Purdue Pharma, LP v. FH Faulding and Co.

Citations: 48 F. Supp. 2d 420; 1999 U.S. Dist. LEXIS 6346; 1999 WL 288074Docket: Civ.A. 96-427-JJF

Court: District Court, D. Delaware; April 23, 1999; Federal District Court

SummaryOriginalCytator Case TreatmentBackward CitatorAnalysis

EnglishEspañolSimplified EnglishEspañol Fácil

Purdue Pharma L.P. and The Purdue Frederick Company initiated legal action against Faulding Inc., Faulding Pharmaceutical Co., Purepac Pharmaceutical Co., and Zeneca, Inc., for infringing U.S. Patent Number 5,672,360 (the '360 Patent). This patent, granted to Purdue on September 30, 1997, pertains to methods for treating pain using a 24-hour oral opioid formulation, specifically morphine, which produces a significant fluctuation in blood concentration levels. Purdue claims that Faulding's use of Kadian, a once-daily sustained-release oral morphine product, infringes specific claims of the patent. In response, Faulding disputes the infringement claim and raises defenses, including the invalidity of the patent due to lack of written description, obviousness, anticipation, public use, and allegations of inequitable conduct by Purdue before the U.S. Patent and Trademark Office (PTO). 

The Court has jurisdiction under 28 U.S.C. § 1338(a) due to the matter arising under U.S. patent laws, with personal jurisdiction established over Faulding and Zeneca as Delaware corporations. Venue is deemed appropriate in Delaware since all defendants are incorporated there. The Court bifurcated the trial into liability and damages phases, conducting a seven-day bench trial on infringement, validity, and enforceability of the patent. On the fourth day, claims against Zeneca were dismissed due to insufficient evidence. This Memorandum Opinion serves as the Court's Findings of Fact and Conclusions of Law regarding the remaining claims and defenses. 

Prior to the '360 Patent, Purdue's MS Contin, a sustained-release morphine formulation, was administered every 12 hours and represented a significant improvement over immediate-release formulations, which required multiple doses throughout the day and often left patients in pain between doses.

Purdue developed MS Contin and, in the mid to late 1980s, aimed to create a once-a-day oral sustained-release opioid formulation. The primary goals included achieving an early Tmax (time to maximum plasma concentration) within the first third of the dosing interval (approximately 2 to 10 hours), allowing for plasma opioid fluctuations exceeding 100%, and providing effective pain relief for 24 hours. These objectives contradicted the prevailing clinical view that sustained-release formulations should maintain minimal fluctuations, defined as no more than 100% variation between maximum and minimum plasma concentrations. By mid-1988, Purdue's inventors communicated these design goals to senior scientist Mr. Oshlack, who subsequently developed two experimental morphine formulations for clinical testing. The clinical study, MC88-0504, confirmed the formulations met the first two goals but failed to ensure adequate pain relief for the full 24-hour period. Despite this setback, Purdue persisted in its development efforts and by 1993 confirmed a formulation that met all design criteria. Purdue collaborated with patent counsel to file applications, resulting in the '360 Patent. However, as of the current date, Purdue does not market any once-a-day opioid products in the U.S. nor have any pending New Drug Applications (NDA) for such products, although it announced plans to seek an NDA for a drug utilizing the '360 invention in early 1999. In parallel, Faulding initiated its sustained-release morphine project, dubbed 'Molly,' in 1987, focusing on a formulation to provide at least 12 hours of pain relief, with aspirations for administration every 12 to 24 hours.

Faulding outlined ten desired characteristics for a morphine formulation, focusing on pharmacokinetics, stability, manufacturing processes, raw material sourcing, and patent protection. Under Dr. Angelo Morella, Faulding developed two initial formulations, Molly 1 and Molly 2, which met many objectives but were further refined into Molly 3, tested in Clinical Trial MOB-2/89. The results led to the issuance of Australian Patent No. AU-B-47732/90. Molly 3 fulfilled Faulding's performance goals and was later registered in Australia and licensed to Glaxo Wellcome as Kapanol. Faulding then pursued U.S. registration for once-a-day use, culminating in FDA approval for Kadian on July 3, 1996, making it the only oral morphine product approved for once-a-day dosing in the U.S. 

The excerpt further discusses the presumption of validity for issued patents under 35 U.S.C. § 282, noting that the burden of proof to challenge a patent's validity lies with the challenger, who must provide clear and convincing evidence. The burden is heightened when the prior art used in the challenge has already been evaluated by the Patent and Trademark Office (PTO), which is presumed to have performed its duties properly.

