Levaquin®: JNJ likely to prevail against Mylan

October 18, 2002

A.  Introduction and Summary

The patent infringement case brought by Johnson & Johnson and Daiichi against Mylan over the anti-bacterial drug Levaquin^® was tried in Morgantown, West Virginia in two phases: the first from November to December 2003 and the second in May 2004.  The case is now fully briefed and ready for a decision by Chief Judge Irene Keeley (a Bush 41 appointee) of the West Virginia federal court.  Verdict has reviewed the patent, the trial transcript, the two sets of post-trial briefs and the judge’s March 31, 2003 claim interpretation ruling.  Based on that review, Verdict believes the plaintiffs will prevail because Mylan has admitted infringement and the judge is likely to reject Mylan’s three remaining issues: obviousness, inequitable conduct and inherent anticipation:

• Judge Keeley is likely to reject Mylan’s obviousness defense because:
  • The judge expressed little concern about it;
  • She disregarded other testimony by Mylan’s obviousness expert; and,
  • Daiichi presented evidence of the long and difficult road to the invention.

• Judge Keeley will ultimately reject Mylan’s defense of inequitable conduct in the prosecution of the ‘407 patent, because Mylan failed to prove, by clear and convincing evidence, that the inventor Dr. Hayakawa’s had specific intent to mislead the patent examiner, notwithstanding that the judge:
  • Accepted Daiichi’s admission that Dr. Hayakawa was the source of all allegedly false and misleading statements to the Patent and Trademark Office (“PTO”);
  • Heard conflicting expert testimony about whether Hayakawa’s statements were true or false; and,
  • Gave mixed signals on whether she found Dr. Hayakawa to be credible.

• Judge Keeley is likely to reject Mylan’s defense that the ‘407 patent is invalid for inherent anticipation because:
  • She will “distinguish” the recent appellate cases involving CLARATIN^® that Mylan relies upon;
  • Although she may modify her claim interpretation that is now extremely helpful to the plaintiffs, it will be not be enough for Mylan to invalidate claim 5; and,
  • She is likely to find that, even if ofloxacin inevitably turns into some levofloxacin in the body or in solution (on which the experts disagreed), that is not enough to anticipate claim 5 which requires administration of anti-bacterially effective amounts of levofloxacin.

Caveat:

§  Both the inequitable conduct & inherent anticipation defenses ultimately depend on the credibility of witnesses.  Because Verdict did not attend the trial but only reviewed the transcript, assessing credibility is difficult because we did not watch the witnesses, the judge’s reactions, the documents and demonstrative exhibits flashed shown on the screen in the courtroom, or see the videotaped deposition excerpts which were presented during trial.

B.  Background

1.  The Parties

• Plaintiff, Daiichi Pharmaceutical, is a Japanese firm that developed Levaquin, a financially successful antibacterial drug which is the successor to its antibacterial Floxin.  The active ingredient in Levaquin (known generically as levofloxacin) is covered by U.S. Patent No. 5,053,407 (“407 patent”).  Daiichi held a now-expired patent covering ofloxacin, the active ingredient in Floxin.
• Plaintiff Ortho-McNeil Pharmaceutical, a subsidiary of Johnson & Johnson, is the exclusive U.S. licensee of the ‘407 patent.
• Johnson & Johnson Research and Development LLC is a separately named plaintiff.
• Levofloxacin is an isomer of the ofloxacin racemate.  The plaintiff’s claim that levofloxacin is more active, more soluble, and less toxic than ofloxacin.  According to the plaintiffs, this is the reason Levaquin replaced Floxin.

2. The Patent

The ‘407 patent issued in 1991 and expires in 2010.  It claims the compound (levofloxacin by its chemical name), claims the antibacterial treatment process of administering it to patients, and discloses (but does not claim) three processes for separating it from ofloxacin.  Ofloxacin is a racemic mixture of enantiomeric molecules that are chemically identical but are not super-imposable images of each other.  The enantiomers are optically active: one will rotate to the right in a plane of polarized light (dextrorotatory or +) and the other will rotate to the left  (levorotatory or -).  The ‘407 patent claims the levorotatory enantiomer of ofloxacin which was found to be the more antibacterially active, more soluble and less toxic than the ofloxacin racemate.

