Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • Federal Circuit Upholds Patent Term Extensions in LEVAQUIN and METVIXIA Cases

    Ortho-McNeil and Daiichi Sankyo v. Lupin, No. 2009-1362 (Fed. Cir. 2010)

    Photocure v. Kappos, No. 2009-1393 (Fed. Cir. 2010)

    In separate cases decided today, the Federal Circuit upheld two patent term extensions under 35 U.S.C. § 156–one relating to LEVAQUIN (levofloxacin) and the other relating to METVIXIA (methyl aminolevulinate).  The cases were argued on the same day last year to the same three-judge panel, and Judge Newman authored both of today's opinions.

    In the LEVAQUIN case, the Federal Circuit affirmed a district court decision sustaining the term extension of U.S. Patent No. 5,053,407, assigned to Daiichi and exclusively licensed to Ortho-McNeil, and enjoining Lupin from infringement during the extended term of the patent.  The '407 patent claims levofloxacin, which is the levorotatory enantiomer of racemate ofloxacin.  Levofloxacin and ofloxaxin are both antibiotics.

    In the METVIXIA case, the Federal Circuit affirmed a district court decision reversing the USPTO's denial of a term extension of U.S. Patent No. 6,034,267, owned by Photocure.  The '267 patent claims methyl aminolevulinate ("MAL"), the methyl ester of the known drug aminolevulinic acid ("ALA").  MAL and ALA are both indicated for the treatment of actinic keratoses–precancerous cell growths on the skin.

    Under § 156, the term of a patent that claims a drug product, a method of using a drug product, or a method of manufacturing a drug product may be extended by up to five years if the drug product was subject to FDA regulatory review prior to its commercial marketing or use.  The Federal Circuit explained the policy behind § 156:

    The Patent Term Extension statute was enacted in recognition of the lengthy procedures associated with regulatory review of a new drug product, for the patent term continues to run although the product cannot be sold or used until authorized by the Food and Drug Administration (FDA).  The statute was designed to restore a portion of the patent life lost during the period of regulatory review, in order to preserve the economic incentive for development of new therapeutic products.

    A key feature of § 156 is that only one patent term extension is allowed per "drug product".  This is reflected in the statutory language: "the permission for the commercial marketing or use of the [drug] product after such regulatory review period [must be] the first permitted commercial marketing or use of the [drug] product."  In turn, the statute defines a "drug product" as the "active ingredient" of a new drug, antibiotic drug or human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act).

    The issue in both of the cases decided today was whether the FDA approval sought for each drug was for the "first permitted commercial marketing or use" of the drug.  In the levofloxacin case, Lupin argued that the enantiomer levofloxacin is an "active ingredient" of the previously-marketed racemate ofloxacin; levofloxacin is therefore the same "drug product" as ofloxacin; and therefore levofloxacin is not eligible for a patent term extension.  Similarly, in the MAL case, the PTO argued that "active ingredient" means "active moiety"; MAL, as the methyl ester of ALA, is the same product as ALA because the "underlying molecule" ("active moiety") of MAL is ALA; and therefore MAL is not eligible for a patent term extension.   But the Federal Circuit rejected these arguments.

    In the levofloxacin case, the court agreed with Ortho that "an enantiomer has consistently been recognized, by the FDA and the PTO, as a different 'drug product' from its racemate."  The court further observed that, in this case, "levofloxacin was viewed by the FDA as a new product requiring full regulatory approval, and that levofloxacin was viewed by the PTO as separately patentable."

    The Federal Circuit applied similar reasoning in the Photocure case:

    [A]s the '267 patent illustrates, the pharmacological properties of MAL differ from those of ALA, supporting the separate patentability of the MAL product.  MAL hydrochloride is a different chemical compound from ALA hydrochloride, and it is not disputed that they differ in their biological properties, warranting separate patenting and separate regulatory approval, although their chemical structure is similar.

    Notwithstanding this reasoning, the PTO argued that pursuant to Pfizer v. Dr. Reddy's, 359 F.3d 1361 (Fed. Cir. 2004), the statutory term "active ingredient" does not mean the compound that is present in the approved drug, but instead it means the "active moiety" of the compound; that is, the part responsible for the pharmacological properties.  The Federal Circuit, however, rejected the PTO's construction.  Further, the Federal Circuit distinguished the Pfizer case, stating: "Pfizer did not hold that [an] extension is not available when an existing product is substantively changed in a way that produces a new and separately patentable product having improved properties and requiring full FDA approval."

