|
Dae Oh joined Genericsweb in August 2006 as a patent searcher/analyst to provide quality patent information for generic pharmaceutical companies. Before joining Genericsweb, Dae worked as a Korean patent attorney specialised in biotechnology and biochemistry for Zenith Patent & Law Firm in Korea, drafting patent specification and investigating registration possibility of patents. Dae’s educational background is in microbiology, plant pathology, biotechnology and natural product chemistry. During his Master of agricultural biotechnology in Seoul National University, he researched new molecules isolated from fungal metabolites and new genes related to producing fungal toxins. |
 |
Drug In Focus: Topiramate
The active ingredient Topiramate (Topamax) produced by Ortho-McNeil, a division of Johnson & Johnson, will lose patent protection in some major territories in the near future.
A new indication, the prophylaxis of migraine headache, approved in 2004 and a significant growth in sales in the US despite current economic downturn, suggests that Topamax is likely to attract the attention of generic manufacturers around the world.
Based on information contained in the GenericsWeb Pipeline Selector report for Topiramate, this month’s Drug In Focus analyses the patent landscape surrounding the Topamax product with a view to launching generic equivalents.
The Topiramate General Information (Table 1) indicates that, at present, only two oral dosage forms of Topiramate are available in the form of tablets and sprinkle capsules. Currently approved indications generally include the treatment of seizures and prophylaxis of migraine headache.
Table 1: Topiramate General Information
The Key Patent Indicator (Table 2) for Topiramate confirms that the patent protecting the Topiramate active ingredient expires in the US September 2008, whilst the equivalent patent in Australia, Germany and the UK has been extended until September 2009. Generic competitors should be aware that US FDA has recently granted paediatric exclusivity for Topamax regarding partial onset seizures, extending the exclusivity of the patent protecting the active ingredient by six months until March 2009.
Due to an absence of pharmaceutical patent extension provisions in Canada, the patent protecting the active ingredient has already expired there in September 2005, providing a convenient ‘springboard’ for Canadian manufacturers who ultimately want to enter the US market.
Table 2: Topiramate Key Patent Indicator
The Regulatory Data demonstrates that data exclusivity has expired in all major territories with the exception of orphan drug exclusivity on the Lennox-Gastaut syndrome related seizures in the US however this will expire on 28 August 2008 prior to the active ingredient patent protection.
Table 3: Topiramate First Marketing Authorisation Dates
The marketing authorisation data for Canada and Australia shows a large number of companies already holding approvals for generic versions of this product. It is also clear from the DMF filings that a number of generic API manufacturers are interested in supplying API for generic products to be launched in the US market, this is confirmed by the number of tentative approvals granted for generic versions this product in the US as mentioned in the indexed news articles.
Interestingly, it can also be seen from the data that Mylan and Cobalt submitted a paragraph IV certification according to the recent legal challenge against the innovator. However, the validity of the patent protecting Topamax active ingredient was confirmed upon the challenge by Mylan in the US District Court for the District of New Jersey in 2007. Cobalt, which Ortho-McNeil sued in 2005, agreed to be bound by the decision. Even though the FDA has approved Mylan’s generic product as the first filer, the Appeals Court for the Federal Circuit dismissed their appeal and injuncted them from selling the product until expiry of the active ingredient patent, according to the News articles indexed in the Pipeline Selector report.
In addition to the molecule patent family, two other constraining patent families have been identified by the Key Patent Indicator relating to indicated use and formulations. These claims in the patent family clearly protect the approved indication for prophylaxis of migraine headache till October 2015 in the US, whilst the indication for treatment of seizures was disclosed in the active ingredient patent and will become public domain upon its expiry in the US, September 2008. Interestingly, there are no equivalent granted patents for the indication of prophylaxis of migraine headache observed outside of the US. This may present opportunities in launching generics with all approved indications in some countries much earlier than in the US.
With regard to the patent family protecting the formulation, the claims only protect a taste masked form of Topiramate particles for oral administration till March 2019. It might appear that circumventing the patent would not be difficult for generics competitors. Indeed, according to the information accessed by subscribing to the GenericsWeb Pipeline Developer report, quite a few of other oral formulations as well as general formulations are already protected by patent filings. Interestingly, topical formulations, which are not uncommon in other anti-migraine drugs, have not been observed.
These analyses suggest that Ortho-Mcneil have made some attempt to extend the lifecycle of this product by protecting more than one element of the marketed product. This suggestion is reinforced by the patent filing trends graph (Figure 1). This graph clearly shows some patent filing activity prior to the first major launch of the product in the UK in 1995, most of which has been undertaken by the innovator.
Figure 1: Topiramate Patent Filing Trends
Subsequent to launch, a significant increase in filing activity can be seen, indicating generic interest in the product compounded by the complex patent landscape laid down by the innovator. The Top Patent Applicants analysis (Figure 2) reveals that the innovator has filed close to half of the published applications (Ortho-McNeil and Alza) while three generics firms occupy 10 % of the applications.
Figure 2: Topiramate Top Patent Applicants
In summary, it appears that Ortho-McNeil has undertaken a considerable amount of lifecycle management in regards to Topiramate and has laid down a number of constraints for generic competitors to overcome should they seek to market a generic product on the day of expiry of the active ingredient patent. However, as generic competitors become more sophisticated at circumventing or challenging patents, such innovator patents become less troublesome and of little use in preventing generic competition. Of course, none of this would be possible without first comprehensively identifying the relevant patents for the development from the 50 million+ published patent documents worldwide, and keeping this information up to date. This is not an area where leading generic companies take chances so they use experts such as GenericsWeb to assist in this area.
Comprehensive data for patent families relating to Topiramate, based on professional patent searching, may be accessed by subscribing to the GenericsWeb Pipeline Developer report 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.
For questions and comments about this article please contact the author at d.oh@genericsweb.com.
|
Home
INNform