Buprenorphine - Norway

On Sep 08, 2017, Oslo District Court of Norway issued a decision in buprenorphine transdermal patch case & found patents-in-suit invalid under lack of inventive step.

The case concerns the validity of the Norwegian patents NO 334290 (NO’290), NO 332248 (NO’248), & alternative sets of claims A and B, and NO 333139 (NO’139). The defendant, Mundipharma AS (Mundipharma), is the holder of the patents-in-suit in the case. One of Mundipharma's products is a transdermal patch for the administration of buprenorphine over a period of seven days. The transdermal patch marketed by the above companies has the commercial name of Norspan in Norway, while in certain other countries it is marketed under the commercial name of BuTrans.

The plaintiff, Orifarm Generics A/S, Orifarm Generics AS and Orifarm AS (Orifarm) is the holder of three marketing authorisations for a transdermal patch containing buprenorphine under the trade name of Buprefarm. The marketing authorisations encompass three products of different strengths; 5 micrograms/hour, 10 micrograms/hour and 20 micrograms/hour, respectively. On the basis of their marketing authorisations, Orifarm planned to enter the Norwegian market with Buprefarm. On 17 June 2016 Mundipharma petitioned for an interim injunction to stop Orifarm's sale of Buprefarm. On 20 June 2016, Oslo Court of Execution and Enforcement issued a ruling whereby the petition was accepted. On 19 August 2016, Orifarm issued a writ of summons before Oslo District Court, with the prayer for relief that all three patents should be declared invalid and that Mundipharma should be ordered to pay compensation for the loss Orifarm suffered as a consequence of the interim injunction. The main hearing in the case was held from 19 to 28 April 2017.

All three of the patents-in-suit concern a transdermal delivery device that includes buprenorphine for the treatment of pain. A shared feature of the patents is that they according to the patent description make it possible to produce a medicament that enables reduced plasma concentrations of buprenorphine over a longer period of time than what is possible according to prior art, while at the same time causing effective pain relief. Orifarm submits that all of the patents-in-suit are invalid. None of the patents-in-suit fulfill the requirement of inventive step and do thus not fulfill the requirements of section 2 of the Patents Act. The ground for patent for all of the patent claims is the dosing time period described in claim 1 of the patents. At the priority date, it is obvious to the skilled person to use transdermal delivery devices for buprenorphine as described in the patents for both 5 and 7 days, and the skilled person would have had a reasonable expectation of success.

Court defined technical problem as obtaining a more convenient and effective pain relief/pain treatment by means of the transdermal administration of buprenorphine. Court further held that it can be seen from the referenced literature that the patent concerns a problem of a nature that those skilled in the art were generally focused on solving. A dosage interval of one week was considered an advantage, both to make the medicinal product user friendly and economical to use. Other advantages are also described, like constant plasma values over an extended period of time, which would lead to fewer side effects. With respect to the reasonable expectation of success there are no indications to suggest that it will not work. In the literature there are also suggestions that one might simply increase the amount of active ingredient, possibly also adjuvants in the same proportion, to obtain a longer period of effect. It will only be by trying that the skilled person will be able to find any possible adjustments that must be made to the formulation to obtain an extended duration, but the Court finds it clear that the skilled person would have done this with a reasonable expectation of success.

Finally court held that based on an overall assessment to the skilled person it was obvious to solve the problem of finding a more effective and suitable transdermal administration of buprenorphine by choosing the solutions indicated in the patent. Thus Patents NO334290, NO332248, including the alternative sets of claims A and B, and NO 333139, are ruled invalid.

Testosterone – USA

On Nov 22, 2017, the Federal Circuit upheld a district court’s decision finding one patent for Axiron (testosterone solution) invalid in Perrigo, Actavis & Lupin case & other patent valid & infringed in cross appeal by Amneal.

