synthetic biology and ip

CRIBIQ event on Synthetic BiologySynthetic Biology: an IP perspective

Serge Lapointe, Ph.D.Partner, Patent Agent

February 29, 2012

2

Introduction

• Synthetic biology is a new area which intersects with biotechnology, computer and engineering

• Broad range of potential applications:

• Environment: clean up tasks, detection of pollutants

• New source of energy:hydrogen, cellulosic ethanol

• Medical: delivery vehicles,drug factories

• Food: preservatives,reconstructed plants

• Etc.

3

Introduction

• More ambitious than modifying components of living cells to achieve a desired functionality

• “extreme genetic engineering” or “genetic engineering on steroids

• Ultimate objective is to use “synthetic” raw material to create novel biological systemsand to create programmablemicroorganisms from scratch

• “There is no technical barrier tosynthesizing plants and animals,it will happen as soon asanyone pays for it.”

--Drew Endy, MIT

4

Presentation Plan

• Patenting activity in this emerging field

• Patent requirements applicable to synthetic biology

• Freedom to operate issues

5

Patenting Activity in Syn Bio

Number of Synthetic Biology-related Patents*

0

20

40

60

80

100

120

140

160

1982-1986 1987-1991 1992-1996 1997-2001 2002-2006 2006-2011

* Presence of key words such as “synthetic biology”, “synthetic gene”, ”synthetic genome”

“synthetic organism”, “synthetic cell” in the Title, Abstract or Claims.

6


19Developing biobased alternatives to petroleum-based products using

a combination of synthetic biology and chemistry.

Engelwood

CO, USA

Gevo

www.gevo.com

700One of the pioneer in the field of industrial biotechnology. Now part

of Dupont. Develops and manufactures a wide range of industrial

enzymes, including for generation of biofuels.

Rochester

NY, USA

Genencor

www.genencor.com

20Develops genetic diagnostic assays based on artificial base paring.Madison

WI, USA

EraGen Biosciences

www.eragen.com

153Employs directed evolution to produce customized biocatalysts for

drug and biofuel production.

Redwood city

CA, USA

Codexis

www.codexis.com

35Developing synthetic microbes to produce pharmaceuticals, fine

chemicals, nutraceuticals, vitamins, flavors and biofuels

Emeryville

CA, USA

Amyris Biotechnologies

www.amyrisbiotech.com

81Develops biopharmaceuticals utilizing artificial amino acidsLa Jolla

CA, USA

Ambrx

www.ambrx.com

Nb of Patent FamiliesSyn Bio Business AreaLocationAssignee

7


133Created from the merger of Diversa and Celunol in 2007.

Developing specialty enzymes products for the production of

cellulosic ethanol

San Diego

CA, USA

Verenium

www.verenium.com

27Designing metabolic pathways for the production of

biochemicals and next generation biofuels

La Jolla

CA, USA

Synthetic Genomics

www.syntheticgenomics.com

81Produce engineered “zinc finger” proteins for controlling gene

expression

Richmond

CA, USA

Sangamo Biosciences

www.sangamo.com

26Developing microbes to convert agricultural feedstock into

cellulosic ethanol

Waltham

MA, USA

Mascoma

www.mascoma.com

18Designs microbial factories for the production of biofuels and

sustainable biochemicals

S. San Francisco

CA, USA

LS9

www.ls9.com

52Developing synthetic biology platform with applications in

human therapeutics, protein production, industrial products,

agricultural biotech and animal sciences

Blacksburg

VA, USA

Intrexon

www.dna.com

Nb of Patent FamiliesSyn Bio Business AreaLocationAssignee

8

Patent Requirements

• Patentable subject matter

• Novelty

• Nonobviousness

• Utility

• Description

9

Patent Requirements

Subject matter eligibility

• U.S. law:

• “…any new and useful process, machine, manufacture or

composition of matter, or any new and useful improvement

thereof…” (Emphasis added)

• Isolated genetic material (DNA, RNA, genes, vectors, etc), proteins, compositions, methods of making, methods of use, etc. are patentable subject matter

• Genetically engineered microorganism and multicellular organism have been patentable for 30 years in the US

• “anything under the sun that is made by man”

• Diamond v. Chakrabarty (U.S. Supreme Court, 1980)

10

Patent Requirements

Patentable Subject Matter

• Innovative concepts to be patented can be summarized by:

• Parts

• Pathways

• Genomes

• Systems

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Patent Requirements


Parts

• A single “part” such as a gene or enzyme to perform a particular function

• Goal is to reduce biological systems to their modular and additive parts that can be assembled (engineered) to perform new functions

• Example: BioBricks™

• BioBricks registry of parts at: http://partsregistry.org

• Patent Claims:

• nucleic acid sequences for primers, probes, ribosome binding

site, transcription factors, regulatory proteins

• constructs, cassettes, vectors

• method of amplification or ligation, etc.

