API and IP Newsletter
Contents
FDA approval: Vorasidenib
We follow FDA approvals, especially for small molecules.
The objective of analysing these FDA approvals is not from the view of the drug's mechanism of action but mainly to study chemistry and IP and analyse import-export data to understand which companies are trying to develop generic versions of FDA-approved products.
In August 2024, FDA approved Vorasidenib.
Vorasidenib is a tablet taken orally that treats certain types of glioma, a common brain tumour in adults. It's also known by the brand name VORANIGO. Vorasidenib is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor.
The innovator is Agios Pharmaceuticals.
In 2021, Agios completed the sale of its oncology portfolio, including vorasidenib to Servier.
As part of that divestiture, Agios is owed a milestone payment of $200 million upon vorasidenib’s approval by the FDA and a 15% royalty on U.S. net sales of vorasidenib. Agios Pharmaceutical kept its interest and retained the right to the approval milestone from Servier.
Royalty Pharma plc recently acquired an interest in Agios Pharmaceuticals’ royalty on Servier’s vorasidenib for $905 million. Royalty Pharma will receive 15% on US sales of vorasidenib, up to $1bn, and at a 12% rate beyond that.
The company projected more than $1bn in annual peak sales for vorasidenib, giving it $150m annually in royalties. Royalty Pharma expects to generate royalties until 2038. This is the year of the expiration of the hemicitric acid hemihydrate co-crystal patent for vorasidenib.
The chemical name of the co-crystal is 6-(6-chloropyridin-2-yl)-N2,N4-bis[(2R)-1,1,1trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine, 2-hydroxypropane-1,2,3-tricarboxylic acid, hydrate (2:1:1). It has the following chemical structure:
Vorasidenib hemicitric acid hemihydrate is a white to off-white solid practically insoluble in aqueous solutions between pH 1.2 to 6.8.
VORANIGO is a 10 mg and 40 mg strength film-coated tablet for oral administration. The strengths reflect the amount of active ingredient vorasidenib in each tablet. Each tablet core contains the following inactive ingredients:
Croscarmellose sodium, magnesium stearate, microcrystalline cellulose, silicified microcrystalline cellulose and sodium lauryl sulfate. The tablet coating includes hypromellose, lactose monohydrate, macrogol and titanium dioxide.
Each tablet is printed with black ink that contains black iron oxide, hypromellose and propylene glycol.
Three broad processes were reported in patent literature.
WO 2013/102431
The patent family is from the brand company Agios Pharmaceuticals, Inc.
Synthesis of 6- (6-chloropyridin-2-yl) -1,3, 5-triazine-2, 4 (1 h,3 h) -dione by using biuret and 2-chloro-6-methyl formate pyridine, then addition of phosphorus pentachloride and phosphorus oxychloride for chlorination to obtain 2, 4-dichloro-6- (6-chloropyridin-2-yl) -1,3, 5-triazine, and then reaction of 2, 4-dichloro-6- (6-chloropyridin-2-yl) -1,3, 5-triazine and (R) -1,1-trifluoroisopropylamine hydrochloride to obtain the target product Vorasidenib.
WO2023174235A1
Betta Pharmaceuticals Co filed this family, discloses the synthesis of vorasidinib using cyanuric chloride, pyridine boric acid and noble metal catalysts.
WO2019090059A1
This patent family, which covers the marketed product, was also filed by the Brand Agios Pharmaceuticals and is being prosecuted in many jurisdictions.
Vorasidenib is present as the hemicitric acid hemihydrate co-crystal in the formulations. It would be interesting to note how generic companies deal with this patent family. The Indian equivalent of this patent family is granted, IN 495793. Post-grant opposition could be filed until January 2025.
Vorasidenib synthesis requires Methyl 6-chloropicolinate as a starting material.
ZCL and Vasudha are importing this raw material and might be working on API development.
This intermediate is also required for the agrochemical product, so commercial availability should not be an issue when starting the development.