    Thus, after Photocure, we will likely see the PTO grant patent term extensions in cases where it would not have granted an extension before.

  • Orange Book Blog at BIO 2010

    The 2010 BIO International Convention is in Chicago this week and Orange Book Blog will be there covering it all.

    I'll be hanging out at the MBHB booth on Tuesday from 5-6:30 and Thursday from 3-5.  The rest of the time, I'll be meeting with clients, hearing talks from industry leaders, checking out the BIO Exhibition and BIOPark, and going to parties–including the MBHB reception at Fadó Irish Pub on Tuesday night.

    It would be great to meet any Orange Book Blog readers who will be at BIO this year.  If we don't bump into each other, send me an e-mail (barkoff@mbhb.com) to get together.

  • Federal Circuit Affirms Invalidity of Concerta Patent for Lack of Enablement

    ALZA Corp. v. Andrx Pharms., No. 2009-1350 (Fed. Cir. 2010)

    Earlier this week, the Federal Circuit affirmed a district court decision finding ALZA's U.S. Patent No. 6,919,373 invalid for lack of enablement.  The '373 patent claims methods for treating Attention Deficit and Hyperactivity Disorder ("ADHD") and is listed in the Orange Book for Concerta, an extended-release formulation of methylphenidate.

    Last year, following a bench trial held in late 2007, the U.S. District Court for the District of Delaware found the '373 patent not invalid for obviousness, but invalid for lack of enablement and also not infringed by Andrx's ANDA for a generic version of Concerta.  The Federal Circuit affirmed the lack-of-enablement finding, and therefore did not address the other issues.

    Claim 1 of the '373 patent reads:

    A method for treating ADD or ADHD comprising administering a dosage form comprising methylphenidate that provides a release of methylphenidate at an ascending release rate over an extended period of time.

    According to the Federal Circuit opinion, the specification of the '373 patent "focuses on how osmotic systems can be adapted to create an ascending release dosage form to treat ADHD.  The specification also mentions non-osmotic dosage forms."  Both Concerta and Andrx's product are non-osmotic dosage forms that contain an outer immediate-release coating around a sustained-release inner core.

    On appeal, ALZA argued that the district court erred in finding claim 1 invalid for lack of enablement on the grounds that the specification does not enable the full scope of claim 1, which covers both osmotic and non-osmotic dosage forms.  The parties agreed that osmotic dosage forms are enabled, but disputed whether the specification would have enabled a person of ordinary skill in the art to create non-osmotic oral dosage forms–namely, tablets and capsules–with ascending release rates without undue experimentation.

    The test of enablement is whether the specification would have taught someone having ordinary skill in the art, at the time of invention, how to make and use the full scope of the claimed invention without undue experimentation.  In the Wands case, the Federal Circuit set forth eight factors (the "Wands factors") that a court may consider when determining whether undue experimentation would have been required:

    (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.

    ALZA asserted that creating non-osmotic dosage forms and manipulating their release rates were well known to a person of ordinary skill in the art at the time of invention.  In addition, ALZA argued that the specification provides sufficient guidance regarding non-osmotic dosage forms because "it identifies a variety of suitable non-osmotic dosage forms and cites to a portion of a standard text to explain how to make and use such non-osmotic, sustained-release dosage forms" with mere routine experimentation.

    Andrx disputed ALZA's contention that enablement can be satisfied by referring to what persons of ordinary skill in the art would know "because what one of the proper skill in the art knows cannot substitute for disclosure of novel aspects of the invention, i.e., the non-osmotic dosage forms exhibiting ascending release rates."  In addition, Andrx pointed to three Wands factors in particular–the sparse guidance provided by the specification, the absence of working embodiments, and the breadth of the claims–in support of its argument that creating non-osmotic dosage forms with ascending release rates would have required undue experimentation.

    The Federal Circuit rejected ALZA's first argument:

    To the extent that ALZA argues that the knowledge of a person of ordinary skill in the art satisfies the enablement requirement, we disagree.  As this court has repeatedly stated, "the rule that a specification need not disclose what is well known in the art is merely a rule of supplementation, not a substitute for a basic enabling disclosure."  Auto. Tech., 501 F.3d at 1282.