This litigation relates to Abbreviated New Drug Applications filed by the defendants for generic equivalents of Eli Lilly’s Axiron® testosterone applicator. Eli Lilly, in turn, sued the defendants for patent infringement. After a nine-day bench trial, the district court issued a thorough, well-considered opinion over 200 pages long. Eli Lilly appeals the district court’s opinion that claim 20 of U.S. Patent No. 8,435,944 (the ’944 patent) is invalid for obviousness under 35 U.S.C. § 103. Claim 20 of the ’944 patent recites a transdermal delivery method of applying testosterone to the axilla of a patient. Amneal cross-appeals the district court’s opinion that claims 9 and 10 of U.S. Patent No. 8,807,861 (the ’861 patent) are (1) not invalid; and (2) infringed by Amneal’s applicator.

The ’944 Patent:

Federal circuit agreed with the district court that the prior art (e.g. the Aschkenasy ’268 publication and the Cutter 2000 and 2001 references) teach and suggest that applying testosterone to the axilla will increase a patient’s testosterone level with a reasonable expectation of success. Eli Lilly’s arguments against those references lack merit and/or are based on a misreading of the lower court’s opinion. Eli Lilly argued that the prior art teaches away from applying testosterone to the axilla due to concerns over causing an undesired elevated level of dihydrotestosterone (DHT); and the claimed method yielded unexpected results. As the district court noted, Eli Lilly’s teaching away theory rested on a position that the scrotal skin and the axilla have comparably high 5-alpha reductase activity, which can result in an elevated DHT level. But Lilly’s reference to support that assertion, Takayasu, did not include measurements from the scrotal area in its study. Thus, even if the prior art sought to avoid areas that had the same level of 5-alpha reductase activity as scrotal skin, Lilly did not present any evidence that the axilla and scrotal skin have comparably high activity. Thus, the district court correctly found, on this record, that the only teaching relating to DHT levels in the axilla was by Cutter, which reported a normal DHT level after application of testosterone to the axilla.

On unexpected results, Federal circuit held that Eli Lilly made no meaningful argument contesting the district court’s rejection of Lilly’s theory of unexpected results. On review, we see no error in the district court’s explanation that Lilly’s asserted ‘seven-fold increase’ in skin permeability was based on a flawed extrapolation of data reported in a prior art reference. In sum, the lower court correctly found that Lilly’s objective indicia lacked weight. As a result federal circuit uphold the district court’s judgment of invalidity.

The ’861 Patent:

Claims 9 and 10 of the ’861 patent are directed to an applicator with a “resiliently deformable wall” used to administer a testosterone solution to the axilla. Federal circuit detected no error in the district court’s conclusions that the claims, as construed, are not invalid over the asserted prior art (e.g. Gueret ’187 and Gueret ’986) and were infringed by Amneal’s applicator. As to Amneal’s argument that its applicator does not infringe because it does not deform in a “blade-like manner,” the phrase “blade-like manner” appears nowhere in the claims and appears only in the context of a specific embodiment in the specification. Thus, federal circuit agreed with the district court that the claims require only that the applicator wall be “resiliently deformable” and do not require a specific mode of resilient deformation.

Federal circuit finally considering entire appellant’s and cross-appellant’s other arguments affirmed the district court's decision.

Teduglutide - USA

On Nov 15, 2017, Court of appeal for the federal circuit in a non-precedential opinion affirmed the decision of paten trial & appellate board (PTAB) which found formulation patent of Teduglutide (Gattex) invalid. Previously PTAB found NPS pharmaceutical’s U.S. Patent Number 7,056,886 invalid under obviousness in two IPR proceedings (IPR2015-00990 & IPR2015-01093).

US’886 claims GLP-2 (teduglutide) composition with histidine, phosphate buffer &  mannitol /sucrose. PTAB in its decision held that use of histidine & mannitol was well known in protein formulation and experimentation needed to confirm successful application with GLP-2 analog was nothing more than routine practice.

