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Abraxis Bioscience, Inc. v. Navinta

August 3, 2009

ABRAXIS BIOSCIENCE, INC. PLAINTIFF,
v.
NAVINTA, LLC, DEFENDANT.



The opinion of the court was delivered by: Pisano, District Judge.

OPINION

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"),*fn1 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. Defendant also counterclaimed for a declaration of noninfringement of the '086, '524 and '489 patents.*fn2

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.*fn3

I. 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 Picard, 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 Plaintiff's 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 Sandoz 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 "Ropivacaine 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% enantiomerically 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)-(-)-1-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)-(-)-1-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 R-enantiomer's lesser solubility than the desired S-enantiomer. Thus, Dr. Sandberg created in a solution both the R and the S-enantiomers 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)-(-)-1-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 cardiotoxicity," 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 HCl or (S)-(-)-1-propyl-2',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)-(-)-1-propyl-2',6'- pipecoloxylidide 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)-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride, wherein the compoundis in the form of its monohydrate;" and (ii) "(S)-(-)-1-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. 1995). 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 (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. Lubrizoil 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)-(-)-1-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 Plaintiff's 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 a 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. US 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)-(-)-1-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)-(-)-1-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. Mylan Labs., Inc., 348 F. Supp. 2d 713, 725-26, 729 (N.D. W. Va. 2004) (where claim referred to "S(-)" enantiomer of levofloxacin but intrinsic record did not claim or identify a minimum level of optical purity, court construed claim to cover substantially optically pure levofloxacin 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 ...


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