Patent Docs

Washington Legal Foundation Files Amicus Brief in Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co.

By Kevin E. Noonan --

The Washington Legal Foundation (WLF), a self-styled "non-profit public interest law and policy center that regularly appears before federal and state courts to promote economic liberty, free enterprise, and a limited and accountable government," filed an amicus curiae brief on September 8th, urging the Federal Circuit to rehear en banc Eli Lilly's appeal of the Court's affirmance of an invalidity finding of U.S. Patent 5,464,826.  The Federal Circuit affirmed a District Court determination that the claims of the '826 patent were invalid over the claims of Lilly's U.S. Patent No. 4,808,614 under the judicially-created doctrine of obviousness-type double patenting.  The '826 patent claimed methods for using gemcitabine (sold by Lilly under the name GEMZAR®) for treating cancer, and the earlier '614 patent disclosed but did not claim this use.  The lawsuit between the parties arose after Sun filed an ANDA for generic gemcitabine, and Sun Pharmaceuticals filed a declaratory judgment action that the '614 and '826 patents (both of which were listed in the FDA's Orange Book) were invalid.

The Federal Circuit in its panel decision based affirmance on its earlier decisions in Geneva Pharm., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353 (Fed. Cir. 2008), that the only type of applications that qualify for the "safe harbor" provisions of 35 U.S.C. § 121 were divisional applications, i.e., applications filed in response to a Patent Office-promulgated restriction requirement.  Restriction is proper if the Office determines that an application claims more than one patentably-distinct invention, and the safe harbor protects applicants from inconsistent determinations from the Office that the claims are patentably-distinct for restriction purposes but fall within the scope of the obviousness-type double patenting doctrine.

Here, the '614 patent was a continuation-in-part of an earlier-filed application whose description of methods of using gemcitabine were limited to the compound's antiviral activities.  The '826 patent, which arose from an application filed on the same day as the '614 patent, claimed the use of gemcitabine for treating cancer.  The District Court's obviouness-type double patenting determination as well as the Federal Circuit's affirmance were ultimately grounded in the policy considerations enunciated in Pfizer and Geneva Pharm.:

It would shock one's sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . . and then prevent the public from making any beneficial use of such product by securing patent upon each of the uses to which it may be adapted.

Pfizer, 518 F.3d at 1368 n.8; Geneva Pharm., 349 F.3d at 1386.

The WLF objects to this "expansion" of the obviousness-type double patenting doctrine in its amicus brief.  The group argues that the Court's decisions threaten to lower the incentive to innovate by limiting a patentee's ability to protect improvements in their inventions.  Citing Miller v. Eagle Mfg. Co., 151 U.S. 186, 198 (1894), the brief argues that it is settled law that "an inventor may obtain 'a separate patent' for a 'new improvement on his own invention.'"  Id. at 199.  Indeed, the brief argues that "[h]ad anyone other than Eli Lilly discovered this method of treating cancer with gemcitabine, quite clearly they would have been entitled to a patent," citing Lilly's brief in support of its petition for rehearing en banc.  WLF's brief also argues that "Miller specifically precludes the possibility that a patent that merely describes a separately patentable invention renders another patent claiming that invention invalid under the doctrine of double patenting." 151 U.S. at 198, an interpretation directly contrary to the panel decision here.

The brief recognizes that the panel believes that its decision was consistent with the Geneva Pharm. decision, but distinguished this case by characterizing the panel decision here as "extending" the holding in Geneva Pharm -- specifically, asserting that in that case, a compound and its "only" use were not patentably distinct, whereas gemcitabine had "two separate methods of use," making Takeda v. Doll, 561 F.3d 1372 (Fed. Cir. 2009), the appropriate prior precedent.  In the Takeda case, the Court held that a later-claimed method of making a claimed pharmaceutical was patentably distinct provided that "a second method of making the same pharmaceutical was discovered before the filing of the application that led to the second patent."  Id. at 1377.  Since the application leading to the '826 patent was filed on the same day as the invalidating '614 patent, "the new method necessarily was discovered prior to the filing of either patent" (emphasis in original).  Thus, the brief concludes, "discovery of the second method of using the compound should have rendered both the new method and the older method patentably distinct from the compound."

The brief also notes that the Court's decision here is contrary to Patent Office restriction practice, which "categorically barred an applicant from presenting claims to a compound and two distinct methods of using that compound.  37 C.F.R. §§ 1.141(a)-(b) (1984)."  Had Lilly presented claims to both methods of use in the same patent, the brief argues that the application would have been subject to a restriction requirement, which would have forced these claims to be pursued in two separate patents.  This part of the brief implies strongly that it is equally "a shock to a sense of justice" to have substantive rights so influenced by procedural details of whether the claims are presented in the same or separate applications (an argument that depends on the unique facts here that the '614 and '826 application were effectively filed on the same day), in view of these established rules of practice.  The brief argues that the en banc Court should solicit the PTO's views on this question.

Eli Lilly & Co. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2010)

By Kevin E. Noonan --

The old proverb "success has many fathers, while failure is an orphan" comes to mind when considering the Federal Circuit's decision in Eli Lilly & Co. v. Teva Pharmaceuticals USA, Inc.  In the Court's decision, repeated failures, even by Lilly scientists in developing its osteoporosis drug Evista® (raloxifene hydrochloride), were sufficient to defeat Teva's counterclaim that patent claims related to methods of use were obvious.

The action arose following Teva's ANDA filing containing a Paragraph IV certification that the patents-in-suit were invalid (there was no discussion in the opinion of any inequitable conduct allegations below).  The patents fell within three broad categories, and included the Bone Loss patents (U.S. Patent No. 6,906,086 and Reissue Patents Nos. RE39,049; and RE38,968), the Low Dose patent (Reissue Patent No. RE39,050) and the Particle Size patents (U.S. Patents Nos. 6,458,811 and 6,894,064).  Specific claims representative of the patents-in-suit include the following:

Claim 1 of the '086 patent (Bone Loss patent):

A method of inhibiting post-menopausal bone loss in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis comprising administering a single daily oral dose to said woman of an effective amount of [raloxifene] hydrochloride.

Claim 14 of the '050 reissue patent (Low Dose patent):

A method of preventing post-menopausal osteoporosis in a post-menopausal woman in need of treatment to prevent post-menopausal osteoporosis comprising administering to said woman a hydrochloride salt of . . . [raloxifene] in an amount of 60 mg/day.

Claim 1 of the '811 patent (Particle Size patent; emphasis added):

A compound of formula I . . . [raloxifene] and pharmaceutically acceptable salts and solvates thereof, characterized in that the compound is in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns.

The District Court (Judge Sarah Evans Parker) found the Bone Loss and Low Dose patents not invalid under §§ 103 and 112, 1st paragraph (enablement), but that the Particle patents were invalid for failing to satisfy the written description requirement under 112, 1st paragraph, and granted a permanent injunction keeping generic raloxifene hydrochloride off the market until Lilly's patents expire.

Relevant to the Federal Circuit's analysis was the developmental history of raloxifene.  Originally pursued as an "antiestrogen" breast cancer treatment (similar in mode of action to tamoxifen), clinical experience with the drug showed low bioavailability in humans (despite significant bioavailability in experimental animals).  This result appeared to be related to the presence of free hydroxyl groups in raloxifene that were modified by conjugation with glucaronide as part of the detoxification and elimination pathways in humans.  The Court cited several prior art references disclosing low bioavailability and that raloxifene underwent "rapid metabolic conversion."  These included the Buzdar reference (1988) that disclosed results showing that raloxifene elicited no complete or partial responses for breast cancer patients resistant to tamoxifen (although the reference did not directly attribute these results to low bioavailability).  These bioavailability concerns regarding raloxifene were an express ground for the District Court to find that Lilly's claims for its Bone Loss and Low Dose patents were non-obvious, since the known low bioavailability for raloxifene would have precluded the skilled worker from having a reasonable expectation that the drug would be clinically useful for treating osteoporosis.

In its opinion, written by Chief Judge Rader joined by Judge Linn and Judge Prost, the Court affirmed the District Court's determination that Teva had not provided clear and convincing evidence that the claims of the Bone Loss or Low Dose patents were obvious.  On appeal, Teva argued three prior art references in support of its obviousness arguments.  U.S. Patent No. 5,075,321 (Schreiber patent) disclosed the use of raloxifene for treating autoimmune disorders (and according to the opinion was the basis for Lilly reissuing three of the patents-in-suit).  The Court found that this reference did not provide clear and convincing evidence of obviousness, because osteoporosis is not an autoimmune disease, and the evidence suggested different mechanisms of action.  "Without a closer relationship, Teva cannot show that an ordinarily skilled artisan would have expected Dr. Schrieber's article to have relevance for the treatment of postmenopausal osteoporosis," the Court said.  The opinion also rejected Teva's argument that the reference is relevant for showing clinically-significant bioavailability for raloxifene, based on the different uses (osteoporosis versus autoimmune disorders) as well as the fact that what was prior art in the Schrieber reference was based on animal studies that did not address the bioavailability issue in humans.

