Otsuka Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd.
Otsuka Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd.
Opinion of the Court
MARKMAN OPINION
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”).
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;2 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.
The Court has had the benefit of extensive briefing, argument and testimony at an all-day Markman hearing.
*532 [[Image here]]
II. BACKGROUND
A. Factual and Procedural Background
As this Court has summarized previously, Otsuka holds New Drug Application
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,
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,”
The asserted claims of'the ’615, the ’796, and the ’760 Patents, in turn, teach the
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.”
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
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,
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.”
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,.”
In terms of defining ‘Anhydrous Aripiprazole Crystals B,” the parties advance the following competing constructions:
[[Image here]]
21
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 opin
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.
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
[[Image here]]
(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
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.
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:
*541 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 <d, J-8.1 Liz, .1H ), 7.11 - 7,17 ppm (ra, IH), 7.28-7.32 ppm (m, 2H) and, 10.CK) ppm (s, l tl).
The Anhydrous Aripiprazole Crystals B obtained above had ft powder x-ray diffraction spectrum which was substantially the same as the powder x-ray diffraction, spectrum shown in FIG. 5. Specifically, they had characteristic peaks at 20-i 2.0°, 16.6°, 19.3°, 20.3° and 22.1°. - ■ -
The Anhydrous Aripiprazole Crystals B obtained above had remarkable infrared absorption bands at 2945, 2812, 1678, 1627, 1448, 1377, 11.73, 960 and 779 cm"1 on die IR (KBr) spectrum.
'Hie Anhydrous Aripiprazole Crystals B obtained above exhibited an endothermic peak near about 141.5“ C. in ther-mogravimetric/diilbrential thermal analysis,
"Hus Anhydrous Aripiprazole Crystals B obtained above exhibited an endothermic peak near about 140.7° C. ixt differential scanning calorimetry.
Even when the Anhydrous Aripiprazole Crystals 13 obtained above were fell for 24 hours in a dessicator set at humidity 100%, temperature 60° C., they did not exhibit hygroseopicity exceeding 0.4% (See Table 1 below).
(See, e.g., ’615 Patent at 26:2-37.) In other words, Example 2 describes “Anhydrous Aripiprazole Crystals B” based upon the results of all , of the characterization techniques, namely, NMR, XRPD, IR, TGA/ DTA, DSC, and hygroseopicity. (See, e.g., ’796 Patent at 26:1-28:15.) Dependent Examples 2 through 10 then consistently state that the “hygroscopic anhydrous ari-piprazole crystals” obtained through various methods exhibited “the same ... phy-sicochemical properties of the Anhydrous Aripiprazole Crystals B.” (See, e.g,, ’615 Patent at 26:39-28:16 (emphasis added).) This consistent usage lends itself to only one conclusion,
Moreover, even in the absence of this consistent language, the' Court finds creditable Defendants’ position that Otsuka has, on numerous occasions, admitted that “Anhydrous Aripiprazole Crystals B” should be defined by reference to five analytical techniques, and not the “one dr more” construction it advances here. Indeed, in prosecuting the European equivalent of the ’615, ’796, and the ’760 Patents, EP1330249 (hereinafter, “EP1”), Otsuka repeatedly defined the “Aripiprazole anhydrous form B” disclosed in the EP1 in terms of its “XRD pattern, the IR spectrum, the endothermic peak in thermogra-vimetric/differential thermo analysis, the endothermic peak in DSC and, most importantly, the low hygroscopicity.” (Ex. K to Second Buckton Dec. at 1 (emphasis in original); see also Second Buckton Dec. at ¶¶ 19-22.)
In other words, Otsuka insisted, in connection, with an indisputably familial pat-en^ that the five crystal characterization techniques — XRPD, IR, TGA/DTA, DSC, and low hygroscopicity — together, and not alone, defined “Anhydrous Aripiprazole Crystals B” from other crystal forms.
For all of these reasons, the Court finds that the specification explicitly teaches that the phrase should be construed by reference to all of the analytical tests,
B. ‘mean particle size'
Asserted claim 3 of the ’615 Patent generally discloses, in relevant part, low hygroscopic Anhydrous Aripiprazole Crystals B, where in these Crystals ‘have a mean particle size of 50 p.m or less...‘ (’615 Patent at 44:59 (emphasis added).) With respect to the phrase ‘mean particle size/ the parties advance the following competing constructions:
*544 [[Image here]]
Otsuka argues, in particular, that the intrinsic record make “clear that a person of ordinary skill in the art would readily have understood that ‘mean particle size’ refers to volume mean particle size,” particularly because the claims teach that “mean particle size” should be measured using a “laser diffraction particle size analyzer.” (Otsuka’s Responsive Claim Constr. Br. at 12 (citation omitted).) Defendants, by contrast, take the position that the term proves “indefinite” (or, incapable of construction), because it’s amenable to multiple meanings. (Defs.’ Opening Claim Constr. Br. at 12-15; Defs.’ Responsive Claim Constr. Br. at 11-16.) Defendants specifically argue that the ordinary artisan would, in reviewing the disclosures, confront a number of unresolved issues that “directly affect the output of the particle size analysis,” particularly given the array of possible interpretations for the terms “‘means’ .and ‘sizes.’”
’ The parties’ construction positions hinge upon issues of indefmiteness, an area of law that has undergone fundamental changes following Nautilus, Inc. v. Biosig Instruments, Inc., — U.S. -, 134 S.Ct. 2120, 189 L.Ed.2d 37 (2014), which is next addressed.
1. Standard for Indefiniteness
“A patent must ’conclude with one ór more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as [the] invention.’” Media Rights Techs., Inc. v. Capital One Fin. Corp., 800 F.3d 1366, 1371 (Fed.Cir. 2015) (citing 35 U.S.C. § 112). A claim fails to satisfy this statutory requirement and proves “invalid for indefiniteness if its
A claim may, for example, prove indefinite if its language “might mean-several different things” and the patent itself identifies “no informed and confident choice ... among the contending definitions.” Nautilus, — U.S. -, 135 S.Ct. at 2130 n.8. Stated differently, in order to overcome an indefiniteness challenge, “the patent and prosecution history must disclose a single known approach or establish that, where multiple known approaches exist, a person having ordinary skill in the art would know which approach to select.”
In Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., 789 F.3d 1335 (Fed.Cir. 2015), the Federal Circuit applied the legal standards set forth in Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., — U.S. -, 135 S.Ct. 831, — L.Ed.2d - (2015) and Nautilus, Inc. v. Biosig Instruments, Inc. — U.S. -, 134 S.Ct. 2120, 2124, 189 L.Ed.2d 37 (2014), in order to resolve the question of indefiniteness- regarding a claim- limitation of U.S. Patent No. 5,800, 808 (the “’808 patent”) — “molecular weight of about 5 to 9 kilodaltons.” 789 F.3d at 1338. The Teva parties agreed that “molecular weight” could refer to peak average molecular weight (Mp), number average molecular weight (Mn), and weight average molecular weight (Mw), and that each of those measures required a different calculation and would typically yield “a different result for -a given polymer sample.” Id. at 1338. The ’808 patent specification, however, did not expressly define “molecular weight,” nor did it use the terms Mp, M„, or Mw. Id. Even more, the prosecution history contained inconsistent statements, with the patentee stating in one instance that “molecular weight” referred to Mw, and in another than it meant Mp. Id. at 1345. As a result, the -Teva court found the term indefinite, despite testimony from the patentee’s expert that someone skilled in the art could, despite any ambiguity, have determined the intended measure. Id. at 1338, 1341, 1344-45.
Most recently, in Dow Chemical Co. v. Nova Chemicals Corp. (Canada), 803 F.3d 620 (Fed.Cir. 2015), the Federal Circuit again applied the recent Supreme Court decisions (as well as its own decision in
2. The ’615 Patent fails to inform, with reasonable certainty, the meaning of the phrase “mean particle size”
In applying this standard here, the Court finds that the facts of Teva and Dow closely resemble the claim limitation at issue here — “mean particle size,” - Indeed, even a cursory inspection of the intrinsic record demonstrates that the ’615 Patent fails to provide the required guidance.
Indeed, Otsuka readily acknowledges the susceptibility of “mean particle size” to multiple measurements, each' of which could yield varied results. (See Otsuka’s Opening Claim Constr. Br. at 16-17; Otsu-ka’s Responsive Claim Constr. Br. at 12-18.) Nevertheless, Otsuka submits that the ’615 Patent, when viewed through the eyes of the person of ordinary skill in the art, reveals-that “mean particle size” -refers to “volume mean particle size.” (Otsu-ka’s Opening Claim Constr. Br. at 16.) In support of this position, Otsuka points to a narrow portion of the specification that identifies a laser diffraction particle size analyzer,
The Court notes that only the asserted dependent claims of the ’615 Patent, claims 15 and 16, limit particle size measurement to the laser diffraction technique. (See id. at 44:40-45:22.) The specification, however,
Nevertheless, it remains undisputed that' the laser diffraction measurement technique generates two “mean” measures: a volume weighted mean and a surface area weighted mean. (See, e.g., Second Buckton Dec. at ¶¶ 30-34, 40-41; Byrn Dep. at 200-01; Markman Hr’g Tr. at 76:19-22.) Despite these alternate measures, the parties’ experts appear to agree, at least superficially, that the volume weighted mean constitutes one of the more frequently used measures for particle size analysis. (See, . e.g., Markman Hr’g Tr. at 77:9-12; Byrn Dec. at ¶ 58 (arguing- that secondary sources reflect the understanding a. person of ordinary skill in the art would have had at the time of filing that “mean particle size” refers to the volume mean particle size).) A closer inspection of their various submissions, however, reveals the lack of uniform understanding in the relevant scientific community. -
Specifically, Otsuka’s expert, Dr. Byrn, states in his declaration that “volume mean particle size” constitutes the default meaning of “mean particle size” to one of ordinary skill. (See Byrn Dec. at ¶¶.55-58; but see Byrn Dep. at 200:5-209 (discussing d(0.5) or the median distribution).) In reviewing a typical laser diffraction results analysis report during his deposition, however, Dr. Byrn took the position that “mean particle size” refers to the median volume distribution, or d(0.5), not the “volume weighted mean” or the “surface weighted mean,” and that such approach comported with the ordinary understanding. (Byrn Dep. at 200:5-209) Defendants’ expert, Dr. Buckton, then testified that the “median is the most frequently used” measurement for particle size analysis (Markman Hr’g Tr. at 77:9-12 (emphasis added)), but acknowledges that “the volume-weighted mean” serves as the “the most frequently” presented mean. (Buck-ton Dep. at 424:4-9; see also Second Buck-ton Dec. at ¶39 (stating that volume weighted mean “is the most frequently used mean value, in [his] experience”).)
Even more, the ’615 Patent makes nó connection between “mean particle size” and volumetric measures (although it speaks in terms of volume in unrelated contexts), and therefore provides no information from which to divine, with reasonable certainty, the appropriate measure of the “mean” for purposes of the ’615 Patent. (See generally ’615 Patent at 19:38-40.) ‘
Nor does the ’615 Patent instruct on the manner in which to- characterize the “size” of the particle (see generally ’615 Patent at 22:51-55), which can be defined by reference to any one of the following measures:
*548 [[Image here]]
(Ex. S to Second Buckton Dec.)
In order to fill these gaps in the intrinsic record, Otsuka resorts entirely to the opinion of its own expert, Dr. Byrn. (See generally Byrn Dec. at ¶ 58; see also Otsuka’s Responsive Claim Constr. Br. at 13 (arguing that “[n]one of Defendants’ allegations prove Dr. Byrn wrong”).) Nevertheless “a claim term is indefinite if it ’leave[s] the skilled artisan to consult the ’unpredictable vagaries of any one person’s opinion,”’ Dow Chem. Co., 803 F.3d at 635 (quoting Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1371 (Fed.Cir. 2014)), and Otsu-ka’s reliance upon Dr. Byrn requires just that.