12

Patent Requirements


Sangamo Biosciences• U.S Public company founded in 1995

(Nasdaq: SGMO)

• Sangamo is developing engineered transcriptionfactors for the regulation and modification of genes

• Its technology platform is based upon the engineering of a naturally occurring class of DNA transcription factors referred to as zinc finger DNA-binding proteins, or ZFPs

• Owns more than 80 patent families, including several broad patent on foundational technologies

• U.S. patent 7,951,925 issued May 31, 2011

“ 1. A protein comprising an engineered zing finger protein DNA-binding

domain, wherein the DNA-binding domain comprises four zinc finger

recognition regions ordered F1 to F4 from N-terminus to C-terminus, and

wherein F1, F3, and F4 comprise the following amino acid sequences: …”

13

Patent Requirements


Pathways

• Several “parts” working together to perform an overall process

• Goal is to develop organisms which can serve as “chemical

factories” on a commercial scale

• Examples:

• production of cellulosic ethanol

• production of pharmaceutical compounds

• degradation of waste products

• Patent Claims:

• unique combination of genes, enzymes or recombinant organisms

• genetically modified host cells comprising a heterologous nucleic

acid

• methods of making or producing the chemical product

14

Patent Requirements


Amyris Biotechnologies• Public company founded in 2003 (Nasdaq: AMRS)

• Started in 2004 a project to produce copious quantities

of synthetic artemisinin (an antimalarial drug) in E. coli

• Now focuses on genetically engineered yeast that contains

synthetic DNA to break down sugarcane to produce isoprenoids

which are then converted to biofuels

• 27 patent families

• U.S. patent 7,659,097 granted February 2010“ 1. A method for producing isoprenoid comprising:

(a) obtaining a plurality of bacterial or fungal host cells that comprises a heterologous nucleic acid encoding one or more enzymes of a mevalolate pathway for making isopentenyl pyrophosphate,…wherein said mevalolate pathway comprises (1) an enzyme that condenses acetoacetyl-CoA with acetyl-CoA to form HMG-CoA; (ii) en enzyme that converts …; (iii) an enzyme that phosphorylates …; (iv) an enzyme that converts…; v) an enzyme that converts …; and

(b) culturing the bacterial or fungal host cells in a medium …”

15

Patent requirements


Genomes• Designing, modifying, reconstructing and synthesizing entire

genomes

• Goal is to fully synthesize a genome and insert it into a “biological shell”, resulting into a fully engineered organism with new functions

• Examples:

• complete chemical synthesis of a viral genome

• creating bacteria with a genome that was produced in yeast

• minimal genome (Synthetic Genomics’)

• Patent Claims:

• synthetic cells and host cells comprising a heterologous nucleic acid

• methods of synthesis, replication and transplantation of large DNA

molecules

• new set of genes and proteins

• products produced by these synthetic organisms

16

Patent Requirements


Synthetic Genomics• Co-founded in 2005 by J. Craig Venter

• Venter’s previous company, Celera Genomics,

was in the race to sequence the human genome

• Currently working to produce biofuels on an industrial scale

• Received funding from ExxonMobil and BP

• 27 patent families

• May 2007: publication of U.S. application 20070122826 (filed Oct. 12, 2006)

• Describes a minimally operative genome of the bacterium Mycoplasma

genitalium

• 351 genes believed to be essential for the survival of the bacterium

• Rejected patent application still under examination

“ A plurality of bacterial genes, comprising isolated nucleic acid molecules, wherein each

molecule encodes one of at least 351 proteins, but no more than 450 proteins, wherein:

(i) the at least 351 proteins are required for growth and replication of a free-living bacterial

organism under axenic conditions in a rich bacterial medium; and

(ii) the at least 351 proteins perform at least the functions of the genes set forth in Table 3.”

