P-IV filings in the recent past and an interesting case LG Chem Vs Evonik Operations GmbH

Contents

P-IV filings in the recent past

General information

Lisata collaborates with GATC Health on drug development

China proposes shorter clinical trial reviews in efforts to accelerate drug development

Intellectual Property

LG Chem Vs Evonik Operations GmbH

P-IV filings in the recent past

We follow P-IV filings by generic companies. The FDA published the list on June 9, 2025, and according to the information, a new ANDA was filed on April 22, 2025.

Honour Labs and MSN filed DMFs in 2021 for remdesivir, and MSN may have submitted an ANDA on the NCE-1 date. Alternatively, it is possible that the ANDA filer utilised one of these DMFs in its ANDA submissions. Remdesivir, marketed as Veklury, received FDA approval for treating COVID-19 in adults and certain pediatric patients requiring hospitalisation. It was the first COVID-19 treatment to receive full FDA approval. This product was a top seller for Gilead during the pandemic; however, remdesivir sales are not expected to return to peak pandemic levels. Current sales information is not available in the public domain. However, according to the company’s guidance for 2024, total Veklury sales are projected to be approximately $1.3 billion. The Orange Book lists many patents, and an ANDA filer must have certified against these patents. The compound is generically protected (Markush Claim) until 2030, while the specific compound claim is safeguarded until April 2036. Currently, it seems that launching generics before 2036 may be challenging.

General information

Lisata collaborates with GATC Health on drug development

Lisata Therapeutics has formed a strategic partnership with GATC Health to advance AI-driven drug discovery and development. The collaboration aims to expedite and enhance the success rates of traditional processes involved in drug development. Lisata will utilise GATC’s Multiomics Advanced Technology (MAT) platform that leverages AI to predict combination therapies that may include Lisata’s certepetide drug candidate. News here

China proposes shorter clinical trial reviews in efforts to accelerate drug development

China, already gaining speed in biotechnology, is looking to further accelerate novel drug development by reducing the time regulators take to review clinical trials. In a draft policy posted (Chinese) Monday, China’s National Medical Products Administration (NMPA) is proposing to cut the clinical trial review waiting period for novel medicines to 30 working days down from the current 60 working days. News here

Intellectual Property

LG Chem Vs Evonik Operations GmbH

Overview This write-up presents the decision of the Technical Board of Appeal regarding European Patent EP 3395792, concerning a method for producing methyl tert-butyl ether (MTBE).

Evonik Operations GmbH (the opponent) appealed the Opposition Division's decision to maintain the patent in an amended form. The patent proprietor is LG Chem, Ltd. The core issue revolves around the inventive step of the claimed method, specifically concerning the reactor size and recycle ratio in the MTBE production process. The Board of Appeal ultimately dismisses the appeal, upholding the patent as maintained by the Opposition Division. Background The patent in question describes a method for producing MTBE, a fuel additive, through the reaction of iso-butene-type olefins with methanol. A key aspect of the invention addresses high energy consumption, which results from the necessity of using a distillation column at the reactor's rear end. The patent specification suggests that reducing unreacted iso-butene and impurities can lower thermal energy consumption. The main claim focuses on a method involving a reaction step and a purification step, where the flow ratio of recycle to fresh feed is linked to the reactor size. The opponent filed an appeal based on two main grounds: • The amended claim lacks a basis in the original application (Article 123(2) EPC). • The claimed method lacks an inventive step (Article 56 EPC). The opponent Evonik Operations GmbH argued that limiting the reactor size to greater than 30 m³ had no basis in the application and that the claimed method was obvious in light of prior art, specifically document D1. Claim: A method of preparing methyl tert-butyl ether, the method comprising:

a reaction step of reacting methanol with iso-butene in presence of an acid catalyst to generate methyl tert-butyl ether; and

a purification step of purify the reaction product obtained by the reaction step by introducing the reaction product into a reaction distillation column comprising a packing stage containing an acid catalyst,

wherein the reaction step is performed in a first reaction part comprising one reactor or two or more reactors connected in parallel; and in a second reaction part comprising one or more reactors connected in series to the first reaction part,

wherein a portion of a reaction product discharged from the first reaction part is recycled in the first reaction part, wherein a flow ratio of a recycle to a fresh feed is greater than 0.9 and less than 1.7 when a total volume of the one or more reactors comprised in the first reaction part is 30 m3 or less, a flow ratio of a recycle to a fresh feed is greater than 2.2 and less than 4.8 when a total volume of the one or more reactors comprised in the first reaction part is greater than 30 m3 and 60 m3 or less, and a flow ratio of a recycle to a fresh feed is greater than 3.1 and less than 9.8 when a total volume of the one or more reactors comprised in the first reaction part is greater than 60 m3.

