Case 3:20-cv-18322 Document 1 Filed 12/07/20 Page 1 of 24 PageID: 1
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`LAW OFFICES
`DECHERT LLP
`A PENNSYLVANIA LIMITED LIABILITY PARTNERSHIP
`502 CARNEGIE CENTER, SUITE 104
`PRINCETON, NJ 08540
`(609) 955-3200
`ATTORNEYS FOR PLAINTIFFS PAR PHARMACEUTICAL, INC., PAR STERILE PRODUCTS, LLC, AND
`ENDO PAR INNOVATION COMPANY, LLC
`_____________________________________________________________________________
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
`PAR PHARMACEUTICAL, INC., PAR
`STERILE PRODUCTS, LLC, and ENDO PAR
`INNOVATION COMPANY, LLC
`
`Civil Action No. _____________
`
`Plaintiffs,
`
`v.
`
`AMNEAL EU, LTD., AMNEAL
`PHARMACEUTICALS COMPANY GMBH,
`AMNEAL PHARMACEUTICALS OF NEW
`YORK, LLC, AMNEAL BIOSCIENCES LLC,
`and AMNEAL PHARMACEUTICALS PVT.
`LTD,
`
`Defendants.
`
`COMPLAINT
`
`Plaintiffs Par Pharmaceutical, Inc., Par Sterile Products, LLC, and Endo Par Innovation
`
`Company, LLC (collectively “Par”), for their complaint against Amneal EU, Ltd., Amneal
`
`Pharmaceuticals Company GmbH, Amneal Pharmaceuticals of New York, LLC, Amneal
`
`Biosciences LLC, and Amneal Pharmaceuticals Pvt. Ltd. (collectively “Amneal” or the “Amneal
`
`Defendants”), hereby allege as follows:
`
`

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`PARTIES
`
`1.
`
`Plaintiff Par Pharmaceutical, Inc. (“Par Pharmaceutical”) is a corporation
`
`organized and existing under the laws of the State of New York, having a principal place of
`
`business at 1 Ram Ridge Road, Chestnut Ridge, New York 10977. Par Pharmaceutical develops,
`
`manufactures, and markets pharmaceutical products in the United States.
`
`2.
`
`Plaintiff Par Sterile Products, LLC (“Par Sterile Products”) is a limited liability
`
`company organized and existing under the laws of Delaware, having its principal place of
`
`business at 1 Ram Ridge Road, Chestnut Ridge, New York 10977. Par Sterile Products
`
`develops, manufactures, and markets injectable pharmaceutical products, and provides
`
`manufacturing services to the biopharmaceutical and pharmaceutical industry.
`
`3.
`
`Plaintiff Endo Par Innovation Company (“EPIC”) is a limited liability company
`
`organized and existing under the laws of Delaware, having its principal place of business at
`
`1 Ram Ridge Road, Chestnut Ridge, New York 10977.
`
`4.
`
`Upon information and belief, Defendant Amneal EU, Limited (“Amneal EU”) is a
`
`limited liability company organized and existing under the laws of Ireland, having its principal
`
`place of business at Cahir Road, Cashel, Co. Tipperary, E25 ZD51, Ireland. Upon information
`
`and belief, Amneal EU is a pharmaceutical company engaged in the research, development,
`
`production, distribution, and sale of generic pharmaceuticals throughout the United States,
`
`including sales within this judicial district.
`
`5.
`
`Upon information and belief, Defendant Amneal Pharmaceuticals Company
`
`GmbH (“Amneal GmbH”) is a limited liability company organized and existing under the laws
`
`of Switzerland, having its principal place of business at Turmtrasse 30 6312, Steinhausen,
`
`Switzerland. Upon information and belief, Amneal GmbH is a pharmaceutical company
`
`2
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`

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`engaged in the research, development, production, distribution, and sale of generic
`
`pharmaceuticals throughout the United States, including sales within this judicial district.
`
`6.