Treprostinil - USA

On Nov 14, 2017, Court of appeal for the federal circuit in a non-precedential opinion affirmed the decision of paten trial & appellate board (PTAB) which found product by process patent of Treprostinil (Remodulin) invalid. In Mar 2017, PTAB found UTC’s U.S. Patent Number 8,497,393 invalid for lack of novelty and obviousness in IPR proceeding (IPR2016-00006) filed by SteadyMed.

PTAB in its decision on novelty held that US’393 patent claims are product by process claims and prior art “Phares” discloses every element of the claims. UTC argued that prior art compound and instant compound are different in terms of purity. However, PTAB held that compound was known and process claims do not add any significant structural or functional characteristics to the claims. Moreover, difference in impurity is because of other factors such as time, solvent used during process of preparation. Therefore, Treprostinil was disclosed in prior art & process steps do not confer novelty to the claims. Hence, claims lack novelty over prior art.

With respect to obviousness, PTAB held that it was obvious to modify “Moriarty” prior art which discloses steps a & b of US’393 patent in view of “Phares” which discloses step c.  Person skilled in that art would have motivated to do so with reasonable expectation of success because by adding ethanolamine to tresprostinil one would eliminate the unnecessary step of purification.

Lacosamide - UK

On Nov 07, 2017, England and Wales High Court (Patents Court) rejected Accord’s invalidity argument & found Lacosamde compound patent valid.

The patent in suit is EP (UK) 0888289, which covers an anti-epileptic drug called lacosamide. The patent expired on 18th March 2017.  There is a supplementary protection certificate (SPC/GB09/007) which extends protection for lacosamide until 2022. Accord contended that the patent is invalid on two grounds viz. lack of priority & obviousness.

With respect to lack of priority, Accord challenged the patentee’s legal entitlement to claim priority from the 1996 priority document.  Accord contended that the assignment of 4^th February 1997 from Prof. Kohn (inventor) to RCT (patent holder) only took effect as an assignment of the bare legal title to the invention and priority claim.  What it did not do was assign the equitable or beneficial title to that property to RCT.  Court after analysing the relevant case laws held that all the indications available to RCT were that the university was aware of what was going on and that Professor Kohn was executing the assignment because he was obliged to do so pursuant to his obligations to the university.  Those indications do not only derive from Professor Kohn but also from the university itself. Court found that on 4^th February 1997 RCT was not on notice of any possible conflicting interest held by the university.  Therefore, RCT acquired good title to the invention including any priority right. 

Accord’s second challenge was on obviousness.  It was based on the state of the art before the priority date, which included a number of papers and other publications from Prof Kohn’s group relating to their work on anticonvulsant compounds.  Accord relies on mainly master’s thesis by a student called Philipe Le Gall. It is entitled 2-Substituted-2-acetamido-N-benzylacetamides Synthesis. Accord argued that given the Le Gall thesis in 1996, the first thing the skilled team would do is a literature search & identification few lead compounds such as LY274959. Court however disagreed & held that the skilled team would not predict that an aliphatic compound mentioned in arts would have good activity. That was because so much of the data related to aromatic rather than aliphatic compounds. Court finally held that putting it all another way, there are just too many uncertainties to justify a finding of obviousness.  Even if the team got as far as deciding to make and test lead compound they would know that the uncertainties meant that either outcome, good or bad, could just as easily be rationalised after the event as the other.  That is not a fair prospect of success.

Ribavirin - Netherlands

On Nov 03, 2017, Supreme Court of the Netherlands reversed the decision of Hague Court of Justice & found Teva’s label indirectly infringing the second medical use patent in Ribavirin case.

MSD is the holder of European Patent EP0956861. Claim 1 relates to use of ribavirin for the preparation of a pharmaceutical composition for the treatment of a patient with chronic hepatitis C infection, together with an active amount of alpha interferon wherein the subject is an anti-viral treatment naive patient with an HCV genotype 1 infection. MSD releases capsules and tablets according to EP’861 on the market under the trade names 'Rebetol' and 'Copegus', respectively. In June or October 2011, Teva introduced its generic ribavirin tablets on the Dutch market. MSD sought declaration of right that Teva generic products fall within the scope of EP 861, and claimed damages for state or profit. Teva counterclaimed in reconciliation (among other things) a declaration of non-infringement of the Dutch part of EP 861, and subject to the assumption of infringement, the destruction of the patent for the Dutch part.

