Patent Docs

Agilent Technologies, Inc. v. Affymetrix, Inc. (Fed. Cir. 2009)

    By Kevin E. Noonan --

The Federal Circuit clarified the role of the written description requirement in interference practice today in an opinion by Judge Rader, one of the Court's most severe critics of its written description jurisprudence.  Unlike the situation where the written description requirement is used to invalidate patents (which is the subject of a petition for en banc review in Ariad v. Eli Lilly), Judge Rader's decision confirms that the written description requirement is particularly relevant to the essential interference question of inventive priority.

The interference at issue was declared against U.S. Patent No. 6,513,968 to Schembri and assigned to Agilent, and U.S. Patent Application Serial No. 10/619,244 to Besemer and assigned to Affymetrix.  Affymetrix provoked the interference by copying claims from the '968 patent; because Affymetrix's application was awarded the earliest priority date, Besemer was declared the senior party, placing the burden of establishing priority on Agilent.

The interference count was identical to claim 20 of the Schembri patent and claim 66 of the Besemer application:

A method comprising:
    providing a first substrate and a second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least one of said inner surfaces is functionalized with polynucleotides, polypeptides, or polysaccharides;
    introducing a fluid containing a plurality of components into the closed chamber so as to provide a quantity of fluid therein in contact with both inner surfaces;
    providing a bubble in the fluid; and
    moving a bubble within the fluid to result in mixing.

As explained in the opinion, Agilent's Schembri patent disclosed a microarray hybridization method performed in a closed chamber in which probe sequences were attached to one or both of two opposing surfaces on the interior of the chamber.  Because of the small volumes of fluid used for hybridization, mixing was effected by producing  bubbles in the fluid (by heating) and using motion of the bubbles in response to a temperature gradient to "cause the bubble to move and mix the fluid sample in the closed chamber," as illustrated in Figures 1 and 4 of the '968 patent:

The Besemer application, on the other hand, disclosed microarrays contained in a chamber operably linked to "circulator" embodiments comprising reservoirs from which hybridization fluid was pumped through the hybridization chamber to effect mixing, as illustrated in Figure 28 (at right).

Alternatively,  the microarrays were contained in a chamber that was agitated at 3000 cycles per minute as shown in Figure 29 (at left).

During interference proceedings in the Patent Office, Agilent challenged the Besemer claim in interference for failure to satisfy the written description requirement of 35 U.S.C. § 112, first paragraph.  The Board disagreed on the grounds that "Schembri had not advanced any 'meaningful evidence' to show that one of ordinary skill in the art would not have understood Besemer's specification to inherently disclose using bubbles to mix fluid in a closed chamber, as required by Besemer's claim 66.  Board Decision, slip op. at 28," awarded priority to the Besemer application and cancelled Schembri's '968 patent.  Agilent appealed, filing an action in the District Court for the Northern District of California pursuant to 35 U.S.C. § 146.  In that action, both parties submitted new expert reports concerning the disclosures of the '968 Schembri patent and the Besemer application.  After holding a claim construction hearing and considering summary judgment motions from both parties, the District Court affirmed the Board's decision that the Besemer application satisfied the written description requirement.  Agilent then appealed to the Federal Circuit, challenging the District Court's claim construction and written description determinations.

The opinion, written by Judge Rader and joined by Judge Mayer and 7th Circuit Judge Richard Posner, sitting by designation, began by considering the question of which specification was to be used to construe Besemer's claim 66.  The District Court had used the disclosure of the Besemer application (termed "the host application" in the opinion), and Agilent contended that the proper reference was the Schembri patent specification.  Judge Rader framed the question in terms of which of the Court's precedents were controlling:  In re Spina or Rowe v. Dror.  In the Spina case, as here, an applicant copied a claim from an issued patent to provoke an interference.  The Board, in determining whether the copier's specification satisfied the written description requirement, construed the copied claim in light of the specification of the granted patent, an approach affirmed by the Federal Circuit:  "'[w]hen interpretation is required of a claim that is copied for interference purposes, the copied claim is viewed in the context of the patent from which it was copied.'  Spina, 975 F.2d at 856."

In the Rowe case, junior party Rowe copied claims from the Dror patent to provoke an interference.  In that case, senior party Dror moved for judgment on the grounds that a third-party patent anticipated certain of Rowe's claims corresponding to the count.  In deciding the subsequent appeal, the Federal Circuit held that the specification of Rowe's application should be used to construe the claim term at issue -- in other words, precisely the opposite result from the rule laid down in Spina.  That panel recognized the inconsistency with the Spina panel's rule, and distinguished the cases as follows:

In Spina, this court considered whether an applicant was eligible to copy a patentee's claim and thereby challenge priority of invention, a question that turned on whether the copying party's specification adequately supported the subject matter claimed by the other party.  This court held, in that context, that a copied claim is interpreted in light of its originating disclosure.  This Spina rule sought to ensure that the PTO would only declare an interference if both parties had a right to claim the same subject matter.  However, that rule does not apply in cases, such as this one, where the issue is whether the claim is patentable to one or the other party in light of prior art.  In this posture, the PTO and this court must interpret the claim in light of the specification in which it appears.  Rowe, 112 F.3d at 479.

In this case, the Federal Circuit held that the rule in Spina applies, because the question was whether "Besemer ha[s an] adequate basis to copy Schembri's claim and thereby challenge Schembri's priority of invention . . . .  This case does not present the Rowe situation, 'where the issue is whether the claim is patentable to one or the other in light of prior art.'"  In making this determination, the Court expressly rejected Affymetrix's contention that it would be contrary to 37 C.F.R. § 41.200(b), stating that "administrative regulations cannot trump judicial directives . . . .  Judicial precedent is as binding on administrative agencies as are statutes" (citing Rowe at 479 n.2).  The Court summarized its holding on this question as follows:

To be clear, as this court explained in Rowe, when a party challenges written description support for an interference count or the copied claim in an interference, the originating disclosure provides the meaning of the pertinent claim language.  When a party challenges a claim's validity under § 102 or § 103, however, this court and the Board must interpret the claim in light of the specification in which it appears.  Thus, the district court erred in construing claim language in light of the host Besemer application, rather than the originating Schembri disclosure.

Turning to the District Court's claim construction, the panel disagreed with two aspects that were dispositive.  First, the panel disagreed with the District Court's construction of the claim term "a closed chamber . . . adapted to retain a quantity of clued" to mean "an enclosed cavity, or some other enclosure or system of enclosures, which is capable of being sealed or set apart from its surroundings to retain a quantity of fluid."  Under the District Court's construction, the configuration set forth in Figure 28 of the Besemer application provided an adequate written description of a "closed chamber," as illustrated at left.

The Federal Circuit held that this construction was "dubious" since it ran counter to the plain meaning of the phrase "a closed chamber" considered in the context of the rest of the claim, which recited that the closed chamber was "'define[d by] a first substrate and second substrate having inner surfaces."  The Court contrasted the chamber thus recited as being "bounded by two discrete substrates" with "a nebulous space that could ambiguously span 'a system of enclosures.'"  The panel's contrary construction of the term was supported by the Schembri specification, rather than the Besemer specification used by the District Court.  As might be expected, the definition of "a closed chamber" in the Schembri specification provided no support for the embodiments disclosed in the Besemer specification.  The Federal Circuit also found functional as well as structural distinctions, including that the "closed chamber" disclosed in the Schembri specification was configured so that nucleated bubbles would be formed that would move in response to an induced temperature gradient to facilitate mixing, in contrast to the embodiments disclosed in the Besemer specification that used fluid flow from external reservoirs to mix hybridization fluid over the microarray surfaces.  The Court's opinion also noted that construing "a chamber" to comprise "several chambers" (as would be required to encompass the Besemer embodiments) would "provide no guidance as to where, amongst the several chambers, the first and second substrates [comprising the probe sequences] are located."  In this regard, the CAFC also held that the District Court's construction was faulty for rendering the word "closed" to be superfluous, finding that the term "closed" was synonymous with "sealed," a quality the embodiments disclosed  by Besemer did not have.

Turning to the written description issue, the panel agreed with Agilent that there was no support in the Besemer specification for the count corresponding to Besemer's copied claim 66.  Summarizing, the opinion states that:

[T]he "circulator" embodiments (illustrated in Figures 28 and 30) do not describe a method that takes place in a "closed chamber," whereas the "vortexer" embodiment (Figure 29) does not describe bubble mixing at all.  Thus, as per Agilent, Besemer cannot show possession of the claimed invention because no embodiments describe a method of both introducing fluid into a closed chamber and using bubbles to mix the fluid.

The panel eliminated the embodiments disclosed in Figures 28 and 30 for failure to describe a closed chamber, and then eliminated the embodiment disclosed in Figure 29 for failure to disclose bubbles to facilitate mixing.  The panel's conclusions were based on the Court's reading of portions of the Besemer specification as well as expert testimony, which the opinion termed "a critical admission" that the vortexer embodiment described in Figure 29 did "not necessarily" generate bubbles in operation, testimony that the Court opined vitiated any inherency argument asserted by Affymetrix.

The Federal Circuit also held that the District Court had improperly failed to consider new evidence presented by Agilent pursuant to the provisions of 35 U.S.C. § 146, directed at supplying what the Board found it had failed to supply during the interference:

Meaningful evidence in this case might, for example, have included an expert declaration stating that one of ordinary skill in the art would not have had the requisite knowledge or skills to conclude from the Besemer '224 specification that the inventor was in possession of the invention as claimed.  Board decision, at 28.

The District Court erred in not considering Agilent's new evidence and thus deferring to the Board's factual determinations.  Accordingly, the panel held that there was "no dispute of material fact that the Besemer application does not teach the claimed method" and thus the Besemer application was entitled to a priority date no earlier than its filing date.  Accordingly, the Federal Circuit held that Agilent was entitled to priority without remand to the District Court.

Agilent Technologies, Inc. v. Affymetrix, Inc. (Fed. Cir. 2009)
Panel: Federal Circuit Judges Mayer and Rader and Seventh Circuit Judge Posner
Opinion by Circuit Judge Rader

Digene Corp. v. Third Wave Technologies, Inc. (Fed. Cir. 2009)

    By Donald Zuhn --

On April 1st, the Federal Circuit affirmed the judgment of the District Court for the Western District of Wisconsin that Defendant-Cross Appellant Third Wave Technologies, Inc. did not infringe U.S. Patent No. 5,643,715, owned by Plaintiff-Appellant Digene Corp.  The panel also affirmed the District Court's grant of summary judgment dismissing Third Wave's antitrust counterclaims.

The '715 patent relates to the diagnosis of human papillomavirus (HPV) type 52, which is one of several HPV strains known to cause cervical cancer.  The '715 patent describes the differentiation of HPV type 52 from other HPV types using "nucleic acid hybridization probes which are specific for HPV type 52."  Both Digene and Third Wave make HPV testing systems; Third Wave's system utilizes a nucleic acid molecule that includes a sequence that is homologous to HPV type 52 and an additional sequence that serves as "an indicator of the HPV's presence."

In January 2007, Digene brought suit against Third Wave for infringement of claims 8, 10-12, and 18-27 of the '715 patent.  Asserted claims 18 and 21 include all of the limitations that were contested on appeal (contested limitations are underlined):

18.  An HPV 52 hybridization probe comprising a member selected from the group consisting of
    (i)  HPV 52 DNA labelled with a detectable label, and
    (ii)  HPV 52 RNA labelled with a detectable label,
    wherein the length of the HPV 52 DNA or HPV 52 RNA is between approximately 15 and 8000 nucleotide bases,
    wherein the HPV 52 DNA consists of all or a fragment of an HPV DNA, wherein the HPV DNA cross-hybridizes to the HPV portion of clone pCD15 to greater than 50% under moderately stringent conditions,
    wherein the HPV 52 RNA consists of all or a fragment of an HPV RNA, wherein the HPV RNA cross-hybridizes to the HPV portion of clone pCD15 to greater than 50% under moderately stringent conditions, and
    wherein the HPV 52 DNA and HPV 52 RNA do not hybridize to DNA from HPV types 1 through 51 under stringent conditions.

