Full opinion text
OPINION PISANO, District Judge. This patent infringement action arises out of the filing of an Abbreviated New Drug Application (“ANDA”) by Navinta, LLC (“Navinta”), a generic drug manufacturer, to market a generic version of an injectable form of the anesthetic Naropin. Naropin is indicated for the production of local or regional anesthesia for surgery and for acute pain management. Plaintiffs, Abraxis Bioscience, Inc. (“Abraxis”) and APP Pharmaceuticals, LLC (collectively, “APP Pharma”), bring this action alleging that Defendant’s filing of the ANDA constituted infringement of three patents relating to the active ingredient in Naropin: United States Patent No. 4,870,-086 (the “'086 patent”), entitled “Optically Pure Compound and a Process for Its Preparation,” United States Patent No. 5,670,524 (the “'524 patent”) entitled “Methods and Compositions for the Treatment of Pain Utilizing Ropivacaine,” and United States Patent No. 5,834,489 (the “'429” patent), also entitled “Methods and Compositions for the Treatment of Pain Utilizing Ropivacaine.” Plaintiff alleges that Navinta has infringed claims 1, 2, 3, and 6 of the '086 patent, and has infringed and will induce infringement of claims 1 and 9 of the '524 patent and claim 1 of the '489 patent. Defendant has asserted counterclaims against APP Pharma alleging unfair competition, violations of the Sherman Act, 15 U.S.C. §§ 1 and 2, and tortious interference with prospective economic advantage. There claims were bifurcated by Order dated July 31, 2008, 2008 WL 2967034. Defendant also counterclaimed for a declaration of noninfringement of the '086, '524 and '489 patents. The filing of the instant lawsuit triggered a 30-month stay on the Federal Drug Administration’s approval of Navinta’s ANDA, and the stay expires on August 5, 2009. At a hearing held on May 29, 2009, the parties requested that the Court schedule a trial date that would permit the Court to decide the issues in the case prior to the expiration of the stay. To that end, a bench trial was held from July 20, 2009 to July 28, 2009. 1. Witnesses Presented at Trial A. Plaintiff’s Witnesses Abraxis proffered the following expert and fact witnesses at trial: Dr. Jerry Atwood, Dr. Leonard Chyall, Dr. Gordon Amidon, Dr. Jeffrey Gudin, and Deena Reyes, and presented testimony of other witnesses through deposition testimony. B. Defendant’s Witnesses Navinta proffered the following expert and fact witnesses at trial: Dr. Robert Gawley, Dr. Raymond Squire, David Pi-card, Dr. Christopher Newton Jobdevairakkam, Dr. Hugo Steinfink, Dr. Pankaj Dave, and Dr. Peter Griffiths, and presented the testimony of other witnesses through deposition testimony. C.Credibility Determinations It is not unusual in a case such as this one that the factfinder is faced with contradicting expert opinions. Such is the case in the instant matter, particularly with respect to the expert testimony of Drs. Atwood and Gawley, each of whom testified about, among other things, the attributes and chemistry of ropivacaine compositions, and each of whom offered starkly differing opinions in this regard. As a result, the Court, as factfinder, must determine what weight and credibility to give to the testimony. See Energy Capital Corp. v. United States, 302 F.3d 1314, 1329 (Fed.Cir.2002) (“As for the relative weight given to the testimony of both sides’ expert witnesses, we accord the trial court broad discretion in determining credibility because the court saw the witnesses and heard their testimony.”); Gyromat Corp. v. Champion Spark Plug Co., 735 F.2d 549, 552 (Fed.Cir.1984) (“The credibility of the witnesses and the weight to be given to their testimony and the other evidence in the record ... is a matter for the trier of the facts.”) The Court finds that although APP Pharma’s expert, Dr. Atwood, and Navinta’s expert, Dr. Gawley, are each highly qualified in their respective specialties, to the extent that Drs. Atwood and Gawley give differing opinions on an issue, the Court accorded Dr. Atwood’s testimony more weight in reaching the factual determinations set forth herein. Dr. Atwood’s more extensive experience in the area of supramolecular chemistry, the manner in which testified, and the reasons he gave in support of his opinion all convinced the Court, as factfinder, to accept Dr. Atwood’s testimony. Additionally, Dr. Atwood’s opinions are consistent with testing performed by another of Plaintiffs expert, Dr. Chyall. With respect to Dr. Gawley, certain inconsistencies in his testimony and Navinta’s own experts’ criticisms of certain materials relied upon by Dr. Gawley, among other things, contributed to the Court according lesser weight to Dr. Gawley’s opinions. With respect to the '524 and '489 patents, the Plaintiffs and Defendant offered the testimony of experts Dr. Gudin and Dr. Squire, respectively. Overall, the Court found their testimony to be largely consistent. However, to the extent that their testimony may have conflicted on a particular issue, the Court accorded Dr. Gudin’s testimony more weight. The Court reached this conclusion based upon Dr. Gudin’s background and experience, the manner in which he testified, and the reasons he gave in support of his opinions. Upon hearing the evidence at trial and considering the testimony and documentary evidence, the Court makes the following findings of fact and conclusions of law. II. FACTUAL BACKGROUND A. The Parties and the Patents 1.Plaintiff Abraxis is a corporation organized and existing under the laws of the State of Delaware, having a principal place of business in Los Angeles, California. Plaintiff APP Pharma is a limited liability company organized and existing under the laws of the State of Delaware, having a principal place of business in Chicago, Illinois. Defendant Navinta is a limited liability corporation organized and existing under the laws of the State of New Jersey, having a principal place of business in Ewing, New Jersey. The parties are drug companies involved in, among other things, the development and manufacture of pharmaceuticals. 2. On March 1, 2007, Navinta entered into a Collaboration Agreement with San-doz AG. This agreement gives Sandoz AG and its U.S. subsidiary Sandoz, Inc. (collectively “Sandoz”) exclusive rights to “sell, market and distribute” the ANDA Products. (Picard Testimony, 7/23/09 Tr. at 732:4-8, 732:19-22; PLT 134.) 3. The United States Patent & Trademark Office issued U.S. Patent No. 4,870,-086, entitled “Optically Pure Compound And A Process For Its Preparation,” on September 26, 1989. The inventor of the '086 Patent is Rune V. Sandberg. The '086 Patent will expire on or about September 24, 2010. 4. The Patent Office issued U.S. Patent No. 5,670,524, entitled “Methods And Compositions For The Treatment Of Pain Utilizing Ropivacaine,” on September 23, 1997. The United States Patent & Trademark Office issued U.S. Patent No. 5,834,-489, also entitled “Methods And Compositions For The Treatment Of Pain Utilizing Ropivacaine,” on November 10, 1998. The inventor of the '524 and '489 patents is Arne Torsten Eek. The '524 and '489 patents will expire on or about September 23, 2014. 5. The '524 and '489 patents claim inventions regarding the use of low concentrations of ropivacaine for pain relief. B. The ANDA 6. On or about November 13, 2006, Navinta submitted to the U.S. Food & Drug Administration ANDA 78-601, which requests approval to engage in the commercial manufacture, use and sale of a “Ropivaeaine Hydrochloride Injection” product. (Pretrial Order, Stipulated Fact 4.) 