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At the intersection of Patent and FDA Law

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  • Federal Circuit Affirms Dismissal of Factor VIII Priority Case for Lack of Interfering Subject Matter

    Genetics Institute, LLC v. Novartis Vaccines & Diagnostics, Inc., No. 2010-1264 (Fed. Cir. 2011)

        by Scott P. McBride

    In 2000, Genetics Institute obtained a patent term extension under 35 U.S.C. § 156 on U.S. Patent No. 4,868,112, based on the time consumed by testing and regulatory review of its commercial recombinant Factor VIII product, ReFacto®, which is indicated for the treatment of hemophilia A.  The PTO extended the term of the '112 patent approximately 3.5 years, to February 28, 2010.

    In May 2008, during the extended term of the '112 patent, Genetics Institute sued Novartis Vaccines and Diagnostics, Inc. under 35 U.S.C. § 291 to determine priority of invention between claims 1, 5, 9 and 10 of the '112 patent and certain claims of Novartis's U.S. Patent Nos. 6,228,620 and 6,060,447.  Genetics Institute asserted that the claims at issue were all directed to the same subject matter, namely truncated Factor VIII proteins lacking all or part of the B domain while retaining procoagulant activity.

    Novartis moved to dismiss the suit on two grounds: (1) lack of subject matter jurisdiction because the extension of the '112 patent under 35 U.S.C. § 156 applied only to certain claims, and not to the entire patent; and (2) lack of interference in fact.

    Last year, the U.S. District Court for the District of Delaware granted Novartis's motion to dismiss, concluding that there was no interference in fact as to any of the allegedly interfering claims.  In an opinion last week, the Federal Circuit affirmed the dismissal on the same grounds.

    Claim 1 of the '112 patent recites:

    A recombinant DNA which upon expression results in a truncated Factor VIII protein which is an active procoagulant wherein the recombinant DNA encodes for a protein having the amino acid sequence of a human Factor VIII:C except for having a deletion corresponding to at least 581 amino acids within the region between Arg-759 and Ser-1709, wherein the amino acid numbering is with reference to Met-1 of the human Factor VIII:C leader sequence.

    In the appeal, Novartis first argued that the Federal Circuit lacked appellate jurisdiction because the '112 patent's extended term expired in 2010.  Novartis argued that an interference between patents under 35 U.S.C. § 291 requires that the allegedly interfering patents be unexpired.  Novartis relied on case law interpreting 35 U.S.C. § 291, specifically Albert v. Kevex Corp., 729 F.2d 757 (Fed. Cir. 1984).  In Albert, the defendant statutorily disclaimed the allegedly interfering claims under 35 U.S.C. § 253, which divested the district court of subject matter jurisdiction.

    The Federal Circuit rejected Novartis's argument that the expiration of the patent term extension had the same effect as a disclaimer, because statutory disclaimers are retroactively considered part of the original patent such that the disclaimed claims are treated as though they "never existed."  In contrast, an expired patent may form the basis of an action for past damages, subject to a defense raising the six-year time limitation on damages.  Moreover, unlike 35 U.S.C. § 135, which relates to interferences between applications or a pending application and an "unexpired patent," Section 291 for interferences between patents is not limited to "unexpired" patents.

    Novartis next argued that the district court lacked subject matter jurisdiction because the extended term allegedly applied to less than all claims of the '112 patent.  Specifically, Genetics Institute’s application to extend the patent term identified only claims 9 and 10 of the '112 patent as relating to its commercial product ReFacto® and claim 10 was allegedly construed by the district court such that it could not cover ReFacto®.

    The Federal Circuit rejected Novartis's arguments based on its conclusions that (1) the language of Section 156 makes clear that the extension applies to the entire patent, not merely on a claim-by-claim basis; (2) the legislative history states that "all provisions of the patent law apply to the patent during the period of extension"; (3) the "rights derived" provision of Section 156(b) was intended to limit the effect of an extension, not to restrict the extension to particular claims (for patents that claim a product, rights in the extended term are "limited to any use approved for the product"); (4) because claim 9 depended from claims 1 and 5, and Novartis conceded that claim 9 covered ReFacto®, Novartis thus conceded that claims 1 and 5 also covered ReFacto®; and (5) the district court did not make any findings of fact that claim 10 did not encompass ReFacto®, but merely stated that claim 10 "may not" encompass ReFacto®.

    Finally, Novartis argued there was no interference in fact between the claims at issue.  An interference in fact under § 291 requires that the two patents claim "the same or substantially the same subject matter," using a "two-way test."  Under the two-way test, an interference exists between two claims if each claim anticipates or renders obvious the other.  The majority opinion (authored by J. Lourie and joined by J. Plager) concluded that the first part of the two-way test (obviousness of Novartis's invention in view of Genetics Institute's invention) was not met.  In reaching this conclusion, the majority held that evidence of unexpected results may be used to rebut a case of prima facie obviousness, even if that evidence was obtained after the patent's filing or issue date.

