Prometheus v. Mayo - Patentable Subject Matter and Personalized Medicine - What Should You Do Next?

Prometheus v. Mayo –
       Patentable Subject Matter and
       Personalized Medicine – What
       Should You Do Next?

Prepared by Teresa A. Lavoie, Ph.D.

                                  May 10, 2012

Overview

I.      Personalized Medicine
II.     Mayo v. Prometheus
III.   What is happening now?
IV.    What should patent attorneys
       and their clients do next?

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What is Personalized Medicine (PM)?

• The customization of healthcare, with decisions and
  practices being tailored to individual patients
• Involves the systematic use of information about an
  individual to aid prevention, diagnosis, early intervention,
  and treatment of disease
• Traditionally used information such as family history,
  environment, behaviors, simple tests
• Now using genomic, proteomic, metabolomic, and
  epigenetic analyses and information, of increasing detail and
  sophistication
• Molecular profiling of individuals and diseases

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Why Personalized Medicine?

•   Goal: right drug for the right patient at the right time at the right dose
•   Also called predictive, preventive, and participatory medicine
•   Shift emphasis from reaction to prevention/early intervention
•   Better patient outcomes and quality of life
•   Optimized therapy vs. trial‐and‐error Rxs
•   Avoidance of adverse drug reactions or interactions
•   Increased patient compliance
•   Revival of failed drugs
•   Better control of overall cost of health care
•   Net: patients, payers, providers, public all benefit

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How different from previous approaches?

• Blockbuster Drug Approach
   • One size fits all
   • The “war” on cancer
• Clearly inefficient from efficacy and economic standpoint:
   • % of patient population for which a particular drug is
     ineffective:
       • 38% for SSRIs; 40% asthma; 43% diabetes; 50%
         arthritis; 70% Alzheimer’s drugs
       • 75% cancer
          – $604M annual cost savings to health care system if
            patients with metastatic colorectal cancer receive
            genetic test for KRAS prior to treatment
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Recent trends in PM

• 13 examples of PM Rx, Dx, treatments in 2006; 72 in 2011
• $300M to sequence genome in 2001; $5000 in 2011
• 30% of treatments in late clinicals rely on biomarker; 60% in
  preclinical development
• 75% increase in investment by industry over last 5 years
• 50% of all clinical trials collect DNA from patients to aid in
  biomarker development
• 33 biomarkers are included on FDA‐approved drug labels
• Two companion diagnostics approved summer 2011:
    • Genentech’s Zelboraf with RMS’s cobas 4800 BRAF V600 Mutation Test
      (melanoma)
    • Pfizer’s Xalkori (crizotinib) with Abbott’s Vysis ALK Break Apart FISH Probe
      (5% of NSCLC ALK positive)
• Market for companion diagnostics could grow to $40B by 2020
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What are the challenges?

• Development costs – $1 ‐ 30M +; unclear Dx/Rx ROI (blockbuster
  mentality vs. nichebuster mentality; hit rate of diagnostic; premium
  pricing?)
• Regulatory Policy
    • Dx kits regulated as medical devices; LDTs‐ typically CLIA certification but
      unclear level of data needed to validate complex tests linked to major
      health decisions
    • Difficult logistical coordination of Dx and Rx approval at FDA for
      companion diagnostics, esp. if two companies
    • Unclear guidance from FDA, although preference for simultaneous review
• Reimbursement – CMS, insurance providers
    • Simple vs. “esoteric” tests
    • Assert that to justify coverage, need rigorous assessment of cost‐
      effectiveness and impact on health outcomes
• Convergence needed: genetic privacy; medical education; health
  care IT; regulation; technology; reimbursement

                                                               7

Overview

I.     Personalized Medicine
II.     Mayo v. Prometheus
III.   What is Happening Now?
IV.    What should Patent Attorneys
       and their clients do next?

                                  8

Patent Eligible Subject Matter

• 35 U.S.C. § 101
   • Four categories of patent‐eligible subject matter: processes,
     machines, manufactures, and compositions of matter.
• Courts
   • Exceptions are “laws of nature,” “natural or physical
     phenomena,” and “abstract ideas.”
• In past, § 101 often used to bar patents when claims
  seen to be overbroad
• Specific/particular use of output of law of nature or
  specific machine – typically patentable
• Analogous use of § 103, § 112 to deal with unease with
  overbreadth

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Mayo v. Prometheus

• Method of monitoring levels of 6‐thiopurine in blood and
  adjusting dose of same, for treatment of immune‐
  mediated GI disorder, based upon upper threshold of
  toxicity and lower threshold of efficacy
• History
   •   District Court held claims invalid
   •   Federal Circuit reversed, holding the claims patent eligible using
       the machine or transformation test
   •   Supreme Court granted cert., vacated, and remanded for
       reconsideration in light of Bilski
   •   Federal Circuit again found all claims patent eligible
   •   Supreme Court found all claims patent ineligible

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Question to the U.S. Supreme Court

Whether 35 U.S.C. § 101 is satisfied by a patent claim
that covers observed correlations between blood test
results and patient health, so that the claim effectively
preempts all uses of the naturally occurring correlations,
simply because well‐known methods used to administer
prescription drugs and test blood may involve
‘transformations’ of body chemistry.

Short Answer? No.

“The question before us is whether the claims do
significantly more than simply describe these natural
relations. To put the matter more precisely, do the patent
claims add enough to their statements of the correlations
to allow the processes they describe to qualify as patent‐
eligible processes that apply natural laws? We believe that
the answer to this question is no.”

Mayo

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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Something more needed

“If a law of nature is not patentable, then neither is a
process reciting a law of nature, unless that process has
additional features that provide practical assurance
that the process is more than a drafting effort designed
to monopolize the law of nature itself.”

Mayo

• Analysis of the Claims
   • “The ‘administering’ step simply refers to the relevant audience …
     doctors who treat patients with certain diseases with thiopurine
     drugs”
   • “The ‘determining’ step tells the doctor to determine the level of
     the relevant metabolites in the blood, through whatever process
     the doctor or the laboratory wishes to use”
   • “The ‘wherein’ clauses simply tell a doctor about the relevant
     natural laws…”
   • Considering the elements together adds nothing
   • So claims are “not sufficient to transform unpatentable natural
     correlations into patentable applications of those regularities”

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Mayo

Supreme Court Holding or Implications
 – To be patentable, a claim that relies on a law
   of nature must do more than simply suggest “consider it”
   or “apply it”
 – Adding elements that are well‐known in the art, routine
   conventional, or that simply identify who uses the claim,
   e.g., steps that are required to get to the natural law,
   won’t save a claim that otherwise relies on a law of nature
 – Need to have an “inventive concept”
 – Patents should not be used to preempt the use of natural
   laws or inhibit their use in the making of further
   discoveries
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Compare Diehr

• Diamond v. Diehr, 450 U.S. 175 (1981) (“Diehr”)
   • Method for molding raw, uncured rubber
      • Used Arrhenius equation and physical measurements to
        determine when to stop the curing process
      • Included installing rubber, closing mold, repeatedly measuring
        temperature and calculating cure time, and opening mold
• Mayo says…
   • The additional steps “added to the formula something that in terms of
     patent law’s objective had significance – they transformed the process into
     an inventive application of the formula.”

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Diehr

1. A method of operating a rubber-molding press for precision molded
compounds with the aid of a digital computer, comprising:
     providing said computer with … [certain data] …,
     initiating an interval timer …upon the closure of the press …,
     constantly determining the temperature (Z) of the mold … [and]
constantly providing the computer with the temperature (Z),
     repetitively calculating …the Arrhenius equation for reaction time during
the cure, which is ln v = CZ + x …,
     repetitively comparing … the total required cure time calculated with the
Arrhenius equation and said elapsed time, and
     opening the press automatically when a said comparison indicates
equivalence.

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Compare Flook

Parker v. Flook, 437 U.S. 584 (1978) (“Flook”)
 – A method for adjusting ‘alarm limits’ in catalytic conversion of
   hydrocarbons
    • Based upon a computation
    • Added only monitoring of certain conditions for computation
 – Mathematical equation not patentable, nor was overall process
Mayo says…
 – “[P]utting the formula to the side, there was no ‘inventive concept’
   in the claimed application of the formula”
 – The instructions added nothing specific to the laws of nature other
   than what is well‐understood, routine, conventional activity,
   previously engaged in by those in the field

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Flook

1. A method for updating the value of at least one alarm limit …
involved in a process comprising the catalytic chemical conversion of
hydrocarbons … compris[ing]:
(1) Determining the present value of said process variable, said present
value being defined as PVL;
(2) Determining a new alarm base B1, using the following equation: B1 =
Bo(1.0—F) + PVL(F) … ;
(3) Determining an updated alarm limit which is defined as B1 + K; and
thereafter
(4) Adjusting said alarm limit to said updated alarm limit value.

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Example: Modified Mayo

A method of identifying a dosage of drug X within an
optimum range, comprising:
administering drug X;
measuring metabolites;
comparing to predetermined levels of the metabolite;
if too high, reducing dose of drug X by 10% until you reach optimum
range; and
if too low, increasing dose of drug X by 10% until you reach
optimum range.

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Overview

I.     Personalized Medicine
II.     Mayo v. Prometheus
III.   What is happening now?
IV.    What should patent attorneys
       and their clients do next?

