Seen up close, many patents are not truly strong enough to block biosimilar commercialization, although patents filed after FDA approval of originator products can bar access to modern manufacturing methods, according to Hans Sauer, deputy general counsel and vice president for intellectual property at the Biotechnology Innovation Organization (BIO).
Patent thickets are often blamed for holding up the launch of biosimilars, but a close look reveals that most patents are tangential and ought to have little effect on how soon a product comes to market, according to Hans Sauer, deputy general counsel and vice president for intellectual property at the Biotechnology Innovation Organization (BIO), a Washington, DC-based trade association.
Sauer discussed which patents genuinely interfere with biosimilar launches, as well as pending legislation that holds the potential to cut down on patent litigation, at the World Biosimilar Congress 2020 at the Festival of Biologics USA in San Diego, California.
“It is very tempting for policymakers, to the extent they feel frustration with the biosimilars market in the United States, to point to patents and intellectual property as the culprit,” Sauer said. In fact, many patents have little to do with essential composition of biologics, and often they relate to innovations in manufacturing processes and product formulation that were developed and patented after the original biologic was launched, he said.
This is evidenced by the fact that some biosimilars appear to have only modest difficulty in getting to market, Sauer noted. There are 15 biosimilars on the US market and the average time to launch, post approval, for this cohort was 7.4 months (median, 5 months). Of those, 8 biosimilars were launched at risk of patent litigation, meaning the threat of patent infringement claims did not deter the biosimilar manufacturers from moving forward with commercialization.
Of 11 biosimilars that have been approved but not launched in the United States, 5 are biosimilars of adalimumab (Humira) and all have negotiated agreements to enter the market in 2023, Sauer said. Of the other 6 products, 2 are biosimilars of etanercept (Enbrel) and remain in litigation. The litigation surrounding the biosimilars for etanercept involves 5 or fewer patents, “depending on whom you ask,” he said.
Of the remaining 4 biosimilars that are approved but not launched, 1 is not coming to market because of business reasons, 2 more are subject to settlement agreements with no launch dates yet announced, and the fourth was approved only recently, in December 2019, Sauer noted.
Given this profile of approved biosimilars, it does not appear that patents are the gargantuan obstacle that they are commonly assumed to be, Sauer said. “The biosimilars that are in the market today, I think you can fairly say, haven’t experienced a lot of launch delays due to litigation. There is nothing that is, on its face, truly alarming, shocking, unexpected, and disappointing.”
Sauer said it’s closer to the truth to conclude that the United States is making fairly good progress with biosimilars, potentially even better progress than has occurred in Europe, which created legislation specifically for biosimilars in 2001 and clarified that in subsequent years. The first biosimilar in Europe was a growth hormone approved in 2006. After 10 years, Europe had 5 biosimilars approved versus 26 for the United States in a 5-year time span. “I think 1 reason why we’re faster in the United States, given that we started later, is that we have the benefit of a lot of experience—developmental and regulatory.”
However, there remains a widespread expectation that the US market should have more biosimilar competition than it does, he said. Although patents can impede the movement of biosimilars to market, case history suggests that there are ways through the patent thicket.
In biosimilar litigation involving 52 Genentech patents for trastuzumab and rituximab, most of these patents related to forms of manufacturing, such as making cells, cell culture media, and protein purification—”a lot of patents, frankly, that aren’t specific to the biosimilar products but that relate more generally to recent modern methods of biologics manufacturing,” Sauer said.
In the case of AbbVie’s adalimumab patents, which famously exceed 100, some are critical formulation patents, but “many are for methods of manufacturing or use—there are a lot of indications for Humira—which on their face, in my view, don’t present an obstacle to market entry.” And many arose after the product was originally approved.
In the case of Amgen’s patents on filgrastim, those that have been litigated in biosimilar disputes all relate to cell culture and manufacturing processes (17). “Think of these patents, realistically, not as patents on the old product that was approved [in 1991]. Think of these as patents that were invented after the product was approved and that allowed their manufacturers to make these products today with greater efficiency, maybe greater purity, greater consistency, and maybe more cheaply than was possible years ago.”
The question to be asked is whether these patents reflecting later innovations in product and manufacturing processes should be allowed to stand in the way of launch for biosimilars, Sauer said. “Should manufacturers be required to make a biosimilar the old way, the way products were made 20 years ago? Shouldn’t they have reasonable access to modern manufacturing technology like everybody else does today, even at the risk of infringing someone’s patent and having to pay license fees?“
There are 3 pieces of legislation that could shift the balance for biosimilars with regard to patent litigation, Sauer said.
House and Senate versions of affordable prescriptions bills (HR 3991, S 1416), would limit the number of late-filed or late-issued patents that could be asserted in Biologics Price Competition and Innovation Act (BPCIA) litigation against a biosimilar.
“Late filing” would apply to patents applied for 4 years after the reference product was first approved. “If you launch a new biologic today and you apply for a patent in 4-and-a-half years, you’re going to be limited in your ability to assert biosimilar patent litigation,” Sauer said. This bill would limit the number of late-filed patents to 20. “I think there’s a pretty good chance that this in one form or another will become policy,” he said.
The Purple Book Continuity Act (HR 1520) would require publication of patents disclosed during the BPCIA patent dance, during which the biosimilar manufacturer and the innovator company jointly discuss potential patent litigation. And another bill, the Lower Health Care Costs Act (S 1895), would require Purple Book listing of all patents that might reasonably be expected to be infringed by a biosimilar.
The Senate bill is problematic, Sauer said. People will have difficulty wading through the potentially voluminous patent information that would be disclosed, and this would suggest to some that the obstacles to biosimilar launch are more formidable than they are.
“We’re going to end up with very large lists of patents that people will not understand.… I don’t think this is going to create a lot of transparency,” he said.