API and IP Newsletter
Contents
FDA approval in April 2022- Oteseconazole
In Sidvim we follow FDA approvals of small molecules.
Oteseconazole was approved for medical use in the United States in April 2022 used for the treatment of vaginal yeast infections. It was developed by Mycovia Pharmaceuticals.
Oteseconazole is a white to off-white crystalline powder and is practically insoluble in water within a pH range of 1 to 9 but is soluble in a variety of organic solvents. Each oteseconazole capsule, for oral use, contains 150 mg oteseconazole.
Process to manufacture oteseconazole is disclosed in example 6 of WO2017049080A1
A compound 4-(2,2,2-Trifluoroethoxy)benzeneboronic acid is starting material (SM) of oteseconazole. As per our understanding this SM is not used for any other API. Syngene and TCG are importing small quantities of 4-(2,2,2-Trifluoroethoxy)benzeneboronic acid. Hence, these companies could be in process of developing generic oteseconazole API. These companies could be at early stages of development noticing quantities of SM they are importing in the recent past.
General information
PharmaZell and Novasep Announce Merger Completion
PharmaZell (Raubling, Germany) and Novasep (Lyon, France) have announced the completion of their merger, following exclusive negotiations initiated in September 2021. This strategic merger creates a technology driven, leading contract development and manufacturing (CDMO) and active pharmaceutical ingredient (API) manufacturer.
News here.
AstraZeneca sues Mylan after securing fresh delivery patent on Symbicort
AstraZeneca has opened another front in its effort to protect its respiratory disease drug Symbicort from generic competition, securing a patent and immediately following up with a lawsuit against Mylan and Kindeva Drug Delivery.
Viatris, the result of the Mylan-Pfizer Upjohn combination, won tentative FDA approval for its generic version of AstraZeneca’s blockbuster asthma and chronic obstructive pulmonary disease drug Symbicort in March 2021. The FDA granted final approval to the generic, which is branded Breyna, earlier this year, but AstraZeneca has now sought to raise another legal barrier to the competitor.
The barrier is built on 11,311,558, a patent issued by the U.S. office last week. The patent relates to the formulation of formoterol and budesonide, the active ingredients in Symbicort, with “HFA 227, PVP and PEG, preferably PVP K25 and PEG 1000” to treat respiratory diseases. The patent goes on to describe the preferred percentages of the various components in the finished product and include them in the claims.
News here.
Intellectual Property
T 2671/19 (Melt extrusion/EURO-CELTIQUE) of 8.4.2022
EP 1586311 was issued to Euro Celtique SA
The alleged invention related to extrusion, and in particular to melt extrusion of multiparticulates which should have provided controlled release of an active ingredient.
Multiparticulates of uniform dimensions with modified drug release properties can readily be manufactured by melt extrusion technology. Melt extrusion is a solvent-free single-step process for manufacturing multiparticulates and is particularly useful for drug release modification. By selection of suitable polymers and additives, melt extrusion technology can be used both to enhance the solubility, and subsequently the bioavailability, of poorly water soluble drugs as well as to retard drug release of moderate to highly water soluble drugs for controlled release products.
Independent claim 1:
"A process for preparing a controlled release pharmaceutical extrudate using a melt extruder,
-wherein the melt extruder comprises a die-head supporting a die-plate in which orifices are located, and a cutter adjacent to the die-head, and
-wherein the cutter cuts the extruded mix as it emerges under pressure and still molten from the orifices of the die-plate,
-wherein a stream of air of reduced temperature is directed into the region of the surface of the die-head during cutting and the rate of extrusion and the speed of the cutter blade are adjusted to give spherical shaped multiparticulates."
(Patentee filed auxiliary request and claim 1 of this auxiliary request granted the following additional feature)
-"and wherein the outer surface of the die-head is coated with a non-stick material."
The appeal was filed by the opponent (appellant) Leistritz Extrusionstechnik GmbH
against the decision of the opposition division to reject the opposition.
Several prior art documents cited. THE Following documents are important for the discussion today.
D6 : Powerpoint-Presentation Mr Alexander Koschmider at the "Pharma Workshop 2003",
D7 : Brochure "Micro Pelletizer Serie - Technische Daten LMP 18 PH / LMP 27 PH" April 2003
D16: Expert Declaration by Treena Nicoll, 29 June 2018
Novelty:
The document D6 is the closest prior art. It discloses the use of the Leistritz Micro Pelletizer (LMP 27 PH) for the preparation of pharmaceutical compositions in the form of spherical pellets.
The Board acknowledged that document D6 and D7 explain the details concerning the LMP 27 PH pelletizer used in particular the position of the cutter and the cooling airstream for carrying off the granulate.
The board recognised, implicit disclosure in document D6 by the reference to the use of the LMP 27 PH pelletizer for the preparation of the pharmaceutical compositions in the form of spherical pellets.
The Board therefore concluded that the subject-matter of claim 1 as granted lacks novelty.
Inventive step
The disclosure in document D6 discloses definition of the non-stick coating.
The declaration in document D16 teaches the skilled person is faced with the problem of smearing of the pellets at the die-head when pharmaceutical extrudates are cut in the molten state on exit from the die-head.
The Board acknowledged that from the mention in the patent of the coating of the die-head with a non-stick material such as polytetrafluoroethylene (PTFE) the skilled person immediately derives the purpose of the coating, namely the prevention of molten extrudate sticking to the die-head.
The board said, it is therefore reasonable to conclude on the basis of the teaching of the patent that, as confirmed in document D16, the non-stick coating is suitable to reduce residual smearing and agglomeration of the extrudate.
The problem to be solved may therefore appropriately be formulated as the provision of an improved process for the preparation of spherical shaped particles.
The Board observed that the versatility of coatings of non-stick material such as PTFE was well known in the art.
The skilled person who is confronted with residual smearing of the pellets when cutting a molten extrudate to produce spherical particles for pharmaceutical formulations as described in document D6 will therefore as a matter of obviousness consider the application of a non-stick coating to prevent the molten extrudate from sticking to the die-head and thereby reduce residual smearing.
The patent proprietor Euro Celtique SA, had not denied the well-known versatility of coatings of non-stick material, but argued that in the absence of evidence of the utility of such coatings in the field of extrusion machinery an inventive step of the claimed process could only be denied on the basis of hind-sight.
The Board did not consider this argument convincing, because the well-known versatility of non-stick coatings already implies the general utility in preventing smearing, including in extrusion machinery in which such smearing may obviously pose a problem when the extrudate is cut in the still molten state.
The Board therefore concludes that the subject-matter of claim 1 lacks an inventive step.
The patent was revoked.
Decision here
