# US 10,500,290 B2 · Peptide reagents and methods for detection and targeting of dysplasia, early cancer and cancer

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- Number: US 10,500,290 B2
- Document ID: US10500290B2
- Status: Granted
- Kind: B2
- Application number: 15/505,846
- Filed: 2015-08-21
- Published: 2017-08-31
- Granted: 2019-12-10
- Earliest claimed: 2014-08-22
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Thomas D. Wang; Juan Zhou; Bishnu P. Joshi
- Web page: https://patentgrep.com/patent/US10500290B2

## CPC

- A61K 49/0056: {Peptides, proteins, polyamino acids}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 49/0032: {Methine dyes, e.g. cyanine dyes}
- A61K 49/0043: {Fluorescein, used in vivo}
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/485: Epidermal growth factor [EGF], i.e. urogastrone
- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- 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)
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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)
- 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

The present invention is directed to EGFR-specific peptide reagents, methods for detecting pre-cancer, early cancer and/or cancer using the peptide reagents, and methods for targeting pre-cancer cells, early cancer cells and/or cancer cells using the peptide reagents. In one aspect, the disclosure provides reagents consisting essentially of a peptide QRHKPRE (SEQ ID NO: 1), HAHRSWS (SEQ ID NO: 2), YLTMPTP (SEQ ID NO: 3), TYPISFM (SEQ ID NO: 4), KLPGWSG (SEQ ID NO: 5), IQSPHFF (SEQ ID NO: 6), YSIPKSS (SEQ ID NO: 7), SHRNRPRNTQPS (SEQ ID NO: 8), NRHKPREKTFTD (SEQ ID NO: 9).

## Claims

### Claim 1

A reagent consisting essentially of a peptide QRHKPRE (SEQ ID NO: 1), HAHRSWS (SEQ ID NO: 2), TYPISFM (SEQ ID NO: 4), KLPGWSG (SEQ ID NO: 5), SHRNRPRNTQPS (SEQ ID NO: 8), NRHKPREKTFTD (SEQ ID NO: 9), TAVPLKRSSVTI (SEQ ID NO: 10), GHTANRQPWPND (SEQ ID NO: 11), LSLTRTRHRNTR (SEQ ID NO: 12), RHRDTQNHRPTN (SEQ ID NO: 13), ARHRPKLPYTHT (SEQ ID NO: 14), KRPRTRNKDERR (SEQ ID NO: 15), or SPMPQLSTLLTR (SEQ ID NO: 16)
or a multimer form of the peptide, wherein the peptide specifically binds to epidermal growth factor receptor.

### Claim 2 (depends on 1)

The reagent of claim 1 comprising a detectable label attached to the peptide.

### Claim 3 (depends on 2)

The reagent of claim 2 wherein the detectable label is detectable by microscopy, photoacoustic, PET, SPECT, ultrasound or magnetic resonance imaging.

### Claim 4 (depends on 3)

The reagent of claim 3 wherein the label detectable by microscopy is fluorescein isothiocyanate (FITC).

### Claim 5 (depends on 3)

The reagent of claim 3 wherein the label detectable by microscopy is Cy5.

### Claim 6 (depends on 3)

The reagent of claim 3 wherein the label detectable by microscopy is Cy5.5.

### Claim 7 (depends on 3)

The reagent of claim 3 wherein the label detectable by microscopy is IRdye800.

### Claim 8 (depends on 1)

The reagent of claim 1 wherein the multimer form of the peptide is a dimer.

### Claim 9 (depends on 2)

The reagent of claim 2 wherein the detectable label is attached to the peptide by a peptide linker.

### Claim 10 (depends on 9)

The reagent of claim 9 wherein a terminal amino acid of the linker is lysine.

### Claim 11 (depends on 10)

The reagent of claim 10 wherein the linker comprises the sequence GGGSK set out in SEQ ID NO: 18.

### Claim 12 (depends on 1)

The reagent of claim 1 comprising a therapeutic moiety attached to the peptide.

### Claim 13 (depends on 12)

The reagent of claim 12 wherein the therapeutic moiety is chemotherapeutic agent.

### Claim 14 (depends on 1)

A composition comprising the reagent of claim 1, and a pharmaceutically acceptable excipient.

### Claim 15 (depends on 14)

A kit for administering the composition of claim 14 to a patient in need thereof, said kit comprising the composition of claim 14, instructions for use of the composition and a device for administering the composition to the patient.

### Claim 16

A peptide consisting of the amino acid sequence QRHKPRE (SEQ ID NO: 1), HAHRSWS (SEQ ID NO: 2), TYPISFM (SEQ ID NO: 4), SHRNRPRNTQPS (SEQ ID NO: 8), NRHKPREKTFTD (SEQ ID NO: 9), TAVPLKRSSVTI (SEQ ID NO: 10), GHTANRQPWPND (SEQ ID NO: 11), LSLTRTRHRNTR (SEQ ID NO: 12), RHRDTQNHRPTN (SEQ ID NO: 13), ARHRPKLPYTHT (SEQ ID NO: 14) or KRPRTRNKDERR (SEQ ID NO: 15).

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

A method for detecting colon pre-cancer, early cancer or cancer in a patient comprising the steps of administering the reagent of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 to the colon of the patient and detecting binding of the reagent to pre-cancer, early cancer or cancer colon cells.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

A method for detecting pre-cancer, early cancer or cancer in a patient comprising the steps of administering the reagent of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 to the patient and detecting binding of the reagent.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

A method of determining the effectiveness of a treatment for cancer and/or cancer metastasis, or recurrence of cancer in a patient comprising the step of administering the reagent of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 to the patient, visualizing a first amount of cells labeled with the reagent, and comparing the first amount to a previously-visualized second amount of cells labeled with the reagent,
wherein a decrease in the first amount cells labeled relative to the previously-visualized second amount of cells labeled is indicative of effective treatment.

### Claim 20 (depends on 19)

The method of claim 19 further comprising obtaining a biopsy of the cells labeled by the reagent.

### Claim 21 (depends on 12)

A method for delivering a therapeutic moiety to dysplastic cells of a patient comprising the step of administering the reagent of claim 12 to the patient.

### Claim 22 (depends on 12)

A method for delivering a therapeutic moiety to early cancer cells or cancer cells of a patient comprising the step of administering the reagent of claim 12 to the patient.