1. The document provides an overview of intellectual property strategies for diagnostics, including a brief review of patent basics, the scope of patent protection for diagnostics, common types of claims, considerations for support and examination procedures, and enforcement and exploitation of patents. 2. Key topics covered include what can be patented in diagnostics, such as inventions, selection patents, subject matter restrictions, medical methods, higher life forms and biotechnological inventions. Common claim types for diagnostics like products, methods, machines and uses are described through examples. 3. Support for patent applications requires meeting criteria like novelty, inventiveness, utility and enablement, with enablement ensuring sufficient disclosure to support the claim scope without undue experiment

1. MaRS Best Practices
Series:
IP Strategies for
Diagnostics
Cynthia Tape
Anna Wilkinson
MaRS, Toronto
February 28, 2008

2. Outline
1. Brief review of patent basics
2. Scope of patent protection for diagnostics
3. Types of claims
4. Support
5. Enforcement and exploitation
2

3. 1. Brief review of patent basics
What is a patent
• Patent is a bargain/contract between an inventor and the
state:
 the inventor discloses his/her know-how so that others can
practice the invention;
 in return for a time limited monopoly
• Restrictions on the type and quality of information that is
patentable
 categories of patentable subject matter
 information must be new, useful, unobvious
3

4. 1. Brief review of patent basics
What is a patent (continued)
• Bargain is reflected in the format of a patent:
 a description (text and maybe drawings), wherein inventor
teaches how to practice the invention
 a set of claims, which define the monopoly
• Bargain assessed during examination of a patent application:
 detailed examination procedure before the patent office
 meant to ensure scope of monopoly reflects new subject matter
that the inventor actually invented and taught to the public
4

5. 1. Brief review of patent basics
The patent monopoly
• Patent monopolies are territorially limited
• generally, must apply for a patent and application must be
examined in each country in which a monopoly is desired
• Patent monopolies are time limited
• generally, 20 years from filing application
• Patent monopolies are exclusionary
• a patent does not give the patentee the right to practice the
invention, only the right to sue someone else who practices
it without permission
5

6. 1. Brief review of patent basics
The monopoly (continued)
• Patent excludes others from making, using or selling
your invention without permission
• Your patent may not allow you to practice the invention:
No guarantee of Freedom to Operate
• Filing preserves your place in line: right to enforce only
when patent issues, which can take many years
6

7. 2. Scope of patent protection for diagnostics
What can be patented?
• An “invention”: defined very broadly, with exceptions carved
out either through legislation or by case law:
 In the United States: “anything new and useful made by man”
 In Canada: any new and useful art, process, machine,
manufacture or composition of matter, or any new and useful
improvement thereon
 In Europe: any inventions, in all fields of technology, provided
that they are new, involve an inventive step and are susceptible
of industrial application…followed by a list of specific exclusions
7

8. 2. Scope of patent protection for diagnostics
What can be patented? (continued)
• Selection patents:
 permit a species of a previously patented genus to be patented
based on a special advantage
• requirements: no prior specific disclosure; unpredictable,
unexpected advantage
 arise in context of chemical patents; could be relevant to
diagnostics
 hot issue in Canadian patent law:
• long recognized in UK and US law; also here
• SCC case being heard in April – whether
they should be recognized in Canada
8

9. 2. Scope of patent protection for diagnostics
What can be patented? (continued)
• Subject-matter restrictions relevant to diagnostics:
 no patents for scientific principles or abstract theorems (Patent
Act, section 27(8))
• E=mc2, Newton’s laws not patentable
• restriction relevant to diagnostics, but distinction may not be
clear: LabCorp v. Metabolite Laboratories, Inc. USSC 2006
 be aware of limitations on methods of medical treatment, higher
life forms, biotech
9

10. 2. Scope of patent protection for diagnostics
What can be patented? (continued)
• LabCorp v. Metabolite Laboratories
 Patent for a test for detecting vitamin B deficiencies by measuring amino acid
homocysteine in a patient’s blood; method claim: assaying levels of homocysteine
and correlating level with vitamin deficiency
 LabCorp, licensee of Metabolite, began using a different method for measuring
homocysteine; stopped paying royalties
 Metabolite sued and was successful at trial: LabCorp enjoined from using any
homocysteine test
 US Supreme Court dismissed appeal by LabCorp without explanation; dissent would
have held that broad method claim was unpatentable for being a basic scientific fact
 value in having a variety of different types of claims
10

