887 F.3d 1117 | Fed. Cir. | 2018
Lead Opinion
Lourie, Circuit Judge.
West-Ward Pharmaceuticals International Limited and West-Ward Pharmaceuticals Corp. (collectively, "West-Ward") appeal from the decision of the United States District Court for the District of Delaware holding, after a bench trial, claims 1-9, 11-13, and 16 ("the asserted claims") of U.S. Patent 8,586,610 ("the '610 patent") infringed and not invalid. See Vanda Pharm. Inc. v. Roxane Labs., Inc. ,
BACKGROUND
I.
Aventisub LLC ("Aventisub") owns and Vanda Pharmaceuticals Inc. ("Vanda" and collectively, with Aventisub, "Plaintiffs") holds an exclusive worldwide license to U.S. Reissue Patent 39,198 ("the '198 patent"). The '198 patent expired on November *112115, 2016.
The '610 patent relates to a method of treating schizophrenia patients with iloperidone wherein the dosage range is based on the patient's genotype. The cytochrome P450 2D6 gene ("CYP2D6") encodes an enzyme known to metabolize a large number of drugs, including iloperidone. '610 patent col. 1 ll. 29-36. The '610 patent teaches "that treatment of a patient, who has lower CYP2D6 activity than a normal person, with a drug[, such as iloperidone,] that is pre-disposed to cause QT
Claim 1 of the '610 patent is representative and reads as follows:
A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:
determining whether the patient is a CYP2D6 poor metabolizer by:
obtaining or having obtained a biological sample from the patient;
and
performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and
if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and
if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day,
wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.
Vanda owns New Drug Application ("NDA") 22-192 for Fanapt® (iloperidone), an atypical antipsychotic approved by the U.S. Food and Drug Administration ("FDA") in 2009 under
*1122II.
In 2013, West-Ward
The proposed ANDA label is substantially identical in all material respects to the Fanapt® label. The proposed label states that: iloperidone is "indicated for the treatment of adults with schizophrenia," J.A. 15104 § 1; "[t]he recommended target dosage of iloperidone tablets is 12 to 24 mg/day," J.A. 15103; "[t]he recommended starting dose for iloperidone tablets is 1 mg twice daily," J.A. 15105 § 2.1; and "[i]loperidone must be titrated slowly from a low starting dose," J.A. 15105 § 2.1. The proposed label provides that the "[i]loperidone dose should be reduced by one-half for poor metabolizers of CYP2D6 [see Pharmacokinetics (12.3) ]." J.A. 15105 § 2.2. Section 5.2, entitled "QT Prolongation," explains: "iloperidone was associated with QTc prolongation of 9 msec at an iloperidone dose of 12 mg twice daily" and that "[c]aution is warranted when prescribing iloperidone ... in patients with reduced activity of CYP2D6 [see Clinical Pharmacology (12.3) ]." J.A. 5106-07 § 5.2.
III.
Meanwhile, the '610 patent issued on November 19, 2013, and on June 16, 2014, Vanda filed Civil Action No. 14-757 ("2014 suit") in the district court alleging infringement of the '610 patent. On January 15, 2015, Vanda listed the '610 patent in the Orange Book for Fanapt®. On May 6, 2015, West-Ward sent Vanda a Paragraph IV notice with respect to the '610 patent notifying Vanda that it amended ANDA 20-5480 to contain a Paragraph IV certification that the '610 patent is invalid and/or not infringed. J.A. 19696; see
Following a bench trial, the district court found that West-Ward's proposed products induce infringement of the asserted claims of the '610 patent, but do not contributorily infringe them. Opinion ,
The district court also held that the asserted claims were not invalid under § 101, § 103, or § 112 for lack of written description. The court did conclude that "the asserted claims depend upon laws of nature," specifically, "the relationship between iloperidone, CYP2D6 metabolism, and QTc prolongation."