In this case, the wording of the claim term “mean” and specification may be construed as designating an instrument by which to conduct a measurement of “mean particle size,” but nothing therein guides the skilled practitioner whether to utilize the “volume weighted mean” or the “surface weighted mean” that such a device reports as measurements. The choice of “volume” or “surface” matters because each type lends to a different result. Looking then to extrinsic evidence, Otsuka has not demonstrated that “volume weighted mean” is the default measurement that the ordinary skilled practitioner would select, given the clear absence of a convergence upon that convention in the field; this is the hallmark of an indefinite term. Similarly, as discussed above, the words “particle size” are likewise indefinite, as there are multiple accepted aspects of “size,” each
For these reasons, the Court finds the term “mean particle size” indefinite. See Teva Pharms. USA, Inc., 789 F.3d at 1344— 45 (finding the term “molecular weight” indefinite); Dow Chemical Co., 803 F.3d at 634-35 (finding the claim term including the phrase “slope of strain” indefinite).
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 á desiccator maintained at a temperature of 60 °C and a humidity level of 100%”
Exemplar claims 3 and 4 of the ’615 Patent disclose “A pharmaceutical solid oral preparation comprising Anhydrous Aripiprazole Crystals B having low hygro-scopicity and one or. more pharmaceutically 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 100%.. .”
*550 [[Image here]]
42 ,43
Otsuka and Defendants (other than Teva, Prinston, Zydus, Aurobindo, and Arnneal) substantively agree that a person of ordinary skill in the art would, look to the specification of the ’615, the ’796, and the ’760 Patents, in order to. guide their understanding of the disputed claim phrase. (See, e.g., Otsuka’s Opening Claim Constr. Br. at 18-19; Otsuka’s Responsive Claim Constr. Br. at 19-20; Defs.’ Responsive Claim Constr. Br. at 17; Markman Hr’g Tr. at 63:18-22.) These parties rely, in particular upon the following portion of the specifications:
(7) Hygroscopicity-Test Method
One g of the sample was accurately weighed in a weighing bottle (diameter 5 cm), covered with kimwipes and left to rest in a 60 °C/100% RH environment (water/dessicator). 24 hours later, the weighing bottle was removed, transferred to an environment of a room temperature and about 30% RH (magnesium chloride hexahydrate saturated water solution/dessicator) and left to rest for 24 hours and the water content of the sample was measured by the Karl Fischer method.
(See ’615 Patent at 22:56-64 (emphasis added); ’796 Patent at 22:59-67; ’760 Patent at 22:56-64.) ,
More specifically, these parties agree that because the disputed claim phrase defines the novelty of reduced hygroscop-icity, it necessarily incorporates the “Hy-groscopicity-Test Method” described by the specification. These parties diverge, however, on whether the specification should be read to account for ‘“reasonable variations’ in the ‘Hygroscopicity-Test Method’” (as argued by Otsuka), or whether the specification should be read as the strict definition of the disclosed test method (as argued by Defendants).
The asserted claims and the specification closely track in language, as reflected in the following illustration:
[[Image here]]
Given the substantive. similarities, the Court finds that a person of ordinary skill in the art would recognize that the claim language itself contains both a definition of “low hygroscopicity” and an unmistakable reference to the “Hygroscopicity Test Method” in the specification.
For that reason, the Court will adopt Defendants construction.
• The phrase “aripiprazole drug substance” appears in asserted claims 1 and 2 of the ’760 Patent, a Patent that discloses, on its face, “an improved form of aripipra-zole having reduced hygroscopicity.” (’760 Patent at 1:21-23 (emphasis added).) In other words, the ’760 Patent teaches a tablet.
The asserted claims, in turn, describe an “Aripiprazole drug substance of low hygro-scopicity 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 100%.” (Id. at44:23-32.)
With respect to this claim term, the parties advance the following competing constructions:
[[Image here]]
The parties’ dispute on this claim .term turns, in essence, upon whether “aripipra-zole drug substance” refers only to the aripiprazole compound, aripiprazole in its finalized formulation, and/or aripiprazole in either capacity.
Nevertheless, the Court finds that “ari-piprazole drug substance” requires no elaborate interpretation. Indeed, claims 1 and 2 of the ’760 Patent identify the claimed invention as “Aripiprazole drug substance of low -hygroscopicity 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 100%.” (’760 Patent at 44:23-32.) In that way, the language makes clear that the “Aripiprazole drug' substance” claimed in the ’760 Patent broadly describes aripiprazole as the active ingredient of the finalized formulation.
E. “a/the pharmaceutical composition” / “in combination with”
In its TRO Opinion, the Court addressed, at great length, the appropriate construction of the phrase “pharmaceutical composition,” as recited in the asserted claims of the ’350 Patent. See Otsuka, '99 F.Supp.3d at 477-83. In connection with the pending Markman submissions, Otsu-ka, in essence, requests that the Court revisit its “preliminary” TRO construction, but largely reiterates positions this Court previously rejected, and again ignores the explicit teachings of its own specification.
The Court finds no reason to depart from its preliminary, but otherwise comprehensive, construction, and again concludes that the disputed phrase requires no elaborate construction.
Indeed, the claims of the ’350 Patent contain identical terms, all of which support this Court’s prior construction, as illustrated below:
*554 [[Image here]]
(’350 Patent at 28:64-30:48.)
The overall structure of the ’350 Patent, throughout its Various sequential components, then consistently and repeatedly teaches that the claimed invention concerns a single dosage form, comprised of two active ingredients.
Indeed, the ’350 patent describes the invention at the outset in its abstract as a “pharmaceutical composition” comprised,of “(1) a carbostyril derivative,” either “aripi-prazole or a metabolite,” together with “(2) a- serotonin reuptake inhibitor,” e.g., citalo-pram- and/or escitalopram, “in a - [single] pharmaceutically acceptable carrier.” (See ■ ’350 Patent at Abstract (emphasis added).) In the disclosure of the invention, the ’350 patent then-reiterates that the claimed invention consists -of at least two ingredients “in a pharmaceutically acceptable carrier.” (Id. at 2:66-6:17:)'.