11. 2. Scope of patent protection for diagnostics
Medical methods
• Medical methods are not patentable in Canada and Europe
• may be able to claim “method” as a new use
e.g. use of drug X for treating Y
• diagnostic methods are not patentable in Europe
• patentability of diagnostics in Canada may depend on whether
invention includes an invasive step and if what you are doing
could also have a therapeutic effect
• Canadian example: diagnostic method that involved injection of
radiolabelled antibodies as tumour markers was permitted on
basis that would not have a therapeutic effect
11

12. 2. Scope of patent protection for diagnostics
Medical methods (continued)
• Medical and diagnostic methods are patentable in the United
States, but medical methods are not enforceable against a
doctor
 can’t sue a doctor for infringement, but can sue a lab technician
12

13. 2. Scope of patent protection for diagnostics
Higher life forms
• Not patentable in Canada per se
• Harvard College v. Commissioner of Patents, SCC 2002
• 5:4 split decision: Harvard Mouse not patentable subject
matter (not a composition of matter)
• But note Schmeiser v. Monsanto, SCC 2004
• 5:4 split decision: claims for genes and cells of genetically
modified canola could be enforced against grower of canola
plants
• Patentable in the U.S. and Europe
13

14. 2. Scope of patent protection for diagnostics
Biotechnological inventions
• Patent Offices and Courts have had to wrestle with
various issues in determining what biotechnological
matter is patentable:
• Basic scientific facts are not patentable
• Novelty: i.e. if sequence is present in nature, can it be
patented as new once isolated and sequenced?
• Utility: what is required to show that a gene sequence is
useful?
14

15. 2. Scope of patent protection for diagnostics
Biotechnological inventions (continued)
• In Europe biological material (including sequence or
partial sequence of a gene) which is isolated from its
natural environment or produced by means of a technical
process even if it previously occurred in nature
• In US novelty is also based on isolation from nature
• Will also need to demonstrate utility of what you have
isolated/sequenced
15

16. 3. Types of claims
Common claim types
• Product
• Structure
• Process by which it is made (product-by-process)
• Physical or chemical properties
• Machine or apparatus
• System
• Method or process
• New use (of a new or known product)
• Kit
16

17. 3. Types of claims
Subject matter
• Subject matter of claims dictated by technological
developments
• In-vitro diagnostic testing (IVD): analyzing
blood/urine/other specimens to screen for or monitor
diseases or other medical conditions
• Molecular diagnostics: determining the function of genes
and gene products
• Pharmacogenomics: functional genomics + molecular
pharmacology
• Personalized medicine
17

18. 3. Types of claims
Subject matter (continued)
• Diagnostic tests can be:
• Predictive
• Screening
• Prognostic
• Monitoring
• Pharmacogenomic
18

19. 3. Types of claims
Participants in field
• When formulating claims, should consider different
participants:
• Innovators
• Manufacturers
• Users:
• Commercial labs
• Hospital labs
• Physician office labs
• Patients
• Supervised
• Over the counter
• Payers
19

20. 3. Types of claims
Structure of a claim
• Preamble (green)
• Transition language (red)
 open: “comprising”, “including”
 closed: “consisting of”
• Body (blue)
• Claims are numbered
• Independent claim (claim 1) does not make reference to
another claim and is broadest in scope; a dependent
claim incorporates the limitations of a preceding claim
and so is narrower
20

21. 3. Types of claims
Examples of subject matter
• Amplification
• Fluorescent in situ hybridization
• DNA probes
• Molecular labels
• Biochips
• Microfluidics
• Signal detection
• Biosensors
• Medical imaging
21

