April 13, 2023
Authored and Edited by Taylor L. Stark; Elliot C. Cook; Stacy Lewis†
In Amphastar Pharms., Inc. v. Aegis Therapeutics, LLC, Amphastar filed a Petition for inter partes review (“IPR”) of claims 1–20 of Aegis’s U.S. Patent No. 10,682,414 (“the ’414 patent”). The ’414 patent is directed to intranasal epinephrine formulations and methods of treating anaphylaxis. Challenged claim 1 presents a method of treating a systemic allergic reaction in a mammal by administering a pharmaceutical nasal spray comprising epinephrine or an epinephrine-containing salt. IPR2021-01324, Paper 43, at *4. That claim reads as follows:
1. A method of treatment of a type-1 hypersensitivity reaction in a mammal comprising administering intranasally to the mammal in need thereof an aqueous nasal spray pharmaceutical formulation; wherein the aqueous nasal spray pharmaceutical formulation comprises
an anaphylaxis active ingredient, wherein the anaphylaxis active ingredient consists of between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof in a single dose.
Claim 3, which depends from claim 1, reads as follows:
3. The method of claim 1, wherein:
intranasal administration of the single dose of the aqueous nasal spray pharmaceutical formulation to the mammal provides a plasma epinephrine concentration that is efficacious for the treatment of anaphylaxis.
The ’414 patent’s specification describes sample formulations and the results of two clinical studies. Id. at *4. The first of these studies compared epinephrine bioavailability after intranasal and intramuscular administration of formulations containing 0.3 mg epinephrine. Id. The second clinical study identified an optimized dosage for the intranasal administration of epinephrine-containing formulations and compared epinephrine bioavailability resulting from this optimized dose to the bioavailability resulting from an intramuscular dose. Id. The results of this second study indicated that “1.0 mg intranasal epinephrine can be formulated to be highly similar to or better than a 0.3 mg intramuscular injection of epinephrine.” Id. at *5.
The Board instituted review on § 102 and § 103 grounds based on the Potta, Maggio, Munjal, and Srisawat references. Id. at *7.
The Board determined that Amphastar adequately demonstrated that Potta anticipates claims 1, 2, and 7–17, but not claims 3–6 and 18. Id. at *20.
Regarding claim 1, the Board found that Potta discloses the intranasal administration of aqueous spray pharmaceutical formulations to humans for systemic allergic reactions like anaphylaxis. Id. at *21. The Board found that Potta “teaches 1% w/w aqueous epinephrine formulations . . . and a preference for intranasal administration,” teachings that it “echoes” in its claim 21. Id. In addition, Potta presents methods for treating anaphylaxis using its formulations and dosing adults with seasonal allergies with intranasal formulations containing 3 mg and 6 mg epinephrine. Id. at *22–23. Aegis argued that Potta did not anticipate claims 1, 2, and 7–17, but the Board found those arguments either not timely raised or unpersuasive. Id. at *23–27.
Regarding claims 3–6 and 18, the Board found that, because Potta did not discuss the actual administration of the formulations, Amphastar could not rely on Potta to anticipate dependent claims setting forth elements relating to how the formulations would be metabolized upon their administration (e.g., plasma epinephrine concentration). Id. at *28. To this point, the Board particularly noted that Amphastar’s declarants struggled to “articulate what the plasma epinephrine concentration of Potta[’s] . . . formulations would be if they were administered,” indicating that Potta included no such disclosure. Id. The Board further rebuffed Amphastar’s attempts to rely on inherent anticipation to argue that a certain plasma epinephrine concentration would “inevitably” or “necessarily” result upon the administration of Potta’s formulations, finding that the Petition and Amphastar’s initial expert declarations did little more than present unsupported conclusions that entirely failed to explain why “administ[ering] Potta’s formulations would necessarily result” in the claimed plasma epinephrine concentration. Id. at *28–30. The Board declined to credit Amphastar’s belated attempts to bolster its inherency argument with new arguments concerning cited prior art and new expert testimony presented in its Reply, noting that such arguments were untimely and/or insufficiently presented and, in any event, were unpersuasive. Id. at *35–36.
The Board determined that claims 1, 2, 7–9, and 11–17 were unpatentable as obvious over Potta, Maggio, and Munjal. Id. at *36. However, the Board concluded that claims 3–6, 10, and 18–20 were not unpatentable over this combination of references. Id. The Board also determined that claims 3–6 and 18–20 were not obvious in view of Srisawat, Maggio and Munjal. Id.
Regarding claims 1, 2, 7–9, and 11–17, the Board found that skilled artisans would have recognized the drawbacks of intramuscular injections to treat anaphylaxis and, in view of those drawbacks, “would have been motivated to use alternate means of epinephrine administration” (e.g., intranasal administration). Id. at *37–38. The Board also noted that skilled artisans developing an intranasal epinephrine spray would have attempted to prepare a fast-acting dose that appropriately optimized the formulation’s efficacy with its potential side effects. Id. at *38. And the Board found that skilled artisans would have accounted for epinephrine’s “dose-dependent side effects and narrow therapeutic window” (i.e., the fact that epinephrine’s efficacious doses are very close to doses that would be toxic) by optimizing nasal formulations incorporating low doses of epinephrine, such as the ones Potta teaches. Id. at *39–40. In the Board’s view, this supported the conclusion that a skilled artisan would have been motivated to optimize Potta’s low-dose intranasal formulations through the inclusion of additional components (e.g., absorption enhancers like DDM), and would have had a reasonable expectation of success in doing so. Id. at *40–41.
