By Kevin E. Noonan --
On October 23, 2007, Amgen procured a jury verdict that Hoffman-LaRoche's Mircera® drug product infringed several Amgen patents. That verdict found Mircera® infringed claims 3, 7, and 8 of Amgen's U.S. Patent No. 5,547,933 (claim 12 was found not to be literally infringed but infringed under the Doctrine of Equivalents); claims 1 and 2 of U.S. Patent No. 5,441,868; and claims 6 through 9 of U.S. Patent No. 5,618,698. Amgen's infringed claims were directed to recombinant methods and recombinant EPO protein, and Roche's Mircera® drug product is a form of recombinant EPO that has been covalently linked to polyethylene glycol.
Since then, Amgen has moved in the District Court for a permanent injunction against Roche to prevent Mircera® from being sold in the U.S. until the last of Amgen's infringed patents has expired; Roche has opposed. Such an injunction is necessary to prevent Mircera® from going on the market, since the U.S. Food and Drug Administration last November granted approval for Roche to market Mircera® in the U.S. The Court granted a preliminary injunction barring Mircera® sales on February 28, 2008, but Judge Young left open the possibility that he would modify his order under certain circumstances. Although the District Court found that Amgen had fulfilled three of the four factors mandated for consideration by the Supreme Court in eBay Inc. v. MercExchange, L.L.C. (i.e., Amgen's asserted claims were infringed and not invalid; Amgen's injury would not be adequately compensated merely with money damages; and the balance of the hardships weighed in favor of granting the injunction), the District Court did not decide in Amgen's favor as to the fourth prong, the public interest, particularly in view of Roche's representations of the advantages of its Mircera® product over Amgen's version of EPO (including inter alia less frequent dosing; see "Long-Acting Drug for Dialysis Anemia Equivalent to Weekly Agent").
The District Court also set forth five conditions that, if fulfilled by Roche, might persuade the Court to lift the injunction. First, Roche would pay Amgen a royalty of 22.5% (Amgen having already rejected an offer for a 20% royalty from Roche). Second, Roche could be introduced to the Medicare patient population at a cost no more than the average sales price of Amgen's EPO products (sold under the names Epogen® and Aranesp®) (a requirement that would prevent Roche from passing its royalty obligations onto patients, but would not prevent Roche from selling Mircera® at a bargain price relative to Epogen®). Third, Roche would have to provide clinical evidence to permit the Court to determine a "dosage conversion factor" between Mircera® and Epogen®. Fourth, Roche would pay for an independent agency to monitor sales and determine royalty payments owed to Amgen. Finally, Roche would agree to supply Mircera® to any patient needing it, at or below the authorized price (presumably, this is a provision that would prevent Roche from abandoning the Medicare market once it has entered it).
Roche agreed to these conditions in its court filing on March 20th (see "Roche Agrees to Court's Conditions for Modifying Preliminary Injunction"). Despite Roche's acquiescence, and perhaps in the face of Amgen's vigorously-pressed argument that lifting the injunction under these circumstances was, in effect, a compulsory license (see "Court Still Cannot Decide on Amgen's Permanent Injunction"), the Court on Monday issued an order that the parties had fifteen days to submit an agreed list of potential special masters to consider the question of how dosing and pricing of Amgen's and Roche's products should be compared. While not being related directly to the public interest question, the special master's report should further inform the Court of whether it will be practicable for the Court to conform its injunction (or compulsory license) to the economic realities of the marketplace for ESAs. The special master, once appointed, will have sixty days to make the inquiries necessary to provide his or her findings to the Court. Presumably, the Court will then make its ruling.
The Federal Circuit's decision in Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc. (issued March 7, 2008; see Patent Docs report) has raised another potentially-dispositive issue, not on the injunction but on the validity of Amgen's patents-in-suit, and Amgen has responded proactively. On March 14th, Amgen filed a bench memorandum with the District Court explaining its understanding of the Pfizer decision, and arguing that this decision has no bearing on the Court's decisions that Amgen's patents-in-suit are not invalid under the judicially-created obviousness-type double patenting doctrine. In Pfizer, a three-judge panel of the Federal Circuit invalidated one of Pfizer's patents as being invalid for obviousness-type double patenting. In that case, the Federal Circuit opined that the "safe harbor" for divisional applications of 35 U.S.C. § 121 (i.e., that divisional applications are not subject to obviousness-type double patenting rejections) did not extend to continuation-in-part applications. The CAFC based its decision in part on the plain language of the statute (which is limited to divisional applications), and on the grounds that, unlike a divisional application, a continuation-in-part application is not identical in disclosure to its parent. Thus, the Federal Circuit held that Congress did not evince an intention to permit an application having additional disclosure to benefit from the § 121 safe harbor.