    Judge Dyk dissented.  Judge Dyk would have held that unexpected results must be disclosed in the junior party's specification or known by the junior party's inventor(s) prior to filing, for such results to be used in determining nonobviousness.  For purposes of the first part of the two-way test, Judge Dyk would have held that unknown and unexpected results would not be usable to (1) show that there was there some reason why the junior inventor would have modified the senior party's invention to arrive at the junior party's invention, and (2) overcome a prima facie case of obviousness.

    It remains to be seen whether and how the court's decision will impact future obviousness cases.

  • Federal Circuit Affirms Summary Judgment of Nonobviousness of FORTICAL Formulation

    Unigene Labs and Upsher-Smith v. Apotex, No. 2010-1006 (Fed. Cir. 2011)

    In a decision yesterday, the Federal Circuit affirmed a district court opinion granting Unigene's motion for summary judgment that claim 19 of U.S. Patent No. RE40,812 is not invalid for obviousness.  Claim 19 of the '812 patent covers the pharmaceutical formulation of FORTICAL (calcitonin nasal spray).  The Federal Circuit also affirmed the district court's denial of Apotex's motion to breach the attorney-client privilege under the crime-fraud exception and the district court's determination that Apotex had waived certain counterclaims, but the validity decision is the most interesting.

    Claim 19 of the '812 patent recites:

    A liquid pharmaceutical composition for nasal administration comprising about 2,200 MRC units of salmon calcitonin, about 20 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(2) sorbitan monooleate.

    Unigene filed its NDA for FORTICAL under section 505(b)(2), naming Novartis's MIACALCIN as the reference listed drug.  Whereas MIACALCIN contains benzalkonium chloride ("BZK"), an absorption enhancer, preservative and surfactant, FORTICAL contains citric acid (absorption enhancer), phenylethyl- and benzyl-alcohol (preservatives) and polysorbate 80 (surfactant).  Unigene also filed a patent application on its formulation, which issued as the '812 patent.

    Apotex filed an ANDA for a generic version of FORTICAL, alleging that claim 19 of the '812 patent is invalid for obviousness.  Apotex argued that the formulation of claim 19 would have been obvious in light of MIACALCIN, a prior art patent (disclosing solid formulations of salmon calcitonin) and a prior art publication authored by Day.  The district court granted summary judgment of nonobviousness, which is relatively rare in Hatch-Waxman cases.

    On appeal, the Federal Circuit began its obviousness analysis with an extensive discussion of KSR, in which the Supreme Court held that the teaching-suggestion-motivation (TSM) test is not a required part of the obviousness analysis.  The Federal Circuit acknowledges this, quoting from KSR:  "The obviousness analysis cannot be confined by a formalistic conception of the words, teachings, suggestion, and motivation . . . ."  But in the next paragraph, the Federal Circuit seems to rely on the TSM test, quoting from its 2006 decision in Eli Lilly v. Zenith Goldline:

    to establish a prima facie case of obviousness based on a combination of elements in the prior art, the law requires a motivation to select the references and to combine them in the particular claimed manner to reach the claimed invention.

    The Federal Circuit then explained how KSR should be applied in cases involving pharmaceutical formulation patents.  The court compared the obviousness analysis in pharmaceutical compound cases to that in pharmaceutical formulation cases:

    A prima facie case of obviousness in the chemical arts is often based on a known compound, called a "lead compound," which serves as a starting point for a person of ordinary skll developing the claimed invention.  Where the patent at issue claims a chemical compound, a lead compound is often used to show structural similarities between the claimed compound and prior art.  In the context of a composition or formulation patent where the patented formulation was made to mimic a previously FDA-approved formulation, the functional and pharmaceutical properties of the "lead compound" can be more relevant than the actual chemical structure (though not always mutually exclusive).  Thus, the term "reference composition" is more appropriate than "lead compound" when considering obviousness for a chemical composition. . . .

    Addressing Apotex's obviousness position specifically, the Federal Circuit stated:  "To a person of ordinary skill in the art, citric acid would not be an obvious substitute for BZK's functions as an absorption enhancer and as a surfactant because citric acid has a vague role in even the closest prior art."  The court further found that the prior art actually teaches away from using citrict acid "as an absorption enhancing agent or stabilizing agent in a liquid formulation with a salmon cacitonin active ingredient."

    The court concluded:  "There is no genuine dispute of material fact that a person of ordinary skill attempting to make a liquid composition to deliver salmon calcitonin into a human body through nasal administration, would not have considered using about 20 mM citric acid with the narrowly claimed amounts of benzyl alcohol, phenylethyl alcohol, and polysorbate 80, because the formulation would not be expected to perform properly to meet the specificity of a pharmaceutical use."

