Citations
- 151 F. Supp. 3d 525
Full opinion text
MARKMAN OPINION
SIMANDLE, Chief Judge
Table of Contents
I. INTRODUCTION .. .529
II. BACKGROUND .. .532 ’
A.Factual and Procedural Background ...532
1. Aripiprazole, Generally ... 533
2. The ’615, ’796, and ’760 Patents: Otsu-ka’s Aripiprazole Polymorph Patents ...533
3; The ’350 Patent:: Otsuka’s Asserted Method of Use Patent... 534
4. Otsuka’s Infringement Litigation in this District .. .535
III. CLAIM CONSTRUCTION STANDARD...536
IV. DISCUSSION .. .537
A. “Anhydrous Aripiprazole Crystals B” ...537
B. “mean particle size” ... 543
• 1. Standard for Indefiniteness ... 544
2. The ’615 Patent fails to inform, with reasonable certainty, the meaning of the ■ phrase “mean particle size” ... 546
C. “wherein said low hygroscopicity is defined as a moisture content of [0.40%/0.10%] or less after placing said substance/Crystals for 24 hours in a desiccator maintained at a temperature of 60° C and a humidity level-of 100%” .. .549
D. “aripiprazole drug substance” ... 552
E. “a/the pharmaceutical composition” / “in combination with” .. .553
V. CONCLUSION .. 1557
I. INTRODUCTION
These related -patent infringement actions under the HatchWaxm’an Act, 35 U.S.C. §§ 271, 281, generally concern Plaintiff Otsuka Pharmaceutical Co, Ltd.’s (hereinafter, “Otsuka”) position that Defendants’- submissions' of abbreviated new drug applications (hereinafter,. “ANDAs”) infringe the various patents covering Otsu-ka’s Ability® aripiprazole product, U.S. Patent Nos. 5,006,528 (“the ’528 patent”), 7,053,092 (“the ’092 patent”), 8,017,615 (“the ’615 patent”),' 8,580,796 (“the ’796 patent”), 8,642,600 (“the ’600 patent”), 8,642,760 (“the ’760 patent”), and 8,759,350 (“the, ’350 patent” and collectively, the “patents-in-suit”).
Following Otsuka’s preliminary injunction motion practice,' see Otsuka Pharm. Co., Ltd. v. Torrent Pharm. Ltd., Inc., 99 F.Supp.3d 461 (D.N.J.2015), and the parties’ lengthy period for claims construction discovery (marked by a plethora of discovery disputes and discovery motion practice before this Court), the parties now request that the Court construe the following five claim phrases:
1. “Anhydrous Aripiprazole Crystals B,” as it appears in asserted claims 3, 4, 15, and 16 of the ’615 Patent, claims 1 and 2 of .the ’796 Patent, and claims 4 and 12 of the ’350 Patent;
2. “mean particle size,” as it appears in asserted claims 3, 4, 15, and 16 of the ’615 Patent;
3. “wherein said low hygroscopicity is defined as a moisture content of [0,40%/0.10%] or less after placing said substance/Crystals for 24 hours in a desiccator. maintained at a temperature of 60° C and a humidity level of 100%,” as- it appears in asserted claims 3, 4, 15,- and -16 of the ’615 Patent, claims 1 and 2■ of the ’796 Patent, and claims 1 and 2 of the ’760 Patent;
4. “aripiprazole drug substance,” as it ■appears in asserted claims 1 and 2 of the ’760 Patent; and
5. “a/thé pharmaceutical composition” / “in combination with,” as it appears in asserted claims 1 through 18 of the ’350 Patent.
Otsuka, for its part, largely eschews the need for formal claim construction and submits, in each instance, that the disputed claim phrase should be construed in accordance with its plain and ordinary meaning as understood by a person of ordinary skill in the art. (See, e.g., Otsu-ka’s Opening Claim Constr. Br at 2 (arguing that claim construction proves overall unnecessary, bécausé the disputed phrases have “readily ascertainable and understandable” plain and ordinary meanings).) Defendants argue, by contrast, that the intrinsic record provides a specific definition for each of the disputed phrases, and/or demonstrates that the various claim phrases prove incapable of construction on indefiniteness grounds. (See, e.g., Defs.’ Opening Claim Cpnstr-. Br. at 2-3.)