The second reference, a scientific journal article by Jordan, disclosed rat studies on the effects of tamoxifen and raloxifene on bone density.  According to the Court's opinion, "Dr. Jordan concluded that these results 'may have important implications for the clinical [human] applications of antiestrogens'" and that "'[i]t is possible . . . that in the future, tamoxifen could be considered to be used as a substitute for estrogen [for the prevention of osteoporosis in postmenopausal women]'" (emphasis added).  The reference also contained an assertion calling for clinical investigation of the use of tamoxifen for treating osteoporosis.  Unfortunately for Teva's argument, the Federal Circuit did not consider these teachings relevant for the use of raloxifene, because the reference suggested that tamoxifen, not raloxifene, be explored for use as an osteoporosis treatment.  In addition, not only was the reference silent as to the bioavailability issue, but the opinion cited the District Court's reasoning that the Jordan reference "exemplified" the bioavailability concerns with raloxifene and that the skilled worker "'would not have had a reasonable expectation of success in using raloxifene to treat human postmenopausal osteoporosis.'"  The Federal Circuit particularly faulted the portion of Teva's arguments relying on how Lilly scientists interpreted the Jordan results in support of its case for obviousness, since these inventors have greater than ordinary skill.  In addition, the Lilly scientists possessed internal information relating to the capacity for conjugation of raloxifene to be reversed in vivo (resulting in improved bioavailability), but this knowledge was also unavailing in support of Teva's arguments the court held, relying on KSR Int'l. Co. v. Teleflex Inc. ("The question is not whether the combination was obvious to the patentee but whether the combination was obvious to a person of ordinary skill in the art.")  Not expressly stated in the Court's opinion was the extent to which its determination was affected by Lilly scientists possessing information not within the knowledge of the worker of ordinary skill.

Finally, with regard to the Jones patent (which disclosed raloxifene), the opinion relied on this patent having been filed before any of the bioavailability results were obtained or concerns were raised, and that "[t]he record does not contain any reason that a person of ordinary skill would have ignored those later publications."  The Court also said that further evidence, specifically the results of the "failed" Buzdar study, would have precluded the skilled worker from having a reasonable expectation of success using raloxifene.  The Court rejected Teva's arguments that the Buzdar reference did not attribute its results to bioavailability issues, saying the skilled worker could draw that inference.

The Court came to the same conclusions and affirmed the lower court's non-obviousness determination for the claims of the Low Dose patent.  On appeal, Teva also argued that these claims were invalid under the doctrine of obviousness-type double patenting, based in part on the District Court's finding that the nature of the experiments to determine a clinically-effective low dose were routine (in its analysis addressing Teva's enablement challenge to these claims).  The Federal Circuit noted that this challenge was not raised below, and that the "record is insufficiently clear for it to conclude that the proper resolution is beyond any doubt."  Possibly significant (in view of the several recent instances of claims being invalidated for obviousness-type double patenting), the Court expressly stated that the policy rationales raised by Teva (that these patents extended Lilly's exclusivity term for Evista®) were not great enough to overcome the procedural deficiencies.

Teva also challenged the Bone Loss and Low Dose patents in the District Court on enablement grounds, and the Federal Circuit also affirmed the District Court's determination that the claims of these patents were enabled.  Teva's enablement challenge sounded in operability under 35 U.S.C. § 112, 1st paragraph (which the Court has held has its own utility requirement distinct from the utility requirement under § 101; In re Brana).  Here, the opinion cites the Manual of Patent Examining Procedure for its provisions relating to the effect of human clinical trials on the question of operability raised under 35 U.S.C. § 112, 1st paragraph (i.e., that having an on-going clinical trial is evidence that the invention is sufficiently operable for patenting purposes):

Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration) that the investigation may be successful.  Such a rational would provide a basis for the sponsor's expectation that the investigation may be successful.  In order to determine a protocol for phase I testing, the first phase of the clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary.  Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.  MPEP (2008) § 2107.03 at IV (emphasis added).

The Court's opinion recognized that Teva's arguments relate to an inherent "Catch 22" regarding the relationship between the enablement requirement and the lack of a reasonable expectation of success in an obviousness determination:

To the extent that Teva revisits this [obviousness] argument in the enablement context, it appears to contend that Lilly's actions provide circumstantial evidence that an ordinarily skilled artisan would not have found helpful the facts on which the district court relied to hold that the patents are enabled.  This court rejects that argument as well, and for essentially the same reason:  it conflates the expertise of Lilly scientists with the knowledge of one of ordinary skill in the art.  . . .  Indeed, Lilly appears to have had many advantages that a person of ordinary skill would not have had, not the least of which was the FDA's prior approval of Lilly's IND application.  Lilly's reliance on those advantages rather than its knowledge of Black's conjugate studies [relating to greater than expected bioavailability] to proceed with human trials does not create clear and convincing evidence that a person of ordinary skill would fail to find comfort in the latter.

The Federal Circuit also affirmed the District Court's finding that the asserted claims of the Particle Size patents were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112, 1st paragraph.  These patents disclosed a range of particle sizes that increased bioavailability, wherein "within the claimed particle size range, the raloxifene particles provide 'surprisingly consistent in vivo absorption/bioavailability characteristics.'"  The District Court construed the relevant claim language, "in particulate form," to include the size of the particles either in the pure active pharmaceutical ingredient (API) or in the tablet after formulation (which construction benefited Lilly's contention that the API had been prepared with easily-dissociated particles so that the API, but not the formulated tablet, would fall outside the scope of the Particle Size patent claims).  Unfortunately for Lilly, however, the District Court found that the patent specifications did not disclose or describe determining particle size in the formulated tablet, and the Federal Circuit agreed:

[A]fter reading the patent, a person of ordinary skill in the art would not understand how to extract raloxifene particles from a formulation in order to determine whether they fall within the claimed particle size range and, in fact, would have no indication that size measurements on anything other than unformulated raloxifene would bear any relevance to the invention.

The Court affirmed, because since satisfaction of the written description requirement is a question of fact, it could not find that the District Court's decision was clearly erroneous, in particular due to admissions by Lilly's own expert regarding whether these embodiments were disclosed.

Since the Federal Circuit affirmed the District Court's decision that neither the Bone Loss nor the Low Dose patents are invalid, the injunction preventing Teva from providing generic raloxifene hydrochloride stands until expiration of the last expiring of these patents (March 2, 2014).

Eli Lilly & Co. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2010)
Panel:  Chief Judge Rader and Circuit Judges Linn and Prost
Opinion by Chief Judge Rader

Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co. (Fed. Cir. 2010)

By Andrew Williams --

On Wednesday, in Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., the Federal Circuit affirmed a finding that claims of Lilly's U.S. Patent No. 5,464,826 ("the '826 patent) were invalid for obviousness-type double patenting over U.S. Patent No. 4,808,614 ("the '614 patent").  The '614 patent claims gemcitabine, and methods of using gemcitabine to treat viral infections, while the '826 patent claims methods of using gemcitabine for treating cancer.  Lilly markets the drug GEMZAR, which contains gemcitabine as the active ingredient, for the treatment of various forms of cancer.  Correspondingly, both the '614 patent and the '826 patent were listed in the Orange Book with respect to GEMZAR.  Sun filed an ANDA in 2006 to market a generic version of GEMZAR, and filed a declaratory judgment action in 2007, asserting, among other things, that the '826 patent was invalid.  Ultimately, the U.S. District Court for the Eastern District of Michigan granted Sun's motion for partial summary judgment because the asserted claims of the '826 were invalid based on obviousness-type double patenting.

Lilly's '614 patent was a continuation-in-part ("CIP") application of U.S. Application No. 06/473,883 ("the '833 application").  The original '833 application only described gemcitabine's antiviral activity.  However, when the CIP application was filed, the specification was amended to include the observation that "certain compounds of the present invention have also demonstrated excellent oncolytic activity in standard cancer screens" ('614 patent, col. 17, ln. 54-56).  Nevertheless, the '614 patent did not claim any methods of treating cancer.  In fact, Sun and Lilly did not dispute that the '614 patent was entitled to the benefit of the '833 application filing date.  On the same date that Lilly filed the application that resulted in the '614 patent, it also filed an application that gave rise to the '826 patent.  Because both of these applications were filed prior to 1995 (December 4, 1984 to be exact), the patent term was calculated based on the issue date.  Lilly obtained patent term extension for the '614 patent, and as a result, the patent expired on May 15, 2010.  The '826 patent was set to expire two-and-a-half years later, on November 7, 2012.  Lilly did not file a terminal disclaimer.