`
`Upon information and belief, Defendant Amneal Pharmaceuticals of New York,
`
`LLC (“Amneal New York”) is a limited liability company organized and existing under the laws
`
`of Delaware, having its principal place of business at 50 Horseblock Road, Brookhaven, New
`
`York 11719. Upon information and belief, Amneal New York is the U.S. Agent for Amneal EU
`
`and Amneal GmbH. Upon information and belief, Amneal New York is a pharmaceutical
`
`company engaged, among other things, along and/or in concert with other Amneal Defendants,
`
`in the development, production, distribution, and sale of generic pharmaceuticals throughout the
`
`United States, including sales within this judicial district.
`
`7.
`
`Upon information and belief, Defendant Amneal Biosciences LLC (“Amneal
`
`Biosciences”) is a limited liability company organized and existing under the laws of Delaware,
`
`having its principal place of business at 400 Crossing Boulevard, Floor 3, Bridgewater, New
`
`Jersey 08807. Upon information and belief, Amneal Biosciences is a pharmaceutical company
`
`engaged, among other things, in the distribution of pharmaceutical products throughout the
`
`United States, including in this judicial district.
`
`8.
`
`Upon information and belief, Defendant Amneal Pharmaceuticals Pvt. Ltd.
`
`(“Amneal India”) is a corporation organized and existing under the laws of India, having its
`
`principal place of business at Plot No. 15, PHARMEZ Special Economic Zone, Sarkhej-Bavia
`
`N.H., No. 8A, Vil.: Matoda, Tal.: Sanand Ahmedabad, Gujarat 382213, India. Upon information
`
`and belief, Amneal India is a pharmaceutical company engaged, among other things, in the
`
`manufacturing, packaging, testing, distribution, and sale of pharmaceutical products sold in and
`
`imported into the United States.
`
`3
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`NATURE OF ACTION
`
`9.
`
`This is an action for infringement of United States Patent No. 10,844,435 (the
`
`’435 Patent” or “the Patent in Suit”). This action is based upon the Patent Laws of the United
`
`States, 35 U.S.C. § 100, et seq.
`
`10.
`
`Par seeks declaratory judgment under the Patent Laws of the United States, 35
`
`U.S.C. § 100 et seq., and the Declaratory Judgment Act, 28 U.S.C. § 2201 et seq., that Amneal’s
`
`marketing and sale of its Proposed ANDA Products (as detailed below), if approved, would
`
`induce infringement of the ’435 Patent.
`
`JURISDICTION AND VENUE
`
`11.
`
`This Court has jurisdiction over the subject matter of this action pursuant to 28
`
`U.S.C. §§ 1331, 1338(a), 2201 and 2202 (patent infringement).
`
`12.
`
`Venue is proper in this district pursuant to 28 U.S.C. §§ 1391(b), 1391(c), and
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`1400(b) because, inter alia, Amneal has a regular and established place of business in this
`
`judicial district and they have engaged in and will engage in infringing conduct in and from this
`
`judicial district. Moreover, Amneal EU, Amneal GmbH, and Amneal India are not resident in
`
`the United States, and pursuant to 28 U.S.C. § 1391(c)(3), venue as to those defendants is proper
`
`in any judicial district, including this judicial district.
`
`13.
`
`This Court has personal jurisdiction over Defendants because, inter alia, they
`
`have committed and will commit acts of infringement in this judicial district, have purposely
`
`availed themselves of the benefits and protections of the laws of New Jersey, and have had
`
`continuous and systematic contacts with this judicial district, including conducting business in
`
`New Jersey, including by acting in partnership and agency with each other, and marketing,
`
`4
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`selling, and distributing pharmaceutical products throughout the United States and in this judicial
`
`district. In addition, Amneal Biosciences has a principal place of business in this judicial district.
`
`FACTUAL BACKGROUND
`
`The Drug Approval Process
`
`14.
`
`A company seeking to market a new pharmaceutical drug in the United States
`
`must first obtain approval from the U.S. Food and Drug Administration (“FDA”), typically
`
`through the filing of a New Drug Application (“NDA”). See 21 U.S.C. § 355(a). The sponsor of
`
`the NDA is required to submit to FDA information on all patents claiming the drug that is the
`
`subject of the NDA, or a method of using that drug, and FDA then lists the patent information in
`
`its publication, the Approved Drug Products with Therapeutic Equivalence Evaluations, which is
`
`referred to as the “Orange Book.” See 21 U.S.C. § 355(b)(1) and (c)(2).
