Patent Eligibility Under AttackLab Corp., Myriad, Classen & Prometheus: The New World in U.S. Biotech?

Mercedes K. Meyer, Ph.D.March 5, 2013

Disclaimer These materials are public information and have been

prepared solely for educational and entertainment purposes to contribute to the understanding of U.S. intellectual property law and practice. These materials reflect only the personal views of the speaker and are not individualized legal advice. It is understood that each case is fact-specific, and that the appropriate solution in any case will vary. Therefore, these materials may or may not be relevant to any particular situation. Thus, Drinker Biddle & Reath LLP and the speaker cannot be bound either philosophically or as representatives of their various present and future clients to the comments expressed in these materials. The presentation of these materials does not establish any form of attorney-client relationship with Drinker Biddle & Reath LLP and the speaker. 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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Where do we stand?

Method claims – Lab Corp., Classen, Prometheus & Myriad—Personalized medicine

Have Akamai & McKesson helped?

Composition claims - Gene claims under fire—Gene Claims – Myth v. Fact

Politics & Health Care in the U.S.

35 USC 101

§ 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, subject to the conditions and requirements of this title.

The Exceptions to Eligibility:—Law of nature (naturally occurring correlates) MPEP §2106.01—Algorithm—Abstract idea—AIA § 33 (a). Notwithstanding any other provision or law, no

patent may issue on a claim directed to or encompassing a human organism

• See also MPEP § 2105 and 1077 Off. Gaz. Pat. Off 24 (1987) – multicellular organisms including animals are patent eligible.

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Treatment Method ClaimsStatus Check

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We saw it coming - Lab Corp.Lab Corp.. v. Metabolite Laboratories, Inc., 548 U.S. 124 (2006)

Certiorari was dismissed as improvidently granted.

Claim 13 (still valid):— A method for detecting a

deficiency of cobalamin or folate in warm-blooded animals comprising the steps of:

• assaying a body fluid for an elevated level of total homocysteine; and

• correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.

Personalized Medicine

Obtain biological sample.

Measure biomarker with diagnostic. —Metabolites, single & multiple biomarkers,

genes, alleles, polymorphisms

Correlate biomarker with therapy.

Administer therapy.—The problem was that no therapy had to be

administered in the Prometheus claims.

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Stakeholders & Innovations Ziagen (GSK, Infectious disease) Epito / Tegreto (Novartis, Neuropsychiatric

disease) Erbitux (BMS, Cancer) Herceptin (Genentech, Cancer) Tasigna (Novartis, Cancer) Sprycel (BMS, Cancer) Tarceva (Genentech, Cancer) Trisenox (Cephalon, cancer) Vectibex (Amgen, Cancer) Tyverg (GSK, Cancer) Iressa (Astra Zeneca / Teva, Cancer) 8

Prometheus – Claim 1USPN 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 ad ministered to said subject.

INELIGIBLE SUBJECT MATTER 9

Prometheus – Claim 1USPN 6,680,302

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 a level of 6-thioguanine or 6-methyl-

mercaptopurine in said subject having said immune-mediated gastrointestinal disorder,

—wherein a 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 a level of 6-thioguanine greater than about 400 pmol per 8x108 red blood cells or a level of 6-methyl-mercaptopurine greater than about 7000 pmol per 8x108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

INELIGIBLE SUBJECT MATTER 10

Rewriting Claim 1 from the ‘623 Patent

Perhaps a patentable alternative?—A method of administering 6-thiopurine to a patient

in need thereof for treating an immune-mediated gastrointestinal disorder, comprising the step of administering a therapeutically effective amount of the drug that produces a level of 6-thiopurine

no less than 230 pmol and no more than 400 pmol per 8x108 red blood cells in blood from the patient.

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A Look Back to Classen

Classen Immunotherapies Inc. v. Biogen IDEC (2011):—Remanded from the Supreme

Court in light of Bilski.—2 of 3 claims were

found patent eligible.

