Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 1 of 24 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE EASTERN DISTRICT OF NEW YORK
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`Plaintiff,
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`
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`v.
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`Biofer S.p.A.,
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`
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`Vifor (International) AG.,
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`
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`Defendant.
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`C.A. No. ____________
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`COMPLAINT FOR PATENT
`INFRINGEMENT
`
`JURY TRIAL DEMANDED
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`COMPLAINT FOR PATENT INFRINGEMENT
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`Plaintiff Biofer S.p.A. (“Plaintiff” or “Biofer”), by its undersigned attorneys brings this
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`action against Defendant Vifor (International) AG. (“Vifor” or “Defendant”), and hereby alleges
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`as follows:
`
`NATURE OF THE ACTION
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`1.
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`This is an action for infringement of United States Patent Nos. 8,759,320 (“the ’320
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`Patent” or “the Asserted Patent”) under the Patent Laws of the United States, 35 U.S.C. § 100 et
`
`seq., including §§ 271(a) and (g), arising from Vifor’s unauthorized development, manufacturing,
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`importation, commercial marketing, distribution, offers for sale, sales and/or use of ferric
`
`carboxymaltose active pharmaceutical
`
`ingredient
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`(“API”) and/or
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`Injectafer®
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`(ferric
`
`carboxymaltose injection), an iron replacement product, as detailed herein. A true and correct copy
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`of the ’320 Patent is attached as Exhibit A.
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`

