# US 8,541,177 B2 · Treatment and diagnosis of abnormal bone density with an inhibitor of the glypican-sclerostin interaction

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- Number: US 8,541,177 B2
- Document ID: US8541177B2
- Status: Granted
- Kind: B2
- Application number: 12/160,761
- Filed: 2007-01-15
- Published: 2010-05-27
- Granted: 2013-09-24
- Earliest claimed: 2006-01-13
- Assignees: A Chan Holding B.V.
- Applicants: Alan Barry Chan
- Inventors: Alan Barry Chan
- Web page: https://patentgrep.com/patent/US8541177B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61P 19/10: for osteoporosis
- C07K 16/18: against material from animals or humans
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2333/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
- G01N 2440/38: addition of carbohydrates, e.g. glycosylation, glycation
- G01N 2500/02: Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
- G01N 2800/105: Osteoarthritis, e.g. cartilage alteration, hypertrophy of bone
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Compositions and methods of treatment for abnormal bone density are disclosed based upon the finding that sclerostin must be bound to glypican in order to inhibit bone deposition. Methods for identifying agents that inhibit the glypican-sclerostin interaction are disclosed for treatment of bone deposition disorders. Diagnostic methods are also disclosed.

## Claims

### Claim 1

An in vitro method for identifying an inhibitor of the glypican-sclerostin interaction comprising the steps of:
a) contacting sclerostin with glypican in the presence and absence of the candidate inhibitor under conditions permitting the binding of the glypican to sclerostin; and
b1) measuring binding of the glypican to sclerostin, wherein a decrease in binding in the presence of the candidate inhibitor, relative to binding in the absence of the candidate inhibitor, identifies the candidate inhibitor as an inhibitor of the glypican-sclerostin interaction, or
b2) measuring the signaling response induced by the glypican-sclerostin interaction in the presence of the candidate inhibitor, and comparing it with the signaling response induced by the glypican-sclerostin interaction in the absence of the candidate inhibitor, wherein a change in the signaling response identifies the candidate inhibitor as an inhibitor of the glypican-sclerostin interaction;
wherein the glypican is selected from the group consisting of glypican-1, glypican-2, glypican-3, glypican-4, glypican-5, and glypican-6.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said measuring in step
b1) is performed using a method selected from the group consisting of label displacement, surface plasmon resonance, fluorescence resonance energy transfer, bioluminescence resonance energy transfer, fluorescence quenching, and fluorescence polarization.

### Claim 3 (depends on 1)

The method according to claim 1, wherein in step b2) a change in the signaling response by at least 10% in the presence of the candidate inhibitor relative to the absence of the candidate inhibitor identifies the candidate inhibitor as an inhibitor of the glypican-sclerostin interaction.