`
`15.
`
`Alternatively, a company seeking to market a generic version of a previously
`
`approved drug is not required to submit a full NDA. Instead, it may file an Abbreviated New
`
`Drug Application (“ANDA”). See 21 U.S.C. § 355(j). The generic drug approval process is
`
`considered “abbreviated” because the generic manufacturer may piggyback on the innovator
`
`company’s data and FDA’s prior finding of safety and efficacy by demonstrating, among other
`
`things, that the generic product is bioequivalent to the previously approved drug (the “reference
`
`listed drug” or “branded drug”).
`
`16.
`
`In general, and with a few exceptions, the labeling for a proposed ANDA product
`
`must track the labeling for the FDA-approved branded drug. Accordingly, pursuant to 21 C.F.R.
`
`§ 314.94(a)(8)(iv), an ANDA filer must include as part of the ANDA a side-by-side comparison
`
`of the applicant’s proposed labeling for its ANDA product with the approved labeling for the
`
`branded drug, with all differences annotated and explained.
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`17.
`
`If the labeling for the branded drug is updated or amended while the applicant’s
`
`ANDA is being reviewed by FDA, the applicant must submit an appropriate amendment to its
`
`ANDA to update the proposed labeling for its ANDA product as needed before obtaining final
`
`approval of the ANDA by FDA. Thus, FDA Guidance to ANDA applicants states that:
`
`It is incumbent on the ANDA applicant (1) to monitor for updates
`related to the applicant’s drug product (e.g., changes in bioequivalence
`recommendations or requirements; RLD labeling changes or updates;
`or USP changes or updates) and (2) to ensure that amendments
`addressing these updates are timely submitted to and are clearly
`identified for FDA either before a request for final approval (i.e., in a
`post-TA amendment) or in the request for final approval amendment
`itself, permitting FDA sufficient assessment time to meet the ANDA’s
`earliest lawful approval date (see sections III and IV of this draft
`guidance).
`
`See Exhibit C hereto at 11 (Guidance for Industry, “ANDA Submissions – Amendments and
`
`Requests for Final Approval to Tentatively Approved ANDAs”, U.S. Dep’t of Health and
`
`Human Services, Food and Drug Administration, Center for Drug Evaluation and Research
`
`(September 2020)).
`
`18.
`
`Furthermore, in conjunction with this “abbreviated” application process, Congress
`
`has put in place a process for resolving patent disputes relating to generic drugs, pursuant to
`
`which an ANDA filer must provide certifications addressing each of the patents listed in the
`
`Orange Book for the branded drug. See 21 U.S.C. § 355(j)(2)(A)(vii); 21 C.F.R.
`
`§ 314.94(a)(12). An ANDA filer may certify, for instance, that it believes a patent is invalid or
`
`will not be infringed by the manufacture, use, or sale of the generic drug for which the ANDA is
`
`submitted. See 21 U.S.C. § 355(j)(2)(A)(vii)(IV). See also 21 C.F.R. § 314.94(a)(12)(i)(A)(4).
`
`This is known as a “Paragraph IV Certification.”
`
`19.
`
`The filer of an ANDA with a Paragraph IV Certification must also provide notice
`
`to both the owner of the listed patents and the holder of the NDA for the referenced listed drug.
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`6
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`This “Paragraph IV Notice” must include a detailed statement of the factual and legal bases for
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`the applicant’s belief that the challenged patent is invalid or not infringed by the proposed
`
`generic product. See 21 U.S.C. § 355(j)(2)(B); 21 C.F.R. § 314.95.
`
`20.
`
`If a new patent issues and is listed on the Orange Book with respect to the
`
`reference listed drug while an ANDA is being reviewed by FDA, the ANDA filer must submit an
`
`appropriate amendment to its patent certification, which could include, among other things, a
`
`Paragraph IV Certification indicating that the applicant seeks FDA approval to market its
`
`proposed ANDA product prior to the expiration of the new patent. See 21 C.F.R.
