Source: http://de.findacase.com/research/wfrmDocViewer.aspx/xq/fac.20180122_0000032.DDE.htm/qx
Timestamp: 2019-04-21 04:23:09+00:00

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Plaintiff brought this patent infringement action against Amneal Pharmaceuticals, LLC in 2015. (D.I. 1). At issue in this case are ready-to-use formulations of the compound dexmedetomidine. Dexmedetomidine itself is claimed in U.S. Patent No. 4, 910, 214 ("the '214 patent"), which is not at issue in this case. The '214 patent issued on March 20, 1990 and expired on July 15, 2013. (Trial Transcript ("Tr.") 1081:9-12, 1082:10-15; '214 patent; D.I. 96-1 at37).Dexmedetomidine, which is the d-enantiomer of racemic 4-[l-(2, 3-dimethylphenyl)ethyl]-lH-imidazole, is a sedative and is the active ingredient in Hospira's Precedex products. ('106 patent at 1:26-28, 1:34-37; Tr. 5:6-9). Amneal filed Abbreviated New Drug Application ("ANDA") No. 207551, seeking to engage in the commercial manufacture, use, and sale of generic versions of Hospira's 4μg/mL dexmedetomidine products ("Precedex premix") in 50 mL and 100 mL glass vials. (D.I. 96-1 at 3-4; PTX-63 at p. 6).
Since its FDA approval in 1999, Hospira's original Precedex product (100 μg/mL dexmedetomidine hydrochloride), also known as Precedex concentrate, has been sold in a 2 mL glass vial. (Tr. 6:11-15; D.I. 96-1 at 2). Before Precedex concentrate is administered to a patient, it must be diluted to an appropriate concentration per the instructions on the Precedex concentrate label. (Tr. 6:17-20). The delay in drug administration to patients and increased risks of dosing error and contamination associated with this dilution step led Hospira to develop ready-to-use formulations of Precedex. (Id. at 7:7-10). In 2013, Hospira received FDA approval for 50 mL and 100mL glass bottles containing a ready-to-use 4μg/mL formulation of dexmedetomidine hydrochloride. (D.I. 96-1 at 2). FDA approval of the same formulation in a 20 mL glass vial followed in 2014. (Id. at 3).
The Court held a bench trial from August 21-24, 2017. Plaintiff asserts that Defendant's ANDA submission constitutes infringement of claims 3 and 4 of U.S. Patent No. 8, 242, 158 ("the '158 patent"), claim 4 of U.S. Patent No. 8, 338, 470 ("the'47O patent"), claim 5 of U.S. Patent No. 8, 455, 527 ("the'527 patent"), and claim 6 of U.S. Patent No. 8, 648, 106 ("the '106 patent"). (Tr. 3:15-20; D.I. 101 at 3). The asserted patents are part of the same patent family and share a common specification. (D.I. 96 at 4).
1. A ready to use liquid pharmaceutical composition for parenteral administration to a subject, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 4 μg/mL disposed within a sealed glass container.
2. The ready to use liquid pharmaceutical composition of claim 1, further comprising sodium chloride at a concentration of between about 0.01 and about 2.0 weight percent.
3. The ready to use liquid pharmaceutical composition of claim 2, wherein the sodium chloride is present at a concentration of about 0.9 weight percent.
4. The ready to use liquid pharmaceutical composition of claim 1, wherein the composition is formulated as a total volume selected from the group consisting of 20 mL, 50 mL and 100 mL.
('158 patent at claims 1-4).
1. A ready to use liquid pharmaceutical composition for parenteral administration to a subject, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 0.005 to about 50 μg/mL disposed within a sealed glass container.
4. The ready to use liquid pharmaceutical composition of claim 1, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is at a concentration of about 1 to about 7 μg/mL.
('470 patent at claims 1, 4).
