Supplementary Materials

Supplementary Material for:

Factor XIa–specific IgG and a reversal agent to probe factor XI function in thrombosis and hemostasis

Tovo David, Yun Cheol Kim, Lauren K. Ely, Isaac Rondon, Huilan Gao, Peter O?Brien, Michael W. Bolt, Anthony J. Coyle, Jorge L. Garcia, Eric A. Flounders, Thomas Mikita,* Shaun R. Coughlin*

*Corresponding author. Email: shaun.coughlin{at}ucsf.edu (S.R.C.); thomas.mikita{at}pfizer.com (T.M.)

Published 24 August 2016, Sci. Transl. Med. 8, 353ra112 (2016)
DOI: 10.1126/scitranslmed.aaf4331

This PDF file includes:

  • Fig. S1. Schematic of coagulation cascade with emphasis on FXI and the intrinsic pathway.
  • Fig. S2. Schematic of phage selection and anti-FXI human mAb screening and optimization.
  • Fig. S3. FXIa-C24 binding is SDS-labile.
  • Fig. S4. C24 and DEF bind and inhibit FXIa but not other coagulation proteases, APC, or PKa.
  • Fig. S5. Effect of anti-FXIa antibodies on FXIIa-induced thrombin generation in human plasma.
  • Fig. S6. Effect of C24 on tissue factor–activated thrombin generation in human plasma.
  • Fig. S7. Addition of albumin at up to 40 mg/ml (human plasma levels) does not alter C24 or DEF inhibition of human FXIa–mediated small-substrate hydrolysis.
  • Fig. S8. Single-dose rabbit pharmacokinetics and pharmacodynamics study: Antibody levels and APTT.
  • Fig. S9. Pharmacokinetics and pharmacodynamics of DEF exposure during exploratory toxicology in cynomolgus macaques.
  • Fig. S10. Reversal of DEF inhibition of FXIIa-induced thrombin generation in human plasma by revC4 IgG1.
  • Fig. S11. Effect of DEF and revC4 IgG on PT clotting time.
  • Fig. S12. revC4 IgG and revC4 Fab block inhibition of FXIa-mediated SN-59 hydrolysis by DEF. www.sciencetranslationalmedicine.org/cgi/content/full/8/353/353ra112/DC1
  • Fig. S13. FXIIa-triggered thrombin generation in FXI-deficient human plasma reconstituted with normal plasma or FXI.
  • Fig. S14. APTT in FXI-deficient human plasma reconstituted with normal human plasma or human FXI.
  • Table S1. Summary of potency data for D4, B11, C24, and DEF IgGs across biochemical, plasma- and blood-based, and in vivo assays.

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