DISCOVERYKGI is dedicated to education and research aimed at translating into practice, for the benefit of society, the power and potential of the life sciences.

Winter 2013

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insid

e KGI School of BioPharmacy Update

Meet KGI’s Post-Modern Medicine Man

Easing Rabies Burden in the Developing World

Continued on page 9

President Sheldon Schuster will soon

have a “powerhouse” new resource

at his disposal as he works with the

Board of Trustees to determine what

opportunities KGI should pursue in

the future. Last March, the Board of

Trustees approved the formation of

the institute’s first president’s council,

which is comprised of an elite group of

life science industry leaders. Although

not responsible for governance of the

institute or the implementation of plans,

council members will serve as confidential

advisors to the president and the board,

providing the institute with a vast wealth

of knowledge and industry expertise.

“KGI is experiencing significant

growth, while at the same time the health

care industry is undergoing dramatic

changes,” President Schuster said. “To

have this type of brain trust available to

me personally as an administrator and to

KGI as an organization during this period

of uncertainty, change and opportunity is

absolutely invaluable.”

Members of the inaugural council

will include James Cornelius; Michael

Friedman, MD; Robert Grubbs, PhD;

Freda Lewis-Hall, MD; Harlyne Norris;

Peter Salk, MD; and David Walt, PhD.

KGI Establishes President’s Council

In the spring of 2005, Robert Grubbs

received a call letting him know

that he had won the Nobel Prize in

Chemistry for his work on catalysis or

more specifically “for the development

of the metathesis method in organic

synthesis.”

He describes it as a “huge surprise.”

“There are always rumors going

around so you never know for certain,”

h e e x p l a i n s .

“There are many

people who do

incredible work

and who are

ment ioned as

being potential

recipients for

years, but they never win.”

Metathesis is a chemical reaction

in which an element or radical in one

compound exchanges places with another

element or radical in another compound.

Before the work of Grubbs and his fellow

Nobel recipients Yves Chauvin and

Richard Schrock, scientists had a very

limited understanding of metathesis

and little idea of the promise it held for

developing new materials. But Grubbs,

through his work in olefin metathesis in

particular, was able to develop highly

effective new catalysts that essentially

allowed for the creation of custom-built

molecules whose specialized properties

have a myriad of applications in industry

from the development of better drug

treatments to specialized plastics.

KGI welcomes Dr. Grubbs as an inaugural member of the President’s Council

An Interview with Nobel Laureate and Caltech Chemist Dr. Robert Grubbs

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By now you have probably heard from us through the mail, phone or email that we are in the midst of our 2012-2013 Annual Fund campaign. It’s a great time of year to give—you can sup-port KGI and get a tax benefit before the end of 2012. Thank you for your support.

Ways to give:• Please use the enclosed envelope to send a check or credit card number• Log on to support KGI.org to give online • Call (909) 607-8587 to donate over the phone

KGI to Pursue Independent School of BioPharmacy

For the past several years, KGI has been planning to launch

an innovative new School of BioPharmacy (SBP) that would

redefine the traditional Doctor of Pharmacy Degree. KGI’s

Board of Trustees determined that this ambitious undertaking

would introduce important innovations in pharmacy

education, enhance the institute’s standing as a leader in

bioscience graduate education and advance its mission to

develop the power and potential of the life sciences for the

benefit of society. Since the fall of 2011, Chapman University

has been a participant in this endeavor. The collaboration

held many potential benefits for both institutions. Chapman’s

programs in health informatics and health economics, as

well as a growing health sciences program, were a draw for

KGI, while Chapman’s leadership was intrigued with KGI’s

mission and concept for the school and valued the institute’s

expertise in niche education and its strong ties to industry.

Earlier this year, Chapman and KGI signed a memorandum

of understanding to establish the school, with a target date

to admit the first class on the KGI campus in the fall of 2014.

However, as the plans for the Chapman-KGI School

of BioPharmacy continued to take shape, it became clear

that, while the collaboration had been entered into with the

common goal of advancing healthcare education in our region

and furthering the missions of both schools, each institution

had a different vision for the SBP.

One of the major differences concerned the site of the new

school. It had originally been decided that classes would

be held on the KGI campus, recognizing that Chapman

would plan for a second SBP campus after accreditation

was achieved. Chapman University’s leadership concluded

this fall that the initial program should be moved to Irvine

in an industrial park facility it recently purchased for this

and other programs comprising its graduate health sciences.

KGI’s leadership believes equally strongly that it is vital for

the initial program to be held on KGI’s campus in order to

fully integrate the crucial KGI–related mission and services

with the SBP concept. Discussion to find common ground

around this fundamental issue was not productive.

“We are disappointed that, ultimately, this partnership

was not feasible,” said KGI President Sheldon Schuster.

“However, we have the full support of KGI’s Board of

Trustees’ Executive Committee to continue to pursue the

original School of BioPharmacy concept, which will be a

novel program among pharmacy schools in California and the

nation. We are energized by the return of control to KGI and

will pursue the concept for the school with our key strengths

at its core.”

KGI is continuing to work toward a January 2013

accreditation submission deadline for the new KGI School of

BioPharmacy. However, meeting this goal is strictly dependent

upon the funds being donated, pledged and/or loaned to give

the school a substantial financial footing. If substantial

funding is not acquired, submission of the application will

be delayed until January 2014 and admission of the first class

will be rescheduled to fall 2015.

“We believe that the SPB will greatly contribute to the

broadening of KGI’s recruiting base, building our faculty and

expanding our reputation,” President Schuster said. “With the

help of our strong supporters and generous donors, we have

no doubt that—just as 15 years ago we were able to launch

the bold undertaking to create the only graduate institution

in the country solely devoted to bioscience education and

discovery—the new KGI School of BioPharmacy will also

soon become a reality.”

ANNUAL FUND

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Since being elected to the KGI Board of Trustees

in 2009, Jim Widergren has brought invaluable

business expertise to the institute. In fact, his career

with its roots in both business and engineering embodies

the KGI professional model. “Jim’s knowledge base is

truly exceptional,” said KGI President Sheldon Schuster.

“His keen insight combined with his willingness to step

up and do whatever is necessary to help KGI grow and

thrive make him an outstanding board member and

supporter.”

Widergren, himself, credits much of his success

in business to his ability to understand the tech side

of industry. “I started in the automotive industry

designing turbochargers as an applications engineer,”

said Widergren, who retired in July of this year as the

senior vice president of Global Customer Operations for

Beckman Coulter. “At the beginning of my career, as an

applications engineer for Allied Signal Corp., I worked

directly with engineers at a major customer helping them

to design their engines using our turbochargers. I also

worked a lot with the service engineers who supported

end-user customers directly. This interaction with

customers made me interested in learning more about

the business side of technology.”

In order to learn more about the business side,

Widergren, who already held bachelors and master

degrees in engineering from Harvey Mudd College,

enrolled in UCLA’s Anderson School of Business. He

earned an MBA in finance and operations, which led to

positions on the business side of an engineering consulting

firm, Malcolm Lewis Associates, and a commercial real

estate development firm, Ferguson Partners. In 1992,

he joined the finance team at Beckman Instruments,

which later merged with Coulter Corporation to become

Beckman Coulter. “I have been on the business side ever

since, but the technical background was critical in my

success, as Beckman Coulter is a high-tech company

with technical customers. I could understand and solve

their problems.”

In fact, KGI’s unique educational program which

combines business with science and technology is what

initially intrigued him about the institute. “I think the

KGI MBS (Master of Bioscience) program is superb, and

I wish there had been such a program when I was in

college,” he said. “Rather than having to do two more

general master’s degrees, as I did, the MBS program

combines the best of both in a very industry-focused

way.”

Widergren also points specifically to the Team

Masters Project as one of the MBS program’s

distinguishing factors and representative of the type of

industry-focused experience that KGI offers its students.

