top of page
Search

"A generic need for more treatment options did not provide motivation to combine." CAFC

Writer's picture: IP Pundit LLCIP Pundit LLC

Forest Laboratories v. Sigmapharm Laboratories, LLC (CAFC; 14-Mar-2019)


This case is an appeal from the United States District Court for the District of Delaware, and relates to an Abbreviated New Drug Application (ANDA) with the Food and Drug Administration (FDA) seeking to market generic versions of Saphris. It is a sublingually administered, atypical antipsychotic containing asenapine maleate, sold by Forest Laboratories, LLC ("Forest").

Forest sued for patent infringement, asserting that Appellants' proposed generic products would infringe claims 1–2, 4–6, and 9–10 of U.S. Patent No. 5,763,476 ("the ’476 patent").


The District Court held Appellants had not established claims 1–2, 4–6, and 9–10 to be invalid, and held Forest had not established infringement of claims 4, 9, and 10 as to Alembic and Breckenridge.

Appellants appeal the district court’s construction of claim 1 and its determination that the claims have not been established to be invalid. Forest cross-appeals, arguing the district court’s finding that Breckenridge and Alembic do not infringe claim 4 was clearly erroneous.


The CAFC vacated and remanded the district court’s validity determination, and further vacated and remanded for the district court to reconsider infringement under a corrected claim construction.

Claims 1 and 4 recite:

1. A pharmaceutical composition comprising as a medicinally active compound: trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole or a pharmaceutically acceptable salt thereof; wherein the composition is a solid composition and disintegrates within 30 seconds in water at 37° C.

4. A method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders, comprising administering sublingually or buccally an effective amount of a pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5- c]pyrrole or a pharmaceutically acceptable salt thereof.


I. Construction of Claim 1:

Standard of Review - district court’s ultimate claim construction and its interpretations of intrinsic evidence de novo and any subsidiary fact findings about extrinsic evidence for clear error.

CAFC saw no error in the district court's construction that claim 1 is to be limited to buccal and sublingual formulations. It reasoned that "although claim 1 does not expressly refer to buccal or sublingual administration, the claims “must be read in view of the specification, of which they are a part.”" In response to the argument that the above claim construction "improperly reads a method step into the claim by requiring a particular method of administration, namely sublingual or buccal," the CAFC stated that "[g]iven the claim language and the language in the specification, we hold the district court properly construed claim 1 to be limited to buccal and sublingual formulations."


II. Obviousness:

Standard of Review - district court’s conclusion of obviousness de novo and the underlying factual findings for clear error.


Motivation to combine:

The district court, following a bench trial, concluded that claims 1 and 4 would not have been obvious. While it is undisputed that both oral formulations of asenapine and sublingual formulations of other drugs were known in the prior art, the district court found that there was no motivation in the art to develop sublingual or buccal formulations of asenapine.


On appeal, Appellants argued that an ordinarily skilled artisan would have been motivated to administer asenapine maleate sublingually or buccally (i) to address compliance problems and swallowing difficulties in special patient populations, and (ii) to obtain more treatment options.

With respect to compliance concerns, the CAFC considered testimony that "sublingual dosage forms are more burdensome to schizophrenic patients...sublingual administration would not improve patient compliance," and concluded that "summarizing testimony...is not a clear finding." CAFC further stated that "our review would be aided by an express finding regarding whether compliance concerns regarding patients with swallowing difficulties would provide a motivation to combine."


With respect to the benefits of having multiple treatment options available, the CAFC held that the district court did not clearly err in rejecting Appellants’ contention that the benefits would provide a motivation to combine. "The district court did not clearly err, however, in concluding that a generic need for more antipsychotic treatment options did not provide a motivation to combine these particular prior art elements." CAFC considered Appellants’ various arguments as to motivation to combine and found them unpersuasive. However, in light of the district court’s failure to make an express finding as to whether compliance concerns for patients with trouble swallowing would provide a motivation to combine, CAFC remanded for the district court to address this question.


Long-Felt Need:

The district court found that at the time of the invention, there was a long-felt, but unmet, need for “a safe, effective, and tolerable atypical antipsychotic useful to treat schizophrenia and mania.” Accordingly, the district court found that ordinarily skilled artisans “recognized the need for additional antipsychotic drugs” with improved side effect profiles, and that asenapine met this profile.

While the fact that - although there were a variety of existing antipsychotics, they had debilitating negative side effects, which evidence indicates are reduced in Saphris - "may not be a particularly strong demonstration of long-felt need," CAFC found that "the district court did not clearly err in finding it weighs in favor of non-obviousness."


Unexpected Results:

Although there was nothing in the prior art that indicated cardiotoxic problems existed with other routes of administration; the district court found that it was “surprising and unexpected” that the claimed “sublingual route of administration successfully resolved the serious cardiotoxic event reported in the ’476 patent.”

CAFC held that the district court erred in its analysis of unexpected results. It reasoned that a person of ordinary skill could not have been surprised that the sublingual route of administration did not result in cardiotoxic effects because the person of ordinary skill would not have been aware that other routes of administration do result in cardiotoxic effects.

Thus, given the lack of an express finding that compliance concerns with patients who have trouble swallowing would not provide a motivation to combine, CAFC vacated the district court’s judgment of non-obviousness and remanded.


III. Written Description:

Standard of Review - Written description is a question of fact, which is reviewed for clear error.


Appellants argued that "the specification fails to describe asenapine free base in a rapidly disintegrating, sublingual, or buccal solid composition." The CAFC held that "while Appellants cite evidence that the properties of asenapine free base make it unsuitable for use in pharmaceutical development, the district court did not clearly err in finding that Appellants had not established invalidity for lack of written description by clear and convincing evidence."


IV. Infringement of Claim 4:

Standard of Review - the ultimate claim construction de novo and any subsidiary fact findings about extrinsic evidence for clear error.


The proposed generic products are indicated for the treatment of “manic episodes” associated with bipolar I disorder. Claim 4 is directed to “a method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders.” The district court construed claim 4 to not cover the treatment of bipolar disorders, and found that the proposed generic products do not infringe claim 4 directly, indirectly, or under the doctrine of equivalents. CAFC held that the district court erred in its claim construction, and vacated and remanded as to infringement of claim 4.


The decision further emphasizes the importance of disclosing clearly the full scope of the invention in the specification at the time of drafting the application. The decision also highlights importance of arguments related to compliance concerns that can be raised during Hatch Waxman or ANDA proceedings. Also, it raises a question as to the strength of the argument that the properties of a[t least asenapine] free base make/made it unsuitable for use in pharmaceutical development...at least to establish invalidity for lack of written description.


Feel free to leave comments, and/or contact me to further discuss the decision.

2 views0 comments

Recent Posts

See All

PTAB designates Huawei* as precedential

By way of highlighting what was not done in this case to show a good cause for submitting new evidence, the Board provides guidance...

Comments


© Copyright 2019 IP Pundit LLC. All rights reserved. All photographs and text included herein are the property of IP Pundit LLC. The use of any images or other materials included herein, in whole or part, for any purpose, including, but not limited to, reproduction, storage, manipulation, digital or otherwise, is expressly prohibited without the written permission from IP Pundit LLC. 

bottom of page