The Impact of Academic and Government Partnerships on ...

The Impact of Academic and The Impact of Academic and Government Partnerships on Biofuel R&D Innovation at Novozymes

Kurt Creamer, Connectivity Manager

Presentation at Rutgers

6-November-2009

NOVOZYMES PRESENTATION10/11/20092

Roles of a Connectivity Manager at Novozymes

Grantwriting – manage proposals for large government proposal efforts and be point of contact for projects where Novozymes is subordinate partner

Research Collaboration Facilitator – develop and facilitate partnerships and collaborations with universities and government labs

Technology Scouting and Screening – insource adjacent, Technology Scouting and Screening insource adjacent, enabling or complementary IP from universities, government labs


Background for a Connectivity Manager

Brown: B.A. in BiologyUC Davis: M.S. in Agricultural Engineering g g g(Biomass Gasification)Battelle: Research Scientist in Process Engineering DepartmentNCSU: Technology Transfer Office, gy ,managed IPNCSU: Directed Energy Crops for NC Program: evaluated agronomics, economics, processing capacity for energy cropscropsNCSU: Organized/coordinated NC Biomass Council to promote economic development, emissions reductions and energy security through biomass gy y gutilization, produced a Biomass Roadmap for North Carolina.NCSU: Part-time Ph.D. in Agricultural Engineering from NCSU – growth rate kinetics in thermophilic anaerobic kinetics in thermophilic anaerobic digesters

Novozymes in brief

World leader in industrial enzymes & o d eade dus a e y es &microorganisms and market leader in all industries where present

Products sold in 130 countries in 40 different industries

Total sales of USD 1.6bn in 2008

13–14% of revenue invested in R&D

New products represented around 25% of total sales in 2008

43 new products launched during the last 5 years

Distribution of Novozymes’ businessRevenue 2008 ~ USD 1.5 billion

Enzymes for industrial useMarket size ~ USD 2.9 billion

p g y

Source: Novozymes' 2008 estimates


R&D Structure

R&DR&D

Molecular Biotechnology

Applications Development

Biofuels & StarchStarch

F d F d Food, Feed, and Technical

10/11/20096

Enzymes are used to produce many of our daily life products

10/11/20097

Quality control of Novozymes’ LCA studies

LCA studies used in Novozymes’ external communication areLCA studies used in Novozymes external communication are

Carried out in accordance with the requirements of the ISO 14040 standard on LCA

Subject to external critical review and/or

Published in the International Journal of life cycle assessmentlife cycle assessment

10/11/20098

LCA studies address four environmental indicators

Smog Nutrient AcidificationGlobal Smog formation

Nutrient enrichment

AcidificationGlobal warming

10/11/20099

LCA studies address three resource indicators

Fossil fuel Agricultural land

Minerals

10/11/200910

Greenhouse gas reduction when enzymes are used in different production processes

100 kg CO / ton

6-150kg CO2 / ton

280kg CO2 / kg CO2 / ton

hidekg CO2 / ton pulp/paper

kg CO2 / ton cheese

190kg CO2 / ton fatty acid ester

Leather Pulp / paper Cheese

5-80kg CO2 / ton feed

110kg CO2 / ton bread ester

Bread Pig feed Cosmeticgs1000

kg CO2 / ton yarn

44kg CO2/ ton oil

150kg CO2 / ton detergent

Vegetable oil

Cotton yarn

Laundry detergent


Government CollaborationsCollaborations

NOVOZYMES PRESENTATION

10/11/200912

G t C ll b tiGovernment CollaborationsCollaborations with government laboratories, such as NREL d PNNLNREL and PNNL

Funding from government agencies, primarily the Office of the Biomass Program at the Department of Energy

Bioenergy – 2001-2005

Project DECREASE – 2008-2011

P j t LIBERTY ( b t t t POET) 2009 2010Project LIBERTY (subcontractor to POET) – 2009-2010


Pitfalls of Accepting Government G tGrants

Patent Waiver and USA Competitiveness Clause.

"Government purpose" and "march-in rights”. The government gets a royalty-free license for their own (non-commercial) use. "March-in" rights are used in a case where a company that has technology deemed to be in the national interest doesn't commercialize it.

