Curia IP Holdings, LLC v. Salix Pharm., Ltd.

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CURIA IP HOLDINGS, LLC, Plaintiff, v. SALIX PHARMACEUTICALS, LTD., et al., Defendants.

Civil Action No. 21-19293 (ES) (JRA)

United States District Court, D. New Jersey

January 26, 2024

Not for Publication

OPINION

Esther Salas, U.S.D.J.

Plaintiff Curia IP Holdings, LLC brought this patent infringement suit against Defendants Salix Pharmaceuticals, Ltd.; Salix Pharmaceuticals, Inc.; Bausch Health Companies, Inc. Alfasigma S.p.A.; and Alfasigma USA, Inc. (together “Defendants”) alleging infringement of U.S Patent No. 9,186,355 (the “'355 Patent”), No 10,556,915 (the “'915 Patent”), No 10,745,415 (the “'415 Patent”), and No. 10,961,257 (the “'257 Patent”). (D.E. No. 69 (“Am. Compl.”) ¶¶ 77- 113). Before the Court is the parties' request for claim construction with respect to terms in all four patents. (D.E. No. 79 (“Def Open. Br.”); D.E. No. 80 (“Pl. Open. Br.”); D.E. No. 93 (“Def. Resp. Br.”); D.E. No. 95 (Pl. Resp. Br.”). The Court held a Markman hearing on April 27, 2023. (D.E. No. 135). This Opinion sets forth the Court's constructions of the disputed terms.

I.BACKGROUND

A. Technology Overview

In October 2021, Plaintiff Curia IP Holdings, LLC brought this patent infringement suit against Defendants Salix Pharmaceuticals, Ltd.; Salix Pharmaceuticals, Inc.; Bausch Health Companies, Inc.; Alfasigma S.p.A.; and Alfasigma USA, Inc. (D.E. No. 1). Plaintiff alleges infringement of the following four patents: the '355 Patent, the '915 Patent, the '415 Patent, and the '257 Patent (together the “patents in suit”). (See Am. Compl. ¶¶ 77-113). The patents in suit contain claims directed to mixtures of polymorphic forms of the antibiotic rifaximin, pharmaceutical compositions comprising the same mixtures, and methods of treatment for administering those rifaximin mixtures and pharmaceutical compositions. (See generally D.E. No. 79-2, Ex. 1 (“'355 Patent”) to D.E. No. 79-1 (“Weisbruch Decl.”); D.E. No. 79-3 Ex. 2, (“'915 Patent”) to Weisbruch Decl.; D.E. No. 79-4, Ex. 3 (“'415 Patent”) to Weisbruch Decl.; D.E. No. 79-5, Ex. 4 (“'257 Patent”) to Weisbruch Decl.; Am. Compl. ¶¶ 36-40).

Rifaximin is an antibiotic with a low gastrointestinal (“GI”) absorption. ('355 Patent at 4:6-8; '915 Patent at 1:24-31; '415 Patent at 1:26-33; '257 Patent at 1:26-33; D.E. No. 79-16 “Myerson Decl.”) ¶ 47). Because it is poorly absorbed into the bloodstream, rifaximin acts locally in the GI tract and can be used in therapy for the treatment of GI infections such as traveler's diarrhea and hepatic encephalopathy. ('915 Patent at 1:24-31; see also D.E. No. 79-9, Ex. 8 to Weisbruch Decl. at 1074). Like other active pharmaceutical ingredients (“APIs”), rifaximin can exist in numerous crystalline forms, referred to as polymorphs. (See, e.g., '915 Patent at 1:58-67; D.E. No. 80-4 (“Swift Decl.”) ¶ 44). While polymorphs share the same chemical composition, they possess different three-dimensional packing arrangements based on the configuration of individual molecules within their crystal structure. ('355 Patent at 3:40-46; Swift Decl. ¶ 44). Different polymorphs can exhibit different properties-including chemical and physical stability- because of their distinct three-dimensional packing arrangements. (Swift Decl. ¶ 46; Myerson Decl. ¶ 39). These different properties are significant to pharmaceutical manufacturers because they can affect the handling properties and ease with which a drug can be formulated, as well as the stability and bioavailability of the drug product. (Swift Decl. ¶ 46; Myerson Decl. ¶ 40). For example, as the specification of the '355 Patent explains, “different crystalline polymorphs of an organic compound can display differing physical properties, such as rate of dissolution, which can be important in the formulation of the compound for use as a medicinal substance.” ('355 Patent at 3:65-4:2). The specifications of the patents in suit identify at least the following polymorphic forms of rifaximin: α, β, γ, ε, δ, ζ, η, α dry, ι, κ, and θ. ('355 Patent at 1:55-2:45; '915 Patent at 1:58-67; '415 Patent at 1:60-67; '257 Patent at 1:60-67).

