Momenta Pharmaceuticals: The Hatch-Waxman “Safe Harbor” Widens to Include Post-FDA Approval Activity*

By Eric Guttag
August 7, 2012

A key provision of the Hatch-Waxman Act resides in 35 U.S.C. § 271(e)(1) which provides immunity from a patent infringement suit where the testing of the patented invention is for the purpose of securing regulatory approval from the FDA.  Or to use the specific language of 35 U.S.C. § 271(e)(1), there is no patent infringement if the use of the patented invention is “solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs.”

This Hatch-Waxman provision, commonly known as the “safe harbor,” has been construed twice by the Supreme Court, and in an expansive manner to immunize alleged infringing activity.  First, in the 1990 case of Eli Lilly & Co. v. Medtronic, Inc., the Supreme Court ruled that this “safe harbor” applied to medical devices, not just drugs as was originally believed (including by the respective House and Senate floor managers for the Hatch-Waxman Act).  In fact, the basis for the holding in the Medtronic case makes this “safe harbor” essentially applicable to the testing of any patented invention that is for the purpose of securing regulatory approval from the FDA (e.g., food additives, cosmetics, etc.).  See Guttag, “The Ever Expanding ‘Safe Harbor’ of Hatch-Waxman:  The Merck v. Integra Lifesciences Case,” Cincinnati Bar Association Report, page 16 (August 2005).

Second, in 2005, Supreme Court ruled in Merck KgaA v. Integra Lifesciences I, Ltd. that this “safe harbor” applied to pre-clinical research, not just clinical research.  What I found startling in reviewing the Supreme Court’s opinion was just how far the Merck case might have expanded this “safe harbor.”  There are statements in Merck that suggest such pre-clinical research would be protected by the “safe harbor” even if:  (1) that research was for the purpose of developing new drugs or new uses of existing drugs (not simply safety testing); or (2) the results of such research were later not submitted to the FDA to secure regulatory approval, i.e., the immunity would not be lost or stripped because of later non-use of the research results.  In other words, as long as the pre-clinical research was “reasonably related” to potentially securing regulatory approval from the FDA, the “safe harbor” of Hatch-Waxman would apply.

While the Supreme Court may have expanded the reach of the Hatch-Waxman “safe harbor,” the Medtronic and Merck cases only involved pre-marketing FDA approval activity.  But the recent split Federal Circuit panel decision in Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc. has now (alarmingly in my view) further widened the applicability of this “safe harbor” beyond such pre-marketing FDA approval activity.  In Momenta Pharmaceuticals, Judge Moore (writing for the majority joined by Judge Dyk) ruled that this “safe harbor” could also apply to post-FDA approval activity, even if that activity was at least arguably commercial in nature.

[Bio-Pharma]

Not surprisingly, Chief Judge Rader vociferously dissented, arguing (in my opinion correctly) that Judge Moore’s opinion reads 35 U.S.C. § 271(e)(1) in a manner contrary to the statutory language, and more importantly, completely inconsistent with the legislative intent for when this “safe harbor” provision was to apply.  Even more troubling, Judge Moore’s majority opinion in Momenta Pharmaceuticals cannot be easily squared with the earlier Federal Circuit case of Classen Immunotherapies, Inc v. Biogen IDEC (where Judge Moore dissented from the Federal Circuit’s majority opinion written by Judge Newman and joined by Chief Judge Rader).  For reasons I’ll discuss below, Classen strongly suggests (if it does not specifically hold) that the Hatch-Waxman “safe harbor” does not apply to such post-FDA approval activity.  In fact, for other reasons I’ll discuss below, it is questionable whether Momenta’s patented analytical method is even qualifies as a “patented invention” that is subject to this “safe harbor” provision.

The Momenta Pharmaceuticals centers on the drug enoxaparin (a low molecular weight version of the anti-coagulant, heparin) for preventing blood clots.  Enoxaparin is made by breaking the heparin polysaccharide into smaller oligosaccharides.  Because of how it is made (and because of the diversity of starting material), the resulting enoxaparin may comprise a range of molecules of differing sizes.  This diversity in molecular sizes makes it much more difficult to establish generic versions of enoxaparin are “bioequivalent” to Lovenox (Aventis’ FDA approved marketed version of enoxaparin) for the purpose of obtaining approval by the FDA of an Abbreviated New Drug Application (ANDA) to market the generic enoxaparin.

