# US 10,864,215 B2 · Use of phosphoinositide 3-kinase inhibitors for treatment of vascular malformations

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- Number: US 10,864,215 B2
- Document ID: US10864215B2
- Status: Granted
- Kind: B2
- Application number: 15/811,973
- Filed: 2017-11-14
- Published: 2018-05-03
- Granted: 2020-12-15
- Earliest claimed: 2015-05-15
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan-Kettering Cancer Center
- Inventors: Eulalia Baselga; Pau Castel; Jose T. Baselga
- Web page: https://patentgrep.com/patent/US10864215B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase (“PI3K”).

## Claims

### Claim 1

A method of treating a venous malformation in a subject in need thereof, comprising administering to the subject an effective amount of BYL719 (Alpelisib),
wherein the venous malformation is not associated with congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (CLOVES), Klippel-Trenaunay syndrome (KTS), or fibro-adipose vascular anomaly (FAVA), and
wherein the subject has a gain-of-function mutation in the PI3K/AKT pathway.

### Claim 2 (depends on 1)

The method of claim 1, wherein the gain-of-function mutation is an activating mutation of PIK3CA, or a mutation in at least one of AKT1, AKT2, AKT3, and IRS2.

### Claim 3 (depends on 2)

The method of claim 2, wherein the activating mutation is selected from the group consisting of R88Q, E542K, E545K, E545Q, H1047L, H1047Q, H1047R, C420R, and I143V.

### Claim 4 (depends on 1)

The method of claim 1, wherein the venous malformation is located in the brain, and/or within the skin.

### Claim 5 (depends on 1)

The method of claim 1, wherein:
a) the subject suffers from multiple venous malformations, a malignancy, a multisystem genetic disorder, or a combination thereof; or
b) the surgical treatment of the venous malformation would be high-risk.

### Claim 6 (depends on 1)

The method of claim 1, wherein BYL719 (Alpelisib) is administered systemically or locally.

### Claim 7 (depends on 1)

The method of claim 1, wherein BYL719 (Alpelisib) is administered topically, parenterally, or orally.

### Claim 8 (depends on 1)

The method of claim 1, further comprising administering to the subject a second agent that inhibits the PI3K/AKT pathway, wherein the second agent is in an amount that, together with the agent of claim 1, effectively treats the venous malformation.

### Claim 9 (depends on 1)

The method of claim 1, wherein the venous malformation is a sporadic venous malformation.