The promise and challenges of bioengineered recombinant clotting factors

Journal of Thrombosis and Haemostasis

Volumn 3, Issue 8, 2005, Pages 1692-1701

  Pipe, Steven W ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Bioengineering; Factor IX; Factor VIIa; Factor VIII; Recombinant

Indexed keywords

RECOMBINANT BLOOD CLOTTING FACTOR 8;

ANTIGENICITY; BIOASSAY; BIOENGINEERING; BIOSYNTHESIS; CONFERENCE PAPER; DRUG ACTIVITY; DRUG HALF LIFE; GENE THERAPY; HEMOPHILIA; HUMAN; IMMUNOGENICITY; LONG TERM CARE; NONHUMAN; PRIORITY JOURNAL; THROMBOGENICITY; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; BLOOD COAGULATION FACTORS; DISEASE MODELS, ANIMAL; FACTOR IX; FACTOR VIIA; FACTOR VIII; GENE THERAPY; HEMOPHILIA A; HUMANS; PROTEIN ENGINEERING; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS;

EID: 28244484911     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2005.01367.x     Document Type: Conference Paper

References (87)

1. Hilgartner MW. The need for recombinant factor VIII: historical background and rationale. Semin Hematol 1991; 28: 6-9.
2. Gitschier J, Wood WI, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM. Characterization of the human factor VIII gene. Nature 1984; 312: 326-30.
3. Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC, Amphlett WB, Coe ML, Knutson GJ, Fass DN. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature 1984; 312: 342-7.
4. White GC II, McMillan CW, Kingdon HS, Shoemaker CB. Use of recombinant antihemophilic factor in the treatment of two patients with classic hemophilia. N Engl J Med 1989; 320: 166-70.
5. Mitterer A, Mundt W, Bjornson E, Dorner F. Development of an advanced category recombinant FVIII, anti-hemophilic factor (recombinant) plasma albumin-free method (rAHF-PFM). J Thromb Haemost 2003; 1: P1652.
6. Barrowcliffe TW, Raut S, Hubbard AR. Discrepancies in potency assessment of recombinant FVIII concentrates. Haemophilia 1998; 4: 63440.
7. Bond M, Jankowski M, Patel H, Karnik S, Strang A, Xu B, Rouse J, Koza S, Letwin B, Steckert J, Amphlett G, Scoble H. Biochemical characterization of recombinant factor IX. Semin Hematol 1998; 35: 11-17.
8. White G, Shapiro A, Ragni M, Garzone P, Goodfellow J, Tubridy K, Courter S. Clinical evaluation of recombinant factor IX. Semin Hematol 1998:35: 33-38.
9. Roth DA. Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood 2001; 98: 3600-6.
10. Ragni MV, Pasi KJ, White GC, Giangrande PL, Courter SG, Tubridy KL. Use of recombinant factor IX in subjects with haemophilia B undergoing surgery. Haemophilia 2002; 8: 91-97.
11. Shapiro AD, Paola JD, Cohen A, Pasi KJ, Heisel MA, Blanchette VS, Abshire TC, Hoots WK, Lusher JM, Negrier C, Rothschild C, Roth DA. The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B. Blood 2005; 105: 518-25.
12. Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol 2004; 127: 379-91.
13. Dimichele D, Rivard G, Hay C, Antunes S. Inhibitors in haemophilia: clinical aspects. Haemophilia 2004; 10 (Suppl. 4): 140-5.
14. Kreuz W, Ettingshausen CE, Auerswald G, Saguer IM, Becker S, Funk M, Heller C, Klarmann D, Klingebiel T. Epidemiology of inhibitors and current treatment strategies. Haematologica 2003; 88: EREP04.
15. Peerlinck K, Arnout J, Gilles JG, Saint-Remy JM, Vermylen J. A higher than expected incidence of factor VIII inhibitors in multi-transfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. Thromb Haemost 1993: 69: 115-8.
16. Laub R, Di Giambattista M, Fondu P, Brackmann HH, Lenk H, Saenko EL, Felch M, Scandella D. Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain. Thromb Haemost 1999; 81: 39-44.
17. Lusher J, Abildgaard C, Arkin S, Mannucci PM, Zimmermann R, Schwartz L, Hurst D. Human recombinant DNA-derived antihemophilic factor in the treatment of previously untreated patients with hemophilia A: final report on a hallmark clinical investigation. J Thromb Haemost 2004; 2: 574-83.
18. Giles AR, Rivard GE, Teitel J, Walker I. Surveillance for factor VIII inhibitor development in the Canadian hemophilia A population following the widespread introduction of recombinant factor VIII replacement therapy. Transfus Sci 1998; 19: 139-48.