Although the Federal Circuit's rationale was clearly based on this distinction between divisional and CIP applications, the Court's language was less than crystal clear on the status of continuation applications. Such applications share with divisionals the limitation that their disclosure is coextensive with the disclosure of the parent application. Unlike a divisional application (whose filing is compelled by a determination by the U.S. Patent and Trademark Office that the application discloses more than one invention), however, continuation applications are filed at an applicant's volition, to pursue claims that the applicant has not been able to persuade the Patent Office are patentable within the examination time limit (i.e., before a final rejection has been issued).
Amgen argues in its bench memorandum that its patents do not fall within the ambit of the Pfizer Court's invalidating decision. First, Amgen argues that its applications are continuations, not CIPs, and that the Pfizer decision was limited to precluding the § 121 safe harbor from encompassing CIP applications. Second, Amgen argues that its applications, while termed "continuations" satisfy the requirements of divisional applications: "the '178 and '179 applications were 'later application[s]' (than the '298 application), 'carved out of a pending application' (the '298 application), containing claims to 'a distinct and independent invention' (restriction Groups I and V, not Group II), and 'disclosing and claiming only subject matter disclosed in the earlier or parent application' (as 37 C.F.R. § 1.60 applications, the disclosure and claim language was identical to that in the parent '298 application)" M.P.E.P. § 201.06. (Amgen further argues that Pfizer cannot be taken to mean that how an application is designated, as a "continuation" or a "divisional," can by itself be enough to determine whether or not an application was entitled to § 121 safe harbor. Indeed, Amgen notes that the District Court expressly rejected Roche's argument that the parent applications to the '933 and '349 patents were invalid for obviousness-type double patenting "because Amgen's patent counsel failed to check the 'divisional application' box on the application cover forms.") Amgen provides the following chart to show the relationship between its applications, as compared to the relationships between the Pfizer applications:
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Amgen also argues that the Pfizer decision is inconsistent with Federal Circuit precedent, with regard to continuation applications, in Applied Materials, Inc. v. Advanced Semiconductor Materials Am., Inc., 98 F.3d 1563 (1996) and Symbol Technologies, Inc. v. Opticon, Inc., 935 F.2d 1569 (Fed. Cir. 1991). In these cases, Amgen argues, the § 121 safe harbor was applied to continuations that fulfilled the statutory requirements, providing the following diagrams of the relationships between the patents in those decisions:
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Amgen further argues that insofar as the Pfizer decision is inconsistent with either the Applied Materials or Symbol Technologies decisions, the Court is bound by the earlier decisions, citing Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 765 (Fed. Cir. 1988) ("This court has adopted the rule that prior decisions of a panel of the court are binding precedent on subsequent panels unless and until overturned in banc. Where there is direct conflict, the precedential decision is the first.").
Roche has not yet been heard on this issue. Interestingly, the lawyer representing Pfizer before the Federal Circuit, Leora Ben-Ami of Kaye Scholer LLP, is also the lead trial attorney representing Hoffman-LaRoche against Amgen.
For now, the answer to the title question is "probably not," but it is clear that Amgen will once again be forced to vigorously protect its EPO franchise.
Patent Docs thanks Calvert (Cal) Crary of Litigationnotes.com for alerting us to this issue.
