API and IP Newsletter
Contents
FDA approvals in September 2024: 505 (b) (2)
We follow 505 (b) (2) approvals every month.
There is only one 505 (b) (2) approval this month, and that is for Sun Pharma. The company submitted a new drug application (NDA) to the USFDA in March 2019 for a Bynfezia pen (octreotide acetate) injection under section 505 (b) (2).
The FDA has found that Bynfezia Pen and Sandostatin are pharmacokinetically bioequivalent based on data from the comparative PK study submitted with the NDA. The FDA expects the benefits and risks of Bynfezia pen used at the proposed doses to be like those associated with Sandostatin for the treatment of acromegaly, severe diarrhoea/flushing episodes associated with metastatic carcinoid tumours, and profuse watery diarrhoea associated with Vasoactive Intestinal Peptide (VIPoma) secreting tumours.
Pen injectors have been used successfully to manage several chronic diseases and provide advantages over injections administered in clinical settings, including improved treatment adherence, ease of use, convenience, dose accuracy, and social acceptability. Studies that tested similar devices suggested that patients and caregivers prefer using a pen injector over a preloaded syringe or other injectable dosage forms.
The details about clinical studies are reported here.
Dosage for Bynfezia Pen
The initial dose of Bynfezia Pen to treat acromegaly is 50 mcg thrice daily. The typical dosage is 100 mcg three times a day. The dose of Bynfezia Pen to treat carcinoid tumours is 100-600 mcg daily in 2-4 divided doses for the first 2 weeks. The dose of Bynfezia Pen to treat VIPomas is 200-300 mcg daily in 2-4 divided doses for the first 2 weeks.
Though this is a Bynfezia pen (octreotide acetate), Sandostatin LAR Depot had annual sales of $826 million in the US as of July 2024.
Patent situation
Sun Pharma had earlier filed a patent application US20130303453A1, related to a sterile solution comprising octreotide acetate in a pen injection device. Sun Pharma later abandoned this application in the USA.
Sun Pharma is now prosecuting the WO2018211526 patent family. This family relates to a sterile octreotide solution at a concentration equivalent to 2.0 mg/ml to 2.5 mg/ml of octreotide base in the pen injection device. This family is being prosecuted in many countries. It is granted in India and the US. Sun will list this in the Orange Book. This must cover their marketed product, Bynfezia Pen.
General information
How the EU can strengthen pharmaceutical competitiveness
By prioritising competitiveness and regulatory efficiency, the EU can empower its pharmaceutical sector to innovate and excel, addressing rare diseases and unmet needs.
In its new mandate, the European Commission has highlighted competitiveness as a cornerstone of its agenda. This renewed focus is timely and essential, especially in light of the Enrico Letta report on the future of the European single market, published in April, and the recent Mario Draghi report on the future of European competitiveness.
News here
How Platform Technologies Are Shaping The Gene Therapy Landscape
The concept of platforms has shifted from being something within a single company to more of a manufacturing process established at CDMOs that serve multiple sponsors. Variations to platform processes are introduced with each sponsor’s product.
News here
Intellectual Property
Astellas Pharma, Inc Vs Sandoz
This litigation involved US 10,842,780 issued to Astellas Pharma. It relates to a sustained-release formulation of Astellas’ drug Myrbetriq® (mirabegron), used to treat an overactive bladder.
During the development of Myrbetriq, Astellas discovered that immediate-release formulations of mirabegron exhibit an undesirable “food effect,” meaning that the bioavailability of the drug is affected by the presence or absence of food in a patient’s stomach.
Astellas observed that when patients took the drug with a meal, the levels of mirabegron that were absorbed into the blood were too low to impart any therapeutic benefit.
However, when patients took the drug on an empty stomach, mirabegron was absorbed too rapidly, reaching potentially toxic concentrations in the blood. To solve this problem, Astellas developed sustained-release formulations of mirabegron, which abated the undesirable food effect. The claims of the ’780 patent cover those formulations. The patent was granted in November 2020, and Astellas listed it in OB in December 2020 and sued generics, including Sandoz, that wanted to launch the generic sustained-release formulation Myrbetriq.
Sandoz agreed to limit its invalidity defences to Sections 103 and 112 in a joint proposed pretrial order in the District Court.
Section 103 of the US patent law deals with the conditions for patentability and non-obvious subject matter
Section 112 of US patent law establishes the minimum amount of information that must be included in a patent application and the structure of the description.
In short, initially, Sandoz argued patent was invalid
Because Sandoz believes it is obvious (broadly section 103) and
The specification needs a full description of the invention; in the case of the ’780 patent, it does not enable a skilled person to reproduce, make, and use it fully, clearly, concisely, and exactly.(broadly section 112)
In a subsequent joint stipulation, Astellas agreed to assert only claims 5, 20, and 25 of the '780 patent, and Sandoz agreed to limit its invalidity defences to Section 112.
The district court held claims 5, 20, and 25 of the '780 patent invalid as directed to ineligible subject matter under 35 U.S.C. § 101, finding the claims to state a natural law applied via well-known methods. It also denied Sandoz's motion for further findings on the issues presented at trial, namely its invalidity defence under Section 112.
Section 101 of the US Patent Act defines the types of inventions that can be patented, and it should be noted that no party, neither Sandoz nor Astellas, had argued Section 101.
The matter went on to appeal in CAFC.
On appeal, the Federal Circuit reversed the district court's decision in a precedential opinion. While reversing the District Court decision, the Federal Circuit said,
Although we have concerns with the district court's analysis, we are not convinced that the judge, who has overseen nearly two hundred patent cases and has ruled in favour of innovative and generic manufacturers alike, cannot resolve the outstanding issues impartially and fairly, particularly now that we have clarified the proper course for adjudication.
Significantly, other than the court’s two rulings, Astellas cannot identify any instance in the life of this nearly four-year-old litigation in which the district court judge acted in a way that called into question his ability to do just that.
The district court incorrectly disregarded the principle of party presentation and abused its discretion because the principle allows the parties to shape the course of litigation, and no party advanced the issue of invalidity under Section 101 in the proceedings.
Decision here