19. Toole JJ, Pittman DD, Orr EC, Murtha P, Wasley LC, Kaufman RJ. A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. Proc. Natl Acad Sci U S A 1986; 83: 5939-42.
20. Sandberg H, Almstedt A, Brandt J, Gray E, Holmquist L, Oswaldsson U, Sebring S, Mikaelsson M. Structural and functional characteristics of the B-domain deleted recombinant factor VIII protein, r-VIII SQ. Thromb Haemost 2001; 85: 93-100.
21. Fijnvandraat K, Berntorp E, ten Cate JW, Johnsson H, Peters M, Savidge G, Tengborn L, Spira J, Stahl C. Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients. Thromb Haemost 1997; 77: 298-302.
22. Li X, Gabriel DA. The physical exchange of factor VIII (FVIII) between von Willebrand factor and activated platelets and the effect of the FVIII B-domain on platelet binding. Biochemistry 1997; 36: 10760-7.
23. Mikaelsson M, Oswaldsson U, Sandberg H. Influence of phospholipids on the assessment of factor VIII activity. Haemophilia 1998; 4: 646-50.
24. Mikaelsson M, Oswaldsson U, Jankowski MA. Measurement of factor VIII activity of B-domain deleted recombinant factor VIII. Semin Hematol 2001; 38: 13-23.
25. Pittman DD, Alderman EM, Tomkinson KN, Wang JH, Giles AR, Kaufman RJ. Biochemical, immunological, and in vivo functional characterization of B-domain-deleted factor VIII. Blood 1993; 81: 2925-35.
26. Eaton DL, Wood WI, Eaton D, Hass PE, Hollingshead P, Wion K, Mather J, Lawn RM, Vehar GA, German C. Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule. Biochemistry 1986; 25: 8343-7.
27. Meulien P, Faure T, Mischler F, Harrer H, Ulrich P, Bouderbala B, Dott K, Sainte Marie M, Mazurier C, Wiesel ML. A new recombinant procoagulant protein derived from the cDNA encoding human factor VIII. Protein Eng 1988; 2: 301-6.
28. Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously treated patients. Semin Hematol 2001; 38: 44-51.
29. Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously untreated patients. Semin Hematol 2001; 38: 52-59.
30. Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 2: 899-909.
31. Parameswaran R, Shapiro AD, Gill JC, Kessler CM, Investigators HR. Dose effect and efficacy of rFVIIa in the treatment of hemophilia patients with inhibitors: Analysis from the Hemophilia and Thrombosis Research Society Registry. Haemophilia 2005; 3: in press.
32. Kenet G, Lubetsky A, Luboshitz J, Martinowitz U. A new approach to treatment of bleeding episodes in young hemophilia patients: a single bolus megadose of recombinant activated factor VII (Novo-Seven). J Thromb Haemost 2003; 1: 450-5.
33. Key NS, Aledort LM, Beardsley D, Cooper HA, Davignon G, Ewenstein BM, Gilchrist GS, Gill JC, Glader B, Hoots WK, Kisker CT, Lusher JM, Rosenfield CG, Shapiro AD, Smith H, Taft E. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost 1998; 80: 912-8.
34. Lusher JM. Early treatment with recombinant factor VIIa results in greater efficacy with less product. Eur J Haematol Suppl 1998; 63: 7-10.
35. Negrier C, Goudemand J, Sultan Y, Bertrand M, Rothschild C, Lauroua P. Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity. Thromb Haemost 1997; 77: 1113-9.
36. Kaufman RJ, Pipe SW. Can we improve on nature? 'Super molecules' of factor VIII. Haemophilia 1998; 4: 370-9.
37. Saenko EL, Ananyeva NM, Shima M, Hauser CA, Pipe SW. The future of recombinant coagulation factors. J Thromb Haemost 2003; 1: 922-30.
38. Soukharev S, Hammond D, Ananyeva NM, Anderson JA, Hauser CA, Pipe S, Saenko EL. Expression of factor VIII in recombinant and transgenic systems. Blood Cells Mol Dis 2002; 28: 234-48.
39. Pipe SW. Coagulation factors with improved properties for hemophilia gene therapy. Semin Thromb Hemost 2004; 30: 227-37.
40. Pipe SW, Saint-Remy JM, Walsh CE. New high-technology products for the treatment of haemophilia. Haemophilia 2004; 10 (Suppl. 4): 55-63.
41. Plantier JL, Rodriguez MH, Enjolras N, Attali O, Negrier C. A factor VIII minigene comprising the truncated intron I of factor IX highly improves the in vitro production of factor VIII. Thromb Haemost 2001; 86: 596-603.
