Antagonists of human fgf23
OwnerChristian Wenzel Tornoee, Camille Villequey +2inventors
InventorsChristian Wenzel Tornoee, Camille Villequey, Marina Kasimova, Franziska Schoeppe
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Abstract
The present invention relates to novel hFGF23 antagonistic polypeptides and long-acting derivatives thereof, and their use in medicine and in particular for inhibiting hFGF23-induced signalling in patients in need thereof, such as patients suffering from hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH), as well as pharmaceutical compositions comprising such compounds.
Claims24
A hFGF23 antagonistic polypeptide, which is capable of binding an epitope comprising the amino acid residues selected from the group consisting of:
- a) R76, T86, R91 and R114;
- b) M74, R76, T86, R91, F108, P110, R114, L166, I167 and N170;
- c) R76, T86, R91, Y93, Y107, R114, F169 and N170;
- d) W36, R76, T86, R91, Y107, R114, 1167, F169 and N170;
- and
- e) R76, T86, R91, R114, L166 and F169;
- on hFGF23 according to SEQ ID NO:1 as determined at 3.5 Å.
A hFGF23 antagonistic polypeptide, which is capable of binding hFGF23 according to SEQ ID NO:1, comprising a binding motif (BM) which consists of an amino acid residue sequence selected from
- i)
- XaXbXcWXdEIXeXfXgPXhLXiDXjQWPAFIEXkLH
- according to SEQ ID NO:
- 2
- wherein, independently of each other,
- Xa is F or Y;
- Xb is F, I, L or V;
- Xc is A or Q;
- Xd is A, F, H, Y or W;
- Xe is F or Y;
- Xf is N, Q or T;
- Xg is A or L;
- Xh is C, H, N, Q, W or Y;
- Xi is D, N, Q, S or T;
- Xj is A, D, E, G, H, L, N, Q, S, T or Y;
- Xk is A, Q or S;
- and
- ii) an amino acid residue sequence having at least 93% identity to the sequence defined in i).
An hFGF23 antagonistic polypeptide, which is capable of binding hFGF23 according to SEQ ID NO:1, having at least 93% identity to a hFGF23 antagonistic polypeptide selected from the group consisting of:
- Chem. 197 according to SEQ ID NO:168;
- Chem. 201 according to SEQ ID NO:176;
- Chem. 204 according to SEQ ID NO:234;
- Chem. 206 according to SEQ ID NO:236;
- Chem. 207 according to SEQ ID NO:237;
- and
- Chem. 208 according to SEQ ID NO:238.
A compound selected from the group consisting of:
(canceled)
A method of treating tumor-induced osteomalacia, fibrous dysplasia, McCune-Albright syndrome, autosomal dominant hypophosphatemic rickets (ADHR) or X-linked hypophosphatemic rickets (XLH) comprising administering an effective amount of the hFGF23 antagonistic polypeptide, polypeptide derivative, compound, or composition according to to a patient in need thereof.
Dependencies are inferred from the claim text.