21.  An HPV hybridization probe composition comprising
    (a)  a member selected from the group consisting of
        (i)  HPV 52 DNA labelled with a detectable label and
        (ii)  HPV 52 RNA labelled with a detectable label,
    wherein the length of the HPV 52 DNA or HPV 52 RNA is between approximately 15 and 8000 nucleotide bases,
    wherein the HPV 52 DNA consists of all or a fragment of an HPV DNA, wherein the HPV DNA cross-hybridizes to the HPV portion of clone pCD15 to greater than 50% under moderately stringent conditions,
    wherein the HPV 52 RNA consists of all or a fragment of an HPV RNA, wherein the HPV RNA cross-hybridizes to the HPV portion of clone pCD15 to greater than 50% under moderately stringent conditions, and
    wherein the HPV 52 DNA and HPV 52 RNA do not hybridize to DNA from HPV types 1 through 51 under stringent conditions, and
    (b) DNA or RNA of at least one other HPV type labelled with a detectable label.

The District Court construed the contested limitations as follows:

• "HPV 52 hybridization probe" (claim 18) means a "nucleic acid molecule that is specific for HPV 52 DNA and that differentiates HPV 52 DNA from DNA of all other types";

• "HPV 52 DNA labelled with a detectable label" (claims 18 and 21) means "HPV 52 DNA that has a detectable label that is not DNA" (since, given the Court's other constructions, the label could not be DNA);

• "between approximately 15 and 8000 nucleotide bases" (claims 18 and 21) means "between 15 and approximately 8000 nucleotide bases" (since the applicant disavowed fewer than 15 bases during prosecution);

• "HPV hybridization probe" (claim 21) means a "nucleic acid molecule that is specific for the DNA of any one type of HPV and differentiates the DNA of that type from DNA of all other HPV types"; and

• "HPV 52 DNA consists of all or a fragment of an HPV DNA" (claim 21):  "HPV 52 DNA" means "a DNA molecule that is only type 52 HPV" (since the applicant disclaimed a molecule including fragments of later-discovered HPV types by stating during prosecution that "the claimed HPV 52 DNA must be derived from only type 52 HPV DNA") and "consists of all or a fragment of an HPV DNA" means "consists of all or a fragment of one HPV DNA that does not contain any other DNA" (since "an" means "one and only one" when following the transitional phrase "consists of").

On appeal, Digene argued that the District Court misconstrued the phrase "HPV 52 DNA consists of all or a fragment of an HPV DNA" by disregarding the inventor's definition of "HPV 52 DNA" in the prosecution history and claims themselves.  In particular, Digene argued that in the context of the '715 patent, "HPV 52 DNA" is defined by length (approximately 15 and 8000 nucleotides), cross-hybridization with a deposited clone under moderately stringent conditions, and failure to cross-hybridize with HPV types 1-51 under stringent conditions (as opposed to being defined by nucleotide sequence).  In other words, Digene contended that HPV 52 sequences in which "certain" nucleotides had been replaced were still HPV 52 DNA sequences.  As for the statement made during prosecution (i.e., "the claimed HPV 52 DNA must be derived from only type 52 HPV DNA"), Digene argued that it referred to the origin of the DNA and not its specific structure.

Digene also argued that the District Court erroneously limited the term "an HPV DNA" in the contested claim 21 limitation "HPV 52 DNA consists of all or a fragment of an HPV DNA" to "one HPV DNA that does not contain any other DNA."  With respect to this claim term, Digene contended that the overall transitional phrase in the claim was "comprising," and therefore, the term "an" in "an HPV DNA" should have been construed as "one or more."  Digene also argued that the District Court's construction would result in the exclusion of mutations, subtypes, and synthesized DNA.

Third Wave, not surprisingly, took an opposite position with respect to each of Digene's arguments.  In addition, Third Wave asserted that because claim 21 recites both "HPV 52 DNA" and "DNA . . . of at least one other HPV type," the term "HPV 52 DNA" must be limited to DNA of only type 52 and not include DNA of another HPV type.

Siding with Third Wave, the Federal Circuit found that the District Court reasonably construed the phrase "HPV 52 DNA consists of all or a fragment of an HPV DNA."  In particular, the panel agreed that by reciting both "HPV 52 DNA" and "DNA . . . of at least one other HPV type" in claim 21, Digene distinguished HPV 52 DNA from the DNA of other HPV types, thereby supporting Third Wave's position that "HPV 52 DNA" means "a DNA molecule that is only type 52 HPV."  The Court also found that applicant's statement that "the claimed HPV 52 DNA must be derived from only type 52 HPV DNA" indicated that applicant had disclaimed a meaning of "HPV 52 DNA" that was derived from anything but HPV 52 DNA.  In addition, the panel noted that the District Court had been correct in construing "an" after the transitional phrase "consisting of" as meaning "one," stating that "[i]f the term 'consists of' appears in the body of a claim, it does not limit the entire claim as such, but it does limit the clause for which it acts as a transition to only those elements found in that particular clause."  Finally, the Court agreed with Third Wave that the District Court's construction did not exclude possible mutations or subtypes.  With respect to the other claim terms, the panel noted that because "Digene candidly conceded that it could not prove infringement under the district court's claim constructions of 'HPV 52 DNA consists of all or a fragment of an HPV DNA'" at oral argument, the panel did not need to address the remaining terms in light of Digene's concession."

Digene Corp. v. Third Wave Technologies, Inc. (Fed. Cir. 2009)
Nonprecedential disposition
Panel: Circuit Judges Lourie, Rader, and Prost
Opinion by Circuit Judge Lourie

For additional information regarding this case, please see:
• "Digene Files Infringement Suit against Third Wave Technologies," January 17, 2007

Claim Construction at the Federal Circuit: A District Court Judge's View

Medegen MMS, Inc. v. ICU Medical, Inc. (Fed. Cir. 2008)

    By Kevin E. Noonan --

The Federal Circuit recently had the opportunity to appreciate firsthand the frustrations of district court judges with its review of claim construction under Markman v. Westview Instruments, Inc.  This teaching came in a dissenting opinion from the Honorable Vaughn R. Walker, Chief Judge, U.S. District Court for the Northern District of California, sitting by designation in Medegen MMS, Inc. v. ICU Medical, Inc. decided November 20, 2008.

The case involves "needle-free valve[s] for intravenous (I.V.) therapy used to administer fluids to a medical patient."  The claimed devices are used to connect a syringe to a catheter, without suffering from "retrograde flow."  The opinion characterizes retrograde flow as being "the reverse flow of fluid out of the patient's body and back into the catheter tubing, the connector, and the syringe, caused by the negative pressure suction that occurs as the syringe is withdrawn from the connector."  Such retrograde flow can result in blood fouling the catheter, with clotted blood necessitating flushing or replacement of the catheter.  Positive pressure produced using a plug counteracts the negative pressure that produces retrograde flow.

After a Markman hearing construing several claim terms, including "plug," ICU filed and the District Court granted a motion for summary judgment of non-infringement.  The basis for this judgment was that the ICU product embodied a rigid, inflexible plug, while the District Court's construction of plug required a flexible, elastomeric plug.

According to the majority opinion, written by Judge Dyk and joined by Judge Rader, this construction of the term "plug" was error.  The opinion characterized the construction as "relying heavily" on the fact that the specification consistently described the plug as having an elastomeric character, and that the specification "nowhere describe[d] a non-elastomeric or rigid plug."  The CAFC agreed with Medegen, that the term "plug" should be given "its ordinary meaning" as "a moveable member between an open and closed position."  The bases of the Court's opinion included that the term "plug" was claimed "broadly"; that the term was "not expressly limited by the language of the claims"; that there was "no contention that the ordinary meaning of the term 'plug' does not include a rigid plug or that it has a special meaning in the medical field that requires elastomericity"; and that there was no "clear disclaimer of non-elastomeric plugs in the specification."

The opinion expressly disagreed with ICU's contention that the skilled worker "would read the specification as limited to elastomeric plugs," and characterized elastomeric plugs as being "merely an example" of how to practice the invention.  The Court reached its determination even though the Detailed Description section of the patent disclosed elastomeric or "rubber" plugs twenty-one times (and never discussed non-elastomeric or rigid plugs).  This disclosure merely reflects "preferred embodiments," and limiting the claims to preferred embodiments is improper.  According to the opinion, ICU's construction "relies on a single embodiment theory," a construction "specifically rejected" in Phillips v. AWH Corp.  In view of this disagreement on the proper construction of the term "plug," the Federal Circuit vacated and remanded to the District Court for trial using this more expansive construction of plug.

Judge Walker (at left) dissented.  He asserted that the issues before the CAFC presented "a conundrum often faced by district courts when construing" claim terms.  He cited the "twin axioms" of claim construction that produced the conundrum:  "[o]n the one hand, claims 'must be read in view of the specification'," citing Markman, while "[o]n the other hand, it is improper to read a limitation from the specification into the claims," citing Arlington Indus. Inc. v.  Bridgeport Fittings, Inc.  The problem with these axioms, according to Judge Walker, is that "the axioms themselves seldom provide an answer, but instead merely frame the question to be resolved."  Here, Judge Walker contended that the majority based its decision to overrule the District Court's construction on the second axiom without properly assessing the term by taking both axioms into consideration.  While recognizing the sound policy reasons for a patent drafter to be required to include "all claim limitations in the claims of a patent," he also admonished that "patents must be read as well as written."  Citing Phillips, this analysis must be performed with due consideration of a term's "ordinary and customary meaning" informed by the "context of the entire patent, including the specification."  The majority's construction gave too little weight to the specification, in Judge Walker's view, in favor of "broad dictionary definitions."

In contrast, the "very able district court . . . looked first to the patent" in performing its construction of the term "plug," basing its decision on the "repeated" description of the plug as having "elastomeric, pivoting and buckling limitations" that the District Court included in its construction.  Moreover, the claimed invention would not work using a rigid, non-elastomeric plug, and for this reason alone, Judge Walker contended that the District Court's construction of the term was more consistent with an elastomeric plug being "an essential element" of the invention.  In addition to the intrinsic evidence, the District Court also relied on extrinsic evidence from expert witnesses, including evidence that Medegen's expert could not explain how a rigid plug would be operable in the claimed invention.

Judge Walker raises the essential paradox of the Federal Circuit's practice under Cybor Corp. v. FAS Technologies, Inc. of giving no deference to claim construction by district courts:  "[a]s a jurist more accustomed to working on the front lines of patent litigation than reviewing decisions from above, it is my experience that claim construction -- determining how one of ordinary skill in the art would understand the patent at the time of invention -- often requires making fact-like determinations not well suited to appellate review."  The "uniformity and predictability" desired by the CAFC as a general, guiding principle is not always best served in the individual determinations necessary to construe claim terms.  In this he cites with approval Judge Lourie's point in Phillips, that while there is (and perhaps cannot be) formal deference by the CAFC to a district court's claim construction, it is better policy for the Federal Circuit to affirm "in the absence of a strong conviction of error."  Despite the fact that current academic research suggests that Federal Circuit affirmance rates of district court claim construction has "improved" to from 60-70%, these broad statistics do not inform how each Federal Circuit panel addresses, and resolves, specific claim construction issues in any particular case.  And so long as a majority of the Federal Circuit judges continue to resist en banc reconsideration of Cybor, and the Supreme Court appears singularly disinterested in the issue, the inconsistencies resulting from the Federal Circuit's "no deference" standard of review will continue to produce the type of results decried by Judge Walker in Medegen.

Medegen MMS, Inc. v. ICU Medical, Inc. (Fed. Cir. 2008)
Panel: Circuit Judges Rader and Dyk and Chief District Judge Walker
Opinion by Circuit Judge Dyk

General Atomics Diazyme Lab. Division v. Axis-Shield ASA (Fed. Cir. 2008)

    By Kevin E. Noonan --

In the non-precedential General Atomics case decided earlier this month, the Federal Circuit applied its Markman claim construction practice to a Jepson claim, a venerable claim format seen more frequently in the mechanical and electrical arts than in the chemical or biotechnology arts (1).  The case illustrates the tendency for the CAFC to parse claim language very finely and almost hyper-technically, and the prevailing attitude on the Federal Circuit that patentees should and must pay the price for claim language that does not adequately protect their technology from being practiced in a non-infringing manner.

