Sclerostin epitopes

• US 8,003,108 B2
• Filed: 04/25/2006
• Issued: 08/23/2011
• Est. Priority Date: 05/03/2005
• Status: Active Grant

• Current Assignee: Amgen Inc., UCB SA
• Original Assignee: Amgen Inc., UCB SA
• Inventors: Robinson, Martyn Kim, Warmington, Kelly Sue, Henry, Alistair James, Winters, Aaron George, Winkler, David, Paszty, Christpher, Lu, Hsieng Sen, Latham, John, Lawson, Alastair
• Primary Examiner(s): Kemmerer; Elizabeth C
• Assistant Examiner(s): Xie; Xiaozhen
• Application Number:
  US11/410,540
• Publication Number:
  US 20070072797A1
• Time in Patent Office: 1,946 Days
• Field of Search: None
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression

Abstract

Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.

Claims

1. A composition comprising a fragment of a polypeptide of SEQ ID NO:

1, the fragment consisting of the amino acid sequence of SEQ ID NO;

5.

2. A composition comprising a fragment of a polypeptide of SEQ ID NO:

1, the fragment consisting of the amino acid sequence of SEQ ID NO;

2.

3. A composition comprising two different fragments of a polypeptide of SEQ ID NO:

1, each fragment consisting of any one of the amino acid sequences of SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4 or SEQ ID NO;

5.

4. A composition comprising three different fragments of a polypeptide of SEQ ID NO:

1, each fragment consisting of any one of the amino acid sequences of SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4 or SEQ ID NO;

5.

5. A composition comprising four different fragments of a polypeptide of SEQ ID NO:

1, each fragment consisting of any one of the amino acid sequences of SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4 or SEQ ID NO;

5.

7. The composition of claim 5 or claim 6 wherein the fragment retains the tertiary structure of the corresponding polypeptide region of human sclerostin of SEQ ID NO:

1.

8. The composition of claim 7, wherein the fragment is produced by proteolytic digestion of the polypeptide of SEQ ID NO:

1.

6. A composition comprising a fragment of a polypeptide of SEQ ID NO:

1, the fragment consisting of the amino acid sequences of SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4 and SEQ ID NO;

5, wherein SEQ ID NO;

2 and 4 are joined by a disulfide bond at amino acid positions 57 and 111 with reference to SEQ ID NO;

1, and SEQ ID NO;

3 and 5 are joined by at least one of (a) a disulfide bond at amino acid positions 82 and 142 with reference to SEQ ID NO;

1, and (b) a disulfide bond at amino acid positions 86 and 144 with reference to SEQ ID NO;

1.

9. A composition comprising (a) a fragment consisting of 7 to 14 amino acids of SEQ ID NO:

2, (b) a fragment consisting of 8 to 17 amino acids of SEQ ID NO;

3, (c) a fragment consisting of 8 to 17 residues of SEQ ID NO;

4, and (d) a fragment consisting of 6 to 12 amino acids of SEQ ID NO;

5.

10. The composition of claim 9, wherein the fragment consisting of 7 to 14 amino acids of SEQ ID NO:

2 is attached to the fragment consisting of 8 to 17 residues of SEQ ID NO;

4 by a disulfide bond, and the fragment consisting of 8 to 17 amino acids of SEQ ID NO;

3 is attached to the fragment consisting of 6 to 12 residues of SEQ ID NO;

5 by one or two disulfide bonds.

11. The composition of claim 10, wherein

(a) the fragment consisting of 7 to 14 amino acids of SEQ ID NO:

2 comprises amino acid position 57 with reference to SEQ ID NO;

1,

(b) the fragment consisting of 8 to 17 amino acids of SEQ ID NO;

3 comprises amino acid position 82 and/or 86 with reference to SEQ ID NO;

1,

(c) the fragment consisting of 8 to 17 residues of SEQ ID NO;

4 comprises amino acid position 111 with reference to SEQ ID NO;

1, and

(d) the fragment consisting of 6 to 12 amino acids of SEQ ID NO;

5 comprises amino acid position 142 and/or 144 with reference to SEQ ID NO;

1,

wherein SEQ ID NO;

2 and 4 are joined by a disulfide bond at amino acid positions 57 and 111 with reference to SEQ ID NO;

1, and SEQ ID NO;

3 and 5 are joined by at least one of (i) a disulfide bond at amino acid positions 82 and 142 with reference to SEQ ID NO;

1, and (ii) a disulfide bond at amino acid positions 86 and 144 with reference to SEQ ID NO;

1.

12. The composition of claim 9, wherein

(a) the fragment consisting of 7 to 14 amino acids of SEQ ID NO:

2 is SEQ ID NO;

72,

(b) the fragment consisting of 8 to 17 amino acids of SEQ ID NO;

3 is SEQ ID NO;

70, and

(c) the fragment consisting of 6 to 12 amino acids of SEQ ID NO;

5 is SEQ ID NO;

71.

13. The composition of claim 9, wherein the fragment retains the tertiary structure of the corresponding polypeptide region of human sclerostin of SEQ ID NO:

1 and is produced by proteolytic digestion.

14. A composition comprising a peptide consisting of the amino acid sequence of SEQ ID NO:

70, a peptide consisting of the amino acid sequence of SEQ ID NO;

71, a peptide consisting of the amino acid sequence of SEQ ID NO;

72, and a peptide consisting of the amino acid sequence of SEQ ID NO;

73, wherein SEQ ID NO;

70 and SEQ ID NO;

71 are joined by a disulfide bond, and SEQ ID NO;

72 and SEQ ID NO;

73 are joined by a disulfide bond.

15. The composition of claim 14, wherein the fragment retains the tertiary structure of the corresponding polypeptide region of human sclerostin of SEQ ID NO:

1 and is produced by proteolytic digestion.