Compounding: Can It Legally Involve You? Part 1

R ecently, DUSA Pharmaceuticals, the manufacturer of 5-aminolevulinic acid (Levulan Kerastick) has sued several physicians who allegedly used aminolevulinic acid (ALA) obtained from private compounding pharmacies as a substitute for DUSA’s Levulan brand of ALA.1 Levulan is the only FDA approved form of ALA; a drug used in photodynamic therapy (PDT) treatments. What is the basis for these suits and could you also be at risk of being named in a similar suit? This article will explore these issues and answer these questions. Exploring the Basis for the Suits The unusual circumstance of physicians coming under such legal action involves DUSA’s enforcement of this and other “method of use” patents covering a multitude of dermatological applications of ALA. In this situation, DUSA claims that the compounding pharmacies actually induced their physician customers to infringe the DUSA patent when they bought and used drugs not regulated in quality or purity by the FDA. The new suits are in addition to earlier suits this year in which DUSA took action against two compounding pharmacies. These cases highlight two legal issues: 1. “method of use” medication patents 2. pharmacy compounding. What Does the Patent Cover? DUSA holds 14 patents. In particular, DUSA holds patent 5,489,279 that covers a: method of applying photodynamic therapy to dermal lesion located at a dermal treatment site in skin which includes the stratum corneum, including the steps of hydrating the stratum corneum at the dermal treatment site to enhance the chemical and optical transparency of the stratum corneum at the dermal treatment site and to enhance the passage therethrough of photopharmaceutical and light, introducing photopharmaceutical into the treatment site through the hydrated stratum corneum, and introducing light into the treatment site through the hydrated stratum corneum to photoactivate the photopharmaceutical to treat the dermal lesion. So what does this mean to you in terms of whether you use Levulan for ALA/PDT vs. ALA purchased from a compounding company? In an article, Todd Martin outlined the issues regarding “method of use” patents, and the following discussion is substantially adapted from a paper he wrote titled “Patentability of Methods of Medical Treatment: A Comparative Study.”2 The patent laws of the United States regarding patentability of methods of medical treatment are expansive. The law defining inventions patentable is contained in 35 U.S.C. § 101 “inventions patentable”, which states:2 whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title. Basic Requirements of Patentability The three basic requirements of patentability flowing from section 101 are novelty, non-obviousness and usefulness. U.S. courts liberally decide what constitutes patentable subject matter. Generally, “anything under the sun that is made by man” is patentable, subject to the usual minor exceptions of printed matter, methods of doing business, purely mental steps, naturally occurring phenomena or laws of nature and mathematical formulae and algorithms.2 In reference to “use” claims, the U.S. Patent and Trademark Office (USPTO) allows “use” claims as long as the patent enumerates the steps. A claim for a use of a composition in making a medication, for example, will be rejected unless the claimant recites discrete steps. Also, claiming the use of prior art compositions (that is the design of previous patents) will not be allowed if the use is merely directed to other properties of that composition. However, the USPTO allows a new process of use patent in cases where the claim is not directed to a property or result.2 In reference to medical discoveries, patent courts have found medical and surgical methods patentable. In the nineteenth century, however, courts considered medical and surgical methods of treatment unpatentable processes because they involved the “natural functions of an animal.”2 Ex Parte Brinkerhoff. This reasoning was later used to support the Commissioner of Patent’s decision in Ex Parte Brinkerhoff that “the methods or modes of treatment of physicians of certain diseases are not patentable.” The Ex Parte Brinkerhoff decision was later rejected by other USPTO decisions that found that medical methods were patentable.2 Martin v. Wyeth. In Martin v. Wyeth, the court discussed public interest concerns, noting that public interest favored widespread dissemination of knowledge over monopolies in the medical field. The court then invalidated the patent under litigation, but on non-public interest reasons. 2 Pallin v. Singer. The Pallin v. Singer patent infringement case involving a surgical eye procedure provoked a legislative response resulting in a substantial reduction in remedies available for medical method patent infringement. In the case, one eye surgeon sued another eye surgeon over infringement of a medical method patent disclosing a new cataract surgery technique. The case was resolved after the defendant argued that the patent was invalid for lack of novelty as well as being obvious. Physicians were concerned that one physician would actually sue another over a surgical technique. The American Medical Association lobbied the Congress, and it enacted a new subsection to the patent statute. The new subsection (c), part (1) generally eliminates infringement remedies with respect to a “medical practitioner’s performance of a medical activity.” Part (2) then goes on to define the scope of part (1) by including definitions of “medical activity” and “medical practitioner.” 