`
`§ 314.94(a)(12)(viii)(C)(1)(ii).
`
`VASOSTRICT®
`
`21.
`
`On September 25, 2012, JHP Pharmaceuticals (“JHP”) submitted NDA No.
`
`204485, under § 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA), seeking FDA
`
`approval for a vasopressin injection product to increase blood pressure in adults with
`
`vasodilatory shock. On April 17, 2014, the FDA approved NDA 204485 as the first FDA-
`
`approved vasopressin injection product for use in a clinical setting in the United States.
`
`22.
`
`On February 20, 2014, Par Pharmaceutical Companies, Inc. acquired JHP
`
`Pharmaceuticals, LLC. On February 26, 2014, JHP Pharmaceuticals, LLC changed its name to
`
`Par Sterile Products, LLC. Par Sterile Products is the holder of NDA 204485, including all
`
`supplements thereto, for VASOSTRICT®.
`
`23.
`
`Vasopressin, the active ingredient in VASOSTRICT®, is a polypeptide hormone
`
`that causes contraction of vascular and other smooth muscle cells. VASOSTRICT® is a
`
`lifesaving drug often used when the blood pressure of a critical care patient drops precipitously.
`
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`24.
`
`VASOSTRICT® is approved as indicated to increase blood pressure in adults
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`with vasodilatory shock (e.g., post-cardiotomy or sepsis) who remain hypotensive despite the
`
`provision of fluids and catecholamines. Par markets and sells its VASOSTRICT® products to
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`hospitals, both directly and via group purchasing organizations and wholesalers.
`
`The Patent-in-Suit
`
`25.
`
`Since obtaining FDA approval for VASOSTRICT® in April 2014, Par has
`
`continued to innovate and make significant investments in the research and development of safer
`
`and more effective formulations and uses of vasopressin.
`
`26.
`
`For example, Par developed a reformulated version of VASOSTRICT® with a
`
`higher pH and new buffer system that has an improved stability and impurity profile, and also
`
`developed a safe and effective multi-dose version of VASOSTRICT®. Par submitted
`
`supplemental NDAs seeking FDA approval for these developments—supplemental NDA Nos.
`
`204485/S-003 (reformulated version of VASOSTRICT®) and 204485/S-004 (multi-dose vials).
`
`On March 18, 2016, the FDA approved NDA No. 204485/S-003, and on December 17, 2016, it
`
`approved NDA No. 204485/S-004.
`
`27.
`
`In addition, in an effort to improve patient care and make clinicians’ use of
`
`vasopressin to treat vasodilatory shock even safer and more effective, Par has continued to study
`
`the clinical effects of the use of vasopressin on different sub-populations of patients.
`
`28.
`
`Septic shock is a life-threatening condition that occurs when a person’s blood
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`pressure drops to a dangerously low level after a bacterial, fungal, or viral infection. It can lead
`
`to respiratory or heart failure, stroke, failure of other organs, and ultimately death. Indeed, septic
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`shock is the most common cause of death in intensive care units (ICUs) and is reported to have a
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`mortality rate of 40% - 60%.1 VASOSTRICT® is one of the medications commonly used to
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`treat septic shock (among other forms of vasodilatory shock) in hospital emergency rooms and
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`ICUs across the country, and it can literally save a patient’s life.
`
`29.
`
`But, it is known that overdosage of VASOSTRICT® can cause an over-narrowing
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`of the patient’s blood vessels, leading to adverse results such as ventricular tachyarrhythmias,
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`rhabdomyolysis, hyponatremia, and a variety of gastrointestinal symptoms. Accordingly, as with
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`many drugs, there is a delicate balance between ensuring that patients being treated for septic
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`shock receive an amount of vasopressin sufficient to quickly and effectively raise their blood
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`pressure, and administering too much vasopressin.
`
`30.
`
`Vasopressin is fast acting, but also clears from the body quickly. It was known
`
`that the enzyme leucyl/cystinyl aminopeptidase (“LNPEP”) degrades vasopressin and is
`
`primarily responsible for the short half-life of the drug. For this reason, researcher Taka-Aki
`
`Nakada and his coworkers hypothesized that genetic variations in the vasopressin pathway
`
`genes, including the gene that encodes for LNPEP, may cause a downstream clinical effect in
`
`patients experiencing septic shock.
