Anatomy of a billion dollar patent drug dispute - the Merck Keytruda patent

February 23 2018

Keytruda, the Merck brand name for pembrolizumab, is a humanized antibody used in cancer treatment. According to Reuters, Keytruda bought in more than $1 billion in sales in the third quarter of 2017, and is expected to generate peak annual sales of USD8.2 billion in 2020. No wonder then, that a recent positive trial report was enough to increase the value of Merck shares by 6%.

Pembrolizumab was first invented by three scientists at the Dutch pharma company Organon, which was purchased by Schering-Plough, in turn acquired by Merck, who according to Wikipedia were at one stage preparing to outlicense the drug, before its potential was recognised. Since then its use has moved from melanoma to other cancers, even if at a cost to patients of up to $150,000 per year.

Not surprisingly, there has been patent litigation this area. Back in January 2017, Merck announced a settlement with Bristol-Myers Squibb and Ono Pharamceutical, that included an upfront payment of USD625 million, and royalties of 6.5% or 2.5% of sales. 

This patent dispute has been reviewed by Mathieu Collin of INSERM, who noted that was in relation to the Bristol Myers Squib patent family that included US8779105 Monoclonal antibodies to programmed death 1 (PD-1)   (priority date of May 2005), while the Pembrolizumab patent family corresponding to US8354509   Antibodies to human programmed death receptor PD-1  (priority date of June 2007).

Ambercite has developed both graphical and list based tool to analyse patent families and their relationships with other patent families - so what Ambercite show in this case?


Amberscope analysis 

For the Amberscope analysis, we might start with the Bristol Myers Squibb patent.

The Amberscope image below shows the direct patent network family for US8779105 (the patent number shown in the details box is US8008449 - the first granted US family member for this patent family).


US8779105 patent network.gif

There are a few points to note in this image. First of all, this network is very packed - our data suggests that 313 different patent families cite this Bristol Myers patent families, while 142 separate patent families have been cited against it. This area is clearly commercially important. Not surprisingly, this has led to a very high value of the Ambercite patent value predictor Amberscore - this value is 28, compared to the average value of 1 for Amberscore against all patent families in our database. 

While descriptive, this network is almost too packed to work with. Luckily. Amberscope comes with some tools that can simplify networks, and in the image below our priority date filter has been set so that only patents with priority date of 2005 and later are shown, and our Similarity filter has been set so that only the 10% most similar patents are shown (see the small orange segment).



In this image below, the similarity filter has been further focused so that only the most similar 1% of patents are shown:


Of note, one of the three remaining patents after this analysis is US8354509, the (now owned by Merck) pembrolizumab patent. This has an Amberscore value of 6.5 - still much higher than average, but not as high as the Bristol Myers Squibb patent.

If we look carefully at the details box for US8354509, there is a button that says '30 more'. This means that if we press this button, Amberscope will refocus the network onto this patent, and there will be 30 additional patents not found in the network for the Bristol Myers Squibb patent.

And this refocussed patent network looks like this - also a very packed network, suggesting  high patent value.

US8354509 patent network.gif


Ambercite analysis of the pembrolizumab patent

Ambercite allows you to do a similar analysis in table form. If we start from the pembrolizumab patent in this case, and ask for the 5 most similar patents, the resulting list looks like this:

Pembrolizumab_most similar 5 patents.jpg

And in fact, we could choose to display the most similar 10, 50..up to the most similar 2000 patents if we wished, and then apply a series of filters on the results

But in this case, the 5 most similar patents is enough, particularly at the top of this list is US8008449B2 - or the first granted US family member to the US8779105 Bristol Myers Squibb patent that Merck have agreed to license. 


The value of Ambercite Similarity scores

If we look at the third column in the table above, this shows a list of "Similarity Scores". This shows value trending down from 181 for the Bristol Myers Squibb patent family - and the higher the value, the most similar the patents found by Ambercite. 181 is a very high score for similarity.

Similarity scores are a key benefit of Ambercite. Conventional citation analysis is often based on individual patents, and in the case of US8779105 would provide a list of 325 forward citations, at least on 23 February 2018. Ok, there is plenty of information - but where do you start?

In contrast, with the Ambercite analysis, it is clear that you should start with the pembrolizumab patent - the patent that leads you to the very lucrative payday that Bristol Myers Squibb had last year. 


Mike Lloyd