Download pdf - 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 H H

H

R 1

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

Num

ber

of pate

nt

applic

ations w

hic

h

mention “

CR

ISP

R”*

*in WIPO’s PatentScope database

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The main players

Feng Zhang

(Broad Institute)

Jennifer Doudna

(University of California)

https://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCO6qxYjPgMcCFceQLAodazEMfw&url=https://mcb.berkeley.edu/news-and-events/department-news/doudna-honored-martin-meyerson-faculty-research-lecture&ei=Iey4Va6WG8ehsgHr4rD4Bw&bvm=bv.99028883,d.bGg&psig=AFQjCNENAZyVgajpqhQU1uPHYC0BW3lNJA&ust=1438268484706250


http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCOGk483PgMcCFchcLAodLN4M1g&url=http://www.the-scientist.com/?articles.view/articleNo/40582/title/Feng-Zhang--The-Midas-of-Methods/&ei=suy4VeGDJ8i5sQGsvLOwDQ&bvm=bv.99028883,d.bGg&psig=AFQjCNGtEs9TE7jSBq1eXm_JFsTWOxeNfg&ust=1438268918467339


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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 [email protected]

Dehns www.dehns.com

Willow Court

West Way

Oxford

UK

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Granted

patents

National examination stage

SearchPublication

Priority Individual country Patentsapplication 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)

SearchPublication

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/ExamPublication

Priority International patent National Grantedapplication 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 £ ££ £ ££ £ £ £