For additional information regarding this topic, please see:
• "Court Still Cannot Decide on Amgen's Permanent Injunction," March 26, 2008
• "Amgen Inc. v. International Trade Commission (Fed. Cir. 2008)," March 20, 2008
• "Roche Agrees to Court's Conditions for Modifying Preliminary Injunction," March 20, 2008
• "Roche's Mircera® Remains Off the Market (For Now)," March 2, 2008
• "Amgen Survives Another EPO Challenge," October 28, 2007
Last Friday, Herbert Wamsley, the Executive Director of the Intellectual Property Owners Association (IPO), sent out an "Urgent IPO Legislative Alert" to IPO members, urging them to contact their Senators to oppose the Applicant Quality Submission (AQS) provision of the Senate patent reform bill (S. 1145). According to the e-mail alert, the Senate bill "may be considered for a vote within the next few weeks," and therefore, the "time to speak out against this proposal" was growing short.
While the IPO has voiced its opposition to certain provisions of the Senate bill before, and in fact, sent a letter opposing the provision to the Chairman of the Judiciary Committee last November (as noted in its e-mail alert and discussed in a previous 
Claim drafting is somewhat of an art that takes time and practice to learn. Practitioners typically develop various styles and formats over time. One of the best ways to assist in developing good claim drafting skills is to be mindful of the types of claims that are being issued by the U.S. Patent and Trademark Office that relate to particular fields of interest. For example, a claim drafter may use issued claims as models and templates to facilitate prosecution to avoid many 35 U.S.C. § 112 rejections that might otherwise arise. In addition, the drafter may be able to maximize claim scope by covering more aspects of an invention in dependent claims by modeling the claim sets others have successfully prosecuted to issuance. Practitioners are likely to develop their own style of claim drafting by monitoring and studying issued claims, as different claim language can be used to cover similar subject matter.
About
Court Report: Each week we will report briefly on recently filed
biotech and pharma cases, and a few interesting cases will be selected
for periodic monitoring.
March 31-April 1, 2008 - 
A full program for the Prior Art & Obviousness 2008 conference can be found 
Obtaining an injunction against an adjudged infringer has become much more difficult for patentees since the Supreme Court's decision in 
Nowhere, perhaps, is this difficulty illustrated more starkly than in the U.S. District Court for the District of Massachusetts (Judge William G. Young, presiding) concerning Amgen's motion for permanent injunction to prevent Roche from launching its Mircera® drug product. Amgen procured a jury judgment on October 23, 2007 that Mircera® infringed several Amgen patents. That verdict found Roche's Mircera® infringed claims 3, 7, and 8 of Amgen's U.S. Patent No. 
The District Court entered a preliminary injunction on February 28, 2008 foreclosing Roche from launching Mircera®; Roche had been 
Roche agreed to these conditions in its court filing last week (see "
It seems that these arguments did nothing to help the District Court come to a decision on whether it should modify its preliminary injunction. Instead, in an order entered today, the Court decided it needed to appoint a special master to consider the question of how dosing and pricing of Amgen's and Roche's products should be compared. This question is not related to the public interest directly, but should further inform the Court of whether it will be practicable for the Court to conform its injunction (or compulsory license) to the economic realities of the marketplace for ESAs. The Court gave the parties fifteen days to submit a list of "agreed" candidates to be appointed special master, and then the Court intends to give that candidate another sixty days to make the inquiries necessary to provide his or her findings to the Court. Presumably, the Court will then make its ruling.
It is difficult to understand the Supreme Court's eBay decision as intending (or anticipating) that a District Court would undertake setting out the type of modified "injunction" that Judge Williams is contemplating here, as being in the nature of a compulsory license. Importantly, of course, all the District Court's ruling will do is to refuse to prohibit Roche from marketing Mircera® provided that it complies with the pricing and other affirmative provisions of the Court's order. This is not a license, however, but simply the limits to which the Court is willing to enjoin Roche (i.e., it will not enjoin Roche under the terms of the injunction). But whatever Judge Williams does, Amgen's intention to press its damages and willful infringement claims are certain to place before the Federal Circuit (and perhaps ultimately the Supreme Court) the issue of how far a District Court may go in fashioning a remedy having the properties of a compulsory license. There is some poetic justice in the possibility that the Supreme Court may have to address, and right soon, the consequences of eBay and its philosophical inclination to be parsimonious with regard to patent rights. In view of the Supreme Court's recent track record, however, any such thirst for justice should be strongly tempered with trepidation about how much further the Supreme Court may be willing to restrict a patentee's right to exclude.
