January 14, 2025
On December 20 the Federal Circuit in Teva Branded Pharmaceutical Products R&D, Inc. (Teva) v. Amneal Pharmaceuticals (Amneal) affirmed the district court’s decision that medical devices were not listable in the Orange Book and Teva had improperly listed patents in the Orange Book and required Teva to remove them.
Medical devices which serve as both packaging for a drug and drug delivery device are considered by the FDA to be combination products treated as drugs for regulatory purposes. The FDA maintains the Orange Book which is a listing of patents for each approved drug which claims the drug (API) or drug product (finished dosage form), formulations or compositions, or methods of using such drug, 21 U.S.C. § 355(b)(1)(A)(viii). Since the FDA treated these combinations as a drug, companies have listed patents directed to such products in the Orange Book even though the patent claimed only the medical device and not the active drug, the “active pharmaceutical ingredient” (API), the component which treats the body.
The Orange Book lists all FDA approved drugs plus generic equivalents, if any, to put generic drug companies on notice of the patents allegedly protecting the product. When an application is filed with the FDA for a generic drug the applicant must certify that no patents are listed in the Orange Book, they are seeking for approval after the patents expire, or the generic product does not infringe the listed patents or the patents listed are invalid, the latter two are the “PIV notice”. A copy of the PIV notice must be provided to the patentee and if patent litigation is initiated within 45 days of receiving notice of the PIV notice, the approval of the generic application is stayed by the FDA for 30 months. This 30-month stay is often worth hundreds of millions of dollars and sometimes billions of dollars to the pharmaceutical company originally receiving FDA approval and listing the patent.
Examples of such combinations include injector pens, (GLP-1 agonists such as Wegovy®), prefilled syringes, oral metered inhalers, drug patches and IV bags. IV bags can be approved as a combination device with an API. In the case of IV bags the challenge is compatibility and drug life in the bag which is drug specific resulting in these patents claiming the API in combination with the bag. Similarly, the specific API and substrate in drug patches are of necessity claimed together since the invention resides in the combination. Oral metered inhalers are different since the drug is normally a powder and comparability with the inhaler is not normally an issue. The issue lies in delivery of consistent API dosages which is independent on the drug composition but dictated by drug particle size in the powder plus other physical properties. In theory an inhaler can be used with different APIs if the powder flow properties and particle sizes are similar. While the inhalers are often designed for a specific API the potential of other applications has led many patent attorneys to draft the inhaler applications without limitation as to the API. While often the inhaler application will list possible APIs for combining with the inhaler, often the claims do not recite a specific API. It is these patents which, when listed in the Orange Book, have drawn the ire of the FTC. See blog post here.
Teva obtained a number of patents protecting portions of the inhaler used with its ProAir® HFA Inhalation Aerosol approved October 29, 2004, “for the use of albuterol sulfate HFA Inhalation Aerosol for the treatment or prevention of bronchospasm with reversible obstructive airway disease in adults and children 12 years of age or older.” The ProAir® combines albuterol sulfate (the active ingredient) with a propellant, ethanol, and an inhaler device to administer the drug. Teva listed nine patents in the Orange Book for its ProAir® HFA. Five are relevant here: U.S. Patent Nos. 8,132,712 (“the ’712 patent”), 9,463,289 (“the ’289 patent”), 9,808,587 (“the ’587 patent”), 10,561,808 (“the ’808 patent”), and 11,395,889 (“the ’889 patent”). They expire in 2028, 2031, or 2032. All five patents claim improvements in the inhalation device; none claim the inhaler in combination with albuterol sulfate. The patent on albuterol sulfate, U.S.P. 6,451,289 expired on March 22, 2021. Teva was using the inhaler patents to protect its product.
The listing statute, 21 U.S.C. § 355(b)(1)(A)(viii)(I), provides:
(A) Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a). Such persons shall submit to the Secretary as part of the application—
. . .
(viii) the patent number and expiration date of each patent for which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use, or sale of the drug, and that—
(I) claims the drug for which the applicant submitted the application and is a drug substance (active ingredient) patent or a drug product (formulation or composition) patent; or
(II) claims a method of using such drug for which approval is sought or has been granted in the application. (Parentheticals added in 2020) [Emphasis added]
The ’712 patent claims the inhaler with specific emphasis on the dose counter and mentions in the specification some specific inhalation drugs including salbutamol, the international name for albuterol. The other patents are silent on the drugs to be administered except by reference to the metered dose inhaler which implies an active drug is present in the device. None of the patents have a claim which includes albuterol or any other drug. Since the inhalers were reviewed in the FDA as drugs, Teva asserted that it could list them in the Orange Book. While none of Teva’s patents had a claim to albuterol sulfate, Teva considered that since the FDA had reviewed its product including the metered inhaler as a drug, it could properly list the patents.
After Amneal filed its ANDA application for ProAir® HFA Inhalation Aerosol, Teva initiated a patent infringement action under 35 U.S.C. 271(e)(2) in New Jersey District Court and Amneal counterclaimed in part to have the listed Teva patents delisted from the Orange Book and for unfair competition because of the improper listing of the patents. Teva moved to dismiss both of these counterclaims which the district court denied. The district relied on two previous appellate decisions in the First and Second Circuits. In Cesar Castillo, Inc. v. Sanofi-Aventis U.S., LLC (In re Lantus Direct Purchaser Antitrust Litig.), 950 F.3d 1, 3 (1st Cir. 2020), the First Circuit rejected an argument that § 355 authorized listing patents that claim only a component of the drug:
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 NDA. 21U.S.C. § 355(b)(1). For that reason alone, the patent for the drive mechanism does not qualify for listing in the Orange Book as claiming the Lantus SoloSTAR.
. . .
The statute and regulations clearly require that only patents that claim the drug for which the NDA is submitted should be listed in the Orange Book. The ‘864 patent, which neither claims nor even mentions insulin glargine or the Lantus SoloSTAR, does not fit the bill.
Teva had argued that since it had a reasonable argument that the Amneal product, metered inhaler plus albuterol sulfate, infringed its patent claims, it was entitled to list its patents in the Orange Book. It ignored that its patent claims did not include the albuterol sulfate and, thus, did not claim the product for which it sought approval, albuterol sulfate plus the inhaler. Teva also argued that since its patent claims could be infringed by the Amneal product (or any other generic), the listing was proper.
This argument had been torpedoed a second time by the Second Circuit in United Food & Commercial Workers Local 1776 v. Takeda Pharmaceutical Co., 11 F.4th 118 (2d Cir. 2021), relied upon by the district court. In United. The court concluded “although the concepts are closely related, ‘the plain meaning of “claims” is not the same as the plain meaning of infringement.’” 11 F.4th at 134. Teva had attempted to conflate the two.
The Federal Circuit in a lengthy opinion affirmed the district for essentially the reasons cited by the First and Second Circuits only with substantially more verbiage.
The solution to the dilemma facing companies like Teva which are attempting to patent the device portion of a combination product is to include at least one claim to the combination of the device portion and the API. This requires listing the API in the specification as Teva did in the’712, but also reciting it as a claim limitation in at least one claim. Where the device can be used for more than one API, one can claim them in a Markush claim along with medical device. In the case of a metered inhaler, the claim could add the drug container containing the drug or Markush group of drugs. For patents already issued which only list the drugs in the specification, a narrowing reissue could be filed adding a claim which contains the API as a further claim limitation. Since it’s a narrowing issue, it can be added after the two-year limitation on a broadening reissue has expired. There is no requirement that all claims in a listed patent must meet the statutory requirement; one is sufficient. The key is to have a claim with the API as a limitation.