    The Federal Circuit next addressed ALZA's argument that the disclosure in the '373 patent specification enables a person of ordinary skill to make and use the claimed dosage forms.  According to the court, ALZA pointed to "ten lines of the specification, which mention non-osmotics and refer to a textbook discussing how to make and use various types of non-osmotic sustained-release dosage forms."  The court agreed with the district court that "this disclosure provides no guidance as to how to achieve ascending release with non-osmotic oral dosage forms."  The court again quoted the Auto. Tech. case:

    The omission of minor details does not cause a specification to fail to meet the enablement requirement.  However, when there is no disclosure of any specific starting material or of any of the conditions under which a process can be carried out, undue experimentation is required.

    The Federal Circuit concluded with a statement akin to "you've made your bed, now lie in it":

    As we stated in Liebel-Flarsheim . . ., "The irony of this situation is that Liebel successfully pressed to have its claims include a jacketless system, but, having won that battle, it then had to show that such a claim was fully enabled, a challenge it could not meet."  In this case, ALZA successfully argued to the district court that the claims encompassed both osmotic and non-osmotic dosage forms.  However, ALZA's patent specification does not enable the full scope of the claims, namely non-osmotic oral dosage forms with ascending release rates.

    ADDITIONAL READING:

  • Dr. Reddy’s Wins Attorney’s Fees from AstraZeneca in Prilosec OTC Case

    AstraZeneca v. Dr. Reddy's, No. 07–6790 (S.D.N.Y. 2010)

    After Dr. Reddy's filed an ANDA for Prilosec OTC (omeprazole), AstraZeneca filed suit, alleging infringement of U.S. Patent Nos. 5,690,960 and 5,900,424.  The patents claim omeprazole formuilations comprising a magnesium salt "having more than 70% crystallinity" and related processes of manufacture.

    In response, Dr. Reddy's provided independent test results purporting to show that their product did not infringe the patents and offered to produce samples for Astra to test, suggesting that this matter could be resolved quickly.  The district court subsequently required Dr. Reddy's to produce samples of their omeprazole product and ordered Astra to test those samples.  Astra’s tests confirmed that the Dr. Reddy's samples were less than 1% crystalline (essentially amorphous).  Dr. Reddy's then moved for summary judgment on the ground of noninfringement.

    But Astra pressed on, filing a request for additional discovery under Rule 56(f), arguing that further discovery was necessary to adequately access whether to maintain the suit.  Astra provided Dr. Reddy's and the court with proposed additional interrogatories, document requests and deposition requests, alleging that Dr. Reddy's may be manufacturing a crystalline product and then converting it into an amorphous form.  The court allowed limited discovery, requiring Dr. Reddy's to produce portions of their ANDA and DMF and to make available a witness with knowledge of Dr. Reddy's process for manufacturing omeprazole magnesium.  After completing discovery, Astra was unable to provide any evidence to the court's satisfaction that Dr. Reddy's product and process infringed the listed patents.  Nevertheless, Astra declined to withdraw its Complaint and instead requested a Markman hearing to construe the phrase "by addition of water."

    In March 2009, the district court ruled on summary judgment that there was "no evidence whatever that Dr. Reddy's makes or uses a salt with the requisite degree of crystallinity."  Late last year, the Federal Circuit affirmed the ruling without further opinion.

    Last month, the district court granted Dr. Reddy's motion for attorney's fees.  Analyzing a motion for attorney's fees is a two-step process:  (1) the court considers the "totality of the circumstance" in determining whether the case is exceptional under 35 U.S.C. § 285; (2) if found exceptional, the court determines whether granting attorney's fees is appropriate.

    In finding this case to be exceptional, the court weighed the "reasonableness" of Astra's decision not to withdraw the suit despite evidence from an independent source and Astra itself that Dr. Reddy's product did not infringe.  The court reasoned that "an inference of bad faith exists when a patentee is manifestly unreasonable in assessing infringement, while continuing to assert infringement in court."  The court thus concluded:

    [Astra] had an obligation not to file a lawsuit unless it had some evidence that Dr. Reddy's was in fact infringing.  The fact that a competitive product comes onto the market is not, without more, evidence of infringement.  Dr. Reddy's provided Astra with evidence of noninfringement prior to plaintiff’s filing suit.  Given the evidence in record before this court . . . I am hard pressed to see why the act of filing this lawsuit did not violate Fed. R. Civ. P. 11.

    The court reacted strongly to AstraZeneca's arguments against a finding of exceptional case:

    AstraZeneca insists that its litigation conduct here was appropriate because a lot of money was on the line.  That is a ridiculous claim to make.  Astra was not free to throw up roadblocks or to assert a claim construction in bad faith — to abuse the court system — just because it was to its economic advantage to keep a competitor out of the marketplace.

