Ariosa v. Sequenom : The End of Precision Medicine? Hassen A. - - PowerPoint PPT Presentation

ROPES & GRAY LLP

Presented To New York Pharma Forum

Ariosa v. Sequenom: The End of Precision Medicine?

Hassen A. Sayeed, M.D. March 29, 2016

This presentation represents solely the personal views of the author. It should not be construed as legal advice or a legal opinion

• n any specific facts or circumstances. This information is not intended to create, and receipt of it does not constitute a lawyer-

client relationship. The contents are intended for general informational purposes only, and you are urged to consult your own lawyer concerning your own situation and any specific legal questions you may have.

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Disclaimer

This presentation represents solely the personal views of the author and does not reflect the view of Ropes & Gray LLP or any of its clients. It should not be construed as legal advice or a legal opinion on any specific facts or

• circumstances. This information is not intended to create,

and receipt of it does not constitute, a lawyer-client

• relationship. The contents are intended for general

informational purposes only, and you are urged to consult your own lawyer concerning your own situation and any specific legal questions you may have. While every attempt was made to insure that these materials are accurate, errors or omissions may be contained therein, for which any liability is disclaimed.

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Agenda

• Why Does Precision Medicine Matter?
• How Has The Patent System Endangered It?
• What Does The Future Hold?

ROPES & GRAY

Agenda

• Why Does Precision Medicine Matter?
• How Has The Patent System Endangered It?
• What Does The Future Hold?

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The Age Of “Imprecision” Medicine?

• The top ten-highest drugs in the United States

help between 1 in 25 and 1 in 4 of the people who take them

• For some drugs, such as statins, as few as 1 in

50 may benefit

• The US announced a $215 million national

Precision Medicine Initiative in January 2015

• Includes the establishment of a national

database of the genetic data of one million people

Source: Nature Comment, “Personalized Medicine: Time for one-person trials”, Nichols J. Schork, Nature 520, 609-611 (30 April 2015), available at: http://www.nature.com/news/perosnalized-medicine-time-for-one- person-trials-1.17411

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The “One-Size-Fits-All” Drug Regime Fails Many Patients

Source of data: Spear, B.B., Heath-Chiozzi, M., & Huff, J. (2001). Clinical application of pharmacogenetics. TRENDS in Molecular Medicine, 7(5), 201-204.); graphic from: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PersonalizedMedicine/UCM372421.pdf

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What Is Precision Medicine?

• Also known as: “Personalized Medicine”,

“Targeted Medicine”, “Stratified Medicine”

• The use of molecular analysis to better manage

disease or predisposition to disease

• Generally involves the use a diagnostic device

and a therapeutic product to tailor treatment

• Pharmacogenomics (the study of DNA and RNA

variation and effect on treatment response) is a critically important area of precision medicine

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Agenda

• Why Does Precision Medicine Matter?
• How Has The Patent System Endangered It?
• What Does The Future Hold?

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What Is Patentable Subject Matter?

• 35 U.S.C. § 101:

– “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter,

• r any new and useful improvement thereof, may obtain a

patent therefor, subject to the conditions and requirements

• f this title”
• Exception to Section 101 patentability:

– Laws of nature, natural phenomenon, and abstract ideas – Logic of pre-emption

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The Application Of Section 101

• Three key legal opinions have narrowed what

Section 101 means in the context of life sciences

– Mayo v. Prometheus Labs, 132 S.Ct. 1289 (2012) – Ass’n Molecular Pathology v. Myriad, 133 S.Ct. 2107 (2013) – Ariosa Diagnostics, Inc. v. Sequenom Inc., 788 F.3d 1371 (Fed. Cir. 2015)

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Patentability Of Diagnostic Methods

• Mayo v. Prometheus Labs (2012)

– Method of determining proper dosage of drug is not patentable subject matter – Set forth a two-part test for evaluating patentability

• (1) Are the patent claims directed to a non-patentable

law of nature, algorithm or natural phenomenon?

• (2) If so, do the additional elements of the claim “add

enough to their statements of the correlations to allow the processes they describe to qualify as patent eligible processes that apply natural laws” or are the additional elements routine, well-understood, and conventional?

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Patentability Of Diagnostic Methods

Representative claim

A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising: (a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and (b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder, wherein the level of 6-thioguanine less than about 230 pmol per 8x108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8x108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

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Patentability Of A Natural Product

• Ass’n Molecular Pathology v. Myriad (2013)

– Naturally occurring DNA segment, even when isolated from the body, is a non-patentable product of nature – cDNA was patent eligible subject matter since the removal of the unwanted codes created something new (i.e., no longer a product of nature)

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Patentability Of A Diagnostic Method Incorporating A Natural Product

• Ariosa Diagnostics, Inc. v. Sequenom Inc.(2015)

– U.S. Patent No. 6,258,540 (the “’540 patent”) titled “Non-Invasive Prenatal Diagnosis” – Sequenom‘s ’540 patent was based on the discovery that cell-free fetal DNA (“cffDNA”) can be detected in maternal serum and plasma samples – Claimed methods for detecting paternally inherited nucleic acid of fetal origin in maternal serum, blood or plasma – Marketed as MaterniT21

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Ariosa Diagnostics, Inc. et al. v. Sequenom Inc. et al.

• Representative claims--USP 6,258,540
• 1. A method for detecting a paternally inherited nucleic acid of fetal
• rigin performed on a maternal serum or plasma sample from a pregnant female,

which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

• 25. A method for performing a prenatal diagnosis on a maternal blood

sample, which method comprises

• btaining a non-cellular fraction of the blood sample

amplifying a paternally inherited nucleic acid from the non-cellular fraction and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.

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Ariosa v. Sequenom The Federal Circuit Decision

• On June 12, 2015 the Federal Circuit found the

claims unpatentable (as had the District Court)

– Authored by J. Reyna and joined by J. Linn and J. Wallach

• The decision applied the two step test for patent

eligibility set forth in Mayo

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Ariosa v. Sequenom The Federal Circuit Decision

• Step 1: The ’540 claims are directed to naturally
• ccurring phenomenon

– “It is undisputed that the existence of cffDNA in maternal blood is a natural phenomenon. Sequenom does not contend that [the inventors] created or altered any of the genetic information encoded in the cffDNA, and it is undisputed that the nucleic acids existed in nature before [the inventors] found them. The method ends with paternally inherited cffDNA, which is also a natural

• phenomenon. The method therefore begins and ends

with a natural phenomenon. Thus, the claims are directed to a thing that is naturally occurring.”

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Ariosa v. Sequenom The Federal Circuit Decision

• Step 2: Practicing of the claimed methods does not

result in an inventive concept

– “Sequenom contends that the claimed methods are patent eligible applications of a natural phenomenon, specifically a method for detecting paternally inherited cffDNA. Using methods like PCR to amplify and detect cffDNA was well- understood, routine, and conventional activity . . . . Because the method steps were well-understood, conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful. The

• nly subject matter new and useful as of the date of the

application was the discovery of the presence of cffDNA in maternal plasma or serum.”

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Ariosa v. Sequenom The Federal Circuit Decision

• The Federal Circuit rejected Sequenom’s argument

that its methods were patentable because they did not preempt every use of cffDNA

– “While preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility. In this case, Sequenom’s attempt to limit the breadth of the claims by showing alternative uses of cffDNA outside of the scope of the does not change the conclusion that the claims are directed to patent ineligible subject matter.”

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Breakthrough Technology Can Be Patent-Ineligible

• It is undisputed that before the ’540 patent, no one

was using the plasma or serum of pregnant mothers to amplify and detect paternally-inherited cffDNA

– “This argument implies that the inventive concept lies in the discovery of cffDNA in plasma or serum. Even if so, this is not the invention claimed by the ’540 patent.” – “[G]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry” (citing AMP v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2117 (2013)).

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Concurring Opinion (J. Linn)

• “I join the court’s opinion invalidating the claims of the ’540

patent only because I am bound by the sweeping language of the test set out in Mayo.”

– “In applying the second part of the test, the Supreme Court in Mayo discounted, seemingly without qualification, any ‘[p]ost-solution activity that is purely conventional or obvious.’” – “The Supreme Court’s blanket dismissal of conventional post- solution steps leaves no room to distinguish Mayo from this case, even though here no one was amplifying and detecting paternally- inherited cffDNA using the plasma or serum of pregnant mothers.’” – “It is hard to deny that Sequenom’s invention is truly meritorious.”

• “But for the sweeping language in the Supreme Court’s Mayo
• pinion, I see no reason, in policy or statute, why this

breakthrough invention should be deemed patent ineligible.”

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Sequenom ….cont’d.

• Sequenom petitions for rehearing en banc
• Federal Circuit denies petition

– J. Lourie (joined by J. Moore) and J. Dyk each author concurring opinions – J. Newman authors a dissenting opinion

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• J. Lourie’s Concurring Opinion
• No principled basis to distinguish this case from Mayo.

BUT...

• Claims should not be patent-ineligible on the ground that

they set forth natural laws or are abstractions, but because they may be indefinite or too broad

– “The claims recite innovative and practical uses for the natural material of cffDNA, particularly for diagnostic testing” – “It is undisputed that before this invention, the amplification and detection of cffDNA from maternal blood, and use of these methods for prenatal diagnoses, were not routine and conventional” – “But, applying Mayo, we are unfortunately obliged to divorce the additional steps from the asserted natural phenomenon to arrive at a conclusion that they add nothing innovative to the process”

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• J. Dyk’s Concurring Opinion
• Mayo is controlling precedent that governs the outcome here.

BUT…

• “A too restrictive test for patent eligibility under 35 U.S.C. § 101 with

respect to laws of nature may discourage development and disclosure

• f new diagnostic and therapeutic methods in the life sciences, which

are often driven by discovery of new natural laws and phenomena.”

• “[T]here is a problem with Mayo insofar as it concludes that inventive

concept cannot come from discovering something new in nature—e.g., identification of a previously unknown natural relationship or property. In my view, Mayo did not fully take into account the fact that an inventive concept can come not just from creative, unconventional application of a natural law, but also from the creativity and novelty

• f the discovery of the law itself. This is especially true in the life

sciences, where development of useful new diagnostic and therapeutic methods is driven by investigation of complex biological systems.”

