CRISPR - The patent

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CRISPR – The Patent Wars
Dr. Philip Webber
European Patent Attorney
September 2016

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Patent & Trademark Attorneys
Summary of Presentation
• Introduction to intellectual property (IP)
• Biotech inventions
• Criteria for patentability
• CRISPR patents
• Freedom to operate

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Why patent your invention?
Glaxo $1 billion Phaxo $10 million

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A Simple Invention

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What protection is available?
Copyright
• Protects original works (documents, pictures,
photos, music, software)
• Automatic (no registration procedure)
• Infringement by copying only
• © Philip Webber (2016)
• Duration: Life of author + 70 years

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Trade Marks
• Signs that distinguish goods/services
• Distinctive words, numbers, designs,
shape, colour
• Registered® (examined) / unregisteredTM
• Duration: indefinite
ANADIN®

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Copyright
Trade marks
Patents

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How to get a patent
1. Inventor Makes the invention
2. Patent attorney Writes patent application
Files patent application at Patent Office
3. PatOff Examiner Examines patent application
Decides to grant or refuse application
4. Courts Enforce the patent against infringers

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What is a patent attorney?
A patent attorney is:
• a scientist (graduate/PhD)
• a lawyer (UK and worldwide patent laws)
• a communicator (inventors/CEOs/Patent Examiners)
A patent attorney will guide you through the patent
process from invention to granted patent

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Anatomy of a Patent
Front page Bibliographic information, abstract, drawings
Description What is the invention about?
Background to the invention
Statements of invention, preferred features
Examples of the invention
Claims Define the scope of the invention in words
Drawings Illustrations of examples of the invention

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Umbrella Patent Application
CLAIMS
1. An apparatus for use with a beverage container,
comprising:
a means for removably attaching the apparatus
to the beverage container;
a shaft, coupled to the means for removably
attaching the apparatus, and extending vertically
with respect to the beverage container;
an umbrella, coupled to the shaft at a point
above the means for removably attaching, so as
to shade the beverage container.

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Biotech Inventions – Can you patent it?

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A compound of formula
wherein R1 is C1-20 alkyl or amino,
or a pharmaceutically acceptable salt thereof.
N
N N
H
N
HH
H
R1
Medicines
X Products of nature

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Claims to DNA and Proteins
1. An isolated nucleic acid molecule
comprising the nucleotide sequence
shown in SEQ ID NO: 1.
2. A purified polypeptide comprising the
amino acid sequence shown in SEQ ID
NO: 2.
X Genomic DNA
X Products of nature

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Biological Molecules – Other Claims
3. A vector which comprises a nucleic acid molecule as claimed in
claim 1.
4. A host cell comprising a vector as claimed in claim 3.
5. An antibody which specifically recognises a polypeptide as
claimed in claim 2 but which does not recognise a polypeptide
having the sequence of SEQ ID NO: 5.
6. A pharmaceutical composition comprising a polypeptide as
claimed in claim 2, optionally together with one or more carriers,
adjuvants or excipients.
7. A vaccine comprising a polypeptide as claimed in claim 2,
optionally together with one or more adjuvants.

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Example of a claim to a bacteria
An E. coli mutant
which contains genes encoding
proteins X and Y,
and which is capable
of producing ethanol.
Bacteria and Cells

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Example of a claim to a plant
A transgenic rice plant
which produces vitamin A in its seeds
at a level of at least 50mg vitamin
A/gram seed.
Plants

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Example of a claim to an animal
A transgenic cow
comprising a nucleotide sequence
encoding human insulin,
wherein the human insulin is
secreted into the cow’s milk.
Animals

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“The human body,
at the various stages of its
formation and development, …
cannot constitute patentable
inventions.”
(EU Biotech Directive)
Claims to human beings

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Methods and Processes
Standard method and process claims
A process for producing a polypeptide of formula ... comprising the steps ...
An in vitro method of assaying for the presence of Staphylococcus bacteria
comprising ...
Use of a nucleotide primer of SEQ ID NO: 1 for determining ...
A method of producing a transgenic plant comprising ...
A method of diagnosing cancer comprising ...
X Diagnostic methods

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X
You can patent most of it ...

