C, 20559, where it is registered under U.S. Copyright Registration No. TXU510087.
  • the ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Table 1 below.
  • the ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D.
  • % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D is calculated as follows:
  • Tables 4 and 5 demonstrate how to calculate the % nucleic acid sequence identity of the nucleic acid sequence designated "Comparison DNA” to the nucleic acid sequence designated "PRO-DNA” , wherein "PRO-DNA” represents a hypothetical PRO-encoding nucleic acid sequence of interest, “Comparison DNA” represents the nucleotide sequence of a nucleic acid molecule against which the "PRO-DNA” nucleic acid molecule of interest is being compared, and "N", “L” and “V” each represent different hypothetical nucleotides.
  • a % nucleic acid sequence identity value is determined by dividing (a) the number of matching identical nucleotides between the nucleic acid sequence of the PRO polypeptide-encoding nucleic acid molecule of interest having a sequence derived from the native sequence PRO polypeptide-encoding nucleic acid and the comparison nucleic acid molecule of interest (i.e. , the sequence against which the PRO polypeptide-encoding nucleic acid molecule of interest is being compared which may be a variant PRO polynucleotide) as determined by WU-BLAST-2 by (b) the total number of nucleotides of the PRO polypeptide-encoding nucleic acid molecule of interest.
  • nucleic acid sequence A is the comparison nucleic acid molecule of interest and the nucleic acid sequence B is the nucleic acid sequence of the PRO polypeptide- encoding nucleic acid molecule of interest.
  • Percent nucleic acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)).
  • NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov.
  • % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D is calculated as follows:
  • PRO variant polynucleotides are nucleic acid molecules that encode an active PRO polypeptide and which are capable of hybridizing, preferably under stringent hybridization and wash conditions, to nucleotide sequences encoding a full-length PRO polypeptide as disclosed herein.
  • PRO variant polypeptides may be those that are encoded by a PRO variant polynucleotide.
  • the term "positives”, in the context of sequence comparison performed as described above, includes residues in the sequences compared that are not identical but have similar properties (e.g. as a result of conservative substitutions, see Table 6 below).
  • the % value of positives is determined by dividing (a) the number of amino acid residues scoring a positive value between the PRO polypeptide amino acid sequence of interest having a sequence derived from the native PRO polypeptide sequence and the comparison amino acid sequence of interest (i.e., the amino acid sequence against which the PRO polypeptide sequence is being compared) as determined in the BLOSUM62 matrix of WU-BLAST-2 by (b) the total number of amino acid residues of the PRO polypeptide of interest.
  • % value of positives is calculated as described in the immediately preceding paragraph.
  • amino acid sequence identity comparisons performed as described for ALIGN-2 and NCBI-BLAST-2 above includes amino acid residues in the sequences compared that are not only identical, but also those that have similar properties.
  • Amino acid residues that score a positive value to an amino acid residue of interest are those that are either identical to the amino acid residue of interest or are a preferred substitution (as defined in Table 6 below) of the amino acid residue of interest.
  • % value of positives of a given amino acid sequence A to, with, or against a given amino acid sequence B is calculated as follows:
  • X is the number of amino acid residues scoring a positive value as defined above by the sequence alignment program ALIGN-2 or NCBI-BLAST2 in that program's alignment of A and B
  • Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % positives of A to B will not equal the % positives of B to A.
  • Isolated, when used to describe the various polypeptides disclosed herein, means polypeptide that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes.
  • the polypeptide will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain.
  • Isolated polypeptide includes polypeptide in situ within recombinant cells, since at least one component of the PRO polypeptide natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step.
  • An "isolated" PRO polypeptide-encoding nucleic acid or other polypeptide-encoding nucleic acid is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the natural source of the polypeptide-encoding nucleic acid.
  • An isolated polypeptide-encoding nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated polypeptide-encoding nucleic acid molecules therefore are distinguished from the specific polypeptide- encoding nucleic acid molecule as it exists in natural cells.
  • an isolated polypeptide-encoding nucleic acid molecule includes polypeptide-encoding nucleic acid molecules contained in cells that ordinarily express the polypeptide where, for example, the nucleic acid molecule is in a chromosomal location different from that of natural cells.
  • control sequences refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism.
  • the control sequences that are suitable for prokaryotes include a promoter, optionally an operator sequence, and a ribosome binding site.
  • Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
  • Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence.
  • DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide;
  • a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or
  • a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.
  • "operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.
  • antibody is used in the broadest sense and specifically covers, for example, single anti-PRO monoclonal antibodies (including agonist, antagonist, and neutralizing antibodies), anti-PRO antibody compositions with polyepitopic specificity, single chain anti-PRO antibodies, and fragments of anti-PRO antibodies (see below).
  • monoclonal antibody refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e. , the individual antibodies comprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts.
  • “Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology. Wiley Interscience Publishers, (1995).
  • “Stringent conditions” or “high stringency conditions”, as defined herein, may be identified by those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1 % sodium dodecyl sulfate at 50°C; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1 % bovine serum albumin 0.1 % Ficoll/0.1 % polyvinylpyrrolidone/50mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42°C; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1 % sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 ⁇ g/ml), 0.1 % SDS
  • Modely stringent conditions may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent that those described above.
  • washing solution and hybridization conditions e.g., temperature, ionic strength and %SDS
  • moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50 °C
  • the skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.
  • epitope tagged when used herein refers to a chimeric polypeptide comprising a PRO polypeptide fused to a "tag polypeptide" .
  • the tag polypeptide has enough residues to provide an epitope against which an antibody can be made, yet is short enough such that it does not interfere with activity of the polypeptide to which it is fused.
  • the tag polypeptide preferably also is fairly unique so that the antibody does not substantially cross-react with other epitopes.
  • Suitable tag polypeptides generally have at least six amino acid residues and usually between about 8 and 50 amino acid residues (preferably, between about 10 and 20 amino acid residues).
  • immunoadhesin designates antibody-like molecules which combine the binding specificity of a heterologous protein (an “adhesin”) with the effector functions of immunoglobulin constant domains.
  • the immunoadhesins comprise a fusion of an amino acid sequence with the desired binding specificity which is other than the antigen recognition and binding site of an antibody (i.e., is “heterologous"), and an immunoglobulin constant domain sequence.
  • the adhesin part of an immunoadhesin molecule typically is a contiguous amino acid sequence comprising at least the binding site of a receptor or a ligand.
  • the immunoglobulin constant domain sequence in the immunoadhesin may be obtained from any immunoglobulin, such as IgG-1, IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE, IgD or IgM.
  • immunoglobulin such as IgG-1, IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE, IgD or IgM.
  • Active or “activity” for the purposes herein refers to form(s) of a PRO polypeptide which retain a biological and/or an immunological activity of native or naturally-occurring PRO, wherein "biological” activity refers to a biological function (either inhibitory or stimulatory) caused by a native or naturally-occurring PRO other than the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring PRO and an "immunological” activity refers to the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring PRO.
  • antagonist is used in the broadest sense, and includes any molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native PRO polypeptide disclosed herein.
  • agonist is used in the broadest sense and includes any molecule that mimics a biological activity of a native PRO polypeptide disclosed herein.
  • Suitable agonist or antagonist molecules specifically include agonist or antagonist antibodies or antibody fragments, fragments or amino acid sequence variants of native PRO polypeptides, peptides, antisense oligonucleotides, small organic molecules, etc.
  • Methods for identifying agonists or antagonists of a PRO polypeptide may comprise contacting a PRO polypeptide with a candidate agonist or antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the PRO polypeptide.
  • Treatment refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder.
  • Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.
  • Chronic administration refers to administration of the agent(s) in a continuous mode as opposed to an acute mode, so as to maintain the initial therapeutic effect (activity) for an extended period of time.
  • Intermittent administration is treatment that is not consecutively done without interruption, but rather is cyclic in nature.
  • “Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is human.
  • Carriers as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers which are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution.
  • physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt- forming counterions such as sodium; and/or nonionic surfactants such as TWEENTM, polyethylene glycol (PEG), and PLURONICSTM.
  • buffers such as phosphate, citrate, and other organic acids
  • antioxidants including ascorbic acid
  • proteins such as serum albumin
  • Antibody fragments comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody.
  • antibody fragments include Fab, Fab' , F(ab') 2 , and Fv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
  • Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual "Fc” fragment, a designation reflecting the ability to crystallize readily.
  • Pepsin treatment yields an F(ab') 2 fragment that has two antigen-combining sites and is still capable of cross-linking antigen.
  • Fv is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen- binding site on the surface of the V H -V L dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.
  • the Fab fragment also contains the constant domain of the light chain and the first constant domain
  • Fab fragments differ from Fab' fragments by the addition of a few residues at the carboxy terminus of the heavy chain CHI domain including one or more cysteines from the antibody hinge region.
  • Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group.
  • F(ab') 2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.
  • the "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains.
  • immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g. , IgGl , IgG2, IgG3, IgG4, IgA, and IgA2.
  • immunoglobulins There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g. , IgGl , IgG2, IgG3, IgG4, IgA, and IgA2.
  • Single-chain Fv or “sFv” antibody fragments comprise the V H and V L domains of antibody, wherein these domains are present in a single polypeptide chain.
  • the Fv polypeptide further comprises a polypeptide linker between the V H and V L domains which enables the sFv to form the desired structure for antigen binding.
  • a polypeptide linker between the V H and V L domains which enables the sFv to form the desired structure for antigen binding.
  • Diabodies are described more fully in, for example, EP 404,097; WO 93/11161 ; and Hollinger et al., Proc. Natl. Acad. Sci. USA. 90:6444-6448 (1993).
  • an “isolated” antibody is one which has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials which would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes.
  • the antibody will be purified (1) to greater than 95 % by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain.
  • Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.
  • label when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the antibody so as to generate a "labeled” antibody.
  • the label may be detectable by itself (e.g. radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable.
  • solid phase is meant a non-aqueous matrix to which the antibody of the present invention can adhere. Examples of solid phases encompassed herein include those formed partially or entirely of glass (e.g., controlled pore glass), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol and silicones.
  • the solid phase can comprise the well of an assay plate; in others it is a purification column (e.g., an affinity chromatography column).
  • This term also includes a discontinuous solid phase of discrete particles, such as those described in U.S. Patent No. 4,275,149.
  • a “liposome” is a small vesicle composed of various types of lipids, phospholipids and/or surfactant which is useful for delivery of a drug (such as a PRO polypeptide or antibody thereto) to a mammal.
  • the components of the liposome are commonly arranged in a bilayer formation, similar to the lipid arrangement of biological membranes.
  • a “small molecule” is defined herein to have a molecular weight below about 500 Daltons.
  • PR0317-associated disorder refers to a pathological condition or disease wherein PR0317 is over- or underexpressed.
  • disorders include diseases of the female genital tract or of the endometrium of a mammal, including hyperplasia, endometritis, endometriosis, wherein the patient is at risk for infertility due to endometrial factor, endometrioma, and endometrial cancer, especially those diseases involving abnormal bleeding such as a gynecological disease.
  • diseases involving angiogenesis include diseases involving angiogenesis, wherein the angiogenesis results in a pathological condition, such as cancer involving solid tumors (the therapy for the disorder would result in decreased vascularization and a decline in growth and metastasis of a variety of tumors).
  • the angiogenesis may be beneficial, such as for ischemia, especially coronary ischemia.
  • these disorders include those found in patients whose hearts are functioning but who have a blocked blood supply due to atherosclerotic coronary artery disease, and those with a functioning but underperfused heart, including patients with coronary arterial disease who are not optimal candidates for angioplasty and coronary artery by-pass surgery.
  • the disorders also include diseases involving the kidney or originating from the kidney tissue, such as polycystic kidney disease and chronic and acute renal failure.
  • /* w*/ 6,-5 -8 -1, ,-1: , 0, ,-7, ,-3, ,-5. , . ,-3. ,-2,-4 ,-4, , M ,-6, ,-5,2,-2,-5,0,-6,17,0,0,-6 ⁇ ,
  • filel and file2 are two dna or two protein sequences.
  • Max file length is 65535 (limited by unsigned short x in the jmp struct)
  • a sequence with 1/3 or more of its elements ACGTU is assumed to be DNA
  • the program may create a tmp file in /tmp to hold info about traceback.
  • dumpblockO * putline() put out a line (name, [num], seq, [num]): dumpblockO
  • static nm matches in core — for checking */ static lmax; /* lengths of stripped file names */ static ij[2]; /* jmp index for a path */ static nc[2]; /* number at start of current line */ static nip]; /* current elem number - for gapping */ static siz[2]; static char *ps[2]; /* ptr to current element */ static char *po[2]; /* ptr to next output char slot */ static char oouutt[[22]][[IP_LINE]; /* output line */ static char starfP 1 2]; /* set by stars() *//
  • *ps[i] toupper(*ps[i]); po[i]++; ps[i] + +;
  • *py++ *px; else if (islower(*px))
  • *py++ toupper(*px); if (index( " ATGCU “ , *(py- 1 ))) natgc++;
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO polypeptides.
  • cDNAs encoding various PRO polypeptides have been identified and isolated, as disclosed in further detail in the Examples below. It is noted that proteins produced in separate expression rounds may be given different PRO numbers but the UNQ number is unique for any given DNA and the encoded protein, and will not be changed.
  • PRO/number the protein encoded by the full length native nucleic acid molecules disclosed herein as well as all further native homologues and variants included in the foregoing definition of PRO, will be referred to as "PRO/number", regardless of their origin or mode of preparation.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0211 and PR0217.
  • Applicants have identified and isolated cDNA encoding PR0211 and PR0217 polypeptides, as disclosed in further detail in the Examples below.
  • BLAST FastA format sequence alignment computer programs, Applicants found that cDNA sequences encoding full-length native sequence PR0211 and PR0217 have homologies to known proteins having EGF-like domains.
  • the cDNA sequence DNA32292-1131 ( Figure 1, SEQ ID NO:l) has certain identify and a Blast score of 209 with PAC6_RAT and certain identify and a Blast score of 206 with Fibulin- 1, isoform c precursor.
  • the cDNA sequence DNA33094-1131 ( Figure 3, SEQ ID NO:3) has 36% identity and a Blast score of 336 with eastern newt tenascin, and 37 % identity and a Blast score of 331 with human tenascin- X precursor. Accordingly, it- is presently believed that PR0211 and PR0217 polypeptides disclosed in the present application are newly identified members of the EGF-like family and possesses properties typical of the EGF-like protein family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO230.
  • Applicants have identified and isolated cDNA encoding a PRO230 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a cDNA sequence encoding full-length native sequence PRO230 has 48% amino acid identity with the rabbit tubulointerstitial nephritis antigen precursor.
  • PRO230 polypeptide disclosed in the present application is a newly identified member of the tubulointerstitial nephritis antigen family and possesses the ability to be recognized by human autoantibodies in certain forms of tubulointerstitial nephritis.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0232.
  • PR0232 polypeptides referred to in the present application as PR0232.
  • Applicants have identified and isolated cDNA encoding a PR0232 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a portion of the full-length native sequence PR0232 (shown in Figure 9 and SEQ ID NO: 18) has 35 % sequence identity with a stem cell surface antigen from Gallus gallus. Accordingly, it is presently believed that the PR0232 polypeptide disclosed in the present application may be a newly identified stem cell antigen.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0187.
  • PR0187 polypeptides referred to in the present application as PR0187.
  • Applicants have identified and isolated cDNA encoding a PRO 187 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a full-length native sequence PR0187 (shown in Figure 15) has 74% amino acid sequence identity and BLAST score of 310 with various androgen-induced growth factors and FGF-8. Accordingly, it is presently believed that PRO 187 polypeptide disclosed in the present application is a newly identified member of the FGF-8 protein family and may possess identify activity or property typical of the FGF-8-like protein family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0265.
  • PR0265 polypeptides referred to in the present application as PR0265.
  • Applicants have identified and isolated cDNA encoding a PR0265 polypeptide, as disclosed in further detail in the Examples below.
  • programs such as BLAST and FastA sequence alignment computer programs, Applicants found that various portions of the PR0265 polypeptide have significant homology with the fibromodulin protein and fibromodulin precursor protein.
  • the DNA encoding the PR0265 polypeptide has significant homology with platelet glycoprotein V, a member of the leucine rich related protein family involved in skin and wound repair.
  • PR0265 polypeptide disclosed in the present application is a newly identified member of the leucine rich repeat family and possesses protein protein binding capabilities, as well as be involved in skin and wound repair as typical of this family.
  • PR0219 Full-length PRQ219 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0219.
  • Applicants have identified and isolated cDNA encoding a PR0219 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0219 polypeptide have significant homology with the mouse and human matrilin-2 precursor polypeptides. Accordingly, it is presently believed that PR0219 polypeptide disclosed in the present application is related to the matrilin-2 precursor polypeptide.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0246.
  • PR0246 polypeptides referred to in the present application as PR0246.
  • Applicants have identified and isolated cDNA encoding a PR0246 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a portion of the PR0246 polypeptide has significant homology with the human cell surface protein HCAR. Accordingly, it is presently believed that PR0246 polypeptide disclosed in the present application may be a newly identified membrane-bound virus receptor or tumor cell-specific antigen.
  • PR0228 nucleotide sequences encoding polypeptides referred to in the present application as PR0228.
  • Applicants have identified and isolated cDNA encoding a PR0228 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0228 polypeptide have significant homology with the EMRl protein.
  • Applicants have also found that the DNA encoding the PR0228 polypeptide has significant homology with latrophilin, macrophage-restricted cell surface glycoprotein, B0457.1 and leucocyte antigen CD97 precursor.
  • PR0228 polypeptide disclosed in the present application is a newly identified member of the seven transmembrane superfamily and possesses characteristics and functional properties typical of this family.
  • PR0228 is a new member of the subgroup within this family to which CD97 and EMRl belong.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0533.