Lower court held that Teva does not infringe the Dutch part of EP 861 as no acts of Teva fall within the scope of the claimed Swiss-type claims. Teva has adequately managed to ensure that it is out of scope for the Swiss-type claims of the patent by a so-called 'carve-out'. Teva has excluded the MSD-claimed patient category (naive and genotype 1 infection). That is enough to fall outside the scope of the patent. Based on the mentioned SmPCs and leaflets, therefore, there is no direct or indirect patent infringement by Teva, whether or not doctors or pharmacists prescribe Teva’s generic ribavirin (treatment of the G1N subgroup) and whether naive genotype 1 patients use that drug. In its action against unlawful action, MSD has not found any other facts than its claims for direct and indirect patent infringement. Merck appealed.

Supreme Court assumed that indirect infringement of a Swiss-type claim is conceivable. According to Art. 73 if a person offers or supplies resources for the use of the patented invention in or for his business, provided that person knows or is aware of the circumstances are clear that those means for that application are appropriate and intended. Court finally held that the manufacturer of a generic drug may indirectly infringe a patent for a second medical indication, namely if he offers or supplies the medicine to persons not entitled to use the invention and he know whether it is clear to him that the medicine is suitable and will be used for the patented second medical indication. Thus Supreme Court reversed the decision of Hague Court of Justice & referred the case for further consideration & decision.

Dronedarone – USA

On Nov 09, 2017, Court of Appeal for Federal Circuit affirmed the district court’s judgment of infringement & validity of two patents against Watson & Sandoz in Multaq (Dornedarone) case.

Sanofi owns U.S. Patent Nos. 8,318,800 and 8,410,167, which describe and claim compositions and uses of the cardiovascular (specifically, antiarrhythmic) drug dronedarone. The ’800 patent, which expires in 2019, claims pharmaceutical compositions containing dronedarone. The ’167 patent, which expires in 2029, claims methods of reducing hospitalization by administering dronedarone to patients having specified characteristics. After a three-day bench trial, the district court ruled that Watson’s and Sandoz’s sale of their proposed generic drugs, with their proposed labels, would induce physicians to infringe asserted claims and they did not prove that any of the asserted claims were invalid for obviousness. Watson and Sandoz appealed.

Federal circuit reviewed the district court’s finding of inducement based on encouragement and inferred intent for clear error. Federal circuit did not find error. It held that the reference to the Clinical Studies section (14) of the label expressly directs the reader to that section for elaboration of the class of patients for whom the drug is indicated to achieve the stated objective, i.e., reduced hospitalization. Section 14 leads with and features a subsection on the ATHENA study, which sets forth the positive results, relating to reduced hospitalization, for patients having the risk factors. There was considerable testimony that this label encourages—and would be known by Watson and Sandoz to encourage—administration of the drug to those patients, thereby causing infringement.

With respect to obviousness, Watson and Sandoz initially argued that the district court committed legal error by applying too high a standard for proving a reasonable expectation of success. Federal circuit however disagreed. Federal circuit held that Watson and Sandoz did not carry their burden of showing that a person of ordinary skill in the art in February 2008 would have had a reasonable expectation that dronedarone would succeed in reducing cardiovascular hospitalization in the ATHENA patient population.

Budesonide - USA

On Oct. 27, 2017, Chief Judge Leonard P. Stark of district of Delaware issued an order granting Defendants' (Teva & Alvogen) motions for judgment of non-infringement of the US 8,784,888 patent in Uceris (Budesonide ER tablet) case. Claim 1 of US’888 patent reads:

“A controlled release oral pharmaceutical composition consisting essentially of: (1) a tablet core consisting essentially of: a) budesonide in an amount effective to treat intestinal inflammatory disease; and b) a macroscopically homogeneous composition comprising at least one lipophilic excipient, at least one amphiphilic excipient, and at least one hydrogel-forming hydrophilic excipient other than a gum, wherein said budesonide is dispersed in said macroscopically homogeneous composition; and (2) a coating on said tablet core, said coating consisting essentially of a gastro-resistant film”.

