The Difficulties in Diagnostic Patents, post-Mayo

Since the Supreme Court issued its opinion in the Association for Molecular Pathology v. Myriad Genetics, Inc. and Mayo Collaborative Services v. Prometheus Laboratories, Inc., it has been increasingly difficult for medical diagnostics to become patented or survive a patentability challenge.  In 2012, the U.S. Supreme Court decisions, which applied to a breast cancer test relying on BRCA1 gene mutations and test determining appropriate dosages of thiopurine drugs that are used in autoimmune diseases, determined that any test that relied upon a correlation between naturally occurring events, such as the presence of a mutated gene or drug metabolite, was related to natural laws and natural phenomena and hence not patent eligible subject matter without more inventive material in the claims.[i]  These decisions also stated that any well-understood, routine, or conventional activity previously engaged in by researchers in the field, would be insufficient to overcome a finding of patent ineligibility.[ii]

Recently, the Federal Circuit released a precedential opinion into a myasthenia gravis diagnostic relying on antibody levels against a membrane protein, muscle-specific tyrosine kinase (MuSK).[iii] Myasthenia gravis is an autoimmune neuromuscular disorder typically caused by antibodies targeting acetylcholine receptors that are responsible for nerve transmission.[iv]  There are three other variations, where antibodies target MuSK, where antibodies target LRP4, and congenital variations that result in defects in nerve transmission, such as in acetylcholine.[v]  In typical muscle nerve transmission, a nerve (presynaptic) releases acetylcholine out of the cell, which is taken up by the next cell (postsynaptic) causing the nerve signal to continue.[vi] LRP4 and MuSK act together to maintain the acetylcholine receptors together and adjacent to the presynaptic cell, which is required for the signaling.[vii]

Myasthenia gravis is diagnosed by physical examinations and various tests, including antibody levels.[viii] In the present case, the inventors of the patent at issue discovered the link between MuSK antibodies and myasthenia gravis.[ix] The patent resulting from this discovery included diagnostic tests that used radiological labeling of MuSK or an antigenic epitope to determine levels of anti-MuSK antibodies in a patient;[x] or adding a reporter or label (usually fluorescent) to MuSK or an antigenic epitope for the same purpose.[xi] The Federal Circuit analyzed the claims, and unsurprisingly found the claims drawn to a correlation between MuSK antibodies and myasthenia gravis.[xii] The court moved to the next step in the analysis, whether the claims include an inventive aspect that elevates the claims to patentable subject matter.[xiii] Despite the fact that the claims included man-made acts of radioactive labeling or other labeling of a molecule, the Federal Circuit found all of these acts to be well known in the field and insufficient to make the claims patentable.[xiv]

Moving on to the multimillion-dollar question; what can be done to provide protection of new discoveries, to thereby move those discoveries into patentable inventions? First, realizing that extremely broad claims for diagnostics are largely dead.  Second, identifying and researching molecules that may bring more man-made aspects into the claims, and specifically man-made aspects that are not commonly used research protocols.  I used radiolabeling and fluorescent labeling of molecules in research in the early 2000’s.  During that time, these labeling procedures were not considered cutting edge, but were regularly employed (though radiolabeling much less so due to administrative and safety concerns with radioactive materials). However, using the MuSK diagnostic as an example, identifying specific epitopes, which are not simply a portion of the MuSK protein, and that bind particularly well to the antibodies and/or provided a very strong signal-to-noise ratio would have been helpful to convince the court of patentability.  For example, a labeled and quenched diagnostic molecule[xv] may have saved this patent, which had a priority date of June 2000.  For medical companies seeking intellectual property protection for their research, especially in diagnostic areas, it is critical to think outside the box. Creative problem solving with a patent attorney provides avenues to protection that would otherwise be unavailable.

[i] See, Assoc. for Molec. Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 133 S.Ct. 2107, 2116-7 (2013); Mayo Collaborative Svcs. v. Prometheus Labs., Inc., 566 U.S. 66, 132 S.Ct. 1289, 1300 (2012).

[ii] Mayo Collaborative Svcs. v. Prometheus Labs., Inc., 566 U.S. 66, 132 S.Ct. 1289, 1294 (2012).

[iii] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 4 (Fed. Cir. 2019); Koneczny, et al., The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat. 2014 Jan; 224(1): 29-35.

[iv] Myasthenia Gravis Fact Sheet, Nat’l Inst. Of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet, last accessed February 13, 2019.