1. A method of providing sedation to a patient in need thereof, the method comprising administering to the patient an effective amount of a composition, wherein the composition comprises dexmedetomidine or a pharmaceutically acceptable salt thereof at a concentration of about 0.005 to about 50 μg/mL, wherein the composition is a ready to use liquid pharmaceutical composition for parenteral administration to the patient disposed within a sealed glass container.
5. The method of claim 1, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is at a concentration of about 4 μg/mL.
('527 patent at claims 1, 5).
1. A ready to use liquid pharmaceutical composition for parenteral administration to a subject, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof disposed within a sealed glass container, wherein the liquid pharmaceutical composition when stored in the glass container for at least five months exhibits no more than about 2% decrease in the concentration of dexmedetomidine.
6. The ready to use liquid pharmaceutical composition of claim 1, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is at a concentration of about 4 μg/mL.
('106 patent at claims 1, 6).
"[T]he words of a claim are generally given their ordinary and customary meaning. . . . [This is] the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application." Id. at 1312-13. "In some cases, the ordinary meaning of claim language as understood by a person of skill in the art may be readily apparent even to lay judges, and claim construction in such cases involves little more than the application of the widely accepted meaning of commonly understood words." Id. at 1314.
Apatent claim is invalid as obvious under 35 U.S.C. § 103 "if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." 35 U.S.C. § 103; see also KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 406-07 (2007). The determination of obviousness is a question of law with underlying factual findings. See Kinetic Concepts, Inc. v. Smith & Nephew, Inc., 688 F.3d 1342, 1360 (Fed. Cir. 2012). "The underlying factual inquiries include (1) the scope and content of the prior art; (2) the differences between the prior art and the claims at issue; (3) the level of ordinary skill in the art; and (4) any relevant secondary considerations . . . ." Western Union Co. v. MoneyGram Payment Sys., Inc., 626 F.3d 1361, 1369 (Fed. Cir. 2010) (citing Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966)).
A court is required to consider secondary considerations, or objective indicia of nonobviousness, before reaching an obviousness determination, as a "check against hindsight bias." See In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig., 676 F.3d 1063, 1078-79 (Fed. Cir. 2012). Relevant secondary considerations include commercial success, long felt but unsolved needs, failure of others, praise, unexpected results, and copying, among others. Graham, 383 U.S. at 17-18; Ruiz v. A.B. Chance Co., 234 F.3d 654, 662-63 (Fed. Cir. 2000); Tex. Instruments Inc. v. U.S. Int'l Trade Comm'n, 988 F.2d 1165, 1178 (Fed. Cir. 1993). Secondary considerations of nonobviousness are important because they "serve as insurance against the insidious attraction of the siren hindsight.. .." W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1553 (Fed. Cir. 1983).
A patentee is not required to present evidence of secondary considerations. See Prometheus Labs., Inc. v. Roxane Labs., Inc., 805 F.3d 1092, 1101-02 (Fed. Cir. 2015). There must be enough evidence, however, for a finding that a given secondary consideration exists by a preponderance of the evidence. See Apple, Inc. v. Samsung Elec. Co., Ltd., 839 F.3d 1034, 1053 (Fed. Cir. 2016) (en banc). If there is, then the probative value of each secondary consideration will be considered in light of the evidence produced. That does not mean, though, that the burden of persuasion on the ultimate question of obviousness transfers to the proponent of the secondary consideration. Pfizer, Inc. v. Aptoex, Inc., 480 F.3d 1348, 1359 (Fed. Cir. 2007). That burden stays always with the patent challenger. Id. at 1359-60.
A party asserting that a patent is invalid as obvious must "show by clear and convincing evidence that a skilled artisan would have been motivated to combine the teachings of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success in doing so." Id. at 1361. That "expectation of success need only be reasonable, not absolute." Id. at 1364. "Whether an ordinarily skilled artisan would have reasonably expected success ... is measured as of the date of the invention...." Amgen Inc. v. F. Hoffman-La Roche Ltd, 580 F.3d 1340, 1362 (Fed. Cir. 2009).
