Transcript 2016-5-18-AIPLA-Joint Biotech

“Mars 101-International and
Interplanetary Considerations for
GMOs: Patents, Export control,
Biodiversity and Regulation”
JOINT BIOTECH AND FDA COMMITTEE CLE
MAY 18, 2016 , 3:30-5:30 pm
1
INTRODUCTIONS
 Marian Flattery, Assistant Chief IP Counsel,
DuPont Pioneer and DuPont Crop Protection,
featured as “Soteria’s General Counsel”
 Kan Wang, professor in the Department of
Agronomy, Director of the Center for Plant
Transformation and Co-PI of the Crop
Bioengineering Consortium at Iowa State
University, featured as “Soteria’s CSO.”
 Vicki G. Norton, Leader of Life Sciences IP
and Co-Leader, Global Life Sciences at
Duane Morris LLP featured as the Host of
“VicIPdia”—for all your IP news!
2
INTRODUCTIONS
 Debora Plehn-Dujowich, partner at Prismatic
Law Group and Chair of AIPLA’s Biotech
Committee, featured as “genetic resources”
outside counsel
 Kathryn Nikolai Hibbard, partner at Greene
Espel, selected as a Rising Star in Minnesota
Super Lawyers (2013-2015), as “Soteria’s
Chief Litigation Counsel”
 Mark Pidkowich, Associate at Smart & Biggar,
Vancouver, as ace investigative journalist
 Alice O. Martin, Partner at Barnes & Thornburgh, as
founder of “Put the Genie in a Bottle” NGO
 Katharine Koenig, Patent Attorney with Christopher &
Weisberg
3
Soteria Biosciences Timeline (1 of 2)
 2001: Launched its 1st drug, NoPainNoGain (an extract from Humor
plants from Cameroun)
 2015 Launched its 2nd generation therapeutic, Soterigen® NPGB, a
biologic drug (polypeptide) with pain relieving effects, which does not
cause weight gain or memory loss (NoPain/NoGain/Better Brain
(NPGB))
 Find out more about Soteria at
http://www.aipla.org/committees/committee_pages/Biotechnology/Soteria/SitePa
ges/Home.aspx
Soteria Biosciences Timeline (2 of 2)
 2020: After winning a contest to run an experiment
on the US Mars Space Station—Soteria developed
high CO2/drought tolerant plants (Gene-E Strain);
Off target effect resulted in production of
“Sweeteria”–a natural sweetener.
 2022: Mars mutation of non GMO control plants
yielded Humor plants more drought tolerant than
Gene-E version (Red Genie)
 2020-22: Filed patent applications on the Gene-E,
Red Genie and Sweeteria technologies
 When Gene-E plants and Red Genie plants were
sent back to Earth they were quarantined on the
landing pad
VICIPDIA
NEWSFLASH
Breeding technologies
 Conventional
 Natural mutation and
recombination
 Selection
 Observation-based, trial/error
 Time consuming
Kan Wang (Iowa State U)
 Modern
 Targeted mutation and
recombination
 Selection
 Data-based, in vitro analysis
 Expensive
May 18, 2016
7
Genetic diversity: source for trait improvement
 Natural variations
 Point mutation, deletion, rearrangement, gene duplication,
transposable elements
 Genome is dynamic and fluid
www.lowes.com
en.wikipedia.org
Kan Wang (Iowa State U)
*http://www.harvesttotable.com
May 18, 2016
8
Modern strawberries never existed in nature
Marina Gambardella,
Santiago, Chile
http://www.ncwildflower.org
Fragaria chiloensis
Chile
Fragaria virginiana
Eastern North America
X
Fragaria ananassa
Europe, 1740's
Corbis
Kan Wang (Iowa State U)
May 18, 2016
9
Gene transfer, 1950’s style
Ln-9 gene for leaf rust resistance from Aegilops to wheat
Problem: Grass will
not cross with wheat
Need to move
gene from
grass to wheat
Cross hybrid
repeatedly to wheat
So cross with wheat relative
x
x
Grass with
trait
Wheat
Grass chromosome with desired gene
}
Kan Wang (Iowa State U)
•Break grass chromosome with X-Rays
•Let pieces integrate into wheat
•Get wanted gene + many unknown
Wheat chromosomes
Final product
May 18, 2016
10.
