Biofer Spa v. Vifor Intl AG

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Case Name: Biofer S.p.A. v. Vifor (International) AG
  • Plaintiff’s Counsel: Greenberg Traurig, LLP
• Case Identification: 1:22-cv-02180, E.D.N.Y., 09/15/2023
• Venue Allegations: Venue is asserted based on Defendant being a foreign corporation and having sufficient contacts with the district. Allegations include that Defendant, through a partnership with U.S.-based American Regent, markets and sells the accused product in New York, derives substantial revenue from the state, and has an established place of business in the district.
• Core Dispute: Plaintiff alleges that the process used by Defendant to manufacture its intravenous iron-deficiency drug, Injectafer®, infringes a U.S. patent covering an improved method for preparing trivalent iron-sugar complexes.
• Technical Context: The technology relates to the chemical synthesis of iron-carbohydrate complexes, which are active pharmaceutical ingredients in drugs used to treat iron deficiency anemia, a common and significant medical condition.
• Key Procedural History: The complaint notes that Defendant Vifor previously filed an opposition against the European counterpart to the patent-in-suit. More recently, Vifor filed an inter partes review (IPR) petition challenging the validity of the patent-in-suit, which the U.S. Patent and Trademark Office rejected as insufficient on the merits as to all claims.

Case Timeline

Date	Event
2005-03-15	U.S. Patent No. 8,759,320 Priority Date
2011-07-20	European counterpart patent EP 1858930 B1 issues
2012-04-20	Vifor files opposition against European counterpart patent
2013-07-25	FDA approves Injectafer®
2013-09-19	Vifor files Patent Term Extension request on a related patent
2014-06-24	U.S. Patent No. 8,759,320 issues
2023-04-24	USPTO denies Vifor's IPR petition against the '320 Patent
2023-09-15	First Amended Complaint filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,759,320 - “Process for the Preparation of Trivalent Iron Complexes with Mono-, Di- and Polysaccharide Sugars”

• Issued: June 24, 2014 (Compl. ¶1, ¶29).

The Invention Explained

• Problem Addressed: The patent addresses difficulties in synthesizing stable and pure trivalent iron-sugar complexes for pharmaceutical use (Compl. ¶32; ’320 Patent, col. 3:5-28). Specifically, it notes that prior art methods using bromine to "activate" the sugar component were difficult and dangerous to carry out on an industrial scale ('320 Patent, col. 6:2-11).
• The Patented Solution: The invention is a process that avoids handling pure bromine by generating it in situ (within the reaction mixture itself) ('320 Patent, Abstract). This is accomplished through the slow, controlled addition of a hypochlorite solution to a mixture of a bromide salt and the sugar, which creates the necessary bromine for the reaction as needed (’320 Patent, col. 6:30-36). This method is described as enabling a "clean and complete reaction" that specifically oxidizes the desired part of the sugar molecule without causing unwanted degradation ('320 Patent, col. 6:57-65).
• Technical Importance: The patented approach provides a safer and more repeatable process for industrial-scale manufacturing, avoiding the need to handle hazardous reagents while achieving a more controlled chemical reaction ('320 Patent, col. 6:36-43).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 7 ('320 Patent, claims 1, 7; Compl. ¶99).
• Independent Claim 1 recites the core process of preparing an "activated sugar" and requires:
  • Reacting a sugar (dextrin or dextran) having an aldehyde end group with bromine at a pH of 7.0-9.0.
  • Producing the bromine in situ by adding a hypochlorite and a metal bromide to the solution.
  • Adding the hypochlorite in "stoichiometric quantities" with respect to the sugar's aldehyde end groups.
  • Adding the hypochlorite "instant by instant, such that an excess of hypochlorite in solution is never present."
• Independent Claim 7 recites:
  • The process of claim 1, followed by a step of adding a Fe(III) salt to the activated sugar to form a Fe(III)-activated sugar complex.
• The complaint reserves the right to assert additional claims (Compl. ¶99).

III. The Accused Instrumentality

Product Identification

The complaint targets the process for manufacturing Injectafer® (ferric carboxymaltose injection) and its active pharmaceutical ingredient (API), ferric carboxymaltose (Compl. ¶1). The infringement claim is brought under 35 U.S.C. § 271(g), which governs the importation, sale, or use of a product made by a process patented in the United States (Compl. ¶99).

Functionality and Market Context

Injectafer® is described as an intravenous iron replacement product for the treatment of iron deficiency anemia (Compl. ¶70). The API, ferric carboxymaltose, is a colloidal iron (III) hydroxide in a complex with a carbohydrate shell (Compl. ¶76). The complaint provides a diagram representing the chemical structure of the ferric carboxymaltose complex in Injectafer® (Compl. ¶73). It is alleged that Vifor manufactures the API outside the U.S. and licenses the final product to American Regent for commercial sale in the U.S. (Compl. ¶13, ¶18).