`
`31.
`
`Genes consist of DNA, which is a molecule composed of strands of four types of
`
`nucleotides: A, T, C and G. Each of the nucleotides on one side of the strand pairs with a
`
`specific nucleotide on the other side of the strand, and this makes up the double helix.
`
`Accordingly, the genetic code for each gene is written in the form of a string of As, Ts, Cs, Gs.
`
`1 See, e.g., Russell et al, “Vasopressin versus Norepinephrine infusion in patients with septic
`shock,” N. Engl. J. Med. 358 (9):877-887 (2008).
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`32.
`
`A variation in a gene is known as an allele, and an individual’s collection of genes
`
`is known as the genotype. A single genetic variation, for instance when some people have an
`
`“A” in a particular location and some have a “T”, is known as a single nucleotide polymorphism
`
`(“SNP”). Human beings typically carry two copies of each gene. When an SNP is present, the
`
`genes may have different nucleotides at the SNP location. Thus, if A is dominant at a particular
`
`location, but T is also present in some members of a population, there would be three possible
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`combinations of genotypes: “AA”, “AT”, “TT”.
`
`33.
`
`Nakada and his coworkers analyzed available data from a multicenter,
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`randomized, double blind, controlled trial evaluating the efficacy of vasopressin versus
`
`norepinephrine in treating patients with septic shock, and found that the major [T] allele of
`
`LNPEP rs4869317 [A/T] SNP correlated with an increase in 28-day mortality. From this, they
`
`established a major allele model (TT vs. AA/AT genotype) and found that patients with the TT
`
`genotype appeared to have a higher hazard ratio and an increase in vasopressin clearance as
`
`compared with the AA or AT genotyped patients.
`
`34.
`
`In view of the findings by Nakada and other researchers, and the unpredictable
`
`nature of pharmaceutical dosing needed to achieve safety and efficacy, there was a need to better
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`understand the dosing, efficacy, and safety of administering vasopressin to patients having the
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`TT, AA, and AT genotypes. Accordingly, Par designed and implemented a clinical study to
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`determine the effects of the TT, AA, and AT genotypes on the safe and effective use of
`
`vasopressin to treat septic shock. Par surprisingly found that patients with the AA or AT
`
`genotype unexpectedly exhibit lower concentrations of vasopressin in the bloodstream and
`
`increased vasopressin clearance, while those with TT genotype exhibit increased vasopressin
`
`blood levels and lower vasopressin clearance as compared to the AA or AT genotyped patients.
`
`Par further determined that treating patients suffering from septic shock with AA or AT
`
`genotypes differently than other patients would result in improved survival rates and reduced
`
`adverse events. In particular, Par discovered that patents with AA or AT genotypes could and, if
`
`medically warranted under the circumstances, should be treated with a dose of vasopressin that is
`
`higher than the currently-labelled maximum dose of VASOSTRICT®.
`
`35.
`
`Par has reported results from its clinical study in, inter alia, a patent application it
`
`filed with the United States Patent and Trademark Office (“PTO”) on July 17, 2020—U.S. Patent
`
`Application No. 16/932,351. This difference in treatment of patients depending on their
`
`genotype is reflected in the following flow-chart included as Figure 1 of that application:
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`36.
`
`On November 24, 2020, the PTO granted Par a patent on its new treatment
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`regimen, and duly and legally issued the ’435 Patent, entitled “Method to Treat Hypotension
`
`Using Vasopressin in Certain Genotypes.” A true and correct copy of the ’435 Patent is attached
`
`as Exhibit A. Par Pharmaceutical owns the ’435 Patent. EPIC is the exclusive licensee of the
`
`’435 Patent.
`
`37.
`
`This innovative treatment regimen represents an important medical advance in the
`
`way patients suffering from septic shock can and should be treated with vasopressin. Upon
`
`information and belief, armed with the knowledge obtained from Par’s clinical study, medical
`
`practitioners have begun to and/or will increasingly alter their use of vasopressin to treat septic
`
`shock patients based on patient genotypes, and will continue to do so in the future. Indeed,
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`failure to treat patients with AA or AT genotypes in accordance with Par’s new treatment
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`regimen could mean that they are treated less effectively with an insufficient amount of
`
`vasopressin, thereby creating a risk of an adverse treatment outcome including, in a worst-case
`
`scenario, death.