  • Applicants have identified and isolated cDNA encoding a PR0533 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST-2 and FastA sequence alignment computer programs Applicants found that a full-length native sequence PR0533 (shown in Figure 22 and SEQ ID NO: 59) has a Blast score of 509 and 53% amino acid sequence identity with fibroblast growth factor (FGF). Accordingly, it is presently believed that PR0533 disclosed in the present application is a newly identified member of the fibroblast growth factor family and may possess activity typical of such polypeptides.
  • FGF fibroblast growth factor
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0245.
  • PR0245 polypeptides referred to in the present application as PR0245.
  • Applicants have identified and isolated cDNA encoding a PR0245 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a portion of the amino acid sequence of the PR0245 polypeptide has 60% amino acid identity with the human c-myb protein. Accordingly, it is presently believed that the PR0245 polypeptide disclosed in the present application may be a newly identified member of the transmembrane protein tyrosine kinase family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO220, PR0221 and PR0227.
  • PRO220 has amino acid identity with the amino acid sequence of a leucine rich protein wherein the identity is 87 % .
  • PRO220 additionally has amino acid identity with the neuronal leucine rich protein wherein the identity is 55 % .
  • the neuronal leucine rich protein is further described in Taguchi, et al, Mol. Brain Res.. 35:31-40 (1996).
  • PR0221 has amino acid identity with the SLIT protein precursor, wherein different portions of these two proteins have the respective percent identities of 39%, 38%, 34%, 31 %, and 30% .
  • PR0227 has amino acid identity with the amino acid sequence of platelet glycoprotein V precursor. The same results were obtained for human glycoprotein V. Different portions of these two proteins show the following percent identities of 30%, 28%, 28%, 31 %, 35%, 39% and 27%. Accordingly, it is presently believed that PRO220, PR0221 and PR0227 polypeptides disclosed in the present application are newly identified members of the leucine rich repeat protein superfamily and that each possesses protein-protein binding capabilities typical of the leucine rich repeat protein superfamily. It is also believed that they have capabilities similar to those of SLIT, the leucine rich repeat protein and human glycoprotein V.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0258.
  • PR0258 polypeptides referred to in the present application as PR0258.
  • Applicants have identified and isolated cDNA encoding a PR0258 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0258 polypeptide have significant homology with the CRTAM and poliovirus receptors. Accordingly, it is presently believed that PR0258 polypeptide disclosed in the present application is a newly identified member of the Ig superfamily and possesses virus receptor capabilities or regulates immune function as typical of this family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0266.
  • PR0266 polypeptides referred to in the present application as PR0266.
  • Applicants have identified and isolated cDNA encoding a PR0266 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0266 polypeptide have significant homology with the SLIT protein from Drosophilia. Accordingly, it is presently believed that PR0266 polypeptide disclosed in the present application is a newly identified member of the leucine rich repeat family and possesses ligand-ligand binding activity and neuronal development typical of this family.
  • SLIT has been shown to be useful in the study and treatment of Alzheimer's disease, supra, and thus, PR0266 may have involvement in the study and cure of this disease.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0269.
  • PR0269 polypeptides referred to in the present application as PR0269.
  • Applicants have identified and isolated cDNA encoding a PR0269 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST Altschul et al.
  • FAST Altschul et al.
  • sequence alignment computer programs Applicants found that the amino acid sequence encoded by nucleotides 314 to 1783 of the full-length native sequence PR0269 (shown in Figure 35 and SEQ ID NO:95) has significant homology to human urinary thrombomodulin and various thrombomodulin analogues respectively, to which it was aligned. Accordingly, it is presently believed that PR0269 polypeptide disclosed in the present application is a newly identified member of the thrombomodulin family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0287.
  • PR0287 polypeptides referred to in the present application as PR0287.
  • Applicants have identified and isolated cDNA encoding a PR0287 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0287 polypeptide have significant homology with the type 1 procollagen C-proteinase enhancer protein precursor and type 1 procollagen C-proteinase enhancer protein. Accordingly, it is presently believed that PR0287 polypeptide disclosed in the present application is a newly identified member of the C-proteinase enhancer protein family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0214.
  • Applicants have identified and isolated cDNA encoding a PR0214 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a full-length native sequence PR0214 polypeptide (shown in Figure 40 and SEQ ID NO: 109) has 49% amino acid sequence identity with HT protein, a known member of the EGF-family.
  • the comparison resulted in a BLAST score of 920, with 150 matching nucleotides.
  • PR0214 polypeptide disclosed in the present application is a newly identified member of the family comprising EGF domains and may possess activities or properties typical of the EGF-domain containing family. 17.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0317.
  • cDN A encoding a PR0317 polypeptide has been identified and isolated, as disclosed in further detail in the Examples below.
  • BLASTTM and FastATM sequence alignment computer programs it was found that a full-length native-sequence PR0317 (shown in Figure 42 and SEQ ID NO: 114) has 92% amino acid sequence identity with EBAF-1. Further, it is closely aligned with many other members of the TGF- superfamily.
  • PR0317 disclosed in the present application is a newly identified member of the TGF- superfamily and may possess properties that are therapeutically useful in conditions of uterine bleeding, etc.
  • PR0317 may be useful in diagnosing or treating abnormal bleeding involved in gynecological diseases, for example, to avoid or lessen the need for a hysterectomy.
  • PR0317 may also be useful as an agent that affects angiogenesis in general, so PR0317 may be useful in anti-tumor indications, or conversely, in treating coronary ischemic conditions.
  • PR0317 has shown up in several tissues as well, but it does look to have a greater concentration in uterus. Hence, PR0317 may have a broader use by the body than EBAF-1. It is contemplated that, at least for some indications, PR0317 may have opposite effects from EBAF-1.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO301.
  • Applicants have identified and isolated cDNA encoding a PRO301 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a full-length native sequence PRO301 (shown in Figure 44 and SEQ ID NO: 119) has a Blast score of 246 corresponding to 30% amino acid sequence identity with human A33 antigen precursor.
  • PRO301 disclosed in the present application is a newly identified member of the A33 antigen protein family and may be expressed in human neoplastic diseases such as colorectal cancer.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0224.
  • Applicants have identified and isolated cDNA encoding a PR0224 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that full-length native PR0224 ( Figure 46, SEQ ID NO: 127) has amino acid identity with apolipoprotein E receptor 2906 from homo sapiens.
  • the alignments of different portions of these two polypeptides show amino acid identities of 37% , 36% , 30% , 44% , 44% and 28% respectively.
  • Full-length native PR0224 (Figure 46, SEQ ID NO: 127) also has amino acid identity with very low-density lipoprotein receptor precursor from gall. The alignments of different portions of these two polypeptides show amino acid identities of 38% , 37% , 42% , 33% , and 37% respectively. Additionally, full-length native PR0224 (Figure 46, SEQ ID NO: 127) has amino acid identity with the chicken oocyte receptor P95 from Gallus gallus. The alignments of different portions of these two polypeptides show amino acid identities of 38%, 37%, 42%, 33 % , and 37% respectively. Moreover, full-length native PR0224 (Figure 46, SEQ ID NO: 127) has amino acid identity with very low density lipoprotein receptor short form precursor from humans.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0222.
  • Applicants have identified and isolated cDNA encoding a PR0222 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that a sequence encoding full-length native sequence PR0222 (shown in Figure 48 and SEQ ID NO: 132) has 25-26% amino acid identity with mouse complement factor h precursor, has 27-29% amino acid identity with complement receptor, has 25-47% amino acid identity with mouse complement C3b receptor type 2 long form precursor, has 40% amino acid identity with human hypothetical protein kiaa0247.
  • PR0222 polypeptide disclosed in the present application is a newly identified member of the complement receptor family and possesses activity typical of the complement receptor family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0234.
  • Applicants have identified and isolated cDNA encoding a PR0234 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST FastA- format sequence alignment computer programs
  • Applicants found that a cDNA sequence encoding full-length native sequence PR0234 has 31 % identity and Blast score of 134 with E-selectin precursor. Accordingly, it is presently believed that the PR0234 polypeptides disclosed in the present application are newly identified members of the lectin selectin family and possess activity typical of the lectin/selectin family.
  • PR0231 Full-length PRQ231 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0231.
  • Applicants have identified and isolated cDNA encoding a PR0231 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that the full-length native sequence PR0231 polypeptide (shown in Figure 52 and SEQ ID NO: 142) has 30 % and 31 % amino acid identity with human and rat prostatic acid phosphatase precursor proteins, respectively. Accordingly, it is presently believed that the PR0231 polypeptide disclosed in the present application may be a newly identified member of the acid phosphatase protein family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0229.
  • PR0229 polypeptides referred to in the present application as PR0229.
  • Applicants have identified and isolated cDNA encoding a PR0229 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0229 polypeptide have significant homology with antigen wcl. l, M130 antigen, T cell surface glycoprotein CD6 and CD6. It also is related to Sp-alpha.
  • PR0229 polypeptide disclosed in the present application is a newly identified member of the family containing scavenger receptor homology, a sequence motif found in a number of proteins involved in immune function and thus possesses immune function and /or segments which resist degradation, typical of this family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0238.
  • PR0238 polypeptides referred to in the present application as PR0238.
  • Applicants have identified and isolated cDNA encoding a PR0238 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0238 polypeptide have significant homology with reductases, including oxidoreductase and fatty acyl-CoA reductase. Accordingly, it is presently believed that PR0238 polypeptide disclosed in the present application is a newly identified member of the reductase family and possesses reducing activity typical of the reductase family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0233.
  • PR0233 polypeptides referred to in the present application as PR0233.
  • Applicants have identified and isolated cDNA encoding a PR0233 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0233 polypeptide have significant homology with the reductase protein.
  • the DNA encoding the PR0233 polypeptide has significant homology with proteins from Caenorhabditis elegans. Accordingly, it is presently believed that PR0233 polypeptide disclosed in the present application is a newly identified member of the reductase family and possesses the ability to effect the redox state of the cell typical of the reductase family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0223.
  • PR0223 polypeptides referred to in the present application as PR0223.
  • Applicants have identified and isolated cDNA encoding a PR0223 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that the PR0223 polypeptide has significant homology with various serine carboxypeptidase polypeptides. Accordingly, it is presently believed that PR0223 polypeptide disclosed in the present application is a newly identified serine carboxypeptidase.
  • PR0235 Full-length PRQ235 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0235.
  • Applicants have identified and isolated cDNA encoding a PR0235 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0235 polypeptide have significant homology with the various plexin proteins. Accordingly, it is presently believed that PR0235 polypeptide disclosed in the present application is a newly identified member of the plexin family and possesses cell adhesion properties typical of the plexin family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0236 and PR0262.
  • Applicants have identified and isolated cDNA encoding PR0236 and PR0262 polypeptides, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0236 and PR0262 polypeptides have significant homology with various ⁇ -galactosidase and ⁇ - galactosidase precursor polypeptides. Accordingly, it is presently believed that the PR0236 and PR0262 polypeptides disclosed in the present application are newly identified ⁇ -galactosidase homologs.
  • PR0239 Full-length PRQ239 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0239.
  • Applicants have identified and isolated cDNA encoding a PR0239 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0239 polypeptide have significant homology with densin proteins. Accordingly, it is presently believed that PR0239 polypeptide disclosed in the present application is a newly identified member of the densin family and possesses cell adhesion and the ability to effect synaptic processes as is typical of the densin family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0257.
  • PR0257 polypeptides referred to in the present application as PR0257.
  • Applicants have identified and isolated cDNA encoding a PR0257 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0257 polypeptide have significant homology with the ebnerin precursor and ebnerin protein. Accordingly, it is presently believed that PR0257 polypeptide disclosed in the present application is a newly identified protein member which is related to the ebnerin protein.
  • PRO260 Polypeptides The present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO260.
  • Applicants have identified and isolated cDNA encoding a PRO260 polypeptide, as disclosed in further detail in the Examples below.
  • programs such as BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PRO260 polypeptide have significant homology with the alpha-1-fucosidase precursor. Accordingly, it is presently believed that PRO260 polypeptide disclosed in the present application is a newly identified member of the fucosidase family and possesses enzymatic activity related to fucose residues typical of the fucosidase family.
  • PR0263 Full-length polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0263.
  • Applicants have identified and isolated cDNA encoding a PR0263 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0263 polypeptide have significant homology with the CD44 antigen and related proteins.
  • PR0263 polypeptide disclosed in the present application is a newly identified member of the CD44 antigen family and possesses at least one of the properties associated with these antigens, i.e., cancer and HIV marker, cell-cell or cell-matrix interactions, regulating cell traffic, lymph node homing, transmission of growth signals, and presentation of chemokines and growth facors to traveling cells.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO270.
  • Applicants have identified and isolated cDNA encoding a PRO270 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST Altschul et al.
  • FastA sequence alignment computer programs
  • Applicants found that that various portions of the PRO270 polypeptide have significant homology with various thioredoxin proteins. Accordingly, it is presently believed that PRO270 polypeptide disclosed in the present application is a newly identified member of the thioredoxin family and possesses the ability to effect reduction-oxidation (redox) state typical of the thioredoxin family.
  • redox reduction-oxidation
  • PR0271 Full-length PRQ271 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0271.
  • Applicants have identified and isolated cDNA encoding a PR0271 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that the PR0271 polypeptide has significant homology with various link proteins and precursors thereof. Accordingly, it is presently believed that PR0271 polypeptide disclosed in the present application is a newly identified link protein homolog.
  • PR0272 nucleotide sequences encoding polypeptides referred to in the present application as PR0272.
  • Applicants have identified and isolated cDNA encoding a PR0272 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0272 polypeptide have significant homology with the human reticulocalbin protein and its precursors.
  • Applicants have also found that the DNA encoding the PR0272 polypeptide has significant homology with the mouse reticulocalbin precursor protein. Accordingly, it is presently believed that PR0272 polypeptide disclosed in the present application is a newly identified member of the reticulocalbin family and possesses the ability to bind calcium typical of the reticulocalbin family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0294.
  • PR0294 polypeptides referred to in the present application as PR0294.
  • Applicants have identified and isolated cDNA encoding a PR0294 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0294 polypeptide have significant homology with the various portions of a number of collagen proteins. Accordingly, it is presently believed that PR0294 polypeptide disclosed in the present application is a newly identified member of the collagen family.
  • PR0295 nucleotide sequences encoding polypeptides referred to in the present application as PR0295.
  • Applicants have identified and isolated cDNA encoding a PR0295 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0295 polypeptide have significant homology with integrin proteins. Accordingly, it is presently believed that PR0295 polypeptide disclosed in the present application is a newly identified member of the integrin family and possesses cell adhesion typical of the integrin family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0293.
  • PR0293 nucleotide sequences encoding polypeptides referred to in the present application as PR0293.
  • Applicants have identified and isolated cDNA encoding a PR0293 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that portions of the PR0293 polypeptide have significant homology with the neuronal leucine rich repeat proteins 1 and 2, (NLRR-1 and NLRR-2), particularly NLRR-2.
  • PR0293 polypeptide disclosed in the present application is a newly identified member of the neuronal leucine rich repeat protein family and possesses ligand-ligand binding activity typical of the NRLL protein family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0247.
  • PR0247 polypeptides referred to in the present application as PR0247.
  • Applicants have identified and isolated cDNA encoding a PR0247 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0247 polypeptide have significant homology with densin.
  • the DNA encoding the PR0247 polypeptide has significant homology with a number of other proteins, including KIAA0231. Accordingly, it is presently believed that PR0247 polypeptide disclosed in the present application is a newly identified member of the leucine rich repeat family and possesses ligand binding abilities typical of this family.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PRO302, PRO303, PRO304, PRO307 and PR0343.
  • Applicants have identified and isolated cDNA encoding PRO302, PRO303, PRO304, PRO307 and PR0343 polypeptides, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PRO302, PRO303, PRO304, PRO307 and PR0343 polypeptides have significant homology with various protease proteins. Accordingly, it is presently believed that the PRO302, PRO303, PRO304, PRO307 and PR0343 polypeptides disclosed in the present application are newly identified protease proteins.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0328.
  • PR0328 polypeptides referred to in the present application as PR0328.
  • Applicants have identified and isolated cDNA encoding a PR0328 polypeptide, as disclosed in further detail in the Examples below.
  • GLIP human glioblastoma protein
  • Applicants found that various portions of the PR0328 polypeptide have significant homology with the cysteine rich secretory protein (“CRISP”) as identified by BLAST homology [ECCRISP3 1, S68683, and CRS3 HUMAN].
  • CRISP cysteine rich secretory protein
  • PR0328 polypeptide disclosed in the present application is a newly identified member of the GLIP or CRISP families and possesses transcriptional regulatory activity typical of the GLIP or CRISP families. 42. Full-length PRQ335. PRQ331 and PRQ326 Polypeptides
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0335, PR0331 or PR0326.
  • Applicants have identified and isolated cDNA encoding a PR0335, PR0331 or PR0326 polypeptide, as disclosed in further detail in the Examples below.
  • BLAST and FastA sequence alignment computer programs Applicants found that various portions of the PR0335, PR0331 or PR0326 polypeptide have significant homology with LIG-1, ALS and in the case of PR0331, additionally, decorin.
  • PR0335, PR0331 and PR0326 polypeptides disclosed in the present application are newly identified members of the leucine rich repeat superfamily, and particularly, are related to LIG-1 and possess the biological functions of this family as discussed and referenced herein.
  • the present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as PR0332.
  • Applicants have identified and isolated cDNA encoding PR0332 polypeptides, as disclosed in further detail in the Examples below.
  • a full-length native sequence PR0332 (shown in Figure 108 and SEQ ID NO:310) has about 30-40% amino acid sequence identity with a series of known proteoglycan sequences, including, for example, fibromodulin and fibromodulin precursor sequences of various species (FMOD_BOVIN, FMOD_CHICK, FMOD_RAT, FMOD_MOUSE, FMOD.HUMAN, P_R36773), osteomodulin sequences (AB000114_1, AB007848 ), decorin sequences (CFU83141_1, OCU03394 , P R42266, P R42267, P.R42260, P R89439), keratan sulfate proteoglycans (BTU48360.1 , AF022890 .
  • fibromodulin and fibromodulin precursor sequences of various species FMOD_BOVIN, FMOD_CHICK, FMOD_RAT, FMOD_MOUSE, FMOD.HUMAN, P_R36773
  • PR0332 disclosed in the present application is a new proteoglycan-type molecule, and may play a role in regulating extracellular matrix, cartilage, and/or bone function.