The Court has had the benefit of extensive briefing, argument and testimony at an all-day Markman hearing. For the rea-
sons that follow, the Court construes the • disputed phrases as follows:
II. BACKGROUND
A. Factual and Procedural Background
As this Court has summarized previously, Otsuka holds New Drug Application (hereinafter, “NDA”) No. 21-436, approved by the Food and Drug Administration (hereinafter, the “FDA”), for aripiprazole tablets, which Otsuka markets for the treatment of certain psychiatric conditions under the trade name Ability®. In''connection with Ability's® listing in the Orange Book, the FDA’s book of drug products approved under the Food, Drug, and Cosmetic Act (hereinafter, the “Orange Book”), 21 U.S.C. § 355(3), Otsuka" identifies, in relevant part, the ’615, the ’796, the ’760, and the ’350 Patents.
1, Aripiprazole, Generally .
Aripiprazole, an older compound with a complex molecular structure, acts as an atypical antipsychotic agent useful for the treatment of schizophrenia, among other central nervous system disorder^.' (See) e.g., Markman Hr’g Tr. at 21:19-22:2, 39:8-12.)
2. The ’615, ’796, and ’760 Patents: Otsuka’s Aripiprazole * ■ Polymorph Patents
The ’615, the ’796, and the ’760 Patents issued on separate dates, but all disclose a “Low Hygroscopic Aripiprazole Drug Substance and Processes for the' Preparation Thereof.” (See, e.g., ’615 Patent at 1:45-52.) In simple terms, these patents claim novel forms of anhydrous aripiprazole that have low hygroscopicity. i
Prior art anhydrous' aripiprazole forms proved “significantly, hygroscopic,” meaning that the forms would readily take on water and convert to a hydrous form if exposed to moisture. (Id at 1:50-57.) As a result, these prior art forms suffered from less bioavailability and dissolubility, bateh-to-batch variability, and a “significantly decreased” shelf-life. (Id. at 1:58-2:13; see also Markman Hr’g Tr. at 33:13-24; 60:22-61:12.)
■ The novel forms disclosed by the ’615, the.’796, and the ’760 Patents claim to have solved these problems, particularly the susceptibility to moisture that plagued pri- or art anhydrous aripiprazole forms. (See, e.g., ’615 Patent at 1:45-52.) The anhydrous aripiprazole forms disclosed by these patents specifically consist of “novel anhydrous aripiprazole crystals” that have “reduced ' hygroscopicity,” rendering them more amenable than prior art formulations to “pharmaceutical processing and formulation,” and eiihancing their overall shelf-life, dissolubility, and bioavailability. (’615 Patent at 2:29-52; see also Markman Hr’g Tr. at' 33:7-34:4.) In other words, these ' aripiprazole-crystals have a decreased tendency to take on water, thereby enhancing the claimed aripiprazole tablets overall efficacy for the treatment of various mood disorders. (See generally Markman Hr’g Tr. at 33:7-34:4.)
The asserted claims of'the ’615, the ’796, and the ’760 Patents, in turn, teach the process for preparing the low hygroscopic aripiprazole (the ’615 Patent), as well as claiming two of-its forms: one’in-a pure crystal form (the ’796 Patent) and the other in a- finalized form (the ’760 Patent). Independent claim's 3 and '4 of the ’615 Patent, for example, disclose: • ’
3. and 4. A pharmaceutical solid oral preparation comprising Anhydrous Ari-piprazole Crystals B having low hygro-scopicity and one or more pharmaceuti-cally acceptable'carriers, wherein said low hygroscopicity is a moisture content of [0.40%/0.10%] or less after placing said Crystals for 24 hours in a desiccator maintained at a temperature of 60°C and a humidity level of Í00%; ’
wherein said crystals
have a powder x-ray diffraction spectrum having characteristic peaks at 20=11.0°, 16.6°, 19.3°, 20.3°, and 22.1°;
.have particular infrared absorption / bands at 2945, 2812, 1678, 1627, 1448, 1377, 1173, 960, and 779 cm-1. on the IR (KBr) spectrum; ,
exhibit an , endothermic peak near about 141.5°C in thermogravimetric/differen-..tial thermal analysis (heating rate 5° C/min); , ■
exhibit an endothermic peak near about 140.7°C in differential scanning calorimetry (heating rate 5°C/min); and
have a mean particle size of 50 |xm or less, wherein said pharmaceutical solid oral preparation has at least one dissolution rate selected from the group consisting 60% or more at pH 4.5 after 30 minutes, 70% or more at pH 4.5 after 60 -minutes, and 55% or more at pH 5.0 after 60 minutes.