42. Swaroop M, Moussalli M, Pipe SW, Kaufman RJ. Mutagenesis of a potential immunoglobulin-binding protein-binding site enhances secretion of coagulation factor VIII. J Biol Chem 1997; 272: 24121-4.
43. Miao HZ, Sirachainan N, Palmer L, Kucab P, Cunningham MA, Kaufman RJ, Pipe SW. Bioengineering of coagulation factor VIII for improved secretion. Blood 2004; 103: 3412-9.
44. Powell JS, Ragni MV, White GC II, Lusher JM, Hillman-Wiseman C, Moon TE, Cole V, Ramanathan-Girish S, Roehl H, Sajjadi N, Jolly DJ, Hurst D. Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood 2003; 102: 2038-45.
45. Roth DA, Tawa NE Jr, O'Brien JM, Treco DA, Seiden RF. Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A. N Engl J Med 2001; 344: 1735-42.
46. Van Cott KE, Monahan PE, Nichols TC, Velander WH. Haemophilic factors produced by transgenic livestock: abundance that can enable alternative therapies worldwide. Haemophilia 2004; 10 (Suppl. 4): 70-6.
47. Lindsay M, Gil GC, Cadiz A, Velander WH, Zhang C, Van Cott KE. Purification of recombinant DNA-derived factor IX produced in transgenic pig milk and fractionation of active and inactive subpopulations. J Chromatogr A 2004; 1026: 149-57.
48. Paleyanda RK, Velander WH, Lee TK, Scandella DH, Gwazdauskas FC, Knight JW, Hoyer LW, Drohan WN, Lubon H. Transgenic pigs produce functional human factor VIII in milk. Nat Biotechnol 1997; 15: 971-5.
49. Pipe SW, Kaufman RJ. Characterization of a genetically engineered inactivation-resistant coagulation factor VIIIa. Proc Natl Acad Sci U S A 1997; 94: 11851-6.
50. Gale AJ, Pellequer JL, Griffin JH. A novel engineered interdomain disulfide bond stabilizes human blood coagulation factor VIIIa. J Thromb Haemost 2003; 1: OC094.
51. Lenting PJ, Neels JG, van den Berg BM, Clijsters PP, Meijerman DW, Pannekoek H, van Mourik JA, Mertens K, van Zonneveld AJ. The light chain of factor VIII comprises a binding site for low density lipoprotein receptor-related protein. J Biol Chem 1999: 274: 23734-9.
52. Saenko EL, Yakhyaev AV, Mikhailenko I, Strickland DK, Sarafanov AG. Role of the low density lipoprotein-related protein receptor in mediation of factor VIII catabolism. J Biol Chem 1999; 274: 37685-92.
53. Schwarz HP, Lenting PJ, Binder B, Mihaly J, Denis C, Dorner F, Turecek PL. Involvement of low-density lipoprotein receptor-related protein (LRP) in the clearance of factor VIII in von Willebrand factor-deficient mice, Blood 2000; 95: 1703-8.
54. Sarafanov AG, Ananyeva NM, Shima M, Saenko EL. Cell surface heparan sulfate proteoglycans participate in factor VIII catabolism mediated by low density lipoprotein receptor-related protein. J Biol Chem 2001; 276: 11970-9.
55. Turecek PL, Schwarz HP, Binder BR. In vivo inhibition of low density lipoprotein receptor-related protein improves survival of factor VIII in the absence of von Willebrand factor. Blood 2000; 95: 3637-8.
56. Ananyeva NM, Kouiavskaia DV, Shima M, Saenko EL. Catabolism of the coagulation factor VIII: can we prolong lifetime of fVIII in circulation? Trends Cardiovasc Med 2001; 11: 251-7.
57. Bovenschen N, Herz J, Grimbergen JM, Lenting PJ, Havekes LM, Mertens K, van Vlijmen BJ. Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor-related protein deficiency. Blood 2003; 101: 3933-9.
58. Parker ET, Craddock HN, Barrow RT, Lollar P. Comparative immunogenicity of recombinant B domain-deleted porcine factor VIII and Hyate:C in hemophilia A mice presensitized to human factor VIII. J Thromb Haemost 2004; 2: 605-11.
59. Parker ET, Healey JF, Barrow RT, Craddock HN, Lollar P. Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope. Blood 2004; 104: 704-10.
60. High KA. Clinical gene transfer studies for hemophilia B. Semin Thromb Hemost 2004; 30: 257-67.
61. Enjolras N, Rodriguez MH, Plantier JL, Maurice M, Attali O, Negrier C. The three in-frame ATG, clustered in the translation initiation sequence of human factor IX gene, are required for an optimal protein production. Thromb Haemost 1999; 82: 1264-9.
62. Kurachi S, Hitomi Y, Furukawa M, Kurachi K. Role of intron I in expression of the human factor IX gene. J Biol Chem 1995; 270: 5276 81.