Sears, E.R. 1956. The transfer of leaf-rust resistance form Aegilops umbellulata to wheat. Genetics in Plant Breeding Brookhaven Symposium #9
Gene transfer, 1950’s style
Ln-9 gene for leaf rust resistance from Aegilops to wheat

Things to notice



Move many genes
No one knows what genes got moved
No regulations
Kan Wang (Iowa State U)
May 18, 2016
11
Mutation breeding
 3217 known varieties developed from
mutation breeding
 FAO/IAEA database (http://wwwinfocris.iaea.org/MVD/)
 DNA changes





4 bp to 8 kb deletions
Inversions of up to 1.5 kb
Insertions ~200 bp
Frame-shift mutations
Premature stop codons
Institute of Radiation Breeding
Ibaraki-ken, JAPAN
www.irb.affrc.go.jp/
Kan Wang (Iowa State U)
May 18,
Specialtyproduce.com
Corbis.com
www.nationalpastaday.com
2016
12
Top: Peggy Lemaux, John Meade, Raúl Coronado
Bottom: Corbis
13
May 18, 2016
Kan Wang (Iowa State U)
Examples of genetic modification
Photos Corbis
Cauliflower, Li
Li, ARS
Kan Wang (Iowa State U)
May 18, 2016
14
Feeding the world
Energy
Population
Grain
Kan Wang (Iowa State U)
May 18, 2016
15
Feeding the world: more land?
http://static.guim.co.uk/sys-images/Guardian/Pix/pictures/2008/07/01/deforest3.jpg
http://www.iccfoundation.us/e-updates/20080331cleanenergy/1.jpg
Kan Wang (Iowa State U)
http://www.usnews.com/dbimages/master/5042/FE_DA_080523brazil.jpg
May 18, 2016
16
3
Statement of Achievement
Marc Van Montagu
Mary-Dell Chilton
Robert T. Fraley
… each conducted groundbreaking
molecular research on how a plant
bacterium could be adapted as a tool
to insert genes from another organism
into plant cells, which could produce
new genetic lines with highly favorable
traits.
The revolutionary biotechnology discoveries of these three individuals —each working in separate
facilities on two continents—unlocked the key to plant cell transformation using recombinant DNA.
Their work led to the development of a host of genetically enhanced crops, which, by 2012, were
grown on more than 170 million hectares around the globe by 17.3 million farmers, over 90
percent of whom were small resource-poor farmers in developing countries.
The combined achievements of the 2013 World Food Prize Laureates, from their work in the
laboratory to applying biotechnology innovations in farmers’ fields, have contributed significantly to
increasing the quantity and availability of food, and can play a critical role as we face the global
challenges of the 21st century of producing more food, in a sustainable way, while confronting an
increasingly volatile climate.
Kan Wang (Iowa State U)
May 18, 2016
17
How did we convert a pathogen to a tool
Agrobacterium tumefaciens
Crown
Gall
Kan Wang (Iowa State U)
May 18, 2016
18
Genetic Transformation, a natural process
Tumor on a walnut-tree
Transgenic wood bowl
Kan Wang (Iowa State U)
May 18, 2016
19
Agrobacterium tumefaciens
– a genetic hijacker
Plant cell
• Eukaryotic promoters
• Plant growth hormone
synthesis
• Special amino acids production
only for Agrobacterium
Agrobacterium
Kan Wang (Iowa State U)
May 18, 2016
20
Agrobacterium – mediated transformation
Disarmed
Engineered plasmid bearing the
gene of interest and an antidote gene
Agrobacterium
tumefasciens
Infection
Transformable
plant
Isolated tissue
(immature embryo,
wounded cotyledon,…)
Infected tissues are
cultured on media
containing poison
Only the transformed
cell can resist the
poison thanks to the
antidote gene.
