Patent SG-11201805809W-A (SG)
Title: Inhibition of protein degradation for improved production
Inventor: JAQUES COLIN MARK
IPC: G01N33/50
Filed: 2017-01-06
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -, Organization 1111111101111011101010111110101111101110111011111101111101111101111101111011111 International Bureau ... .1 j ..... ....!;,,, (10) International Publication Number (43) International Publication Date WO 2017/118726 Al 13 July 2017 (13.07.2017) WI P0 I P CT (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, G01N 33/50 (2006.01) C12N 5/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (21) International Application Number: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, PCT/EP2017/050259 MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (22) International Filing Date: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 6 January 2017 (06.01.2017) 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, (25) Filing Language: English 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, 62/275,691 6 January 2016 (06.01.2016) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/276,339 8 January 2016 (08.01.2016) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: LONZA LTD [CH/CH]; Lonzastrasse, 3930 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Visp (CH). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventors: JAQUES, Colin Mark; 132 St Stephen's Road, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, London E3 5JQ (GB). SMALES, Christopher Mark; 37 GW, KM, ML, MR, NE, SN, TD, TG). Ethelbert Road, Canterbury Kent CT1 3NF (GB). Published: KNIGHT, Tanya Jeane; 32 Kings Road, Herne Bay Kent — CT6 5DA (GB). — with international search report (Art. 21(3)) — — before the expiration of the time limit for amending the (81) Designated States (unless otherwise indicated, for every claims and to be republished in the event of receipt of = kind of national protection available): AE, AG, AL, AM, amendments (Rule 48.2(h)) = = AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, = = = (54) Title: INHIBITION OF PROTEIN DEGRADATION FOR IMPROVED PRODUCTION = 450.00 400.00 — = 350.00 = — f — 300.00 3' = . 2 — = e 250.00 = Fi § 200.00 = tj 100.00 — 50.00 N , II 11 ET — IMIfflurrnMligl 0.00 1 r— iiiMM % IM 48 96 168 Time (hours) tD 0 37.5pM MSX El 15.6,25nM MG132 + 37.50 MSX ea 31.25nM MG132 + 37.50 MSX el 06.25oM EPDX + 37.5pM MSX 8112.5nM EPDX + 37.5M MSX M25nAil EPDX + 37.5pM MSX I...' III0.1pM EEY -, 37.5pM MSX 110.5uM EEY + 37.50 MSX li UM EEY + 37.5uM MSX cc Figure 14 1-1 1-1 -..... I N (57) : Disclosed herein are methods and compositions useful for evaluating, selecting, identifying, or making a cell or cell 1-1 C line that has improved production capacity for generating higher yields of products and/or improved capacity to produce higher qual - el ity products. Products, as described herein, can include a polypeptide that is endogenously expressed by the cell, a recombinant 0 polypeptide that is not endogenously expressed, or a non-naturally occurring recombinant polypeptide. The methods described ,..1: herein include modulating, e.g., inhibiting, the protein degradation pathway by using a proteasome inhibitor, an ER-associated de- .,. gradation (ERAD) inhibitor, or a ubiquitin pathway inhibitor.