7. On or about February 2, 2007, Navinta mailed to, among others, Abraxis a “Notification of Certification of Invalidity, Unenforceability, and/or Non-Infringement for U.S. Patent No. 4,870,086 Pursuant to § 505(j)(2)(B)(iv) of the Federal Food, Drug and Cosmetic Act.” (Pretrial Order, Stipulated Fact 5.) C. The Prior Art 8. In 1985, WO 085/00599 to Thuresson (hereafter “Thuresson”) disclosed a ropivacaine composition that was about 90% enantiomerieally pure and 80% optically pure. As a result of its impurity, the 1-propyl-2',6'-pipecoloxylidide hydrochloride compound of Thuresson was unsuitable and not in use as an anesthetic in 1985. ('086 Patent at 1:11-35, PLT 1; Atwood Testimony, 7/20/09 Tr. at 22:16-24, 24:20-21, 26:22-25.) 9. The Thuresson compound was hygroscopic, meaning it did not have a defined water content and would take on water from the atmosphere. This is not a desirable trait for a pharmaceutical compound or composition because it would require one to analyze the compound’s water content on a daily or perhaps even hourly basis. It would put an undue burden on the analytical process, either in the plant or in a pharmacy. For example, if there is a certain desired dosage and if one has a high water content, the dosage that is administered might be too low for the effective use of the pharmaceutical. (Atwood Testimony, 7/20/09 Tr. at 25:23-26:4, 29:8-17, 30:3-6.) 10. A “Navinta Process Development Report” prepared by Navinta’s Research and Development Department under the supervision of its Chief Scientific Officer, Dr. Newton, states that the quantity of “optical isomer” in the compound used in Thuresson is at about 90%, which would translate to an optical purity of about 80%. The report states that the purpose of Navinta’s project was to “resolve the drawbacks observed with the literature methods,” including Thuresson. (Newton Testimony, 7/24/09 Tr. at 831:11-833:10; Gawley Testimony, 7/23/09 Tr. at 675:7-676:14; PLT 161-0010 & 161-0011.) 11. The Thuresson compound did not ever result in a commercial product. (Atwood Testimony, 7/20/09 Tr. at 26:18-25.) 12. The Thuresson compound was cited by the patent examiner during the prosecution of the '086 Patent. (Gawley Testimony, 7/22/09 Tr. at 595:7-8.) However, the Patent Office ultimately issued the '086 Patent over Thuresson. (PLT 1-0001.) D. The Invention of the '086 Patent 13. The '086 Patent discusses optically-pure enantiomer compositions. Many chemical compounds can exist as mirror images of each other. Researchers refer to one “image” of a compound as the “S” enantiomer, and refer to its mirror image as the “R” enantiomer. (Atwood Testimony, 7/20/09 Tr. at 18:6-23; PLT 378-0008.) 14. “Enantiomeric purity” is a measure of how much more of one enantiomer there is than the other enantiomer in a mixture of enantiomers. For example, a mixture of 90% S-enantiomer and 10% R-enantiomer has 90% enantiomeric purity. (Atwood Testimony, 7/20/09 Tr. at 19:23-20:1; PLT 378-0009.) 15. One enantiomer will rotate light in a clockwise direction while its mirror image will rotate light in the opposite direction. The ability of enantiomers to rotate light is called “optical activity” and is designated by the symbols (+) and (-). Thus, (-) indicates there is more (S)-enantiomer than there is R-enantiomer. (Atwood Testimony, 7/20/09 Tr. at 19:5-10; 20:2-16; 28:20-25, 68:25-69:3, 78:3-6, 231:17-20.) 16. Measured optical activity of an enantiomer inherently indicates that the enantiomer is “optically pure.” A mixture having 90% enantiomeric purity contains 90% S enantiomer and 10% R enantiomer. This is equivalent to an optical purity of 80% because 20% of the mixture would consist of 10% S enantiomer and 10% R enantiomer. This 20% of the mixture would not have any optical activity, because the optical activity of the 10% R enantiomer would cancel out the 10% S enantiomer. (Atwood Testimony, 7/20/09 Tr. at 20:17-21:2; 7/21/09 Tr. at 231:17-20; PLT 378-0011, 378-0031.) 17. The (S) enantiomer of the compound (S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride is more potent and more stable than the (R) enantiomer. ('086 Patent, PLT 1 at 1:27-29.) 18. One objective of the '086 Patent was “to obtain a product consisting of the substantially pure (S)-(-)-enantiomer.” ('086 Patent, PLT 1 at 1:32-35; Atwood Testimony, 7/20/09 Tr. at 27:8-10.) Another objective of the '086 Patent was to produce the compound (S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride in a form “which is stable and which does not change by storing at ordinary room temperature and humidity.” ('086 Patent, PLT 1 at 1:29-32; Atwood Testimony, 7/20/09 Tr. at 27:8-10.) 19. Example 1 in the '086 specification details how Dr. Sandberg realized high optical purity and stability. Dr. Sandberg conceived of taking the optically impure materials, heating them with water and acetone, and then taking advantage the Renantiomer’s lesser solubility than the desired S-enantiomer. Thus, Dr. Sandberg created in a solution both the R and the Senantiomers of the desired compound and, due to the low solubility of the R-enantiomer, was able to filter out the R-enantiomer to produce an aqueous solution of the optically pure S-enantiomer. (Atwood Testimony, 7/20/09 Tr. at 33:7-19, 34:13-17; Atwood Testimony, 7/21/09 Tr. at 256:20-25; '086 Patent, PLT 1 at 2:56-3:5; PLT 378-0013, 378-0020.) 20. In Example 1 of the '086 Patent specification, a second filtration step is performed to produce the S-enantiomer with an optical purity greater than or equal to 99.5%. (Atwood Testimony, 7/20/09 Tr. at 36:10-15.) 21. Thus, the optically pure compound (S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride disclosed in the '086 patent achieved the objective of a greatly increased amount of the (S) enantiomer relative to the (R) enantiomer. (Atwood Testimony, 7/20/09 Tr. at 21:18-20.) 22. A person of skill in the art would understand that a goal of the '086 invention was a compound with a defined water content. Claim 1 of the '086 Patent, by claiming the monohydrate form of the compound (ropivacaine hydrochloride monohydrate, or “RHM”), accomplished this objective by providing the compound in a form that was stable and not hygroscopic. RHM has exceptional stability in both solution and in the solid state. (Atwood Testimony, 7/20/09 Tr. at 34:22-25, 39:20-25.) 23. RHM as a solid is so stable that, according to the '086-Patent, it has to be heated at 75°C for 16 hours under a high vacuum to remove the water. This indicates that the water is locked into the structure of the RHM composition. The locked-in nature of the water is a key to understanding the stability of RHM, both in the solid state and in solution. (Atwood Testimony, 7/20/09 Tr. at 42:15-21; PLT 1 at 1:44-51.) 24. The stable water content offered by RHM is desirable for pharmaceuticals because it allows for extended storage and accurate dispensation by weight. Studies have confirmed a shelf life of up to five years for RHM. (Atwood Testimony, 7/21/09 Tr. at 232:7-11, 232:13-233:1.) 