API and IP Newsletter
Contents
FDA approval in February 2023
We follow FDA approvals for small molecules.
Travere gets FDA accelerated approval for FILSPARI (Sparsentan ) for proteinuria in IgAN
Jefferies is predicting Filspari will reach $35 million in sales this year, and $745 million at peak. Here
Sparsentan is a white to off-white powder, which is practically insoluble in water. Sparsentan has pH-dependent solubility, with intrinsic solubility of 1.48 and 0.055 mg/mL under pH 1.2 and 6.8, respectively.
FILSPARI is available as film-coated 200 mg and 400 mg strength immediate release tablets for oral administration.
The inactive ingredients in FILSPARI are colloidal silicon dioxide, lactose anhydrous, magnesium stearate, silicified microcrystalline cellulose, and sodium starch glycolate. Film-coating is composed of macrogol/polyethylene glycol, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide.
WO2010135350: Family filed by Pharmacopeia, Llc claims intermediates and processes, but this was not validated in any country after filing PCT.
WO2020132594A1: Relates to Amorphous sparsentan and its compositions.
WO2018071784A1: Relates to pharmaceutical composition.
Most of these patent families are filed by Retrophin Inc. In November 2020 Retrophin Inc changed its global corporate name to Travere Therapeutics. Hence marketing authorisation for Sparsentan is issued to Travere.
Sparsentan may be prepared by methods such as those described in WO2018/071784 A1 , WO2010114801A1, and US 6,638,937 B2 (BMS). The compound 172 in US 6,638,937 represents Sparsentan.
It could be challenging for innovator seek compound protection for this old compound and it would be interesting to study how innovator protects its IP rights. There could be possibility that several players will be filing ANDA on NCE-1 date.
In India Watson (Teva) and Aragen are importing 1-bromo-2,4-dimethylbenzene or 1-Iodo 2,4-dimethylbenzene in small quantities, less than a kilogram. This is possible RM of synthesis of sparsentan. These companies could be working on Sparsentan development in R&D.
General information
Zevra to get US patent linked to sleep disorder therapy
Zevra Therapeutics (NASDAQ:ZVRA) said the U.S. Patent and Trademark Office (USPTO) issued a patent which covers Serdexmethylphenidate (SDX), the sole active pharmaceutical ingredient in the company's sleep disorder therapy KP1077.
The U.S. Patent No. 11,505,537 is titled, 'Compositions Comprising Methylphenidate-Prodrugs, Processes of Making and Using the Same.'
The company noted that the patent provides methods of use governing d-methylphenidate conjugates and/or salts to treat excessive daytime sleepiness linked with central hypersomnia disorders, including idiopathic hypersomnia (IH) and narcolepsy in various dosage forms.
News here.
Bayer to Spend $1 Billion on US Drug R&D
Bayer is looking to spend $1 billion on drug research and development in the United States during 2023 as part of a plan to double its sales in the country by the end of the decade.
The German group has increased the number of US employees working in pharmaceutical marketing by around 50% over the past three years and wants to expand that by a further 75% up to 2030, US pharma chief Sebastian Guth said in an interview with Reuters.
News here.
Intellectual Property
Orkla Health Vs Hyben Vital Licens ApS
EP2872135 was granted with a set of four claims and was issued to Orkla Health. Claim 1 reads as follows:
"1. A process for the manufacture of dried rose hip powder comprising the steps of
providing harvested rose hip,
drying and chopping the rose hip,
separating the chopped rose hip and isolating the shells,
grinding the shells, and
optionally sieving the ground rose hip shells to a particle size below 1 mm, wherein cooling is applied during the grinding step so that the grinding is performed at a constant temperature, said temperature being below 40°C, preferably below 30°C, more preferred below 25°C even more preferred below 20°C."
The patent was opposed for lack of novelty and inventive step and was not disclosed in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.
The patent proprietor requested that the opposition be rejected (main request) and submitted five sets of amended claims (auxiliary requests 1 to 5).
Let us discuss inventive step primarily for the main request in this write-up.