     

    AstraZeneca also argues that finding this case "exceptional" will "act to chill zealous advocacy by other litigants."  I certainly hope that this ruling chills the sort of unreasonable, frivolous, anti-competitive, anti-consumer litigation in which plaintiffs here engaged.  This lawsuit was nothing more than an effort to keep a legitimate competitor out of the market on flimsy-to-nonexistent grounds.  Plaintiffs did not engage in zealous advocacy here; they engaged in litigation misconduct.  They abused the litigation process and needlessly consumed the scarce time of the court.  A case in which such tactics are employed ought be deemed exceptional.

    The court further found that attorney's fees were appropriate, citing the "public’s interest in getting non-infringing generic drugs to the market without delay" and as a means to protect the courts "from patentees who maintain abusive and frivolous litigations."  The court concluded:

    It was obvious from very early on that plaintiffs had brought and were maintaining this lawsuit in a desperate effort to keep any competing product from hitting the shelves — even if the competing product was not an infringing product.  For choosing that bad faith business strategy, and for cluttering a busy court with work that should never have had to be done, [plaintiffs] should pay the full measure of the fees and expenses incurred by defendants in getting rid of AstraZeneca’s baseless lawsuit.

    ADDITIONAL READING:

  • District Court Declines to Stay Integrilin Case, Putting Teva At Risk of Forfeiting 180-Day Exclusivity

    Millenium Pharms. and Schering Corp. v. Teva, No. 09–105 (D. Del. 2010)

    Under the “failure to market” forfeiture provision, the first ANDA filer forfeits its exclusivity is it fails to market its ANDA product within 75 days of a Federal Circuit decision of patent invalidity or noninfringement.  See 21 U.S.C. 355(j)(5)(D)(i)(I)(bb)(AA).  This presents a dilemma to ANDA applicants who wish to file a Paragraph III certification on a patent that will not expire until far in the future—specifically, more than 75 days after a Federal Circuit decision would be reached.

    In this case, Teva filed an ANDA for generic versions of Integrilin (eptifibatide), an antiplatelet drug that is used to reduce the risk of acute cardiac ischemic events.  Teva’s ANDA included Paragraph III certifications to U.S. Patent Nos. 5,686,570 and 5,756,451, which expire in 2014; and Paragraph IV certifications to U.S. Patent Nos. 5,807,825, 5,747,447 and 5,968,902, which expire in 2015.

    Teva duly provided notice of its Paragarph IV certifications to Millenium and Schering, who last year responded by filing suit for infringing the ‘825, ‘447 and ‘902 patents under 35 U.S.C. 271(e)(2).  Last month, believing that the case will take roughly 2.5 years to litigate, and not wishing to forfeit its 180–day exclusivity, Teva filed a motion to stay the action until May 11, 2012 (2.5 years before the patents-in-suit will expire).  In its motion, Teva relied on last year’s decision by the Northern District of Illinois in Abbott v. Matrix, which granted a motion to stay in similar circumstances.

    Unfortunately for Teva, the District of Delaware saw things differently.  Last week, the court denied Teva’s motion.  According to the court:

    Given that Plaintiffs have demonstrated more than “a fair possibility” that they will be harmed by the entry of a stay, Defendants must show that they have a “clear case of hardship or inequity” in order to justify the granting of a stay.  Admittedly, Defendants have shown that they will be harmed if a stay is not entered, as they will likely forfeit their 180-day exclusivity period.  Defendants, however, have only themselves to blame for this result.  Defendants were aware of the statutory preconditions necessary for them to obtain the 180–day exclusivity period, and were aware of the potential that this could be forfeited given the timing of the filing of their ANDAs.  Although Defendants did not file this suit, they were well aware that their ANDA triggered the start of a 45-day period for Plaintiffs to defend the validity of their patents, and, in this sense, did control the timing of the present litigation.  Rather than wait until they could fully take advantage of their position as first filer, however, Defendants sought to prematurely reserve their place at the front of the line, and now seek an order from this Court that allows them to preserve that position.  This is not the type of hardship or balance of inequities that can appropriately convince this Court to issue a stay in the present proceedings.  Although Defendants may suffer a hardship, it is one of their own creation and, therefore, we do not think that it can outweigh the harm caused to Plaintiffs by granting this stay.