25. The '086 inventions were significant to the fields of chemistry and medicine. The inventions represented “elegant and exceptionally well-practiced chemistry” because they addressed serious problems that had plagued chemists for a long time. The '086 Patent solved both an optical purity problem and a stability problem. (Atwood Testimony, 7/20/09 Tr. at 38:24-39:4.) Dr. Sandberg’s inventions received the 1995 Gaston Labat Lecture award from the American Society of Regional Anesthesia, at which it was noted that RHM was the “ ‘white knight slaying the dragon’ of eardiotoxicity,” a reference to the use of the anesthetic bupivacaine, in the late 1970s and early 1980s, which resulted in a significant number of cases of cardiac arrest, including numerous fatalities during childbirth. (Gudin Testimony, 7/22/09 Tr. at 465:6-14; 481:13-20; Squier Testimony, 7/23/09 Tr. at 701:6-7; Atwood Testimony, 7/28/09 at Tr. 1121:11-13; PLT 37.) E. Naropin 26. Naropin is a branded drug marketed and sold in the United States by Plaintiff APP Pharma. The U.S. Food and Drug Administration approved NDA 20-533 for Naropin on September 24, 1996. (Gudin Testimony, 7/22/09 Tr. at 464:19-22.) 27. APP Pharma sells Naropin in concentrations of 0.2%, 0.5%, 0.75% and 1.0% by weight. (Gudin Testimony, 7/22/09 Tr. at 539:24-540:1; PLT 50-0004.) 28. Naropin is substantially optically pure and has less than 0.5% of the (R)-( +) enantiomer. (Atwood Testimony, 7/20/09 Tr. at 82:2-5; PLT 369-0002.) 29. On November 21, 1996, the original assignee of the '086 Patent, Astra Lakemedel Aktiebolag (“Astra LA”), applied for an extension of the '086 Patent term pursuant to 35 U.S.C. § 156. (PLT 277.) 30. Astra LA stated in its application: “The sole active ingredient in Naropin is Ropivacaine HC1 or (S)-(-)-l-propyl2',6'-pipecoloxylidide hydrochloride monohydrate.” Astra further stated that the “active ingredient in Naropin ... is claimed in the patent.” Astra also presented in its application a claim chart stating that Claim 1 of the '086 Patent covers Naropin because RHM is the active ingredient. Astra AL explained that the claims covered the drug product as an isotonic solution, not just as a bulk drug in solid form. (PLT 277-0001, 277-0002, 277-0004, 277-0006.) 31. Two different legal advisors within the Patent Office reviewed Astra’s application and concluded that the '086 claims covered the Naropin solution. (PLT 4-0140, 4-0142.) 32. In several letters from FDA officials to high-ranking PTO officials, the FDA stated its conclusion that the “human drug product claimed by the patent is NAROPINtm (ropivacaine hydrochloride monohydrate).” (PLT 4-0141, 4-0145, 4-0149.) 33. A Notice published in the Federal Register, at 62 Fed.Reg. 38565 (July 1997), states in part: “FDA recently approved for marketing the human drug product NAROPINtm (ropivacaine hydrochloride monohydrate).” (PLT 4-0148. See also id. 4-0147.) 34. Based on the PTO’s and FDA’s independent conclusion that the Naropin solution contains RHM and is covered by the '086 Patent claims, the Patent Office extended the term of the '086 Patent by 1,400 days. (PLT 373.) III. DISCUSSION A. Claim Construction The parties have requested that the Court construe the certain claim terms found in claims 1, 2, 3 and 6 of the '086 patent. Claim 1 of the '086 patent claims “(S)-(-)-l-propyl-2',6'pipeeoloxylidide hydrochloride, wherein the compound is in the form of its monohydrate.” ('086 Patent at 4:10-12.) Claim 2 of the '086 Patent states: “The compound according to claim 1, wherein it is substantially optically pure.” ('086 Patent 4:13-14.) Claim 3 of the '086 Patent states: “The compound according to claim 1, wherein it contains less than 0.5% by weight of the corresponding (R)-(+)-enantiomer.” ('086 Patent at 4:15-17.) Claim 6 of the '086 Patent states: “A method for inducing local anesthesia, which comprises administering to mammals including man needing local anesthesia an anesthetizing amount of the compound according to claim 1.” ('086 Patent, PLT 1 at 4:35-38.) The following terms from claim 1 are in dispute: (i) “(S)-(-)-l-propyl-2',6'pipecoloxylidide hydrochloride, wherein the compound is in the form of its monohydrate;” and (ii) “(S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride.” Also, the term “the compound according to claim 1,” which is found in claims 2, 3 and 6 of the '086 patent, is likewise in dispute. a. Claim Construction Principles 35. In order to prevail in a patent infringement suit, a plaintiff must establish that the patent claim “covers the alleged infringer’s product or process.” Markman v. Westview Instrs., Inc., 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). “It is a bedrock principle of patent law that the claims of a patent define the invention to which the patentee is entitled the right to exclude.” Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed.Cir.2005) (internal quotations omitted) (citing Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576 (Fed.Cir.1996)) (“we look to the words of the claims themselves ... to define the scope of the patented invention”); Markman, 52 F.3d at 980 (“The written description part of the specification itself does not delimit the right to exclude. That is the function and purpose of claims.”). Consequently, the first step in an infringement analysis involves determining the meaning and the scope of the claims of the patent. Johnson Worldwide Assocs., Inc. v. Zebco Corp., 175 F.3d 985, 988 (Fed.Cir.1999). Claim construction is a matter of law, Markman v. Westview Instrs., 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), therefore, it is “[t]he duty of the trial judge ... to determine the meaning of the claims at issue.” Exxon Chem. Patents, Inc. v. Lubrizol Corp., 64 F.3d 1553, 1555 (Fed.Cir.1995). 36. Generally, the words of a claim are given their “ordinary and customary meaning,” which is defined as “the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention.” Id. at 1312-13 (citations omitted). In this regard, the Federal Circuit has noted that It is the person of ordinary skill in the field of the invention through whose eyes the claims are construed. Such person is deemed to read the words used in the patent documents with an understanding of their meaning in the field, and to have knowledge of any special meaning and usage in the field. The inventor’s words that are used to describe the invention — the inventor’s lexicography — must be understood and interpreted by the court as they would be understood and interpreted by a person in that field of technology. Thus the court starts the decisionmaking process by reviewing the same resources as would that person, viz., the patent specification and the prosecution history. Id. (quoting Multiform Desiccants, Inc. v. Medzam, Ltd., 133 F.3d 1473, 1477 (Fed. Cir.1998)). 37. A person of ordinary skill in the art at the time of the '086 patent would be a person with a degree in pharmaceutical chemistry, pharmacy, or medicine, or its equivalent. This person also would have at least two years experience, either in the area of pharmaceutical compounds, pharmaceutical products and/or pharmaceutical preparations, or in the area of anesthetics and/or anesthesiology. (Atwood Testimony, 7/20/09 Tr. at 43:25-44:5.) 