Canada: Clean Sweep For Teva In VELCADE Patent Action

Last Updated: August 29 2018
Article by Bryan Norrie

In a Judgment dated July 18, 2018, Justice Locke allowed Teva's claim for section 8 damages in relation to its bortezomib product, and dismissed Millennium's counterclaim for the infringement of three patents, holding the asserted claims of two patents as invalid, and the asserted claims of a third patent not infringed.

As the parties had already reached agreement regarding matters of liability and quantification of damages, the trial only concerned Millennium's claim for infringement of three patents and Teva's defences based on non-infringement and invalidity.

Patent 2,203,936 (compound)

Claim 37 covered 6 boronic acid peptide analogs including bortezomib, whereas Claim 69 covered the compound (N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid), also known as bortezomib, having the following structure:

Skilled Person: The parties had agreed that the relevant person skilled in the art was a team comprising a medicinal chemist with experience in boronic acid chemistry and a biochemist having experience with the proteasome and peptide chemistry. The common general knowledge included synthesis of N-terminal protected peptidyl boronic ester and acid compounds, and their effectiveness at inhibiting proteases.

Justice Locke accepted that WO 91/13904 describes a broad genus peptidyl compounds disclosed to inhibit proteases, including the proteasome. Justice Locke also ejected Millennium's arguments that he 904 Application did not disclose the N-terminal blocking group of bortezomib, holding:

[169] ... the broad range of possible N-terminal blocking groups that are expressly contemplated, together with the reference to known equivalents, leaves room for pyrazine carbonyl, provided it can be shown to be "known to protect molecules from degradation by aminopeptidases

Rather, Justice Locke held that while pyrazine carbonyl was an unusual choice, multiple references in the prior art established that it was a known N-terminal blocking group such that bortezomib falls within the broad genus of compounds contemplated in the 904 Application, and therefore the 936 Patent is effectively a selection patent and must meet the requirements for validity thereof.

Obviousness: Despite falling within the scope of compounds contemplated in the 904 Application, bortezomib was not specifically disclosed in the prior art. Millennium argued that bortezomib could not be obvious because a skilled person could not predict that bortezomib and the other claimed compounds would be effective inhibitors of the proteasome. Justice Locke rejected this argument holding nothing in the combination of the components of bortezomib prompts a conclusion that the selection of all of them together was any less obvious.

Further, the selection of bortezomib was not in respect of a "quality of a special character peculiar to the selected group", as the compounds of the asserted claims did not contain anything would have been found by the unimaginative skilled technician without the exercise of inventive ingenuity.

Justice Locke also noted held that commercial success could not save the claims from obviousness because the 936 Patent was not sufficient to create a commercially successful product.

Patent 2,436,146 (formulation)

Justice Locke determined that claims 30, 45, 46 and 81-84 of the 146, generally directed to the lyophilized bortezomib mannitol ester, and methods for making it, were obvious.

Justice Locke accepted Teva's argument that the skilled person is not only a pharmaceutical formulator, but is a team also containing a medicinal chemist. Boronic acid and ester compounds, including bortezomib, were known as part of the common general knowledge.

The parties agreed that the skilled person would be aware that lyophilizing a solution of bortezomib and mannitol could result in the formation of an ester. However, Millennium's expert, Dr. Anderson, contended that the potential for ester formation would make the use of mannitol a non-starter because it would not be inert (a desired characteristic of a bulking agent). Justice Locke accepted the evidence of Teva's expert, Dr. Bachovchin, that a skilled person would expect that any ester formation would be readily reversible by hydrolysis.

Justice Locke determined that the inventive concept of claim 30 is lyophilized bortezomib mannitol ester with its improved stability, rejecting Millennium's argument that the inventive concept also includes other properties associated with the compound, including solubility and dissolution rate. This distinction was not critical, as Justice Locke found the claim to be obvious, even assuming the inventive concept included solubility and dissolution rate.

As mannitol had been used in the formation of an ester of another boronic acid, Justice Locke determined that the difference between the inventive concept and the state of the art was the use of mannitol and lyophilisation to form an ester of bortezomib.. In determining that it was more or less self-evident to try to form lyophilized bortezomib mannitol ester, Justice Locke concluded that it was more or less self-evident that the lyophilized bortezomib mannitol ester ought to work, holding:

[263] As indicated in paragraph [242] above, it was well-known to use lyophilisation to address aqueous instability. Of course, this is a general statement that does not take into account the other known possibility that lyophilizing a solution of bortezomib and mannitol could result in the formation of an ester (or several different esters). This possibility would introduce an additional uncertainty, but as indicated above, the skilled person would expect such ester formation to be readily reversible. The skilled person would also still expect improved stability as a result of lyophilisation.

[264] In my view, it was indeed more or less self-evident that what was being tried ought to work. It was not certain to succeed, but skilled person would have considered the probability good.

Justice Locke also held that the inventors' actual course of conduct that was disclosed in the prior art was less helpful in determining whether the solution provided by the inventors was obvious to try at the claim date, holding that the skilled person would have had more information than the inventors, and would not need to go through all of the same steps that the inventors did.

Furthermore, the inventors' initial search was found lacking, as it failed to identify prior art that was clearly relevant. An inventor, Dr. Stella, thought about trying lyophilization relatively early in his work, but the project manager initially opposed this approach. Once Dr. Stella began working on lyophilisation, he had the solution described in the patent within a month or two, and improved stability was verified with routine testing.

Patent No. 2,738,706 (synthetic method)

Justice Locke found that Teva's processes did not infringe the 706 Patent, which is generally directed to a large-scale process for making bortezomib. At trial, Millennium had argued that several claim elements were not essential and therefore need not be in the Teva process in order for the Court to find infringement.

Justice Locke rejected Millennium's proposed construction, holding that in purposively construing a patent, the language of the claims is prime. More specifically, Millennium had argued that a definition of "large scale" in the 706 Patent as requiring at least 5 moles of a starting reagent did not apply to the claims because it was directed to a different invention claimed in a separate divisional application. Justice Locke noted that this construction was not supported by any expert evidence, and held that the other passages in the disclosure do not detract or alter the explicit definition of "large scale", holding:

[307] In my view, the passages cited above from paragraphs 8 and 25 of the 706 Patent do not detract from or alter the definition provided in paragraph 31. Those passages essentially serve to emphasize that there is no specific upper limit to the scale contemplated in the 706 Patent. On the other hand, the definition in paragraph 31 provides a lower limit to the scale. That definition applies to the term "large-scale".

Justice Locke also held that the specific solvents recited in step (aa) of asserted claim 1 were "clear and unambiguous" and were essential elements that could not be substituted for other solvents. Justice Locke further held that the solvents employed by Teva work in a substantially different way than the solvents claimed in the 706 Patent, such that Teva did not infringe the 706 Patent.

Justice Locke similarly rejected Millennium's arguments that various elements of steps (bb) and (cc) were not essential, explaining as follows:

[320] ...As with step (aa), I can decide the issue of essentiality based on whether the skilled reader would have understood from the language of the claim that the patentee intended that strict compliance with the primary meaning was an essential requirement of the invention. As in step (aa), I see no ambiguity in the terms used in step (bb) that would lead to a conclusion that they encompass a range of alternatives.

In view of his findings of non-infringement, Justice Locke found it unnecessary to address the validity of the 706 Patent.

A copy of Justice Locke's public Judgment and Reasons may be found here.

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.

Authors
Similar Articles
Relevancy Powered by MondaqAI
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
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
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
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.

Disclaimer

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.

General

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