# US 10,307,460 B2 · Compositions and methods for inhibiting cellular adhesion or directing diagnostic or therapeutic agents to RGD binding sites

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- Number: US 10,307,460 B2
- Document ID: US10307460B2
- Status: Granted
- Kind: B2
- Application number: 15/867,101
- Filed: 2018-01-10
- Published: 2018-07-12
- Granted: 2019-06-04
- Earliest claimed: 2009-11-10
- Assignees: Allegro Pharmaceuticals, LLC
- Applicants: Allegro Pharmaceuticals, Inc.
- Inventors: Michael John Mackel; John Park
- Web page: https://patentgrep.com/patent/US10307460B2

## CPC

- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 38/07: Tetrapeptides
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1709: {from mammals}
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 51/065: {conjugates with carriers being macromolecules}
- A61K 51/082: {the peptide being a RGD-containing peptide}
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24}
- A61L 31/043: {Proteins; Polypeptides; Degradation products thereof}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/08: Vasodilators for multiple indications
- 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 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 17/08: Antiseborrheics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 27/04: Artificial tears; Irrigation solutions
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/00: Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH2—SO3H)COOH or Arg-Gly-NH—CH(CH2—SO3H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting cellular adhesion to RGD binding sites or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.

## Claims

### Claim 1

A method for inhibiting integrin-extracellular matrix interactions in a human or animal subject in need thereof, said method comprising the step of:
administering to the subject an effective amount of a cyclic or linear compound comprising either
i) a peptide which comprises Glycinyl-Arginyl-GlycinylCysteic-Threonyl-Proline-COOH or
ii) a peptide which has the formula:
X1—R-G-Cysteic Acid-X
where X and x1 are selected from: Phe-Val-Ala, -Phe-Leu-Ala, -Phe-Val-Gly, -Phe-Leu-Gly, -Phe-Pro-Gly, -Phe-Pro-Ala, -Phe-Val; or fromAru, Gly, Cysteic, Phe, Ala, Lea, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof.

### Claim 2 (depends on 1)

A method according to claim 1 wherein the compound comprises:
Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH.

### Claim 3 (depends on 2)

A method according to claim 2 wherein the compound has the formula:

### Claim 4 (depends on 2)

A method according to claim 2 wherein the compound is linear.

### Claim 5 (depends on 2)

A method according to claim 2 wherein the compound is cyclic.

### Claim 6 (depends on 1)

A method according to claim 1 wherein the method is carried out to treat an eye disorder.

### Claim 7 (depends on 6)

A method according to claim 6 wherein the method is carried out to treat a disorder selected from; neovascularization, neovascular glaucoma, diabetic retinopathy, retinal degeneration, dry macular degeneration, wet macular degeneration, corneal neovascularization, edematous sclerosis, corneal graft neovascularization, neovascular glaucoma, diabetic retinopathy, pterygium retinal degeneration, dry and wet macular degeneration, conical neovascularization, ischemic optic nerve, rubiosis iridis, central vein occlusion, aberrant epiretinal membranes, retrolental fibroplasia, granular conjunctivitis.

### Claim 8 (depends on 6)

A method according to claim 6 wherein the administration is topical.

### Claim 9 (depends on 6)

A method according to claim 6 wherein the administration is intraocular.

### Claim 10 (depends on 6)

A method according to claim 6 wherein the administration is intravitreal.