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How to get a patent
1. Inventor Makes the invention
2. Patent attorney Writes patent application
Files patent application at Patent Office
3. PatOff Examiner Examines patent application
Decides to grant or refuse application
4. Courts Enforce the patent against infringers

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Criteria for patentability
Invention (as defined in the Claims) must be:
• Novel
• Inventive
Description section of the patent application must:
• Describe at least one way of putting the invention
into practice
• Justify the breadth of the claims

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Novelty
Article 54 EPC
1) An invention shall be considered to be new if it does
not form part of the state of the art.
2) The state of the art shall be held to comprise everything
made available to the public by means of a written or
oral description, by use, or in any other way, before the
date of filing of the European patent application.
The prior art is everything that the Examiner can find …
The “prior art”

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Is it novel?

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Inventive step
Article 56 EPC
An invention shall be considered as involving an
inventive step if,
having regard to the state of the art,
it is not obvious to a person skilled in the art.
What is obvious?

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Is it obvious?

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How to make the invention
Article 83 EPC (Sufficiency/Enablement)
The European patent application must disclose the invention
in a manner sufficiently clear and complete
for it to be carried out
by a person skilled in the art.

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Rights conferred by a patent
After grant of patent, you can prevent others from:
• making
• using
• selling or
• importing
your invention
• for up to 20 years
• but only in the countries where you have patents.
Patent rights have to be enforced in the courts – by you!

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Summary so far ...
• You can patent products, processes and methods.
• Patentable inventions must be novel, inventive and
capable of use in industry.
• Patent Office Examiners produce Search and
Examination Reports, and they grant patents.
• Patents give you the right to stop others (via the courts)
from using your invention without permission.
• One patent – one country.

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Patent & Trade Mark Attorneys
CRISPR patents
Your patents
• Your CRISPR-based inventions
Other people’s CRISPR patents
• Freedom to operate
• Zhang v Doudna
• Research exemptions

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Your CRISPR inventions
New Products New Methods
Nature Reviews Microbiology 9, 467-477 (June 2011)

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• The main players - Zhang
- Doudna
• Zhang’s patents
• Doudna’s patent applications
• The CRISPR wars

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CRISPR patent applications
0
50
100
150
200
250
300
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Claims
Description
Numberofpatentapplicationswhich
mention“CRISPR”*
*in WIPO’s PatentScope database

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The main players
Feng Zhang
(Broad Institute)
Jennifer Doudna
(University of California)

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Zhang’s patents
US patents EP patents
US 8945839 US 8771945 EP 2771468
US 8795965 US 8865406 EP 2784162
US 8871445 US 8889356 EP 2764103
US 8889418 US 8895308 EP 2896697
US 8906616 US 8932814 EP 2921557
US 8999641 US 8697359 EP 2898075
US 8993233 EP 2931898

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“and the money kept rolling in ...”
CRISPR
licenses
Reagent
suppliers
Human
therapeutics
(Editas)
Research /
Commercial

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1. A non-naturally occurring or engineered composition comprising:
a Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-CRISPR-
associated (Cas) (CRISPR-Cas) system chimeric RNA (chiRNA) polynucleotide
sequence, wherein the polynucleotide sequence comprises
(a) a guide sequence of between 10-30 nucleotides in length, capable of
hybridizing to a target sequence in a eukaryotic cell,
(b) a tracr mate sequence, and
(c) a tracr RNA sequence
wherein (a), (b) and (c) are arranged in a 5' to 3’ orientation,
wherein when transcribed, the tracr mate sequence hybridizes to the tracr RNA sequence
and the guide sequence directs sequence-specific binding of a CRISPR complex to the
target sequence,
wherein the CRISPR complex comprises a Type II Cas 9 protein complexed with
(1) the guide sequence that is hybridized to the target sequence, and
(2) the tracr mate sequence that is hybridized to the tracr RNA sequence,
wherein the tracrRNA sequence is 50 or more nucleotides in length.
EP 2 771 468 B – Zhang