38. In the process of determining the meaning of a claim as understood by a person skilled in the art, a court may look to various sources from which the proper meaning may be discerned. These sources include “the words of the claims themselves, the remainder of the specification, the prosecution history, and extrinsic evidence concerning relevant scientific principles, the meaning of technical terms, and the state of the art.” Phillips, at 1314. While a court is permitted to turn to extrinsic evidence, such evidence is generally of less significance and less value in the claim construction process. Id. at 1317. Extrinsic evidence would include evidence that is outside the patent and prosecution history, and may include expert testimony, dictionaries and treatises. Id. 39. Claims should not be construed so as to exclude preferred embodiments. OSRAM GmbH v. U.S. Int’l Trade Comm’n, 505 F.3d 1351, 1358 (Fed.Cir. 2007) (reversing ITC’s claim construction, and stating: “[t]his conclusion is reinforced by the undisputed fact that the volume-based measure would exclude the OSRAM products that the patents were designed to cover”); Hoechst Celanese Corp. v. BP Chems. Ltd., 78 F.3d 1575, 1581 (Fed.Cir.1996) (a claim construction that excludes the preferred embodiment is rarely, if ever, correct). 40. Limitations should not be read into the claims based on the disclosure of a preferred embodiment. Eolas Techs. Inc. v. Microsoft Corp., 399 F.3d 1325, 1336 (Fed.Cir.2005) (refusing to limit claims to embodiments disclosed in specification because “absent a clear disclaimer in the specification, the embodiments in the specification do not limit broader claim language”). See also Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282, 1288 (Fed.Cir.2009) (“When the specification describes a single embodiment to enable the invention, this court will not limit broader claim language to that single application ‘unless the patentee has demonstrated a clear intention to limit the claim scope using “words or expressions of manifest exclusion or restriction.” ’ ”); Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 904, 906 (Fed.Cir. 2004) (it is error to import a limitation from the specification into the claim; standing alone, an embodiment disclosed in the specification does not limit the claims); Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1327 (Fed.Cir.2002) (when specification describes only a single embodiment, claims of patent are not to be construed as restricted to that embodiment unless patentee demonstrates a clear intention to limit claim scope using words or expressions of manifest exclusion or restriction). 41. Likewise, limitations should not be read into the claims based on examples disclosed in the specification. See, e.g., JVW Enters., Inc. v. Interact Accessories, Inc., 424 F.3d 1324, 1335 (Fed.Cir.2005) (improper to import limitations into claims from examples or embodiments, even when specification describes very specific embodiment); Dow Agrosciences LLC v. Crompton Corp., 381 F.Supp.2d 826, 831 (S.D.Ind.2005) (“particular formulations or examples appearing in the specification may not be read to limit the claim”); Heil Co. v. Curotto Can Co., 2004 WL 2600134 (N.D.Cal. Nov. 1, 2004) (“it is generally improper to limit the scope of the claim to the examples set forth in the specification”). 42. To disavow or disclaim claim scope, the inventor must clearly state such an intent. Voda v. Cordis Corp., 536 F.3d 1311, 1320 (Fed.Cir.2008) (while “specification may reveal an intentional disclaimer, or disavowal, of claim scope by the inventor,” any such disclaimer or disavowal “must be clear”); Conoco, Inc. v. Energy & Environmental Int'l, L.C., 460 F.3d 1349, 1357-58 (Fed.Cir.2006) (while inventor may “use the specification to intentionally disclaim or disavow the broad scope of a claim,” this “intention must be clear” and “cannot draw limitations into the claim from a preferred embodiment”). b. Construction of the Disputed Terms “(S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride, wherein the compound in the form of its monohydrate” 43. This disputed term in claim 1 of the '086 patent shall be construed consistent with Plaintiffs proposed construction to cover solutions and shall not be not limited in the manner proposed by Defendant, i.e., to solid, crystalline RHM. 44. The words of claim 1 do not specify any physical state. The words of claim 1 also do not specify any characteristics of the claimed compound (e.g., melting point) that would suggest a particular physical state. (Gawley Testimony, 7/23/09 Tr. at 653:24-654:8.) The '086 patent applicant never disclaimed or disavowed RHM in solution or in any other way indicated that the claimed monohydrate was limited to a solid. No disavowal or disclaimer exists in the claim language, in the '086 specification, or in the '086 prosecution history. (Atwood Testimony, 7/21/09 Tr. at 260:15-16.) 46. Other claims of the '086 Patent support the conclusion that claim 1 is not limited to a solid: (1) claim 4 indicates RHM can be in solution by referring to “isolating the monohydrate” after it is created in solution. ('086 Patent at 4:18-29.) References to “isolating” the monohydrate means the monohydrate already exists in solution. When one isolates a substance, the substance has to already exist, and one is just harvesting the substance by eliminating the carrier material. (Atwood Testimony, 7/20/09 Tr. at 36:20-25, 73:1-8.) (2) claim 6 indicates that RHM can be in solution by referring to administering solutions. ('086 Patent, PLT 1 at 4:35-38.) (Atwood Testimony, 7/20/09 Tr. at 73:11-19.) 47. The '086 specification supports a construction that claim 1 is not limited to solid, crystalline RHM. In several places, the '086 specification refers to RHM either being created in, or existing in, solution. (E.g., PLT 1 at 1:55-2:3 (RHM created in solution), 2:58-64 (referring to RHM created in solution being left for crystallization), 2:27-2:50 (referring to pharmaceutical preparations in solution containing the new compound as an active ingredient), 3:15-19 (describing solution of RHM), 3:30-31 (describing solution of RHM).) (Atwood Testimony, 7/20/09 Tr. at 69:17-72:20.) 48. The '086 Patent and specification refers to RHM existing in solution and existing as a solid. (Atwood Testimony, 7/21/09 Tr. at 260:15-23; Atwood Testimony, 7/28/09 Tr. at 1119:3-8.) 49. Navinta’s assertions that the '086 specification teaches that Claim 1 is limited to solid, crystalline RHM is based on either disclosures relating to a preferred embodiment, or examples. Furthermore, Example 1, which Navinta purports teaches that RHM must be a solid, actually refers to RHM in solution. (Atwood Testimony, 7/20/09 Tr. at 36:2-5.) 50. Statements in the '086 specification about crystallization steps do not teach that claim 1 is limited to solid, crystalline RHM. Crystallization is not a necessary step to create RHM. It is a means of harvesting or isolating the RHM that resides in solution. (Atwood Testimony, 7/21/09 Tr. at 227:20-228:19.) 51. A well-defined water content does not dictate that RHM must be a solid. Whether in a solid form or in solution, the well-defined water content of RHM is based on the water that is bonded tightly within the essential structures of RHM. The water content of RHM in solution is about 5.4% to 5.6%. Dr. Sandberg calculated the water content of RHM by harvesting it from solution and then applying the Karl Fischer method of measurement. This is set forth in Example 1 of the '086 Patent. (Atwood Testimony, 7/28/09 Tr. at 1116:25-1118:23.) 52. The statement in the '086 Patent specification regarding an implied water content of 5.5% refers to the theoretical calculated value for an actual mole of water per ropivacaine hydrochloride. It is á theoretical value. It is not a measured value. (Atwood Testimony, 7/21/09 Tr. at 226:22-227:7.) 