Cosmo filed suit against Actavis/ Teva and Alvogen in February 2015, after the companies sent notice with P-IV certification that their products would not infringe US’888 patent & other patents. Plaintiffs at one time asserted a number of patents and decided to drop patents at various stages of this litigation. Bench trial was completed on May 23, 2017. Court found that Plaintiffs did not meet the threshold to establish infringement. As the opinion was sealed, the court asked parties to sort out the final judgment, including other stipulations and orders about the other patents. Thereafter, the Court will issue a public version of its Memorandum Opinion.

Tadalafil - UK

On Nov. 01, 2017, the England and Wales Court of Appeal issued a decision in CIALIS (tadalafil) case & found that the patent for treatment of male erectile dysfunction is invalid for obviousness.

The patent, EP (UK) 1,173,181 relates to the use of tadalafil in a dosage form and is entitled "Compositions comprising phosphodiesterase inhibitors for the treatment of sexual dysfunction". The claimants, Actavis, Teva and Mylan, began these proceedings to revoke the EP’181 patent on various grounds and so clear the way for the marketing of their own products. Birss J handed down judgment on Aug 10, 2016 ([2016] EWHC 1955 (Pat)) where he found that patent is valid & infringed by claimants. Claimant appealed.

Three claims were at issue, namely claims 1, 7 and 10. Claims relate to pharmaceutical unit dosage composition comprising 1 to 5mg of tadalafil wherein maximum total daily dose is 5 mg per day for treatment sexual dysfunction. Critical issues before the court of appeal were whether the subject matter of each of claims 7 and 10 was derivable directly and unambiguously, using common general knowledge from the priority document & whether there was enablement. Court of appeal held that skilled person would not have had any difficulty making the compositions the subject of claims 7 and 10 based on disclosure of the priority document. With respect to added matter & novelty court of appeal agreed with Judge Birss J and held that patent is novel & there is no added matter.

Obviousness:

Primary reference, Daugan teaches the use of PDE5 inhibitors for the treatment of ED. Tadalafil (compound A) is specifically disclosed, its IC50 against PDE5 is given and examples of a tablet containing a 50mg dose are described. It explains that doses of tadalafil will generally be in the range of from 0.5 to 800mg daily for the average adult patient.  The differences between the disclosure of Daugan and the subject matter of claims 7 and 10 are that Daugan does not specifically disclose a 5mg daily dose of tadalafil or that such a dose is an effective treatment for sexual dysfunction.

Court held that at the start of the programme and given Daugan, the skilled team would have had no idea whether or not a 5mg daily dose of tadalafil would be a safe, tolerable and effective treatment of sexual dysfunction, still less that it would be both efficacious and have minimal PDE5 related side effects. Summarizing the position in relation to the skilled team's expectations, Judge Bliss J found that they would not have a reasonable expectation that a dose of 5mg per day (on demand) would provide a useful treatment for ED, nor any expectation at all that this would produce a clinically relevant effect but with minimal side effects. However, they would discover that this dose is both effective and has reduced side effects and this would be a surprise.

Court of appeal overturning the decision held that the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials' process. The skilled but non-inventive team would embark on that process with a reasonable expectation of success and in the course of it they would carry out Phase IIb dose ranging studies with the aim of finding out, among other things, the dose response relationship. It is very likely that in so doing they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention. Therefore claims 7 and 10 of EP’181 are invalid.

Pemetrexed - Europe

The dispute all over Europe is basically related to Eli Lilly’s European patent EP1313508 B1 (“EP ‘508”) entitled “Combination containing an antifolate and methylmalonic acid lowering agent”.  The EP’508 patent protects the drug marketed by Eli Lilly under brand name “ALIMTA” (Pemetrexed disodium). Generic filers have sought declaration of non-infringement with respect to their product which utilizes salt other than disodium.

