Is There Life (Science) After Prometheus?

Robert S. MacWright, Ph.D., Esq.

Executive Director

Salk Institute Office of Technology Development

A Seminal Case in Biotech Law• The Supreme Court decision in Mayo

Collaborative Services v. Prometheus Laboratories, Inc., is the most important biotech decision since Chakrabarty v. Diamond held that living organisms are patentable.

• The decision was unanimous, so will be the law of the land for the foreseeable future.

• The impact of this case is only beginning to be felt, but it seems likely to be enormous.

Disclaimer• The proper application of this case to the examination and

issue of patents will not be clear until tested in the courts, which will take years. Any statements here about this are subject to change as the law further develops.

• Statements about the potential impact on patentability of various inventions are very preliminary in nature, are just my personal opinion, and do not represent the official position of Salk.

• Nothing in this talk should be construed to be an admission that any Salk invention or claim is unpatentable. Salk relies on the case-specific guidance of outside counsel and the patent examination process for all such determinations.

In the Court’s Own Words (Well, almost.)

• The best way to understand the Court’s reasoning is to hear them explain it in their own words.

• Here, some liberty has been taken to condense and simplify the opinion and the claims at issue, while retaining the Court’s wording and the meaning of the claims as much as possible. Case references and quotation marks have been omitted.

claim 1 of the ’623 PatentA method comprising:

(a) administering a drug providing 6-thioguanine to a subject having an immune-mediated gastrointestinal disorder; and

(b) determining the level of 6-thioguanine,

Wherein a level less than about 230 pmol per 8x108 red blood cells indicates a need to increase the amount of the drug, and

wherein a level greater than about 400 pmol per 8x108 red blood cells indicates a need to decrease the amount of the drug.

What They Really Contributed• Thiopurine drugs are difficult to use,

because each patient’s body metabolizes them differently

• A toxic dose to one would be too low to work in another

• It was already known that metabolite 6-thioguanine was a valuable biomarker for appropriate dosing

• Prometheus only found the precise dosage limits

Case History• Prometheus sold kits for this test• Mayo stopped buying kits and ran tests on

its own, using slightly different cut-offs• The District Court found Mayo infringed

the patent, but that it was invalid because it claimed a law of nature

• The CAFC reversed, saying the “machine or transformation” test was satisfied

• The Supreme Court granted certiorari

Case History• In In re Bilski, the Supreme Court held that

the “machine or transformation test” was not the sole test for patentable subject matter, but just a “useful clue”

• The Supreme Court remanded Mayo v. Prometheus to the CAFC, in view of Bilski

• The CAFC looked at the “useful clue,” and again decided the patent was valid

• The Supreme Court granted cert. again

Preamble:Laws of Nature Are Not Patentable• Laws of nature, natural phenomena, and

abstract ideas are not patentable. • A new mineral discovered in the earth or a

new plant found in the wild is not patentable.• Einstein could not have patented E=mc2; nor

could Newton patent the law of gravity. • Such discoveries are ‘manifestations of . . .

nature, free to all men and reserved exclusively to none.’”

But Applications Are Patentable• Too broad an interpretation of this could

eviscerate patent law. • All inventions at some level rest upon or

apply laws of nature, natural phenomena, or abstract ideas.

• A process is not unpatentable because it contains a law of nature.

• An application of a law of nature to a known structure or process may well be deserving of patent protection.

Cautions of Precedent Cases• The Court’s precedents warn us:• Against making patent eligibility “depend

simply on the draftsman’s art” • Against patents that too broadly preempt

the use of a natural law• That a process that uses a natural law must

contain an “inventive concept” so it is significantly more than a patent upon the natural law itself.

• The claims here fail these tests.

The Patents Recite Laws of Nature• Prometheus’ patents set forth laws of nature -

namely, relationships between concentrations of metabolites and whether a given drug dosage will be ineffective or cause harm.

• The relationships exist apart from any human action, as a consequence of the ways in which the drug is metabolized -entirely natural processes.

• A patent that simply describes that relation sets forth a natural law.

