API and IP Newsletter
Contents
- DMF filings in October 2024
- General information
- Patent Litigation Impacts on US Biosimilar Market Entry
- West Virginia AG Reaches $17M Settlement With Pfizer and Ranbaxy Over Antitrust and Consumer Protection Violation Claims
- Intellectual Property
- Bausch and Lomb Vs Sandoz AG
DMF filings in October 2024
FDA publishes a list of DMF filings every quarter. The 4th quarter (CY 24) list was published recently.
This month, we are analysing October 2024 DMF filings. Of the 78 DMFs filed that month, 35 were submitted by Chinese companies and 28 by Indian companies.
The top DMF filing companies are listed below:
Some of our other DMF-specific comments are as below.
General information
Patent Litigation Impacts on US Biosimilar Market Entry
1. Patent litigation reform could accelerate US biosimilar market entry, which lags behind the EU due to protracted legal processes.
2. Biosimilar manufacturers face options like pre-clearance, "at-risk" launches, and settlements, each with unique risks and benefits.
3. The Sandoz v. Amgen ruling aids biosimilar companies by not mandating pre-marketing licensing application sharing.
4. Early patent challenges during phase 3 trials could align biosimilar launches with patent expirations, reducing market entry delays.
5. Experts suggest a two-track system to facilitate earlier litigation, enhancing biosimilar market access and affordability.
News here
West Virginia AG Reaches $17M Settlement With Pfizer and Ranbaxy Over Antitrust and Consumer Protection Violation Claims
West Virginia Attorney General (AG) Patrick Morrisey announced a total $17 million settlement agreement with pharmaceutical companies, Pfizer and Ranbaxy after more than a decade of litigation regarding the companies’ alleged “pay-for-delay” antitrust violations related to the cholesterol drug, Lipitor.
News here
Intellectual Property
Bausch and Lomb Vs Sandoz AG
EP patent EP3470059 was granted based on a set of 15 claims. The patent was issued to Bausch and Lomb Inc. Sandoz AG filed the opposition.
The granted claim was as follows:
1. An ophthalmic suspension comprising an ophthalmic active ingredient suspended in a formulation vehicle, wherein the ophthalmic active ingredient is loteprednol etabonate (LE) and is present as particles that have Dv90 < 5 m and Dv50 < 1 m, and the formulation vehicle comprises polycarbophil as a suspending agent, hydroxypropylmethylcellulose as a non-ionic cellulose derivative, a poloxamer surfactant, glycerin, propylene glycol, and a borate buffer agent, and wherein the suspension is storage stable for at least one year."
The patent was opposed under Article 100 (a), (b), (c) EPC because its subject matter allegedly lacked an inventive step, was not sufficiently disclosed, and extended beyond the content of the application as filed.
The appeal is based on the opposition division's decision, which found that the amended patent meets the requirements of the EPC.
The documents cited during the opposition proceedings included the following:
In this write-up, we will discuss the inventive step.
The claimed invention relates to ophthalmic suspensions of loteprednol etabonate (LE) that are storage stable for at least one year. This means that the active agent will remain effectively suspended in the formation vehicle for this period of time without having to stir the packaged composition.
This applies in particular to suspensions comprising sub-micron particles of LE in polycarbophil, which are physically not stable and tend to aggregate over time, making it difficult or impossible to re-suspend the active ingredient, as would be needed for safe and effective administration to the eye.
Moreover, the formulation provides a gel that gradually transforms into a liquid when instilled in the eyes.
The opposition division considered D5 the closest state-of-the-art (Prior Art) since it shared the most features and disclosed a suspension formulation that inherently concerns suspension stability. It considered documents D2, D3, and D12 as less appropriate starting points for assessing inventive steps.
The respondent (the Patentee, Bausch and Lamb) shared the opinion of the opposition division regarding the choice of D5 as the closest prior-art.
The appellant Sandoz maintained that D2, D3 or D12 were equally promising starting points as D5.