IV. Analysis of Infringement Allegations

’320 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A process for the preparation of an activated sugar comprising the step of reacting a sugar having an aldehyde end group...	The process for making Injectafer® allegedly involves preparing an "activated maltodextrin sugar," which is a sugar with an aldehyde end group.	¶81, ¶82	col. 6:1-4
...with bromine in a solution at a pH between 7.0 and 9.0 with the specific oxidation of the end aldehyde...	The process allegedly reacts the maltodextrin with bromine at a pH between 7.0 and 9.0 to achieve specific oxidation of the aldehyde end groups.	¶82	col. 6:30-36
wherein i) said sugar is selected from the group consisting of dextrins and dextrans...	The sugar used in the process is allegedly a maltodextrin, which the complaint states is a type of dextrin or dextran.	¶83	col. 9:8
and wherein ii) said bromine is produced in situ through the addition of a hypochlorite and an alkaline or earth alkaline metal bromide...	Bromine is allegedly produced in situ by adding sodium hypochlorite and sodium bromide. The complaint supports this by citing examples in Vifor's own patents for similar products.	¶84	col. 6:30-36
...said hypochlorite being added in stoichiometric quantities with respect to the aldehyde end groups...	The hypochlorite is allegedly added in stoichiometric quantities relative to the aldehyde end groups.	¶85	col. 6:50-57
...wherein said hypochlorite is added instant by instant, such that an excess of hypochlorite in solution is never present.	The hypochlorite is allegedly added "instant by instant" to prevent any excess. The complaint cites Vifor’s own arguments in a European opposition that slow addition is required.	¶86, ¶87	col. 7:1-4

Identified Points of Contention

• Evidentiary Questions: The complaint's allegations regarding Defendant's confidential manufacturing process rely on indirect evidence, such as "Reverse Engineering Studies," Vifor's other patents, and statements made in a Patent Term Extension request (Compl. ¶63-69, ¶80). A central issue will be whether this evidence is sufficient to prove that the commercial process for Injectafer® meets the specific claim limitations. Plaintiff notes that Vifor has refused to produce its manufacturing records, which it argues is evidence of a "substantial likelihood" of infringement (Compl. ¶93-94).
• Scope Questions: The complaint alleges the use of "maltodextrin" infringes the claim limitation "dextrins and dextrans" (Compl. ¶83). While the patent appears to treat these terms as related (e.g., ’320 Patent, claim 25), the precise scope of "dextrins and dextrans" relative to the accused "maltodextrin" may become a point of claim construction.

V. Key Claim Terms for Construction

"added instant by instant, such that an excess of hypochlorite in solution is never present"

• Context and Importance: This limitation describes the precise manner of addition for a key reagent and appears to be a central point of novelty for the claimed process. Its interpretation is critical because proving that a commercial-scale process meets such a strict, absolute-sounding condition ("never present") could be a significant challenge for the Plaintiff and a key defensive point for the Defendant.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A party could argue that this phrase, read in the context of the patent’s purpose, functionally means a controlled, gradual addition that avoids a material buildup of excess hypochlorite that would cause unwanted side reactions ('320 Patent, col. 7:14-19). The patent contrasts this with dumping reagents in all at once, suggesting the focus is on the method of addition rather than achieving a literal zero-excess state at all times.
  • Evidence for a Narrower Interpretation: The plain language "never present" is absolute. A party could argue this requires a process where the hypochlorite is consumed immediately upon addition, a very high bar for infringement. The specification emphasizes that this careful addition ensures "all the added hypochlorite only serves for the bromide oxidation" ('320 Patent, col. 7:1-2), language which could be used to support a strict interpretation.

"produced in situ"

• Context and Importance: This term captures the core inventive concept of creating the reactive agent within the mixture rather than adding it pre-formed. Practitioners may focus on this term because the infringement theory depends on showing Vifor's process generates bromine this way.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent claims define the term structurally: it is produced "through the addition of a hypochlorite and an... metal bromide" ('320 Patent, claim 1). This could be interpreted as simply requiring that these precursors are combined in the solution to generate the bromine.
  • Evidence for a Narrower Interpretation: The specification frames in situ generation as the solution to the dangers of handling pure bromine ('320 Patent, col. 6:30-45). This context suggests "in situ" implies more than just the presence of precursors, but a process designed to keep the concentration of free, hazardous bromine low at all times by generating it only as needed for the reaction.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Vifor induces infringement by American Regent, its U.S. partner (Compl. ¶107, ¶115). The alleged inducement is based on contractual and business agreements encouraging American Regent to market, use, and sell the imported Injectafer® product in the U.S. with knowledge of the '320 Patent (Compl. ¶116).

Willful Infringement

Willfulness is alleged based on Vifor's purported pre-suit knowledge of the patent family, dating back to at least its 2012 opposition to the European counterpart (Compl. ¶30). The complaint further alleges that Vifor's infringement continued even after its own IPR challenge against the '320 Patent was denied by the USPTO, which it claims is evidence of knowing, deliberate, and intentional conduct (Compl. ¶95-96).

VII. Analyst’s Conclusion: Key Questions for the Case

The resolution of this dispute may hinge on the answers to two primary questions:

1. A Question of Proof: Can the Plaintiff compel the production of, or otherwise prove through its indirect evidence, the specific, granular details of the Defendant's confidential manufacturing process? The case will likely involve a significant discovery dispute over whether Vifor's process meets the highly specific claim limitations, such as the "instant by instant" addition of hypochlorite.
2. A Question of Definitional Precision: How will the court construe the phrase "such that an excess of hypochlorite in solution is never present"? The case may turn on whether this requires a literal, absolute absence of excess—a standard that may be difficult to prove in a commercial process—or a more functional interpretation focused on a controlled rate of addition that avoids material side reactions.