In an attempt to resolve disputes on patent invalidity and infringement among brand drug companies and generic drug companies, a patent linkage system has been promulgated and introduced into the Pharmaceutical Affairs Act. When a patent infringement lawsuit against a generic drug manufacturer is filed based upon a patent with medical use claims, the indications specified on the generic drug approval will become a key factor to be considered in the infringement lawsuit. If the indications specified on the generic drug approval involves an explicit exclusion of the medical use defined in the claims of the patent in dispute, will the generic drug manufacturer be immune from patent infringement? There is now an opportunity to take a look at the perspective of the Intellectual Property and Commercial Court around this subject from a Judgment rendered in October, 2021 at the first instance.
The patent holder for a patented Drug Crestor for treatment of hyperlipoproteinemia filed a patent infringement lawsuit with the Intellectual Property and Commercial Court against a generic drug manufacturer. The patent entitled “pharmaceutical composition for use in the treatment of heterozygous familial hypercholesterolemia,” was registered in the Taiwan patent linkage system to link with the new drug at issue. There are two sets of the claims of the patent calling for “a pharmaceutical composition for treating a patient suffering heterozygous familial hypercholesterolemia” and “a pharmaceutical composition for reducing LDL-C, raising HDL-C, reducing Apo B and raising Apo A-I in a patient suffering from heterozygous familial hypercholesterolemia”, respectively, both of which comprise an active ingredient.
The active ingredients are one and the same and thus, whether or not an infringement case is established will hinge upon the indications specified on the generic drug approval.
The indications specified in the application for drug approval filed with Taiwan FDA are “primary hypercholesterolemia, as a dietary adjuvant therapy, for patients with primary hypercholesterolemia (heterozygous familial hypercholesterolemia is excluded) or for the patient with mixed dyslipidemia to reduce elevated total cholesterol, low-density lipoprotein (LDL-C), lipoprotein (Apo-B), non-HDL cholesterol (non-HDL-C) and triglycerides and to increase HDL-C. protein cholesterol.” After the infringement was initiated by the patentee, and during the examination of the generic drug by Taiwan FDA, the indications of the generic drug were revised to “primary hypercholesterolemia (heterozygous familial hypercholesterolemia is excluded).”
The court expressed that since the claims of the patent in dispute are calling for a pharmaceutical composition with an effective medical use limitation, the limitation “a patient suffering from heterozygous familial hypercholesterolemia” shall be taken into account in determining whether or not the generic drug is read by the claims of the patent in dispute. In light of the presence of the exclusion of patients suffering from heterozygous familial hypercholesterolemia on the generic drug approval, would the generic drug literally infringe upon the patent in dispute?
The court made the following comments:
First, according to the description in the specification of the patent in dispute, the hypercholesterolemia can be classified as shown the following chart. The patent is directed only to the heterozygous familial hypercholesterolemia.
Secondly, whether or not the generic drug is literally read by the claims of the patent in dispute hinges upon the indications for said generic drug. To this end, apart from the indications specified on the drug approval/leaflet for the generic drug, the clinical results and therapeutic effects obtained from the clinical trials referred to by said generic drug should be considered. The indications set out on the approval/leaflet are indeed an important reference for clinical practitioners or pharmacists to use as a guideline for use of the drug. However, considering the amendment of indications during the prosecution of the infringement lawsuit, the indications of the generic drug should further be supportable by the clinical results and therapeutic effects of the clinical trials carried out by the generic drug manufacturer besides being reasonable in medical practice.
Turning to the reasonableness in medical practice, the court indicated that in accordance with the witness testimony, the physicians generally would not distinguish patients suffering from heterozygous familial hypercholesterolemia from primary hypercholesterolemia when treating such diseases. Such an exclusion is not reasonable in medical practice.
The court further expressed that the clinical trials for the generic drug did not involve the classification of patients into patients suffering from heterozygous familial hypercholesterolemia or from primary hypercholesterolemia. Moreover, there were more than 11,000 patients included in the clinical trial. According the known statistical analysis of the patient distribution provided by the witness testimony, it is reasonable to infer from the clinical trial that the generic drug exhibits therapeutic effects on patients suffering the non-familial hypercholesterolemia and heterozygous familial hypercholesterolemia. From such results, the exclusion in the indications on the generic drug approval involves merely circumventing the wording of the claims of the patent in dispute, and thus, the indications with such exclusion cannot serve as a basis to determine patent infringement and whether or not the generic drug can exhibit therapeutic effects on patients with heterozygous familial hypercholesterolemia. As a consequence, the court reached a conclusion that the generic drug even with an exclusion still falls within the scope of the patent in dispute.
The case is still at the appellate stage in the second instance. We will keep an eye on the development of the case to see whether the higher court, when determining the patent infringement, will consider the indications for the generic drug from the substantive therapeutic effects and the reasonableness in medical practice, instead of merely from the plain, literal wording of the indications on the drug approval.