Modified factor VII polypeptides and uses thereof
OwnerEdwin L. Madison, Christopher Thanos +2inventors
InventorsEdwin L. Madison, Christopher Thanos, Sandra Waugh Ruggles, Shaun Coughlin
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Abstract
Modified factor VII polypeptides and uses thereof are provided. Such modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.
Claims100
A modified factor VII (FVII) polypeptide, comprising a modification in a FVII polypeptide, allelic and species variant thereof or active fragments thereof;
- wherein
- the modification is at a position corresponding to position D196, K197 or K199 in a FVII polypeptide having a sequence of amino acids set forth in SEQ ID NO:3 or in corresponding residues in a FVII polypeptide;
- and
- the modification is replacement by a hydrophobic or acidic amino acid, wherein
- the hydrophobic or acidic amino acid is selected from among Val (V), Leu (L), Ile (I), Phe (F), Trp (W), Met (M), Tyr (Y), Cys (C), Asp (D) and Glu (E).
A modified factor VII (FVII) polypeptide, comprising a modification in a FVII polypeptide, allelic or species variant thereof or active fragments thereof, selected from among amino acid modifications corresponding to D 196R, D 196Y, D196F, D196W, D196L, D196I, K197Y, K197E, K197D, K197L, K197M, K197M, K197I, K197V, K197F, K197W, K199D, K199E, G237W, G237I, G237V, R290M, R290V, K341M, K341D, G237T238insA, G237T238insS, G237T238insV, G237T238insAS, G237T238insSA, D196K197insK, D196K197insR, D196K197insY, D196K197insW, D196K197insA, D196K197insM, K1971198insE, K1971198insY, K1971198insA or K1971198insS in a FVII polypeptide having a sequence of amino acids set forth in SEQ ID NO:3 or in corresponding residues in a FVII polypeptide.
A modified factor VII (FVII) polypeptide, comprising two or more modifications in a FVII polypeptide, allelic and species variant thereof or active fragments thereof, wherein:
- the two or more amino acid modifications are selected from among amino acid modifications corresponding to D196K, D196R, D196A, D196Y, D196F, D196M, D196W, D196L, D196I, K197Y, K197A, K197E, K197D, K197L, K197M, K197I, K197V, K197F, K197W, K199A, K199D, K199E, G237W, G237T, G237I, G237V, T239A, R290A, R290E, R290D, R290N, R290Q, R290K, K341E, K341R, K341N, K341M, K341D, K341Q, G237T238insA, G237T238insS, G237T238insV, G237T238insAS, G237T238insSA, D196K197insK, D196K197insR, D196K197insY, D196K197insW, D196K197insA, D196K197insM, K1971198insE, K1971198insY, K1971198insA or K1971198insS in a FVII polypeptide having a sequence of amino acids set forth in SEQ ID NO:3 or in corresponding residues in a FVII polypeptide.
A modified factor VII (FVII) polypeptide, comprising a heterologous Gla domain, or a sufficient portion thereof to effect phospholipid binding.
The modified FVII polypeptide, comprising a sequence of amino acids residues whose sequence is forth in any of SEQ ID NOS:
- 18-43 and 125-146 and 206-250.
Dependencies are inferred from the claim text.