Formulations of phosphoramidate derivatives of nucleoside drugs

Patent metadata

Field	Value
Publication number	US-11786544-B2
Application number	US-202117231606-A
Country	US
Kind code	B2
Filing date	Apr 15, 2021
Priority date	Dec 23, 2015
Publication date	Oct 17, 2023
Grant date	Oct 17, 2023

Abstract

This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3′-deoxyadenosine-5′-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

First claim

What is claimed is:

1. A pharmaceutical stock solution to prepare a formulation for infusion to a human patient in need thereof comprising:
100 or more mg/mL 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L alaninyl)] phosphate (NUC-3373) or a pharmaceutically acceptable salt thereof; 30-95% by volume dimethyl acetamide (DMA); an aqueous vehicle, and optionally one or more pharmaceutically acceptable excipients.

2. The formulation of claim 1 , wherein the formulation comprises between 30-95% DMA, and 5-50% aqueous vehicle.

3. The formulation of claim 2 , wherein the aqueous vehicle is saline.

4. The formulation of claim 2 , wherein the aqueous vehicle is water for injection.

5. The formulation of claim 1 , wherein the formulation comprises a solubilizer.

6. The formulation of claim 5 , wherein the formulation comprises two or more solubilizers.

7. The formulation of claim 5 , wherein the solubilizer is a polyethoxylated fatty acid or a mixture thereof.

8. The formulation of claim 1 , wherein the formulation comprises:
from 20% to 55% by volume DMA;
35% or more by volume a solubilizer or solubilizers; and
from 100 to 400 mg per mL NUC-3373.

9. The formulation of claim 1 , wherein the formulation is suitable for infusion by a central venous access device.

Assignees

• NuCana plc

Inventors

• Kennovin Gordon
• Griffith Hugh

Classifications

• A61P31/12

  Antivirals · CPC title

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title