The court determined that
West-Ward timely appealed from the district court's final judgment. We have jurisdiction under
DISCUSSION
On appeal from a bench trial, we review a district court's conclusions of law de novo and its findings of fact for clear error. Golden Blount, Inc. v. Robert H. Peterson Co. ,
I. Jurisdiction
We must first address whether the district court properly exercised jurisdiction over the 2014 suit. On November 16, 2017, we directed supplemental briefing on jurisdiction. Both parties responded with supplemental briefing, which, inter alia , addressed whether there is district court jurisdiction under the Drug Price Competition and Patent Term Restoration Act of 1984 ("the Hatch-Waxman Act"), *1124Pub. L. No. 98-417,
Vanda argues that its allegations of infringement under
West-Ward argues that
We agree with Vanda that the district court had jurisdiction over this case. We have previously explained that:
By enacting § 271(e)(2), Congress thus established a specialized new cause of action for patent infringement. When patentees pursue this route, their claims necessarily arise under an Act of Congress relating to patents. In short, "[o]nce Congress creates an act of infringement, jurisdiction in the district courts is proper under28 U.S.C. § 1338 (a)."
AstraZeneca Pharm. LP v. Apotex Corp. (AstraZeneca II ),
Here, Vanda's complaint alleged that West-Ward infringed the '610 patent under
West-Ward's arguments relating to whether there was a qualifying act of infringement raise potential merits problems, not jurisdictional issues. We have previously rejected the argument that a court's jurisdiction "hinged on whether [plaintiff] asserted a 'valid' claim under § 271(e)(2)."
Moreover, an actual controversy has existed between the parties from the time when the suit was commenced. See Teva Pharm. USA, Inc. v. Novartis Pharm. Corp. ,
Thus, the district court properly had jurisdiction over the '610 patent under the Hatch-Waxman Act.
II. Infringement
In a bench trial, infringement is a question of fact that we review for clear error. Alza Corp. v. Mylan Labs., Inc. ,
A. The Applicability of
We first address whether, beyond the jurisdictional question, a claim for infringement of the '610 patent under
*1126Vanda argues that it proved an act of infringement under
West-Ward responds that there can be no infringement under § 271(e)(2) because the ANDA was filed before the '610 patent issued. West-Ward contends that the statutorily defined act of infringement excludes amendments to an ANDA and "only reaches ANDAs submitted 'for a drug claimed in a patent or the use of which is claimed in a patent '-not a drug that might or might not later be claimed in a patent or one that has been claimed in a provisional patent application or a patent-pending." Reply Br. 33 (emphases in original) (quoting
The Hatch-Waxman Act amended the Federal Food, Drug, and Cosmetic Act and the patent laws to enable generic drugs to be more easily approved and to respond to loss of effective patent life resulting from the requirement that drug products require premarket testing and then must undergo FDA review, actions that consume significant portions of a patent term. See Eli Lilly & Co. v. Medtronic, Inc. ,
Section 202 of the Act, codified at
It shall be an act of infringement to submit ... an application under section 505(j) of the Federal Food, Drug, and Cosmetic Act[, codified at21 U.S.C. § 355 (j),] ... for a drug claimed in a patent or the use of which is claimed in a patent , ... if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use, or sale of a drug ... claimed in a patent or the use of which is claimed in a patent before the expiration of such patent.
Although we agree with West-Ward that only an issued patent can give rise to a valid infringement claim under § 271(e)(2)(A), we disagree that that conclusion precludes Vanda's infringement claim in this case. The '610 patent is a patent "for a drug ... the use of which is claimed in a patent,"
*1127Ferring B.V. v. Watson Labs., Inc.-Fla. ,
Here, it is undisputed that West-Ward amended the ANDA by submitting a Paragraph IV certification regarding the '610 patent after that patent issued. J.A. 19696; J.A. 6414-15; Appellant Br. 10; Appellee Br. 59. Such an act is a qualifying act of infringement under § 271(e)(2)(A).
The FDA regulatory framework and the legislative history further demonstrate that West-Ward is incorrect in asserting that "application" in § 271(e)(2)(A) excludes amendments to the ANDA. Sections 101 and 102 of the Hatch-Waxman Act amended the Federal Food, Drug, and Cosmetics Act to create an abbreviated regulatory pathway for approval of generic drugs, codified at
ANDA applications must contain one of four certifications for patents "for which information is required to be filed under [
The type of certification under
As originally enacted, the Hatch-Waxman Act provided for a thirty-month stay as long as the suit was brought within 45 days of receipt of the Paragraph IV notice. See Hatch-Waxman Act, Pub. L. 98-417, § 101, 98 Stat. at 1589. Multiple thirty-month stays could therefore be triggered for the same ANDA as a consequence of the ANDA applicant submitting Paragraph IV certifications and notices for patents listed in the Orange Book that issued both before and after the submission of the original ANDA application. See Andrx ,
In 2003, Congress amended
B. Inducement
We now turn to the merits of the infringement finding. West-Ward argues that the district court clearly erred in finding that it would induce infringement because Vanda failed to prove the requisite direct infringement and specific intent to induce infringement. Vanda responds that the district court correctly found that *1129West-Ward will induce infringement of the asserted claims.