     ADDITIONAL READING:

  • Federal Circuit Vacates Injunction that Directed Novo Nordisk to Revise Patent Use Code for Prandin

    Novo Nordisk v. Caraco Pharm. Labs. et al., No. 2010-1001 (Fed. Cir. 2010)

    In the Medicare Modernization Act of 2003, Congress gave ANDA applicants who have been sued for patent infringement the statutory right to file a counterclaim seeking the delisting of the patent from the Orange Book:

    If an owner of the patent or the holder of the [NDA] for the drug that is claimed by the patent or a use of which is claimed by the patent brings a patent infringement action against the [ANDA] applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder . . . on the ground that the patent does not claim either—(aa) the drug for which the application was approved; or (bb) an approved method of using the drug.  21 USC 355(j)(5)(C)(ii).

    Pursuant to this provision, after Novo Nordisk sued Caraco for infringement of U.S. Patent No. 6,677,358 based on Caraco’s paragraph IV certification, Caraco filed a counterclaim requesting an order directing Novo to change the Orange Book patent use code for the ‘358 patent, and thereby “correct the patent information” for the ‘358 patent.

    Prandin (repaglinide) is FDA-approved for three uses:  (1) repaglinide by itself (i.e., monotherapy); (2) repaglinide in combination with metformin; and (3) repaglinide in combination with thiazolidinediones.  The ‘358 patent, which is the only patent listed in the Orange Book for Prandin, claims, “A method for treating non-insulin dependent diabetes mellitus (NIDDM) comprising administering to a patient in need of such treatment repaglinide in combination with metformin.”  Accordingly, the original patent use code for Prandin was “Use of repaglinide in combination with metformin to lower blood glucose.”

    Caraco’s ANDA contained a paragraph IV certification to the ‘358 patent and a section viii statement declaring that Caraco was not seeking approval for the repaglinide-metformin combination therapy.  Because there was no overlap between Caraco’s proposed carve-out label and the repaglinide-metformin use code, FDA accepted the proposed label.

    Thereafter, Novo changed the use code for the ‘358 patent to broaden it from the repaglinide-metformin combination therapy to “A method for improving glycemic control in adults with type 2 diabetes mellitus.”  The new use code covered all three approved uses for Prandin, even though the ‘358 patent covered only one approved use.  Caraco’s carve-out label now overlapped with the use code, and therefore FDA retracted its approval of Caraco’s proposed label and section viii statement.  As a result, Caraco’s current label now includes the repaglinide-metformin combination therapy, which is stipulated to infringe claim 4 of the ‘358 patent.  This prompted Caraco’s counterclaim seeking an order directing Novo to replace the new use code with the former listing.

    On September 24, 2009, the U.S. District Court for the Eastern District of Michigan ruled that Caraco was entitled to the requested injunction.  The court stated, “Novo, by the change in the use code narrative is attempting to extend the life of an expired patent”—namely, U.S. patent RE37,035, which broadly claims repaglinide.  According to the court, “the clear legislative intent behind the 2003 amendments to Hatch-Waxman that added the counterclaim provision, section 355(j)(5)(C)(ii), [was] to curb Orange Book abuses arising from misinformation regarding listed patents.”  The next day, the court issued an order granting the injunction sought by Caraco.

    On Wednesday, in a 2-1 decision—over a 28–page dissent from Judge Dyk—the Federal Circuit reversed and vacated the injunction.  The majority reasoned that the statutory language is clear on its face:  “an approved method of using the drug” means “any approved method” (as Novo urged) rather than “all approved methods” (as Caraco argued).  Further, according to the majority, its decision to vacate the injunction is consistent with the legislative intent:  the counterclaim provision in the 2003 Act “sought to correct the specific issue raised in Mylan v. Thompson (Fed. Cir. 2002), i.e., to deter pioneering manufacturers from listing patents that were not related at all to the patented product or method.”  In addition, the majority concluded that “the patent information” referred to in the counterclaim provision meant “the patent number and the expiration date”—not also the use code narrative.

    In dissent, Judge Dyk expressed strong disagreement with the majority.  He wrote:

    In 2003, Congress enacted the counterclaim provision of the Hatch-Waxman Act in order to prevent manipulative practices by patent holders with respect to the Orange Book listings.  These practices were designed to delay the onset of competition from generic drug manufacturers.  In my view, the majority, in reversing the district court, now construes the statute contrary to its manifest purpose and allows the same manipulative practices to continue in the context of method patents.

    Judge Clevenger, in a short concurring opinion, stated that, in his view, “Novo did nothing that was illegal or forbidden.”  He acknowledged that FDA “may have inadvertently upset the careful balance of interests represented by the efficient dispute resolution mechanism Congress created in the Hatch-Waxman Act.”  But, he concluded, “Congress is the appropriate entity to readjust, if necessary, the delicate balance it has struck between original drug manufacturers and their generic counterparts.”

