Patent Docs

Dey, L.P. v. Sunovion Pharmaceuticals, Inc. (Fed. Cir. 2013)

By Kevin E. Noonan --

Enactment of the Leahy-Smith America Invents Act in 2011 focused the patenting community on the changes of U.S. patent law from "first to invent" under the 1952 Patent Act to "first inventor to file" under the AIA as the basis for deciding priority and defining the scope of prior art to a claimed invention.  Nevertheless, the provisions of the 1952 Act remain in force for any application filed prior to March 16, 2013, and the Federal Circuit's recent decision in Dey, L.P. v. Sunovion Pharmaceuticals, Inc., illustrates that there remain issues in the "old" law that will continue to be explicated and addressed.

The issue in the Dey case is the patentability bar under 35 U.S.C. § 102(b) that arises from "public use" of an invention more than one year prior to an applicant's filing date.  The circumstances surrounding the assertion of invalidity under this provision of the statute were somewhat unusual, as recognized by the Court:  typically it is the accused infringer who asserts a patentee's own prior public use as invalidating, but here defendant Sunovion asserted its own prior clinical trial as a public use of Dey's claimed invention.  Specifically, both Sunovion and Dey developed pharmaceutical formulations of a known drug, formoterol, as a nebulized formulation for treating chronic obstructive pulmonary disorders (COPS) such as emphysema.  Both companies owned patents on their formulations:  No. 6,040,344 to Sunovion (filed in 1998 and issued in March 2000); and Nos. 7,348,362; 7,462,645; 7,465,756; 7,473,710; and 7,541,385 to Dey (all claiming priority to July 10, 2003).  Sunovion was the first to market in 2007 with its Brovana product, after what the Court terms a "long" path to obtaining regulatory approval.  Sunovion's clinical trials began in 1998, and of interest in the decision is a particular Phase III clinical trial, Study 50, that began in February 2002, wherein one of the formulations tested was identical to the Brovana formulation.

Just prior to launch, Dey sued Sunovion for infringement of its patents, and Sunovion filed a motion for summary judgment of invalidity for prior public use under § 102(b), based on its own clinical trials.  Under Sunovion's legal theory, the Phase III clinical trial identified as Study 50 included a formulation (given to 124 clinical trial participants) that was within the scope of Dey's patent claims and the conditions of the clinical trial constituted a prior public use that occurred more than one year before Dey's earliest filing date of July 10, 2003.  The conditions Sunovion cited in support of the prior art status of its clinical trial were:

• Patients were told that they were being given a formulation of formoterol
• Patients enrolled in the trial were told they could (and indeed should) inform their personal physicians about the trial
• Patients enrolled in the study were under no conditions of confidentiality
• At least some of the vials ("a fraction of one percent") of the formulated drug were unaccounted for during and after the clinical trial

The District Court granted summary judgment against Dey, finding that Sunovion had established by clear and convincing evidence that the asserted claims of Dey's patents in suit were invalid as being anticipated under the "public use" prong of § 102(b).

The Federal Circuit reversed, in an opinion by Judge Bryson, joined by Judge O'Malley over a dissent by Judge Newman.  The panel noted that the purpose of the bar was to "discourage[e] the removal, from the public domain, of inventions that the public reasonably has come to believe are freely available," citing Tone Bros., Inc. v. Sysco Corp., 28 F.3d 1192, 1198 (Fed. Cir. 1994).  The test for deciding whether a prior use was a "public use" under the statute has two elements:  "'whether the purported use:  (1) was accessible to the public; or (2) was commercially exploited,'" citing Invitrogen Corp. v. Biocrest Mfg., L.P., 424 F.3d 1374, 1380 (Fed. Cir. 2005).  Factual issues to be considered when determining whether a prior use constitutes a "public use" include "'the nature of the activity that occurred in public; the public access to and knowledge of the public use; [and] whether there was any confidentiality obligation imposed on persons who observed the use'" according to the opinion, citing Bernhardt, L.L.C. v. Collezione Europa USA, Inc., 386 F.3d 1371, 1379 (Fed. Cir. 2004).  In the absence of commercial exploitation a confidentiality agreement could "negate" the status of a prior use as a public use.  Invitrogen at 1382.

The status of a prior use as a public use is not dependent on the public use being an applicant's use; activities of third parties (such as Sunovion here) can constitute an invalidating prior public use.  Eolas Techs. Inc. v. Microsoft Corp., 399 F.3d 1325, 1334 (Fed. Cir. 2005).  But such a third party use must be a public not a private use (i.e., the fact that there was a prior use by another does not by itself constitute a public use) according to the Court, citing Woodland Trust v. Flower- tree Nursery, Inc., 148 F.3d 1368, 1371 (Fed. Cir. 1998), and W.L. Gore & Assocs. v. Gar- lock, Inc., 721 F.2d 1540, 1549-50 (Fed. Cir. 1983).  The opinion notes that, as with all question under § 102 this is a question of fact depending on the circumstances, such as a situation where there is no confidentiality agreement:  there, "the skill and knowledge of those observing an invention can shed light on the degree to which it was kept confidential" and even "limited disclosure" may suffice if it is to "those who are skilled enough to know, understand, and 'easily demonstrate the invention to others,'" citing Netscape Commc'ns Corp. v. Konrad, 295 F.3d 1315, 1321 (Fed. Cir. 2002).

The Federal Circuit reversed the District Court's summary judgment because it found disputed issues of material fact that made summary judgment inappropriate.  However the majority opinion went on to set forth the considerations important for making the determination and the places where in the majority's opinion the District Court went astray.  The majority identified two issues important to the District Court's decision that warranted comment.  The first was the lower court's determination that the use of the particular "infringing" formulation during the clinical trial was "open and free," a determination with which the Court disagreed.  The basis for this disagreement revolved around the incapacity of the clinical trial participants to "reverse engineer" the formoterol formulation even knowing the identity of the drug.  In addition, the panel majority disagreed that the study participants were provided with a "personal supply" of the formulations that they could use "however they saw fit" and that provided them with an "unfettered use of the composition for weeks at a time."  The panel agreed with Dey that the use by the study participants was anything but "unfettered," citing the restrictions contained in agreements between the clinical trial administrators and participants, including requirements that the participants be the only individuals taking the medication and that they keep "accurate usage logs"; the Court also noted that despite the extremely low level of the formulation that was unaccounted for the participants and administrators in the trials were required to return all unused portions of the drug and to account for all administered and inventory supplies of the formulated drug.  Specifically the opinion states:

The fact that a tiny fraction of the thousands of vials were lost without penalizing the responsible test subject(s), or that the practicalities of the study required self-administration at home rather than physician administration in a closed facility, does not preclude a reasonable jury from concluding that the use of Batch 3501A was sufficiently controlled and restricted, rather than unfettered and public.

The majority also disagreed that the details of the clinical trial were not required to be kept confidential by trial participants.  The issue for the Court was what information was kept confidential and here the panel noted that "the particulars of its invention -- embodied in the formulation and stability characteristics of Batch 3501A -- were kept sufficiently confidential to avoid a finding of 'public use.'"  Also important for the panel's decision were the confidentiality obligations imposed on the clinical investigators (clearly more knowledgeable than the patients), who were required to sign confidentiality agreements.  The panel majority found that the individuals most likely to have sufficient disclosure for the clinical trial to be a public use were under an obligation not to disclose (thereby negating the clinical trial as a public use as to those individuals), and that the individuals (the patients) not under  any confidentiality obligations had insufficient information to constitute prior disclosure of the invention.

The panel majority noted that the circumstances surrounding the clinical trial were common and that prior precedent "routinely rejected the argument that such an arrangement necessarily strips the trial of confidentiality protection or renders it accessible to the public," citing Bayer Schering Pharma AG v. Barr Labs., Inc., No. 05- CV-2308 (PGS), 2008 WL 628592, at *11-12, *38-42 (D.N.J. Mar. 3, 2008); Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., 364 F. Supp. 2d 820, 873-75, 912-13 (S.D. Ind. 2005), aff'd, 471 F.3d 1369, 1380-81 (Fed. Cir. 2006); Janssen Pharmaceutica N.V. v. Eon Labs Mfg., Inc., 374 F. Supp. 2d 263, 276 (E.D.N.Y. 2004), aff'd, 134 F. App'x 425, 430-31 (Fed. Cir. 2005); and In re Omeprazole Patent Litig., 490 F. Supp. 2d 381, 508 (S.D.N.Y. 2007), aff'd on other grounds, 536 F.3d 1361 (Fed. Cir. 2008).  Circumstances in common in such cases and the case at bar noted by the Court is that study participants were informed as to the identity of the administered drug, that such patients were entrusted to administer doses themselves not under the control or supervision of a study administrator or doctor and that these prior participants were permitted to discuss the trial with their personal physicians.

Finally, the panel majority identified several other "misconceptions" underlying the District Court's decision.  These included that lack of any confidentiality obligations to Dey by Sunovion's clinical trial participants, which the panel recognized would require any third party prior use (even a secret use) to be a patent-invalidating public use.  And the panel rejected Sunovion's attempt, in their view, to stretch precedent related to "experimental use," such as New Railhead Mfg., L.L.C. v. Vermeer Mfg. Co., 298 F.3d 1290, 1299 (Fed. Cir. 2002), and City of Elizabeth v. American Nicholson Pavement Co., 97 U.S. 126, 136 (1877), to apply in this situation.  In those cases the invention was "public" but was not appreciated by the public under circumstances where the use was necessary to demonstrate reduction to practice of the invention ("During experimentation, the public might have knowledge of an invention (because they see it), but may not be using the invention within the meaning of the statute (because the inventor is experimenting)").  Accordingly, the Court remanded the case to the District Court for reconsideration on the merits.

Judge Newman's dissent was not based on her disagreement with the outcome but rather because she would prefer the Court remand with instructions to deny the motion on the grounds that the Sunovion clinical trials did not constitute a "public use."  "No sound reason appears for remanding for findings or trial, when the matter is readily resolved on undisputed facts.  Nor is there any reason for casting judicial doubt on the standard confidentiality procedures of clinical trials, at this late date of decades of established practice," in Judge Newman's view.

Dey, L.P. v. Sunovion Pharmaceuticals, Inc. (Fed. Cir. 2013)
Panel: Circuit Judges Newman, Bryson, and O'Malley
Opinion by Circuit Judge Bryson; dissenting opinion by Circuit Judge Newman

In re Ditto (Fed. Cir. 2012)

Cats and the Federal Circuit

By Kevin E. Noonan --

Unlike dog breeds that tend to be of ancient vintage (Labra-doodles and Yorkie-poos to the contrary), many cat breeds are of relatively recent parentage.  While there are many naturally occurring breeds (such as Maine Coons and Norwegian Forest Cats), a surprising number of cat breeds were developed in the last 50 years or so.  The most recent (and perhaps most extreme) are Savannahs, that are the result of breeding between a domestic short-haired cat and a serval, a wild, undomesticated African cat.  The Federal Circuit had the opportunity to opine on whether another (relatively) recent cat breed, the Pixie-Bob (at right), was patent-eligible subject matter or novel in an appeal from rejection on both these grounds before the Patent Office.  While the Court avoided the statutory subject matter question, it affirmed rejection for lack of novelty for the remarkably named applicant, Frank Robert Ditto.

Mr. Ditto claimed a breed of cats produced by mating a bobcat, lynx or bobcat-lynx mix with a domestic cat.  The sole independent claim is directed to "[a] domestic cat breed produced by breeding a purebred cat produced by mating a Bobcat, Lynx, or Bobcat Lynx species with a domestic cat," with dependent claims reciting various phenotypic characteristics of the cats (in most part relating to the cats' propensity to vocalize).  As explained in the specification, the breed has a unique combination of domesticated behaviors and "the spirit and disposition of the wild" cat as well as other specific traits (including "a variety of colors, have hind legs that are larger than their front legs, may have spotted fur or a stump tail, and have 'sturdy muscular bodies.'"

The Board affirmed the Examiner's rejection of §§ 101 and 102 grounds.  The basis for the § 101 rejection was that the breed was a "product of nature" that resulted from breedings that occurred in the wild.  The Board affirmed this rejection insofar as the claims did not require any particular degree of interbreeding and that naturally occurring cats could satisfy the limitations recited in claim 1.  With regard to the § 102 rejections, the Examiner cited two prior art references:  a 1994 Seattle Times article by Green relating to a Pixie-Bob produced by mating of a wild bobcat and a domestic cat (in a family barn without human intervention); and a 1995 Bellingham Herald article by Porter describing the Pixie-Bob breed and its introduction to The International Cat Association (TICA) as an "official" cat breed.  These references also satisfied the limitations recited in claim 1 on similar grounds, i.e., that there was no limitation as to the degree of breeding required and that "there was no evidence . . . suggest[ing] any difference between the Pixie-Bob cat [described in the cited prior art] and the claimed cats."

The Federal Circuit affirmed in a per curiam opinion before Judges Dyk, Prost, and Reyna.  Their opinion did not address the § 101 rejection, finding sufficient evidence that the claims were anticipated under § 102.  According to the panel, the term "purebred" was properly given its "broadest reasonable interpretation," particularly in view of the lack of any particular definition in Inventor Ditto's specification.  And the panel apparently relied on a dictionary definition of "breed" as meaning "a distinctive group of domestic animals differentiated from the wild type under the influence of man and usu[ally] incapable of maintaining its distinctive qualities in nature," citing Webster's Third New International Dictionary of the English Language 274 (1993).  Like the Board, the panel rejected Inventor Ditto's argument that the Green and Porter references did not describe a breeding that had achieved the desired level of domesticity (particularly with reference to the TICA "SBT" breeding standards).  Tellingly, Inventor Ditto's filing date (March 25, 1999) was after the date (May 1, 1998) when TICA accepted the Pixie-Bob as a recognized breed.  According to the panel, both the Green and Porter references disclosed characteristics and features of the Pixie-Bob cats that are distinctive and comprise the "desired effects" recited as a limitation in Inventor Ditto's claims.