22. 3. Types of claims
Example: Method (US 5314809)
1. A method for nested amplification of a sequence within a target nucleic acid in a sample, the
method comprises:
(a) simultaneously mixing said sample in an amplification reaction mixture containing an outer
primer pair and an inner primer pair, wherein said outer primer pair is capable of amplifying a
target nucleic acid to provide an amplified target sequence, and said inner primer pair is
capable of amplifying a subsequence within said target sequence;
(b) treating the amplification reaction mixture of step (a) in an amplification reaction at a
temperature for annealing and extending said outer primer pair on said target nucleic acid
and at a temperature for denaturing the extension products of said outer primer pair to
provide an amplified target sequence, wherein said temperature for annealing and extending
said outer primer pair is higher than the temperature for annealing and extending said inner
primer pair to said target nucleic acid and said temperature does not allow efficient extension
of at least one member of said inner primer pair; and
(c) treating the mixture of step (b) in an amplification reaction at said temperature for annealing
and extending said inner primer pair on said amplified target sequence, and at an
temperature for denaturing the extension products of said inner primer pair to provide an
amplified subsequence.
22

23. 3. Types of claims
Example: Product (US 6576424)
1. An array comprising a solid substrate and a plurality of
positionally distinguishable sequence specific
polynucleotides attached to the solid substrate of at least
100 polynucleotides per cm2, at least a plurality of said
polynucleotides comprising at least 25 nucleotides.
23

24. 3. Types of claims
Example: Apparatus (US 7238323)
1. A sequencing apparatus comprising: a body having a top portion, a bottom portion and an
interior portion;
the interior portion comprising at least two intersecting channels, wherein at least one of the
two intersecting channels has at least one cross sectional dimension between about 0.1 µm
and 500 µm;
an electrokinetic fluid direction system for moving a first sequencing reagent through at least
one of the two intersecting channels;
a source of sequencing primers;
an electropipettor for introducing sequencing primers from the source of sequencing primers
to the at least two intersecting channels;
a mixing zone fluidly connected to the at least two intersecting channels for mixing the first
sequencing reagent with a second sequencing reagent;
a size separation zone fluidly connected to the mixing zone for separating sequencing
products by size, thereby providing the sequence of a target nucleic acid; and
a computer having computer-readable code for selecting a sequencing primer.
24

25. 3. Types of claims
Example: System (US 6816742)
1. A sampling system for monitoring the concentration of an analyte present in a
subject, said sampling system comprising:
a sensing device comprising a collection reservoir comprising an enzyme capable
of reacting with the analyte to produce hydrogen peroxide and a sensor element in
operative contact with the reservoir, wherein said sensor element reacts
electrochemically with the hydrogen peroxide produced in the reservoir to provide a
detectable signal, and said sensor element comprises an electrode having a
geometric surface area which ranges from about 0.1 to 3 cm2, a background
current which ranges from about 2 to 60 nA or less when measured in a buffer
solution at 0.6V, and a sensitivity which ranges from about 6 to 180 nA/µM of
hydrogen peroxide when measured in a buffer solution at 0.6V, and
one or more microprocessors in operative communication with the sensing device
comprising programming to control operation of the sensing device.
25

26. 3. Types of claims
Example: Use (EP 0241106)
1. The use of detectably labeled immunoglobulin or a fragment thereof,
wherein said immunoglobulin or fragment
(a) substantially accumulates at an inflammation site when said site is
inflamed,
(b) has no substantial epitopic specificity for said inflamed site, and
(c) comprises one or more of:
(i) pooled, human, polyclonal immunoglobulin;
(ii) Fc fragment of pooled, human immunoglobulin;
(iii) monoclonal antibody;
(iv) Fc fragment of monoclonal antibody;
in the preparation of an agent for the detection of an inflammation site
in vivo.
26

27. 3. Types of claims
Example: Use (US 785 216)
1. Use of an isolated nucleic acid which comprises the
coding sequence set forth in SEQ ID NO: 1 from
nucleotide position 229 to nucleotide position 10482 and
further comprising the mutation associated with a
predisposition to breast cancer, wherein T at nucleotide
position 6174 is deleted, for diagnosing a predisposition
to breast cancer in Ashkenazi-Jewish women in vitro.
27

28. 3. Types of claims
Example: Kit (US 7122324)
1. A diagnostic test kit for assaying for the presence of C-
terminal human glycoprotein IIb (hGPIIb) fragments in a body
fluid sample, comprising a package containing an antibody
composition comprising antibody molecules that:
a) immunoreact with a polypeptide having an amino acid
residue sequence as shown in SEQ ID NO: 3 from residues
173 to 193, 173 to 181, residues 179 to 189, residues 187 to
200, or residues 194 to 200;
b) do not immunoreact with a second polypeptide having the
amino acid residue sequence REQNSLDSWGPK, as shown
in SEQ ID NO: 3 from residue 113 to residue 124.
28

