Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir. 2013)

by McDonnell Boehnen Hulbert & Berghoff LLP
Contact

NovozymesIt has long been a practice in prosecuting a patent application to keep a continuation application pending during the term of any granted patent.  This practice is advantageous because it permits the patentee to pursue specific claims in a later-filed application to a competitor's product that falls within the scope of the invention as disclosed in the specification.  Of course, this strategy requires that later-filed claims be disclosed in the specification as originally filed to satisfy the enablement and written description requirements of 35 U.S.C. § 112.  In re Ruschig, 379 F.2d 990 (CCPA 1967).

These considerations arose in the Federal Circuit's decision in Novozymes v. DuPont Nutrition Biosciences in a patent infringement lawsuit involving modified alpha-amylase enzymes.  Alpha-amylases are enzymes produced in microorganisms and higher plants and animals (including man) and catalyze the breakdown of certain polysaccharides.  The enzymes are used commercially, inter alia, in detergents, sugar refining, and ethanol production, but as enzymes are sensitive to elevated temperatures and pH extremes.  Novozymes' commercial embodiment of this enzyme is obtained from Bacillus licheniformis (BLA) and sold as Termamyl™.

Traditionally, alpha-amylases are stabilized against the deleterious effects of heat and extreme pH by complexing with calcium, which "represents an added cost and often imposes undesirable effects on industrial equipment."  In an effort to avoid these costs and undesirable effects, Novozymes "pursued two parallel strategies in attempting to identify promising mutation sites among the approximately 500 amino acids that make up a Bacillus alpha-amylase polypeptide:  rational protein design [which attempted to use knowledge and information on the effects of mutations in amino acid sequence on protein structure] and random mutagenesis [which did not]."  The priority application of the patent-in-suit at issue in this case disclosed 17 amino acid sequence positions identified by rational design and 16 positions identified by random mutagenesis that were candidates for amino acid changing mutations in two bacterial alpha-amylases:  the B. licheniformis species that comprised the company's Termamyl™ product and a species from B. stearothermophilus ("BSG"), as well as five other bacterial alpha-amylase species.  As disclosed in the specification of the priority document, these changes could involve substitution of the amino acid at each of these 33 positions with one of the other 19 naturally occurring amino acids, or could involve deletion of the amino acid at that position (a total of 20 possible changes for each of the 33 candidate positions).  Accordingly, the total number of variant B. licheniformis species disclosed generically in the priority document amounted to about 8.6 x 1042.  In fact, the specification of the priority document provided but two specific examples with actual experimental data.  However, many of the substitutions were found not to provide variant alpha-amylase enzymes having "improved stability at 'high temperatures (i.e., 70-120°C.) and/or extreme pH (i.e., low or high pH, i.e., pH 4-6 or pH 8-11), in particular at free (i.e., unbound, therefore in solution) calcium concentrations below 60 ppm.'"

DuPont's accused product was a B. stearotherophilus variant species having an amino acid sequence change at position 239 from a serine to a glutamic acid (abbreviated "S239Q").  As noted in the Federal Circuit opinion, "DuPont produced approximately 1,500 alpha-amylase variants with substitutions covering 150 of the 515 amino acid positions in the parent BSG enzyme.  . . .  DuPont then screened its panel of 1,500 variants for increased thermostability under low-calcium conditions and identified a variant substituted at position 239 [the S239Q variant] as the best performer."

In response, Novozymes filed a continuation application that resulted in the patent-in-suit, U.S. Patent No. 7,713,723; claim 1 is representative:

1.  An isolated variant of a parent alpha-amylase, wherein:
    (a) the variant has at least 90% sequence identity to SEQ ID NO: 6 [BSG alpha-amylase],
    (b) the variant comprises a substitution of serine at position 239 relative to the parent alpha- amylase, using the amino acid sequence of SEQ ID NO: 8 [BLA alpha-amylase] for determining position numbering, and
    (c) the variant has increased thermostability relative to the parent alpha-amylase, wherein thermostability is determined at pH 4.5, 90° C. and 5 ppm calcium and has alpha-amylase activity

(emphasis in opinion).

The District Court granted summary judgment of infringement against DuPont and denied DuPont's summary judgment motion of invalidity under 35 U.S.C. § 112 for failure to satisfy the written description requirement, based on there being disputed issues of fact.  (The Court also denied Novozymes' preliminary injunction motion on the grounds that there was considerable question of whether Novozymes would prevail on the merits in view of DuPont's invalidity challenge.)  The Court submitted to the jury the question of whether the claims were invalid under 35 U.S.C. § 112 for failure to satisfy the enablement or written description requirements, and the jury found (using a special verdict form) that the claims were not invalid, awarding Novozymes a judgment of more than $18 million.  The Court granted DuPont's JMOL motion, on the grounds that the specification did not provide an adequate written description of the invention as claimed, relying on both Federal Circuit and CCPA precedent including Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011); Billups-Rothenberg, 642 F.3d 1031, 1036 (Fed. Cir. 2011); Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004); Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320 (Fed. Cir. 2000); In re Ruschig, 379 F.2d 990 (CCPA 1967).

