Presentation title

Page 1

Genetic testing in the wake of the Australian and

US decisions re Myriad’s breast cancer patent

Jacinta Flattery-O’Brien, PhD

BRCA 1 protein

Zinc finger

Serine cluster domain

Isoforms (>1800 aa)

BRCA 1 gene on Ch 17 (43Mb)

Hundreds of mutations in BRCA1

Some variations carry 80% risk of

breast cancer

BRCA 1

An Australian problem

• Myriad startup established in US in 1994

• “Complete” Patent Application BRCA 1 lodged 1995

• Exclusive license to Genetic Technologies in Australia to conduct

breast cancer susceptibility tests BRCA-1 and BRCA-2

• In 2008 GT attempted to charge licensing fees

“genetic scanning on potential cancer victims has stopped in all

publicly funded laboratories, potentially placing many women’s lives

at risk”.

• GT backed down... too late...

Attempts to exclude gene

patents

• Inquiry by the Senate's community affairs committee into the

patentability of genes and other biological material

- recommended no exclusion of genes or biological materials

• Private members bill to exclude genes and biological materials from

patentability 2010

- rejected by the Senate Committee

Cancer Voices Australia v Myriad

Genetics Inc. [2013] FCA 65

(single judge)

• Invention means any manner of manufacture …. within section 6 of the

Statute of Monopolies1623

• Manner of manufacture = an artificially created state of affairs with

economic utility (NRDC v The Commissioner of Patents (1959) 102 CLR

252)

• Inconsistent with NRDC for a person whose skill and effort culminated in

the isolation of biological material not to be rewarded by the grant of a

patent.

• Decision in favour of Myriad

“Naturally occurring DNA and RNA as they exist in a cell are not within

the scope of any of the disputed claims and could never, at least not until

they had been isolated, result in the infringement of any such claim”.

D’Arcy and Myriad Genetics [2014]

FCAFC 115

(Full Federal Court – 5 judges)

• The Court considered

– patentability boundaries must encompass the development of

science and technology and human ingenuity;

– human intervention that creates an artificial state of affairs that

has some discernible effect is essential;

– expressions such as “the work of nature” or “the laws of nature”

are not found in the statute; nor are they useful tools of analysis.

• Unanimous decision in favour of Myriad.

D’Arcy v Myriad Genetics Inc [2015]

HCA 35

Nettle Gageler Kieffel French Bell Keane Gordon

Are Myriad’s claims in substance directed to a molecule or to “information”?

Australian Patent 686004

Claim 1: An isolated nucleic acid coding for a mutant or polymorphic BRCA1

polypeptide, said nucleic acid containing in comparison to the BRCA1 polypeptide

encoding sequence set forth in SEQ.ID No:1 one or more mutations or

polymorphisms selected from the mutations set forth in Tables 12, 12A and 14 and

the polymorphisms set forth in Tables 18 and 19.

High Court decision

• Unanimous: claims not directed to a “manner of manufacture” i.e. claimed

nucleic acids are not an “artificially created state of affairs”.

• Claims directed to “information embodied in the arrangement of

nucleotides” and “this information is not made by human action”.

• The fact that the invention lay at the boundaries of what constitutes a

manner of manufacture coupled with the breadth of the monopoly defined

by the claims, raised the risk of a “chilling effect” on legitimate innovative

activity and risked an unwarranted de facto monopoly impeding the

activities of legitimate improvers and inventors.

• cf. Centre for International Economics: “Patents play a key role in

promoting innovation and the public-private partnerships required to bring

new human gene-based medicines and diagnostics to market.”

Extension of HC decision to

exclude cDNA from patentability?

• Majority: “Used in that sense, the information stored in

the sequence of nucleotides coding for the mutated or

polymorphic BRCA1 polypeptide is the same

information as that contained in the DNA of the person

from which the nucleic acid was isolated. [...] The

product is the medium in which that information resides.

That characteristic also attaches to cDNA, covered by

the claims which is synthesised but replicates a naturally

occurring sequence of exons.”

Patent Office Guidelines

• When the substance of the claimed invention is genetic information

that was not “made”, claiming of the invention as an isolated product

does not confer patent eligibility.

• High Court not concerned with “gene patenting” generally

• NO findings re probes, vectors, methods of production and methods

of diagnosis.

• NO general rule that isolated natural products or their derivatives are

excluded from patentability.

Patent ineligible subject matter

• Isolated naturally occurring nucleic acid molecules

whether:

– DNA or RNA

– Human or non-human

– Coding or non-coding

• Claims to the following are excluded where they merely

replicate the genetic information of a naturally occurring

organism:

– cDNA and synthetic nucleic acids

– Probes and primers

Patent eligible subject matter

• Isolated naturally occurring material other than gene

sequences

• Recombinant or isolated proteins/microorganisms

• Pharmaceuticals and other chemical substances

• Methods of treatment and diagnosis

Method of diagnosis claims NOT challenged in Myriad

What does this mean for

pathologists?

