API and IP Newsletter
Contents
- DMF filings in November 2024
- General information
- Merck Issues Statement on GARDASIL® Litigation
- Indian pharma faces decline in R&D productivity, patent expiries, turns to AI to mitigate challenges
- Intellectual Property
- Taiho Pharmaceutical Vs MSN
DMF filings in November 2024
The FDA publishes a list of DMF filings every quarter. The fourth quarter (CY 24) list was recently published.
This month, we are analysing November 2024 DMF filings. Of the 70 DMFs filed that month, 36 were submitted by Chinese companies and 29 by Indian companies.
The top DMF filing companies are listed below:
Some of our other DMF-specific comments are as below.
General information
Merck Issues Statement on GARDASIL® Litigation
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today reaffirmed its commitment to defending the safety and efficacy of its HPV vaccines.
Merck is a defendant in product liability lawsuits in the United States involving GARDASIL® (Human Papillomavirus Quadrivalent [Types 6, 11, 16 and 18] Vaccine, Recombinant) and GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant).
News here
Indian pharma faces decline in R&D productivity, patent expiries, turns to AI to mitigate challenges.
Intellectual Property
Taiho Pharmaceutical Vs MSN
Plaintiffs Taiho Pharmaceutical Co., Ltd. and Taiho Oncology, Inc. ( “Taiho”) filed this action against Defendants MSN Laboratories Private Ltd. and MSN Pharmaceuticals Inc. (collectively, “MSN”).
The complaint alleges that MSN submitted an Abbreviated New Drug Application (ANDA) for the approval of a generic version of Lonsurf® that infringed on certain Taiho patents, including U.S. Patent Nos. RE46,284 E (the “ʼ284 patent”) and 10,457,666 (the “’666 patent”).
After the Court resolved the parties’ disputes regarding the ’284 Patent, the case was reassigned to Hon. Judge Jennifer L. Hall of the District Court of Delaware.
In April 2024, the Hon. Judge Hall presided over a two-day bench trial concerning the ’666 patent.
One of the active ingredients in Lonsurf® is tipiracil. The ʼ666 patent is titled “Stable Crystal Form of Tipiracil Hydrochloride and Crystallization Method for the Same.”
The specification states that the present invention pertains to a stable crystal form of tipiracil hydrochloride, which has excellent preservation stability and is useful as an active ingredient in medicaments, as well as a method for crystallisation of the same.
The patent describes three crystal forms of tipiracil hydrochloride: Crystal Form I, Crystal Form II, and Crystal Form III. It provides a powder X-ray diffraction chart for each form. The specification further details the specific advantages of Crystal Form I for use in medicaments.
Taiho only asserts claim 3. It provides:
3. Crystal Form I of 5-chloro-6-(2-iminopyrrolidin-1- yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride exhibiting peaks at angles of 11.6°, 17.2°, 17.8°, 23.3°, 27.1°, and 29.3° as a diffraction angle (2θ±0.2°), and having a purity of at least 90% by mass.
The parties disputed the meaning of the term “purity” in claim 3.
Taiho argued that the term pertains to chemical purity, while MSN states it relates to crystal form purity.
Claim 3 requires, among other things, a “Crystal Form I” of tipiracil hydrochloride “having a purity of at least 90% by mass.” The parties dispute the meaning of the term “purity.” Taiho asserts that “purity” refers to “chemical purity.”
In other words, Taiho indicates that the 90% figure refers to the percentage of the mass that is tipiracil hydrochloride, rather than chemical impurities. MSN claims that “purity” denotes “polymorphic purity.”
In other words, MSN argued that the 90% figure relates to the proportion of the mass in Crystal Form I rather than in other forms.
Taiho contended that the term “purity” is typically understood by those skilled in the art to mean chemical purity. However, the question here is whether a skilled artisan would assign that meaning in the context of claim 3 of the ʼ666 patent. After carefully considering all the intrinsic and extrinsic evidence on record, the Judge concurred with MSN that the term refers to polymorphic purity.
The remainder of the specification strongly supports MSN’s contention that a skilled artisan would understand that “purity,” as used in the context of claim 3 of the ʼ666 patent, refers to polymorphic purity.
The specification acknowledges that methods for producing tipiracil hydrochloride were known in the art, but it explains that prior art methods resulted in mixtures of different crystal forms.
Then, under the heading “Technical Problem,” the specification states that “an objective of the present invention is to provide a stable crystal form of tipiracil hydrochloride useful as an active ingredient in medicaments.” It continues to describe the inventors’ characterisation of three distinct crystal forms of tipiracil hydrochloride, concluding that the properties of Crystal Form I, particularly its stability, make it advantageous for use as a medicament. Under the heading “Solution to Problem,” the specification indicates that the inventors have “through trial and error, found a production method for advantageously obtaining a highly pure Crystal I under specific conditions.”
The specification describes how to create high-purity Crystal I. It explicitly defines “high purity” as polymorphic purity: "High purity in the present invention means that at least 90% by mass, preferably 95% by mass, and more preferably 99% by mass of the crystals of tipiracil hydrochloride are the crystals of the present invention.
The specification discloses that controlling the crystallisation temperature is vital for making “ high-purity” crystals of Crystal Form I. This prevents the formation of Crystal Form II during the crystallisation step. When the temperature is 40ºC or lower, Crystal Form II, which is poor in long-term storage stability, is precipitated.
The results show that Crystal Form II, which has poor storage stability, was obtained when the crystallisation temperature was below 35ºC. When the temperature was maintained at 44ºC or higher, Crystal Form I, which has high storage stability, was efficiently obtained with high purity.
Notably, claim 3 requires purity of at least 90%, and the only mention in the specification of a “90%” figure is the specification’s reference to polymorphic purity. In contrast, the specification does not refer to any chemical impurities by percentage of mass or otherwise.
For the above reasons, the Court construed “purity” as used in claim 3 of the ’666 patent as “polymorphic purity.”
Decision here
