by Chris Holman
A branded drug manufacturer can sometimes extend its exclusive right to market a drug by patenting a method of using the drug and successfully suing a potential generic competitor for infringement based on the premise that an instruction or warning appearing on the generic product’s label will induce doctors and/or patients to infringe the patent. In some cases, a generic company can skirt infringement by means of a “skinny label” that carves out the patented method, a practice that is the subject of a pending petition for certiorari in Teva v. GSK, as discussed by Dennis in a recent post (see an earlier post for a more detailed discussion of Teva and skinny labels).
In Teva, the drug is approved for the treatment of multiple indications, two of which are unpatented, and the generic company attempted to avoid infringement by carving out (unsuccessfully, absent Supreme Court intervention) an indication covered by the patent. In a case in which a patent covers a method of using the drug safely, as opposed to a new indication, the skinny label option is generally not available, and the generic product label will be required to closely track the label of the branded product. A remaining option for a generic company facing such a patent is to challenge it in a Hatch-Waxman proceeding and successfully argue that the patent claims are invalid and/or not infringed. An example of this appears in the Federal Circuit’s recent decision in Genentech v. Sandoz.
The active ingredient at issue in Genentech is pirfenidone, marketed by Genentech under the tradename ESBRIET. Pirfenidone was first studied as an investigational new drug in 1973. In 2004, the United States Food and Drug Administration (“FDA”) granted pirfenidone orphan drug status for treatment of patients with idiopathic pulmonary fibrosis (“IPF”), a chronic, irreversible lung disease. In 2008 it was approved for the treatment of IPF in Japan under the trade name of PIRESPA. Approvals in the European Union and Canada followed in 2011 and 2012, respectively.
When Genentech obtained approval to market pirfenidone (ESBRIET) in the U.S. in 2014, it was granted seven years of orphan drug exclusivity, which expired in 2021. However, Genentech still holds 19 Orange Book-listed patents purportedly covering ESBRIET. The patents were issued between 2009 and 2014, and expire between 2026 and 2033.
Sandoz submitted Abbreviated New Drug Applications (“ANDAs”) seeking approval from the FDA to market a generic version of pirfenidone, to which Genentech responded by bringing a Hatch-Waxman suit, asserting that Sandoz’s generic product would induce the infringement of five of the Orange Book-listed patents. The asserted patents do not claim pirfenidone itself, or the use of pirfenidone to treat IPF. Instead, the patents claim methods for managing certain side effects that can occur when using pirfenidone to treat IPF. The patents fall into two categories: the Liver Function Test (“LFT”) patents and the Drug-Drug Interaction (“DDI”) patents.
The LFT patents are directed to methods for administering pirfenidone to a patient who has exhibited abnormal biomarkers of liver function in response to pirfenidone administration. The asserted claims in these patents recite various options, including: (1) temporarily reducing the dose of pirfenidone and then returning to the full dose, (2) maintaining the full dose of pirfenidone, (3) reducing the dose of pirfenidone, (4) discontinuing pirfenidone for a week and then returning to the full dose, and (5) discontinuing pirfenidone for a week and then returning to a reduced dose.
The DDI patents are directed to methods for avoiding adverse interactions between pirfenidone and fluvoxamine, a drug that can interfere with drug metabolism. The three asserted DDI claims involve methods for administering pirfenidone to a patient taking fluvoxamine by either discontinuing fluvoxamine or modifying the dose of pirfenidone and continuing fluvoxamine.
The district court found the LFT patents invalid for obviousness over a 2005 publication reporting the results of clinicals trials involving the use of pirfenidone in patients with IPF (the “Azuma” reference), combined with the PIRESPA label and “known, standard medical practices.” Prior to reviewing the district court’s analysis, the Federal Circuit noted its:
initial perception that, as the district court noted, varying doses in response to the occurrence of side effects would seem to be a well-established, hence obvious, practice. Thus, claiming it as an invention would appear to be at best a long shot. The district court gave it careful scrutiny, however, as do we.
The Federal Circuit then proceeded to affirm the district court’s obviousness determination, stating that:
The asserted claims in the LFT patents do not represent the invention of a new drug, nor do they recite a novel application of an existing drug. Instead, these claims recite adjusting doses in the presence of side effects, which clinicians routinely do, and which would have been obvious in view of the prior art.
As to the DDI patents, the district court found that although warnings appearing on Sandoz’s proposed label appeared to encourage, recommend, and/or promotes infringement of the patents, there was insufficient evidence of direct infringement. The district court stated that:
Genentech had not shown that any patient would be prescribed both pirfenidone and fluvoxamine such that the methods of the DDI patents would even be relevant. [E]ven if an IPF patient were prescribed fluvoxamine, a physician would likely choose a non-infringing treatment adjustment over any of the claimed methods.
The Federal Circuit affirmed, noting that the evidence of record included testimony from physicians that, in their decades of treating IPF patients, they had never prescribed pirfenidone to an IPF patient taking fluvoxamine; and were they to find themselves in that position, they would choose a noninfringing response—i.e., prescribing nintedanib instead (nintedanib is another drug approved by FDA for the treatment of IPF).
Genentech argued that if an IPF patient needed fluvoxamine, instead of a doctor prescribing nintedanib to treat their IPF, the doctor could prescribe pirfenidone and an alternative to fluvoxamine. However, the court credited Sandoz’s expert testimony to the effect that:
a pulmonologist prescribing pirfenidone would not be able to alter another physician’s prescription of fluvoxamine or take over that aspect of the patient’s treatment. Therefore, the pulmonologist would prescribe nintedanib to be taken in conjunction with the patient’s preexisting prescription of fluvoxamine.
This was a split decision, with Judge Newman dissenting without offering an opinion.
“A branded drug manufacturer can sometimes extend its exclusive right to market a drug by patenting a method of using the drug”
I cannot believe that this sentence was written by someone in the IP field. Patents never provide the right to market a drug…..ugh! Who edited this piece?
“A branded drug manufacturer can sometimes obtain patents on novel methods of using a drug which it may use as the basis to successfully sue a potential generic competitor…”
Re this Genentech v. Sandoz cert petition on a patent on using an earlier-to-expire patented drug in combination with a known side-effect-reducing drug: yesterday the Gannett newspaper chain published an article attacking “patent evergreening” pharma patents by an economics prof claiming expertise in the economic effect of follow-on pharma patents on methods of use, salts versus liquids, etc. Further evidence of the political pressure the pharma industry is under on this issue.
The Pharma industry “under pressure” is not the same as the general attack of patents (notably in the Rest Of the innovation sphere).
I agree – the political pressure on the pharma industry which includes such attacks on “evergreening” is apparently primarily due to the high cost of drugs in the U.S. for Medicare and Medicaid taxpayers, and patients, after expiration of initial drug patents, and that seems to be unique to that particular industry.
Not to be disagreeable (for its own sake), but you are still off, Paul (my emphasis added):
“due to the high cost of drugs in the U.S. …, after expiration of initial drug patents,”
is a part of the fallacy.
It is well known that such coming off of a patent face a price (and Pharma profit) cliff.
ran into an odd filter message, so trying again:
Your comment is awaiting moderation.
December 28, 2022 at 10:44 am
Not to be d1s agreeable (for its own sake), but you are still off, Paul (my emphasis added):
“due to the high cost of drugs in the U.S. …, after expiration of initial drug patents,”
is a part of the fallacy.
It is well known that such coming off of a patent face a price (and Pharma profit) cliff.
Of course “It is well known that such coming off of a patent face a price (and Pharma profit) cliff ” – that is the precisely why it is a political hot topic. The “evergreening” argument is that the drug does NOT come off -patent due to additional patents of longer term related to the FDA-approved form of, or method of use of, the drug. There is no such political issue re other technologies.
Ah, we may well be talking past each other, as the problem is not the (accused) evergreening, but instead is the government not permitting a previous version (which was good enough earlier to exist in the market place aside along the improved variants.
Saying “patents are the Bad” is a fallacy (there are plenty of non-patent ‘Bad’ in the Pharma ecosystem).
“Judge Newman dissenting without offering an opinion.”
Weird.
“ as the district court noted, varying doses in response to the occurrence of side effects would seem to be a well-established, hence obvious, practice. Thus, claiming it as an invention would appear to be at best a long shot. ”
No doubt about it. And this is why so many claims attempt to “run around” this issue by “detecting” a “side effect” and using that step as a platform for arguing non-obviousness (sometimes by including a range of measured values in the claim as well). The problem with that approach, as we have seen, is eligibility. If the detection step is old (and ineligible), and the “dose-altering to avoid side effects” method is obvious (which it almost always is), the claim can be seen as an attempt to capture ineligible subject matter (detection using old detection method) in an obvious context.
Nice analysis, Prophet. Seems a no-brainer. Would have liked to know what Judge Newman’s reasoning is.
Malcolm’s “analysis” is as hackneyed as ever.
This is nothing more than his attempted parse of eligibility to individual claim elements (not taking the claim as a whole for eligibility evaluation), and is equivalent to his old “well this part is entirely within the human mind, let’s ignore the rest of the claim” gambit.
“well this part is entirely within the human mind, and we can ignore the rest of the claim which is in the prior art or totally obvious in view of the prior art”
Fixed for accuracy. If you have a problem with this, explain why. Alternatively, please just advocate for patents on methods of thinking about stuff and stop playing your silly derpity derp games.
You fixed nothing — and your error has been made evident to you countless times in that you seek to conflate the law as written by Congress with its separate sections of 101 and 103 as some willy nillly hodge-podge (getting both wrong in the process).
“Judge Newman dissenting without offering an opinion.”
Weird.
She has been doing this surprisingly often of late. I hate to say it, but I think that age is catching up with her.
Here’s a dissent without opinion from 1996.
link to scholar.google.com
Here’s one from 2014.
link to scholar.google.com
I’m aware of only 3 in the past year from Judge Newman. It’s not a common practice, but many other Federal Circuit judges have dissented without writing opinions. link to scholar.google.com
Comments are closed.