Patent Necromancy - or - Domestic and Foreign Treatment of Patentability and Infringement Concerning
Access to affordable generic drugs is central among issues of debate concerning healthcare access and affordability. Between you and your drug access stands a zombie menace—one might imagine—a horde of undead pharmaceutical patents reanimated by an unholy combination of necromancy and back door deals with the Director of the USPTO. Patent Zombification, also called “evergreening,” is the term generally applied to pharmaceutical companies’ attempts to use continuing research to maintain and extend patent protection on previously developed drug lines. This practice sometimes strikes fear—or at least strong feelings—into the hearts of analysts and the public. However, as with real zombies, better understanding of this beast reveals that they are often quite harmless, and when they do attempt to feed off the flesh of the living, they can be quite easily dispatched.
To gain a better understanding of pharmaceutical zombie patents, it is helpful to know where they come from. Pharmaceutical companies may only manufacture and market a generic drug after the patent owner’s patent has expired. During the patent’s lifetime, the patentee enjoys a period of exclusivity, during which it holds a monopoly and can charge higher prices for its drugs. This temporary monopoly is crucial in allowing pharmaceutical companies to recoup their financial investment in research and development.
Often, when a pharmaceutical patent is about to expire, the company will apply for patents to variations of the patented drug. These tactics help pharmaceutical companies maximize their profits from each invention. However, these “second generation” patents can also appear to refresh an expired patent and allow a pharmaceutical company to maintain a monopoly well beyond the original patent’s exclusivity period. Pharmaceutical companies routinely seek to improve their drugs; however, sometimes the patentee will try to use a new patent on a variation of the old drug to prevent generic manufacturers from practicing the old patent. Labeling the practice “evergreening,” critics see this as an improper attempt to cheat the patent system by effectively refreshing the expired patent to maintain an effective monopoly on the initial drug.
Patents on pharmaceutical salts and crystalline forms of previously patented drugs are one way that pharmaceutical companies have attempted to revive dying patents. Though the new salt or crystalline form may have some advantages over the original drug, it is still the same chemical compound, and it may or may not be truly innovative. However, companies will use the patent on the new form to prevent competition on the market regarding the new form or, in some cases, even claim generic companies infringe by practicing the old patent.
Different members of the World Trade Organization treat pharmaceutical patent evergreening differently, especially between developed and developing countries. Fairly recent in this argument was the Indian case, Novartis, AG v. Union of India & Others, in which the Supreme Court of India upheld the Indian Patent Office’s rejection of Novartis’s application for a patent for Gleevec, a polymorphic form of a previously patented leukemia medication. That recent decision drew approval from generic manufacturers and health organizations and condemnation from big pharmaceutical corporations. Where interpretation allows, upholding patentability of new pharmaceutical salts and crystalline forms of previously patented drugs while refusing abusive infringement claims would maintain incentive for pharmaceutical companies to invest in research and development without negatively impacting availability of affordable generic versions of earlier forms.
II. ISSUES SPECIFIC TO PHARMACEUTICAL INNOVATIONS
In order for an invention to be eligible for a patent, it must be 1) useful, 2) novel, 3) nonobvious—referred to as “inventive step” outside the United States—and 4) include specification or disclosure for the invention. Pharmaceutical second-generation patents often face difficulties meeting the first three grounds. In fact, pharmaceutical products were not patentable until fairly recently, even in industrialized nations.
Pharmaceutical inventors and companies face several unique challenges. Pharmaceutical inventions rarely come in the form of brand-new compounds or products. Rather, pharmaceutical innovations generally arise in incremental steps. However, even these incremental steps require an extraordinary investment of resources in research and development. For this reason, pharmaceutical companies can have a very difficult time recouping their investments. What is more, pharmaceutical companies spend years seeking market approval from the Food and Drug Administration (“FDA”), which detracts from the patentee’s exclusivity period. This only exacerbates the difficulties pharmaceutical companies face in covering their research and development costs and profiting from their inventions. In the United States, the Drug Price Competition and Patent Term Restoration Act of 1984 has ameliorated this last situation by providing extensions of up to five years beyond the normal patent term to compensate for marketing time lost seeking FDA approval of a new drug.
In order to recover research and development expenses and maximize profits, pharmaceutical companies often try to extend a drug’s period of exclusivity by applying for secondary patents. Pharmaceutical companies can do this by applying to patent different aspects and forms of the original active compound. Applying for a patent for a new use of an old drug is one commonly employed technique. This method can be useful both when a patent for a drug expires and when testing of a previously patented drug reveals that the drug is inappropriate for the original use but suitable for another use. However, in this second scenario patent companies would find difficulty in enforcing their patents, as patients could easily purchase the generic drug marketed for the original use and then use it for the newly-patented use.
Another method pharmaceutical companies have employed to extend patent life is patenting of metabolites. Often when pharmaceutical companies create new drugs, they do not know the exact mechanism by which they are effective. It is frequently the case that the original manufactured compound is not active in the body. Instead, the compound is metabolized—broken down—by enzymes inside the body, creating a new form called a metabolite. In some of these cases, it is the metabolite, formed inside the body, which produces the therapeutic effect. The pharmaceutical company may not identify this metabolite or its efficacy until well into the marketing life of the original patent. However, in several cases, companies have attempted to patent the new metabolite. These companies have then tried to enforce the patent by suing generic manufacturers of the original drug on a theory of infringement or contributory infringement. The idea is that the generic manufacturer aided the patient in ingesting the drug which then breaks down into the patented metabolite, thereby infringing the new patent. While the courts and patent systems of different countries have addressed these issues from different angles, none of them have actually enforced these patents and found infringement in this way.
Companies also use delivery systems—the solid forms of the medication—to extend patent life. When pharmaceutical companies originally patent a new drug, they often patent it in its free base form—that is, the active molecule suspended in a solution. The delivery system incorporates both the active compound and the medium in which it is delivered. This can take the form of a liquid suspension or solution to be ingested, injected, or atomized and inhaled, or it could be a solid form, such as a pill. The solid form is often a pharmaceutical salt and may be an amorphous jumble of molecules or a crystalline form. In either case, the active molecule is exactly the same, only the arrangement of the molecules is different.
Often the salt or crystalline form exhibits improved characteristics, such as enhanced stability in storage and increased bioavailability. Patents on solid forms confer several different advantages. They enable the company to move to an improved form. In addition, they can allow the company to extend the exclusivity period for a drug, thereby holding off competition from generic manufacturers. Unfortunately, they also create confusion regarding patentability and infringement. While it seems clear that the courts are unwilling to allow second-generation patents on salts and crystalline forms to prevent generic manufacture of the form described in the original expired patent, other aspects seem less clear.
Courts can address problems raised by second-generation patents of metabolites, salts, and crystalline forms in two ways—patentability and infringement. When addressing the patentability of the new form, the court ultimately determines whether the claimed invention merits any protection and exclusivity period. However, invalidating the patent can have extreme consequences because it would allow the generic manufacturer to produce the superior form as well as the original form.
Alternatively, courts can hold a patent valid, yet also hold that generic manufacture of the original drug does not infringe on the new patent. By preserving the patent, courts may also preserve the incentive for companies to continue to make incremental improvements to existing drugs. While Taiwan has taken this avenue concerning active metabolites, United States and European courts have tended to invalidate patents on various theories of patent law.
Though evergreening pharmaceutical companies use metabolites and solid forms much in the same way, they may present different virtues in and of themselves. Because of these differences, the question of their patentability and utility may require different treatment by courts.
III. COURTS’ THEORIES ON PATENTABILITY AND INFRINGEMENT: DISCUSSION AND ANALYSIS
Courts in the United States and abroad generally analyze patentability and infringement cases under theories of novelty, inherent anticipation, obviousness, and in some countries under statutory limitations. Contrary to fears of some analysts, second generation patents are rarely if ever held infringed by generic manufacture of compounds for which patents have expired. The most common result of such litigation is the invalidation of the second generation patent.
A. Lack of Novelty
When evaluating inventions for novelty, the relevant question in the United States and other countries is generally whether a person of average skill in the relevant discipline would have been able, prior to the claimed invention, to achieve the invention. In invalidating a patent for a crystalline form of paroxetine methanesulfonate (Paxil), the British House of Lords considered this question of novelty and anticipation, addressing the degree of experimentation such an endeavor could require of a skilled artisan without the claimed invention attaining novelty. In finding anticipation, or lack of novelty, the House of Lords made it clear that the skilled artisan need not know that he or she is practicing the invention. Furthermore, he made it clear that need for routine experimentation did not render the new invention and claims “novel.”
B. Inherent Anticipation
The doctrine of inherent anticipation speaks to the novelty of an invention. Specifically, this doctrine provides that, where an invention would have resulted from practice of a previous invention—though perhaps unknown at the time—the previous invention has anticipated the latter invention. The latter invention, therefore, is not novel and not eligible for patent. In SmithKline v. Apotex, the United States Circuit Court for the Federal Circuit reasoned that claims directed to a compound which would have been present, though unknown, in a previously patent invention were anticipated by that previous invention, rendering the invention ineligible for patent.
