# US 7,465,434 B2 · Diagnosis of blood clots using fibrin-binding proteins bound with contrast agents

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- Number: US 7,465,434 B2
- Document ID: US7465434B2
- Status: Granted
- Kind: B2
- Application number: 11/411,256
- Filed: 2006-04-25
- Published: 2006-11-16
- Granted: 2008-12-16
- Earliest claimed: 2005-04-25
- Inventors: Jacob Benford
- Web page: https://patentgrep.com/patent/US7465434B2

## CPC

- C12N 9/6459: {t-plasminogen activator (3.4.21.68), i.e. tPA}
- C12N 9/6424: {Serine endopeptidases (3.4.21)}
- C12Y 304/21069: Protein C activated (3.4.21.69)
- G01N 33/58: involving labelled substances (G01N33/53 takes precedence)
- G01N 33/86: involving blood coagulating time {or factors, or their receptors}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- 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

This invention describes how to modify a fibrin-binding protein, such as tPA, with a contrast agent, such as iodine. This substance could then be given to a patient suspected of having a blood clot by an intravenous route, and then detected by a radiographic study at a short pre-determined time later. Appropriate therapy is started immediately as determined by the radiographic study.

## Claims

### Claim 1

A method for detecting a blood clot in a mammalian patient, the method comprising:
(a) using a nucleic acid sequence to express a fibrin-binding protein wherein the sequence has been modified to delete a coding sequence that codes for the serine protease domain to remove fibrinolytic activating properties of the fibrin-binding protein;
(b) producing a compound comprising the fibrin-binding protein and a contrast agent;
(c) introducing the compound into the patient via bolus by an intravenous or intra-arterial insertion;
(d) binding the compound to a blood clot; and
(e) detecting the compound bound to the blood clot using a radiographic study.

### Claim 2 (depends on 1)

The method of claim 1 wherein the fibrin-binding protein comprises:
(a) Alteplase;
(b) TNK;
(c) Reteplase;
(d) Streptokinase, or
(e) combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1 wherein the fibrin-binding protein before modification includes Alteplase.

### Claim 4 (depends on 1)

The method of claim 1 wherein the contrast agent includes:
(a) Iodine;
(b) Gadolinium, or combinations thereof.

### Claim 5 (depends on 1)

The method of claim 1 wherein the contrast agent includes iodine.

### Claim 6 (depends on 1)

The method of claim 1 wherein the contrast agent includes gadolinium.

### Claim 7 (depends on 1)

The method of claim 1 wherein the fibrin-binding protein-contrast agent compound is administered to a human being in an amount between about 0.001 and 100 mg/kg.

### Claim 8 (depends on 1)

The method of claim 1 wherein the fibrin-binding protein-contrast agent compound is administered to a human being in an amount between 0.25 and 0.75 mg/kg.

### Claim 9 (depends on 1)

The method of claim 1 wherein the mammal is a human being.

### Claim 10 (depends on 1)

The method of claim 1 wherein the patient is a human being and the fibrin-binding protein-contrast agent compound is administered to the human being in an amount between about 0.05 and 5 mg/kg.

### Claim 11 (depends on 1)

The method of claim 1 wherein detecting the compound occurs about 5-10 minutes after introducing the compound into the patient.

### Claim 12 (depends on 1)

The method of claim 1 wherein the radiographic study includes an x-ray.

### Claim 13 (depends on 1)

The method of claim 1 wherein the radiographic study includes computed tomography.

### Claim 14 (depends on 1)

The method of claim 1 wherein the nucleic acid sequence is a naturally occurring nucleic acid sequence.

### Claim 15

A method for detecting a blood clot in a mammalian patient, the method comprising:
(a) using a nucleic acid to express a fibrin-binding protein wherein a sequence of the nucleic acid has been modified to delete a coding sequence that codes for the serine protease domain to remove fibrinolytic activating properties of the fibrin-binding protein;
(b) producing a compound comprising the fibrin-binding protein and a contrast agent;
(c) introducing the compound into the patient via bolus by an intravenous or intra-arterial insertion;
(d) binding the compound to a blood clot; and
(e) detecting the compound bound to the blood clot using a radiographic study.