Biogen Int’l GmBH v. Mylan Pharmaceuticals Inc. (N.D.W. Va. 2020)


The written description requirement has had a twenty-five 12 months renaissance, notably within the chemical and biotechnology arts as a approach of proscribing declare scope to what an inventor has truly invented (see Regents of the University of California v. Eli Lilly & Co. and “Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.“).  In view of the unpredictability of those arts (in contrast with the mechanical arts; however see Tronzo v. Bionet and Gentry Gallery, Inc. v. Berkline Corp.), the identical proof that helps non-obviousness (as a result of expert employee not having the requisite cheap expectation of success) may also limit the scope of what has been described (as a result of there could be a lot much less reliance and supplementation of what the particular person of odd talent would know for disclosures that fail to fulfill the possession check of written description as a result of that unpredictability).  These conflicting rubrics have been a part of the District Court’s resolution final week that Biogen failed to offer ample written description in ANDA litigation styled Biogen Int’l GmBH v. Mylan Pharmaceuticals Inc.

The case arose over Mylan’s try to get regulatory approval and are available to market with a generic equal of Biogen’s Tecfidera® (dimethyl/monomethyl fumarate) a number of sclerosis drug.  Biogen asserted Orange Book-listed U.S. Patent Nos. 6,509,376; 7,320,999; 7,619,001; 7,803,840; 8,399,514; and eight,759,393, however the events dismissed their causes of motion on all patents besides the ‘514 patent, the place Biogen asserted claims 1-4, 6, 8-13, and 15-16; declare 1 is consultant:

1.  A way of treating a topic in want of remedy for a number of sclerosis comprising orally administering to the topic in want thereof a pharmaceutical composition consisting basically of (a) a therapeutically efficient quantity of dimethyl fumarate, monomethyl fumarate, or a mix thereof, and (b) a number of pharmaceutically acceptable excipients, whereby the therapeutically efficient quantity of dimethyl fumarate, monomethyl fumarate, or a mix thereof is about 480 mg per day.

While this litigation was continuing, Mylan efficiently petitioned the Patent Trial and Appeal Board to institute an inter partes assessment continuing, on the grounds that the asserted claims of the ‘514 patent have been apparent.  The Board issued a Final Written Decision that Mylan had not proven obviousness by a preponderance of the proof, and the District Court held that Mylan was collaterally estopped from asserting obviousness as a foundation for invalidating the ‘514 patent on this litigation.  Accordingly, the one floor Mylan pursued earlier than this Court was that the specification of the ‘514 patent didn’t fulfill the written description requirement of 35 U.S.C. § 112(a).

Mylan’s arguments on its written description protection have been grounded on sure traits of the ‘514 specification and its prosecution historical past.  The ‘514 patent mirrored Biogen’s extra basic analysis purpose of discovering therapies for neurological issues, together with however not restricted to a number of sclerosis (MS).  Mylan famous that the unique named inventor was not a clinician however moderately a analysis scientist investigating the mechanism of motion of the claimed compound.  Specifically, the analysis underlying the ‘514 patent disclosure confirmed that DMF might activate a specific metabolic pathway (the Nrf2 pathway).  One necessary consequence of this inventor’s testimony is that he “denied that his research could be extrapolated to a clinical dose of DMF; it ‘was never the focus of [his] work to inform the clinical dosing of [DMF].’”  This inventor, Dr. Lukashev, was the one named inventor on the earliest precedence purposes from which the ‘514 patent claimed precedence.

As initially filed, the claims of the appliance that matured into the ‘514 patent didn’t recite strategies of remedy however moderately have been drawn to strategies for figuring out compounds that affected the Nrf2 pathway.  However, in April 2011, Biogen obtained the outcomes of a Phase III medical examine exhibiting {that a} 480mg/day dose of DMF was efficient in treating MS (particularly).  Apparently in response, Biogen changed the then-pending claims with claims that finally issued, modified the title of the appliance, and added as an inventor the scientist who posited that this dosage could be notably efficient as an MS remedy; considerably to the written description calculus Biogen didn’t complement its specification which permitted it to depend on a February 8, 2007 earliest precedence date.  In addition, Biogen filed a stand-alone provisional software expressly directed to MS remedy with 480mg/day of DMF.  Biogen subsequently deserted this software when the ‘514 patent was allowed.

Mylan’s argument was easy:  the invention described within the specification filed in 2007 “bears no resemblance to the invention claimed in 2011.”  Mylan supported this assertion with two arguments.  First,  Mylan argued that “a POSA [person of skill in the art] would not have expected the claimed invention—a 480mg/day dose of DMF (BID)—to effectively treat MS” and “that nothing in the specification of the ‘514 Patent teaches otherwise.”  Second, Mylan argued that “when viewed as an integrated whole, the combination of selectively-plucked disclosures in the specification of the ‘514 Patent fails to sufficiently describe the claimed invention—a method of treating MS with a therapeutically effective amount of DMF, i.e., 480mg/day of DMF (BID).”  According to Mylan, the explanation for this case is that “Biogen grafted the ‘514 claims onto a specification written to cover an entirely different set of inventions, conceived of by an entirely different inventor, and filed more than four years before Biogen’s 2011 Phase III trial results demonstrated the effectiveness of the 480[mg/day] dose.”

