# US 2013/0156785 A1 · Novel diagnostic and therapeutic target in inflammatory and/or cardiovascular diseases

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

- Number: US 2013/0156785 A1
- Document ID: US20130156785A1
- Status: Published application
- Kind: A1
- Application number: 13/819,335
- Filed: 2011-08-29
- Published: 2013-06-20
- Earliest claimed: 2010-08-27
- Assignees: University of Zurich
- Inventors: Chad Brokopp; Simon Hoerstrup
- Web page: https://patentgrep.com/patent/US20130156785A1

## CPC

- C07K 16/40: against enzymes
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 38/4813: {Exopeptidases (3.4.11. to 3.4.19)}
- A61K 38/482: {Serine endopeptidases (3.4.21)}
- A61K 38/55: Protease inhibitors
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- C12Q 1/37: involving peptidase or proteinase
- C12Q 1/56: involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
- C12Q 1/6876: Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- G01N 33/573: for enzymes or isoenzymes
- G01N 33/6893: {related to diseases not provided for elsewhere}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12Y 304/14005: Dipeptidyl-peptidase IV (3.4.14.5)
- C12Y 304/21026: Prolyl oligopeptidase (3.4.21.26), i.e. proline-specific endopeptidase
- G01N 2333/96433: Serine endopeptidases (3.4.21)
- G01N 2800/32: Cardiovascular disorders
- 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)
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- C12Y: ENZYMES

## Abstract

Methods for diagnosing inflammatory and/or cardiovascular diseases by assaying for Fibroblast Activation Protein (FAP) expression in a body fluid is provided as well as therapeutic means based thereon.

## Claims

### Claim 1

A method of determining the presence of an inflammatory and/or cardiovascular disease or condition in a patient comprising assaying
(i) a sample of a body fluid taken from said patient for expression of Fibroblast Activation Protein (FAP), wherein expression or an increased expression of said FAP compared to a control sample is indicative for the disease or condition in said patient; and/or
(ii) a sample of a thrombus or plaque taken from said patient for expression of FAP, wherein an increased expression of FAP as compared to its expression in a sample of a body fluid taken from said patient is indicative for the disease or condition.

### Claim 2 (depends on 1)

The method of claim 1, wherein said body fluid is blood.

### Claim 3 (depends on 1)

The method of claim 1, wherein said disease is selected from the group atherosclerosis, rheumatoid arthritis, stroke or an acute coronary syndrome such as myocardial infarction, heart attack, chronic liver disease, cerebral venous thrombosis, deep venous thrombosis or pulmonary embolism.

### Claim 4 (depends on 2)

The method of claim 2, wherein the condition is vulnerable atherosclerotic plaques or atherothrombosis.

### Claim 5 (depends on 1)

The method of claim 1, comprising assaying said sample for FAP protein or mRNA.

### Claim 6 (depends on 5)

The method of claim 5, wherein said assay is an immunoassay.

### Claim 7 (depends on 6)

The method of claim 6, wherein said assay is an immunohistochemical assay.

### Claim 8 (depends on 7)

The method of claim 7, wherein said assay comprises fluorescence activated cytometry (FACS), indirect ELISA, sandwich ELISA or cell culture ELISA.

### Claim 9 (depends on 6)

The method of claim 6, wherein said immunoassay comprises contacting said sample with a monoclonal or polyclonal antibody which binds specifically to FAP.

### Claim 10 (depends on 9)

The method of claim 9, wherein said monoclonal antibody is a mouse anti-human antibody.

### Claim 11

A method of treating a disease selected from the group atherosclerosis, rheumatoid arthritis, stroke or an acute coronary syndrome such as myocardial infarction, heart attack, chronic liver disease, cerebral venous thrombosis, deep venous thrombosis or pulmonary embolism, said method comprising administering to a patient a composition comprising a compound capable of inhibiting the activity of FAP or its expression.

### Claim 12 (depends on 11)

The method of claim 11, wherein the composition is a pharmaceutical composition and comprises a pharmaceutically acceptable carrier.

### Claim 13 (depends on 11)

The method of claim 11, wherein said activity is enzymatic activity.

### Claim 14 (depends on 13)

The method of claim 13, wherein the composition inhibits blood clotting.

### Claim 15 (depends on 11)

The method of claim 11, wherein said compound is capable of binding to FAP or its encoding nucleic acid molecule.

### Claim 16 (depends on 15)

The method of claim 15, wherein said compound is a monoclonal antibody which specifically birds to FAP.

### Claim 17 (depends on 6)

The method of claim 6, wherein said monoclonal antibody is a human antibody.

### Claim 18 (depends on 11)

The method of claim 11, wherein said compound is a FAP antagonist.

### Claim 19 (depends on 18)

The method of claim 18, wherein said FAP antagonist is a peptide or peptide analog.

### Claim 20 (depends on 11)

The method of claim 11, wherein the patient has been diagnosed in accordance with a method comprising determining the presence of an inflammatory and/or cardiovascular disease or condition in the patient comprising assaying
(i) a sample of a body fluid taken from said patient for expression of Fibroblast Activation Protein (FAP), wherein expression or an increased expression of said FAP compared to a control sample is indicative for the disease or condition in said patient; and/or
(ii) a sample of a thrombus or plaque taken from said patient for expression of FAP, wherein an increased expression of FAP as compared to its expression in a sample of a body fluid taken from said patient is indicative for the disease or condition.

### Claim 21

A method of preventing or treating a coagulation disorder, said method comprising administering to a patient a pharmaceutical composition comprising FAP.

### Claim 23

A method of using FAP as a reagent for enhancing blood clotting in vitro.

### Claim 24

A method of using ROTEM/NATEM for testing the therapeutic effect and/or efficiency of FAP blocking agents in a patient.

### Claim 25

A method of diagnosing a disease selected from the group atherosclerosis, rheumatoid arthritis, stroke or an acute coronary syndrome such as myocardial infarction, heart attack, chronic liver disease, cerebral venous thrombosis, deep venous thrombosis or pulmonary embolism using a composition comprising a compound capable of detecting the presence or activity of FAP.

### Claim 26 (depends on 25)

The method of claim 25, wherein the composition is a diagnostic composition comprising a suitable means for detection of the compound and/or of FAP.

### Claim 27 (depends on 21)

The method of claim 21, wherein the coagulation disorder is hemophilia.