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`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 2 of 24 PageID #: 2
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`THE PARTIES
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`2.
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`Plaintiff Biofer S.p.A. is a company organized and existing under the laws of Italy,
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`having a registered address of Via Canina, 2A, 41036 Medolla MO, Italy.
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`3.
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`Biofer is the owner of all rights, including the right to enforcement, of the Asserted
`
`Patent.
`
`4.
`
`Biofer is in the business of, inter alia, developing pharmaceutical products,
`
`including pharmaceutical products containing iron complexes.
`
`5.
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`Upon information and belief, Defendant Vifor is a company organized and existing
`
`under the laws of Switzerland having a registered address of Rechenstrasse 37, CH-9001, St.
`
`Gallen, Switzerland.
`
`6.
`
`Upon information and belief, Vifor is a pharmaceutical company in the business of,
`
`among other activities, developing, manufacturing, and/or commercializing pharmaceutical
`
`products containing iron.
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`7.
`
`Upon
`
`information and belief, Vifor developed
`
`the drug product ferric
`
`carboxymaltose injection, and commercially manufactures, distributes, markets, offers for sale
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`and/or sells it under the name Ferinject® outside of the United States.
`
`8.
`
`Upon further information and belief, Ferinject® is known as Injectafer® (ferric
`
`carboxymaltose injection) in the United States.
`
`9.
`
`Upon information and belief, both Ferinject® and Injectafer® contain the same or
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`substantially identical API, known as ferric carboxymaltose.
`
`10.
`
`Upon information and belief, Vifor manufactures the API contained in Ferinject®
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`and Injectafer®.
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`2
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`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 3 of 24 PageID #: 3
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`11.
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`Upon information and belief, the API in Ferinject® and Injectafer® is
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`manufactured using the same or substantially identical processes.
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`12.
`
`Upon information and belief, the drug product Ferinject® is the same or
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`substantially identical to Injectafer®.
`
`13.
`
`Upon information and belief, Vifor manufactures ferric carboxymaltose API and/or
`
`Injectafer® outside of the United States.
`
`14.
`
`Upon further information and belief, Vifor imports ferric carboxymaltose and/or
`
`Injectafer® into the United States.
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`15.
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`Upon further information and belief, Vifor licenses Injectafer® to American Regent
`
`Inc. (“American Regent”) for the commercial marketing, distribution, and sales of Injectafer® to
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`residents throughout the United States, including in this district.
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`16.
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`Upon information and belief, American Regent is a corporation organized and
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`existing under the laws of the State of New York, with a principal place of business at 5 Ramsey
`
`Road, Shirley, New York 11967. Upon information and belief, American Regent was formerly
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`known as Luitpold Pharmaceuticals, Inc., until January 2, 2019, when its New York Certificate of
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`Incorporation was amended to change the name of the corporation to American Regent, Inc. Upon
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`information and belief, American Regent is a subsidiary of Daiichi Sankyo, Inc., which is located
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`at 211 Mt. Airy Road, Basking Ridge, New Jersey 07920.
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`17.
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`Upon information and belief, American Regent is a pharmaceutical company in the
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`business of, among other activities, developing, manufacturing, and/or commercializing
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`pharmaceutical products containing iron complexes.
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`18.
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`Upon information and belief, American Regent licenses Injectafer® from Vifor in
`
`the United States.
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`3
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`19.
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`Upon information and belief, American Regent purchases ferric carboxymaltose
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`and/or Injectafer® from Vifor in the United States.
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`20.
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`Upon further information and belief, American Regent commercially markets,
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`offers for sale, and/or sells Injectafer® to residents throughout the United States, including in this
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`District.
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`JURISDICTION AND VENUE
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`21.
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`This is an action for patent infringement arising under the patent laws of the United
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`States, 35 U.S.C. §§ 100 et seq., including §§ 271(a) and 271(g).
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`22.
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`This Court has subject matter jurisdiction over this action under 28 U.S.C. §§ 1331,
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`1332 and 1338(a).
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`23.
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`24.
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`This Court has personal jurisdiction over Vifor.
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`Upon information and belief, this Court has personal jurisdiction over Vifor, under
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`New York’s long arm statute, New York Civil Practice Law § 302, because Vifor, through
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`partnership with American Regent, commercially markets, distributes, offers for sale and sells
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`Injectafer® to residents throughout the United States, including in New York. Upon further
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`information and belief, Vifor regularly does business in New York, derives substantial revenue
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`from goods used or consumed in New York, and expects or should reasonably expect its acts to
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`have consequences in New York. Upon further information and belief, Vifor has established, and
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`will continue to maintain, minimum contacts with this forum such that the exercise of jurisdiction
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`over Vifor would not offend traditional notions of fair play and substantial justice.