Abstract

L'invention concerne des nouveaux polypeptides et des molécules d'acides nucléiques codant pour ces polypeptides. L'invention concerne également des vecteurs et des cellules hôtes comprenant ces séquences d'acides nucléiques, des molécules polypeptidiques chimères comportant les polypeptides selon l'invention, réunis par fusion à des séquences polypeptidiques hétérologues, des anticorps qui se lient aux polypeptides selon l'invention ainsi que des méthodes de production des polypeptides selon l'invention.
PCT/US2000/004414 1994-09-08 2000-02-22 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides WO2001004311A1 (fr)

Priority Applications (781)

Application Number Priority Date Filing Date Title
AU28839/00A AU2883900A (en) 1999-07-07 2000-02-22 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2000603378A JP2003531811A (ja) 1999-03-08 2000-02-24 血管形成及び心臓血管新生の促進又は阻害
AU33816/00A AU768694B2 (en) 1999-03-08 2000-02-24 Promotion or inhibition of angiogenesis and cardiovascularization
KR1020017011378D KR20010104373A (ko) 1999-03-08 2000-02-24 혈관신생 및 심혈관형성의 촉진 또는 억제 방법
CA002361849A CA2361849A1 (fr) 1999-03-08 2000-02-24 Activation et inhibition de l'angiogenese et de la cardiovascularisation
EP00912015A EP1159419A1 (fr) 1999-03-08 2000-02-24 Activation et inhibition de l'angiogenese et de la cardiovascularisation
KR1020017011378A KR100553300B1 (ko) 1999-03-08 2000-02-24 혈관신생 및 심혈관형성의 촉진 또는 억제 방법
PCT/US2000/005004 WO2000053757A2 (fr) 1999-03-08 2000-02-24 Activation et inhibition de l'angiogenese et de la cardiovascularisation
CA002362427A CA2362427A1 (fr) 1999-03-08 2000-03-02 Compositions et methodes de traitement des maladies immunitaires
KR1020017011406A KR20010103046A (ko) 1999-03-08 2000-03-02 면역 관련 질환 치료용 조성물 및 치료 방법
PCT/US2000/005841 WO2000053758A2 (fr) 1999-03-08 2000-03-02 Compositions et methodes de traitement des maladies immunitaires
JP2000603379A JP2004516227A (ja) 1999-03-08 2000-03-02 免疫関連疾患を治療するための組成物と方法
EP00913764A EP1220905A2 (fr) 1999-03-08 2000-03-02 Compositions et methodes pour le traitement de maladies immunitaires
AU35144/00A AU3514400A (en) 1999-03-08 2000-03-02 Compositions and methods for the treatment of immune related diseases
JP2001521746A JP2004500037A (ja) 1999-09-08 2000-03-09 繊維芽細胞成長因子−１９（ｆｇｆ−１９）核酸及びポリペプチド並びに肥満の治療のための利用の方法
ES00917878T ES2264929T3 (es) 1999-09-08 2000-03-09 Acidos nucleicos y polipeptidos del factor 19 de crecimiento fibroblastico (fgf-19) y procedimientos de utilizacion para el tratamiento de la obesidad.
IL14818800A IL148188A0 (en) 1999-09-08 2000-03-09 Fibroblast growth factor-19 (fgf-19) nucleic acids and polypeptides and methods of use for the treatment of obesity
CNA2004100465359A CN1560249A (zh) 1999-09-08 2000-03-09 成纤维细胞生长因子-19（fgf-19）的核酸和多肽以及用于治疗肥胖的方法
CN00815274A CN1387570A (zh) 1999-09-08 2000-03-09 成纤维细胞生长因子－19(fgf－19)的核酸和多肽以及用于治疗肥胖的方法
DE60028054T DE60028054T2 (de) 1999-09-08 2000-03-09 Fibroblasten-wachstumsfaktor-19 (fgf-19) nukleinsäure und polypeptide und verfahren zu deren verwendung für behandlung von fettleibigkeit
PT00917878T PT1214409E (pt) 1999-09-08 2000-03-09 Acidos nucleicos e polipeptidos do factor de crescimento de fibroblastos-19 (fgf-19) e metodos de utilizacao para o tratamento de obesidade
PCT/US2000/006471 WO2001018210A1 (fr) 1999-09-08 2000-03-09 Acides nucleiques et polypeptides du facteur 19 de croissance du fibroblaste, et procedes d'utilisation dans le traitement de l'obesite
AT00917878T ATE326532T1 (de) 1999-09-08 2000-03-09 Fibroblasten-wachstumsfaktor-19 (fgf-19) nukleinsäure und polypeptide und verfahren zu deren verwendung für behandlung von fettleibigkeit
KR1020027003131A KR20020059591A (ko) 1997-10-27 2000-03-09 섬유모세포 성장 인자-19 (ｆｇｆ-19) 핵산 및폴리펩티드, 및 비만 치료를 위한 사용 방법
AU38784/00A AU783117B2 (en) 1999-09-08 2000-03-09 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity
EP00917878A EP1214409B1 (fr) 1999-09-08 2000-03-09 Acides nucleiques et polypeptides du facteur 19 de croissance du fibroblaste, et procedes d'utilisation dans le traitement de l'obesite
DK00917878T DK1214409T3 (da) 1999-09-08 2000-03-09 Fibroblast vækstfaktor-19 (FGF-19) nucleinsyrer og polypeptider samt anvendelsesmetoder til behandling af fedme
CA002384089A CA2384089A1 (fr) 1999-09-08 2000-03-09 Acides nucleiques et polypeptides du facteur 19 de croissance du fibroblaste, et procedes d'utilisation dans le traitement de l'obesite
SI200030879T SI1214409T1 (sl) 1999-09-08 2000-03-09 Nukleinske kisline in polipeptidi fibroblastnega rastnega faktorja-19 (FGF-19) in postopki za uporabo za zdravljenje debelosti
MXPA02002491A MXPA02002491A (es) 1999-09-08 2000-03-09 Acidos nucleicos y polipeptidos del factor 19 de crecimiento de fibroblastos y metodos de uso para tratamiento de la obesidad.
PCT/US2000/008439 WO2000073454A1 (fr) 1999-06-02 2000-03-30 Polypeptides transmembranaires secretes et acides nucleiques codants pour ceux-ci
EP00916675A EP1210418B1 (fr) 1999-06-02 2000-03-30 Polypeptides secretes et transmembranaires ainsi que les acides nucleiques codant pour ceux-ci
AT00916675T ATE478145T1 (de) 1999-06-02 2000-03-30 Sekretierte und transmembran polypeptide und dafür kodierende nukleinsäuren
CA002383254A CA2383254A1 (fr) 1999-06-02 2000-03-30 Polypeptides transmembranaires secretes et acides nucleiques codants pour ceux-ci
AU37743/00A AU3774300A (en) 1999-06-02 2000-03-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2001500766A JP2004522402A (ja) 1999-06-02 2000-03-30 同一のものをコードする分泌及び膜貫通ポリペプチドと核酸
CA2372511A CA2372511C (fr) 1999-06-15 2000-05-22 Polypeptides secretes et transmembranaires et acides nucleiques les codant
AT07025116T ATE449109T1 (de) 1999-06-15 2000-05-22 Sekretierte und transmembran-polypeptide sowie nukleinsäuren zu deren kodierung
AT07025118T ATE448246T1 (de) 1999-06-15 2000-05-22 Sekretierte und transmembran-polypeptide sowie nukleinsäuren zu deren kodierung
EP07025118A EP1956030B1 (fr) 1999-06-15 2000-05-22 Polypeptides sécrétés et transmembranaires, et acides nucléiques les codant
EP07025117A EP1978029A3 (fr) 1999-06-15 2000-05-22 Polypeptides sécrétés et transmembranaires, et acides nucléiques les codant
PCT/US2000/014042 WO2000077037A2 (fr) 1999-06-15 2000-05-22 Polypeptides secretes et transmembranaires et acides nucleiques les codant
EP07025116A EP1953173B1 (fr) 1999-06-15 2000-05-22 Polypeptides sécrétés et transmembranaires, et acides nucléiques les codant
EP00936172A EP1208195A2 (fr) 1999-06-15 2000-05-22 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
AU51527/00A AU5152700A (en) 1999-06-15 2000-05-22 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2001503894A JP2003529324A (ja) 1999-06-15 2000-05-22 分泌及び膜貫通ポリペプチドとそれをコードする核酸
PCT/US2000/015264 WO2000073452A2 (fr) 1999-06-02 2000-06-02 Compositions et methodes de traitement de maladies liees a l'immunite
AU63910/00A AU6391000A (en) 1999-07-28 2000-07-28 Method of preventing the injury or death of retinal cells and treating ocular diseases
PCT/US2000/020710 WO2001009327A2 (fr) 1999-07-28 2000-07-28 Procede de prevention de la deterioration ou de la mort des cellules de la retine et de traitement des troubles oculaires
EP05019538A EP1623992A3 (fr) 1999-09-01 2000-08-24 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
ES05019537T ES2341257T3 (es) 1999-09-01 2000-08-24 Polipeptidos secretados y transmembrana y acidos nucleicos que los codifican.
AU75730/00A AU7573000A (en) 1999-09-01 2000-08-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
CA002645727A CA2645727A1 (fr) 1999-09-01 2000-08-24 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
EP05019540A EP1621620A3 (fr) 1999-09-01 2000-08-24 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
CA002380355A CA2380355A1 (fr) 1999-09-01 2000-08-24 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
DE60043951T DE60043951D1 (de) 1999-09-01 2000-08-24 Ausgeschiedene Polypeptide und Transmembranpolypeptide und dafür kodierende Nukleinsäuren
EP05019539A EP1623993A3 (fr) 1999-09-01 2000-08-24 Protéines sécrétées et transmembranaire et acides nucléiques les codant
EP00964919A EP1208202A2 (fr) 1999-09-01 2000-08-24 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
PCT/US2000/023328 WO2001016318A2 (fr) 1999-09-01 2000-08-24 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
EP07019808A EP1892249A1 (fr) 1999-09-01 2000-08-24 Polypeptides sécrétés et transmembranaires, et acides nucléiques les codant
JP2001520864A JP3951035B2 (ja) 1999-09-01 2000-08-24 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
EP05019537A EP1637541B1 (fr) 1999-09-01 2000-08-24 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
AT05019537T ATE459645T1 (de) 1999-09-01 2000-08-24 Ausgeschiedene polypeptide und transmembranpolypeptide und dafür kodierende nukleinsäuren
EP05019536A EP1623991A3 (fr) 1999-09-01 2000-08-24 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
CA002492049A CA2492049A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
CA002492070A CA2492070A1 (fr) 1999-12-01 2000-12-01 Polypeptides pro4329 marqueurs de tumeurs du poumon et acides nucleiques codant lesdits polypeptides
EP06000581A EP1666494A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretés et transmembranaires et acides nucléiques les codant
CA002490909A CA2490909A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
CA002490853A CA2490853A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
EP06000588A EP1690873A3 (fr) 1999-12-01 2000-12-01 Composition et procédés de diagnostic de tumeurs
CA002496312A CA2496312A1 (fr) 1999-12-01 2000-12-01 Polypeptides du type pro4799, marqueurs de tumeurs du colon, et acides nucleiques codant lesdits polypeptides
CA002494705A CA2494705A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
PCT/US2000/032678 WO2001040466A2 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
CA2709291A CA2709291A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
JP2001542531A JP2004522404A (ja) 1999-12-01 2000-12-01 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
EP06000583A EP1686134A3 (fr) 1999-12-01 2000-12-01 Polypeptides transmembranaires et secrétés et les acides nucléiques codant ceux-ci
CA002491610A CA2491610A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
EP06000586A EP1688497A1 (fr) 1999-12-01 2000-12-01 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
EP05025102A EP1672070A3 (fr) 1999-12-01 2000-12-01 Polypeptides secrétés et transmembranaires et acides nucléiques codant pour ceux-ci
EP06000589A EP1661997A1 (fr) 1999-12-01 2000-12-01 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
CA002491433A CA2491433A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
EP06000582A EP1666495A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretés et transmembranaires et acides nucléiques les codant
EP10005292A EP2228446A1 (fr) 1999-12-01 2000-12-01 Polypeptides secrétés et transmembranaires et acides nucléiques codant pour ceux-ci
EP00983846A EP1250426A2 (fr) 1999-12-01 2000-12-01 Polypeptides transmembranaires et secretes et les acides nucleiques codant ceux-ci
CA002491258A CA2491258A1 (fr) 1999-12-01 2000-12-01 polypeptides transmembranaires et secretes et acides nucleiques codant ces polypeptides
CA002391455A CA2391455A1 (fr) 1999-12-01 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
EP06000584A EP1669371A3 (fr) 1999-12-01 2000-12-01 Composition et procédés de diagnostic de tumeurs
AU20554/01A AU2055401A (en) 1999-12-01 2000-12-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
EP06000585A EP1661996A1 (fr) 1999-12-01 2000-12-01 Polypeptides sécrétés et transmembranaires ainsi que les acides nucléiques codant pour ceux-ci
EP06000587A EP1690872A3 (fr) 1999-12-01 2000-12-01 Composition et procédés de diagnostic de tumeurs
US09/767,609 US20020042367A1 (en) 1997-11-25 2001-01-22 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity and related disorders
US09/828,366 US20020010137A1 (en) 1997-09-18 2001-04-05 Methods and compositions for inhibiting neoplastic cell growth
US09/866,028 US6642360B2 (en) 1997-12-03 2001-05-25 Secreted polypeptides that stimulate release of proteoglycans from cartilage
US09/902,736 US20030049676A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,692 US20030054400A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,572 US20030108983A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,903 US20030044839A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,775 US6686451B1 (en) 1997-10-24 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,736 US6894148B2 (en) 1997-11-12 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,759 US20030077654A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,634 US20030082540A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,853 US20020192659A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,979 US20030113718A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,615 US20030092002A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/902,713 US20030082541A1 (en) 1997-09-17 2001-07-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,749 US7147853B2 (en) 1997-09-17 2001-07-11 Anti-pro211 polypeptide antibodies
US09/903,640 US7208308B2 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,119 US20030049621A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids enconding the same
US09/903,925 US20030096233A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,011 US20030003530A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,786 US20030044793A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,562 US6965015B2 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,603 US6767995B2 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,823 US20030104381A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,806 US20030130489A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,520 US20030054401A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,603 US20030148419A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/903,943 US20030054349A1 (en) 1997-09-17 2001-07-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,125 US6664376B2 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,766 US20030152999A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,992 US20030135025A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,786 US7557192B2 (en) 1997-09-17 2001-07-12 Anti-PRO335 antibodies
US09/904,877 US20030186358A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,088 US20030073077A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,938 US20030211569A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,056 US20030054441A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,291 US20020160374A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,805 US20030211568A1 (en) 1997-10-27 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,859 US20030036060A1 (en) 1997-09-17 2001-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,553 US20030059828A1 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,348 US20030064923A1 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,381 US6818746B2 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,462 US6878807B2 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,485 US20030064367A1 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/905,075 US7169906B2 (en) 1997-09-17 2001-07-13 PRO211 polypeptides
US09/905,449 US6965011B2 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,838 US20030148370A1 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,920 US6806352B2 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,820 US20030036094A1 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,532 US7151160B2 (en) 1997-09-17 2001-07-13 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/904,956 US20030049622A1 (en) 1995-12-01 2001-07-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,722 US6946262B2 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,700 US6723535B2 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,618 US6828146B2 (en) 1997-09-17 2001-07-16 Nucleic acid encoding PRO229 polypeptides
US09/906,815 US7094567B2 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,777 US20030148371A1 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,742 US20030023054A1 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,838 US7070979B2 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,760 US20030096340A1 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/906,679 US6974689B1 (en) 1997-09-18 2001-07-16 Nucleic acid encoding PRO211 polypeptides
US09/906,646 US6852848B2 (en) 1997-09-17 2001-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,841 US7033825B2 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,613 US20030027145A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,979 US20030082542A1 (en) 1994-09-08 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/908,093 US20030017498A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,794 US6635468B2 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,728 US20030190611A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,575 US20030073079A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,942 US7087738B2 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,925 US20030054352A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,824 US20020197671A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/907,652 US20030104469A1 (en) 1997-09-17 2001-07-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/909,320 US7074592B2 (en) 1997-09-17 2001-07-18 Secreted and transmembrane polypeptides nucleic acid encoding
US09/909,088 US20020146709A1 (en) 1997-09-17 2001-07-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/909,204 US20030036061A1 (en) 1997-09-17 2001-07-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/908,576 US20040005553A1 (en) 1997-09-17 2001-07-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/909,064 US6818449B2 (en) 1997-09-17 2001-07-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/924,647 US20020155543A1 (en) 1997-11-25 2001-08-07 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity and related disorders
US09/941,992 US20030082546A1 (en) 1996-11-06 2001-08-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/943,780 US20030096742A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/943,762 US20020142958A1 (en) 1998-09-16 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,396 US20020132981A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,413 US20020156004A1 (en) 1998-09-16 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,457 US6734288B2 (en) 1997-12-03 2001-08-30 Antibodies against a secreted polypeptide that stimulates release of proteoglycans from cartilage
US09/944,449 US20020102647A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/943,851 US20020150976A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/943,664 US20040091972A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,403 US20020165143A1 (en) 1997-12-03 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,432 US20020142419A1 (en) 1998-09-16 2001-08-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,862 US20020115145A1 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,852 US20030083479A1 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,654 US20020142959A1 (en) 1998-09-16 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/945,587 US6936254B2 (en) 1997-12-03 2001-08-31 Method of inducing fetal hemoglobin synthesis
US09/944,896 US7189566B2 (en) 1997-12-03 2001-08-31 PRO347 nucleic acids
US09/944,929 US7550573B2 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/945,584 US6908993B2 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,944 US6929947B2 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/945,015 US20020132768A1 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/944,884 US7018837B2 (en) 1997-12-03 2001-08-31 Nucleic acids encoding secreted polypeptides that stimulate release of proteoglycans from cartilage
US09/944,907 US20020198147A1 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,438 US20030027754A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,436 US20020198148A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/993,583 US7074897B2 (en) 1997-06-16 2001-11-14 Pro943 polypeptides
US09/993,667 US20030022187A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,726 US20030054359A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,562 US20030027985A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/991,163 US20020132253A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,456 US20020137890A1 (en) 1997-03-31 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/993,469 US20030068623A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/992,598 US6956108B2 (en) 1997-06-16 2001-11-14 PRO1184 antibodies
US09/990,427 US20030073809A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,442 US20020132252A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/991,854 US20030059780A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,444 US6930170B2 (en) 1997-06-16 2001-11-14 PRO1184 polypeptides
US09/991,073 US20020127576A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,443 US20030054987A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/993,687 US20020198149A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,711 US20030032023A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/992,521 US20030083461A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,440 US20030060407A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/993,748 US20030069403A1 (en) 1997-06-16 2001-11-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,573 US20030049682A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,653 US7034122B2 (en) 1997-06-16 2001-11-15 Antibodies to PRO1159 polypeptides
US09/997,641 US20030224358A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,683 US20030059783A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,666 US20030027163A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,857 US20030064375A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,585 US20030119055A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/002,796 US20030032057A1 (en) 1997-08-26 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,641 US7112656B2 (en) 1997-06-16 2001-11-15 PRO1312 polypeptides