`
`38.
`
`Par has submitted a request to FDA seeking approval pursuant to 21 CFR
`
`§ 314.70 for a proposed amendment to the current label for VASOSTRICT®, in order to include
`
`new instructions concerning the dosage and administration of VASOSTRICT® in view of the
`
`important, newly discovered information concerning the improved method of administering
`
`VASOSTRICT® to patients with AA or AT genotypes. In particular, if approved,
`
`VASOSTRICT®’s label would instruct, in relevant part, as follows:
`
`Patients with AA/AT rs4869317 genotype
`For post-cardiotomy shock, start with a dose of 0.03 units/minute. For septic shock,
`
`start with a dose of 0.01 units/minute. If the target blood pressure response is not
`achieved, titrate up by 0.005 units/minute at 10- to 15-minute intervals. The maximum
`dose for post-cardiotomy shock is 0.121 units/minute and for septic shock 0.085
`units/minute. After target blood pressure has been maintained for 8 hours without the
`use of catecholamines, taper Vasostrict® by 0.005 units/minute every hour as tolerated
`to maintain target blood pressure.
`Table 3 Dosing recommendation for patients with AA/AT rs4869317 genotype
`
`AA/AT
`rs4869317
`Genotype
`
`Post-cardiotomy shock
`Starting
`Titrating
`Maximum
`Dose
`Dose
`Dose
`0.03 U/min
`0.005 U/min
`0.121
`every 10 to
`U/min
`15 min
`
`Starting
`Dose
`0.01
`Units/min
`
`Septic shock
`Titrating
`Dose
`0.005 U/min
`every 10 to
`15 min
`
`Maximum
`Dose
`0.085
`Units/min
`
`See Exhibit B hereto (true and correct copy of proposed new labeling).
`
`39.
`
`In addition to submitting that request, Par has also timely submitted information
`
`regarding the ’435 Patent to the FDA for listing in the Orange Book with respect to
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`VASOSTRICT®, pursuant to 21 U.S.C. § 355(b)(1) and (c)(2). Upon information and belief,
`
`the FDA has listed, or shortly will list, the ’435 Patent in the Orange Book, pursuant to 21 C.F.R.
`
`§ 314.53(e).
`
`Amneal’s Infringing Conduct
`
`40.
`
`On or before March 5, 2019, Amneal submitted ANDA No. 212944 (the “Amneal
`
`Single-Dose ANDA”) pursuant to 35 U.S.C. § 355(j), seeking FDA approval to engage in the
`
`commercial manufacture, use, and sale of a proposed generic Vasopressin Injection USP, 20
`
`units/1 mL (20 units/mL) product, referencing Par’s VASOSTRICT® products as the reference
`
`listed drug (the “Proposed Single-Dose ANDA Product”).
`
`41.
`
`On or before March 5, 2019, Amneal submitted ANDA No. 212945 (the “Amneal
`
`Multi-Dose ANDA”) pursuant to 35 U.S.C. § 355(j), seeking FDA approval to engage in the
`
`commercial manufacture, use, and sale of a proposed generic Vasopressin Injection USP, 200
`
`units/10 mL (20 units/mL) product, referencing Par’s VASOSTRICT® products as the reference
`
`listed drug (the “Proposed Multi-Dose ANDA Product,” together with the Proposed Single-Dose
`
`ANDA Product, the “Proposed ANDA Products”).
`
`42.
`
`Amneal’s ANDAs are still being reviewed by FDA, and Amneal is seeking FDA
`
`approval to market its Proposed ANDA Products prior to expiration of the ’435 Patent.
`
`43.