29. 4. Support
The Examination Procedure: Key Criteria
• Subject matter: is it a patentable invention?
• Novelty: is it new?
• Inventiveness: is it obvious?
• Utility: is it useful?
• Enablement or sufficiency: do the teachings you have
provided entitle you to the scope of the monopoly you are
seeking?
• Specifics vary among jurisdictions
29

30. 4. Support
Enablement
• Description must enable a person skilled in the art to
practice the invention without undue experimentation
• How much disclosure is necessary to support broad
claims?
Fact dependent
• May involve sequence listing for amino acid or nucleic
acid sequences
• May involve deposit of biological material
30

31. 4. Support
Enablement: Factors to consider
• Breadth of claims
• Nature of invention
• Predictability of art
• State of prior art
• Relative skill of those in art
• Quantity of experimentation necessary
• Presence of working examples
31

32. 4. Support
Utility
• What is the use or function?
• Credible, specific, substantial (i.e. real world use)
• Unpredictable factors associated with chemical reactions
and physiological activity may make standard harder to
meet than in some other art fields
32

33. 4. Support
Sound prediction
• Do not have to test every species in a genus – may be able to
rely on the Doctrine of Sound Prediction
 Apotex v. Wellcome Foundation, SCC 2002
• AZT – new use for an old compound
• issue: Could the data in the patent support claims to the
treatment and prevention of HIV?
• test for establishing a sound prediction:
1.Factual basis
2.Sound line of reasoning
3.Proper disclosure
33

34. 4. Support
Sound prediction (continued)
• Patent can be defeated if challenger can show that the
prediction was not sound (i.e., if any element of 3-part test not
met):
 Eli Lilly v. Apotex, Federal Court 2008: factual basis and sound
line of reasoning, but lack of proper disclosure  patent invalid
 interesting because SCC gave little guidance on this issue in
Apotex v. Wellcome case
 note: proper disclosure a hot button issue generally
• Patent can also be defeated if, despite soundness of
prediction, invention in fact does not work
34

35. 4. Support
Description requirements: diagnostics
• Generally molecular diagnostic applications will require
working examples
• Prophetic examples have been sanctioned by court, but
must not be written in past tense
• For utility:
• With genetic sequences, “research tool” not enough
• Gene probe will require disclosure of specific target
• Claim to receptor will only be granted with disclosure of
disease or condition
35

36. 5. Enforcement and exploitation
Developing a patent portfolio
• Patent as a commercial tool:
• To develop or insure market position
• To find an investment partner
• To license
• May enable access to other technologies
36

37. 5. Enforcement and exploitation
Decision to obtain patent protection
• Importance of invention
• Scope of likely patent protection
• Potential commercial life of invention
• Simple or complex technology
• Ability to keep secret
• Ability to police patent
• Role in larger portfolio/strategy
• Financing/licensing
• Defensive reasons
37

38. 5. Enforcement and exploitation
When to seek patent protection
• Key considerations:
 Timing of your own disclosure
 State of development of technology: ability to satisfy
description requirements
• Want sufficient disclosure, but do not want to wait too
long and be blocked by somebody else
• Filing patent at the time of genetic discovery increases
probability that funding can be found to develop actual
clinical test
38

39. 5. Enforcement and exploitation
Diagnostics field
• Includes large entrenched participants
• Stand alone IVD companies
• Companies affiliated with pharmaceutical or medical
device companies
• Large diagnostic laboratories
39

40. 5. Enforcement and exploitation
Business models
• Different models:
 Build a business
 License out
 Something in between, e.g. a partnering model
• Appropriate model can depend on a number of factors:
• Who funded the research?
• How much funding is available for ongoing R&D, testing, regulatory processes?
• What is the scope of your patent protection?
• Are there roadblock patents? Can you obtain licenses or work around them?
• What jurisdictions will you be working? e.g. socialized versus private healthcare
• What is likelihood/timeline of regulatory approval?
40

41. 5. Enforcement and exploitation
Motivation to partner
• Well-established companies looking for new molecular
markers; junior partner gets access to other necessities,
including funding and regulatory expertise
• Likely to involve a cross-licensing arrangement
• Technology in field rapidly progressing, requires
significant R & D investments to remain competitive
• Diagnostic tests require regulatory approval: requires
funding and expertise
41