US09/997,542 US20030068647A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,440 US20030059833A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,628 US20030059782A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,601 US7189814B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/998,041 US7309775B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,529 US20030134284A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,529 US7309761B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,428 US20030027162A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/998,156 US20030044806A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,585 US7166282B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,559 US20030054403A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,349 US7034106B2 (en) 1997-06-16 2001-11-15 Pro1159 polypeptides
US09/997,384 US7119177B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,614 US20030124531A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/998,041 US20030119001A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,333 US6953836B2 (en) 1997-06-16 2001-11-15 PRO844 polypeptides
US09/997,666 US7244816B2 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,601 US20030054404A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/997,514 US7019116B2 (en) 1997-06-16 2001-11-15 PRO 1387 polypeptides
US09/997,384 US20030087305A1 (en) 1997-06-16 2001-11-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/991,172 US20030050457A1 (en) 1997-06-16 2001-11-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,437 US20030045463A1 (en) 1997-06-16 2001-11-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/991,150 US20030194760A1 (en) 1997-06-16 2001-11-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/991,181 US6913919B2 (en) 1997-06-16 2001-11-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/990,441 US7041804B2 (en) 1997-06-16 2001-11-16 Antibodies to PRO1387 polypeptides
US09/991,157 US7101687B2 (en) 1997-06-16 2001-11-16 Nucleic acids encoding PRO943
US09/989,862 US20030130182A1 (en) 1997-11-05 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,723 US20020072092A1 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,328 US7056736B2 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,729 US20030059831A1 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,734 US7491529B2 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,726 US7018811B2 (en) 1997-06-16 2001-11-19 Nucleic acids encoding PRO189 polypeptides
US09/989,279 US7083978B2 (en) 1997-06-16 2001-11-19 Nucleic acid encoding PRO1111 polypeptides
US09/989,732 US7037679B2 (en) 1997-06-16 2001-11-19 Nucleic acids encoding PRO1184 polypeptides
US09/989,735 US6972185B2 (en) 1997-06-16 2001-11-19 Nucleic acids encoding PRO844 polypeptides
US09/989,721 US20020142961A1 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,727 US20020072497A1 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,722 US20020072067A1 (en) 1997-06-16 2001-11-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,293 US7034136B2 (en) 1997-06-16 2001-11-20 Nucleic acids encoding PRO1159 polypeptides
US09/989,725 US20030139329A1 (en) 1997-06-16 2001-11-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,728 US7029873B2 (en) 1997-06-16 2001-11-20 Nucleic acids to PRO1387 polypeptides
US09/989,731 US20020103125A1 (en) 1997-06-16 2001-11-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US09/989,730 US7157247B2 (en) 1997-06-16 2001-11-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/006,867 US7160985B2 (en) 1997-10-29 2001-12-06 Pro180 polypeptide
US10/028,072 US20030004311A1 (en) 1997-06-18 2001-12-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,244 US20020192668A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/032,996 US20030054447A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/032,990 US20030032060A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,301 US20020098506A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,245 US20020160392A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,223 US20020164646A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,167 US20020182618A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,326 US20020098507A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,435 US20030027256A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,396 US20030077657A1 (en) 1998-08-04 2001-12-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/033,246 US20020098505A1 (en) 1998-08-04 2001-12-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/052,586 US20020127584A1 (en) 1997-09-18 2002-01-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,500 US20020177165A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding
US10/066,198 US20030170721A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,273 US7317092B2 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,269 US20030040014A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,203 US20030180796A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,211 US20030044844A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,494 US20030032063A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/066,193 US20030044902A1 (en) 1997-08-26 2002-02-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/081,056 US20040043927A1 (en) 1997-09-19 2002-02-20 Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis
US10/119,480 US20040087769A1 (en) 1998-09-10 2002-04-09 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,046 US20030194791A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,042 US20030096386A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,051 US20030092147A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,044 US20030190717A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,059 US20030190721A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,045 US20030073210A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,041 US20030077776A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,040 US20030082759A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,047 US20030077778A1 (en) 1997-03-31 2002-04-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,049 US20030022239A1 (en) 1997-06-18 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,043 US7220831B2 (en) 1997-03-31 2002-04-12 PRO235 polypeptides
US10/121,061 US20030082761A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,053 US20030199053A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,048 US20030199051A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,058 US20030190720A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,062 US20030077779A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,055 US20030190718A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,056 US20030082760A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,052 US20030199052A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,054 US20030199054A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,050 US20030054516A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,057 US20030190719A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,060 US20030190722A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/121,063 US20030199055A1 (en) 1997-03-31 2002-04-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,236 US20030068795A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,109 US20030190723A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,322 US20030199059A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,261 US20030068796A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,213 US7193048B2 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,214 US7343721B2 (en) 1997-03-31 2002-04-15 PRO4406 polypeptide
US10/123,154 US20030190724A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,292 US20030073211A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,156 US20030194792A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,212 US7276577B2 (en) 1997-03-31 2002-04-15 PRO1866 polypeptides
US10/123,215 US7291329B2 (en) 1997-03-31 2002-04-15 Antibodies against PRO4406
US10/123,108 US7635478B2 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,155 US20030068794A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,235 US20030082762A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,262 US20030049816A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,213 US20030199057A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,291 US20030199058A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,157 US20030190725A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,292 US7045603B2 (en) 1997-11-24 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,771 US20030199060A1 (en) 1997-03-31 2002-04-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,913 US20030203462A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,909 US7193049B2 (en) 1997-03-31 2002-04-16 PRO862 polypeptides
US10/123,910 US7329404B2 (en) 1997-03-31 2002-04-16 Antibodies against PRO1310
US10/123,902 US20030077781A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,907 US7084258B2 (en) 1997-03-31 2002-04-16 Antibodies against the PRO862 polypeptides
US10/123,906 US20030190726A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,911 US7408032B2 (en) 1997-03-31 2002-04-16 PRO1188 polypeptides
US10/123,905 US7285625B2 (en) 1997-06-18 2002-04-16 PRO536 polypeptides
US10/123,905 US20030087344A1 (en) 1997-06-18 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,903 US20030073212A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,908 US7335728B2 (en) 1997-03-31 2002-04-16 PRO1310 polypeptides
US10/123,904 US20030022328A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/123,912 US20030100087A1 (en) 1997-03-31 2002-04-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,821 US20030199023A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,824 US20030077659A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,817 US20030077786A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,814 US7105335B2 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,818 US20030082763A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,820 US20030190729A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/125,166 US20030039648A1 (en) 1998-09-16 2002-04-17 Compositions and methods for the diagnosis and treatment of tumor
US10/124,816 US20030190728A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,823 US20030199062A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,813 US7312307B2 (en) 1997-03-31 2002-04-17 PRO1056 polypeptides
US10/125,795 US7304131B2 (en) 1997-03-31 2002-04-17 PRO1483 polypeptides
US10/124,819 US7285626B2 (en) 1997-03-31 2002-04-17 PRO1076 polypeptides
US10/125,805 US20030194794A1 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/124,822 US7109305B2 (en) 1997-03-31 2002-04-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/125,704 US7357926B2 (en) 1997-03-31 2002-04-17 Antibodies against PRO1879 and the use thereof
US10/125,931 US20030199063A1 (en) 1997-03-31 2002-04-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/125,922 US7309762B2 (en) 1997-03-31 2002-04-19 PRO1360 polypeptides
US10/125,924 US7342097B2 (en) 1997-03-31 2002-04-19 PRO1309 polypeptides
US10/125,927 US20030190731A1 (en) 1997-03-31 2002-04-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/125,932 US7317079B2 (en) 1997-03-31 2002-04-19 PRO812 polypeptides
US10/127,831 US20030082689A1 (en) 1997-03-31 2002-04-22 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/128,689 US20030087365A1 (en) 1997-03-31 2002-04-23 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/131,817 US7291701B2 (en) 1997-03-31 2002-04-24 PRO1777 polypeptides
US10/131,815 US20030092103A1 (en) 1998-12-22 2002-04-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/131,823 US7304132B2 (en) 1997-03-31 2002-04-24 PRO1693 polypeptides
US10/131,825 US7282566B2 (en) 1997-03-31 2002-04-24 PRO1779 polypeptide
US10/137,867 US20030207349A1 (en) 1997-03-31 2002-05-03 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/137,865 US20030032155A1 (en) 1997-03-31 2002-05-03 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/137,868 US20030082764A1 (en) 1997-03-31 2002-05-03 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,024 US20040058424A1 (en) 1997-03-31 2002-05-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/139,963 US7288625B2 (en) 1997-03-31 2002-05-06 PRO4395 polypeptides
US10/139,980 US7247710B2 (en) 1997-03-31 2002-05-06 PRO4395 antibodies
US10/140,023 US20030207416A1 (en) 1997-03-31 2002-05-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,020 US20030207415A1 (en) 1997-03-31 2002-05-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,474 US20030032156A1 (en) 1997-03-31 2002-05-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,470 US20030022331A1 (en) 1997-03-31 2002-05-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,928 US20030068798A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,808 US7425621B2 (en) 1997-03-31 2002-05-07 Antibodies against the PRO4401 polypeptide
US10/140,805 US20030207417A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/063,651 US7193057B2 (en) 1997-10-29 2002-05-07 Antibodies to a polypeptide encoded by a nucleic acid underexpressed in rectal tumor
US10/140,925 US20030073215A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,865 US20030207420A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,860 US7307151B2 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,921 US7317080B2 (en) 1997-03-31 2002-05-07 PRO4303 polypeptides
US10/140,864 US20030207419A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/140,809 US20030207418A1 (en) 1997-03-31 2002-05-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/141,756 US7488586B2 (en) 1997-03-31 2002-05-08 PRO4409 polypeptides
US10/141,701 US20030207421A1 (en) 1997-03-31 2002-05-08 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/141,754 US7361732B2 (en) 1997-03-31 2002-05-08 PRO4400 polypeptides
US10/141,760 US7342104B2 (en) 1997-03-31 2002-05-08 Antibodies against the PRO4320 polypeptide
US10/141,755 US7297764B2 (en) 1997-03-31 2002-05-08 PRO4318 polypeptides
US10/143,113 US7329730B2 (en) 1997-03-31 2002-05-09 PRO4348 polypeptides
US10/143,114 US20030036180A1 (en) 1997-03-31 2002-05-09 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/142,425 US20030207424A1 (en) 1997-03-31 2002-05-09 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/142,430 US7309766B2 (en) 1997-03-31 2002-05-09 PRO5774 polypeptides
US10/142,417 US7304133B2 (en) 1997-03-31 2002-05-09 PRO4389 polypeptides
US10/143,032 US7408033B2 (en) 1997-03-31 2002-05-10 PRO5995 polypeptides
US10/142,419 US7153941B2 (en) 1997-03-31 2002-05-10 Antibodies that bind PRO4994 polypeptides
US10/142,431 US7285629B2 (en) 1997-03-31 2002-05-10 Pro5005 polypeptides
US10/142,423 US20030049817A1 (en) 1997-03-31 2002-05-10 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/145,627 US20030180869A1 (en) 1997-09-17 2002-05-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/145,753 US20030207372A1 (en) 1997-11-03 2002-05-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/145,876 US20030134371A1 (en) 1997-10-29 2002-05-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/145,875 US20030166079A1 (en) 1997-09-17 2002-05-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/146,792 US20030207428A1 (en) 1997-03-31 2002-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/146,789 US20030180872A1 (en) 1997-11-24 2002-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/146,730 US20030207427A1 (en) 1997-03-31 2002-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/146,786 US20030203438A1 (en) 1997-11-24 2002-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/146,794 US20030207375A1 (en) 1997-10-24 2002-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/147,528 US20030219885A1 (en) 1997-03-31 2002-05-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/147,536 US20040077064A1 (en) 1997-03-31 2002-05-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/147,492 US20030082765A1 (en) 1997-03-31 2002-05-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/147,519 US20030077791A1 (en) 1997-03-31 2002-05-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/152,373 US20030186367A1 (en) 1998-12-22 2002-05-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/152,395 US7189534B2 (en) 1997-03-31 2002-05-21 PRO4320 polynucleotide
US10/153,934 US20030129695A1 (en) 1997-03-31 2002-05-22 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/156,843 US20030207805A1 (en) 1997-06-18 2002-05-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/157,786 US20030208055A1 (en) 1997-03-31 2002-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/157,782 US20030077792A1 (en) 1997-03-31 2002-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/158,782 US20030082766A1 (en) 1997-03-31 2002-05-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/160,498 US20030073216A1 (en) 1997-03-31 2002-05-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/158,791 US20030207429A1 (en) 1997-03-31 2002-05-30 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,701 US20030104538A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,707 US20030166110A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,690 US20030166105A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,695 US20030032101A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,703 US20030170794A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,706 US20030022293A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,699 US20030166109A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,704 US20030170795A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,696 US20030082767A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,702 US20030170793A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,708 US20030040053A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,698 US20030166108A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,689 US20030166104A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,691 US20030166106A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,694 US20030166107A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,700 US20030027262A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,693 US20030073169A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,697 US20030032102A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,705 US20030032103A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/173,692 US20030166188A1 (en) 1997-09-18 2002-06-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,582 US20030027265A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,740 US20030027268A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,588 US20030027266A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,583 US7211645B2 (en) 1997-09-18 2002-06-18 PRO268 polypeptides
US10/174,574 US20030170796A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,587 US20030166113A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,589 US20030166114A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,590 US20030008352A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,591 US20030166115A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,572 US20030027263A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,579 US20030027264A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,570 US20030211572A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,578 US20030073170A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,569 US20030166111A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,585 US20030032105A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,586 US20030032106A1 (en) 1997-09-18 2002-06-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/174,581 US7153939B2 (en) 1997-09-18 2002-06-18 PRO354 antibodies
US10/174,576 US7125962B2 (en) 1997-09-18 2002-06-18 Anti-Pro268 antibodies
US10/175,750 US20030073172A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,749 US20050196832A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,747 US20030032107A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,743 US20030027269A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,748 US20030166121A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,741 US20030073171A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,739 US20030027267A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,738 US20030022294A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,735 US20030082715A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,751 US20030166122A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,746 US20030027270A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,754 US20030166123A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,752 US20030022295A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,744 US20030166119A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,753 US20030077732A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,742 US20030166118A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,737 US20030013153A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,736 US20030166117A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/175,745 US20030166120A1 (en) 1997-09-18 2002-06-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,746 US20030068680A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,989 US20030170803A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,747 US20030027273A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,479 US20030040054A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,757 US7317082B2 (en) 1997-09-18 2002-06-20 PRO1018 polypeptides
US10/176,981 US20030170800A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,749 US20030017542A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,754 US7709602B2 (en) 1997-09-18 2002-06-20 PRO1078 polypeptides
US10/176,921 US20030027276A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,482 US20030022296A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,911 US20030032113A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,484 US20030059876A9 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,919 US20030032114A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,483 US20030017541A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,485 US20030032109A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,990 US20030036119A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,487 US20030032110A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,918 US7495083B2 (en) 1997-09-18 2002-06-20 PRO940 antibodies
