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IN RE OMEPRAZOLE PATENT LITIGATION

United States District Court, S.D. New York


May 19, 2004.

In re OMEPRAZOLE PATENT LITIGATION

The opinion of the court was delivered by: BARBARA JONES, District Judge

Opinion

I. Introduction *fn1

The consolidated trial in this case addressed claims raising issues of infringement, invalidity, and unenforceability asserted in eight different lawsuits involving four groups of Defendants. On October 16, 2002, this court issued an Opinion and Order that decided the issues raised during Phase I and Phase III of the consolidated trial in this case and involved all parties to this suit. See In re Omeprazole Patent Litig., 222 F. Supp.2d 423 (S.D.N.Y. 2002) (hereinafter Omeprazole I), m naff'd, (Fed. Cir. Dec. 11, 2003) (unpublished decision) (hereinafter Omeprazole II). This decision resolves the issues that were presented in Phase II and Phase IV of the trial and that pertain only to claims pending between Plaintiffs, referred to collectively as "Astra," and Defendant Andrx Pharmaceuticals, Inc. ("Andrx"). Phase II of the trial of this action presented proof on infringement and validity of U.S. Patent Number 6,013,281 (the "`281 patent"), which is owned by Astra. Phase IV of the trial of this action presented proof on Andrx's defenses of inequitable conduct and unclean hands. This case was tried to the court sitting without a jury. The court has considered trial testimony, deposition testimony, exhibits, and pre-trial and post-trial briefing submitted by the parties. The court has made determinations as to the relevance and materiality of the evidence and assessed the credibility of each witness. Upon the record before the court, pursuant to Federal Rule of Civil Procedure 52(a), the court finds the following facts to have been proven by the appropriate standard of proof and sets forth its conclusions of law.

  For the reasons stated below, the court finds the following: Defendant Andrx literally infringes claims 1, 2, 3, 7, 9, 16 and 20-21 of the `281 patent. Claims 1, 2, 3, 7, 16 and 20-21 of the `281 patent are invalid as anticipated. Claim 9 of the `281 patent is invalid as obvious. The asserted claims of the `505 and `230 patents are not unenforceable against Andrx. II. Phase II

  A. Claim Construction of the `281 Patent

  Astra filed the application for the `281 patent based on PCT Application No. PCT/SE96/00161, claiming priority on a Swedish patent application filed on February 9, 1995. The `281 patent addresses methods of making a pharmaceutical dosage form containing proton pump inhibitors, like omeprazole, which are useful for inhibiting gastric acid secretion.*fn2 (See, e.g., P3, col. 4: 41-43; Langer Tr. 5240: 2-11.) Those drugs are susceptible to degradation in acidic reacting and neutral media. (See, e.g., P3, col. 4:58-60.) Therefore, the proton pump inhibitor preferably is protected from contact with acidic reacting gastric juice so that it is transferred intact to the portion of the gastrointestinal tract where the pH is higher and where absorption of the proton pump inhibitor can occur. (See, e.g., id., col. 4: 64 — col. 5 : 4.) Formulation of proton pump inhibitors such as omeprazole is preferably accomplished through the use of a dosage form that has, among other things, a core containing an alkaline reacting compound ("ARC"), an enteric coating, and a separating layer between the core and the enteric coating. (See id., col. 5:5-11.) The `281 patent claims processes for forming a separating layer. (See, e.g., id., col. 5: 44-49.) Specifically, the `281 patent concerns a process for creating a separating layer between the core and the enteric coating by causing an in situ reaction involving the applied enteric-coating material and the ARC in the substrate being coated. (See, e.g., id. ) That reaction creates a salt form of the enteric-coating polymer(s) that is situated between the core and the enteric-coating layer. Thus, the result of the `281 process is to manufacture a formulation for a proton pump inhibitor like that claimed in the `505 and `230 patents, which has three distinct layers. (See id., Ex. C.)

  According to the claims of the `281 patent, one prerequisite for forming the in situ layer is the concentration of the ARC in the substrate, which must be more than 0.1 mmol/g dry ingredients in the alkaline-containing part of the core. (See, e.g., id., claim 1 and Certificate of Correction.) In addition, the specification of the `281 patent teaches that process variables used during the enteric-coating process must be adjusted to take into account the particular enteric coatings and equipment. (Langer Tr. 5240:16-5241:11.) The `281 patent states that "process parameters such as inlet air temperature, air flow, atomizer air flow and spraying rate are adjusted with respect to the equipment used for the process as well as the specific enteric coating polymer(s)." (P3, col. 8:51-55.) For example, the `281 patent teaches that when using hydroxypropyl methylcellulose acetate succinate LF ("HPMCAS LF"), the following process information is included for applying the enteric coating to a tablet: 100 grams of core material was coated at a rate of 3.8 grams per minute, inlet air temperature was 42° Celsius and flow was set to 40 Nm3/hr, atomizer airflow was 2.1 Nm 3/hr obtained with a pressure of 1.7 bar. In addition, after enteric coating, the inlet air temperature was raised to 60° Celsius, and the product was kept at that temperature for approximately five minutes. (See id., col. 11:41-65.) The `281 patent also explains that the in situ layer has certain characteristics: it shows intense fluorescence when analyzed by confocal laser scanning microscopy ("CLSM") (see id., col. 5:60 — col. 6:3; see also Lovgren Tr. 1763:19-1764:1), and the salt of the enteric-coating polymer that forms the separating layer is not soluble in acetone (see P3, col. 9:42-48).