The panel's decision finishes the patenting process for Inventor Ditto.  However, the "product of nature" rejection before the Office remains unscrutinized and intriguing (and, truthfully and in full compliance with the Supreme Court's analytical protocol, is based in part on the prior existence -- i.e., on § 102 grounds -- of the breeding in nature).  But the question can be presented more starkly with the Savannah cat mentioned above.  This cat is bred solely with human intervention (there is no evidence that the African serval ever mated in the wild with a domestic cat and certainly not with an American domestic cat).  In addition, males in the F1 generation are sterile; indeed, it is not until the F4 generation that fertile males are produced.  This required backcrossing into the domesticated cat stock in order to produce cats that breed "true," i.e., that have both parents of the Savannah breed.  All of these aspects evince the "hand of man" and represent something that is the "product of human ingenuity 'having a distinctive name, character [and] use,'" Chakrabarty at 310, citing Hartranft v. Wiegmann, 121 U. S. 609, 121 U. S. 615 (1887).  Thus it is clear under prevailing precedent that the Savannah cat should comprise patent-eligible subject matter.  Although this question is beyond the scope of the question presented to the Supreme Court in the Myriad case or in Mayo v. Prometheus, the question remains whether this Court would find these "routine" and "conventional" breeding methods to provide "enough" for the Savannah cat to be "more than" a product of nature and become a patent-eligible product of man.

In re Ditto (Fed. Cir. 2012)
Panel: Circuit Judges Dyk, Prost, and Reyna
Opinion per curiam

Image of Pixie-bobs (above) by Angie 1900, from the Wikipedia Commons under the Creative Commons Attribution 3.0 Unported license.

In re Antor Media Corp. (Fed. Cir. 2012)

By Kevin E. Noonan --

In a case otherwise of little interest to the biotech/pharma community, the Federal Circuit last month increased the burden on proving patentability created by prior art references for patent applicants and patentees.  This was accomplished by defining a presumption of enablement not only for prior patents and published patent applications but also for all prior printed publications, regardless of source of provenance.

The case involved an appeal from a U.S. Patent and Trademark Office rejection (in five ex parte reexaminations merged for consideration by the Office) of claims in U.S. Patent No. 5,734,961 directed to "to a method and apparatus for transmitting information recorded on digital disks from a central server to subscribers via a high data rate telecommunications network."  For completeness, independent method claim 1 is set forth as follows:

1.  Method of receiving information from one of a plurality of information systems via a high data rate telecommunication network in response to a request from one of plural subscriber stations, said method comprising the steps of:
    initiating a two-way transmission from subscriber computer means of said one of said plural subscriber stations to one of said in formation systems via said telecommunication network,
    outputting on output means of said one of said plural subscriber stations data related to plural information stored at one of said information systems,
    selecting at said one of said plural subscriber stations at least one of said information by means of input means of said one of said plural subscriber stations and transmit- ting a signal identifying said at least one selected information from said subscriber computer means to a selected information system via said telecommunication network,
    receiving at said one of said plural subscriber stations from said selected information system digital signals via said telecom- munication network, expanding by expansion means said transmitted signals, converting said expanded digital signals into analog signals and delivering said analog signals to transducer means.

This claim and others (including some that added a "controller" limitation) were rejected over four prior art references:

• Arif Ghafoor et al., A Distributed Multimedia Database System, Dep't of Elec. & Comp. Eng'g, Syracuse Univer sity (1988 IEEE).

• Stavros Christodoulakis & Theodora Velissaropoulos, Issues in the Design of a Distributed Testbed for Multimedia Information Systmems (MINOS), Journal of Mgmt. Inf. Sys., Vol. 4, No. 2 (1987).

• H.K. Huang et al., Picture Archiving and Communications Systems (PACS) for Radiological Images: State of the Art, CRC Critical Reviews in Diagnostic Imaging, Vol. 28, Issue 4 (1988).

• Barrett, U.S. Patent 4,918,588 (granted April 17, 1990).

In an opinion by Judge Lourie, joined by Chief Judge Rader and Judge Bryson, the Federal Circuit affirmed the PTO determination that the claims were either anticipated or obvious.  In arriving at this conclusion, the Court addressed Antor's argument that the Board erred when it considered the prior art printed publications to be presumptively enabled.  The Court set out the following reasoning for its disagreement with this argument.

The opinion cites Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354 (Fed. Cir. 2003), for the proposition that "both claimed and unclaimed materials disclosed in a patent are presumptively enabling," noting that during prosecution "the examiner is entitled to reject application claims as anticipated by a prior art patent without conducting an inquiry into whether or not that patent is enabled or whether or not it is the claimed material (as opposed to the unclaimed disclosures) in that patent that are at issue," citing In re Sasse, 629 F.2d 675, 681, 207 USPQ 107, 111 (C.C.P.A. 1980).  This is not determinative, however, because the applicant can then rebut the presumption by submitting evidence that the reference is not enabled.

The panel recognizes, however, that the Amgen case "did not decide whether a prior art printed publication, as distinguished from a patent, is presumptively enabling during patent prosecution," although in so going the Amgen Court did suggest that such a presumption was likely, saying that "[w]e note that by logical extension, our reasoning here might also apply to prior art printed publications as well, but as Sugimoto is a patent we need not and do not so decide today."

Accordingly, the opinion makes express that "logical extension":  "the issue regarding non-patent publications [being] squarely before the court [], we now hold that a prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant or patentee."  In coming to this conclusion, the panel rejected Antor's argument that printed publications should be treated differently than patents because of the statutory presumption of validity that attaches to a patent.  35 U.S.C. § 282.  The basis here was the same basis the panel used in Amgen:  § 282 is not the source of the presumption; rather, the panel here notes that the precedent cited in the Amgen case applied the logic that "it is procedurally convenient to place the burden on an applicant who is in a better position to show, by experiment or argument, why the disclosure in question is not enabling or operative" and thus that prior art patents can be presumed enabling for both claimed and unclaimed subject matter.  Finally, closing the logical loop this panel explained that the undisclosed subject matter in a patent is not examined at all and thus in no different a posture than what is contained in a non-patent prior art publication.  (The same could also be said, but it was not mentioned in the opinion, for prior art published applications.)

The consequence of this decision, according to the panel, changes nothing for patentees or applicants, because in any case the examiner "is governed by 35 U.S.C. § 132, which requires notification to an applicant of the reasons for a rejection with 'such information and references as may be useful in judging of the propriety of continuing the prosecution of his application.'"  Provided that an examiner has included in an Office Action "the theory of the rejection, the prior art basis for the rejection, and where each limitation of the rejected claims is shown in the prior art reference" she has met her burden under the statute.  As a practical matter, the Court is aware that the examiner, having "no access to experts or laboratories, is not in a position to test each piece of prior art for enablement in citing it, and requiring him to do so would be onerous, if not impossible."  Thus:

Consistent with the statutory framework and our precedent, we therefore hold that, during patent prosecution, an examiner is entitled to reject claims as anticipated by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling.  As long as an examiner makes a proper prima facie case of anticipation by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement.

This decision has important implications for practitioners attempting to provide patent protection for biotechnology-based inventions.  A great deal of biotechnology research and inventions have derived from university inventors, and even for those inventions that do not their inventiveness is assessed in view of prior art produced by university researchers.  It is a feature of some of this art that portions therein are reserved for what can most kindly be called discussions of possible future implications and applications of a scientific result (unkindly, these can be nothing less than unsupported flights of fancy).  However, the presence of such language in scientific references such as journal articles not expressly provides a much more robust source of prior art, insofar as anything said in a prior art printed publication now falls expressly within the presumption that it is enabled.  While in many cases this will not pose an insurmountable challenge, it can be expected at the very least to increase the difficulties and cost of obtaining patents, and to open up a host of new prior art for use in invalidity defenses (the panel here noted that in Amgen "that presumption applies in the district court as well as the PTO, placing the burden on the patentee to show that unclaimed disclosures in a prior art patent are not enabling").  And while the heightened burden of "clear and convincing" evidence may serve to ameliorate this change in the district courts, the situation is very different during patent prosecution or reexamination, due to the "substantial evidence" standard of review used by the Federal Circuit for factual determinations by the Office.  In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000).  These consequences are even more significant in view of the expanded potential for post-grant review occasioned by enactment of the Leahy-Smith America Invents Act.

One hypothetical example may suffice.  (NOTE to the literal minded:  what follows is generally not patentable or patent eligible; it is just an example in extremis to make the point).  As noted previously, perhaps the most beautiful sentence in scientific literature is this one:

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.

James Watson & Francis Crick, "Molecular Structure of Nucleic Acids; A Structure for Deoxyribose Nucleic Acid," Nature 171: 737-38 (April 25, 1953).  Now let's assume that patent protection was being sought for any of the practical applications of specific basepair hybridization (solution reassociation, various "blotting" techniques, even recombinant DNA production requiring proper hybridization of DNA fragments asymetrically cut with different restriction enzymes) and ask, what would the effect of this sentence be on such claims, keeping in mind that when Watson and Crick wrote this sentence they had no experimental evidence (of their own) and that the accuracy of their insight on the structure of DNA would take years to conclusively establish.

In re Antor Media Corp. (Fed. Cir. 2012)
Panel: Chief Judge Rader and Circuit Judges Lourie and Bryson
Opinion by Circuit Judge Lourie

In re Montgomery (Fed. Cir. 2012)

By Kevin E. Noonan --

In an otherwise unremarkable case of a PTO rejection based on anticipation, Judges Dyk and Lourie engaged in an interesting colloquy on the proper interpretation of what constitutes inherent anticipation, in In re Montgomery.  The case involved claims to methods for "treating or preventing" stroke, using "renin-angiotensin system (RAS)" inhibitors, specifically ramipril.  The claims at issue included the following:

42.  A method for the treatment or prevention of stroke or its recurrence, wherein said method comprises administering, to a patient diagnosed as in need of such treatment or prevention, an inhibitor of the rennin-angiotensin system, said inhibitor having a ClogP of greater than about 1.

43.  The method as claimed in claim 42, wherein the inhibitor of the rennin-angiotensin system comprises at least one inhibitor of angiotensin-converting enzyme.

45.  The method as claimed in claim 43, wherein the inhibitor of angiotensin-converting enzyme comprises ramipril.

(Emphasis in original)

The claims were rejected based on any of four prior art references:

• AIRE (The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators, Effect of Ramipril on Mortality and Morbidity of Survivors of Acute Myocardial Infarction with Clinical Evidence of Heart Failure, 342 Lancet 821 (1993));
• Frampton (James E. Frampton & David H. Peters, Ramipril: An Updated Review of Its Therapeutic Use in Essential Hypertension and Heart Failure, 49 Drugs 440 (1995) (abstract));
• HOPE (The HOPE Study Investigators, The HOPE (Heart Outcomes Prevention Evaluation) Study: The Design of a Large, Simple Randomized Trial of an Angiotensin- Converting Enzyme Inhibitor (Ramipril) and Vitamin E in Patients at High Risk of Cardiovascular Events, 12 Can. J. Cardiology 127 (1996)); or
• Gohlke (Peter Gohlke et al., Angiotensin-Converting Enzyme Inhibition Improves Cardiac Function, 23 Hypertension 411 (1994)) as evidenced by Richer (C. Richer et al., Antihypertensive Drugs in the Stroke-Prone Spontaneously Hypertensive Rat, 19 Clinical & Experimental Hypertension 925 (1997) (abstract), available here.

The Examiner, and the Board, found that each of these references taught administration of ramipril to individuals at risk for stroke (the Court's opinion noting that the limitation that the RAS inhibitor had "a ClogP of greater than about 1" was inherently a property of ramipril).

Specifically, the Board made the factual determinations that "[h]ypertension is a known risk for stroke" and that the cited references described studies showing treatment of patients with hypertension with ramipril (although at least in the AIRE study the results were not statistically significant).  The HOPE study was described as involving the combination of ramipril and Vitamin E "in the prevention of myocardial infarction, stroke, or cardiovascular death."  (The HOPE study showed statistically significant reduction in stroke risk, but not until after Montgomery's priority date.)  The Gohlke reference showed "the effects of . . . ramipril on functional and biochemical cardiac parameters in stroke-prone spontaneously hypertensive rats," which found that the treatment "improves cardiac function even at low doses," where Richer established that "[t]he stroke-prone spontaneously hypertensive rat . . . is an experimental model that has been widely used to investigate the potential preventive effects vs stroke and mortality of numerous antihypertensive agents."  The Board construed the claims as having two elements:  "(1) 'to administer an inhibitor of the rennin-angiotensin system,' and (2) 'the patient population receiving the inhibitor . . . encompasses patients diagnosed as required stroke treatment or prevention.'"  The Board held that each reference provided these elements and hence anticipated the claims.

The Federal Circuit opinion noted that the Board did not rule "directly" on the question of whether the claims contained a requirement that the method be effective at treating or preventing stroke, but said it "appeared to assume that they did include such a requirement."  In rejecting Montgomery's argument that the references did not demonstrate efficacy for using ramipril to treat stroke, the Board found that efficacy was "inherent" and need not be demonstrated, citing In re Cruciferous Sprout Litig., 301 F.3d 1343, 1350 (Fed. Cir. 2002).

The Federal Circuit upheld the Board's decision, in an opinion by Judge Dyk joined by Judge Prost; Judge Lourie dissented.  In the majority opinion, Judge Dyk set forth the analytical framework:  first the claims are construed giving claim terms their "broadest reasonable interpretation consistent with the specification," citing In re Bond, 910 F.2d 831, 833 (Fed. Cir. 1990).  Then, the claims are compared to the prior art, and anticipation found if every limitation is contained in a single reference.  In re Aoyama, 656 F.3d 1293, 1296 (Fed. Cir. 2011).  Regarding inherent anticipation, an unrecited limitation is present so long as it is "necessarily present, or inherent, in the single anticipating reference," citing Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1377 (Fed. Cir. 2003); but the opinion emphasized the word "necessarily" in this context, finding authority for this proposition in In re Oelrich, 666 F.2d 578, 581 (CCPA 1981).

