# US 10,500,178 B2 · LTB4 inhibition to prevent and treat human lymphedema

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- Number: US 10,500,178 B2
- Document ID: US10500178B2
- Status: Granted
- Kind: B2
- Application number: 15/554,931
- Filed: 2016-03-11
- Published: 2018-07-12
- Granted: 2019-12-10
- Earliest claimed: 2015-03-13
- Assignees: The Board of Trustees of the Leland Stanford Junior University
- Applicants: The Board of Trustees of the Leland Stanford Junior University
- Inventors: Stanley G. Rockson; Mark R. Nicolls; Wen A. Tian; Xinguo Jiang; Jeanna Kim
- Web page: https://patentgrep.com/patent/US10500178B2

## CPC

- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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

Provided are therapeutic methods for treating a patient with lymphedema, or prophylactically treating an individual susceptible to lymphedema, by inhibiting synthesis activity of leukotriene B4.

## Claims

### Claim 1

A method for the treatment of lymphedema in a human patient, the method comprising:
administering to the patient (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid in an amount effective to prevent or reduce lymphedema symptoms restore architecture of lymphedematous tissue in acquired lymphedema.

### Claim 2 (depends on 1)

The method of claim 1, wherein dermal thickness of lymphedematous tissue is reduced by at least about 2 mm following treatment.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient has lymphedema at stage 0, 1, 2 or 3.

### Claim 4 (depends on 1)

The method of claim 1, wherein the effective amount is about 10-1500 mg/day.

### Claim 5 (depends on 1)

The method of claim 1, wherein the effective amount is about 10-500 mg/day.

### Claim 6 (depends on 1)

The method of claim 1, wherein (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyllamino]-4-methylpentanoic acid is administered twice daily.

### Claim 7 (depends on 1)

The method of claim 1, wherein (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyllamino]-4-methylpentanoic acid is administered three times daily.

### Claim 8

A method for the treatment of lymphedema in a human patient, the method comprising:
administering to the patient (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid at a dose of about 10-500 mg/day to restore architecture of lymphedematous tissue in acquired lymphedema.

### Claim 9 (depends on 1)

The method of claim 1, wherein the method further comprises administering an effective amount of a second therapeutic agent.

### Claim 10 (depends on 9)

The method of claim 9, wherein the second therapeutic agent is a diuretic.

### Claim 11 (depends on 1)

The method of claim 1, wherein administration of (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid is commenced following surgical wound healing.

### Claim 12 (depends on 8)

The method of claim 8, wherein administration of (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid is commenced following surgical wound healing.