Identical' disclosures appear in the Detailed'Description, which‘describes in detail the “first” and “sécónd” ingredients, “contained,” “combined,”- or “mixed” in the single “pharmaceutical composition.” (See, e.g„ id. at 6:47-55, 10:52-57, 11:47-48 (“Combination of the First Ingredient with the Second. Ingredient”), 13:56-62' (“the amounts of the first ingredient and the second ingredient to.be contained in the pharmaceutical composition of the present invention...”), and 20:27-41 (describing aripiprazole in a combined administration with citalopram and/or escitalopram).) Indeed, the introduction of: the Detailed Description states that, “[t]he,pharmaceutical composition of the present invention comprises a first ingredient..comprising a car-bostyil derivative active as a. dopamine-serotonin system stabilizer and a second ingredient comprising ■ a serotonin reup-take inhibitor, in a pharmaceutically ..acceptable carrier.” (id. at .6:47-51 (emphasis added).) In that regard, the syntax of the introduction alone indicates that the single “pharmaceutically acceptable carrier’,’- describes and limits the- preceding composition to a carrier, or dosage, comprised, of two ingredients. Even, more, however, the Detailed Description contains the following illustrative subheadings: “The Pharmaceutical Composition: The First Ingredient,”
The eighteen “non-limiting formulation examples of (aripiprazole” then uniformly disclose formulations for “the [claimed] tablet” that contain multiple active pharmaceutical ingredients, namely aripipra-zole combined with at least one SRI, together in a single “tablet.” (Id. at-20:46-25:17 (emphases added); see-also 11:54-58 (setting forth a non-exhaustive list of the relevant SRIs).)
Otsuka does not genuinely dispute the volume and pervasiveness of these consistent intrinsic references to a composition in a single dosage form.
The amount of intrinsic evidencé that consistently discloses a single' dosage form can hardly be described as anything less than substantial, and the Court again finds no support for Otsuka’s position that- the “pharmaceutical composition” identified by the ’350 Patent should be construed to teach that aripiprazole and the at least one SRI (namely, escitalopram and/or eitalo-pram) may be presented in separate and/or multiple dosage forms. For all of these reasons, the Court construes the phrase to refer to a single dosage form, or “pharmaceutical composition,” containing at least two active ingredients: aripiprazole and at least one of citalopram,' eseitalo-pram and salt thereof.
y. CONCLUSION
An accompanying Order will be entered.
. For example, on September 25, 2015, this Court granted in part and denied in part Otsuka’s motions to strike certain portions of Defendants’ responsive Markman expert declarations, See Otsuka Pharm. Co., Ltd. v. Torrent Pharms. Ltd., Inc,, 133 F.Supp.3d 721, 2015 WL 5665771 (D.N.J. Sept. 25, 2015), and then separately denied Defendants Apotex Corp.’s and Apotex Inc.’s motion for a protective order barring any additional deposition‘of Graham. Buckton, Ph.D. (hereinafter, "Dr. Buckton” or "Dr. Graham Buckton”), See Otsuka Pharm. Co., Ltd. v. Apotex Corp., 310 F.R.D. 256 (D.N.J. 2015).
. Defendants initially requested time to argue the phrase "aripiprazole drug substance” during the Markman hearing. Nevertheless, by letter dated October 16, 2015, the majority of Defendants withdrew their request to present any argument on the term, and instead rested upon their papers. [See, e.g., Docket Item 160 in Civil Action No. 14-1078.]
. Actavis Staked out and briefed claims construction positions on "Anhydrous Aripipra-zole Crystals B” and “aripiprazole drug substance” separately from the remaining generic Defendants. (See generally Actavis’s Opening Claim .Constr. Br.) Nevertheless, because Otsuka voluntarily dismissed its claims against Actavis on November 10, 2015, the Court need not reach the .merits of Actavis’s claims construction positions.
. The Court conducted a Markman hearing on October 19, 2015, at which time the Court received a technical tutorial from Otsuka’s experts, Stephen R. Byrn, Ph.D (hereinafter, "Dr. Byrn”) and Christoph U. Correll, M.D,
. The record amassed by the parties in connection with the pending Markman submissions spans thousands of pages and includes lengthy declarations from Otsuka’s two experts, Dr. Byrn and Dr. Correll,. and Defendants’ four experts, Dr. Graham Buckton, Dr. Rogers, Anthony Palmieri III, Ph.D, R.Ph (hereinafter, "Dr. Palmieri”), and Dr. Halper. Defendants initially a 1 so relied upon Robert J. Orr, Ph. D (hereinafter, ' Dr. Orr') in support of their construction positions relative to the phrase 'aripiprazole drug substance. ' Nevertheless, by letter dated October 16, 2015, Defendants withdrew their reliance upon Dr. Orr’s opening and responsive declarations (and opted, as stated above, to rest upon their written submissions on this term). [See, e.g,, Docket Item 160 in Civil Action No. 14-1078.] As a result, Dr. Orr did not appear at t he Markman hearing, and the Court disregards, as it must, any arguments that rested upon his opinions.
. For purposes of the pending Markman submissions, the Court need not retrace the detailed factual and procedural history of these complex infringement actions, and writes primarily for the parties.
. Otsuka’s Orange Book listing also identifies the ’528 Patent, the primary aripiprazole compound patent, as well' the ’600 Patent, which claims certain methods of treatment in connection with the administration of aripi-prazole.
. The ’615 Patent issued on September 13, 2011, the ’796 Patent issued on November 12, 2013, and the ’760 Patent issued on February 4, 2014.
. As acknowledged by the parties, the ’615,-’796, and ’760 Patents share a common specification; and for that reason, the Court only cites to one illustrative specification, unless otherwise indicated.
. As' explained by Dr.' Byrn and Dr. Rogers, hygroscopicity specifically refers to the tendency of a material to absorb water, and includes both adsorption (where the water molecules interact with, but do not penetrate the crystal surface) and absorption (where the water molecules actually penetrate into the crystals). (See, é.g. Markman Hr’g Tr. at 24:11-13, 39:15-21.)
. Claims 3 and 4 of the ’615 Patent differ only in specific moisture content, with claim 3 teaching 0.40% or legs, while claim 4 teaches 0.10% or less. (Compare ’61.5 Patent at 44:43-46 (claim 3), with ’,615 Patent at 45:1-4 (claim 4).)
. The '350 Patent issued on June 24, 2014, and therefore serves as the most.recent of Otsuka’s asserted follow-on patents.
. The remaining claims of the ’350" Patent, namely claims 4 through 8 arid 12' through 18, all depend upon independent claims 1 through 3 and 9 through 11.