  • Federal Circuit Affirms Validity of Argatroban Patent

    Mitsubishi Chemical Corp. v. Barr Labs., No. 2010-1432 (Fed. Cir. 2011)

    Mitsubishi Chemical owns U.S. Patent No. 5,214,052, which claims a "method for dissolving an arginineamide, comprising dissolving [argatroban] and/or its salt in a solvent containing ethanol, water and a saccharide"; and a "pharmaceutical composition for injection, comprising [argatroban] and/or its salt together with ethanol, water and a saccharide."  Barr filed an ANDA for a generic version of argatroban, alleging that each claim of the '052 patent is invalid due to anticipation and/or obviousness.

    [As an aside, process patents may not be listed in the Orange Book.  In this case, however, the '052 patent also claims pharmaceutical formulations, which makes the patent eligible for listing.  Mitsubishi asserted both the process claims and composition claims in the litigation, and it appears that was just fine with Barr.]

    Last year, the U.S. District Court for the Southern District of New York held following a trial that the claims of the '052 patent are not invalid, and enjoined Barr from marketing a generic version of argatroban until the '052 patent expires (in 2014).  Earlier this week, the Federal Circuit affirmed that decision.

    Barr's primary invalidity argument was that the claims of the '052 patent were anticipated by a Japanese article published in 1986 by a Mitsubishi employee, Toshihiro Yamamoto.  The key dispute concerned the English translation of a single sentence in the Yamamoto article describing the preparation of an argatroban solution that was administered to laboratory rats.

    The district court agreed with Mitsubishi's translation of that sentence: "In 7.5% D-sorbitol-4% ethanol, an argipidine solution dissoved under hydrochloric acid acidity (pH 1.5 to 1.7) was intraperitoneally administered at a dosage of 1 ml/kg, 15 minutes before common carotid artery occlusion."  The court further credited corroborating testimony that Yamamoto teaches dissolution of argatroban in hydrochloric acid, followed by formulation of the dissolved argatroban with D-sorbitol and ethanol.  Barr, on the other hand, argued that the Yamamoto reference taught dissolution of argatroban in a solution containing HCl, D-sorbitol and ethanol, thereby anticipating the process claims of the '052 patent.

    Addressing the district court's findings regarding the correct translation of Yamamoto, the Federal Circuit stated:

    The fact-finder's selection of a particular translation as the best translation of a foreign language reference raises pure questions of fact.  The district court's selection of the appropriate translation in this case was based in large part on a credibility determination, and such determinations are "virtually never" overturned for clear error.  Although Barr contends that [Mitsubishi's] translation should be disregarded because it was prepared for purposes of litigation, that is not a sufficient reason to conclude that the district court's choice of [that] translation was clearly erroneous.

    The Federal Circuit further observed that "the district court took note of the fact that Yamamoto's description of the argatroban solution was quite cryptic because, as both experts agreed, Yamamoto focused on the pharmacological activity of the argatroban molecule, rather than on argatroban's solubility or on treating the rats."  According to the Federal Circuit, "In order to anticipate, the teaching of a reference must be clear and unambiguous."

    With respect to the formulation claims, the district court found that the solution disclosed in Yamamoto is not a "pharmaceutical composition for injection"–i.e., "a composition that is suitable for treating medical conditions by injection"–because to be suitable for injection into human patients a pharmaceutical composition must have a pH above 3, and the Yamamoto solution has a pH between 1.5 and 1.7.  The key dispute here concerned the proper construction of "pharmaceutical composition for injection."  The Federal Circuit affirmed the district court's construction, and thus affirmed the validity of the formulation claims.

  • ACI “Maximizing Pharmaceutical Patent Lifecycles” Conference, New York, October 4-5

    American Conference Institute will be holding its 12th annual "Maximizing Pharmaceutical Patent Lifecycles" conference in New York City on October 4-5, 2011.  I will have the pleasure of speaking at this conference once again–this time on method-of-use patents and inducement of infringement.  The discounted early-registration rate expires Friday, August 12th, so move quickly!

    The conference agenda includes:

    • Understanding How the Patent Cliff Will Redefine the Endgame
    • USPTO Keynote: The Impending Reality of Patent Reform and its Potential Impact on Pharmaceutical Patents
    • Life Cycle Management Controversies Posed by the Biosimilars Act
    • Patent Term Adjustment and Patent Term Extensions Update: Strategies and Considerations for Small and Large Molecules
    • Exploring Post-Issuance PTO Procedures in the Era of the Patent Cliff: Focus on Reexam and Reissue Proceedings
    • The Combined Impact of Prior Art Obviousness and Obvious-Type Double Patenting on Pharmaceutical Patent Life Cycle Strategies
    • Personalized Medicine and Patent Life Cycle Considerations Vis-a-Vis Sections 101, 112, and Allowable Research Exceptions
    • CAFC and Supreme Court Watch: Three Cases That May Have a Radical Impact on Pharmaceutical Patent Life Cycle Strategies
    • FTC Keynote: Analysis of Competitive Behaviors in Pharmaceutical Patent Life-Cycle Management Strategies
    • REMS Studies and Generic Entry: Exploring the Latest Regulatory Conundrum Affecting Pharmaceutical Patent Life Cycle Strategies
    • Carve-Outs, Skinny Labeling and Use Codes: Understanding Their Role in Orange Book Listing Strategies and Life Cycle Management
    • Inducement Actions and Divided Infringement: How Method-of-Use Claims Controversies are Influencing Orange Book Listings (I'll be speaking on this panel)
    • Exclusivities and Forfeitures: New Developments, Controversies and Concerns
    • FDA Keynote: Update on FDA Activities Impacting Pharmaceutical Patent Life Cycles for Small and Large Molecules
    • Safe Harbor or Stormy Port?  Calming the Legal Tempest Left by Proveris

    In addition to the main conference, ACI will offer two pre-conference workshops on October 3rd:  "PTA-PTE Boot Camp: Basic Training in the Essentials of Patent Term Adjustment and Patent Term Restoration for Patent Lawyers Serving the Biopharmaceutical Industry"; and "Working Group on Global Pharmaceutical Patent Life Cycle Management Strategies for Established and Emerging Markets: A Practical, Hands-On Guide to Patent Extensions and Exclusivities Available to Pharmaceutical Products Around the World".

    Orange Book Blog is a media partner of this conference, so readers are eligible for a $200 discount (beyond any other discounts) by using registration code OBB 200.  For more information or to register, please visit the conference website.

  • Federal Circuit Confirms that Isolated DNA May Be Patented

    Assoc. for Molecular Pathology v. Myriad Genetics, No. 2010-1426 (Fed. Cir. 2011)

        by Nabeela Rasheed

    In a decision last Friday, the Federal Circuit confirmed that isolated DNA may be patented.  Judge Lourie brought his considerable chemistry background to bear in writing the court's opinion in a case presenting the question of whether isolated DNA is patent-eligible subject matter.

    Myriad appealed a district court decision that held, on summary judgment, that the claims of a number of patents relating to the breast and ovarian cancer genes BRCA1 and BRCA2 were invalid because the gene sequences were products of nature and therefore unpatentable.  The Federal Circuit addressed this question, and it also addressed whether the plethora of plaintiffs had standing to challenge the patents.  The following précis discusses the merits of the patent eligibility of isolated DNA molecules and methods of diagnosis.  The opinion clearly answered the first question in the affirmative for isolated DNA molecules and provided a "maybe" for diagnostic methods, but not in the form presented by Myriad.

    In reviewing the patent eligibility of DNA-related claims, the court reverted to the reasoning from the Supreme Court's decision in Chakrobarty, 447 US 1981, the ancestor of most biotechnology decisions in the area of 35 U.S.C. 101.  The test fashioned since that decision focuses on whether a man-made composition is patent-eligible subject matter and answers that it is if the claimed subject matter is a non-naturally occurring composition of matter having a distinct name, character and use.

    Applying the test to isolated DNAs, the Federal Circuit concluded here that the challenged claims are drawn to patentable subject matter because the claims cover molecules that are markedly different–-they have distinctive chemical identity and nature–from molecules that exist in nature.  The DNA molecules claimed by Myriad are in an isolated state: they are not the same molecules as those existing in the body.  It took human intervention in cleaving or synthesizing these new chemicals and this human intervention imparts on that isolated DNA a distinctive chemical identify from that possessed by such a chemical within native DNA.

    The court took pains to explain that isolated DNA is not merely purified DNA but rather it is a distinct chemical entity defined by separate molecular species joined together by an all-important chemical bond.  In addressing the patent eligibility of the underlying DNA claims, the court dismissed the argument that the DNA should not be patent-eligible because it does not have markedly different characteristics from the characteristics of the DNA in native form.  The court again reiterated that the subject matter is a distinct chemical entity and that focusing on the properties or use of that chemical entity improperly conflates the patent eligibility inquiry with an obviousness inquiry.

    In the same vein, the Federal Circuit dismissed the middle-ground arguments advanced by the Patent Office: that isolated DNAs should not be patentable because they can be seen using a "magic microscope" whereas cDNAs cannot.  The court rejected the Patent Office’s argument as it fails to understand the difference between science and invention and fails to recognize that the DNA molecules are separate chemical entities regardless of whether they are cDNA molecules or isolated genomic DNA molecules.  The court noted that the ability to visualize a DNA molecule is "worlds apart" from possession of an isolated DNA.  Noting that this is the difference between knowledge of nature and a reduction of that knowledge to a concrete form, the latter activity being the very ingenuity that the patent laws seek to encourage through protection, the court provided its imprimatur to DNA composition-of-matter claims regardless of whether they are cDNA claims or isolated genomic DNA claims.