“Apply the Law” Isn’t Enough

• 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 monopolize the law of nature itself.

• A patent, for example, could not simply recite a law of nature and then add the instruction “apply the law.”

The “Administering” Step

• The “administering” step simply refers to the relevant audience, namely doctors who treat patients with certain diseases with thiopurine drugs.

• The prohibition against patenting abstract ideas cannot be circumvented by “attempting to limit the use of the formula to a particular technological environment.”

The “Determining” Step

• The “determining” step tells the doctor to determine the level of the relevant metabolites in the blood, through whatever well-known process the doctor or the laboratory wishes to use.

• Purely “conventional or obvious” “pre-solution activity” is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law.

The “Wherein” Clauses

• The “wherein” clauses recite an upper limit beyond which the drug is toxic, and a lower limit beyond which the drug is ineffective.

• The “wherein” clauses simply tell a doctor about the relevant natural laws, at most adding a suggestion that he should take those laws into account when treating his patient.

The Upshot• The upshot is that the three steps simply tell

doctors to gather data from which they may draw an inference in light of the correlations.

• The claims inform a relevant audience about certain laws of nature; any additional steps consist of routine activity; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.

The Net ResultBeyond picking out the right doctors, the claim simply tells doctors to: 1. Measure (somehow) the current level of the relevant

metabolite,

2. Use (unpatentable) laws of nature to calculate toxicity/inefficacy limits, and

3. Reconsider the drug dosage in light of the law.

These steps must be taken to apply the laws in question, so the effect is simply to tell doctors to apply the laws somehow when treating patients.

Laws of Nature Should Not Be Preempted

• This Court has emphasized that patent law should not inhibit further discovery by tying up future use of laws of nature.

• E.g., in Morse the Court found unpatentable a claim for “the use of the motive power of the electric or galvanic current . . . however developed, for making or printing intelligible characters, letters, or signs, at any distances,” as it would inhibit the development of simpler, faster, cheaper methods of doing so.

Limits of the “Machine or Transformation” Test

In stating that the “machine-or-transformation” test is an “important and useful clue” to patentability, we have neither said nor implied that the test trumps the “law of nature” exclusion. That being so, the test fails here.

Scope of the Law of Nature Not a Factor• A patent upon a narrow law of nature may

not inhibit future research as seriously as would a patent upon Einstein’s law of relativity, but the creative value of the discovery is also considerably smaller.

• As we have previously pointed out, preempting even a narrow law of nature (such as the one before us) can inhibit future research.

Impact of This Decision is Debatable• Prometheus argues that denying patent

coverage here will interfere with the ability of researchers to make valuable discoveries in diagnostic research.

• But others (such as the AMA) argue that exclusive rights over the body’s responses to illness and treatment will produce a thicket of exclusive rights to critical scientific data that must remain widely available in order to provide sound medical care.

A Two-Edged Sword• We do not find this difference of opinion

surprising, because patent protection is a two-edged sword.

• The promise of exclusive rights provides monetary incentives that lead to creation, invention, and discovery. But that very exclusivity can impede the flow of information that might permit, indeed spur, invention.

General Rules Can Have Disparate Effects

• Patent law’s general rules must govern inventive activity in many different fields, and such general rules may have different practical effects from one field to another.

• We must hesitate before departing from established general legal rules, lest a new protective rule that seems to suit the needs of one field produce unforeseen results in another.

So, What May Be Unpatentable?• General Biomarker Diagnostic Claims.

Gene X is overexpressed in prostate cancer (“law of nature”). Test for product of Gene X; if increased, probably prostate cancer. (“apply the law”).

• General Drug Screening Claims. Gene X is overexpressed in prostate cancer (“law of nature”). Find new prostate cancer drugs by screening for compounds that reduce expression of X (“apply the law”).

So, What May Be Unpatentable?• General Method of Treatment Claims.

Gene X is overexpressed in prostate cancer (“law of nature.”) Treat prostate cancer by administering any compound that reduces expression of Gene X (“apply the law.”)