`
`In accordance with FDA regulations (discussed in more detail above), if Par’s
`
`request seeking to update and amend the labeling for VASOSTRICT® is approved by FDA prior
`
`to approving Amneal’s ANDAs, Amneal will be required as a matter of law to amend the
`
`proposed labeling for its Proposed ANDA Products to conform to the amendments to the
`
`labeling for VASOSTRICT®. This is further reflected, for example, in FDA Guidance to
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`generic manufacturers, which includes the following on the list of common developments that
`
`may impact the grant of final approval and require an amendment to the ANDA:
`
`See Ex. C at 9-11.
`
`* * * *
`
`44.
`
`In that event, the proposed labeling for Amneal’s Proposed ANDA Products
`
`would include, as part of the instructions regarding the dosage and administration of the product,
`
`the same instructions for treating patients with the AA or AT genotypes as is quoted in paragraph
`
`38 above—i.e., that when treating such patients: “. . . For septic shock, start with a dose of 0.01
`
`units/minute. If the target blood pressure response is not achieved, titrate up by 0.005
`
`units/minute at 10- to 15-minute intervals. The maximum dose . . . for septic shock [is] 0.085
`
`units/minute.”
`
`45.
`
`Upon information and belief, if Amneal were to obtain FDA approval to market
`
`and sell its Proposed ANDA Products, it would market and sell it to hospitals and/or group
`
`purchasing organizations and other distributors throughout the United States, including in this
`
`District, as a generic substitute for VASOSTRICT® to be used and administered in the same
`
`manner as VASOSTRICT®.
`
`46.
`
`For the reasons detailed above, upon approval, the proposed labeling for
`
`Amneal’s Proposed ANDA Products is likely to include specific instructions directing physicians
`
`and other medical professionals to use the product to treat patients with AA or AT genotypes in
`
`accordance with the methods claimed in the ’435 Patent, thereby inducing direct infringement of
`
`the ’435 Patent.
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`Case 3:20-cv-18322 Document 1 Filed 12/07/20 Page 16 of 24 PageID: 16
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`47.
`
`Even if the FDA were to approve Amneal’s ANDAs without those instructions
`
`included in the labeling for the Proposed ANDA Products, Amneal will nevertheless still induce
`
`infringement of the ’435 Patent. Upon FDA approval, Amneal will market and sell its Proposed
`
`ANDA Products as a generic substitute for VASOSTRICT® to be used and administered in the
`
`same manner as VASOSTRICT®, with the knowledge and expectation that physicians will treat
`
`patients based on the most up-to-date clinical information available—including Par’s discovery
`
`that in order to improve the treatment of septic shock patients with AA or AT genotypes, those
`
`patients can and should be treated in accordance with the new treatment regimen claimed in the
`
`’435 Patent.
`
`48.
`
`Indeed, it would irresponsible for Amneal to do otherwise. As described above,
`
`septic shock is a life-threatening condition that needs to be treated on an emergent basis. The
`
`proper treatment of septic shock patients can, quite literally, be a matter of life or death. Failure
`
`to treat septic shock patients with AA or AT genotypes in accordance with Par’s new treatment
`
`regimen could result in a sub-optimal treatment of those patients, thereby creating a risk of an
`
`adverse treatment outcome including, in a worst-case scenario, death.
`
`49.
`
`Par expects that Amneal will act in accordance with the best interests of patients,
`
`and that in doing so, Amneal will market and sell its Proposed ANDA Products (if approved)
`
`with explicit or implicit instructions, and the specific intent, that its product be used to treat
`
`septic shock patients with AA or AT genotypes in accordance with Par’s new treatment regimen.
`
`50.
`
`In these ways, Amneal would be inducing infringement of at least claim 1 of the
`
`’435 Patent, which recites the following:
`
`1. A method of increasing blood pressure to a target blood pressure in
`a human patient with septic shock wherein the patient has an LNPEP
`AA or AT rs4869317 genotype, the method comprising: intravenously
`administering to the patient a pharmaceutical formulation comprising
`
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`Case 3:20-cv-18322 Document 1 Filed 12/07/20 Page 17 of 24 PageID: 17
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`vasopressin at a starting dose of 0.01 units/minute and titrating the
`dose up by 0.005 units/minute at 10 to 15 minute intervals to maintain
`the target blood pressure, wherein the maximum dose is 0.085
`units/minute.