The statute provides that "[w]hoever actively induces infringement of a patent shall be liable as an infringer."
We have held that "[i]nducement can be found where there is '[e]vidence of active steps taken to encourage direct infringement,' which can in turn be found in 'advertising an infringing use or instructing how to engage in an infringing use.' " Takeda Pharm. U.S.A., Inc. v. W.-Ward Pharm. Corp. ,
West-Ward argues that the district court clearly erred in finding that its proposed label "satisfies" the asserted claims because the language of the label itself cannot constitute direct infringement of the asserted method claims. See Opinion ,
Vanda responds that it did not need to prove instances of direct infringement by physicians because this is a Hatch-Waxman case where infringement is statutorily-defined to be the filing of an ANDA or an amendment thereto, not by selling a product. Even though not required, Vanda contends, it identified a doctor, Dr. Alva, who practiced the steps of the asserted claims with Fanapt®. Vanda argues that the asserted claims do not require that a single physician administer iloperidone to both poor and non-poor CYP2D6 metabolizers, and that West-Ward's argument to the contrary is waived because it was raised for the first time on appeal.
We agree with Vanda that a patentee does not need to prove an actual past instance of direct infringement by a physician to establish infringement under
*1130Bristol-Myers Squibb ,
Similarly, patentees in Hatch-Waxman litigations asserting method patents do not have to prove that prior use of the NDA-approved drug satisfies the limitations of the asserted claims. See, e.g. , Sanofi ,
Accordingly, Vanda can satisfy its burden to prove the predicate direct infringement by showing that if the proposed ANDA product were marketed, it would infringe the '610 patent. The district court made factual findings that the proposed label "recommends" that physicians perform the claimed steps, see Opinion ,
Turning to specific intent, West-Ward argues that Vanda failed to prove that its proposed label would " 'encourage' or 'recommend' a direct infringer (a psychiatrist or other physician) to perform each step of the claimed methods." Appellant Br. 36 (quoting Takeda ,
Vanda responds that the district court did not clearly err in finding that the proposed label recommends performance of all the claimed steps. Vanda argues that potential noninfringing uses do not preclude a finding of specific intent to induce infringement in this case.
We agree with Vanda that the district court did not clearly err in finding induced infringement of independent claims 1, 9, *1131and 13.
Iloperidone must be titrated slowly from a low starting dose.... The recommended starting dose for iloperidone tablets is 1 mg twice daily. Dose increases to reach the target range of 6 to 12 mg twice daily (12 to 24 mg/day ) may be made with daily dosage adjustments not to exceed 2 mg twice daily (4 mg/day). The maximum recommended dose is 12 mg twice daily (24 mg/day ).... Prescribers should be mindful of the fact that patients need to be titrated to an effective dose of iloperidone.
Section 12.3 of the proposed label, entitled "Pharmacokinetics," states:
Approximately 7 to 10% of Caucasians and 3 to 8% of Black/African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are intermediate, extensive or ultrarapid metabolizers. Co-administration of iloperidone with known strong inhibitors of CYP2D6 like fluoxetine results in a 2.3 fold increase in iloperidone plasma exposure, and therefore one-half of the iloperidone dose should be administered.
Similarly, PMs of CYP2D6 have higher exposure to iloperidone compared with [extensive metabolizers] and PMs should have their dose reduced by one-half. Laboratory tests are available to identify CYP2D6 PMs .
J.A. 15121 § 12.3 (emphasis added).
