Myriad & PrometheusMyriad & Prometheus

The Aftermath & Future The Aftermath & Future ConcernsConcerns

Mercedes Meyer, Ph.D.Mercedes Meyer, Ph.D.

AIPLA

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I am NOT Your Lawyer

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 this 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.

And nothing represents the views Drinker Biddle & Reath, its members, or any sentient life form on the earth or universe, or any parallel universe, alive or dead, fictitious, or real!

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Myriad Decided1. The Court asked: Are human genes patentable?

ANSWER: NO

cDNAs or complementary DNAs are patentable

No decision on method claims in Round 2.

2. What do these answers mean? CONFUSION

3. Why?

They got the science wrong

Nucleotides that do not code for amino acids are introns. Slip. Op. 2

They confused the law

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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 Algorithm Abstract idea AIA § 33. Notwithstanding any other provision or law, no

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

Genes

Myriad Claims

Claim 1 of the 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.

The Supreme Court found that this claim would include a gene No claim construction performed Term “isolated DNA” did not make it patent eligible This was the USPTO authorized way of claiming all the DNAs

that could encode the same protein A practitioner would not have considered this to include a

gene Claim is PATENT INELIGIBLE

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Myriad DNA ClaimsUSPN 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. Ineligible

2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1. Patent eligible

5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1. Ineligible

6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2. Valid? Yes, according to Myriad!

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.

Apparently valid

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The Science - 1

Eukaryotic Genes

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The Science - 2

The RNA is spliced to form mRNA For BRCA1 and BRCA 2 there are multiple splice forms BRCA1 is 110 kb and BRCA2 is 70 kb BRCA2 has 22 exons / BRCA1 has 27Only 5,500 and 10,200 bases approximately are claimed

Protein

Good News / Bad News

Gave credence to Funk Brothers Funk Bros. relates to obviousness – legal confusion

Claim 5 of ‘282 patent ineligible This style of claim was a problem for freedom to operate

opinions – at least in the US, the problem is saved Still a problem elsewhere globally

How to claim single nucleotide mutations? “The location and order of the nucleotides existed in nature

before Myriad found them. Nor did Myriad create or alter the genetic structure of DNA.” Op. at 12. Composition may not be patentable unless using “consisting of”

language or synthetic language Use in a method of diagnosis should be patentable

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Impact on Genes?

First isolated genes / proteins – patents now expired

Human genome project – done in early 2000 Most of those patent applications stand abandoned

In silico data only Many of the patents are expired for failure to pay

maintenance fees No real DNA drugs approved yet Polypeptide drugs are still eligible Most biologic drugs are modified or non-natural (e.g.,

antibodies) BUT….

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Future Problem in Other Areas??

DNA from bacteria Does not contain “introns” – is it patentable just by

saying cDNA?

Purified compounds Allegedly examiners are rejecting naturally occurring

polypeptides What about purified silica? Purified gold? What about product-by-process claims for natural

compositions? Stem cells? Plant extracts? Taxol? Enzymes from newly identified organisms that have

unusual properties?

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Claiming Solutions - DNA

Isolated / purified will not work!How to claim DNA?

cDNA An isolated cDNA coding for a BRCA1 polypeptide, said

polypeptide having the amino acid sequence set forth in SEQ ID NO: 2. [Eligible]

Synthetic DNA DNA lacking genomic sequences (intronic sequences) Using “consisting of” v. “comprising” to exclude

genomic sequencesOther DNAs – fusion DNA, siRNAs, antisense DNA, DNAs /

RNAs modified with a chemical - eligibleDNAs obtained by directed evolution?

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MORE Claiming Solutions

Proteins – “Synthetic” polypeptide not produced in its native cell? Chemical modifications - Unglycosylated or lacking

another native modification (fatty acid, unphosphorylated, etc.)

Modified protein – non-naturally occurring variants, non-naturally encoded amino acids, pegylation, fusion proteins, etc.

Product – By – Process Do we have to demonstrate that the product does not exist

in nature? How do we claim purified compositions? Will product characterization require evidence that it is not

naturally-occurring?

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Myriad – The Fight Continues

Myriad has sued Ambry and Gene-by-Gene for infringement based on their “other” BRCA1/2 patents

Ambry argues that Myriad prohibits enforcing synthesized DNA that mirrors genomic DNA, including probes

Quest Diagnostics has sued Myriad in California on 14 patents, 4 are not part of the other suit

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Prometheus – What is the PTO Saying?

• Inquiry 1 – Part I: – Does the claim include additional elements/steps that integrate the natural principle into the process? • It is not necessary that every step show integration. • If the additional elements/steps do not integrate the natural principle, there is no practical application. – If not, the claim fails the analysis and should be rejected.

See http://www.cabic.com/bcp/090512/BIO_9_2012_101_Train_Update(HANDOUT)_TC1600.pdf

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Prometheus and the PTO

• Inquiry 2 – Part II: – Does the claim include additional elements/steps that amount to significantly more than the natural principle itself? • Is the claim as a whole more than a natural principle plus the general instructions to simply “apply it”? – If not, the claim fails the analysis and should be rejected.

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Aria Diagnostics, Inc. v. Sequenom, Inc.

(Fed. Cir. 2013)

A method for detecting a paternally inherited nucleic acid of fetal origin performed on maternal serum… “detecting the presence of a paternally inherited nucleic acid of fetal origin of the sample.” Reversed and remanded. Claim construction assessed.

See also Digitech Image Technologies v. Konica Minolta Holdings, Inc. 2013 WL 3947158 (C.D. Cal. July 31, 2013)

Claim construction is going on in these 101 applications!

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Method Claiming Solutions?

Claim the product or method at least in a picture claim You will avoid written description and enablement issues in

the US and globally

Claim the method where the steps are taken by one actor McKesson/Akamai issue

Claim the compound to distinguish it over natural compositions

Claim narrowly Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir.

2013)

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Thank You

MERCEDES MEYER, PH.D.DRINKER BIDDLE & REATH LLP

WASHINGTON, DCMERCEDES.MEYER@DBR.COM

202-842-8821

USPTO Example

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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Example Claim – Not Patent Eligible

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.

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USPTO Example

2. The method of claim 1 further comprising:providing a positive control sample; andcontacting the positive control sample with an anti-IgM antibody,wherein the step of determining that the patient has rheumatoid arthritis or increased likelihood of developing rheumatoid arthritis comprises a step of comparing the anti-IgM antibody in the serum sample to the positive control sample. NOT ELIGIBLE3. The method of claim 1 or 2, wherein the anti-IgM antibody is antibody XYZ. ELIGIBLE

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PTO Guidelines

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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