The Federal Circuit agreed with the District Court in finding that this case was analogous to the prior decisions in Geneva Pharm., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353 (Fed. Cir. 2008).  In Geneva Pharm., an earlier patent claimed the compound potassium clavulanate, and the specification disclosed its utility in inhibiting B-lactamase, while a later patent claimed the method of using the compound to inhibit B-lactamase.  Because the second patent did no more than claim the previously disclosed utility of a previously claimed compound, the two patents were not patentably distinct.  In Pfizer, an earlier patent claimed several COX-2 inhibitors, and disclosed that they could be used to treat both inflammation and inflammation-associated disorders.  A later patent claimed these previously disclosed methods of use.  Again, the Court found that these two patents were not patentably distinct.

Lilly asserted two reasons why the present case was different from both Geneva Pharm. and Pfizer.  First, Lilly pointed out that in the earlier cases, there was only one disclosed utility -- the methods of use that were claimed in the later patents.  In contrast, Lilly's earlier patent disclosed more than one utility -- treating viral infections and cancer.  Because the treatment of cancer was not the "essential utility," Lilly argued, the two patents were patentably distinct.  The Court rejected this argument because the Pfizer case, in fact, did involve more than one essential utility -- the treatment of inflammation, and the treatment of inflammation-associated disorders.  Of course, the Court does not address whether these were results of the same utility, namely, whether the treatment of the inflammation-associated disorders would flow naturally from the treatment of the inflammation.  But, on the other hand, it is not clear from the discussion whether the anti-cancer properties of gemcitabine would not naturally result from the treatment of the viral infections.  Nevertheless, the Court determined that the holdings of Geneva Pharm. and Pfizer extend to any and all uses disclosed in the earlier specification.

The Federal Circuit also rejected Lilly's second argument that the trial court erred in consulting the specification of the issued patent instead of the specification of the priority document, the '833 application.  In support of this argument, Lilly relied on claim construction concepts as articulated in Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005).  Specifically, Lilly argued that a claim term should be given its ordinary and customary meaning as understood by one of ordinary skill in the art at the time of invention.  Gemcitabine's anti-cancer properties were unknown at the time the '614 patent was invented.  However, the Federal Circuit pointed out that its claim construction precedent establishes that claim terms must be construed in light of the entire issued patent, and therefore found no support for Lilly's argument.

Ultimately, the Federal Circuit appears to justify its decision on the policy considerations as articulated in both Pfizer and Geneva Pharm.:

It would shock one's sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . . and then prevent the public from making any beneficial use of such product by securing patent upon each of the uses to which it may be adapted.

Pfizer, 518 F.3d at 1368 n.8; Geneva Pharm., 349 F.3d at 1386.

Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co. (Fed. Cir. 2010)
Panel: Circuit Judges Bryson, Gajarsa, and Prost
Opinion by Circuit Judge Prost

Re-examination Ordered on "Expired" Harvard Oncomouse Patent

    By Kevin E. Noonan --

On Monday, the U.S. Patent and Trademark Office granted an ex parte reexamination request for U.S. Patent No. 5,925,803, the latest-filed and last-granted member of the Harvard Oncomouse patent family.  Remarkable about the petition is that the third party requester (TPR), Ellen Gonzales of Gonzales Patent Services, contends that the '803 patent has expired by operation of a terminal disclaimer filed in an earlier-filed application, but maintains that despite the putative expiration, the Office retains jurisdiction to consider the re-examination request.

There are three claims in the '803 patent, all directed to methods for testing a compound suspected to be a carcinogen:

1.  A method of testing a material suspected of being a carcinogen, comprising exposing a transgenic mouse to said material and detecting neoplasms as an indication of carcinogenicity, wherein the germ cells and somatic cells of said mouse contain an activated oncogene sequence introduced into said mouse, or an ancestor of said mouse, at an embryonic stage.

2.  A method of testing a material suspected of conferring protection against the development of neoplasms, said method comprising
    (1) providing a first and a second transgenic mouse, the germ cells and somatic cells of which contain an activated oncogene sequence introduced into said mice, or an ancestor of said mice, at an embryonic stage,
    (2) treating said first mouse with said material, and
    (3) detecting, as an indication of said protection, a reduced incidence of development of neoplasms in said first mouse, compared to the incidence in said second mouse, which is not so treated.

3.  The method of claim 1, further comprising exposing said first and second mice to a carcinogen prior to, after, or simultaneously with treating said first mouse with said material.

The TPR asserted six substantial new questions (SNQ) of patentability against these claims:

• SNQ1:  Claim 1 of the '803 Subject Patent is obvious in view of Claims 1, 11, and 12 of [grandparent U.S. Patent No. 4,736,866] in view of Ward et al. or Schach et al. under the doctrine of judicially-created obviousness-type double patenting.

• SNQ2:  Claims 1-3 of the '803 Subject Patent are unpatentable in view of the Claims 1-12 of the '866 Grandparent Patent under the doctrine of judicially-created obviousness-type double patenting.

• SNQ3:  Claims 2-3 of the '803 Subject Patent are obvious in view of the claims of the '866 Grandparent Patent in view of the Proctor Patent, under the doctrine of judicially-created obviousness-type double patenting.

• SNQ4:  Claims 1-3 of the '803 Subject Patent are obvious under 35 U.S.C. 103(a) in view of Schwab et al.

• SNQ5:  Claims 2-3 of the '803 Subject Patent are obvious under 35 U.S.C. 103(a) over Jaenisch et al. in view of the Proctor patent.

• SNQ6:  Claim 1 of the '803 Subject Patent is obvious under 35 U.S.C. 103(a) over Jaenisch et al. in view of the either Ward et al. or Schach et al.

TPR contends that the following describes the priority chain and the relationship between the grandparent '866 patent, parent U.S. Patent No. 5,087,571, and the '803 patent.  The '866 patent, according to the TPR, contained claims 1-12 directed to the Harvard oncomouse; claims 13-19 directed to methods for testing a compound suspected of being a carcinogen; and claims 20-22 directed to plasmid constructs; claim 1 is representative:

1.  A transgenic non-human mammal all of whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal, or an ancestor of said mammal, at an embryonic stage.

The TPR contends in her request that the applicant cancelled the claims to the testing methods and let claims to the Harvard Oncomouse proceed to grant as the '866 patent.

The application that gave rise to the parent '571 patent, the TPR contends, was improperly designated as a "divisional application," despite the fact that no restriction requirement was raised against any of the claims of the '866 patent and that the patentee voluntarily cancelled the testing method claims in the '866 patent as part of their patenting strategy.  This application was filed initially with original claims 13-24 that had been cancelled during prosecution of the '866 patent.  Prosecution of the '571 patent resulted in two granted claims:

1.  A method of providing a cell culture comprising
    (1) providing a transgenic non-human mammal, all of whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal, or an ancestor of said mammal, at an embryonic stage; and
    (2) culturing one or more of said somatic cells.

2.  A cell derived from a somatic cell obtained from a transgenic non-human mammal, all of whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal, or an ancestor of said mammal, at an embryonic stage which cell contains said recombinant activated oncogene sequence.

Significantly, applicants filed a terminal disclaimer over the claims of the '866 patent in order to overcome an obviousness-type double patenting rejection raised against these claims.  The following language in the terminal disclaimer is important for the arguments successfully raised in the request (with emphasis added):

Your petitioner, President and Fellows of Harvard College, hereby disclaims any portion of an patent granted on the above-identified application or on any application which is entitled to the benefit of the filing date of this application under 35 U.S.C. 120 not extending the term of any patent granted on that application beyond the term of issued U.S. Patent No. 4,736,866 issued April 12, 1988.

The TPR contended that this language was not required in a terminal disclaimer and the patentees were bound by it (i.e., that it cannot be rescinded by certificate of correction, reissue, or reexamination, even if it was filed in error).  As in the '866 patent, patentees cancelled the testing method claims in the application that granted as the '571 patent.

The application that granted as the '803 patent was the first member of the priority chain having a restriction requirement, which was filed with claims 1-13 and 15-24 of the grandparent application.  This restriction requirement identified three groups:  claims 1-12 and 15-17, directed to a transgenic animal and methods for producing such an animal; claims 13, 18 and 19, drawn to suspected carcinogen testing methods; and claims 20-24 being drawn to plasmids; applicants elected to prosecute the testing method claims.  During prosecution the applicants overcame an obviousness rejection based on the '866 patent and the Ward and Schah references on the grounds that 35 U.S.C. § 121 "prohibits the USPTO from rejecting a later divisional application 'where (as here) the divisional application is filed as the result of a restriction requirement in the original case.'"  The TPR contended that this statement is inaccurate, insofar as there was no restriction requirement issued during prosecution of either the grandparent '866 patent or the '571 patent.