35 U.S.C. § 287(c)(2)(A) provides that the elimination of remedies will not apply to a patented machine, item of manufacture, or composition of matter, biotechnological patents, and importantly, patented uses of a composition of matter.2 The practical effect of 35 U.S.C. § 287(c) is to eliminate infringement liability for physicians and related entities with regard to surgical procedures not involving a patented composition of matter procedure. This transforms medical method patents, in the words of one U.S. commentator, into “. . . a rather expensive certificate of merit.”2 The subsection is narrowly tailored to affect the patent system only enough to accomplish its intended purpose: protection of medical practitioners from patent liability. However, in many cases, even without the new law, it is unfeasible to sue individual physicians, although DUSA is doing just that. Plaintiffs who bring infringement actions against individual physicians risk losing the customer good will of other physicians for a damage award that entails a higher risk of non-collection. This is why infringement suits between physicians are relatively rare.2 The earlier-mentioned Pallin case has been cited as the first of its type to go to trial. The holder of a method of medical treatment patent is more likely to obtain significant damage recovery from medical device manufactures and pharmaceutical companies. Furthermore, the new law does not limit the remedies that may be applied against such companies. Part 3 of 35 U.S.C. § 287(c) allows an action to be brought against medical device manufacturers and pharmaceutical companies on the basis of contributory infringement, or active inducement.2 Jansen v. Rexall Sundown, Inc. Courts can narrowly construe medical method of use patent infringement claims in particular for non-prescription medications. Jansen v. Rexall Sundown, Inc., 342 F.3d 1329 (Fed. Cir. 2003), the Federal Circuit affirmed a summary judgment by the United States District Court for the Southern District of Indiana, holding that Rexall Sundown Inc. (Rexall) had not infringed U.S. Patent 4,945,083 (the ‘083 patent). The Federal Circuit held that the lower court correctly construed the patent claims and correctly found that there was no genuine issue of material fact regarding infringement. Christian Jansen (Jansen) was the inventor and owner of the ‘083 patent, a patent for a method of treating or preventing macrocytic-megaloblastic anemia by administering specific doses of a combination of vitamin B12 and folic acid. According to the patent specification, deficiencies in either of these nutrients can cause macrocytic-megaloblastic anemia, and deficiencies of the former can also cause neurological problems. Because a treatment where only folic acid is administered may mask a vitamin B12 deficiency, Jansen’s invention administers both nutritional supplements together. The ‘083 patent went through several continuations before allowance of Jansen’s claim, which was narrowed to require that the treatment/prevention be: 1. directed to a specific type of anemia, namely macrocytic-megaloblastic (as recited in the preamble) 2. administered to a human in need thereof (as recited in the claim body). Rexall sold an over-the-counter dietary supplement that contains vitamin B12 and folic acid within the ranges claimed in the ‘083 patent. Rexall labeled and advertised its supplement for the maintenance of proper blood homocysteine levels, but did not mention any effectiveness in treating macrocytic-megaloblastic anemia. Jansen sued Rexall for inducement and contributory infringement of the method claimed in the ‘083 patent. In construing the claims, the district court held that the claims required a human subject to take the supplement with the intent of treating or preventing macrocytic-megaloblastic anemia. The district court found no evidence of such intent on the part of Rexall customers, and granted summary judgment of non-infringement. On appeal, Jansen argued that the district court incorrectly construed the patent claims by adding an intent element. Thus, according to Jansen, the phrase a human in need thereof included people who did not know whether they consumed an adequate amount of vitamin B12 and folic acid, and that there was sufficient evidence of infringement by Rexall customers. Rexall countered that the claim language added an intent element because the claims required that the infringer be a human in need thereof. Thus, according to Rexall, the alleged infringer must take the supplement for the specific purpose of treating or preventing macrocytic-megaloblastic anemia. Rexall also contended that it only marketed its supplement for the regulation of blood homocysteine levels. Moreover, Rexall asserted that even if some evidence of infringement by its customers existed, it was not liable for infringement because there were substantial non-infringing uses of its supplement, and it had not intended to cause infringement. Addressing claim construction, the Federal Circuit determined that the central issue was how to interpret the