53. The water content of RHM cannot be measured in solution because the RHM structural elements are surrounded by carrier water. To measure the water content, one would need to harvest the RHM structures from the solution. Even then, measuring water is difficult because extra water might be associated with the structural elements because it is coming out of water. For this reason, Dr. Sandberg quoted a range of values (5.4% to 5.6%) as the water content resulting from one example of RHM. A water content of 5.5.% for RHM is a theoretical construct, not a measured amount. (Atwood Testimony, 7/21/09 at 264:13-25.) 54. A measurement of an exact 1:1 ratio of water to ropivacaine hydrochloride would be an accident of analysis because of the difficulty of measuring the water content of RHM. Consequently, it would be more accurate to use the term “about a monohydrate” in talking about RHM. (Atwood Testimony, 7/21/09 at 265:6-13.) 55. In RHM, the ratio of waters to ropivacaine cations to chlorides is about 1:1:1. Even though the structure is 1:1:1, each ropivacaine cation has two waters closely associated with it, and each water has two ropivacaine cations closely associated with it. (Atwood Testimony, 7/20/09 Tr. at 49:6-18.) 56. Statements in the '086 specification (or prosecution history) regarding a melting point for RHM merely identify a characteristic of RHM when it is in a solid state. They do not teach that RHM can only exist as a solid. (Atwood Testimony, 7/21/09 Tr. at 260:24-261:3.) 57. People of skill in the art would understand that RHM can exist in different physical states, including in solution, and therefore would not read claim 1 as being limited to a solid state. (Atwood Testimony, 7/20/09 Tr. at 69:14-16.) 58. RHM is a member of a class of compounds known as “amino amides.” Amides are known to form monohydrates in solution, among other hydrated states. (PLT 44.) 59. When placed in a solution, RHM crystals lose the long range order associated with the crystalline solid but maintain the essential structural features and characteristics that make RHM a unique compound, including great stability, a high melting point, and water locked tightly into the structure. (Atwood Testimony, 7/20/09 Tr. at 52:10-21, 53:11-16; PLT 378-0026.) 60. When RHM is introduced to an aqueous solution, the ropivacaine, chloride and water structures do not break up or disassociate and go their own way throughout the solution, as Navinta’s experts asserted during trial. Instead, water within the RHM structure stays in place locking two ropivacaine cations together. Also, due to electrostatic and hydrogen bonding, the chlorides would stay in place and hold the structure together. Accordingly, the essential structural units of RHM would hold up in solution. (Atwood Testimony, 7/20/09 Tr. at 64:7-11; Atwood Testimony, 7/21/09 at 245:14-246:1, 263:8-11; Atwood Testimony, 7/28/09 Tr. at 1124:16-1125:4, 1138:6-1139:5, 1161:1-8; PLT 378-0027.) 61. The ropivacaine cations in RHM have a special shape. The ropivacaine cations in a structural RHM unit have a xylidine ring to the right and a piperidine ring to the left that do not interact well with water. For bulk water to penetrate the structural RHM unit, the water must fight through the hydrophobic matter and then displace the water that is already well anchored inside the structural RHM unit. (Atwood Testimony, 7/20/09 Tr. at 58:11-16, 66:5-12; PLT 378-0027.) 62. For a simple compound like sodium chloride, “dissolving” a solid will result in complete disassociation. This not the case for a complex organic compound like RHM. When RHM is “dissolved,” the appearance of the solid goes away but the essential structure does not break up. When speaking about RHM, “dissolve” does not mean that the particles disassociate or break up. (Atwood Testimony, 7/21/09 Tr. at 237:14-23, 250:14-18.) 63. Certain of the structural elements of RHM subsisting in solution would contain “unit cells” that are the building blocks of a crystal lattice. The structural elements of RHM surviving in solution may combine to form additional “unit cells,” which is what occurs when RHM is harvested from a solution through crystallization (or some other method). (Atwood Testimony, 7/21/09 Tr. at 243:23-244:20, 261:14-20.) 64.Navinta’s U.S. Patent Application Publication No. U.S.2006/0276654 A1 (“the '654 Application”) indicates that when a solution of RHM is cooled down it crystallizes quickly. This result indicates that the essential structural units of RHM subsist in solution and that the process of crystallization quickly organizes these already-existing structural units into a crystal. (Atwood Testimony, 7/20/09 Tr. at 56:12-57:2.) “(S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride. ” 65. This disputed term in claim 1 shall be construed to mean a compound with an (s)-enantiomer with an optical purity of more than 99.0%. 66. “Optical purity” is a function of how much more of one enantiomer there is than of another enantiomer. In the (S)(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride compound recited in claim 1 of the '086 Patent, the “(S)” denotes that the compound is the “S” enantiomer. The “(-)” denotes that the compound has some level of optical purity. (Atwood Testimony, 7/20/09 Tr. at 68:18-69:3; Atwood Testimony, 7/21/09 Tr. at 231:17-20.) See also Ortho-McNeil Pharm., Inc. v. Myland, Labs., Inc., 348 F.Supp.2d 713, 725-26, 729 (N.D.W.Va.2004) (where claim referred to “S(-)” enantiomer of levofloxaein but intrinsic record did not claim or identify a minimum level of optical purity, court construed claim to cover substantially optically pure levofloxaein and held that person skilled in the art would understand “S(-)” to require substantial optical purity). 67. A construction that “the compound” of claim 1 has an optical purity of more than 99.0% is consistent with other claims of the '086 Patent. For example, Claim 3 states that “the compound” contains “less than 0.5% by weight of the corresponding (R)~( + )-enantiomer.” This indicates that greater than 99.5% of the (S)-(-) enantiomer is present, giving the compound an enantiomeric purity of greater than 99.5%. This translates into an optical purity of more than 99%. 68. The '086 patent specification indicates that the patent achieves multiple and different objectives, one being a compound that is optically pure, another being the compound in the form of its monohydrate. '086 Patent, PLT 1 at col. 1, lines 32-35. 69. The '086 applicant emphasized the optical purity of the claimed compound during the prosecution history of the '086 patent. The applicant pointed out to the Patent Office Examiner that WO 085/00599 to Thuresson disclosed a compound that is “neither hydrated nor optically pure,” while further noting that “the claimed compound [i.e., the (S)-enantiomer] was the only compound prepared having an optical purity of over 99.0%.” (PLT 4 at p. 72; Atwood Testimony, 7/20/09 Tr. at 31:22-32:3, 78:3-6.) 70. The originally filed application for the '086 Patent describes (S)-(-)-l-propyl0.2',6'-pipecoloxylidide hydrochloride as having an optical purity of greater than 99%. Original claim 3 stated: “Compound according to claim 1 characterized in that it contains less than 0.5% by weight of the corresponding D-enantiomer.” This also translates into an enantiomeric purity of greater than 99.5% and an optical purity of greater than 99.0%. (PLT 4-0020.) “the compound according to claim 1” 71. Claim 2 of the '086 Patent states: “The compound according to claim 1, wherein it is substantially optically pure.” ('086 Patent 4:13-14.) Claim 3 of the '086 Patent states: “The compound according to claim 1, wherein it contains less than 0.5% by weight of the corresponding (R)-( + )-enantiomer.” ('086 Patent at 4:15-17.) Claim 6 of the '086 Patent states: “A method for inducing local anesthesia, which comprises administering to mammals including man needing local anesthesia an anesthetizing amount of the compound according to claim 1.” ('086 Patent, PLT 1 at 4:35-38.) 