The Chicken Sandwich Conundrum: Parts is Parts . . . or Not

 Orange Book Insights No. 43 (revised Feb. 24, 2024): The Chicken Sandwich Conundrum: Parts is Parts . . . or Not

Parts may be parts (thinking back to that old Wendy’s commercial where they compared their chicken sandwich made solely from chicken breast meat to their competitor’s chicken sandwich that was allegedly made from various unknown parts of a chicken). However, all of the claims of Pat. No. 7500444 (‘444 patent) that Glaxo had listed in the Orange Book for their ADVAIR HFA (fluticasone propionate; salmeterol xinafoate) product, are directed to something called an “actuation indicator” which is nothing more than  a mechanical part of the ADVAIR HFA device rather than a drug!

Steve Auten had previously shared news about a November 7 FTC announcement that the FTC had submitted patent disputes to the FDA under 21 CFR 314.53(f) for patents that the FTC believes do not qualify for listing in the Orange Book. The FTC also sent the responsible drug manufacturers letters informing the manufacturers about FTC’s ineligibility opinions. You can download each of the letters sent by the FTC. I have additionally placed an alphabetical list of the products addressed by the FTC’s letters on the Orange Book Companion’s web site. Each link will take you to a list of the patents, in Orange Book Companion format, identified in the FTC letter. Each patent number in the list is a direct link to the patent at the USPTO’s Patent Public Search system.

Many of the patents identified by the FTC claim a part of a device, such as the “actuation indicator” claimed in the ‘444 patent mentioned above. The independent claim of the ‘444 patent is as follows:

1. An actuation indicator comprising a drums sub-assembly comprising a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, wherein the slipping clutch arrangement comprises a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl.

Glaxo identified the’444 patent to the FDA as a drug product (“DP”) patent. FDA regulations define the term “drug product” as:

a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo. 21 CFR 210.3(4)

So is claim 1 of the ‘444 patent directed to a “drug product” that is analogous to a tablet, capsule or solution and also contains an active ingredient? The answer to that question certainly appears to be “no.” The claimed invention, an actuation indicator, is a mechanical doohickey that does not contain an active ingredient, and certainly does not play any part in the delivery of an active ingredient to the patient as do tablets, capsules and solutions. Nor is claim 1 of the ‘444 patent directed to the ADVAIR HFA product for which Glaxo submitted NDA 021254. The actuation indicator in the Advair HFA may have something to do with the use of Glaxo’s ADVAIR HFA product by the patient, such as by mechanically displaying the number of doses administered from, or remaining in, the ADVAIR HFA.  But how can that be enough to identify the claimed “actuation indicator” doohickey of the ADVAIR HFA as a drug product?

Some comments to the FDA’s request for comments on patent listings (Fed. Reg. 85, 33169 (June 1, 2020) Docket No. FDA-2020-N-1127) distinguished parts of a device that the authors believed were “integral” to the delivery of the drug substance from those parts of a device that were somehow not integral. The comments submitted by Apotex proposed that patents claiming “integral” parts of a drug administration device should be eligible for listing in the Orange Book, while patents claiming non-integral parts should not be eligible:

FDA should be clear that device-oriented patents should only be listed if the device is included in the approved product and integral to use of the drug product, e.g., precise dosing or the device performs its own function other than drug delivery. [Apotex comments at 2].

A unanimous panel of judges from the 1st Circuit Court of Appeals do not agree with Apotex. The court’s opinion in the Lantus Direct Purchaser Antitrust Litigation, 950 F.3d 1 (1st Cir. 2020) held that a drive mechanism that was claimed in a patent and used in an injection device called the Lantus® SoloSTAR® could not be considered to be a “drug” even if the drive mechanism was an integral part of the injection device:

 

We see nothing in the statute or regulations that welcomes such a further expansion of the already stretched statutory terms, whereby an integral part of an injector pen becomes the pen itself, and in turn is a drug. Lantus at 8 (emphasis added). 