phrases treating or preventing macrocytic-megaloblastic anemia and to a human in need thereof. Specifically, the court found the issue to be whether “such a human must know that he is in need of either treatment of prevention of that condition.” Rapoport v. Dement. In making this determination, the court compared the facts of this case to those in Rapoport v. Dement, 254 F.3d 1053 (Fed. Cir. 2001). The court highlighted that the claim at issue in Rapoport, similar to the claims in the present case, specified a method of treatment and a target population in need of that treatment. In Rapoport, the Federal Circuit interpreted the claim to require that the method of treatment be practiced with the intent to cure a specific disorder. The court then pointed out that, as in Rapoport, the ‘083 patent’s preamble sets out the specific objective of treating and preventing a specific disease/disorder (i.e., macrocytic-megaloblastic anemia in the current case), and the body of the claim indicates that the method must be performed on someone in need. The court then reiterated the rule that a preamble must be treated as a limitation if it gives life and meaning to a claim. It stated that in both Rapoport and the current case, the recitation of a patient or human in need gave life and meaning to the preamble’s stated purpose of treating or preventing the recited disease. In other words, the language of treating or preventing macrocytic-megaloblastic anemia together with the phrase to a human in need thereof compelled a claim construction that required an infringer to take the supplement with the intent to treat or prevent macrocytic-megaloblastic anemia. The Federal Circuit also considered the prosecution history of the ‘083 patent when interpreting the claims. Specifically, the court noted that the patent only issued after nearly 20 years of unallowable claims because applicants added the two phrases treating or preventing macrocytic-megaloblastic anemia and to a human in need thereof. In light of this prosecution history, the court determined that the phrases were central to construction of the claims. The court also reasoned that because applicants added the two phrases simultaneously to overcome the same rejection, the phrases should be interpreted together — i.e., to mean that that the need related directly to the treatment or prevention of macrocytic-megaloblastic anemia. Moreover, according to the court, the need must be recognized and appreciated by one practicing the method because otherwise the phrases would “not carry the meaning that the circumstances of the addition suggest that they carry.” In affirming the lower court’s construction of the ‘083 claims, the court next rejected Jansen’s argument that there was circumstantial evidence of direct infringement based on the possibility that some Rexall customers might have knowingly taken the supplement to prevent or treat macrocytic-megaloblastic anemia. In so doing, the Federal Circuit distinguished the current case from one where the product in question was available by prescription only. As stated by the court, a “prescription is evidence of a diagnosis and a knowing need to use the product for the stated purpose.” For Rexall’s over-the-counter supplement, however, those who purchased it did not necessarily know that they were in need of preventing or treating macrocytic-megaloblastic anemia. While the court agreed that it was theoretically possible for some of the customers to know, this possibility was ultimately too circumstantial and weak to give rise to a genuine issue of material fact. The court reiterated its holding in Rapoport that when analyzing infringement of a method of treatment or prevention claim, one must consider the intent of the direct infringer if the claims limit the method to a subject in need thereof. The intent of an alleged infringer can be critical in an infringement analysis, even if the limitation reciting for treatment or prevention of a particular disease/disorder resides only in the preamble. The presence of the in need thereof limitation ensures that the preamble limits the claims to apply to those who intend to engage in the specific method of treatment or prevention of the recited disease or disorder. Interestingly, the court indicated that a showing of such intent is easier to prove in the case of prescription drugs, as opposed to over-the-counter drugs such as those of Rexall. How the DUSA Claim Fits In In sum, method of use patents are valid, and the preamble of a claim directed to a method of treating or preventing a particular disease requires that, in order to infringe a patent, a human subject of the claimed method must take the compound with the intent of treating or preventing the recited disease defined in a patent. In conclusion, the DUSA claim for infringement of its method of use claim flows from established case law. It is likely not covered by the surgical method exemption. However, this does not mean DUSA will prevail. For example, hypothetically, those whom DUSA is suing might claim that they are not treating dermal lesions, which DUSA’s patent covers, but rather essential structures of the dermis itself and hence the patent does not apply to their actions. In any case, the DUSA case brings up important issues that will interest dermatologists in the years to come.