API and IP Newsletter
Contents
How One Biotech Is Using FDA 505(b)(2) To Get Drugs To Patients Quicker And Cheaper
Pathways for non-manufacturers to drive generic drug repurposing for cancer in the U.S.
FDA approvals in September 2024: ANDAs
We follow ANDA approvals every month.
In September 2024, there were 76 ANDA approvals, of which 11 were tentative.
Top companies who sought ANDA approvals in September are as below
Some other comments about a few approved ANDAs:
General information
How One Biotech Is Using FDA 505(b)(2) To Get Drugs To Patients Quicker And Cheaper
Terran Biosciences has been patiently awaiting the FDA approval of Bristol Meyers Squibb’s Cobnefy (xanomeline and trospium chloride), the first new drug to treat schizophrenia in more than 30 years . And when the FDA gave it the OK, Terran was one of the first to celebrate.
It might sound strange that a biotech would applaud the approval of a lead asset by Big Pharma, but the approval means Terran can now forge ahead with a 505(b)(2) for its own therapy, TerXT.
News here
Pathways for non-manufacturers to drive generic drug repurposing for cancer in the U.S.
Patients need new and affordable treatment options for diseases like cancer that have a devastating societal impact, and repurposing generic drugs can help address this need. Due to a lack of interest from pharmaceutical companies, nonprofits and other non-manufacturers are driving these efforts forward. Yet it is difficult for non-manufacturers to seek FDA approval, so off-label prescribing can be an effective strategy for new uses for generic drugs to be adopted into the standard of care in oncology.
News here
Intellectual Property
T 1975/19 (Travoprost composition / ALCON)
Two oppositions were filed against EP 2 599 475 because its subject matter lacked an inventive step, was not sufficiently disclosed, and extended beyond the content of the (earlier) application as filed. The patent was issued to Alcon Research, Ltd.
The grounds for the lack of novelty were mentioned but needed to be substantiated.
In this write-up, we will discuss only inventive step/obviousness.
The appeals were filed by Alfred E. Tiefenbacher and Generics [UK] Limited /Mylan.
Claim 1 of the patent as granted reads as follows:
"An aqueous ophthalmic pharmaceutical composition, comprising:
a pharmaceutical vehicle suitable for topical application to an eye of a human;
travoprost;
a polymeric quaternary ammonium compound as preservative;
one or more polyols selected from mannitol, glycerin, xylitol, sorbitol and propylene glycol; and
a surfactant wherein the surfactant is ethoxylated and hydrogenated castor oil at a concentration in the composition of less than 0.3 w/v %, wherein
i. the ethoxylated and hydrogenated castor oil surfactant is entirely or substantially entirely the only surfactant in the composition; and
ii. the composition is free of any benzalkonium chloride."
The following documents were cited in the appealed decision:
The opposition division at the first instance decided the following:
The ground for opposition to the lack of novelty raised by Tiefenbacher had to be substantiated and was disregarded.
The subject matter of the main request only extended to the content of the application as filed or the earlier application as filed.
The criteria of sufficiency of disclosure were met.
Regarding the inventive step, starting from D26 as the closest prior art, the differentiating features were the surfactant concentration of less than 0.3 w/v% and the presence of polymeric quaternary ammonium compounds (PQAC) in the absence of benzalkonium chloride (BAC).
The technical problem was providing a stable, preserved aqueous ophthalmic composition of travoprost that is free from BAC but has improved bioavailability. The claimed solution involved an inventive step.
Alternatively, starting from D2 or D1 as the closest prior art, the claimed compositions differed by the PQAC, the absence of BAC, and the hydrogenated surfactant. The technical problem was providing an aqueous ophthalmic composition with improved bioavailability of travoprost. The claimed solution involved an inventive step.
The patent was upheld at the first instance. Tiefenbacher and Mylan appealed to the Board of Appeals.
