Implications for Patent Protection for Avonex® Anti-Multiple Sclerosis Drug
By Kevin E. Noonan --
That is happening in the wake of regulatory filings with the Securities and Exchange Commission regarding U.S. Patent 7,588,755 (the '755 patent), issued on September 15, 2009, and owned by Biogen Idec. The undesired outcome (by some) is the possibility that this patent will protect Biogen Idec's blockbuster multiple sclerosis drug, Avonex® (human interferon beta 1a), from generic competition for an additional 13 years (until September 15, 2026) after expiration of current patents in May 2013. That may happen, but a review of the history of the application shows that the patenting process worked as it is supposed to, with no evidence that Biogen Idec was not diligent in prosecuting this application within Patent Office rules. If anything, it is the diligence with which the Office examined the application that resulted in the delay that may extend Biogen Idec's exclusivity period.
The '755 patent claims priority to a first application filed in 1981 and a divisional application filed in 1989, both abandoned. The application that resulted in the '755 patent was filed on May 25, 1995, and thus has a patent term of 17 years from issue, determined by U.S. law prior to the adoption of the GATT provision limiting U.S. patent term to 20 years from the earliest priority date. A history of patent prosecution reveals "why it took so long" for this patent to issue:
The longest period of delay extended from March 12, 1998 to January 15, 2003 -- almost five years -- while prosecution was suspended because of a potential interference. (For those uninitiated in the arcane world of interferences, the most likely reason for this delay was to give a potential interfering application time to be prosecuted until interfering claims were deemed allowable.) As it turns out, no interference was declared, and the Examiner renewed prosecution by asserting anticipation rejections based on two patents to Sugano (U.S. Patent Nos. 5,514,567 or 5,326,859). (Ironically, '755 patent applicant Fiers was involved in an earlier interference against Sugano, and a second party, Revel, almost 20 years ago, in which Sugano prevailed in claims for human ß-interferon.) The second extensive period of delay involved the appeal of the asserted anticipation rejection, which was complicated by the new formalities rules for appeal briefs promulgated (and strictly enforced) by the Office. This delayed prosecution of the application to allowance by another 3 years, from June 24, 2005 to May 29, 2008. Ultimately, the Board of Patent Appeals and Interferences reversed the rejections based on the Sugano patents, paving the way for allowance and issue of the '755 patent (a process that took another 16 months).
Something like this could not occur today.
Besides these procedural aspects, whether the '755 patent will be useful for preventing generic competition for Avonex® will depend on the scope of the granted claims. The '755 patent has but three claims, set forth below:
1. A method for immunomodulation or treating a viral conditions, a viral disease, cancers or tumors comprising the step of administering to a patient in need of such treatment a therapeutically effective amount of a composition comprising:
a recombinant polypeptide produced by a non-human host transformed by a recombinant DNA molecule comprising a DNA sequence selected from the group consisting of:
(a) DNA sequences which are capable of hybridizing to any of the DNA inserts of G-pBR322(Pst)/HFIF1, G-pBR322(Pst)/HFIF3 (DSM 1791), G-pBR322(Pst)/HFIF6 (DSM 1792), and G-pBR322(Pst)/HFIF7 (DSM 1793) under hybridizing conditions of 0.75 M NaCl at 68.degree. C. and washing conditions of 0.3 M NaCl at 68.degree. C., and which code for a polypeptide displaying antiviral activity, and (b) DNA sequences which are degenerate as a result of the genetic code to the DNA sequences defined in (a);
said DNA sequence being operatively linked to an expression control sequence in the recombinant DNA molecule.
2. The method according to claim 1, wherein said DNA sequence is selected from DNA sequences of the formulae:
3. The method according to claim 1 wherein the polypeptide is selected from polypeptides of the formulae:
The relevance of these claims to Avonex® will
depend on whether Avonex® administration falls within the ambit of the method
claim, which requires:
a) immunomodulation or
b) treating a viral condition, a viral disease, cancers or tumors
c) administering to a patient in need of such treatment
d) a therapeutically effective amount of a composition comprising:
e) a recombinant polypeptide
f) produced by a non-human host transformed by a recombinant DNA molecule comprising a DNA sequence
g) encoding human ß-interferon or sequence homolog thereof
h) which code for a polypeptide displaying antiviral activity
While elements e)
through h) are apparently encompassed by Avonex®, whether these
claims will be useful for precluding generic entry will depend on whether
treatment of MS involves immunomodulation or viral disease (since it is
self-evidently neither cancer or a tumor). In this regard the scientific literature is littered with
reports linking MS with a variety of viral infections (including Epstein-Barr
virus and measles virus), but no definitive linkage has been established. While MS treatment is likely to involve some type of immunomodulation, Biogen Idec would have the burden of establishing such a mechanism should they sue an ANDA filer for infringement.
The importance of the question about the scope of this patent, and its effects on generic competition over Avonex® can be appreciated from the sales figures for the drug in the second quarter of 2009, which amount to almost $600 million (or $2.4 billion per year), according to an Associated Press article cited in Forbes magazine.
As the Forbes article suggests, the outcome of the Avonex® patent regime has relevance to the current follow-on biologics legislation, at least because of the emotional appeal regarding the length of patent protection. Understanding the history of this patent defuses any apprehension about the likelihood of similar outcomes going forward, and the Avonex® patent estate can be seen to be nothing more than a historical accident that cannot be replicated. However, the tendency for dissatisfaction with outcomes like this one to guide political activity, and legislation, should not be underestimated.