Engineered human-derived kunitz domains that inhibit human neutrophil elastase
AssigneeDyax Corp.
InventorsArthur Charles Ley, Robert Charles Ladner, Sonia Kosow Guterman, Bruce Lindsay Roberts, William Markland, Rachel Baribault Kent
Life of this patent
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Abstract
Certain Kunitz domain derived proteins which bind and inhibit human neutrophil elastase with a K.sub.i of less than 10 picomolar are described.
Claims9
A protein that binds and inhibits human neutrophil elastase with a K.sub.i less than about 10 picomolar comprising an amino acid sequence picked from the set of sequences EpiNE1, EpiNE2, EpiNE3, EpiNE4, EpiNE5, EpiNE6, EpiNE7, EpiNE8, EPI-HNE-2, EPI-HNE-3, EPI-HNE-4, BITI-E7, BITI-E7-141, BITI-E7-1222, MUT1619, MUTP1, AMINO1, AMINO2, MUTQE, MUTT26A, EpiNE7.6, EpiNE7.8, EpiNE7.9, EpiNE7.31, EpiNE 7.11, EpiNE7.7, EpiNE7.4, EpiNE7.14, EpiNE7.5, EpiNE7.10, EpiNE7.20, EpiNE7.1, EpiNE7.16, EpiNE7.19, EpiNE7.12, EpiNE7.17, EpiNE7.21, EpiNE7.22, EpiNE7.23, EpiNE7.24, EpiNE7.25, EpiNE7.26, EpiNE7.27, EpiNE7.28, EpiNE7.29, EpiNE7.30, EpiNE7.32, EpiNE7.33, EpiNE7.36, EpiNE7.37, EpiNE7.38, EpiNE7.39, and EpiNE7.40.
A protein that binds and inhibits human neutrophil elastase with a K.sub.i less than about 10 picomolar that comprises an amino-acid sequence of at least about 51 amino acids that differs from an amino-acid sequence found in a protein of human origin by no more than about eight amino acids.
A protein that binds and inhibits hNE with an K.sub.i less than about 10 picomolar that comprises an amino-acid sequence derived from a parental Kunitz domain, said parental Kunitz domain having a K.sub.i for hNE greater than about 1.0 nanomolar and said derived Kunitz domain carrying at least the mutations X18F and a mutation picked from the set comprising X15V and X15I.
A protein that binds and inhibits human neutrophil elastase with a K.sub.i less than 10 picomolar comprising an amino acid sequence that is substantially homologous to a sequence picked from the set of sequences consisting of EpiNE1, EpiNE2, EpiNE3, EpiNE4, EpiNE5, EpiNE6, EpiNE7, EpiNE8, EPI-HNE-2, EPI-HNE-3, EPI-HNE-4, BITI-E7, BITI-E7-141, BITI-E7-1222, MUT1619, MUTP1, AMINO1, AMINO2, MUTQE, MUTT26A, EpiNE7.6, EpiNE7.8, EpiNE7.9, EpiNE7.31, EpiNE 7.11, EpiNE7.7, EpiNE7.4, EpiNE7.14, EpiNE7.5, EpiNE7.10, EpiNE7.20, EpiNE7.1, EpiNE7.16, EpiNE7.19, EpiNE7.12, EpiNE7.17, EpiNE7.21, EpiNE7.22, EpiNE7.23, EpiNE7.24, EpiNE7.25, EpiNE7.26, EpiNE7.27, EpiNE7.28, EpiNE7.29, EpiNE7.30, EpiNE7.32, EpiNE7.33, EpiNE7.36, EpiNE7.37, EpiNE7.38, EpiNE7.39, and EpiNE7.40.
Dependencies are inferred from the claim text.