The case involved a diagnostic assay for homocysteine, an amino acid derivative normally found in trace amounts in blood and urine.  Elevated levels have been associated with a variety of ailments, including cardiocascular disease.  Axis-Shield, the patentee, asserted two patents, U.S. Patent Nos. 5,631,127 and 5,958,717, in its countersuit to General Atomics' declaratory judgment action.  Claim 1 of the '127 patent reads:

1.  In a method for assaying homocysteine in a sample, said method comprising the steps of:

    (i) contacting said sample with a homocysteine converting enzyme and at least one substrate for said enzyme other than homocysteine, and

    (ii) assessing an analyte which is a substrate for said enzyme,

    wherein the improvement comprises in step (i) contacting said sample with a said substrate other than homocysteine and in step (ii) without chromatographic separation assessing a non-labelled analyte selected from the group consisting of a homocysteine co-substrate and the homocysteine conversion products of the enzymic conversion of homocysteine by said enzyme.

Claim 1 of the '717 reads:

1.  In a method for assaying homocysteine in a sample, said method comprising the steps of:

    (i) contacting said sample with a homocysteine-converting enzyme and

    (ii) assessing an analyte,

    wherein the improvement comprises in step (ii) without chromatographic separation assessing a non-labelled analyte selected from the group consisting of the homocysteine conversion products of the enzymic conversion of homocysteine by said enzyme.

(underlining was added in the case as reported, to identify the limitations that were the focus of the Federal Circuit's determinations).

Consistent with Jepson claiming, the novel aspects of these claims are the limitations following the word "improvement" in each claim; the recitations prior to "improvement" are in the prior art.

The accused assays detected homocysteine using an assay having the following steps:

1) a co-substrate referred to as S-adenosyl-L-methionine ("SAM") is added to the sample;
2) an enzyme referred to as homocysteine-methionine methyl transferase ("HMTase") is then added;
3) the HMTase acts to remove a methyl group from the co-substrate SAM and attach it to the homocysteine, converting the homocysteine into methionine and SAM into S-adenosyl-L-homocysteine ("SAH");
4) simultaneously, a second enzyme is added, SAH-hydrolase, which catalyzes a reaction that converts SAH to adenosine and non-sample homocysteine;
5) additional steps occur, involving adenosine deaminase and spectrophotometric monitoring, to determine the level of SAH produced.

The assay took advantage of the following reaction pathway:

The basis for General Atomics' assay was that the amount of SAH was proportional to the levels of homocysteine in a sample; the assay assessed the amount of SAH by spectrophotometry.

Axis-Shield asserted two theories of infringement:  that sample homocysteine was coverted by HMTase (the "homocysteine converting enzyme") by combination with SAM (the "homocysteine co-substrate").  The assay produced two "homocysteine conversions products," SAH and methionine, and the assay detected SAH without chromatographic separation.  In its alternative theory, Axis-Shield asserted that SAH hydrolase was the homocysteine converting enzyme, adenosine was the homocysteine co-substrate, and SAH was the homocysteine conversion product.

The case turned, as is frequently the case, on the meaning of the claim terms (underlined above).  In order to infringe, according to the District Court, the analyte detected ("assessed") in the General Atomics assay must either be a homocysteine co-substrate or a homocysteine conversion product.  And the District Court found the analyte assessed in the accused assay (SAH) was neither, based on either of Axis-Shield's infringement theories.

The Federal Circuit, in a unanimous decision written by Judge Lourie (Judges Gajarsa and Dyk concurring) construed the claims de novo in the face of Axis-Shield's contention that the District Court had misconstrued the claims, specifically the terms "homocysteine conversion product," "homocysteine converting enzyme," and "homocysteine co-substrate."  Judge Lourie reviewed the District Court's definition of the term "homocysteine conversion product" as a product that must be derived from homocysteine, and agreed with this construction based on the plain meaning of the claim language.  Specifically, the claim itself recites that the homocysteine conversion products are products of "enzymic conversion of homocysteine by said enzyme."  Judge Lourie made a distinction between the language of the claim and hypothetical language more in keeping with the construction Axis-Shield argued on appeal, "homocysteine conversion reaction products."  In Judge Lourie's view, this language would permit the claim to be construed to encompass detection of "any product" produced by the homocysteine conversion reaction.  In contrast, according to Judge Lourie, the actual claim language specifically recited a homocysteine conversion product, which would include methionine but not SAH.  SAH, in the CAFC's opinion, is a conversion product of SAM, not homocysteine.  The opinion finds support in the specification as well, citing the "first embodiment" of the invention disclosed therein as being the production of SAH by SAH hydrolase.  In this reaction, according to the Federal Circuit, adenosine is the homocysteine co-substrate, SAH hydrolase is the homocysteine converting enzyme, and SAH is the homocysteine conversion product.

The CAFC also rejected Axis-Shield's contention that the specification disclosed embodiments wherein homocysteine acted as an inhibitor of SAH hydrolase, so that detection of the adenosine content of the reaction is a measure of the amount of homocysteine in the sample.  The Federal Circuit noted that claims do not always (and are not required to) encompass all disclosed embodiments, particularly in view of prosecution strategies.  In this case, Axis-Shield had originally asserted another patent, No. 6,063,581, having claims to the inhibitor embodiments, and the Federal Circuit characterized as "inapt" Axis-Shield's claim construction arguments to have these embodiments fall within the scope of either the '717 or '127 claims.

The CAFC also affirmed the District Court's construction that General Atomics' assay did not infringe under Axis-Shield's alternative infringement theory, because it "cannot differentiate between SAH produced from SAH hydrolase reaction and from the HMTase reaction.

Besides the rarity of having the Federal Circuit construe a Jepson claim in a biotechnology patent, this case is another example of the CAFC's propensity to place the burden of an unfavorable claim construction on the patentee (at least with regard to constructions that do not support a finding of infringement); see Sage Products Inc. v. Devon Indust. Inc.  This has some logic as policy, since the patentee is in the best position to claim her invention as broadly as her disclosure and the prior art permit.  In addition, it provides incentives (if not rewards) for third parties to design around the patentee's claims, especially when the construction is based on the "plain meaning" of the claim language.  But it also requires something akin to a crystal ball for patent prosecutors and inventors to craft claim language that adequately protects technology, and it is not yet clear whether the Federal Circuit is balancing these competing interests to provide the optimum amounts of both incentive and certainty.

(1)  For example, the term "nucleic acid" yields 20,706 granted patents as a claim term, while the term "improvement" occurs in only 265 (1.3%) of them.  In contrast, the term "attached" occurs 380,895 times, while the term "improvement" occurs in 21,409 (5.6%) of them.

General Atomics Diazyme Lab. Division v. Axis-Shield ASA (Fed. Cir. 2008)
Panel: Circuit Judges Lourie, Gajarsa, and Dyk
Opinion by Circuit Judge Lourie

Ortho-McNeil Pharmaceutical, Inc. v. Cobalt Pharmaceuticals Inc. (Fed. Cir. 2008)

    By Donald Zuhn --

Last week, the Federal Circuit issued an opinion in Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc.  In Mylan Laboratories, the Federal Circuit determined that the District Court for the District of New Jersey properly construed claim 1 of U.S. Patent No. 4,513,006, owned by Plaintiff-Appellee Ortho-McNeil Pharmaceutical, Inc., to encompass Ortho-McNeil's epilepsy drug topiramate, and affirmed the District Court's decision to (1) permanently enjoin Defendants-Appellees Mylan Laboratories, Inc. and Mylan Pharmaceuticals, Inc. (Mylan) from infringing the '006 patent, (2) dismiss Mylan's invalidity defenses based on obviousness, inequitable conduct, and non-enablement, and (3) reset the effective date of Mylan's Abbreviated New Drug Application (ANDA).  A full discussion of Mylan Laboratories can be found here.

On the same day that the Federal Circuit issued its decision in Mylan Laboratories, it also issued a nonprecedential opinion in a companion case: Ortho-McNeil Pharmaceutical, Inc. v. Cobalt Pharmaceuticals Inc.  In this case, Defendant-Appellant Cobalt Pharmaceuticals Inc. (Cobalt) stipulated that it would be bound by the District Court's final judgment order in Mylan Pharmaceuticals.  Although Cobalt retained its right to appeal, it also stipulated that the appeal would be based on the record in Mylan Pharmaceuticals.  Thus, in affirming the District Court's judgment against Mylan, the Federal Circuit affirmed the District Court's judgment against Cobalt.

Cobalt attempted to present an additional argument on appeal; namely, that claim 1 is rendered indefinite by the use of the term "may be."  The Federal Circuit, however, declined to consider this argument in view of Cobalt's stipulation that its appeal be based on the record in Mylan Pharmaceuticals.

Ortho-McNeil Pharmaceutical, Inc. v. Cobalt Pharmaceuticals Inc. (Fed. Cir. 2008)
Nonprecedential disposition
Panel: Chief Judge Michel and Circuit Judges Rader and Linn
Opinion by Circuit Judge Rader

Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc. (Fed. Cir. 2008)

    By Donald Zuhn --

Last week, the Federal Circuit determined that the District Court for the District of New Jersey properly construed claim 1 of U.S. Patent No. 4,513,006 to encompass Plaintiff-Appellee Ortho-McNeil Pharmaceutical, Inc.'s epilepsy drug topiramate, and affirmed the District Court's decision to (1) permanently enjoin Defendants-Appellees Mylan Laboratories, Inc. and Mylan Pharmaceuticals, Inc. (Mylan) from infringing the '006 patent, (2) dismiss Mylan's invalidity defenses based on inequitable conduct, obviousness, and non-enablement, and (3) reset the effective date of Mylan's Abbreviated New Drug Application (ANDA).

Ortho-McNeil manufactures and sells TOPAMAX®, which is used to treat epilepsy and which comprises the active ingredient topiramate.  Ortho-McNeil researcher Dr. Bruce Maryanoff invented topiramate during a search for new antidiabetic drugs, discovering that the reaction intermediate topiramate had unexpected anticonvulsant properties.

Seeking approval to market generic topiramate, Mylan filed an Abbreviated New Drug Application (ANDA) with the FDA.  In response, Ortho-McNeil filed an infringement suit under 35 U.S.C. § 271(e)(2) in the District Court of New Jersey.

Following a Markman hearing, the District Court rejected Mylan's construction of claim 1 as excluding topiramate.  On summary judgment, the District Court also rejected Mylan's affirmative defenses of invalidity based on obviousness and non-enablement and unenforceability due to inequitable conduct.  As a result of these determinations, the District Court enjoined Mylan from infringing the '006 patent and reset the effective date of Mylan's ANDA.

On appeal, Mylan argued that the District Court improperly construed the word "and" in claim 1 of the '006 patent, which recites:

 

According to Mylan, the phrase "R2, R3, R4 and R5 are independently hydrogen or lower alkyl and R2 and R3 and/or R4 and R5 together may be a group of formula (II)" in claim 1 specifies two independent limitations:

[1] R2, R3, R4 and R5 are independently hydrogen or lower alkyl and
[2] R2 and R3 and/or R4 and R5 together may be a group of formula (II),

both of which must be met for a compound to infringe the claim.  In topiramate (at left), R2 and R3 and R4 and R5 together are a group of formula (II), and therefore, none of R2, R3, R4 and R5 are hydrogen or lower alkyl.  Mylan argues that when claim 1 is properly construed, it does not encompass topiramate.

The Federal Circuit disagreed with Mylan's construction, finding that the District Court properly interpreted claim 1.  According to the CAFC, the term "and appears in conjunction with the adverbs independently and together," and therefore, "links alternatives that occur under the different conditions of independence or togetherness."  In other words, R2, R3, R4 and R5 need not always be hydrogen or lower alkyl.

In support of this construction, the Federal Circuit noted that if the term "and" were construed to require a conjunctive meaning, dependent claims 2, 5, 9, and 10 would be rendered meaningless.  The CAFC also noted that the specification supported the above construction.  Finally, while stating that it need not consult extrinsic evidence, given the plain language of claim 1, the dependent claims, and the specification, the Federal Circuit pointed out that "dictionary definitions of [the term] and, while most often listing the additive sense as the most common usage of the term, also show usage of the term to connote alternatives."

With respect to the issue of unenforceability, the Federal Circuit rejected Mylan's argument that during prosecution of the '006 patent, Ortho-McNeil made statements about prior art compounds that were inconsistent with its own testing of those compounds.  Instead, the CAFC agreed with the District Court that Ortho-McNeil "merely accurately characterizes the references as claiming limited utility."