• Gene “Comparing” Claims. Gene X has a mutation at #43 in prostate cancer cells. (“law of nature.”) Compare a patient’s Gene X with the normal gene; if a mutation at #43, probably prostate cancer. (“apply the law.”)

What Might Make Them Patentable?• Assay-specific Biomarker Diagnostic

Claims. Gene X is overexpressed in prostate cancer. Test for Gene X mRNA levels using the novel cDNA probe having Sequence ID #1; if increased, probably cancer.

• Assay-specific Drug Screening Claims. Gene X is overexpressed in prostate cancer. Find new prostate cancer drugs by screening for compounds that reduce Gene X mRNA levels by using the novel cDNA probe having Sequence ID #1.

What Might Make Them Patentable?• Specific Method of Treatment Claims.

Gene X is overexpressed in prostate cancer. Treat prostate cancer by administering (new or known) compound Y or an analog thereof that reduces expression of Gene X.

• Gene “Comparing” Claims. Perhaps nothing. Correlation between a gene mutation and a disease state is a law of nature. Reciting a specific, known means of sequencing will not make it patentable.

What About Claims In-Between?• The opinion tells what is not patentable, but

gives no clear answer about what still is• How small of an “inventive concept” would

still make the claim “significantly more” than a claim to the natural law itself?

• It will probably take 10-20 years for case law to draw a clear outline!

• Deciding what to do in the meantime will be a challenge for applicants and attorneys

Science Discoveries Alone Probably Not Enough

• A newly-identified metabolic pathway is not likely to be patentable, nor any foreseeable use of that knowledge.

• To get a patent, you probably need to use that knowledge to develop or identify specific assays, reagents or drug compounds that can be used to apply that knowledge.

• If you want solid patents, so-called translational research is virtually essential.

Downsides and Upsides• Downsides: • Others can develop competing diagnostics,

screens and treatments using different assays, probes and compounds

• Reduced claim scope may mean lower royalties

• Upsides: • You can develop diagnostics and screens that

compete with those of others, and may be better• Some research and diagnostic method patents may

be invalid, allowing you to avoid having to buy kits or reagents (please seek legal advice!)

Important Patents That May Be Dead

• The PSA test for prostate cancer; others can probably do the test with other antibodies

• The BRCA1 and BRCA2 tests for breast cancer; most method claims were killed by the CAFC in the Myriad case, the last one will probably die on remand

• Thousands of drug screening and mechanism of action patents held by academic institutions

Other Biotech Claims are OK!• Isolated genes and cDNAs (but the Supreme

Court remanded Myriad Genetics…)• Treating a new disease with a known drug • New drug compounds• New antibodies and new antigens/epitopes• New assay methods• Method of drug screening with a novel assay• Cell lines, plasmids, gene constructs• Genetically modified animals and plants

What Makes Sense Strategically?• PTO examiner guidance should be issued

soon, may be best to hold pat until then• Cost of a long fight for broad claims should

be balanced against the economic value of those claims (It’s an investment)

• Claims that mirror those of Prometheus probably aren’t worth the fight

• A legislative fix to 35 USC 101? Possible, this case is only based on judicial doctrine

An Optimistic Final Thought

• Some say Prometheus will be whittled at by the lower courts, limiting it to the particular facts, e.g., no patent if you only define a numerical range for known markers

• Others argue that Prometheus may become a sliding scale between novelty and claim scope; perhaps if one discovers a truly novel biomarker, claims to assaying for it to detect disease may survive?

Disclaimer• The proper application of this case to the examination and

issue of patents will not be clear until tested in the courts, which will take years. Any statements here about this are subject to change as the law further develops.

• Statements about the potential impact on patentability of various inventions are very preliminary in nature, are just my personal opinion, and do not represent the official position of Salk.

• Nothing in this talk should be construed to be an admission that any Salk invention or claim is unpatentable. Salk relies on the case-specific guidance of outside counsel and the patent examination process for all such determinations.

Thanks!

Bob MacWright

Executive Director

Salk Office of Technology Development

Ext. 1703

rmacwright@salk.edu

www.salk.edu/otd