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WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T

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WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T (51) International Patent Classification: David [US/US]; 13539 N . 95th Way, Scottsdale, AZ C12Q 1/68 (2006.01) 85260 (US). (21) International Application Number: (74) Agent: AKHAVAN, Ramin; Caris Science, Inc., 6655 N . PCT/US20 12/0425 19 Macarthur Blvd., Irving, TX 75039 (US). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 14 June 2012 (14.06.2012) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, English (25) Filing Language: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, Publication Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (30) Priority Data: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/497,895 16 June 201 1 (16.06.201 1) US MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 61/499,138 20 June 201 1 (20.06.201 1) US OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, 61/501,680 27 June 201 1 (27.06.201 1) u s SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 61/506,019 8 July 201 1(08.07.201 1) u s TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 61/506,598 11 July 201 1 ( 11.07.201 1) u s 61/506,606 11 July 201 1 ( 11.07.201 1) u s (84) Designated States (unless otherwise indicated, for every 61/507,989 14 July 201 1(14.07.201 1) u s kind of regional protection available): ARIPO (BW, GH, 61/5 11,455 25 July 201 1(25.07.201 1) u s GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/523,763 15 August 201 1(15.08.201 1) u s UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/526,623 23 August 201 1(23.08.201 1) u s 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, (71) Applicant (for all designated States except US): CARIS MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, LIFE SCIENCES LUXEMBOURG HOLDINGS, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, S.A.R.L. [LU/LU]; Rue De Maraichers, L2124 Luxem ML, MR, NE, SN, TD, TG). bourg, Grand-Duche De Luxembourg (LU). Published: (72) Inventors; and (75) Inventors/Applicants (for US only): BROWN, Kirk — without international search report and to be republished [US/US]; 14256 North Coral Gables Drive, Phoenix, AZ upon receipt of that report (Rule 48.2(g)) 85023 (US). PAWLOWSKI, Traci [US/US]; 2014 N Milkweed Loop, Phoenix, AZ 85037 (US). SPETZLER, < ∞ - (54) Title: BIOMARKER COMPOSITIONS AND METHODS ¾ (57) Abstract: Biomarkers can be assessed for diagnostic, therapy-related or prognostic methods to identify phenotypes, such as a condition or disease, or the stage or progression of a disease, select candidate treatment regimens for diseases, conditions, disease stages, and stages of a condition, and to determine treatment efficacy. Circulating biomarkers from a bodily fluid can be used in pro - ¾ filing of physiological states or determining phenotypes. These include nucleic acids, protein, and circulating structures such as ves - icles, and nucleic acid-protein complexes. BIOMARKER COMPOSITIONS AND METHODS CROSS REFERENCE [0001] This application claims the benefit of U.S. Provisional Patent Application Nos. 61/497,895, filed June 16, 201 1; 61/499,138, filed June 20, 201 1; 61/501,680, filed June 27, 201 1; 61/506,019, filed July 8, 201 1; 61/506,606, filed July 11, 201 1; 61/506,598, filed July 11, 201 1; 61/507,989, filed July 14, 201 1; 61/5 11,455, filed July 25, 201 1; 61/523,763, filed August 15, 201 1; and 61/526,623, filed August 23, 201 1, all of which applications are incorporated herein by reference in their entirety. [0002] This application is a continuation-in-part of International Patent Application PCT/US20 12/04 1387, filed June 7, 2012, which application claims the benefit of U.S. Provisional Patent Application Nos. 61/494,196, filed June 7, 20 11; 61/494,355, filed June 7, 20 11; and 61/507,989, filed July 14, 20 11; all of which applications are incorporated herein by reference in their entirety. [0003] This application is also a continuation-in-part of International Patent Application PCT/US2012/025741, filed February 17, 2012, which application claims the benefit of U.S. Provisional Patent Application Nos. 61/446,3 13, filed February 24, 201 1; 61/501,680, filed June 27, 201 1; 61/471,417, filed April 