US10/176,988 US20030170802A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,759 US20030166128A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,917 US20030044918A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,491 US20030087373A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,753 US20030044917A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,493 US20030032111A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,993 US20030027280A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,913 US20030022298A1 (en) 1997-09-15 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,914 US20030017543A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,920 US20030166129A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,490 US20030170798A1 (en) 1997-09-18 2002-06-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,481 US20030032108A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,982 US20030044919A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,991 US20030027324A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,492 US20030027272A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,488 US20030027271A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,915 US20030017544A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,985 US20030027277A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,992 US20030027279A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,748 US20030040055A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,489 US20030166125A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,979 US20030087374A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,750 US20030027274A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,758 US20030008353A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,983 US20030170801A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,924 US20030166131A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,756 US20030032112A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,916 US20030040056A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,978 US20030032116A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,760 US7339033B2 (en) 1998-06-26 2002-06-21 Pro1481
US10/176,923 US20030068681A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,925 US20030032115A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,986 US20030073173A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,751 US20030036117A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,755 US20030166127A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,922 US20030166130A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,987 US20030027278A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,486 US7354999B2 (en) 1997-09-18 2002-06-21 PRO1481 polypeptides
US10/176,480 US20030166124A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/176,752 US20030170799A1 (en) 1997-09-18 2002-06-21 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,515 US20030166135A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,508 US20030166133A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,511 US20030104539A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,522 US20030044923A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,506 US20030044920A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,523 US20030215909A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,512 US20030166134A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,507 US20030040057A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,525 US20030040060A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,516 US20030040058A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,520 US20030096353A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,514 US20030044922A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,521 US20030170806A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,518 US20030104540A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,519 US7339024B2 (en) 1997-09-18 2002-06-24 PRO1772 polypeptides
US10/179,509 US20030207392A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,510 US20030032117A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,513 US20030044921A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,517 US20030170805A1 (en) 1997-09-18 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/179,526 US20030100061A1 (en) 1998-06-26 2002-06-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,555 US20030032123A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,549 US20030032122A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,541 US20030036120A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,550 US20030064440A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,544 US20030032119A1 (en) 1998-06-26 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,560 US20030044925A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,548 US7696319B2 (en) 1997-09-18 2002-06-25 PRO1772 antibodies
US10/180,556 US7355000B2 (en) 1997-09-18 2002-06-25 PRO1380 polypeptides
US10/180,542 US20030036121A1 (en) 1998-06-26 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,546 US20030032120A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,559 US20030032124A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,557 US20030022301A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,552 US7348415B2 (en) 1997-09-18 2002-06-25 PRO1316 antibodies
US10/180,554 US20050202526A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,547 US20030032121A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,540 US20030040061A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,553 US7365156B2 (en) 1997-09-18 2002-06-25 PRO1316 polypeptides
US10/180,545 US20030040062A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,551 US20030036123A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,543 US20030032118A1 (en) 1997-09-18 2002-06-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,018 US20030104541A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/180,999 US7297767B2 (en) 1997-09-18 2002-06-26 PRO1374 polypeptides
US10/183,010 US20030032126A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,011 US20030068682A1 (en) 1998-06-26 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,006 US7297776B2 (en) 1997-09-18 2002-06-26 PRO1374 antibodies
US10/180,998 US7087421B2 (en) 1997-09-18 2002-06-26 Pro1278 polypeptides
US10/183,002 US20030054454A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,015 US20030044926A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,001 US7084255B2 (en) 1997-09-18 2002-06-26 PRO1278 polypeptides
US10/181,000 US7319137B2 (en) 1997-09-18 2002-06-26 PRO1339 polypeptides
US10/183,016 US20030082717A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,014 US20030064441A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,012 US7718770B2 (en) 1997-09-18 2002-06-26 PRO1305-polypeptides
US10/183,013 US7309769B2 (en) 1997-09-18 2002-06-26 PRO1487 polypeptides
US10/183,003 US20030082716A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,008 US20030040064A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/183,009 US7339034B2 (en) 1997-09-18 2002-06-26 PRO1305 antibodies
US10/183,005 US7317093B2 (en) 1997-09-18 2002-06-26 PRO1339 antibodies
US10/183,019 US7425605B2 (en) 1997-09-18 2002-06-26 PRO1486 polypeptides
US10/183,017 US20030040065A1 (en) 1997-09-18 2002-06-26 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,627 US20030040070A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,651 US7291704B2 (en) 1997-09-18 2002-06-27 PRO1758 polypeptides
US10/184,612 US20030036127A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,618 US7393917B2 (en) 1997-09-18 2002-06-27 PRO1482 polypeptides
US10/184,628 US7309770B2 (en) 1997-09-18 2002-06-27 PRO1757 polypeptides
US10/184,641 US20030073174A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,631 US20030036134A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,613 US20030119105A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,652 US20030032134A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,630 US20030036133A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,627 US7282569B2 (en) 1997-09-18 2002-06-27 PRO1508 antibodies
US10/184,638 US20030054456A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,630 US7304143B2 (en) 1997-09-18 2002-06-27 PRO1571 antibodies
US10/184,615 US20030044927A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,616 US20030036128A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,619 US20030049738A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,642 US7332573B2 (en) 1997-09-18 2002-06-27 PRO1571 polypeptides
US10/184,654 US7378486B2 (en) 1997-09-18 2002-06-27 PRO1482 antibodies
US10/184,614 US20030032128A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,640 US7271250B2 (en) 1998-06-26 2002-06-27 PRO1757 antibodies
US10/184,633 US20030068683A1 (en) 1997-09-18 2002-06-27 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,646 US20030032132A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,632 US20030036135A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,626 US20030040069A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,636 US20030036136A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,647 US20030032133A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,658 US20030027281A1 (en) 1998-06-26 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,617 US20030036129A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,656 US20030044931A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,645 US7291718B2 (en) 1998-06-26 2002-06-28 PRO1758 antibodies
US10/184,637 US20030032131A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,635 US20030032130A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,650 US20030036138A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,625 US20030040068A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,657 US20030104543A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,624 US20030104542A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,643 US20030044929A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,655 US20030040073A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,629 US20030036132A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,634 US20030068684A1 (en) 1998-06-26 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,621 US20030054455A1 (en) 1998-06-26 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,623 US20030032129A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,644 US20030044930A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,620 US20030044928A1 (en) 1997-09-18 2002-06-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/184,622 US20030036130A1 (en) 1997-09-18 2002-06-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,594 US7294335B2 (en) 1998-06-26 2002-07-01 PRO19645 antibodies
US10/187,598 US20030036142A1 (en) 1997-09-18 2002-07-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,739 US7291706B2 (en) 1998-06-26 2002-07-01 PRO4352 polypeptides
US10/187,588 US7351795B2 (en) 1998-06-26 2002-07-01 PRO19563 polypeptides
US10/187,887 US7285645B2 (en) 1997-09-18 2002-07-01 PRO4356 antibodies
US10/187,747 US7291707B2 (en) 1997-09-18 2002-07-01 PRO1337 polypeptides
US10/187,597 US20030036141A1 (en) 1997-09-18 2002-07-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,886 US7291708B2 (en) 1997-09-18 2002-07-01 PRO1785 polypeptides
US10/187,884 US20030036155A1 (en) 1997-09-18 2002-07-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,601 US7291705B2 (en) 1997-09-18 2002-07-01 PRO19645 polypeptides
US10/187,754 US20030036153A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,770 US7358340B2 (en) 1997-09-18 2002-07-02 PRO19563 antibodies
US10/187,596 US20030032136A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,600 US20030036143A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,603 US20030036146A1 (en) 1998-06-26 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,746 US20030036149A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,743 US20030036148A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,747 US20030036150A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,751 US20030036151A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,780 US7268217B2 (en) 1998-06-26 2002-07-02 PRO4421 polypeptides
US10/188,773 US20030036159A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,775 US20030040075A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,602 US20030036145A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,767 US7312310B2 (en) 1997-09-18 2002-07-02 PRO6015 polypeptides
US10/188,774 US20030040074A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,769 US20030036157A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,885 US20030032138A1 (en) 1998-06-24 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,757 US7276578B2 (en) 1997-09-18 2002-07-02 PRO4334 polypeptides
US10/187,753 US20030036152A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,781 US20030036160A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/187,741 US20030036147A1 (en) 1997-09-18 2002-07-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/188,766 US7351804B2 (en) 1998-06-26 2002-07-02 Antibodies against PRO4421
US10/187,745 US7250490B2 (en) 1997-09-18 2002-07-02 PRO1480 polypeptides
US10/192,010 US20030044932A1 (en) 1997-09-18 2002-07-09 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/194,365 US7381791B2 (en) 1998-06-26 2002-07-12 PRO9739 polypeptides
US10/194,461 US20030054459A1 (en) 1998-06-26 2002-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/194,423 US7339025B2 (en) 1998-06-26 2002-07-12 PRO6246 polypeptides
US10/194,361 US20030036161A1 (en) 1998-06-26 2002-07-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/194,462 US7388073B2 (en) 1998-06-26 2002-07-12 PRO9835 polypeptides
US10/195,902 US20030038826A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,893 US20030206188A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,897 US20030036164A1 (en) 1997-09-18 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,883 US20060073544A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,894 US20030043176A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,892 US7385033B2 (en) 1998-06-26 2002-07-15 PRO12970 polypeptides
US10/195,889 US7534856B2 (en) 1998-06-26 2002-07-15 PRO19624 antibodies
US10/195,888 US20060073545A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/195,901 US20030036165A1 (en) 1998-06-26 2002-07-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/196,743 US20030038827A1 (en) 1998-06-26 2002-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/196,745 US7423120B2 (en) 1997-09-18 2002-07-16 PRO19814 polypeptides
US10/196,759 US20030071835A1 (en) 1998-06-26 2002-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/196,760 US7408034B2 (en) 1998-06-26 2002-07-16 PRO20025 polypeptides
US10/196,756 US7304145B2 (en) 1998-06-26 2002-07-16 PRO19646 antibodies
US10/196,762 US20030040078A1 (en) 1998-06-26 2002-07-16 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/199,316 US20030068726A1 (en) 1998-06-26 2002-07-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/199,464 US20030032140A1 (en) 1997-09-18 2002-07-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/198,768 US20030049756A1 (en) 1998-06-26 2002-07-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/199,462 US20030054468A1 (en) 1998-06-26 2002-07-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/202,938 US20030104551A1 (en) 1997-10-31 2002-07-24 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/205,904 US20030073813A1 (en) 1998-06-26 2002-07-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/215,371 US20040137561A1 (en) 1997-10-17 2002-08-08 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/226,739 US7390879B2 (en) 1999-06-15 2002-08-23 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2002341509A JP4017507B2 (ja) 1999-06-02 2002-09-25 ポリペプチドを含有する医薬
US10/265,542 US20030171568A1 (en) 1998-09-16 2002-10-03 Use of A33 antigens and JAM-IT
US10/299,976 US20030180312A1 (en) 2000-02-22 2002-11-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/299,937 US20030185846A1 (en) 1998-09-16 2002-11-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/298,993 US20030211576A1 (en) 2000-02-22 2002-11-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/336,979 US20050026243A1 (en) 1997-11-25 2003-01-02 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity and related disorders
US10/425,447 US20040023331A1 (en) 1997-10-24 2003-04-28 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/429,667 US20030207401A1 (en) 1997-12-03 2003-05-01 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/439,249 US20030228664A1 (en) 1998-12-16 2003-05-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/448,713 US20040006211A1 (en) 1997-10-24 2003-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/448,923 US7241865B2 (en) 1997-10-24 2003-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/449,656 US20040005665A1 (en) 1997-10-24 2003-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/448,580 US7208312B1 (en) 1997-09-17 2003-05-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/633,008 US7192589B2 (en) 1998-09-16 2003-07-31 Treatment of inflammatory disorders with STIgMA immunoadhesins
US10/712,560 US20040146908A1 (en) 1997-11-25 2003-11-12 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity and related disorders
US10/735,014 US7442772B2 (en) 1997-12-03 2003-12-12 Antibodies to PRO361 polypeptide
JP2003420475A JP2004154140A (ja) 1999-03-08 2003-12-18 血管形成及び心血管新生の促進又は阻害
US10/771,187 US7355002B2 (en) 1997-11-12 2004-02-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/797,366 US7378507B2 (en) 1997-09-18 2004-03-09 PRO217 polypeptides
US10/855,211 US20050026832A1 (en) 1997-11-25 2004-05-26 Fibroblast growth factor-19 (FGF-19) nucleic acids and polypeptides and methods of use for the treatment of obesity and related disorders
US10/916,250 US7368250B2 (en) 1997-10-28 2004-08-11 Compositions and methods for the diagnosis and treatment of tumor
US10/943,353 US20050059115A1 (en) 1997-12-03 2004-09-17 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/955,952 US20050153396A1 (en) 1998-09-16 2004-09-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/963,467 US7223586B2 (en) 1997-09-18 2004-10-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/964,241 US20070026487A1 (en) 1997-11-24 2004-10-12 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/970,823 US7307152B2 (en) 1997-10-17 2004-10-20 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/972,317 US7208321B2 (en) 1998-06-02 2004-10-22 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/050,559 US7157267B2 (en) 1997-10-17 2005-02-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/050,154 US7122631B2 (en) 2000-02-22 2005-02-02 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/057,268 US20060084144A1 (en) 1997-09-17 2005-02-11 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/057,966 US20050187379A1 (en) 1997-09-17 2005-02-14 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2005054646A JP2005224245A (ja) 1999-09-01 2005-02-28 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
US11/080,062 US7619062B2 (en) 1997-10-17 2005-03-14 PRO214 polypeptides
US11/081,485 US20050170465A1 (en) 1997-10-17 2005-03-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/100,159 US7425613B2 (en) 1997-11-05 2005-04-05 PRO1375 polypeptides
JP2005118579A JP2005253468A (ja) 1999-09-01 2005-04-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2005118817A JP2005245460A (ja) 1999-09-01 2005-04-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2005118968A JP2005270107A (ja) 1999-09-01 2005-04-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2005118701A JP2005253469A (ja) 1999-09-01 2005-04-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2005119030A JP2005261437A (ja) 1999-09-01 2005-04-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
US11/110,133 US20050181445A1 (en) 1997-09-17 2005-04-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/176,863 US20050266490A1 (en) 1997-10-24 2005-07-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/189,442 US20060246465A1 (en) 1998-06-04 2005-07-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2005235120A JP2006068006A (ja) 1999-06-15 2005-08-15 分泌及び膜貫通ポリペプチドとそれをコードする核酸
JP2005264293A JP2006068016A (ja) 1999-12-01 2005-08-15 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2005238244A JP2006061156A (ja) 1999-06-15 2005-08-19 分泌及び膜貫通ポリペプチドとそれをコードする核酸
JP2005238217A JP2006051031A (ja) 1999-06-15 2005-08-19 分泌及び膜貫通ポリペプチドとそれをコードする核酸
JP2005238274A JP2006051032A (ja) 1999-06-15 2005-08-19 分泌及び膜貫通ポリペプチドとそれをコードする核酸
JP2005238266A JP2006025795A (ja) 1999-06-15 2005-08-19 分泌及び膜貫通ポリペプチドとそれをコードする核酸
US11/240,891 US20060246540A1 (en) 1997-08-26 2005-09-29 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/283,473 US20090142800A1 (en) 1998-08-04 2005-11-18 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/296,155 US20060127983A1 (en) 1997-12-03 2005-12-06 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/323,117 US20070092941A1 (en) 1998-09-16 2005-12-29 PRO1298 polypeptides
US11/341,175 US7468427B2 (en) 1997-03-31 2006-01-27 Antibodies to PRO1275 polypeptide
US11/353,554 US7417126B2 (en) 1997-10-17 2006-02-13 PRO246 antibodies
US11/355,441 US7449551B2 (en) 1997-09-18 2006-02-15 PRO211 polypeptides
US11/471,396 US20060233803A1 (en) 1998-09-16 2006-06-19 Use of A33 antigens and JAM-it
US11/518,609 US20070077623A1 (en) 1997-09-17 2006-09-07 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/542,578 US20070031405A1 (en) 1998-09-16 2006-10-02 Use of A33 antigens and jam-it
US11/642,816 US20070088151A1 (en) 1997-09-18 2006-12-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US11/725,076 US20070190049A1 (en) 1998-09-16 2007-03-15 Use of A33 antigens and JAM-IT
US11/725,063 US7741056B2 (en) 1998-09-16 2007-03-15 Use of A33 antigens and JAM-IT
US11/725,027 US20080312421A1 (en) 1998-09-16 2007-03-15 Use of A33 antigens and JAM-it
JP2007172879A JP5512073B2 (ja) 1999-06-02 2007-06-29 ポリペプチドを含有する医薬
JP2007326609A JP2008148701A (ja) 1999-12-01 2007-12-18 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2007326424A JP2008167749A (ja) 1999-12-01 2007-12-18 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2007326613A JP2008161190A (ja) 1999-12-01 2007-12-18 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
JP2007325484A JP2008148699A (ja) 1999-12-01 2007-12-18 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
US12/031,612 US7514538B2 (en) 1997-10-28 2008-02-14 Compositions and methods for the diagnosis and treatment of tumor
US12/079,178 US20090170158A1 (en) 1997-12-03 2008-03-25 Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2008256822A JP2009095345A (ja) 1999-09-01 2008-10-01 分泌及び膜貫通ポリペプチドとそれをコードしている核酸
US12/393,224 US20090227776A1 (en) 1997-10-28 2009-02-26 Compositions and methods for the diagnosis and treatment of tumor
JP2011138276A JP2011236224A (ja) 1999-06-02 2011-06-22 ポリペプチドを含有する医薬