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USPN 6,638,739 – ClassenImmunization Schedule = Patent Eligible

1. A method of immunizing a mammalian subject which comprises: (I) screening a plurality of immunization schedules, by (a) identifying a first group of mammals and at least a second group of mammals, said mammals being of the same species, the first group of mammals having been immunized with one or more doses of one or more infectious disease-causing organism-associated immunogens according to a first screened immunization schedule, and the second group of mammals having been immunized with one or more doses of one or more infectious disease-causing organism-associated immunogens according to a second screened immunization schedule, each group of mammals having been immunized according to a different immunization schedule, and (b) comparing the effectiveness of said first and second screened immunization schedules in protecting against or inducing a chronic immune-mediated disorder in said first and second groups, as a result of which one of said screened immunization schedules may be identified as a lower risk screened immunization schedule and the other of said screened schedules as a higher risk screened immunization schedule with regard to the risk of developing said chronic immune mediated disorder(s), (II) immunizing said subject according to a subject immunization schedule, according to which at least one of said infectious disease-causing organism-associated immunogens of said lower risk schedule is administered in accordance with said lower risk screened immunization schedule, which administration is associated with a lower risk of development of said chronic immune-mediated disorder(s) than when said immunogen was administered according to said higher risk screened immunization schedule. 13

PTO Example – Ineligible9/5/12 Customer Partnership Meeting

1. A method of determining the increased likelihood of having or developing rheumatoid arthritis in a patient, comprising the steps of:—obtaining a serum sample from a patient;—contacting the serum sample with an anti-IgM

antibody; and—determining that the patient has rheumatoid arthritis

or an increased likelihood of developing rheumatoid arthritis based upon the increased binding of the anti-IgM antibody to IgM rheumatoid factor in the serum sample.

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PTO Example – Why Ineligible? Inquiry 1: The claim is a process claim. Inquiry 2: The claim includes the limitation of

the correlation between rheumatoid arthritis and the rheumatoid factor IgM, which is a natural principle/law of nature.

Inquiry 3: All of the additional steps integrate or relate to the correlation.—The additional steps of obtaining and contacting are well

understood steps that are routinely conducted to analyze a serum sample.

—The steps are claimed at a high level of generality. —Considered as a whole, the steps taken together amount to

no more than recognizing the law of nature itself.15

But, Claim 3 is eligible!

3. The method of claim 1 or 2, wherein the anti-IgM antibody is antibody XYZ.—Inquiry 1: The claim is a process claim.—Inquiry 2: The claim includes the limitation of the correlation

between rheumatoid arthritis and the rheumatoid factor IgM, which is a natural principle/law of nature.

—Inquiry 3: The additional step of using a particular anti-IgM antibody (especially one that is not known in the field) integrates the law of nature as it is used to express the principle and is also sufficient to limit the application of the law of nature.

• The claim does not cover substantially all practical applications of the correlation between IgM and arthritis, because the claim is limited to those applications that use the antibody XYZ.

• Considered as a whole, the steps taken together amount to a practical application of the law of nature.

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And finally, Myriad

All of the method claims except for claim 20 of the USPN 282 were patent ineligible. —20. A method for screening potential cancer therapeutics

which comprises: growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

—“…at the heart of claim 20 is a transformed cell, which is made by man, in contrast to a natural material.”

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Claiming Methods – Legal Twister

Avoid claims that use comparison or analysis alone.—If process is to obtain data, make sure

the data is applied.—Transform the object.

Recast claims into method of treatment claims.

Write claims in a kit format if possible.

When writing claims, always consider whether a single actor or multiple actors are needed to carry out the method…—But what about Akamai and McKesson? 18

Akamai & McKessonGame Changer?

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The Tension

How do you write a claim that is patentable and enforceable?

—The origin of the claims in Prometheus and Lab Corp. was to claim the essential components of the invention that generally only require one actor in order to practice the process.

