Patenting Diagnostic Methods After Mayo v. Prometheus

Playing with Fire?

Christopher D. Gram, J.D., M.S.

•March 2011

I am REALLY glad to be here

•March 2011 •April 4, 2014

Patent Eligibility

35 U.S.C. 101 Inventions patentable.

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.”

Patentability

35 U.S.C. §102: Novelty35 U.S.C. §103: Nonobvious35 U.S.C. §112 Is the invention enabled?Does the application describe the full

scope of what is claimed?Are the claims clear to a person of

ordinary skill in the art?

Back to 35 U.S.C. §101

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor…”

Back to 35 U.S.C. §101

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor…”

Congress intended statutory subject matter to “include anything under the sun that is made by man.” – Diamond v. Chakrabarty, 447 U.S. 303 (1980)

Exceptions to 35 U.S.C. §101

Judge-made exceptions to patentable subject matter Natural Products Natural Laws/Natural Phenomena Abstract Ideas/Mental

Processes/Algorithms

Exceptions to 35 U.S.C. §101

Judge made exceptions to patentable subject matter Natural Products Natural Laws/Natural Phenomena Abstract Ideas/Mental Processes/Algorithms

They are “part of the storehouse of knowledge … free to all men and reserved exclusively to none.” – Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948)

Patent Eligibility vs. Patentability

Traditionally, patent-eligibility has been a low standardAlmost any human involvement is

sufficientPatentability a more demanding

standard§102, §103, and §112

Prometheus – the discovery

Thiopurine drugs for treatment of autoimmune diseases

6-thioguanine prodrugMetabolized to 6-thioguanine (6-TG)Further 6-TG metabolites known to

correlate with: Efficacy Toxicity

Precise metabolite levels previously unknown

U.S. Patent No. 6,355,623

6-TG nucleotidesToxicity at >400 pmoles/8x108 cellsLow efficacy at <230 pmoles/8x108

cells

6-methyl-mercaptopurine (6-MMP)Toxicity at >7000 pmoles/8x108 cells

U.S. Patent No. 6,355,623

1. 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.

U.S. Supreme Court analysis

1. A method comprising:(a) administering a drug; and (b) determining the level

of 6-thioguanine in the patient;(c) results indicate a need to change dosing

Correlation is a law of nature “…namely, relationships between concentrations

of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.”

U.S. Supreme Court analysis

1. A method comprising:(a) administering a drug; and (b) determining the level

of 6-thioguanine in the patient;(c) results indicate a need to change dosing

Claim is, essentially, “apply the correlation”No affirmative change in treatment requiredNo limits on the determining step

Conventional methods S.Ct. says the claim preempts all use of the

correlation

What’s happened since?

S.Ct. Mayo v. Prometheus decision came out in October 2011

No case has made it to the Federal Circuit

What is the USPTO doing? Issued Examiner Guidelines for

Patent Eligibility Analysis

What’s happened since?

S.Ct. Mayo v. Prometheus decision came out in October 2011

No case has made it to the Federal Circuit

What is the USPTO doing? Issued Examiner Guidelines for

Patent Eligibility AnalysisMarch 4, 2014

USPTO Guidelines

Three questions1. Is the claim directed to a statutory

category—process, machine, manufacture, composition?

2. Does the claim fall within a judicial exception?

3. Does the claim recite something significantly different than the judicial exception?

What is significantly different?

Includes elements or steps in addition to the natural law/phenomenon that practically apply the natural law/phenomenon in a significant way

Includes features or steps that demonstrate the claimed subject matter is markedly different from what exists in nature

Examples – U.S. Pat. 6,033,857

A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequences identifies a mutant BRCA2 nucleotide sequence.

This claim was held ineligible by the Federal Circuit in AMP v. Myriad.

Examples – U.S. Pat. 5,710,001 26. A method for screening a tumor sample from a human

subject for the presence of a somatic alteration in a BRCA1 gene…, wherein said comparing is performed by

(i) detecting either a full length polypeptide or a truncated polypeptide in each sample or

(ii) contacting an antibody which specifically binds to either an epitope of an altered BRCA1 polypeptide or an epitope of a wild-type BRCA1 polypeptide to the BRCA1 polypeptide from each sample and detecting antibody binding, wherein a difference between the BRCA1 polypeptide from said tumor sample from the BRCA1 polypeptide from said nontumorsample indicates the presence of a somatic alteration in the BRCA1 gene in said tumor sample.

Examples – U.S. Pat. 8,642,2701. A method of treating breast cancer in a subject having a triple

negative (TN) breast cancer, the method consisting of the steps:(a) quantifying mRNA expression level of biomarkers STK3

and KLF6, and at least one biomarker selected from CD24 and KRAS in a test sample from a subject using a biological assay;

(b) comparing said mRNA expression level of said biomarkers selected from STK3, KLF6, and at least one of CD24 and KRAS quantified in step (a) to the expression level of said biomarkers quantified using the biological assay in a standard sample indicative of a recurrent TN breast cancer; and

(c) administering an aggressive cancer treatment regimen to the subject based on an increase in the expression level of the biomarkers between the standard sample and the test sample.

Examples – U.S. Pat. 8,568,9741. A method for treating high risk B-precursor acute lymphoblastic

leukemia (B-ALL) in a patient in need comprising: A) determining whether said patient is a candidate for

traditional therapy for B-ALL comprising i) obtaining a biological sample from said patient; ii) analyzing said sample to determine the expression level

of the gene products MUC4 (Mucin 4) and IGJ (immunoglobulin J) in said sample; and

iii) comparing the observed gene expression levels for each of said gene products to a control gene expression level…; wherein an observed expression level that is higher than the control gene expression for both of said gene products is indicative of therapeutic failure with traditional leukemia therapy; and…

Examples – U.S. Pat. 8,568,9741. (cont.)

B). treating B-ALL in said patient with non-traditional leukemia therapy if the observed expression level is higher than control level.

Examples – U.S. Pat. 8,568,974

Filed before Prometheus v. MayoClaim 1, cast as a diagnostic method, was

rejected under 35 U.S.C. §101Claim 1 amended to recite the treatment stepApplication allowed

Examples – USPTO Guidelines

A method for determining whether a human patient has degenerative disease X, comprising: obtaining a blood sample from a human patient; determining whether misfolded protein ABC is present in the blood sample, wherein said determining is performed by contacting the blood sample with antibody XYZ and using flow cytometry…; and diagnosing the patient as having degenerative disease X if misfolded protein ABC was determined to be present in the blood sample.

Strategies

Specify a particular manner of detection Avoids preempting the entire scope of the

correlationRecast as a method of treatment and/or

specify a treatment regimen “aggressive treatment” or “palliative treatment”

may be enough specificity Induced infringement

Conclusions

In many cases, diagnostic methods remain patent-eligible

Inventors can assist STC and patent attorney be thinking about “limitations” that, as a practical matter, don’t narrow the scope of the methods

Questions?