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`25.
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`Venue is proper in this Judicial District as to Defendant Vifor under 28 U.S.C. §
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`1400(b) at least because, upon information and belief, Vifor has committed acts of infringement
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`and has a regular and established place of business in this Judicial District.
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`4
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`26.
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`Upon further information and belief, venue is proper in this judicial district as to
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`Vifor under 28 U.S.C. §§ 1391 and 1400(b) for at least the reason that Vifor is a foreign corporation
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`not residing in any United States district and may be sued in any judicial district that has personal
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`jurisdiction, including this judicial district.
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`FACTUAL BACKGROUND
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`Iron Replacement Therapy Introduction
`
`27.
`
`Iron replacement therapy is an important field of medicine due to the prevalence of
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`iron deficiency anemia (IDA). IDA is a common type of anemia, a condition in which blood lacks
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`adequate healthy red blood cells for carrying oxygen to the body’s tissues. IDA occurs due to
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`insufficient iron. Without enough iron, a person cannot produce enough hemoglobin in red blood
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`cells to carry adequate amounts oxygen throughout the body. As a result, IDA may cause a person
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`to be tired and/or short of breath. IDA can be treated with iron supplementation.
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`28.
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`Trivalent iron (III) complexes have been used in the treatment of IDA. However,
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`it is important that such complexes possess certain characteristics, such as high bioavailability,
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`low toxicity, and ease of production. In addition, stability of the complex is important because it
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`impacts not only the shelf life of the selected pharmaceutical form, but also the bioavailability of
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`the complexed iron.
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`The Asserted Patent
`
`29.
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`Biofer is owner of all title, right and interest in the ’320 Patent and has the right to
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`enforce it. The ’320 Patent, entitled “Process for the Preparation of Trivalent Iron Complexes with
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`Mono-, Di- and Polysaccharide Sugars,” was duly and legally issued on June 24, 2014 and lists
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`Stefania Sacchi, Mauro Montorsi, and Egidio Marchi as inventors. The ’320 Patent issued from
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`5
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`U.S. Patent Application No. 11/908,575 (“the ’575 Application”), which is the national stage entry
`
`of PCT/IB2006/000560, filed on March 14, 2006. The ’320 patent is presumed valid.
`
`30.
`
`In Europe, Biofer’s PCT/IB2006/000560 issued as EP 1858930 B1 on July 20,
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`2011. On April 20, 2012, Vifor filed an opposition before the European Patent Office against EP
`
`1858930 B1. Accordingly, Vifor was aware of Biofer’s PCT/IB2006/000560 at least as of the
`
`filing date of its opposition against Biofer’s EP 1858930 B1 on July 20, 2011, and was further
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`aware of the ’575 Application prior to issuance of the ’320 Patent and was aware of the ’320 Patent
`
`on or shortly after its date of issuance.
`
`31.
`
`The ’320 Patent describes, inter alia, improved methods of making iron complexes.
`
`For example, the ’320 Patent describes improved processes for preparation of trivalent iron (III)
`
`complexes with mono-, di- and polysaccharide sugars. (Ex. A (’320 Patent) at 1:6-8.)
`
`32.
`
`The iron (III) complexes manufactured according to the processes described in the
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`’320 Patent are characterized by good physical-chemical stability over time, low toxicity, safety
`
`and good bioavailability. (Id. at 8:54-59.)
`
`33.
`
`The manufacturing processes described in the ’320 Patent include four steps: (1)
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`activation of mono-, di- or polysaccharide sugar; (2) complexation of the activated sugar with
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`ferric hydroxide generated in solution; (3) purification of the ferric hydroxide/sugar complex still
`
`not stabilized; and (4) stabilization of the ferric hydroxide/sugar complex. (Id. at 9:60-67.)
`
`34. With respect to the first step, it is known that sugars having an aldehyde end group
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`can be oxidized using bromine, but such methods can be difficult to carry out. (Id. at 6:2-11.)
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`However, the inventors of the ’320 Patent discovered that the problems associated with the use of
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`bromine as an oxidizing agent can be overcome by producing the bromine oxidizing agent in situ.
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`This can be done by the controlled addition of sodium hypochlorite in an aqueous solution
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`6
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`containing an alkaline or alkaline earth bromide (such as sodium bromide) and the sugar, at a pH
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`between 7.0 and 9.0. (Id. at 6:30-36.)
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`35.
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`The ’320 Patent further explains that sugar activation is advantageously carried out
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`on an industrial scale using the methods of the invention due to the ease of handling of the reagents
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`and the repeatability of the reaction itself. (Id. at 6:36-43.)
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`36.
`
`An advantage of the method according to the ’320 Patent is the handling of reagents
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`which require particular precautions, such as bromine, is avoided and the activation reaction is
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`carried out in controlled conditions. The amount of bromide used may be between 0.5% and 5%
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`by weight of the sugar to be activated. Therefore the bromine quantity which is formed during the
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`activation reaction is low with respect to the quantity of sugar to be activated. (Id. at 6:43-52.)
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`37.
`
`The novel manufacturing processes discovered by the Biofer inventors for making
`
`iron complexes is reflected in exemplary claims 1 and 7 of the ’320 Patent which recite:
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`1. A process for the preparation of an activated sugar comprising the step of reacting