Thus, the district court did not clearly err in finding that § 12.3 "recommends that practitioners perform or have performed a genotyping assay to determine whether patients are CYP2D6 poor metabolizers." Opinion ,
The label instructs practitioners that "PMs should have their dose reduced by one-half. [Genotyping tests] are available to identify CYP2D6 PMs." J.A. 15121 § 12.3. The court did not clearly err in finding that this constitutes a recommendation to perform genotyping tests on iloperidone patients. That West-Ward introduced other evidence that could have supported a contrary finding does not compel the conclusion that the district court clearly erred. See *1132Anderson v. City of Bessemer City ,
We reject West-Ward's contention that the lack of an express finding by the district court that the label recommends obtaining a biological sample requires a remand. The district court found induced infringement of the independent claims, which necessarily required a finding of inducement of the limitation requiring "obtaining or having obtained a biological sample from the patient." '610 patent col. 17 ll. 7-8 (claim 1), col. 18 ll. 9-10 (claim 9), col. 18 ll. 34-35 (claim 13). West-Ward has pointed to no evidence in the record to dispute the testimony of Vanda's witnesses at trial that the genotyping assays the court found were recommended by the label require obtaining a biological sample. J.A. 6928 (190:14-191:1); J.A. 6939 (235:18-23). Given this undisputed evidence and the court's finding that the label recommends genotyping assays, we see no clear error in the court's implicit finding that the proposed label recommends obtaining a biological sample. See, e.g. , Para-Ordnance Mfg., Inc. v. SGS Importers Int'l, Inc. ,
The district court also did not clearly err in finding that "[t]he label recommends oral administration of iloperidone tablets at 12 to 24 mg/day to non-genotypic CYP2D6 poor metabolizers and 12 mg/day or less to genotypic CYP2D6 poor metabolizers." Opinion ,
Similarly, the fact that the target dose range for genotypic non-poor metabolizers (12 to 24 mg/day) includes 12 mg/day does not compel a finding of noninfringement. The independent claims require administering "greater than 12 mg/day, up to 24 mg/day" of iloperidone to non-poor metabolizers. '610 patent col. 17 ll. 17-20 (claim 1), col. 18 ll. 16-18 (claim 9), col. 18 ll. 44-47 (claim 13). Even if not every practitioner will prescribe an infringing dose, that the target dose range "instructs users to perform the patented method" is sufficient to "provide evidence of [West-Ward's] affirmative intent to induce infringement." AstraZeneca I ,
Finally, West-Ward's reliance on Warner-Lambert , an off-label use case, is misplaced. In Warner-Lambert , we explained that "it defies common sense to expect that [ANDA applicant] will actively promote the sale of its approved [ANDA product], in contravention of FDA regulations, for a *1133use that (a) might infringe [NDA holder's] patent and (b) constitutes such a small fraction of total sales." Warner-Lambert ,
Accordingly, even if the proposed ANDA product has "substantial noninfringing uses," West-Ward may still be held liable for induced infringement. " Section 271(b), on inducement, does not contain the 'substantial noninfringing use' restriction of section 271(c), on contributory infringement." Sanofi ,
III. Patent Subject Matter Eligibility
We next address whether the asserted claims are directed to patent-eligible subject matter. West-Ward argues that the asserted claims are ineligible under § 101 because they are directed to a natural relationship between iloperidone, CYP2D6 metabolism, and QT prolongation, and add nothing inventive to those natural laws and phenomena. West-Ward contends that the asserted claims are indistinguishable from those held invalid in Association for Molecular Pathology v. Myriad Genetics, Inc. ,
Vanda responds that the asserted claims are patent-eligible under § 101 at both steps of Mayo / Alice . Vanda contends that the district court erred in holding that the asserted claims are directed to a law of nature. According to Vanda, the court's "conclusions that the asserted claims 'depend upon,' 'touch[ ] upon,' and 'address' laws of nature and natural phenomena do not, as a matter of law, establish that the asserted claims are directed to a patent-ineligible concept under Step 1 of the Alice / Mayo analysis." Appellee Br. 45 (alteration and emphasis in original).
Section 101 of the Patent Act states that "[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title."
The Supreme Court has established a two-step framework to determine patent subject matter eligibility under
First, we determine whether the claims at issue are directed to one of those patent-ineligible concepts. If so, we then ask, "[w]hat else is there in the claims before us?" To answer that question, we consider the elements of each claim both individually and "as an ordered combination" to determine whether the additional elements "transform the nature of the claim" into a patent-eligible application. We have described step two of this analysis as a search for an " 'inventive concept' "-i.e., an element or combination of elements that is "sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the [ineligible concept] itself."
