# US 8,771,645 B2 · Composition comprising a cell death marker and a wavelength-optimized label

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- Number: US 8,771,645 B2
- Document ID: US8771645B2
- Status: Granted
- Kind: B2
- Application number: 12/808,012
- Filed: 2008-12-15
- Published: 2010-11-11
- Granted: 2014-07-08
- Earliest claimed: 2007-12-14
- Assignees: UCL Business PLLC
- Applicants: Francesca Cordeiro; Stephen Moss; Frederick Fitzke
- Inventors: Francesca Cordeiro; Stephen Moss; Frederick Fitzke
- Web page: https://patentgrep.com/patent/US8771645B2

## CPC

- A61K 51/087: {the peptide being an annexin, e.g. annexin V}
- A61K 49/0004: {Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions}
- A61K 49/0032: {Methine dyes, e.g. cyanine dyes}
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0056: {Peptides, proteins, polyamino acids}
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61K 51/08: Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins}
- 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 invention relates to the use of a cell death marker labelled with a wavelength-optimised label for identifying cell death in the eye. Suitable cell death markers are the Annexins and fragments and derivatives thereof. The invention also relates to a pharmaceutical composition comprising a cell death marker labelled with a wavelength-optimised label and a method for monitoring cell death in the eye using a cell death marker labelled with a wavelength-optimised label.

## Claims

### Claim 1

A method for identifying cell death in the eye, comprising providing a composition comprising a cell death marker labeled with a wavelength-optimized label, wherein the cell death marker is an annexin and the wavelength-optimized label is Dy-776 having the structure:
or
Dy-781 having the structure:

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell death marker is annexin 5, 11, 2 or 6.

### Claim 3 (depends on 1)

The method of claim 1, wherein the wavelength-optimized label is Dy-776.

### Claim 4 (depends on 1)

The method of claim 1, wherein the marker is for identifying retinal cell death.

### Claim 5 (depends on 4)

The method of claim 4, wherein the marker is for identifying retinal nerve cell death.

### Claim 6 (depends on 1)

The method of claim 1, wherein the marker is for identifying single cell death.

### Claim 7

A method for monitoring cell death in the eye, comprising the steps of:
(a) administering a composition comprising a cell death marker labeled with a wavelength-optimized label to a subject, wherein the cell death marker is an annexin and the wavelength-optimized label is Dy-776 having the structure:
or Dy-781 having the structure:
(b) generating an image of emission wavelength from the subject's eye using an imaging device; wherein the image is a representation of cell death in the eye.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cell death marker is an annexin.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cell death marker is annexin 5.

### Claim 10 (depends on 8)

The method of claim 8, wherein the wavelength-optimised label is Dy-776.

### Claim 11 (depends on 7)

The method of claim 7, wherein the marker is for identifying retinal cell death.

### Claim 12 (depends on 11)

The method of claim 11, wherein the marker is for identifying retinal nerve cell death.

### Claim 13 (depends on 7)

The method of claim 7, wherein the marker is for identifying single cell death.

### Claim 14 (depends on 7)

The method of claim 7, wherein the labeled marker is administered systemically, topically or ocularly.

### Claim 15 (depends on 7)

The method of claim 7, wherein the step of generating an image is repeated.

### Claim 16 (depends on 15)

The method of claim 15, wherein the step of generating and image is repeated to allow real time imaging.

### Claim 17 (depends on 7)

The method of claim 7, wherein the method is for diagnosing a degenerative disease of the eye.

### Claim 18 (depends on 17)

The method of claim 17, wherein the disease is glaucoma or diabetic retinopathy.

### Claim 19 (depends on 7)

The method of claim 7, wherein the disease is a neurodegenerative disease of the brain.

### Claim 20 (depends on 19)

The method of claim 19, wherein the disease is Alzheimer's disease.

### Claim 21

A composition comprising a cell death marker labeled with a wavelength-optimized label, wherein the cell death marker is an annexin and the wavelength-optimized label is Dy-776 having the structure:
or
Dy-781 having the structure:

### Claim 22 (depends on 21)

The composition of claim 21, wherein the composition is in a form suitable for intravenous, ocular or topical administration.

### Claim 23 (depends on 21)

The composition of claim 21, wherein the cell death marker is annexin 5, 11, 2 or 6.

### Claim 24 (depends on 21)

The composition of claim 21, wherein the wavelength-optimized label is Dy-776.