The appellants (Tiefenbacher and Mylan ) had filed a few other documents in the appeal proceedings D50-D52 and D81, contested the validity of the priority for lack of entitlement, and raised objections of lack of novelty over D81 and lack of inventive step in view of D51.
Since this write-up is related to the inventive step, we are not providing the list of additional documents added to the appeal proceedings. However, the list is on pages 3 and 4 here.
Articles 100(a) and 56 EPC, inventive step
According to the patent, the invention relates to ophthalmic compositions with relatively low surfactant concentrations that promote the bioavailability of a therapeutic agent (e.g., travoprost).
The patent further indicates that the use of the amounts of surfactant specified herein can increase bioavailability in a manner that can at least partially or substantially entirely offset losses in bioavailability that may occur when benzalkonium chloride (BAC) or other such ingredients are not present.
As a possible objective, achieving the desired degree of stability is mentioned.
During the appeal proceedings, the appellants (Tiefenbacher and Mylan) contested that the claimed subject matter does not involve an inventive step starting from the Travantan -Z composition of D26, from example 2 of D2, or from example 5 of D1.
In this write-up, we will note the Board of Appeals' observations about inventive steps based on all three prior art documents cited by the appellants.
Starting from D26 / Travatan -Z
D26 discloses Travatan -Z, a BAC-free travoprost-containing ophthalmic formulation. D26 addresses the need to avoid BAC due to its ocular toxicity and the resulting loss in bioavailability compared to the BAC-containing product Travatan.
Travatan -Z contains travoprost, the surfactant polyoxyl 40 hydrogenated castor oil (HCO-40), propylene glycol, sorbitol, and boric acid. The parties agreed that the concentration of HCO-40 in the known Travatan -Z formulation is 0.5 w/v%.
The board of appeals agreed to the following distinguishing features starting from D26.
(i) the surfactant concentration is less than 0.3 w/v% and
(ii) the composition contains a polymeric quaternary ammonium compound (PQAC) as a preservative.
Technical problem and obviousness:
Considering the effect of the claimed surfactant amounts on bioavailability, the technical problem is providing an aqueous ophthalmic composition of travoprost, which is free from BAC but has improved ocular bioavailability.
The patentee Alcon submitted data of various formulations.
The Board of Appeals was satisfied with this comparison. The board said that these comparisons with a modified variant of the prior art D26 convincingly demonstrate that the effect on bioavailability originates from the distinguishing feature of surfactant amount.
Starting from Example 2 of D2
Example 5 of D2 shows compositions comprising travoprost, BAC, as well as 0.2 w/v % HCO-40 and 0.05 w/v % N-lauroylsarcosine as surfactants
The Board said that the appellants' (Tiefenbacher and Mylan ) objection would assume that the skilled person starts from the formulation of Example 2 of D2, despite this formulation being the least stable composition of D2. The board found this could be unlikely.
The board further questioned why the skilled person might modify this formulation by removing BAC despite the prior art's expectation that such a modification would be detrimental to travoprost bioavailability.
Travatan BAC-free formulation (Travatan Z) provided lower intraocular concentrations and AUC values than Travatan. This disadvantage is observed in vivo in D26
Accordingly, the skilled person seeking to provide a travoprost formulation with adequate bioavailability and stability would not arrive at the claimed subject matter starting from D2 in an obvious manner.
The Board said that the appellants' objection needs to be more convincing.
Starting from D1
D1 relates to sulfonated styrene/maleic anhydride copolymers, which enhance the preservation of ophthalmic compositions containing the cationic drug travoprost. These copolymers are additionally present in some examples.
D1, like D2, is silent about travoprost bioavailability. As with D2, example 5 of D1 does not disclose the absence of BAC and the presence of PQAC. In example 5 of D1, the ethoxylated and hydrogenated castor oil surfactant is not entirely or substantially the only surfactant in the composition.
The Board of Appeals said the assessment of inventive steps starting from D1 is analogous to D2, so the same conclusion applies.
Accordingly, the criteria of the inventive step are met. The patent was upheld.
Decision here
