In-house sources at Sanofi, Bristol-Myers Squibb and a European pharma innovator say the differences in how the US and European patent offices and national courts review monoclonal antibody applications make filing patents clearer and safer in the former.In Amgen v Sanofi, the Federal Circuit concluded that claiming a broad class of antibodies that could bind to a sequenced target is not enough, and that innovators must provide sufficient examples of new antibodies to support their claims.
This is not the case at the EPO; which, unlike its counterpart across the pond, still considers applications with broad functional class claims. And the added clarity that limits the scope of what can be protected in a claim gives more certainty for drug makers filing at the USPTO.
“The antibody case law is more developed in the US than in the EPO or national European courts,” says Karine Crepin, vice president and head of biologic patents at Sanofi in Paris. “We hope to get more clarity and guidance with time when cases arrive at the Technical Boards of Appeal.”
These therapies are worth a lot of money for pharma innovators. Humira, a monoclonal antibody therapy for rheumatoid arthritis, generated $25.6 billion for AbbVie in 2016. Getting the right patent protection can be worth billions of dollars for drug makers.
“A fundamental difference between the offices is the inventive step approach in Europe for antibodies – compared to the US, where sequence-based claims are generally viewed as non-obvious,” says Paul Golian, vice president and general counsel of IP for Bristol-Myers Squibb in New York.
“The US office has taken the view that an antibody with a novel structure, defined by the amino acid sequences of the variable regions, is not obvious and, therefore, meets the non-obviousness requirement,” he adds.
Golian says the EPO, by contrast, has taken the view that the same antibody would be obvious.
To overcome an antibody inventive step rejection at the EPO, the patent applicant must establish that the claimed antibody has an unexpected technical effect or functional characteristic.
“When drafting and prosecuting a patent application directed to a new antibody, one must consider the patentability inventive step requirements in Europe,” he explains.
The complexity involved in producing these therapies accounts for some of the different examination procedures established between patent offices. Unlike small molecules, antibodies require protection on their mechanism for how they bind to the desired target and their manufacturing process, rather than just their structure.
“With small molecules, there are maybe one or two patents and one way to make them which is standard. If you have an antibody, you have a manufacturing process,” says the chief IP counsel for a European pharma innovator. “There is a lot more to protect with an antibody than just its structure. The discussion is what patent can you get around the actual antibodies.”
For example, sequenced-based claims describe the antibody based on the sequence of the target antigen that the antibody binds to. In the past in the US, it was sufficient to describe an antibody as new and non-obvious based on its target, but not on structural elements alone.
“The EPO still grants purely functional antibody patents,” says Crepin at Sanofi. “They are treating antibodies as a specific class of proteins, and there is no reason to do this. So what is gone, under the ‘newly characterized antigen’ concept, or is being reviewed – written description – in the US still exists in Europe.”
Clarity repercussionsCrepin argues that a consequence of the way the EPO reviews antibody applications is that third parties have a harder time figuring out if their invention falls under the scope of another claim.
“Purely functional claims should not be allowed because they squash further innovation and competition, thereby limiting possible alternatives to help people with medical needs. And they create a monopoly which is disproportionate with the extent of the disclosure,” she says.
“We are facing two extremes. The EPO still grants very broad functional claims in Europe. At the same time, because the EPO does not recognise structural non-obviousness, they deny your claim if you cannot prove a real antibody invention’s advantages over existing antibodies.”
Another factor exacerbating how different patent offices review antibody patents is that every office has its own accepted tradition of how much data they require to support the application.
The chief IP counsel says: “The problem with patent offices is they have certain traditions. That tradition gets established with small molecules, an area where applicants know the data needed to prove their claim; and that becomes the established practice.
“People say the rules for the patent offices aren’t fair, but people aren’t doing the work to move away from that tradition.”
He adds that antibody applicants need to do more work and provide more data on how the antibody functions, and then patent offices need to start granting claims with bigger data packages.
“The applicants need to do more homework and the patent offices should reward that homework,” he says.
Crepin at Sanofi adds that the EPO probably has an oversimplified view of the complexities of developing therapeutic antibodies.
“I would say the EPO generally thinks it is a routine thing to make antibodies, and they do not acknowledge the new structure of the antibody which leaves the applicant in an uphill battle. They do not recognise the structure of a new antibody is what makes it special and non-obvious over an existing antibody,” she says.
The human body produces antibodies naturally to protect itself from foreign agents. Another problem innovators face from patent offices as such is the notion that antibodies do not need protection because they are naturally occurring in nature.
“There is no reason why an antibody should be treated any differently than a small molecule,” says Crepin. “The therapeutic function of a designed antibody does not exist by itself in nature.
“We have several techniques for making antibodies on a large scale, and it is only after several tests that we arrive at the desired function. This is not done by nature or by chance.”
The chief IP counsel agrees and believes antibodies are more complex than patent offices consider them to be: “The basic notion is that making antibodies is routine. It is never that simple, but that is the perception of patent offices.”
Antibodies are enormously expensive to produce and innovators need to be able to protect these inventions to get a significant return on investment. Greater legal clarity on this matter in Europe – and the US to a lesser extent – will go a long way to helping drive innovation.
Protecting an antibody should not be as complicated as developing one.
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