42. 5. Enforcement and exploitation
Freedom to operate
• Something to consider from the outset
• Other market participants may control roadblock (e.g. a
patented process that must be practised in order to use your
kit) or complementary technologies (e.g. reagents, devices
beneficially used in conjunction with your invention)
• Early investigation might stop wasted outlay on
research/patents/regulatory approval
• FTO opinion a search of current patents (pending
applications) and an analysis of the scope (likely scope) of
their claims
42

43. 5. Enforcement and exploitation
Freedom to operate (continued)
• Steps taken at the outset to ensure proper IP protection
is obtained increase the chance of a partnering
opportunity in the future
• If going to “build a business” rather than licensing out,
then will be important to ensure from the outset access to
the necessary technologies
• Even if plan is only to license out technology, can be a
covenant to hold licensee harmless
43

44. 5. Enforcement and exploitation
Licensing
• Open license i.e. available to all for payment of a “toll”
• Results in more extensive use
• May be better for a test with broad applicability
• May insulate the patent from challenge
• Exclusive license i.e. single vendor
• May yield more money at the outset
• May be better for a test with more specific applicability
• Something in between these two extremes e.g. license to
specifically selected class of licensees
44

45. 5. Enforcement and exploitation
Licensing (continued)
• Issues to consider:
 “patent thickets” and “royalty stacking”:
• overlapping rights can lead to complicated scenarios
• for a single test, licenses may be necessary from a number of
parties
 large payers may have significant influence
 public and private cost v. return on investment: one size fits all?
45

46. 5. Enforcement and exploitation
Example: Cancer susceptibility genes
BRCA1 and BRCA2
• Myriad Genetics – patents for genes, mutation detection
• Built business around performing the tests itself:
 BRACAnalysis® assesses a woman's risk of developing breast
or ovarian cancer based on detection of mutations in the BRCA1
and BRCA2 genes
 blood sent to Myriad’s laboratories (or very small group of
licensed laboratories), then results sent to doctor who discusses
them with the patient
46

47. 5. Enforcement and exploitation
Example: Cancer susceptibility genes
BRCA1 and BRCA2
• United States:
• Myriad licensed the rights to perform these tests to about a
dozen laboratories in exchange for high royalties on each test
performed
• federal government brokered deal to pay lower royalties when
the genes are used by NCI and NIH-sponsored research
institutions and investigators
47

48. 5. Enforcement and exploitation
Example: Cancer susceptibility genes
BRCA1 and BRCA2
• Canada:
 provinces performing genetic testing using BRCA genes but a
different method
• in 2001, Myriad sent cease and desist letters:
• provincial governments infringing Myriad gene patents
• stop using any tests to detect the BRCA1 and 2 genes other
than BRACAnalysis®
• use Myriad testing at higher cost
• BC stopped testing for a time; Ontario continued testing
(now using a different system)
48

49. 5. Enforcement and exploitation
Example: Cancer susceptibility genes
BRCA1 and BRCA2
• Europe:
 opposition from research institutes, ministries of health and political
parties
 October 2007, Board of Appeal of EPO upheld revocation of one
Myriad patent (EP 705 902) regarding the BRCA1 gene and its
applications (other opposition proceedings ongoing)
 patent claimed isolated gene, corresponding protein, therapeutic
applications and diagnostic kits (use of probes or primers specific to
certain mutations)
 revoked on basis of lack of novelty (i.e. sequence had already been
isolated and determined)
49

50. 5. Enforcement and exploitation
Example: Cancer susceptibility genes
BRCA1 and BRCA2
• Diagnostic patents can raise highly politicized issues
related to access and publicly funded research and
treatment
• But, this time limited monopoly has been put in place to
try to provide an appropriate reward for inventor
disclosure of useful inventions
50

51. Thank You!
Any Questions?
Ogilvy Renault LLP
200 Bay Street, Suite 3800
P.O. Box 84
Royal Bank Plaza, South Tower
Toronto, Canada
M5J 2Z4
Cynthia Tape
T 416.216.4063
ctape@ogilvyrenault.com
Anna Wilkinson
T 416.216.3975
awilkinson@ogilvyrenault.com