Patent Profile: VM Institute of Research Receives Patent for Method of Treating Triple Negative Breast Cancer

by McDonnell Boehnen Hulbert & Berghoff LLP
Contact

Triple Negative Breast Cancer DayThe U.S. Patent and Trademark Office recently issued U.S. Patent No. 8,642,270, which is entitled "Prognostic biomarkers to predict overall survival and metastatic disease in patients with triple negative breast cancer."  The '270 patent, which is assigned to the VM Institute of Research (Montreal, Canada), contains claims to a method of treating breast cancer in a subject having triple negative breast cancer.

For some time doctors and scientists hypothesized that the diversity observed among breast tumors might be accompanied by diversity in gene expression patterns.  Over ten years ago, Perou and colleagues published their work on the "Molecular portraits of human breast tumours" (Perou et al., 2000 Nature 406: 747-52) classifying human breast tumors based their gene expression profiles.  This work was soon followed up with studies that linked the gene expression profiles of each breast cancer subtype with patient overall survival and disease free survival.  One of the subtypes identified was the basal-like subtype.  The basal-like subtype is also described as triple-negative breast cancer because it generally does not express estrogen receptor (ER), progesterone receptor (PR), and expresses only normal, but not amplified, levels of the human epidermal growth factor receptor 2 (HER2).  Given the nature of the triple-negative breast tumors, this subtype does not respond to cancer drugs that target ER, PR or HER2 (i.e., Taxol® or Herceptin®), and has poorer overall survival and disease-free survival than other breast cancer subtypes.  The triple negative paradox (Carey et al., 2007 Clin Cancer Res. 13(8): 2329-34) is that these tumors often respond well to the initial chemotherapy treatments, and yet patients have significantly poorer overall survival.  The work by the inventors of the `270 patent helps to develop effective methods to determine whether a triple negative breast cancer patient is likely to have a recurrence or progress to the aggressive, metastatic disease in order to aid clinicians in deciding the appropriate course of treatment.

The '270 patent provides a method of treating breast cancer in a subject having a triple negative breast cancer.  The inventors were able to identify a 12 gene set that correlates with overall survival of the triple negative breast tumors.  More specifically, the inventors determined that the expression of STK3, KLF6, CD24 and KRAS, could be indicative of a recurrent triple negative breast tumor.

The '270 patent has one independent claim which recites:

1.  A method of treating breast cancer in a subject having a triple negative (TN) breast cancer, the method consisting of the steps:
    (a)  quantifying mRNA expression level of biomarkers STK3 and KLF6, and at least one biomarker selected from CD24 and KRAS in a test sample from a subject using a biological assay;
    (b)  comparing said mRNA expression level of said biomarkers selected from STK3, KLF6, and at least one of CD24 and KRAS quantified in step (a) to the expression level of said biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer; and
    (c)  administering an aggressive cancer treatment regimen to the subject based on an increase in the expression level of the biomarkers between the standard sample and the test sample.

A review of the file history of the '270 patent indicates that a rejection under 35 U.S.C. § 101 rejection was issued in the first Office Action.  The Action stated that the claimed invention is directed to non-statutory subject matter because it is not a patent-eligible practical application of a law of nature and because the claimed method does not result in a physical transformation of matter.  Specifically, the Action asserted that the claims do not recite additional elements or steps such that the method is sufficient to ensure that the claim amounts to significantly more than the natural principle itself or merely more than mental tasks.

The original claim 1 as filed recited:

1. A method of predicting the overall survival (OS) potential of a triple negative (TN) breast cancer in a subject, the method comprising the step:
    (a)  comparing expression level of at least one biomarker determined in a test sample from a subject to the expression level of the at least one biomarker in a standard sample indicative of a recurrent TN breast cancer, wherein the at least one biomarker is chosen from ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN; and wherein a difference in the expression level of the at least one biomarker between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

In response, the Applicant amended claim 1 to introduce an additional step of modifying a treatment regimen of the subject based on the results of step (a).  The Applicant asserted that with the new step, the method as amounted to "significantly more than the application of a natural principle."

Claim 1 as amended recited:

1.  (Currently Amended) A method of predicting the overall survival (OS) potential of a triple negative (TN) breast cancer in a subject, the method comprising the step:
    (a)  comparing a mRNA expression level of at least threeone biomarkers chosen from STK3, KLF6, and one of CD24 or KRAS determinedquantified using a biological assay in a test sample from a subject to the expression level of the at least threeone biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer, wherein the at least one biomarker is chosen from ANK3, CD24, EIF1, KLF6, KRAS, KRT1, MAP2K4, SDC4, SLC2A3, STK3, TFAP2C, and WRN; and
    (b)  modifying a treatment regimen of the subject based on the results of step (a) wherein a difference in the expression level of the at least one biomarkers between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

In the next and final Office Action mailed July 30, 2013, the Office maintained the rejection of the claims under 35 U.S.C. § 101 because the invention was not a patent-eligible practical application of a law of nature.  The Action noted that the claims recited methods steps for detecting or determining and comparing marker levels from samples, but asserted that these steps are routine or conventional, and do not add anything substantial to the claim that amounts to significantly more than observing the natural principle itself.  Regarding the step of "modifying a treatment regimen," the Action stated that such a step can be "accomplished mentally by thinking or designing a new treatment plan, and does not set forth any physical steps."

Furthermore, in the final Office Action, the Examiner suggested "amending the claims to recite an active step of administering a specified treatment regimen based on specific results (specific results such as increased or decreased mRNA levels of STK3, KLF6, and CD24 or KRAS relative to specific controls) to a patient population identified by such specific results."  Additionally, the Action stated that "prediction of survival rates as correlated to naturally occurring mRNA levels are considered an observation of a naturally occurring principle and an active step must be added to the claimed method that amounts to significantly more than the observation of the natural principle."

On September 17, 2013, in the response to the final Office Action, the Applicant stated "without conceding the correctness of the Examiner's position and for the purpose of expediting prosecution, Claim 1 has been amended to introduce an additional step (c), as suggested by the Examiner."  Claim 1 was amended claim 1 as shown below:

1.  (Currently Amended) A method of predicting the overall survival (OS) potential of a triple negative (TN) treating breast cancer in a subject having a triple negative (TN) breast cancer, the method comprisingconsisting of the steps:
    (a)  quantifying mRNA expression levels of biomarkers STK3 and KLF6, and at least one biomarker selected from CD24 and KRAS in a test sample from a subject using a biological assay;
    (b)  comparing [[a]]said mRNA expression level of at least three said biomarkers chosen selected from STK3, KLF6, and at least one of CD24 andor KRAS quantified in step (a) using a biological assay in a test sample from a subject to the expression level of said the at least three biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer; and
    (c[[b]])  modifyingadministering an aggressive cancer treatment regimen ofto the subject based on the results of step (b[[a]]) wherein a difference an increase in the expression level of the biomarkers between the standard sample and the test sample is used to predict the OS potential of the TN breast cancer in the subject.

A notice of allowance was mailed on October 1, 2013.

 

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.