API and IP Newsletter
Contents
DMF filed in the month of August 2022
We analyse DMF filings by Indian companies. We had not it for a while and in this week we analysed DMFs filed in the month of August.
Total 51 DMFs were filed in August 2022.
General information
HC imposes ₹10 lakhs on Sun Pharma for concealing facts
The Delhi High Court in its order passed on Tuesday levied a penalty of ₹10 lakhs on Sun Pharmaceutical Industries for concealing facts in order to obtain an ex-parte injunction order in its trademark matter with DWD Pharmaceuticals.
News here.
The FDA Just Approved the Most Expensive Drug in The World
At first glance, the price is gob smacking, but a recent analysis on the cost-effectiveness of the drug suggests that's a relatively 'fair' price for what the treatment achieves – at least in the US.
The medicine, called Hemgenix, is a gene therapy treatment for hemophilia B, which is a rare genetic disease that causes reduced clotting of the blood. The most serious symptoms include spontaneous and repeated bleeding episodes that are difficult to stop
News here.
Intellectual Property
Teva vs Novartis: England and Wales High Court (Patents Court)
Background
Since the 1960s iron chelation treatments, removing excess iron from a patient's blood, have been available using a compound called deferoxamine. Removing iron is typically required where the patient has been given a blood transfusion or is suffering from certain blood conditions. Up to the late 1980s the treatments required subcutaneous infusions lasting 8-12 hours at least 5 days a week.
In 1987 a product called deferiprone came into use with dosing needed 3 times a day. This was still far from ideal and there remained side effects.
A third drug, deferasirox was first marketed in the EU in 2006. It came as a dispersible tablet with the brand name Exjade (by Novartis) and marked a significant advance since it could be taken just once a day, with correspondingly improved patient compliance. Less helpfully, each dose required between 3 and 7 tablets which had to be dispersed in water or other liquid, creating an unpalatable sludgy drink to be consumed on an empty stomach. Some patients suffered from side effects, principally in the form of nausea, vomiting, diarrhoea or abdominal pain.
Novartis filed patents for further improvements and tried to cover a swallowable film-coated tablet formulation of deferasirox. The patents were granted. Granted EP patents were EP (UK) 2,964,202 ("EP 202") and EP (UK) 3,124,018 ("EP 018"). Expiration 2034.
Teva brought the action for revocation of two patents. Both Patents have been upheld in the Opposition Division of the EPO with amended claims. Appeals are pending.
This matter was before England and Wales High Court (Patents Court)
Teva also sought a declaration of non-infringement in relation to their product Teva DFX, used for iron chelation
The application for EP 018 was divisional of EP 202 and so they share the same priority date, 8 March 2013. Their specifications are almost identical.
The first two claims of EP 202 as unconditionally proposed to be amended:
"Claim 1
A swallowable film coated tablet for oral administration comprising deferasirox or a pharmaceutically acceptable salt thereof present in an amount from 45% to 60% by weight based on the total weight of the tablet, wherein the tablet is without sodium lauryl sulfate and lactose and comprises
i. microcrystalline cellulose;
ii. crospovidone;
iii. povidone;
iv. poloxamer 188;
v. colloidal silicon dioxide;
vi. magnesium stearate.
Claim 2
The swallowable film coated tablet for oral administration according to claim 1 wherein:
i. microcrystalline cellulose is present in a total amount of 10% to 40 % by weight based on total weight of the tablet;
ii. crospovidone is present in a total amount of 1% to 10 % by weight based on total weight of the tablet;
iii. povidone is present in a total amount of 1% to 5 % by weight based on total weight of the tablet;
iv. poloxamer 188 is present in a total amount of up to 2% by weight based on total weight of the tablet;
v. colloidal silicon dioxide is present in a total amount of 0.1% to 1% by weight based on total weight of the tablet;
vi. magnesium stearate is present in a total amount of 0.1% to 2% by weight based on total weight of the tablet;
vii. the coating comprises a functional or non-functional polymer."