The TPR argued in the request that the '803 patent expired by operation of the terminal disclaimer filed in the '571 patent on July 12, 2005, the expiration date of the '866 patent.  Reexamination is still proper, she contended, because a reexamination "may be declared for an expired patent at any time during the enforceability of the patent" (emphasis in original), which will run until July 12, 2011 (i.e., six years after the patents expiration date; M.P.E.P. § 2211).  Moreover, a question arising as a result of obviousness-type double patenting is appropriate for raising a substantial new question of patentability in a reexamination (M.P.E.P. § 2217).  Finally, the TPR argued that public policy concerns supported the Office granting her request for reexamination:

TPR respectfully requests that a Reexamination nonetheless be declared to serve the public notice function of Reexaminations (i.e., to make it clear on the record that the '803 Subject Patent is only avoiding the double-patenting rejections because of the terminal disclaimer in the '571 Parent Patent, which likewise informs the public that the patent expired on July 12, 2005).  In such a case, even if a Reexamination is not declared, to serve the public notice function, TPR respectfully requests that the Patent Office indicate in writing that the terminal disclaimer in the '571 Parent Patent application insulates the '803 Subject Patent from obviousness type double patenting rejections, and further, affirmatively state that the '803 Subject Patent therefore expired on July 12, 2005.  This public notice function is particularly important in this case as the Patentee is publicly advertising that the '803 Subject Patent does not expire until July of 2016, which is 11 years past the actual expiration date.

The Office agreed.  As set forth under Reexamination Control No. 90/010,955, the Office granted the reexamination based on all six substantial new questions of patentability.  Although the paper granting the request cited revisions to the reexamination statute (35 U.S.C. § 301 et seq.) enacted by Congress in 2002 in response to the Federal Circuit's decision in the In re Portola Packaging case, which permit a reexamination request to be granted on art considered by the Office during ex parte prosecution provided that a substantial new question of patentability is raised, the paper also notes that all of the art cited by the TPR (except for the Ward reference) had not been considered by the examiner during prosecution of the '803 patent.  Moreover, the Office did not separately address the standing issue raised by the TPR, apparently agreeing that a reexamination is properly granted on an expired patent during the period where the patent right can be enforced.

The reexamination will be considered by Primary Examiners Brenda Brumback, Padmashri Ponnaluri, and SPE Deborah Jones.

Boehringer Ingelheim Int'l. v. Barr Laboratories, Inc. (Fed. Cir. 2010)

The Metes and Bounds of Obviousness-type Double Patenting

    By Kevin E. Noonan --

Obvious-type double patenting has become an important issue in patent litigation (Amgen Inc. v. F. Hoffman-La Roche Ltd., Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., Proctor & Gamble Co. v. Teva Pharmaceuticals USA, Inc.) and in the Patent Office (In re Fallaux).  While in many ways an anachronism with the change in U.S. patent term to 20 years from earliest priority date, the doctrine is still viable as a way to prevent third parties from having to defend related patents against different patent assignees, due to the provision that terminally-disclaimed patents be commonly assigned.

The Federal Circuit had occasion to opine on the doctrine once again in Boehringer Ingelheim Int'l. v. Barr Laboratories, Inc.  The patent at issue, U.S. Patent No. 4,866,812, was found invalid by the District Court under the doctrine of obviousness-type double patenting.  This patent claimed priority as a divisional application to U.S. Patent No. 4,843,086, which in turn claimed priority as a divisional application to U.S. Patent No. 4,731,374.  The subject matter was directed to tetrahydrobenzthiazoles, particularly pramipexole, marketed as Mirapex for the treatment of Parkinson's disease.

During prosecution of the grandparent '374 patent, the examiner imposed a restriction requirement listing 10 overlapping groups of 15 originally-filed claims.  These groups comprised product (Groups I-V), "utility" (VIII-X) or process (VI) claims.  The examiner permitted applicant to pick one group from the product and utility groups or the process group, and the applicant picked Group II and IX for prosecution that resulted in the '374 patent.  The first filed divisional application, that resulted in the '086 patent, encompassed claims from Groups VIII, IX and X, but "none of the claims [in this divisional] covered subject matter claimed [in the '374 patent]."  The second-filed divisional application encompassed claims from Groups I, III, IV and V "and [did] not cross the examiner's lines of demarcation with either the claims of the grandparent '947 application (the '374 patent) or those of the parent '197 application (the '086 patent)."  The applications "were therefore divided as between applications along the lines of demarcation drawn by the examiner in the restriction requirement."  The '812 patent received a patent term extension under 35 U.S.C. § 156 of 1,564 days (4 years and about 15 weeks), which extended the expiration date from December 12, 2006 to March 25, 2011.

Litigation ensued as the result of ANDAs being filed by Barr (the original filer) and Mylan, and during the ensuing bench trial Boehringer filed a terminal disclaimer of the '812 patent over the '086 patent (which had expired by that time).  In doing so, "Boehringer sought to disclaim the approximately six months of the '812 patent's original term that extended beyond the term of the '086 patent, and then to apply its 1,564-day extension to this shortened original term."  The District Court held that this terminal disclaimer was ineffective, since the '086 had expired, and also rejected Boehringer's claim that 35 U.S.C. § 121 "safe harbor" precluded application of the '086 patent against the '812 patent for obviousness-type double patenting.

Consequently, the District Court found the patent invalid for obviousness-type double patenting:  "On the merits, the district court concluded that the compound claims of the '812 patent were obvious in view of the method-of-use claims of the '086 patent."

The Federal Circuit reversed and remanded (and awarded costs to Boehringer) in an opinion by Judge Linn, joined by Judge Prost and joined in part by Judge Dyk, who also filed a dissent-in-part.  The Court opined on two issues raised by Boehringer:  Was the terminal disclaimer effective?  Do the safe-harbor provisions of 35 U.S.C. § 121 apply?

As to the first issue, the Court rejected Boehringer's characterization of the District Court's decision, saying that the basis was not that Boehringer attempted to disclaim term during litigation, but that the terminal disclaimer was filed after the expiration of the '086 patent.  The issue was retroactivity -- the opinion "agree[s] with Boehringer . . . that a patentee may file a disclaimer after issuance of the challenged patent or during litigation, even after a finding that the challenged patent is invalid for obviousness-type double patenting."  The problem with permitting such retroactive terminal disclaimers, according to the Court, is that:

[T]he later patent purports to remain in force even after the date on which the patentee no longer has any right to exclude others from practicing the claimed subject matter.  By permitting the later patent to remain in force beyond the date of the earlier patent's expiration, the patentee wrongly purports to inform the public that it is precluded from making, using, selling, offering for sale, or importing the claimed invention during a period after the expiration of the earlier patent.

This constitutes "an unjustified advantage" for the patentee, the Court opined, that cannot be undone by retroactive disclaimer "because it has already enjoyed rights that it seeks to disclaim" (emphasis in original).  For this reason, and that permitting such retroactive terminal disclaimer "would be inconsistent with '[t]he fundamental reason' for obviousness-type double patenting, namely, 'to prevent unjustified timewise extension of the right to exclude'," Boehringer argued that the patent term extension vitiated any such "unjustified advantage" because the '812 patent enjoyed a patent term extension that covered the term after the '086 patent expired.  The Court disagreed, distinguishing "the rights enjoyed by a patentee during the term of a patent" from "the rights enjoyed by a patentee during the term of an extension under § 156."  The Court says these are "not the same" because "the rights of a patentee during a term extension are limited in ways that do not normally apply to granted patents."  In this regard the Court cited the provisions of 35 U.S.C. § 156(d)(5)(F):

The rights derived from any patent the term of which is extended under this paragraph shall, during the period of interim extension --
    (i) in the case of a patent which claims a product, be limited to any use then under regulatory review;
    (ii) in the case of a patent which claims a method of using a product, be limited to any use claimed by the patent then under regulatory review; and
    (iii) in the case of a patent which claims a method of manufacturing a product, be limited to the method of manufacturing as used to make the product then under regulatory review.

(emphases added).  The point is that the claims extended under § 156 are only those claims identified by Boehringer as reading on "the use of pramipexole for the treatment of the 'signs and symptoms of idiopathic Parkinson's disease.'"  Since there were claims (5 and 6) that were not eligible for extension, the pubic would have been misinformed that Boehringer was entitled to exclude the practice of these claims after the '086 patent expired -- constituting an "unjustified advantage":

[A] competitor that performed a patent search on June 28, 2006 would have wrongly been led to believe that the '812 patent continued to cover the specific compounds claimed in claims 5 and 6, and that it precluded use of pramipexole for treatment of conditions beyond those approved by the FDA.  This is precisely the type of "unjustified timewise extension of the right to exclude" that the doctrine of obviousness-type double patenting is designed to prevent.