*1134Alice Corp. Pty. v. CLS Bank Int'l , --- U.S. ----,
Step one requires determining "whether the claims at issue are directed to one of those patent-ineligible concepts."
Consistent with Supreme Court precedent, we agree with Vanda that the asserted claims are not directed to patent-ineligible subject matter.
West-Ward contends that the Supreme Court held that similar claims were patent ineligible in Mayo and Myriad . The patent in Mayo claimed a method for "optimizing" the dosage of thiopurine drugs by administering thiopurine drugs to a patient and measuring the level of certain metabolites in the blood, wherein the level of metabolites indicates whether to adjust the dosage. Mayo , 566 U.S. at 74-75,
This case, however, is not Mayo . First, the claims in Mayo were not directed to a novel method of treating a disease. Instead, the claims were directed to a diagnostic method based on the "relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm."
Although the representative claim in Mayo recited administering a thiopurine drug to a patient, the claim as a whole was not directed to the application of a drug to treat a particular disease. See
In this case, the '610 patent claims are directed to a method of using iloperidone to treat schizophrenia. The inventors recognized the relationships between iloperidone, CYP2D6 metabolism, and QTc prolongation, but that is not what they claimed. They claimed an application of that relationship. Unlike the claim at issue in Mayo , the claims here require a treating doctor to administer iloperidone in the amount of either (1) 12 mg/day or less or (2) between 12 mg/day to 24 mg/day, depending on the result of a genotyping assay. The specification further highlights the significance of the specific dosages by explaining how certain ranges of administered iloperidone correlate with the risk of QTc prolongation. See, e.g. , '610 patent at col. 4 ll. 1-15. Thus, the '610 patent claims are "a new way of using an existing drug" that is safer for patients because it reduces the risk of QTc prolongation. Mayo , 566 U.S. at 87,
Moreover, unlike the claim in Mayo , to the extent that preemption is a concern, the '610 patent claims do not "tie up the doctor's subsequent treatment decision."
Here, the '610 patent claims recite the steps of carrying out a dosage regimen based on the results of genetic testing. The claims require doctors to "internally administer[ ] iloperidone to the patient in an amount of 12 mg/day or less" if the patient has a CYP2D6 poor metabolizer genotype; and "internally administer[ ] iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day" if the patient does not have a CYP2D6 poor metabolizer genotype. '610 patent col. 17 ll. 13-20. These are treatment steps. In contrast, as shown above, the claim in Mayo stated that the metabolite level in blood simply "indicates" a need to increase or decrease dosage, without prescribing a specific dosage regimen or other added steps to take as a result of that indication. Mayo , 566 U.S. at 75,
Our decision in CellzDirect supports concluding that these claims are patent eligible. In that case, we held that "a method of producing a desired preparation of *1136multi-cryopreserved hepatocytes cells" was patent eligible. CellzDirect ,
Nor does Myriad compel a different outcome. The Supreme Court in Myriad held "that a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but that cDNA is patent eligible because it is not naturally occurring." Myriad ,
At bottom, the claims here are directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome. They are different from Mayo . They recite more than the natural relationship between CYP2D6 metabolizer genotype and the risk of QTc prolongation. Instead, they recite a method of treating patients based on this relationship that makes iloperidone safer by lowering the risk of QTc prolongation. Accordingly, the claims are patent eligible.
IV. Written Description
We next consider West-Ward's argument that the district court erred in finding that the claims are not invalid for lack of adequate written description. To satisfy the written description requirement the patent disclosure must "reasonably convey[ ] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharm., Inc. v. Eli Lilly & Co. ,
West-Ward argues that the asserted claims are invalid for lack of written description because nothing in the '610 patent demonstrates possession of the claimed dosage ranges for poor and non-poor CYP2D6 metabolizer genotypes. West-Ward contends that the description does not contain experiments with doses of 12 mg/day or less given to poor metabolizers, and reports data that does not support the claimed poor-metabolizer dose range.
Vanda responds that the district court did not clearly err in finding that the '610 patent adequately describes the claimed dosages for poor metabolizers. Vanda contends that West-Ward waived any written description challenge to the dosages for non-poor metabolizers, and that West-Ward's argument is, in any event, meritless.