    Perhaps Congress will "readjust" the Act–time will tell.  Caraco and Novo Nordisk have not yet commented on the Federal Circuit’s decision.

  • ACI “Paragraph IV Disputes” Conference, New York, April 27-28

    American Conference Institute’s 4th Annual “Paragraph IV Disputes" conference will take place in New York City on April 27–28.

    I am looking forward to speaking at the conference in a session entitled “Recent Decisions Impacting Paragraph IV Challenges and Motion Practice”.  My presentation will be about recent judicial decisions concerning declaratory judgment jurisdiction and method-of-treatment patents.

    A highlight of the conference will be a panel discussion with the Honorable Garrett E. Brown, Jr., U.S. District Judge; Honorable Joel A. Pisano, U.S. District Judge; and Honorable Tonianne Bongiovanni, U.S. Magistrate Judge.  All three have very active paragraph IV litigation dockets in the District of New Jersey.  Another highlight will be an FTC presentation on “pay for delay” settlements, by Markus H. Meier, Assistant Director of the Health Care Division, Bureau of Competition, Federal Trade Commission.  Mr. Meier will provide an update on FTC's activities to end such settlements.

    Other presentations include:

    • Pre-suit due diligence strategies in anticipation of the paragraph IV challenge
    • Assessing the ANDA applicant’s initial obligations
    • New takes on obviousness: pre-suit considerations for brand names and generics
    • Throwing down the gauntlet: the paragraph IV notice letter — delivery and receipt
    • Let the games begin: the start of the paragraph IV law suit — pleadings and considerations
    • Exploring exclusivity and forfeiture dilemmas relative to paragraph IV litigation
    • A closer look at generic v. generic lawsuits
    • Discovery strategies and pre-trial maneuvering tactics for brand names and generics
    • Assessing danger and mitigating liabilities associated with injunctions and “at-risk launches”

    In addition, a pre-conference workshop is offered on Monday, April 26, entitled “Hatch-Waxman Boot Camp — A Primer on IP Basics and Regulatory Fundamentals” and a post conference workshop is offered on Thursday, April 29, entitled “Master Class on Settling Paragraph IV Disputes: Brand-Name and Generic Perspectives”.

    Orange Book Blog readers may receive a substantial discount on registration fees with the “media partner discount”.

    For more information or to register, please visit the conference website.

  • Walking the Enablement/Non-obviousness Tightrope

    In re '318 Patent Litigation, Nos. 2008-1594, 2009-1070 and 2009-1088 (Fed. Cir. 2009)

    Eli Lilly & Co. v. Actavis Elizabeth LLC, et al., No. 07-3770-DMC (D.N.J. 2009)

    Two recent cases illustrate how owners of pharmaceutical method-of-use patents may find themselves walking a tightrope when their patents are attacked simultaneously on enablement and obviousness grounds.

    First, in a 2–1 decision last September, the Federal Circuit affirmed the invalidity of U.S. Patent No. 4,663,318.  The ‘318 patent claims “a method of treating Alzheimer’s disease and related dementias which comprises administering . . . a therapeutically effective amount of glanthamine. . . .”  The ‘318 patent is the only Orange Book-listed patent for Janssen’s Alzheimer’s drug, Razadyne.

    Then, in an opinion filed in December, denying motions for summary judgment, the U.S. District Court in New Jersey clearly indicated that Eli Lilly would have a hard time at trial surviving the defendants’ lack-of-enablement and obviousness challenges to U.S. Patent No. 5,658,590.  The ‘590 patent claims a method of treating Attention Deficit/Hyperactivity Disorder (ADHD) with atomoxetine.  The ‘590 patent is the only Orange Book-listed patent for Lilly’s ADHD drug, Strattera.

    In both cases, the generic drug company defendants asserted that the patents were invalid for both lack of enablement and obviousness.  More specifically, they argued that the claimed methods were not enabled because the patentees had not properly established that the claimed methods had utility.

    The Federal Circuit described the relationship between the enablement and utility requirements in Process Control v. HydReclaim:

    The enablement requirement of 35 U.S.C. 112, requires that the specification adequately discloses to one skilled in the relevant art how to make, or in the case of a process, how to carry out, the claimed invention without undue experimentation.  The utility requirement of 35 U.S.C. 101 mandates that any patentable invention be useful and, accordingly, the subject matter of the claim must be operable.  If a patent claim fails to meet the utility requirement because it is not useful or operative, then it also fails to meet the how-to-use aspect of the enablement requirement.