"Preference for US Industry" provisions in the Bayh-Dole Preference for US Industry provisions in the Bayh Dole Act. One cannot grant an exclusive licence for a subject invention to an entity that will sell a product in the US unless the product embodying the subject invention will be manufactured substanitally in the US.

Shifting priorities such that development not sustained

Gaps in government support for biofuelsGaps in government support for biofuels

NOVOZYMES PRESENTATION14 10 November, 2009

Cellulose − The most abundant organicpolymer on earth

Like starch cellulose is Schematic representation of the lignified plant cell wallSource: Boudet et al., 2003. Trends Plant Sci. 12:576.

Like starch, cellulose is composed of long chains of the sugar glucose

The cell walls of woody plants and grasses are composed predominantly of cellulose, lignin, and hemicellulose

Cellulose fibrils are embedded in a network of hemicellulose a et o o e ce u oseand lignin


Our Role in Cellulosic EthanolOur Role in Cellulosic Ethanol


Past R&D in Enzyme Development for y pCellulosic Ethanol

DOE/NREL/Novozymes 2001–2005

Enzyme cost reduction on NREL acid pre-treated stover

USD 17.8 million grant

30-fold cost reduction based on enzyme improvements and alternative production scenariosp


Cost Reduction Tools – Enzyme Activity

Increased thermostability Proteomics

N l t d t i

Microarray•Novel mRNA’s

Fungal Expression•Expression of new genes Fungal ExpressionProteomics

N l t d t i

Microarray•Novel mRNA’s

Fungal Expression•Expression of new genesFungal Expression•Expression of new genes Fungal Expression

Resistance to inhibition

Synergistic

Bioinformatics•New fungal cellulases•Homologue analysis

•Novel secreted proteins •Fermentation

Biochemical Characterization

g p•Fungal host development•Fermentation optimization

Bioinformatics•New fungal cellulases•Homologue analysis

•Novel secreted proteins •Fermentation•Fermentation

Biochemical CharacterizationBiochemical Characterization

g p•Fungal host development•Fermentation optimization

combinations of enzymes and adjutants Directed Evolution

•Rational designR i ifi t i

Biochemical Characterization•Protein purification•Substrate specificity •Thermostability•SynergyDirected Evolution

•Rational designR i ifi t i

Directed Evolution•Rational designR i ifi t i

Biochemical Characterization•Protein purification•Substrate specificity •Thermostability•Synergy

Biochemical Characterization•Protein purification•Substrate specificity •Thermostability•Synergy

•Regio-specific mutagenesis•Random mutagenesis•Shuffling•Screening!!!




DOE/NREL Project Summary

Fully characterized the primary cellulase system utilized today (from T reesei)(from T. reesei)

Identified, cloned, and expressed over 80 new cellulases (CBHI, CBHII EG βG)CBHII, EG, βG)

Used directed evolution to create more thermostable CBH and BG

Created over 400 new cellulase-producing fungal strains co-expressing various combinations of native cellulases new enzymes and native cellulases, new enzymes and proteins

Tested over 200 strains for cellulose degrading activitycellulose-degrading activity

NOVOZYMES PRESENTATION19

10 November, 2009

Project DECREASENovozymes awarded $12.3 M contract from US DOE

2.5 year contract w/ matching funds -

Global collaboration between Novozymes researchers

California

2.5 year contract w/ matching funds

$25 M research project

Novozymes’ project DECREASE North CarolinaDenmarkChina

(Development of a Commercial-Ready

Enzyme Application System for Ethanol)

External partners: Pacific Northwest National LaboratoryNational Renewable Energy Laboratory Cornell University

Goals: Improve performance of

Novozymes’ most advanced cellulase

system, further decreasing the cost of

cellulosic ethanol productionCentre National de la Recherche

Scientifique, France

cellulosic ethanol production


Academic CollaborationsAcademic Collaborations


Ch ll W ki ith A d iChallenges Working with Academia

In difficult times, external research budget is gan easy target

Projects often have substantial background and k hknow how

Don’t always have to know how things work –GH61 as exampleGH61 as example

Intellectual property always a major challenge – fear of losing “freedom to operate”fear of losing freedom to operate

