A single Chain variant of factor VIII Fc fusion protein retains normal in vivo efficacy but exhibits altered in vitro activity

PLoS ONE

Volumn 9, Issue 11, 2014, Pages

  Buyue, Yang ^a   Liu, Tongyao ^a   Kulman, John D ^a   Toby, Garabet G ^a   Kamphaus, George D ^a   Patarroyo White, Susannah ^a   Lu, Qi ^a   Reidy, Thomas J ^a   Mei, Baisong ^a   Jiang, Haiyan ^a   Pierce, Glenn F ^a   Sommer, Jurg M ^a   Peters, Robert T ^a  

^a BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 8; FC RECEPTOR; HYBRID PROTEIN; RECOMBINANT BLOOD CLOTTING FACTOR 8 FC; SINGLE CHAIN RECOMBINANT BLOOD CLOTTING FACTOR 8 FC; THROMBIN; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; ASSAY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG HALF LIFE; HEMOPHILIA A; IN VITRO STUDY; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; ANIMAL; BLEEDING; BLOOD; CHEMISTRY; DISEASE MODEL; GENETICS; HALF LIFE TIME; HUMAN; METABOLISM; MOLECULAR CLONING; PROCEDURES;

ANIMALS; CLONING, MOLECULAR; DISEASE MODELS, ANIMAL; FACTOR VIII; HALF-LIFE; HEMOPHILIA A; HEMORRHAGE; HUMANS; IN VITRO TECHNIQUES; MALE; MICE; RECOMBINANT FUSION PROTEINS; THROMBIN; VON WILLEBRAND FACTOR;

EID: 84913557635     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0113600     Document Type: Article

References (27)

1. Ljung RC (1998) Prophylactic treatment in Sweden-overtreatment or optimal model? Haemophilia 4: 409-412
2. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, et al. (2007) Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 357: 535-544
3. Bjorkman S (2003) Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective. Haemophilia 9 Suppl 1:: 101-108; discussion 109-110
4. White GC, 2nd, Courter S, Bray GL, Lee M, Gomperts ED (1997) A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. The Recombinate Previously Treated Patient Study Group. Thromb Haemost 77: 660-667
5. Dumont JA, Liu T, Low SC, Zhang X, Kamphaus G, et al. (2012) Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. Blood 119: 3024-3030
6. Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, et al. (2012) Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood 119: 3031-3037
7. Mahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, et al. (2014) Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 123: 317-325
8. Junghans RP, Anderson CL (1996) The protection receptor for IgG catabolism is the beta2- microglobulin-containing neonatal intestinal transport receptor. Proc Natl Acad Sci U S A 93: 5512-5516
9. Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7: 715-725
10. Peters RT, Toby G, Lu Q, Liu T, Kulman JD, et al. (2013) Biochemical and functional characterization of a recombinant monomeric factor VIII-Fc fusion protein. J Thromb Haemost 11: 132-141
11. Fay PJ, Anderson MT, Chavin SI, Marder VJ (1986) The size of human factor VIII heterodimers and the effects produced by thrombin. Biochim Biophys Acta 871: 268-278
12. Sandberg H, Almstedt A, Brandt J, Castro VM, Gray E, et al. (2001) Structural and functional characterization of B-domain deleted recombinant factor VIII. Semin Hematol 38: 4-12
13. Regan LM, Fay PJ (1995) Cleavage of factor VIII light chain is required for maximal generation of factor VIIIa activity. J Biol Chem 270: 8546-8552
14. Sandberg H, Kannicht C, Stenlund P, Dadaian M, Oswaldsson U, et al. (2012) Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. Thromb Res 130: 808-817
15. Thim L, Vandahl B, Karlsson J, Klausen NK, Pedersen J, et al. (2010) Purification and characterization of a new recombinant factor VIII (N8). Haemophilia 16: 349-359
16. Thim L, Gram L, Pelzer H, Knudsen H, Balling K, et al. (2011) Thursday, 28 July 2011. Journal of Thrombosis and Haemostasis 9: 712-959
17. Kelley B, Jankowski M, Booth J (2010) An improved manufacturing process for Xyntha/ReFacto AF. Haemophilia 16: 717-725
18. Siner JI, Iacobelli NP, Sabatino DE, Ivanciu L, Zhou S, et al. (2013) Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype. Blood 121: 4396-4403
19. Zollner SB, Raquet E, Muller-Cohrs J, Metzner HJ, Weimer T, et al. (2013) Preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII. Thromb Res 132: 280-287
20. Zollner S, Raquet E, Claar P, Mü ller-Cohrs J, Metzner HJ, et al. (2014) Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII. Thrombosis Research 134: 125-131
21. Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, et al. (2002) The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb 32: 249-253
22. MacDonald RC, MacDonald RI, Menco BP, Takeshita K, Subbarao NK, et al. (1991) Small-volume extrusion apparatus for preparation of large, unilamellar vesicles. Biochim Biophys Acta 1061: 297-303
23. Chang JY, Monroe DM, Stafford DW, Brinkhous KM, Roberts HR (1997) Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B. J Clin Invest 100: 886-892
24. Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, et al. (2010) Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 115: 2057-2064
25. Pan J, Liu T, Kim JY, Zhu D, Patel C, et al. (2009) Enhanced efficacy of recombinant FVIII in noncovalent complex with PEGylated liposome in hemophilia A mice. Blood 114: 2802-2811
26. Eaton D, Rodriguez H, Vehar GA (1986) Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry 25: 505-512
27. Pittman DD, Kaufman RJ (1988) Proteolytic requirements for thrombin activation of anti-hemophilic factor (factor VIII). Proc Natl Acad Sci U S A 85: 2429-2433.