The FDA had identified five criteria (“standards for identity”) for establishing the “bioequivalency” of generic forms of enoxaparin, which include equivalence in terms of:  disaccharide building blocks; (2) fragment mapping; and (3) sequence of oligosaccharide species.  Following “exhaustive enzymatic digestion” of a sample of the generic enoxaparin, the resulting constituent disaccharide building blocks are separated and may then be quantified by various analytical techniques.  Momenta had developed a patented method (U.S. Pat. No. 7,575,866 or the ‘866 patent) for analyzing enoxaparin samples (after such “exhaustive enzymatic digestion”) to determine the presence and amount of non-naturally occurring sugars (resulting from the ?-eliminative cleavage of the enoxaparin starting material) in order to select appropriate batches of generic enoxaparin having bioequivalence to Lovenox.

In 2003, Amphastar filed for an ANDA on its generic version of enoxaparin and received approval from the FDA in September 2011.  Meanwhile, Momenta received earlier FDA approval to market its generic version of enoxaparin in July 2010.  Momenta later alleged that Amphastar infringed Momenta’s ‘866 patent by “manufacturing generic enoxaparin for commercial sale” using Momenta’s patent analytical method.  Specifically, Momenta asserted that Amphastar ‘“included in their process for manufacturing batches of enoxaparin sodium” a description of “a method for determining that a defined percentage of the oligosaccharide chains that make up enoxaparin” included the non-naturally occurring sugars (referred to as “quality control batch testing”).

The district court granted Momenta’s request for a preliminary injunction based on its belief that Amphastar’s “quality control batch testing” of its generic enoxaparin infringed Momenta’s ‘886 patent.  While agreeing that Amphastar’s use of Momenta’s patented analytical method was for the purpose of developing information to submit to the FDA, the district court concluded that the Hatch-Waxman “safe harbor” did not apply where the generic manufacturer continues “in an otherwise infringing activity after obtaining such [marketing] approval” from the FDA.  The district court apparently reached this conclusion by focusing on the legislative history of the “safe harbor” provision, as quoted in Classen.  In fact, Judge Newman’s majority opinion in Classen said that the House Report on Hatch-Waxman is “replete with statements that the legislation concerns premarketing approval of generic drugs.”  (Emphasis added.)

Judge Moore’s majority opinion in Momenta Pharmaceuticals vacated the preliminary injunction, agreeing with Amphastar that the “quality control batch testing” fell within the “safe harbor” provision of Hatch-Waxman.  The majority opinion focused first on whether the language of 35 U.S.C. § 271(e)(1) had a “plain and unambiguous meaning” with respect to this “safe harbor” provision.  While Judge Moore acknowledged that this “safe harbor” provision was enacted in the context of the ANDA approval process, she construed this “broad language” of 35 U.S.C. § 271(e)(1) to apply to activities beyond the ANDA approval process.  In support of her position, Judge Moore observed that Congress had specifically excluded certain patented inventions (i.e., new animal drug or veterinary biological product made by using certain genetic techniques) from this “safe harbor.”  Judge Moore further noted that, unlike the “closely related infringement provision” 35 U.S.C. § 271(e)(2) (which provides for “technical infringement” of the patented invention to be based simply on filing of the ANDA), 3 5 U.S.C. § 271(e)(1) did not link the “safe harbor” to such ANDA approval.  Accordingly, Judge Moore said that the “scope of the Hatch-Waxman safe harbor does not stop at activities reasonably related to development of information submitted in an ANDA.”

Judge Moore’s opinion says that her analysis “is not groundbreaking” in view of the Supreme Court’s decision in Medtronic which she asserts “came to essentially the same conclusion.”  But Judge Moore’s analysis is, in fact, “groundbreaking” because Medtronic only addressed what “patented inventions” (e.g., medical devices) fell within the scope of the Hatch-Waxman “safe harbor.”  Judge Moore’s further assertion that the Supreme Court “reaffirmed this expansive view” in Merck only goes so far as that “view” expanded the “safe harbor” to include a wide range of pre-marketing FDA approval activities.  Nothing in either Medtronic or Merck suggests that the Supreme Court intended the “safe harbor” to reach post-FDA approval activity.

While Judge Moore’s opinion acknowledges that the “safe harbor” is limited to uses “reasonably related to the federal regulatory process,” she omits a very important further limitation on such use:  it must be “solely” for such uses.  In fact, Judge Moore’s opinion essentially glosses over this “solely for uses” language when distinguishing the holding in Classen as applying only to “information that may be routinely reported to the FDA, long after marketing approval has been obtained.”  Rather than being a “routine” submission, Judge Moore’s opinion viewed Amphastar’s “quality control batch testing” information to be “necessary both to the continued approval of the ANDA and to the ability to market [its] generic [enoxaparin] drug.”  Accordingly, Judge Moore’s opinion concluded that, “[u]nder such circumstances, the information can be said to have been gathered solely for submission to the FDA and not, as in Classen, primarily for non-FDA purposes.”