We agree with Vanda that the district court did not clearly err in finding that the '610 patent contains adequate written description for the claimed "12 mg/day or less" dosage range for poor metabolizers. The patent reports the results of tests *1137comparing the concentrations of P88 and P95, iloperidone's two main metabolites, and changes in QTc interval upon administration of doses of iloperidone, both with and without the addition of a CYP2D6 inhibitor, to individuals with wildtype or a poor metabolizer genotype associated with two common CYP2D6 polymorphisms. '610 patent col. 4 l. 62-col. 10 l. 56. The patent reports that "QTc prolongation is correlated to the ratios of P88/P95 and (iloperidone+P88)/P95."
The '610 patent further explains that the reported results "show that patients can be more safely treated with iloperidone if the dose of iloperidone is adjusted based on the CYP2D6 genotype of each patient," id . col. 9 ll. 31-34; accord
The district court heard testimony that the data reported in the '610 patent show a trend for higher QTc prolongation among genotypic CYP2D6 poor metabolizers given a 24 mg/day dose, and support a reduction in dose for CYP2D6 poor metabolizers by a factor of 1.5 to 3.5. West-Ward introduced some testimony challenging the sufficiency of the data and the lack of statistical analysis, but that does not render the court's reliance on testimony supporting validity impermissible. See Anderson ,
Moreover, West-Ward waived its written description challenge with respect to non-poor metabolizers by failing to properly present it to the trial court. The Supreme Court has observed that as a "general rule ... a federal appellate court does not consider an issue not passed upon below." Singleton v. Wulff ,
West-Ward points only to a single page in each of its opening and reply post-trial briefs to support its claim that this issue is not waived. Those pages make passing reference to the dosage range for non-poor metabolizers in the context of the written description arguments West-Ward advanced for poor metabolizers. West-Ward does not point us to any argument or evidence that it advanced before the district court specifically with respect to non-poor metabolizers. Indeed, West-Ward did not identify lack of written description with respect to non-poor metabolizer dose range in its pretrial submissions identifying the issues to be tried. West-Ward has thus waived any further argument that the *1138non-poor metabolizer dosage range was not adequately supported by the written description.
V. Injunctive Relief
We finally address the propriety of the injunctive relief awarded by the district court. West-Ward argues that the injunctions were not supported by the courts "general equitable power," and the lack of jurisdiction or an infringing act under
Vanda responds that the district court's injunctions can be affirmed under
We agree with Vanda that
For an act of infringement described in paragraph (2)-
(A) the court shall order the effective date of any approval of the drug or veterinary biological product involved in the infringement to be a date which is not earlier than the date of the expiration of the patent which has been infringed,
(B) injunctive relief may be granted against an infringer to prevent the commercial manufacture, use, offer to sell, or sale within the United States or importation into the United States of an approved drug, veterinary biological product, or biological product,
...
The remedies prescribed by subparagraphs (A), (B), (C), and (D) are the only remedies which may be granted by a court for an act of infringement described in paragraph (2), except that a court may award attorney fees under section 285.
West-Ward's reliance on the FDA's letter approving a different company's ANDA 20-7231 for iloperidone tablets is misplaced. The letter indicates that because the '610 patent was "submitted to the [FDA] after submission of [that] ANDA," litigation with respect to the '610 patent"would not create a statutory stay of approval." https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/207231Orig1s000ltr.pdf. The FDA letter merely recognizes that the issuance of the '610 patent after submission of that ANDA
*1139renders the thirty-month statutory stay inapplicable. See
In fact, where "the FDA has already approved the ANDA, the district court's [ § 271(e)(4)(A) ] order would [only] alter the effective date of the application, thereby converting a final approval into a tentative approval." In re Omeprazole Patent Litig. ,
Because we sustain the district court's infringement finding under § 271(e)(2), we also affirm the court's grant of injunctive relief. Although the district court erred in concluding that the remedies pursuant to § 271(e)(4) were unavailable, the court granted Vanda injunctive relief consistent with those remedies. We may thus affirm the district court's grant of injunctive relief pursuant to § 271(e)(4).
