Thank you for the response... but it apears the majority of that article is discussing KSR/O with respect to the USPTO setting, and not in a Federal Court setting such as we have here

An example:

Forest Labs., Inc. v. Ivax Pharm., Inc. (Fed. Cir. 2007)

    By Kevin E. Noonan --

The Federal Circuit today affirmed a District Court finding that ANDA filer Ivax Pharmaceuticals and co-Defendant Cipla had not shown by clear and convincing evidence that Forest Laboratories' patent-in-suit for Lexapro® was invalid.  In doing so, the CAFC answered (for now) the question of whether a patent on a particular, biologically-active enantiomer of a patented drug is obvious.

The case was brought by Forest under 37 U.S.C. § 271(e)(2)(A) upon Ivax's filing of an ANDA for Lexapro®, a selective serotonin reuptake inhibitor used to treat depression.  The patent-in-suit, U.S. Reissue Patent No. 34,712, claimed the substantially pure (+)-enantiomer of citalopram (termed "escitalopram"):

A compound selected from substantially pure (+)-1-(3-Dimethylaminopropyl)-1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof.

('712 patent, Claim 1); Lexapro® is an oxalate salt formulation.  The parties stipulated that the subject of Ivax's ANDA would infringe the '712 patent, and that if valid, filing the ANDA constituted infringement under the statute.  Accordingly, the issue at trial was whether the '712 was invalid as alleged in Ivax's Paragraph IV certification.

There were three grounds of invalidity asserted by Ivax and Cipla before the District Court.  First, the Defendants alleged that the compound claims of the patent-in-suit were invalid as being anticipated by a prior art reference (the Smith reference) that discussed selective serotonin reuptake inhibitors (including citalopram).  However, "substantially pure" (+)-enantiomer of citalopram was not explicitly disclosed in the reference, and the District Court found that the reference did not enable the skilled worker to produce it.  Specifically, the technique taught in the reference for separating enantiomers was new and unpredictable, and there was evidence that Smith himself, as well as others including the inventor of the '712 patent, failed in attempting to produce escitalopram using the method.  The District Court found that the Smith reference was not enabled for producing escitalopram, and thus that the claims of the '712 patent were not anticipated.

On the question of obviousness, the District Court found that the Smith reference would not provide the skilled worker with a reasonable expectation of success at separating the citalopram enantiomers, and that success was sufficiently uncertain that the worker would be motivated to discover new compounds rather than try to separate the enantiomers.  Regarding the method claim (claim 11), the District Court found that the art did not describe the reactions recited in the claim.

Finally, the District Court found that claim 11 was not invalid for being impermissibly broadened more than two years after the patent issued.  In reissue, claim 11 was amended to recite that a (-)diol intermediate was converted to (+)citalopram; the claim as issued recited that (+)citalopram was produced from a (+)diol intermediate.  The District Court found that the error was merely a typographical error, and would have been appreciated by a worker of ordinary skill.

The Federal Circuit affirmed the District Court on all three asserted grounds of invalidity in an opinion written by Judge Lourie; the opinion was unanimous on all issues except extension of the statutory injunction to co-Defendant Cipla (Judge Schall dissenting that the statute did not permit Cipla to be enjoined).  For both anticipation and obviousness, the Federal Circuit found that Ivax did not establish that the District Court had committed clear error; instead, the CAFC stated that Ivax had merely "emphasize[d] the evidence that is favorable to their desired outcome without addressing the evidence favorable to Forest."  In doing so, Ivax did not establish "why the district court was not entitled to rely on the evidence favorable to Forest or demonstrate that the evidence favorable to them heavily outweighed the evidence favorable to Forest" and thus did not satisfy their burden on appeal of showing that the District Court's factual determinations were clearly erroneous.

On the question of obviousness, the Federal Circuit relied on the District Court's factual determinations that were, according to the panel, applied using the analysis set forth in Graham v. John Deere Co.; KSR Int'l Co. v. Teleflex, Inc. was not cited by the CAFC, or apparently by the parties.  The Federal Circuit also affirmed that correction of the typographical error was not an impermissible broadening under the reissue statute.

The significance of this decision is found more in what the Federal Circuit did not say than in its relatively pedestrian affirmance.  An open question remaining after KSR is whether enantiomer patents would fall within the ambit of the Supreme Court's seemingly-expansive dicta regarding what is obvious to try:

When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.

Enantiomer patents can be fitted within at least a portion of this framework.  There are typically "market pressures" for producing a more effective drug; in cases where only one of the enantiomers is biologically-active, effectiveness should double.  Enantiomers also provide the ultimate in "finite number" of "identified" solutions:  namely, two.  The question is whether the "solution" - the substantially purified enantiomer - is sufficiently predictable and leads to anticipated success.  In the Lexapro® case, the art did not identify which of the two enantiomers was the active one, and the evidence established that separation of the enantiomers was sufficiently unpredictable that the District Court opined that the skilled worker was motivated to investigate new drugs rather than tackle separation of the enantiomers.  On these facts, the enantiomer claim satisfied the requirements for non-obviousness.

The dissent raises an interesting issue of statutory interpretation.  The majority affirmed the scope of the injunction to include Cipla, who was to have produced the drug for distribution by Ivax.  Cipla had not supplied Ivax with any infringing drug, however, and its contributions to Ivax's ANDA were limited to information on bioequivalence.  Judge Schall in dissent considered Cipla immunized from the District Court's injunction on two grounds:  first, that 35 U.S.C. § 271(e)(4)(B) provides for an injunction only against the ANDA filer; and second, that Cipla's activities fell within the scope of 35 U.S.C. § 271(e)(1) under the interpretation of that statute by the Supreme Court in Merck KGaA v. Integra Lifesciences I, Ltd.  Although the majority's policy imperative is understandable (without the injunction Cipla could partner with another ANDA filer and challenge the validity of the '712 patent anew), Judge Schall's analysis seems more firmly rooted in the plain language of the statute.

Forest Labs., Inc. v. Ivax Pharm., Inc. (Fed. Cir. 2007)
Panel: Senior Circuit Judge Friedman and Circuit Judges Lourie and Schall
Opinion by Circuit Judge Lourie, concurring-in-part and dissenting-in-part opinion by Circuit Judge Schall

Additional information regarding this case can be found at the Orange Book Blog and Patently-O. 

 

 http://www.patentdocs.net/patent_docs/articles_cases_obviousness/index.html

 

 

Be well