Patent SG-11201903509Q-A (SG)
Title: Methods and systems for tumor detection
Inventor: NAMSARAEV EUGENI
IPC: C12Q1/68
Filed: 2017-10-24
Abstract: d cfDNA Extraction 2210 (54) Title: METHODS AND SYSTEMS FOR TUMOR DETECTION FIG. 22 2207 Negative Target Assess EBV Enrichment Sequenci quantity and Library Prep (or EBV ng on size profile Target Enrichment] NextSeq of EBV DNA fragments 2214 2213 2211 2212 2201 2202 Yes 2204 2205 qPCR setup • 4m1 plasma for NGS workflow Blood Plasma Samples y Separation collected in 2X spin + 2 tubes automation 2203 Plasma for qPCR workflow cfDNA Extraction (51) International Patent Classification: C12Q 1/68 (2018.01) GOOF 19/18 (2011.01) GO1N 33/574 (2006.01) (21) International Application Number: PCT/US2017/058099 (22) International Filing Date: 24 October 2017 (24.10.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/411,929 24 October 2016 (24.10.2016) US 62/450,541 25 January 2017 (25.01.2017) US 62/507,154 16 May 2017 (16.05.2017) US (71) Applicants: THE CHINESE UNIVERSITY OF HONG KONG [CN/CN]; Room 301, Pi Ch'iu Building, Shatin, New Territories, Hong Kong (CN). GRAIL, INC. [US/US]; 1525 O'Brien Drive, Menlo Park, California 94025 (US). (72) Inventors: NAMSARAEV, Eugeni; 3772 La Donna Av- enue, Palo Alto, California 94306 (US). LO, Yuk-Ming Dennis; 4th Floor, 7 King Tak Street, Homantin, Kowloon, Hong Kong (CN). CHUI, Rossa Wai Kwun; House 31, Double Haven, 52 Ma Lok Path, Shatin, New Territories, Hong Kong (CN). CHAN, Kwan Chee; Flat C, 15th Floor, Block 5, Peak One, Mei Tin Road, Shatin, New Territo- ries, Hong Kong (CN). JIANG, Peiyong; Flat 7, 1/F, Block B, Kwong Lam Court, 62-66 Siu Lek Yuen Road, Shatin, New Territories, Hong Kong (CN). SUN, Kun; Rm 711, Block A, Staff Quarters, Prince of Wales Hospital, 30-32 Ngan Sling ST., Shatin, New Territories, Hong Kong (CN). 1-1 O co O co O C (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 03 May 2018 (03.05.2018) WIP0 I PCT Hu omit VIII °nolo III m 01110111110 111110 oimIE (10) International Publication Number WO 2018/081130 Al ( Report ) 2215 (57) : Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times). [Continued on next page] WO 2018/081130 Al MIDEDIMOMOIDEIREEMOOMMH10100110MEHOIS LAM, Wai Kei; Flat B, 3/F, Block 14, Beacon Heights, 14 Lung Ping Road, Kowloon, Hong Kong (CN). (74) Agent: HARIHARAN, Venkatesh et al.; WILSON SONSINI GOODRICH & ROSATI, 650 Page Mill Road, Palo Alto, California 94304 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h))