The first two claims of EP 018:
"Claim 1
A swallowable film coated tablet for oral administration which contains deferasirox or a pharmaceutically acceptable salt thereof present in an amount of from 45% to 60% by weight based on the total weight of the tablet, and wherein the tablet contains 90 mg, 180 mg or 360 mg of deferasirox, or a pharmaceutically acceptable salt thereof
wherein the tablet further comprises,
i. at least one filler in a total amount of 10% to 40 % by weight based on total weight of the tablet, wherein the filler is microcrystalline cellulose;
ii. at least one disintegrant in a total amount of 1% to 10% by weight based on the total weight of the tablet, wherein the disintegrant is cross-linked polyvinylpyrrolidone (crospovidone);
iii. at least one binder in a total amount of 1% to 5% by weight based on the total weight of the tablet, wherein the binder is polyvinylpyrrolidone (PVP);
iv. optionally, at least one surfactant in a total amount of 0.0% up to 2% by weight based on the total weight of the tablet, wherein the surfactant is poloxamer;
v. at least one glidant in a total amount of 0.1% to 1% by weight based on the total weight of the tablet, wherein the glidant is colloidal silicon dioxide;
vi. at least one lubricant in a total amount of less than 0.1% to 2% by weight based on the total weight of the tablet, wherein the lubricant is magnesium stearate; and
vii. a coating.
and wherein the tablet does not contain sodium lauryl sulfate and does not contain lactose.
Claim 2
The swallowable film coated tablet for oral administration according to claim 1, wherein the tablet contains 90 mg of deferasirox or a pharmaceutically acceptable salt thereof."
Cited prior art documents:
International Patent Application No. WO 2007/045445 ("Battung").
International Patent Application No. WO 2009/067557 ("Zadok").
Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks, Séchaud R. et al., International Journal of Clinical Pharmacology and Therapeutics, 2008 Vol. 46, no. 2/2008, 102-108 ("Séchaud").
Battung expressly discloses poloxamer as a suitable alternative filler. The inventive concept specifies poloxamer 188, but Dr Rigby-Singleton (Novartis' expert formulator ) said that 188 would be one of the obvious choices among the poloxamers available. Battung expressly discloses MCC as an alternative filler.
Novartis has provided a plausible reason why swallowable deferasirox was not developed sooner than it was.
Professor Shah (Novartis’ expert, Associate Professor of Medicine at the Duke University School of Medicine, North Carolina) said Novartis would have wished to market a medicine that was clinically, and therefore commercially, successful.
Novartis argued before their work on swallowable deferasirox, the expected bioavailability in "conventional tablets", i.e. swallowable film-coated tablets, was such that in order to provide patients with the required dose, it would have been necessary to take too many of them.
The necessary dose would have required patients to take so many tablets that there would have been problems with compliance. Alternatively, the patient would receive an insufficient dose of deferasirox from the number of tablets he or she was prepared to take.
The product would not have been clinically or commercially successful. For a time Novartis felt it had to stick with the dispersible formulation.
The judged opined if this is correct, there was no perceived technical barrier to making a product, but there could be a commercial barrier.
The Judge opined Claims 1 and 2 of both EP 202 and EP 018 lack an inventive step over Battung.
Further, Novartis did not argue that having the content of deferasirox anywhere in the range of 45-60% was inventive over the disclosure of 20-80% in Zadok. Nor did Novartis press for any inventive significance in the ranges of excipients stated in claim 2 of EP 202 and claim 1 of EP 018.
So the judge found that a skilled team would have thought it's obvious to reformulate dispersible deferasirox to make a swallowable tablet, though there may have been limited commercial pressure to try. The Patents lack an inventive step over Zadok.
Decision by England HC.
The Patents lack an inventive step over Battung and Zadok. Teva DFX does not fall within the scope of the claims of the Patents.
Decision here