The opinion focused on claim 45, with expressly recited ramipril, saying that the other two claims, being broader in scope would also be anticipated.  The Federal Circuit relied on the HOPE reference, finding that its determination that this reference anticipates eliminates any reason to address Montgomery's arguments on the other references.  The HOPE reference satisfied the limitation that ramipril be administered to "a patient diagnosed as in need of [stroke] treatment or prevention" according to the Court, and the opinion states that Montgomery did not dispute this Board finding.

Turning to the preamble ("for the treatment or prevention of stroke or its recurrence") (which the Board and the Court construed as an affirmative limitation), the opinion noted that while the Board "appeared to assume that the patent included an efficacy requirement," the majority was "skeptical that a proper interpretation of the claims would include an efficacy requirement."  The opinion bases its skepticism on its opinion in Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc., 246 F.3d 1368, 1371, 1375 (Fed. Cir. 2001), which it characterized as concerning a "similar "method of treatment" claim; in that case, the Court held that a method "for reducing hematologic toxicity" "merely express[ed] a purpose [] rather than requiring a particular result."  That construction "is even more appropriate here," says the majority, because the Board and the Court applies the "broadest reasonable interpretation" standard.

After this semantic sojourn, however, the majority finds that its resolution is not necessary, because it agrees with the Board that "even if the claim includes an efficacy requirement, efficacy is inherent in carrying out the claim steps."  "[T]here is no question here that treating stroke-prone patients with ramipril does in fact inevitably treat or prevent stroke," according to the majority, and of course Montgomery does not (and cannot) disagree, since the efficacy of ramipril to treat or prevent stroke is "the entire premise of [Montgomery's] patent."  Relying on Bristol-Myers Squibb, Cruciferous Sprout, and King Pharmaceuticals, Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1270 (Fed. Cir. 2010), the majority held that the HOPE reference disclosed administration of ramipril to "stroke-prone" patients, which "inevitably treats or prevents stroke."  Nor does the law require that ramipril had ever been administered to treat or prevent stroke, provided that the treatment was at least "merely proposed," citing for support the outcome in Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1377 (Fed. Cir. 2003), and SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1343-44 (Fed. Cir. 2005).

Judge Lourie dissented, calling inherency "a very tricky concept in patent law."  Judge Lourie uses Schering Corp. v. Geneva Pharm., Inc. as an example, contrasting the "salutary goal" of the principle in "prevent[ing] subject matter that is effectively in the public's possession from being retrieved by a patent and withdrawn from the public domain" with the risk of "withholding patent protection from that which the public knew nothing about until a later inventor found it."  Sounding like an antipode to Justice Breyer, the dissent states that an "unbounded concept of inherency [] threatens to stymie innovation by withdrawing from the realm of patentability that which has not before been known, used, or benefited from."  This is not Judge Lourie's conception of inherent anticipation, which requires "inevitability," which the Court's cases have been "steadfast" in requiring, citing Bettcher Indus., Inc. v. Bunzl USA, Inc., 661 F.3d 629, 639 (Fed. Cir. 2011); Hansgirg v. Kemmer, 102 F.2d 212, 214 (CCPA 1939); and Glaxo Inc. v. Novopharm Ltd., 52 F.3d 1043, 1047 (Fed. Cir. 1995), the latter case illustrating that "even a very high likelihood" is not enough.

The alternative, according to Judge Lourie, would be that "a mere proposal for further experimentation could anticipate a claimed invention"; "[a]n invitation to investigate is not an inherent disclosure."  Metabolite Labs., Inc. v. Lab. Corp. of Am. Holdings, 370 F.3d 1354, 1367 (Fed. Cir. 2004).  "[I]nnovation should not be impeded by mere speculation."  Turning to the majority's interpretation of the HOPE reference, Judge Lourie states that "[a] description of a process, even if not carried out, is an anticipation of that process.  But a mere description of a process that, if it had been carried out, might yield a particular undisclosed result is not an inherent anticipation of that result"; Judge Lourie considers the HOPE reference to be better characterized as the latter of these two situations and thus not to anticipate the claims.

While perhaps not invoking the establishment of a trend, the dissent does make a case that the current members of the Court have become more likely to find inherent anticipation under a broader set of circumstances than have been applied heretofore.  Whether this is another example of the turn of this Court, under persistent influence by the Supreme Court, to be less "patent friendly" than it was previously (at least as some have perceived) will depend on whether and to what extent this trend continues.

In re Montgomery (Fed. Cir. 2012)
Panel:  Ciercuit Judges Lourie, Dyk, and Prost
Opinion for the court by Circuit Judge Dyk; dissenting opinion by Circuit Judge Lourie

In re Mousa (Fed. Cir. 2012)

By Donald Zuhn --

Last month, in In re Mousa, the Federal Circuit affirmed a decision by Board of Patent Appeals and Interferences sustaining the invalidity of U.S. Application No. 10/667,216 for anticipation and obviousness.  The '216 application is directed to chemically fractured and modified heparin.  Heparin, an anticoagulant typically used to prevent blood clots from forming, can also be used to prevent new blood vessel growth (i.e., angiogenesis) in tumors by blocking the action of fibroblast growth factor 2 (FGF2).  This latter use is limited because heparin's anticoagulant properties can cause bleeding complications.  Heparin can be chemically fractured into fragments called heparin fractions, which retain the anticoagulant and angiogenesis properties of heparin.

The '216 application is directed to super-sulfated, oxidized heparin fractions, which are produced by oxidizing some of the hydroxyl groups on the heparin fraction and by substituting sulfate groups for the hydrogen atoms in other hydroxyl groups.  The '216 application discloses that increased oxidation of the heparin fractions fully inhibits FGF2-induced angiogenesis, and further, that the bleeding complications normally associated with heparin use can be eliminated by using these super-sulfated, oxidized heparin fractions because they possess weaker anticoagulant properties than heparin.

During prosecution, several claims of the '216 application were rejected as anticipated by, and obvious in view of, U.S. Patent No. 4,727,063 ("Naggi"), which discloses the treatment of heparin with a mixture of sulfuric acid and chlorosulfonic acid (i.e., strong oxidizing agents) to produce a super-sulfated heparin fraction having weak anticoagulant properties.  Because Naggi discloses the treatment of heparin with strong oxidizing agents, the Examiner found that the Naggi heparin fractions were inherently oxidized.  The Examiner also found that because the Naggi heparin fractions possessed weak anticoagulant activity, the Naggi heparin fractions inherently possessed the anti-angiogenesis properties of the heparin fractions disclosed in the '216 application.

Mousa appealed the Examiner's rejection to the Board, arguing that Naggi's method would not produce super-sulfated, oxidized heparin fractions with a chemical structure that is the same as the heparin fractions of the '216 application because Naggi did not disclose O-sulfating a first oxidized heparin fraction as in the '216 application.  Mousa also argued that Naggi did not disclose a heparin fraction that fully inhibits FGF2-induced angiogenesis (a claim limitation that Mousa added during prosecution).  The Board affirmed the Examiner's rejection, finding that Naggi discloses, inherently or expressly, each and every limitation of the '216 claims.  In particular, the Board found that Naggi discloses super-sulfated, oxidized heparin fractions (because Naggi treats heparin with sulfuric and chlorosulfonic acids), and a weak anticoagulant property as compared to heparin.  The Board concluded that the Examiner had established that the heparin fractions disclosed by Naggi and the '216 application were the same or substantially the same, and that the Examiner had properly shifted the burden of proof to Mousa to show that the Naggi heparin fractions did not inherently possess the anti-angiogenesis properties recited in the '216 claims.

On appeal, Mousa argued that Naggi does not disclose an oxidized heparin fraction or a heparin fraction that fully inhibits FGF2-induced angiogenesis.  The U.S. Patent and Trademark Office countered that the Examiner established that treating heparin with the strong oxidizing agents (as disclosed by Naggi) necessarily results in oxidized heparin and that the Examiner properly shifted the burden of proof to Mousa to show that those oxidizing agents did not oxidize heparin, as well as to show that the Naggi heparin fractions did not possess the same FGF2-inhibiting characteristics as the heparin fractions of the '216 application.  In affirming the Board's decision, the Federal Circuit determined that the Board's findings that the Naggi heparin fractions were inherently oxidized and possessed weak anticoagulant properties constituted substantial evidence in support of the Board's determination that Naggi discloses a super-sulfated, oxidized heparin fraction identical to the heparin fraction of the '216 application.  The Court noted that:

Having established that the two heparin fractions are "the same or substantially the same compound" and that the Naggi fractions necessarily possessed the FGF2-inhibiting characteristic recited in claim 1, the Examiner properly shifted the burden of proof to Mousa to prove that the structures were different and that the claimed properties were not inherent.  . . .  Mousa failed to satisfy this burden.  Although Mousa argues that oxidizing agents do not oxidize every substance and that the Examiner did not establish that these chemicals can oxidize heparin, Mousa provided no proof in support of this contention to the Examiner or to the BPAI.

The Court also noted that "once the Examiner established that the Naggi patent read identically on the limitations of the '216 claims, Mousa bore the burden to show that the Naggi heparin fractions did not inherently possess the FGF2-inhibiting characteristics of the '216 heparin fractions as recited by claim 1," adding that "Mousa again failed to satisfy his burden of proof."  Finding that the Board's factual findings were supported by substantial evidence, the Court affirmed the Board's decision sustaining invalidity.

In re Mousa (Fed. Cir. 2012)
Nonprecedential disposition
Panel: Circuit Judges Prost, Schall, and Reyna
Opinion by Circuit Judge Reyna

Teva Pharmaceutical Industries Ltd. v. AstraZeneca Pharmaceuticals LP (Fed. Cir. 2011)

By Andrew Williams --

Last week, in Teva Pharma. Indus. Ltd. v. AstraZeneca Pharma. LP, the Federal Circuit reiterated that, in the context of 35 U.S.C. § 102(g), "[t]o establish prior invention, the party asserting it must prove that it appreciated what it had made."  The complication is, however, how do you define what the invention is?  This is because the invention is not necessarily what is claimed -- "'[t]he invention is not the language of the [claim] but the subject matter thereby defined'"(citing Dow Chemical Co. v. Astro-Valcour, Inc., 267 F.3d 1334 (Fed. Cir. 2001)).  Therefore, in this case, because AstraZeneca "appreciated" that it had a formulation with a stable compound (the defined invention), and it knew what the components of the formulation were, it conceived and reduced to practice a stabilized pharmaceutical composition of rosuvastatin (a statin) before Teva's date of invention, even though AstraZeneca did not appreciate the stabilizing property of one of the components, which was a limitation found in Teva's claims.

The technology at issue in this case involved statin formulations, which are inherently unstable and as a result need to be stabilized to be medically viable.  Teva discovered that, among other things, amido-group containing polymeric compounds ("AGCP compound") can be used to stabilize statins, and obtained a patent (RE39,502) with the following representative claim:

1.  A stabilized pharmaceutical composition for the treatment of dyslipidemia, comprising
    an active component consisting essentially of one or more compounds selected from the group consisting of (i) an HMG-CoA reductase inhibiting ring-opened 7-substituted-3,5-dihydroxyheptafloic acid or a pharmaceutically acceptable acid salt thereof, and (ii) an HMG-CoA reductase inhibiting ring-opened 7-substituted-3,5-dihydroxyheptenoic acid or a pharmaceutically acceptable acid salt thereof, and
    a stabilizing effective amount of at least one amido-group containing polymeric compound or at least one amino-group containing polymeric compound, or combination thereof, wherein said stabilized pharmaceutical composition does not contain a stabilizing effective amount of another stabilizer or a combination of other stabilizers.

(emphasis as found in the opinion).  Teva's earliest effective filing date was April 10, 2000, and the earliest date that it alleges it could establish conception and reduction to practice was December 1, 1999.  Teva sued AstraZeneca for infringement in October 2008 for the stabilized statin (rosuvastatin calcium) formation that it was marketing for the treatment of dyslipidemia.  The relevant facts were uncontested, and AstraZeneca conceded infringement for the limited purpose of advancing its summary judgment motion (AstraZeneca appears to have been able to challenge infringement because its formulation contained a second stabilizer, tribasic calcium).  The facts related to AstraZeneca's prior invention allegation included:  (1) AstraZeneca had manufactured a 10,000-unit batch of the formulation with the same ingredients as its commercial drug in mid-1999, (2) it had made additional batches in the summer and fall of 1999, (3) it had disclosed the ingredients and quantities for the formulation that match all commercial drug dosage strengths, and (4) it included crospovidone, an AGCP-compound, as a disintegrant, but did not understand that it had a stabilizing effect on the statin.  As a result, the sole legal question for the Court was whether AstraZeneca conceived and reduced to practice the claimed invention before Teva.

It is clear that prior invention in the context of 102(g) requires a showing that the challenging party (1) reduced its invention to practice first, or (2) was the first to conceive and then exercised due diligence in reducing the invention to practice.  In order to conceive, the inventor needs a specific and settled idea, a particular solution to a problem at hand.  Reduction to practice, on the other hand, requires that the inventor constructed an embodiment that met all of the claim limitations, and determined that it would work for its intended purpose.  However, the inventor need not understand precisely how the invention worked.  There is another requirement that is relevant in the chemical and biotech arts -- conception of something reduced to practice requires more than an unrecognized accidental creation, but instead, the inventor must appreciate what he has invented.  In other words, "'a party who first reduced to practice, but who 'fail[ed] to recognize that he had produced a new form [of matter] . . . is indicative that he never conceived the invention''" (quoting Dow at 1341 (quoting Heard v. Burton, 333 F.2d 239, 243 (C.C.P.A. 1964)).

