Patent AU-2020264278-A1 (AU)
Title: Optimized human clotting Factor VIII gene expression cassettes and their use
Inventor: XIAO XIAO
IPC: A61K38/37
Filed: 2020-11-03
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) 
(19) World Intellectual Property 
Organization 
International Bureau 
(10) International Publication Number 
(43) International Publication Date W O 2016/127057 A1 
11 August 2016 (11.08.2016) WIPOIPCT 
(51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every 
C07K 14/755 (2006.01) C12P 21/02 (2006.01) kind of national protection available): AE, AG, AL, AM, 
C12N15/12 (2006.01) A61K38/37(2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 
C12N15/85 (2006.01) A61P 7/04 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 
C12N 5/10 (2006.01) DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, 
HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 
(21) InternationalApplicationNumber: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 
PCT/US2016/016777 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 
(22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 
5 February 2016 (05.02.2016) 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.  
(25) Filing Language: English 
(84) Designated States (unless otherwise indicated, for every 
(26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, 
(30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 
62/112,901 6 February 2015 (06.02.2015) 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: THE UNIVERSITY OF NORTH CARO- DK, EE, ES, Fl, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 
LINA AT CHAPEL HILL [US/US]; 100 Europa Drive, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 
Suite 430, Chapel Hill, North Carolina 27517 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, 
(72) Inventors: XIAO, Xiao; 4205 Taylor Hall Place, Chapel GW, KM, ML, MR, NE, SN, TD, TG).  
Hill, North Carolina 27517 (US). LI, Juan; 4205 Taylor Published: 
Hall Place, Chapel Hill, North Carolina 27517 (US). withinternationalsearchreport(Art.21(3)) 
YUAN, Zhenhua; 102 Old Cooper Square, Chapel Hill, 
North Carolina 27517 (US). - with sequence listing part of description (Rule 5.2(a)) 
(74) Agent: MYERS BIGEL SIBLEY & SAJOVEC, PA; PO 
Box 37428, Raleigh, North Carolina 27627 (US).  
(54) Title: OPTIMIZED HUMAN CLOTTING FACTOR VIII GENE EXPRESSION CASSETTES AND THEIR USE 
CTGTTTACTCTGGTTAATTTTTAAAGGAGGGTAAACAGTGCCTGAAAG 
HNF3 HNF1 HNF3 
CTGACCTTTGCCCACATTCCTCCGGTAGACATTAACTTATTAAATT 
HNF4A TEF 
GATTCTGATTACAAATCTGACCTTTGCCCCCATCTCACCCAGTAACAATGCAA 
CEBPA HNF4A 
GAGTTGATGTCAGTCTATAAAAAGCGAAGCGCGCGGTGGGCGGGGTTCGCTGC 
API TATA SPI 
FIG. 1 
(57) Abstract: The invention relates to synthetic liver-specific promoters and expression constructs for producing polypeptides and 
functional nucleic acids in the liver of a subject. The invention further relates to Factor VIII proteins containing modifications in the 
amino acid sequence of the Factor VIII protein, as well as nucleic acid constructs encoding the Factor VIII proteins and methods of 
using these compositions to treat a bleeding disorder.