Herein below is the quick snapshot of recent proceedings/decisions in major countries across Europe.

Netherlands: By judgment of 24 October 2017, the PI judge of District Court of the Hague held that Fresenius and Teva’s  generic drug with pemetrexed diacid infringes EP’508 patent.

Switzerland: By judgment of 20 October 2017, The Swiss Federal Supreme court overturned the previous declaratory judgment of non-infringement of the Swiss Federal Patent Court and found Actavis’ generic pemetrexed diacid product, Amtiris, to directly infringe Eli Lilly’s patent E’508.

Italy: By judgment of 10 September 2017, The Milan court ruled that Fresenius, with its pemetrexed product, does not infringe EP’508.

United Kingdom:  By judgment of 12 July 2017, The UK Supreme Court has ruled that the scope of EP’508 patent extends to other salts than pemetrexed disodium, so that the pemetrexed products mentioned by Actavis directly infringes EP’508.

Germany: By judgment of 14 June 2016, The Federal Court of Justice (Bundesgerichtshof – BGH) referred the case back to the Oberlandesgericht Düsseldorf, since BGH held that the Oberlandesgericht (which found non-infringement of pemetrexed dipotassium) had not properly applied the German equivalent theory. The case is pending before Oberlandesgericht Düsseldorf court.

Portugal, Sweden and Finland:  Lilly and Actavis also have procedures in Portugal, Sweden and Finland. None of these matters have yet been decided.

Vardenafil – USA

On Nov. 01, 2017, Federal circuit reversed the Delaware court’s decision of non-obviousness in Staxyn® (Vardenafil) & found that Bayer’s patent is invalid as obvious handing a win to generics maker Teva (Actavis). Federal circuit held that Delaware federal judge “clearly erred” when he found that the patent was not invalid.

Watson Laboratories, Inc. appealed the District of Delaware’s final judgment holding Watson failed to prove by clear and convincing evidence that claims 9 and 11 of U.S. Patent No. 8,613,950 (“the ’950 patent”) would have been obvious. The US’950 patent is directed to a formulation of vardenafil “in the form of an uncoated tablet which disintegrates rapidly in the mouth comprising vardenafil hydrochloride trihydrate, and at least two sugar alcohols.” Two sugar alcohols are a mixture of sorbitol and mannitol.  The parties agree that claim 8’s requirement that the formulation “releases the drug in the mouth” means it is an immediate-release formulation.

The district court held a six-day bench trial to consider the validity of the ’950 patent. Watson argued the claimed formulation of vardenafil would have been obvious to a person of ordinary skill in the art based on multiple exemplary references showing a motivation to: (1) create an ODT formulation of vardenafil; (2) select mannitol and sorbitol as sugar alcohols; and (3) make the ODT formulation immediate-release. The district court rejected each of Watson’s arguments. It found a person of ordinary skill in the art would not have been motivated to create an ODT formulation of vardenafil and would not have used mannitol and sorbitol as excipients. It found the prior art taught away from formulating vardenafil ODT as immediate-release. The district court also addressed Bayer’s objective evidence of nonobviousness and found it supported its conclusion that Watson failed to prove by clear and convincing evidence that claims 9 and 11 would have been obvious. This determination rested largely on the court’s finding the testimony of Bayer’s expert, Dr. Wicks, more persuasive than the testimony of Watson’s expert, Dr. Jacobs.

