Expanding the "on-sale bar" for patents, the U.S. Court of Appeals for the Federal Circuit invalidated two patents protecting The Medicines Co.'s (MDCO) big-hitter Angiomax.

While Thursday's ruling in The Medicines Co. v. Hospira Inc. is a loss for MDCO, it also could give drug- and device-makers pause about how they draw up "experimental" manufacturing contracts involving yet-to-be-filed process claims.

What tripped the Angiomax product-by-process claims was MDCO's payment to contract manufacturer Ben Venue Laboratories to produce three batches of the drug as part of an "optimization study" and to prove to the FDA that the drug met the agency's approved specifications for finished bivalirudin, according to the Federal Circuit decision.

The process claimed in the patents filed in 2008 was a solution to a problem the Parsippany, N.J.-based drugmaker had experienced a few years earlier when Ben Venue produced a batch of bivalirudin with levels of Asp9-bivalirudin impurity exceeding the FDA's approved maximum of 1.5 percent. A consultant the company hired discovered that adding a pH-adjusting solution during the compounding process would minimize the impurity to less than 0.6 percent.

Although MDCO had successfully validated the process in a previous study, it identified several opportunities for further optimization, which led to the optimization study with Ben Venue, according to the court. In producing the study batches, valued at more than $10 million each, Ben Venue used the process more than a year before patents were filed to protect it.

The new batches were marked with a commercial product code and a customer lot number. While one batch was "released" to MDCO for commercial and clinical packaging, it remained at Ben Venue pending shipping instructions, the court said. Release of the other two batches was pending validation.

MDCO "paid Ben Venue for performing services that resulted in the patented product-by-process, and thus a 'sale' of services occurred," the Federal Circuit maintained. The decision overturned a lower court that had determined the manufacturing invoices were not a commercial sale because the manufacturing was primarily for an experimental purpose.

Likewise, MDCO asserted that the invoices didn't meet the on-sale bar because it hadn't reduced the invention to practice at that time. The company didn't "appreciate the maximum impurity level limitation of the claimed invention until after 25 batches of bivalirudin were manufactured according to the . . . new process," the appeals court acknowledged.

But if a product offered for sale inherently possesses the limitations of the patent claims, then the invention is on sale, even if the parties don't recognize that it has the claimed characteristics, the court explained. "Experimental use cannot occur after a reduction to practice," it added.

The court carved out possible experimental use exceptions to the on-sale bar. If an inventor is unaware that an invention meets the intended purpose and continues to experiment, then the experimental use defense may be valid, the Federal Circuit said.

Also, "when an evaluation period is reasonably needed to determine if the invention will serve its intended purpose, the . . . bar does not start to accrue while such determination is being made," the court noted.

The Federal Circuit did uphold the lower court's finding that the claimed invention was "ready for patenting" at the time of the manufacturing invoices. MDCO had appealed that finding, arguing that there was no reduction to practice and no drawings or written descriptions to enable a person skilled in the art to practice the invention.

That doesn't matter, the appellate court said. Because the invention was sold via the manufacturing invoices, the batches produced by Ben Venue reduced the claims to practice, making the invention ready for patenting.

GENERIC COMPETITION

Although the two patents invalidated by the Federal Circuit's ruling weren't set to expire until 2028, MDCO was preparing for generic Angiomax competition in a few years. It had agreements that would have allowed two drugmakers to launch the anticoagulant generics in 2019. Thursday's decision will clear the way for more competition much earlier.

MDCO also has been acquiring and developing other products to help weather the impact Angiomax generics would have on its bottom line. Last year, Angiomax delivered $599.5 million in U.S. sales, which comprised nearly 83 percent of the company's global net revenue, according to MDCO's 2014 annual report.

The company is evaluating the Federal Circuit's decision and considering its next steps, MDCO CEO Clive Meanwell said. In the meantime, it's focusing on this month's launch of Kengreal (cangrelor), a platelet inhibitor that won FDA approval a few weeks ago. It also is working on the launch and launch preparations for Orbactiv (oritavancin), a new formulation of Minocin (minocycline) for injection and Ionsys, a patient-controlled analgesia system for fentanyl delivery. (See BioWorld Today, June 23, 2015.)