Receptor-binding determinant from leukaemia inhibitory factor
AssigneeAmrad Corporation Limited
InventorsMeredith Jane Layton, Catherine Mary Owczarek, Nicos Antony Nicola, Nicholas Martin Gough, Donald Metcalf
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Abstract
The present invention relates generally to molecules carrying one or more binding determinants for α-chain of human Leukaemia Inhibitory Factor binding receptor and to genetic sequences encoding same. More particularly, the present invention contemplates a molecule which is non-naturally occurring and which comprises a carrier portion and an active portion and wherein the active portion comprises amino acid residues or chemical equivalents thereof which constitute a binding determinant for the α chain of the human leukaemia inhibitory factor (hLIF) binding receptor.
Claims22
A substantially biologically pure molecule as set forth in FIG. 1 comprising:
- (i) a polypeptide backbone having a tertiary structure;
- (ii) amino acid residues constituting a binding determinant for the a chain of hLIF binding receptor inserted into said polypeptide backbone such that the arrangement of said amino acid residues in the tertiary structure of the polypeptide provides a hLIF receptor-binding face;
- and wherein said molecule exhibits at least about 50% hLIF-like activity as defined by the equation:
- log X m - log X c log X m - log X h ≥ 0.50
- wherein Xm is a dose of unlabelled mLIF;
- Xh is a dose of unlabelled hLIF;
- and XC is a dose of said molecule required to give 50% inhibition of 125I-hLIF binding to murine LIF binding protein.
An isolated murine-human leukemia inhibitory factor (mhLIF) hybrid molecule, as set forth in FIG. 1 comprising a polypeptide backbone of murine LIF, wherein at least one amino acid of said murine LIF is substituted with an amino acid of human LIF thereby providing a binding determinant for the α-chain of a hLIF binding receptor, and wherein said hybrid molecule exhibits at least 50% hLIF-like activity as defined by the equation:
- LOG X m - LOG X c LOG X m - LOG X h ≥ 0.50
- wherein Xm is a dose of unlabeled mLIF having SEQ ID NO:1;
- Xh is a dose of unlabeled hLIF having SEQ ID NO:2;
- and Xc is a dose of said molecule required to give 50% inhibition of 125I-hLIF binding to murine LIF binding protein.
An isolated nucleic acid molecule which encodes a substantially biologically pure molecule as set forth in FIG. 1 comprising:
- (ii) a polypeptide backbone having a tertiary structure;
- (ii) amino acid residues constituting a binding determinant for the α chain of hLIF binding receptor inserted into said polypeptide backbone such that the arrangement of said amino acid residues in the tertiary structure of the polypeptide provides a hLIF receptor-binding face;
- and wherein said substantially biologically pure molecule exhibits at least about 50% hLIF-like activity as defined by the equation:
- log X m - log X c log X m - log X h ≥ 0.50
- wherein Xm is a dose of unlabelled mLIF;
- Xh is a dose of unlabelled hLIF;
- and Xc is a dose of said substantially biologically pure molecule required to give 50% inhibition of 125I-hLIF binding to murine LIF binding protein.
An isolated nucleic acid molecule which encodes an isolated murine-human leukemia inhibitory factor (mhLIF) hybrid molecule as set forth in FIG. 1, comprising a polypeptide backbone of murine LIF, wherein at least one amino acid of said murine LIF is substituted with an amino acid of human LIF thereby providing a binding determinant for the α-chain of a hLIF binding receptor, and wherein said hybrid molecule exhibits at least 50% hLIF-like activity as defined by the equation:
- log X m - log X c log X m - log X h ≥ 0.50
- wherein Xm is a dose of unlabeled mLIF having SEQ ID NO:1;
- Xh is a dose of unlabeled hLIF having SEQ ID NO:2;
- and Xc is a dose of said hybrid molecule required to give 50% inhibition of 125I-hLIF binding to murine LIF binding protein.
Dependencies are inferred from the claim text.