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US 5,688,760 AGranted
Polypeptides having bone resorption inhibitory activity comprising PTHrP-derived sequences
AssigneesGenentech, Inc., The University of Melbourne
InventorsBruce E. Kemp, Geoffrey C. Nicholson, Thomas J. Martin, Anna J. Fenton, R. Glenn Hammonds
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Abstract
Polypeptides comprising an N-terminal amino acid sequence corresponding to amino acids 107-111 of parathyroid hormone related protein (PTHrP) having bone resorption inhibitory activity are provided. The polypeptides are provided in pharmaceutical compositions for the treatment of diseases and disorders where inhibition of bone resorption is indicated.
Claims19
A polypeptide having bone resorption inhibitory activity, said polypeptide having an amino acid sequence:
- Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.4 -Xaa.sub.5 -Z,
- wherein:
- Xaa.sub.1 is an amino acid selected from the group consisting of Thr, Ala, Cys, Pro, D-Trp and n-methylalanine;
- Xaa.sub.2 is an amino acid selected from the group consisting of Arg, Lys, His, and D-Ala;
- Xaa.sub.3 is an amino acid selected from the group consisting of Ser, Ala, Cys, and D-Ser;
- Xaa.sub.4 is an amino acid selected from the group consisting of Ala, n-methylalanine, (3-(2-napthyl)-alanine), and D-Arg;
- Xaa.sub.5 is an amino acid selected from the group consisting of Tyr, Trp, D-Thr, .alpha.-phenylglycine, and .alpha.-napthylalanine;
- Z is present or absent, and when present consists of an amino acid sequence beginning at PTHrP amino acid residue 112 as shown in FIG. 1 (SEQ ID NO:1) and ending at any PTHrP amino acid from 112 to 173 as shown in FIG. 1 (SEQ ID NO:1);
- or wherein Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.4 -Xaa.sub.5 -Z is the sequence RTRSAW (SEQ ID NO:4) or TRCAWPGTC (SEQ ID NO:15), and
- where "D" refers to the D-amino acid isomer;
- excluding PTHrP(107-138) and PTHrP(107-141).
8 more elements
Dependencies are inferred from the claim text.