`a sugar having an aldehyde end group with bromine in a solution at a pH between
`7.0 and 9.0 with the specific oxidation of the end aldehyde, wherein
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`i) said sugar is selected from the group consisting of dextrins and dextrans
`and wherein
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`ii) said bromine is produced in situ through the addition of a hypochlorite
`and an alkaline or earth alkaline metal bromide to said solution, said
`hypochlorite being added in stoichiometric quantities with respect to the
`aldehyde end groups, wherein said hypochlorite is added instant by instant,
`such that an excess of hypochlorite in solution is never present.
`
`7. The process according to claim 1, where, in a following step, Fe(III) salt is added
`to react with said activated sugar to form a Fe(III)-activated sugar complex.
`
`(Id. at claims 1, 7.)
`
`The Injectafer® Product is Manufactured Using an Infringing Process
`
`38.
`
`Upon information and belief, American Regent is the owner of NDA No. 203565
`
`for Injectafer® (ferric carboxymaltose) which the FDA approved on July 25, 2013. Upon
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`
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`7
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`information and belief, the FDA’s Orange Book originally listed the owner of NDA No. 203565
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`as Luitpold Pharmaceuticals, Inc. (“Luitpold”). Upon information and belief, Luitpold changed its
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`name to American Regent, Inc., effective January 2, 2019.
`
`39.
`
`Upon information and belief, Vifor is the manufacturer of the API (ferric
`
`carboxymaltose) for Injectafer®
`
`40.
`
`Upon information and belief, Vifor is the holder of the Drug Master File (DMF) for
`
`the API contained in Injectafer®.
`
`41.
`
`Upon information and belief, the API contained in Injectafer® is made in
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`accordance with Drug Master File (DMF) No. 16967.
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`42.
`
`Upon information and belief, Vifor is the holder of Drug Master File (DMF) No.
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`16967.
`
`43.
`
`Upon information and belief, the code “VIT-45” is an internal Vifor code for the
`
`active ingredient, ferric carboxymaltose.
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`44.
`
`Upon information and belief, the active pharmaceutical ingredient (API) in
`
`Injectafer, i.e., ferric carboxymaltose is manufactured by Vifor using a process which meets every
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`limitation of at least one claim of the ’320 Patent.
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`45.
`
`Upon information and belief, the active pharmaceutical ingredient (API) in
`
`Injectafer, i.e., ferric carboxymaltose, is manufactured outside of the United States by or on behalf
`
`of Vifor.
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`46.
`
`Upon information and belief, the ferric carboxymaltose API in Injectafer is
`
`imported into the United States by or on behalf of Vifor.
`
`47.
`
`Upon information and belief, Injectafer® is imported into the United States.
`
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`8
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`48.
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`Upon information and belief, Injectafer® is imported into the United States by or
`
`on behalf of Vifor.
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`49.
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`Upon information and belief, once the Injectafer® product is imported into the
`
`United States by or on behalf of Vifor, it is commercially marketed, distributed, used, offered for
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`sale, and/or sold by American Regent, pursuant to a license from Vifor, throughout the United
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`States.
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`50.
`
`Upon further information and belief, American Regent commercially markets,
`
`distributes, offers for sale, sells, and/or uses the Injectafer® product throughout the United States
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`in the same form in which it is manufactured by Vifor.
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`51.
`
`Upon information and belief, Vifor manufactures ferric carboxymaltose and/or
`
`Injectafer® using a process which infringes one or more claims of the ’320 Patent, and the product
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`is not materially changed by any subsequent processes and does not become a trivial and
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`nonessential component of another product. Rather, Injectafer® is imported and commercially
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`marketed, distributed, offered for sale, sold and/or used, in the United States in the same or
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`substantially the same form in which it is produced using a manufacturing process which infringes
`
`the claims of the ’320 Patent. Upon information and belief there are no additional manufacturing
`
`processes which materially alter the Injectafer® product. Upon information and belief, ferric
`
`carboxymaltose is an essential component of the Injectafer® product.
`
`52.
`
`Upon information and belief, American Regent licenses Injectafer® and certain
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`Orange Book listed patents from Vifor, and American Regent commercially markets, distributes,
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`offers for sale, sells, and/or uses Injectafer®, in this judicial district and throughout the United
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`States.
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`9
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`53.
`
`Upon information and belief, the FDA Orange Book lists United States Patent Nos.
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`7,612,109 (“the ’109 Patent”); 7,754,702 (“the ’702 Patent”); 8,895,612 (“the ’612 Patent”);
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`9,376,505 (“the ’505 Patent”), and 11,123,321 (“the ’321 Patent”) (collectively, “the Orange Book
`
`Patents”) with respect to Injectafer®. Upon information and belief, Vifor is the assignee of the
`
`’109 Patent, the ’505 Patent, and the ’321 Patent. Upon information and belief, American Regent
`
`is the assignee of the ’702 Patent and the ’612 Patent. Upon information and belief, American
`
`Regent licenses the ’109 Patent, the ’505 Patent, and the ’321 Patent from Vifor.
`
`54.
`
`Upon information and belief, the Orange Book Patents for which Vifor is the
`
`assignee, i.e., the ’109 Patent, the ’505 Patent and the ’321 Patent, each recite purported
`
`manufacturing methods in Examples 1-8.
`
`55.
`
`Each of the Examples 1-8 appearing in the ’109 Patent also appear in the ’505
`
`Patent and ’321 Patent, and citations to the ’109 Patent are representative of the identical citations
`
`in the ’505 Patent and ’321 Patent.
`
`56.
`
`Each of Examples 3-8 of the ’109 Patent recite the step of oxidizing a maltodextrin
`
`with a sodium hypochlorite solution and sodium bromide.
`
`57.
`
`Example 3 of the ’109 Patent recites:
`
`equivalent measured
`(9.6 dextrose
`100 g maltodextrin
`gravimetrically) are dissolved by stirring in 300 ml water at 25° C.
`and oxidized by addition of 30 g sodium hypochlorite solution (13
`to 16 weight percent active chlorine) and 0.7 g sodium bromide at
`pH 10.
`At first the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`Then the pH is adjusted to 6.5 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 60 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 30
`minutes and then heated to 97-98° C. and the temperature is kept for
`
`
`
`10
`
`

