Polypeptide variants with increased heparin-binding capacity
AssigneeOsteopharma Inc.
InventorWalter Sebald
Life of this patent
Estimating the term…
Abstract
The invention pertains to polypeptide variants with increased heparin-binding ability. Increased heparin-binding ability is achieved by addition, insertion, and/or substitution of an amino acid sequence X1X2X3X4X5X6 (SEQ ID NO. 1 or NO.2). Polypeptide variants according to the invention are particularly suited for stimulation of chondrogenesis, osteogenesis, and wound healing. The invention also pertains to amino acid molecules that encode said polypeptide variants, host cells containing said nucleic acid molecules, and processes for producing the polypeptide variants.
Claims28
A bone morphogenetic protein (BMP) or a growth differentiation factor (GDF) polypeptide variant with increased heparin-binding ability, characterized in that
- (i) added to the amino acid sequence of a BMP or GDF polypeptide is at least one oligopeptide comprising the amino acid sequence X1X2X3X4X5X6;
- and/or
- (ii) inserted into the amino acid sequence of a BMP or GDF polypeptide is at least one oligopeptide comprising the amino acid sequence X1X2X3X4X5X6;
- and/or
- (iii) at least one oligopeptide sequence naturally occurring within the amino acid sequence of a BMP or GDF polypeptide is substituted by an oligopeptide comprising an amino acid sequence X1X2X3X4X5X6,
- wherein
- X1=K, R, or H;
- X2=K, R, or H;
- X3=K, R, or H;
- X4=not K, R, H, but any other amino acid;
- X5=not K, R, H, but any other or no amino acid;
- X6=not K, R, H, but any other or no amino acid (SEQ ID NO:
- 1).
A bone morphogenetic protein (BMP) or a growth differentiation factor (GDF) polypeptide variant with increased heparin-binding ability, characterized in that
- (i) added to the amino acid sequence of a polypeptide is at least one oligopeptide comprising the amino acid sequence RKRA (SEQ ID NO:3) or RKRAKHKQ (SEQ ID NO:4);
- and/or
- (ii) inserted into the amino acid sequence of a polypeptide is at least one oligopeptide comprising the amino acid sequence RKRA (SEQ ID NO:3) or RKRAKHKQ (SEQ ID NO:4);
- and/or
- (iii) at least one oligopeptide sequence naturally occurring within the amino acid sequence of a polypeptide is substituted by an oligopeptide comprising an amino acid sequence RKRA (SEQ ID NO:3) or RKRAKHKQ (SEQ ID NO:4).
A bone morphogenetic protein 2 BMP-2) polypeptide variant with increased heparin-binding ability, characterized in that said BMP-2 polypeptide variant has the amino acid sequence SEQ ID NO:5 (T3) or SEQ ID NO:6 (T4).
Dependencies are inferred from the claim text.