`
`See Ex. A.
`
`51.
`
`And, Amneal would be doing so with full knowledge of the ’435 Patent and the
`
`claimed inventions thereof. Upon information and belief, Amneal has been monitoring the
`
`PTO’s website for the issuance of any patents obtained by Par relating to vasopressin. Thus,
`
`upon information and belief, Amneal has been aware of the ’435 Patent since the day it issued.
`
`In any event, at the very latest, Amneal became aware of the ’435 Patent upon the filing of this
`
`lawsuit.
`
`COUNT I
`INFRINGEMENT OF THE ‘435 PATENT UNDER 271(e)(2) (AMNEAL ANDA 212944)
`
`52.
`
`53.
`
`Par incorporates each of the preceding paragraphs as if fully set forth herein.
`
`Section 271(e)(2) of the Patent Act provides in relevant part that: “It shall be an
`
`act of infringement to submit – (A) an [ANDA or 505(b)(2) NDA] for a drug claimed in a patent
`
`or the use of which is claimed in a patent … .” 35 U.S.C. § 271(e)(2). The ’435 Patent is just
`
`such a patent—it claims the use of an FDA-approved drug product (VASOSTRICT®).
`
`54.
`
`Accordingly, Amneal’s submission of the Amneal Single-Dose ANDA to the
`
`FDA, which seeks approval to engage in the commercial manufacture, use, and sale of its
`
`Proposed Single-Dose ANDA Product prior to the expiration of the ’435 Patent, constitutes
`
`infringement of the ’435 Patent under § 271(e)(2).
`
`55. Moreover, for the reasons discussed above, if the FDA were to approve Amneal’s
`
`Single-Dose ANDA, Amneal’s commercial manufacture, use, offer for sale, sale, and/or
`
`importation into the United States of the Proposed Single-Dose ANDA Product would induce
`
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`Case 3:20-cv-18322 Document 1 Filed 12/07/20 Page 18 of 24 PageID: 18
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`physicians and other medical professionals to use and administer Amneal’s Proposed Single-
`
`Dose ANDA Product in a manner that directly infringes at least Claim 1 of the ’435 Patent.
`
`56.
`
`Amneal would knowingly, intentionally, and actively induce and encourage that
`
`infringement, by virtue of the labeling to be included for the product and Amneal’s marketing of
`
`the product as a generic substitute for VASOSTRICT® to be used and administered in the same
`
`manner as VASOSTRICT®.
`
`57.
`
`Any launch by Amneal of its Proposed Single-Dose ANDA Product before
`
`expiration of the ’435 Patent would cause Par to suffer immediate and irreparable harm.
`
`58.
`
`Amneal’s inducement of infringement of the ’435 Patent would be willful.
`
`COUNT II
`DECLARATORY JUDGMENT OF INDUCED
`INFRINGEMENT OF THE ‘435 PATENT UNDER 271(b) (AMNEAL ANDA 212944)
`
`59.
`
`60.
`
`Par incorporates each of the preceding paragraphs as if fully set forth herein.
`
`Section 271(b) of the Patent Act provides that: “Whoever actively induces
`
`infringement of a patent shall be liable as an infringer.” 35 U.S.C. § 271(b). As detailed at
`
`length herein, if the FDA were to approve Amneal’s Single-Dose ANDA, Amneal would
`
`actively induce infringement of the ’435 Patent by others.
`
`61.
`
`In particular, if the FDA were to approve Amneal’s Single-Dose ANDA,
`
`Amneal’s commercial manufacture, use, offer for sale, sale, and/or importation into the United
`
`States of the Proposed Single-Dose ANDA Product would induce physicians and other medical
`
`professionals to use and administer the Proposed Single-Dose ANDA Product in a manner that
`
`directly infringes at least Claim 1 of the ’435 Patent.
`
`62.
`
`Amneal would knowingly, intentionally, and actively induce and encourage that
`
`infringement, by virtue of the labeling to be included for the product and Amneal’s marketing of
`
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`Case 3:20-cv-18322 Document 1 Filed 12/07/20 Page 19 of 24 PageID: 19
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`the product as a generic substitute fo