Prior art cited during the proceedings.

Arguments and Evidence

Appellant’s (Opponent’s ie Evonik Operations GmbH) Arguments:

1. The amended claim, including the feature of a reactor size greater than 30 m³, lacked basis in the original application. The core of the invention didn't relate to a process where the reactor volume was limited to more than 30 m³.
2. The aim of the invention was to reduce thermal energy in the distillation step, but this wasn't achieved by restricting reactor size. Instead, energetic input was reduced by limiting unreacted isobutene, not by increasing reactor volume.
3. The objective technical problem solved by the invention was merely providing an alternative method, making the selection of reactor size obvious to a skilled person.
4. The technical effect (reduced energy consumption) was not caused by the reactor size alone but by the recycle-to-feed ratio. The ASPEN simulations suggested the reaction was dependent on temperature, which was not accounted for in the contested patent.

Respondent’s (Patent Proprietor’s ie LG Chem) Arguments:

1. The amended claim found a basis in the application, disclosing the use of reactor(s) in the MTBE preparation reaction step. The application disclosed three different reactor size ranges with corresponding flow ratios.
2. The limitation of reactor volume to more than 30 m³ didn't conflict with thermal energy savings. Preferred reactor sizes of 25 m³ were disclosed, but embodiments with more than one reactor in the first reaction part also existed.
3. The amended claim was a result of limiting the original claim, retaining two of the three methods disclosed.
4. The combination of a specific reactor size with a selected flow ratio reduced thermal energy use. The prior art didn't suggest such a combination to improve thermal energy use.

Board's Reasoning Admissibility and Amendments: 1. The Board found the appeal admissible. 2. The Board determined that amended claim 1 met the requirements of Article 123(2) EPC (amendments). The claim had been amended by removing the option of a flow ratio of 0.9-1.7 when the reactor volume was 30 m³ or less, and by adding the feature of a reactor volume greater than 30 m³. The Board concluded that the claim had been limited to two of the original three options and thus was based on the application as filed. Inventive Step:

• The Board identified document D1 as the closest prior art, relating to the production of MTBE from isobutylene.
• The Board agreed that the contested method differed from D1 in the reactor size (greater than 30 m³) and the use of a reaction distillation column.
• The Board acknowledged that the experimental results in the contested patent showed that a method using a reactor size and flow rate according to the claim required less thermal energy compared to a method with a smaller reactor size or a combination not according to the claim.
• The Board disagreed with the appellant's (Evonic) argument that the difference was solely due to the reactor size. The comparison within table 1 showed that a different reactor size in combination with a corresponding flow rate led to a difference in energy used.

• The Board stated that they were not convinced by the appellant's conclusion of the contested document based on figure 2 of document D6. The Board noted, however, that the argument that the technical effect was caused by the differing feature identified above was not refuted.
• The Board concluded that the objective technical problem was to provide an improved method for MTBE preparation with reduced thermal energy consumption.
• The Board determined that D1 didn't disclose or suggest that low thermal energy use could be achieved when selecting the reactor size depending on the recycle ratio.
• The Board was satisfied that the claimed method solved the technical problem and wasn't obvious to a person skilled in the art.
• The Board concluded that the objective technical problem was to provide an improved method for MTBE preparation with reduced thermal energy consumption.
• The Board determined that D1 didn't disclose or suggest that low thermal energy use could be achieved when selecting the reactor size depending on the recycle ratio.
• The Board was satisfied that the claimed method solved the technical problem and wasn't obvious to a person skilled in the art.

Decision The Board dismissed the appeal, concluding that claim 1 of the main request met the requirements of Article 56 EPC (inventive step). It decided that the appellant's arguments did not prejudice maintaining the patent as maintained by the Opposition Division. Key Takeaways

1. The decision highlights the importance of linking specific process parameters (reactor size and recycle ratio) to achieve a technical effect (reduced thermal energy consumption) in a chemical process.
2. The Board emphasised that while other factors may influence the energy consumption, the identified differentiating feature led to demonstrable technical effects.
3. The Board's analysis was based on a detailed review of the experimental evidence and a comparison with the closest prior art.
4. The decision provides a clear framework for assessing inventive step in chemical process patents.

Decision here