  The `281 patent contains 21 claims. Astra asserts claims I, 2, 3, 7, 9, 16 and 20-21 of the `281 patent against Andrx. Claim 1, an independent process claim, is the only independent claim contained in the `281 patent. The remaining asserted claims of the `281 patent are process claims that depend on claim 1, but then add other features or specify requirements applicable to particular aspects of or ingredients used in the process. The first claim of the `281 patent requires the following process:

A process for preparing an oral pharmaceutical formulation comprising the steps of: forming a core material comprising a proton pump inhibitor and at least one alkaline reacting compound, wherein the concentration of the alkaline reacting compound is more than 0.1 mmol/g dry ingredients in the alkaline containing part of the core material, and applying an enteric coating polymer so as to surround the core material thereby forming in situ a separating layer as a water soluble salt product between the alkaline compound and the enteric coating polymer.
  (P3, col. 15:65 — col. 16:9, Certificate of Correction.) The only terms in dispute for the purposes of claim construction appear in the first claim. Claim construction disputes exist with regard to the following two terms found in the claims of the `281 patent: "in situ " and "separating layer." For a detailed description of the legal standards applicable to the court's interpretation of the claim terms at issue in this case, see Omeprazole I, at 441-44.

  1. The Term "In Situ "

  According to the claim language itself, the core material lies on one side of the separating layer, while the enteric coating lies on the other side: "thereby forming in situ a separating layer as a water soluble salt product between the alkaline compound and the enteric coating polymer." (P3, col. 16:7-9 (emphasis added).) "In situ" is a scientific or technical term of Latin origin that literally means "in place." or, in the original location. (Astra's Cl. Constr. Mem. of 11/5/01, Ex. 31, McGraw Hill Dictionary of Scientific and Technical Terms, 5th ed. at 1023 (1994).) A person of ordinary skill in the art would understand the term "in situ " to have that meaning. (See Langer Tr. 5245:19-5246:1.)

  "In situ" in the context of claim 1 of the `281 patent refers to the formation of the separating layer within the formulation, as compared to its separate application, a process covered by the claims of the `505 and `230 patents. This construction of "in situ " is supported by the specification:

According to a second aspect [,] the present invention provides a process for the manufacture of two functionally different layers in one manufacturing step. By such a process a separating layer comprising a water soluble salt of an enteric coating polymer is obtained, as well as the enteric coating layer itself.
According to said process the separating layer is formed by an in situ reaction between the enteric coating polymer and the alkaline core material comprising the pharmaceutically active substance.
(P3, col. 5:44-58.) Thus, the separating layer is created within the formulation-in place-by the chemical reaction of an alkaline reacting compound and the enteric coating.

  The patent specifications repeatedly describe the separating layer as forming "spontaneously" during the enteric-coating process. (See id., col. 9:49-50 ("separating layer is spontaneously formed in situ during the process"), col. 10:32-33, col. 11:2-3, col. 12:6-7, col. 13:46-47, col. 14:45-46.) Citing the testimony of its expert Dr. Banakar concerning that language in the specification, Andrx argues that a person of ordinary skill in the art of pharmaceutical formulation would have understood the term "forming in situ " to mean forming immediately during the enteric-coating process. (See Banakar Tr. 5217:16-17 ("The plain meaning of the word `spontaneous' is right away, immediately.").) However, there is no temporal requirement in either the claims or the specification for when the separating layer must form. The fact that the specification refers to the separating layer forming spontaneously means that it forms without additional human effort. (Langer Tr. 5251:14-23.)

  2. The Term "Separating Layer"

  Andrx argues that the terms "subcoating" and "separating layer" are used interchangeably throughout the `505, `230 and `281 patents, so that both terms should be accorded the same definition throughout. (See Andrx Cl. Constr. Mem. of 11/5/01, at 22.) In fact, the terms "subcoating" and "separating layer" are not used interchangeably in the `505 and `230 patents. The court has analyzed the ordinary meaning of the terms "subcoating" and "separating layer" in detail in the context of construing the term "subcoating" as used in the claims of the `505 and `230 patents. See Omeprazole I, at 464-68. The court defined the term "subcoating" to mean "a layer that is physically on and conforms to the contours of a core and is underneath another layer-the enteric coating." Id. at 464. The court also found that the specifications of the `505 and `230 patents make clear that the subcoating required by the claims of the `505 and `230 patent is a type of separating layer, as that term is used in the specifications of the `505 and `230 patents. Id. at M465. Thus, the subcoating required by the claims of the `505 and `230 patents is a species of the more generic term "separating layer" as used in the `505 and "230 patents, id., and the terms "subcoating" and "separating layer" do not have the same definition in the `505 and `230 patents.

  Like its use in the `505 and `230 patents, the term "separating layer" as used in the `281 patent is a generic term, which includes different species like subcoatings and capsules. As the `281 patent explains, there are different kinds of separating layers:

The discoloration can be avoided by applying some type of separating layer between the core material. . . .
Thus, there are a lot of patent applications describing such a separating layer between a core material comprising the pharmaceutically active substance and an enteric coating layer. See for instance, U.S. Pat. No. 4,786,505. . . .
(P3, col. 5:18-25 (emphasis added).) The `505 patent identifies gelatin capsules as one kind of separating layer and subcoatings as another. See Omeprazole I, at 465-66. (See also Pl, col. 4:8-11.) The difference then, is not the definition that the patents ascribe to the term `'separating layer," which has the same meaning in all three patents. Rather, the difference is in the choice of claim language. The `505 and `230 patents claim only the species of separating layer that is a subcoating, while the `281 patent contains broader claim language that covers not only subcoatings but all species of separating layers.*fn3