17

Patent Requirements


Systems• Goals are to:

• engineer an organism as a genetic biosensor or computer

• combine engineered organisms with existing computer or electronic systems for performing new functions

• Examples:

• programming bacterial to take photographs (Nature, 438: 441-442 (2005))

• synthetic multicellular system programmed for pattern formation that may be useful for detection of environmental pollutants (Nature, 433: 1130-34 (2005))

• Patent Claims:

• synthetic cells; methods of making these cells

• computer and electronic systems having biological components

• methods of use

18

Patent Requirements


US 6,774,222

• Issued: August 10, 2004

• Title: MOLECULAR COMPUTING ELEMENTS, GATES AND

FLIP-FLOPS

• Assignee: U.S. government (Department of Health)

• Claims:

“ 51. A method of storing information, said method comprising the step of:

binding a nucleic acid binding protein to a first protein binding site on a

nucleic acid, …”

“64. A method of transforming binary information, said method

comprising the steps of:

(i) binding a nucleic acid binding protein to an input protein binding

site on a first nucleic acid; and (ii) determining whether or not a

nucleic acid binding protein can bind to an output protein binding site

on a second nucleic acid; ...”.

19

Patent Requirements


Human beings are excluded

• Only non naturally occurring, nonhuman multicellular living organisms are patentable

• Patent will be rejected if thebroadest reasonableinterpretation of the claimedinvention encompasses ahuman being

20

Patent Requirements

Utility

Invention must provide some identifiable benefits

• EP: industrial applicability

• US: utility must be specific, credibleand substantial

• Moral utility issues?

• invention should not be frivolous or

injurious to the well-being, good policy

or sound morals of society

• rarely invoked but in the case of

synthetic biology innovations,

possibility of failing this test

21

Patent Requirements

Novelty and Nonobviousness

• Novelty

• invention must not have been previously publicly disclosed

anywhere in the world before the filing of the patent application

• Nonobviousness

• not a modification that would be considered trivial to someone

skilled in the art

• Patentability will revolves around the differences in view of:

• known molecular biology methods, existing tools, etc.

• the naturally occurring products on which the synthetic ones

are based

22

Patent Requirements

Description and Enablement

• Need a complete disclosure of the invention such that the person skilled in the art:

(1) Can unambiguously identify what has been invented; and

(2) Is enabled to practice the invention

• Written description:

• Invention must be adequately described in the patent

application such that one skilled in the art would recognize

Applicant was in possession of the claimed invention at the

time of filing

• Various considerations:• actual reduction to practice

• disclosure

• identifying characteristics (complete vs. partial structure)

• predictability

• etc.

23

Patent Requirements


Enablement

• Claimed invention must be enabled so that any person skilled in the art can make and use the invention without undue experimentation

• Various factors

• breadth of the claims

• nature of the invention

• state of the art

• level of predictability

• amount of guidance provided by the inventor

• etc.

24

Patent Requirements


Challenges

• File early to be first

• Actual reduction to practice

• Sufficient number of examples

• Foresee and describe possible alternatives

• Acceptable scope of protection

25

Freedom to Operate Issues

• Innovations in this field will require the use of many elements or methods for which patents exist

• nucleic acid sequences, promoters, genes, etc.

• constructs, cassettes, vectors, plasmids, etc.

• genetically modified host cells

• methods of amplification, ligation,replication and transplantation ofDNA molecules

• etc.

• “Patent thickets” and Stacking royalties

• “Hold-up” patents?

• Critical to make appropriate search in

order to assess the patent landscapebefore and during the R&D project

26

Freedom to Operate Issues

• Open source as an alternative?

• BioBricks Foundationwww.biobrick.org

• registry of more than 18 000 fundamental building blocks or

“BioBrick™” parts of synthetic biology (partsregistry.org)

• the BioBrick™ parts are freely

available for open innovation

• Biological Innovation for OpenSociety (BIOS) www.bios.net

• this group owns a few key patent

gene transfer technologies

• force licensees to make patented

improvements to these enabling

technologies available to others

27

Conclusions

• Synthetic biology is not a new idea but has recently been expanded to include whole genomes and organisms

• Patentability generally not an issue

• long recognized patentable subject matter

• advisable not to wait and be early in the game to obtain broad claims

• Challenging infringements issues

• possible that many licenses will be required for the various patented pieces and methods

• essential to search for existing patents and pending patent applications and monitor competitors’ activities

28

Questions

Thank you!

Serge Lapointe, Ph.D.

Partner, Patent Agent514-397-5219

[email protected]

synthetic biology and ip

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