Additionally, Vanda did not need to file a cross-appeal to allow us to affirm the district court's grant of injunctive relief with respect to the FDA. Without filing a cross-appeal, "an appellee may 'urge in support of a decree any matter appearing in the record, although his argument may involve an attack upon the reasoning of the lower court,' but may not 'attack the decree with a view either to enlarging his own rights thereunder or of lessening the rights of his adversary.' " El Paso Nat. Gas Co. v. Neztsosie ,
The district court expressly ordered relief that Vanda argues may be affirmed on the basis of § 271(e)(4). See J.A. 33. Thus, our affirmance does not enlarge Vanda's rights under the judgment *1140or require its amendment. Indeed, Vanda could not have filed a cross-appeal in this case because "[a] party that is not adversely affected by a judgment lacks standing to [cross-appeal]." TypeRight Keyboard Corp. v. Microsoft Corp. ,
We have considered West-Ward's remaining arguments but find them to be unpersuasive.
CONCLUSION
For the foregoing reasons, we affirm the district court's decision.
AFFIRMED
The parties have not appealed any determinations with respect to the '198 patent. The parties stipulated to the infringement of claim 3 of the '198 patent and the court concluded that claim 3 would not have been obvious.
The QT interval is the time between the Q and T waves of the heart rhythm. When corrected for the patient's heart rate it is abbreviated QTc.
During the pendency of this appeal, ownership of ANDA 20-5480 transferred from Roxane Laboratories Inc. to West-Ward. For simplicity, we refer to the ANDA applicant throughout as West-Ward.
The court specifically stated that Vanda was "not entitled to relief pursuant to
Because we determine that
We note that West-Ward did not argue to the district court at the pleadings stage that the complaint should be dismissed for failure to state a claim upon which relief could be granted on this basis. Cf. AstraZeneca II ,
Because we conclude that the district court did not clearly err in finding induced infringement, we need not and do not reach Vanda's arguments in the alternative on contributory infringement.
Because we affirm the district court's infringement findings with respect to these independent claims, we need not reach this issue regarding the dependent claims because any error in the district court's analysis of the dependent claims is harmless. See TiVo, Inc. v. EchoStar Commc'ns Corp. ,
For purposes of validity, the parties did not argue the claims separately, so they rise or fall together.
Dissenting Opinion
I would find the asserted patent claims to be directed to a law of nature. The majority finds the claims herein are not directed to a natural law at step one of the § 101 analysis, but its efforts to distinguish Mayo cannot withstand scrutiny. The majority relies on the claims' recitation of specific applications of the discovery underpinning the patent to find no natural law is claimed. But it conflates the inquiry at step one with the search for an inventive concept at step two. Once the natural law claimed in the '610 patent is understood in a manner consistent with Mayo , what remains fails to supply the requisite inventive concept to transform the natural law into patent-eligible subject matter. Although I agree with the majority's reasoning that the district court had jurisdiction under the Hatch-Waxman Act, I would not reach the issues of written description, infringement, and injunctive relief because I would find the '610 patent claims ineligible subject matter. Accordingly, I respectfully dissent.
In order "to transform an unpatentable law of nature into a patent-eligible application of such a law, a patent must do more than simply state the law of nature while adding the words 'apply it.' " Mayo Collaborative Servs. v. Prometheus Labs., Inc. ,
The '610 patent itself identifies its invention as "compris[ing] the discovery that treatment of a patient, who has lower CYP2D6 activity than a normal person, with a drug that is pre-disposed to cause QT prolongation and is metabolized by the CYP2D6 enzyme, can be accomplish[ed] more safely by administering a lower dose of the drug than would be administered to a person who has normal CYP2D6 enzyme activity." '610 patent col. 2 ll. 15-21. Nevertheless, the majority concludes that the claims here are not directed to ineligible subject matter at step one of the Mayo / Alice inquiry. Majority Op. at 28. I disagree.
The representative claim in Mayo , i.e., Claim 1, recited:
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder ; and
(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,
wherein the level of 6-thioguanine less than about 230 pmol per 8x108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and
wherein the level of 6-thioguanine greater than about 400 pmol per 8x108 red blood cells indicates a need to decrease *1141the amount of said drug subsequently administered to said subject.
Mayo , 566 U.S. at 74-75,
The Court stated that the patent in Mayo "set forth laws of nature-namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm."
In the present case, Claim 1 of the '610 patent reads as follows:
A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:
determining whether the patient is a CYP2D6 poor metabolizer by:
obtaining or having obtained a biological sample from the patient;
and
performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and
if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and
if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day,
wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.
'610 patent col. 17 ll. 2-25.