  Like the definition Andrx proposed for the term "subcoating" in the claims of the `505 and `230 patents, the definition Andrx proposes for the term "separating layer" in the claims of the `281 patent would impose numerous additional requirements on the separating layer that are not stated in the claims. See Omeprazole I, at 470-71. For example, Andrx's construction of the term "separating layer" would require that the layer be continuous so that the core and the enteric coat do not come into contact with each other. (See Andrx Cl. Constr. Mem. of 11/5/01, at 21-22; Andrx Cl. Constr. Reply Mem. of 11/12/01, at 8.) Andrx argues that if the separating layer is not continuous, then it cannot perform its intended function, which is to keep the omeprazole in the core from coming into contact with the enteric coating. (Andrx Cl. Constr. Mem. of 11/5/01, at 22.) The court has already decided that, as understood by a person of ordinary skill, a "sub-coating" need not exhibit these qualities that are not stated in the claims. See Omeprazole I, at 539-40. Similarly, the "separating layer" of the `281 patent, as understood by those of ordinary skill, may have imperfections.

  Andrx also argues that evidence presented during Phase II of the trial demonstrated that the "separating layer" claimed by the `281 patent cannot contain that which it is "separating." (See Andrx Updated Proposed Findings of 5/30/03, at 5.) However, it is clear that the separating layer required by the claims of the `281 patent can contain components other than the enteric-coating polymer salt product itself. For instance, Example 1 of the `281 patent, which is one of the preferred embodiments of the invention and has the highest concentration of ARC in any exemplified core, employs an enteric-coating layer that contains HPMCAS as well as triethylcitrate, sodium laurylsulphate and talc. (P3, col. 8:65 — col. 9:51.) Persons skilled in the art would understand that each of those components are also present in the in situ layer generated by the claimed process, as well as in the enteric-coating layer. See Dow Chemical Co. v. Sumitomo Chemical Co., 257 F.3d 1364, 1378 (Fed. Cir. 2001) ("It is unlikely that an inventor would define the invention in a way that excludes the preferred embodiment, or that persons of skill in this field would read the specification in such a way."). The court cannot ignore this preferred embodiment when construing the term "separating layer;" therefore, the court finds that Andrx's proposed construction cannot be adopted. See id. ("It is axiomatic that claims, not the specification embodiments, define the scope of the protection. . . . However, it is also well established that a claim construction that excludes a preferred embodiment is rarely, if ever, correct.") (internal quotations and citations omitted); Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed. Cir. 1996).

  B. Infringement of the `281 Patent

  Andrx admits that its ANDA process meets all but one portion of claim 1 of the `281 patent, the clause that requires the in situ formation of a separating layer. (P270, Andrx Admission Nos. 8, 20; P271, Andrx's Responses and Supplemental Responses to Pls.' First Request for Admissions Concerning the `281 Patent Nos. 1, 3, 10, 12, 18; see also Tr. 5242:23-5245:4.) Andrx only disputes whether a separating layer is formed in its product. (Banakar Tr. 5323:7-11 (indicating that sole non-infringement position for Andrx is absence of separating layer).) The court's previous Order and Opinion set forth its findings of fact concerning the presence of an HPMCP-salt separating layer in the Andrx product. See Omeprazole I, at 529, 538-39 (finding that Andrx's product has a subcoating "composed of an HPMCP salt that is rapidly soluble in water and is a polymeric film forming compound"). Astra has proven that the Andrx ANDA product contains a separating layer. The only requirement above and beyond the court's findings with respect to Phase I is that Astra must prove that the HPMCP-salt layer forms in situ.*fn4

  After determining that the HPMCP-salt layer in fact existed, Dr. Davies considered how that salt layer formed. (Davies Tr. 836:16-22.) Dr. Davies identified the ingredients in Andrx's active layer that could react to form the salt layer. (Id. 836:23-837:5; see P1036 (Dem. Ex.) at 7.) The court credits Dr. Davies' opinion that the salt layer forms from an interaction between the HPMCP enteric coating and the disodium hydrogen phosphate ("DHP"). (See Davies Tr. 837:2-11.) Dr. Davies conducted a series of tests to confirm his initial opinion on how the HPMCP salt formed. (Id. 837: 12-844: 25.) Based on his review of Andrx's ANDA and his testing, Dr. Davies explained his understanding of how and when the HPMCP-salt layer forms in Andrx's ANDA product:

Well, I believe that it does form during the production process, as the particles . . . of the enteric coating are hitting the surface. . . . When that hits the surface, I believe that interacts to form the HPMCP salt at that time. It's during that process that I believe that it forms.
(Id. 1026: 22-1027: 11 (emphasis added); see also Langer Tr. 5248:11-16.) On the basis of this and other evidence presented at trial, the court finds that the HPMCP-salt layer forms in situ during the Andrx ANDA process. See also Omeprazole I, at 532-33 ("[A]n HPMCP-salt layer forms in the Andrx products as a result of a reaction between the DHP in the core and the HPMCP in the enteric coating."). Thus, the court concludes that Andrx's ANDA process literally infringes claim 1 of the `281 patent.*fn5 Claims 2 and 3 depend on claim 1 of the `281 patent and specify the proton pump inhibitor to be from different groups of compounds. Claim 2 of the `281 patent specifies that the proton pump inhibitor must be one of the compounds included within a recited chemical formula. (P3, col. 16:10 — col. 17:23.) Claim 3 reads: "The process according to claim I, wherein the proton pump inhibitor is omeprazole, an alkaline salt of omeprazole, a pure enantiomer of omeprazole or an alkaline salt of the enantiomer." (Id., col. 17: 24-27.) Andrx has not raised any additional claim construction disputes with respect to these claims, and the parties do not dispute that omeprazole satisfies the requirements of both claims 2 and 3. Andrx admitted that its product contains omeprazole. (P270, Admission No. 7; Trial Tr. 5248: 25-5249: 5.) Therefore, the court finds that Andrx's ANDA process literally infringes claims 2 and 3 of the `281 patent. Claim 7 covers "[t]he process according to claim 1, wherein the alkaline reacting compound is selected from the group consisting of an alkaline reacting organic compound, a hydroxide of an alkali metal, an alkaline salt of phosphoric acid, carbonic acid or silicic acid, and an alkaline ammonium salt." (P3, col. 17:38-42.) These ARCs include, among other things, a hydroxide of an alkali metal such as magnesium hydroxide, an alkaline salt of phosphoric acid such as disodium phosphate ("DHP"), and organic compounds such as meglumine. (Id., col. 6:63.) No additional claim construction disputes beyond those raised with respect to claim 1 have been raised with respect to claim 7. Like claim 7, claim 9 depends upon claim 1; however, claim 9 narrows the scope of ARCs listed in claim 7. Claim 9 calls for "[t]he process according to claim 1, wherein the alkaline reacting compound is an alkaline salt of phosphoric acid, carbonic acid or silicic acid." (Id., col. 18:3-5.) Again, no additional claim construction disputes have been raised. The disodium hydrogen phosphate in Andrx's products is an alkaline salt of phosphoric acid. (P270, Admission No. 31; Trial Tr. 5249:6-12.) Therefore, the court finds that Andrx's ANDA process literally infringes claims 7 and 9 of the `281 patent. —

  Claim 16 requires "[t]he process according to claim 1, wherein the enteric coating polymer a hydroxypropyl cellulose derivative." (P3, col. 18:26-27.) This claim specifies that the "enteric coating polymer" is one of the claims of hydroxypropyl cellulose-related polymers, such as hydroxypropyl methylcellulose phthalate ("HPMCP"). Andrx uses HPMCP as an enteric-coating polymer, and that material is a hydroxypropyl methylcellulose derivative. (P270, Admission No. 32; Trial Tr. 5249:13-17.) Therefore, the court finds that Andrx's ANDA process literally infringes claim 16 of the `281 patent.

  Claim 20 describes "[t]he process according to claim 1, wherein the core material further comprises a pharmaceutically acceptable excipient." (P3, col. 18:36-38.) This claim requires the presence of components in the core in addition to those required by claim 1. Such an additional component must be a "pharmaceutically acceptable excipient," including surfactants like sodium lauryl sulfate. (Id., col. 8:16, col. 9:37.) Andrx does not dispute that its product contains such an excipient in the core. Therefore, the court finds that Andrx's ANDA process literally infringes claim 20 of the `281 patent.

  Claim 21 covers "[t]he process according to claim 1, wherein the core material is in the form of a pellet or a plurality thereof." (Id., col. 18:39-40.) This claim requires the core to have a particular physical form. (Id., col. 12:13-59.) Andrx's core material, referred to by Andrx as "the Omeprazole Active Pellet" is in the form of a pellet, which may also be called a bead. (P270, Admission No. 6; Trial Tr. 5249:18-23.) Therefore, the court finds that Andrx's ANDA process literally infringes claim 21 of the `281 patent.

  C. Validity of the `281 Patent

  The `281 patent distinguishes the prior art of the `505 and `230 patents by focusing on the step of applying the separating layer that is described in the specifications of the `505 and `230 patents. The specification of the `281 patent describes the preparation detailed in the `230 patent as "contain [ing] an alkaline core material comprising the active substance, a separating layer, and an enteric coating layer." (P3, col. 5:9-11.) The `281 patent specification describes the `505 patent as teaching the application of "a separating layer between a core material comprising the pharmaceutically active substance and an enteric coating layer." (Id., col. 5:23-26.) The `281 patent explains that the prior art, including the `505 and `230 patents, "appl[ies] at least two different layers on a pellet core." (Id., col. 5:26-27.) According to the `281 patent, the prior art techniques of applying two different layers on the core "is rather complicated and there is a demand for finding new processes and formulations to simplify the manufacturing of such enteric coated articles." (Id., col. 5:28-30.)

  In the "SUMMARY OF THE INVENTION," the specification of the `281 patent explains: The present invention is characterized by the presence of a separating layer between an alkaline reacting core material comprising a pharmaceutically active acid labile substance and an enteric coating layer, wherein the separating layer comprises a water soluble salt of an enteric coating polymer.

 

According to a second aspect the present invention provides a process for the manufacture of two functionally different layers in one manufacturing step. By such a process a separating layer comprising a water soluble salt of an enteric coating polymer is obtained, as well as the enteric coating layer itself.
According to said process, the separating layer is formed by an in situ reaction between the enteric coating polymer and the alkaline core material comprising the pharmaceutically active substance.
(Id., col. 5:40-58 (emphasis added).) Thus, the `281 patent clearly and unmistakably distinguishes the claimed invention over the `505 and `230 patents because it claims that the prior art applied two different layers on the core to create the three-layered preparation, whereas the `281 patent achieved a three-layered preparation in only two processing steps.

