By Dani Kass

Law360 (August 21, 2020, 7:32 PM EDT ) In the middle of a pandemic where antibodies are at the center of prevention and treatment research, the Federal Circuit is weighing a case that could deeply impact how drugmakers can patent biologics, an issue that is not only critical to coronavirus research but to pharma at large.

In Amgen v. Sanofi, the Federal Circuit will be deciding whether two Amgen patents claiming an entire genus meet enablement requirements under Section 112 of the Patent Act. Following an Aug. 17 request by the appeals court, the parties and court are working on scheduling oral arguments.

Species are the smallest classification of organisms in biology, and genus is one step up from that. Sanofi and Regeneron say Amgen must tailor its patent claims to specific species within a genus, whereas Amgen says genus claims are fair game.

Stepping back from the science, the sparring drugmakers — both with big-name amici on their sides — are fighting over whether broad claiming is needed to ensure companies can get coverage for discoveries that will lead to important drugs, or whether such broadness is unfairly shutting out competition and laying claim over antibodies they didn't actually discover.

"I agree with the law promoting innovation through this type of research by allowing one to claim a broad genus of antibodies without having to identify each and every one, but I also understand the opposite argument, which is if you're claiming too many [antibodies] without support, then you're essentially just claiming a wishlist ... and that's not what patents are for," said Venable LLP partner Ha Kung Wong.

What's the background?

The dispute pitting Amgen Inc. against Sanofi and Regeneron Pharmaceuticals Inc. involves patents for a class of cholesterol drugs called PCSK9 inhibitors. Amgen's drug is Repatha, while Sanofi and Regeneron have Praluent.

Amgen sued for infringement in 2014, which Sanofi and Regeneron have conceded, meaning the case now rests on whether the patents are valid. The fight is at the Federal Circuit for the second time, specifically looking at U.S. District Judge Richard G. Andrews' post-trial finding that three patent claims aren't enabled.

The judge in August 2019 had held that it would take "undue experimentation" to practice the claimed invention because the patents claim a "vast" class of antibodies.

As this dispute is playing out, a trio of law professors released a study that shows Amgen is unlikely to find much support at the Federal Circuit. Their Aug. 6 paper concluded that the Federal Circuit has essentially made genus claims impossible to maintain over the last 25 years.

The U.S. Patent and Trademark Office is still issuing genus patents, but they don't hold up in courts, the professors said. The study accuses the Federal Circuit of being too focused on finding the exact boundaries of an invention, rather than focusing practically on how inventors could use the claimed invention.

"This 'full scope possession' theory invalidates a genus claim unless the patentee can show exactly which species within the genus will work as intended — an impossible task for a genus of any nontrivial size," the paper states. "Given the importance of patents to these industries, and given the importance of genus claims to those patents, we find the death of genus claims in modern courts troubling."
 
One of the authors, George Washington University Law School's Dmitry Karshtedt, said Amgen v. Sanofi will serve as a test to see if genus claims are truly dead.

"I see this as an opportunity for the Federal Circuit to clarify the doctrine or face the fact that the doctrine has been inconsistent, or shifted to a very patentee unfriendly analytical framework," he told Law360.

What makes antibodies special?

When deciding whether a genus claim is enabled, the court has to figure out how many potential species exist in that genus in order to pin down the actual species, according to an amicus brief by attorney and biologist Stanley D. Liang. The "undue experimentation" question raised by Judge Andrews deals with the gap between the potential and actual species.

The problem with antibody science though, is that it's a time-consuming and inexact science, and companies have to choose between patenting something broad quickly, or something narrow after more time in the lab.

"When you're going through the research and development process, you may have 50 or 60 legitimate promising candidates at a time, or even more," Venable's Wong said. "How long do you wait before you file your patent? Do you wait until you're down to your top 10 candidates? By that time, somebody might have filed a patent that covers 20 antibodies, some of which overlap with the 10 you want, and then you're out of luck."

Amgen's two patents specifically name 26 antibodies, and the company said it includes a "roadmap" to teach skilled artisans how to find other antibodies. Overall, the patent owner says there are about 400 distinct antibodies in the genus.

Sanofi and Regeneron, however, convinced the district court the number is actually in the millions, leading to Judge Andrews' conclusion that Amgen claimed inventions it never actually found and locked out other companies who may actually find them first.

Why do so many companies care?

Many of the world's top-selling drugs are antibody-based, including autoimmune treatment Humira, cancer treatments Avastin and Herceptin and arthritis treatment Remicade. It's no wonder that big pharma is lining up to take sides: Bristol-Myers Squibb Co. and Merck Sharp & Dohme Corp. backed Amgen in amicus briefs, and Eli Lilly & Co. and Pfizer Inc. supported Sanofi and Regeneron.

BMS and Merck said the "first step" of developing an antibody-based drug includes identifying the underlying molecular structure that the antibody binds to and tying that to a disease. Only then can the inventor figure out the specific antibodies.

This process is "complex and expensive," with antibody-based biologics costing on average $2.6 billion to bring to market, the joint brief states. It warned that narrowing how antibodies can be patented will discourage innovation.

"It is easy to create variations of an antibody once the target and application are identified," BMS and Merck said. "The patentee, having invested enormous sums in discovering the underlying target, has provided a blueprint for others who, now aware of the targets, can quickly make their own version of an effective antibody. The scope of the invention in this space is therefore the genus of antibodies that successfully binds the target, rather than any particular antibody that serves as an example."

On the other side, Lilly accused Amgen of understating how unpredictable antibody science is, particularly in the functional way Amgen claimed the antibodies. Functional patent claims describe what the invention does instead of how to do it, and are only allowed if there is a corresponding structure in the specification.

Lilly also cited a threat to innovation, but says that chilling effect would come from Amgen's patent being upheld.

"Purely functional claims like those at issue preempt future inventions and are thus inconsistent with one of the most fundamental policies underlying patent law," the drugmaker said.

Pfizer said the "undue breadth" of Amgen's claims is part of a "deliberate strategy" to ward off any competition for this type of drug.

Ostrolenk Faber LLP patent attorney Andrew Berks said if Amgen wins, it will discourage biosimilar makers in particular, and potentially thwart innovation that doesn't come directly from big pharma.

"The concern is maybe small companies without deep pockets will be scared away [as will] universities that don't want to get involved in litigation," Berks said. "If Amgen wins, it will have a stifling effect on competitors."

Casimir Jones SC shareholder Lisa Mueller seemed less convinced of a chilling effect, saying companies are just going to have to get more creative with how they patent their innovations.

"I think people are going to keep plugging along and keep filing broad claims, and see what happens at the Federal Circuit," she said. "I suspect big companies doing this research are already claiming in several ways."

So, how does this affect COVID-19 research?

Lilly's brief drew on the novel coronavirus to show that allowing a patent like Amgen's could be disastrous.

"Imagine the public detriment from a patent directed to all antibodies to the SARS CoV-2 virus," the brief states. "Such a patent would, in violation of laws intended to promote science, preempt the more than a dozen pharmaceutical companies developing therapeutic antibodies to combat this viral pandemic."

But attorneys that spoke with Law360 weren't entirely swayed, saying the pressure of addressing a public health crisis overrides patent concerns, no matter which side wins. Karshtedt said the "accolades and acclaim" for helping can outweigh the patent incentives.

Likewise, Mueller said "right now, we're banking on big pharma to be our saviors, so I think they're walking a fine line. I think they're going to go ahead and find a treatment and continue on as always."

--Editing by Emily Kokoll.

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