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• J. Newman’s Dissent
• The facts of this case diverge significantly from the facts of Mayo and

Myriad.

• “[T]he inventors are not claiming the scientific fact of the discovery of

paternal DNA in the blood of a pregnant woman; they are claiming the discovery and development of a new diagnostic method of using this information.”

• “Precedent does not require that all discoveries of natural phenomena
• r their application in new ways or for new uses are ineligible for

patenting; the Court has cautioned against such generalizations.”

• “Such caution takes hold for the case at bar. The new diagnostic

method here is novel and unforeseen, and is of profound public benefit—‘a significant contribution to the medical field,’ … a ‘breakthrough’.”

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All Is Not Lost. . . .

• USPTO Patent Database searches

– (Biomarker and diagnos*) in the claims and an issue date between January 1, 2015 and March 22, 2016

• 43 patents
• 40 with method claims
• ~15 with claims directed to diagnostic methods

using a panel of biomarkers

– USPTO is allowing some limited diagnostic claims

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Agenda

• Why Does Precision Medicine Matter?
• How Has The Patent System Endangered It?
• What Does The Future Hold?

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Ariosa v. Sequenom Appeal To The Supreme Court

• March 21, 2016 -- Question Presented:

– Whether a novel method is patent eligible where: (1) a researcher is the first to discover a natural phenomenon; (2) that unique knowledge motivates him to apply a new combination of known techniques to that discovery; and (3) he thereby achieves a previously impossible result without preempting other uses of the discovery?

• Requests that the Supreme Court clarify its

Mayo ruling

– A new combination of otherwise conventional techniques should be patent eligible even if it is motivated by a patentee’s unique discovery of a natural law or phenomenon

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Ariosa v. Sequenom Appeal To The Supreme Court

• Sequenom argues that the Federal Circuit’s
• pinion will be fatal to life science innovation
• Focuses on the uncertainty created by the

decision

• How can companies confidently invest in

research, development, clinical trials, etc. if they do not know that their innovation will be rewarded with patent protection?

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Ariosa v. Sequenom The Impact

• Until the Supreme Court decides if it will hear the

case, what if any diagnostic methods are patentable?

• The 2014 and 2015 PTO-issued guidance:

– Example of what constitutes “significantly more”:

• “Improving another technology, a limitation that is not well-

understood, routine, and conventional, [or] mere instructions to ‘apply it’ . . . .” (July 2015 Update To Appx. 2).

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USPTO Guidelines

• 2014 Interim Guidance on Patent Subject Matter Eligibility

(Federal Register, Vol. 79, No. 242, pp. 74618-33 (December 16, 2014))

– http://www.uspto.gov/patents/law/exam/2014_eligibility_qrs.pdf – Nature based product examples – Abstract idea examples (1/27/2015)

• July 2015 Update (Federal Register, Vol. 80, No 146, pp.

45429 (July 30, 2015))

– http://www.uspto.gov/sites/default/files/documents/ieg-july-2015- update.pdf – Additional abstract ideas and laws of nature examples

• Diagnostic method examples are on the way

– Further explanation of the markedly different characteristics analysis

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And As If Things Weren’t Tough Enough . . .

• Can you even prove infringement?

– If the claimed steps involve “action steps” performed by multiple actors, consider the potential obstacles to proving infringement

• In order to show induced infringement, there must be a direct

infringer

• If your method includes multiple steps, can all acts be

attributed to one actor?

• Multi-party infringement is an evolving issue

under US law (Akamai Techs, Inc. v. Limelight Networks, Inc. (Fed. Cir. August 13, 2015))

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Akamai v. Limelight Divided Infringement

• Direct infringement under § 271(a)

– “Where more than one actor is involved in practicing the steps, a court must determine whether the acts of

• ne are attributable to the other such that a single

entity is responsible for the infringement. We will hold an entity responsible for others’ performance of method steps in two sets of circumstances: (1) where that entity directs or controls others’ performance, and (2) where the actors form a joint enterprise.”

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Akamai v. Limelight Divided Infringement

• Before Akamai, the acts of a third party could be

attributed to the accused infringer where:

– Acting through an agent – Contracted with a third party to perform one or more steps – There was a joint enterprise

• After Akamai:

– “[L]iability under § 271(a) can also be found when an alleged infringer conditions participation in an activity or receipt of a benefit upon performance of a step or steps of a patented method and establishes the manner or timing

• f that performance.”

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• Include detailed, non-routine steps in your claimed

method

– Methods that include specific, non-routine steps – claim the new technologies if possible – Argue no preemption – try to limit to specific mutations

• If multiple actors are involved:

– Draft claims so that additional actors are receiving a benefit from carrying out method steps – Draft claims to include steps that encompass acting thorough others

• Amicus Briefs and Congress

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Takeaways

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Thank You

Questions? Hassen A. Sayeed, M.D. Ropes & Gray, LLP 1211 Avenue of the Americas New York, New York 10036 (212) 596-9122 hassen.sayeed@ropesgray.com

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