. Otsuka filed the first infringement' action in this large series of actions on February 18, 2014, see Otsuka Pharm. Co., Ltd, v. Torrent Pharm., Inc., Civil Action No. 14-1078 (JBS/KMW), followed shortly thereafter by a cascade of thirty related actions: Otsuka Pharm. Co., Ltd. v. Alembic Global Holding SA, Civil Action No. 14-2982 (JBS/KMW), 2014 WL 2050687 (filed May 9, 2014); Otsuka Pharm. Co., Ltd. v. Zydus Pham. USA Inc., Civil Action No. 14-3168 (JBS/KMW), 2014 WL 2192878 (filed May 16, 2014); Otsuka Pharm. Co., Ltd. v. Aurobindo Pharma Ltd., Civil Action No. 14-3306, (JBS/KMW), 2014 WL 4683649 (filed May 23, 2014); Otsuka Pharm. Co., Ltd, v. Intas Pharm. Ltd., Civil Action No. 14-3996 (JBS/KMW), 2014 WL 4683656 (filed June 20, 2014); Otsuka Pharm. Co., Ltd. v. Zydus Pham. USA Inc., Civil Action No. 14-3168 (JBS/KMW), 2014 WL 2192878 (filed May 16, 2014); Otsuka Pharm. Co., Ltd. v. Sun Pharm. Indus., Ltd., Civil Action No. 14-4307 (JBS/KMW), 2014 WL 4682315 (filed July 7, 2014); Otsuka Pharm. Co., Ltd. v. Mylan Inc., Civil Action No. 14-4508 (JBS/KMW), 2014 WL 4682279 (filed July 11, 2014); Otsuka Pharm. Co., Ltd. v. Torrent Pharm., Inc., Civil Action No. 14-4671 (JBS/KMW), 2015 WL 5950091 (filed July 25, 2014); Otsuka Pharm. Co., Ltd. v. Zhejiang Huahai Pharm. Co., Civil Action No. 14-5537 (JBS/KMW), 2014 WL 4682310 (filed September 4, 2014); Otsuka Pharm. Co., Ltd. v. Ajanta Pharm. Ltd., Civil Action No. 14-5876 (JBS/KMW), 2014 WL 4913223 (filed September 19, 2014); Otsuka Pharm. Co., Ltd. v. Teva Pharm. USA, Inc., Civil Action No. 14-5878 (JBS/KMW), 2014 WL 4913290 (filed September 19, 2014); Otsuka Pharm. Co., Ltd. v. Intas Pharm. Ltd., Civil Action No. 14-6158 (JBS/KMW), 2014 WL 5241794 (filed October 2, 2014); Otsuka Pharm. Co., Ltd. v. Sun Pharm. Indus., Ltd., Civil Action No. 14-6397 (JBS/KMW), 2014 WL 5241803 (filed October 6, 2014); Otsuka Pharm. Co., Ltd. v. Teva Pharm. USA, Inc., Civil Action No. 14-6398 (JBS/KMW) (filed September 19, 2014) (filed October 10, 2014); Otsuka Pharm. Co., Ltd. v. Aurobindo Pharma Ltd., Civil Action No. 14-6890 (JBS/KMW) (filed October 31, 2014); Otsuka Pharm. Co., Ltd. v. Lupin Ltd., Civil Action No. 14-7105 (JBS/KMW) (filed November 3, 2014); Otsuka Pharm. Co., Ltd. v. Actavis Elizabeth LLC, Civil Action No. 14-7106 (JBS/KMW) (filed November 10, 2014; voluntarily dismissed November 12, 2015); Otsuka Pharm. Co., Ltd. v. Zydus Pham. USA Inc., Civil Action No. 14-7252 (JBS/KMW) (filed November 20, 2014); Otsuka Pharm. Co., Ltd. v. Alembic Pharm., Ltd., Civil Action No. 14-7405 (JBS/KMW) (filed November 26, 2014); Otsuka Pharm. Co., Ltd. v. Apotex Corp., Civil Action No. 14-8074 (JBS/KMW) (filed December 24, 2015); Otsuka Pharm. Co., Ltd. v. Hetero Drugs, Ltd., Civil Action No. 15-161 • (JBS/KMW) (filed January 8; 2015); Otsuka Pharm. Co., Ltd, v. Amneal Pharm. Co., Ltd., Civil Action No. 15-1585 '(JBS/KMW) (filed March 2, 2015); Otsuka Pharm. Co., Ltd, v. Sandoz Inc., Civil Action No. 15-1716 (JBS/KMW) (filed March 9, 2015; voluntarily dismissed on November 4, 2015); Otsuka Pharm. Co,, Ltd, v. Indoco Remedies Ltd., Civil Action No. 15-1967 (JBS/KMW) (filed March 17, 2015; stayed and administratively terminated on September 15, 2015); Otsuka Pharm. Co., Ltd. v. Macleods Pharms. Ltd., Civil Action No. 15-5109 (JBS/KMW) (filed July 2, 2015); Otsuka Pharm. Co., Ltd. v. Standard Chem. & Pharm. Co., Civil Action No. 15-6353 (JBS/KMW) (filed August 21, 2015); Otsuka Pharm. Co., Ltd. v. Aurobindo Pharma Ltd., Civil Action No. 15-7584 (JBS/KMW) (filed October 19, 2015); Otsuka Pham Co., Ltd. v. Zydus Pharm. USA Inc., Civil Action No. 15-7802 (JBS/KMW) (filed October 30, 2015); and Otsuka Pharm Co., Ltd. v. Amneal Pharm. LLC, Civil Action No. 15-7803 (JBS/KMW) (filed October 30, 2015).
. As the lengthy exclusivity period of the patent covering the primary aripiprazole compound came to a close, Otsuka moved to enjoin the defendants from launching competing generic aripiprazole products, on the . grounds that the package inserts or labels for the proposed generic products in all of the related infringement actions would induce infringement of claim 1 of the ’350 Patent. See generally Otsuka Pharm. Co., Ltd., 99 F.Supp.3d at 470-72 (hereinafter, the "TRO Opinion”). Otsuka moved to amend its Complaints in order to assert the ’350 Patent, for the first time, against Zydus, Torrent, and Teva. See id. On April 16, 2015, the Court granted Otsuka’s motions to amend, principally in light of the liberal standard for amendment under Federal Rule of Civil Procedure 15(a). See id. at *471-75; see also Otsuka Pharm. Co. v. Zydus Pharm. USA, No. 14-3168, 151 F.Supp.3d 515, 529-30, 2015 WL 5950091, at *1 (D.N.J. Oct. 13, 2015).
