E cdip/15/inf/2 original: english date: january 8, 2015 Committee on Development and Intellectual Property (cdip) Fifteenth Session Geneva, April 20 to 24, 2015

Finding and linking patents to active ingredients

We have data on all patent applications filed with the Chilean patent office (INAPI) between 1991 and 2010. This includes all patent filings by domestic as well as foreign entities. The objective is to identify those patents that protect the active ingredients listed in ISP’s pharmaceutical product database. We also attempt to identify patents that protect the processes used in the production of the products, but this is more difficult because these cannot necessarily be identified directly from our data sources.

Linking patents to active ingredients is difficult for the following reasons:

1. 
   Active ingredients are registered at the ISP using the International Nonproprietary (INN)³⁸ classification whereas patents rely on the International Union of Pure and Applied Chemistry (IUPAC)³⁹ classification. These classifications differ substantially. For example, the INN denomination for the active ingredient Imatinib is “imatinib mesilate” and its IUPAC is
   “4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide.”
   

4.While the ISP register lists the active ingredients that belong to a given pharmaceutical product, patents may protect a family of different pharmaceutical ingredients related to the active ingredient in question.⁴⁰ This means that a single patent may protect several different active ingredients. Specific ingredients covered by the patent can only be identified through the examples given in the patent application.

5.A product registered at ISP can be associated with a number of different patents. Only some of these patents protect the relevant active ingredient. This can occur for several reasons. First, other patents protect different forms of the active ingredient, related ingredients, or for example the manufacturing process of the drug. Second, in the early stages of the development of a new drug, producers commonly patent a large number of molecules, formulations and compositions that have potential to be developed into new active ingredients. This means while there can be a large number of patents related to the eventually developed active ingredient, they need not all protect the ingredient. Third, it is possible to patent the “second use” of a drug.
Mindful of these challenges, we proceed as follows. As a starting point, we use data compiled by INAPI that contain the active ingredient-patent mapping for all active ingredients contained in new pharmaceutical products registered with ISP between 2005 and 2010. The mapping was undertaking by patent examiners specialized in pharmaceutical patents.
For all remaining products registered with the ISP we proceed as follows:

1. 
   The ISP products are grouped by active ingredients. For example, focusing on the active ingredients Imatinib and Drospirenone, we group thirteen ISP products under the active ingredient Imatinib and thirty-three products under the active ingredient Drospirenone. For the cases that a product has more than one active ingredient, we include the product in each group of its active ingredients. For example, the product “Femelle Fol Comprimidos Recubiertos” has three active ingredients: Drospirenone, Ethinyl Estradiol and Levomefolate. Therefore, the drug will be part of three different groups, one for each active ingredient.
   
2. 
   Each active ingredient is translated from Spanish into English using online translators and our own expertise.
   
3. 
   Each active ingredient is searched in the Merck Index (MI). The MI contains the first filings of patents on an active ingredient, which can be at any patent office around the world. This provides us with the direct association between active ingredient and corresponding patent(s). We search the priority dates, inventor names, title and abstract of the patent(s) listed in the MI. For example, Imatinib has two patents in the MI: EP564409 and US5521184 with priority date 03/04/1992. The inventor name for both patents is “Juerg Zimmerman.”
   

4. 
   The Orange Book (OB) of the U.S. Food and Drug Administration (USFDA) is used to identify U.S. patents on or related to the active ingredients of the products registered in Chile. The OB provides the patent-active ingredient mapping for all drugs registered with the USFDA, and patents filed with the USPTO. Patents may not only protect the active ingredient directly but also other features of a registered drug. We search for each active ingredient in the OB.⁴¹ If an active ingredient is found in the OB, we extract the corresponding list of products that contain the active ingredient and the patents associated with these products.⁴² We obtain priority dates, inventor names, title and abstract for the USPTO patents identified through the OB. The main challenge is to determine whether the patents found in this way protect the active ingredient or a related ingredient or process. For example, we found two registered products in the FDA that contain Imatinib: Gleevec 100mg and Gleevec 400mg. Each product has the same four USPTO patents. One of the four patents listed in the OB corresponds to the MI priority patent (US5521184), which means this is the one that protects the active ingredient Imatinib. If the product has only a single ingredient, it is likely that the other patents that do not protect the active ingredient directly, but a modification, a related process, manufacturing method, a second use, or treatment. If the product has several ingredients, the patents can also be associated with other ingredients. To determine this, each patent has to be assessed individually. We do not assess this directly, but rely on the assessment of the Chilean equivalent by patent examiners specialized in pharmaceutical patents. So for example, the three other U.S. patents found in the OB in the case of Imatinib (US6894051, US7544799 and US6958335) are indeed related to Imatinib. The first two patents are a crystal modification of the active ingredient and the third one is a treatment using Imatinib. This would only be relevant, however, if any of these patents had a Chilean equivalent.
   
5. 
   The WIPO-INAPI database is searched for Chilean equivalents of the patents found in the MI and OB. We do this through inventor names, priority date, title and abstract of the patents found in the MI and OB. The Chilean patents found in this way, where we distinguish between the patents protecting directly the active ingredient and related patents, represent the patents that protect a given active ingredient and hence pharmaceutical product. For example, in the case of Imatinib we did not find a Chilean equivalent for US5521184 but we found an equivalent for US689405, a crystal modification of Imatinib (CL199801692). In this way we create patent families related to each active ingredient and pharmaceutical product.
   

In case we were unable to find an active ingredient in the MI or the OB, we link patents to ingredients directly. However, this is not straightforward as explained above and was therefore done by Chilean patent experts specialized in pharma patents. Due to the large number of pharmaceutical patents and the extremely labor-intensive process of matching patents and pharmaceutical products, we limited the direct match to the remaining set of unmatched granted pharmaceutical patents (approximately 3,000 patents).⁴³
The ISP database contains additional information on pharmaceutical products such as the registration, expiration and renovation date, the owner of the drug, whether the drug is produced domestically or abroad, and drug packaging information. The information on the owner of the drug is especially useful for the patent-compound matching as it provides a possible cross-check with the assignee names of patents.

The match between drug names on the ISP and these various patent data bases yielded 504 unique Chilean patents matched to 322 unique active ingredients from 4,304 ISP registrations. There are 619 unique patent-active ingredient combinations. Table A3 below shows a count of the number of ISP reistrations and the number of unique active ingredient names that are matched to no, one, two, etc. patents. The drug and active ingredient with the largest number of associated Chilean patents (9) is ciprofloxacin, an antibiotic. One third of the ISP registrations but only 12 per cent of the unique active ingredients match to at least one patent. Only 3 per cent of the patents in the organic fine chemistry, biotechnology, and pharmaceutical classes match to an active ingredient, but that is not too surprising, because many of the patents in these classes are associated with agriculture or aquaculture.

Table A3

In Table A4 we look at the patent-active ingredient match by the grant status of the patents. We again restrict the Chilean patent database to those patents classified in ISIO 14 (organic fine chemistry), 15 (biotechnology), and 16 (pharmaceutical). Only 6 of our matched patents lie outside these classes and we have added these manually to the sample. In this table we show the match by the patent status. Clearly granted patents are more likely to be matched (at 8%) and abandoned/withdrawn patents are the least likely to be matched (<2%). However the overall match rate is fairly low (3%).

Table A4