The Federal Circuit affirmed, in an opinion by Judge Schall joined by Judge Bryson, with Chief Judge Rader dissenting.  The majority opinion rejected Novozymes' contentions that any deficiencies in the disclosure in its specification was ameliorated by the general understanding, knowledge and skill in the art, citing Snitzer v. Etzel, 465 F.2d 899 (CCPA 1972), and Union Oil Co. of California v. Atlantic Richfield Co., 208 F.3d 989 (Fed. Cir. 2000).  DuPont, in contrast, relied on In re Ruschig, arguing successfully that Novozymes' disclosure amounted to nothing more than an "invitation to experiment," and unsuccessfully at that, pointing out that Novozymes' "application fails to disclose a single alpha- amylase variant substituted at position 239 that actually exhibits increased thermostability, noting that the only disclosed substitution at that position (S239W) disclosed in the 2000 application does not work as required by the '723 patent's claims."

The majority stated its holding expressly:  "no reasonable jury could find that the claims of the '723 patent meet the written description requirement of § 112, ¶ 1, and that the district court therefore correctly entered judgment as a matter of law invalidating those claims."  The opinion contrasts the specificity of the claims with the generic disclosure of the specification, noting that Novozymes provided only "generalized guidance listing several variables that might, in some combination, lead to a useful result."  This determination was mandated by "[n]umerous prior decisions" from both the CCPA and the Federal Circuit, citing most of the canonical precedent including In re Ruschig, Boston Scientific Corp. v. Johnson & Johnson, Univ. of Rochester v. G.D. Searle & Co., and distinguishing Snitzer v. Etzel and Union Oil Co. of California v. Atlantic Richfield Co.  In the Snitzer case, the majority noted that each provided disclosure of a small number of distinctly recited species, in stark contrast to the overwhelming number of species falling within the ambit of the '723 patent specification, while in the Union Oil case the specification "defined the claimed gasoline compositions in terms of various chemical and physical properties" and that "ordinarily skilled petroleum refiners would immediately appreciate that the qualitative chemical properties recited in the claims translated to specific, manifest compositions that would yield those properties."

The majority expressly found that the '723 specification, and the disclosure of the priority document, "contains no disclosure of any variant that actually satisfies the claims, nor is there anything to suggest that Novozymes actually possessed such a variant at the time of filing."  While the opinion recognizes distinctions between Novozymes' specification and the deficiencies in the specifications in the authorities it cites to support their opinion, "[o]n closer inspection these 'analogies fall flat.'"  "Taking each claim -- as we must -- as an integrated whole rather than as a collection of independent limitations, one searches the ['723 priority] application in vain for the disclosure of even a single species that falls within the claims or for any 'blaze marks' that would lead an ordinarily skilled investigator toward such a species among a slew of competing possibilities," according to the opinion, and "working backwards" from the claims (and the accused product) impermissibly "seeks to derive written description support from an amalgam of disclosures plucked selectively from the 2000 application."  Even Novozymes' expert agreed with DuPont that "one could not know which, if any, individual substitutions at any of the seventeen sites selected by rational protein design would yield increased thermostability without actually making and testing the variants," and it was evident that the '723 specification and its priority document did not disclose the specifically claimed thermostable variant.  Further:

In this case, to actually possess the variant enzymes claimed in the '723 patent would have required Novozymes to confirm its predictions by actually making and testing individual variants or at least identifying subclasses of variants that could be expected to possess the claimed properties, which it did not do before filing the ['723 priority] application.  At best, the ['723 priority] application describes a roadmap for producing candidate alpha-amylase variants and then determining which might exhibit enhanced thermostability.  A patent, however, "is not a reward for the search, but compensation for its successful conclusion."  Ariad [Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010) (en banc)] (quoting University of Rochester, 358 F.3d at 930 n.10).  For that reason, the written description requirement prohibits a patentee from "leaving it to the . . . industry to complete an unfinished invention."  Id.

Chief Judge Rader dissented.  While his continued dissatisfaction with the written description requirement was evident ("[a]lthough a separate written description requirement, and the vague notion of "possession" that it embodies, still troubles me"), his dissent does not trod that old ground of disagreement with his brethren.  Instead, the Chief Judge contends that, having established a separate written description requirement it is a question of fact, and the jury deserves deference to its factual determinations that should not lightly be overturned by JMOL.  On the facts in this case, Chief Judge Rader finds substantial evidence (including expert testimony, the weight and persuasiveness being particularly within a jury's purview) supporting the jury's verdict and thus would let it stand:

[T]he jury received expert testimony, heard from skilled protein engineers, reviewed visual aids and publication excerpts, and examined the patent document as guided by those skilled in the art, over an eight day trial.  The jury was given a special verdict form asking whether DuPont had proven by clear and convincing evidence that the claims at issue were invalid for lack of written description.  . . .  The jury answered in favor of Novozymes, and substantial evidence supports this determination.


Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir. 2013)

Panel: Chief Judge Rader and Circuit Judges Schall and Bryson
Opinion by Circuit Judge Schall; dissenting opinion by Chief Judge Rader

 

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

© McDonnell Boehnen Hulbert & Berghoff LLP | Attorney Advertising

Written by:

McDonnell Boehnen Hulbert & Berghoff LLP
Contact
more
less

McDonnell Boehnen Hulbert & Berghoff LLP on:

Readers' Choice 2017
Reporters on Deadline

"My best business intelligence, in one easy email…"

Your first step to building a free, personalized, morning email brief covering pertinent authors and topics on JD Supra:
Sign up using*

Already signed up? Log in here

*By using the service, you signify your acceptance of JD Supra's Privacy Policy.
Custom Email Digest
Privacy Policy (Updated: October 8, 2015):
hide

JD Supra provides users with access to its legal industry publishing services (the "Service") through its website (the "Website") as well as through other sources. Our policies with regard to data collection and use of personal information of users of the Service, regardless of the manner in which users access the Service, and visitors to the Website are set forth in this statement ("Policy"). By using the Service, you signify your acceptance of this Policy.

Information Collection and Use by JD Supra

JD Supra collects users' names, companies, titles, e-mail address and industry. JD Supra also tracks the pages that users visit, logs IP addresses and aggregates non-personally identifiable user data and browser type. This data is gathered using cookies and other technologies.

The information and data collected is used to authenticate users and to send notifications relating to the Service, including email alerts to which users have subscribed; to manage the Service and Website, to improve the Service and to customize the user's experience. This information is also provided to the authors of the content to give them insight into their readership and help them to improve their content, so that it is most useful for our users.

JD Supra does not sell, rent or otherwise provide your details to third parties, other than to the authors of the content on JD Supra.

If you prefer not to enable cookies, you may change your browser settings to disable cookies; however, please note that rejecting cookies while visiting the Website may result in certain parts of the Website not operating correctly or as efficiently as if cookies were allowed.

Email Choice/Opt-out

Users who opt in to receive emails may choose to no longer receive e-mail updates and newsletters by selecting the "opt-out of future email" option in the email they receive from JD Supra or in their JD Supra account management screen.

Security

JD Supra takes reasonable precautions to insure that user information is kept private. We restrict access to user information to those individuals who reasonably need access to perform their job functions, such as our third party email service, customer service personnel and technical staff. However, please note that no method of transmitting or storing data is completely secure and we cannot guarantee the security of user information. Unauthorized entry or use, hardware or software failure, and other factors may compromise the security of user information at any time.

If you have reason to believe that your interaction with us is no longer secure, you must immediately notify us of the problem by contacting us at info@jdsupra.com. In the unlikely event that we believe that the security of your user information in our possession or control may have been compromised, we may seek to notify you of that development and, if so, will endeavor to do so as promptly as practicable under the circumstances.

Sharing and Disclosure of Information JD Supra Collects

Except as otherwise described in this privacy statement, JD Supra will not disclose personal information to any third party unless we believe that disclosure is necessary to: (1) comply with applicable laws; (2) respond to governmental inquiries or requests; (3) comply with valid legal process; (4) protect the rights, privacy, safety or property of JD Supra, users of the Service, Website visitors or the public; (5) permit us to pursue available remedies or limit the damages that we may sustain; and (6) enforce our Terms & Conditions of Use.

In the event there is a change in the corporate structure of JD Supra such as, but not limited to, merger, consolidation, sale, liquidation or transfer of substantial assets, JD Supra may, in its sole discretion, transfer, sell or assign information collected on and through the Service to one or more affiliated or unaffiliated third parties.

Links to Other Websites

This Website and the Service may contain links to other websites. The operator of such other websites may collect information about you, including through cookies or other technologies. If you are using the Service through the Website and link to another site, you will leave the Website and this Policy will not apply to your use of and activity on those other sites. We encourage you to read the legal notices posted on those sites, including their privacy policies. We shall have no responsibility or liability for your visitation to, and the data collection and use practices of, such other sites. This Policy applies solely to the information collected in connection with your use of this Website and does not apply to any practices conducted offline or in connection with any other websites.

Changes in Our Privacy Policy

We reserve the right to change this Policy at any time. Please refer to the date at the top of this page to determine when this Policy was last revised. Any changes to our privacy policy will become effective upon posting of the revised policy on the Website. By continuing to use the Service or Website following such changes, you will be deemed to have agreed to such changes. If you do not agree with the terms of this Policy, as it may be amended from time to time, in whole or part, please do not continue using the Service or the Website.

Contacting JD Supra

If you have any questions about this privacy statement, the practices of this site, your dealings with this Web site, or if you would like to change any of the information you have provided to us, please contact us at: info@jdsupra.com.

- hide
*With LinkedIn, you don't need to create a separate login to manage your free JD Supra account, and we can make suggestions based on your needs and interests. We will not post anything on LinkedIn in your name. Or, sign up using your email address.