This Shield of Patents Protects the World’s Best-Selling Drug

Over Humira’s lifetime, AbbVie has secured more than 100 patents to prevent anyone from attempting to copy the biologic, with $16 billion in annual sales.

By Cynthia Koons

Humira, a treatment for inflammatory diseases such as rheumatoid arthritis and psoriasis made by AbbVie Inc. is the planet’s best-selling drug. It’s also been around almost 15 years. Those two facts alone would normally have rival drugmakers eagerly circling, ready to roll out generic versions that could win a piece of the aging medicine’s $16 billion in annual sales. Yet last year, when the patent on Humira’s main ingredient expired, not a single competitor launched a copycat version. Figuring out how to manufacture it wasn’t the obstacle. The real challenge was the seemingly impregnable fortress of patents AbbVie has methodically constructed around its prized moneymaker.
The more than 100 patents AbbVie has secured over Humira’s lifetime make it difficult for another company to replicate the drug without using processes and techniques to which the pharma giant continues to hold rights. Many of those patents were issued over the past few years as the expiration of Humira’s main patent grew closer. Typical drugs, made through chemical synthesis, usually have no more than a dozen or so patents, if that. But biologic medicines such as Humira, which accounts for more than 60 percent of AbbVie’s revenue and can carry a list price of more than $50,000 per patient, are typically made in living cells rather than chemically manufactured. That process often involves more steps and a higher level of complexity, which opens the door to more potential steps to patent. What’s more, companies can claim any changes to their drugs over the years—say, using a slightly different medium in which to grow cells or adjusting the dosing—warrant new legal protections that can keep generic competitors at bay.

If you have a $16 billion-a-year drug, “every month is a good month that you’re on market alone,” says Mike Fuller, chair of the biotechnology practice group at law firm Knobbe Martens. “So you’re going to spend whatever it takes to be as aggressive as possible and get as many patents as possible.”

AbbVie’s not the only one relying on patents to protect popular biologic medications. Johnson & Johnson’s Remicade, for instance, is another blockbuster anti-inflammatory biologic drug with more than 100 patents. But AbbVie has been especially outspoken about its strategy. After seeing it laid out in a company presentation, Ronny Gal, a research analyst for Sanford C. Bernstein & Co., said at a conference of makers of biosimilars (generic-like drugs, in biologic drug parlance) last fall: “I’m pretty sure every CEO in biopharma sent that to their head of IP [intellectual property] and said, ‘Can we do that?’ ”

While most drugmakers have been frightened off, Amgen Inc. has decided that the prize is too rich not to try breaching AbbVie’s patent defenses. Amgen is in the first wave of what’s likely to be a protracted legal battle with AbbVie to launch a biosimilar version of Humira in the U.S. AbbVie has filed suit in federal court in Delaware to block the effort, insisting that Amgen has violated 61 patents. The trial for the first 10 is set for late 2019. “The AbbVie vs. Amgen case is very interesting to a lot of us because it’s the first time the patent thicket strategy has been tried in biologics litigation” in the U.S., says Robert Cerwinski, a partner at law firm Goodwin Procter. “The sheer number of patents does not guarantee success.” German drugmaker Boehringer Ingelheim GmbH has also started to develop its own version of Humira, to which AbbVie has responded by filing suit, arguing that Boehringer infringed on 74 Humira patents.

In a statement in response to questions about this story, AbbVie spokeswoman Adelle Infante said that Humira “represents true innovation in the field of biologics and is protected by a strong portfolio of intellectual property.” When asked about patent challenges on an investor conference call earlier this year, Chief Executive Officer Rick Gonzalez suggested it won’t be easy for a competitor to defeat Humira’s intellectual property. “The strategy that we have in place is not one that hinges on one or two patents,” he said.

In a presentation by AbbVie in October 2015, a slide titled “Broad U.S. Humira Patent Estate” detailed its strategy: patents covering every aspect of the drug’s life, from its origins to the diseases it’s approved for. The company listed 22 patents for various diseases or methods of treatment, 14 on the drug’s formulation, 24 on its manufacturing practices, and 15 “other” patents. The latest expiration date is 2034—providing more than double the protection span a drug such as Humira might normally expect. “Congress had extensive discussion about how long should biologics get exclusivity before they get competition,” says Jeff Francer, general counsel at the Association for Accessible Medicines, the lobbying group formerly known as the Generic Pharmaceutical Association. “They settled at 12 years, and if you take 12 years from when Humira was approved, that brings you to 2014, so they’re now trying to get that extended to 2034.”

The Humira patents, often with arcane names and descriptions, cover everything from what’s inside the drug to how it’s dosed. For example, a patent called the Fed-Batch Method of Making Anti-TNF-Alpha Antibody protects the way AbbVie produces an antibody used in a cell culture medium with a specific pH, Cerwinski says.

If the science behind the patents appears exotic to the nonscientist, the legal strategy is easy to grasp. In 2014, for instance, AbbVie stepped up its pace of patent filings in advance of last year’s expiration of its main patent. A review of Humira’s patents by the Association for Accessible Medicines shows the drugmaker has been obtaining patents at a feverish clip in recent years: 21 in 2016 and 32 in 2015. “There’s a lot of innovation in biologics and in biologic manufacturing,” says Fiona Scott Morton, professor of economics at Yale. “Of graver concern is that this multistep process of making biologics can be patented. The firm can strategically choose when to file.”

Still, AbbVie isn’t home free. A rival drugmaker can technically launch a biosimilar version of Humira while patents are still outstanding, a practice known as launching “at risk.” Should a court find the biosimilar drugmaker in the wrong in that scenario, the company would end up owing substantial damages. But if courts rule the other way, AbbVie could suffer a breach in its patent armor that likely would invite other companies to challenge its drug’s hegemony—and could lower prices.

Until that happens, though, AbbVie continues to rake in big Humira bucks. U.S. sales in the most recent quarter were up 18 percent, to $3.2 billion in the three months ended June 30, from a year earlier.

“It is that portfolio of patents that provides us confidence that ultimately we can protect the position which Humira based on all the innovation that we’ve done and the investment we’ve made,” said CEO Gonzalez.

— With assistance by Caroline Chen

This entry was posted in Biologics/Biosimilars, Uncategorized. Bookmark the permalink.

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