United States: Lumigan Patents Upheld By Unexpected Results

In Allergan, Inc. v. Sandoz, Inc., the Federal Circuit affirmed the district court decision that upheld the validity of the Allergan patents relating to Lumigan® 0.01% glaucoma eye drops. This decision shows that it is still possible to defend a patent to a pharmaceutical formulation, at least when it is associated with truly unexpected results.

The Lumigan® Products

As described in the Federal Circuit decision, Lumigan® 0.01% is an improvement over Lumigan® 0.03%, which was approved in 2001 for the treatment of open angle glaucoma and ocular hypertension. Lumigan® 0.03% includes 0.03% by weight of bimatoprost and 50 parts per million ("ppm") benzalkonium chloride ("BAK"). In contrast, Lumigan® 0.01% includes 0.01% bimatoprost and 200 ppm BAK.

The active ingredient in both products is bimatoprost, a prostaglandin analog that is effective to reduce intraocular pressure but can cause hyperemia (eye redness) that led many patients to discontinue use of Lumigan® 0.03%. The other ingredient at issue, BAK, is an effective preservative for ophthalmic solutions, but was known to cause side effects. Thus, Lumigan® 0.01% has one third the amount of active ingredient and four times the amount of BAK as Lumigan® 0.03% and yet:

Lumigan 0.01% has similar efficacy to Lumigan 0.03%, viz., IOP-lowering within 0.5 mmHg of that of Lumigan 0.03%, but it causes less frequent and severe hyperemia than Lumigan 0.03%.

The Lumigan® 0.01% Patents At Issue

The patents at issue were U.S. Patent Nos. 7,851,504; 8,278,353; 8,299,118; 8,309,605; and 8,338,479, which stemmed from the same application and are listed in the Orange Book for Lumigan® 0.01%. The Federal Circuit cited Claim 2 of the '504 patent as representative of the Group I composition claims:

2. A composition having a pH of about 7.3 which comprises about 0.01% bimatoprost, about 200 ppm benzalkonium chloride, citric acid monohydrate, a phosphate buffer, and NaCl wherein said composition is an aqueous liquid which is formulated for ophthalmic administration.

The defendants asserted that the claims were invalid as obvious over eight prior art references, and also invalid for lack of written description and enablement. After a bench trial, the district court upheld the asserted claims and found them to be infringed.

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Lourie and joined by Judges Linn and Hughes.

establishing non-obviousness within a prior art range

Of interest for other cases is the court's discussion of what it may take to withstand an obviousness challenge when the prior art discloses ranges that encompass the claimed amounts:

As we explained in Galderma [Laboratories, L.P. v. Tolmar, Inc. (Fed. Cir. 2013)], where there is a range disclosed in the prior art, and the claimed invention falls within that range, a relevant inquiry is whether there would have been a motivation to select the claimed composition from the prior art ranges. ... In those circumstances, "the burden of production falls upon the patentee to come forward with evidence that (1) the prior art taught away from the claimed invention; (2) there were new and unexpected results relative to the prior art; or (3) there are other pertinent secondary considerations."

The Federal Circuit cited In re Peterson (Fed. Cir. 2003), for the proposition that there can be situations where "the disclosed range[s are] so broad as to encompass a very large number of possible distinct compositions" ... such that they do not teach any specific amounts or combinations and that the burden of producing evidence of teaching away, unexpected results, and other pertinent secondary considerations [does] not shift," but did address whether this was such a case.

Turning to the case before it, the Federal Circuit found no error in the district court's findings that the prior art taught away from using 200 ppm BAK, and that "the claimed formulation exhibited 'unexpected results,' which differed in kind, not just in degree, from the prior art." Indeed, the court cited two "unexpected results": that BAK enhanced the permeability of bimatoprost and that bimatoprost was effective and exhibited less hyperemia at 0.01%.

Those results exhibited by the claimed formulation thus constitute an unexpected difference in kind, viz., the difference between an effective and safe drug and one with significant side effects that caused many patients to discontinue treatment.

inherent properties support nonobviousness when they differ in kind

The Federal Circuit also rejected arguments based on inherency:

[W]e reject the Appellants' argument that the that the unexpected results do not support nonobviousness because they are merely the inherent properties of an otherwise obvious formulation. As indicated, the prior art did not disclose, either explicitly or implicitly, the claimed formulation; rather, it taught away from such a formulation. .... The unexpected properties of the claimed formulation, even if inherent in that formulation, differ in kind from the prior art, thereby supporting a conclusion of nonobviousness.

This is not a case where the claims merely recite the unknown properties of an otherwise obvious formulation. .... Here, the previously unknown and unexpected properties of a new and nonobvious formulation constitute additional, objective evidence of nonobviousness.

The Federal Circuit therefore affirmed the district court's finding that the patents had not been shown to be obvious, and also affirmed its other findings.

Patentability Of Pharmaceutical Formulations

While patent owners may welcome this decision upholding pharmaceutical formulation patents, they also may wonder if the court has set too high a bar. The primary reference cited against the Allergan patents was Woodward, which disclosed a composition comprising 0.001%–1% bimatoprost and 0–1000 ppm of a preservative, including BAK. It seems clear from the discussion of the side effects of both bimatoprost and BAK that Woodward embraces both ineffective and dangerous formulations. Yet, precedent that supports a presumption that all embodiments disclosed in a patent are enabled shifts the burden to the patent owner to prove otherwise.

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
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must 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