The Federal Circuit also rejected Mylan's arguments for invalidity.  As to obviousness, the CAFC stated that "this invention, contrary to Mylan's characterization, does not present a finite (and small in the context of the art) number of options easily traversed."  Moreover, "the ordinary artisan in this field would have had to (at the time of invention without any clue of potential utility of topiramate) stop at that intermediate and test it for properties far afield from the purpose for the development in the first place (epilepsy rather than diabetes)."  As to Mylan's assertion that claims 6-8 are not enabled, the Federal Circuit again agreed with the District Court, stating that it would not require undue experimentation to determine an "anticonvulsively effective amount" of topiramate.

Finally, with respect to Mylan's argument that the District Court's order resetting the effective date of Mylan's ANDA was inconsistent with 21 U.S.C. § 355(j)(5)(B)(iii), the Federal Circuit determined inter alia that 21 U.S.C. § 355 is directed to the FDA and does not limit a court's authority to reset the effective date of an ANDA that is approved before the court grants a preliminary injunction or finds infringement, as in the instant case.

Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc. (Fed. Cir. 2008)
Panel: Chief Judge Michel and Circuit Judges Rader and Linn
Opinion by Circuit Judge Rader

Additional information regarding this case can be found at the Orange Book Blog and Patently-O.

Regents of the Univ. of California v. DakoCytomation California, Inc. (Fed. Cir. 2008)

    By Donald Zuhn --

On February 28th, the Federal Circuit, in Regents of the Univ. of California v. DakoCytomation California, Inc.:  (a) affirmed the denial by the District Court for the Northern District of California of a preliminary injunction sought by the Regents of the University of California, Abbott Molecular Inc., and Abbott Laboratories Inc. (Appellants), (b) affirmed in part the District Court's grant of summary judgment of noninfringement as to U.S. Patent No. 6,596,479, (c) reversed in part the District Court's grant of summary judgment of noninfringement as to U.S. Patent No. 5,447,841, (d) affirmed the District Court's construction of "heterogeneous mixture of labeled unique sequence nucleic acid fragments," (e) reversed the District's Court's construction of "morphologically identifiable cell nucleus," and (f) reversed the District Court's determination that Appellants were estopped from asserting that Dako's products meet a limitation of the '841 patent under the doctrine of equivalents.  The Federal Circuit remanded the case to the District Court.

The '841 and '479 patents, which are owned by the Regents of the University of California and are exclusively licensed by Abbott, are directed to improved methods for identifying and classifying chromosomes in order to detect chromosomal abnormalities.  The improved methods of the '841 and '479 patents seek to overcome two problems that existed in the prior art:  (1) the requirement of prior art methods that chromosomes be in the metaphase stage of the cell-division cycle (when the chromosomes are condensed and microscopically visible) as opposed to the interphase stage (when the chromosomes are not condensed and therefore not microscopically visible), and (2) the nonspecificity of prior art methods that use nucleic acid probes to detect particular chromosomal sequences, which leads to unacceptable false-positive results.  This nonspecificity is caused by the hybridization of the nucleic acid probes to repetitive nucleotide sequences scattered throughout the chromosomes; in effect, the repetitive sequences "interfere" with the ability of the nucleic acid probes to hybridize only with particular chromosomal sequences.

The claimed methods of the '841 and '479 patents overcome the problems in the prior art by eliminating the "interference" caused by repetitive sequences.  In the methods of the '841 patent, the interference is eliminated by blocking repetitive sequences, and in the methods of the '479 patent, the interference is eliminated by removing the repetitive sequences.  In particular, in the methods of the '841 patent, "blocking nucleic acid . . . fragments which are substantially complementary to repetitive segments" are added to "labeled nucleic acid . . . fragments which are substantially complementary to nucleic acid segments within the chromosomal DNA for which detection is desired," and in the methods of the '479 patent, "a heterogeneous mixture of labeled unique sequence nucleic acid fragments which are substantially complementary to nucleic acid segments within the interphase chromosomal DNA for which detection is desired" is used.

In September of 2005, Appellants brought suit against Dako for patent infringement, and then in October of 2005 filed a motion for preliminary injunction seeking to enjoin Dako from manufacturing and selling its HER2 kit.  Based on the District Court's construction of the limitations "morphologically identifiable chromosome or cell nucleus" and "heterogeneous mixture of labeled unique sequence nucleic acid fragments" of the '479 patent, and its conclusion that Dako's product did not meet the "blocking nucleic acid" limitation of the '841 patent under the doctrine of equivalents, the District Court determined that Appellants had failed to show a likelihood of success on the merits with respect to their infringement claims, and therefore denied Appellants' motion.

The District Court subsequently issued a second order, amending the basis for its denial of Appellants' preliminary injunction motion.  In particular, the District Court maintained its rejection of Appellants' proposed construction of "heterogeneous mixture of labeled unique sequence nucleic acid fragments," but on the grounds that adopting such a construction would render the '479 patent invalid under the doctrine of obviousness-type double patenting (the District Court had previously determined that adopting Appellants' construction, which only appears in the '479 patent, would render the '479 patent invalid in view of the '841 patent, which the Court determined to be prior art to the '479 patent).  Appellants appealed both orders to the Federal Circuit.

While these appeals were pending, Dako moved for summary judgment of noninfringement.  Following a Markman hearing, the District Court granted summary judgment of noninfringement as to the '479 patent based on the Court's construction of the "heterogeneous mixture of labeled unique sequence nucleic acid fragments" limitation, and granted summary judgment of noninfringement as to the '841 patent based on the Court's conclusion that Appellants were barred from asserting that two of Dako's products met the "blocking nucleic acid" limitation under the doctrine of equivalents (the Court denied summary judgment as to the '841 patent for twenty other Dako products).  Following the District Court's order, the parties filed a joint motion to certify for immediate appeal, which the District Court granted, and the Federal Circuit then granted permission to appeal the interlocutory order.

On appeal, Appellants argued that the District Court had erred in:  (1) construing the limitation "heterogeneous mixture of labeled unique sequence nucleic acid fragments," (2) applying prosecution history estoppel to the "blocking nucleic acid" limitation, and (3) construing the limitation "morphologically identifiable cell nucleus."  With respect to the first issue, Appellants argued that the District Court erred in construing the limitation to mean that the heterogeneous mixture excludes repetitive sequences (Dako's kits contain repetitive sequences).  Appellants based their argument on the doctrine of claim differentiation (some of the patent's dependent claims require repetitive sequences) and the District Court's improper reliance on the prosecution history (Appellants asserted that the term "unique sequence" was added during prosecution to clarify that the claimed method was related to the detection -- and not necessarily use -- of unique sequences).

Despite finding that the District Court erred in first concluding that the '841 patent was prior art to the '479 patent and then concluding that the '479 patent would be rendered invalid due to obviousness-type double patenting, the Federal Circuit affirmed the District Court's construction of the heterogeneous mixture limitation as well as the District Court's determination that some of Dako's kits contain repetitive sequences, and therefore, do not infringe the '479 patent.  The basis of the Federal Circuit's affirmance was Appellants' ability to overcome an enablement rejection (the examiner argued that a mixture containing repetitive sequences would not work due to nonspecific hybridization) by limiting the heterogeneous mixture's composition to unique sequences.  As for Appellants' claim differentiation argument, the Federal Circuit noted that "the presumption created by the doctrine of claim differentiation is 'not a hard and fast rule and will be overcome by a contrary construction dictated by the written description or prosecution history.'"

With respect to the "blocking nucleic acid" limitation, Appellants argued that the District Court erred in barring them from asserting that the peptide nucleic acids (PNAs) used in Dako's kits were an equivalent of the blocking nucleic acids recited in the claims (the parties had stipulated that the "nucleic acid" portion of the term was limited to DNA and RNA).  In particular, Appellants asserted that since the "blocking nucleic acid" limitation was never narrowed during prosecution, the District Court improperly applied the doctrine of prosecution history.

The Federal Circuit concluded first that "[b]ecause the prosecution history suggests that the patentees limited the claim to the blocking method at least in part to overcome the examiner's rejections, the patentees presumptively surrendered all equivalents of the 'blocking nucleic acid' limitation."  The CAFC then concluded that Appellants "met their burden of showing that the amendment did not surrender the equivalent in question because the narrowing amendment was only tangential to the accused PNA equivalent," and therefore, determined that the District Court erred in finding that Appellants were estopped from asserting that Dako's products infringe under the doctrine of equivalents.  The Federal Circuit based its conclusion on the fact that when the patentees amended the claims to add the "blocking nucleic acid" limitation, they  "argued that that the invention was new and nonobvious because it used the blocking method in connection with in situ hybridization for the detection of unique sequences" (emphasis added).  Thus, the CAFC concluded that Appellants' narrowing amendment focused on the "blocking" aspect and not on the "nucleic acid" aspect of the limitation.  The Federal Circuit, therefore, reversed the District Court's determination that Appellants were barred from asserting that Dako's PNA-containing kits infringed under the doctrine of equivalents.

Finally, with respect to the "morphologically identifiable cell nucleus" limitation, Appellants argued that the District Court erred in construing the term to mean "a single cell nucleus that contains the full complement of chromosomal DNA."  Appellants asserted that the limitation "merely requires that the nucleus be 'capable of being identified by its form or function' and does not require the full set of DNA."  The Federal Circuit agreed with Appellants, stating that "[s]ignificantly, nowhere in the prosecution history, or the specification for that matter, do we find any indication that the 'morphologically identifiable' language was added to impose a requirement that the cell nucleus must retain its full complement of chromosomal DNA."  The CAFC, therefore, determined that the District Court erred in construing this limitation.

Judge Prost dissented with respect to the portion of the majority opinion that holds that the doctrine of equivalents is not precluded by prosecution history estoppel because the tangential exception applies, writing that the majority's finding "is contrary to this court's precedent and to the proper application of prosecution history estoppel as set forth by the Supreme Court."  Citing Norian Corp. v. Styker Corp., Judge Prost noted that:

[I]t frequently happens that patentees surrender more through amendment than may have been absolutely necessary to avoid particular prior art.  In such cases, we have held the patentees to the scope of what they ultimately claim, and we have not allowed them to assert that claims should be interpreted as if they had surrendered only what they had to.

Observing that the patentees narrowed the scope of the claims from any method of eliminating interference from repetitive sequences to just the use of "blocking nucleic acid," Judge Prost stated that:

It is irrelevant to the determination of the scope of the surrendered territory that to overcome the prior art references the patentee did not need to amend the claims to a method of disabling the hybridization capacity of repetitive sequences by blocking with a "blocking nucleic acid," but instead could have amended the claims to a method of disabling repetitive sequences by blocking.

Judge Prost concluded that:

To overcome the presumption of prosecution history estoppel "[t]he patentee must show that at the time of the amendment one skilled in the art could not reasonably be expected to have drafted a claim that would have literally encompassed the alleged equivalent."  Here, the appellants could reasonably have been expected to have drafted a claim that encompassed blocking repetitive sequences using PNA.  The appellants should, therefore, be estopped from asserting that PNA is an equivalent to "blocking nucleic acid" in the '841 patent.

Regents of the Univ. of California v. DakoCytomation California, Inc. (Fed. Cir. 2008)
Panel: Circuit Judges Mayer, Lourie, and Prost
Opinion by Circuit Judge Lourie; opinion dissenting-in-part by Circuit Judge Prost

Additional information regarding this case can be found at Patently-O.

In re Gabapentin Patent Litigation (Fed. Cir. 2007)

    By Donald Zuhn --

Last Friday, the Federal Circuit reversed a District Court's finding on summary judgment that eight generic drug manufacturers did not infringe U.S. Patent No. 6,054,482 (the '482 patent), and affirmed the District Court's construction of two disputed claim limitations.

Plaintiffs-Appellants Warner Lambert Co., Pfizer Inc., and Gödecke Aktiengesellschaft (Warner Lambert) manufacture and sell Neurontin®, which is used to treat cerebral disorders such as epilepsy and which comprises the active ingredient gabapentin.  Warner Lambert discovered that under certain manufacturing conditions, gabapentin can form a lactam.  To minimize the formation of the lactam, which is twenty-five times more toxic than gabapentin and which causes - rather than prevents - seizures, Warner Lambert developed a process for preparing stable and safe gabapentin formulations.  The '482 patent is directed towards this process as well as to gabapentin compositions that are substantially free from a lactam contaminant.