"To show that a patent claim is invalid as anticipated, the accused infringer must show by clear and convincing evidence that a single prior art reference discloses each and every element of a claimed invention." Silicon Graphics, Inc. v. ATI Techs., Inc., 607 F.3d 784, 796 (Fed. Cir. 2010). "[E]very element of the claimed invention [must be] described, either expressly or inherently, such that a person of ordinary skill in the art could practice the invention without undue experimentation." Callaway Golf Co. v. Acushnet Co., 576 F.3d 1331, 1346 (Fed. Cir. 2009). As with infringement, the court construes the claims and compares them against the prior art. See Enzo Biochem, Inc. v. Applera Corp., 599 F.3d 1325, 1337 (Fed. Cir. 2010).
A patent must "inform those skilled in the art about the scope of the invention with reasonable certainty." Nautilus, Inc. v. BiosigInstruments, Inc., 134 S.Ct. 2120, 2129 (2014). To determine indefiniteness, courts examine "the patent record-the claims, specification, and prosecution history-to ascertain if they convey to one of skill in the art with reasonable certainty the scope of the invention claimed." Teva Pharms. USA, Inc. v. Sandoz, Inc., 789 F.3d 1335, 1341 (Fed. Cir. 2015). "[I]f necessary, a court may consult extrinsic evidence to understand the meaning of a term in the relevant art." Transcend Med., Inc. v. Glaukos Corp., 2015 WL 5546988 at * 5 (D. Del. Sept. 18, 2015) (citation omitted).
A patent is infringed when a person "without authority makes, uses, offers to sell, or sells any patented invention, within the United States ... during the term of the patent...." 35 U.S.C. § 271(a). A two-step analysis is employed in making an infringement determination. See Markman, 52 F.3d at 976. First, the court must construe the asserted claims to ascertain their meaning and scope. See Id. The trier of fact must then compare the properly construed claims with the accused infringing product. See Id. This second step is a question of fact. Bai v. L&L Wings, Inc., 160 F.3d 1350, 1353 (Fed. Cir. 1998). "Literal infringement of a claim exists when every limitation recited in the claim is found in the accused device." Kahn v. Gen. Motors Corp., 135 F.3d 1472, 1477 (Fed. Cir. 1998). "If any claim limitation is absent from the accused device, there is no literal infringement as a matter of law." Bayer AG v. Elan Pharm. Research Corp., 212 F.3d 1241, 1247 (Fed. Cir. 2000). The patent owner has the burden of proving infringement by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988).
For jurisdictional purposes, 35 U.S.C. § 271(e)(2)(A) defines filing an ANDA application for a drug covered by a patent as an act of infringement. 35 U.S.C. § 271 (e)(2)(A); see also Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 1569 (Fed. Cir. 1997) ("[Section] 271(e)(2) provided patentees with a defined act of infringement sufficient to create case or controversy jurisdiction to enable a court to promptly resolve any dispute concerning infringement and validity."). "Because drug manufacturers are bound by strict statutory provisions to sell only those products that comport with the ANDA's description of the drug, an ANDA specification defining a proposed generic drug in a manner that directly addresses the issue of infringement will control the infringement inquiry." Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002). Therefore, "when a drug manufacturer seeks FDA approval to market a generic compound within the scope of a valid patent, it is an infringement as a matter of law." Sunovion Pharms., Inc. v. Teva Pharms. USA, Inc., 731 F.3d 1271, 1280 (Fed. Cir. 2013). When an ANDA is silent with respect to at least one claim limitation of the patents at issue, however, Sunovion does not apply, and "the relevant inquiry is whether the patentee has proven by a preponderance of the evidence that the alleged infringer will likely market an infringing product." Ferring B.V. v. Watson Labs., Inc.-Fla., 764F. 3d 1382, 1388 (Fed. Cir. 2014) (citation omitted).