Transgenic plantlets are
isolated and transferred
to the greenhouse
Transgenic tissue is
isolated and plant
regeneration is induced
Transgenic plant
ready for further
analysis
Kan Wang (Iowa State U)
May 18, 2016
21
Sweet Potato Is a Natural
GMO
Kyndt et al. (2015) The genome
of cultivated sweet potato
contains Agrobacterium TDNAs with expressed genes: An
example of a naturally
transgenic food crop. PNAS,
112: 5844-5849
 The Agrobacterium genes were present in 291 sweet potato cultivars
tested, as well as a few wild related species.
 One of the T-DNAs was present in all cultivated sweet potato clones, but
not in the crop’s closely related wild relatives, which would suggest that
the T-DNA provided an advantageous trait that was selected for during
domestication.
Kan Wang (Iowa State U)
May 18, 2016
22
Two traits
 Insect resistance gene
www.ediblegeography.com
 Herbicide tolerance genes
Bt corn
Kan Wang (Iowa State U)
RR soybean
May 18, 2016
23
Damage of corn field by European Corn Borer
Kan Wang (Iowa State U)
May 18, 2016
24
Reduced fumonisin concentrations in Bt corn
www.pioneer.com
Kan Wang (Iowa State U)
May 18, 2016
25
Bt corn uptake and insecticide use in US corn fields
• Insecticide use on corn
farms declined from
0.21 pound per planted
acre in 1995 to 0.02
pound in 2010.
• The establishment of
minimum refuge
requirements (planting
sufficient acres of the
non-Bt crop near the Bt
crop) has helped delay
the evolution of Bt
resistance.
Enserink et al., 2013, Science 16: 728-729
Kan Wang (Iowa State U)
May 18, 2016
26
Government regulations
Process based:
• EU
• Japan
• ……
Both product and
process based:
• USA
Product-based:
 Canada
Kan Wang (Iowa State U)
May 18, 2016
Classification: PUBLIC
27
Crop Bioengineering Consortium
New Breeding Technologies (NBT)
- Precise, Targeted Double-strand Breaks
• TALENs (Transcription
activator-like effector nuclease):
effector proteins from
plant pathogenic bacteria,
combined with nuclease
domain of FokI
• CRISPR/Cas9 (clustered
regularly interspaced short
palindromic repeats): bacterial
immunity systems for
targeted disruption of
viral DNA
DNA double strand breaks (DSBs)
 Random DNA breaks caused by chemicals,
radiation
 DSBs repair mechanisms
 Homologous recombination
 Non-homologous end join (NHEJ)
 Restoration or disruption
• Homologous recombination occur
but rare in eukaryotic organisms
(1x10-3 to 1x10-6)
• Nuclease mediated DNA DSBs
increases recombination up to
1x10-2 to 10-3
Kan Wang (Iowa State U)
http://www.hindawi.com/journals/jna/2010/646109/fig1/
May 18, 2016
29
Nature (April 21, 2016)
U Penn browning resistant white button mushroom
Kan Wang (Iowa State U)
May 18, 2016
30
Science (April 20, 2016)
Dupont Pioneer high quality waxy corn
Kan Wang (Iowa State U)
May 18, 2016
31
High-efficiency TALEN-based gene editing
produces disease-resistant rice
Li et al., Nat Biotechnol. 2012. 30(5):390-2.
Resistance phenotype
displayed by two T2 mutant
plants
Lesion lengths of mutant
plants caused Xoo(AvrXa7) by
20 T1 mutant plants generated
from TALEN pair 2
Kan Wang (Iowa State U)
May 18, 2016
From B. Yang
32
GMO vs CRISPR:
what are the differences?