Seeking approval to market generic gabapentin, Defendants-Appellees Purepac Pharmaceutical Co., Faulding Inc., Teva Pharmaceutical Industries, Inc., Teva Pharmaceuticals USA, Inc., Zenith Laboratories, Inc. (now IVAX Pharmaceuticals NV, Inc.), Zenith Goldline Pharmaceuticals, Inc. (now IVAX Pharmaceuticals, Inc), IVAX Corp., and Eon Labs Manufacturing, Inc. (Appellees) filed Abbreviated New Drug Applications (ANDAs) with the FDA.  In response, Warner Lambert brought number of infringement actions against the Appellees; the suits were consolidated in the District Court of New Jersey.

In pretrial proceedings, the Appellees moved for summary judgment of noninfringement and invalidity of the '482 patent.  The District Court granted Appellees' motion for summary judgment of noninfringement, determining that Warner Lambert had failed to establish that the accused products contained no more than 20 parts per million (ppm) of anions of mineral acid as required by the asserted claims (more anions of mineral acid indicates the presence of gabapentin hydrochloride - the salt form of gabapentin, which in turn indicates that the gabapentin sample is less pure, and therefore, less stable; less stable formulations of gabapentin contain lactam contaminant).  In addition, the District Court construed two claim terms in Warner Lambert's favor.  In particular, the District Court construed the term "anion of a mineral acid" as an "anion derived from a mineral acid" and the term "adjuvant" as a "subset of [eight particular] inactive ingredients that is intimately mixed with gabapentin to form the drug mixture, and thus [does not] refer to the ingredients of capsule shells or tablet coatings."

On appeal, Warner Lambert argued that the District Court, in granting summary judgment of noninfringement, erred by resolving factual disputes.  In opposing the Appellees' motion for summary judgment, Warner Lambert had submitted the results of a comparative pH test that established that four of five of the Appellees' samples tested contained not more than 17 ppm of anions of mineral acid.  In response, the Appellees challenged the accuracy and reliability of Warner Lambert's comparative pH test.

The Federal Circuit, however, noted that the Appellees had "waived any argument challenging the validity, including challenges to the accuracy or reliability, of the pH testing method for purposes of summary judgment," and were therefore confined to arguing against "the undisputed limits of the test's precision" (i.e., a ± 5 ppm margin of error).  When so confined, the CAFC concluded that the Appellees could not counter Warner Lambert's demonstration that the Appellees' gabapentin (at left) samples contained less than 20 ppm of anions of a mineral acid, as recited in the claims.  Thus, the Federal Circuit concluded that "the district court erred in granting summary judgment of noninfringement based on Warner Lambert's purported failure to meet its burden of proof" since "[t]he record shows that Warner Lambert proffered sufficient evidence to create a genuine issue of material fact regarding whether the accused products met the 20 ppm claim limitation of the '482 patent."

With respect to the District Court's construction of the term "anion of a mineral acid," the Appellees argued that the term refers to total chloride content and is not limited to acid-derived chloride ions. The Appellees also argued that the term "adjuvant" refers to any ingredient other than the active ingredient, and thus encompasses ingredients included in the capsule shell or tablet coating.

In affirming the District Court's construction of the first disputed claim term, the Federal Circuit determined that "the construction adopted by the district court gives full meaning to every word of the entire claim term," and that "[h]ad the patentees intended the anion to refer to any anion, regardless of its source, the patentees could have simply claimed 'anions' and omitted the phrase 'of a mineral acid.'"  With respect to the second disputed claim term, the CAFC noted that the District Court had "found nothing in the patent or prosecution history indicating that ingredients found in the capsule shell or coating affects stability, and also relied on several dictionary definitions in support of its construction."  As a result, the Federal Circuit concluded that the District Court also did not err in construing the term "adjuvant."

In re Gabapentin Patent Litigation (Fed. Cir. 2007)
Panel: Circuit Judges Lourie, Lyn, and Moore
Opinion by Circuit Judge Lourie

Additional information regarding this case can be found at the Orange Book Blog and Patently-O.

Trying to Understand What's Not Obvious about What's "Obvious to Try"

    By Kevin E. Noonan --

The Supreme Court's recent KSR Int'l Co. v. Teleflex Inc. decision is stunning in the amount of dicta it contains (and confusing dicta at that).  The Court succumbed to imprecise language (albeit not quite gobbledygook) even when addressing the merits of the case, particularly its reasoning for reversing the Federal Circuit's opinion.  Nowhere is this more evident than in its foray into the question of when something that is "obvious to try" is also obvious under 35 U.S.C. § 103.

This portion of the Court's opinion consists of a mere 124 words, but has raised the temperature of commentators and less measured members of the patent bar, who opine that it somehow lowers the bar for courts (and more fearfully, the Patent and Trademark Office) to find inventions obvious:

The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was "obvious to try."  Id., at 289 (internal quotation marks omitted).  When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.

The take-home message for many are the words "error" in conjunction with "that a patent claim cannot be proved obvious merely by showing that the combination of elements was 'obvious to try.'"  Having created the impression that something that is "merely . . . obvious to try" can be obvious, the Court then contradicts its own statement by qualifying it:  something that is "[m]erely . . . obvious to try" is also obvious only when there is a design need or market pressure (or, in the words of the TSM test, "motivation") and "a finite number of identified, predictable solutions" that "leads to the anticipated success."

Part of the difficulty in explicating the KSR text is the Court's penchant (not limited, of course, to patent law) in reciting established legal principles as if newly-minted by the Court.  In this case, a close reading of the text reveals the not surprising (and close to mundane) conclusion that things that are obvious can also be obvious to try, and that under limited circumstances (i.e., a limited – "finite" – number of "identified, predictable solutions" that "lead to the anticipated success") things that are "obvious to try" are also obvious.  This is consistent with twenty years of Federal Circuit precedent, as illustrated by two cases: In re O'Farrell (Fed. Cir. 1988) and Pfizer, Inc. v. Apotex, Inc. (Fed. Cir. 2007).

In O'Farrell, the Federal Circuit had this to say about the relationship between obviousness and what is "merely obvious to try":

It is true that this court and its predecessors have repeatedly emphasized that "obvious to try" is not the standard under §103.  However, the meaning of this maxim is sometimes lost.  Any invention that would in fact have been obvious under §103 would also have been, in a sense, obvious to try.  The question is: when is an invention that was obvious to try nevertheless nonobvious?

The admonition that "obvious to try" is not the standard under § 103 has been directed mainly at two kinds of error.  In some cases, what would have been "obvious to try" would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful.  In others, what was "obvious to try" was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it.

Obviousness does not require absolute predictability of success.  Indeed, for many inventions that seem quite obvious, there is no absolute predictability of success until the invention is reduced to practice.  There is always at least a possibility of unexpected results, that would then provide an objective basis for showing that the invention, although apparently obvious, was in law nonobvious.  For obviousness under § 103, all that is required is a reasonable expectation of success.  (Citations omitted).

And in Pfizer v. Apotex:

Parties before this court often complain that holdings of obviousness were based on the impermissible "obvious to try" standard, and this court has accordingly struggled to strike a balance between the seemingly conflicting truisms that, under 35 U.S.C. § 103, "obvious to try" is not the proper standard by which to evaluate obviousness, but that, under O'Farrell and other precedent, absolute predictability of success is not required.  Reconciling the two is particularly germane to a situation where, as here, a formulation must be tested by routine procedures to verify its expected properties.  The question becomes then, when the skilled artisan must test, how far does that need for testing go toward supporting a conclusion of non-obviousness?

First, this is not the case where there are "numerous parameters" to try.  Rather, the only parameter to be varied is the anion with which to make the amlodipine acid addition salt.  Although we recognize some degree of unpredictability of salt formation, the mere possibility that some salts may not form does not demand a conclusion that those that do are necessarily non-obvious.  This is especially true here, where (1) as noted above, the skilled artisan had a reasonable (although not guaranteed) expectation that amlodipine besylate would form; (2) Pfizer conceded in prior litigation that the type of salt had no effect on the therapeutic effect of the active ingredient, amlodipine, and was practically interchangeable, and (3) numerous other publications (described above) clearly directed the skilled artisan to a pharmaceutically-acceptable acid addition salt made from benzene sulphonate, including, significantly, the Carabateas patent which taught the besylate acid addition salt form of another dihydropyridine pharmaceutical compound.

Second, this is not the case where the prior art teaches merely to pursue a "general approach that seemed to be a promising field of experimentation" or "gave only general guidance as to the particular form of the claimed invention or how to achieve it."  Here, as admitted by Mr. Davison, in selecting an acid addition salt formulation, one skilled in the art looked to pharmacopoeias and compendia to find a salt that was previously approved by the FDA and used successfully within the pharmaceutical industry.  Berge clearly pointed the skilled artisan to 53 anions that, as of 1974, were pharmaceutically acceptable.  As Dr. Wells' testimony and the Carabateas patent demonstrated, one of ordinary skill in the art was capable of further narrowing that list of 53 anions to a much smaller group, including benzene sulphonate, with a reasonable expectation of success.

Finally, Pfizer protests that a conclusion that amlodipine besylate would have been obvious disregards its "discovery" because it was obtained through the use of trial and error procedures.  While the pharmaceutical industry may be particularly adversely impacted by application of an "obvious to try" analysis, that Pfizer had to verify through testing the expected traits of each acid addition salt is of no consequence because it does not compel a conclusion of non-obviousness here.  In coming to this conclusion, we have not ignored the fact that "[p]atentability shall not be negatived by the manner in which the invention was made."  35 U.S.C. § 103(a).  Nor are we ignorant of the fact that reference to "routine testing" or "routine experimentation" is disfavored.

*  *  *

However, on the particularized facts of this case, consideration of the "routine testing" performed by Pfizer is appropriate because the prior art provided not only the means of creating acid addition salts but also predicted the results, which Pfizer merely had to verify through routine testing.

Thus, while patentability of an invention is not negated by the manner in which it was made, "the converse is equally true: patentability is not imparted where 'the prior art would have suggested to one of ordinary skill in the art that this process should be carried out and would have a reasonable likelihood of success.'"  (Citations omitted).

Taken in the context of established Federal Circuit (and C.C.P.A. precedent), the Supreme Court's latest assertion of the relationship between obviousness and what it "obvious to try" accomplishes nothing other than to create the (false) impression that new law, or a new interpretation of the law, has been made.  Not so:  it remains the case that what is obvious is also frequently "obvious to try," because there are a limited number of parameters to be varied or new technological methods are applied to an old problem.  And what is merely "obvious to try," without more (i.e., the limited number of finite and predictable solutions that lead to a predictably successful result) is frequently nonobvious, particularly when the result is unpredictable or indeed, suprising and unexpected.  Perhaps it would have been better had the Supreme Court heeded the cautionary note sounded by the Federal Circuit in DyStar Textilfarben GmbH v. C.H. Patrick Co. (Fed. Cir. 2006):

Obviousness is a complicated subject requiring sophisticated analysis, and no single case lays out all facets of the legal test.  [There is] danger inherent in focusing on isolated dicta rather than gleaning the law of a particular area from careful reading of the full text of a group of related precedents for all they say that is dispositive and for what they hold.  When parties . . . do not engage in such careful, candid, and complete legal analysis, much confusion about the law arises and, through time, can be compounded.

For additional information and commentary regarding the KSR decision, please see:

• "Like a Penny Saved for a Rainy Day (Albeit, Unintentionally): The Renewed Relevance of 35 U.S.C. § 103(b)," May 13, 2007
• "BIO's Reaction to KSR v. Teleflex," May 8, 2007
• "Implications of the Supreme Court's KSR v. Teleflex Decision for Biotechnology," May 4, 2007
• "The Patent Office Reacts to KSR: A First Look," May 3, 2007
• "KSR Int'l Co. v. Teleflex Inc. (2007)," April 30, 2007
• "Conference & CLE Calendar," which provides an updated list of upcoming KSR CLE's

Supreme Court Denies Amgen Certiorari Petition to Reverse Cybor

    By Kevin E. Noonan --

The U.S. Supreme Court today denied without comment Amgen's petition for certiorari to review the Federal Circuit's reversal (for the second time) of the District Court's construction of the term "therapeutically effective amount" in its patent infringement suit against Sanofi-Aventis over erythropoietin (EPO).

This lawsuit has been reviewed twice by the Federal Circuit from a bench trial in the Massachusetts District Court (before Judge Young), and each time the Federal Circuit has disagreed with the District Court's interpretation of the term "therapeutically effective amount" in claim 1 of U.S. Patent No. 5,955,422:

A pharmaceutical composition comprising a therapeutically effective amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant, or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture.

