Drugmakers in Para IV Litigation

Hoffman – La Roche has slapped a lawsuit at Indian generic drugmaker Orchid Chemicals & Pharmaceuticals Ltd. over a newly issued patent for Roche’s blockbuster osteoporosis drug Boniva. The US Patent was issued (US Patent 7410957 – Method of treatment using bisphosphonic acid) on August 12, 2008 and Orchid had filed an ANDA (Abbreviated New Drug Application) with the USFDA under Para IV of the Hatch-Waxman Act. Interestingly, Orchid was sued in September last year over the alleged infringement of another patent of Boniva by Roche. Orchid was accused of infringing US Patent 7192938 (US Patent Issued on March 20, 2007) following its paragraph IV ANDA submission to manufacture a generic version of Boniva.

The Drug Price Competition and Patent Term Restoration Act of 1984, commonly known as the Hatch-Waxman Act, strikes a balance between the interests of pioneer pharmaceutical companies, competing generic manufacturers and consumers. It creates several modifications to conventional patent law. One of the several is a bounty for challenging patent validity, infringement or enforceability in the form of 180 days of market exclusivity to the first generic applicant to file a patent challenge against any approved drug. Hatch-Waxman employs a unique procedural framework to manage the interplay between pioneer New Drug Application (NDA) and their generic Abbreviated New Drug Application counterparts (ANDA). Upon filing an NDA, a pioneer firm must provide a list of relevant patents, which are then listed in an FDA publication known as the Orange Book. Subsequent ANDAs must reference these Orange Book listings and make one of four certifications for each patent:

I. The required patent information has not been filed;

II. The patent has already expired;

III. The patent has not yet expired, but will do so prior to FDA approval of the ANDA; or

IV. The patent is invalid or will not be infringed by the ANDA.

The most significant and contentious of these is the Paragraph IV certification, because a generic firm is seeking market entry prior to patent expiration. Generic applicants making Paragraph IV certifications must notify the pioneer firm, which then has forty-five days to initiate a patent infringement lawsuit. Pioneer drug makers typically pursue litigation, automatically triggering a thirty-month stay that prevents FDA approval of the ANDA until the earliest of the following dates: patent expiration, a final resolution of the patent litigation, or expiration of the thirty-month period. If the generic drug manufacturer prevails in the Paragraph IV patent litigation, it is rewarded with a 180-day marketing exclusivity period, during which the FDA cannot approve subsequent generic versions of that drug. This 180-day monopoly can be immensely profitable, and it thus rewards the first Paragraph IV filer for bearing the risks and expenses of patent litigation. Once the exclusivity period has been triggered and expires, the FDA may approve subsequent generics to enter the market.

The independent claim of the US Patent 7410957 reads as follows –

What is claimed is: 1. A method for treating osteoporosis comprising commencing treatment by orally administering to a subject in need of such treatment, on a single day, a first dose in the form of a tablet, wherein said tablet comprises an amount of a pharmaceutically acceptable salt of ibandronic acid that is equivalent to about 150 mg of ibandronic acid and continuing said treatment by orally administering, once monthly on a single day, a tablet comprising an amount of a pharmaceutically acceptable salt of ibandronic acid that is equivalent to about 150 mg of ibandronic acid.

Under the Indian Patents Act, Section 3(i) makes such inventions non-patentable which are any process for the medicinal, surgical, curative, prophylactic, diagnostic, therapeutic treatment of human beings or animals. The patent claim [mentioned above] in its description of oral administration of the tablet (a pharmaceutically acceptable salt of ibandronic acid) evidently is for a process for the medicinal treatment of osteoporosis (a disorder involving abnormal bone resorption) which makes it patent non-eligible. The composition of the tablet, which is a salt of ibandronic acid, will show patent eligibility once, under section 3(d), it differs from the known substance, significantly in properties with regard to efficacy.

On a separate note, the mounting litigation costs and diminishing possibility of victory are probably forcing the domestic generic drug firms to stay away from patent rows. Authorized generics, manufactured by firms under license from innovator companies as well as diminishing blockbuster drugs are thought to force the domestic drug companies to shun the legal route to benefit from patented drugs.