Traditional genetic engineering
Gene of interest
cross with
wild type
+
Segregation
transformation
GMO
Wild type
GMO
Wild type
CRISPR/Cas9
Edits
CRISPR/Cas9
Genome editing
CRISPR/Cas9
cross with
wild type
Segregation
transformation
Wild type
CRISPR/Cas9
Edits
Edits
Kan Wang (Iowa State U)
+
Wild type
May 18, 2016
33
Government regulations
Process based:
• EU
• Japan
• ……
Both product and
process based:
• USA
Product-based:
 Canada
Kan Wang (Iowa State U)
May 18, 2016
Classification: PUBLIC
34
Audience questions: Are Soteria’s new
techologies patent eligible?
 GENE-E vs. Red Genie mutants; methods of detecting the
Mars mutation
 Mars mutants patent eligible on Earth?
 What about on Mars? (The Interplanetary Patent Office,
under Commissioner Kappos does not have a section 101,
but does US patent law control?)
 Does the 1967 Outer Space Treaty prohibit patenting Red
Genie?
 Will a genetic diversity database have ramifications on 101
for engineered traits which had a previously unidentified
“natural” counterpart
Patent Eligibility Gene-E vs.
Red Genie
[T]he mere ascertaining of the character or quality of
trees that grow in the forest and the construction of the
woody fiber . . . is not a patentable invention, . . .
any more than to find a new gem . . . would entitle
the discoverer to patent all gems which should be
subsequently found, so that generally it may be said
that fiber such as is described in this application is
old . . . . Otherwise it would be possible for an
element or a principle to be secured by patent, . . ., to
the exclusion of all other men, . . . the fiber which
nature has produced and which nature has intended to
be equally for the use of all men.
Ex Parte Latimer, 46 O.G. 1638 (1889)
Methods of Detecting the Mars Mutation
1. A method of detecting the Mars mutation in a plant, said
method comprising:
a. obtaining a sample from a plant; and
b. detecting whether the Mars mutation is present in the plant
sample by contacting the plant sample with a Mars mutation
probe and detecting binding between the probe and the mutant
sequence
Example 29—Diagnosing and Treating Julitis
Eligible?
claim
1
1. A method of detecting JUL—1 in a patient, said method
comprising:
a. Obtaining a plasma sample from a human patient, and
b. Detecting whether JUL-1 is present in the plasma
sample by contacting the plasma sample with an antiJUL-1 antibody and detecting binding between JUL-1
and the antibody
Sequenom U.S. Patent 6,258,540
1. A method for detecting a paternally inherited nucleic acid of
fetal origin performed on a maternal serum or plasma sample
from a pregnant female, which method
comprises amplifying a paternally inherited nucleic acid from the
serum or plasma sample and detecting the presence of a
paternally inherited nucleic acid of fetal origin in the sample.
yes
Held
ineligible
Directed to a
Judicial
Exception?
No
Is Gene-E patent eligible
under §101
 Gene-E is a high CO2/drought tolerant plant created by
genome editing
 Step 1: Yes. A plant is a patent eligible composition of
matter
 Step 2A: No. The Gene-E, because it is a genome edited
plant that does not occur naturally the invention is not
directed to a judicial exception (law of nature, natural
phenomenon or abstract idea)
 Gene-E is patent eligible subject matter in the U.S.
Is Red Genie patent eligible
under §101
 Red Genie is a Mars mutation of non GMO Humor plant
that exhibits greater CO2/drought tolerance that the GMO
version
 Step 1: Yes. A plant is a patent eligible composition of matter
 Step 2A: Yes. Red Genie is a natural phenomenon or product of
nature judicial exception
 Step 2B: No. If the claim only covers Red Genie as it occurs in
nature without additional limitations, it is likely patent ineligible
 If Red Genie is introduced into a breeding program to bring
the greater CO2/drought tolerance trait into elite genetics,
then the resultant varieties are likely patent eligible
Is Sweeteria patent eligible
under §101
 Sweeteria is a “natural” sweetener produced as an off-target
effect of the genetically engineered Gene-E strain
 Step 1: Yes. A sweetener is a patent eligible composition of
matter
 Step 2A: ???