    The court was not so forthcoming with the same endorsement for the diagnostic method claims as presented in the patents.  All but one of the method claims at issue covered "analyzing" or "comparing" a patient's DNA sequence with the DNA sequence from wild-type or normal patients that do not have cancer to effectively correlate a difference in the DNAs with a cancer.  The court noted that the "analyzing" or "comparing" step is the entire process claimed, and can in fact be a mental step without being tied to some additional transformative test–and hence these method claims fail the test of patent eligibility.  However, that is not to say that Myriad provides the death knell for diagnostic method claims.  Rather, the court stated that "isolating genes to provide useful diagnostic tools and medicines is surely what the patent laws are intended to encourage and protect."

    With the above encouragement in mind, it is still possible to obtain claims to methods of diagnosis of a disease as long as the diagnostic methods that involve analysis or comparison of a diseased state with a wild-type or normal state are crafted to include a physical step such as "extraction" or other manipulation of the underlying chemical to be analyzed or compared in the diagnostic step.  Crafting the appropriate language for this additional element in diagnostic method claims will become ever more important with the dawning of the age of personalized medicine and the need for protection of underlying intellectual property focused on personalized medicine.

    The court seems to have applied well-established law under 35 U.S.C. 101, including the recent guidance provided by the Supreme Court in Bilski, making it a more remote possibility that the Supreme Court would accept the case review.

  • Federal Circuit Affirms Summary Judgment of No DOE Infringement in CENESTIN Case

    Duramed Pharms., Inc. v. Paddock Labs., Inc., No. 2010-1419 (Fed. Cir. 2011)

        by Scott P. McBride

    CENESTIN is a conjugated estrogen pharmaceutical composition used to reduce the symptoms of menopause.  In a 3-0 decision last week, the Federal Circuit affirmed that Paddock's generic version of CENESTIN would not infringe U.S. Patent No. 5,908,638, directed to conjugated estrogen compositions, under the Doctrine of Equivalents.

    Claim 1 of the '638 patent recites:

    A pharmaceutical composition in a solid, unit dosage form capable of oral administration for the hormonal treatment of peri-menopausal, menopausal and post-menopausal disorders in a woman comprising: conjugated estrogens coated onto one or more organic excipients forming a powdered conjugated estrogen composition where said composition is substantially free of inorganic excipients and further comprises about 30-70% gel-forming organic excipient and about 30-70% non-gel forming organic excipient by weight and having less than about 2.5% free water by weight and greater than 2.5% total water wherein said solid unit dosage form is coated with a moisture barrier coating comprising ethylcellulose.

    In 2008, Paddock filed an ANDA for a generic version of CENESTIN, after which Duramed filed suit for infringement of the '638 patent.  Duramed asserted infringement of independent claim 1 and dependent claims 4 and 6-8 under the doctrine of equivalents only.

    In an opinion last year, District Judge Sand (S.D.N.Y.) concluded on summary judgment that the four asserted claims were not infringed under the doctrine of equivalents due to prosecution history estoppel.  During prosecution, claim 1 originally recited a conjugated estrogen pharmaceutical composition "coated with a moisture barrier coating" (MBC).  Original dependent claim 7 limited "said moisture barrier coating" to one that "comprises ethylcellulose."  After initially rejecting both claims as obvious, the examiner later advised that he would allow the application if Duramed amended claim 1 to include the limitations of claim 7.  In response, Duramed amended claim 1 to recite pharmaceutical compositions with "a moisture barrier coating comprising ethylcellulose."

    Judge Sand concluded that the amendment adding the ethylcellulose limitation was substantially related to patentability and narrowed the claim scope, thus triggering the Festo presumption that Duramed had surrendered all territory between the original and amended claim scope (i.e., between "coated with a moisture barrier coating" and coated with a moisture barrier coating "comprising ethylcellulose").  Judge Sand also concluded that Duramed had failed to rebut the Festo presumption based on an argument of the unforeseeability of the use of polyvinyl alcohol (PVA) MBC, used in Paddock's proposed generic product and marketed as Opadry AMB.  Judge Sand concluded that PVA MBCs were foreseeable at the time of Duramed's narrowing amendment (December 1998) because, among other things: (1) a Colorcon PCT application published in January 1996 described PVA as "a moisture barrier coating for pharmaceutical tablets and the like"; (2) pre-September 1996 invoices existed for the sale (by Colorcon) of Opadry AMB; and (3) a 1976 patent to Groppenbächer disclosed the use of PVA in moisture-tight tablets.

    In affirming, the Federal Circuit noted that Duramed could rebut the presumption of prosecution history estoppel by showing that the alleged equivalent would have been unforeseeable at the time of the amendment and was thus beyond a fair interpretation of what was surrendered.  Duramed argued that the district court applied the wrong legal test for foreseeability, and that an equivalent is not foreseeable unless it was understood by one of ordinary skill to be suitable for use in the invention as originally claimed.  But the Federal Circuit rejected Duramed's arguments.