Because different polymorphic forms of an API exhibit different chemical and physical properties, pharmaceutical manufacturers often wish to characterize the crystalline form(s) of an API to determine its structure and physical properties. (Swift Decl. ¶¶ 46 & 49). X-ray diffraction (“XRD” or “DRX”) is the primary analytic technique for characterizing the structure of crystalline forms of APIs. (Id. ¶ 49; Myerson Decl. ¶ 41). XRD experiments can be carried out on single crystals or on polycrystalline powdered samples. (Swift Decl. ¶ 53). When performed on powders, this technique is known as X-ray powder diffraction (“XRPD” or “PRXD”). (Myerson Decl. ¶ 41; Swift Decl. ¶ 54). XRPD is performed by exposing a crystalline powder sample to X-rays of a certain wavelength. (Myerson Decl. ¶ 42; Swift Decl. ¶ 54). When X-rays are directed at a crystalline sample, they are diffracted by the atoms contained within the sample at a unique set of “scattering angles” which differ in their intensities based on the type and arrangements of atoms and molecules in the sample. (Swift Decl. ¶ 53). An instrument known as an X-ray diffractometer measures the intensity of the X-rays that diffract across a range of angles. (Id. ¶¶ 50 & 53; Myerson Decl. ¶ 44). The output of an XRPD experiment is typically reported as a graphical pattern known as a diffractogram, where the x-axis plots the scattering angle of the diffracted X-ray beam in terms of 2θ (“two theta” or “2theta”) given in units of degrees, and the y-axis plots the intensity of the diffracted X-ray beam either in absolute units, or relative units as compared to the most intense peak in the diffractogram. (Swift Decl. ¶ 55; Myerson Decl. ¶¶ 44- 45). A sample diffractogram taken from the '915 Patent is reproduced below.

(Image Omitted)

('915 Patent, Figure 4). Each crystalline compound has a unique diffraction pattern, analogous to a “fingerprint.” (Swift Decl. ¶ 57 (citing D.E. No. 80-16, Ex. L. (“USP 941”) to Swift Decl.)). And the diffraction pattern of an unknown sample can be compared to other samples or standard reference patterns of known compounds, to identify the sample. (Id. ¶¶ 51 & 57).

B. The '355 Patent

The '355 Patent is entitled “Rifaximin Crystalline Forms and Methods of Preparation Thereof and issued on November 17, 2015. ('355 Patent Face Page). It is generally directed to a “composition comprising mixed crystalline polymorphs rifaximin α and rifaximin β.” ('355 Patent Abstract). The parties only dispute the construction of Claim 1 and Claim 3 in the '355 Patent, which read as follows:

1. A rifaximin composition comprising mixed crystalline polymorphs rifaximin α and rifaximin β containing about 3-12% (w/w) of the rifaximin β crystalline polymorph in mixture with a remaining percentage of the rifaximin α crystalline polymorph and from about 2% to about 5% by weight water relative to the weight of the total composition wherein the aqueous dissolution rates of the α and β forms provide a fast acting portion and a slow acting portion of rifaximin antibiotic.

3. A pharmaceutical composition suitable for treatment of gastrointestinal bacterial infections by oral administration comprising an effective amount of a rifaximin composition of claim 1 and a pharmaceutically acceptable carrier.

('355 Patent at 12:62-13:3 & 13:6-9). The '355 Patent is a part of one patent family with its own distinct patent specification separate from the other three patents in suit.

C. The '915 Patent, '415 Patent, and '257 Patent

The remaining three patents in this case-the '915, '415, and '257 Patents-are part of a second patent family and share a nearly identical patent specification.^[1] The '915, '415, and '257 Patents are each entitled “Polymorphic Mixture of Rifaximin and its Use for the Preparation of Solid Formulations” and were issued on February 11, 2020, August 18, 2020, and March 30, 2021, respectively. Each of these patents discloses a “Rifaximin polymorphic mixture of α/β form” that exists in a specific ratio, namely “in a relative ratio of 85/15±3 and a process for its preparation.” ('915 Patent Abstract; '257 Patent Abstract; '415 Patent Abstract). While the '915 and '257 Patents are directed to rifaximin mixtures and pharmaceutical compositions comprising the same mixtures, the '415 Patent is directed to methods of treatment for administering those rifaximin mixtures and pharmaceutical compositions. (See, e.g., '915 Patent at 10:50-57; '257 Patent at 10:66-11:3; '415 Patent at 10:64-11:9). The claimed polymorphic α/β rifaximin mixture in the '915 Patent is also characterized by X-ray diffraction with certain characteristic 2theta scattering angle values and relative intensity values. (See, e.g., '915 Patent at 10:50-57). The claimed polymorphic α/β rifaximin mixtures in the '415 and '257 Patents are characterized with certain characteristic 2theta scattering angle values only. (See, e.g., '257 Patent at 10:66-11:3; '415 Patent at 10:64-11:9). Claims 1, 2, and 3 of the '915 Patent are at issue and read as follows:

1. A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3, characterized by an X-Ray spectrum with characteristic 2theta values at (relative intensity): 5.32 (11%), 5.78 (19%), 6.50 (27%), 7.24 (45%), 7.82 (61%), 8.80 (100%), 10.50 (59%), 11.02 (35%), 11.58 (32%), 13.08 (20%), 14.42 (26%), 17.32 (48%), 17.68 (93%), 18.58 (79%), 19.52 (61%), 21.04 (52%), 21.60 (30%), and 21.92 (46%).

2. A pharmaceutical composition comprising the polymorphic mixture of Rifaximin of claim 1, and a vehicle, excipient, or formulative ingredient.

3. A tablet, comprising the Rifaximin polymorphic mixture of claim 1 and a film

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