The Court is the final authority on legal questions like patent validity, notwithstanding the deference owed to the Patent and Trademark Office (PTO). Faulding asserts that the '360 Patent is invalid and cannot be infringed, citing four grounds: (1) lack of written description under 35 U.S.C. § 112; (2) anticipation by the Morella patents under 35 U.S.C. §§ 102(a), (b); (3) prior public use under § 102(b); and (4) obviousness under 35 U.S.C. § 103. The Court has determined that the '360 Patent is invalid due to a lack of written description as mandated by 35 U.S.C. § 112.

According to § 112, the specification must adequately describe the invention and its implementation in clear terms to enable those skilled in the art to make and use it, and must disclose the best mode contemplated by the inventor. The specification must convey that the applicant possessed the invention at the filing date, including all elements and limitations of the claims. The written description requirement aims to prevent overreaching and ensure claims are consistent with the original invention.

Faulding argues that the '360 Patent fails this requirement, specifically pointing out that the specification does not disclose the Cmax/C24>2 limitation and the Tmax of about 2 to about 8 hours limitation in Claim 2. Faulding claims that Purdue did not possess these elements until a new set of claims was added in June 1997, thereby exceeding the original invention's scope. Furthermore, Faulding invokes the 'omitted element test' from § 112, arguing that the '360 Patent omits essential elements disclosed in an earlier application, rendering it invalid.

Purdue asserts that the '360 Patent clearly indicates a Cmax/C24 ratio greater than 2 is a component of its invention, despite the absence of explicit terminology regarding this claim in the patent's specification. Purdue argues that the inventors illustrated plasma opioid fluctuations by comparing them to conventional desirable ranges for sustained-release formulations. It maintains that the patent states its treatment methods do not produce a "substantially flat serum concentration curve," which is interpreted by skilled professionals as allowing fluctuations of 100% or less, thereby implying that the invention results in fluctuations exceeding 100%.

Purdue does not address Faulding's 'omitted element test' argument relating to the Reiffin decision, asserting instead that there is no inconsistency between the claims and disclosures in the patent. It further states that the PTO, after reviewing new claims, supported them and did not reject them for including new matter, suggesting adherence to the written description requirement of Section 112.

However, the Court finds that the '360 Patent does not satisfy the written description requirement of 35 U.S.C. § 112, concluding that the specification and its examples do not support the Cmax/C24>2 limitation present in Claims 2, 4, and 11. The Court identifies omissions of critical elements originally disclosed in the patent application. While Purdue cites language about not being "substantially flat," the Court indicates that the complete context of this language contradicts Purdue's claim that the specification adequately covers the Cmax/C24>2 limitation, instead focusing on the formulation's rapid initial opioid release. Thus, the Court ultimately rules the '360 Patent invalid.

The specification of the '360 Patent, despite changes from the original claims of the '688 application, consistently references the concept of an initially rapid rise in opioid plasma concentration, characterized by an absorption half-life (T1/2(abs)) of 1 to 8 hours. This rapid release is critical for achieving effective analgesic concentration in patients experiencing significant pain. However, the specification does not elaborate on the Cmax/C24>2 element of the '360 Patent, nor does it quantify the phrase 'substantially flat,' failing to provide support for Purdue's assertion that it refers to fluctuations of 100% or less. The Court finds that evidence presented by Purdue, including testimony from Dr. Goldenheim and references to other patents, does not convincingly establish that 'flat' means a fluctuation of 100% or less. Notably, Dr. Goldenheim's inconsistent testimony and the Kabi Pharmacia patent's descriptions of formulations with both low and high fluctuations undermine Purdue's position, indicating that there is no clear threshold for defining a 'flat profile' among skilled professionals in the field.

The specification language in Purdue's '360 Patent uses the term "substantially flat," which indicates that "flat" does not refer to a precise measurement as suggested by Purdue. Purdue's attempt to define its invention by stating it is not "substantially flat" raises concerns about the clarity and definitiveness of the description, as courts often struggle with overly broad negative definitions. The Court highlights that there is no established definition for "flat" among experts in the field, leading to a conclusion that Purdue's description does not satisfy the written description requirement.