Applications Claiming Priority (32)

Application Number Priority Date Filing Date Title
USPCT/US99/30911 1999-02-20
US14304899P 1999-07-07 1999-07-07
US60/143,048 1999-07-07
US14569899P 1999-07-26 1999-07-26
US60/145,698 1999-07-26
US14622299P 1999-07-28 1999-07-28
US60/146,222 1999-07-28
USPCT/US99/20594 1999-09-08
PCT/US1999/020594 WO2000015666A2 (fr) 1998-09-10 1999-09-08 Compositions et methodes de traitement des tumeurs
USPCT/US99/20944 1999-09-13
PCT/US1999/020944 WO2000015792A2 (fr) 1998-09-14 1999-09-13 Promotion ou inhibition d'angiogenese et de cardiovascularisation
PCT/US1999/021090 WO2000015796A2 (fr) 1998-09-16 1999-09-15 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides
PCT/US1999/021547 WO2000015797A2 (fr) 1998-09-17 1999-09-15 Compositions et methodes de traitement des maladies relatives au syteme immunitaire
USPCT/US99/21090 1999-09-15
USPCT/US99/21547 1999-09-15
PCT/US1999/023089 WO2000021996A2 (fr) 1998-10-13 1999-10-05 Procedes et compositions inhibant la croissance des cellules neoplasiques
USPCT/US99/23089 1999-10-05
USPCT/US99/28214 1999-11-29
PCT/US1999/028214 WO2001019987A1 (fr) 1999-09-13 1999-11-29 Promotion ou inhibition de l'angiogenese et de la vascularisation cardiaque
PCT/US1999/028313 WO2000032221A2 (fr) 1998-12-01 1999-11-30 Promotion et inhibition de l'angiogenese et de la vascularisation cardiaque
USPCT/US99/28313 1999-11-30
PCT/US1999/028564 WO2000055319A1 (fr) 1999-03-12 1999-12-02 Procedes et compositions pour inhiber la croissance des cellules neoplasiques
USPCT/US99/28564 1999-12-02
PCT/US1999/028565 WO2000037638A2 (fr) 1998-12-22 1999-12-02 Methodes permettant d'inhiber la croissance de cellules neoplasiques
USPCT/US99/28565 1999-12-02
USPCT/US99/30095 1999-12-16
PCT/US1999/030095 WO2000037640A2 (fr) 1998-12-22 1999-12-16 Compositions et methodes de traitement d'une tumeur
PCT/US1999/030999 WO2001005836A1 (fr) 1999-07-20 1999-12-20 Compositions polypeptidiques et methodes de traitement des tumeurs
PCT/US1999/030911 WO2000075316A1 (fr) 1999-06-02 1999-12-20 Procedes et compositions pour l'inhibition de la croissance de cellules neoplastiques
USPCT/US99/30999 1999-12-20
USPCT/US99/00219 2000-01-05
PCT/US2000/000219 WO2000053753A2 (fr) 1999-03-08 2000-01-05 Activation ou inhibition de l'angiogenese et de la cardiovascularisation