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Zhang’s granted EP patents
EP patent number Date of grant
EP 2771468 (B1) 11 February 2015 Opposed
EP 2784162 (B1) 8 April 2015 Opposed
EP 2764103 (B1) 19 August 2015 Opposed
EP 2896697 (B1) 2 September 2015 Opposed
EP 2898075 (B1) 9 March 2016 Opposed
EP 2931898 (B1) 9 March 2016 Opposed
EP 2921557 (B1) 13 July 2016 Opposed

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WO 2013/176772 Claims 1-2
1. A DNA-targeting RNA comprising:
(i) a first segment comprising a nucleotide sequence that is complementary
to a sequence in a target DNA; and
(ii) a second segment that interacts with a site-directed modifying
polypeptide.
2. The DNA-targeting RNA of Claim 1, wherein the first segment comprises 8
nucleotides that have 100% complementarity to a sequence in the target DNA.
Doudna’s PCT application

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WO 2013/176772 Claims 3-5
3. The DNA-targeting RNA of Claim 1, wherein the second segment comprises a
nucleotide sequence with at least 60% identity over a stretch of at least 8 contiguous
nucleotides to any one of the nucleotide sequences set forth in SEQ ID NOs: 563-682
[targeter RNA], or a complement thereof.
4. The DNA-targeting RNA of Claim 1, wherein the second segment comprises a
nucleotide sequence with at least 60% identity over a stretch of at least 8 contiguous
nucleotides to any one of the nucleotide sequences set forth in SEQ ID NOs: 431-562
[tracrRNAs] or a complement thereof.
5. The DNA-targeting RNA of Claim 1, wherein the site-directed modifying polypeptide
comprises an amino acid sequence having at least about 75% amino acid sequence
identity to amino acids 7-166 or 731-1003 of the Cas9/Csnl amino acid sequence depicted
in Figure 3 [Streptococcus pyogenes], or to the corresponding portions in any of the amino
acid sequences set forth as SEQ ID NOs: 1-256 and 795- 1346 [a wide variety of other
Cas9/Csnl protein sequences from other species]
Doudna’s PCT application

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The Big Issue
Zhang’s US provisionals
US 61/736,527 12 Dec 2012
US 61/748,427 2 Jan 2013
US 61/758,468 30 Jan 2013
US 61/769,046 25 Feb 2013
(... 12 provisional applications in total)
Doudna’s US provisionals
25 May 2012 US 61/652,086
19 Oct 2012 US 61/716,256
28 Jan 2013 US 61/757,640
15 Feb 2013 US 61/765,576

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What’s next?
Cpf1
• Uses single guide RNA (like Cas9)
• Produces a double-stranded break in the target DNA (like Cas9)
• Produces staggered DNA ends (whereas Cas9 produces blunt ends)
• Cpf1 recognises a different PAM site
Cell 163: 1-13, 22 October 22 (2015)

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Section 60 UK Patents Act 1977
(5) An act [ will not infringe if ] -
(b) it is done for experimental purposes
relating to the subject-matter of the invention …
US – Madey v Duke
University academics are not immune from patents!
“Research Exemptions”

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Summary
Your patents
• Be aware of what you can patent
• Understand the basic criteria for patentability
• Keep your inventions confidential until you file your patent applications!
• Zhang’s granted patents
• Do you need a license?

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Dr. Philip Webber pwebber@dehns.com
Dehns www.dehns.com
Willow Court
West Way
Oxford
UK

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Granted
patents
National examination stage
Search
Publication
Priority Individual country Patents
application patent applications
Examination
Getting patents granted abroad
Priority year
0 12 18 ... months ...
Costs:
£2-6K £2-8K ££ ££ ££ ££ ££ £ £ £ £ £
(per country)

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Validation
stage
European Patent Office (EPO)
Search
Publication
Priority EP patent Granted EP
application application patent
Examination
Getting patents in Europe
Priority year
0 12 18 ... months ...
Costs:
£2-6K £5-6K £500 £££ ££ ££ ££££ £ £ £ £

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Search/Exam
Publication
Priority International patent National Granted
application application applications patents
Examination
International patent applications
Priority year International phase National phases
0 12 18 30 months ...
Costs:
£2-6K £5-8K £500 £2-8K/country £ ££ £ ££ £ £ £

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