Purdue also points to specific examples in the patent, arguing that Examples 1 and 3 demonstrate Cmax/C24 ratios greater than 2, supporting the written description. However, while the Federal Circuit acknowledges that drawings can fulfill the written description requirement, the examples must clearly convey that the inventor possessed the claimed invention at the time of filing. The specification presents examples with both Cmax/C24 ratios greater and less than 2, without clarifying that ratios below 2 are excluded from the invention’s scope. 

Purdue contends that the inquiry should focus on the claim language and examples together, asserting that they collectively describe the invention. Nevertheless, since the claims did not include the Cmax/C24>2 limitation at the time of filing, this newly added element cannot be retrospectively used to justify the examples. Testimonies from the inventors, Dr. Goldenheim and Dr. Kaiko, further support the Court's finding, indicating that understanding the examples requires referencing the claims and that the specification lacks sufficient detail to determine whether certain examples align with the claims of the patent. Thus, the examples fail to meet the written description requirement.

The Court finds that the examples presented illustrate a Cmax/C24 ratio between 1.48 and 3.43 but do not adequately describe an invention with a claim limitation requiring a ratio greater than 2. In analyzing the written description requirement under Section 112, the Court references the Gentry Gallery, Inc. v. Berkline Corp. case, where the Federal Circuit invalidated claims for failing to limit the placement of controls to a console, stating that claims must not omit essential elements described in the original patent. This interpretation has been termed the "omitted element test." The Reiffin court supports this test with earlier case law, indicating that omitting critical steps or elements renders a reissue void. The Court concludes that the '360 Patent omits a critical element necessary for the invention as originally disclosed and that the Cmax/C24>2 limitation is unsupported by the patent's specification. This leads to the determination that Purdue was not in possession of the claimed invention when the application was filed, as allowing such claims would undermine the policy against overreaching in patent claims. Furthermore, the Court is not convinced by Purdue's argument that the Patent Examiner's lack of a new matter rejection validates the adequacy of the specification, emphasizing that the concepts of new matter and written description are distinct under 35 U.S.C. § 132.

The rejection of the patent claims is based on 35 U.S.C. § 112, which addresses the issue of "new matter." The absence of a new matter rejection by the Examiner does not imply support for the newly added claims in the specification at the time of filing. Instead, it indicates that Purdue did not introduce any new content to the original submission. The Court clarifies that the Examiner's inaction does not equate to validation of the claims; the adequacy of the specification must be assessed through its text, examples, and their interpretation by skilled individuals in the field. The Court finds no support for the Cmax/C24>2 limitation in Claims 2, 4, and 11 of the '360 Patent, concluding that Purdue's claims are not adequately described. Additionally, the Court determines that the '360 Patent lacks essential elements present in the original application, indicating that Purdue did not possess the claimed invention at the time of filing. Consequently, the '360 Patent is deemed invalid under the 'written description' requirement of Section 112, and the Court refrains from considering other grounds for invalidity. Despite this invalidity ruling, the Court will examine whether Faulding's use of Kadian infringes the '360 Patent. Purdue alleges that Faulding's once-daily use of Kadian infringes Claims 2, 4, and 11, which requires a finding of direct infringement before establishing liability for inducing infringement under Section 271(b). A patent is infringed when an unauthorized person makes, uses, or sells the patented invention, while inducing infringement involves actively encouraging it. The patent owner bears the burden of proof to demonstrate infringement by a preponderance of the evidence.

In SmithKline Diagnostics, Inc. v. Helena Lab. Corp., the Federal Circuit outlines key legal standards for proving patent infringement. The preponderance of the evidence standard requires that a party's evidence must be more persuasive than that of the opposing party. Patent owners can establish infringement through two theories: literal infringement and the doctrine of equivalents. Literal infringement occurs when every element of at least one patent claim is present in the accused product. A claim is infringed only if it fully aligns with the accused product, meaning any missing element can avoid infringement.

In contrast, the doctrine of equivalents allows for infringement findings even if some elements are absent, provided the accused product performs the same function in a similar manner to achieve the same result. To determine infringement under either theory, courts must first interpret the claims, a legal question that involves analyzing the claim language, patent specifications, and prosecution history. Courts may also utilize extrinsic evidence, including expert testimony and dictionaries, to clarify the meaning of the claims. Claims are generally interpreted using their ordinary meanings, unless the inventor has provided a specific definition. Courts are encouraged to interpret claims in a way that upholds their validity whenever possible.