Genes involved in a patented method of diagnosis of one

disorder may be used for diagnosis of another disorder

Note:

• Research exemption

• Actions in course of obtaining regulatory approval not an

infringement

Methods of diagnosis using genetic testing are patentable in

Australia

- exercise care when using patented methods

- consider patent protection for your methods of

diagnosis

United States vs Australia

Subject matter Patent eligibility in US Patent eligibility in

Australia Isolated naturally occurring gene

sequences

No No

Isolated naturally occurring gene

sequences having modified

nucleotides

Yes Depends whether the

modification contributes to the

working of the invention

Codon optimised gene

sequences

Yes Yes

cDNA Yes No

Interfering RNA molecules Yes Yes

Isolated naturally occurring

proteins

No Yes

Isolated micro-organisms No Yes

United States

Mayo Collaborative Services v

Prometheus

• Use of thiopurines to treat intestinal autoimmune

diseases such as Crohn’s disease and ulcerative colitis.

• Problem:

– The way each individual responds to thiopurines

varies markedly

– Difficult to determine an appropriate therapeutic dose

– Easy to administer either a toxic or a sub-therapeutic

dose

Mayo v Prometheus

Prometheus invention (personalised medicine)

– Administer an amount of thiopurine drug to a subject;

– Check the blood concentration of the metabolite 6-thioguanidine;

– Adjust the dose of thiopurine administered to attain a 6-

thioguanidine concentration of between 230 - 400pmol per 8x108

red blood cells

– The amount of drug metabolite, rather than the drug

administered, was key to successful treatment.

Court: “nothing significantly more than an instruction to apply applicable

laws when treating patients”

NOT patentable!

United States

Ariosa Diagnostics, Inc. v.

Sequenom, Inc. (Fed. Cir. 2015)

• Pregnant women’s blood contains large amounts of

cell-free fetal DNA (cffDNA).

• cffDNA can be used to determine a number of fetal

characteristics and abnormalities, e.g. Down Syndrome.

• Eliminates the need for amniocentesis and chorionic villus

sampling, which incur risks to both mother and child.

Claims US 6,258,540

• 1. A method for detecting a paternally inherited nucleic acid of fetal

origin performed on a maternal serum or plasma sample from a

pregnant female, which method comprises amplifying a paternally

inherited nucleic acid from the serum or plasma sample and

detecting the presence of a paternally inherited nucleic acid of fetal

origin in the sample.

• 24. A method for detecting a paternally inherited nucleic acid on a

maternal blood sample, which method comprises:

removing all or substantially all nucleated and anucleated cell

populations from the blood sample, amplifying a paternally inherited

nucleic acid from the remaining fluid and subjecting the amplified

nucleic acid to a test for the paternally inherited fetal nucleic acid.

Arguments

• Sequenom: methods are patentable as they define novel

uses of a natural phenomenon rather than the natural

phenomenon itself.

• Ariosa: the method does not "add enough" to a natural

phenomenon (the existence of cffDNA in maternal blood) to

render the claims patent eligible.

• The District Court agreed with Ariosa and stated that

Sequenom needed to invent novel ways of detecting cffDNA.

US Federal Circuit

• Using methods like PCR to amplify and detect cffDNA was well

understood, routine and conventional activity in 1997.

• The method amounts to an instruction to apply routine, conventional

techniques when seeking to detect cffDNA.

• The method of detecting paternally inherited cffDNA is not new and

useful (????).

• The only new and useful subject matter was the discovery of the

presence of cffDNA in maternal plasma or serum.

• The existence of cffDNA in maternal blood is a natural phenomenon.

Begins and ends with a natural

phenomenon?

• What comes out of the method is an artificially-enriched

substance that, unlike the naturally-occurring cffDNA

can be used for many diagnostic purposes.

• The method ends with a substance that is anything but a

natural phenomenon.

Comparing Mayo and

Sequenom

• Prometheus” every step of method had been performed

in the prior art; the only new aspect in those claims was

the therapeutic ratio, which the Court found to be a

"natural law."

• In Sequenom the inventors claimed something not

done before, ie detecting cffDNA in maternal blood for

diagnosis.

The big picture

• Methods of diagnosis are now very difficult to patent in

the United States

• Question: should diagnostic methods, genetic testing

methods in particular, be patentable?

• What is the purpose of the patent system?

• To encourage innovation?

Presentation title

Page 24

Thank you!

Questions?

Shelston IP Pty Ltd ABN 23 608 104 070

Jacinta Flattery-O’Brien, PhD