Our MTA for key pre-commercial enzymes is not compatible with MTAs of leading research institutions


C it i f W ki ith A d iCriteria for Working with Academia

Good source of talent for recruitment

Proximity to one of our sites in North AmericaFranklinton, NC (North Carolina State University)

Davis, CA (University of California, Davis)

Salem, VA (Virginia Tech)

Effective technology transfer apparatus as Effective technology transfer apparatus as measured by objective indices (licenses, patents, startups, etc)

Innovative basic research that could lead to major (vs incremental) advances in the state-of-the-artof the art


C it i f W ki ith A d iCriteria for Working with Academia

Strong commitment to working with industrial g gpartners

Possesses a “critical mass” of faculty that d t h i f i t t t NZconduct research in areas of interest to NZ

Home to a relevant Federally-supported Center that would allow NZ to leverage its external that would allow NZ to leverage its external research funds;

Home to a professor whose unique talents are Home to a professor whose unique talents are important to NZ’s research agenda

Land Grant universities seem to meet our criteria most often


Peer Reviewed Technical Journal LiteraturePeer-Reviewed Technical Journal LiteratureMost Active – Biomass Pretreatment

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Ranking Based on AUTM Data

Rank Name of Institution KEFRank Name of Institution KEF

1 Univ. of California System 13.57

2 St f d U i 4 872 Stanford Univ. 4.87

3 Massachusetts Inst. of Technology (MIT) 4.81

4 N Y k U i 4 534 New York Univ. 4.53

5 Univ. of Wisconsin at Madison 3.60

36 Michigan State Univ. 1.11

37 U i f N th C li Ch l Hill 1 0937 Univ. of North Carolina, Chapel Hill 1.09

38 Rutgers, The State Univ. of NJ 1.08


Radical Innovation Catalysts

What is RIC (Radical Innovation Catalysts) ?

RIC is a community for those who play a role in

ki id h

RIC links technical ideas with business

making ideas happen

RIC educate those who thrive on RIC is a place for

opportunities

RIC is also:who thrive on

innovationRIC is a place for people to go with

new ideas• Cross-functional collaboration between R&D and

Business Divisions

• Idea qualification by allocated R&D and business developer resources

RIC joins together competences and creates a network of entrepreneurs

RIC stimulates and captures

breakthrough ideas

• Focus on ideas, falling adjacent and outside cure businesses

of entrepreneurs

RIC assists in managing radical ideas RIC evaluates and

breakthrough ideas

managing radical ideas and in transitioning

them to projects

matures new ideas

How does it look ? How does it look ?

Inn

o

Man

-Pro

ject ap

DISCOVERY DEVELOPMENTFRONT END

ovato

rs

nag

emen

tpproval an

d re

RIC TeamRICCore

Portfolio Management

eview

RIC Team:Scientists throughout company that have committed to evaluate ideas

RIC Core:Key individuals from Innovation Office and New Business Development

Ideas for RIC-assessment


Ideas for RIC assessment

Ideas are submitted in different ways

And they come from different sources

What happens when an idea is submitted?What happens when an idea is submitted?- RIC Core decides go/no-go with innovator

Forward to established business area / thanks for now !

RICCore

member

area / thanks for now !

RIC Ideainnovator innovator

Core Qualification

RIC+

RICTeam

innovator

Team work during - qualificationTeam work during qualification

Length of qualification period: ~ 3 months

Each team member spends up to 50% of time during period

Finalizing is a presentation and recommendation of the idea Finalizing is a presentation and recommendation of the idea

A successful evaluation of an idea

will provide a substantiated base from where a clear go/no-go p g / gdecision can be made on continuance as a front end project.

innovator

RICCore

innovator

+RIC

Team

RIC Team + Innovator start Idea

Qualification(2-3 months)


Connectivity


C ti it NA G l f 2010Connectivity NA Goals for 2010Align scouting efforts with Innovation Office by seeking to find solutions to global technology gaps in North America

Refocus efforts to support technology needs that are firmly anchored within the Novozymes sites in North America.