Infringement analysis requires a court to compare the accused products with the claims of the relevant patent to assess potential infringement under literal infringement or the doctrine of equivalents. In the case of the '360 Patent, Faulding contends that the patent only covers drugs that produce specified pharmacokinetic (PK) results on average and questions the meaning of "effective treatment of pain." Aside from these points, the parties do not dispute other claim meanings. Faulding argues that the patent's specification presents only average data, implying that the claims cover formulations yielding average PK results (Cmax/C24>2 and Tmax of 2 to 8 or 10 hours). Purdue counters that the claims pertain to treating individual patients, asserting that Faulding's interpretation misrepresents the claims' plain language and overemphasizes prior art. The court emphasizes that the claim language is paramount and while the specification and prosecution history can provide context, they cannot limit the claims beyond their explicit wording. Courts focus on interpretation rather than rewriting claims, adhering to established legal standards.

The claims in the '360 Patent do not use "average" or "mean," indicating they pertain to treatment methods for individual patients, not averages across a population. The language explicitly mentions administering a sustained-release oral opioid dosage form to "a human patient" and achieving specific pharmacokinetic (PK) and efficacy results in that patient. The Court concludes that these terms clearly refer to individual patients, supported by the patent's specification, which consistently refers to individual patients at least 22 times and lacks any mention of average results. 

Faulding argued for the inclusion of "average" based on examples containing average PK data, but the Court rejected this argument, noting that the specification explicitly states these examples are illustrative and do not limit the claims. Testimony from Purdue's expert indicated that average results are merely a method of summarizing clinical study results meant to illustrate desired outcomes for individual patients. Legal precedent prohibits using examples in a specification to narrow the scope of claims, leading the Court to dismiss Faulding's proposed interpretation as an improper limitation. 

Regarding "effective treatment of pain," Faulding's expert, Dr. Gelmann, defined it as pain control acceptable to the patient, emphasizing that complete pain relief is not necessary for treatment to be deemed effective. He asserted that patient satisfaction, rather than total pain alleviation, is the key measure of effectiveness, and that an effective regimen could incorporate "rescue medication."

Additional doses of immediate release morphine, nonopioid analgesics (such as aspirin, acetaminophen, or ibuprofen), and adjuvant drugs (like laxatives) are included in treatment regimens alongside sustained release morphine. Dr. Goldenheim, an inventor of the '360 Patent, testified that the patent envisions combining rescue medications and other medicines with morphine sulfate. Faulding asserts that the claims of the '360 Patent encompass this comprehensive treatment regimen. Purdue, in its response, states there is "no real dispute" regarding the phrase "effective treatment of pain," agreeing with Faulding that the claimed methods involve the appropriate use of rescue medications and other drugs with sustained release opioids. Both parties concur that this phrase implies adequate pain relief without unacceptable side effects for the individual patient. Faulding, however, challenges Purdue's interpretation, arguing that Purdue has not clearly defined "adequate relief" and criticizes the redundancy of requiring that the sustained release form itself provide adequate pain relief. The Court determines that Faulding's objections represent a disagreement over terminology rather than substance. It concludes that both parties agree on the inclusion of rescue medications and the focus on individual patient experiences in defining effective pain treatment, with Purdue emphasizing the predominance of sustained release opioids in achieving this balance.

The Court concludes that Purdue's interpretation of "effective treatment of pain" accurately reflects the parties' agreement, defining it as providing adequate pain relief from a sustained release opioid dosage without unacceptable side effects. In assessing the literal infringement of Claims 2, 4, and 11 of the '360 Patent by Kadian, the Court notes that these claims are dependent on independent claims, necessitating a comparison of the claims' language to Kadian's use. 

For Claim 2, the Court finds that Purdue has demonstrated, by a preponderance of evidence, that all elements are present in Kadian's use: Kadian is an oral, sustained-release opioid administered once daily. This conclusion relies on Dr. Lipman’s credible testimony, the FDA-approved labeling of Kadian, and Faulding's admissions confirming Kadian’s formulation and administration schedule. 

The Court also determines that the Tmax (time to maximum plasma concentration) for Kadian, post-administration, aligns with the claim's requirement. Although Kadian's average Tmax is reported as 10.3 hours, the Court accepts Dr. Lipman's testimony that individual Tmax values may fall within the specified range of 2 to 8 hours for some patients, thus satisfying the claim’s criteria.