Moreover, on the following page of their opinion, the 1st Circuit panel applied the statute governing patent listings that is found in 21 USC 355(b)(1) that requires that the patent must be one that “claims the drug for which the applicant submitted the application” (emphasis added). Just for the sake of argument the Court allowed that even if the drive mechanism part might be considered to be a drug, the patent that claimed the part would still be ineligible for listing: since the patent did not claim the drug for which Sanofi filed the application, i.e., the LANTUS SoloSTAR:

 

More importantly, even assuming that the drive mechanism claimed by the ‘864 patent is itself a drug, we still find Sanofi falling short of its goal because the drive mechanism is not the “drug for which [Sanofi] submitted” the sNDA. 21 U.S.C. § 355(b)(1). For that reason alone, the patent for the drive mechanism does not a qualify for listing in the Orange Book as claiming the Lantus SoloSTAR.  Lantus at 9 (emphasis added).

So it seems that the FTC struck a nerve by including the ‘444 patent in their list. In Vol. 43, Supp 12 of the Orange Book, which was published not long after the FTC list was made public, the ‘444 patent was no longer listed. So I guess that Glaxo took another look at the ‘444 patent and concluded that the FTC might be right afterall.

While the FTC may be correct in questioning the eligibility of a lot of the patents that they had identified, I do not agree that they are correct for each and every one. One patent in particular seems likely to qualify for listing, even though it may take some analysis to come to that conclusion. That patent is Pat. No. 8,474,447 listed for Boehringer Ingelheim’s ATROVENT HFA (ipratropium bromide) inhaler. Independent claim 1 of the ‘447 patent generally defines the invention as a “hand-held device for metered dispensing of sprayable substances that are medicaments for inhalation.” In other words, the patent claims a handheld inhaler (a type of finished dosage form) that contains one or more medicaments (i.e., active drug ingredients), and so meets the “drug product” definition found in 21 CFR 210.3(4). 

The ATROVENT HFA label that was approved on August 30, 2012, prior to the listing of the ‘447 patent on May 28, 2015, describes the drug product as a metered dose inhaler made up of a stainless steel canister and a mouthpiece:

16 How supplied/Storage and Handling

ATROVENT HFA is supplied in a pressurized stainless steel canister as a metered-dose inhaler with a white mouthpiece that has a clear, colorless sleeve and a green protective cap (NDC 0597-0087-17). " (emphasis added).

The mouthpiece further acts to display the approximate number of remaining doses that may be dispensed from the canister:

The mouthpiece has an actuation indicator visible through a small window. The indicator typically moves during every 5 to 7 actuations. It displays the approximate number of actuations remaining in increments of 20, starting at "200" and decreasing until it reaches "0].

Once the labeled number of doses have been administered, the combined canister and mouthpiece that together constitute the ATROVENT HFA inhaler should be discarded:

The inhaler should be discarded after the labeled number of actuations has been used when the indicator displays "0". The amount of medication in each actuation cannot be assured after this point, even though the canister is not completely empty. [emphasis added].

Moreover, the “Instructions for Use” of the ATROVENT HFA inhaler that appear at the end of the label that was approved on August 30, 2012 describes the inhaler as a metal canister and mouthpiece as follows:

Inhaler Description

ATROVENT HFA Inhalation Aerosol (Figure 1) consists of a metal canister containing the medicine and a mouthpiece that releases the medicine from the canister.

Thus, the label makes clear that the approved drug product is the inhaler which is the canister that contains the active ingredient combined with the mouthpiece. So even though the patient may have to put the canister and mouthpiece together to form the final approved inhaler drug product claimed by the ‘447 patent, I believe that the ‘447 patent claims a drug product as defined in 21 CFR 210.3(4), and so is eligible for listing.

However, if your company has a patent listed that is directed to a specific doohickey built into your drug product, the patent should be looked at skeptically and delisted if there is no reasonable basis for concluding that the invention claimed by the patent is, itself, a “finished dosage form” that “contains an active drug ingredient.” So while “parts may be parts” when talking about chicken sandwiches, a part used within a finished dosage form should not automatically be looked at as a finished dosage form for Orange Book listing purposes.