  The file history of the `281 patent confirms that the claimed invention of the `281 is the discovery that a separating layer is formed as a result of the spontaneous chemical reaction between the alkaline core and the enteric coat rather than the separate step of applying the subcoating layer. Certain claims of the application that eventually matured into the `281 patent were initially rejected over the `230 patent, among others. (See Andrx Cl. Constr. App. of 11/5/01, Ex. F, `281 File History at 67-73.) The Patent Examiner found much of the subject matter of the `281 patent fully disclosed in the `230 patent. (Id.) To overcome that rejection, the inventors amended Claim 1 to include the language "thereby forming in situ." (Id. at 87.) The amendment states that "[t]he invention is based on the surprising discovery that a separating layer is formed in situ by a reaction between the enteric coating polymer and the alkaline reacting compound in the core material during the enteric coating process." (Id. at 93.) All that was changed by this amendment was the number of processing steps, not the characteristics of the required separating layer.

  Defendant Andrx argues that certain prior art renders this invention of the `281 patent asserted by Astra invalid for either lack of novelty or obviousness. Andrx's invalidity defense to Astra's claims of infringement under the `281 patent is based primarily on a process for formulating omeprazole developed by the Korean company Chong Kun Dan ("CKD") that was publicly disclosed more than a year before the relevant priority date, February 9, 1995. That process, as well as the ingredients used therein, was disclosed in CKD's patent application for public inspection, which was laid open by the Korean government on April 20, 1993, to enable members of the public to challenge its patentability (the "CKD Laid Open Patent Application" or the "CKD Application"). (See A323A; A325A; Shin Tr. 5440-49, 5471-72.) Astra's principal arguments in opposition to Andrx's anticipation defense are that (1) the CKD process was not disclosed in a "printed publication" and (2) the CKD Application does not disclose that the CKD process results in the formation of an in situ separating layer. As is discussed more fully below, the court finds claims 1, 2, 3, 7, 16 and 20-21 of the `281 patent invalid as anticipated by the CKD Laid Open Patent Application.*fn6 The court finds claim 9 of the `281 patent invalid as obvious in light of the prior art.

  1. Anticipation

  Astra challenges the publication status of the references relied upon by Andrx in support of its invalidity defense, including the CKD Laid Open Patent Application. To qualify as prior art, a reference must be a "printed publication" under the statutory definition of that term. The question of whether a document is a "printed publication" is a legal determination based on underlying issues of fact, which must be decided on a case-by-case basis. N. Telecom, Inc. v. Datapoint Corp., 908 F.2d 931, 936 (Fed. Cir. 1990). A document may be deemed a printed publication "upon a satisfactory showing that such document has been disseminated or otherwise made available to the extent that persons interested and [of ordinary skill] in the subject matter or art, exercising reasonable diligence, can locate it and recognize and comprehend therefrom the essentials of the claimed invention without need of further research or experimentation." In re Wyer, 655 F.2d 221, 226 (C.C.P.A. 1981); see MPEP §§ 901.05.II.C & 2129.01 ("If anyone can inspect or obtain copies of the laid open application, then it is sufficiently accessible to the public to constitute a "publication" within the meaning of 35 U.S.C. § 102(a) and (b).") (citing Wyer). Public availability may be proven by evidence of the regular practices of the repository institution concerning indexing and public availability of similar documents. See In re Hall, 781 F.2d 897, 899-900 (Fed. Cir. 1986) (no need to show a "specific date of cataloging and shelving before the critical date").

  The court finds that Andrx has established that the CKD Laid Open Patent Application was available to the public prior to the relevant priority date of February 9, 1995, by demonstrating that Korean law requires the KIPO to lay open patent applications, notify the public of such applications in the Patent Gazette, and provide copies of the applications to members of the public that request them.*fn7 KIPO is a governmental agency in Korea that examines patent and trademark applications and hears scope confirmation disputes at the trial and appellate levels. (Shin Tr. 5429:60-5430:5.) The Korean Patent Act in effect in 1993 provided that the KIPO "shall lay open the patent application in the Patent Gazette after one year and six months from the filing date of an application for a patent" unless the patent "has already been published." (A263A; Shin Tr. 5431:17-25, 5445:20-5446:2, 5446:21-25.) Under Korean law, the CKD Application was available and accessible to any member of the public who requested copies from the KIPO as of April 20, 1993, when it was "laid open" for public inspection and when the KIPO published a notice of the CKD Application in its Patent Gazette.*fn8 (A325A; Shin Tr. 5442:1-7, 5443:17-25, 5447:17-5448:19.) As of April 20, 1993, anybody interested in that application could go to the KIPO to "get a copy of the underlying patent application to question the validity of the patent application." (A325A at 1; Shin Tr. 5442:1-7, 5443:17-25, 5447:17-5448:19.) Moreover, the CKD Laid Open Patent Application was also referenced in the June 1993 edition of Pharma Koreana, a reference that included the name of the applicant, the country where the application was filed, and the application's identification number. (See A284 at 3.) Thus, on the basis of the evidence presented by Andrx at trial, the court concludes that the CKD Laid Open Patent Application constitutes a printed publication that was available before the priority date. See Wyer, 655 F.2d at 224 (holding laid-open Australian patent was a printed publication where microfilm copy was available to the public at patent office and abstract was published); see also Friction Div. Prods., Inc. v. E.I. DuPont De Nemours & Co., 658 F. Supp. 998, 1008 (D. Del. 1987) ("Cataloging a paper in a technical or scientific library makes the publication sufficiently accessible to those interested in the art to satisfy the requirements of § 102(b).") (citing Hall, 781 F.2d at 900 (holding single copy of thesis in German university library indexed by subject matter was publicly accessible printed publication)).