3. Trial Proceedings

In an order before trial, Judge Keeley interpreted the claims language by defining:

• “Pharmaceutical preparation” as the levorotatory enantiomer of racemic ofloxacin, levofloxacin, not  the racemic (ofloxacin, [1]);
• “Comprised principally of levofloxacin;” and,
• “Having unique pharmacological properties.”[2]

Before trial, the plaintiffs limited the claims they were asserting against Mylan to 2 and 5:

• Claim 2 claims the compound levofloxacin, as interpreted by the court;[3] and
• Claim 5 claims the application of levofloxacin for antimicrobial therapy.[4]

At the conclusion of Mylan’s testimony, Judge Keeley dismissed two of Mylan’s defenses:

• The “prior invention defense” was dismissed because Mylan failed to prove that its expert (Dr. Mitscher) isolated levofloxacin before Daiichi; and,

• The “indefiniteness of the claims” defense was dismissed because:
  • Persons of ordinary skill in the art would have understood the claims; and,
  • The judge would have to change her interpretation of claim 2 to make it indefinite.

The second half of the November-December trial phase focused on Mylan’s obviousness and inequitable conduct defenses: the judge announced the plaintiffs would not have to offer rebuttal evidence to Mylan’s inherent anticipation case, unless she determined that Mylan had established a prima facie[5] case of inherent anticipation.  Mylan added the inherent anticipation defense after the Schering case decided on August 1, 2003.

The court conducted Phase II because Mylan established a prima facie case of inherent anticipation.  In opening Phase II of the trial in May 2004, Judge Keeley commented that:

• The issue in Phase II is whether “levofloxacin is inevitably produced a result of the administration of ofloxacin”;
  • if so, inherent anticipation is established.
• Mylan has the burden of proving such inevitability by clear and convincing evidence; and,
• It is no secret that Mylan seeks a “massive rewrite” of her March 31 claim construction.

C.  Remaining Issues

1.  Obviousness

Mylan contends that the ‘407 patent is invalid as obvious because of:

• The structural similarity between the ofloxacin and levofloxacin molecules;
• Motivation[6] existed to make the invention because:
  • Prior art suggested that isomers of the same racemate had different properties and that beneficial and harmful properties of the racemate could reside in different isomers.
  • There were regulatory pressures by the FDA (and its Japanese counterpart) on pharmaceutical firms to explore the use of isomers of racemates; and,
  • Improved methods for separating racemates into their isomers emerged in the 1980’s.
• The commercial success of Levaquin should not count as a secondary consideration of non-obviousness because:
  • The products are essentially the same; and,
  • The plaintiffs intentionally sacrificed Floxin sales to increase Levaquin sales because the ofloxacin patent expired before the levofloxacin patent.

The plaintiffs contend that the ‘407 patent is not obvious because:

• Structural similarity of the two molecules is not enough;
• Structural similarity is negated by the “surprising” or “unexpected” advantages of levofloxacin compared  to ofloxacin;
• It took four years of intense research to successfully separate the levofloxacin isomer from the ofloxacin racemate;
• All the prior art Mylan relies upon for invalidation was considered by the PTO making it more difficult to prove obviousness;
• Regulatory pressure does not count as motivating those in the art; and,
• The commercial success of Levaquin is evidence of non-obviousness.

2.  Inequitable Conduct

• Mylan contends that the ‘407 patent is unenforceable due to inequitable conduct during the prosecution of the ‘407 patent because:
• The plaintiffs made false, misleading, or omitted statements to the PTO;
• Daiichi admits that Dr. Hayakawa made all the statements and omissions;
• The allegedly false statements concerned the improved therapeutic activity, solubility and toxicity of levofloxacin over ofloxacin that led to the issuance of the patent after initial rejections by patent examiner;
• ∆ One such statement concerned a representation that the water solubility of ofloxacin is “unsatisfactory for aqueous preparations”; and,
• ∆ One omission involved the plaintiffs’ failure to include the confidence level data on comparative toxicity from a chart in the patent
• when a Daiichi internal memo concluded the data was statistically insignificant.

• Daiichi withheld a 1985 power point presentation regarding the process of separation of isomers at a conference by a Dr. Gerster; and,
• Dr. Hayakawa (the inventor of the ‘407 patent) intended to deceive the PTO;

o   Which the court should infer from the “totality of circumstances”; and,

o    By his “deliberate destruction” of some of his notebooks.