The problem with this expansive view expressed by Judge Moore is that it reads the phrase “solely” virtually out of the “safe harbor” provision.  Ironically, footnote 1 of Judge Moore opinion expresses “puzzle[ment]” at Chief Judge Rader’s claim that the word “solely” (as well as the word “submitted”) required limitation of the “safe harbor” provision to pre-FDA approval activities.  But as Chief Judge Rader’s dissent correctly observes, Judge Moore’s opinion not only “discounts” the word “solely” to “facilitate [an infringing] post-[FDA] approval, continuous, commercial use,” but even repeatedly cites the language of the “safe harbor” provision without even mentioning this crucial word.  If the phrase “solely for uses” is to mean anything in limiting the scope of this “safe harbor,” Chief Judge Rader’s view that “solely for uses” means Amphastar’s use of Momenta’s patented analytical method (i.e., “for the purpose of manufacturing a product to sell on the market in commerce”) is outside the “safe harbor” has to be the correct one.

More significantly, and as Chief Judge Rader’s dissent correctly points out, Judge Moore’s opinion completely “circumvents” the purpose of this “safe harbor” provision which is manifestly “evident from the legislative history.”  As the legislative history repeatedly shows, this “safe harbor” provision was to be applied “only in limited situations, namely pre-approval experiments to obtain FDA approval.”  In fact, as Chief Judge Rader also correctly observed, this “safe harbor” provision only “won approval because it was limited in time, quantity, and type” (the “time” being only during “pre-marketing approval).  In particular, this “safe harbor” provision was not intended by Congress to “apply to commercial sales.”

A much weaker argument made by Momenta was that the phrase “solely for uses” in 35 U.S.C. § 271(e)(1) means that the patented invention must be the “sole” means for providing the “information” for the “safe harbor” provision to apply.  (The situation in Momenta Pharmaceuticals is unusual in that the asserted infringing activity relates not to the patented FDA-approved drug, or even to the use of that patented drug, but instead to a patented method for analyzing the FDA-approved drug.)  Judge Moore’s view that “solely for uses” does not “mandate the use of other, non-patented, testing methods” for the “development and submission” of such information is, in my opinion, the correct one.  In this respect, Chief Rader’s dissent goes too far in suggesting that Judge Moore’s opinion is based on Momenta’s patented analytical method being “mandated” by the FDA, rather than that the “information” resulting from that patented method was “mandated.”

Of particular concern in Momenta Pharmaceuticals is that Judge Moore’s basis for distinguishing Classen (routine submissions for non-FDA purposes) reads Judge Newman’s ruling in Classen far too narrowly.  (Or as Chief Judge Rader’s dissent says, “this court must stretch too far to claim [that] Classen did not turn on a pre-/post- approval distinction.)  Judge Newman’s opinion in Classen agreed with the patentee’s position there that the “safe harbor” provision of Hatch-Waxman provided an exception to patent infringement “in order to expedite development of information for regulatory approval of generic counter-parts of patented products.”  In fact, Judge Newman’s opinion in Classen also cites to and relies upon the same legislative history that Chief Judge Rader’s dissent cites to in Momenta Pharmaceuticals that shows this “safe harbor” provision was intended Congress to apply only to pre-marketing FDA approval.

Even more relevant (and contrary to what Judge Moore’s opinion in Momenta Pharmaceuticals suggests), Judge Newman’s opinion says that every decision reviewing 35 U.S.C. § 271(e)(1), including the Supreme Court’s Medtronic and Merck decisions, has “appreciated that [the “safe harbor” provision] is directed to premarketing approval of generic counterparts before patent expiration.”  In fact, in footnote 4 of her majority opinion, Judge Newman directly refutes Judge Moore basis for distinguishing Classen in Momenta Pharmaceuticals by observing that Judge Moore’s dissent in Classen “strays from [35 U.S.C. § 271(e)(1)] and precedent in arguing that any activity by any entity concerning any adversely patented product or method is exempted from infringement by [the “safe harbor” provision], provided only that the information obtained is ‘reasonably related to submitting any information under the FDCA.’”