63. Chang J, Jin J, Lollar P, Bode W, Brandstetter H, Hamaguchi N. Straight DL, Stafford DW. Changing residue 338 in human factor IX from arginine to alanine causes an increase in catalytic activity. J Biol Chem 1998; 273: 12089-94.
64. Hopfner KP, Brandstetter H, Karcher A, Kopetzki E, Huber R, Engh RA, Bode W. Converting blood coagulation factor IXa into factor Xa: dramatic increase in amidolytic activity identifies important active site determinants. Embo J 1997; 16: 6626-35.
65. Schuettrumpf J, Herzog RW, Schlachterman A, Kaufhold A. Stafford DW, Arruda VR. Factor IX variants improve gene therapy efficacy for hemophilia B. Blood 2004.
66. Lisman T, de Groot PG, Lambert T, Rojkjaer R, Persson E. Enhanced in vitro procoagulant and antifibrinolytic potential of superactive variants of recombinant factor VIIa in severe hemophilia A. J Thromb Haemost 2003: 1: 2175-8.
67. Tranholm M, Kristensen K, Kristensen AT, Pyke C, Rojkjaer R, Persson E. Improved hemostasis with superactive analogs of factor VIIa in a mouse model of hemophilia A. Blood 2003; 102: 3615-20.
68. Aronson DL. The current status of recombinant human factor VIII. Semin Hematol 1991; 28: 55-6.
69. Bi L, Lawler AM, Antonarakis SE, High KA, Gearhart JD, Kazazian HH Jr. Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat Genet 1995; 10: 119-21.
70. Bi L, Sarkar R, Naas T, Lawler AM, Pain J, Shumaker SL, Bedian V, Kazazian HH Jr. Further characterization of factor VIII-deficient mice created by gene targeting: RNA and protein studies. Blood. 1996; 88: 3446-50.
71. Lin HF, Maeda N, Smithies O, Straight DL, Stafford DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood. 1997;90: 3962-6.
72. Kundu RK, Sangiorgi F, Wu LY, Kurachi K, Anderson WF, Maxson R, Gordon EM. Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice. Blood. 1998; 92: 168-74.
73. Wang L, Zoppe M, Hackeng TM, Griffin JH, Lee KF, Verma IM. A factor IX-deficient mouse model for hemophilia B gene therapy. Proc Natl Acad Sci U S A 1997; 94: 11563-6.
74. Jin DY, Zhang TP, Gui T, Stafford DW, Monahan PE. Creation of a mouse expressing defective human factor IX. Blood. 2004; 104: 1733-9.
75. Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995; 345: 152-5.
76. Kraaijenhagen RA, in't Anker PS, Koopman MM, Reitsma PH, Prins MH, van den Ende A, Buller HR. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.
77. O'Donnell J, Tuddenham EG, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
78. Lensen R, Bertina RM, Vandenbroucke JP, Rosendaal FR. High factor VIII levels contribute to the thrombotic risk in families with factor V Leiden. Br J Haematol 2001; 114: 380-6.
79. Butenas S, van't Veer C, Mann KG. 'Normal' thrombin generation. Blood 1999; 94: 2169-78.
80. O'Donnell J, Mumford AD, Manning RA, Laffan MA. Marked elevation of thrombin generation in patients with elevated FVIII:C and venous thromboembolism. Br J Haematol 2001; 115: 687-91.
81. Journeycake JM, Quinn CT, Miller KL, Zajac JL, Buchanan GR. Catheter-related deep venous thrombosis in children with hemophilia. Blood 2001; 98: 1727-31.
82. Kawasaki T, Kaida T, Arnout J, Vermylen J, Hoylaerts MF. A new animal model of thrombophilia confirms that high plasma factor VIII levels are thrombogenic. Thromb Haemost 1999; 81: 306-11.
83. Singh I, Smith A, Vanzieleghem B, Collen D, Burnand K, Saint-Remy JM, Jacquemin M. Antithrombotic effects of controlled inhibition of factor VIII with a partially inhibitory human monoclonal antibody in a murine vena cava thrombosis model. Blood 2002; 99: 3235-40.
84. Varadi K, Turecek PL, Schwarz HP. Thrombin generation assay and other universal tests for monitoring haemophilia therapy. Haemophilia 2004; 10(Suppl. 2): 17-21.
85. Landskroner KA, Olson NC, Jesmok GJ. Enhanced factor VIII activity measurements using ROTEG and factor VIII-/- mice whole blood. J Thromb Haemost 2004; 2: 2274-5.
86. Macfarlane RG, Biggs R. A thrombin generation test; the application in haemophilia and thrombocytopenia. J Clin Pathol 1953: 6: 3-8.
87. Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74: 134-8.