API and IP Newsletter
Contents
Patent applications filed by Suven Life Sciences
We analyse patent filings by many Indian companies. This week analysed patent portfolio of Suven Life Sciences for last 2-3 years. Most of the applications are filed for their proprietary molecules, which are in different stages of clinical studies. Here.
From IP portfolio, it seems masupirdine and abiraterone acetate/derivatives are the most interesting candidates.
General information
Piramal upgrading UK sites
Indian-based CDMO Piramal Pharma Solutions (PPS) is to invest about £55 million to expand two sites in the UK. It will expand its antibody-drug conjugate (ADC) capabilities at Grangemouth in Scotland and new API infrastructure at Morpeth in north-east England
News here.
Molnupiravir supplies dominate in times of Paxlovid scarcity
Despite the early and sustained enthusiasm for Pfizer’s oral antiviral Paxlovid, lagging supply has meant that most places in the US have higher demand than availability for the drug, as per an analysis of antiviral allocations.
Data gleaned from the US Department of Health and Human Services (HHS) indicates most states that experienced a surge in cases due to the Omicron variant have been heavily reliant on the antiviral molnupiravir, while supplies of Pfizer’s Paxlovid and GlaxoSmithKline and Vir Biotechnology’s monoclonal antibody (mAb) Xevudy (sotrovimab) trickle by.
News here.
Intellectual Property
T 1131/18 (Combination of Pimobendan and Benazepril/ ELANCO) of 19.10.2021
FORTEKOR PLUS is a new product which contains two previously authorised substances (benazepril, and pimobendan) for the treatment of congestive heart failure due to atrioventricular valve insufficiency or dilated cardiomyopathy in dogs.
EP 2793866 was granted on the basis of a set of 13 claims. Patent was issued to Elanco Tiergesundheit AG (Elanco)
Independent claim 1 as granted read as follows:
"1. A fixed dose combination comprising benazepril hydrochloride and pimobendan in a ratio of 2 : 1, in form of a bilayer tablet, wherein the benazepril layer comprises 2.5, 5 or 10 mg benazepril hydrochloride which are contained in the form of pellets, and wherein the pimobendan layer comprises 1.25, 2.5 or 5 mg pimobendan."
An opposition was filed by Boehringer Ingelheim Vetmedica GmbH (BI) under the grounds that the subject-matter of the granted patent lacked novelty and inventive step, was not sufficiently disclosed, and extended beyond the content of the application as filed.
The present appeal lies from the decision of the opposition division that the patent in amended form met the requirements of the EPC.
In this write-up we will study inventive step discussion at second instance at EPO.
The first step in any opposition is to decide the closest prior art.
The opposition division considered D5 (O'Grady M. et al., J. Vet. Intern. Ned., 2008, 22, 897-904) as the closest prior art compared to D8 (WO 2011/111066) which was the choice of BI.
The difference between the claimed subject-matter and D5 was the fixed dose combination in form of a bilayer tablet and benazepril HCl being comprised in the form of pellets.
Patentee Elanco argued, the technical effect was a more convenient administration and better compliance in dogs. The problem was the provision of a stable solid dosage form comprised a fixed dose combination comprising pimobendane and benazepril HCl for the treatment of congestive heart failure in dogs showing improved compliance. The claimed solution was inventive.
During oral proceedings, BI considered D5 to be the closest prior art.
BI said, the distinguishing features between the claimed subject-matter and D5 were the bilayer tablet, the presence of pellets and the exact doses of the active agents. No technical effect could be attributed to the use of pellets and thus this feature could not be taken into account for assessing inventive step. Furthermore, there was no evidence in the opposed patent that a bilayer tablet is better than any other dosage form, in which benazepril and pimobendan are spatially separated. BI alleged, the problem was mere provision of an alternative dosage form. The skilled person had a strong incentive to provide both active ingredients in a combination product for convenient and regular administration. The skilled person was aware of the stability and incompatibility problems of benazepril and pimobendan. He was also aware of numerous advantages of bilayer tablets. Therefore, the granted claim of the opposed patent was obvious in view of document D5 and common general knowledge.
In short,
BI defined the problem to be solved as the provision of an alternative composition comprising benazepril and pimobedan.
Elanco defined the problem as the provision of a stable solid dosage form comprising a fixed dose combination comprising pimobendan and benazepril HCl.
The opposition division in its decision (1st instance) defined the problem to be solved as the provision of a stable solid dosage form comprising a fixed dose combination comprising pimobendane and benazepril HCl for the treatment of congestive heart failure in dogs showing improved compliance.
Analysis of the Board
D5 discloses the oral and separate administration of pimobendan (0.25 mg/kg), benazepril HCl (0.5 mg/kg) and furosemide in dogs for the treatment of congestive heart failure.
The dose ratio between pimobendan and benazepril is 1:2 (see Materials and Methods). This document does neither disclose bilayer tablets, nor the precise claimed dosages, nor the presence of pellets.
D5 does also not mention a possible interaction between pimobendan and benazepril.
Other prior art documents relied by BI relate to dosage forms of amlodipine and benazepril such as bilayer tablets
D8 relates to the treatment of conditions associated with hyperglycemia or hypertriglyceridemia by an association between a) an inhibitor of phosphodiesterase 3 and b) an inhibitor of angiotensin receptor activity.
Consequently, the disclosure of D8 is technically remote from the claimed subject-matter and does not relate to the same technical problem
So, the Board did not find any reason to deviate from the decision of the opposition division as regards the choice of the closest prior art, which is document D5.
The Board stated, examples 1 and 2 of the patent show a comparison between a monolayer tablet comprising pimobedan and pellets of benazepril and a bilayer tablet comprising respectively pimobedan and pellets of benazepril in each separate layer.
Further, as shown by the examples, the presence of pimobedan and pellets of benazepril in the same monolayer tablet results in a greater level of the benazepril hydrolytic degradation product "Impurity C" in comparison to the situation in which the two ingredients are in separated layers.
Moreover, the experimental results of examples 1, 2 and 3 show that the stability is reached for a large palette of weight ratios of pimobendan and benazepril, which invalidates the BI’s argument that it was not shown.
The Board agrees with the opposition division that the combination of two active agents in one single dosage form enables a more convenient administration and better compliance in dogs.
Accordingly, the technical problem is as it was defined by the opposition division or the BI, i.e. the provision of a stable solid dosage form comprising a fixed dose combination comprising pimobendane and benazepril HCl for the treatment of congestive heart failure in dogs showing improved compliance.
So Board defined what is the closest prior art and what is the technical problem solved by the invention.
It remains to determine whether the claimed solution was obvious.
Board said, there is no suggestion or guidance in D5 to prepare a combined medication comprising pimobedan and benazepril.
There is furthermore no mention in D5 of a possible instability when both drugs are combined together and the skilled person would not have any reason to prepare a combined dosage form separating both drugs, even less with pellets of benazepril.
None of the other documents cited by BI shows furthermore the preparation of a bilayer tablet with benazepril, or a tablet combining pellets of benazepril with another active compound.
Consequently, the Board opined, the claimed solution is not obvious.
Patent was upheld.
Decision here.