(’615 Patent át 44:40-45:22.) The ’796 and ’760 Patents, each of which contain only two claims, then identify a specific low hygroscopic form of “anhydrous aripipra-zole crystals B” and an “aripiprazole drug substance,” both of which have a moisture content below either 0.40% or 0.10% even after being placed in a desiccator maintained at a temperature of 60° C and a humidity level of 100%. (See ’796 Patent at 44:23-32; ’760 Patent at 44:23-32.) Simply put, these forms do not take on water, despite exposure to a high-moisture environment.
3. The ’350 Patent: Otsuka’s Asserted Method of Use Patent
The ’350 Patent, by contrast, generally relates to a method of treating major, depressive disorders through the adjunctive use-of aripiprazole in conjunction with certain serotonin reuptake inhibitors (hereinafter, “SRIs”), and specifically discloses a “Carbostyril Derivatives and Serotonin Reuptake Inhibitors for Treatment of Mood Disorders.” The Patent describes, on its face, “.pharmaceutical compositions” consisting of “carbostyril derivatives ... in combination with serotonin reuptake inhibitors in a pharmaceutically acceptable carrier” for the treatment of “mood disorders such as depression and major depressive disorder.” (’350 Patent at 1:18-24.)
Independent claims 1-3, in turn, teach: a pharmaceutical composition comprising ar-ipiprazole in combination with at least one serotonin reuptake inhibitor selected from citalopram, escitalopram and salts thereof. (See ’350 Patent at 28:64-29:6.) The remaining independent claims 9-llr then describe methods of treating specific mood disorders by administering an “effective amount” of the combination “pharmaceutical composition” disclosed in claims 1-3. (Id. at 29:26-30:20.) ^
4. Otsuka’s Infringement Litigation in this District
Beginning in early January 2014, the generic Defendants involved in these related infringement actions began to filé AN-DAs with the FDA, seeking approval to market generic aripiprazole tablets and/or orally disintegrating aripiprazole tablets, prior to the expiration of the ’615, ’796,- ‘ ’760, ’350 Patents. Each Defendants’ ANDA, however, included a “paragraph iv” certification, advancing their positions that their ANDAs would not infringe any of the valid patents-in-suit, and/or a “section viii” statement, certifying that the applicant would not seek approval for any indications or uses asserted to be covered by the ’350 Patent. See Otsuka, 99 F.Supp.3d at 472-74, 484-85. In other words, each Defendant, and indeed all generic defendants in these related infringement actions, purport to seek approval for a. noninfringing aripiprazole product. See generally id.
Otspka filed infringement actions in this District, alleging that these Defendants proposed generic aripiprazole products will infringe at least one claim of the ’615,-’796, ’760, and/or th'é ’350 patents, among the other patents covering Otsuka’s Abilify® product.
III. CLAIM CONSTRUCTION STANDARD
Claim construction focuses upon the intrinsic evidence, “including the claims themselves, the specification, and the prosecution history of the patent.” Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271, 1276 (Fed.Cir. 2013) (citing Phillips v. AWH Corp., 415 F.3d 1303, 1315-17 (Fed.Cir.2005) (en banc); Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996)). Claim terms,.must, however, ordinarily be “given their plain and- ordinary meanings to one of skill in the art” at the time of the invention “when read in the context of the specification and .prosecution history.” Golden Bridge Tech., Inc. v. Apple Inc., 758 F.3d 1362, 1365 (Fed.Cir.2014) (citing Phillips, 415 F.3d at 1315-17). Nevertheless, the Court of Appeals for the Federal Circuit has routinely stated that ‘“[t]he construction that stays true to the claim language and most naturally aligns with the patent’s description of the invention will be, in the end, the correct construction.’” Shire Dev., LLC v. Watson Pharms., Inc., 746 F.3d 1326, 1330 (Fed. Cir.2014) (quoting Phillips, 415 F.3d at 1316).