An e-Alert sent out on March 26, 2008 by the U.S. Patent and Trademark Office contained information regarding enhancements in Private PAIR 7.2, e-Office action and reminder postcards, and a quick way to link to recent e-filing acknowledgment receipts.
the certification page once a user logs in. When the "My Workplace" radial button is selected, you can view the acknowledgment receipts for your forty most recent filings. The listings include all application information (serial number, first named inventor, title, and docket number) as well as a link that opens the associated confirmation receipt as a PDF file.
In an Op-Ed piece appearing in last Saturday's edition of The Boston Globe, Alnylam Pharmaceuticals Inc. Chief Executive Officer 
Alluding to 
Biologic drugs are generally peptides and proteins, particularly monoclonal antibodies, but can also include vaccines. Currently-available biologic drugs include Humulin® (recombinant human insulin); Epogen® (recombinant human erythropoietin); Herceptin® (anti-Her2/neu monoclonal antibody); beta-interferon (for treating multiple sclerosis); Cerezyme® (for treating Gaucher's disease); Enbrel® (soluble TNF receptor); and Gleevac® (anticancer monoclonal antibody). The average costs of biologic drug treatment is about $72,000/year (compared to about $1,000 for conventional "small molecule" pharmaceuticals). Part of the difference in costs reflects the difficulties in bringing these drugs to market. And some of these differences in costs has to do with the increase complexity of biologic drugs and the methods by which they are produced.
Biologic drugs are regulated under the Public Health Service Act (rather than the Food, Drug and Cosmetic Act), because the first biologic drugs to be regulated were vaccines in the early Twentieth century. Although administered by the Food and Drug Administration (specifically, the Center for Biologics Evaluation and Research), approval for biologic drugs is sought by submitting a Biologics Licensing Application (BLAs), rather than a New Drug Application. Legislation directed towards facilitating approval of "follow-on" biologic drugs seek to amend the section of the PHSA concerning BLAs. There have been three bills introduced in Congress relating to follow-on biologics: H.R. 1038, the "Access to Life-saving Medicine Act" (introduced by Congressman Waxman); H.R. 1956, the "Patient Protection and Innovative Biologics Medicines Act" (introduced by Congressman Inslee); and H.R. 5629, the "Pathway for Biosimilars Act" (introduced by Congresswoman Eshoo). None of these bills have been acted upon, in the face of intensive lobbying from both sides of the "follow-on" debate.
The bills differ in the requirements for showing biosimilarity. The Waxman bill provides a number of different types of evidence that can be required to establish such similarity, but also contains provisions that would permit a wider range of differences between the follow-on and the innovator drug (including amino acid sequence variants). The Inslee bill entrusts the Secretary of Health and Human Services with substantially more discretion as to the requirements for biosimilarity on a case-by-case basis, coupled with a requirement that the Secretary promulgate "guidances" for its criteria that are subject to public comment. The Eshoo bill is some ways is a compromise, having a regime of analytical testing, animal experiments, and human clinical trials for gaining approval, but giving the Secretary the discretion to waive the requirements on a case-by-case basis (limited, as with the Inslee bill, by published guidances that have been subjected to public comment).
These are not merely theoretical problems. In one instance, changing the cell line used to produce the experimental biologic CNT085 resulted in changed pharmacokinetics of the drug. An innovator's new production facility (expressly designed to minimize differences in the production protocol) produced drug product that had 40% lower drug levels in patients' blood. Changing formulation to reduce detergent levels led to an increase in microclumping that affected bioavailability. And in perhaps the most significant event, administration of a recombinant blood cell growth factor produced an immunological response that not only inhibited bioactivity of the recombinant but also the endogenous species of the factor.
Patents and the requirements for patentability must be considered in this climate. There are no more stringent requirements for patentability for biologic drugs (more properly, pharmaceutical composition claims comprising a biologic compound) than for conventional drugs, nor does U.S. patent law require disclosure of clinical trials or safety and efficacy data for pharmaceutical composition claims. However, the extent of disclosure required for a claim depends on claim scope, since 35 U.S.C. § 112, first paragraph, has been interpreted to require disclosure of how to make and use an invention throughout the full scope of the claim. It is not unreasonable to expect that pharmaceutical composition claims will be required to be supported by disclosure that would enable one of ordinary skill in the art to produce a useful biologic drug (see In re Wands, 858 F.2d 731 (Fed. Cir. 1988)). Indeed, the trial court in Amgen Inc. v. Hoechst Marion Roussel, Inc. disqualified prior art (that also must satisfy an enablement requirement) relating to purification of human urinary erythropoietin based on testimony that the method did not yield uEPO in sufficient quantities or purity to have a biological effect. And the Federal Circuit has shown a penchant recently to give significantly closer scrutiny to the correspondence between claim scope and disclosure. Examples include:
Redpoint Bio Corp. 
