# US 9,518,976 B2 · Methods for identifying or assaying for agents that increase beta-cell proliferation, insulin secretion, insulin sensitivity, glucose tolerance and decrease fat mass

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,518,976 B2
- Document ID: US9518976B2
- Status: Granted
- Kind: B2
- Application number: 12/441,060
- Filed: 2007-09-13
- Published: 2010-02-25
- Granted: 2016-12-13
- Earliest claimed: 2006-09-13
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: Gerard Karsenty; Patricia F. Ducy
- Inventors: Gerard Karsenty; Patricia F. Ducy
- Web page: https://patentgrep.com/patent/US9518976B2

## CPC

- G01N 33/54306: {Solid-phase reaction mechanisms}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 3/14: for calcium homeostasis (vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04)
- A61P 5/48: of the pancreatic hormones
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5023: {on expression patterns}
- G01N 33/5038: {involving detection of metabolites per se}
- G01N 33/5088: {of vertebrates}
- G01N 2333/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- G01N 2333/916: acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
- G01N 2333/988: Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to cell-based and non-cell based methods of drug screening to identify agents, or assay agents, that reduce OST-PTP or gamma-carboxylase activity or expression, or increase the level of undercarboxylated osteocalcin or adiponectin activity or expression. Such agents find use in treating or preventing a disorder related to the OST-PTP signaling pathway. Such disorders include, metabolic syndrome, glucose intolerance, type 1 or type 2 diabetes, atherosclerosis, or obesity. Such agents may be used to treat disorders characterized by decreased insulin production, deceased insulin sensitivity, and decreased glucose tolerance or increased fat mass.

## Claims

### Claim 1

A method for identifying an agent that reduces osteocalcin carboxylation comprising:
(a) determining a first level of carboxylated osteocalcin in a first cell that expresses osteocalcin,
(b) contacting a second cell that expresses osteocalcin with the agent and determining a second level of carboxylated osteocalcin in the second cell, and
(c) comparing the first level of carboxylated osteocalcin with the second level of carboxylated osteocalcin,
wherein the first cell and the second cell have been genetically engineered to overexpress osteocalcin, and wherein the agent is identified as an agent that reduces osteocalcin carboxylation if the first level of carboxylated osteocalcin is higher than the second level.

### Claim 2 (depends on 1)

The method of claim 1, wherein the agent is effective to treat metabolic syndrome, type 1 or type 2 diabetes, atherosclerosis, obesity, or glucose intolerance.

### Claim 3 (depends on 1)

The method of claim 1, wherein the first and second cells are osteoblasts.

### Claim 4 (depends on 1)

The method of claim 1, wherein a library of agents is screened.