Daiichi contends that Mylan has not established inequitable conduct because:

• The statements were all true;

o   The trial involved multiple fact and expert witnesses explaining the science behind the experimentation and testing of these parameters;

• The “unsatisfactory for aqueous solutions” statement was not material because:

o   An attorney, not Dr. Hayakawa, made the statement and the statement was made in a written an argument not in a presentation;

o   The ‘407 patent clearly discloses and the patent examiner knew that ofloxacin was used in aqueous solutions; and,

o   The examiner knew that Daiichi did not claim that ofloxacin was not soluble, but that levofloxacin was 10 times more soluble.

§  The toxicity test confidence levels were not material because an applicant is not required to submit all experimental data that bear on the conclusion that levofloxacin is less toxic, (which itself is true); and,

§  The other statements were not material.

3. Inherent Anticipation

a. Bacground

An invention must be new to be “patentable.”  If the PTO issues a patent on an invention that turns out was previously invented by another it is not new, it is “anticipated.”  If the PTO issues a patent that a court finds was anticipated, the patent is invalid.  In most cases anticipation is proved by prior art disclosures in other patents, trade, professional journal articles, published Ph. D. theses, or by an actual device or process that was previously made or used.

However, if the public has been using the invention of the patent but no one realized there can be “inherent anticipation.”  While inherent anticipation can occur in a number of technological areas, the issue arises frequently in the chemical and pharmaceutical field where the exact sequence of intermediate compounds may not be known, may not be detectable or may not matter if the starting or final product or process works.  This is particularly true in pharmaceuticals where the ingestion of a drug creates reactions within the body that yield metabolites or other new or intermediate compounds.

In the case of pharmaceutical racemates, which show differences when separated into their constituent isomers, the issue is whether anything occurs within the body to separate the good isomers from the bad isomers and use only the good ones.  In the case of levofloxacin, ofloxacin is prior art.  If people have been taking Floxin for years and the body necessarily separates the levorotatory isomer (levofloxacin) from the dextro isomer and uses only the levo isomer, then Levaquin is not new, it is inherently anticipated.

b.  The Parties Contentions

Mylan contends that claims 2 and 5 of the  ‘407 patent are invalid under the doctrine of inherent anticipation.  A claim is anticipated when each element of the claim is found in a single prior art reference.  As noted inherent anticipation occurs when the invention was unknowingly but necessarily used by the prior art.

Before the judge can decide whether the ofloxacin inherently anticipates levofloxacin the judge will:

§  First decide what levofloxacin is; and,

§  Then, depending on the definition, may have to decide how ofloxacin works.

Specifically, Mylan argues that the court must find inherent anticipation because:

• The claim language defines the compound levofloxacin by its molecular structure;
  • Therefore, the claim should be construed to cover the presence of any trace amount, even a single molecule of levofloxacin under the proper claim construction required by the recent appellate decisions in the Schering and Apotex cases;
• The claims of the ‘407 patent (as Mylan would change the construction) encompass the prior art of ofloxacin, because ofloxacin necessarily:
  • Separates at least some levofloxacin molecules in vivo after administration to a patient; and,
  • Separates at least some levofloxacin molecule in vitro when in solution outside the body;
• Plaintiffs did not adequately rebut Mylan’s evidence with fact testimony, but offered only expert testimony, implying that plaintiff’s evidence is contrived; and,
• Even if the claims are not re-construed, but continue to define “principally” or “substantially pure” levofloxacin, they are still inherently anticipated because:
  • The principal interaction of ofloxacin is by the levofloxacin enantiomers binding at DNA receptor sites in the body to achieve antimicrobial activity.

Plaintiffs contend that:

• That neither the Schering nor the Apotex case govern;
• The court properly construed the claims to cover a preparation or compound comprised principally of levofloxacin;
  • A “preparation” or “compound” is not just a single molecule; and,
  • The PTO in a related proceeding construed the claim as calling for “enantiomerically pure” levofloxacin;
• Single molecules would lack “antimicrobial effectiveness” and “administration” required by claim 5;
• Mylan has not established the science of its necessary in vivo and in vitro creation contentions by clear and convincing evidence; and,
• There is no proof of inherent anticipation even if the court changes the claim construction because:
  • Isolated levofloxacin molecules (“monomers”) do not have the optical activity that distinguish the levo negative form of the isomer from dextro positive isomer that are both contained in the racemic mixture; and,
  • Mylan has not proved that such transient monomers would be pharmacologically useful.