Biogen, for its half, asserted that Mylan was counting on arguments it had asserted for obviousness, and that the ‘514 specification contained categorical disclosure — in Method Four supplied in an Example — that linked every of those three recited components of the claims (“(1) a method of treating MS with (2) DMF and/or MMF (3) at a dose of 480 mg per day”) in a approach adequate to fulfill the written description requirement.[1]

The District Court held that the ‘514 specification didn’t present that the inventors possessed the invention on its earliest claimed precedence date.  The Court famous that, though the ‘514 specification “[s]pan[s] 30 columns,” with the primary column specializing in MS, the specification is then directed to disclosure of “how ‘the Nrf2 pathway may be activated in neurodegenerative and neuroinflammatory diseases as an endogenous protective mechanism,’ and how ‘[e]merging evidence suggests that [plant-derived] compounds may exert their neuroprotective effects by activating cellular stress-response pathways, including the Nrf2 pathway, resulting in the upregulation of neuroprotective genes.”  As set forth within the Court’s opinion, the ‘514 specification discloses 5 strategies:

1) strategies of screening for not less than one new candidate compound for treating a neurological illness;2) strategies of evaluating neuroprotective properties of not less than one drug candidate for treating a neurological illness;3) strategies of evaluating (e.g., for bioequivalence) not less than two pharmaceutical compositions which comprise fumaric acid derivatives;4) strategies of treating a neurological illness by administering to the topic in want thereof not less than one compound that’s partially structurally much like DMF or MMF; and

5) strategies of treating a neurological illness by a mix remedy that contains administration of not less than one first compound that upregulates the Nrf2 pathway and not less than one second compound that doesn’t upregulate the Nrf2pathway.

Even Biogen conceded that Methods 1-Three have been directed to screening drug strategies and never therapeutic strategies, and Method 5 was restricted to mixture therapies utilizing DMF and different medication having totally different actions.  The solely disclosure regarding the claimed strategies was Method 4, which Biogen contended supplied the linkage between the weather of the asserted claims.  The opinion is blunt:  it says plainly “[t]his simply is not so.”  The Court understands this technique to “broadly describe[] treating neurological diseases with a therapeutically effective amount of DMF; MS is merely one such disease ‘among a slew of competing possibilities,’” citing Novozymes A/S v. DuPont Nutrition Biosciences APS by analogy in assist of the inadequacy of the ‘514 patent disclosure.  As additional indicia of the dearth of obligatory specificity of the ‘514 patent disclosure, the Court cites “an exhaustive list of ‘diseases suitable for the [five] methods described’ in the ‘514 Patent.”  In view of this itemizing of a “plethora of neurological diseases,” the Court held that there have been no blaze marks that may train the expert employee to deal with MS with DMF at this dosage.  The Court notably rejected Biogen’s competition that the specification would train the POSA that the ‘480 mg/day dosage was the popular dosage, crediting Mylan’s knowledgeable Dr. Greenberg’s testimony on this regard.  The Court notably centered on the truth that the specification mentions the 480mg/day dosage solely as soon as, as a part of a most popular vary (“from about 480 to about 720mg/day”).  The Court discovered “neither credible no persuasive” Biogen’s argument {that a} POSA would perceive that utilizing the bottom efficient dose of the narrowest vary was most popular.  The Court discovered it extra in line with what was identified on the time the appliance was filed that dosages of 720 mg/day have been efficient in treating MS, and 120 and 360 mg/day have been ineffective.  In this context, the Court discovered {that a} POSA would perceive from the ‘514 patent specification that 720mg/day was efficient, to the extent that this was the higher vary of each efficient dosage vary disclosed within the ‘514 patent.

In the “battle of the experts” the Court was unpersuaded by Biogen’s knowledgeable (whose credibility Mylan impeached on cross-examination, in keeping with the Court) and clearly persuaded by Mylan’s knowledgeable.*

The Court additionally was satisfied that the explanation for this failure to explain the invention claimed within the ‘514 patent was that the specification contained predominantly the work and innovations of 1 inventor (Dr. Lukashev) directed to strategies for figuring out medication for treating neurological issues, whereas the claims have been directed to the opposite inventor’s (Dr. O’Neill) work on creating an efficient therapeutic agent for treating MS:

From the proof offered at trial, Dr. Lukashev’s analysis concerning the activation of the Nrf2 pathway and screening drug compounds had nothing to do with the medical growth of Tecfidera®.  That process fell to Dr. O’Neill and later Dr. Dawson.  Notably, Dr. O’Neill’s speculation, {that a} 480mg/day dose of DMF (BID) could be efficacious in treating MS, advanced from his assessment of Fumapharm’s confidential research of Fumaderm®  [an early Biogen acquisition target], not Dr. Lukashev’s unrelated analysis concerning the mechanism of motion [citations to the record omitted].