  Under the patent statutes, a patent is invalid if "the invention was . . . described in a printed publication in this or a foreign country . . . more than one year prior to the date of the application for patent in the United States." 35 U.S.C. § 102(b). "That which infringes if later anticipates if earlier." Brown v. 3M, 265 F.3d 1349, 1352 (Fed. Cir. 2001). A claim is anticipated if a single prior art reference under section 102(b) contains each element of the claim either expressly or inherently. Bristol-Myers Squibb Co. v. Ben Venue Labs, Inc., 246 F.3d 1368, 1374 (Fed. Cir. 2001). "A reference is no less anticipatory if, after disclosing the invention, the reference then disparages it." Bristol, 246 F.3d at 1378. "[T]he question whether a reference `teaches away' from the invention is inapplicable to an anticipation analysis." Id. Where a patent claims a genus, prior art disclosing even one species within the genus invalidates the entire claim. In re Gosteli, 872 F.2d 1008 (Fed. Cir. 1989).

  After considering all the testimony and the documents received into evidence, the court finds that Andrx has established by clear and convincing evidence that the inventions of claims 1, 2, 3, 7, 16 and 20-21 of the `281 patent are anticipated by the CKD Laid Open Patent Application. Each element of each claim of the `281 patent that Astra asserts against Andrx (with the exception of claim 9, which will be discussed below), was disclosed, either explicitly or inherently, in the CKD Application. Andrx proved that the functional elements of the processes disclosed in the CKD Application are identical to the preferred embodiment of the `281 patent (Example 1). In fact, the CKD Laid Open Patent Application discloses the principal ingredients of Example 1 of the `281 patent-the "best mode" of the `281 patent (P3 at col. 15: 59-60)-in the exact same proportions and for the exact same functions. (Compare P3, with A323A; see also A807; A809.) During his testimony, Andrx's expert Dr. Banakar painstakingly compared the words, terms and elements in each relevant claim asserted by Astra with the text of the CKD Application. He showed, both through his testimony (see Banakar Tr. 5299-5318) and through a detailed demonstrative (A719) that there is explicit identity between the disclosures in the CKD Application and each element of claims 1, 2, 3, 7, 16 and 20-21, save one: the `281 patent contains the language "thereby forming in situ a separating layer." Yet, other evidence presented by Andrx proves that the in situ formation of a separating layer is inherently disclosed in the CKD Application. Thus, the best that can be said of the invention of the `281 patent is that the inventors "discovered" that using the exact same method and ingredients as CKD exhibited a separating layer. However, the law is settled that "[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect." General Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 248-49 (1945); see Eli Lilly & Co. v. Barr Labs, Inc., 251 F.3d 955, 970 (Fed. Cir. 2001) (finding inherency established where effect of prior art was "natural result" in the vast majority of cases); Elan Pharm., Inc. v. Mayo Found. for Med. Educ. & Research, 175 F. Supp.2d 1209, 1214-15 (N.D.Cal. 2000).

  In its attempt to defeat the mountain of evidence Andrx has amassed, Astra first argues that two patents-U.S. Patent Number 5,045,321 (the "`321 patent") (P923) and U.S. Patent Number 5,232,706 (the "`706 patent") (P944)-that Astra disclosed to the USPTO in applying for the `281 patent are closer prior art to the `281 patent than the CKD Application. Astra's argument is neither legally nor factually persuasive. Invalidating references need not be "closer" or more pertinent that those considered by the examiner.*fn9 Constant v. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1572 n.6 (Fed. Cir. 1988); Aktiebolaget Karlstads Mekaniska Werkstad v. Int'l Trade Comm'n, 705 F.2d 1565, 1577 (Fed. Cir. 1983).

  Second, Astra argues that the CKD Application does not provide detailed processing conditions allegedly disclosed in the `281 patent that are critical to the creation of an in situ separating layer. Astra's argument is flawed. In fact, the CKD Application discloses the same level of detail regarding the processing conditions as Astra disclosed in the claims of the `281 patent. (See, e.g., A323A; A719 (Dem. Ex.).) Astra's claims sweep in any direct enteric-coating processes using an amount of the ARC in excess of the stated minimum that forms a separating layer. Indeed, Astra's theory that detailed processing parameters beyond those spelled out in the CKD Application must be known to form an in situ layer during direct enteric coating was repeatedly contradicted by Dr. Lovgren, one of the inventors, who explained that processing conditions for applying an enteric coating need not be detailed because they are obvious to a person of ordinary skill in the art. (Lovgren 4/27/01 Dep. Tr. 566:7-23, 569:8-24.)

  Third, Astra argues that the CKD Application does not anticipate the formation of an in situ separating layer because it "teaches away" from and expressly disavows the formation of such a separating layer. Even if that were factually true, legally it would not matter. See Bristol, 246 F.3d at 1378. In any event, the CKD Application does not disavow the spontaneous formation of a separating layer; it merely states that no separating layer is "applied." (See A323A.) The court finds that Andrx has clearly proven, as Astra itself has repeatedly asserted in other foreign patent proceedings involving CKD, that the formation of an in situ separating layer is inherent in the CKD process as set forth in the CKD Patent Application. Dr. Banakar testified that if a formulator followed the CKD process as described in the CKD Application, the separating layer would form in situ "each and every time." (Banakar Tr. 5346:12-16.) While Dr. Langer asserted that he could not see how a person following the CKD process would "arrive at" the in situ formation of a separating layer (Langer Tr. 5507:4-9), his testimony is entitled to little if any weight, as Astra did not provide Dr. Langer, its own expert, with any of the submissions (including test results) on which Astra relied in Korea to prove that the formation of a separating layer naturally results from the CKD process (see Langer Tr. 5527:14-5531:4). See Crown Operations Int'l, Ltd. v. Solutia Inc., 2002 WL 976249, at *7 n.4 (Fed. Cir. May 13, 2002) (suggesting that the most "direct route" to proving inherency may be to create and test an embodiment of the patent).

  Astra itself asserted in Korean patent proceedings *fn10 that the CKD process resulted in the in situ formation of a separating layer in CKD's OMP tablet, thereby proving that the formation of such a layer is inherent in the process disclosed in the CKD Application. (See, e.g., A802B; A804B; A825; A74; A193; A516.) In its initial submission to the KIPO Appeal Board (A802B), Astra asserted that the process used by CKD (referred to in its submission as "Invention A" or "Method A") forms a separating layer, even though the CKD process does not have a separate step of applying the separating layer. (See, e.g., A802B at 4 ("Method A has an inner coating layer forming process between the enteric coating layer and the core, as claimed."; "[F]ormulations prepared by Method A do include such a [separating] layer.").) During the Korean proceedings, Astra conducted tests on the OMP product that resulted from the CKD process. Specifically, Astra explained to the Appeal Board that it performed confocal laser scanning microscopy tests on tablets sold by CKD under the name "OMP", which Astra represented were made in accordance with "Method A." (A802B at 2-3.) Astra maintained that the "results of the experiment in the photograph clearly show that (3) the thin coating layer indicated in white, i.e., the separating layer, does exist between the aforementioned enteric coating layer and the core of omeprazole." (Id. at 3.) In the Rebuttal Submission to the KIPO Appeal Board, Astra made it clear that Method A formed a separating layer and that such formation is inherent in the process of Method A. (See, e.g., A804B at 1, 3 ("The construction of the inner coating layer formed in Method A is exactly that of the inner coating layer claimed in this Case Patent."), 4 ("[u]ltimately Method A contains the inner coating layer process"), 5 (the inner coating layer of the `OMP tablet' is created instantly at the point of time when the substance of coating the enteric coating is sprayed"), 6-7, 16; see also A804B at 2-5 (According "to the content of the Expert opinion described above, with the start of the process of the enteric coating of the OMP tablet, HPMCAS, which is an enteric coating substance, instantly reacts with the L-arginine that is in the core and forms a thin membrane, i.e., an inner coating layer.").)

  Moreover, Dr. Lovgren-one of the inventors of the `281 patent-signed or swore to at least two statements of Astra's position in the CKD dispute. In both statements, Dr. Lovgren contended that the CKD process resulted in the formation of a separating layer. (See A825 (dated 10/1993); A74 at 4 (dated 10/27/1998).) Finally, in both the patent infringement litigation that it initiated against CKD in the Korean courts and in the proceedings before the KIPO, Astra relied upon an expert affidavit of Dr. Rhodes (A193), who opined that, based on his study of the CKD product and processes, the CKD product contained an in situ layer. (A193 at 6, 8; Banakar Tr. at 5290-92, 5294-95.) If Astra had scientific proof with which to rebut or refute its prior admissions of inherency, it surely would have put on such proof. Astra did not. As such, the court finds that the disclosure of the CKD process in the CKD Laid Open Patent Application-one species of the process claimed by the `281 patent-anticipates and invalidates claims 1, 2, 3, 7, 16 and 20-21 of the `281 patent. The court will discuss each claim in turn:

  Claim 1 is anticipated by the CKD Application because the Application discloses "a process for preparing an oral pharmaceutical formulation" in which a core is formed using omeprazole, which is a "proton pump inhibitor", and arginine, which is an ARC, wherein the concentration of the ARC is "more than 0.1 mmol/g dry ingredients in the alkaline containing part of the core material," and HPMCAS or Eudragit L30D, "an enteric coating polymer layer" is applied "so as to surround the core material" with the inherent result of forming "in situ a separating layer as a water soluble salt product between the alkaline reacting compound and the enteric coating polymer." (Banakar Tr. 5301:1-5303:2, 5311:18-5313:11; A323A, Examples 4, 5, 7, 10, 11; see also A719 (Dem. Ex.) at 1.)

  Claim 2 is anticipated by the CKD Application because the Application discloses "[t]he process according to claim 1, wherein" the "proton pump inhibitor" is omeprazole, which is "a compound of the general formula I" as defined in the patent. (Banakar Tr. 5303:9-10; 5313: 12-5314: 4; A323A, Examples 4, 5, 7, 10, 11; A719 (Dem. Ex.) at 2.) Likewise, claim 3 is anticipated by the CKD Application because the Application discloses "[t]he process according to claim 1, wherein the proton pump inhibitor is omeprazole." (Banakar Tr. 5308:15-22, 5314:5-19; A323A, Examples 4, 5, 7, 10, 11; A719 (Dem. Ex.) at 2.)

  Claim 7 is anticipated by the CKD Application because the CKD Application discloses "[t]he process according to claim 1, wherein the alkaline reacting compound" is arginine, "an alkaline reacting organic compound." (Banakar Tr. 5308:23-5309:5, 5314: 20-5315: 16; A323A, Examples 4, 5, 7, 10, 11; A719 (Dem. Ex.) at 2.) *fn11

  Claim 16 is anticipated by the CKD Application because the Application discloses "[t]he process according to claim 1, wherein the enteric coating polymer" is HPMCAS, "a hydroxypropyl cellulose derivative." (Banakar Tr. 5309: 10-5310: 1, 5315: 23-5316:19; A323A, Examples 5, 7, 10, 11; A719 (Dem. Ex.) at 3.) Claim 20 is anticipated by the CKD Application because the Application discloses "[t]he process according to claim 1, wherein the core material", microcrystalline cellulose, sodium lauryl sulfate, corn starch, magnesium stearate and talc (all "very commonly used" pharmaceutical excipients) comprises or includes "a pharmaceutically acceptable excipient." (Banakar Tr. 5310:2-12, 5316:20-5317:10; A323A, Examples 4, 5, 7, 10, 11; A719 (Dem. Ex.) at 3.)