D.  Verdict’s Analysis

1.  Obviousness

The plaintiffs should easily prevail on the issue of obviousness and the court will find that the ‘407 patent is valid, because Mylan’s obviousness arguments are not convincing because:

• Mylan’s reliance on supposed admissions by Daiichi limits Mylan’s need to offer extensive proof on the issue and this is a trial tactic that is frequently used by a party when it has no compelling evidence;
• Mylan relies on a discredited expert (Dr. Mitscher) on obviousness:
  • The judge was not persuaded by Dr. Mitscher’s testimony when she dismissed Mylan’s prior invention defense during the trial mid-trial;
  • On cross-examination, Dr. Mitscher admitted to several mistakes in his expert report; and,
  • Judge Keeley admonished him several times for being non-responsive.
• Mylan’s obviousness defense was effectively rebutted by:
  • Daiichi’s long paper trail of unsuccessful experimentation with separating levofloxacin;
  • Daiichi relied on the testimony of the principal inventor, Dr. Hayakawa, who was given a medal and had a private audience with the Emperor in recognition of his invention; and,
  • Mylan’s own argument that Daiichi’s experimentation was incompetent.

• Mylan’s argument suffers from Verdict’s general perception that fact witnesses (even biased ones like the inventor himself) are generally more credible than paid experts pushing their client’s position:
  • Particularly where as here the expert, has the additional personal self-interest of (unsuccessfully) claiming to be the prior inventor.

2.  Inequitable Conduct

Verdict believes that Mylan’s inequitable conduct defense is likely to fail:

• On one hand, Verdict would not find inequitable conduct on the paper record;

• • However, Verdict’s review of the trial transcripts and briefs:

• • • Did not expose the witnesses’ demeanor;
    • Did not show the judges reaction to the witnesses;
    • Did not provide a view of the documents flashed on the screen at trial;
    • Does not permit full assessment of the witnesses’ credibility; and,
    • Did not allow any exposure to a number of Daiichi witnesses whose testimony was offered by Mylan and shown at trial in un-transcribed videotapes;

• On the other hand, Judge Keeley expressed concern about the inequitable conduct charge:

• • At mid-trial of Phase I, after hearing Mylan’s case but before Dr. Hayakawa testified live, Judge Keeley said that:

• • • Dr. Hayakawa’s testimony was evasive in his videotaped depositions excerpts; and,
    • Daiichi “has real problems” with Dr. Hayakawa’s statement that ofloxacin’s solubility was unsatisfactory in aqueous solutions;

• • During Dr. Hayakawa’s live testimony, the judge got frustrated and gave mixed messages:

• • • Early in his cross-examination, without obvious provocation, Judge Keeley lectured Dr. Hayakawa about being responsive:

Dr. Hayakawa, you are now on what we call in our courts cross-examination where the lawyer will ask you probing questions. And part of those questions may be about your recollection of your testimony. Those questions are appropriate, and you have an obligation under our rules to answer those questions even if you may not care for those questions.  Tr. 4246.

• • • In overruling an objection by Daiichi counsel on cross-examination by Mylan counsel, Judge Keeley said:

I was finding this very probative and very relevant not only on impeachment of this witness, but on what I think are some of the critical issues in the case.  Tr. 4370.

§  Later in the same colloquy, Judge Keeley warned Mylan counsel:

I’m ready to move on and I want you to take to heart what I said, Mr. Wallace. What I’m looking for on cross-examination of a witness such as this is an attack on the substantive statements that have been made so that I can make a determination ultimately on these issues in the case. I think I have — I’m not saying you can’t,  you can’t impeach on credibility if you think that that’s an  important thing to do, but we spent a lot of time on that  yesterday. I don’t know how much more time on issues like this you’re going to spend. But this is where I would prefer you spend your time. Tr. 4372.

