Patent SG-11201407972R-A (SG)
Title: High-affinity monoclonal antibodies to glypican-3 and use thereof
Inventor: HO MITCHELL
IPC: A61P35/00
Filed: 2013-05-31
Abstract: (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 5 December 2013 (05.12.2013) WIPOIPCT (10) International Publication Number WO 2013/181543 A1 (51) International Patent Classification: C07K16/30 (2006.01) A61P 35/00 (2006.01) A61K39/395 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/US2013/043633 31 May 2013 (31.05.2013) English English (30) Priority Data: 61/654,232 1 June 2012 (01.06.2012) US (71) Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPT. OF HEALTH AND HUMAN SERVICES [US/US]; National Institute of Health, Office of Technology Transfer, 6011 Executive Boulevard, Suite 325, MSC 7660, Bethesda, MD 20852-7660 (US). (72) Inventors: HO, Mitchell; 4009 Tottenham Ct., Urbana, MD 21704-7388 (US). PHUNG, Yen, T.; 4500 Banff Street, Annandale, VA 22003 (US). GAO, Wei; 263 Con­ gressional Lane, Apt. 712, Rockville, MD 20852 (US). ZHANG, Yifan; 5346 Chaffms Farm Ct., Haymarket, VA 20169 (US). (74) Agent: CONNOLLY, Jodi, L.; Klarquist Sparkman, LLP, One World Trade Center, Suite 1600, 121 SW Salmon Street, Portland, OR 97204 (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, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, 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, 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, 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). Declarations under Rule 4.17: — of inventorship (Rule 4.17(iv)) [Continued on next page] (54) Title: HIGH-AFFINITY MONOCLONAL ANTIBODIES TO GLYPICAN-3 AND USE THEREOF = \"E 1200 = £ 1000 = g 800 ^ | 600 400 •t •H 00 i-H o CJ o & 200 FIG. 4A -vehicle -YP7 5 10 15 20 25 Days after inoculation _l 30 (57) Abstract: Described herein is the identifica­ tion of a panel of high affinity monoclonal anti­ bodies that bind GPC3. The disclosed antibodies recognize native GPC3 on the surface of cancer cells, as well as soluble GPC3. The highest affinity antibody (YP7) was further characterized and shown to be highly sensitive in that it was capable of detecting cancer cells with low expression of GPC3. YP7 also exhibited significant HCC tumor growth inhibition in vivo. Immunotoxins compris­ ing the antibodies disclosed herein fused to PE38 exhibited very high binding affinity for GPC3-ex- pressing cells and significantly inhibited GPC3- expressing cancer cell growth. Thus, the high- affinity monoclonal antibodies disclosed herein can be used for the diagnosis and treatment of GPC3-expressing cancers. WO 2013/181543 A11 lllll llllllll II llllll lllll III lllll III III III lllll lllll lllll lllll llll lllll llll lllllll llll llll 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)) — with sequence listing part of description (Rule 5.2(a))