IP Verse

Modified Release Gamma-Hydroxybutyrate Formulations Having Improved Pharmacokinetics

Patent No. US10973795 (titled "Modified Release Gamma-Hydroxybutyrate Formulations Having Improved Pharmacokinetics") was filed by Rtw Investments Lp on May 22, 2019.

What is this patent about?

’795 is related to the field of modified-release drug formulations , specifically those designed for gamma-hydroxybutyrate (GHB). GHB, primarily used to treat narcolepsy, is currently administered as an immediate-release liquid solution requiring twice-nightly dosing. This inconvenient regimen disrupts sleep and impacts patient compliance. The background highlights the challenges in creating a once-nightly modified-release GHB formulation that maintains adequate bioavailability and avoids excessive drug levels in the bloodstream upon waking.

The underlying idea behind ’795 is to achieve a comparable bioavailability with a once-nightly dose of modified-release GHB to that of the existing twice-nightly immediate-release formulation. This is accomplished by carefully controlling the *in vitro* release profile of the drug. The formulation is designed to rapidly release a portion of the GHB in an acidic environment (simulating the stomach) and the remaining portion in a more neutral environment (simulating the intestines), thus mimicking the absorption profile of the split-dose immediate-release regimen.

The claims of ’795 focus on a modified-release GHB formulation that, when administered once at night, produces specific plasma concentration versus time curves. These curves are defined by reference to figures in the patent, effectively claiming formulations that achieve similar pharmacokinetic profiles to those shown in the figures. Some claims also define the invention by reference to specific *in vitro* dissolution profiles, measured using standard USP apparatus and conditions.

In practice, the invention uses a combination of immediate-release and modified-release microparticles . The modified-release particles are coated with a combination of a pH-sensitive polymer and a hydrophobic compound. This coating delays the release of GHB until the particles reach a specific pH environment in the intestines. The ratio of immediate-release to modified-release components, along with the coating composition, is carefully controlled to achieve the desired pharmacokinetic profile.

The invention differentiates itself from prior approaches by focusing on a specific *in vitro* dissolution profile that correlates with improved *in vivo* bioavailability. Previous attempts at once-nightly GHB formulations suffered from reduced bioavailability compared to the twice-nightly immediate-release product. The ’795 formulation, through its unique release characteristics, aims to overcome this limitation and provide a more convenient and effective treatment option for narcolepsy.

How does this patent fit in bigger picture?

Technical landscape at the time

In the mid-2010s when ’795 was filed, modified release formulations were at a time when systems commonly relied on specific release profiles to achieve desired drug concentrations over time. At that time, achieving consistent bioavailability with modified release formulations, especially for drugs with variable absorption rates, was a non-trivial challenge.

Novelty and Inventive Step

The examiner approved the application because an updated prior art search did not reveal any reference that taught the specific limitations of the claimed once-nightly modified release formulation of gamma-hydroxybutyrate, which includes both immediate release and modified release portions. Therefore, the examiner concluded that the claimed invention was novel and non-obvious.

Claims

This patent contains 24 claims, with independent claims numbered 1, 2, 3, 9, 13, 14, 15, 16, 17, 23, and 24. The independent claims generally focus on a once-nightly modified release formulation of gamma-hydroxybutyrate, defining it by its plasma concentration versus time curve or dissolution profile when administered under specific conditions. The dependent claims generally elaborate on the dissolution profiles of the formulations described in the independent claims.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
Dissolution profile
(Claim 3, Claim 9, Claim 17)		“The inventors have discovered a novel relationship between the in vitro release profile of gamma-hydroxybutyrate modified release formulations and in vivo absorption which permits, for the first time, a modified release formulation of gamma-hydroxybutyrate that approximates the bioavailability of a twice-nightly equipotent immediate release liquid solution of sodium oxybate, and that does so across a range of therapeutic doses.”A characterization of how quickly and completely the gamma-hydroxybutyrate is released from the formulation in a specific dissolution medium.
Immediate release and modified release portions
(Claim 1, Claim 2, Claim 3, Claim 9, Claim 13, Claim 14, Claim 15, Claim 16, Claim 17, Claim 23, Claim 24)		“The modified release formulations of gamma-hydroxybutyrate preferably have both immediate release and modified release portions. The release of gamma-hydroxybutyrate from the immediate release portion is practically uninhibited, and occurs almost immediately in 0.1N hydrochloric acid dissolution medium. In contrast, while the modified release portion also preferably releases its gamma-hydroxybutyrate almost immediately when fully triggered, the release is not triggered until a predetermined lag-time or the drug is subjected to a suitable dissolution medium such as a phosphate buffer pH 6.8 dissolution medium.”The formulation contains two distinct parts: one that releases gamma-hydroxybutyrate quickly and another that releases it in a controlled manner.
Once-nightly modified release formulation
(Claim 1, Claim 2, Claim 3, Claim 9, Claim 13, Claim 14, Claim 15, Claim 16, Claim 17, Claim 23, Claim 24)		“Accordingly, one object of the present invention is to provide modified release formulations of gamma-hydroxybutyrate that are administered only once at bed-time with improved dissolution and pharmacokinetic profiles.”A formulation designed to release gamma-hydroxybutyrate in a modified manner and is administered only once per night.
Plasma concentration versus time curve
(Claim 1, Claim 2, Claim 13, Claim 14, Claim 15, Claim 16, Claim 23, Claim 24)		“Formulations that achieve this improved bioavailability can be described using several different pharmacokinetic and in vitro dissolution parameters.”A graphical representation showing how the concentration of gamma-hydroxybutyrate in the blood changes over time after administration of the formulation.
Standardized evening meal
(Claim 1, Claim 2, Claim 13, Claim 14, Claim 15, Claim 16, Claim 23, Claim 24)		“For example, the inventors have discovered that a modified release composition of gamma-hydroxybutyrate according to the invention administered once approximately two hours after a standardized evening meal at the dose equivalent to 7.5 g of sodium oxybate results in a similar pharmacokinetic profile as an immediate release liquid solution of sodium oxybate given in two separate equal doses of 4.5 g of sodium oxybate each administered at t0 and t4h.”A meal with a consistent composition and timing, used to control for the effects of food on drug absorption.

Litigation Cases New

US Latest litigation cases involving this patent.

Case NumberFiling DateTitle
1:25-cv-00435Apr 8, 2025Avadel Cns Pharmaceuticals, Llc V. Jazz Pharmaceuticals, Inc.
1:25-cv-00405Apr 1, 2025Avadel Cns Pharmaceuticals, Llc V. Jazz Pharmaceuticals, Inc.
1:25-cv-00221Feb 25, 2025Avadel CNS Pharmaceuticals, LLC et al v. Jazz Pharmaceuticals, Inc. et al
1:25-cv-00196Feb 18, 2025Avadel Cns Pharmaceuticals, Llc V. Jazz Pharmaceuticals, Inc.
1:25-cv-00057Jan 14, 2025Avadel Cns Pharmaceuticals, Llc V. Jazz Pharmaceuticals, Inc.

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US10973795

RTW INVESTMENTS LP
Application Number
US16419616
Filing Date
May 22, 2019
Status
Granted
Expiry Date
Aug 20, 2037
External Links
Slate, USPTO, Google Patents