From the proof offered at trial, the District Court recognized the next deficiencies in Biogen’s failure to fulfill the written description requirement:  “[i]n sum, Biogen has attempted to satisfy the written description requirement of § 112 by selectively plucking specific words from the specification that correspond to each element of the claimed invention.”  Citing Nuvo Pharm. (Ir.) Designated Activity Co. v. Dr. Reddy’s Labs. Inc., Enzo Biochem, Inc. v. Gen–Probe Inc., and Novozymes A/S v. DuPont Nutrition Biosciences APS, the Court states that “the Federal Circuit has clearly rejected” the strategy Biogen has taken.  Precluded from prevailing on these arguments, the Court discovered that Biogen should depend on inventor O’Neill’s testimony that he invented the claimed invention, which the Court discovered inadequate underneath Nuvo Pharm. (“inventor testimony cannot establish written description support where none exists in the four corners of the specification”).

The Court additionally thought-about “extrinsic” proof (together with the disclosure of the deserted Biogen software filed instantly after Biogen obtained the Phase III medical trial outcomes).  The comparability, whereby this software “provided and discussed in detail a wealth of data generated during Biogen’s Phase III study” confirmed in stark reduction the inadequacies of the ‘514 patent specification.

Finally, the Court took word of the truth that:

At each stage of this case and the associated IPR continuing, Biogen defended in opposition to Mylan’s obviousness problem by insisting {that a} POSA wouldn’t have anticipated a 480mg/day dose of DMF to be efficacious in treating MS. . . .  This assertion solely underscores the failure of the specification to show a POSA, who would count on in any other case, {that a} 480mg/day dose of DMF (BID) is efficacious in treating MS.

The District Court discovered the information and circumstances of this case most analogous to the Nuvo Pharm. case, whereby the patent at difficulty was invalidated on written description grounds.  The Court summarized its findings as follows:

Mylan has established by clear and convincing proof that the asserted claims of the ‘514 Patent are invalid for lack of written description.  First, the textual content of the specification doesn’t fairly convey to a POSA that Dr. Lukashev and Dr. O’Neill “actually invented” a technique of treating MS with a therapeutically efficient quantity of DMF, i.e., 480mg/day BID, as of February 8, 2007.  This studying of the textual content is confirmed by the testimony of Dr. Greenberg, Dr. Lukashev, Dr. O’Neill, and Dr. Wynn.  Second, the context of the ‘514 Patent’s prosecution historical past and the numerous omissions from the specification additional underscore the failure to adequately describe the claimed invention.  Biogen’s try to keep away from this conclusion by combining a number of selectively plucked disclosures from the specification of the ‘514 Patent has been squarely rejected by the Federal Circuit.

Satisfaction of the written description requirement is a query of truth reviewed for clear error from a bench trial.  In addition, the District Court cited trial testimony from inventors and consultants, and the Federal Circuit give substantial deference to the fact-finder for selections primarily based on the trial courtroom’s capacity to evaluate witness credibility and demeanor. Finally, the Federal Circuit has not too long ago elevated the stringency with which is assesses satisfaction of the written description requirement (see “Amgen Inc. v. Sanofi“).  These components recommend that Biogen will face fairly a problem in getting the Federal Circuit to reverse the District Court’s judgment on enchantment.

* In a footnote, the Court illustrated how an knowledgeable witness can inform a truth finder concerning complicated scientific ideas utilizing commonplace relationships for example the underlying rules:

As described by Mylan’s knowledgeable witness, Benjamin M. Greenberg, M.D., autoimmune ailments reminiscent of MS are very similar to a confused home cat that errors a curtain, or different house-hold objects, for an invading mouse.  Instead of attacking the mouse, the confused cat assaults a portion of the home it’s meant to guard.  The cat’s breed, and the kind of pleasant object it assaults, will assist establish which autoimmune illness is inflicting the confusion.  For instance, a Siamese cat (i.e., a number of sclerosis) could also be confused and assault one a part of the home (i.e., the central nervous system), and a Tabby cat (i.e., psoriasis) could also be confused and assault one other a part of the home (i.e., the pores and skin).

[1] Biogen additionally asserted that Mylan was underneath a heightened burden of proof as a result of the Patent Office had addressed the written description requirement throughout prosecution and issued the ‘514 patent when Biogen efficiently overcame this floor of rejection.  This argument was notably unavailing:  the District Court rejected it out of hand.