Teaching Old Drugs New Tricks



First, a couple of comments on Supplement 9 (September) of Orange Book Volume 39 (2019):

There were 60 new patents listed, including one process patent. The process patent, 8,318,201, was listed for NOURIANZ (istradefylline) from Kyowa Kirin. All six claims are directed to “[a] method for suppressing formation of impurities due to dimerization” through “the step of providing iron oxide in the solid formulation.”

Genus Lifesciences listed another patent (10,413,505) for its cocaine hydrochloride product, GOPRELTO. It is the third method patent listed for GOPRELTO that is directed to a method of inducing local anesthesia. A fourth method patent listed for GOPRELTO is directed to a method of administering a local anesthetic.

Meanwhile, Hyman, Phelps & McNamara’s FDA Law Blog has a report from contributor Sara Koblitz about a new controversy concerning GOPRELTO. Genus Lifesciences is taking issue with the FDA’s acceptance of a second submission under 505(b)(2) from Lannett Company following GOPRELTO’s receipt of NCE exclusivity. The FDA had issued a Complete Response Letter (“CRL”) for Lannett’s initial 505(b)(2) application that had been filed prior to GOPRELTO’s receipt of NCE exclusivity. Read Ms. Koblitz’s report for all of the details, including the FDA’s rationale for accepting Lannett’s post-CRL submission despite their intervening grant of GOPRELTO’s NCE exclusivity.

Teaching old drugs new tricks

So how many ways can one claim (and get new patents) covering the treatment of pain and fever with an old drug known for its activity in treating pain and fever? The drug in question is acetaminophen (paracetamol in many places outside the U.S.). Acetaminophen is most famously known in the U.S. under the trademark TYLENOL® which is currently owned by J&J. And the answer to my question is apparently “many” since a new patent (10,383,834) claiming the use of acetaminophen for treating pain and fever was issued in August 2019 and listed in the Orange Book the following month.

The acetaminophen product in question is OFIRMEV from Mallinckrodt Hospital Products, and it is a solution for intravenous administration. The newly issued ‘834 patent was actually the fourth patent listed by Mallinckrodt in the Orange Book from the same patent family that are all directed to variations of treating pain and fever with intravenous acetaminophen. However, it was while I was categorizing the claims of newly listed patents for Supplement 9 of my Orange Book Companion® that I finally took notice of the indications that were being covered by the ‘834 patent and its earlier family members. Acetaminophen for treating pain? For treating fever? Those indications are practically ancient, right? So how did they get those four patents?

The key was keeping the claims narrow. Apparently, the state of the art for intravenous acetaminophen administration was 1000mg at six hour intervals. The specification of 9,399,012, the first patent in the ‘834 patent’s family to be issued and listed in the Orange Book, says that this regimen was used “to minimize the potential for hepatotoxicity.” [Col. 3, line 16]. The regimen claimed in the ‘012 patent is directed to doses of less than 1000mg which are given at intervals of less than six hours. The claimed regimen is meant to reduce a drop off in efficacy that might occur during the prior art six-hour waiting period.

The broadest claim in the ‘012 patent, is:
  • 1. A method for the treatment of pain or fever in an adult human or an adolescent human subject weighing at least 50 kg, in need thereof, comprising administering to the subject, by an intravenous route of administration, a therapeutically effective amount of a pharmaceutical composition comprising about 550 mg to about 800 mg of acetaminophen; and repeating said administration at least once at an interval of about 3 to about 5 hours.
The issuance of the ‘012 patent followed a lengthy prosecution (over seven years!), and was finally obtained through the submission of a declaration supporting the unexpected efficacy of the claimed lower dose/shorter dosing interval. As stated by the Examiner in her “Reasons for Allowance”:
  • The unexpected benefits in the declaration of producing analgesic and fever-reducing effect by using the herein claimed dosing regimen of intravenous acetaminophen is not taught or fairly suggested by the prior art.
So through perseverance and determination, it is possible to teach an old drug new tricks! The allowance of the later-issued three patents in the family were all obtained without incident by filing terminal disclaimers over the ‘012 patent.

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