• 35 USC § 271 (b) for induced infringement is difficult to prove.

• Direct infringement under § 271 (a) is easier to prove.

—Claims were written for proving direct infringement.

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Akamai & McKesson(Fed. Cir. 2012)

A patent owner claiming induced infringement no longer has to show that a single actor is liable for direct infringement.

IMPACT: Huge implications for method claims, medical diagnostics, medical devices, banking, telecommunications and other technologies.

BUT, we are awaiting cert from the Supreme Court…..stay tuned

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STAY TUNEDSTAY TUNED

Myriad – DNA Claims

Myriad

The Question: “Are human genes patentable?”

3 patents, 10 claims left standing

Issues unaddressed:—Standing—Method claim 20—9 DNA claims

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Prediction

Human genes are not patentable!—Oral hearing April 15, 2013

But, what are we really claiming?

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The Problem

Claim construction is not an inviolable prerequisite to a validity determination under § 101—Bancorp Services, L.L.C. v. Sun Life Assur. Co. of Canada

It is evident from the Myriad CAFC en banc decision, including the dissents and separate concurring opinions, that claim construction did not occur.

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The Science - 1

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Eukaryotic Genes

The Science - 2

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The RNA is spliced to form mRNA For BRCA1 and BRCA2 there are multiple splice forms BRCA1 is 110 kb and BRCA2 is 70 kb BRCA2 has 22 exons / BRCA1 has 27 Only 5,500 and 10,200 bases approximately are claimed

Protein

Myriad: USPN 5,747,282 1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide

having the amino acid sequence set forth in SEQ ID NO:2. Gene? 2. The isolated DNA of claim 1, wherein said DNA has the nucleotide

sequence set forth in SEQ ID NO:1. cDNA? 5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

Fragment of a gene? 6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2. Fragment of a cDNA? 7. An isolated DNA selected from the group consisting of:

—(a) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having T at nucleotide position 4056;

—(b) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having an extra C at nucleotide position 5385;

—(c) a DNA having the nucleotide sequence set forth in SEQ ID NO: 1 having G at nucleotide position 5443; and, (d) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having 11 base pairs at nucleotide positions 189-199 deleted. cDNA variants? 28

Myriad: USPN 5,837,492

—1. An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:1. Gene variant?

—6. An isolated DNA molecule coding for a mutated form of the BRCA2 polypeptide set forth in SEQ ID NO:2, wherein said mutated form of the BRCA2 polypeptide is associated with susceptibility to cancer. Gene variant?

—7. The isolated DNA molecule of claim 6, wherein the DNA molecule comprises a mutated nucleotide sequence set forth in SEQ ID NO:1. cDNA variant?

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Myriad - USPN 5,693,473

1. An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:1. Gene variant?

Some Amici Arguments

Isolated & Purified—USPTO §101 Guidelines (2001)—DOJ

Infringement of the claims? Yes or No?—Whole genome sequencing

Damages limitations under 282—Doctors are excused under 35 USC 282(c)(1)—Moral and Ethical Considerations Are for Congress, Not the

Courts

Myriad's Claims Do Not Improperly Preempt The Field 31

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Is Licensing “THE” Issue?

Single Providers—Myriad / BRCA1 & 2—Canavan Disease – Miami

Children’s Hospital

Multiple Providers—Long QT Syndrome has two

providers with separate blocking patents

—Hearing loss – multiple providers for patents and unpatented genes

—Hereditary hemochromatosis – multiple LDTs; no IP impact

—Alzheimer’s Disease—Lynch Syndrome (HNPCC) —Familial adenomatous

polyposis (FAP)—Spinocerebellar ataxia

Politics & Health Care in the U.S.

Myriad, Timing and Sec. 27 of AIA

SEC. 27. STUDY ON GENETIC TESTING. (a) IN GENERAL.--The Director shall conduct a study on effective ways to

provide independent, confirming genetic diagnostic test activity where gene patents and exclusive licensing for primary genetic diagnostic tests exist.