Federal circuit on appeal said that the clear error in the district court fact finding that there was no motivation to formulate ED drugs in ODTs & that the record did not contain an indication that ED drugs would be good candidates for ODT formulations. Watson relied on nine prior art references to support its assertion that there would have been a motivation to create an ODT formulation of vardenafil. Dr. Jacobs testified that the Chang reference states “drugs for [ED] would be good candidates for ODT formulation.” He testified the Boolell and Fryburg references each disclose formulating vardenafil as an ODT. He testified that numerous companies had already begun formulating ODT versions of ED drugs: Pfizer filed the Bell-Huff patent application directed to sildenafil ODT; Eisai filed the Furitsu patent application claiming an ODT formulation of phosphodiesterase inhibitors; and Lavipharm filed the Chen international patent application, identifying ODT versions of sildenafil. These six references—Chang, Boolell, Fryburg, BellHuff, Furitsu, and Chen—are absent from the district court’s decision. These references are highly relevant to whether a person of ordinary skill in the art would have been motivated to formulate ODT vardenafil. And their express disclosures cause the district court fact finding regarding motivation to combine to be clear error.

Bayer argued that Watson’s arguments concerning many of its references, such as Chang, Boolell, and Fryburg, were insignificant and the district court did not clearly err by failing to address them. It argued that while Watson asserted on appeal that the district court ignored its key prior art, Watson flooded the district court with references without adequately addressing them. Federal circuit however disagreed. Court held that while it may at times be unwise for a party to rely on numerous prior art references when challenging a patent on obviousness grounds, Watson’s approach were not untenable here. Watson produced these nine references to support a narrow point: they each “disclosed formulating vardenafil and other approved ED drugs into ODTs.” Also Dr. Wicks’ testimony does not cast doubt on the weight of Watson’s evidence regarding the vardenafil ODT limitation. Many of the references Watson relied on for this limitation were unchallenged by Dr. Wicks. Therefore the district court’s finding that ODTs were not considered applicable to ED drugs is clearly erroneous in light of Watson’s evidence.

The remainder of the district court’s findings underlying the motivation to formulate vardenafil ODT focused too heavily on the commercial availability of ODT formulations of ED drugs as of the ’950 patent’s priority date. It is unclear why the district court found it important that no ODT ED drug had gained FDA approval as of ’950 patent’s priority date. The motivation to combine inquiry is not limited to what products are forthcoming or currently available on the market. Particularly given the lengthy FDA approval process, the pharmaceutical industry is no exception. Any motivation, “whether articulated in the references themselves or supported by evidence of the knowledge of a skilled artisan, is sufficient.” Here, the motivation to formulate an ODT version of vardenafil is plainly evident from the face of multiple prior art references disclosing ODT formulations of ED drugs. No further rationale for developing vardenafil ODT was necessary. Therefore here also district court clearly erred when it found there would not have been a motivation to formulate vardenafil ODT.

With respect to combination of mannitol & sorbitol in a formulation District court found Dr. Wicks’ testimony persuasive that “every ODT on the market in the relevant prior art time frame contained only a single sugar alcohol: mannitol,” and that “there were no known problems with the use of mannitol in the existing ODTs.” It found “there was nothing in the prior art that would have given the [person of ordinary skill in the art] a reason to use sorbitol in addition to mannitol in an ODT. Federal circuit held that we do not question the district court’s credibility determinations. However, the district court’s analysis for the sorbitol and mannitol limitation again focused on the commercial availability of products while failing to address relevant prior art. Upon consideration of the entire record and under a proper analysis, we conclude that the district court clearly erred in finding a person of ordinary skill in the art would not have been motivated to formulate an ODT with sorbitol and mannitol.

Federal circuit further held that the district court did not clearly err in its fact finding that a person of ordinary skill in the art would have had concerns using an immediate-release formulation due to vardenafil’s expected bitter taste and bioavailability; however, it clearly erred when it concluded that those findings taught away from the immediate release. The fact that there may be reasons a skilled artisan would prefer one over the other does not amount to a teaching away from the lesser preferred but still workable option. The district court’s finding that a person of ordinary skill in the art would have first pursued a delayed-release formulation over an immediate-release formulation is insufficient to support a finding of teaching away.

Federal circuit held that Bayer presented evidence of copying and unexpected results that weigh in favor of a conclusion of nonobviousness. But weighing all four Graham factors, court concluded that claims 9 and 11 of the ’950 patent would have been obvious & reversed the district court’s holding.