72. The phrase “the compound according to claim 1,” as used in claims 2, 3 and 6 of the '086 patent shall be construed to refer to the optically pure compound of Claim 1: (S)-(-)-l-propyl-2' ,6 '-pipecoloxylidide hydrochloride. This limitation does not refer to the “compound in the form of its monohydrate” as specified in Claim 1. (Atwood Testimony, 7/20/09 Tr. at 74:6-75:11, 78:12-20; Gawley Testimony, 7/23/09 Tr. at 682:5-22; PLT 378-0029.) 73. The plain language of claims 1-3 indicates that the “compound according to claim 1” is not RHM. Claim 1 is divided into two clauses. The first is “(S)-(-)-lpropyl-2',6'-pipecoloxylidide hydrochloride,” and the second is “wherein the compound is in the form of its monohydrate.” Similarly, Claims 2, and 3 are divided into two clauses, the first of which in both claims is “The compound according to claim 1.” The second clause in Claim 2 reads “wherein it is substantially optically pure” and the second clause in Claim 3 reads “wherein it contains less than 0.5% by weight of the corresponding (R)-( + )- enantiomer.” Thus, in each of these three claims, the first clause announces a particular compound. The second clause refers to a compound identified in the first clause, and then adds a limitation to that compound. As exemplified by claim 1, the compound identified in the first clause is the optically pure compound of claim 1:(S)— (~)-l-propyl-2',6'-pipecoloxylidide hydrochloride. 74. Use of the phrase “the compound” in the second clause of claim 1 indicates an antecedent basis in the claim. Thus “the compound” referenced in the second clause of claim 1 can only refer to (S) — (—)—1— propyl-2', 6'-pipeeoloxylidide hydrochloride, not that compound in the form of its monohydrate. See AmeriFab, Inc. v. Voest-Alpine Indus., Inc., 2005 WL 1827907, at *9 (S.D.Ind. July 29, 2005) (holding that the phrase “a method of cooling the interior wall of an electric-arc furnace” provides “an antecedent basis for the claim’s reference to ‘the electric-arc furnace’ in elements two and three” of the disputed claim); Robert C. Faber, Landis on Mechanics of Patent Claim Drafting § 10:7.4 at 10-44 (2007) (“When a previously identified element or step is repeated, it is introduced by a definite article ‘the’ or ‘said.’ ”). 75. When claims 2, 3 and 6 use the phrase “the compound according to claim 1,” the rules of claim construction require that the term “compound” as used in those claims be given the same meaning that “compound” has in Claim 1. Because the term “the compound” in Claim 1 only refers to optically pure (S)-(-)-l-propyl2',6'-pipecoloxylidide hydrochloride, this same construction must be applied to claims 2, 3 and 6. See Rexnord Corp. v. Laitram Corp., 274 F.3d 1336, 1342 (Fed. Cir.2001) (“A claim term should be construed consistently with its appearance in other places in the same claim or in other claims of the same patent.”); Phonometrics, Inc. v. Northern Telecom Inc., 133 F.3d 1459, 1465 (Fed.Cir.1998) (“A word or phrase used consistently throughout a claim should be interpreted consistently.”). 76. The specification teaches that the '086 patent claims an invention of optically pure (S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride that is distinct from the invention of that compound in the form of its monohydrate. Indeed, the '086 specification teaches that the three composition claims of the '086 Patent are directed to different objectives. Claim 1, by claiming the monohydrate form, satisfies the objective of a stable compound. Claims 1, 2, 3, and 6, by claiming optically pure (S) — (—)—1— propyl-2' ,6 '-pipecoloxylidide hydrochloride, satisfy the other objective of obtaining a product consisting of the substantially pure (S)-( -) enantiomer. B. Infringement Analysis 77. Submission of an ANDA is an act of patent infringement if the ANDA seeks approval for a drug that is claimed in a patent or the use of which is claimed in a patent. 35 U.S.C. § 271(e). 78. Determination of infringement is a “two-step process, wherein the court first construes the claims and then determines whether every claim limitation, or its equivalent, is found in the accused device.” Roche Palo Alto LLC v. Apotex, Inc., 531 F.3d 1372, 1377 (Fed.Cir.2008). 79. In a Hatch-Waxman infringement case, the proper infringement inquiry focuses on the actual product that will enter the market upon FDA approval. Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 1569 (Fed. Cir.1997) (court “must focus on what the ANDA applicant will likely market if its application is approved”); Ben Venue Labs. v. Novartis Pharm. Corp., 146 F.Supp.2d 572, 579 (D.N.J.2001) (“the statute requires that an infringement inquiry be focused on what is likely to be sold following FDA approval, not necessarily on the ANDA itself’). In analyzing infringement in a Hatch-Waxman case, “the Court must look to the whole of the product, which means considering its ultimate useable state, as well as the ANDAcontemplated process and compound.” EKR Therapeutics, Inc. v. Sun Pharm. Indus., Ltd., 633 F.Supp.2d 187, 199 (D.N.J.2009) (determining that infringement analysis should include state of drug at point of administration). 80. A comparison between an accused product and a commercial embodiment of a patented product can be used to establish infringement where the commercial product demonstrates the presence of the relevant claim limitations. Glaxo Group, Ltd. v. TorPharm, Inc., 153 F.3d 1366, 1374 (Fed.Cir.1998). 81. Indirect infringement may be established by demonstrating either (1) inducement of infringement, or (2) contributory infringement. 35 U.S.C. § 271(b) and (c); AquaTex Indus., Inc. v. Techniche Solutions, 419 F.3d 1374, 1379-80 (Fed.Cir. 2005). 82. A party is liable for inducement of infringement if it is shown that: (1) another party directly infringes the claim; (2) the party intentionally encourages the acts that constitute direct infringement; and (3) the party knows or should know that its actions will cause direct infringement. 35 U.S.C. § 271(b); DSU Med. Corp. v. JMS Co., Ltd., 471 F.3d 1293, 1305-06 (Fed.Cir. 2006) (en banc). 83. The trier of fact considers the totality of the circumstances in determining whether a party is liable for inducement of infringement, recognizing that inducement can be “established through circumstantial evidence.” Broadcom Corp. v. Qualcomm, Inc., 543 F.3d 683, 699 (Fed.Cir. Sept. 24, 2008) (“the district court did not err in instructing the jury to consider ‘all of the circumstances’ ”). 84. The encouraging actions need not be communicated to the direct infringer. Ricoh Co., Ltd. v. Quanta Computer, Inc., 550 F.3d 1325, 1341-42 (Fed.Cir. 2008). See also Dennison Mfg. Co. v. Ben Clements & Sons, Inc., 467 F.Supp. 391, 428 (S.D.N.Y.1979) (inducement may be found where defendant does not actually instruct ultimate users of the product in its use, if the intended use of the product is readily apparent). 