This claim, which is representative of the '610 patent, also sets forth a natural relationship-namely, the relationship between the CYP2D6 genotype and the likelihood that a dosage of iloperidone will cause QTc prolongation. The majority notes that the claims in Mayo were directed to the relationships that comprised the natural law, and not "to a novel method of treating a disease." Majority Op. at 29. Here, according to the majority, while the inventors recognized a natural law, "that is not what they claimed." Id. at 30. Rather, the claims of the '610 patent require a treating doctor to administer iloperidone in "specific dosages" based on the results of a genotyping assay. Id. But reciting specific metes and bounds in the claims did not prevent the Supreme Court from concluding those claims set forth a natural law in Mayo . We are not free to depart from the Supreme Court's holding.
*1142As the majority notes, the '610 patent claims a method of treating schizophrenia with iloperidone "that is safer for patients because it reduces the risk of QTc prolongation." Majority Op. at 30. This is no more than an optimization of an existing treatment of schizophrenia, just as the claims in Mayo concerned "optimizing therapeutic efficacy" of thiopurine drugs. Mayo warned against "drafting effort[s] designed to monopolize the law of nature itself." 566 U.S. at 77,
The Court in Mayo found that the claim limitation concerning "administering" a thiopurine drug to a patient "simply refer[red] to the relevant audience, namely doctors who treat patients with certain diseases with thiopurine drugs"-an audience that existed long before the patent disclosure.
The majority fails to reconcile this substantive similarity between our case and Mayo . Instead, it points to the specific dosages as a distinction between the administering step here and that in Mayo . But Mayo examined the significance of the "administering" step in its search for an inventive concept, not as part of the determination whether the claims were directed to a natural law at the threshold. And the specific dosage adds nothing inventive to the claims beyond the natural law.
Nor does the other element of specificity identified by the majority rescue the claims. The claims here specify a means of identifying a patient's genotype (a "genetic assay"), while the claims in Mayo left open the means of measuring the relevant metabolite. But the genetic assay is purely conventional pre-solution activity that cannot be used to circumvent eligibility under § 101. See Mayo , 566 U.S. at 79,
The majority notes the claims here require treatment with iloperidone within the dosage range indicated, while the claims in Mayo could be infringed by treatment with thiopurine "whether that treatment does, or does not, change in light of the inference " indicated by the natural law. Mayo , 566 U.S. at 86,
The majority points to the Supreme Court's statement in Mayo that "[u]nlike, say, a typical patent on a new drug or a new way of using an existing drug, the patent claims do not confine their reach to particular applications of those laws." Majority Op. at 29-30 (quoting Mayo , 566 U.S. at 87,
Whatever weight can be ascribed to the foregoing statements about methods of *1143treatment, we remain beholden to the holding of Mayo , which, in my view, requires us to find the claims directed to a natural law at step one. (And I find no inventive concept in the claims once the natural law at issue is properly understood in view of Mayo .)
My conclusion is not at odds with CellzDirect . There, the alleged law of nature was the capability of hepatocyte cells to survive multiple freeze-thaw cycles. Because the "end result" of the claims therein was "not simply an observation or detection of the ability of hepatocytes to survive multiple freeze-thaw cycles" but rather "a new and useful method of preserving hepatocyte cells," we held the claims were not directed to a law of nature.
Here, the end result of the claimed process is no more than the conclusion of a natural law. The fact that a reduction of iloperidone dosage in poor metabolizers to the may reduce QTc prolongation is both the means and the ends of this claim. The recitation of the specific dosages adds no more than a conventional application of that natural law. I see no distinction from Mayo , so I would hold the asserted claims directed to ineligible subject matter and lacking an inventive concept sufficient to transform it into patent-eligible subject matter. I respectfully dissent.
Indeed, the unpredictable results of clinical testing regarding the relationship among CYP2D6, iloperidone, and QTc prolongation formed the basis of the district court's finding of non-obviousness. See J.A. 13-15. In particular, the district court pointed to West-Ward's evidence that "it was unpredictable whether any dosage adjustment would be needed for CYP2D6 poor metabolizers, much less the amount of adjustment needed to achieve the pharmacokinetic profile seen in normal metabolizers." J.A. 14. That is, the district court found non-obviousness based on the revelation of the natural law underpinning the claims, not in any other aspect of the claims.