`

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`30 minutes at this range. After cooling the solution to room
`temperature the pH is adjusted to 6-7 by the addition of sodium
`hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 139 g (corresponding to 88% of the theoretical value)
`of a brown amorphic powder having an iron content of 26.8%
`weight/weight (measured complexometrically).
`Molecular weight mw 140 kDa.
`
`(Id. at 6:6-33.)
`
`58.
`
`Example 4 of the ’109 Patent recites:
`
`A mixture of 45 g maltodextrin (6.6 dextrose equivalent measured
`gravimetrically) and 45 g maltodextrin (14.0 dextrose equivalent
`measured gravimetrically) is dissolved by stirring in 300 ml water
`at 25° C. and oxidized by addition of 25 g sodium hypochlorite
`solution (13 to 16 weight percent active chlorine) and 0.6 g sodium
`bromide at pH 10.
`At first the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`Then the pH is adjusted to 11 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 30 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 30
`minutes and then heated to 97-98° C. and the temperature is kept for
`30 minutes at this range. After cooling the solution to room
`temperature the pH is adjusted to 6-7 by the addition of sodium
`hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 143 g (corresponding to 90% of the theoretical value)
`of a brown amorphic powder having an iron content of 26.5%
`weight/weight (measured complexometrically).
`Molecular weight mw 189 kDa.
`
`
`
`11
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`

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`(Id. at 6:35-62.)
`
`59.
`
`Example 5 of the ’109 Patent recites:
`
`equivalent measured
`(14.0 dextrose
`90 g maltodextrin
`gravimetrically) are dissolved by stirring in 300 ml water at 25° C.
`and oxidized by addition of 35 g sodium hypochlorite solution (13
`to 16 weight percent active chlorine) and 0.6 g sodium bromide at
`pH 10.
`At first, the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`Then the pH is adjusted to 11 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 30 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 30
`minutes and then heated to 97-98° C. and the temperature is kept for
`30 minutes at this range. After cooling the solution to room
`temperature the pH is adjusted to 6-7 by the addition of sodium
`hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 131 g (corresponding to 93% of the theoretical value)
`of a brown amorphic powder having an iron content of 29.9%
`weight/weight (measured complexometrically).
`Molecular weight mw 118 kDa.
`
`(Id. at 6:64-7:23.)
`
`60.
`
`Example 6 of the ’109 Patent recites:
`
`A mixture of 45 g maltodextrin (5.4 dextrose equivalent measured
`gravimetrically) and 45 g maltodextrin (18.1 dextrose equivalent
`measured gravimetrically) is dissolved by stirring in 300 ml water
`at 25° C. and oxidized by addition of 31 g sodium hypochlorite
`solution (13 to 16 weight percent active chlorine) and 0.7 g sodium
`bromide at pH 10.
`At first the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`
`
`
`12
`
`