Table 2 in the patent highlights that compositions comprising HPMC in a concentration between 0.05% and 0.25% show better size stability than those without a stabiliser or an alternative stabiliser.
A composition containing a very low concentration of 0.0006% HPMC has also been shown to be ineffective.
Therefore, this example appears to confirm HPMC's nucleation-inhibiting and size-stabilizing effect in the presence of polycarbophil polymer.
Example 4 compares various compositions containing LE, including polycarbophil, but all omitting HPMC. It demonstrates that micronized and sub-micronized compositions penetrated better into ocular tissues than the commercial product Lotemax, except for the tear fluid and bulbar conjunctiva, which are not considered target tissues.
Sandoz considered that the alleged effect has not been shown over the (whole) scope of claim 1, in particular, given examples 2 and Table 2 of the patent.
The patent teaches in the paragraph that only a specific grade of HPMC in a certain minimum amount produces a stable formulation, while claim 1 is not limited to such formulations.
Bausch and Lomb contended that it is implausible for all formulations included in claim 1 to demonstrate enhanced stability, regardless of whether the vehicle could be an oily one that is not excluded from the scope of claim 1.
In the Board's view, this argument is irrelevant to assessing the inventive step in the present case for the following reasons.
1. Claim 1 is constrained by a functional aspect of achieving a specific result, namely, "storage stable for at least one year," which must be considered. When an effect is not stated in a claim but is part of the problem to be addressed, it can lead to issues with inventive-step.
2. In the present case, however, the effect is part of the claim as the description provides guidance enabling the skilled person to ascertain how to obtain the desired stability.
3. In view of examples 2 and 4 of the patent, the existence of a technical effect has to be acknowledged. The problem, as defined by Bausch and Lomb, is the provision of an LE formulation with improved efficacy while maintaining storage stability.
4. The claimed solution is the presence of HPMC.
5. Sandoz AG mentioned documents D2, D3, D4, D12, D6, and D8 concerning the obviousness of the solution.
6. D5 does not provide the skilled person with the required teaching to solve the underlying objective technical problem. D5 only mentions HPMC as a test vehicle for a short-term preclinical study with LE, but it does not teach or suggest that it can be used in a composition with further excipients.
7. Documents D2, D3, or D12 do not provide any information regarding the excipients used in the formulations disclosed within them. They are particularly silent about the possible presence of polycarbophil and HPMC in the gel compositions. While these documents may suggest that submicron-sized particles could lead to improved efficiency, there is, however, no indication or guidance in these documents on how to enhance or maintain efficacy while ensuring storage stability.
8. D4 suggests that LE particles may be milled. Furthermore, it relates to a formulation that includes only LE, a surfactant, and water, and it does not provide the skilled person with either the motivation or the means to solve the objective technical problem.
9. HPMC is a known excipient for ophthalmic formulations, as shown in D8 (page 346). D8 discloses that HPMC can be added as a thickening agent to vehicles for eye drops. However, D8 does not relate to the improvement of therapeutic efficacy of ophthalmic active ingredients, let alone LE, or the stabilization of nanoparticulate suspensions. The only conclusion that can be drawn from D8 is that HPMC is a recognized excipient and may be used in ophthalmic preparations. The same is true, however, for other compounds, such as carboxymethylcellulose or povidone, which failed to adequately stabilize the inventive compositions (Table 2 of the patent). Consequently, D8 cannot render the claimed subject obvious matter.
10. D6 discusses cellulosic polymers as stabilisers, specifically to prevent Ostwald's ripening and agglomeration of nanosuspensions. HPMC is not explicitly mentioned; rather, D6 presents several alternatives for stabilisers, such as poloxamer, polysorbate, povidone, or specific lecithin. D6 does not indicate that HPMC is a suitable agent for stabilising the claimed composition, nor does it suggest an association of HPMC with polycarbophil.
As a result, the proposed solution is inventive over D5 in conjunction with any documents D2, D3, D12, D6, and D8. The patent was upheld.
Decision here
