Inhibitors of human plasmin derived from the kunitz domains
AssigneeDyax Corp.
InventorsWilliam Markland, Robert Charles Ladner
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Abstract
This invention provides: novel proteins, which are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and which are capable of inhibiting plasmin; uses of such novel proteins in therapeutic, diagnostic, and clinical methods; and polynucleotides that encode such novel proteins.
Claims11
A plasmin inhibiting protein that comprises an amino-acid sequence that is substantially homologous to residues 5 through 55 of a reference sequence selected from the group comprising SPI11, SPI15, SPI08, SPI23, SPI51, SPI47, QS4, and NS4 as shown in Table 4.
A plasmin inhibiting protein wherein said protein comprises a Kunitz domain meeting the requirements shown in Table 14 with residues number by reference to BPTI, and wherein said protein has at the Kunitz domain positions 12-21 and 32-39 one of the amino-acid types listed for that position in Table 15 and wherein the sequence of said Kunitz domain is more similar in amino-acid sequence to a reference sequence selected from the group SPI11, SPI15, SPI08, SPI23, SPI51, SPI47, QS4, NS4, Human LACI-K2, Human LACI-K3, Human collagen α3 KuDom, Human TFPI-2 DOMAIN 1, Human TFPI-2 DOMAIN 2, Human TFPI-2 DOMAIN 3, HUMAN ITI-K1, Human ITI-K2, HUMAN PROTEASE NEXIN-II, Human APP-I, DPI-1.1.1, DPI-1.1.2, DPI-1.1.3, DPI-1.2.1, DPI-1.3.1, DPI-2.1, DPI-3.1.1, DPI-3.2.1, DPI-3.3.1, DPI4.1.1, DPI4.2.1, DPI4.2.2, DPI4.2.3, DPI4.2.4, DPI4.2.5, DPI-5.1, DPI-5.2, DPI-6.1, and DPI-6.2 than is the amino acid sequence of said Kunitz domai n to the sequence of BPTI.
A plasmin inhibiting protein having a Ki of about 100 pM or less.
Dependencies are inferred from the claim text.