PTAB Denies Challenge Of Abbvie Humira Patents

19 January 2016 PharmaPatents Blog

The USPTO Patent Trial and Appeal Board (PTAB) denied institution of two Inter Partes Review challenges brought by Amgen, Inc. against two Humira patents covering stable formulations of anti-human Tumor Necrosis Factor alpha antibodies. The PTAB decisions illustrate the potential importance of establishing unpredictability in the field when defending against obviousness challenges.

The Humira Patents At Issue

The patents at issue were U.S. Patent 8,916,157 and U.S. Patent 8,916,158, assigned to AbbVie Biotechnology Ltd.

Claim 1 of the ‘157 patent recites:

1. A stable liquid aqueous pharmaceutical formulation comprising
(a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,
(b) a tonicity agent,
(c) a surfactant, and
(d) a buffer system having a pH of 4.0 to 8.0,
wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7.

Claim 1 of the ‘158 patent recites:

1. A stable liquid aqueous pharmaceutical formulation comprising
(a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, or an antigen-binding portion thereof, at a concentration of 20 to 150 mg/ml,
(b) a polyol,
(c) a surfactant, and
(d) a buffer system having a pH of 4 to 8,
wherein the antibody comprises the light chain variable region and the heavy chain variable region of D2E7.

Unpredictability Forecloses Obviousness

In its petitions, Amgen asserted that certain claims of both patents were invalid as obvious in view of (i) Lam and Barrera or (ii) Salfeld and Heavner. Taken together, the asserted references appear to disclose each aspect of the claimed formulations, but AbbVie convinced the PTAB that the preparation of stable liquid aqueous formulations of antibodies at the recited concentration was an unpredictable undertaking:

[O]n this record, we are not persuaded that the prior art provided sufficient guidance such that a skilled artisan would have had a reasonable expectation of success in arriving at the formulation of stable, liquid pharmaceutical compositions comprising antibodies at a concentration of 20 to 150 mg/ml.

For example, Amgen fails to direct us to a commercially available antibody product that was available in liquid form, within the claimed antibody concentration range. As noted above, REMICADE™ was sold in lyophilized form, and its product information indicated it should be used within three hours of liquid reconstitution. …. In other words, REMICADE™ was not a stable liquid antibody formulation.

Further, Amgen does not persuade us that the Wang article “provide[d] guidance on how to formulate such composition” … to a sufficient degree to have provided a skilled artisan at the time with a reasonable expectation of success to arrive at the claimed composition. Although the Wang article indeed provides general guidance, the Wang article also underscores the unpredictability of the undertaking. See Ex. 1017, 2 (noting that “the structural differences among different proteins are so significant that generalization of universal  stabilization strategies has not been successful”). …. [Under the applicable burden of persuasion,] Amgen has not persuaded us that Wang provides a reasonable expectation of success in making stable liquid antibody formulations as a general matter. In contrast, we agree with AbbVie that, on the whole, Wang suggests a high degree of unpredictability in the antibody formulation art.

Turning to the asserted references, the PTAB did not find sufficient guidance to support the selections required to arrive at the claimed formulations or a basis for finding a reasonable expectation of success. Thus, the PTAB refused to institute Inter Partes Review of these Humira patents.

Be Careful What You Wish For 

Unlike the world of small molecule drugs where most companies consider themselves to be primarily an “innovator” or a “generic” company, in the world of biologics the same companies are leading the way on both sides of the originator/biosimilar divide. In this case Amgen likely was trying to clear the patent landscape for its own biosimilar of Humira, but Amgen is the BLA holder/patent holder in the first case where the Federal Circuit interpreted the biosimilar patent dispute resolution procedures of the Biologics Price Competition and Innovation Act (BPCIA). While the PTAB didn’t comment on it in its decisions, AbbVie argued in its Patent Owner Preliminary Responses that Amgen’s arguments regarding obviousness and likelihood of success were inconsistent with positions Amgen took when pursuing its own antibody formulation patents. The probability of finding themselves on both sides of antibody/biosimilar disputes may make companies more cautious about the positions they advance, or at least pause to consider the potential implications when they are on the other side.

This blog is made available by Foley & Lardner LLP (“Foley” or “the Firm”) for informational purposes only. It is not meant to convey the Firm’s legal position on behalf of any client, nor is it intended to convey specific legal advice. Any opinions expressed in this article do not necessarily reflect the views of Foley & Lardner LLP, its partners, or its clients. Accordingly, do not act upon this information without seeking counsel from a licensed attorney. This blog is not intended to create, and receipt of it does not constitute, an attorney-client relationship. Communicating with Foley through this website by email, blog post, or otherwise, does not create an attorney-client relationship for any legal matter. Therefore, any communication or material you transmit to Foley through this blog, whether by email, blog post or any other manner, will not be treated as confidential or proprietary. The information on this blog is published “AS IS” and is not guaranteed to be complete, accurate, and or up-to-date. Foley makes no representations or warranties of any kind, express or implied, as to the operation or content of the site. Foley expressly disclaims all other guarantees, warranties, conditions and representations of any kind, either express or implied, whether arising under any statute, law, commercial use or otherwise, including implied warranties of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Foley or any of its partners, officers, employees, agents or affiliates be liable, directly or indirectly, under any theory of law (contract, tort, negligence or otherwise), to you or anyone else, for any claims, losses or damages, direct, indirect special, incidental, punitive or consequential, resulting from or occasioned by the creation, use of or reliance on this site (including information and other content) or any third party websites or the information, resources or material accessed through any such websites. In some jurisdictions, the contents of this blog may be considered Attorney Advertising. If applicable, please note that prior results do not guarantee a similar outcome. Photographs are for dramatization purposes only and may include models. Likenesses do not necessarily imply current client, partnership or employee status.

Related Services

Insights

Hatch Comments on DNC-Related Construction Projects in Milwaukee
14 June 2019
Milwaukee Business Journal
Bernard Quoted on Debt-Relief Settlement with ITT Tech Lender
14 June 2019
Wall Street Journal
Dodd and Daughter Profiled in Wisconsin Golf
13 June 2019
Wisconsin Golf
Brinckerhoff Comments on SCOTUS Ruling in Patent Case
11 June 2019
Intellectual Property Magazine
Review of 2020 Medicare Changes for Telehealth
11 December 2019
Member Call
2019 NDI Executive Exchange
14-15 November 2019
Chicago, IL
Association for Corporate Counsel Annual Meeting 2019
27-30 October 2019
Phoenix, AZ
Foley's Government Contracts Annual Update
16 October 2019
Liviona, MI