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`Then the pH is adjusted to 11 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 30 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 30
`minutes and then heated to 97-98° C. and the temperature is kept for
`30 minutes at this range. After cooling the solution to room
`temperature the pH is adjusted to 6-7 by the addition of sodium
`hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 134 g (corresponding to 88% of the theoretical value)
`of a brown amorphic powder having an iron content of 27.9%
`weight/weight (measured complexometrically).
`Molecular weight mw 178 kDa.
`
`(Id. at 7:25-52.)
`
`61.
`
`Example 7 of the ’109 Patent recites:
`
`equivalent measured
`(9.6 dextrose
`100 g maltodextrin
`gravimetrically) are dissolved by stirring in 300 ml water at 25° C.
`and oxidized by addition of 29 g sodium hypochlorite solution (13
`to 16 weight percent active chlorine) and 0.7 g sodium bromide at
`pH 10.
`At first the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`Then the pH is adjusted to 11 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 30 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 70
`minutes. After cooling the solution to room temperature the pH is
`adjusted to 6-7 by the addition of sodium hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 155 g (corresponding to 90% of the theoretical value)
`of a brown amorphic powder having an iron content of 24.5%
`weight/weight (measured complexometrically).
`
`
`
`13
`
`

`

`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 14 of 24 PageID #: 14
`
`Molecular weight mw 137 kDa.
`
`(Id. at 7:54-8:12.)
`
`62.
`
`Example 8 of the ’109 Patent recites:
`
`equivalent measured
`(6.6 dextrose
`126 g maltodextrin
`gravimetrically) are dissolved by stirring in 300 ml water at 25° C.
`and oxidized by addition of 24 g sodium hypochlorite solution (13
`to 16 weight percent active chlorine) and 0.7 g sodium bromide at
`pH 10.
`At first the oxidized maltodextrin solution and then 554 g sodium
`carbonate solution (17.3% weight/weight) are added at room
`temperature to 352 g of a stirred iron (III) chloride solution (12%
`weight by weight Fe).
`Then the pH is adjusted to 11 by addition of sodium hydroxide and
`the solution is heated to 50° C. and kept for 30 minutes at 50° C.
`Then, acidification to a pH of 5 to 6 is effected by addition of
`hydrochloric acid, the solution is kept at 50° C. for a further 70
`minutes. After cooling the solution to room temperature the pH is
`adjusted to 6-7 by the addition of sodium hydroxide.
`The solution is then filtered through a sterilisation filter and then
`examined for sediments. Thereafter, the complex is isolated by
`precipitation with ethanol in a range of 1:0.85 and then dried in
`vacuum at 50° C.
`The yield is 171 g (corresponding to 86% of the theoretical value)
`of a brown amorphic powder having an iron content of 21.35%
`weight/weight (measured complexometrically).
`Molecular weight mw 170 kDa.
`
`(Id. at 8:14-39.)
`
`63.
`
`Upon information and belief, Vifor’s Drug Master File (DMF) for ferric
`
`carboxymaltose includes a step of using sodium hypochlorite and sodium bromide to oxidize
`
`aldehyde end groups of maltodextrin.
`
`64.
`
`Upon information and belief, Vifor filed a patent term extension (PTE) request
`
`dated September 19, 2013 (“Vifor’s PTE Request”) with respect to the ’109 Patent.
`
`65.
`
`In Vifor’s PTE Request, it asserted that the “marketing applicant for the approved
`
`product upon which this application for extension is based is Luitpold Pharmaceuticals, Inc.”
`
`
`
`14
`
`

`

`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 15 of 24 PageID #: 15
`
`(Vifor’s PTE Request at 1.) In Vifor’s PTE Request, Vifor further asserted that “Luitpold
`
`Pharmaceuticals is a corporation organized under the laws of New York and is the licensee of U.S.
`
`Patent No. 7,612,109.” (Id.) In Vifor’s PTE Request, Vifor further asserted that “Luitpold
`
`Pharmaceuticals, Inc. is authorized under that license to register, import, manufacture, market,
`
`distribute, use and sell the approved product.” (Id.) Upon information and belief, Luitpold
`
`Pharmaceuticals changed its name to American Regents, as set forth above.
`
`66.
`
`In Vifor’s PTE Request, Vifor asserted that the “ferric carboxymaltose in
`
`Injectafer® is a water soluble iron carbohydrate complex and has a weight average molecular
`
`weight (Mw) of approximately 120,000 to 200,000 Da.” (Id. at 5.)
`
`67.
`
`In Vifor’s PTE Request, Vifor asserted that “[t]he approved process for
`
`manufacturing ferric carboxymaltose includes each process step identified in claim 1” of the ’109
`
`Patent. (Id.) Claim 1 of the ’109 Patent recited the following:
`
`1. A water soluble iron carbohydrate complex having a weight
`average molecular weight (Mw) of 80,000 to 400,000, comprising
`the reaction product of:
`(a) an aqueous solution of an iron (III) salt and
`(b) an aqueous solution of the oxidation product of
`(i) at least one maltodextrin and
`(ii) an aqueous hypochlorite solution at an alkaline
`pH, wherein,
`when one maltodextrin is present, the maltodextrin has a dextrose
`equivalent of between 5 and 20, and wherein,
`when a mixture of more than one maltodextrin is present, the
`dextrose equivalent of each individual maltodextrin is between 2
`and 40, and the dextrose equivalent of the mixture is between 5 and
`20.
`
`(Id. at 5; see also ’109 Patent at claim 1.)
`
`68.
`
`In Vifor’s PTE Request, Vifor further asserted the manufacturing process used to
`
`manufacture Injectafer® purportedly included the following steps:
`
`
`
`15
`
`