    Duramed argued that foreseeability requires that PVA must have been known as an MBC for moisture-sensitive pharmaceutical compounds, like the claimed conjugated estrogens.  Relying on Schwarz Pharma, Inc. v. Paddock Labs., Inc., 504 F.3d 1371, 1377 (Fed. Cir. 2007), the Federal Circuit stated that when the language of the original and issued claims begins with the words "[a] pharmaceutical composition," that language (and not merely the specifically-claimed constituent ingredient (here, conjugated estrogens)) defines the field of the invention for purposes of determining foreseeability.  Accordingly, PVA MBCs need only to have been known in the field of pharmaceutical compositions, as of the time of Duramed's narrowing amendment.  Because the Colorcon PCT discloses PVA MBCs, including Opadry AMB, in the field of pharmaceutical compositions, such PVA MBCs were "known in the field of the invention," and thus foreseeable.  Thus, the Federal Circuit held that the Colorcon PCT established foreseeability as a matter of law.

    The Federal Circuit also explained that "foreseeability does not require . . . precise evidence of suitability.  . . .  Foreseeability does not require flawless perfection to create an estoppel."  Thus, the Federal Circuit rejected Duramed's arguments that the Colorcon PCT did not establish foreseeability due to its inclusion of (1) technical drawbacks, and (2) conclusory statements, rather than test data showing precise characteristics or precise suitability.

    Finally, the Federal Circuit held that no genuine issue of fact precluded a finding that a December 1995 article in the scientific journal "Manufacturing Chemist" was publicly available to assess foreseeability.  In reaching this conclusion, the Federal Circuit emphasized that the amendment date (December 1998), not the application date (July 1995), was the pertinent time for determining foreseeability.

  • Federal Circuit Affirms Summary Judgment of Invalidity for Obviousness in Temazepam Case

    Tyco Healthcare Group LP v. Mutual Pharm. Co., No. 2010-1513 (Fed. Cir. 2011)

       by Scott P. McBride

    RESTORIL (temazepam) is a hypnotic (sleep-inducing) drug marketed for the treatment of insomnia.  In a decision last month, the Federal Circuit affirmed the invalidity of two claims of U.S. Patent No. 5,211,954 directed to temazepam formulations.  Claim 1 recites:

    A hard gelatin capsule containing a temazepam formulation consisting essentially of 6 to 8 milligrams of crystalline temazepam having a surface area of from 0.65 to 1.1 m2/g and 95% of the temazepam having a particle size of less than 65 microns in admixture with a pharmaceutically acceptable carrier therefor.

    Claim 2 "is identical except that it recites a composition containing 7.5 milligrams of crystalline temazepam."

    In 2006, Mutual filed an ANDA for a generic version of 7.5 mg temazepam capsules, after which Tyco filed suit for infringement of the '954 patent.  In 2009, after Mutual received tentative FDA approval of its ANDA, Tyco moved for a preliminary injunction, which was denied due to "uncontroverted evidence" of no literal infringement due to the "surface area" limitation.

    In an opinion last year, District Judge Chesler (D.N.J.) concluded on summary judgment that the two asserted composition claims were invalid for obviousness.  Judge Chesler noted that (1) RESTORIL capsules had been sold in the United States in 15 mg and 30 mg dosages more than a year before the 1986 priority date of the '954 patent, (2) a 1983 volume of the British National Formulary, a UK medical reference book, directed physicians to the use of temazepam at a dosage between 5 and 15 mg for the treatment of insomnia in the elderly, and (3) it was undisputed that "physicians always seek to prescribe the lowest effective dose of any medication, particularly hypnotics such as temazepam."

    In affirming, the Federal Circuit noted that, when Tyco's predecessor filed a Supplemental NDA with the FDA for manufacture and sale of 7.5 mg temazepam capsules within the scope of both '954 claims, the application stated that:

    [t]he formulation and manufacture of RESTORIL Capsules, 7.5 mg are similar to that used for the 15 and 30 milligram capsules . . . .  The [7.5 mg] formulation differs only in the reduction of the dose.  . . .  The capsule manufacturing method is exactly the same as has been described for the currently marketed doses.

    The Federal Circuit stated, "[g]iven that uncontested description, the only limitation of the two '954 claims that was not fully disclosed by the prior art RESTORIL capsules is the lower dosage of temazepam."

    The district court and the Federal Circuit relied on, among other things, the 1983 British National Formulary book.  The British National Formulary book stated that, for temazepam, the dose for "elderly patients [could be] 5-15 mg."  According to the district court, "[t]his entry plainly tells one of skill in the art to treat insomnia in the elderly by administering a dose in the range of 5 to 15 mg."  Moreover, the summary judgment record included evidence of a 1984 statement by an FDA representative to a group that included the named inventor of the 954 patent, that "the doses proposed in [certain] studies may be too high, [given] that in Great Britain, temazepam doses from 5-15 mg are recommended for geriatrics."