IV. DISCUSSION
The parties, as stated 'above, request construction of the following five phrases: (1) “Anhydrous Aripiprazole Crystals B,” (2) “mean particle size,”'(3) “wherein said low hygroscopicity is defined as a moisture content of [0.40%/0.10%] or less after placing said substanee/Crystals for 24 hours in a desiccator maintained at a temperature of 60° C and a humidity level of 100%,” (4) “aripiprazole drug substance,” and (5) “a/ the pharmaceutical composition” / “in combination with.”. The Court will address each claim phrase in turn.
A. “Anhydrous Aripiprazole Crystals B”
The ’615, ’796, and ’760 Patents aim, as stated above, to provide “novel anhydrous aripiprazole crystals,” and specifically to disclose the inventors’ discovery of a reduced-hygroscopic crystal line form of ari-piprazole, “Anhydrous Aripiprazole Crystals B,.” (See, e.g., ’796 Patent at 2:47-48.)
In terms of defining ‘Anhydrous Aripiprazole Crystals B,” the parties advance the following competing constructions:
In other words, Otsuka argues that the specifications should be read in the disjunctive — requiring that the crystalline form of aripiprazole be identified by reference to one or more, but not all, of the analytical tests identified in the specification. (See generally Otsuka’s Opening Claim Constr. Br, at 7-14.) In support of this position, Otsuka, armed with the opinion of its expert, submits that a person of ordinary skill would, in reviewing the Patents, use “judgment and scientific reasoning” to select the “one or two” appropriate techniques to characterize the aripiprazole crystals, rather than resorting to the full panoply of characterization methods. (Ot-suka’s Opening Claim Constr. Br. at 7-14; Otsuka’s Responsive Claim Constr. Br. at 3-11.) Even more, Otsuka claims that defining the term “Anhydrous Aripiprazole Crystals B” by .reference to all analytical techniques would contravene the “cardinal rule” of claim construction, by importing a limitation from the specifications into the claims. (Markman Hr’g Tr, at 62:24-63:7, 118:9-119:23.) As a result, Otsuka submits that “Anhydrous Aripiprazole Crystals B” should be construed as an aripiprazole form marked by “low hygroscopicity,” and identified by one or more of the characterization techniques provided in the specification. (Id. at 119:16-132:12.)
Defendants, by contrast, take the position that the specification must be read in the conjunctive, requiring that all of the enumerated characteristics be present in order to identify the claimed aripiprazole crystal form. (Defs,’ Opening Claim Constr. Br. at 4-10; Defs.’ Responsive Claim Constr. Br. at 3-11.) In support of this construction, Defendants, supported by their own experts, submit that the spec-, ideation .contains an express definition of the novel “Anhydrous Aripiprazole Crystals B,” and therefore contend that their proposed construction rightly incorporates the -specification in its entirety. (See Markman Hr’g Tr. at 158:21-179:20.)
The Court begins by- noting that the parties and their experts all acknowledge that a person of ordinary skill in the art would ordinarily identify a polymorph form through one or more of the illustrative characterization techniques identified in the-specifications, namely, proton nuclear magnetic resonance spectroscopy (hereinafter, “NMR”), x-ray powder diffraction (hereinafter, “XRPD”), infrared spectroscopy (hereinafter, “IR”), thermo-gravimetric/differential thermal analysis (hereinafter, ' “TGA/DTA”), differential scanning calorimetry (hereinafter, “DSC”), and hygroscopicity testing, (See, e.g., Markman Hr’g Tr. at 31:4-16 (testimony of Otsuka’s expert, Dr. Byrn, concerning his practice of selecting “one or two of the best methods”); 84:8-85:16 (testimony of Defendants’ expert, Dr. .Buckton, concerning his view that a scientist would “look at a raft of techniques for a particular material and depending [up]on the complexity ... would [then] decide which would be the appropriate techniques for that material”), 90:2-8 (testimony of Dr. Buckton concerning the ability to identify polymorphs without reference to the “large suite of techniques”); see also Byrn Dec. at ¶¶ 41-46.) Indeed, the parties’ experts and their own submissions plainly reflect the industry practice of selecting the one or two most appropriate characterization methods based upon the nature of . the tested material. (See, e.g., id. at 57:20-58:12.)
Nevertheless, the parties and their experts equally recognize that each analytical technique produces slightly different information relative to the identification of the polymorphic form (gee, e.g., id. at 23:11-13, 31:12-16, 57:20-58:12), and consistently, assert that the appropriate construction of the phrase “Anhydrous Aripiprazole Crys-tais B” flows directly from some portion of the following language in the specifications:
(See ’615 Patent at 9:36-63; ’760 Patent at 9:37-63; ’796 Patent at 9:34-60.)