`

`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 16 of 24 PageID #: 16
`
`The complex is obtained from an aqueous solution of iron (III)
`chloride and an aqueous solution of the oxidation product of one or
`more maltodextrins. The oxidation product is made by dissolving a
`maltodextrin with a dextrose equivalents between 5 and 20 in water.
`The resulting aqueous solution is oxidized by adding a sodium
`hypochlorite solution at an alkaline pH. The oxidized maltodextrin
`solution is then mixed with an iron (III) chloride solution. The
`resulting solution is filtered, precipitated, and dried in a vacuum.
`The dry product is then reconstituted with water and sealed in glass
`vials for injection.
`
`(Vifor’s PTE Request at 6.)
`
`69.
`
`In Vifor’s PTE Request, Vifor further asserted that claim 6 of the ’109 Patent “reads
`
`on the currently approved method used to manufacture the approved product.” (Id.) Claim 6 of the
`
`’109 Patent recited the following:
`
`6. A process for producing a water soluble iron carbohydrate
`complex having a weight average molecular weight (Mw) of 80,000
`to 400,000, comprising the steps of:
`(a) oxidizing at least one maltodextrin in an aqueous solution at an
`alkaline pH with an aqueous hypochlorite solution to form an
`oxidized maltodextrin solution, and
`(b) contacting the oxidized maltodextrin solution with an aqueous
`solution of an iron (III) salt, wherein,
`when one maltodextrin is present, the maltodextrin has a dextrose
`equivalent of between 5 and 20, and wherein,
`when a mixture of more than one maltodextrin is present, the
`dextrose equivalent of each individual maltodextrin is between 2
`and 40, and the dextrose equivalent of the mixture is between 5 and
`20.
`
`(Vifor’s PTE Request at 6; see also ’109 Patent at claim 6.)
`
`70.
`
`Upon information and belief, Injectafer® is approved and marketed in the United
`
`States as an iron replacement product indicated for the treatment of iron deficiency anemia (IDA)
`
`in adults and pediatric patients 1 year of age and older who have either intolerance to oral iron or
`
`an unsatisfactory response to oral iron, and adult patients who have non-dialysis dependent chronic
`
`kidney disease. (Injectafer® Prescribing Information at § 1.)
`
`
`
`16
`
`

`

`Case 1:22-cv-02180-AMD-SJB Document 1 Filed 04/15/22 Page 17 of 24 PageID #: 17
`
`71.
`
`Upon information and belief, Injectafer® contains the active ingredient ferric
`
`carboxymaltose, which is an iron carbohydrate complex with the chemical name polynuclear iron
`
`(III)-hydroxide
`
`4(R)-(poly-(14)-0-α-D-glucopyranosyl)-oxy-2(R),3(R),5(R),6-tetrahydroxy-
`
`hexanoate. (Id. at § 11.)
`
`72.
`
`Upon further information and belief, the ferric carboxymaltose in Injectafer® has a
`
`relative molecular weight of approximately 150,000 Da corresponding to the following empirical
`
`formula: [FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k, wheren n ≈ 103, m ≈ 8, l ≈ 11, and k ≈
`
`4, further wherein l represents the mean branching degree of the ligand. (Id. at § 11.)
`
`73.
`
`A schematic representation of the chemical structure of the f