[v] Koneczny, et al., The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat. 2014 Jan; 224(1): 29-35; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867884/, last accessed February 13, 2019.

[vi] Koneczny, et al., The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat. 2014 Jan; 224(1): 29-35; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867884/, last accessed February 13, 2019.

[vii] Koneczny, et al., The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat. 2014 Jan; 224(1): 29-35; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867884/, last accessed February 13, 2019.

[viii] Myasthenia Gravis Fact Sheet, Nat’l Inst. Of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet, last accessed February 13, 2019.

[ix] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 3 (Fed. Cir. 2019).

[x] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 5 (Fed. Cir. 2019).

[xi] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 6 (Fed. Cir. 2019).

[xii] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 9-10 (Fed. Cir. 2019).

[xiii] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 15, et seq. (Fed. Cir. 2019).

[xiv] Athena Diagnostics, Inc. v. Mayo Collaborative Svcs., LLC, No. 2017-2508, slip 16 (Fed. Cir. 2019).

[xv] See, Bogdanov, Jr., et al., Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment. Neoplasia. 2002 May; 4(3): 228-36; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1531696/

Update on Brexit Implications on Trademarks

The withdrawal of the United Kingdom from the European Union, i.e. Brexit, is about 8 months from now, and the EU has begun issuing notifications of the implications on various sectors of the economy, including trademarks.[i]  The EU permits entities to obtain trademarks locally from specific countries, like Germany or France, or obtaining EU trademarks, which are valid in all EU member countries.  Absent an interim agreement between the UK and the EU covering trademarks, the EU has warned that all EU trademarks rights will cease in the UK on March 30, 2019.[ii]  This includes both trademarks filed with the European Union Intellectual Property Office (EUIPO) and international applications filed through the Madrid Agreement/Protocol that designate the EU. However, as on April 26, 2018 the UK has not begun implementing policies to cover EU trademark holders.[iii] For example, there are no identified policies covering entities wishing to file a UK trademark application and relying on EU trademark rights, such as priority or converting an EU trademark to a UK national trademark.  Read More

Obviousness and NSDP Tests

The Federal Circuit Refines Patentability Requirements in pharmaceutical and Chemical Technologies

A decision from the Federal Circuit Court of Appeals has refined what is required to show obviousness and anticipation in a pharmaceutical patent.  The patent involved lacosamide, an amino acid-like drug used in epilepsy treatment, shown below:

Accord, a generic drug manufacturer, submitted an abbreviated new drug application (ANDA) to the FDA seeking to manufacture and distribute a generic version of lacosamide, prompting the owner of the patent, UCB, to file a patent infringement suit.[i]  Accord challenged the validity of the lacosamide patent, arguing the UCB patent fails to meet the nonobviousness and novelty patenting requirements and that other UCB patents protect a patentably indistinguishable compound, known as nonstatutory double patenting. Read More

New Patent Eligibility Guidelines Require Evidence of Routine, Conventional, or Well-Known Knowledge

The U.S. Patent and Trademark Office recently issued new guidelines to determine patent eligibility.  For years after Alice,[i] Mayo,[ii] and Myriad,[iii] software and biotechnology patent applicants have had difficulty patenting many inventions, particularly in the trending “personalized medicine” field where patient genetics and proteomics are considered when selecting treatment regimens. Read More

Updates in Patent-Eligible Subject Matter

The Federal Circuit recently issued a much needed development in patentability case law, in Vanda Pharma. Inc. v. West-Ward Pharma. Int’l Ltd.[i]  Beginning in 2012, the U.S. Supreme Court upended years of patent law regarding patentable subject matter in biotechnology, relying on earlier case law stating natural laws and natural phenomena were not patent eligible subject matter.[ii]  These decisions included a commentary about elements of the patented work that was, in the Court’s opinion, well-understood, routine, conventional activity previously engaged in by researchers in the field, thereby adding an element of obviousness and anticipation analysis to the patent-eligibility inquiry.[iii]  A test issued by the Supreme Court, and further clarified by the Federal Circuit, provide that where a claim recites a natural law, the elements of the claim must be considered to determine if the claim as a whole is directed to an application of the recited law.  However, since these decisions, significant questions still plague patent examiners, attorneys, and courts regarding the requirements to meet patent eligibility. Most notably, to what constitutes sufficient material to distinguish a claim directed to a natural law versus an application of that law.  Since 2014, the U.S. Patent and Trademark Office released at least one new guideline each year to the patent examining corps providing amended instruction on determining patent eligibility.[iv] Read More