(b) ITEMS INCLUDED IN STUDY.--The study shall include an examination of at least the following:— (1) The impact that the current lack of independent second opinion testing has

had on the ability to provide the highest level of medical care to patients and recipients of genetic diagnostic testing, and on inhibiting innovation to existing testing and diagnoses.

— (2) The effect that providing independent second opinion genetic diagnostic testing would have on the existing patent and license holders of an exclusive genetic test.

— (3) The impact that current exclusive licensing and patents on genetic testing activity has on the practice of medicine, including but not limited to: the interpretation of testing results and performance of testing procedures.

— (4) The role that cost and insurance coverage have on access to and provision of genetic diagnostic tests.

Results 9 months after enactment – June 2012 No study results

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Patents are not the Bogeyman Report alleged that gene patents impeded innovation and

increased health care costs.— Report was allegedly relied upon by the White House.

Fear Mongering - Report could not provide clear evidence of any significant negative implications from patented technology.— Relied on the “anti-commons” (patent thicket) theory of Rebecca Eisenberg,

which she now admits is unsupported by facts.— Report could only identify a “potential” for negative impact due to gene

patents. J. Breyer: If I am correct in my conclusion in Part III that the

patent is invalid, then… we should decide this case. To fail to do so threatens to leave the medical profession subject to the restrictions imposed by this individual patent and others of its kind. Those restrictions may…. force doctors to spend unnecessary time and energy to enter into license agreements. Lab Corp.

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Questions?Mercedes K. Meyer, Ph.D., J.D.Drinker Biddle & Reath LLP1500 K Street, NWSuite 1100Washington, DC 20005

www.drinkerbiddle.com36

Resources— Akamai Technologies Inc. v. Limelight Networks Inc. (Fed. Cir. 2012); McKesson Technologies Inc. v. Epic

Systems Corp., 692 F.3d 1301 (Fed. Cir. 2012)— Ass’n for Mol. Path. et al. v. Myriad Genetics, Inc., 689 F.3d 1303 (Fed. Cir. 2012)— Bancorp Services, L.L.C. v. Sun Life Assur. Co. of Canada, 687 F.3d 1266 (Fed. Cir. 2012)— Coliainni et al., “Impact of gene patents and licensing practices on access to genetic testing and carrier

screening for Tay-Sachs and Canavan disease.” Genet. Med. 12(4 Suppl): S5-S14 (2010) available at: http://www.ncbi.nlm.nih.gov/pubmed/20393311.

— HHS Draft Report on Gene Patents: http://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Consultation%20Draft%203%209%202009.pdf

— HHS Report on Access to Medical Testing: http://oba.od.nih.gov/oba/sacghs/reports/SACGHS_patents_report_2010.pdf

— Laboratory Corp. of America Holdings v. Metabolite Laboratories Inc. , 548 U.S. 124 (2006)— Classen Immunotherapies Inc. v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011)— Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S.Ct. 1289 (2012)— MPEP: http://www.uspto.gov/web/offices/pac/mpep/index.html— Public Consultation Draft Report on Gene Patents and Licensing Practices and Their Impact on

Patient Access to Genetic Tests.” 74 F.R. 11730— Recent Examiner Training and Developments Under 35 USC §101 (Sep. 5, 2012):

http://www.cabic.com/bcp/090512/BIO_9_2012_101_Train_Update(HANDOUT)_TC1600.pdf— Smartgene Inc. v. Advanced Biological Lab., SA (D.D.C. Mar. 30, 2012) Case 1:08-cv-00642-BAH –

claims found ineligible in view of Prometheus.37

Classen Claim 1 - Ineligible 1. A method of determining whether an

immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals, which comprises immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens, according to said immunization schedule, and comparing the incidence, prevalence, frequency or severity of said chronic immune-mediated disorder or the level of a marker of such a disorder, in the treatment group, with that in the control group. 38