Kerry Fluhr - Navigating the CRISPR IP Landscape · Palindromic Repeats CRISPR, in its native state, is effectively a ... Navigating the CRISPR IP Landscape | Kerry Fluhr. To accomplish

Navigating the CRISPR IP Landscape

BD&C

Dr Kerry Fluhr| Intellectual Property Team Leader

29 November 2017

Disclaimer

This talk is intended to provide as a general overview, and none of the information supplied herein should be construed in any way to be legal advice.

Navigating the CRISPR IP Landscape | Kerry Fluhr2 |

What is CRISPR?

Cas9 = CRISPR ASsociatedprotein 9

*(There are other relevant CRISPR proteins, such as Cpf1).


Clustered

Regularly

Interspaced

Short

Palindromic

Repeats

CRISPR, in its native state, is effectively a

prokaryotic immune system that has been adapted

for genome editing.

How CRISPR Works


The Key Advantage: allows cutting of DNA at any specific location within the

genome.

New Development! A recent publication has demonstrated a Cas nuclease that

targets RNA.

In other words…


CRISPR is like a bounty hunter holding a mug shot.

Question that I get:

“Hi Kerry. I have been thinking about using CRISPR to knock out a few genes in a cell line/plant/organism. It’s only early stage, and I don’t even know if it will work, but if it does, we would like to partner with X (company/funding organisation) to develop it further. I heard that there is this big patent thing going on with CRISPR. Do I need to worry about it?”


CRISPR is a complex issue.


Scientific Developments

Licensing Landscape

Social License to Operate

and Regulatory

Issues

Patenting Developments

and Landscape

CSIRO is a complex

organisation.

Agriculture

and Food

Land and

Water

Health and

Biosecurity

Data61

My goal is to develop a decision framework for in-

licensing CRISPR.

Key aspects of the decision framework:

• What activities require a license for CRISPR?

• Which party (or parties) is the likely licensor for particular CRISPR activities?

• How do we address the concerns of external parties who are licensing from us?

• Can we develop a “one CSRIO” approach to in-licensing CRISPR despite divergent fields of use?


To accomplish this, the following needs to be

understood:

• The patent landscape

• The licensing landscape

• How CSIRO is using/planning to use CRISPR

• How CSIRO plans to commercialise constructs made using CRISPR


What I will focus on in this talk:

Scientific Developments


Licensing Landscape

Social License to Operate and

Regulatory Issues

Patenting Developments and Landscape

• Overview of

patenting issues.

• Licensing

landscape.

• CRISPR and Gene

Drives.


The CRISPR Patent Landscape

A quick primer about patents.

• Patents exclude others from making, using or selling an invention.

• It is the claims of the patent that define the scope of an invention.

• Patents are temporary and country-specific.

• Only granted patents are legally enforceable, but pending applications are regularly licensed.


Source: Andulau; www.creativecommons.org

The CRISPR patent situation is complex and

uncertain.

• There are 763+ patent families claim Cas9.

• Types of CRISPR patents include:

– CRISPR components

– CRISPR activity

– Vectors

– Delivery mechanisms

– Specific applications

• There are multiple parties who own or hold rights to CRISPR.

• In particular, there is a major patent dispute in the US between two CRISPR patent owners.


Duelling Patent Portfolios“Berkeley”Key Scientists: Jennifer Doudna and Emmanuelle Charpentier

Universities: The University of California, Berkely and the University of Vienna

Licensing Entity: Caribou Biosciences

“Broad”* Key Scientist: Feng Zhang

Universities: MIT, Harvard

Licensing Entity: The Broad Institute


*(pronounced “brode”)

Two Different Approaches to Patenting

Berkeley Broad


One broad application covering all

cell types.

Only prokaryotic cells exemplified.Multiple, slightly-different

applications.

Only eukaryotic cells covered.


Patent Filing Timelines: Berkeley vs Broad

May 2012Jennifer Doudna

Emanuelle Charpentier

CRISPR-Cas9 system

for genomic editing

(in vitro/prokaryotic data)

Dec 2012Feng Zhang

CRISPR-Cas9 system

for genomic editing

in eukayrotes

(U.S. accelerated

examination)

Apr 2014First CRISPR-Cas9 patent

awarded

U.S. 8,697,359

Application of CRISPR-

Cas9 in eukaryotes.

MIT/Broad/HarvardMIT/Broad/Harvard

Apr 2015Request to

USPTO for

Interference

UC-BerkeleyUC-Berkeley

?

What is a patent interference?

• Prior to March 2013, the US Patent Office was a “first-to-invent” system (as opposed to a first-to-file).

• Therefore, when two similar patent applications were filed, there was sometimes a need to determine who was the first to invent.

• Interferences are decided within the Patent Office (as opposed to the courts).

• Generally, the outcome of an interference is a decision about who was first to invent (and who was second).



Patent Filing Timelines: Berkeley vs Broad

May 2012Jennifer Doudna

Emanuelle Charpentier

CRISPR-Cas9 system

for genomic editing

(in vitro/prokaryotic data)

Dec 2012Feng Zhang

CRISPR-Cas9 system

for genomic editing

in eukayrotes

(U.S. accelerated

examination)

Apr 2014First CRISPR-Cas9 patent

awarded

U.S. 8,697,359

Application of CRISPR-

Cas9 in eukaryotes.