Turning to the safe-harbor issue, the Court noted that the safe-harbor is available when the claims of a patent are divided by the Patent Office, and "is not lost if an applicant does not file separate divisional applications for every invention or when independent and distinct inventions are prosecuted together" -- it is not limited to filing "only one divisional application":

[W]here the third sentence of § 121 refers to a patent issuing on an application filed as a result of a restriction requirement, it is referring to patents issuing from any number of multiple divisional applications and precludes any one from being used as a reference against any other.

The opinion states that the basis of the District Court's decision (that the safe harbor did not apply) was that the application that resulted in the '812 patent was not filed "as the result of" a restriction requirement in the '086 (parent) patent, but in the '374 (grandparent) patent.  The Federal Circuit characterizes the questions raised regarding the safe harbor as "(1) whether § 121 can ever apply to a divisional of a divisional of the application in which a restriction requirement was entered; and (2) whether the 'as a result of' requirement of § 121 applies to the '812 patent and is satisfied here," which the Court reviewed de novo.

With regard to the first question, the Court construed the safe-harbor provisions of 35 U.S.C. § 121:

A patent issuing on an application with respect to which a requirement for restriction under this section has been made, or on an application filed as a result of such a requirement, shall not be used as a reference either in the Patent and Trademark Office or in the courts against a divisional application or against the original application or any patent issued on either of them, . . .

as meaning that the safe harbor applies "when the PTO issues a restriction requirement that leads to more than two separate applications."  In addition, the Court noted that § 121 refers broadly to "a divisional application," and does not state that the divisional must be a direct divisional of the original application, and that Congress could have worded the statute to be limited to "a divisional application of the original application" if that was its intention.  The Court noted that in other situations the safe harbor has been applied to applications "sharing a common lineage (Geneva Pharms., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1378 (Fed. Cir. 2003)) or to continuation applications of divisional applications (Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1354 (Fed. Cir. 2009))."  Thus, the Court held that there is no basis to conclude that the safe harbor does not apply to "a divisional of a divisional" as here.

With regard to the "as a result of" provision of the statute, the Federal Circuit agreed with the District Court that this provision must be satisfied by both the '086 ('reference") and '812 ("challenged") patents, citing Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 1360 (Fed. Cir. 2008).  In this case, the Court agreed with Boehringer that "so long as consonance is met, it makes no difference in terms of compliance with the 'as a result of' requirement whether the applicant responds to the examiner's restriction requirement by filing one or more divisional applications from the original application, or instead files a single divisional application followed by successive additional divisionals," where "consonance" is defined as the situation where "the line of demarcation between the 'independent and distinct inventions' that prompted the restriction requirement be maintained."  Here, Boehringer filed two divisionals encompassing various combinations of claims comprising the "different inventions" set forth as being distinct in the restriction requirement assessed against the (grandparent) '374 application, but not overlapping any of these different classes between the different patents.  In the way Boehringer prosecuted these patents it "neither violated the examiner's restriction requirement nor risked loss of the safe harbor of § 121."  In making this determination, the Court rejected defendant's argument that the safe harbor only applies where an applicant "strictly follow[s] an examiner's election procedure and [does] not overlap claims to independent and distinct inventions in any single divisional application":

An overlap of claims to independent and distinct inventions within a given divisional application is neither contrary to the restriction requirement nor relevant to the requirements of the third sentence of § 121.  Rather, what consonance requires is that the claims prosecuted in two or more applications having common lineage in a divisional chain honor, as between applications, the lines of demarcation drawn by the examiner to what he or she considered independent and distinct inventions in the restriction requirement.

Because "[n]one of the inventions claimed as between the '374 original patent, the '086 division, and the '812 division of the division, crosses the examiner's lines of demarcation of inventions identified in the restriction requirement, . . . consonance is met and the '086 patent cannot be used as a reference against the '812 patent any more than if both patents had issued from direct divisions from the application in which the restriction requirement was made."

While this decision appears to be a straightforward (and sensible) application of the statute (as well as the policy concerns behind the statute and a common-sense approach to how patent prosecution is performed), Judge Dyk (at left) dissented to this aspect of the Court's opinion.  In Judge Dyk's opinion, the majority opinion "significant expands" the scope of the safe harbor.  His interpretation of the safe harbor is as a narrow exception to the general rule precluding unwarranted extension of patent term for closely-related inventions that are obvious variants.  His objection is not that the majority's determination that the safe harbor applies to "later" divisional applications filed as the result of a restriction requirement.  Rather, his dissent is based on consonance, which he defines as requiring a complete adherence with the contours of the restriction.  His reasoning is that Federal Circuit precedent was based on an applicant being "compelled to comply with a restriction requirement" and who "faithfully follows" the requirement.

In Judge Dyk's view, neither the '086 patent nor the '812 patent are consonant with the restriction requirement, because while the claims prosecuted in these patents did not overlap with the claims in the '374 patent or each other, they were not limited to one of the groups of claims set forth in the original restriction.  Rather, each of the '086 and '812 patents contained non-overlapping combinations of claims from several of these groups.  It is not enough that there is no overlap -- Judge Dyk believes that "preserving the lines of demarcation" requires applicants to file divisional applications for each of the groups set forth in the restriction requirement asserted in the grandparent '374 application.  He supports his position by citing several cases that he contends are inconsistent with the majority opinion.  These include Gerber Garment Tec., Inc. v. Lectra Sys. Inc., 916 F.2d 683, 688 (Fed. Cir. 1990); Symbol Techs., Inc. v. Opticon, Inc., 935 F.2d 1569, 1569 (Fed. Cir. 1991); Texas Instruments Inc. v. U.S. International Trade Commission, 988 F.2d 1165 (Fed. Cir. 1993); and Applied Materials, Inc. v. Advanced Semiconductor Materials America, Inc., 98 F.3d 1563 (Fed. Cir. 1996).

Judge Dyk also believes that a proper interpretation of the statute would preclude the '812 (daughter) patent from the benefit of the safe harbor from the '086 (parent) patent regardless of whether the '812 patent was entitled to the benefit of the safe harbor over the '374 (grandparent) application, because the '812 patent was not filed "as the result of" a restriction requirement imposed against the '086 patent.  This portion of his dissent seems to imply that divisional applications would need to be filed on the same date to maintain the safe harbor, and seems to contradict his apparent agreement with the majority that "a divisional of a divisional" was entitled to safe harbor protection.  His rationale is that "the child was not separated from the parent 'as a result of' the restriction requirement, but rather as the result of the applicant's voluntary choice" and "[s]ince the separation was not 'due to the administrative requirements imposed by the Patent and Trademark Office,' . . . the child application should not be afforded the protections of section 121 with respect to the parent application."  This situation would permit a patentee to file successive applications, none of which could be asserted against each other due to the safe harbor, resulting in "multiple unjustified extensions of the patent term."  He characterizes this as "abuse," saying that "[t]he majority's opinion is devoid of any justification for this untenable result.  It hardly requires argument to demonstrate that Congress could not have intended section 121 to operate in this perverse fashion."

Boehringer Ingelheim Int'l. v. Barr Laboratories, Inc. (Fed. Cir. 2010)
Panel:  Circuit Judges Linn, Dyk, and Prost
Opinion by Circuit Judge Linn; opinion dissenting-in-part by Circuit Judge Dyk

Obviousness-type Double Patenting after Amgen v. F. Hoffmann-La Roche

    By Kevin E. Noonan --

Although Amgen's erythropoietin franchise has weathered its most recent challenge by F. Hoffmann-La Roche's pegylated EPO analog, Mircera® (see Amgen Inc. v. F. Hoffman-La Roche Ltd. (Fed. Cir. 2009)), the victory was not absolute.  The status of three of the patents-in-suit -- U.S. Patent Nos. 5,547,933 (the '933 patent), 5,955,422 (the '422 patent, claim 1) and 5,756,349 (the '349 patent, claim 7) -- were put in jeopardy by the Federal Circuit's reversal of summary judgment and remand to the District Court on the question of whether these patents are invalid for obviousness-type double patenting.  If the District Court were to make a determination that they are invalid, Amgen's EPO patent estate will expire almost two years earlier than expected, with loss of at least a portion of the company's significant revenues from its flagship product.  The likelihood of this outcome will depend on the parties' reaction to the latest installment of Federal Circuit jurisprudence on obviousness-type double patenting following its decision last year in Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc.