General information
Eli Lilly is expanding its research and development (R&D) in India
Eli Lilly is planning to expand the research centre in India and will be partnering with other Indian companies
News here
The World First Liquid Formulation of Recombinant Botulinum Toxin Type A Has Obtained IND Approval by the FDA
MingMed Biotechnology, an innovative company focused on the in-house discovery and development of novel drugs, recently announced that its partially owned subsidiary, Claruvis Pharmaceutical Co., has received approval from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for YY003, the world’s first liquid formulation of recombinant BoNT/A, packaged in a pre-filled syringe, developed for the treatment of glabellar lines.
News here
Intellectual Property
Frito-lay Trading company-GMBH Vs The Assistant Controller of Patents and Designs India: Dated 07 July 2024
This Appeal has been preferred under Section 117-A of the Patents Act, 1970, challenging the order passed by the respondent, The Assistant Controller of Patents and Designs, refusing to grant a Patent in respect of the Patent Application of the Appellant Frito-Lay Trading Company-GMBH in Patent Application No.4689/CHENP/2010.
The patent application pertains to an invention relating to food products containing table salt formulations.
Claim:
A table salt formulation comprising aggregates of a mixture of at least two types of primary particles of one or more physiologically acceptable inorganic salts and wherein at least 50% weight of the said primary particle are 5-5000 nanometer in diameter, and wherein each said aggregate comprises sintered primary particles.
The Assistant Controller of Patents has rejected Frito-Lay Trading Company-GMBH’s Patent Application because it lacks inventive steps (Section 2(1)(ja)) and that the claim is only a mixture of two types of inorganic salts (Section 3(e)).
The learned counsel for Frito-Lay would attack the Controller's order on the ground that the Controller fundamentally misunderstood the claim of the Appellant Frito-Lay, misdirected himself, and failed to appreciate the inventive steps shown by Frito-Lay. He also misapplied Section 3(e) of the Indian Patents Act, 1970, to the instant Application. He would take me through the impugned order, the various annexures that have been filed, and other relevant records.
Frito-Lay would further submit that the reference to prior art D1 was also misleading since D1 teaches away from the concept of agglomeration or aggregation, which is the foundation of Frito-Lay's claim.
The prior art, D2, did not disclose aggregates of primary particles. In D2, citric acid was used as an enhancer, but no citric acid is used in the claim of the present invention. Therefore, the prior art was in a different direction altogether.
Further, Frito-Lay achieved the result by forming aggregates, and in fact, the teachings of prior arts were diametrically opposite to Frito-Lay ‘s claim, especially since the Appellant Frito-Lay was able to achieve smoother, smaller-sized particles compared to the prior arts.
In the present order, the Judge discussed various case laws and mentioned principles formulated earlier by Delhi High Cort, which pertain to whether an invention is obvious. Some of the relevant principles are extracted for easy reference:
“a) A hindsight reconstruction by using the patent in question as a guide through the maze of prior art references in the right way to achieve the result of the claim in the suit must be avoided.
b) There should be no teachings away from the patent in question in the prior art.
c) Though a mosaic of prior art documents may be done to claim obviousness, however, in doing so, the party claiming obviousness must be able to demonstrate not only prior art exists but how the person of ordinary kill in the art would have been led to combine the relevant components from the mosaic of prior art.”
The Assistant Controller of Patents stated that the invention is not patentable under Section 3(e) since it is not different from the object of prior art D1.
About the use of citric acid, the controller stated that in D2 prior art, citric acid is not an enhancer, and the mixture of components was different. The controller submitted that the claim of the Appellant Frito-Lay to have achieved smaller size particles could not be an invention, and the Appellant Frito-Lay has not been able to substantiate or explain how the aggregates were formed, and in such view of the matter, no synergistic effect has also been shown, and consequently, the application was rightly refused.
The Hon. Judge said that in either of the prior arts, there is nothing buried or tucked away in as much as it does not involve anything to do with the formation of aggregators or large-sized primary particles.
The judge did not find any obviousness in the prior arts and opined that Frito-Lay is entitled to a patent grant.
The Judge said he has no hesitation in holding that the prior arts only disclose a process or technique incompatible with the Frito-Lay claim. Thus, the prior arts clearly teach away from the claimed invention, and the filed patent application exhibits novelty and non-obviousness.
The Appellant is entitled to a grant of Patent in Indian Patent Application No.4689/CHENP/2010.
Decision here