                                      22

District Court Level

SmartGene v. Adv. Biol. Labs., CA No. 08‐00642, March 30,
2012 (D. DC 2012) (“SmartGene”)
 – D.J. lawsuit where ABL is the patentee.
 – Patents 6,081,786 and 6,188,988, entitled “Systems,
   Methods and Computer Program Products for Guiding the
   Selection of Therapeutic Treatment Regimens”
 – MSJ of invalidity for ineligible patent subject matter
   granted March 30, 2012, relying heavily on Mayo
 – All claims at issue; claim 1 of the ’786 representative

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Smart Gene (citing Mayo)

1. A method for guiding the selection of a therapeutic treatment regimen for a
patient with a known disease or medical condition, said method comprising:
(a) providing patient information to a computing device comprising:
a first knowledge base comprising … therapeutic treatment regimens …;
a second knowledge base comprising … expert rules for evaluating and
selecting a therapeutic treatment regimen …;
a third knowledge base comprising … information useful for the treatment of
a patient …; and
(b) generating … a ranked listing of available therapeutic treatment regimens
for said patient; and
(c) generating … information for one or more therapeutic treatment regimens
… based on said patient information and said expert rules.

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Smart Gene (citing Mayo)

Summary of Analysis
 – Reviews and relies upon Benson, Flook, Diehr, Bilski, and Mayo
 – Does step‐by‐step analysis
    • Preamble of “guiding selection” is a mental step
    • Providing info is what a doctor does when taking patient history,
      getting info on the condition as in the 3 databases, and
      documenting that in the patient’s medical chart
    • Generating a ranking is what a doctor does in deciding upon
      treatment
    • Generating advisory information is what a doctor does when
      prescribing treatment
    • Taken as a whole, nothing more is added

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USPTO Level

March 21 “Preliminary Guidance” Memo
 – Examiners should continue to examine patent
   applications for compliance with section 101 using
   the Interim Bilski Guidance issued July 27, 2010
 – Examiner should also consider “other elements or
   combination of elements such that, in practice, the
   claimed product or process amounts to
   significantly more than a law of nature, a natural
   phenomenon, or an abstract idea with
   conventional steps specified at a high level of
   generality appended thereto.”

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Overview

I.     Personalized Medicine
II.     Mayo v. Prometheus
III.   What is happening now?
IV.    What should patent attorneys
       and their clients be doing now?

                                     27

Claim drafting got us into this mess…

Prior precedent "warn us against interpreting patent
statutes in ways that make patent eligibility depend simply
on the draftsman's art without reference to the principles
underlying the prohibition against patents for [natural
laws]. They warn us against upholding patents that claim
processes that too broadly preempt the use of a natural
law.”

Characteristics of diagnostic method claims

• Characterized by one or more “determining” steps that involve
  assays, etc.
    • Often broadly claimed, no specific method in the claim
• Include “mental step” of reaching a conclusion or arriving at an
  inference based on outcome of “determining” step(s)
    • No subsequent steps, “nothing more” typically added
• Claim preamble directs method to certain activity (e.g.,
  “diagnosing”) based on inference
• Implicate doctor‐patient relationship
• Produce “information” – not necessarily action, not a
  “manufacture” under Bayer AG v. Housey Pharm, Inc.

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Claim drafting can help get us out of the
  mess…
• Existing Cases
   •   Review pending claim sets and file CONs (flexibility)
   •   Narrower claim sets (contrary to instincts)
   •   Confusion reigns at PTO – call PE or SPE, ask advice
   •   Add “something more” to the claims – activity, specificity
         • a therapeutic treatment step; a particular method of
           assaying, provided support in Specification
   •   Make sure natural law (correlation) is not the only novel feature
       of the claim
   •   Joint infringement?
   •   Sec. 112 issues?
   •   Mine specification
         • Claims to compositions of matter (biomarker, kits) or
           analytical methods (if novel/nonobvious)
   •   Be sensitive to issues of overbreadth and preemption

Claim drafting can help get us out of the
  mess…
• New Cases
   • Similar strategies as for existing cases … and remember: you’re not
     that cute.
   • Focus: client’s ultimate business objectives:
       • What type of Dx?
       • What is regulatory path?
       • Is TS an option?
       • Who/what is the market? Pharma partner? Bundled?
       • Who trying to exclude? Competitors? Generics?
       • Are there other types of exclusivities?
       • Market leader? Other competitive advantages?
       • Pricing? Reimbursement?
   • Approach coverage from multiple angles
       • Could this be pre‐emption?
   • Joint infringement and §112 may cause problems

Thank You!

  Teresa Lavoie
  Principal
  858‐678‐4307 (San Diego)
  612‐766‐2006 (Twin Cities)
  lavoie@fr.com

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