85. The U.S. Supreme Court has held that “instructing how to engage in an infringing use” constitutes “active steps” to “encourage direct infringement.” Metro-Goldwyn-Mayer Studios Inc. v. Grokster, Ltd., 545 U.S. 913, 936, 125 S.Ct. 2764, 162 L.Ed.2d 781 (2005). 86. A defendant who is aware of a patent and supplies a product to a customer with instructions on how to use the product, which instructions when followed lead to infringement, encourages acts which constitute direct infringement. Minn. Mining and Mfg. Co. v. Chemque, Inc., 303 F.3d 1294, 1305 (Fed.Cir.2002). See also Biotec Biologische Naturverpackungen GmbH & Co. v. Biocorp, Inc., 249 F.3d 1341, 1351 (Fed.Cir.2001) (defendant induced infringement by providing instructions to customers on how to use a product in a manner that constituted direct infringement). 87. Statements in a package insert that encourage infringing use of a drug product are alone sufficient to establish intent to encourage direct infringement. AstraZeneca LP v. Apotex, Inc., 623 F.Supp.2d 615 (D.N.J.2009) (where patent claimed once daily dosing and accused ANDA product was indicated for twice daily dosing, court found statements in package insert suggesting “downward titration” and “taper[] to the lowest effective dose” encouraged once daily dosing and were sufficient to evidence inducement). See also EKR Therapeutics, Inc. v. Sun Pharm. Indus., Ltd., 633 F.Supp.2d 187 (D.N.J.2009) (granting summary judgment of infringement, and determining that the court need not engage in traditional inducement analysis, based on express instructions in drug packaging); Alcon Labs., Inc. v. Bausch & Lomb, Inc., 52 U.S.P.Q.2d 1927, 1933-34 (N.D.Tex. 1999) (granting preliminary injunction against infringement of method claims in view of express indication of package insert); Bio Technology Gen. Corp. v. Duramed Pharms., Inc., 325 F.3d 1356 (Fed. Cir.2003) (reversing and remanding for factual determination of whether consumers using product in accordance with package instructions would infringe patent). 88. A party is liable for contributory infringement if the defendant: (1) sells or offers to sell a material component of a composition for use in a patented method; and (2) the component is not a staple article or commodity of commerce suitable for substantial non-infringing use. 35 U.S.C. § 271(c). 89. Navinta bears the burden of proving substantial non-infringing uses. University of California v. Hansen, 54 U.S.P.Q.2d 1473, 1480 (E.D.Cal.1999) (granting plaintiffs motion for summary judgment of contributory infringement because, “Aside from defendants’ statements that the slides can be used for other uses than diagnosing FIV and that ‘from time to time customers mention their intent’ to use the slides for another use, defendants have shown no facts indicating that anyone actually does use the slides for anything other than diagnosing FIV” (emphasis in original)); CFMT, Inc. v. Steag Microtech, Inc., 14 F.Supp.2d 572, 592 (D.Del.1998) (denied JMOL because jury had sufficient evidence to conclude that defendant contributed to infringement where plaintiff produced no evidence regarding substantial non-infringing use and defendant failed to offer “any evidence that customers use the Marangoni dryer in some non-infringing way”). 90. In analyzing whether something is “suitable for substantial non-infringing use,” the Court should consider whether the product infringes other patents in addition to the method of use patents asserted in the instant action. See Sony Corp. of Am. v. Universal City Studios, Inc., 464 U.S. 417, 104 S.Ct. 774, 78 L.Ed.2d 574 (1984) (in analyzing liability for contributory infringement, U.S. Supreme Court considered infringement of copyrights owned by non-parties to constitute an infringing use). a. The '086 Patent i. Navinta’s ANDA Product Infringes Claim 1 of the '086 Patent 91. Claim 1 of the '086 Patent states: “(S)-(-)-l-propyl-2',6'-pipecoloxylidide hydrochloride, wherein the compound is in the form of its monohydrate.” ('086 Patent, PLT 1 at 4:10-12.) Thus, claim 1 has two elements: (1) (S)-(-)-lpropyl-2', 6' -pipecoloxylidide hydrochloride, which has an optical purity of more than 99%, and (2) is in the form of its monohydrate. As set forth below, Navinta’s ANDA products have both of these elements, and, therefore, infringe claim 1. • Navinta’s ANDA Products Contain (S)(-)-l-propyl-2', 6'^pipecoloxylidide hydrochloride With an Optical Purity of More than 99% 92. Navinta’s Package Insert states that its “Ropivacaine Hydrochloride Injection is a sterile, isotonic solution that contains the enantiomerically pure drug substance.” (Newton Testimony, 7/24/09 Tr. at 829:25-830:2.) The ropivacaine base that Navinta uses to make its ANDA Products is essentially 100% enantiomerically pure. (PLT 72-0007.) If the base is 100% enantiomerically pure, the RHM that results from the manufacturing process for the ANDA Products will be 100% enantiomerically pure. (Atwood Testimony, 7/20/09 Tr. at 109:2-7; Newton Testimony, 7/24/09 Tr. at 818:12-15.) 93. Various Certificates of Analysis submitted by Navinta to the FDA, and provided by SMS Pharmaceuticals Ltd. and Emcure Pharmaceuticals Ltd., specify a finished product specification of not less than 99.5% optical purity. These same Certificates of Analysis confirm that the enantiomeric purity of both Navinta’s actual starting ropivacaine API and the final Navinta ANDA Products is essentially 100%. (PLT 72-0007; Atwood Testimony, 7/20/09 Tr. at 105:20-106:9; Gawley Testimony, 7/23/09 Tr. at 656:1-21.) 94. Other Navinta manufacturing documents confirm the essentially 100% enantiomeric and optical purity of the ANDA Products. A test on Batch VRVB 001 reported 99.94%. enantiomeric purity of 99.92%, and tests on batch number VRVC 002 reported the Navinta ANDA Products shows that the R-enantiomer was present in an amount of less than 0.08% and that the S-enantiomer was present in an amount of approximately 99.92%. (PLT 11-0448; PLT 11-0463; 3/3/09 Newton Depo. at 80:7-81:24, 96:1-16, 98:20-99:4.) 95. The essentially 100% enantiomeric purity of the Navinta ANDA Products indicates the ANDA Products are 100% optically pure. (Atwood Testimony, 7/20/09 Tr. at 151:12-15; 3/3/09 Newton Depo. at 27:23-28:21.) 96. Navinta’s ANDA Products are supplied as the “pure (S)-(-) enantiomer.” The Navinta ANDA Products do not contain any significant or even measurable quantity of racemate (R)-( +) enantiomer. (Atwood Testimony, 7/20/09 Tr. at 154:22-155:5; PLT 72-0002, 72-0004 and 72-0006.) Navinta’s certificates of analysis exhibit quality control and are based on an actual batch of a Navinta ANDA Product sample. Even though it is relatively easy to detect the R-( +) enantiomer, none was detected in Navinta’s batch. This indicates that racemization would not occur during the shelf life of Navinta’s ANDA Products. (Atwood Testimony, 7/21/09 at 267:3-268:1; PLT 72-0004.) 97. The optical purity of RHM in an aqueous solution will not change during the shelf-life of the drug, which the testing indicates is three to five years for RHM. (Atwood Testimony, 7/21/09 Tr. at 232:4-11.) 98. Statements made by Abraxis in its Patent Term Extent application regarding the possible racemization of Naropin are only a disclosure of a possibility, and it is an unlikely possibility. (Atwood Testimony, 7/21/09 Tr. at 235:1-5; PLT 277 at p. 6.) • Navinta’s ANDA Products Contain the RHM Composition Claimed in Claim 1 of the '086 Patent 99. In its original November 2006 ANDA filing, Navinta’s ANDA sought approval for solutions that contain enantiomerically pure “ropivacaine hydrochloride,” and water for injection, in single dose containers in 0.2%, 0.5% and 1.0% concentrations. (PLT 48-0002.) 