Teva argued that because AstraZeneca did not appreciate that crospovidone was a stabilizing agent, it could not have appreciated the invention of a formulation with "a stabilizing effective amount" of an AGCP.  The lower court, however, held that all AstraZeneca had to appreciate was the stabilization of its overall pharmaceutical composition that contained crospovidone.  On appeal, Teva complained that the District Court implicitly construed the claims to encompass stabilized statin formations that contained AGCP, without taking into account that AGCP had to act as a stabilizer.  However, the Federal Circuit pointed out, while quoting William Shakespeare, that AstraZeneca was not required to appreciate the invention in the same terms as those recited by the claims ("[T]hat which we call a rose [b]y any other name would smell as sweet.").  Therefore, because AstraZeneca appreciated that the statin in its formulation was stable, and because it appreciated what the components of the formation were, it appreciated the invention.

On its face, this outcome appears to be inequitable.  After all, reducing Teva's claim to "a stabilized [statin-containing] pharmaceutical composition" appears to ignore the rest of the claim, including Teva's alleged inventive contribution.  In fact, the panel questioned both sides during the hearing as to whether Teva should be entitled to this patent because it provided the public with something that it didn't have before the filing of the application -- the knowledge that AGCPs can act as stabilizing agent for statins.  Nevertheless, this line of reasoning has its limits, in part because Teva did not claim the use of AGCPs as stabilizing agents in this patent.  Instead, Teva claimed a composition that used such stabilizing agents.  The important thing to consider is that AstraZeneca was using its composition (the same one that Teva alleged infringed) before Teva's elucidation of the mechanism of action of AGCPs.  And, it is still true that, that which infringes after, anticipates before, even if the use before was without the benefit of the knowledge as to why it worked.  Teva should not be allowed to now take this composition out of the public domain just because it discovered why the composition was so successful -- specifically, because it determined the inherent stabilizing effect that crospovidone has on statins.  This case does have the flavor of inherent anticipation.  The panel was very clear in its opinion and during the hearing that the concept of inherency was not implicated in this case or its decision.  However, one cannot help think that this outcome smells a lot like inherency jurisprudence.  Perhaps this rose just has a different name.

Teva Pharmaceutical Industries Ltd. v. AstraZeneca Pharmaceuticals LP (Fed. Cir. 2011)
Panel: Chief Judge Rader and Circuit Judges Linn and Dyk
Opinion by Circuit Judge Linn

Star Scientific, Inc. v. R.J. Reynolds Tobacco Co. (Fed. Cir. 2011)

By Kevin E. Noonan --

The Federal Circuit reaffirmed the primacy of the factual disclosures used to establish obviousness, and how deficiencies thereof can defeat an obviousness claim, in reversing an invalidity determination in Star Scientific, Inc. v. R.J. Reynolds Tobacco Co.  It also showed how persistently defendants pursue the tarnish of inequitable conduct even under circumstances where the Federal Circuit has held that no inequitable conduct occurred.

The patents-in-suit, U.S. Patent Nos. 6,202,649 and 6,425,401 (filed as a continuation of the '649 patent), were directed to methods for curing tobacco in a way that reduced the amount of a carcinogen, tobacco-specific nitrosamines (TSNAs), in the cured product used in cigarettes and other tobacco-containing products.  The patents were specifically directed to "indirect" flue curing with gas or propane heaters.  Former methods used "direct" flue curing that mixed the exhaust gasses with the tobacco, but this resulted in an oxygen-free environment that fostered the growth of bacteria on the leaves, leading to production by the bacteria of the carcinogenic TSNAs.  The patented methods can be used with either direct or indirect curing methods by using "controlled conditions" involving humidity, temperature, rate of temperature exchange, carbon monoxide levels, carbon dioxide levels, oxygen levels, and how the tobacco plants are arranged in the curing shed.  The claims specify "controlling conditions" by "determining and selecting" the "appropriate" values for these variables that results in the reduction of TSNA production "at least one").  However, the patents admit that the choice of these conditions are "more art than science," so need to choose the appropriate combination of these variables; however, the important consideration is maintaining an aerobic environment that prevents bacterial growth.

Claims 4 and 12 of the '649 patents are set forth for the Court as being representative (emphasis in the opinion):

4.  A process of substantially preventing the formation of at least one nitrosamine in a harvested tobacco plant, the process comprising:
    drying at least a portion of the plant, while said portion is uncured, yellow, and in a state susceptible to having the formation of nitrosamines arrested, in a controlled environment and for a time sufficient to substantially prevent the formation of said at least one nitrosamine;
    wherein said controlled environment comprises air free of combustion exhaust gases and an airflow sufficient to substantially prevent an anaerobic condition around the vicinity of said plant portion; and
    wherein said controlled environment is provided by controlling at least one of humidity, temperature, and airflow.

12.  The process according to claim 4, wherein the treatment time is from about 48 hours up to about 2 weeks.

The lawsuit arose after R.J. Reynolds (RJR) acquired previous licensee Brown and Williamson and terminated the license.  In addition, RJR has its own patents (referenced in the opinion as the Peele reference), issued as U.S. Patent No. 6,805,134 that specified a "not direct" heat source and curing in the absence of nitrocv oxide gas, which was performed by retrofitting direct cure barns into indirect-cure barns.

As an initial matter, the District Court granted summary judgment that the '649 and '401 patents were not entitled to priority to a provisional application, based on disclosure in the provisional that the claimed methods utilized an air flow of "at least 28,000 cubic feet per meter (CFM)" whereas the common specification of the '649 and '401 patents specified an air flow of "approximately 25,000 CFM."  As a consequence, the District Court was able to consider intervening art to be prior art, and to decide that the patentee did not disclose the best mode (based on development of the commercial embodiment (and acknowledged best mode) in the period between the provisional and non-provisional filing dates.

In an earlier decision, the Federal Circuit reversed a finding that the claims were indefinite for reciting the term "anaerobic condition" and reversed a finding of inequitable conduct for failure to disclose a purported prior art reference (termed the "Burton letter").  Despite this decision, the District Court permitted defendants to display a slide (below) during closing argument showing a shadowy person disclosing information to the PTO examiner but holding the disputed Burton letter reference behind his back, during part of closing argument relating to invalidity rather than inequitable conduct.

The jury delivered a verdict of non-infringement and invalidity based on obviousness, anticipation, indefiniteness, and failure to disclose the best mode.  The obviousness determination was based on a prior art scientific journal review relating to methods for air curing and a published Japanese patent.  In view of the District Court's decision on the priority question, the jury applied the method disclosed in the Peele '134 patent as well as the practice of methods at two farms (Spindletop and the Brown farm) as a public use (the Brown tobacco farm being under contract to RJR).  The indefiniteness determination was directed at the term "controlled environment," which the Court found as a matter of law was incapable of being construed because the disclosed "controlled environment" conditions overlapped with "conventional" curing conditions so that the skilled worker could not understand the difference.  The best mode determination was based squarely on the District Court's priority determination, since it was uncontested that the best mode commercial embodiment was not disclosed and had been developed prior to the non-provisional filing dates.  Finally, the jury found that there was no infringement, based on oxygen levels in RJR's barns alleged to be infringing.  The District Court denied Star's motions for JMOL of these adverse decisions.

The Federal Circuit, in an opinion by Chief Judge Rader, joined by Judge Linn and by Judge Dyk in part, who dissented as to the Court's decision to reverse invalidation for indefiniteness, reversed the District Court's grounds for invalidating the '649 and '401 patents, and affirmed the District Court's denial of JMOL on the jury's non-infringement decision.  The Federal Circuit also reversed the finding that the '649 and '401 patents were not entitled to the provisional filing date, on the basis that the specification satisfied the priority standard:  that the specification disclosed an adequate written description and enabled the patents' claims.

This part of the opinion was supported by an intervening decision by the USPTO in a reexamination of the '649 and '401 patents that these patents were entitled to the priority date (although the PTO found certain of the claims were invalid for obviousness).  The Court based its decision on language in the provisional specification that the recited air flow speed (in CFM) could "vary according to conditions and may be determined on a routine basis," and thus held that the District Court had improperly narrowed the claim scope based on later examples in the non-provisional application.

As a consequence of the Court granting the priority date of the provisional application to the '649 and '401 patents the best mode violation evaporated, since it was equally undisputed that the commercial method was not known at the time the provisional application was filed.  Another consequence, germane to anticipation and obviousness is that the Peele '134 patent was not prior art that could be asserted against the patents in suit.

In reversing the District Court's indefiniteness determination, the majority opinion cites Datamize LLC v. Plumtree Software Inc. for the standard that a claim must be "insolubly ambiguous" or "not amenable to construction" to be found indefinite.  However, the majority cautioned that "[a]bsolute clarity [is] not required" and that the term at issue -- "controlled environment" -- does not require disclosure of exact values for the various parameters because the skilled worker would understand the variable and empirical nature of determining these conditions.  In this the opinion cites language from the Peele '134 patent -- owned by RJR -- consistent with its interpretation of the understanding of the worker skilled in the art.

Regaring obviousness, the Court disagreed with jury verdict that the references render the claims obvious.  The opinion characterized the Japanese patent as being directed at improving fast curing to avoid "nasty odor" (an advantage not related to TSNA production) and found the Wiernik reference to be inconclusive on whether bacteria were involved in TSNA production.  In addition, the opinion notes that neither reference discusses exhaust gases or anaerobic conditions.  Thus, the Court found that there would be no motivation (or in the mantra approved by the KSR Court, "reasoned basis") for the skilled worker to combine these references to arrive at a solution to the problem of TNSA production during tobacco curing.  The Court also found significant evidence of secondary considerations, including:  a recognized, unmet need in the art for reducing TSNA in cured tobacco; unsuccessful attempts (i.e., failure) by others to solve this recognized problem; purported unexpected results (never expressly set forth in the opinion); and commercial success (ironically for RJR, using the lucrative B&W licenses as evidence thereof).

The Court reversed the jury's anticipation finding as to the Peele method because it was no longer prior art in view of the earlier priority date.  The two "public uses" were not prior art, because the Court found that the "Spindletop" use involved tobacco cured before treatment in the drying shed (so that it was not "uncured" tobacco, as required by the claims).  The "Brown farm" use did not anticipate, according to the Court's opinion, because the reported test results were below the detection threshold for TNSAs and thus provided no evidence that this method satisfied the specifically recited range of TSNA reduction required by the claims.

Finally, the Court upheld the non-infringement decision based on the jury's prerogative to believe one (RJR's) expert over another (Star's), and that the evidence did not establish that no reasonable jury could come to such a decision (i.e., the District Court properly denied Star's JMOL motion).

The Court also refused to deny Star's appeal on evidentiary rulings permitting (inter alia) display of the "shadowy figure" slide (although the Court found its use "troubling"), because Star did not show harm resulting from the objectionable evidence.

Judge Dyk dissents in part, arguing that the patents are invalid for indefiniteness -- in his view, the specification did not sufficiently distinguish the "controlled" conditions from "conventional" conditions and thus did not "particularly point out and distinctly claim" the invention so that the skilled worker could not ascertain the metes and bounds of infringing behavior.

Star Scientific, Inc. v. R.J. Reynolds Tobacco Co. (Federal Circuit 2011)
Panel: Chief Judge Rader and Circuit Judges Linn and Dyk
Opinion by Chief Judge Rader; opinion concurring-in-part and dissenting-in-part by Circuit Judge Dyk

Mitsubishi Chemical Corp. v. Barr Laboratories, Inc. (Fed. Cir. 2011)

By Donald Zuhn --

Yesterday, the Federal Circuit affirmed a decision by the District Court for the Southern District of New York finding that Defendants-Appellants Barr Laboratories, Inc. and Pliva-Hrvatska d.o.o. ("Barr") infringed U.S. Patent No. 5,214,052.  The '052 patent, which is assigned to Plaintiff-Appellee Mitsubishi Chemical Corp., relates to argatroban solutions containing ethanol, water, and a saccharide.  Argatroban is an anticoagulant used in the treatment of heparin-induced thrombocytopenia.

The '052 patent discloses that the solubility of argatroban increases dramatically when it is dissolved in ethanol, water, and a saccharide.  At the time the application that issued as the '052 patent was filed, argatroban was known to have low aqueous solubility at neutral pH levels, which presented problems for its use in pharmaceutical compositions.  The '052 patent has four claims:

1.  A method for dissolving an arginineamide, comprising:
    dissolving [argatroban] and/or its salt in a solvent containing ethanol, water and a saccharide.

2.  The method according to claim 1, wherein the saccharide is at least one member selected from the group consisting of sorbitol, glucose, glycerin and sucrose.

3.  A pharmaceutical composition for injection, comprising:
    [argatroban] and/or its salt together with ethanol, water and a saccharide.

4.  The composition according to claim 3, wherein the saccharide is at least one member selected from the group consisting of sorbitol, glucose, glycerin and sucrose.

Seeking approval to market a generic version of Misubishi's Argatroban Injection product, which consists of a high concentration of argatroban dissolved in a solution of ethanol, water, and sorbitol at a pH between 3.2 and 7.5, Barr filed an Abbreviated New Drug Application (ANDA) with the FDA.  In response to Barr's ANDA filing, Mitsubishi brought suit against Barr for infringement of the '052 patent.  The parties stipulated that Barr's ANDA product would infringe all four claims of the '052 patent.  Barr answered by asserting that the claims were invalid as anticipated by an article published by Mitsubishi employee Toshihiro Yamamoto, and rendered obvious by several combinations of nine other references.