The documents cited in the proceedings before the opposition division included the following:
D1: Int. J. Clin. Rheumatol. 9(3), 267-278 (2014)
D2: US 6,024,960 A
D3: WO 2011/113433 A1
D5: Scand J Rheumatol 34, 302-308 (2005)
The opposition division at the first instance revoked the patent. And this matter was before the Appeal Board, which is second instance at European Patent Office.
Inventive step was assessed starting from the technical teaching of document D2.
Claim 1 of the main request differed from the disclosure of D2 by the requirement for cooling and maintaining the temperature below 40°C during grinding.
The objective technical problem was to provide an alternative process for obtaining a rose hip powder.
As the prior art (e.g., D3) contained indications that low temperatures should be maintained during the manufacturing process, the claimed subject-matter did not involve an inventive step.
Inventive step - main request
A comparison of the teaching in document D2 and the patent in suit showed that rose hip shell powder prepared according to the patent in suit must be more potent, since lower amounts of it were required for therapeutic benefit.
This distinction was confirmed by the results of the comparative in vitro test.
Objective technical problem and solution
The alleged technical effect of the claimed process in comparison with the process disclosed in D2 is that because milder process conditions help avoid the degradation of active substances, a higher content of active substances in the ground rose hip shell material may be attained.
The board considers that the alleged technical effect has not been rendered credible, for the reasons set out below.
The nature of the comparison with the closest prior art must be such that the alleged technical effect is convincingly shown to have its origin in the distinguishing technical feature. The alleged technical effect must also be credibly attainable over the whole of the claimed scope.
The association of the alleged technical effect with the distinguishing technical feature is a necessary requirement.
If it were not known which technical features were responsible for the technical effect(s) observed in a comparative test, it would not be possible to infer that the claimed subject-matter indeed provides a specific technical effect in comparison with the closest prior art.
A comparison meeting the criteria:
(a) comparison with the closest prior art
(b) alleged technical effect linked to the distinguishing technical feature
(c) technical effect attainable across scope claimed
was provided neither in the patent in suit nor with the appellant's submissions.
In support of the alleged technical effect, Orkla Health relied, in one approach, on a comparison of statements about dosing found in the prior art and in the patent in suit. While the powder prepared according to D2 was to be administered in an amount of at least 20 g per day, the powder prepared according to the patent in suit could be administered in an amount of 4.5 g or even just 2.25 g per day.
However, comparing statements about dosing in D2 and in the patent in suit does not constitute a direct comparison between powders obtained from the same batch of raw material and with process conditions that only differ by applying, or not applying, the cooling defined in claim 1.
This means that the difference in dosing cannot be conclusively attributed to the distinguishing technical feature (criterion (b)).
Other parameters relating to raw materials, equipment and process conditions may have differed that could have affected the content of active substances in the rose hip shell powders on which the dosing recommendations were based.
The examples described in the patent in suit do not focus on the distinguishing technical feature and (as conceded by Orkla Health) do not provide a direct comparison of the claimed process with that of the closest prior art D2.
Orkla Health argued that, considering the teaching of the prior art (e.g. in D3 or D5), rose hip powder containing seeds, would in any case have been expected to have a higher potency than rose hip powder prepared from shells only, and therefore this choice of comparative sample would not have influenced the outcome in favour of the "inventive" sample.
However, this argument remains speculative, since nothing is known about the content of seed material in the comparative sample or about the qualitative and quantitative content of active components in either sample.
Orkla Health’s argument, in any case, does not overcome the objection relating to criterion (b).
No technical basis is given for the assumption regarding heat exposure, which must, therefore, be regarded as speculative. There is no evidence that without cooling, the heat exposure of the material during the grinding step might indeed be equivalent to five minutes' exposure to 50°C, in any mill that could have been used to implement the grinding step required in D2.
For these reasons, the subject-matter of claim 1 as granted does not involve an inventive step within the meaning of Article 56 EPC.
Patent was revoked.
Decision here; T 0576/19 () of 20.12.2022