4, 201 1; 61/523,763, filed August 15, 201 1; and 61/445,273, filed February 22, 201 1; all of which applications are incorporated herein by reference in their entirety. [0004] This application is also a continuation-in-part of International Patent Application PCT/US201 1/048327, filed August 18, 201 1, which application claims the benefit of U.S. Provisional Patent Application Nos. 61/374,95 1, filed August 18, 2010; 61/379,670, filed September 2, 2010; 61/381,305, filed September 9, 2010; 61/383,305, filed September 15, 2010; 61/391,504, filed October 8, 2010; 61/393,823, filed October 15, 2010; 61/41 1,890, filed November 9, 2010; 61/414,870, filed November 17, 2010; 61/416,560, filed November 23, 2010; 61/421,851, filed December 10, 2010; 61/423,557, filed December 15, 2010; 61/428,196, filed December 29, 2010; all of which applications are incorporated herein by reference in their entirety. [0005] This application is also a continuation-in-part of International Patent Application PCT/ US201 1/026750, filed March 1, 201 1, which application claims is a continuation-in-part application of U.S. Patent Application Serial No. 12/591,226, filed November 12, 2009, which claims the benefit of U.S. Provisional Application Nos. 61/1 14,045, filed November 12, 2008; 61/1 14,058, filed November 12, 2008; 61/1 14,065, filed November 13, 2008; 61/151,183, filed February 9, 2009; 61/278,049, filed October 2, 2009; 61/250,454, filed October 9, 2009; and 61/253,027 filed October 19, 2009; and which application also claims the benefit of U.S. Provisional Application Nos. 61/274,124, filed March 1, 2010; 61/357,5 17, filed June 22, 2010; 61/364,785, filed July 15, 2010; all of which applications are incorporated herein by reference in their entirety. [0006] This application is also a continuation-in-part of International Patent Application PCT/US201 1/03 1479, filed April 6, 201 1, which application claims the benefit of U.S. Provisional Patent Application Nos. 61/321,392, filed April 6, 2010; 61/321,407, filed April 6, 2010; 61/332,174, filed May 6, 2010; 61/348,214, filed May 25, 2010, 61/348,685, filed May 26, 2010; 61/354,125, filed June 11, 2010; 61/355,387, filed June 16, 2010; 61/356,974, filed June 21, 2010; 61/357,517, filed June 22, 2010; 61/362,674, filed July 8, 2010; 61/413,377, filed November 12, 2010; 61/322,690, filed April 9, 2010; 61/334,547, filed May 13, 2010; 61/364,785, filed July 15, 2010; 61/370,088, filed August 2, 2010; 61/379,670, filed September 2, 2010; 61/381,305, filed September 9, 2010; 61/383,305, filed September 15, 2010; 61/391,504, filed October 8, 2010; 61/393,823, filed October 15, 2010; 61/41 1,890, filed November 9, 2010; and 61/416,560, filed November 23, 2010; all of which applications are incorporated herein by reference in their entirety. BACKGROUND [0007] Biomarkers for conditions and diseases such as cancer include biological molecules such as proteins, peptides, lipids, RNAs, DNA and variations and modifications thereof. [0008] The identification of specific biomarkers, such as DNA, RNA and proteins, can provide biosignatures that are used for the diagnosis, prognosis, or theranosis of conditions or diseases. Biomarkers can be detected in bodily fluids, including circulating DNA, RNA, proteins, and vesicles. Circulating biomarkers include proteins such as PSA and CA125, and nucleic acids such as SEPT9 DNA and PCA3 messenger RNA (mRNA). Circulating biomarkers can be associated with circulating vesicles. Vesicles are membrane encapsulated structures that are shed from cells and have been found in a number of bodily fluids, including blood, plasma, serum, breast milk, ascites, bronchoalveolar lavage fluid and urine. Vesicles can take part in the communication between cells as transport vehicles for proteins, RNAs, DNAs, viruses, and prions. MicroRNAs are short RNAs that regulate the transcription and degradation of messenger RNAs. MicroRNAs have been found in bodily fluids and have been observed as a component within vesicles shed from tumor cells. The analysis of circulating biomarkers associated with diseases, including vesicles and/or microRNA, can aid in detection of disease or severity thereof, determining predisposition to a disease, as well as making treatment decisions.
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