Product Profile: Picoxystrobin
3 May 2011 Our first profile, published in February, featured azoxystrobin, which was discovered and developed by ICI (now Syngenta). Azoxystrobin was the first of the highly successful strobilurin class (see table) of products to be commercialized and is now the largest selling fungicide active substance in the world with sales that exceed $1 billion. This month we feature picoxystrobin, also discovered by Syngenta but now commercialized by DuPont. Picoxystrobin was the fourth strobilurin to come to market when it was launched in 2001.
| Active Ingredients | Inventor Company | Mainly Commercialized By |
| Azoxystrobin | Syngenta | Syngenta |
| Picoxystrobin | Syngenta | DuPont |
| Trifloxystrobin | Syngenta | Bayer CropScience |
| Kresoxim-methyl | BASF | BASF |
| Orysastrobin | BASF | BASF |
| Pyraclostrobin | BASF | BASF |
| Dimoxystrobin | Shionogi | BASF |
| Fluoxastrobin | Bayer CropScience | Arysta LifeScience |
| Metominostrobin | Shionogi | SumiAgro |
| Pyrametostrobin | Shenyang Research Institute | In development |
| Pyrazoxystrobin | Shenyang Research Institute | In development |
As with other strobilurin analogues, picoxystrobin inhibits fungal respiration and has both preventative and curative properties, with picoxystrobin exhibiting improved curative properties compared to azoxystrobin in certain crops.
Picoxystrobin was initially launched as Acanto by Syngenta for control of yellow, brown and crown rusts, powdery mildew, sooty mold, net and leaf blotch and tan spot on cereal crops, including: wheat, barley and oats in Europe. Picoxystrobin’s dossier was submitted to the EU review system and was declared complete in 1999. It was included on Annex I as a New Active Substance on Jan. 1, 2004.
In 2006, DuPont acquired worldwide rights to picoxystrobin as part of an agreement which also gave Syngenta rights to DuPont’s insecticide, Rynaxypyr. DuPont has further developed picoxystrobin for use on soybeans in Latin America and in 2010, DuPont applied for authorization for picoxystrobin as Aproach to the US EPA for use on corn, soybeans, cereals, dry beans, peas and canola. Launch in the US is expected in 2012. DuPont has estimated peak year sales potential for picoxystrobin to be $150 million.
Picoxystrobin is currently registered in some 28 countries, including: Argentina, Austria, Belgium, Brazil, Colombia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Kenya, Latvia, Lithuania, the Netherlands, New Zealand, Norway, Poland, Romania, Slovakia, South Africa, Sweden and the UK. Registration is in progress in the US, Italy and Portugal.
Picoxystrobin is marketed as a single ingredient fungicide and also in several mixtures with other fungicides, including: cyproconazole (Furlong, Stinger and Aproach Prima); chlorothalonil (Credo and Plinker); and cyprodinil (Acanto Prima).
Navigating Barriers to Entry
Clearly, picoxystrobin is an attractive target AS for off-patent companies but how easy will it be for these companies to gain significant market share? To answer this we need to assess where the major barriers to market entry exist.
The EU recognized that a significant erosion in effective patent terms existed for pharmaceutical. This resulted in insufficient market exclusivity period to recoup the substantial R&D costs and, as a result, Supplementary Protection Certificates (SPCs) were introduced in 1992. SPCs give up to five years additional patent protection to the normal 20 year term and as a result of extensive lobbying by the agrochemical R&D sector SPCs became law for agrochemicals in 1996.
In the EU, picoxystrobin is protected by EP0447004 (and some national patents) which expired on 14th January 2008. In Austria, Belgium, Switzerland, Germany, Denmark, Great Britain, Hungary, Ireland, Luxembourg, The Netherlands and Romania, SPCs have been granted which provide additional protection until 2013. In addition to these countries, picoxystrobin is registered in Czech Republic, Estonia, Finland, France, Lithuania, Latvia, Poland, Sweden and Slovakia. SPCs have not been granted for these countries which have been open to generic competition since 2008. However, data protection issues have prevented generic market entry.
Picoxystrobin was included into Annex I on 1st January 2004 and the data protection period expires 10 years after this date. The time-line diagram shows the market exclusivity period in the EU for products based on single AS picoxystrobin. Even though in some EU countries there is no existing patent protection, generic competitors would need to generate a full data pack, to negotiate a data compensation agreement or wait until data protection ends in 2014 in order to gain market entry.
Many patents to mixture products containing picoxystrobin have been filed but in practice, only three mixture products appear to be of commercial interest:
- Picoxystrobin + cyproconazole — SPCs have been granted in three countries extending protection to 2013.
- Picoxystrobin + cyprodinil — SPCs have been granted in four countries extending protection to 2013.
- Picoxystrobin + chlorothalonil — an SPC has been granted in Great Britain extending protection to 2013.
In the US, DuPont has applied for registration of picoxystrobin on a variety of crops, a decision on this is scheduled for May 12, 2012 and, if granted, a 10-year period of data protection will exist. Thus, if the market for picoxystrobin is developed in the US, then generic competitors will have to generate a full data pack or negotiate a data compensation agreement with DuPont.
In addition, potential generic competitors will have to carefully analyze the full IPR surrounding picoxystrobin such as secondary patents to:
- Crystalline form
- Formulations
- Processes
- Intermediates
In 2000, Syngenta expanded its production facility at Grangemouth, Scotland (where azoxystrobin is manufactured) to produce picoxystrobin. When DuPont acquired worldwide rights to picoxystrobin (straight and mixtures) in 2006, it was also agreed that Syngenta would continue to manufacture picoxystrobin for another three years.
The chemistry and technology involved in the manufacture of picoxystrobin is relatively straight forward. The availability of key intermediates is an important consideration when assessing how easy it is for generic companies to manufacture an active substance. In the case of picoxystrobin, two intermediates are key to the process:
- 2-hydroxy-6 trifluoromethylpyridine — this intermediate is not used in the synthesis of other agrochemicals and sourcing it may be a problem, alternatively generic manufacturers may manufacturer it in-house from 2-chloro-6-methylpyridine
- 2-methyl benzyl cyanide — this intermediate is also used in the synthesis of Nippon Soda’s acaricide, fluacrypyrim.
Whilst the markets of the EU and US are closed to generic competition in the short term, a number of other markets such as Brazil, Colombia, New Zealand and South Africa, may be available, and it will be interesting to see if generic competitors use these markets to gain a presence in advance of the EU and US markets opening up.
Get The Newsletter Today!