MIT/Broad/HarvardMIT/Broad/Harvard

Apr 2015Request to

USPTO for

Interference

Jan 2016Interference

proceedings

filed before the

USPTO for

consideration

Feb 2017USPTO

declares no interference in fact

Apr 2017Appeal to

Federal Circuit

UC-BerkeleyUC-Berkeley

The outcome of the interference between

Berkeley and Broad:


• NOT who was first and who was second to invent.

• Instead, the outcome was that there was no interference.

Why?

The Berkeley patent had claims to all cell types, whereas

the Broad patents were limited to eukaryotic cells.

Berkeley has appealed this decision. The final claim scope

of the Berkeley patent(s) won’t be clear until after the

appeal.

What does that mean?

• Because Broad has granted patents that specify eukaryotic cells, it is likely that rights would need to be obtained from Broad for any work in eukaryotic cells.

• Work in prokaryotic cells will likely need a license from Berkeley but not Broad.

• If the Berkeley patent grants in its current state, there may be a need to obtain rights from Berkeley and Broad for eukaryotic cells.

• We will have to wait for the appeal to be decided or for a settlement to be reached.



The CRISPR licensing landscape: the

“user interface” for freedom-to-

operate.

Some basics about patent licensing:

• Patents rights can be licensed.

• The licenses can be anything that the licensor and licensee agree to, for example:

– Different terms for commercial vs non-commercial use

– Exclusive

– Non-exclusive

– Field-limited

– Jurisdiction-specific

– Used to influence behaviour


Why we need to understand the CRISPR licensing

landscape:

• To make sure that we are not infringing the rights of other parties.

• To avoid embarking on a “dead end” commercial path.

• To manage reputational risk.

• To be able to factor in CRISPR licensing costs for agreements with external parties.

Challenges in understanding the landscape:

• The patent battle in the US has created uncertainty.

• The $$$ details of many (most?) licensing deals are not publicly disclosed.


The type of CRISPR use is key for assessing the

need for a license: research or commercial use?


Internal R&D

(with MTA)

Selling something

that was made using

CRISPR

Lots of CSIRO work is here.

Co

ntr

act

R&

D

Co

inve

stm

en

t

Sp

in-o

uts

License

probably not

needed.

Commercial

license needed.

Case by case (until there is clarity)

“We make CRISPR tools,

knowledge, methods

and other IP for

genome-editing freely

available to the

academic and non-

profit community. ”

(Broad Website)

The field of use is key for determining the

licensing party.

Research Tools

Human Therapeutics

Drug Validation

Row Crops


Exclusive

Licenses

Jurisdiction is also key for determining the

appropriate licensing party.



CRISPR-CAS9 licensing agreements

Jorge L. Contreras, and Jacob S.

Sherkow Science 2017;355:698-700

(17 February 2017)

Published by AAAS

VERY Preliminary CRISPR Rights Landscape

(exclusive licenses only)


Dow/DuPont/Pioneer

(row crops)

Editas

(human

therapeutics)

ERS

Genomics

Genus

(livestock but

not poultry)

CRISPR

Therapeutics (human

therapeutics)

Vilnius University

Emmanuelle

Charpentier

Monsanto

(agriculture)

Caribou

Biosciences

(U of California at

Berkeley)

Broad Institute

(Harvard and MIT)

Intellia

(human

therapeutics)

New!

What does this mean for CRISPR use in crops?

• Dow/DuPont/Pioneer is the party that we will likely need to negotiate with for a commercial license to CRISPR.

• They appear to have rights from both Berkeley and Broad, as well as their own patents.

• We will investigate this further with specific examples in crops.


CRISPR and Gene Drives: an example of patent

licenses being used to influence behaviour.

What are the considerations for using CRISPR with Gene Drives?


What are Gene Drives?Standard Inheritance vs. Gene Drive Inheritance


Standard Inheritance Gene Drive Inheritance

Images from: https://www.science.org.au/curious/crispr

Gene Drives are an example where patent owners

are using their rights to influence behaviour.

• Kevin Esvelt (the MIT inventor on a number of Gene Drive patents) claims that he will enforce gene drive patents on researchers who don’t disclose their plans for both the research and the accompanying safety and ethical issues.

• The Broad Institute will not issue licenses for CRISPR for use with gene drives (as well as sterile seeds and use in tobacco (for human consumption)).

• Monsanto has stated that “gene drive and terminator genes are not things that we wanted to do with the technology anyway”.


Hope for the future!

• Clarity following the Berkeley appeal.

• Potential for coalescence of rights/patent pools.

• New technologies!

None of this means that research using CRISPR should stop.


How will we address questions about present/future CRISPR use at

CSIRO? Ideally, a decision tree would be helpful (Note!! This is a

hypothetical decision tree).


Are you using

CRISPR?

yes

no

Is your use

internal R&D?

Is the external

party funding

the research?

Are you making

a human

therapeutic?

Are you making

a transgenic

animal?

You don’t need

a CRISPR

license.Are you working

in row crops?

yesno

Your commercial

partner will need a

license from X

You may need a

license from Y

You may need a

license from ZOUTPUTS

yes

Questions?


BD&CDr Kerry FluhrIntellectual Property Team Leader

T +61 2 9490 8226

e [email protected]

BUSINESS DEVELOPMENT AND COMMERCIALISATION

Thank you

Documents

Kerry Fluhr - Navigating the CRISPR IP Landscape · Palindromic Repeats CRISPR, in its native state, is effectively a ... Navigating the CRISPR IP Landscape | Kerry Fluhr. To accomplish