API and IP Newsletter
Contents
Olutasidenib : FDA approval
Olutasidenib is approved in December 2022 by USFDA for the treatment of adults with relapsed or refractory acute myeloid leukaemia with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation. It is also being evaluated in a Phase I trial for glioma.
A preparation of olutasidenib as a lyophilized solid form is described in WO2016/044789. This could be considered as composition of matter patent.
Another patent family WO 2019222551 relates to crystalline form of Olutasidenib The step 5 in WO2019/222551A1 describes the process.
US equivalents of these families could be listed in Orange Book, and there could be an advantage in developing a novel polymorph of Olutasidenib to explore early launch opportunities in many countries.
Synthesis of Olutasidenib starts from 5-fluoropicolinonitrile. This is common chemical, must be available locally and there are not many relevant entries in import export database which could hint which Indian companies are working to develop API. However, some entries for import of 5-fluoropicolinonitrile by Jubilant Chemsys and GVK could be interesting to note.
General information
Pharma MSMEs oppose compulsory QR code on all APIs
The MSMEs have now appealed to the government to suitably amend it to make QR code mandatory only for imported APIs to prevent the menace of spurious or substandard APIs in the country.
According to the new sub-rule, every active pharmaceutical ingredient (bulk drug) manufactured or imported in India shall bear Quick Response code on its label at each level packaging that store-data or information readable with software application to facilitate tracking and tracing.
News here.
An Overview of Emerging Technologies within the Pharmaceutical Industry
The modern pharmaceutical industry along with the healthcare industry is undergoing a significant modification and quick change due to the advancement of numerous technologies. Among the critical pharma business trends are artificial intelligence (AI), data analytics, system biotechnology, and curative medicines. Increased investments, the expansion of technological startups, the expiration of multiple significant patents, increased interorganizational partnerships, and a favourable regulatory environment are all fueling pharmaceutical industry innovation. As a result, as technology breakthroughs and innovation continue to lead the way, the pharmaceutical industry is likely to see even faster development and transitions in order to fulfil expanding healthcare
News here.
Intellectual Property
T 0814/19 Olaparib solid dispersion/KUDOS 19.10.2022- Decision by the Appeal Board at EPO
This is about EP 2346495, issued to Kudos Pharmaceuticals Limited (AstraZeneca Company). This patent was upheld at the first instance. At the first instance, the opposition division opined the patent met the requirements of the EPC.
Teva challenged.
The claim 1 as granted. It read as follows:
"1. A pharmaceutical formulation comprising an active agent in solid dispersion with a matrix polymer, wherein the active agent is olaparib or a salt or solvate thereof, and the matrix polymer exhibits low hygroscopicity and high softening temperature."
The patent had been opposed on the grounds of added subject-matter and lack of inventive step. Let us briefly discuss inventive step.
The prior art documents cited
D2: C. Leuner et at., Eur. J. Pharm. Biopharm., 2000(50), 47-60
D3: US 4,801,460
D5: WO 2008/047082
Objective Technical Problem
The board agreed with Kudos Pharmaceuticals that the objective technical problem is the provision of an olaparib formulation suitable as a pharmaceutical dosage form for administration to patients.
Teva argued that D5 implicitly discloses that olaparib has a low solubility in water. This can be derived from the molecular structure of olaparib and the fact that olaparib was recrystallised from water, water/methanol and water/ethanol
According to Kudos this implicit disclosure is only qualitative; a low solubility in water cannot be equated with an insufficient bioavailability for administration in a conventional dosage form.
In fact, the inventors of D5 suggested formulating olaparib in a conventional form, even though they knew that it had a low solubility in water.
The patent disclosed for the first time that olaparib was not sufficiently bioavailable when administered in a conventional form such as an immediate release tablet.
This was also the case for the finding that the therapeutic dose of olaparib was high, and therefore required formulations having high drug loadings which could raise stability issues.
The main matter of dispute between the parties was whether the formulation of claim 1 stabilises olaparib at any weight ratio of olaparib:matrix polymer, especially at high drug loadings. On this point, Teva referred to the stability results shown in Tables 6 and 12 of D5.
The board said,
The essential point is that, on the filing date of the patent, the skilled person did not know that olaparib was particularly difficult to formulate because it required high drug loadings and presented bioavailability and stability issues.
The skilled person would have formulated olaparib in any of the conventional formulations suggested on pages 18 and 19 of D5, rather than as a solid dispersion.
The skilled person had no motivation to turn to D2 or D3, which are concerned with the issue of improving the bioavailability of sparingly soluble drugs.
Firstly, they (Skilled persons) were not aware of any bioavailability issues in relation to olaparib and believed that conventional formulations were suitable for administration to patients.
Secondly, even if they wished to improve the bioavailability of olaparib and decided to formulate it as a solid dispersion, they would have observed stability issues for which D2 or D3 do not provide any guidance.
D2 even recognises that there is still a need for better prediction of whether a particular drug/carrier combination will lead to a true solution or a partly crystalline dispersion, and whether the dispersion will remain physically stable.
The patent shows that the selection of matrix polymers of claim 1 is particularly suited to addressing this issue for the specific case of olaparib. Therefore, the skilled person would not have arrived at the solid dispersion of claim 1 without the knowledge made available in the patent.
Therefore, the board concludes that the subject-matter of the main request involves an inventive step, as required by Article 56 EPC.
Decision here