On the two most important allegations of inequitable conduct, the judge will ultimately reject the inequitable conduct defense because:

• Judge Keeley will find that the allegedly  statements are scientifically true;
• That if not true, Dr. Hayakawa always believed them to be true; and,
• There is no smoking gun on any intent to deceive the PTO by Dr. Hayakawa:

o   Mylan’s totality of circumstances theory is not enough to prove a specific intent to deceive: and,

o   The document destruction claim (missing notebooks) is a red herring because:

§  Dr. Hayakawa testified that the notebooks were destroyed when the document depository ran out of space;

§  The information in the notebooks had been transcribed into his Ph.D. thesis which was available; and,

§  There was no importance to the notebooks under Japanese first-to-file priority and under then existing U.S. law precluding foreign inventors from “swearing behind” their application dates.

Our inequitable conduct analysis has to be qualified since our prediction:

§  Is based on an incomplete access to the record;

§  Judge Keeley’s first patent case and inequitable conduct decision;

§  Judge Keeley’s early mixed signals about Dr. Hayakawa;

o   At the end she asked no questions of Dr. Hayakawa and was gracious to him in saying goodbye after all and parts of four days on the stand.

With these caveats in mind, we cautiously predict that Judge Keeley will reject Mylan’s inequitable conduct/unenforceability defense.

C.  Inherent Anticipation

Judge Keeley set the agenda for Phase II of the trial as:

• Dependent on whether Mylan made a prima facie case of inherent anticipation in Phase I;
  • That the case went to Phase II should not be construed as giving Mylan some advantage because the judge announced that:
    • The parties would have additional discovery between Phase I and Phase II;
    • Plaintiffs did not have to present any evidence on inherency in Phase I;
    • But, if plaintiffs did present evidence in Phase I, they could not back track over it in Phase II;
  • Plaintiffs wisely chose not to address inherency during Phase I.
• To determine whether levofloxacin is inevitably produced as a natural result of the administration of ofloxacin; and
• Placing the burden on Mylan of proving inherency by “clear and convincing” evidence; and
• Regarding Mylan’s request for a “massive rewrite” of the March 31, 2004 claim interpretation order, Judge Keeley hinted that she may tweak her claim interpretation to remove the qualifier “pharmaceutical preparation” that she imported from the specification into the definition of levofloxacin.

Here are additional points putting Phase II into context:

• During the trial, Judge Keeley understood the difference between claim 2 covering a composition of matter and claim 5 covering a process of administering a drug;
• Judge Keeley also hinted at times that she might uphold claim 5 regardless of what she did with claim 2;
• During Phase II, Judge Keeley repeatedly admonished Dr. Mitscher, Mylan’s expert, to answer the questions on cross-examination rather than fight with plaintiff’s counsel;
• No witness on either side was able to provide direct, targeted, factual evidence of what happens to ofloxacin when ingested, at the DNA receptor site in the body or in solution outside the body such as in IV, and eye drop preparations;
• Instead Mylan’s expert Dr. Mitscher tried to take oblique data and conclusions from a Daiichi commissioned university study (Kumumato) and published peer reviewed professional journal articles and extrapolate, argue by analogy; and,
• Daiichi presented three experts whose testimony, also unsupported by independent factual foundation, sought to poke holes in the protocol of experiments, the conclusions of the studies, and Dr. Mitscher’s extrapolations and the logic of his analogies.

1.  Case Law Driving Phase II

Although Schering prompted Phase II, it has little relevance to Levaquin.  The decision in Schering v. Geneva came down August 1, 2003.  In Schering the Court of Appeals for the Federal Circuit held that the original prior art patent covering loratadine, (the active ingredient in the antihistamine CLARITIN^®), inherently anticipated the patent in suit covering a metabolite of loratidine.  The principal differences between Schering and the levofloxacin case are that:

• There was no dispute in Schering that the claims at issue covered structure of a metabolite of loratidine;
• There was no factual dispute that the human body inevitably created the metabolite after ingestion;
• There was no dispute as to claim construction; and,
• The generic companies sought to market the same loratidine as in the CLARITIN product covered by the expired patent.