    The Federal Circuit stated that where there is a range disclosed in the prior art, and the claimed invention falls within that range, the claim is presumed obvious.  That presumption is rebuttable either by a showing that the prior art taught away from the invention or by a showing of new and unexpected results. 

    The Federal Circuit did not accept Tyco's arguments that the prior art taught away from the claimed invention or that secondary considerations of new and unexpected results and commercial success permitted a conclusion of non-obviousness.  The Federal Circuit also rejected, as "silly," one assertion made by Tyco's counsel at oral argument that the language "5-15 mg" did not actually disclose a range of doses (even though Tyco's expert had called it a "range").

    Regarding that same range, the Federal Circuit also concluded that even if some of the references in the record taught away from the claimed dose generally, those teachings did not undermine the teachings in the British National Formulary book that related to the dosage in elderly patients. 

    Finally, the Federal Circuit acknowledged, as correct, Tyco's expert's statements that the British National Formulary book (1) "nowhere states that a temazepam dose of 5 mg, 6 to 8 mg, or 7.5 mg, is effective in treating insomnia," (2) nor does it "state that 7.5 mg was effective," and (3) the British National Formulary book provides "[n]o clinical or statistical evidence . . . demonstrating that a dose within a range of 5-15 mg would work" in treating insomnia.  But the Federal Circuit also concluded that these observations do not undermine the district court's conclusions as to obviousness because the 954 patent's composition claims do not discuss the intended use of the capsules in a particular treatment regimen.

  • Federal Circuit Changes Course, Denies Stay of Injunction of Mylan’s Generic AMRIX Sales

    In Re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litigation, No. 2011–1399 (Fed. Cir. 2011)

    This case has an unusual history.  Here is a brief summary of recent events:

    • April 8: U.S. District Court for the District of Delaware enjoins Mylan from launching its generic AMRIX until the court issues its opinion on the patent infringement and validity issues in the case
    • April 17: 30–month stay of FDA approval of Mylan's cyclobenzaprine ANDA expires
    • April 18: FDA grants final approval of Mylan's ANDA
    • May 12: District court issues its opinion (following seven-day bench trial held in September and October of 2010), finding asserted claims of the patents-in-suit invalid for obviousness (link)
    • May 13: Mylan launches its generic AMRIX with 180–day exclusivity
    • May 20: District court grants Cephalon's motion for a temporary restraining order, explaining that “plaintiffs' success on appeal is just as likely as not” (link)
    • May 24: District court issues an Injunction Order, enjoining Mylan's further sales of generic AMRIX; enjoining Cephalon's licensing of an authorized generic version of AMRIX; and ordering Mylan and Cephalon to recall any already-sold generic AMRIX from the market
    • May 25: Federal Circuit issues an Order (1) directing Cephalon to file a response to Mylan's motion for a stay, pending appeal, of the district court injunction; and (2) granting “Mylan's request for an immediate stay . . . to the extent that the injunction is temporarily stayed pending the court's receipt of the response and the court's consideration of the papers submitted.”

    In an Order issued today, the Federal Circuit granted Mylan's motion for a stay, pending appeal, of the district court's injunction—but only in part.  Citing a 1987 Supreme Court case, the Federal Circuit stated the standard for obtaining a stay:

    The party requesting a stay bears the burden of showing that the circumstances justify an exercise of that discretion based on consideration of four factors, the first two of which are the most critical: (1) whether the stay applicant has made a strong showing that he is likely to succeed on the merits; (2) whether the applicant will be irreparably injured absent a stay; (3) whether issuance of the stay will substantially injure the other parties interested in the proceeding; and (4) where the public interest lies.

    In view of these factors, the court concluded:

    Based on the arguments in the motions papers, and without prejudicing the ultimate disposition of this case by a merits panel, we determine that Mylan has met their burden to obtain a stay, pending appeal, of the district court's injunction in part.  We deem it proper to stay the injunction as to Paragraph 3 of the Injunction Order only.  Mylan's motion to stay the remainder of the injunction provisions is denied.

    Paragraph 3 of the Injunction Order directed Mylan and Cephalon to “take all reasonable steps to recall their respective generic cyclobenzaprine extended-release products promptly from the market. . . .”  It is not clear why, if “Mylan has met their burden to obtain a stay,” the Federal Circuit lifted only that part of the injunction requiring Mylan to recall its generic AMRIX from the market, and not also the part ordering Mylan to stop selling its generic AMRIX.