100. According to Navinta’s current Package Insert Labeling, Navinta’s ANDA seeks approval for sterile isotonic solutions that contain enantiomerically pure “ropivacaine hydrochloride,” and water for injection. The Labeling calls the ANDA Products “Ropivacaine Hydrochloride” and “Ropivacaine Hydrochloride Injection.” (PLT 156-0001.) 101. Navinta’s original and current Labeling each assert that Navinta’s “Ropivacaine Hydx’ochloride Injection” products contain ropivacaine hydrochloride, which is chemically described as “S(-)-l-propyl2',6'-pipecoloxylidide hydrochloride.” (PLT 48-0002; PLT 156-0001.) 102. The ingredients of the Navinta ANDA Products are non-hygroscopic ropivacaine base, hydrochloric acid, sodium hydroxide as a pH adjusting agent, sodium chloride as an isotonic agent, water for injection as a vehicle, and hydrochloric acid or sodium hydroxide as a pH adjusting agent. (PLT 39-0002, 39-0003, 39-0004; Atwood Testimony, 7/20/09 Tr. at 93:2-7; 3/3/09 Newton Depo. at 171:20-172:1,173:20-174:3.) 103. Batch Manufacturing Records in Navinta’s ANDA describe the complete procedures for manufacturing the accused ANDA Products. (PLT 60, 62, 251, 252; Newton Testimony, 7/23/09 Tr. at 778:21-23.) 104. The manufacturing process disclosed in Navinta’s ANDA for the ANDA Products includes these steps: • Create an aqueous solution out of hydrochloric acid and water; • Add ropivacaine base and stir to create a clear solution; • Add an excess of hydrochloric acid and stir to create a homogenous solution; • Add sodium hydroxide to adjust pH; • Add water for injection as a vehicle and stir; • Add sodium chloride, stir, and adjust pH; and • Filter the solution. (Newton Testimony, 7/23/09 Tr. at 781:6-16.) 105. Water is a “vehicle” in Navinta’s ANDA Products. A “vehicle” is a carrier. It is not an active ingredient; it does not have any chemical reactions with the pharmaceutical ingredient. It is a way of delivering the active ingredient and perhaps certain excipients into the system. (PLT 51-0003; Atwood Testimony, 7/20/09 Tr. at 93:8-20, 108:6-14; Newton Testimony, 7/24/09 Tr. at 834:6-9; Dave Testimony, 7/27/09 Tr. at 989:23-25; 3/3/09 Newton Depo. at 61:25-62:2,159:24-160:5.) 106. The manufacturing method disclosed in Navinta’s ANDA creates a Navinta ANDA product that is an aqueous solution of RHM. In the key step of 4.9.2 (some Navinta Batch Records identify this same step as 4.6.13), ropivacaine base is added to a hydrochloric acid solution and stirred until a clear solution forms. RHM is created at step 4.9.2 — by this time the ropivacaine base has all been reacted to RHM. (PLT 62-0029; Atwood Testimony, 7/20/09 Tr. at 109:8-110:4; Atwood Testimony, 7/28/09 Tr. at 1127:7-1128:8; PLT 60-0030, 251-0035, 252-0036, 378-0050 to 378-0052.) 107. When ropivacaine base is added to a solution of hydrochloric acid and water, the base immediately interacts with the acid. A chemical reaction occurs in which the acid transfers a hydrogen atom to the ropivacaine base. The positively charged hydrogen, referred to as a proton, binds to the piperdine ring, resulting in a ropivacaine cation and a chloride anion. (Atwood Testimony, 7/28/09 Tr. at 1127:9-14, 1127:19-22,1129:19-23.) 108. A consequence of the reaction between hydrochloric acid and ropivacaine base is to increase the solubility of the ropivacaine base, exposing the carbonyl oxygen and amide proton (the parts of the ropivacaine base that interact favorably with water) to water. Once a water molecule from the surrounding solution locks into this key position, it forms a strong hydrogen bond with the ropivacaine hydrochloride, and the essential unit structure of RHM is formed. This essential unit structure is capable of binding with other nearby structures, due to favorable interactions between the structures. (Atwood Testimony, 7/28/09 Tr. 1127:23-1128:6, 1129:5-9, 1129:15-18,1130:2-3, 9-11.) 109. Abraxis’s scientific testing verified the presence of RHM in Navinta’s ANDA products. Abraxis engaged Dr. Leonard J. Chyall, Ph.D., a principal at SSCI, a division of Aptuit, Inc., and others working under Dr. Chyall’s direction (individually or collectively, hereafter “Aptuit”), to determine whether Navinta’s ANDA Produets contain RHM. (Chyall Testimony, 7/21/09 at 276:4-12.) 110. Dr. Chyall and his colleagues conducted their tests at Aptuit’s laboratory in West Lafayette, Indiana. (Chyall Testimony, 7/21/09 at 274:8-20-275:17-23.) 111. X-ray powder diffraction (“XRPD”) is an established, sensitive technique scientists can use to, among other things, determine the identities of molecules, their corresponding 3-dimensional structures, and the bonding that exists between molecules. An XRPD pattern is unique to the chemical being studied and serves as a “chemical fingerprint” that scientists can interpret or compare to an XRPD pattern of a reference sample. (Atwood Testimony, 7/20/09 Tr. at 123:25-124:5; Chyall Testimony, 7/21/09 at 276:15-23.) 112. Aptuit performed XRPD testing on three sets of samples: (1) Samples of the 0.2%, 0.5% and 1.0% strengths of APP Pharma’s Naropin drug products; (2) Samples of the 0.2%, 0.5% and 1.0% ANDA Products that Navinta produced during discovery; and (3) Samples of 0.2%, 0.5% and 1.0% solutions generated by Aptuit by partially simulating the critical steps (i.e., step 4.9.2) of the manufacturing process Navinta has represented its collaborators will use to prepare the ANDA Products. 113. Aptuit compared the XRPD patterns for these samples to an XRPD pattern Aptuit obtained from RHM reference material that Aptuit sourced from the U.S. Pharmacopeia (USP). Aptuit independently verified that the USP reference sample was the solid monohydrate form of ropivacaine hydrochloride by comparing the XRPD pattern of the USP sample to a computer-generated XRPD pattern based on published information regarding the structure of RHM. (PLT 123; Atwood Testimony, 7/20/09 Tr. at 123:17-21; Chyall Testimony, 7/21/09 at 277:16-278:1, 281:8-282:6, 294:23-297:18; PLT 60-0030; PLT 382-0023.) 114. Aptuit placed a portion of each sample in an open glass Petri dish and allowed each sample to naturally evaporate at ambient temperature in a fume hood. This process removed the carrier or vehicle water. Aptuit subjected the remaining solid material to XRPD testing. (Atwood Testimony, 7/20/09 at 125:7-9; Chyall Testimony, 7/21/09 at 278:12-24, 279:7-25.) 115. Aptuit found that RHM was present in each of the 0.2%, 0.5% and 1.0% samples of Naropin. (PLT 125; Atwood Testimony, 7/20/09 Tr. at 127:15-22; Chyall Testimony, 7/21/09 at 284:20-285:12, 287:10-288:3, 288:4-9.) 116. Aptuit found that RHM was present in each of the 0.2%, 0.5% and 1.0% samples generated by partially replicating Navinta’s disclosed method of manufacture for the ANDA Products, thus indicating that a monohydrate of ropivacaine hydrochloride is formed in an aqueous solution during the manufacture of Navinta’s ANDA Products. (PLT 127; Atwood Testimony, 7/20/09 Tr. at 131:19-132:10; Atwood Testimony, 7/28/09 Tr. at 1109:14-19; Chyall Testimony, 7/21/09 at 298:19-299:11, 300:21-301:2, 301:6-19, 301:22-302:9.) 117. Aptuit found that RHM was present in the 0.2% and 0.5% samples of the ANDA Products in an amount that was identical to the results for the corresponding Naropin samples. (PLT