At trial, Mitsubishi and Barr battled over the proper translation of a single sentence in the Yamamoto reference that described the preparation of an argatroban solution administered to rats for experimental purposes.  The District Court considered four translations of the sentence, concluding that the translation submitted by Mitsubishi's expert was the only reliable translation.  Mitsuibishi's expert translated the relevant sentence as follows:  "In 7.5% D-sorbitol-4% ethanol, an argipidine solution dissolved under hydrochloric acid acidity (pH 1.5 to 1.7) was intraperitoneally administered at a dosage of 1 ml/kg, 15 minutes before common carotid artery occlusion."  Using this translation, the District Court determined that Yamamoto does not anticipate claims 1 and 2 because a person of ordinary skill in the art would have understood Yamamoto to teach dissolution of argatroban in hydrochloric acid alone, i.e., without ethanol or a saccharide (another Mitsubishi expert, and native Japanese speaker, testified that the disputed sentence from the Yamamoto reference should be understood to mean "in hydrochloric acid the [argatroban] was dissolved and after that it's been put into D-sorbitol and ethanol").  The District Court concluded, therefore, that the phrase "[i]n 7.5% D-sorbitol-4% ethanol" referred to how the argatroban solution was administered and not how it was dissolved.  As for claims 3 and 4, the District Court concluded that Yamamoto's argatroban solution was not "[a] pharmaceutical composition for injection" because a pharmaceutical composition must have a pH above 3 (the District Court based this conclusion on the testimony of a third Mitsubishi expert).

With respect to Barr's obviousness argument, the District Court dismissed four of Barr's nine references as not addressing argatroban solubility or methods of formulating the drug.  The District Court found that while the other five references described solvent systems including ethanol, water, and a saccharide, none of these references directed the skilled artisan to use ethanol, water, and a saccharide to dissolve argatroban.  The District Court therefore determined that the claims of the '052 patent would not have been obvious.

On appeal, Barr first challenged the District Court's selection of the Mitsubishi expert's translation of Yamamoto, arguing that two other translations were not prepared for purposes of this litigation.  The Federal Circuit noted that "[t]he district court's selection of the appropriate translation in this case was based in large part on a credibility determination, and such determinations are 'virtually never' overturned for clear error."  The opinion also discounted Barr's argument that the translation adopted by the District Court should be disregarded because it was prepared for purposes of this litigation, stating that this was "not a sufficient reason to conclude that the district court's choice of the [Mitsubishi expert's] translation was clearly erroneous."

With respect to claims 3 and 4, Barr argued that the phrase "pharmaceutical composition for injection" in the preamble of claim 3 means "a medicinal drug composition that can be administered by injection," and that this claim therefore covers any composition that includes a "medicinal drug" (i.e., argatroban), along with ethanol, water, and a saccharide, regardless of whether it can be injected into a patient with therapeutic effect.  In dismissing Barr's argument, the Court noted that "[t]he problem with Barr's construction is that the word 'pharmaceutical' in claim 3 modifies the entire 'composition' referred to in the claim, not simply the argatroban component of the composition."  The Court pointed out that "Barr's claim construction would allow a 'plainly toxic composition, such as a cleaning fluid or a pesticide,' to meet the limitations of claim 3, even though such a composition would not be medicinal under any definition of that word."  The Court "therefore reject[ed] Barr's attempt to broaden the phrase 'pharmaceutical composition for injection' to cover any composition that includes a medicinal product, regardless of its suitability for injection into humans."  Because the District Court concluded that the pH of the Yamamoto argatroban solution was below 3, and that such a solution would not be acceptable for use as a medicine, the Federal Circuit determined that Barr had failed to show by clear and convincing evidence that Yamamoto disclosed a pharmaceutical composition for injection.

As for Barr's obviousness argument, the Federal Circuit determined that the District Court did not clearly err in determining that the prior art taught away from the use of ethanol to dissolve argatroban.  The Federal Circuit also found no reason to disturb the District Court's determination that a number of Barr's references were not specific to argatroban, despite describing solvent systems including ethanol, water, and a saccharide.

Mitsubishi Chemical Corp. v. Barr Laboratories, Inc. (Fed. Cir. 2011)
Nonprecedential disposition
Panel: Circuit Judges Bryson, Dyk, and Prost
Opinion by Circuit Judge Bryson

Billups-Rothenberg, Inc. v. Associated Regional and University Pathologists, Inc. (Fed. Cir. 2011)

By Donald Zuhn --

Last week, in Billups-Rothenberg, Inc. v. Associated Regional and University Pathologists, Inc., the Federal Circuit determined that the District Court for the Central District of California had properly granted summary judgment of invalidity with respect to U.S. Patent Nos. 5,674,681 and 6,355,425.  In particular, the panel affirmed the District Court's decision that the asserted claims of the '681 patent were invalid for lack of written description, and its decision that the asserted claims of the '425 patent were invalid as anticipated by U.S. Patent No. 6,025,130.

In 2009, Plaintiff-Appellant Billups-Rothenberg, Inc. sued Defendants-Appellees Associated Regional and University Pathologists, Inc. (doing business as ARUP Laboratories) and Bio-Rad Laboratories, Inc. ("ARUP"), asserting that ARUP infringed certain claims of the '681 and '425 patents by providing or using diagnostic assays or kits for detecting Type I hereditary hemochromatosis.  Type I hereditary hemochromatosis, which is an iron disorder characterized by excessive iron absorption by the body, is caused by specific mutations in the High Fe ("HFE") gene, which is located on the short arm of chromosome six in humans.

The '681 patent, which issued from an application filed by Billups in 1994, discloses that the gene responsible for hemochromatosis is located on human chromosome six.  The '681 application also discloses that "[a] mutation in a nucleic acid sequence can be detected by various methods to analyze nucleic acids [which] are well known to those in the art."  Claim 2 of the '681 patent recites:

2.  A method to identify an individual having or predisposed to having hemochromatosis, comprising the steps of:
    a)  providing from the individual a sample containing a gene encoding a nonclassical MHC class I heavy chain and
    b)  detecting a mutation in said gene, which mutation results in the reduced ability of said heavy chain to associate with said β2 microglobulin, wherein the presence of said mutation identifies said individual as having or predisposed to having hemochromatosis.

The '681 patent does not, however, disclose the HFE gene or identify any mutations associated with hemochromatosis.

In 1996, a different group of researchers isolated and sequenced the hemochromatosis (or HFE) gene and identified three mutations in the gene that are associated with hemochromatosis:  C282Y, H63D, and S65C.  This research led to the issuance of the '130 patent, which discloses the HFE gene sequence and the C282Y, H63D, and S65C mutations (identified in the '130 patent as 24d1, 24d2, and 24d7, respectively):

The '130 patent, which is owned by Bio-Rad and licensed to ARUP, also discloses genetic tests for hemochromatosis that utilize the mutations and sequence variants identified in the patent.

Using the sequences disclosed in the '130 patent, Billups developed a method for diagnosing an iron disorder by testing for the S65C mutation.  In 1999, Billups filed an application directed to this method, which issued as the '425 patent.  Claim 1 of the '425 patent recites:

1.  A method of diagnosing an iron disorder or a genetic susceptibility to developing said disorder in a mammal, comprising determining the presence of a mutation in exon 2 of an HFE nucleic acid in a biological sample from said mammal, wherein said mutation is not a CàG substitution at nucleotide 187 of SEQ ID NO: 1 and wherein the presence of said mutation is indicative of said disorder or a genetic susceptibility to developing said disorder.

At trial, Billups and ARUP filed cross-motions for summary judgment, Billups seeking summary judgment of infringement and ARUP seeking summary judgment of invalidity.  The District Court denied Billups' motion and granted ARUP's motion of invalidity for lack of written description (as to the '681 patent) and anticipation (as to the '425 patent).  With respect to the '681 patent, the District Court noted that neither the sequence of the HFE gene nor any mutations in the HFE gene were disclosed in the patent, and the "patentee has merely directed the person of ordinary skill in the art to a general location of a mutation on a chromosome and suggested that the mutation may be found in that vicinity."  With respect to the '425 patent, the District Court determined that the '130 patent was prior art to the '425 patent, and further, that the '425 patent claims the same genetic test for the S65C mutation that is disclosed in the '130 patent.

Writing for the Federal Circuit, and addressing the issue of written description first, Judge Gajarsa noted that "Billups claims that its disclosure of the mutation's general location somewhere 'within less than a 300 base pair region of a defined exon of a well studied multi-gene family,' combined with the knowledge that existed at the time of filing the '681 patent, established that [the inventors] possessed the claimed invention."  While "[t]he '681 patent claims a test for mutations," he also noted that "it is undisputed that the specification and originally filed claims of the '681 patent disclose neither the hemochromatosis gene sequence nor any specific mutations within that gene."  In summarizing Billups' argument on appeal, Judge Gajarsa stated that:

Billups contends that the '681 patent taught structure, i.e., that hemochromatosis has a genetic basis, and function, namely, its adverse effect upon the binding of β2 microglobulin with a non-classical MHC class I heavy chain.  Specifically, Billups argues that the '681 patent's correlation of function with the general location of the C282Y mutation, combined with the knowledge of a person of ordinary skill in the art in the field at the time of filing, satisfied the written description requirement by localizing the mutation to a 300 base pair region.

Agreeing with the District Court's findings that "[p]atentee's general location disclosure is too imprecise to constitute structural features necessary to meet the written description requirement," and that the "specification for the '681 patent contains only functional, not structural, characteristics of the predicted mutations," Judge Gajarsa determined that the District Court properly granted summary judgment of invalidity for lack of written description.

Turning to the issue of anticipation, Judge Gajarsa quickly concluded that:

The asserted claims of the '425 patent are invalid because they are anticipated by the '130 patent.  The '130 patent was filed nearly three years before the '425 patent and is prior art under § 102(e).  The district court correctly ruled that the '130 patent discloses use of the S65C mutation as a "HH [(hereditary hemochromatosis)] diagnostic," and, thus, Billups was not the first to disclose diagnosis of hemochromatosis using the S65C mutation.

While Billups argued on appeal that the '130 patent concludes that "the S65C mutation was only a clinically insignificant polymorphism unrelated to disease state," and therefore that "the '130 patent did not teach using the S65C mutation to diagnose hemochromatosis," Judge Gajarsa countered that "[d]espite the inventors' uncertainty regarding the utility of the S65C mutation because of their small sample size, the '130 patent describes two genetic tests for hemochromatosis that involve detection of the S65C mutation as an input for the diagnosis of hemochromatosis."  Citing Celeritas Techs., Ltd. v. Rockwell Int’l Corp., 150 F.3d 1354, 1361 (Fed. Cir. 1998), Judge Gajarsa noted that "[a]lthough the '130 patent discounts the utility of the S65C mutation in diagnosing hemochromatosis, we have held that a 'reference is no less anticipatory if, after disclosing the invention, the reference then disparages it.'"  Thus, "[e]ven though the inventors of the '425 patent performed experiments revealing greater diagnostic utility of the S65C mutation than initially suspected," Judge Gajarsa concluded that "the use of the S65C mutation as a diagnostic tool was already contemplated by the '130 patent," and therefore affirmed the District Court's finding of invalidity with respect to the '425 patent.

Billups-Rothenberg, Inc. v. Associated Regional and University Pathologists, Inc. (Fed. Cir. 2011)
Panel: Circuit Judges Gajarsa, Linn, and Moore
Opinion by Circuit Judge Gajarsa

King Pharmaceuticals, Inc. v. Eon Labs, Inc. (Fed. Cir. 2010)

Inherent Anticipation and Inherent Obviousness?

By Andrew Williams --

Last week, in King Pharmaceuticals, Inc. v. Eon Labs, Inc., the Federal Circuit affirmed a grant of summary judgment of invalidity of U.S. Patent Nos. 6,407,128 (the "'128 patent") and 6,683,102 (the "'102 patent"), although not necessarily for the same reasons articulated by the U.S. District Court for the Eastern District of New York.  King initiated the litigation after Eon filed an ANDA to market and sell a generic 800 mg metaxalone tablet for the treatment of "discomforts associated with acute, painful musculoskeletal conditions."  Metaxalone was first discovered in the 1960s, and had been sold under the brand name Skelaxin since 1962 -- first by A.H. Robins Co., then by Elan Pharma, Inc ("Elan"), and finally by King.  The '128 and '102 patents issued on June 18, 2002 and January 27, 2004, respectively, and claimed methods for increasing the bioavailability of metaxalone, and methods of using metaxalone in the treatment of musculoskeletal conditions.  The inventors of these two patents discovered and claimed that the oral bioavailability of metaxalone increases when it is administered with food.  The Federal Circuit determined, however, that all of the claims could be found inherently in the prior art.

Inherent Anticipation of Claims 1-3, 8-11, and 15-17 of the '128 Patent

Claim 1 of the '128 patent recites:

A method of increasing the oral bioavailability of metaxalone to a patient receiving metaxalone therapy comprising administering to the patient a therapeutically effective amount of metaxalone in a pharmaceutical composition with food.

The Federal Circuit agreed with the District Court that three references -- Fathie, Musculoskeletal Disorders and Their Management with a New Relaxant, Clinical Medicine 678 (April 1965) ("Fathie II"); Joseph A. Albanese, Nurses' Drug Reference 427 (2nd ed. 1982) ("Albanese"); and Anne C. Abrams, Clinical Drug Therapy 145 (1995) ("Abrams") -- each inherently anticipated this claim, because they each taught taking metaxalone with food.  Specifically, Fathie II taught that nausea associated with metaxalone treatment can be alleviated if taken with food, Albanese taught that administration of metaxalone with meals can help reduce gastric upset, and Abrams instructed nurses to give metaxalone with "milk or food" to decrease gastrointestinal distress.  Therefore, the only potential point of novelty was the preamble requiring the increase of oral bioavailability of the drug.  Nevertheless, the District Court held that an increase in metaxalone bioavailability was an inherent property of taking metaxalone with food as taught by all three of these references.

