This document summarizes a presentation on intellectual property perspectives in synthetic biology. It discusses the growing patenting activity in synthetic biology, with many companies filing patents on parts, pathways, genomes and systems. It outlines the patent requirements of subject matter eligibility, utility, novelty, non-obviousness, description and enablement. Challenges in meeting these requirements for synthetic biology inventions are noted. Issues around freedom to operate are also discussed, given the potential for many existing patents to cover various elements in this emerging field.
Reverse-and forward-engineering specificity of carbohydrate-processing enzymes
Synthetic Biology and IP
1. CRIBIQ event on Synthetic Biology
Synthetic 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.
2
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 systems
and to create programmable
microorganisms from scratch
• “There is no technical barrier to
synthesizing plants and animals,
it will happen as soon as
anyone pays for it.”
--Drew Endy, MIT
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4. Presentation Plan
• Patenting activity in this emerging field
• Patent requirements applicable to synthetic biology
• Freedom to operate issues
4
5. Patenting Activity in Syn Bio
Number of Synthetic Biology-related Patents*
160
140
120
100
80
60
40
20
0
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.
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6. Patenting Activity in Syn Bio
Nb of Patent
Assignee Location Syn Bio Business Area Families
Ambrx La Jolla Develops biopharmaceuticals utilizing artificial amino acids 81
www.ambrx.com CA, USA
Amyris Biotechnologies Emeryville Developing synthetic microbes to produce pharmaceuticals, fine 35
www.amyrisbiotech.com CA, USA chemicals, nutraceuticals, vitamins, flavors and biofuels
Codexis Redwood city Employs directed evolution to produce customized biocatalysts for 153
www.codexis.com CA, USA drug and biofuel production.
EraGen Biosciences Madison Develops genetic diagnostic assays based on artificial base paring. 20
www.eragen.com WI, USA
Genencor Rochester One of the pioneer in the field of industrial biotechnology. Now part 700
www.genencor.com NY, USA of Dupont. Develops and manufactures a wide range of industrial
enzymes, including for generation of biofuels.
Gevo Engelwood Developing biobased alternatives to petroleum-based products using 19
www.gevo.com CO, USA a combination of synthetic biology and chemistry.
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7. Patenting Activity in Syn Bio
Nb of Patent
Assignee Location Syn Bio Business Area Families
Intrexon Blacksburg Developing synthetic biology platform with applications in 52
www.dna.com VA, USA human therapeutics, protein production, industrial products,
agricultural biotech and animal sciences
LS9 S. San Francisco Designs microbial factories for the production of biofuels and 18
www.ls9.com CA, USA sustainable biochemicals
Mascoma Waltham Developing microbes to convert agricultural feedstock into 26
www.mascoma.com MA, USA cellulosic ethanol
Sangamo Biosciences Richmond Produce engineered “zinc finger” proteins for controlling gene 81
www.sangamo.com CA, USA expression
Synthetic Genomics La Jolla Designing metabolic pathways for the production of 27
www.syntheticgenomics.com CA, USA biochemicals and next generation biofuels
Verenium San Diego Created from the merger of Diversa and Celunol in 2007. 133
www.verenium.com CA, USA Developing specialty enzymes products for the production of
cellulosic ethanol
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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)
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10. Patent Requirements
Patentable Subject Matter
• Innovative concepts to be patented can be
summarized by:
• Parts
• Pathways
• Genomes
• Systems
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11. Patent Requirements
Patentable Subject Matter
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.
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12. Patent Requirements
Patentable Subject Matter
Sangamo Biosciences
• U.S Public company founded in 1995
(Nasdaq: SGMO)
• Sangamo is developing engineered transcription
factors 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: …”
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13. Patent Requirements
Patentable Subject Matter
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
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14. Patent Requirements
Patentable Subject Matter
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 …”
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15. Patent requirements
Patentable Subject Matter
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
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16. Patent Requirements
Patentable Subject Matter
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.”
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17. Patent Requirements
Patentable Subject Matter
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
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18. Patent Requirements
Patentable Subject Matter
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; ...”.
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19. Patent Requirements
Patentable Subject Matter
Human beings are excluded
• Only non naturally occurring, nonhuman multicellular living
organisms are patentable
• Patent will be rejected if the
broadest reasonable
interpretation of the claimed
invention encompasses a
human being
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20. Patent Requirements
Utility
Invention must provide some identifiable benefits
• EP: industrial applicability
• US: utility must be specific, credible
and 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
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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
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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.
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23. Patent Requirements
Description and Enablement
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.
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24. Patent Requirements
Description and Enablement
Challenges
• File early to be first
• Actual reduction to practice
• Sufficient number of examples
• Foresee and describe possible alternatives
• Acceptable scope of protection
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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 of
DNA molecules
• etc.
• “Patent thickets” and Stacking royalties
• “Hold-up” patents?
• Critical to make appropriate search in
order to assess the patent landscape
before and during the R&D project
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26. Freedom to Operate Issues
• Open source as an alternative?
• BioBricks Foundation
www.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 Open
Society (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
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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
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