About
Court Report: Each week we will report briefly on recently filed
biotech and pharma cases, and a few interesting cases will be selected
for periodic monitoring.
March 30-April 1, 2008 - 
The Federal Circuit in a decision handed down on Wednesday affirmed the International Trade Commission's grant of summary judgment against Amgen in its attempts to block importation of Roche's Mircera® peglylated erythropoietin product. In so doing, the Federal Circuit continued its parsing of the expansive scope of the "safe harbor" provisions of 35 U.S.C. § 271(e)(1) established by the Supreme Court in 
Amgen's complaint was based on alleged infringement of the following patents: U.S. Patent Nos. 
The ITC agreed with Roche, that the imported Mircera® was exempt from infringement under the safe harbor provisions of § 271(e)(1). The ITC made this determination on summary judgment, despite allegations by Amgen that: (1) the importation at issue occurred after Roche had submitted its Biologic License Application to the U.S. Food and Drug Administration; (2) the imported Mircera® drug product was used for marketing surveys, infringement analysis, and activities related to Amgen's patent infringement litigation with Roche and not for activities "reasonably related to the development and submission of information" to the FDA; and (3) these activities were not protected under the safe harbor provisions of § 271(e)(1).
The Federal Circuit (in an opinion by Judge Newman, joined by Judge Lourie and in part by Judge Linn) affirmed the ITC's interpretation of the interactions of 19 U.S.C. § 1337, 35 U.S.C. § 271(e)(1) and § 271 (g), but reversed and remanded on the jurisdictional issue. The CAFC rejected Amgen's argument that the ITC, pursuant to § 1337, had the authority to bar importation of any product made by the infringing use of a patented process, regardless of any exemption from infringement that may apply to the product. Amgen's argument was that the exemption vel non of Roche's Mircera® drug product under § 271(e)(1) was irrelevant, since the act of importing a product made using an infringing method was sufficient. The Federal Circuit refused to adopt this rationale, since to do so would have permitted Amgen to use the ITC to prevent Roche from importing Mircera® solely for purposes falling within the safe harbor provisions of § 271(e)(1). This outcome would contravene the Supreme Court's determination that § 271(e)(1) should be read broadly to prevent a patentee from any action that would prevent or inhibit another from using a patented invention for activities (even otherwise infringing ones) that are "reasonably related" to producing information for submission in support of obtaining regulatory approval (e.g., for a generic version of a patented drug).
On Tuesday, Roche filed its brief in support of U.S. District Court
for the District of Massachusetts (Judge William G. Young, presiding)
modifying its preliminary injunction granted on February 28th, barring
Roche from launching its FDA-approved Mircera® drug product. The
Court's preliminary injunction was entered pursuant to a jury judgment
on October 23, 2007 that Mircera® infringed several Amgen patents. That verdict found Roche's Mircera® infringed claims 3, 7, and 8 of
Amgen's U.S. Patent No. 
Absent this jury verdict, Roche would be in a position
to launch Mircera®, because the U.S. Food and Drug Administration
For its part, Amgen countered by casting the proposed
modification as a compulsory license in favor of Roche. Amgen argued
that it would be inequitable to "reward" Roche, an adjudged infringer,
with such a license. Moreover, Amgen argued that compulsory licensing
was not within the province or the power of the Court to impose, but
that it could either grant or deny the injunction and nothing more. Congress, Amgen argued, had several times considered introducing
compulsory licensing provisions into the patent statute but had not,
and Amgen argued that the Court did not have the power to impose such a
license in the face of Congressional disapproval, citing in support of
this argument the Federal Circuit's decision in 
OPKO Health, Inc. 
