Inventions made in a particular country are generally first-filed in that country before entering the United States via a direct Paris Convention filing or, more commonly, a PCT national stage entry. Convenience, national pride, and foreign filing license laws encourage such home country first-filings.
It is well known that the U.S. biosimilar market has developed slower than others, particularly in comparison to Europe’s biosimilar market. But how does the United States compare to other countries regarding biologic innovation in the first place? Where was the initial patent application filed for the biologic reference product?
There have been 354 individual U.S. patents asserted across the 54 BPCIA litigations to date (many of those individual patents have been asserted repeatedly in different litigations). Of those 354 individual U.S. patents, only 49 claimed priority to a prior foreign patent application. That represents only 14% foreign first-filed biologic patents, which is significantly lower than the overall rate of foreign first-patent filings of issued patents of about 20-25% for Technology Center 1600, which examines all biotechnology and organic chemistry patent applications.
Where are these few initial foreign patent filings for biologics-related inventions being made? The vast majority (36/49) were filed in the European Patent Office (“EPO”). Next, eight were filed in Japan. Three were filed in Germany. And two were filed in the United Kingdom.
Interestingly, every one of these foreign first-filed patents asserted by a Reference Product Sponsor in BPCIA litigation is assigned to Roche or a Roche subsidiary. Most (33/49) are assigned to Hoffman-La Roche Inc. One is assigned to Roche Diagnostics GmbH. Ten are assigned to Chugai Seiyaku Kabushiki Kaisha, which is a Roche subsidiary. One is assigned to Genentech, Inc., which is also a Roche subsidiary. And five are assigned to both Hoffmann-La Roche Inc. and Chugai Seiyaku Kabushiki Kaisha. No other company has first-filed any patents outside the United States that have been asserted by a Reference Product Sponsor in BPCIA litigation.
Of course, the patents asserted in BPCIA litigation can be skewed by time—first by the delay between the approval of older biologic reference products and the enactment of the BPCIA and then by the delay between the development of a biologic reference product and the institution of BPCIA litigation years after approval. Thus, the patents asserted in BPCIA litigation often do not include the original composition patent because those patents have expired, or even been invalidated in a separate proceeding.
To understand whether this phenomenon affected our results, we identified the original composition patent for the 15 biologic reference products that have been involved in BPCIA litigation and examined where their corresponding applications were filed. Due to a combination of expirations and design arounds, only four of these 15 original composition patents have been asserted across 10 BPCIA litigations. Of the 15 biologic reference products involved in BPCIA litigation, only one composition patent claimed priority to a prior foreign patent application. That represents less than 7% foreign first-filed biologic patents, which is significantly lower than the overall rate for Technology Center 1600 of foreign first-patent filings of issued patents of about 20-25%, as well as the 14% rate of patents asserted in BPCIA litigation. Once again, Roche was the sole company to first-file a patent outside the United States that disclosed the original biologic reference product, via its Chugai subsidiary in Japan (for tocilizumab).
Was Roche really the only company that was successfully innovating original biologics outside the United States from the 1980s through the early 2010s? That seems implausible, but these data seem to indicate that the United States is even more dominant in biologic R&D (at least when it comes to initial discovery) than generally understood. Indeed, looking at the residence of the 65 inventors listed on these original compound patents (excluding the five inventors on Chugai’s tocilizumab patent), 55 reside in the United States, and only 10 reside outside the United States. Similarly, looking at the original composition patent for Keytruda (pembrolizumab)—discovered at Organon’s facility in Oss, Netherlands—reveals it was initially filed in the United States, likely because the first-named inventor worked at Organon’s site in Cambridge, Massachusetts.
Perhaps these results throw further light on the nine-year delay between when Europe and the United States each approved their first biosimilar. While this delay has generally been attributed to a desire to protect the non-price controlled U.S. market as a source of profits to fund biopharma research and development worldwide, perhaps some of the delay also stemmed from a more specific recognition that a reference product would most likely be invented in the United States.
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