Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI)

An isolated human monoclonal IgG antibody that binds specifically to human tissue factor pathway (TFPI) inhibitor, wherein the antibody comprises at least one amino acid substitution:

• (a) a human heavy chain comprising:
• a CDR 1 region with the amino acid sequence shown in SEQ ID NO:
• 41, optionally comprising a substitution at N32 relative to SEQ ID NO:
• 3;
• a CDR2 region with the amino acid sequence shown in SEQ ID NO:
• 42, optionally comprising a substitution selected from the group consisting of K55 and D62 relative to SEQ ID NO:
• 3;
• a CDR3 region that binds specifically to TFPI and has the amino acid sequence shown in SEQ ID NO:
• 43 optionally comprising a substitution at Y112 relative to SEQ ID NO:
• 3, and
• optionally, an amino acid substitution at G44 relative to SEQ ID NO:
• 3;
• (b) a human light chain comprising:
• a CDR1 region with the amino acid sequence shown in SEQ ID NO:
• 44, optionally comprising a substitution of a position selected from the group consisting of S32 and N35 and combinations thereof relative to SEQ ID NO:
• 4;
• a CDR2 region with the amino acid sequence shown in SEQ ID NO:
• 45;
• a CDR3 region that binds specifically to TFPI and has the amino acid sequence shown in SEQ ID NO:
• 46.