Faulding admitted that Kadian product labeling and available data indicate that Tmax for morphine is reached between 2 and 8 hours after administration in some patients. The Court concluded that the accused use of Kadian exhibits a maximum plasma concentration (Cmax) exceeding twice the plasma level of the opioid approximately 24 hours post-administration. This finding is supported by Dr. Lipman's testimony and Kadian's product labeling, which shows that, on average, Cmax is above 30 ng/ml while the average plasma morphine concentration at 24 hours is below 15 ng/ml. The Court also determined that Kadian provides effective pain relief for about 24 hours or more in some patients based on the FDA's conclusions, promotional materials, and Faulding's admissions. Consequently, the Court found that all elements of Claim 2 of the '360 Patent are present in the accused use of Kadian, leading to a conclusion of literal infringement. Furthermore, upon assessing Claim 4 of the '360 Patent, the Court found that all elements of Claim 4 are also present in the accused use of Kadian, with the specific opioid being morphine sulfate and a Tmax of about 2 to 10 hours.

The Court finds that Claim 4 of the '360 Patent is literally infringed by the accused use of Kadian. Key elements shared with Claim 2 are present, specifically identifying Kadian as containing morphine sulfate as per product labeling. The Tmax requirement for Claim 4, which specifies a Tmax of about 2 to about 10 hours, is satisfied based on Dr. Lipman's testimony, product labeling, and Faulding's admissions. Notably, Kadian shows an average Tmax of 10.3 hours, with some patients achieving Tmax between 2 and 8 hours, thereby falling within the required range. 

Furthermore, the Court concludes that Claim 11 of the '360 Patent is also infringed, as it encompasses all elements of Claim 4 along with the additional requirement that PK parameters are achieved at a "steady-state." This "steady-state" is defined in the patent as achieving consistent plasma opioid levels effective for pain treatment. The Court finds this element present as supported by Dr. Lipman's testimony and the available PK data, indicating that Kadian meets the parameters outlined in both Claims 4 and 11.

The Court incorporates its findings from Claims 2 and 4 into Claim 11, determining that the accused use of Kadian meets all elements of Claim 11 of the '360 Patent, resulting in a conclusion of literal infringement. Faulding argues that Purdue has not demonstrated actual once-daily administration of Kadian in the U.S. since the patent's issuance on September 30, 1997. Purdue counters that it is not required to present direct evidence of specific patients but can rely on circumstantial evidence, such as the sale of Kadian and its labeling instructions for once-daily use. The Court acknowledges that circumstantial evidence can suffice to prove infringement, especially when pharmacokinetic (PK) parameters are involved. Faulding admitted to selling Kadian in the U.S. and the product labeling suggests once-daily use, leading the Court to conclude that it is more likely than not that some patients have used Kadian as claimed since the patent's issuance. Consequently, the Court rejects Faulding's non-infringement arguments. Additionally, the Court finds that the '360 Patent is invalid for lack of a written description under Section 112.

The Court determined that U.S. Patent No. 5,672,360 is invalid under 35 U.S.C. § 112 due to a lack of written description. However, if the patent were valid, Faulding’s once-a-day use of Kadian would infringe Claims 2, 4, and 11, resulting in liability for direct infringement under 35 U.S.C. § 271(a) and for inducing infringement under 35 U.S.C. § 271(b).

The Court's order specifies that the validity issue hinges on the sufficiency of the written description in the '688 application, which is the original application for the '360 Patent. The Court concluded that the '688 application does not support the newly amended claims, thereby negating the need to evaluate Purdue's arguments regarding priority from other applications. Additionally, the Court's findings regarding the lack of support for a specific limitation (Cmax/C24>2) are applicable to all asserted claims, making further consideration of Faulding's arguments about the Tmax range unnecessary.

The Court reiterated that validity and infringement are distinct; a patent can be invalid yet still be infringed. An appropriate order will be entered following these conclusions.

Claims can be found to be infringed yet invalid, indicating that the validity of a patent claim does not influence the determination of infringement. Claim 2 of the '360 Patent specifies that Tmax occurs between 2 to 8 hours after oral administration. For the infringement analysis, the Court will detail all elements of Claim 1 but will replace the Tmax element with that from Claim 2. Claim 4 states that the opioid analgesic is morphine sulfate, and its Tmax element corresponds to that of Claim 1. Additionally, Claim 11 builds upon Claim 9, detailing a method for treating pain in humans by administering an oral sustained release dosage form containing an opioid analgesic, with specific Tmax and Cmax requirements to ensure effective pain relief for 24 hours or more.