Binding molecules for human factor VIII and factor VIII-like proteins
AssigneeDyax Corp.
InventorsJinan Yu, M. Daniel Potter, Brian D. Kelley, Jeffrey S. Deetz, James E. Booth
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Abstract
It is an object of the present invention to provide novel binding molecules for factor VIII and factor VIII-like proteins. Preferred binding molecules of the present invention exhibit not only distinct characteristics for binding of the target factor VIII polypeptides but also specific and desirable characteristics for release (elution) of the target polypeptides. Especially preferred binding molecules according to the invention are short polypeptide sequences, characterized by a stable loop structure.
Claims63
A polypeptide comprising the amino acid sequence Ser-Trp-X1-X2-Pro-Cys (SEQ ID NO:
- 45), wherein X1 is Val, Ile, Leu or Phe, and wherein X2 can be any amino acid, such that the polypeptide binds factor VIII.
A polypeptide comprising the amino acid sequence X1-X2-Cys-Ser-Trp-X3-X4-Pro-Cys-X5-X6 (SEQ ID NO:
- 55), wherein:
- X1 is Arg or Phe;
- X2 is Leu or Gly;
- X3 is Val, Ile, Leu or Phe;
- X4 is Ser or Phe;
- X5 is Ser or Pro;
- and
- X6 is Ala or Phe,
- such that the polypeptide binds factor VIII.
The polypeptide of claim 12, wherein X1 is Arg, X2 is Leu, X4 is Ser, X5 is Ser and X6 is Ala.
A polypeptide comprising the amino acid sequence His-X1-Cys-X2-X3-Trp-X4-X5-Pro-Cys-X6-X7 (SEQ ID NO:
- 59), wherein:
- X1 is Val, Ile, Leu or Phe;
- X2 is Gly or Phe;
- X3 is Ala or Ser;
- X4 is Leu or Phe;
- X5 is Arg, Phe, Asn or His;
- X6 is Tyr, Lys, Phe, Ala, Asp or His;
- and
- X7 is Asn, His or Ala,
- such that the polypeptide binds factor VIII.
A polypeptide comprising the amino acid sequence Phe-Cys-X1-Val-Phe-X2-X3-X4-His-Cys-X5 (SEQ ID NO:
- 70), wherein:
- X1 is Trp or His;
- X2 is Ala, Pro, Asn or Gln;
- X3 is Phe or Trp;
- X4 is Asp, Gln, Ser, Asn, Val, Arg or His;
- and
- X5 is His, Ala, Ser, Asp or Phe,
- such that the polypeptide binds factor VIII.
A composition comprising a polypeptide comprising the amino acid sequence Ser-Trp-X1-X2-Pro-Cys (SEQ ID NO:
- 45), wherein X1 is Val, Ile, Leu or Phe, and wherein X2 can be any amino acid, wherein the polypeptide can bind factor VIII and the polypeptide is attached to a solid support matrix.
A composition comprising a polypeptide comprising the amino acid sequence X1-X2-Cys-Ser-Trp-X3-X4-Pro-Cys-X5-X6 (SEQ ID NO:
- 55), wherein:
- X1 is Arg or Phe;
- X2 is Leu or Gly;
- X3 is Val, Ile, Leu or Phe;
- X4 is Ser or Phe;
- X5 is Ser or Pro;
- and
- X6 is Ala or Phe,
- and wherein the polypeptide can bind factor VIII and the polypeptide is attached to a solid support matrix.
A composition comprising a polypeptide comprising the amino acid sequence His-X1-Cys-X2-X3-Trp-X4-X5-Pro-Cys-X6-X7 (SEQ ID NO:
- 59), wherein:
- X1 is Val, Ile, Leu or Phe;
- X2 is Gly or Phe;
- X3 is Ala or Ser;
- X4 is Leu or Phe;
- X5 is Arg, Phe, Asn or His;
- X6 is Tyr, Lys, Phe, Ala, Asp or His;
- and
- X7 is Asn, His or Ala,
- and wherein the polypeptide can bind factor VIII and the polypeptide is attached to a solid support matrix.
A composition comprising a polypeptide comprising the amino acid sequence Phe-Cys-X1-Val-Phe-X2-X3-X4-His-Cys-X5 (SEQ ID NO:
- 70), wherein the polypeptide can bind factor VIII and the polypeptide is attached to a solid support matrix.
A recombinant bacteriophage expressing exogenous DNA encoding a polypeptide, wherein the polypeptide comprises the amino acid sequence Ser-Trp-X1-X2-Pro-Cys (SEQ ID NO:
- 45), wherein X1 is Val, Ile, Leu or Phe, and wherein X2 can be any amino acid, such that the polypeptide binds factor VIII.
A recombinant bacteriophage expressing exogenous DNA encoding a polypeptide, the polypeptide comprising the amino acid sequence X1-X2-Cys-Ser-Trp-X3-X4-Pro-Cys-X5-X6 (SEQ ID NO:
- 55), wherein:
- X1 is Arg or Phe;
- X2 is Leu or Gly;
- X3 is Val, Ile, Leu or Phe;
- X4 is Ser or Phe;
- X5 is Ser or Pro;
- and
- X6 is Ala or Phe;
- such that the polypeptide binds factor VIII.
A recombinant bacteriophage expressing exogenous DNA encoding a polypeptide, the polypeptide comprising the amino acid sequence His-X1-Cys-X2-X3-Trp-X4-X5-Pro-Cys-X6-X7 (SEQ ID NO:
- 59), wherein:
- X1 is Val, Ile, Leu or Phe;
- X2 is Gly or Phe;
- X3 is Ala or Ser;
- X4 is Leu or Phe;
- X5 is Arg, Phe, Asn or His;
- X6 is Tyr, Lys, Phe, Ala, Asp or His;
- and
- X7 is Asn, His or Ala,
- such that the polypeptide binds factor VIII.
A recombinant bacteriophage expressing exogenous DNA encoding a polypeptide, the polypeptide comprising the amino acid sequence Phe-Cys-X1-Val-Phe-X2-X3-X4-His-Cys-X5 (SEQ ID NO:
- 70), such that the polypeptide binds factor VIII.
Dependencies are inferred from the claim text.