The ultimate parent application, which matured into U.S. Patent No. 4,703,008, was subject to a restriction requirement identifying the following groups of claims:

I.  Claims 1–13, 16, 39–41, 47–54, and 59, drawn to polypeptide, classified in Class 260, subclass 112.
II.  Claims 14, 15, 17–36, 58, and 61–72, drawn to DNA, classified in Class 536, subclass 27.
III.  Claims 37–38, drawn to plasmid, classified in Class 435, subclass 317.
IV.  Claims 42–46, drawn to cells, classified in Class 435, subclass 240.
V.  Claims 55–57, drawn to pharmaceutical composition, classified in Class 435, subclass 177.
VI.  Claim 60, drawn to assay, classified in Class 435, subclass 6.

Pursuant to the restriction requirement, each of these claim groupings defined an independently-patentable invention, and as such would entitle Amgen to a separate patent unfettered by obviousness-type double patenting.  It is undisputed that Amgen prosecuted the claims of Group II in the '008 patent.  Thereafter, Amgen filed two applications claiming priority to the '008 patent, the '178 application and the '179 application; these applications are related to the patents-in-suit according to the following schematic diagram:

The Court characterized "in broad strokes" the claims of the three patents under consideration:

[T]he '933 patent claims recombinant EPO, a pharmaceutical composition comprising recombinant EPO, and methods of treating kidney dialysis patients by administering pharmaceutical compositions comprising recombinant EPO . . . .  The '422 patent claims a pharmaceutical composition comprising recombinant EPO . . . .  The '349 patent claims the process of producing recombinant EPO in vertebrate cells capable of producing EPO at a specific rate.

At first blush, the claims of the '933 patent would appear to correspond to Groups I and V from the '008 restriction requirement, and the claims of the '422 patent correspond to Group V.  Two other patents-in-suit -- U.S. Patent Nos. 5,441,868 (the '868 patent) and 5,618,698 (the '698 patent) -- recite claims for methods of making EPO.

Roche's position, unpersuasive at the District Court, was that the claims of the '933, '422, and '394 patents were invalid for obviousness-type double patenting over the claims of the '868 and '698 patents, and in turn the claims of the '868 and '698 patents were invalid for obviousness-type double patenting over the claims of the '008 patent.  This question depends on the meaning of 35 U.S.C. § 121, which sets forth a "safe harbor" provision protecting claims subject to a restriction requirement (and thus determined by the Patent Office to define separately-patentable inventions) from a determination of obviousness-type double patenting:

A patent issuing on an application with respect to which a requirement for restriction under this section has been made, or on an application filed as a result of such a requirement, shall not be used as a reference either in the Patent and Trademark Office or in the courts against a divisional application or against the original application or any patent issued on either of them, if the divisional application is filed before the issuance of the patent on the other application.

35 U.S.C. § 121, third sentence; see also Applied Materials, Inc. v. Advanced Semiconductor Materials Am., Inc., 98 F.3d 1563 (Fed. Cir. 1996), cited in the Court's opinion.  The District Court held that the '933, '422, and '349 patents were immunized from obviousness-type double patenting, since they had issued from applications in the chain back to the '178 and '179 applications, which were filed pursuant to a Patent Office-imposed restriction requirement.  However, these applications when filed were not designated as "divisional applications," the language of the statute, but rather as "continuation applications," and Roche argued that this difference precluded the '933, '422, and '349 patents from the § 121 safe harbor.

The Federal Circuit agreed, to the extent that summary judgment and JMOL granted by the District Court was improper.  In its opinion, by Judge Schall and joined by Judges Mayer and Clevenger, the CAFC granted no deference to the District Court's decision, first applying its own standard of review regarding summary judgment, next using the 1st Circuit's standard of review for JMOL, and last for the substantive question of obviousness-type double patenting, which it interpreted as being analogous to claim construction, as a "matter of what is claimed" and thus subject to the Federal Circuit's de novo review precedent.  Using these standards, the Federal Circuit held that the '933, '422, and '349 patents were not entitled to the § 121 safe harbor because the '178 and '179 applications were filed as continuation applications and not divisional applications.  In interpreting the statute so literally, the CAFC noted that, unlike the claims in the Pfizer case that arose from a continuation-in-part application, each of the '933, '422, and '349 patents may have satisfied the substantive requirements for divisional application status -- being limited to the subject matter disclosed in the prior parent application, reciting claims determined to define a patentably-distinct invention, and being filed during the pendency of the earlier-filed parent application.  Nonetheless, the Court held that "[t]his distinction . . . does not justify departing from a strict application of the plain language of §121, which affords its [safe harbor] benefits to 'divisional applications.'"  In making this decision, the CAFC distinguished both its Applied Materials and Symbol Technologies, Inc. v. Opticon, Inc., 935 F.2d 1569 (Fed. Cir. 1991) precedent, because in those cases the "continuation" application was filed ultimately from a properly-designated divisional application.

The CAFC reached a different conclusion with regard to the '868 and '698 patents, because the parties litigated the obviousness-type double patenting question on the merits before the District Court.  As characterized in the Federal Circuit's opinion, the claims of the '008 patent recite a recombinant cell that expresses human EPO, and the claims of the '868 and '698 patents recite methods of producing recombinant EPO using such cells, either in vitro or in vivo.  The District Court distinguished the method claims of the '868 and '698 patents and the recombinant cell (product or composition) claims of the '008 patent because:

none of the '008 claims require:  (1) that the recited host cell actually express any EPO polypeptide; (2) that the recited host cell actually express a glycosylated EPO polypeptide; (3) that the host cell be capable of producing an isolatable amount of a glycosylated EPO polypeptide; and (4) that any glycosylated EPO isolated from cells grown in culture have the stated in vivo function.

The District Court relied on expert testimony for the proposition that, even if in possession of the recombinant cell disclosed in the '008 patent, at the priority date claims to methods for making EPO were novel, useful, and non-obvious.  (The lower court also noted that the Patent Office had found these claims to be patentably-distinct.)  The Federal Circuit agreed with this distinction, that while the recombinant cells claimed in the '008 patent might be "capable of producing" recombinant EPO having in vivo biological function, the claim did not recite a limitation that such cells actually produce functional EPO.  This requirement is affirmatively found in the '868 and '698 patent claims, rendering them patentably distinct.

In making this determination, the Federal Circuit invoked a number of recent, post-KSR decisions on obviousness under 35 U.S.C. § 103, the standard used without using the '008 patent as prior art, including In re Kubin, In re O'Farrell (where the application, not the case, is recent), and Pharmastem Therapeutics, Inc. v. Viacell Inc.  The CAFC opined that the skilled artisan would not have reasonably expected to produce recombinant, glycosylated EPO having the properties -- biological activity, post-translational modifications and amount -- required by the claims of the '868 and '698 patents at the time of the invention.  In making this determination, the Federal Circuit rejected Roche's argument that the capacity for making recombinant EPO was inherent in the claimed cells (and did not address the issue of whether the claims of the expired '008 patent would have satisfied the utility or enablement requirements if the claimed cells did not inherently produce functional recombinant EPO).  The CAFC applied the Supreme Court's KSR warning against hindsight in refusing to consider the actuality that the cells claimed in the '008 patent produced biologically-active EPO in determining whether the skilled worker would have had an expectation that they would do so.

Finally, the Federal Circuit clarified the application of the principles it enunciated in Takeda Pharmaceutical Co. v.  Doll regarding the availability of later-disclosed (or discovered) methods to overcome obviousness-type double patenting invalidation of a process claim over an earlier-issued product claim.  In Takeda, the Federal Circuit held that art used by a patentee to support patentable distinctiveness of process claims filed after grant of product claims was limited to art-recognized processes known at the time the later (or "secondary" in the Takeda court's parlance) patent application was filed.  Roche argued that Amgen should not be permitted to introduce evidence relating to processes for producing recombinant EPO after the 1984 filing date of the '008 patent where Roche was precluded from asserting art available after the 1984 priority date.

Here, the Federal Circuit held that Roche's arguments "collide" with 35 U.S.C. § 120, wherein Amgen's later-filed applications are entitled to the benefit of priority to the '008 patent.  The CAFC found that interpreting its Takeda precedent as Roche advocated would "violate the plain language" of § 120, which entitles all of Amgen's patents-in-suit to the priority benefit of the '008 patent and accordingly prevents any of Amgen's patents-in-suit from being invalidated based on art available after the November 30, 1984 priority date of the '008 patent.  The Court's opinion acknowledged (and asserted that the Takeda court recognized) that this rule "could 'provide the patentee with the best of both worlds:  the applicant can use the filing date as a shield, enjoying the earlier priority date in order to avoid prior art, and rely on later-developed alternative processes as a sword to defeat double patenting challenges.'"  Nonetheless, the Federal Circuit characterized this seeming one-sidedness as being limited and hence not inequitable.  However, the CAFC noted that the '349 patent could not benefit from the application of the principles in the Takeda opinion, since it (unlike the '933 and '422 patents) recited claims to methods and not products.  Thus:

Takeda will permit Amgen, if it wishes to do so, to rely on alternative processes for making the products claimed in the '933 and '422 patents up to their filing dates to prove that the claims of those patents and the claims of the '868 and '698 patents are patentably distinct.  If Amgen pursues that course, Roche will be free to rely on subsequent developments in the art up to the filing dates of the '933 and '422 patents to prove that any alternative processes put forth by Amgen do not render the claims of the '933 and '422 patents and the claims of the '868 and '698 patents patentably distinct.

