MONITORING HEALTH AND DISEASE STATUS USING CLONOTYPE PROFILES

摘要

(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date H(10) International Publication Number 10 November 2011 (10.11.2011) PCT W O 2011/139371 Al (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, GO1N 33/48 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/US2011/000791 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 4 May 2011 (04.05.2011) NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (25) Filing Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/332,175 6 May 2010 (06.05.2010) US GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, 61/455,743 25 October 2010 (25.10.2010) US ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, 61/446,822 25 February 2011 (25.02.2011) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, Fl, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (71) Applicant (for all designated States except US): SE- LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, QUENTA, INC. [US/US]; 409 Illinois Street, San Fran- SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, cisco, CA 94158 (US). GW, ML, MR, NE, SN, TD, TG). (72) Inventors; and Published: (75) Inventors/Applicants (for US only): FAH AM, Malek _ with international search report (Art. 21(3)) [US/US]; 139 Panorama Court, Pacifica, CA 94044 (US). WILLIS, Thomas [US/US]; 1040 Filbert Street, San - before the expiration of the time limit for amending the Francisco, CA 94133 (US). claims and to be republished in the event of receipt of - amendments (Rule 48.2(h)) (74) Agent: MACEVICZ, Stephen, C.; Sequenta, Inc., 409 Illinois Street, San Francisco, CA 94158 (US). - with sequence listing part of description (Rule 5.2(a)) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: MONITORING HEALTH AND DISEASE STATUS USING CLONOTYPE PROFILES 404 406 408 - ~40041 Z Fig .4A squ 424 (57) Abstract: There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, in cluding autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, Nautoinmme disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. i particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.