King argued that the District Court erred because Eon did not provide any evidence that these references would necessarily result in the claimed invention, as required for a finding of inherent anticipation.  King noted that the '128 patent specification provides precise conditions for food consumption that can accomplish the stated goal of the claim, while the prior art references only provide vague conditions.  The Federal Circuit found this position untenable.  Even though the specification provided examples with specific conditions, the disclosure did not indicate that these conditions were essential, and the Federal Circuit pointed out that the claim terms cannot be limited by specific conditions found within the specification.  In other words, the patentees erred by broadly claiming "with food," and perhaps they would have been better served by narrowing the claim scope to specific conditions required to achieve the stated goal of increasing oral bioavailability.  Of course, this is conditional on whether there were, in fact, specific conditions.  Moreover, the Federal Circuit pointed out the general rule that discovering a new benefit of an old process cannot render the process patentable again.  To inherently anticipate, the prior art need only meet the limitation to the extent the patented method does.  And because the claimed methods require no more than taking metaxalone with food, the prior art references that teach the same thing inherently anticipate.  The Federal Circuit also found that because claims 2-3, 8-11, and 15-17 had the same or similar preamble, they were also inherently anticipated.

Inherent Anticipation of Claims 4-6, 12-14, and 18-20 of the '128 Patent

The '128 patent also contained dependant claims that limit the time-frame in which the food must be ingested.  These ranged from "30 minutes prior to 3 hours after consumption," to "substantially at the same time," to "immediately after the consumption of food up to 1 hour after."  Even though none of the prior art references recited specific time requirements, King's own experts explained that "with food," as taught in the prior art, could mean "1 hour prior to up to about 2 hours after eating."  Because every claim included at least part of this range, the Federal Circuit had no difficulty finding that claims 4-6, 12-14, and 18-20 of the '128 patent were also inherently anticipated.

Claim 21 of the '128 Patent is Patent Eligible, but Nonetheless is Inherently Anticipated

Claim 21 depended from claim 1 (shown above), but included the limitation "informing the patient that administration of a therapeutically effective amount of metaxalone in a pharmaceutical composition with food results in an increase in the maximal plasma concentration (Cmax) and extent of absorption (AUC(last)) of metaxalone compared to administration without food."  The District Court invalidated this claim as patent ineligible pursuant to 35 U.S.C. § 101, because the act of informing was not transformative, as required by In re Bilski.  The Federal Circuit disagreed, pointing out that the District Court focused on the "informing" limitation, and not the claim as a whole.  Instead, the Court noted that Claim 21 as a whole is a method of treatment claim, and as such is always transformative, citing Prometheus Labs., Inc. v. Mayo Collaborative Serv., 581 F.3d 1336, 1346 (Fed. Cir. 2009).

Nevertheless, the Federal Circuit also found this claim invalid, not as patent ineligible, but as inherently anticipated.  As claim 1 was already found anticipated, the only potential source of novelty was the "informing" limitation.  The Court considered whether an inherently anticipated claim could be rendered novel by requiring that the patient be told about the existence of the inherent property.  Answering its own question, the Federal Circuit analogized the case to "printed matter" cases, such as In re Gulack, 703 F.2d 1381, 1385 (Fed. Cir. 1983), which hold that if claimed printed matter is not functionally related to a claimed product, it cannot be used to distinguish the invention from the prior art.  And because informing the patient about the benefits of a drug do not transform the process of taking the drug (even if it increased the likelihood that the patient will take the drug), claim 21 was inherently anticipated.

Claim 22 of the '128 Patent is Also Inherently Anticipated

Claim 22 also depends from claim 1, but includes the further limitation that the container have a printed label advising that administration with food results in an increase in the maximal plasma concentration (Cmax) and extent of absorption (AUC(last)) of metaxalone compared to administration without food.  This, of course, brings the case squarely within the "printed matter" cases as described above.  King tried to distinguish on the bases that this claim was a method claim, and the previous "printed matter" cases involved product claims.  However, the Federal Circuit found this to be a distinction without a difference and invalidated the claims based on inherent anticipation.

The Claims of the '102 Patent Are Inherently Anticipated or Inherently Obvious?

Claim 1 of the '102 recited:

A method of using metaxalone in the treatment of musculoskeletal conditions comprising:
providing the patient with a therapeutically effective amount of metaxalone; and
informing the patient that the administration of metaxalone with food results in an increase in at least one of C(max) and AUC(last) of metaxalone compared to administration without food.

Again, the District Court invalidated this claim as patent ineligible, but the Federal Circuit affirmed on alternate grounds, specifically that the claim was inherently anticipated.

Of more interest, the District Court also found claim 5 invalid, but as inherently obvious.  Claim 5 depends from claim 1, and limits metaxalone to a "unit dosage form."  The District Court found this claim obvious over Albanese in view of 18 R.W. Dent Jr. and Dorthey K. Ervin, A Study of Metaxalone (Skelaxin) vs. Placebo in Acute Musculoskeletal Disorders: A Cooperative Study, Current Therapeutic Research (1975) ("Dent").  King's apparently only new challenge to this holding was that the District Court did not consider the secondary considerations of non-obviousness.  Specifically, King alleged that the District Court failed to consider sales of Skelaxin from 1998 to 2003.  However, the Federal Circuit noted that sales of the drug actually began to increase before the discovery that ingesting metaxalone with food increased bioavailability.  Moreover, King apparently did not show any nexus between the alleged commercial success and the claimed invention.  As such, the District Court correctly did not give much weight to commercial success.

The Federal Circuit affirmed the obviousness of this claim because it found that "it would be obvious to a person of ordinary skill in the art to combine Dent's teaching of taking a tablet dosage of metaxalone four times a day with Albanese's teaching of administrating metaxalone with food."  However, no mention was made as to why one of skill in the art would have combined these references.  If Albanese had explicitly anticipated the other claims of these two patents, than obviousness would have probably been clear.  However, Albanese inherently anticipated the prior claims, because the newly claimed property was inherently present.  In other words, it was not known prior to the determination by the patentees.  The obviousness determination needs to take into account why one of skill in the art would have combined these two references, especially when the person of ordinary skill would have been unaware of this inherent property.  It is possible that such a reason existed, for example, it is possible that the use of the unit dosage form would have caused increased nausea and/or gastrointestinal distress (thereby leading one to take it with food).  However, no such reason was articulated in the Federal Circuit's opinion, and without articulating such a reason, it would appear that one of skill in the art would have only combined these references by mere happenstance.  As obviousness determination requires more.  The Court did point out that the person of ordinary skill is also a person of ordinary creativity, and not an automaton.  Nevertheless, such a hypothetically person needs to have a reason to be creative, and the Federal Circuit did not even address this fact.  As such, it is not clear that claim 5 of the '102 patent should have been invalidated.

Jurisdiction of Elan, the Prior Patent Holder

The Federal Circuit also addressed the issue whether the District Court had jurisdiction over Elan, because the lower court had entered the order against both King and Elan.  Elan had previously owned the '128 patent, and the application that led to the '102 patent.  However, before the filing of the present suit, Elan sold the patent and application to King, recording the assignment with the Patent and Trademark office.  Nevertheless, Eon filed declaratory counterclaims against Elan.  Elan even provided a letter to the District Court that stated that it waived any rights to pursue any damages or relief from Eon based on Elan's past ownership of the '128 patent.  The District Court did not address whether it had jurisdiction over Elan.  The Federal Circuit said was a mistake, and found that Eon had not met its burden of demonstrating that an actual case or controversy existed between it and Elan.  The broad and unrestricted covenants not sue were determinative.  Consequently, the Court vacated the order of invalidity as entered against Elan.

King Pharmaceuticals, Inc. v. Eon Labs, Inc. (Fed. Cir. 2010)
Panel: Circuit Judges Bryson, Gajarsa, and Prost
Opinion by Circuit Judge Gajarsa

Enzo Biochem, Inc. v. Applera Corp. (Fed. Cir. 2010)

    By Donald Zuhn --

On March 26, the Federal Circuit reversed the judgment of the District Court for the District of Connecticut that U.S. Patent Nos. 5,328,824 and 5,449,767 are invalid, affirmed the judgment of the District Court that U.S. Patent No. 5,476,928 is anticipated, and affirmed the judgment of the District Court that 5,082,830 is not infringed.

The '824, '767, '928, and '830 patents, which are owned by Plaintiffs-Appellants Enzo Biochem, Inc., Enzo Life Sciences, Inc., and Yale University ("Enzo"), are directed to various techniques for labeling and detecting nucleic acids.  More particularly, the '824, '767, and '928 patents are directed to a compound, or a method of using that compound as a detection probe.  In this compound (shown below), a nitrogenous base B is covalently attached, either directly or through a "linkage group" (dotted line), to a chemical moiety A.

In the asserted claims, the linkage group is recited functionally (rather than structurally) as "not interfering substantially" with both hybridization and detection (in the '824 and '767 patents) or detection alone (in the '928 patent).  Chemical moiety A is a label that facilitates detection, "compris[ing] at least three carbon atoms and represent[ing] at least one component of a signalling moiety capable of producing a detectable signal" (claim 1 of the '824 and '767 patents) or "represent[ing] at least three carbon atoms and an indicator molecule selected from the group consisting of fluorescent dyes, electron-dense reagents, enzymes which can be reacted with a substrate to produce a visually detectable reaction product, and radioisotopes" (claim 1 of the '928 patent).  The '830 patent is directed to a compound and a method of detection using a compound, wherein the claimed compound is a nucleotide labeled with "at least one non-radioactive moiety directly or indirectly attached to each of the 5′ and 3′ end nucleotides thereof," and the detection method is accomplished using a "preformed detectable molecular complex."

In June 2004, Enzo brought suit against Defendants-Appellees Applera Corp. and Tropix, Inc. ("Applera") for infringement of the '824, '767, '928, and '830 patents (as well as U.S. Patent Nos. 4,711,955 and 4,994,373, which were not at issue in the appeal).  In October 2006, the District Court issued a claim construction ruling, determining that the "not interfering substantially" functional language for the linkage group means that "the linkage group neither substantially interferes with the ability of the compound to hybridize with the nucleic acid nor substantially interferes with the ability of [moiety] A to be detected."  As for moiety A, the District Court determined that for the '824 and '767 patents, "[moiety] A may be a part of or the entire signalling moiety"; for the '928 patent, the plain language of the patent "precludes a construction where A is the entire [indicator] molecule"; and for the '830 patent, the term "non-radioactive moiety" means "a moiety that is utilized in indirect detection, i.e., a moiety that can be detected with a preformed detectable molecular complex."

Enzo conceded that under the District Court's construction, it could not prove infringement of the '830 patent, and the District Court granted summary judgment of noninfringement to Applera.  Applera then moved for summary judgment of lack of written description, lack of enablement, indefiniteness, and anticipation with respect to the three remaining patents.  The District Court granted summary judgment of indefiniteness and anticipation, finding the "not interfering substantially" language in the asserted claims to be indefinite because "[t]he specifications neither set forth how one would gauge substantial interference, nor delimit the threshold at which interference with the procedure prevents [the claimed] method from being implemented," and determining that the asserted claims were anticipated by three references (Kasai et al., 1979; Pingoud et al., 1977; and Bauman, 1980).

Indefiniteness

On appeal, Enzo argued that the District Court incorrectly determined that the "not interfering substantially" language in the '824, '767, and '928 patents is indefinite.  In particular, Enzo argued that the specifications provide specific examples of linkage groups that do not substantially interfere with hybridization and detection and a test for measuring the degree of interference (i.e., comparing the melting temperature of a modified polynucleotide with that of an unmodified polynucleotide).  Applera countered that nothing in the patents explains how to measure "interference" or how to determine whether such interference is "substantial."

In determining that the claims of the '824 and '767 patents are not indefinite, the Federal Circuit noted that "[t]he claims in this case provide at least some guidance as to how much interference will be tolerated."  Pointing to a dependent claim that recites the structure –CH=CH–CH₂–NH–, the panel observed that "[a] person of ordinary skill would presume that a structure recited in a dependent claim will perform a function required of that structure in an independent claim," and "[t]hus, it may be presumed that the term 'not interfering substantially' in the independent claims allows for at least as much interference as that exhibited when the linkage group has the structure specified in the dependent claims."

The panel also looked to examples of suitable linkage groups, as well as criteria for selecting such linkage groups, disclosed in the specification.  For example, the specification discloses that more preferred chemical linkage groups be derived from a primary amine and have the structure –CH2–NH–, and further, that thermal denaturation profiles and hybridization properties of a polynucleotide can be used to measure the degree to which a linkage group interferes with hybridization.  In view of the teachings in the specification, the panel concluded that the specification indicates that "when a linkage group is incorporated into a DNA strand having a length and sequence similar to those used in the specification, a decrease in Tm of up to 5 ^oC implies that the linkage group does not 'substantially interfere' with hybridization, and a decrease of up to 15 ^oC is acceptable if the degree of cooperativity and the extent of hyperchromicity are the same for the modified and unmodified strands."

Finally, the panel noted that during the prosecution of the patents, Enzo overcame an indefiniteness rejection by submitting a declaration under 37 C.F.R. § 1.132 listing eight specific linkage groups, including the –CH=CH–CH2–NH– group listed in the patents' dependent claims.  Thus, the panel concluded that:

Because the intrinsic evidence here provides "a general guideline and examples sufficient to enable a person of ordinary skill in the art to determine [the scope of the claims]," the claims are not indefinite even though the construction of the term "not interfering substantially" defines the term without reference to a precise numerical measurement.  When deciding whether a particular linkage group is or is not "substantially" interfering with hybridization within the meaning of the district court's construction, a person of ordinary skill would likely look to the thermal denaturation profiles and hybridization properties (including Tm) of the modified nucleotide, to see whether they fall within the range of exemplary values disclosed in the intrinsic evidence.

(citations omitted).