The ’615, ’796, and ’760 Patents each state, in their introductory sections, that their disclosures define “Anhydrous Aripi-prazole Crystals B” for purposes of the claimed inventions. (See ’615 Patent at 2:32-35 (noting that the ’615 Patent identifies a novel form of aripiprazole defined as “Anhydrous Aripiprazole Crystals B”); ’760 Patent at 2:31-34 (same); ’796 Patent at 2:28-31 (same).) The portion of the specifications relied upon by all parties then state, in clear language and under a heading bearing the title “Characterization of Anhydrous Aripiprazole Crystals B,” that the ‘“Anhydrous Aripiprazole Crystals B’ of the present invention as used herein have the physicochemical properties given in (6)-(12) below.” (See ’615 Patent at 9:36-63; 760 Patent at 9:37-63; 796 Patent at 9:34-60.) Following that disclosure, the specifications delineate six, non-conditional physicochemical properties — or, in simpler terms, characterization techniques — in successively numbered paragraphs.
In that way, these portions of the specifications contain all of the features that signify a special definition of “Anhydrous Aripiprazole Crystals B” that requires all of the specified physicochemical properties (as advanced by Defendants), and not merely one or more (as claimed by Otsu-ka). See AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1051-52 (Fed.Cir.2010) (discussing special definitions revealed by specifications). Indeed, the mandatory language of the specifications, along with them structures, lead to the simple conclusion that the patentee intended to provide the phrase “Anhydrous Aripiprazole Crystals B” with a particular meaning for purposes of the ’615, 796, and 760 Patents. Critically, the specifications not only set off the term “Anhydrous Aripiprazole Crystals B” with quotation marks — a strong indication, by itself, that the disclosures that follow constitute a definition— they also specifically state that the term has a particular meaning in the context of the patents-in-suit. (See, e.g., ’615 Patent at 9:37-38 (“’Anhydrous Aripiprazole Crystals B’ of the present invention as used herein ... ”) (emphasis added); 760 Patent at 9:37-38 (same); 796 Patent at 9:37-38 (same).) See Abbott Labs. v. Andrx Pharms., Inc., 473 F.3d 1196, 1210-11 (Fed.Cir.2007) (explaining that a patentee may expressly define certain claims’ terms through the use of quotation marks and phrases like “as used herein”). Numbered paragraphs (6) through (12) then teach the specific contours of each analytical test, but provide no support for the flexible interpretation proposed by Otsuka. Nor any corresponding indication (like, for example, the inclusion of “or” between each numbered paragraph) that the characterization techniques should be viewed as interchangeable. Rather, these portions of the specification squarely reflect that the novel “Anhydrous Aripiprazole Crystals B” are those identified by each of the characterization techniques.
This construction then finds further support in the remainder of the specifications. The disclosures’ examples, for instance, consistently describe “Anhydrous Aripi-prazole Crystals B” by reference to all of the characterization methods. Indeed, Example 2 provides:
Example 2
450 g of the Aripiprazole Hydrate A (powder) obtained m. Example 1 was dried for'24 hours at 100° C- using a hot air dryer to produce 427 g (yield 98.7%) of Anhydrous Aripipra-zole Crystals B.
'fheso Anhydrous Aripiprazole Crystals H had a melting point (mp) of 139.7° C ' '
The Anhydrous .Aripiprazole Crystals JB obtained above had an ^-NMR spectrum (D>MSO-dfi, TMS) which was sub- . stantially the some as tlxeH-NMR spectrum, shown in FIG. 4. Specifically, they had characteristic peaks at 1.55-1.63 ppm (in, 2i I), 1.68-1.78 ppm (m, 211), 2.35-2.46 ppm (m, 411), 2.48-2.56 ppm, (m, 4H+DMSO), 2,78 ppm (t, -J-7.4 Hz, 2H)S 2.97 ppm (fort, J-4.6 Hz, 4H), 3.92 ppm (t, J-=-6.3 Hz, 2B), 6.43 ppm (d, J-2.4 Hz, HI); 6.49 ppm (dd, J-8.4 Hz, J-2.4 Hz, 11.1), 7.04 ppin