API and IP Newsletter
Contents
The UPC must harness user enthusiasm to ensure a successful launch on 1 June
Gap between EU & US on pharmaceutical investments too wide – industry
FDA approvals in February 2023
We follow FDA approvals, especially small molecules. We would broadly cover reported processes, relevant patent families. We would analyse import-export database and try and understand companies who are active in development of generic versions.
USFDA approved daprodustat in February 2023.
These daprodustat tablets 1 mg, 2 mg, 4 mg, 6 mg, and 8 mg are sold under the brand names Jesduvroq (in US) and Duvroq (in Japan). Daprodustat is approved for the treatment of anaemia due to chronic kidney disease. It is a hypoxia-inducible factor prolyl hydroxylase inhibitor.
Daprodustat was earlier approved for medical use in Japan in June 2020. It is the first oral treatment for anaemia caused by chronic kidney disease for adults.
GSK tipped daprodustat to generate peak sales of 500 million pounds ($674 million) to 1 billion pounds. Here
Brief IP landscape is as follows:
Example 18 of WO2007150011A2 (GSK) teaches the process of manufacturing of daprodustat.
Patent family WO 2019052133 (GSK) relates to crystal form CS1 and CS9. Also a tablet formulation of crystalline forms of daprodustat viz CS1 and CS9 is disclosed in WO2019052133.
Patent family WO2021255159A1 (GSK) relates to the immediate release tablet comprising from 1 to 10 mg (measured as the free acid) daprodustat. This family allegedly solves the problem of having desired tensile strengths sufficient to permit normal storage, distribution and handling of daprodustat tablets.
Patent family WO2020102302A1 relates to crystalline form 3, this family is filed by Teva.
Patent family WO2022263899A1 claims improved process as follows:
Noticing patent applications filed by Teva and Chinese companies on polymorphs and processes it is clear that there are many companies working on the processes and polymorphs of daprodustat.
With all these patent families generic development is going to be challenging. New entrants in generic development must circumvent many of these patents (equivalents of these families are granted or in our view many of these will be granted in many key jurisdictions) or should be ready with invalidity arguments.
One can notice daprodustat formulation import from UK and these could be innovator samples ordered either by CROs for further development work or by generic companies for development of generic versions.
One could see competition on NCE-1 date in February 2027.
General information
The UPC must harness user enthusiasm to ensure a successful launch on 1 June
The UPC ( The Unified Patent Court) Sunrise Period has officially begun. In three months, the Unified Patent Court will launch. What could go wrong? Not much, unless too many technically qualified judges jump ship because the conflict rules are too strict. Or companies swamp individual local chambers, with no plan in place for judges to tackle a high workload. Thus, while the future is bright for the pan-European court, those in charge of the court's development must recognise that much remains at stake.
News here.
Gap between EU & US on pharmaceutical investments too wide – industry
“There are some significant gaps. The investment gap between the US and the EU 20 years ago was €2 billion, and now it's €25 billion," Nathalie Moll, Director General of the European Federation of Pharmaceutical Industries and Associations told Euronews.
"That's a 1,000% increase in the gap and that's very worrying if that trend continues and we want to stop it and reverse it."
It is for this reason that the pharmaceutical industry is taking an alarming view of the Commission's current draft text.
Moll says that 25 years ago, 50% of new treatments came from Europe, with one in five new treatments now coming from Europe, posing a serious threat to employment and competitiveness in Europe.
News here.
Intellectual Property
Xyrem®: Jazz vs Avadel (CAFC decision)
Jazz is holding an approved New Drug Application for the narcolepsy drug Xyrem®.
Xyrem’s active ingredient is sodium gamma-hydroxybutyrate (“GHB”), which is also known as sodium oxybate.
GHB exerts a heavily sedating effect, which is theorized to grant deepened night-time sleep, resulting in improved daytime wakefulness.
GHB is prone to heavy misuse and is infamously known as a date-rape drug. Given that misuse, the FDA conditioned approval of Jazz’s NDA upon development of Risk Evaluation and Mitigation Strategies (“REMS”), which include protocols that must be followed prior to prescribing or dispensing Xyrem.
Xyrem’s REMS originally restricted distribution to a single-pharmacy system, although the FDA waived that requirement in 2017.
The ’963 patent relates to Jazz’s single-pharmacy distribution system, which controls access to abuse-prone prescription drugs prescribed to narcolepsy patients through a central pharmacy and computer database by tracking prescriptions, patients, and prescribers.
In 2014, Jazz listed the ’963 patent in the Orange Book as covering a method of using Xyrem. In 2017, three of the ’963 patent’s 28 claims were found unpatentable in an inter partes review proceeding.
The remaining claims expired in December 2022. Because Jazz received a grant of paediatric exclusivity, however, the ’963 patent prevents the FDA from approving follow-on products until June 2023.
Under the Act, a § 505(b)(2) applicant must file a certification with respect to each patent listed in the Orange Book that claims the drug or method of using the drug for which the applicant seeks approval.
In December 2020, Avadel submitted an NDA for GHB-based drug FT218 (once nightly modified-release formulation of sodium oxybate ), along with amendments pursuant to § 505(b)(2) and a proposed REMS.
Unlike Xyrem, which requires the patient to wake up a few hours into the night to ingest a second dose, FT218 is dosed once nightly.
FT218’s REMS also uses multiple pharmacies and databases for ensuring proper drug handling.
Despite these differences, and the fact that Avadel had filed an NDA, not an ANDA, the FDA required Avadel to file a certification regarding the ’963 patent’s single-pharmacy system.
Jazz subsequently sued Avadel for infringement of the ’963 patent. Avadel contemporaneously sued the FDA, alleging that it violated the Administrative Procedure Act (“APA”) by requiring certification over the ’963 patent.
The district court found that, as a matter of claim construction, the ’963 patent claims a system and thus does not claim an approved ‘method of use’.
The district court subsequently ordered Jazz to ask the FDA to delist the ’963 patent.
Jazz appealed to CAFC.
Jazz contends that the district court abused its discretion in finding that the ’963 patent is not a method-of-use patent for listing and delisting purposes under the FDCA.
CAFC considered whether the district court erred in determining that the ’963 patent is not a method-of-use patent under the FDCA.
Jazz asserts that this inquiry involves asking two questions: (1) what does the patent claim, and (2) is the patented invention either the drug for which the application was approved or an approved method of using the drug.
Court next turned to whether the system claimed in the ’963 patent is an approved method of using the drug.
CAFC said that Jazz misreads the regulation describing method-of-use patents. The regulation for REMS does not broaden the term “method” such that reciting a condition of use turns a system patent into a listable method-of-use patent. Rather, this regulation narrows that category of listable patents. The district court therefore correctly ordered Jazz to seek delisting of the ’963 patent from the Orange Book.
Avadel also highlights that the FDA only requires listing patents for which a claim of patent infringement could reasonably be asserted, and that Congress explicitly prohibited companies from using REMS requirements to block or delay ANDA and § 505(b)(2) approvals. Although the statute does not expressly provide that a REMS patent may not be asserted against potential infringers, Avadel suggested that listing a REMS patent would allow a patent owner to block or delay ANDA and § 505(b)(2) filers in violation of that statute. However, since the Court (CAFC) found that the district court did not err in concluding that the ’963 patent must be delisted, the Court did not address Avadel’s broader arguments about REMS patents, more generally.
Federal Circuit affirmed district court’s decision for delisting of REMS patent of Xyrem® and lifted the stay of the injunction requiring Jazz to ask the FDA to delist the ’963 patent.
Decision here.