Chief Judge Rader’s dissent raises the additional problem that applying the “safe harbor” provision to Momenta’s patented analytical method creates a “disequilibrium” between Section 201 of Hatch-Waxman (which permits patent extensions where there is regulatory delay in marketing the patented invention) and Section 202 (which permits/protects activities, such as those supporting ANDAs, prior to patent term expiration) because Momenta could not obtain patent term extension for its ‘866 patent under Section 201 (now 35 U.S.C. § 156).  In support of this “disequilibrium” argument, Rader cites the 2008 decision in Proveris Scientific Corp. v. Innovasystems, Inc.  In response, Judge Moore’s majority opinion tries to refute this “disequilibrium” argument by citing the 1997 decision in Abtox, Inc. v. Exitron Corp. (holding that “patented invention” of 35 U.S.C. § 271(e)(1) includes all medical devices, whether or not eligible for patent term extension under 35 U.S.C. § 152).

In my opinion, the holding in Proveris Scientific (rather than Abtox) is much more applicable to Amphastar’s use of Momenta’s patented analytical method, but not primarily based on Rader’s “disequilibrium” argument.  While Proveris Scientific discusses this “disequilibrium” issue, that was not the primary basis for the holding in that case that the “safe harbor” provision did not apply.  Instead, Proveris Scientific ruled that the term “patented invention” in the “safe harbor” provision did not include the alleged infringer’s analytical device because it was not subject to pre-market approval by the FDA.  Similarly, it does not appear that Momenta’s patented analytical method was subject to pre-market FDA approval, and was thus outside the “safe harbor” provision, whether or not the information provided by that patented method was “reasonably related to the development and submission of information” required by the FDA.

In my opinion, Judge Moore’s opinion in Momenta Pharmaceuticals simply resurrects her expansive dissenting view in Classen to impermissibly widen the “safe harbor” provision of Hatch-Waxman to include post-FDA approval activities.  Even worse, Momenta Pharmaceuticals permits the continuance of such activities that are least arguably commercial nature and thus not “solely for uses reasonably related to the development and submission of information” for FDA approval.  As Chief Judge Rader correctly observes, the ruling Momenta Pharmaceuticals would “render worthless manufacturing test method patents” like those of Momenta’s ‘866 patent.  In fact, it is very problematical that use of Momenta’s patented analytical method by Amphastar even qualifies as a “patented invention” subject to the “safe harbor” provision in view of the Federal Circuit’s holding in Proveris Scientific.  For at least these reasons, Chief Judge Rader is correct that “[t]his decision should instead request the entire court to resolve the issue en banc.”

*© 2012 Eric W. Guttag.  Posted August, 2012 on IPWatchdog.com

The Author

Eric Guttag

Eric Guttag  
Mr. Guttag has over 38 years of corporate and private intellectual property law experience on patent, trademark, copyright, trade secret and unfair competition matters, computer and Internet law, including patent application drafting, prosecution, and patentability studies; infringement and validity studies; international patent prosecution; patent and know-how licensing; consulting, confidentiality, clinical study and research agreements; trademark searches and opinions; trademark registration and prosecution; trademark freedom-to-use studies and trademark litigation and dispute resolution.

Warning & Disclaimer: The pages, articles and comments on IPWatchdog.com do not constitute legal advice, nor do they create any attorney-client relationship. The articles published express the personal opinion and views of the author as of the time of publication and should not be attributed to the author’s employer, clients or the sponsors of IPWatchdog.com. Read more.

Discuss this

There are currently 5 Comments comments.

  1. David August 7, 2012 5:54 pm

    I’m sorry, but the majority got much the right of this. Momenta and Rader ignore an important fact. Amphastar was close to approval four years before Momenta was approved, and was following FDA’s path toward the use of analytical method. If Amphastar is guilty of infringement, so are FDA and USP. Second, Amphastar did not utilize Momenta’s patents. Third, and soaking directly to Safe Harbor, others in Congress who were far more directly involved in the enactment of Hatch-Waxman than Rader professes to have been agree (on a bipartisan basis) that it is nonsensical to believe that any company would seek an ANDA knowing that they would have to stop at approval, and eschew production because of a bogus analytical method patent designed solely for the purpose of obstructing competition. Moore and Dyk correctly called out Momenta for deliberate subversion of both the patent process and the FDA approval process. Thy also called the anti-competitive judicial abuse of the drug approval process fostered by hacks and shills such as Randall Rader. Whi cares about Classen? It was Rader’s doing. The argument put forward here is as disngenuous asvRader’s dishonest and offensive dissent.