Related Parent Applications (16)

Application Number Title Priority Date Filing Date
PCT/US1998/018824 Continuation-In-Part WO1999014327A2 (fr) 1994-09-08 1998-09-10 Genes amplifies dans des tumeurs, anticorps diriges contre les proteines codees par ces genes, et leur utilisation dans le diagnostic et le traitement du cancer
PCT/US1998/019330 Continuation-In-Part WO1999014328A2 (fr) 1994-09-08 1998-09-16 Polypeptides secretes et transmembranaires et acides nucleiques les codant
PCT/US1998/019437 Continuation-In-Part WO1999014241A2 (fr) 1994-09-08 1998-09-17 Traitement d'affections liees aux fonctions immunitaires et compositions correspondantes
US38013899A Continuation-In-Part 1996-11-06 1999-08-25
US09380139 Continuation-In-Part 1999-08-25
US38013999A Continuation-In-Part 1996-11-06 1999-08-25
PCT/US1999/023089 Continuation-In-Part WO2000021996A2 (fr) 1994-09-08 1999-10-05 Procedes et compositions inhibant la croissance des cellules neoplasiques
PCT/US1999/028313 Continuation-In-Part WO2000032221A2 (fr) 1994-09-08 1999-11-30 Promotion et inhibition de l'angiogenese et de la vascularisation cardiaque
PCT/US1999/030095 Continuation-In-Part WO2000037640A2 (fr) 1994-09-08 1999-12-16 Compositions et methodes de traitement d'une tumeur
PCT/US2000/000219 Continuation-In-Part WO2000053753A2 (fr) 1994-09-08 2000-01-05 Activation ou inhibition de l'angiogenese et de la cardiovascularisation
PCT/US2000/003565 Continuation-In-Part WO2001053486A1 (fr) 1994-09-08 2000-02-11 Compositions et procedes destines au traitement de tumeur
PCT/US2000/003565 Continuation WO2001053486A1 (fr) 1994-09-08 2000-02-11 Compositions et procedes destines au traitement de tumeur
PCT/US2000/004341 Continuation-In-Part WO2000053756A2 (fr) 1996-11-06 2000-02-18 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
PCT/US2000/004342 Continuation WO2000078961A1 (fr) 1997-03-31 2000-02-18 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides
PCT/US2000/004342 Continuation-In-Part WO2000078961A1 (fr) 1997-03-31 2000-02-18 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides
PCT/US2000/014042 Continuation-In-Part WO2000077037A2 (fr) 1994-09-08 2000-05-22 Polypeptides secretes et transmembranaires et acides nucleiques les codant

Related Child Applications (23)

Application Number Title Priority Date Filing Date
US09/284,663 Continuation US20020012961A1 (en) 1997-08-26 1998-11-25 Fibroblast growth factor- 19
PCT/US2000/005004 Continuation-In-Part WO2000053757A2 (fr) 1994-09-08 2000-02-24 Activation et inhibition de l'angiogenese et de la cardiovascularisation
PCT/US2000/005601 Continuation-In-Part WO2000056889A2 (fr) 1997-03-31 2000-03-01 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
PCT/US2000/005601 Continuation WO2000056889A2 (fr) 1997-03-31 2000-03-01 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
PCT/US2000/005841 Continuation WO2000053758A2 (fr) 1994-09-08 2000-03-02 Compositions et methodes de traitement des maladies immunitaires
PCT/US2000/005841 Continuation-In-Part WO2000053758A2 (fr) 1994-09-08 2000-03-02 Compositions et methodes de traitement des maladies immunitaires
US52234200A Continuation-In-Part 1997-08-26 2000-03-09
PCT/US2000/014042 Continuation-In-Part WO2000077037A2 (fr) 1994-09-08 2000-05-22 Polypeptides secretes et transmembranaires et acides nucleiques les codant
US66535000A Continuation 1994-09-08 2000-09-18
US66535000A Continuation-In-Part 1994-09-08 2000-09-18
PCT/US2000/032678 Continuation-In-Part WO2001040466A2 (fr) 1996-11-06 2000-12-01 Polypeptides secretes et transmembranaires et acides nucleiques codant ces polypeptides
US09/866,028 Continuation-In-Part US6642360B2 (en) 1996-11-06 2001-05-25 Secreted polypeptides that stimulate release of proteoglycans from cartilage
US09/903,749 Continuation US7147853B2 (en) 1997-09-17 2001-07-11 Anti-pro211 polypeptide antibodies
US09/944,862 Continuation US20020115145A1 (en) 1997-12-03 2001-08-31 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/028,072 Continuation-In-Part US20030004311A1 (en) 1997-03-31 2001-12-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/028,072 Continuation US20030004311A1 (en) 1997-03-31 2001-12-19 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/052,586 Continuation US20020127584A1 (en) 1997-09-15 2002-01-15 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/081,056 Continuation US20040043927A1 (en) 1997-09-19 2002-02-20 Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis
US10/119,480 Continuation US20040087769A1 (en) 1998-09-10 2002-04-09 Secreted and transmembrane polypeptides and nucleic acids encoding the same
US10/125,166 Continuation US20030039648A1 (en) 1997-10-28 2002-04-17 Compositions and methods for the diagnosis and treatment of tumor
US10/125,166 Continuation-In-Part US20030039648A1 (en) 1997-10-28 2002-04-17 Compositions and methods for the diagnosis and treatment of tumor
US10/265,542 Continuation-In-Part US20030171568A1 (en) 1997-11-21 2002-10-03 Use of A33 antigens and JAM-IT
US11/542,578 Continuation-In-Part US20070031405A1 (en) 1998-09-16 2006-10-02 Use of A33 antigens and jam-it

Publications (1)

Publication Number Publication Date
WO2001004311A1 true WO2001004311A1 (fr) 2001-01-18

Family

ID=56289994

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/004414 WO2001004311A1 (fr) 1994-09-08 2000-02-22 Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides

Country Status (2)

Country Link
AU (1) AU2883900A (fr)
WO (1) WO2001004311A1 (fr)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003025162A2 (fr) * 2001-09-20 2003-03-27 Bayer Healthcare Ag Regulation du precurseur de la sous-unite alpha de prolyl 4-hydroxylase humaine
WO2002064776A3 (fr) * 2001-02-14 2003-08-21 Axaron Bioscience Ag Proteines de transduction de signal 15b3, 15b3-1 et 15b3-2 et sequences d'adn associees
WO2003072773A1 (fr) * 2002-02-08 2003-09-04 Seikagaku Corporation Proteine fusionnee ayant une activite de glucuronyltransferase
WO2003083110A1 (fr) * 2002-03-29 2003-10-09 National Institute Of Advanced Industrial Science And Technology Nouvelles galactose transferases et leurs peptides, et acide nucleique codant pour lesdites transferases
WO2004002515A1 (fr) * 2002-06-28 2004-01-08 Takeda Chemical Industries, Ltd. Agents diagnostiques/preventifs/curatifs pour maladies respiratoires
WO2004063226A2 (fr) * 2002-12-27 2004-07-29 Applied Research Systems Ars Holding N.V. Nouveaux polypeptides de type fibrilline
US6902892B1 (en) 1998-10-19 2005-06-07 Diadexus, Inc. Method of diagnosing, monitoring, staging, imaging and treating prostate cancer
EP1629088A2 (fr) * 2003-05-30 2006-03-01 Agensys, Inc. Variants de l'antigene de cellules souches de la prostate (psca) et utilisations subsequentes de ceux-ci
US7034132B2 (en) 2001-06-04 2006-04-25 Anderson David W Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US7057017B2 (en) 1997-04-16 2006-06-06 Millennium Pharmaceuticals, Inc. Human dickkopf-related protein and nucleic acid molecules and uses therefor
US7169906B2 (en) 1997-09-17 2007-01-30 Genentech, Inc. PRO211 polypeptides
US7192589B2 (en) 1998-09-16 2007-03-20 Genentech, Inc. Treatment of inflammatory disorders with STIgMA immunoadhesins
US7419663B2 (en) 1998-03-20 2008-09-02 Genentech, Inc. Treatment of complement-associated disorders
US7446181B2 (en) 1998-01-15 2008-11-04 Millennium Pharmaceuticals, Inc. Antibodies that bind human Dickkopf-1 proteins
US7449551B2 (en) 1997-09-18 2008-11-11 Genentech, Inc. PRO211 polypeptides
EP2014675A1 (fr) * 2003-08-11 2009-01-14 Genentech, Inc. Compositions et procédés pour le traitement de maladies liées au système immunitaire
US7544659B2 (en) 2004-08-13 2009-06-09 Genentech, Inc. Promotion of axonal regeneration
US7705195B2 (en) 2002-06-07 2010-04-27 Genentech, Inc. Screening method
US7709611B2 (en) 2004-08-04 2010-05-04 Amgen Inc. Antibodies to Dkk-1
US7723478B2 (en) 1998-09-25 2010-05-25 Amgen Inc. DKR polypeptides
US7785829B2 (en) 2003-03-19 2010-08-31 Biogen Idec Ma, Inc. Nogo receptor binding protein
US8007791B2 (en) 2007-05-23 2011-08-30 Genentech, Inc. Prevention and treatment of complement-associated eye conditions
US8007798B2 (en) 1997-11-21 2011-08-30 Genentech, Inc. Treatment of complement-associated disorders
US8058406B2 (en) 2008-07-09 2011-11-15 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
US8067002B2 (en) 2006-11-02 2011-11-29 Genentech, Inc. Humanized anti-factor D antibodies
US8088386B2 (en) 1998-03-20 2012-01-03 Genentech, Inc. Treatment of complement-associated disorders
US8128926B2 (en) 2007-01-09 2012-03-06 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
US8273352B2 (en) 2008-04-28 2012-09-25 Genentech, Inc. Humanized anti-factor D antibodies and uses thereof
US8486893B2 (en) 2004-06-24 2013-07-16 Biogen Idec Ma Inc. Treatment of conditions involving demyelination
US8551476B2 (en) 2005-07-08 2013-10-08 Biogen Idec Ma Inc. SP35 antibodies and uses thereof
US8753625B2 (en) 2005-11-04 2014-06-17 Genentech, Inc. Use of complement inhibitors to treat ocular diseases
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US9234024B2 (en) 2008-05-06 2016-01-12 Genentech, Inc. Affinity matured CRIg variants
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
US9796780B2 (en) 2012-05-14 2017-10-24 Biogen Ma Inc. LINGO-2 antagonists for treatment of conditions involving motor neurons
US10093978B2 (en) 2013-08-12 2018-10-09 Genentech, Inc. Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms
US10179821B2 (en) 2014-05-01 2019-01-15 Genentech, Inc. Anti-factor D antibodies
US10407510B2 (en) 2015-10-30 2019-09-10 Genentech, Inc. Anti-factor D antibodies and conjugates
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
US10435467B2 (en) 2015-01-08 2019-10-08 Biogen Ma Inc. LINGO-1 antagonists and uses for treatment of demyelinating disorders
US10654932B2 (en) 2015-10-30 2020-05-19 Genentech, Inc. Anti-factor D antibody variant conjugates and uses thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997007198A2 (fr) * 1995-08-11 1997-02-27 Genetics Institute, Inc. Sequences d'adn et proteines secretees codees par celles-ci
EP0834563A2 (fr) * 1996-09-26 1998-04-08 Smithkline Beecham Corporation Récepteur transmembranaire humain, membre de la famille des récepteurs de chémokines, appelé aussi Strl-33
WO1999014327A2 (fr) * 1997-09-17 1999-03-25 Genentech, Inc. Genes amplifies dans des tumeurs, anticorps diriges contre les proteines codees par ces genes, et leur utilisation dans le diagnostic et le traitement du cancer
WO1999014328A2 (fr) * 1997-09-17 1999-03-25 Genentech, Inc. Polypeptides secretes et transmembranaires et acides nucleiques les codant