The parties dispute the constructions for "ready to use" and "sealed glass container, " each of which appear in all of the asserted claims. Although the parties stipulated that Defendant's proposed ANDA products meet the "ready to use" limitation for purposes of infringement, they dispute the plain meaning of the term for purposes of assessing invalidity. (Tr. 4:10-15). There was no stipulation with respect to the "sealed glass container" limitation for purposes of assessing infringement. (Id. at 3:22-4:8).
At trial, Plaintiff argued for a construction defining the plain meaning of "ready to use" as "formulated to be suitable for administration to a patient upon manufacture without dilution or reconstitution." (Id. at 262:9-263:1). Defendant asserts that the plain meaning of "ready to use" is "requiring no further dilution or reconstitution before administration to a patient." (Id. at 581:12-19). The common specification of the asserted patents reveals that the patentees acted as their own lexicographers with respect to this term. In a section titled "Definitions, " the specification states that "ready to use" formulations "refer to premixed compositions that are suitable for administration to a patient without dilution." (See, e.g., '106 patent at 3:66-4:2). Therefore, I conclude that the construction of "ready to use" is "suitable for administration to a patient without dilution."
During trial, I proposed several constructions for "sealed glass container." (Tr. 1176:2-21). Among those constructions was "a container that is closed tightly to maintain sterility." (Tr.1176:12-20). The parties appear to have agreed to this construction. (D.I. 100 at 34-35 ("Amneal submits that either of the Court's two proposed definitions of sealed' would be proper, so long as a further tamper-[evident limitation] is not added."); D.I. 101 at 5 n.3 ("So long as this construction includes the limitation of 'glass, ' Hospira agrees that this proposed meaning is supported by the record because a sealed container in this context maintains sterility."); see also '106 patent at 9:9-15 (disclosing a sealed glass container packaging embodiment that "can maintain the sterility of, or prevent the contamination of, a premixed dexmedetomidine composition")). Accordingly, I will construe "sealed glass container" as "a glass container that is closed tightly to maintain sterility."
The '158, '470, and '106 patents each describe ready-to-use pharmaceutical compositions of dexmedetomidine or a pharmaceutically acceptable salt thereof for parenteral administration, disposed within a sealed glass container. The asserted claims of these patents claim or encompass dexmedetomidine concentrations of 4 μg/mL. Certain asserted claims contain additional limitations, such as the presence of sodium chloride at a concentration of about 0.9 weight percent in the dexmedetomidine formulation ('158 patent at claim 3), certain volumes of the dexmedetomidine formulation (id. at claim 4), and formulations losing no more than about 2% dexmedetomidine concentration at 5 months ('106 patent at claim 6). Asserted claim 5 of the '527 patent claims a method of providing sedation to a patient via parenteral administration using a 4 μg/mL dexmedetomidine formulation disposed within a sealed glass container. ('527 patent at claim 5).
Defendant argues that all the asserted claims are invalid as obvious, and further asserts that claim 3 of the '158 patent, claim 4 of the '470 patent, and claim 5 of the '527 patent are invalid as anticipated. (D.I. 100 at 8, 36). Additionally, Defendant contends that claim 6 of the '106 patent is indefinite under 35 U.S.C. § 112. (Id. at 26).
1. For the product claims, the person of ordinary skill in the art ("POS A") holds an advanced degree, such as a Ph.D., M.D., or Pharm.D., in chemistry, pharmacology, or pharmaceutical development.
2. For the method of treatment claim, the POSA would have some formal education in science, chemistry, pharmacology or pharmaceutical development, and would have several years of experience administering pharmaceuticals to patients, including clinical experience in anesthesia or sedation and familiarity with parenteral injections. The POSA's practical experience may vary depending on the POSA's level of formal education.
3. The priority date for the asserted patents is January 4, 2012. (D.I. 96-1 at 5).
4. Each of the asserted patents is assigned to Hospira. (D.I. 96-1 at 2).

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