As of July 20 2017 there had been at least 363 inter partes review petitions filed against patents that were listed in the Food and Drug Administration's (FDA) Orange Book and 74 filed against patents that have been identified as reading on FDA Purple Book Centre for Drug Evaluation and Research (CDER)-listed biologic drugs. Of these 437 drug patent inter partes reviews, 116 resulted in a final written decision. There are a number of lessons to be learned from these final written decisions; this update highlights five of the most interesting.
First, 85% of the 116 final written decisions concerned drug patents that had also been challenged in federal district court litigation. What is interesting, although perhaps not surprising, is that the majority of the final written decisions on litigated drug patents concerned Orange Book-listed patents. Of the 103 final written decisions on Orange Book patents, 94% concerned patents that had been challenged in litigation. The numbers for CDER-listed biologic drug patents are much lower: there were only 13 final written decisions on biologic drug patents, 15% of which concerned patents that had also been challenged in litigation. These lower numbers for biologic drug patents may be unsurprising for a number of reasons:
- Far fewer biologic drug patents have been challenged to date, both in litigation and in inter partes reviews;
- There are far fewer FDA-approved biosimilar drugs than there are generic versions of Orange Book-listed reference drugs; and
- The Biologics Price Competition and Innovation Act 2009 "patent dance" (42 USC Section 262(l)) provides a convenient procedure, in advance of a market launch, to litigate a narrow subset of biologic drug patents, perhaps reducing the value of pre-emptive inter partes review challenges.
Second, in the 116 drug patent final written decisions analysed, the Patent Trial and Appeal Board (PTAB) found:
- all instituted claims unpatentable in 64 decisions (55%);
- some instituted claims unpatentable and some patentable in two decisions (2%); and
- all instituted claims patentable in the remaining 50 (43%) of these final written decisions.
In other words, if a drug patent inter partes review reaches a final written decision, it is likely that at least some of the challenged claims will be found unpatentable. To succeed in an inter partes review, a petitioner must show that the challenged patent claims are unpatentable by a preponderance of the evidence. This is a lower standard than the clear and convincing standard used in litigation, and may – at least in part – explain the relatively high rate at which patents, across all technologies, are being found unpatentable in inter partes reviews. Other reasons include the broader claim construction standard (broadest reasonable interpretation) used in inter partes reviews, and the restricted ability to amend claims in inter partes reviews to avoid prior art.
Third, 62% of the 116 final written decisions analysed were duplicative (ie, final written decisions issued on drug patents that were also the subject of at least one other final written decision, whether or not through joinder). One of these duplicative sets of final written decisions concerned a biologic drug patent – a patent that was identified as reading on Humira – and the remaining 30 duplicative sets concerned various Orange Book-listed patents. In all of these duplicative sets, either all instituted claims were found unpatentable or all instituted claims were found patentable. Further, all of these determinations were made on grounds of obviousness, and in each case the petitioner relied on at least one prior art patent or reference that had been cited during prosecution.(1) A patent claim is deemed unpatentable as obvious if the differences between the subject matter of the challenged claim and the prior art are such that the subject matter of the claim, as a whole, would have been obvious to a person of ordinary skill in the art at the time that the invention was made. Where an obviousness challenge rests on multiple prior art references, the challenger must show that there was a motivation or reason that would have prompted a person of ordinary skill in the art to combine the various teachings of these references in the way that the claimed invention does. A challenger must also show that a person of ordinary skill in the art would have had a reasonable expectation of success when combining such elements. Obviousness is determined by looking at various factors, including:
- the scope and content of the prior art;
- the differences between the subject matter of the challenged patent claims and the prior art;
- the level of skill in the art; and
- objective evidence of non-obviousness (eg, unexpected results, long-felt unmet need, industry praise and commercial success).
All instituted claims were found unpatentable in several sets of final written decisions concerning patents that are Orange Book-listed for at least the following drugs:
- Pomalyst; and
- the CDER Purple Book-listed drug Humira.