 Yes. Sweeteria is a product of nature because it is produced by a plant
 No. Sweeteria is not a product of nature because it is not produced by a
naturally occurring plant
 Step 2B:
 If Step 2A is Yes, then No Sweeteria per se would not be patent eligible.
 If Step 2A is No, then Step 2B analysis is not required and Sweeteria is patent
ineligible
PTO Guidance: Life Science
Examples for Claims to Sweeteners
Example 30 – Dietary Sweeteners
Eligible?
claim
1
2
3
4
5
6
A dietary sweetener comprising:
texiol; and
water
A dietary sweetener comprising:
1-5 percent texiol; and
at least 90 percent water
A dietary sweetener comprising:
1-5 percent texiol;
at least 90 percent water; and
1-2 percent compound N
A dietary sweetener comprising:
5 percent texiol;
water, fruit juice, or a combination of water and fruit juice; and
sufficient amounts of pectin to form a solid gel
A dietary sweetener comprising:
granular particles of texiol having a particle diameter of X10 of 80
microns and X90 of 300 microns
A dietary sweetener comprising texiol in a controlled release formulation
Directed to a Judicial
Exception?
no
yes – product of nature
no
yes – product of nature
yes
no – markedly different
yes
no – markedly different
yes
no – markedly different
yes
no – markedly different
Audience questions: Are Soteria’s new
techologies patent eligible?
 GENE-E vs. Red Genie mutants; methods of detecting the
Mars mutation
 Mars mutants patent eligible on Earth?
 What about on Mars? (The Interplanetary Patent Office,
under Commissioner Kappos does not have a section 101,
but does US patent law control?)
 Does the 1967 Outer Space Treaty prohibit patenting Red
Genie?
 Will a genetic diversity database have ramifications on 101
for engineered traits which had a previously unidentified
“natural” counterpart
Genetic Resources
Related Treaties and Conferences
Copyright © 2016 Debora Plehn-Dujowich
Will cover:
 Convention on Biological Diversity
 Nagoya Protocol
 Intergovernmental Conference on Genetic
Resources and Traditional Knowledge (IGC)
The Convention on
Biological Diversity
Treaty Considerations
Background-Doha
Declaration
 The Doha Declaration was passed in 2001 in Doha,
Qatar, as part of the World Trade Organization
negotiations.
 It stated that each member has the right to grant
compulsory licenses and to determine the grounds
upon which such licenses are granted.
Convention on Biological
Diversity
The main goals of CBD are:
 Conservation of biological diversity
 Sustainable use of its components
 Fair and equitable sharing of benefits arising from
genetic resources
Nagoya Protocol
 The Nagoya Protocol on Access to Genetic Resources
and the Fair and Equitable Sharing of Benefits Arising
from their Utilization is a supplementary agreement to
the CBD.
 It was adopted on October 29, 2010 and entered into
force on October 12, 2014.
 The focus of the Nagoya Protocol is on access and
benefit sharing (ABS) for genetic resources.
Intergovernmental
Committee on GR and TK
WIPO
Background on IGC
Intergovernmental Committee on Intellectual Property and
Genetic Resources, Traditional Knowledge and Folklore
(IGC)
 Has been meeting for fifteen years
 Meetings are held at WIPO
 Holds plenary sessions and seminars
Positions of IGC participating countries:
 Developing countries such as India and Brazil
are in favor of a mandatory disclosure
requirement.
 Developed countries such as the US, Canada,
Japan and Korea are opposed to it.
Remedies for failure to
disclose origin or source
Proposed remedies:
 Some developing countries propose that the
remedies available for failure to disclose the
origin or source of genetic resources include
the revocation of the patent.
 The US is opposed to any remedy that would
include the invalidation of a patent.
th
29
IGC
During the conference, attendees focused on the
following two issues:
 Whether there should be a disclosure requirement for the
use of genetic resources and/or traditional knowledge; and
 Whether databases should be set up where patent offices
(and possibly applicants) could search for genetic resources
and/or traditional knowledge to prevent the erroneous
granting of patents.
