Drug In Focus November 2010

John Wong joined GenericsWeb in March 2010 as a patent searcher and analyst. John has completed several university degrees, including a BE in Chemical Engineering, a Masters in Commerce (major in Information Systems) and a Masters in Intellectual Property. He has been working in the pharmaceutical industry for 15 years and his current interests is in the patent searching area.

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Drug In Focus: Fosaprepitant

Fosaprepitant is a selective Neurokinin-1 (NK-1) receptor antagonist and substance P inhibitor and is used as an anti-emetic agent marketed under the brand name Emend. Available as a powder for injection, Fosaprepitant is a prodrug of the active ingredient Aprepitant found in the oral dosage form sharing the same brand name. Sales of Emend exceeded US$300 million in 2009 and continued with double digit growth in 2010.

This month’s Drug In Focus analyses the patent landscape surrounding Fosaprepitant based on information contained in the corresponding Pipeline Selector report prepared by GenericsWeb.

The Fosaprepitant General Information (Table 1) shows that this product is available as the active dimeglumine form at a strength of 115 mg, and is indicated for the prevention of chemotherapy induced nausea and vomiting (CINV), alone or in combination with other antiemetic medicines.

Table 1: Fosaprepitant General Information

Table 2: Fosaprepitant Key Patent Indicator

The Fosaprepitant Key Patent Indicator (Table 2) identifies two patent families having significant commercial relevance to the marketed product.

The first patent family relates to the general use of a NK-1 receptor antagonist for the treatment of emesis, and therefore encompasses both the Aprepitant and Fosaprepitant products. Although the granted EP0533280 originally claimed “the use of NK-1 antagonists in the preparation of a medicament for use in the treatment of emesis” this was amended to encompass only specific antagonists following opposition. In the US, two of the issued patents protect the use of tachykinin antagonists for the treatment of emesis and are listed in the Orange Book Patents. This family will mostly expire in September 2012 with the exception of US5538982 (one of the Orange Book listed patents) which is due to expire in July 2013, and will protect the Emend product from the launch of any generic equivalent until such time.

Although the Litigation Alerts appearing next to US5538982 and US7214692 identify some litigation in regard to these patents, they are related to a Sandoz ANDA with paragraph IV filing for Aprepitant. The outcome of this litigation is not likely to affect the opportunity for generic launch of Fosaprepitant as this product is further protected by the second identified key patent family claiming the Fosaprepitant active ingredient per se. In Europe the patent term has been extended to February 2020 through SPC extensions in France and Great Britain, with extension applications pending in the Germany and Spain. Likewise in Australia an extension of the patent term is granted. The patent term extension of US5691336 is pending in the US and, if approved, would extend the monopoly over the Fosaprepitant molecule to March 2019.

As there is no patent extension scheme in Canada, the molecule patent will expire in February 2015. However, the availability of data and market exclusivity in Canada will provide protection of Fosaprepitant until April 2017. Therefore in Canada there is no opportunity to launch a generic equivalent until this date. In most other countries the data and market exclusivity will expire before patent expiry thus will not affect the date of generic competition. However, it is interesting to note that although Fosaprepitant is described as a pro-drug of Aprepitant, it is considered (at least by the FDA) as a New Chemical Entity and is therefore entitled to five years NCE exclusivity.

Figure 1: Fosaprepitant Patent Category Distribution

Study of the Fosaprepitant Patent Category Distribution diagram (Figure 1) based on comprehensive patent searching indicates that patenting activity relating to this drug is heavily focused on the use and preparation of the active ingredient, with over two thirds of the total patent families falling into these two categories. This indicates that attention should be paid to identifying and evaluating these patents to ensure that any generic product doesn't infringe later expiring patents at the time of commercialisation.

Figure 2: Fosaprepitant Top Patent Applicants

The Fosaprepitant Top Patent Applicants chart above shows that Merck has filed nearly a third of the total patents - over half of which relate to processes and formulations. This suggests that Merck is managing the lifecycle of the product and has made some attempt to protect incremental advances in the technology within it. It is worth noting that many of the patents may overlap with Aprepitant, which may be the focus of this lifecycle management, but it should not be assumed that such patents do not protect Fosaprepitant in some way.

In conclusion, it appears that Merck has undertaken a significant effort in protecting the intellectual property surrounding Fosaprepitant. Patent protection is very much alive in AU, US and Europe, with data exclusivity being the constraining factor in CA. In order to enter the market successfully, generic companies would need to design around the existing patent barriers and, more importantly, diligently keep themselves informed of the ongoing patent situation surrounding not just Fosaprepitant, but Aprepitant as well, especially in area of patent litigation.

This raises the question: would I need patent information now if the expiry of the molecule patent is going to be 10 years down the line? The patent landscape of a drug is influenced by many factors, for example, government regulations and policies, innovator’s activities and fellow generics competitors’ activities such as patent filings etc. As a generics drug developer, it is imperative that it arms itself with comprehensive information that enables it to make the best informed business decisions. In a market as fierce and competitive as that of generics pharmaceuticals, keeping yourself ahead of the competition is absolutely essential.

Comprehensive data for patent families relating to Fosaprepitant, based on professional patent searching, may be accessed by subscribing to GenericsWeb Pipeline Developer reports which include twelve monthly updates to keep you abreast of recently published patents and applications. GenericsWeb Pipeline Selector reports are available for any active ingredient upon request.

Please visit www.GenericsWeb.com to find our more about Pipeline Patent Intelligence and how it can assist your generic drug development. Register to receive our monthly newsletter INNsight, and a GenericsWeb staff member will call you to discuss your needs.

John Wong
Patent Analyst
GenericsWeb
November 2010
j.wong@genericsweb.com

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