All instituted claims were found patentable in sets of final written decisions concerning patents that are Orange Book-listed for at least Gralise and Prolensa. The final written decisions concerning Prolensa are particularly interesting because they highlight the importance and value of objective evidence in the non-obviousness analysis. In March and April 2015 various InnoPharma and Mylan companies, and various Lupin companies filed two inter partes reviews (IPR2015-00902 and 01099 respectively), challenging all 30 claims of US Patent 8,669,290 (the '290 patent) as obvious, based on one prior art patent that was cited during prosecution and one new prior art patent in each of the two inter partes reviews. The '290 patent concerns aqueous liquid preparations for ophthalmic administration, consisting of two components: bromfenac (or its salts or hydrates) (a non-steroidal anti-inflammatory drug (NSAID)) and tyloxapol (which stabilises the bromfenac component). Oral hearings were held in April and June 2016 before the same panel of PTAB judges, and final written decisions were issued in July and September 2016. In both inter partes reviews, the PTAB found that the prior art patent listed on the face of the '290 patent disclosed every limitation of claim 1, except for one limitation that was supplied by the newly cited prior art references: the use of a specific concentration of tyloxapol instead of polysorbate 80. The PTAB found, based on the evidence in the record, that a person of ordinary skill in the art would have known that polysorbate 80 and tyloxapol could be substituted successfully and predictably, because these compounds had previously been used interchangeably in ophthalmic formulations. The PTAB also found that this known interchangeability was sufficient to establish a prima facie case of obviousness, even in the absence of an express suggestion to use tyloxapol. Applying (in IPR2015-00902) the recent Federal Circuit decision in WBIP, LLC v Kohler Co, 829 F3d 1317, 1328 (Fed Cir 2016) – which rejected the proposition "that objective considerations of non-obviousness can never overcome a strong prima facie case of obviousness" – the PTAB then considered the patent owner's evidence of unexpected results, commercial success and industry acclaim. The PTAB found that:
- substituting polysorbate 80 for tyloxapol had the surprising and unexpected result of a significant improvement in the stability of bromfenac;
- the claimed inventions were embodied in Prolensa, and Prolensa was commercially successful – at least in part – because tyloxapol lowered the pH to close to that of natural tears, so Prolensa lacked the burning and stinging side effects of other treatments; and
- Prolensa had received significant industry acclaim based on benefits flowing from the use of tyloxapol.
In short, on the preponderance of the evidence, this objective evidence tipped the balance in the patent owner's favour.
Fourth, comparing the outcome when a drug patent was challenged in only one final written decision to that when a drug patent was challenged in two or more final written decisions, based on a dataset of 116 final written decisions, claims of drug patents facing multiple challenges were much more likely to be found unpatentable. Combining all duplicative final written decisions on drug patents as of July 20, 2017 – joined and not joined – the PTAB found all instituted claims unpatentable in 45 (63%) and all instituted claims patentable in 27 (38%) of these final written decisions. The equivalent numbers for drug patents challenged in only one final written decision were:
- 19 (43%) (all instituted claims unpatentable);
- two (5%) (some instituted claims patentable, some unpatentable); and
- 23 (52%) (all instituted claims patentable).
In other words, challenged claims of drug patents are 20% more likely to be found unpatentable when there have been multiple final written decisions on the same patent. This difference seems significant – although it may be a result of the strength of the challenged patents themselves rather than a 'second bite of the apple' being more successful.
Finally, focusing specifically on final written decisions concerning biologic drug patents – of which there were at least 13 as of July 20 2017 – the PTAB found all claims unpatentable in 10 (77%) and all claims patentable in the remaining three (23%) of these biologic drug patent final written decisions. While this is a small dataset, the outcome of these final written decisions is markedly different from that for Orange Book-listed patents. The comparative numbers for Orange Book patent final written decisions were as follows:
- All instituted claims were found unpatentable in 54 (52% of) final written decisions;
- At least some instituted claims were found unpatentable in two (2% of) final written decisions; and
- All instituted claims were found not unpatentable in 47 (46% of) final written decisions.
In short, if an inter partes review challenge to a biologic drug patent reaches a final written decision, the odds are significantly higher that all challenged claims will be found unpatentable. It will be interesting to see if this trend continues or changes as the Biologic Drug Patent final written decision dataset becomes larger.
In conclusion, the biggest takeaways from the 116 drug patent final written decisions analysed are as follows:
- The vast majority of these final written decisions concerned patents that had also been litigated, and also concerned patents that had been challenged in at least one other inter partes review.
- If an inter partes review challenge to a drug patent reaches a final written decision, it is likely that at least some instituted claims will be found unpatentable – and this risk may be higher for biologic drug patents based on the current limited dataset (n=13).
- Finally, robust objective evidence remains an important tool in overcoming obviousness challenges.
This article was first published by the International Law Office, a premium online legal update service for major companies and law firms worldwide. Register for a free subscription.
For further information on this topic please contact Corinne E Atton or Ha Kung Wong at Fitzpatrick, Cella, Harper & Scinto by telephone (+1 212 218 2100) or email (firstname.lastname@example.org or email@example.com). The Fitzpatrick, Cella, Harper & Scinto biologics group website can be accessed at www.BiologicsHQ.com.