More troublesome for Judge Keeley is SmithKline Beecham v.  Apotex, decided April 23, 2004, on the eve of Phase II.  In Apotex the Court of Appeals for the Federal Circuit reversed the trial judge’s claim construction limiting claim 1 to “commercially significant” amounts of “crystalline paroxetine hydrochloride hemihydrate (“PHC hemihydrate”),” the active ingredient in the antidepressant Paxil^®.  The defendant had tried to make PHC anhydrate, the predecessor prior art product, but its process was mysteriously and unintentionally infected with trace amounts of PHC hemihydrate.  The claim simply read PHC hemihydrate.  On summary judgment, the trial judge inserted “commercially significant” limitation for “policy reasons” to prevent the unintentional de minimis infringement.  Judge Rader, writing for the appeals court found the trial judge’s policy considerations were well-meaning but irrelevant.  He stripped the qualifying language from the claim to find infringement.  Judge Rader said he could not find anything in either the body of the patent (“specification”) or communications with the PTO (“prosecution history”) limiting the claim to commercially significant amounts.

2. Discussion

If levofloxacin is a pharmaceutical compound, as defined in Judge Keeley’s March 31, 2004, order, then:

• Plaintiffs defeat the inherent anticipation defense as to both claims 2 and 5, because that definition would exclude anything the body does to separate the two isomers; and
• The judge hands Mylan a good issue on appeal because the court of appeals reviews claim interpretation as a matter of law, “without deference” to the trial judge.

If “levofloxacin” is defined to include even trace amounts of levofloxacin (down to a single molecule of the levorotatory isomer) or greater than 50% of the ofloxacin, as Mylan would define it, then:

§  Mylan would prevail on its inherent anticipation defense based upon evidence that when ofloxicin is administered to humans, the body purges the two isomers at slightly different rates;

o   Thereby raising an inference that the body separates at least some  of the two isomers in the body;

§  Under this claim interpretation:

o   Mylan would prevail on inherent anticipation of claim 2; and,

o   Mylan might prevail on inherent anticipation of claim 5 if the judge finds that the two isomers begin separation in vitro, that is when in a solution prior to the administration of ofloxacin to patients;

§  Mylan’s alternative interpretation, that levofloxacin is any solution with greater that 50% levofloxacin, would not materially change things because ofloxacin is by definition 50% levo- and 50% dextro-rotatory isomer.

If levofloxacin is reasonably or substantially pure levorotatory isomer of approximately 95-98%, as plaintiffs urged ( as a fall back from the judge’s March 31, 2004, interpretation) plaintiffs would still prevail on the inherent anticipation defense because no witness has established that ofloxacin comes close to being 95% levofloxacin. In fact, Mylan’s expert, Dr. Mitscher, told the judge in response to her question, that the minimum level of levofloxacin’s purity required to obtain its advantages over ofloxacin was 98% or better.

a.  Claim 2

Claim 2 before Judge Keeley is analogous to claim 1 in Apotex.  Everything else being equal, if Judge Keeley is to followed Apotex she will re-construe claim 2 to eliminate the “pharmaceutical preparation comprised principally” limitation.

The issue is whether everything else is equal:

§  Plaintiffs point to discussions in the specification of the ‘407 patent, but they are no more compelling than the language of the specification in Apotex;

§  Plainitffs also point to expert testimony that persons of ordinary skill in the art would understand that given the way levofloxacin works, it had to be “principally” or “substantially pure” levofloxacin; and,

§  Plaintiffs particularly cite the testimony of Dr. Klibanov that “compound” as used in the claim to mean “a sizeable quantity of material, a quantity that has certain properties, physical properties, chemical properties, and pharmacological properties.”

Verdict predicts that Judge Keeley will reject plaintiffs’ arguments because and change the claim construction because:

• She wants to follow Judge Rader’s Apotex decision;
• The claims and specifications are analogous;
• Dr. Klibanov’s testimony is irrelevant; and
• Judge Keeley is likely to discount Klibanov’s credibility.[7]

Based on the new claim construction, Judge Keeley could find that claim 2 is invalid on the ground of inherent anticipation.

b.  Claim 5

Changing construction of the meaning of levofloxacin in claim 2 will also change it in claim 5, but is not likely to invalidate claim 5 because claim 5 contains additional qualifying language:

§  “A process for treating a patient;”

§  “Antimicrobial therapy;”

§  “Administering to said patient;” and,

§  “Antimicrobial effective amount.”