  2. Valverde August 7, 2012 5:57 pm

    I agree with you about Justice Moore’s practically incoherent opinion regarding the scope of the “safe harbor” provision. Although the court on both sides of the argument emphasized legislative intent and history, I find it quite puzzling that neither side referenced Roche v. Bolar; the case that essentially lead to congress passing the Hatch-Waxman act for the purpose of enabling the use of patented products In experimentation in order to obtain FDA “approval.” Seeking FDA approval means seeking approval for either an NDA or ANDA, how Moore could construe the safe harbor exception to exceed pre-approval use is beyond anyone but her.

    I currently work for a brand name pharmaceutical company and have discussed the negative impacts that the hatch-Waxman act has on both our and other companies alike on various occasions. It takes approximately 1 billion dollars of research and innovation just to get a new drug to market. The Hatch-Waxman Act allows for generic companies to essentially free ride off that billion dollar investment; particularly by allowing for the filing of ANDAs with paragraph 4 certifications which permit generic companies to challenge patents listed in the Orange Book. The expansion of the safe harbor provision is only going to add to the agony that Brand name companies like mine face and will essentially render patents other than just method patents meaningless. The Hatch-Waxman Act was supposed to promote “fair” competition when in reality it’s closer to flat out robbery and unfair exploitation of IP rights.

  3. Gene Quinn August 8, 2012 9:57 am

    David-

    Please explain why the FDA would be infringing the patent? I am dying to hear your “logic.”

    You also say: “it is nonsensical to believe that any company would seek an ANDA knowing that they would have to stop…” That statement is naive in the extreme. The strategic filing of ANDAs is well documented and known. It is in fact why some urge Congress to revisit Hatch-Waxman.

    Your comment in its entirety suggests you know little or nothing about the law. Perhaps you should stick to commenting on things you understand.

    -Gene

  4. EG August 8, 2012 10:34 am

    David,

    With all due respect, the issues you bring up are extraneous to the one addressed by me, as well as by the Federal Circuit: does the “safe harbor” apply to post-FDA approval activity? For the reasons Chief Rader gave and for the reasons I’ve noted in my article, it does not. Judge Moore’s ruling in Momenta Pharmaceuticals to the contrary is simply unsupportable based on the statutory language, the clearly expressed legislative intent, and the prior Classen decision which is binding precedent that Judge Moore can’t distinguish as she’s done.

    I was practicing patent law when the Hatch-Waxman Act was being proposed. Indeed, my boss at the time was actively involved in the drafting of this Act. I can tell you for a fact that Congress intended the “safe harbor’ to apply only to pre-FDA approval activity, such as INDs and ANDAs. In fact, the ruling in Medtronic that the “safe harbor” applied beyond drugs caught many of us by surprise, including, as I mention in my article, the floor managers in Congress for this Act.

    As I also mention in my article, whether Momenta’s patented analytical method even qualifies as a “patented invention” subject to the “safe harbor” is very problematical in view of the Proveris Scientific case. We’re not talking about infringement based on the patented drug or patented use of a drug which is subject to FDA approval. Instead, we’re talking about a patented analytical method which is used to establish whether a particular batch of a generic version of the FDA-approved drug was bioequivalent. As both Rader and Momenta pointed out, Amphastar was free to choose other, noninfringing methods to establish bioequivalency of each batch of generic enoxaparin.

    To the extent that you assert that what I put forward in my article is “disingenuous” I take extreme umbrage at that. You are free to disagree with what I said, but please don’t launch ad hominem attacks like that at me; you simply lose any credibility in my eyes, as well as others who comment on this blog. As anon would say, you can make such ad hominem attacks on Patently-O, but you should not make them here. Also, there is nothing “dishonest” or “offensive” about Rader’s dissent; he simply points out what the majority is unwilling to accept, especially the clear legislative intent that the “safe harbor” does not apply to post-FDA approval activity.

  5. EG August 8, 2012 10:54 am

    Dear Valverde,

    Thanks for your comment. Actually, Rader (but not Moore) reference Roche v. Bolar in the context of what the legislative intent was with respect to what time period the “safe harbor” applies to. In fact, Moore’s opinion tries to finesse this “legislative intent” problem in her ruling by saying that when “the intent of Congress is expressed so clearly and consistently throughout the statute, there is neither the need nor the occasion to refer to the legislative history.” The trouble is that she reads the “intent” in the language of 35 U.S.C. § 271(e)(1) incorreclty by, among other things, disregarding the impact of the phrase “solely for uses” as I note in my article. Also, as Rader’s dissent correctly notes, this language was deemed by SCOTUS in Medtronic “not plainly comprehensilble” (i.e., the legislative intent in the statutory language was “unclear”). And by ignoring the clear legislative intent behind the “safe harbor,” the rug is completely pulled out from under Moore’s basis for the majority opinion.