Federal Register Notice of
March 24, 2016
Notice of commercial marketing must be given after
FDA licensure:
 USPTO representatives before the IGC requested input
from patent practitioners regarding issues to be
discussed at upcoming IGC meetings.
 The deadline for submissions is May 23, 2016.
Issues below would be particularly
helpful to the USPTO
 Are there additional databases with information
about genetic resources and traditional
knowledge that patent examiners should use to
assess patentability?
 What are the best practices for establishing
such a database?
Database Issues
continued…
 Before such a database is made publicly available,
what steps should be taken to ensure that it does not
include confidential information?
 What studies have been done regarding national laws
and practices that require patent applications to
disclose the country of source or origin for genetic
resources or traditional knowledge that may be
implicated in the patent application?
Other Issues
 What codes of conduct (e.g., University or industry
regarding research), practices (e.g., State park
procedures to obtain prior informed consent), and laws
(e.g., tribal laws regarding sharing of culture and
granting prior informed consent) are relevant to the
protection of genetic resources and traditional
knowledge?
 What studies have been done regarding national laws
and practices requiring patent applications to disclose
the country of source or origin for genetic resources or
traditional knowledge?
Seminars
 In order to educate stakeholders, WIPO has organized
a series of workshops and seminars on the topics of
Genetic Resources and Traditional Knowledge.
 The next seminar on Genetic Resources will be held in
Geneva on May 26-27, 2016.
 For those who cannot attend in person, a webcast will
be made available for the seminars as well as for the
plenary session of the 30th IGC.
What international agreements
regulate GMOs?
• Cartagena Protocol: regulates transboundary
movement of “living modified organisms”—requires
advanced informed agreement of the parties
• Nagoya-Kuala Lumpur Supplementary Protocol:
provides international rules and procedures on liability and
redress for damage to biodiversity resulting from living
modified organism
VICIPDIA
BREAKING NEWS!
Compliance: Export Controls
Audience Questions:
Export Controls
1. What risks should Soteria keep in mind with respect to
export markets?
2. How should foreign approvals affect Soteria's decision
to commercialize Gene-E?
3. Do supply chain participants have a right not to handle
Gene-E?
4. What litigation risks exist with respect to the
commercialization of Gene-E without foreign approvals?
Any questions?
Disclaimer
These materials have been prepared solely for educational and
entertainment purposes to contribute to the understanding of U.S.
intellectual property law. These materials reflect only the personal
views of the author and are not individualized legal advice. The
presentation of these materials does not establish any form of
attorney-client relationship with these authors. While every attempt
was made to ensure that these materials are accurate, errors or
omissions may be contained therein, for which any liability is
disclaimed.
Copyright © 2016 Debora Plehn-Dujowich
EXTRA
Patent
Family
Claimed Subject Matter
Filing
Date
Term
(+PTE)
NPGB Main
NPGB--Compositions; formulations
3/17/01
Expired
NPGB Main
NPGB Gene, constructs; recombinantly
expressed NPGB; mammalian expression
systems
3/17/01
Expired
NPGB Humor
(Post AIA)
NPGB-BG Engineered plants; Methods of
expressing in plants
3/17/13
3/17/33
NPGB Humor
Methods of expressing NPGB in plants
3/17/13
3/17/33
NPGB Neuro Methods of treating neurodegenerative
(Post AIA) diseases
3/17/13
3/17/33
1 Soteria
secured 3 years PTE for its NPGB composition patent
66
Patent
Family
Claimed Subject Matter
Filing
Date
Gene-E
Methods of CRISPR editing to produce high
CO2/drought tolerant plants; Gene-E plants
5/01/20
Red Genie
Methods of producing high CO2/drought
tolerant plants under Mars Space Station
growth conditions; Red Gene plants
5/01/22
Term
(+PTE)
67