The Federal Circuit similarly found the claim language not indefinite with respect to detection  (Wherein the '824 and '767 patents concern the effect of the linkage group on hybridization and detection, the '928 patent only concerns the effect of the linkage group on detection.)  In support of this additional finding, the panel noted that the eight linkage groups listed in the declaration "were said not to 'interfere[] with the ability of biotin in an oligo- or polynucleotide probe of this invention to form a detectable complex with one of avidin, streptavidin or antibodies to biotin or iminobiotin.'"  Thus, the panel concluded that:

So long as moiety A can be detected within the level of detection achieved by the applicants using the exemplary linkage groups disclosed in the intrinsic evidence, a person of ordinary skill would understand that a different linkage group (one that is not disclosed in the intrinsic evidence) likewise does not "substantially interfere" with the detection of moiety A.

Anticipation

The Federal Circuit next addressed the issue of anticipation, finding that Enzo had raised a genuine issue of material fact as to the Kasai et al. and Pingoud et al. references sufficient to survive summary judgment of anticipation of the '824 and '767 patents, but that Enzo had failed to raise a genuine issue of material fact with respect to the Bauman reference and '928 patent.  Looking at the first two references, the panel noted that each "employ[s] a –CH2–NH– linkage group, which arguably belongs to the set of linkage groups disclosed in the patents-in-suit as 'even more preferred' embodiments," adding that "[i]f unopposed, this evidence would entitle Applera to judgment as a matter of law."  At trial, Enzo responded by offering an expert declaration stating that the –CH2–NH– linkage group of Kasai et al. "would not provide sufficient rigidity to prevent significant interference with hybridization of a complementary polynucleotide," and "[i]ndeed, one would predict based on the flexibility of this functional group and the concomitant high degree of motion, there would be significant interference due to free rotation about the single bonds."

On appeal, Applera argued that Enzo's expert declaration could not be credited because it conflicted with Enzo's Rule 132 declaration, and further, because Enzo's expert offered no support for his assertion that Kasai et al. would substantially interfere.  The Federal Circuit, however, determined that:

Viewing the [expert] declaration in a light most favorable to Enzo requires that [the expert's] explanation be read as limited to the specific one-carbon aminomethyl group [i.e., –CH2–NH–] disclosed in Kasai and not as a sweeping condemnation of single bonds or an unyielding requirement of double bonds.  . . .  [The expert's] statement that the aminomethyl group disclosed in Kasai would substantially interfere and [the Rule 132 declaration's] statement that a six-carbon diamine group would not are not inconsistent, particularly when viewed in a light most favorable to Enzo, as it must be.

The panel also noted that while Enzo's expert focused on the impact of the nature of the bonds in the linkage group (i.e., single or double) on hybridization and detection, the specification also recognizes that the length of linkage group impacts hybridization and detection.

Lastly, the panel addressed Applera's argument that the –CH2–NH– linkage group, which is described in Kasai et al., was also within Enzo's "even most preferred" embodiments.  In response, the Court determined that Enzo's counterargument that "the 'even more preferred' language is properly read as describing a subset of the preferred embodiments -- i.e., those with carbon-carbon double bonds at the α-positition -- such that the most preferred embodiments have both a carbon-carbon double bond at the α-position, and are derived from a primary amine and include a –CH2–NH– group," was reasonable and should have been credited on summary judgment.

Turning to Pingoud et al., the Court noted that "[o]n its face, Pingoud notes that there was substantial interference with hybridization."  In particular, the panel pointed to a statement in the reference that "[c]odon-anticodon interaction . . . is severely affected by the [fluorescent labeling] modification," stating that "'[c]odon-anticodon interaction' is indicative of hybridization, and 'severely affected' suggests substantial interference."  The panel therefore concluded that there was a genuine issue of material fact as to whether the linkage group disclosed in Pingoud et al. substantially interferes with hybridization.  The Court also rejected Applera's argument that the –CH2–NH– linkage group, which is similarly described in Pingoud et al., was within Enzo's "even most preferred" embodiment.

Turning to the final reference, the panel noted that in Bauman, hybridization is performed before moiety A is attached to base B via the linkage group.  Enzo argued that in view of this chronology, Bauman did not anticipate the '928 patent.  However, the Court determined that "[i]t is irrelevant, for purposes of anticipation, what method is used, much less what order of steps is used, to attach both moiety A and the linkage group to base B."  The Court also noted that because the '928 patent is silent as to hybridization, "[a]ll that is required of this particular linkage group is that it not substantially interfere with the ability of A to be detected."

Infringement

Addressing the last issue on appeal (i.e., infringement of the '830 patent), the Federal Circuit first reviewed the District Court's construction of the term "non-radioactive moiety," which the lower court had found to mean "a moiety that is utilized in indirect detection, i.e., a moiety that can be detected with a preformed detectable molecular complex."  The Federal Circuit found the District Court's construction to be reasonable, and affirmed the lower court's judgment of noninfringement with respect to the '830 patent.  In response to Enzo's argument that the District Court's construction violated the doctrine of claim differentiation because dependent claim 14 adds "a preformed detectable molecular complex" to claim 1, the panel stated that:

[T]he district court's construction imposes no requirement that a preformed detectable molecular complex is actually present in claim 1; rather, it simply requires the "non-radioactive moiety" to be capable of performing a function:  "can be detected with a preformed detectable molecular complex."  Claim Construction, 2006 WL 2927500, at *11 (emphasis added).  Claim 1, unlike claim 14, is infringed even in the absence of a preformed detectable molecular complex.

Enzo Biochem, Inc. v. Applera Corp. (Fed. Cir. 2010)
Panel: Chief Judge Michel and Circuit Judges Plager and Linn
Opinion by Circuit Judge Linn

Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims

    By Kevin E. Noonan --

Albeit a bit anticlimactically, a study published in the journal Genomics assesses the patentability of one of the claims invalidated on Monday by Judge Robert W. Sweet of the Southern District of New York in Association of Molecular Pathology v. U.S. Patent and Trademark Office.  The study is interesting in that it illustrates the pitfalls in patents on oligonucleotides related to isolated genes, filed at a time prior to the elucidation of the human genome by the Human Genome Project.  Most relevant to the question of whether such claims are patentable are the many revelations from the HGP that overturned settled dogma based on a now-recognized unrealistic view of the randomness of genomic DNA sequences, as illustrated by the results reported in this study.

The research was performed by Thomas B. Kepler, from the Department of Biostatistics and Bioinformatics at Duke University, and the Center for Computational Immunology; Colin Crossman, a lawyer and owner of Memento Mori, LLC; and Robert Cook-Deegan from the Institute for Genome Science and Policy and the Sanford School of Public Policy, Duke University (Kepler et al., "Metastasizing patent claims on BRCA1").  According to these authors, one of the claims of U.S. Patent No. 5,747,282 seemed "exceptionally broad" -- this is claim 5 that depends on claim 1 (which is directed to an isolated DNA molecule encoding a BRCA1 polypeptide):

1.  An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

5.  An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

The authors estimate that "the human genome contains over one million oligonucleotides covered by this claim," and follow up this statement with the following calculations:

Accounting for bias in the usage of amino acids as reported, for example, in [7], the usage-weighted geometric mean codon degeneracy per amino acid is 3.107.  Therefore, the mean number of 15-mers encoding a polypeptide of length 5 chosen at random from a vertebrate proteome is 3.107⁵, about 290.  There are 5,575 15-mers in BRCA1, so, if we consider all of the nucleotide sequences that encode the BCRA1 protein, there are about 1.6 x 10⁶ 15-mers embodied by the claim.  There are 4¹⁵=1.07 x 10⁹ different 15-mers altogether, so the probability that a 15-mer chosen at random will be covered by the claim is p=1.6 x 10⁶ / 1.07 x 10⁹=0.0015 (roughly, 1 in 600 possible 15-mers).  A typical human gene (before RNA editing) contains 10,000 bases, so, if human genes were random strings of nucleotides, one would expect a human gene to contain an average of 15 15-mers claimed under the patent.

The predicted results of this analysis were found in the study.  The authors analyzed the nucleotide sequence of human chromosome 1 looking for only a subset of 15-mers encompassed by claim 5.  ("Computing time" was minimized by excluding two of the six degenerate codons for serine, leucine and arginine amino acids, a reduction said to only "slightly underestimate the degree of redundancy and breadth of claim 5.")  The authors reported finding 340,000 "matches" of the claimed sequences in the 250,000,000 nucleotides comprising chromosome 1.

The authors also examined 713 entries in GenBank representing complete coding sequences for human mRNAs deposited in 1994, reporting that 80% (568/713 contained at least one of the claimed 15-mers.

There is nothing incorrect about this analysis; however, it benefits from current knowledge and (in its implied conclusion of intentional overreaching) neglects to consider the state of the genomics art on August 12,1994, the earliest priority date of the '282 patent.  The calculation was much more simple (or perhaps naïve) then:  any particular 15-mer was expected to occur once in every 1.07 x 10⁹ nucleotides, and thus in a completely random genome the size of the human genome (haploid size of about 3 x 10⁹ nucleotides), to occur about 3 times; a 16-mer would be expected to occur four times less frequently, etc.  Thus, the results set forth in this paper were almost completely unexpected when approached from the outlook of the person of skill in the art in 1994.

As it turns out, the human genome (and most other genomes) are much more inhomogeneous than expected, and the effects of evolution and the relatedness of all organisms (as well as the conservation of motifs and functional domains between species) were equally unexpected.  Indeed, even the number of genes encoded in the human genome turns out to be much smaller (2- to 3-fold fewer genes) than was expected.  As the authors state:  "human genes are not random strings [of nucleotides.]"  Evident now, not so evident 16 years ago.

No one wants an invalid patent.  The in terrorem effect of such a patent is greatly exaggerated, particularly when its invalidity is so easily demonstrated.  Here, these claims, as well as similar claims in other patents, turn out to be sufficiently overbroad as to be easily invalidated.  It is unlikely that the University of Utah, the National Institutes of Health, or Myriad Genetics (all owners of this patent) wanted this result.

Nevertheless, the remainder of the paper discussed the policy implications of this invalid claim.  The authors correctly note that their results indicate that claim 5 was anticipated by the 15-mers known in the prior art as exemplified by the GenBank results.  Thus, "[i]f challenged by re-examination or in litigation, claim 5 may be deemed invalid due to readily identifiable prior art covered by the claim."  The paper cites U.S. Patent Examiner James Martinell, examining a 1991 expressed sequence tag patent application, for recognizing that certain 15-mers could be found in "many genes" and that it was impossible using then-current computer technology to search all known sequences for the 700,000 15-mers claimed in that patent.  Perhaps for that reason, there is no evidence in the prosecution history of the '282 patent that such a search was ever performed.

Despite this strong evidence that claim 5 of the '282 patent is invalid (even before the District Court's decision yesterday), the paper speculates on the scope and reach of the claim (including oligonucleotide primers for performing the polymerase chain reaction).  Regarding the effects of this claim (and Myriad's patents) on basic research, the authors recognize what many others have noted:  no appreciable effect (which belies the introductory sentence of this section that "[t]he effect of this claim on research is very difficult to assess"):

A PubMed search for the term "BRCA1" returned 7,107 articles.  This suggests a large body of research on the gene has been published in the technical literature.  Myriad has not enforced its patents against most research, with the exception of laboratories engaged in clinical research that entailed giving test results to individuals beyond their home institutions [11–13].  Any such research that entailed analysis of DNA molecules containing BRCA1 sequences in the United States very likely infringed this claim, however, so enforcement of this claim would have substantial impact on research.  (Claims to BRCA1 sequences are somewhat narrower in other English-language jurisdictions such as Canada, Australia and New Zealand, and a fortiori in Europe, where the claims that emerged from opposition proceedings were dramatically narrowed.)  There is a very narrow "research exemption" from infringement liability in the United States under common law, and a broader exemption for research that results in data contributed to the government for a regulated medical product or service [14].  Since laboratory-developed tests are not currently subject to Food and Drug Administration approval, however, this exemption may not apply.

The simplest conclusion about the effect of claim 5 and Myriad's other BRCA1 patents on research and clinical testing is that Myriad has only rarely enforced its patents in research, has vigorously enforced its patents against commercial genetic testing, and has selectively enforced its patents in clinical research.  It is also apparent that research on BRCA1 for the past 12 years has entailed massive pervasive infringement of this claim, even if the claim's scope were restricted to BRCA1 research.  Any such research in the United States was thus undertaken under risk of infringement liability and its associated uncertainty.  While Myriad has stated publicly that it has not enforced its patents against basic research [11,12,15], it has not stated it will not do so in the future, and therefore BRCA research in the United States continues only with Myriad's indulgence.

The authors are correct that there is no exemption from infringement liability for basic research, but they admit that Myriad has not enforced (or attempted to enforce) the '282 patent against any basic researchers.  The absence of the exemption may be the problem, not claim 5 of the '282 patent (in view of the results of this research).  Myriad's track record with regard to basic research is consistent with its public statements that it would not enforce its patents against basic research; there is very little else it can do.  And after yesterday's decision, basic or clinical researchers or commercial entities that practice the oligonucleotides recited in claim 5 no longer risk infringement liability.

Ortho-McNeil Pharmaceutical, Inc. v. Teva Pharmaceuticals Industries, Ltd. (Fed. Cir. 2009)

    By Donald Zuhn --

The Federal Circuit today vacated-in-part and affirmed-in-part an order by the District Court for the District of New Jersey granting summary judgment of invalidity of U.S. Reissued Patent No. 39,221 based on anticipation and obviousness.

Plaintiff-Appellant Ortho-McNeil Pharmaceutical, Inc. owns the '221 patent, which relates to a tramadol and acetaminophen composition for use in prescription pain relief.  Ortho first claimed this composition in U.S. Patent No. 5,336,691, and after receiving FDA approval, began marketing a tramadol/acetaminophen tablet under the brand name Ultracet®.