Unless the parties settle, on remand it can be expected that the District Court will be compelled to find the asserted claims of the '933, '422, and '349 patents invalid for obviousness-type double patenting, unless Amgen can establish patentable distinctiveness on the merits (i.e., outside the § 121 safe harbor).  Until such time (including any further appeals to the Federal Circuit or the Supreme Court), the significant holding in this decision is that whether a claim is entitled to the § 121 safe harbor depends, in the first instance, on whether the application reciting that claim is designated as a "divisional" and not a "continuation" application.  (Such claims must also satisfy the requirements for divisional applications.)  The Federal Circuit's opinion is stringent, harsh, and unyielding, and provides another "trap for the unwary" for which patent law is infamous.  It also raises the specter of malpractice liability in designating follow-on applications accurately, a practice tip that the patent bar ignores at its peril.

Amgen Inc. v. F. Hoffman-La Roche Ltd. (Fed. Cir. 2009)

Something for Everyone, but the Injunction Stands

 

    By Kevin E. Noonan --

Amgen has several times successfully defended its erythropoietin (EPO) franchise, the company's first commercial success and in many ways the crown jewel of its (or anyone's) biologics drug pipeline.  That string of successes continued today with a decision by the Federal Circuit against its latest challenger, Hoffman-La Roche.  But the decision also put several of the patents protecting Amgen's EPO at risk, making this a mixed victory at best for the biotechnology company.

The case involved the most recent challenge, Roche's Mircera® product, a pegylated derivative of human EPO.  Amgen sued Roche in a declaratory judgment action in Massachusetts asserting six patents:  U.S. Patent Nos. 5,547,933 (the '933 patent), 5,441,868 (the '868 patent), and 5,618,698 (the '698 patent), U.S. Patent Nos. 5,955,422 (the '422 patent, claim 1) and 5,756,349 (the '349 patent, claim 7) and U.S. Patent No. 5,621,080 (the '080 patent).  On October 23, 2007, a jury found that Mircera® infringed the '933 patent, the '868 patent and the '698 patent, and that these patents as well as the '422 patent and the '349 patent were not invalid.  (The jury reached neither infringement nor validity of the '080 patent).  Specifically, the jury found that Roche's Mircera® infringed claims 3, 7, and 8 of the '933 patent (claim 12 was found not to be literally infringed but infringed under the Doctrine of Equivalents); claims 1 and 2 of the '868 patent; and claims 6 through 9 of the '698 patent.  On October 1, 2008, Massachusetts District Court Judge William Young ruled (in Amgen's favor for each) on several post-trial motions, including:  1) affirming the jury's infringement decision by denying Roche's motion for judgment as a matter of law (JMOL); 2) reaffirming its pretrial decision to grant summary judgment regarding infringement of claim 1 of the '422 patent; 3) "explaining" its reasoning for ruling, also pretrial, that the claims of Amgen's patents-in-suit are not invalid for obviousness-type double patenting (despite the intervening Federal Circuit decision in Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc.); 4) denying Roche's motion for JMOL that claim 1 of the '422 patent and claims 3, 7, and 9 of the '933 patent are not invalid for indefiniteness for reciting the term "human erythropoietin"; and 5) granting Amgen a permanent injunction barring "Roche, its agents, servants, employees, counsel, and all persons and entities acting in concert therewith" from infringing the claims of the patents-in-suit for the remaining life of those patents.

The Federal Circuit's decision, written by Judge Schall and joined by Judges Mayer and Clevenger, affirmed most of the determinations by the District Court and the jury.  These will be discussed more extensively in future posts, but can be summarized simply here:  the panel vacated Judge Young's decision on whether the '933 (claims 3, 7, and 8), '349 (claim 7) and '422 (claim 1) patents are not invalid under obviousness-type double patenting and remanded this issue to the trial court; vacated the judgment that claim 7 of the '349 patent was not infringed and remanded for a new trial on that issue; affirmed the judgments that the asserted claims of the '868 patent (claims 1 and 2) and the '698 patent (claims 6-9) are not invalid and were infringed, and that claims 3, 7, and 8 of the '933 patent and claim 1 of the '422 patent were infringed; and finally that claims 9, 11, 12, and 14 of the '933 patent are not infringed by Mircera®.

Because of the number claims asserted and the status of these various claims under the CAFC's opinion, a scorecard seems in order:

The following claims of the '933 patent are infringed but may be invalidated by the trial court for obviousness-type double patenting:

3.  A non-naturally occurring glycoprotein product of the expression in a mammalian host cell of an exogenous DNA sequence comprising a DNA sequence encoding human erythropoietin said product possessing the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells.

7.  The glycoprotein product according to claim 3 . . . wherein the host cell is a non-human mammalian cell.

8.  The glycoprotein product according to claim 7 wherein the non-human mammalian cell is a CHO cell.

The following claim is infringed by Mircera® under the doctrine of equivalents, but its status with regard to the obviousness-type double patenting question is uncertain (it does not fall within the CAFC's remand):

12.  A pharmaceutical composition comprising an effective amount of a glycoprotein product effective for erythropoietin therapy according to claim 7 and a pharmaceutically acceptable diluent, adjuvant or carrier.  [Infringed under the doctrine of equivalents.]

The following claims of the '868 patent are both not invalid and are infringed:

1.  A process for the production of a glycosylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of:
    (a)  growing, under suitable nutrient conditions, mammalian host cells transformed or transfected with an isolated DNA sequence encoding human erythropoietin; and
    (b)  isolating said glycosylated erythropoietin polypeptide therefrom.

2.  The process according to claim 1 wherein said host cells are CHO cells.

The following claims of the '698 patent are not invalid and are infringed:

6.  A process for the production of a glycosylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of:
    a) growing, under suitable nutrient conditions, vertebrate cells comprising amplified DNA encoding the mature erythropoietin amino acid sequence of FIG. 6; and
    b) isolating said glycosylated erythropoietin polypeptide expressed by said cells.

7.  The process of claim 6 wherein said vertebrate cells further comprise amplified marker gene DNA.

8.  The process of claim 7 wherein said amplified marker gene DNA is Dihydrofolate reductase (DHFR) gene DNA.

9.  The process according to claims 2, 4 and 6 wherein said cells are mammalian cells.

Claim 1 of the '422 patent is infringed but may be invalidated for obviousness-type double patenting:

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

Finally, infringement of claim 7 of the '349 patent will be decided in a new trial, but may be invalid under obviousness-type double patenting:

7.  A process for producing erythropoietin comprising the step of culturing, under suitable nutrient conditions, vertebrate cells according to claim 1, 2, 3, 4, 5 or 6.

Wherein claims 1 through 6 of the '349 patent related to vertebrate cells encoding recombinant EPO:

1.  Vertebrate cells which can be propagated in vitro and which are capable upon growth in culture of producing erythropoietin in the medium of their growth in excess of 100 U of erythropoietin per 10⁶ cells in 48 hours as determined by radioimmunoassay, said cells comprising non-human DNA sequences which control transcription of DNA encoding human erythropoietin.

The significance of the Federal Circuit's decision, and the consequences of an adverse decision on remand for the '933, '349 and '422 patents are illustrated by the respective expiration dates of the five patents at issue in the litigation:

*term shortened by terminal disclaimer

Thus, invalidation of the '933, '349 and '422 patents would reduce Amgen's patent protection on its various EPO products (including Aranesp® and Epogen®) from May 2015 to August 2012 (more than 3 years), which would have a significant (negative) effect on the corporate bottom line.  Accordingly, Amgen can be expected to continue this litigation.

The CAFC's opinion did not disturb the permanent injunction imposed by Judge Young, preventing Roche from marketing Mircera® in the U.S. despite obtaining FDA approval in November, 2007, giving Roche more than sufficient incentive to continue as well.

The substance of the Federal Circuit's opinion, including its reasoning on the standards for obviousness type double patenting, will be the subject of later posts.     