. Otsuka has, in some instances, asserted different combinations of the patents-in-suit against a particular generic Defendant, .based upon the nature of its proposed ANDA product. The slight differences in the patents asserted in, each action, however, have no impact on the pending is.sue of claims construction.
. The construction of claim terms constitutes a question of law, Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed.Cir, 1995), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996), and the Court need not follow the parties’ proposed constructions. See Marine Polymer Techs., Inc. v. HemCon, Inc., 672 F.3d 1350, 1359 n. 4 (Fed.Cir. 2012) (en banc).
. If, however, the intrinsic evidence fails to disclose the meaning of a term, the Court may examine extrinsic evidence to determine the meaning of particular terminology to those of skill in the art of the invention. Phillips, 415 F.3d at 1318. The Court of Appeals for the Federal Circuit, however,, cautions against "heavy reliance” upon extrinsic sources divorced from the-intrinsic evidence because it "risks transforming the meaning of the claim term to the artisan into the meaning of the term in the abstract,” and out of the context of the specification. Id. at 1321.
. As stated above, this disputed phrase 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 o f the ’350 Patent
. The '615, '796, and '760 Patent s also disclose 'Anhydrous Aripiprazole Crystals C t o G.‘ (See, e,g„ '615 Patent at 11:3-18:53.) The asserted claims of the '615, '796, and '760 Patents do not, however, recite these alternative crystal line forms.
The Court finds Otsuka’s proposed construction fatally flawed, at the out set, to the extent it attempts to construe the phrase by reference to the exact phrase requiring construction. Such a proposal amounts, at least in part, to no proposed construction at all. Moreover, Otsuka’s reliance upon a “plain and ordinary meaning” is belied by the fact that these patents purport to disclose, for the first time, the novel crystalline form "Anhydrous Aripiprazole Crystals B.” This highly technical term has no plain and ordinary
. Otsuka quibbles with Defendants' construction on the ground that the construction, in- essence, editorializes the specification by , referencing the ánalytical tests by name only, and omitting the specific metrics recited in the specification. (See Markman Hr’g Tr. at 124:12-125:3.) Otsuka’s argument, however, ignores the fact that Defendants' proposed construction plainly incorporates the specification in its entirety by reference. (See,' e.g., Defs.’ Opening Claim Constr. Br. at 4.) For that reason, the Court finds this narrow challenge without merit.
. Although “Anhydrous Aripiprazole Crystals B” 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, no party argues that the claims language itself provides a basis from which to divine the meaning of the disputed term. For that reason, the Court turns, as it must, to the specifications. See Phillips, 415 F.3d at 1315 (citations omitted) (reaffirming the “long emphasized” and often '"disposi-tive”’ importance of the specification in claim construction); see also Safety Rail Source, LLC v. Bilco Co., 656 F.Supp.2d 468, 475 (D.N.J. 2009) (citation omitted) (“the Court must consult the specification in order to determine whether it 'expressly defines terms used in the claims or ... [whether] it defines terms by implication’”);
. The Court finds Otsuka’s reliance upon Aventis Pharms. Inc. v. Impax Labs., Inc., No. 02-1322, 2011 WL 94188, at *3 (D.N.J. Jan. 11, 2011) unconvincing. In Aventis, the court considered whether the following phrase "As used herein, the term 'suitable antiadherent’ includes stearic acid, cetyl alcohol ... and the like" provided a special definition of "suitable antiadherent.” Id. at *3. In rejecting quotation marks and the phrase "as used herein” as an indication of a definition, the Aventis court relied upon the fact that the accompanying sentence contained an array of nonex-haustive "examples” for the disputed term, rather than a clear definition. Id. at *3-*4. The disclosures relative to "Anhydrous Aripi-prazole Crystals B,” by contrast, contain strong definitional language,
. Otsuka’s proposal of a- construction that incorporates "one or more” of the "features" identified in the specifications, by contrast, finds no relevant support in the specification. (See Otsuka’s Opening Claim Constr. Br. at 8; Otsuka’s Responsive Claim Constr. Br. at 3.) Indeed, although the '615, '796, and the '760 -Patents use the phrase “one or more" on 18 separate instances, none appear in relation to the properties of "Anhydrous Aripiprazole
.During the Markman hearing, counsel for Otsuka relied upon select'figures añd alternative embodiments, each of’ which rely upon only two analytical techniques. (See Markman Hr'g Tr. at 127:21-129:17; see also '615 Patent at 6:49-59, 7:9-18.) The Court of Appeals for the Federal Circuit, however, discourages constructions predicated upon figures and alternative embodiments, see Computer Docking Station Corp. v. Dell, Inc., 519 F.3d 1366, 1374 (Fed.Cir. 2008), and the embodiments cited by Otsuka refer only to an “aripiprazole drug substance,” not "Anhydrous Aripipra-zole Crystals B.” For these, reasons, the Court finds that these references have limited relevance to the construction of "Anhydrous Ari-piprazole Crystals B.”
. NMR does not, as stated above, identify crystalline forms. As a result, it comes as little surprise that asserted claims 3 and 4 of the '615 Patent identify the "Anhydrous Aripi-prazole Crystals B” only by reference to XRPD, IR, TGA/DTA, DSC, and low hygro-scopicity. Nevertheless, because it does not limit claim scope, the Court will include NMR in its construction of this disputed term.
. As this Court recently explained, "[t]he Court of Appeals for the Federal Circuit 'cau-tioiis against indiscriminate reliance on the prosecution of corresponding foreign applications in the claim construction analysis,' particularly if the statements made during the foreign prosecution arose in response to unique aspects of foreign patent law.” Baxter, 133 F.Supp.3d at 703, 2015 WL 5646779, at *9 (citations omitted). "Nevertheless, the Federal Circuit has routinely approved reliance upon statements in foreign prosecutions . where they constituted 'blatant admissions' directed at the relevant art, and where the statements proved otherwise 'consistent with
. The Court finds Otsuka’s reliance upon Dr. Buckton’s prior publications and the unrelated aripiprazole patents of Sandoz AG, Hetero Drugs Limited, and Teva Pharmaceutical Industries Ltd. unconvincing. (See Markman Hr’g Tr. at 129:24-132:12.) These extrinsic sources, consisting of non-familial patents and publications on unrelated compounds, .[¡provide further confirmation for the undisputed industry practice in characterizing crystal polymorphs, but do little to inform the special definition analysis in this instance. See Apple Inc. v. Motorola, Inc., 757 F.3d 1286, 1312 (Fed.Cir. 2014) (stating that unrelated patents have no relevance to claim construction), reversed in part on other grounds, William v. Citrix Online, LLC, 792 F.3d 1339 (Fed.Cir. 2015) (en banc).
