Genome Medicine Article Calls for Limits on Patenting of Existing Nucleotide Sequences

by McDonnell Boehnen Hulbert & Berghoff LLP

3In an article published in the current issue of Genome Medicine, Jeffrey Rosenfeld of the University of Medicine & Dentistry of New Jersey and Christopher Mason of Cornell University contend that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences ("Pervasive sequence patents cover the entire human genome," Genome Medicine 5:27 (2013)).  According to the two researchers, the Association for Molecular Pathology v. Myriad Genetics, Inc. case affords the Supreme Court with an opportunity to resolve the "sharp conflict between the public goods of medical knowledge and improved health and the private goods of rewarding innovation and entrepreneurial risk-taking" that is presented by gene patents.

The authors begin by stating that "the broadest intellectual property rights on BRCA sequences" come from four claims in Myriad's U.S. Patent No. 5,747,282:

1.  An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.

2.  The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1.

5.  An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

6.  An isolated DNA having at least 15 nucleotides of the DNA of claim 2.

The article takes the Federal Circuit to task for (twice) "declar[ing] that even a short, isolated DNA molecule such as 'ACGT' is different from the 'NNNNN-ACGT-NNNNN' present within a chromosome (AMP v. Myriad, Federal Circuit 2012), because it will not be connected to sugar via a phosphodiester bond and will have a hydroxyl group instead of a bond to a phosphate."  According to the authors, the Federal Circuit's ruling means that "even a 15 nucleotide fragment of DNA in Claim #6 from Patent '282 is claimed to be 'markedly different'."

The authors, however, find the Federal Circuit's ruling to be overly broad for three reasons:

First, it relies on the sequences having chemical features and side-chains that are not actually present in the patents . . . : the claims are for a linear series of nucleotides, not a specific chemical structure.  Second, if allowed to be so broad, these claims could also create a monopoly on all epigenetic and chemical variations of these sequences. Third, and perhaps most importantly, the non-specificity of 15mer sequences creates unclear infringement liability that has been even noted by the Court.

To investigate this last point, the authors examined the incidence with which 15mers from a given gene matched 15mers in other genes using the Consensus Coding Sequences (CCDS) database of 18,382 high-confidence genes.  This analysis showed that "every gene in the CCDS database had a 15mer that matched the sequence of at least one other gene," with the "[t]he number of matching genes ranged from as few as 5 (for MTRNR2L7) or 689 (for BRCA1) to as high as 7,688 (for TTN), corresponding to 0.01%, 4%, and 42% of all genes in the human genome."  The authors note that 99.999% of 15mers in the human genome are repeated at least twice.

According to the authors, this analysis "demonstrate[s] that short patent sequences are extremely non-specific and that a 15mer patent claim from one gene will always 'cross-match' and patent a portion of another gene as well."  In support of this point, the authors identified 58 patents whose claims covered at least 10% of the bases of all human genes, with the claimed sequences of U.S. Patent No. 7,795,422 matching 91.5% of human genes, and the claimed bovine sequences of U.S. Patent No. 7,468,248 matching 84% of human genes.  Arguing that "[t]he demonstrated non-specificity of sequence uniqueness across the genome suggests that the Supreme Court should use [the Myriad] case to clarify the law on gene patents," the authors contend that "[i]f patent claims that use these 15mer or other short k-mer sizes are enforced, it could potentially create a situation where a piece of every gene in the human genome is patented by a phalanx of competing patents, with potentially harmful consequences for genetic testing laboratories and research groups performing targeted sequencing on any gene, in virtually all species."

The authors' conclusion regarding the broad scope of Myriad's 15mer claims, however, is not particularly ground-breaking given that Kepler et al. similarly concluded in a 2010 Genomics paper that claim 5 of the '282 patent was "exceptionally broad" (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  Kepler et al. suggested that "if human genes were random strings of nucleotides, one would expect a human gene to contain an average of 15 15-mers claimed under the ['282] patent," and in fact found that 80% of 713 human mRNAs deposited in 1994 (the earliest effective filing date of the '282 patent is August 12, 1994) contained at least one of the claimed 15mers.  Thus, Kepler et al. indicates that claims 5 and 6 are sufficiently overbroad as to be easily invalidated.  Because the analysis of Kepler et al. and Rosenfeld and Mason suggest that claims 5 and 6 of the '282 patent (and perhaps 15mer claims in other patents) would likely not withstand an invalidity challenge, it is unlikely that these claims will have the adverse impact on the "medical good" suggested by the authors of the Genome Medicine article.

One interesting result presented in the Genome Medicine article is that even longer nucleotide fragments from known genes matched the sequence of sequences in other genes.  In particular, the paper points out that "even 1,000 nucleotide fragments from known genes could still match 117 other genes."  However, the paper does not present any additional information regarding the 1,000 nucleotide fragment (or fragments) that yielded such matches.

Finally, it should be noted that Dr. Mason submitted two declarations when the Myriad case was before the District Court.  In a Supplemental Declaration submitted in response to Myriad's brief and Statement of Material Facts, Dr. Mason stated that claim 6 of the '282 patent was "so broad that it includes at least 4% and as much as 100% of the genes in the human genome."

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

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):

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.


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 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:

- 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.