(emphasis added).  The meaning of this term is important, because the validity of the claim rests upon whether the term requires that the claimed erythropoietin be capable of treating or curing anemia (see "Amgen Asks Supreme Court to Reverse Cybor").  According to the Federal Circuit, the District Court's interpretation of the term was flawed because the District Court improperly focused on the ability of EPO to cause an increase in hematocrit, which is one of EPO's biological properties recited in the specification, to the exclusion of several others.  Since prior art EPO formulations existed that did not have the capacity to increase hematocrit or cure anemia, the District Court used this distinction for finding that said prior art did not anticipate Amgen's claim.

The Federal Circuit disagreed.  It considered causing an increase in hematocrit to be only one of EPO's biological properties, and remanded to the District Court to consider the prior art in light of its construction of the claim term.

In response, Amgen first petitioned for rehearing en banc, which was denied.  However, the published decision denying rehearing en banc illustrated the fractured consensus on the Federal Circuit over its decision, in Cybor Corp. v. FAS Technologies, Inc., that the court would show no deference to lower courts' claim construction decisions, and would review claim construction (both the legal determinations and the underlying factual findings) de novo.  In its petition, Amgen cited the specific deficiencies of the Federal Circuit in its construction of the claim term relative to the trial court (which Amgen asserted "had received tutorials from an M.I.T. scientist, listened to 32 days of testimony from 35 scientists, and read countless pages of written submissions").  Amgen also based its petition on misappropriation of judicial resources, usurpation of the trial court's duty of assessing the evidence firsthand, and the litany of:

(1) a steadily high reversal rate; (2) a lack of predictability about appellate outcomes, which may confound trial judges and discourage settlements; (3) loss of the comparative advantage often enjoyed by the district judges who heard or read all of the evidence * * * ; and (4) inundation of our court with the minutia of * * * disputed claim terms * * * in nearly every patent case,

citing Judge Michel's dissent from the Federal Circuit's denial of rehearing en banc.

In view of its penchant recently to review (and reverse) Federal Circuit precedent, the Supreme Court's decision to decline this opportunity is both surprising and puzzling.  Perhaps the Court believes it may be time to step back from its more aggressive oversight of the Federal Circuit, particularly since that court seems to "gotten the message" and adapted its recent jurisprudence to Supreme Court mandates (see "Is It Time for the Supreme Court to Stop Flogging the Federal Circuit?" and "Syngenta Seeds, Inc. v. Monsanto Co. (Fed. Cir. 2007)").  Also possible is that the Supreme Court agrees with the Federal Circuit's approach as being consistent with its own thinking in Markman v. Westview Instruments, Inc.  Finally, since a significant minority of the Federal Circuit judges have, in dissent of the en banc rehearing decision, indicated that the application of the Cybor doctrine has not worked well in practice and was ripe for review, the Supreme Court may be content to permit the Federal Circuit to come to its own consensus before stepping in.

Notwithstanding the Supreme Court's decision to deny Amgen's petition, Amgen's EPO franchise would appear to be safe no matter what the District Court decides.  There were four other patents-in-suit in this litigation, and Amgen has prevailed on validity and infringement with respect to two of them.

For additional information regarding this case, please see:

• "Amgen Inc. v. Hoeschst Marion Roussel, Inc. (Fed. Cir. 2006)," October 27, 2006

Amgen Asks Supreme Court to Reverse Cybor

    By Kevin E. Noonan ---

Since the Federal Circuit's en banc decision in Cybor Corp. v. FAS Technologies, Inc. that no aspect of a district court's claim construction was entitled to any deference, courts, commentators, and other critics have disagreed with the Federal Circuit.  Today, Amgen has enlisted the aid of the Supreme Court to rein in what it termed a "power grab" by the Federal Circuit in its petition for certiorari in Amgen Inc. v. Hoechst Marion Roussel, Inc.

This case has gone back and forth from the Massachusetts District Court to the Federal Circuit twice, and each time the Federal Circuit has disagreed with the District Court's interpretation of the term "therapeutically effective amount" in claim 1 of U.S. Patent No. 5,955,422:

A pharmaceutical composition comprising a therapeutically effective amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant, or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture.

The meaning of this term is important, because the validity of the claim rests upon whether the term requires that the claimed erythropoietin (EPO) be capable of treating or curing anemia.  EPO is a naturally-occurring hormone that stimulates the body to produce red blood cells, and its absence (or insufficiency) causes anemia.  The standard clinical measure of anemia is the hematocrit, or the percent of whole blood comprised of red blood cells.  In construing the term "therapeutically-effective amount," the District Court had required that EPO falling within the scope of claim 1 increase hematocrit and have any other biological properties of naturally-occurring EPO.  Prior art EPO formulations existed that did not have the capacity to increase hematocrit or cure anemia, and this distinction was the basis for the District Court's finding that said prior art did not anticipate Amgen's claim.

The Federal Circuit disagreed.  Under the Court's interpretation, the District Court had improperly focused on hematocrit, which is one of EPO's biological properties recited in the specification, to the exclusion of several others, including increasing stimulation of reticulocyte response, development of ferrokinetic effects, erythrocyte mass changes, and stimulation of hemoglobin.  The CAFC noted in particular that the specification recited that the therapeutic properties of recombinant EPO "included" all of these, and that the specification further stated that recombinant EPO was therapeutically useful even if it lacked some but not all of these properties.  For the second time, the Federal Circuit remanded to the District Court for further proceedings based on its more expansive construction of the term "therapeutically effective amount." 

In its petition, Amgen focused on the differences in understanding between the trial court judge (who Amgen asserted "had received tutorials from an M.I.T. scientist, listened to 32 days of testimony from 35 scientists, and read countless pages of written submissions") and the Federal Circuit.  According to Amgen, the Federal Circuit's de novo review jurisprudence misappropriated judicial resources and usurped the trial court's duty of assessing the evidence firsthand.  Amgen cleverly analogized to the Supreme Court's Daubert jurisprudence, where the Court has commented on its confidence in district court judges' ability to understand complex scientific and factual evidence.  In the Daubert analysis, the Supreme Court has directed appellate courts to defer to such factual findings by the district courts, the outcome Amgen advocates here.

Amgen also recites the now-familiar litany of negative consequences of the Federal Circuit's de novo review standard, including "(1) a steadily high reversal rate; (2) a lack of predictability about appellate outcomes, which may confound trial judges and discourage settlements; (3) loss of the comparative advantage often enjoyed by the district judges who heard or read all of the evidence . . .; and (4) inundation of our court with the minutia of . . . disputed claim terms . . . in nearly every patent case," citing Judge Michel's dissent from the Federal Circuit's denial of rehearing en banc.  Finally, Amgen stresses that this issue is ripe for Supreme Court review in light of the disagreement between the Federal Circuit judges, reminding the Supreme Court that it used this rationale for granting certiorari in Warner-Jenkinson and Festo.

Amgen also asked the Supreme Court to review the Federal Circuit's determination that prosecution history estoppel prevented it from prevailing on another of its claims in suit.  This claim recites recombinant EPO containing 166 amino acids, as determined from the predicted amino acid sequence encoded by the EPO cDNA.  In fact, human EPO as it is found in nature contains only 165 amino acids, since the 166th amino acid is cleaved during the protein's maturation process.  The District Court twice found that prosecution history estoppel did not prevent Amgen from asserting this claim against the defendants under the doctrine of equivalents, and twice the Federal Circuit disagreed.  In its certiorari petition, Amgen contends that the manner in which the Federal Circuit is implementing the Supreme Court's edicts regarding the application of the prosecution history estoppel doctrine is tantamount to the Federal Circuit's own, draconian, and Supreme Court-repudiated "no equivalents" standard for any claim amended during prosecution.  In Festo, the Supreme Court had explicitly rejected this approach, mandating that the Federal Circuit's analysis consider whether the amendment was unforeseeable, was tangential to patentability, or for some other reason should not raise an estoppel.  Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 740-41 (2002).  By including the prosecution history estoppel issue in its certiorati petition, Amgen has significantly increased its chances of having the petition granted, since the Supreme Court has been diligent in the past ten years in defending the doctrine of equivalents from a consistent effort by the Federal Circuit to minimize or eliminate application of the doctrine.

Supreme Court review of the Federal Circuit's application in Cybor of the principles it set forth in Markman has been anticipated and welcomed by many.  A significant minority of the Federal Circuit judges have, in dissent, indicated that the Court's application of the Cybor decision (i.e., that the Court owes the District Court no deference even for factual matters related to claim construction) did not work well in practice and was ripe for review.  The Court might have lost its opportunity to address these issues itself, and inadvertently provided the Supreme Court with another opportunity to overturn Federal Circuit precedent, a pastime it has become accustomed to in the last few years.

Roche Diagnostics Corp. v. Home Diagnostics, Inc. (S.D. Ind. 2007)

Court Finds That HDI's Glucometer Does Not Infringe Roche Patent

    By Robert Dailey

A District Court in Indianapolis ruled last week that Home Diagnostics' TrueTrack® and TrackEASE® blood glucose monitoring systems do not infringe U.S. Patent No. 5,366,609, owned by Roche.  The lawsuit had pitted Roche, one of the leaders in the medical diagnostics industry, against a discount seller of competing products.

The Roche patent is directed to a biosensing meter that has a pluggable ROM key.  The pluggable key contains data that enable the meter to perform certain test functions.  The asserted claim contained several means-plus-function elements.  The case largely turned on the District Court's construction of these elements (see Court's Order on Claim Construction).

In typical claim construction, courts should resist reading limitations from the specification into the claims.  The text of the claims establishes their scope.  If the accused device falls within the scope of the claim's periphery, the device infringes.

But the infringement analysis differs for means-plus-function claims.  "Literal infringement of a means-plus-function claim limitation requires that the relevant structure in the accused device perform the identical function recited in the claim and be identical or equivalent to the corresponding structure in the specification."  Even for doctrine of equivalents (DOE) infringement of a means-plus-function limitation, the accused device must "perform the identical function in substantially the same way, with substantially the same result."

Means-plus-function claims can ease some of the headaches of patent prosecution, but they can come back to bite patentees when they try to enforce the claims against an accused infringer.  In drafting means-plus-function claims, patentees should be careful to:  (i) define the function very broadly, and (ii) provide a wealth of embodiments that can serve as corresponding structures.  Otherwise, would-be licensees may find little difficulty designing around the claimed invention.

In this instance, the Court's claim construction left Roche with relatively narrow claims that had little power to exclude potential infringers.

    Roche Diagnostics Corp. v. Home Diagnostics, Inc., 04-cv-1187-LJM-JMS (S.D. Ind. 2007).

    Robert Dailey, Ph.D., is a physical chemist and a third-year law student at the University of North Carolina at Chapel Hill.  Dr. Dailey was a member of MBHB's 2006 class of summer associates, and is a regular Patent Docs contributor.

Ortho-McNeil Pharmaceutical, Inc. v. Caraco Pharmaceutical Laboratories, Ltd. (Fed. Cir. 2007)

    By Donald Zuhn --

In an appeal from a District Court decision granting summary judgment in favor of Defendant-Appellee Caraco Pharmaceutical Laboratories, Ltd. (Caraco), the Federal Circuit concluded that the District Court did not err in construing the term "about 1:5" or in finding no literal infringement or infringement under the doctrine of equivalents, and thus, affirmed the District Court's grant of summary judgment of non-infringement.

Plaintiff-Appellant Ortho-McNeil Pharmaceutical, Inc. (Ortho) owns U.S. Patent No. 5,336,691 (the '691 patent), which relates to a pharmaceutical composition comprising certain weight ratios of the analgesics tramadol and acetaminophen (Ortho sells this composition under the trademark Ultracet®).  The '691 patent discloses that "[c]ertain ratios [of tramadol and acetaminophen] result in a composition which exhibits synergistic analgesic effects," and that "[t]he most preferred ratios are from about 1:19 to 1:50."  The '691 patent also discloses that ratios of "about 1:1 and about 1:5 are encompassed by the present invention."