. Finally, because Otsuka asserts that the term ‘Anhydrous Aripiprazole Crystals B’ should be construed similarly across the ’615 and the ’796 Patents, the Court finds no support for the position that Defendants' proposed construction improperly cross-incorporates limitations between these patents. Nor does' the Court find that the narrower - scope of claims 3 and 4 of the ’615 Patent require adoption of Otsuka’s construction. Rather, these claims further limit ‘Anhydrous Aripiprazole Crystals B‘ for purposes of claims 3 and 4, but do not otherwise restrict the meaning of the term in relation to t he overall Patents. '•
. As stated above, this disputed phrase appears in asserted claims 3, 4, 15, and 16 of the ’615 Patent,
. Otsuka’s proposed construction has, as explained below, changed overtime.
. Because all parties substantively agree that the phrase "mean particle size” has multiple meanings, the Court rejects at the outset Ot-suka’s position that the phrase has any "plain” meaning, and therefore requires no construction. (See, e.g., Otsuka’s Opening Claim Constr. Br. at 18.)
.Defendants further claim that Otsuka’s "many conflicting constructions,” namely, "plain and ordinary meaning,” "analogous to mean equivalent spherical volume diameter by laser light diffraction scattering,” "volume mean particle size,” and "volume weighted mean,” prove indefiniteness. (See Markman Hr’gTr. at 180:17-185:5.)
. In articulating this standard, Nautilus fundamentally "changed the law of indefiniteness.” Dow Chem. Co., 803 F.3d at 630.
. For that reason alone, the Court rejects Otsuka's position that "mean particle size” should be found definite, simply because "other courts have readily construed the term mean particle size.’” (Otsuka’s Opening Claim Constr. Br. at 15 (citing Eli Lilly & Co. v. Teva Pharm. USA, Inc., No. 06-1017, 2008 WL 2410420, at *1 (S.D.Ind. June 11, 2008).) In reality, Otsuka cites to only one case that construed the term, prior to the Supreme Court’s articulation of a new indefiniteness test under Nautilus, and where neither party actually advanced an indefiniteness argument. See Eli Lilly & Co., 2008 WL 2410420, at *4-*5. Beyond these clearly distinguishing features, the indefiniteness inquiry focuses upon whether the relevant patent record discloses a single meaning among multiple possibilities, not whether an unrelated patent contained such disclosures. See Nautilus, Inc., — U.S. -, 134 S.Ct. at 2124 (describing the standard for indefiniteness).
. The cited portion of the specification reads:
(6) Particle Size Measurement
O.lg of the particles to be measured were suspended in a 20 ml n-hexane solution of 0.5g soy lecithin,. and particle size was measured' using a size distribution meter (Microtrack HRA, Microtraclc Co.),
('615 Patent at 22:51-55.)
. As referenced above, Otsuka’s proposed construction of "mean-particle size” has been a moving target, ranging from “plain and ordinary meaning” to “analogous to mean equivalent spherical volume diameter by laser light diffraction scattering” to “volume mean particle size” and finally to “volume weighted mean” -
. As explained by Dr. Buckton, the measurement of particle size varies, in complexity based upon the shape of particle (spherical or irregular) and the number of measured particles, (See Second Buckton Dec. at ¶ 43.) Figure 3.04-1, in turn, depicts the "at least five types of optical microscopy” particle size determinations. (Second Buckton Dec. at ¶ 43 n.5.) These types specifically include length, width, Feret’s diameter, Martin’s diameter, and the maximum horizontal intercept. For that reason, particle size determination requires information on both the type of diameter measured and on the particle shape. The '615 Patent, however, provides no such disclosure.
. As stated above, this disputed phrase 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.
. The asserted claims ¡-of the '796 and the '760 Patents, in turn, claim Anhydrous Aripiprazole Crystals B and/or Aripiprazole drug substance “of low hygroscopicity 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%." (’796 Patent at 44:21-31; '760 Patent at 44:22-32;)
. Defendants proposing this construction consist of all of the generic defendants, except for Teva, Prinston, Aurobindo, and Arnneal.
. Except with respect to the ’615 Patent, which Otsuka has not asserted against Teva.
.These Defendants additionally challenge Otsuka’s construction to the extent it states that “wherein said low hygroscopicity.. has a plain and ordinary meaning. (Defs.’ Responsive Claim Constr. Br. at 17.)
. For the same reason, the Court rejects the indefinite Defendants’ argument that reliare upon the specification for purposes of. claim construction improperly imports a limitation ' from the specification. Indeed, the similarity in language makes plain that the patentee intended the specification to be relied upon as an elucidation of the asserted claim. See Silicon Graphics, Inc. v. ATI Techs., Inc., 607 F.3d 784, 792 (Fed.Cir. 2010) (generally noting that district courts may not rely upon the specification to import limitations into claims, "unless the specification-makes clear that the - patentee intends for the claims and the embodiments in the specification to be strictly coextensive”) (internal quotation marks omitted).
. The indefinite Defendants argue that the disputed phrase fails on indefiniteness grounds, as evidenced by the fact that Otsu-ka’s contention that "when considering the claimed low hygroscopicity test, a POSA would look to the Hygroscopicity Test Method in the specification and consider ’reasonable variations’,to account for ‘practical realties.”’ (Defs.’ Responsive Claim Constr. Br. at 23 (emphasis in original).) Nevertheless, because the Court will not adopted Otsuka’s "reasonable variations” construction, as explained below, it need not reach the issue of indefi-nitenéss. However, even if.it did, the disputed claims provide more than enough information to disclose the scope of the claims (or, the meaning of low hygroscopicity) with reasonable certainty. (See, Buckton Dep. at 167:15-18, 392:14-393:1 (setting forth Dr. Buckton’s opinion that the term, when viewed through the lens of the specification, is reasonable clear).)
