API and IP Newsletter
Contents
FDA approvals-Terlipressin (Terlivaz)
We analyse FDA approvals.
The FDA approved injectable terlipressin (Brand- Terlivaz, Innovator-Mallinckrodt plc) for hepatorenal syndrome (HRS) with rapid reduction in kidney function.
It was approved in September 2022.
This is an old drug. Terlipressin is already available in New Zealand, Australia, the European Union, India, Pakistan & UAE. It is sold under various brand names including Glypressin
In India as per import-export database, Hemmo Pharmaceuticals and Piramal are very active in terlipressin and exporting formulations to many countries including some European countries. Readers would know Hemmo Pharmaceuticals is acquired by Piramal Pharma and Hemmo Pharmaceuticals Pvt Ltd is a wholly owned subsidiary of Piramal Pharma Ltd. News here.
Polypeptide filed DMF in 2019.
Terlipressin was earlier invented by Ferring company, as haemostatic drug in Holland in 1977, trade name Glypressin.
Later Ferring marketed in France, Germany, Britain with brand name Glypressine
There are two formulations, lyophilized injectable powder and injection liquids available in these markets.
The reported preparation of terlipressin is liquid phase synthesizing method, it is disclosed in CZP281589 employing Boc-Gly-chloromethyl resin.
One more method is described in CN1865282A which uses rink amide resin.
The companies who are specialised in peptide chemistry will be filing DMFs.
General information
Biocryst Pharmaceuticals Showing Market Leadership Earns 85 RS Rating
The biotech firm posted 0% earnings growth last quarter. Revenue gains came in at 85%.
BioCryst Pharmaceuticals earns the No. 122 rank among its peers in the Medical-Biomed/Biotech industry group.
How pharma giant Eli Lilly lost billions because of Twitter Blue
American pharmaceutical giant Eli Lilly (LLY) lost billions after stock plunged on Friday because a fake account, verified with a blue tick, claimed “insulin is free now.” The tweet was sent on Thursday.
According to The Star, the company’s stock dropped 4.37 per cent on Friday - erasing over US $15 billion in market cap – after a fake account impersonating Eli Lilly promised free insulin.
News here.
Intellectual Property
T 0784/20 (Composite particles/VECTURA)
EP 2 283 818 was issued to Vectura Limited, it had fifteen claims. Glaxo Group Limited opposed the patent.
Independent claim 1 as granted related to:
"A method for making composite active particles for use in a pharmaceutical composition for pulmonary administration, the method comprising a milling step in which particles of active material are milled in the presence of particles of an additive material which is suitable for the promotion of the dispersal of the composite active particles upon actuation of an inhaler, wherein the additive material is magnesium stearate."
Independent claim 8 as granted related to composite active particles for use in a pharmaceutical composition as made by such method.
Independent claim 12 as granted related to a pharmaceutical composition comprising composite active particles as made by such method.
The patent was opposed on the grounds that its subject-matter lacked novelty and lacked inventive step, that the claimed invention was not sufficiently disclosed and that the patent comprised subject-matter extending beyond the content of the (earlier) application as filed
In this write-up we will briefly discuss inventive-step argument.
The opposition division cited inter alia the following documents:
D1: WO 00/27363
D7: International Journal of Pharmaceutics 173 (1998) 243-251
D15: Handbook of Pharmaceutical Excipients (2nd edition, 1994) p. 280-282
D16: Handbook of Pharmaceutical Excipients (3rd edition, 2000) p. 305-308
Starting point in the prior art
Each of documents D1 (WO 00/27363) and D7 (International Journal of Pharmaceutics 173 (1998) 243-251) describe the provision of surface modified drug particles. Both documents concern the same purpose and effect as the patent, namely the provision of surface modified drug particles with improved inhalation properties.
Document D1 describes surfactants as preferred surface modifiers. The document further mentions calcium stearate in a list of surface modifiers and presents actual preparative examples involving milling using polyvinyl povidone (PVP) as surface modifier. Document D7 describes the use of Aerosil 200 as surface modifier.
The subject-matter of claim 1 of the main request differs from the teaching of document D1 as well as document D7 in the choice of magnesium stearate as the surface modifier.
Problem to be solved
The patentee Vectura Limited identified the provision of an improved method for making particles suitable for inhalation as the problem to be solved.
However, no advantage of the use of magnesium stearate with respect to the prior art of document D1 had been relied upon by the patent proprietor Vectura Limited.
The Board therefore opined that the problem to be solved is the provision of an alternative method of preparing surface modified particles for pulmonary administration.
Assessment of the solution
Document D1 describes surfactants in general as suitable surface modifiers and mentions calcium stearate as an example.
The document refers in this context specifically to the handbook on pharmaceutical excipients from which document D15 (Handbook of Pharmaceutical Excipients (2nd edition, 1994) p. 280-282) originates represent common knowledge, mention in the context of pharmaceutical excipients calcium stearate as a substance related to magnesium stearate.
The Board considers that in the absence of convincing indications to the contrary the skilled person had therefore good reason to expect that magnesium stearate would be suitable as alternative to the surface modifier calcium stearate mentioned in document D1.
The patent proprietor referred in this context to the warnings mentioned in documents D15 and D16 regarding harmful inhalation of magnesium stearate. The Board observes, however, that these warnings evidently concern precautions aimed at avoiding harm from excessive inhalation of magnesium dust when handling the bulk substance.
As pointed out by the opponent GSK and not contested by the patent proprietor, the claimed subject-matter relates to pharmaceutical compositions for pulmonary administration in which only limited amounts of magnesium stearate are inhaled.
The mentioned handling precautions against excessive inhalation are therefore not considered to affect the skilled person's expectation regarding the suitability of magnesium stearate for use as an alternative to the surface modifiers described in document D1.
Accordingly, the Board concluded that the subject-matter of claim 1 does not involve an inventive step and the patent was revoked.