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997007198A2 (fr) * 1995-08-11 1997-02-27 Genetics Institute, Inc. Sequences d'adn et proteines secretees codees par celles-ci
EP0834563A2 (fr) * 1996-09-26 1998-04-08 Smithkline Beecham Corporation Récepteur transmembranaire humain, membre de la famille des récepteurs de chémokines, appelé aussi Strl-33
WO1999014327A2 (fr) * 1997-09-17 1999-03-25 Genentech, Inc. Genes amplifies dans des tumeurs, anticorps diriges contre les proteines codees par ces genes, et leur utilisation dans le diagnostic et le traitement du cancer
WO1999014328A2 (fr) * 1997-09-17 1999-03-25 Genentech, Inc. Polypeptides secretes et transmembranaires et acides nucleiques les codant

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHEN H ET AL: "Cricetulus griseus HT protein mRNA, complete cds", EMBL - EMROD, XP002095039 *
KLEIN R D ET AL: "Selection for genes encoding secreted proteins and receptors", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA,US,NATIONAL ACADEMY OF SCIENCE. WASHINGTON, no. 93, 1 July 1996 (1996-07-01), pages 7108 - 7113, XP002077277, ISSN: 0027-8424 *
REVELLE B M ET AL: "SINGLE AMINO ACID RESIDUES IN THE E- AND P-SELECTIN EPIDERMAL GROWTH FACTOR DOMAINS CAN DETERMINE CARBOHYDRATE BINDING SPECIFICITY", JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 271, no. 27, 5 July 1996 (1996-07-05), pages 16160 - 16170, XP000644685, ISSN: 0021-9258 *
STRAUSBERG ET AL: "oo14f12.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:1566191 3' similar to TR:Q60438 Q60438 HT PROTEIN.;, mRNA sequence", EMBL NUCLEOTIDE SEQU, XP002131427 *
YOKOYAMA-KOBAYASHI M ET AL: "A signal sequence detection system using secreted protease activity as an indicator", GENE,NL,ELSEVIER BIOMEDICAL PRESS. AMSTERDAM, vol. 163, no. 2, 3 October 1995 (1995-10-03), pages 193 - 196, XP004041983, ISSN: 0378-1119 *

Cited By (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7579168B2 (en) 1997-04-16 2009-08-25 Millennium Pharmaceuticals, Inc. Human Dickkopf-related nucleic acid molecules
US7057017B2 (en) 1997-04-16 2006-06-06 Millennium Pharmaceuticals, Inc. Human dickkopf-related protein and nucleic acid molecules and uses therefor
US8202966B2 (en) 1997-04-16 2012-06-19 Millennium Pharmaceuticals, Inc. Human Dickkopf-related protein and nucleic acid molecules and uses therefor
US7645451B2 (en) 1997-04-16 2010-01-12 Millennium Pharmaceuticals, Inc. Human dickkopf-related protein and nucleic acid molecules and uses therefor
US7169906B2 (en) 1997-09-17 2007-01-30 Genentech, Inc. PRO211 polypeptides
US7449551B2 (en) 1997-09-18 2008-11-11 Genentech, Inc. PRO211 polypeptides
US8007798B2 (en) 1997-11-21 2011-08-30 Genentech, Inc. Treatment of complement-associated disorders
US7446181B2 (en) 1998-01-15 2008-11-04 Millennium Pharmaceuticals, Inc. Antibodies that bind human Dickkopf-1 proteins
US7419663B2 (en) 1998-03-20 2008-09-02 Genentech, Inc. Treatment of complement-associated disorders
US8088386B2 (en) 1998-03-20 2012-01-03 Genentech, Inc. Treatment of complement-associated disorders
US7741056B2 (en) 1998-09-16 2010-06-22 Genentech, Inc. Use of A33 antigens and JAM-IT
US7192589B2 (en) 1998-09-16 2007-03-20 Genentech, Inc. Treatment of inflammatory disorders with STIgMA immunoadhesins
US7723478B2 (en) 1998-09-25 2010-05-25 Amgen Inc. DKR polypeptides
US6902892B1 (en) 1998-10-19 2005-06-07 Diadexus, Inc. Method of diagnosing, monitoring, staging, imaging and treating prostate cancer
US7432064B2 (en) 1998-10-19 2008-10-07 Diadexus, Inc. Method of diagnosing, monitoring, staging, imaging and treating prostate cancer
WO2002064776A3 (fr) * 2001-02-14 2003-08-21 Axaron Bioscience Ag Proteines de transduction de signal 15b3, 15b3-1 et 15b3-2 et sequences d'adn associees
US7034132B2 (en) 2001-06-04 2006-04-25 Anderson David W Therapeutic polypeptides, nucleic acids encoding same, and methods of use
WO2003025162A3 (fr) * 2001-09-20 2003-09-04 Bayer Ag Regulation du precurseur de la sous-unite alpha de prolyl 4-hydroxylase humaine
WO2003025162A2 (fr) * 2001-09-20 2003-03-27 Bayer Healthcare Ag Regulation du precurseur de la sous-unite alpha de prolyl 4-hydroxylase humaine
WO2003072773A1 (fr) * 2002-02-08 2003-09-04 Seikagaku Corporation Proteine fusionnee ayant une activite de glucuronyltransferase
JPWO2003083110A1 (ja) * 2002-03-29 2005-08-04 独立行政法人産業技術総合研究所 新規ガラクトース転移酵素、そのペプチド及びこれをコードする核酸
WO2003083110A1 (fr) * 2002-03-29 2003-10-09 National Institute Of Advanced Industrial Science And Technology Nouvelles galactose transferases et leurs peptides, et acide nucleique codant pour lesdites transferases
US7705195B2 (en) 2002-06-07 2010-04-27 Genentech, Inc. Screening method
WO2004002515A1 (fr) * 2002-06-28 2004-01-08 Takeda Chemical Industries, Ltd. Agents diagnostiques/preventifs/curatifs pour maladies respiratoires
EP1558766A4 (fr) * 2002-10-03 2007-12-26 Genentech Inc Utilisation d'antigenes a33 et de jam-it
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
WO2004063226A2 (fr) * 2002-12-27 2004-07-29 Applied Research Systems Ars Holding N.V. Nouveaux polypeptides de type fibrilline
WO2004063226A3 (fr) * 2002-12-27 2004-09-30 Applied Research Systems Nouveaux polypeptides de type fibrilline
US8932821B2 (en) 2003-03-19 2015-01-13 Biogen Idec Ma Inc. NOGO receptor binding protein
US7785829B2 (en) 2003-03-19 2010-08-31 Biogen Idec Ma, Inc. Nogo receptor binding protein
US8765662B2 (en) 2003-03-19 2014-07-01 Biogen Idec Ma Inc. NOGO receptor binding protein
EP1629088B1 (fr) * 2003-05-30 2012-01-11 Agensys, Inc. Variants de l'antigene de cellules souches de la prostate (psca) et utilisations subsequentes de ceux-ci
EP2319524A1 (fr) * 2003-05-30 2011-05-11 Agensys, Inc. Variantes de l'antigène de cellules souches de la prostate (PSCA) et sous-séquences de celles-ci
EP1629088A2 (fr) * 2003-05-30 2006-03-01 Agensys, Inc. Variants de l'antigene de cellules souches de la prostate (psca) et utilisations subsequentes de ceux-ci
EP2182006A2 (fr) * 2003-08-11 2010-05-05 Genentech, Inc. Compositions et procédés pour le traitement de maladies liées au système immunitaire
EP2014675A1 (fr) * 2003-08-11 2009-01-14 Genentech, Inc. Compositions et procédés pour le traitement de maladies liées au système immunitaire
EP2182006A3 (fr) * 2003-08-11 2010-09-15 Genentech, Inc. Compositions et procédés pour le traitement de maladies liées au système immunitaire
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
US8486893B2 (en) 2004-06-24 2013-07-16 Biogen Idec Ma Inc. Treatment of conditions involving demyelination
US9068992B2 (en) 2004-06-24 2015-06-30 Biogen Ma Inc. Screening methods for identifying Sp35 antagonists
US7709611B2 (en) 2004-08-04 2010-05-04 Amgen Inc. Antibodies to Dkk-1
US8101184B2 (en) 2004-08-04 2012-01-24 Amgen Inc. Treatment methods using Dkk-1 antibodies
US7544659B2 (en) 2004-08-13 2009-06-09 Genentech, Inc. Promotion of axonal regeneration
US8551476B2 (en) 2005-07-08 2013-10-08 Biogen Idec Ma Inc. SP35 antibodies and uses thereof
US9066984B2 (en) 2005-07-08 2015-06-30 Biogen Ma Inc. Sp35 antibodies and uses thereof
US8753625B2 (en) 2005-11-04 2014-06-17 Genentech, Inc. Use of complement inhibitors to treat ocular diseases
US10174104B2 (en) 2005-11-24 2019-01-08 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US9751934B2 (en) 2005-11-24 2017-09-05 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US9499609B2 (en) 2005-11-24 2016-11-22 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10738108B2 (en) 2005-11-24 2020-08-11 Astellas Pharma Inc. Monoclonal antibodies against claudin-18 for treatment of cancer
US10017564B2 (en) 2005-11-24 2018-07-10 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US11739139B2 (en) 2005-11-24 2023-08-29 Astellas Pharma Inc. Monoclonal antibodies against Claudin-18 for treatment of cancer
US8193329B2 (en) 2006-11-02 2012-06-05 Genentech, Inc. Nucleic acids encoding anti-factor D antibodies
US8187604B2 (en) 2006-11-02 2012-05-29 Genentech, Inc. Methods of treating with anti-factor D antibodies
US8372403B2 (en) 2006-11-02 2013-02-12 Genentech, Inc. Humanized anti-factor D antibodies and uses thereof
US8753826B2 (en) 2006-11-02 2014-06-17 Genentech, Inc. Methods of detecting factor D with anti-factor D antibodies
US8067002B2 (en) 2006-11-02 2011-11-29 Genentech, Inc. Humanized anti-factor D antibodies
US8128926B2 (en) 2007-01-09 2012-03-06 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
US8609407B2 (en) 2007-01-09 2013-12-17 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
US8268310B2 (en) 2007-05-23 2012-09-18 Genentech, Inc. Prevention and treatment of complement-associated eye conditions
US8497094B2 (en) 2007-05-23 2013-07-30 Genentech, Inc. Prevention and treatment of complement-associated eye conditions
US8007791B2 (en) 2007-05-23 2011-08-30 Genentech, Inc. Prevention and treatment of complement-associated eye conditions
US9676868B2 (en) 2008-04-28 2017-06-13 Genentech, Inc. Humanized anti-factor D antibodies and uses thereof
US8273352B2 (en) 2008-04-28 2012-09-25 Genentech, Inc. Humanized anti-factor D antibodies and uses thereof
US8614306B2 (en) 2008-04-28 2013-12-24 Genentech, Inc. Polynucleotides encoding humanized anti-factor D antibodies
US9234024B2 (en) 2008-05-06 2016-01-12 Genentech, Inc. Affinity matured CRIg variants
US9745375B2 (en) 2008-07-09 2017-08-29 Biogen Ma Inc. Compositions comprising antibodies to LINGO or fragments thereof
US8425910B2 (en) 2008-07-09 2013-04-23 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
US8058406B2 (en) 2008-07-09 2011-11-15 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US10053512B2 (en) 2012-05-09 2018-08-21 Ganymed Pharmaceuticals Ag Antibodies against claudin 18.2 useful in cancer diagnosis
US9796780B2 (en) 2012-05-14 2017-10-24 Biogen Ma Inc. LINGO-2 antagonists for treatment of conditions involving motor neurons
US10947591B2 (en) 2013-08-12 2021-03-16 Genentech, Inc. Compositions and method for treating complement-associated conditions
US10093978B2 (en) 2013-08-12 2018-10-09 Genentech, Inc. Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms
US10179821B2 (en) 2014-05-01 2019-01-15 Genentech, Inc. Anti-factor D antibodies
US10435467B2 (en) 2015-01-08 2019-10-08 Biogen Ma Inc. LINGO-1 antagonists and uses for treatment of demyelinating disorders
US10407510B2 (en) 2015-10-30 2019-09-10 Genentech, Inc. Anti-factor D antibodies and conjugates
US10654932B2 (en) 2015-10-30 2020-05-19 Genentech, Inc. Anti-factor D antibody variant conjugates and uses thereof
US10961313B2 (en) 2015-10-30 2021-03-30 Genentech, Inc. Anti-factor D antibody variant conjugates and uses thereof

Also Published As

Publication number Publication date
AU2883900A (en) 2001-01-30

Similar Documents

Publication Publication Date Title
US6965011B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7208312B1 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
WO2001004311A1 (fr) Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides
US6908993B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US20070077623A1 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
EP1208195A2 (fr) Polypeptides secretes et transmembranaires et acides nucleiques codant pour ceux-ci
EP1114152A2 (fr) Polypeptides secretes et transmembranaires et acides nucleiques codant pour ces polypeptides
US7033825B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7449551B2 (en) PRO211 polypeptides
US20090170158A1 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
WO2000032776A2 (fr) Polypeptides secretes et transmembranaires et acides nucleiques les codant
US7241865B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US6894148B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7169906B2 (en) PRO211 polypeptides
US7307152B2 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7417126B2 (en) PRO246 antibodies
US20040137561A1 (en) Secreted and transmembrane polypeptides and nucleic acids encoding the same
ZA200103574B (en) Secreted and transmembrane polypeptides and nucleic acids and encoding the same.

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 10265542

Country of ref document: US

122 Ep: pct application non-entry in european phase
WWE Wipo information: entry into national phase

Ref document number: 11542578

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 11542578

Country of ref document: US

DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)