United States: Invalidity Of Broad Claims For Lack Of Enablement In The Absence Of Sufficient Disclosure Of The Structure/Function Correlation And Unpredictability In The Art

Last Updated: July 19 2019
Article by Marina I. Miller

Enzo Life Sciences, Inc. ("Enzo") appealed the decision of the U.S. District Court for the District of Delaware granting summary judgment against Enzo and holding that the asserted claims were invalid for lack of enablement. The Federal Circuit affirmed.

In 1981, Dr. David Ward and others at Yale University successfully developed a nonradioactive probe by attaching a label to a polynucleotide via a chemical linker at a base position of a nucleotide. Dr. Ward demonstrated that attaching labels at certain positions of the nucleotide ("the Ward positions") would not disrupt the polynucleotide's ability to hybridize and be detected upon hybridization.   In December 1981, Enzo licensed the exclusive rights to the patent portfolio covering Dr. Ward's discovery. In June 1982, Enzo filed a patent application covering non-radioactive labeling at additional positions on a nucleotide. The two patents in the appeal generally relate to the use of non-radioactively labeled polynucleotides in nucleic acid hybridization and detection applications. The patents share the same specification in relevant parts.

U.S. Patent No. 6,992,180 ("the '180 patent") relates to non-radioactive labeling of polynucleotides where the label is attached at the phosphate position of a nucleotide. The claims are not directed to any specific polynucleotide, nor do they focus on the chemistry or linker used to attach a label, the number of labels to attach to a polynucleotide, or where within the polynucleotide to attach those labels. Instead, the claims encompass all polynucleotides with labels attached to a phosphate, as long as the polynucleotide remains hybridizable and detectable upon hybridization. The claims of U.S. Patent No. 8,097,405 ("the '405 patent") are in situ hybridization claims and liquid phase hybridization claims. In January 2012, Enzo filed suit against Roche Molecular Systems, Inc., Roche Diagnostics Corp., Roche Diagnostics Operations, Inc., and Roche Nimblegen, Inc. ("Roche") alleging infringement of the '180 patent. In March 2012, Enzo filed separate suits against Becton, Dickinson and Co., Becton Dickinson Diagnostics Inc., and GeneOhm Sciences, Inc. ("BD"); and Abbott Laboratories and Abbott Molecular, Inc. ("Abbott") alleging infringement of the '180 patent.

The Court of Appeals for the Federal Circuit ("the Court") identified the issue in the appeal as being "not simply whether the specification enables labeling; the question is whether it enables creation of a labeled probe that is both hybridizable and detectable upon hybridization."

Roche and BD argued that the specification failed to sufficiently disclose internal phosphate labeling. The Court noted that "even if we assume that the specification teaches one of skill in the art how to create the broad range of labeled polynucleotides covered by the claims ... the specification still fails to teach one of skill in the art which combinations will produce a polynucleotide that is hybridizable and detectable upon hybridization, as required by the claim language."

In regard to the functionality required by the claims, the Court relied upon its decision in Wyeth and Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380 (Fed. Cir. 2013), controlling this case. In Wyeth, the Court noted the breadth of the claims, the limited guidance provided in the specification, the large number of possible candidates falling within the claimed genus (tens of thousands), and the fact that it would be necessary to first synthesize and then screen each of those candidates to determine whether it had the required functionality." In Wyeth, "one of the patentee's scientists had confirmed the unpredictability in the art by testifying that one would need to test each compound to understand whether it would have the desired functionality." The Court pointed out that facts in Enzo largely mirrored those in Wyeth, as the asserted claims here required not just a particular structure, but a particular functionality (i.e., the labeled polynucleotides must be hybridizable and detectable upon hybridization), while the specification failed to teach whether the embodiments of the broad claims would exhibit that required functionality.  

The Court explained that claim 1 of the '180 patent encompassed all phosphate-labeled polynucleotides that were hybridizable and detectable. The claim placed almost no limitations on the structure of the claimed polynucleotide, other than the fact that the label was attached to the phosphate portion of the nucleotide. "It does not restrict the chemistry used to attach the label, the chemical linker used, the number of labels within a probe, or the location of the labels on the probe (i.e., whether they are terminal or internal). As to the type of non-radioactive label used, the claim provides broad categories, such as any 'electron dense component' or 'magnetic component.'   The specification's guidance as to how such variables would or would not impact the functionality of the claimed probes is sparse. At the time of the invention, the art was highly unpredictable."  The Court concluded that "[g]iven the unpredictability of the art at the time and the serious doubts held by those of skill in the art regarding whether labels could be attached to non-Ward positions without disrupting hybridization, merely stating that a labeled polynucleotide will work as a probe is not sufficient to enable one of skill in the art to know that it would indeed function as a probe—i.e., be hybridizable and detectable upon hybridization."

Enzo relied on Example V as an example of an internal phosphate-labeled polynucleotide that was hybridizable and detectable. However, during prosecution Enzo admitted that Example V was a "paper" example. Furthermore, Enzo's expert testified that he was not aware of Enzo having ever tested a phosphate-labeled probe for hybridizability and detectability. The Court noted that even viewing Example V as a "working" example, Example V was insufficient to enable the breadth of the claims here, especially in light of the unpredictability in the art. "The deficiencies in the description as to enablement cannot be cured in this case by looking to the knowledge of those skilled in the art at the time of the invention. Although 'a specification need not disclose what is well known in the art,' that rule is 'not a substitute for a basic enabling disclosure.' Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997). As we have said before, a patentee 'cannot simply rely on the knowledge of a person of ordinary skill to serve as a substitute for the missing information in the specification.' ALZA Corp. v. Andrx Pharm., LLC, 603 F.3d 935, 941 (Fed. Cir. 2010). And, more importantly, all parties acknowledge that serious doubts existed in the art as to whether the use of non-radioactive probes at non-Ward positions would be useful as probes."  The Court acknowledged that according to Enzo's expert, the number of possible polynucleotides that would fit within the limitations of claim 1 would be at least "tens of thousands." The Court concluded that even if Example V described one working embodiment with the claimed functionality, undue experimentation would still be required with regard to the many other embodiments of the claims based on the number of possible embodiments and the unpredictability in the art.

The claims of the '405 patent are broader than the claims of the '180 patent and cover not only phosphate-labeled polynucleotides, but also labeling at other locations on a nucleotide, and also require the claimed polynucleotides to be hybridizable and detectable upon hybridization. The Court concluded that because the specification does not enable the narrower scope of polynucleotides claimed in the '180 patent, it also could not enable the broader scope of polynucleotides claimed in the '405 patent. Even though the claims of the '405 patent pertained to certain processes, the claims were still not enabled for the same reasons as in the '180 patent.  

Enzo Life Sciences, Inc. is another example of broad functional claims and a limited disclosure of structural elements that provide the claimed function where the art is unpredictable. It is important to describe common structural elements of a broad group and how to identify molecules/species of the group that have the claimed activity/desired function. More than one example is likely needed in the specification to provide an enabling description for broad functional claims with limited structural elements.

Enzo Life Sciences, Inc. v.  Roche Molecular Systems, Inc., No.17-2498 (Fed. Cir. July 5 2019)


The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

In association with
Related Topics
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Mondaq Free Registration
Gain access to Mondaq global archive of over 375,000 articles covering 200 countries with a personalised News Alert and automatic login on this device.
Mondaq News Alert (some suggested topics and region)
Select Topics
Registration (please scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions