Bispecific binding agents

Patent metadata

Field	Value
Publication number	US-9133272-B2
Application number	US-201213409019-A
Country	US
Kind code	B2
Filing date	Feb 29, 2012
Priority date	Mar 1, 2011
Publication date	Sep 15, 2015
Grant date	Sep 15, 2015

Abstract

The invention relates to bispecific anti-sclerostin/anti-DKK1 binding agents and combinations of anti-sclerostin and anti-DKK1 binding agents, and related methods of treatment.

First claim

What is claimed is:

1. A binding molecule that specifically binds sclerostin and DKK-1 and comprises first and second polypeptide chains, wherein said first polypeptide chain comprises VH1-(X1)n-VH2-C-(X2)n, wherein VH1 comprises the amino acid sequence of SEQ ID NO: 95; wherein VH2 comprises the amino acid sequence of SEQ ID NO: 4086; C is a heavy chain constant domain; (X1)n is a linker set forth in SEQ ID NO: 440 or SEQ ID NO: 441, and (X2)n is an Fc region and wherein said second polypeptide chain comprises a VL1-(X1)n-VL2-C, wherein VL1 comprises the amino acid sequence of SEQ ID NO: 94; wherein VL2 comprises the amino acid sequence of SEQ ID NO: 407; and wherein C is a light chain constant domain.

2. The binding molecule of claim 1 , wherein the binding molecule comprises two first polypeptide chains and two second polypeptide chains.

3. The binding molecule of claim 1 , wherein the Fc region is selected from the group consisting of a native sequence Fc region and a variant sequence Fc region.

4. The binding molecule of claim 1 , wherein the Fc region is selected from the group consisting of an Fc region from an IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, and IgD.

5. The binding molecule of claim 1 , wherein said binding molecule possesses at least one antibody parameter exhibited by said first parent antibody, or antigen binding portion thereof, or said second parent antibody, or antigen binding portion thereof, wherein said antibody parameter is selected from the group consisting of antigen specificity, affinity to antigen, potency, biological function, epitope recognition, stability, solubility, production efficiency, immunogenicity, pharmacokinetics, bioavailability, tissue cross reactivity, and orthologous antigen binding.

6. A binding molecule that binds both sclerostin and DKK-1 comprising four polypeptide chains, wherein first and third polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 62 and wherein second and fourth polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 64.

7. A binding molecule that binds both sclerostin and DKK-1 comprising four polypeptide chains, wherein first and third polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 490 and wherein second and fourth polypeptide chains comprise the amino acid sequence set forth in SEQ ID NO: 492.

8. The binding molecule of claim 1 , wherein said (X1)n of the VL1-(X1)n-VL2-C is SEQ ID NO: 440.

9. The binding molecule of claim 1 , wherein said (X1)n of the VL1-(X1)n-VL2-C is SEQ ID NO: 441.

10. A method for generating a binding molecule that binds sclerostin and DKK-1 comprising the steps of: expressing said first, second, third and fourth polypeptide chains of claim 6 such that a binding molecule that binds sclerostin and DKK-1 is generated.

11. A pharmaceutical composition comprising the binding molecule of claim 6 .

12. The binding molecule of claim 6 in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.

13. A method of treating a bone disorder comprising administering to a patient in need thereof the binding molecule of claim 1 .

14. A method of accelerating bone fracture repair comprising administering to a patient in need thereof the binding molecule of claim 1 .

15. A method of increasing bone density comprising administering to a patient in need thereof the binding molecule of claim 1 .

16. A method of increasing bone strength comprising administering to a patient in need thereof the binding molecule of claim 1 .

Assignees

• Florio Monica
• Arora Taruna
• Paszty Christopher J R
• Richards William G
• Amgen Inc

Inventors

• Florio Monica
• Arora Taruna
• Paszty Christopher J R
• Richards William G

Classifications

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61P19/10

  for osteoporosis · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title