When analyzing an invention for inherent anticipation, it is not necessary that the prior art explain or name a product to anticipate a later invention, so long as that invention is an unavoidable result of the prior art. It is important to note that courts may adhere to a seemingly inflexible standard for claim construction where the claims at issue may be interpreted to claim a new compound without limiting the claim to something such as “commercially significant amounts.” Therefore, patentees would do well to consider carefully how the scope of their claims may be interpreted. Claims limiting themselves to “commercially significant” amounts of the new, though “inherently anticipated” compound or salt may avoid invalidation, though they would not be infringed by previous versions not containing such amounts.
Unlike invalidations for anticipation, invalidations for obviousness (inventive step under patent schemes of other countries) are made on a combination of previously-existing references which would be obvious to combine in order to invention in question. Prior references may consist of sources such as previous patents and application publications, textbooks, research publications, and pharmacopeias. In making such invalidations, courts must find not only that the elements previously existed, but also a motivation for a person of average skill in the art to combine such references.
However, as with analysis for novelty, courts in the United States have allowed substantial, if routine, experimentation to be required in using the prior art to arrive at the invention at issue. Furthermore, some countries, such as South Korea, continue their inventive-step analysis, requiring that the patent clearly delineate differences and advantages from similar predecessors to the invention. This requirement of explanation of qualitative differences is somewhat similar to controversial statutory requirements imposed by patent schemes of countries such as India.
D. Statutory Limitation: Novartis Ag v. Union of India and Others
As previously explained, pharmaceutical compounds did not enjoy patentability in most countries until fairly recently. Many recently industrialized countries have been especially reluctant to allow such protection, which is seen as a threat to their generic manufacturing industries. In 1995, the World Trade Organization, of which India is a member, brought the TRIPS Agreement into force. Article 27 of the agreement provides that members shall make patents available “without discrimination as to the place of invention, the field of technology and whether products are imported or locally produced.” Article 65 provided extra time for developing countries to bring their laws within compliance.
Difficulties in passing complying legislation resulted in clause (d) of Chapter II’s section 3 of India’s Patent Act. Section 3(d) titled “What are not inventions,” stated that “the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance. . . ” is not an invention. The explanation section went on to state that salts, polymorphs, metabolites, etc. are “considered to be the same substance, unless they differ significantly in properties with regard to efficacy.”
In Novartis Ag v. Union of India and Others, the Supreme Court of India found this statute to be compliant with the TRIPS agreement and a prohibition to patentability of a polymorphic form of Imatinib Mesylate, a cancer drug.
E. Final Analysis
In the doctrines discussed above, different courts different methods are used to reach one of two results—either invalidation of the patent or validation of the patent and non-infringement of the generic product. While these theories are important roadmaps instructing courts on how to reach a destination, it is also important to consider the downstream effects which will arise from these holdings. There are strong arguments on both sides of the spectrum. If courts and governments restrict patent protection too much, pharmaceutical companies may have less incentive to invest in research and development. However, allowing pharmaceutical companies too much protection in cases of less significant or less innovative advancements to existing drugs could provide incentive to pursue avenues of research that provide no benefit to the community.
In light of these considerations, Taiwan’s middle-of-the-road approach to patentability of metabolites seems particularly appealing. By allowing patents for the new discovery, the law encourages innovation, while refusing to promote abuse in the form of inappropriate infringement claims. However, unlike the patentability of pharmaceutical metabolites, patentability of pharmaceutical salts and their different forms vary on a case-by-case basis. While the pharmaceutical patents often make general claims to a compound’s pharmaceutically-acceptable salts, they vary on the extent to which they disclose or enable those individual salts and forms. Often courts must decide factual questions as to whether or not a previous patent or reference did in fact anticipate or render obvious the subject of the later-published patent.
In many cases, the facts will leave little room for interpretation as to whether skilled professionals would have truly found a new form to have been obvious to try or previously disclosed. However, in instances where courts find some wiggle room—when they are free to interpret the scope of a claim or the level of inventiveness required to find a superior salt or crystalline form, it may be worth considering the value of maintaining the incentive to continue developing and improving drugs by upholding patents on the new form. Where possible, interpreting patent law and the patent itself in a way that upholds new salts and crystalline forms of previously discovered pharmaceutical compounds while refusing to find infringement by producers of the originally patented form will maintain incentive for pharmaceutical companies to invest in research and development without delaying introduction of affordable generic versions of the original drug to the market.