Seeking approval to market a pharmaceutical composition containing tramadol and acetaminophen having a weight ratio of no less than 1:7.5 and an average weight ratio of 1:8.67, Caraco filed an Abbreviated New Drug Application (ANDA) with the FDA.  In response, Ortho filed suit against Caraco, alleging that the filing of the ANDA infringed claim 6 of the '691 patent.  The asserted claim recites a pharmaceutical composition comprising tramadol and acetaminophen in a weight ratio of "about 1:5."  Caraco then moved for summary judgment of non-infringement.

The threshold issue in this case involves the proper construction of the term "about 1:5."  Before the District Court, Ortho argued that "about 1:5" means "approximately 1:5, and . . . encompasses a range of ratios of at least 1:3.6 to 1:7.1," and Caraco countered that the term means "approximately 1:5, subject perhaps to minor measuring errors of, say, 5 or 10%."  Relying on Ortho's experts, who testified that those of ordinary skill in the art would understand that the term "about 1:5" encompasses a range of ratios between 1:3.6 and 1:7.1, the District Court construed the term "about 1:5" to mean "approximately 1:5, encompassing a range of ratios no greater than 1:3.6 to 1:7.1."

Based on its construction of the term "about 1:5," the District Court concluded that the composition described in Caraco's ANDA did not literally infringe the '691 patent.  In addition, the District Court determined that Caraco's composition - having an average weight ratio of 1:8.67 - did not infringe the '691 patent under the doctrine of equivalents, since such a finding would render the "about 1:5" limitation meaningless.

With regard to the District Court's construction of the term "about 1:5," the Federal Circuit considered the intrinsic and extrinsic evidence in the case, and determined that the District Court had not erred in construing the term "about 1:5" to mean "approximately 1:5, encompassing a range of ratios no greater than 1:3.6 to 1:7.1."  In reaching this determination, the Federal Circuit noted that "[t]he intrinsic evidence points to a meaning for the term 'about 1:5' that is narrow because the 1:5 weight ratio, along with the 1:1 weight ratio, is distinctly claimed and distinguished from other broader weight ratios in the patent."  In particular, the Court noted that because some of the claims in the '691 patent recite a single weight ratio and some claims recite ranges of weight ratios, "one of ordinary skill in the art would understand the inventors intended a range when they claimed one and something more precise when they did not."  The Court also noted that while the inventors tested ratios of 1:1, 1:3, 1:5, 1:5.7, and 1:15, "the patentees chose to specifically claim ratios of 1:1 and 1:5" rather than "claim[] a ratio range of 'about 1:1 to about 1:5,' or even a ratio range of 'about 1:3 to about 1:5.'"

With regard to the District Court's decision to grant summary judgment of non-infringement, the Federal Circuit first determined that under the District Court's claim construction, "there can be no literal infringement because Caraco's formulation must have a weight ratio of tramadol to acetaminophen of no less than 1:7.5."  Turning to the issue of infringement under the doctrine of equivalents, the Federal Circuit agreed with the District Court that to expand the weight ratio of "about 1:5" to encompass a composition having an average weight ratio of 1:8.76 "would eviscerate the limitation."  The Federal Circuit, therefore, concluded that the District Court properly granted summary judgment of non-infringement in favor of Caraco.

Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Lab., Ltd. (Fed. Cir. 2007)
Panel: Circuit Judges Schall and Gajarsa and Chief Judge McKinney
Opinion by Chief Judge McKinney

Abbott Lab. v. Andrx Pharm., Inc. (Fed. Cir. 2007).

    By Kevin Noonan --

Illustrating once again distinctions between permanent and preliminary injunctions in its jurisprudence, the Federal Circuit used a combination of its patent-specific precedent and regional circuit law to affirm a preliminary injunction against only one of three co-defendants.  In Abbott Lab. v. Andrx Pharm., Inc., the Court held that one co-defendant couldn't "piggy-back" its burden of showing a likelihood of success on the merits for its invalidity or unenforceability defenses on a successful showing of either defense made by another co-defendant, leading to different outcomes for the parties.

Abbott sued Andrx Pharmaceuticals, Inc, Ranbaxy Laboratories, Inc., and Teva Pharmaceuticals USA, Inc. for ANDA filings with the FDA for generic versions of Abbott's Biaxin XL, an extended release formulation of the antibiotic clarithromycin.  Abbott asserted against Andrx claims 1, 4, and 6 of U.S. Patent No. 6,010,718; claim 2 of U.S. Patent No. 6,551,616, and claims 8 and 16 of U.S. Patent No. 6,872,407.  The District Court granted Abbott's preliminary injunction motion, holding that Abbott had established a likelihood of success on the merits that Andrx infringed the claims at issue, and that Andrx had failed to establish the likelihood that it would be successful in showing that the claims were invalid.  The District Court's holding was limited to infringement under the doctrine of equivalents for the '718 and '616 patents.

The bases for Andrx's appeal were two-fold:  first, that the District Court was wrong, but more importantly, that Abbott was collaterally estopped from asserting these patent claims due to that court's denial of Abbott's preliminary injunction motion as to the other defendants.  Specifically, the District Court had denied the injunction as to Ranbaxy on the grounds that Ranbaxy had shown a likelihood that it would be able to establish at trial that the '616 and '407 patents were unenforceable for inequitable conduct.  The Court had also denied the injunction as to Teva because it found Teva had shown the required likelihood that claim 2 of the '616 patent was invalid for obviousness, and the Federal Circuit had held, in Abbott's appeal of the District Court's decision denying the injunction as to Teva, that Teva had raised a substantial question of invalidity as to claims 2, 4, and 6 of the '718 patent.

Andrx's appeal was limited solely to the first prong of the preliminary injunction standard:  the likelihood that Abbott would prevail on the merits of its patent infringement case.  Andrx's arguments on appeal were based on Blonder-Tongue Laboratories v. University of Illinois Foundation, that a patentee is collaterally estopped from asserting patent claims against a defendant that had been found invalid or unenforceable against a different defendant.

The Federal Circuit applied the law of the 7th Circuit since the issue was not unique to patent law.  First, the Federal Circuit distinguished Blonder-Tongue on the grounds that the Supreme Court had emphasized the importance of the estoppel-creating decision being a final determination on the merits.  The patentee must have had the opportunity to fully litigate the question of invalidity or unenforceability before a court could preclude it from asserting its patent against another party.  In addition, the collaterally-estopped issues in the later case must be identical to those issues in the prior case.

Andrx acknowledged that Blonder-Tongue required a final determination, but that the holding should be extended to preliminary injunctions because these decisions are "final" as to the question of whether Abbott was entitled to the preliminary injunction.

Under 7th Circuit law, preliminary injunctions were recognized to be made on an incomplete record and to be tentative determinations at best, being decided not on a conclusive determination but on an estimate of the likelihood of success.  The Federal Circuit found that there were "rare instances" where the 7th Circuit would find estoppel in the absence of a final determination.  Under 7th Circuit law, those rare instances arose when the preliminary injunction determination raised an "insuperable obstacle" to a plaintiff's success on the merits.

The Court determined that those circumstances did not apply.  The Federal Circuit found that the District Court in its denial of Abbott's motion for preliminary injunction against Ranbaxy and Teva had not evinced the required intention to "firmly and finally decide" the issues of invalidity and unenforceability.  Under 7th Circuit law, therefore, the Federal Circuit refused to find collateral estoppel against Abbott in its preliminary injunction motion and affirmed.

Andrx's other contention was that the District Court was incorrect, which the Federal Circuit reviewed under the abuse of discretion standard.  Andrx argued on appeal that its product did not infringe because Abbott's patent claims recited the use of a "pharmaceutically-acceptable polymer" whereas Andrx's ANDA generic comprises glyceryl monostearate (GMS).  The Federal Circuit construed the term "pharmaceutically-acceptable polymer" in Abbott's claims and determined that Andrx's GMS was not outside the scope of equivalents.  In so doing, the Court disagreed with the District Court's claim construction, and asserted that the use of Markush language ("selected from the group consisting of") in the specification did not have the limiting effect that such language has in a claim.  In addition, the Court found that the patentee had used the term "means" in the specification consistently when reciting explicit definitions, but had used the word "is" when reciting examples of pharmaceutically-acceptable polymers.  In the Court's view, these differences did not "unambiguously signify" that the patentee had intended to be a lexicographer and limit the scope of the pharmaceutically-acceptable polymers used in the invention.  According to the Court, this determination was supported by the testimony of both parties' experts, neither of whom maintained that the language was explicitly definitional.  Based on this more expansive meaning of the term "pharmaceutically-acceptable polymer" in the claims, the Federal Circuit found that the District Court had not abused its discretion in granting the preliminary injunction based on the likelihood that Abbott would prevail on the merits, that Andrx's generic clarithromycin formulation infringes Abbott's claims under the doctrine of equivalents.  In doing so, the Court explicitly rejected Andrx's contentions that a finding of equivalents would vitiate the "pharmaceutically-acceptable polymer" limitation, or violate the specific exclusion principle (prohibiting a finding as an equivalent of a compound excluded from the claimed limitation).

Abbott Lab. v. Andrx Pharm., Inc. (Fed. Cir. 2007)
Panel: Chief Judge Michel, Circuit Judge Prost, and District Judge Ellis
Opinion by Circuit Judge Prost

Ventana Med. Sys., Inc. v. BioGenex Labs. (Fed. Cir. 2006)

    By Mark Chael --

In an opinion by Circuit Judges Prost and Dyk handed down on December 29, 2006, the U.S. Court of Appeals for the Federal Circuit held that the U.S. District Court for the District of Arizona had incorrectly construed the claim term "dispensing" in U.S. Patent No. 6,352,861 (the '861 patent) as requiring "direct dispensing."  The CAFC, therefore, vacated the lower court's judgment of non-infringement and remanded the case.  In dissent was Circuit Judge Lourie, who agreed with the lower court's claim construction.

The '861 patent at issue in this case claims methods and related devices for performing various biological assays on laboratory slides, including immunostaining, using bar code readers to identify reagents and slides, as well as computers to coordinate the procedures.  On February 11, 2003, Ventana brought suit against BioGenex alleging infringement of claims 1-3, 5, 6, and 8 of the '861 patent.  Following a Markman hearing (Ventana Med. Sys., Inc. v. BioGenex Labs., Inc., No. 03-CV-92 (D. Ariz. 2005)), in which the District Court construed the claim term "dispensing" to mean "direct dispensing," Ventana stipulated to non-infringement, reserving its right to appeal the District Court's claim construction.

All of the asserted claims of the '861 patent contain the term "dispensing" and the sole issue on appeal was the District Court's construction of that term to require "direct dispensing."  As construed by the District Court, "direct dispensing" means that a reagent is dispensed directly from a reagent container onto a slide containing a specimen, without using an intermediate transport system to "sip" reagent from a reagent bottle and "spit" the reagent onto the slide.  According to the District Court, the context of the term in the claims led to the narrow interpretation, since the claims state that a reagent "in" a reagent container is dispensed "onto" a slide.  The District Court also determined that a narrower construction was warranted in view of the written description and figures of the '861 patent, which disclose embodiments in which reagents are dispensed from the bottom of reagent containers onto the slides.  BioGenex also alleged that the inventors had disclaimed indirect dispensing during the prosecution of related patent applications.

The CAFC reviewed the claim construction issue de novo (see Cybor Corp. v FAS Techs., Inc., 138 F.3d 1448 (Fed. Cir. 1998) (en banc)) and determined that the ordinary and customary meaning (see Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc)) of the claim term "dispensing" would not be limited to "direct dispensing" by a person of ordinary skill in the art.  The CAFC disagreed with the District Court's reliance on the words "in" and "onto" in support of the narrowing interpretation to require "direct dispensing," stating that there is nothing in the language of the claims to limit the term "dispensing."  The CAFC also did not agree with BioGenex that certain general statements distinguishing the invention from the prior art in the Background section of the '861 patent constituted a disavowal of claim coverage by the inventors (see e.g., Honeywell Int'l., Inc. v. ITT Indus., Inc., 452 F.3d 1312 (Fed. Cir. 2006) and SciMed Life Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d 1337 (Fed. Cir. 2001).  In addition, the CAFC dismissed BioGenex's allegation that since the disclosure only showed direct dispensing, the claims should be so limited.  The CAFC has "repeatedly warned against confining the claims to [the specific] embodiments [described in the specification]" (see Phillips, 415 F.3d at 1323).  Also, the CAFC noted that "each claim does not necessarily cover every feature disclosed in the specification" and "[w]hen the claim addresses only some of the features disclosed in the specification, it is improper to limit the claim to other, unclaimed features."  Ventana, slip op. at 11, citing Phillips at 1327; Golight, Inc. v. Wal-Mart Stores, Inc., 355 F.3d 1327, 1331 (Fed. Cir. 2004); and E-Pass Techs., Inc. v. 3Com Corp., 343 F.3d 1364, 1370 (Fed. Cir. 2003).  Finally, the CAFC dismissed BioGenex's allegations of prosecution history disclaimer because it was based on statements made in a related application, stating that the doctrine "generally does not apply when the claim term in the descendant patent uses different language."  Ventana, slip op. at 12, citing Invitrogen Corp. v. Clontech Labs., Inc., 429 F.3d 1052, 1078 (Fed. Cir. 2005); ResQNet.com, Inc. v. Lansa, Inc., 346 F.3d 1374, 1383 (Fed. Cir. 2003); and Advanced Cardiovascular Sys., 265 F.3d at 1305-06.  Because the CAFC determined that the related applications upon which BioGenex relied in alleging prosecution history disclaimer used different claim language than the claims at issue, Ventana's statements during prosecution of its related application were not applicable to the present case.