The Board also found that (1) Amphastar demonstrated sufficient motivation to combine the teachings of Potta, Maggio, and Munjal to pursue epinephrine formulations falling within the claimed dose range, id. at *41–46; (2) Amphastar adequately established a motivation to add DDM to Potta’s formulations and a reasonable expectation of success in doing so, id. at *46–56; (3) Aegis failed to demonstrate a long-felt but unmet need for the claimed invention (as it could not establish that prior formulations such as Potta’s had not already met such a need), id. at *56–59; and (4) Aegis failed to show that the nontoxicity of its invention was unexpected in view of the closest prior art available, id. at *59–61. Accordingly, the Board concluded that Amphastar sufficiently demonstrated that claims 1, 2, 7–9, and 11–17 were unpatentable as obvious over the combination of Potta, Maggio, and Munjal. Id. at *61–63. However, the Board concluded that Amphastar’s arguments as to the obviousness of claim 10 in view of the same combination of references were insufficiently presented in the Petition and could not be supplemented after institution to prove the claim unpatentable. Id. at *63–65.
As for Amphastar’s grounds against claims 3–6 and 18 based on Potta, Maggio, and Munjal, the Board noted that Amphastar again attempted to rely on inherency to show that the plasma epinephrine concentration element would have been obvious. Id. at *65–66. However, the Board concluded that Amphastar again failed to establish that the inclusion of DDM in Potta’s low-dose epinephrine formulations would have necessarily resulted in the plasma epinephrine concentration claimed, and therefore did not prove claims 3–6 and 18 obvious under this combination of references. Id. at *66–68. The Board found Amphastar’s obviousness grounds against claims 3–6 and 18–20 based on the combination of Srisawat, Maggio, and Munjal similarly unpersuasive for essentially the same reasons. Id. at *68–72.
Finally, Amphastar argued that because the challenged exhibits and portions of Aegis’s expert declarations post-dated the ’414 patent’s priority date, they were “irrelevant and prejudicial.” Id. at *72–73. The Board explained that (1) post-priority date evidence was not prohibited under any rule and is permissible in particular situations, and (2) the Board had accounted for the fact that the evidence at issue post-dated the priority date. Id. Consequently, the Board denied the Motion to Exclude. Id. at *73.
If you are planning to file an IPR petition, keep in mind that you, as the petitioner, bear the burden to prove unpatentability by a preponderance of the evidence. This burden never shifts to the patent owner. Importantly, too, this burden can only be satisfied by arguments and associated evidence that you present in your IPR petition. If you come up with a new theory or means to supplement an existing theory after filing your petition, you typically cannot supplement your initial arguments in your reply, at oral argument, or otherwise.
Additionally, if you intend to rely on inherency to support an anticipation or an obviousness theory, remember that establishing inherency is a high bar—one that requires you to demonstrate that the element would necessarily exist or result as a consequence of the teachings of the relevant reference. Inherency is not established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient. If, however, the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient. Continental Can Co. USA, Inc. v. Monsanto Co., 948 F.2d 1264, 1267-69 (Fed. Cir. 1991) (quoting In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)).
Finally, this case demonstrates how functional claiming may be utilized to impart patentability. The claim limitation of “provides a plasma epinephrine concentration that is efficacious for the treatment of anaphylaxis” could possibly have been written in means-plus-function format also. Either way, this functional requirement meant that the claim survived the IPR challenge.
†Stacy Lewis is a Law Clerk at Finnegan.
Copyright © 2023 Finnegan, Henderson, Farabow, Garrett & Dunner, LLP.
DISCLAIMER: Although we wish to hear from you, information exchanged in this blog cannot and does not create an attorney-client relationship. Please do not post any information that you consider to be personal or confidential. If you wish for Finnegan, Henderson, Farabow, Garrett & Dunner, LLP to consider representing you, in order to establish an attorney-client relationship you must first enter a written representation agreement with Finnegan. Contact us for additional information. One of our lawyers will be happy to discuss the possibility of representation with you. Additional disclaimer information.
June 10-12, 2024
San Francisco
Lecture
Patent Protection for Software-Related Inventions in Europe and the USA Training Course
June 5, 2024
Hybrid
Due to international data regulations, we’ve updated our privacy policy. Click here to read our privacy policy in full.
We use cookies on this website to provide you with the best user experience. By accepting cookies, you agree to our use of cookies. Please note that if you opt not to accept or if you disable cookies, the “Your Finnegan” feature on this website will be disabled as well. For more information on how we use cookies, please see our Privacy Policy.
Finnegan is thrilled to announce the launch of our new blog, Ad Law Buzz, devoted solely to breaking news, developments, trends, and analysis in advertising law.