    In Janssen, the Federal Circuit further explained:  “The utility requirement prevents mere ideas from being patented. . . .  The utility requirement also prevents the patenting of a mere research proposal or an invention that is simply an object of research.”  Quoting a 1966 Supreme Court decision, Brenner v. Manson, the Janssen court explained the policy behind the utility requirement:  “Allowing ideas, research proposals, or objects only of research to be patented has the potential to give priority to the wrong party and to confer power to block off whole areas of scientific development, without compensating benefit to the public.”

    According to the Janssen decision, “Typically, patent applications claiming new methods of treatment are supported by test results.”  But “human trials are not required for a therapeutic invention to be patentable, as results from animal tests or in vitro experiments may be sufficient to satisfy the utility requirement.”  Further, utility/enablement is determined as of the effective filing date of the patent application and it must be recognizable to one of ordinary skill in the art from the written description.  Therefore, any test results (whether human, animal or in vitro) should be disclosed in the original patent application.  The patentees in Janssen and Lilly ultimately obtained test results supporting the utility of their claimed methods of use, but they did not include those test results in their patent applications.

    Thus, Janssen and Lilly argued that one of skill in the art would have recognized the utility of their inventions from the discussion of prior art in their patent specifications.  For example, Janssen argued that (1) the prior art tests summarized in the specification would lead one skilled in the art to infer that galantamine affected the ability of acetylcholine to bind to both nicotinic and muscarinic receptors in the brain; (2) the animal tests proposed in the specification as a model for Alzheimer’s disease would further lead one skilled in the art to infer that the model’s method of impairing brain acetylcholine availability would allow both muscarinic and nicotinic effects to be observed; and (3) because nicotinic receptors in the brain are involved with the ability to learn, the specification suggested that galantamine could have beneficial effects on learning.  Similarly, Lilly argued that one of ordinary skill in the art would have inferred that: (1) the prior art compounds disclosed in the specification were effective in treating ADHD because they inhibited norepinephrine; (2) atomoxetine was, similarly, an active norepinephrine inhibitor; and (3) atomoxetine would therefore be successful in treating ADHD.

    And this is where Janssen and Lilly’s non-obviousness arguments caused them trouble.

    For instance, in Janssen, the Federal Circuit majority relied upon the following testimony (all of which was provided in support of non-obviousness) to affirm the finding of no enablement:

    • During prosecution, in response to the examiner’s obviousness rejection, the inventor stated that “nothing in this teaching leads to an expectation of utility against Alzheimer’s disease.”
    • The inventor also stated that “predicting that galanthamine would be useful in treating Alzheimer’s disease just becuase it has been reported [in the prior art studies cited in the specification] to have an effect on memory” would be baseless.
    • At trial, Janssen’s expert testified that studying a compound’s effects on scopolamine-induced amnesia [as disclosed in prior art cited in the specification] “ignores the whole other [nicotinic] part that’s damaged in Alzheimer’s disease” and thus “doesn’t mimic Alzheimer’s disease.”
    • Also at trial, the inventor testified, “When I submitted this patent, I certainly wasn’t sure, and a lot of other people weren’t sure that cholinesterase inhibitors, [a category of agents that includes galantamine,] would ever work.”

    In Lilly, the district court relied upon similar testimony:

    • The inventor admitted that treating ADHD with atomoxetine was merely hypothetical.
    • Lilly’s expert testified that if in 1995 he heard the hypothesis that atomoxetine would be effective in treating ADHD, he would have responded:  “you’re wrong, it’s not a good model.”
    • Lilly’s expert also explained that a person of ordinary skill in the art “would not predict atomoxetine would be effective” as “we were moving away from single neurotransmitter drugs.”

    A footnote in the Lilly case nicely summarized the problem that a dual lack-of-enablement/obviousness attack presents to patentees:

    Plaintiff emphasizes the differences between atomoxetine and the prior art for the purposes of refuting Defendant’s obviousness argument, while at the same time asserting that the prior art and atomoxetine are in some ways similar in order to demonstrate enablement/utility.  Defendants argue, then, that the Court must find the patent invalid as either obvious or not enabled.  For example, if the Court determines that a person of ordinary skill in the art would be able to infer utility based upon the patent’s specification, Defendants’ enablement argument might fail, but its obviousness argument would presumably be bolstered.  In essence, Defendants argue that whichever set of experts is credited, Plaintiff’s patent will be invalidated.