The case was remanded to the District Court for further proceedings in light of the CAFC's claim construction.

Ventana Med. Sys., Inc. v. BioGenex Labs. (Fed. Cir. 2006)
Panel: Circuit Judges Lourie, Dyk, and Prost
Opinion by Circuit Judge Prost; dissenting opinion by Circuit Judge Lourie

Additional Disclaimer:  MBHB was involved in the prosecution of the '861 patent.  To the extent that this case summary contains any opinions, the opinions would be of Dr. Chael and not Ventana Medical Systems, Inc. or MBHB.

Abraxis Bioscience, Inc. v. Mayne Pharma (USA) Inc. (Fed. Cir. 2006)

    By Donald Zuhn --

In an appeal from a District Court judgment of infringement of U.S. Patent Nos. 5,714,520; 5,731,355; and 5,731,356, the Federal Circuit reversed the District Court's claim construction and finding of literal infringement, and affirmed the District Court's finding of infringement under the doctrine of equivalents.

The patents at issue relate to an improved formulation of a general anesthetic and sedative containing propofol (2,6-diisopropylphenol), in which an antimicrobial agent has been added.  AstraZeneca Pharmaceuticals LP (AstraZeneca), the original assignee of the patents at issue, had discovered that microbial contamination of its propofol composition had led to an increase in post-operative infections, which necessitated that a patient's infusion device be changed at least every 6-12 hours.  The inventors of the patents at issue discovered that by adding preservatives to its propofol composition, the microbial contamination could be retarded such that a patient's infusion device need be changed only once every 24 hours.  In particular, the inventors discovered that the preservative disodium edetate was unexpectedly effective in retarding microbial growth in the propofol composition.  Abraxis Bioscience, Inc. (Abraxis) subsequently acquired all rights to the patents at issue.

Seeking to develop a generic formulation of AstraZeneca's improved propofol composition, ESI Lederle (ESI) began a research effort aimed at identifying an antimicrobial agent that would work as well as the edetate in AstraZeneca's propofol composition.  ESI's research efforts led to the identification of the calcium trisodium salt of diethylenetriaminepentaacetic acid (calcium trisdoium DTPA) as a suitable antimicrobial additive, and ESI was granted U.S. Patent No. 6,028,108 (the '108 patent) for a propofol composition containing calcium trisodium DTPA.  Following issuance of the '108 patent, Wyeth Pharmaceuticals, Inc. (Wyeth), of which ESI was a division, notified AstraZeneca that it was seeking FDA approval for ESI's propofol composition.  AstraZeneca responded by filing a patent infringement action against Wyeth and ESI.  Mayne Pharma (USA), Inc. (Mayne) subsequently acquired the Abbreviated New Drug Application (ANDA) for ESI's propofol composition, and AstraZeneca filed a second patent infringement action against Mayne.  Ultimately, Mayne was substituted for Wyeth and ESI in the first action, and the two actions were consolidated.

In its Markman ruling, the District Court construed three contested terms, including the term "edetate" (i.e., the antimicrobial agent recited in the asserted claims).  The District Court noted that the patentees defined "edetate" in the patents at issue as "EDTA and derivatives thereof," and thus, construed the term "edetate" as meaning "EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized."  Following a bench trial, the District Court determined that Mayne's propofol composition infringed the asserted claims of the patents at issue both literally and under the doctrine of equivalents.

With respect to the District Court's construction of "edetate," the Federal Circuit noted that the District Court had adopted a broad definition of the term "derivatives" in arriving at a construction of "edetate" that encompassed structural analogs of EDTA as well as synthetic derivatives.  The Federal Circuit determined, however, that the instrinsic evidence failed to support a construction of "edetate" that would encompass structural analogs of EDTA.  For example, while the patents at issue list several derivatives of EDTA that are suitable for the invention, the Federal Circuit observed that none of these derivatives are structural analogs.  The Federal Circuit concluded, therefore, that "the listing of EDTA salts as '[p]articular derivatives of use in the present invention,' coupled with the statements regarding the uniqueness of edetate as the only successful antimicrobial agent, and the patentees' description of EDTA salts as advantageous, preferable, and 'exceptional,' limit the term 'derivatives' to EDTA salts or compounds that maintain the EDTA free acid structure."  Thus, the Federal Circuit determined that the District Court had erred in adopting a broad definition of the term "derivatives," and held that "the proper construction of 'edetate' is EDTA and derivatives of EDTA, such as salts, but not including structural analogs."

With respect to the District Court's finding of literal infringement, the Federal Circuit noted that Abraxis had conceded during oral argument that calcium trisodium DTPA is not a salt of EDTA, and further, that calcium trisodium DTPA is not a derivative of EDTA, since it cannot be synthesized from EDTA in a laboratory.  The Federal Circuit concluded that because neither EDTA nor any of its salts or derivatives was present in Mayne's propofol composition, the District Court had erred in finding that Mayne's propofol composition infringed the patents at issue.

In affirming the District Court's finding of infringement under the doctrine of equivalents, the Federal Circuit rejected three arguments proffered by Mayne in support of its position that the District Court had erred in finding that calcium trisodium DTPA was an equivalent of edetate.  Mayne first asserted that the District Court, in applying the function-way-result test, had improperly defined the "way" in which edetate works.  The Federal Circuit, however, agreed with the District Court's determination that the "way" in which both calcium trisodium DTPA and edetate "function" to retard microbial growth is by metal ion chelation.  Mayne next asserted that because the patentees chose to narrowly claim their invention, it was impermissible as a matter of law to extend the meaning of edetate to calcium trisodium DTPA by equivalence.  The Federal Circuit, however, determined that "[c]ontrary to Mayne’s assertion, the inventors did not clearly disavow other polyaminocarboxylates, including DTPA, by claiming edetate," and further that "[t]here is no evidence that the patentees made a clear and unmistakable surrender of other polyaminocarboxylates, or calcium trisodium DTPA in particular, during prosecution."  Finally, Mayne asserted that the lack of known interchangeability between calcium trisodium DTPA and edetate as an antimicrobial agent indicated that the substitution of calcium trisodium DTPA for edetate was a substantial change.  With respect to Mayne's last argument, which the Federal Circuit stated was largely premised on Mayne's ability to secure a patent for its own propofol composition, the Federal Circuit concurred with the District Court's determination that "the separate patentability of Mayne’s generic formula did 'not outweigh the substantial evidence of equivalence between Mayne’s calcium trisodium DTPA and the claimed edetate.'"

Abraxis Bioscience, Inc. v. Mayne Pharma (USA) Inc. (Fed. Cir. 2006)
Panel: Circuit Judge Lourie, Senior Circuit Judge Plager, and Circuit Judge Rader
Opinion by Circuit Judge Lourie

Amgen Inc. v. Hoechst Marion Roussel, Inc. (Fed. Cir. 2006)

    By Kevin Noonan --

The peripatetic case of Amgen Inc. v. Hoechst Marion Roussel, Inc. has once again been reviewed by the Federal Circuit (decided August 3, 2006).  Once again the CAFC has failed to lay the several issues in the case to rest.  While affirming infringement and validity of two of the patents in suit, the Federal Circuit has remanded the matter once again to the District Court in view of its de novo claim construction, and perhaps predictably disagreed with the lower court and reversed a determination of infringement under the doctrine of equivalents.

The case has two interesting aspects.  First, citing the rubrics of Phillips the Federal Circuit came to its own determination of the meaning of the term "therapeutically effective amount" with regard to a claim for recombinant erythropoietin (EPO).  EPO is a naturally-occurring hormone that stimulates the body to produce red blood cells, and its absence (or insufficiency) causes anemia.  The standard clinical measure of anemia is the hematocrit, or the percent of whole blood comprised of red blood cells.  In construing the term "therapeutically-effective amount," the District Court had required that EPO falling within the scope of the claim containing the term increase hematocrit and have any other biological properties of naturally-occurring EPO.

The Federal Circuit disagreed, and in doing so provided a nice illustration that Phillips has not changed the Court's capacity for arriving at its own idiosyncratic construction.  The CAFC determined that the lower court had improperly focused on hematocrit, which is one of EPO's biological properties recited in the specification, to the exclusion of several others, including increasing stimulation of reticulocyte response, development of ferrokinetic effects, erythrocyte mass changes, and stimulation of hemoglobin.  The Federal Circuit noted in particular that the specification recited that the therapeutic properties of recombinant EPO "included" all of these, and that the specification further stated that recombinant EPO was therapeutically useful even if it lacked some but not all of these properties.

Of course, the CAFC seems to have not considered the fact that all of the recited properties are related to the clinical measurement of hematocrit, since they are all part of the biological developmental pathway leading to an increase in the number of red blood cells in blood.  Thus, by cherry-picking the language of the specification, the Court was able to arrive at a facially-reasonable claim construction that seems to run contra to clinical reality.  This portion of the matter has been remanded, for further consideration in view of the CAFC's claim construction, on the issue of invalidity over prior art references to EPO preparations that did not increase hematocrit but may have had one of the other recited biological properties.

The second issue is the doctrine of equivalents.  The "predicted" recombinant EPO protein contains 166 amino acids, but as produced naturally (and using HMR's recombinant process) EPO has only 165 amino acids.  The issue before the Federal Circuit was whether Amgen was entitled to assert claims to HMR's recombinant EPO as an equivalent.  The District Court twice found in the affirmative, and the Federal Circuit remanded in its first review so the lower court could consider the issue in view of Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 740-41 (2002).  The District Court having arrived at the same conclusion, infringement under the doctrine of equivalents, the Federal Circuit reversed, finding estoppel arising during prosecution.  Specifically, the CAFC held that preliminary amendments resulting in claim language reciting the 166 amino acid species were not made for reasons tangentially related to the asserted equivalent, as found below, but raised prosecution history estoppel that precluded asserting the claim against HMR's 165-amino acid species.  The Federal Circuit's holding was based in part on Amgen's cancellation of claim limitations related to "fragments" of the 166-amino acid species, and in part because it found erroneous the District Court's determination that the amendments were made to limit the species to human EPO (the CAFC noted that if Amgen had intended to so limit the claims the mere addition of the word "human" would have been sufficient).  Finally, the Federal Circuit rejected the notion that amendments made to avoid a double-patenting rejection were "tangential to patentability."

For those keeping score, the Federal Circuit in its two decisions has affirmed the District Court's judgment that two of Amgen's patents are not invalid and are infringed, also affirmed that another Amgen patent is invalid, reversed a finding of infringement under the doctrine of equivalents (but affirmed that this patent is also not invalid), and for one patent remanded the issue of invalidity to the District Court while affirming that if valid this patent is also infringed.  As noted in Judge Michel's dissent (over the claim construction issue), the District Court is now in position to decide whether to grant an injunction, keeping HMR's competing EPO product off the market until at least the expiration of two of Amgen's patents.  For the parties, that may be (or have to be) enough.

Amgen Inc. v. Hoechst Marion Roussel, Inc. (Fed. Cir. 2006)
Panel: Chief Judge Michel, Senior Circuit Judge Clevenger, and Circuit Judge Schall
Opinion by Circuit Judge Schall; dissenting-in-part opinion by Chief Judge Michel

This article was originally published on Patently-O on August 13, 2006.