Expand role beyond the current emphasis on biomass and on government funding

Focus government funding efforts on improving fundamental Focus government funding efforts on improving fundamental understanding of enzymes and substrates

In conjunction with marketing, proactively make enzyme l il bl b dl d i d l bsamples available broadly to academic and government labs

Engage NZ scientists with external scientists through extended visits to spark innovation, with a focus on key academic and government partners


Examples of what successful outcomes

NZ collaborates with University A to develop an ultrasonic

might look like:

polishing of dilute-acid pretreated corn stover that substantially reduces the enzyme loading required for hydrolysis

NZ sends visiting scientist to University B to verify that the pretreatment technology developed by Professor C is a commercially viable biomass pretreatment technologya commercially viable biomass pretreatment technology

NZ licenses from University D a protein that along with our cellulase cocktail, synergistically improves the enzymatic hydrolysis of biomass

Rethinking fuel

The only enzyme id t it t provider to commit to

providing commercially viable cellulosic enzymes by 2010

• Leading enzyme provider for starch-based fuel ethanol enzymes in all regions where we operatey g p

• Over 100 scientists dedicated to the development of biofuel solutions

• Broad insight into cellulosic ethanol work – we are working on various feedstocks and gtechnologies

The cellulosic ethanol industry will be a major contributor to future biofuel growth

Session 4B – Cellulosic Ethanol & Biobutanol Session

Cellulosic ethanol – technologies & challenges

Predictability of industry growth depends upon:

Delivery of advancements to enable commercial viability

Continued support to drive investment in the biofuel industry

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Enzymatic route from biomass to ethanol

SugarcaneSugarcanebagasse

Corn stover

Straw

Wood residues

Industrial waste

Energy crops

Municipal solid waste

Many pretreatment technologies exist – all impacting subsequent hydrolysis and fermentation of sugarsof sugars. Distillation and generation

of energy

Applied Discovery R d t t l t f Reduce total process costs – focus on enzyme costs via holistic innovation

CollectionCollection& Storage& Storage Recovery

pre-treatment Hydrolysis fermentation

• Highly interrelated technologies• Novozymes R&D tools and experienceNovozymes R&D tools and experience

utilizing enzyme technology and application know-how to also provide ideas in p and f

• Partnership is key

By using our biotech tools and focusing on

39

continuous optimization we continue to develop new enzymes for 2G biofuels

Optimizing the Optimizing the Optimizing the production microorganism

Squeezing more enzymes out of the existing production strains being used

industrial production

Traditional engineering optimizing the use of fixed assets employed

enzymes produced

Creating new enzymes with higher potency for the same application

used

Examples of technologies Examples of technologies d

Examples of technologies used

Major allocation of R&D resources directed toward optimizations

used

Genetic engineeringNew microorganisms

used

Industrial engineering Process optimizationEquipment optimizationInput optimizations

used

Protein engineeringHigh-throughput screeningSite-specific mutagenesisRandom mutagenesisInput optimizations gGene shuffling


We have taken a big step forward – Best cost/performance ratio in the industry today

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Cellic® CTec 2000

0 0.04 0.08 0.12 0.16 0.2

Enzyme dosage (ml of product/g of cellulose)

Previously available enzymesCellic CTec 2000 Previously available enzymes


Reaching feasible enzyme costs in 2010…

Enzyme costs are becoming a smaller and smaller smaller percentage of the total process costs


Reaching feasible production costs in 2010…

Production costs for cellulosic ethanol will ethanol will become comparable with production costs for first costs for first generation


Novozymes is leading the way…

Enzyme costs are becoming a smaller pe centage of the total p ocess costs fo

… to a promising biomass future

percentage of the total process costs for cellulosic ethanol

Novozymes Cellic product family is a key step in our path to delivering our 2010 promise for commercially viable enzymes

Through partnerships we will advance enzyme and process technology to enable enzyme and process technology to enable commercial viability of cellulosic ethanol

We will enable the industry through cost effective products and supply logistics.

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