    In the Janssen and Lilly cases, perhaps the only way to avoid this Catch-22 would have been to include preliminary test data in the orignal patent specification.

    UPDATE:  On February 23, 2010, the district court denied Eli Lilly's motion for reconsideration or, in the alternative, for certification for interlocutory appeal.  Trial is scheduled to begin May 18, 2010.

  • ACI “Maximizing Pharmaceutical Patent Life Cycles” Conference, New York, October 7-8

    American Conference Institute is hosting a special 10th Anniversary Edition of its annual "Maximizing Pharmaceutical Patent Life Cycles" conference on October 7th and 8th in New York.  According to ACI, this is "the one and only event that consistently allows brand name and generic
    drug makers to benchmark their companies' current strategies and
    tactics against competitors in both camps.    "

    Here's the agenda:

    • The endgame reinvented:  preparing for an emerging pharmaceutical patent paradigm
    • Patent reform and the pharmaceutical industry:  anticipating and adapting to change
    • Follow-on biologics:  understanding the role of patents in health care reform and related consequences for life cycle strategies
    • Wyeth v. Dudas:  revisiting patent term adjustment calculations
    • Overcoming obviousness:  an analysis of the post-KSR treatment of primary and secondary patents and finding new ways to extend patent life
    • In Re Bilski:  exploring its implications for pharmaceutical method claims
    • Eye on the Federal Circuit and District Courts:  life cycle lessons derived from Paragraph IV litigation
    • FTC keynote:  promoting competition in the pharmaceutical industry
    • EC keynote:  the European Commission Pharmaceutical Sector Inquiry — main findings and policy recommendations
    • Rethinking life cycle strategies for established and emerging international markets:  focus on Europe and Asia
    • A new look at Orange Book listings, delistings and related challenges
    • FDA keynote:  update on FDA activities relative to pharmaceutical patent life cycles
    • Exclusivity:  modes, methods and new interpretations
    • Re-exploring the safe harbor:  learning to navigate the potential limits and boundaries of Proveris

    In addition, an optional pre-conference workshop is offered on October 6th:  "Hatch-Waxman Boot Camp–a primer on IP basics and regulatory fundamentals".  And two optional master classes are offered on October 9th:  "Brand Name Master Class–new strategies for obtaining pharmaceutical patent extensions in a post-KSR world" and "Generic Master Class–updated drafting guidelines for paragraph IV certifications and notice letters".

    ACI is offering Orange Book Blog readers a $500 discount off the standard registration fee (for a flat rate of $1695) when referencing the "Media Partner Discount".  For more information or to register, please visit the conference website.

  • Federal Circuit Affirms Invalidity of Bayer Patent on Yasmin

    Bayer Schering v. Barr Labs, No. 2008-1282 (Fed. Cir. 2009)

    A divided panel of the Federal Circuit today affirmed a district court decision holding Bayer's U.S. Patent No. 6,787,531 invalid due to obviousness.  The '531 patent, which claims pharmaceutical compositions of drospirenone and ethinyl estradiol, protects Bayer's popular birth-control pill Yasmin.  In today's decision, the majority (Judges Mayer and Friedman) held that "the invention would have been obvious to try."  Judge Newman dissented.

    Drospirenone is an acid-sensitive and poorly soluble compound.  The use of drospirenone with ethinyl estradiol was known in the prior art, but, according to Bayer, formulations of micronized drospirenone in a normal (not enteric coated pill) would not have been obvious, especially since the prior art taught that an enteric coating is necessary to protect drospirenone from the acidic environment of the stomach.

    The majority, however, disagreed.  Citing KSR, the majority stated that a person having ordinary skill in the art would have chosen

    between two known options:  delivery of micronized drospirenone by a normal pill . . . or delivery of drospirenone by an enteric-coated pill . . . .  This is a finite number of identifed, predictable solutions.  The prior art would have funneled the formulator toward these two options; he would not have been required to try all possibilities in a field unreduced by the prior art . . . .

    In dissent, Judge Newman argued that the actual experience of the Bayer scientists should be dispositive.  They testified, without contradiction, "that it was not reasonably expected that uncoated micronized drospirenone would be 99+% effective as an oral contraceptive when ingested into the acid stomach, when it was known to degrade rapidly in acid."  According to Judge Newman, "the exercise of judicial expertise to override the clear evidence of how persons of skill in this field actually behaved, is inappropriate."

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