.. The Court will not, however, incorporate the "reasonable variations” proposed by Ot-suka. In advancing a construction that includes "reasonable variations in the test method,” Dr. Byrn appears to envision a construction that accounts for "practical laboratory realities" (Byrn Dec. at ¶ 65), e.g„ laboratory variations, or "[sjomething as simple as a truck driving by the building or power fluctuations.” (Markman Hr’g Tr. at 30:24-31:3.) These sorts of laboratory conditions, however, have no place in the Court’s construction, nor any actual rooting in the intrinsic record. (See Byrn Dep. at 256:6-7 (stating that the Court need not adopt "reasonable variations" as part of its construction).)
. As stated above, only Otsuka present ed arguments on-the term ‘aripiprazole drug substance.'
, Nearly every relevant embodiment of the specification contains a similar disclosure. . (See, e.g„ '760-Patent at 5:64-7:62.)
. Only Otsuka presented expert testimony in support of its proposed construction of "aripi-prazole drug substance.”
. As stated above, this disputed phrase appears in claims 1 through 18 of the '315 Patent.
. Indeed, Otsuka has only augmented its position on this disputed claim phrase through its submission of additional extrinsic evidence, namely, the expert declarations of Dr. Correll and Dr. Byrn. Otsuka no longer relies upon Dr. Bryan L. Roth, the expert Otsuka relied upon in connection with the TRO proceedings.
.As a result, t he Court incorporates by reference the relevant discussion in its prior decision. See Otsuka, 99 F.Supp.3d at 477-83.
. Otsuka argues that claim 9 supports Otsu-ka’s proposed construction.. Nevertheless, reviewing this claim through the spectre of the remaining claims make clear that the paten-
. The Court rejects Otsuka’s reliance upon isolated portions of the specification for the same reasons set forth in the TR.0 Opinion. See Otsuka, 99 F.Supp.3d at 481-83. Critically, these portions of the specification all identify alternative embodiments involving separate dosage forms, not the single composition otherwise disclosed in the plain claim language and throughout the remainder of the specification. (See, e.g., ’350 Patent at 3:52-67, 14:10-21.) The Court need not credit alternative embodiments, particularly those that, as here, "contradict” the relevant claim language. TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1373 (Fed.Cir. 2008) (declining to include alternatively disclosed embodiment because it "would contradict the language of the claims”); see also Rolls-Royce, PLC v. United Techs. Corp., 603 F.3d 1325, 1334-35 (Fed. Cir. 2010) (omitting certain disclosed embodiments to avoid a construction that “outweighs the language of the claim.”). Moreover, even if the Court accepted Otsuka’s' interpretation of these specific portions of the specification, the specification itself cannot be “a substitute .for, nor can [it] be used to rewrite, the chosen claim language.” SuperGuide Corp. v. DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed.Cir. 2004) (“[specifications teach,” "[c]laims claim”).
Reference
- Full Case Name
- OTSUKA PHARMACEUTICAL CO., LTD. v. TORRENT PHARMACEUTICALS LIMITED, INC., Torrent Pharma Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Alembic Pharmaceuticals Limited, Alembic Limited, Alembic Global Holding SA, and Alembic Pharmaceuticals Inc., Defendants Otsuka Pharmaceutical Co., Ltd. v. Zydus Pharmaceuticals USA, Inc. and Cadila Healthcare Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Aurobindo Pharma Limited, Aurobindo Pharma USA, Inc., and Aurolife Pharma LLC, Defendants Otsuka Pharmaceutical Co., Ltd. v. Intas Pharmaceuticals Limited, Accord Healthcare, Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Sun Pharmaceutical Industries Ltd., Sun Pharma Global Inc., Sun Pharma Global FZE, Sun Pharma USA, Sun Pharmaceuticals Industries, Inc., and Caraco Pharmaceutical Laboratories, Defendants Otsuka Pharmaceutical Co., Ltd. v. Mylan, Inc., Mylan Pharmaceuticals Inc., and Mylan Laboratories Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Torrent Pharmaceuticals Limited, Inc., Torrent Pharma Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Zhejiang Huahai Pharmaceutical Co., Ltd., Huahai US Inc., Prinston Pharmaceutical Inc., and Solco Healthcare U.S., LLC, Defendants Otsuka Pharmaceutical Co., Ltd. v. Ajanta Pharma Limited and Ajanta Pharma USA Inc., Defendants Otsuka Pharmaceutical Co., Ltd. v. Teva Pharmaceuticals USA, Inc., Defendant Otsuka Pharmaceutical Co., Ltd. v. Intas Pharmaceuticals Limited, Accord Healthcare, Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Sun Pharmaceutical Industries Ltd., Sun Pharma Global Inc., Sun Pharma Global FZE, Sun Pharma USA, Sun Pharmaceuticals Industries, Inc., and Caraco Pharmaceutical Laboratories, Defendants Otsuka Pharmaceutical Co., Ltd. v. Teva Pharmaceuticals USA, Inc., Defendant Otsuka Pharmaceutical Co., Ltd. v. Aurobindo Pharma Limited, Aurobindo Pharma USA, Inc., and Aurolife Pharma LLC, Defendants Otsuka Pharmaceutical Co., Ltd. v. Lupin Limited, Lupin Atlantis Holding Sa, Lupin Pharmaceuticals, Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Zydus Pharmaceuticals USA and Cadila Healthcare Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Alembic Pharmaceuticals Limited, Alembic Limited, Alembic Global Holding SA, and Alembic Pharmaceuticals Inc., Defendants Otsuka Pharmaceutical Co., Ltd. v. Apotex Corp., Apotex Inc., Apotex Pharmachem Inc., and Hetero Labs Limited, Defendants Otsuka Pharmaceutical Co., Ltd. v. Sciegen Pharmaceuticals Inc. and Bactolac Pharmaceutical, Inc., Defendants Otsuka Pharmaceutical Co., Ltd. v. Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals India Pvt. Ltd., MSN Pharmachem Pvt. Ltd., and Msn Laboratories Pvt. Ltd. Otsuka Pharmaceutical Co., Ltd. v. Hetero Drugs Limited, Hetero Labs Limited, and Hetero USA, Inc.
- Cited By
- 5 cases
- Status
- Published