    In any event, it appears that Mylan must now stop selling its generic AMRIX.  Presumably Mylan has been selling its generic AMRIX since it launched on May 13, meaning that it has received the benefit of 56 days of its 180–day exclusivity period.  Due to the Federal Circuit's calendar for oral argument, however, the appeal won't be heard until September at the earliest.  Meanwhile, Mylan's 180–day exclusivity period will continue to run.  Thus, it is unclear whether, even if Mylan prevails on appeal, it will have any exclusivity remaining by the time the Federal Circuit issues its opinion in the case.

  • Federal Circuit Allows Par’s Appeal of ASACOL Declaratory Judgment Decision to Proceed

    Medeva Pharma Suisse v. Par Pharmaceutical, No. 2011–1391 (Fed. Cir. 2011)

    In an Order issued today, the Federal Circuit denied Medeva's motion to dismiss Par's appeal of a decision from the U.S. District Court for the District of New Jersey that dismissed Par's declaratory judgment claim in paragraph IV litigation involving ASACOL (mesalamine).  Medeva had filed suit against Par for infringement of only one of two Orange Book-listed patents.  Par counterclaimed for a declaratory judgment of invalidity as to the other patent, seeking to trigger forfeiture of the first ANDA filer's 180–day exclusivity.  Medeva then offered a covenant not to sue, after which the district court dismissed Par's declaratory judgment claim.  Click here for FDA Law Blog's excellent summary of the district court's decision.

    After dismissing Par's declaratory judgment claim, the district court entered judgment under Rule 54(b), allowing Par immediately to appeal the decision.  According to the district court, if the decision were to be reversed on appeal, then the court could possibly try the claims on both patents at the same time, because the issues involving the first patent were still in discovery.

    Rule 54(b) permits a district court “to direct the entry of a final judgment as to one or more but fewer than all of the claims or parties only upon an express determination that there is no just reason for delay and upon an express direction for the entry of judgment.”  In today's Order, the Federal Circuit stated that its task was “only to assess whether the movant can establish the district court abused its discretion in finding the final claim should be heard now as opposed to waiting until all claims against all parties have been entered.”  The court concluded:

    Medeva cannot meet this standard.  The trial court appears to have considered both parties' arguments, and provided a thorough explanation for why judicial resources could be conserved if judgment was entered pursuant to Rule 54(b).  Because the court cannot say the district court abused its discretion, we deny the motion to dismiss.

    Accordingly, Par's appeal will go forward, and the Federal Circuit will consider whether the district court properly dismissed Par's declaratory judgment claim against Medeva.

  • Supreme Court Vacates Federal Circuit Opinion on Declaratory Judgment Jurisdiction

    Eisai v. Teva Pharms. USA, No. 10-1070 (U.S. 2011)

    In a little-noticed decision two weeks ago, the Supreme Court vacated the Federal Circuit's decision in Teva v. Eisai and remanded the case with instructions to dismiss it as moot.  The Court's decision (found on the Order List of June 13) is significant in that it vacates a precedential decision of the Federal Circuit that arguably expanded declaratory judgment jurisdiction for subsequent ANDA filers.

    As we explained in a post back in October, when Teva v. Eisai was decided, it appeared that the Federal Circuit found–for the first time–that the possible delay of a first Paragraph IV ANDA filer in launching its product was a sufficient injury to subsequent Paragraph IV ANDA filers so as to create a justiciable case or controversy.  The Federal Circuit thus held that Teva (a subsequent filer in this case) had established declaratory judgment jurisdiction.

    Following that decision, Eisai timely filed a petition for rehearing or rehearing en banc.  While the petition was pending, the first filer (Ranbaxy) launched its ANDA product, thereby triggering its 180-day exclusivity period–which was the sole objective of Teva's declaratory judgment suit in the first place.  Accordingly, Teva and Eisai informed the Federal Circuit that the case was moot, and Eisai requested that the Federal Circuit vacate its opinion and judgment in light of mootness.  The Federal Circuit, however, refused to vacate its opinion, leading Eisai to appeal to the Supreme Court.

    According to Eisai's cert petition,

    The Federal Circuit's denial of vacatur is directly contrary to the line of this Court's precedents beginning with United States v. Munsingwear, Inc. that hold that courts should vacate judgments in a case that becomes moot unless the moving party's actions make vacatur inequitable.  Eisai is unfairly saddled with a preclusive judgment of suspect merit in an important area of federal jurisprudence even though mootness prevents further review by this Court.

    A commentator on SCOTUSblog noted that Teva initially declined to file a response to Eisai's petition (perhaps trying to signal to the Court, "move along, there's nothing to see here"), but the Court asked Teva for a response and twice relisted the case for consideration at its weekly conference, indicating its interest in Eisai's petition.  According to the commentator, "the GVR and mootness dismissal in Eisai is somewhat akin to a summary reversal."

    Thus, district courts in future cases will need to evaluate whether declaratory judgment jurisdiction exists without reference to Teva v. Eisai.

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