These limitations all suggest intentional administration of levofloxacin rather than the unintentional inclusion of levofloxacin in administering the racemate ofloxacin.  In upholding claim 5, Judge Keeley:

• Does not repudiate anything Judge Rader said in Apotex;
• Avoids much of the conflicting scientific testimony about in vivo and in vitro separation of the levo and dextro isomers of ofloxacin;
• Avoids reliance on Dr. Klibanov; and,
• Can place her reliance on more credible witnesses.

Accordingly, Verdict predicts that Judge Keeley will uphold the validity of claim 5, and infringement of claim 5 is not contested.

E.  Additional Observations

• This case was over-lawyered on both sides with;
  • Too many lawyers,
  • Too many issues, sub issues, sub-sub issues,
    • This adds to the unpredictability of the outcome,
  • Too many expert witnesses, who were too pompous, too verbose and appeared too partisan,
  • Overly lengthy examinations eliciting theoretical testimony based on contested assumptions, and,
  • Too little control by the judge.

• Mylan case was a moving target, with:
  • Both inequitable conduct and inherent anticipation were added late;
  • Mylan kept adding expert testimony beyond the scope of the experts’ reports;
  • Mylan kept adding exhibits that were not timely disclosed.
  • This generated numerous, extended disputes, requiring frequent rulings from the court.

• Mylan appeared beleaguered and resorted to gamesmanship in:
  • Offering last minute documents;
  • Cross-examination of plaintiffs’ witnesses;
  • Playing on the local company “just down the road” against the “fine folks over in Japan.”
  • Denigrating Daiichi, its inventions and its witnesses.

• Mylan’s denigration of the inventions in general, the benefits of Levaquin over Floxin, and the success of Levaquin exposed Mylan to a question by plaintiffs which Mylan never answered: if Floxin is just as good as Levaquin, why does Mylan not manufacture Floxin which is in the public domain rather than spend millions on litigation to try to sell Levaquin.

• As a result of all the above and perhaps the individuals involved, Judge Keeley clearly favored plaintiff’s lawyers over Mylan’s on a personal level;
  • She laughed at plaintiffs’ lawyers’ jokes, was cool to Mylan’s lawyer’s attempts at humor; and,
  • Although she tried to be even-handed in her admonishments of counsel, she seemed harder on Mylan’s counsel.

F.  Conclusion

Verdict predicts that:

§  The judge will reject Mylan’s remaining defenses;

§  Plaintiffs will prevail in the trial phase of the case on grounds that Mylan infringes a valid claim 5;

§  Mylan will be barred by the trial court from launching levofloxacin.

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[1] “An examination of the plain meaning of the claim language as understood by persons skilled in the art at the time of invention, the specification and the prosecution history indicate that “An S(-)-pyridobenzoxazine compound” and “S(-)-9-Fluoro-3-methy1-10-(4-methy1-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid” refer to the levorotatory enantiomer of racemic ofloxacin, levofloxacin. These terms do not refer to racemic ofloxacin. Furthermore, as demonstrated by the specification’s resolution methodology, as well as the specification and prosecution history’s repeated emphasis on levofloxacin’s unique pharmacological properties, the disputed language refers more specifically to a pharmaceutical preparation comprised principally of levofloxacin.”

[2] Those properties include increased antibacterial activity, increased solubility and reduced toxicity over ofloxacin.

[3] “S(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7Hpyrido[1,2,3-de][1,4] benzoxa-zine-6-carboxylic acid according to claim 1.”

[4] “A process for treating a patient in need of an antimicrobial therapy in claim 4 which comprises administering to said patient an antimicrobially effective amount of S(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2, 3-dihydro-7Hpyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid.”

[5] Establishing a “prima facie” case means that the party with the burden of proof established (by not necessarily more than a bare minimum of evidence) each of the elements of a claim or defense to allow it go forward.  The party establishing the prima facie case would prevail if the opposing party fails to present any rebuttal.

[6] Motivation strengthens the defense of obviousness: Motivation exists where there are two prior art references and there is a motivation (reason) to combine them to create the invention.

[7] At one point in Phase I of the trial Judge Keeley called counsel to the bench and angrily told them they would have get Dr. Klibanov under control.  Tr. 2171.  Dr. Klibanov did not testify in Phase II.