Amgen Inc. v. F. Hoffman-La Roche Ltd. (Fed. Cir. 2009)
Panel: Circuit Judges Mayer, Clevenger, and Schall
Opinion by Circuit Judge Schall

In re Fallaux (Fed. Cir. 2009)

    By Donald Zuhn --

On May 6, the Federal Circuit affirmed a decision by the Board of Patent Appeals and Interferences affirming the final rejection of U.S. Application No. 10/618,526 for obviousness-type double patenting.  Appellants Frits Jacobus Fallaux, Robert Cornelis Hoeben, Alex Jan Van Der Eb, Abraham Bout, and Domenico Valerio are the named inventors on the '526 application (U.S. Patent Publication No. 2005/0260596), which is directed to an isolated adenovirus packaging cell comprising nucleic acid sequences encoding the adenovirus E1A and E1B gene products but lacking a nucleic acid sequence encoding adenovirus pIX.  Following the examiner's final rejection of the '526 application for obviousness-type double patenting in view U.S. Patent Nos. 6,340,595 and 6,413,776, Appellants appealed the rejection to the Board of Patent Appeals and Interferences, which affirmed the examiner's determination.

The '526 application, which was filed on July 11, 2003, claims the benefit of the following applications:

• U.S. Application No. 08/793,170, filed March 25, 1997, which issued as U.S. Patent No. 5,994,128 on November 30, 1999;
• U.S. Application No. 09/334,765, filed June 16, 1999, which issued as U.S. Patent No. 6,238,893 on May 29, 2001;
• U.S. Application No. 09/506,548, filed February 17, 2000, which issued as U.S. Patent No. 6,602,706 on August 5, 2003;
• U.S. Application No. 10/125,751, filed April 18, 2002, which issued as U.S. Patent No. 7,105,346 on September 12, 2006; and
• U.S. Application No. 10/219,414 (U.S. Patent Publication No. 2003/0104626), filed June 5, 2003.

The patents asserted in the double patenting rejection (i.e., the '595 and '776 patents) are related to the '526 application by way of a single common inventor:  Abraham Bout.  The '776 patent was filed on June 12, 1998 and issued on July 2, 2002, and the '595 patent was filed on July 21, 1999 and issued on January 22, 2002.  In rejecting the '526 application, the examiner applied the one-way test for obviousness-type double patenting.  During prosecution, Appellants argued that the two-way test for obviousness should have been applied.  The examiner, however, determined that Appellants had not provided evidence that the issuance of the '595 and '776 patents before the issuance of the '526 claims was not due to administrative delay on the part of the U.S. Patent and Trademark Office, and further, that the '526 claims could have been introduced (and then allowed) in any of the '526 application's four priority applications that had already issued.

On appeal to the Board, Appellants again argued for the two-way test, but the Board affirmed, determining that the '526 claims could have been filed during prosecution of the '170 application, which issued as the '128 patent before either of the patents asserted in the double patenting rejection.  Thus, the Board concluded that it was Appellants, and not the Patent Office, that dictated the rate of prosecution of the '526 claims.

In affirming the Board's decision, the Federal Circuit first noted that the two-way test for obviousness-type double patenting is a narrow exception to the general rule of the one-way test.  Quoting In re Berg, 140 F.3d 1428, 1432 (Fed. Cir. 1998), the Court also noted that the two-way test:

arose out of the concern "to prevent rejections for obviousness-type double patenting when the applicants filed first for a basic invention and later for an improvement, but, through no fault of the applicants, the PTO decided the applications in reverse order of filing, rejecting the basic application although it would have been allowed if the applications had been decided in the order of their filing."

As a result, "[t]he two-way test is only appropriate in the unusual circumstance where, inter alia, the United States Patent and Trademark Office (PTO) is 'solely responsible for the delay in causing the second-filed application to issue prior to the first'" (citing Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 968 n.7 (Fed. Cir. 2001) (quoting Berg, 140 F.3d at 1437)).

In the instant appeal, the Federal Circuit concluded that:

[Appellants] did not show -- nor is there any evidence to suggest -- that the PTO shared any responsibility for the delay.  There is no dispute that the specification of the '170 application would have supported the ['526] claims.  Nonetheless, [Appellants] elected to prosecute other applications and delay filing the ['526] application until six years after the '170 application was filed.

Thus, the Court found that there was substantial evidence to uphold the Board's finding that the entire delay was attributable to Appellants.

In re Fallaux (Fed. Cir. 2009)
Panel: Circuit Judges Schall, Archer, and Moore
Opinion by Circuit Judge Moore

Procter & Gamble Co. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2009)

    By Donald Zuhn --

The Federal Circuit today affirmed a determination by the District Court for the District of Delaware that U.S. Patent No. 5,583,122 was not invalid as obvious nor invalid for obviousness-type double patenting.  The '122 patent, which is owned by Plaintiff-Appellee Procter & Gamble Co. (P&G), relates to the compound risedronate, which is the active ingredient in P&G’s osteoporosis drug Actonel®.  Risedronate is a member of a class of compounds known as bisphosphonates, which are active in inhibiting bone resorption.

After Defendant-Appellant Teva Pharmaceuticals USA, Inc. notified P&G of its intent to market a generic version of risedronate, P&G filed suit against Teva for patent infringement.  In response, Teva argued that the '122 patent was invalid as obvious in view of P&G's expired U.S. Patent No. 4,761,406, and alternatively, that the '122 patent was invalid for obviousness-type double patenting.  The '406 patent relates to an intermittent dosing method for treating osteoporosis, which allows bisphosphonates to be used in the treatment of osteoporosis without the unwanted side effect of anti-mineralization.  The '406 patent specifies 36 bisphosphonates for use in the claimed method, eight of which are preferred compounds, and one of which is the compound 2-pyr EHDP.  Teva argued that the disclosure of 2-pyr EHDP in the '406 patent rendered the claims of the '122 patent obvious (risedronate and 2-pyr EHDP are positional isomers, with risedronate having a hydroxy-ethane-diphosphonate group connected to the #3 carbon of its pyridine ring, and 2-pyr EHDP having the hydroxy-ethane-diphosphonate group connected to the #2 carbon).

After a bench trial, the District Court determined that the '406 patent would not have led a person of ordinary skill in the art to identify 2-pyr EHDP as a lead compound, the skilled artisan would not have been motivated to modify 2-pyr EHDP to generate risedronate (at left), and unexpected results of risedronate's potency and toxicity rebutted Teva's assertion of obviousness.  As a result, the District Court found the claims of the '122 patent to be non-obvious.  The District Court also determined that the '122 patent was not invalid for obviousness-type double patenting.

The Federal Circuit began its analysis by first noting that the evidence of record did not establish that it would have been obvious to modify 2-pyr EHDP to create risedronate, and therefore, that the Court did not need to reach the question of whether the '406 patent would have led a skilled artisan to identify 2-pyr EHDP as a lead compound.  The panel noted that Dr. Herbert Fleisch, a preeminent authority on bisphosphonates during the relevant time period, wrote in 1984 that "every compound, while remaining a bisphosphonate, exhibits its own physical-chemical, biological and therapeutic characteristics, so that each bisphosphonate has to be considered on its own," and thus, "[t]o infer from one compound the effects in another is dangerous and can be misleading."  The Federal Circuit therefore determined that the District Court had not erred in finding that a person of ordinary skill would not have been motivated to synthesize and test risedronate, and would not have had a reasonable expectation of success in synthesizing and testing risedronate.  Moreover, the panel determined that there was no credible evidence that the structural modification of 2-pyr EHDP would have been routine.  Thus, the Federal Circuit concluded that the District Court did not clearly err in finding that Teva had failed to establish a prima facie case of obviousness.

Notwithstanding Teva's failure to establish a prima facie case of obviousness, the Federal Circuit also determined that P&G had introduced sufficient evidence of unexpected results.  Among these unexpected results were risedronate's potency at low doses and lack of toxicity at higher doses than 2-pyr EHDP could be safely used.  The Federal Circuit also determined that the District Court had not erred in considering evidence that risedronate had satisfied a long-felt but unmet need.

With respect to the issue of obviousness-type double patenting, the Federal Circuit determined that the District Court had correctly found the '406 patent to be prior art to the '122 patent, since P&G's evidence that risedronate had been synthesized in May of 1985 was uncorroborated (i.e., laboratory notebook pages describing the synthesis were unwitnessed).  The panel noted that "the obviousness analysis applies to double patenting," with the exception that non-statutory double patenting compares claims in an earlier patent to claims in a later patent or application, double patenting does not require inquiry into a motivation to modify the prior art, and double patenting does not require inquiry into objective criteria suggesting non-obviousness.  Thus, because risedronate was deemed to be non-obvious in view of the '406 patent, the Federal Circuit concluded that the '122 patent was also not invalid for obviousness-type double patenting in view of the '406 patent.  In addition, the panel determined that Teva failed to present clear and convincing evidence of overlap between the claims of the '122 patent (directed to compounds, including risedronate) and the '406 patent (directed to an intermittent dosing regimen, with no compound claims).

Procter & Gamble Co. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2009)
Panel: Circuit Judges Mayer and Dyk, and District Judge Huff
Opinion by District Judge Huff