Seeking approval to market a generic version of Ortho's tramadol/acetaminophen tablet, a number of generic companies filed Abbreviated New Drug Applications (ANDAs) with the FDA.  In response to these ANDA filings, Ortho filed multiple lawsuits for infringement of the '691 patent.  The generic companies argued that the '691 patent was invalid for anticipation and obviousness in view of U.S. Patent No. 3,652,589, which relates to tramadol, and which discloses a tramadol, p-acetamino-phenol, pentobarbital sodium, and ethoxy benzamide composition.  During the course of this litigation, Ortho learned that p-acetamino-phenol was an archaic name for acetaminophen.  Because the '589 patent discloses a 1:10 ratio of tramadol to p-acetamino-phenol (i.e., acetaminophen) in its four-compound composition, and this ratio falls within the scope of several claims in the '691 patent, Ortho sought to reissue the '691 patent.

During reissue proceedings, Ortho redrafted all but one of the asserted claims of the '691 patent to narrow them, and amended the lone remaining claim to independent form.  The redrafted claims and amended claim (claim 6 of the '221 patent) were allowed to reissue.  Following reissue, Ortho amended its complaints against the generic companies to assert the reissue claims.  Ortho's cases against Defendants-Appellees Teva Pharmaceuticals Industries, Ltd., Teva Pharmaceuticals USA, Inc., Watson Laboratories, Inc. ("Teva"), and Caraco Pharmaceutical Laboratories, Ltd. ("Caraco") were then consolidated.

Teva and Caraco filed summary judgment motions of invalidity, asserting that the '221 patent was anticipated and rendered obvious by the '589 patent and a series of German publications that were cited during the reissue proceedings (and which disclose a method of managing cancer pain by customizing a co-administration of pain relievers and dosing regimens for particular patients).  Ortho disputed Teva's and Caraco's interpretations of the references and submitted expert testimony explaining why the references did not anticipate or render obvious the asserted claims.  The District Court, however, granted summary judgment invalidating claim 6 as anticipated and obvious over the prior art, and invalidating the other asserted claims as obvious over the prior art.

In vacating the District Court's summary judgment invalidating the asserted claims other than claim 6, the Federal Circuit determined that these claims recite a pharmaceutical composition of tramadol and acetaminophen in a ratio of about 1:5 to about 1:19, and that "[a] single tablet containing only tramadol and acetaminophen in a fixed dose ratio within the claimed range is not disclosed in the cited prior art."  The majority also determined that the '589 patent discloses a four-compound composition and "does not suggest that the pentobarbital sodium and ethoxy benzamide are merely optional for the combination to work as desired."  The Court also took note of Ortho's expert testimony that "one of ordinary skill in the art would not find it obvious to try to remove two of the four active ingredients disclosed in [the four-compound composition of the '589 patent] to arrive at the claimed composition."  As for the series of German references, the majority noted that Ortho's expert explained that these references "actually teach away from the claimed composition because they emphasize the importance of flexibility in choosing combinations and doses of medications based on individual needs," and also disparage the claimed fixed-dosage combination tablet.  The majority concluded that Ortho's reading of the prior art, and expert testimony regarding the understanding of one skilled in the art, raised material questions of fact as to whether a skilled artisan would have found the claimed tramadol/acetaminophen composition obvious, and therefore vacated the District Court's grant of summary judgment as to the asserted claims other than claim 6.

Claim 6 of the '221 patent recites a pharmaceutical composition comprising a tramadol material and acetaminophen, wherein the ratio of the tramadol material to acetaminophen is a weight ratio of about 1:5.  With respect to this claim, the Federal Circuit first determined that while the '589 patent discloses a composition comprising tramadol and acetaminophen, the parties were at odds as to whether the '589 patent discloses the recited weight ratio.  Stating that "[t]he district court improperly resolved disputed questions of fact" in agreeing with Teva's and Caraco's interpretation of the '589 patent, the majority vacated the District Court's summary judgment that claim 6 is invalid for anticipation.

The majority, however, affirmed as to the District Court's summary judgment that claim 6 is invalid as obvious.  The Federal Circuit stated that the ratio of tramadol and acetaminophen disclosed for the four-compound composition of the '589 patent (i.e., 1:10) is so close to the Court's prior construction of "about 1:5" (see Patent Docs report on the prior appeal) that the '589 patent "creates a prima facie case of obviousness with regard to claim 6."  The majority concluded that Ortho failed to rebut the prima facie case by "show[ing] that the prior art teaches away from the claimed range, or the claimed range produces new and unexpected results over the prior art range."

Judge Mayer, in his dissent, begins by declaring that:

The claimed invention does nothing more than combine two well-known pain relievers -- acetaminophen and tramadol -- in a single tablet.  Since the prior art clearly and unequivocally taught that these two analgesics could be combined for effective pain relief, the claimed invention is the epitome of obviousness.

With respect to the disclosure of a four-compound composition in the '589 patent, Judge Mayer states that:

The only alleged difference between the tablet disclosed in the asserted claims of the RE221 patent and the tablet disclosed in [the '589 patent] is that the latter also contains two additional ingredients, pentobarbital sodium and ethoxy benzamide.  Given that ethoxy benzamide was a known carcinogen and pentobarbital sodium was known to have antagonistic interactions with analgesics, it would have been obvious to remove these two drugs from [the '589 patent's] formulation.

Observing that "[n]owhere does [the '589 patent] state that pentobarbital sodium and ethoxy benzamide are required components in a tramadol/acetaminophen tablet," Judge Mayer concludes that the removal of these two compounds would have been "a predictable and simple variation" on the formulation disclosed in the '589 patent.  Moreover, in Judge Mayer's view, when the German publications (which disclose combining tramadol with acetominophen to provide pain relief) are read in the light of the '589 patent (which discloses a fixed-dose tablet), "they clearly suggest combining tramadol and acetaminophen in a single fixed-dose tablet."  Thus, in Judge Mayer's eyes "there is nothing even arguably new about what Ortho claims to have invented."

Ortho-McNeil Pharmaceutical, Inc. v. Teva Pharmaceuticals Industries, Ltd. (Fed. Cir. 2009)
Nonprecedential disposition
Panel: Circuit Judges Mayer, Prost, and Moore
Opinion by Circuit Judge Prost; dissenting opinion by Circuit Judge Mayer

In re Gleave (Fed. Cir. 2009)

    By Kevin E. Noonan --

The duality of nucleic acids has long posed a challenge to patent law.  A gene is, in one way of looking at it, "but a chemical compound, albeit a complex one," and this view of the gene's nature has informed the emphasis on "structure, structure, structure" taken by the Federal Circuit from Amgen Inc. v. Chugai Pharmaceutical Co. to Judge Rader's comment in the oral argument for In re Kubin.  On the other hand, a gene also contains, and is defined by, the information it embodies, encoding an amino acid sequence corresponding to a structurally entirely different molecule, a protein.  This aspect of a gene's nature, and the unpredictable variability of it, underlies both the increased stringency with which the written description requirement is applied to nucleic acid claims, as well as the Office's resistance to apply Judge Rader's "structure, structure, structure" rule in determining whether a novel nucleic acid sequence, identified using established methods, is non-obvious.

The latest example of this phenomenon is the Federal Circuit's decision last week to affirm rejection on 102/103 grounds of unpatentability in In re Greave.  The claims at issue include this generic claim:

[a] bispecific antisense oligodeoxynucleotide, wherein substantially all of the oligodeoxynucleotide is complementary to a portion of a gene encoding human IGFBP-2 and substantially all of the oligodeoxynucleotide is also complementary to a gene encoding human IGFBP-5, and wherein the oligodeoxynucleotide is of sufficient length to act as an antisense inhibitor of human IGFBP-2 and human IGFBP-5

(where IGFBP-2 and -5 stand for two different species of insulin growth factor binding protein).  Also among the rejected claims were claims directed to particular species as set forth in applicants' specification.  The prior art asserted in support of the rejection was a PCT Publication to Wraight (WO 00/78431), which disclosed a list of all 15-mer oligonucleotides that could be made from the (publicly-available) full-length IGFBP-2 sequence, as well as disclosure in the Wraight reference that antisense oligonucleotides could comprise any oligonucleotide that specifically could bind to (i.e., hybridize with) any of the disclosed 15-mer sense oligonucleotides, and the existence in the Wraight disclosure of several 15-mer sense oligonucleotides with sequence complimentarity overlap to the specific oligonucleotides disclosed and claimed by Gleave.

The Federal Circuit affirmed the rejection, in a decision by Judge Prost joined by Chief Judge Michel and Judge Moore.  The Court based this decision on its view that anticipation required merely that the oligonucleotide sequence was in the prior art, not that its usefulness was previously disclosed.  Gleave argued that the art disclosed a mere list comprising "ink," not disclosure of any functional antisense oligonucleotide (indeed, the cited art contained no disclosure of an antisense oligonucleotide at all), but such disclosure was unnecessary, according to the Court.  All that is necessary for a prior art reference to anticipate, said the Court, is that it enable the skilled artisan to make the claimed invention, not use it, citing Impax Lab., Inc. v. Aventis Pharm. Inc., 545 F.3d 1312, 1314 (Fed. Cir. 2008); and In re LeGrice, 301 F.2d 929, 940–44 (C.C.P.A. 1962).  The prior art disclosure need not show actual reduction to practice (Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1380–81 (Fed. Cir. 2003); In re Donohue, 766 F.2d 531, 533 (Fed. Cir. 1985)), and the description provided in the putatively anticipating reference "might not otherwise entitle its author to a patent," citing Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991).

Cases that could be interpreted to the contrary, such as Bristol-Myers Squibb Co. v. Ben Venue Lab., Inc., 246 F.3d 1368, 1374 (Fed. Cir. 2001) ("[t]o anticipate, the reference must also enable one of skill in the art to make and use the claimed invention") are "[t]aken out of context," according to the Court, insofar as they are interpreted to impose an operability or utility disclosure requirement for an anticipating reference.  A "thorough" reading of the Court's caselaw (including Novo Nordisk Pharm., Inc. v. Bio-Technology General Corp., 424 F.3d 1347, 1355 (Fed. Cir. 2005); Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. Cir. 2005); and In re Hafner, 410 F.2d 1403, 1405 (C.C.P.A. 1969)) imposes no such requirement, the Court concluded.  And the Court also noted that Gleave's claims themselves contained no limitation restricting their scope to functional antisense oligonucleotides.

The crux of the distinction the Court made, regarding the use of a list of sense oligonucleotides in the cited art and the traditional proscription against using a mere recitation of all possible compounds as anticipating claims to particular species, is found in the Court's consideration of the application of In re Wiggins, 488 F.2d 538, 543 (C.C.P.A. 1973) to the facts before it.  In Wiggins, the Court of Customs and Patent Appeals stated:

In our view, [the alleged anticipatory reference's] listing of the compounds by name constituted nothing more than speculation about their potential or theoretical existence.  The mere naming of a compound in a reference, without more, cannot constitute a description of the compound, particularly when, as in this case, the evidence of record suggests that a method suitable for its preparation was not developed until a date later than that of the reference.

If we were to hold otherwise, lists of thousands of theoretically possible compounds could be generated and published which, assuming it would be within the level of skill in the art to make them, would bar a patent to the actual discoverer of a named compound no matter how beneficial to mankind it might be.

488 F.2d at 543 (emphases added).

The Court noted that the CCPA in Wiggins stated that "'[t]he mere naming of a compound in a reference, without more, cannot constitute a description of the compound.'" 488 F.2d at 543.  But the distinction with this case, according to the Court's opinion, is that Wiggins involved the "mere naming of a theoretical compound, without more," and that was not anticipating.  Indeed, the Court emphasized that "'[w]ithout more' is the key phrase," because what is "more" is the capacity for the person of ordinary skill in the art to be able to make the claimed compound.  Here, these were not "potential or theoretical" compounds, but a class of compounds that fell within so limited a genus that the skilled artisan could "'at once envision each member of this limited class,'" citing Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., 471 F.3d 1369, 1376 (Fed. Cir. 2006).  "In that limited circumstance, a reference describing the genus anticipates every species within the genus.  See Perricone [v. Medicis Pharm. Corp., 432 F.3d 1368, 1377 (Fed. Cir. 2005)]."

What was not anticipated by the cited art are methods of using these oligonucleotides, and the Court suggested that Gleave might be entitled to such claims.  As for the appealed composition of matter claims, the Court found that these sequences "are simply not new," and affirmed.  And here is where the duality of nucleic acids becomes important.  It was undisputed that the Wraight reference did not disclose a single antisense oligonucleotide -- it merely disclosed all 15-mer sense oligonucleotides, coupled with generic disclosure that antisense oligonucleotides would specifically hybridize to the disclosed sense oligonucleotides, and the knowledge in the art that such oligonucleotides could be made without undue experimentation.  Regardless of operability (although Gleave's arguments might have had additional force had they contained a functional limitation regarding operability as antisense oligonucleotides), the Court's decision suggests that nucleic acids can be anticipated by the mere recitation of any sequence, or its complement, in the prior art regardless of any disclosure as to operability.  This raises the question of whether an unidentified open reading frame, published in a publicly-available database, might not be enough to anticipate claims directed to an isolated nucleic acid encoding a novel protein.  Like the antisense oligonucleotides at issue in Gleave, the existence of the sequence in the prior art could be combined with the knowledge of the skilled worker that proteins are encoded by open reading frames to anticipate the sequence.  Known operability is not required, according to this panel opinion, raising the question of whether the availability of the published but unrecognized sequence would be enough.  There are certainly distinctions:  here, the oligonucleotides comprised a known protein, for example.  And there would be an In re Hall question about whether an unannotated open reading frame would be sufficiently accessible to qualify as prior art.  But the Federal Circuit's decision in Gleave amounts to yet another instance of differential application of the law to biotechnology claims, whose effects remain to be fully appreciated.

In re Greave (Fed. Cir. 2009)
Panel: Chief Judge Michel and Circuit Judges Prost and Moore
Opinion by Circuit Judge Prost