  Claim 21 is anticipated by CKD's Patent Application because it discloses "[t]he process according to claim 1, wherein the core material is in the form of a pellet or a plurality thereof." (Banakar Tr. 5317:12-5318:17; A323A, at 5 & Examples 10, 11; A719 (Dem. Ex.) at 3.)

  2. Obviousness

  Even if a claim is not literally anticipated by a reference, it is nevertheless unpatentable "if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." 35 U.S.C. § 103 (a). Obviousness under § 103 is a legal conclusion based on certain factual inquiries. DMI, Inc. v. Deere & Co., 802 F.2d 421, 425 (Fed. Cir. 1986). These factual inquiries include: (1) the scope and content of the prior art; (2) the level of ordinary skill in the art; (3) the differences between the claimed invention and the prior art; and (4) secondary, objective considerations of nonobviousness including long-felt need, commercial success, or the failure of others.*fn12 Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966).

  After considering all the testimony and the documents received into evidence, the court finds that Andrx has established by clear and convincing evidence that claim 9 of the `281 patent is invalid because it would have been obvious to a person of ordinary skill in the art in light of the CKD Laid Open Patent Application to substitute the alkaline salts called for by claim 9 of the `281 patent for the arginine disclosed in the CKD Application because it would have been obvious to substitute one ARC for another. CKD's Application claims that a stable form of omeprazole can be formulated by directly coating a core containing an amino acid or an alkali salt of omeprazole as the "basic part" or "alkali reaction component" of the core. (A323A at 4, 5, 12.) The CKD Application references arginine as one chemical that can be used to form the "basic part" of the core. (A323A at 5.) The court credits Dr. Banakar's testimony that it would have been obvious to a person of ordinary skill in the art of pharmaceutical formulation to replace the arginine referenced in the CKD Application with an alkaline salt of phosphoric acid, carbonic acid or silicic acid, as all such substances are ARCs that can stabilize omeprazole. (Banakar Tr. 5304:11-15, 5306:19-20.) Dr. Banakar's testimony is corroborated by Astra's own admissions that arginine is "just like" other ARCs and "it is easy to substitute" arginine for another ARC.*fn13 (See A312A at 8-9; A802B at 7-8; A804B at 11, 15-16; A298A at 208; A516A at 3.) In fact, the court was presented with evidence that establishes that actual practice by formulation scientists would commonly include substitution of such salts for arginine. (See Banakar Tr. 5305:22-5306:1.) For the foregoing reasons, the court finds claim 9 of the `281 patent invalid as obvious.

  III. Phase IV

  During Phase IV of the trial, Andrx presented evidence in support of its defenses of fraud, inequitable conduct and unclean hands. Andrx asks the court to declare that the `281 patent was procured through fraud and inequitable conduct and is, therefore, unenforceable. Andrx also set out to prove three types of unclean hands in Astra's litigation of the `281 patent, in an effort to obtain a declaration from this court that the claims of the `505 and `230 patent are unenforceable against Andrx as a result of Astra's conduct.*fn14

  As an initial matter, the court notes that Astra has asserted claims of the `281 patent against only one defendant in this case-Andrx. The court will not make detailed findings concerning Andrx's additional defenses pertaining to the `281 patent, which are mooted by this court's rulings that each of the asserted claims of the `281 patent is invalid. Nonetheless, Andrx's arguments concerning unclean hands implicate this court's earlier findings in Omeprazole I that Andrx's ANDA product infringes certain asserted claims of the `505 and `230 patents. Therefore, the court addresses Andrx's unclean hands arguments below.

  Andrx's arguments concerning unclean hands accused Astra of the following: (1) delay of the trial; (2) affirmative use of tainted evidence; and (3) withholding significant documents until after the Phase I and II trials were completed. Andrx argues that Astra's unclean hands as to the `281 patent render the `505 and `230 patents unenforceable against Andrx. After a complete review of the hundreds of pages of proposed findings of fact and conclusions of law submitted by Andrx in support of its unclean hands theory, the court is utterly unpersuaded. The evidence simply does not support a finding that Astra's actions prevented "a full and fair determination of the matters in controversy" such that Astra should be denied any remedy as to the `505 and `230 patents. See Keystone Driller Co. v. Gen. Excavator Co., 290 U.S. 240, 245 (1933). Merely by way of example, the court notes that accusations of delay of the trial in this case could flow equally in either direction, not only toward plaintiffs but also toward defendants, including Andrx.*fn15 Moreover, Andrx itself represented to the court that it did not need or want to reopen proof on Phase I or Phase II when offered the opportunity to supplement the record with additional proof in light of the documents produced by Astra during the trial. (See Tr. at 6118:1-3, 6161:15-6162:5.) For the foregoing reasons and after a complete review of the record developed in Phase IV of the trial, the court declines to find that Astra has acted with unclean hands-the court's prior rulings as to infringement of the `505 and `230 patents by Andrx's ANDA product stand. IV. Conclusion

  The parties are ordered to submit a stipulated judgment incorporating the rulings contained in this decision to the court within three weeks of entry of the decision.

  SO ORDERED:


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