“The TMP, which is modeled after the Harvey Mudd

Clinic Program, is a great way for students to learn to

interact with company deadlines, work with executives

and manage projects in a real-world setting, while still

having the support of the faculty and fellow students,”

he noted. “At Harvey Mudd, the Clinic Program was a

key to my education, and I am sure the TMP is having

the same effect on the KGI students.”

He also appreciates the institute’s large international

student population and believes that international

experience, which has been critical in his own career,

will be a key driver to future success in the life science

industries. “My international focus goes back to a

Thomas J. Watson Fellowship I was awarded while

at Harvey Mudd,” he explained. “I spent a year after

college in Asia studying energy development in rural

parts of Asia. By working at Beckman Coulter I was

able to combine my technical background, my business

experience and my international experience working on

the international side of the company for many years—

first in Finance, then in Operations. I have no doubt

that success in the future will require more international

interaction and understanding.”

KGI TRUSTEE PROFILE:

Jim WidergrenThis retired Beckman Coulter executive with vast business and international expertise is a firm believer in the KGI educational model

BOA

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Continued on page 7

President Sheldon Schuster hosted a luncheon at his new

home in Claremont on October 12 to honor the founding

trustees, donors and supporters of KGI. Among those in

attendance were original donors such as Harlyne Norris, KGI

trustee emerita, member of the President’s Council and of The

Kenneth T. and Eileen L. Norris Foundation, and Wendy Garen,

president and CEO of The Ralph M. Parsons Foundation. Allison

Keller, executive director and chief financial officer, and Maria

Pellegrini, PhD, executive director of programs, represented the

W. M. Keck Foundation. KGI was established in 1997 thanks

to a $50 million founding grant from the Keck Foundation.

Keller lauded KGI as one of the foundation’s best investments:

“From its beginning the W. M. Keck Foundation has put its

money into high-risk, high-impact projects, and I can’t think of a

better example of this than Keck Graduate Institute. Who knew

that you could pull it off and have a 22 percent year-over-year

growth rate? It’s about success, persistence and momentum,

and we can’t thank you enough for allowing us to share in this

success with you.”4

In today’s day and age, when insulin pumps are often

smaller and weigh less than cell phones, it’s hard to imagine

carrying around a backpack- style 18” by 18” insulin pump

weighing approximately 10 lbs. However, visitors to KGI’s

Science Heritage Center can now get an idea of exactly

how much the technology associated with these devices

has progressed by viewing a prototype of the first insulin

pump, which was created by Los Angeles pediatrician Dr.

Arnold Kadish in 1963. The device was donated by Kadish’s

son, John, who toured the Science Heritage Center over the

summer.

Dr. Kadish originally developed the pump for his

daughter, who had type 1 diabetes. The device delivered

both intravenous insulin and glucagon for improved glycemic

control. Through the efforts of the center’s curator, Robert

E. Finnigan Professor of Applied Life Sciences Dr. Jim

Osborne, and a close network of medical device professionals,

inventions such as Kadish’s insulin pump, which might be

otherwise lost, are now available for public display.

In fact, among the center’s recent visitors was Boy Scout

Troop #600. The California Inland Empire Council troop are

Webelos—a program that prepares 4th and 5th grade boys

to join a Boy Scout troop while learning outdoors skills and

participating in 20 different activity badges. “The items in

the Science Heritage Center are wonderful tools for getting

students of all ages interested in science and engineering

careers,” Osborne said.

Science Heritage Center Receives ‘Weighty’ Donation

A Great Day for Founders

Dr. Alan Rothfeld’s storytelling abilities

may be one of the reasons KGI students

consistently rate him as one of their favorite

professors—that and his impressive knowledge base

and wealth of experience. In addition to having spent

35 years as an academic and private practitioner

of pulmonary and critical care medicine, he’s also been

teaching medical students at the Keck School of Medicine

of the University of Southern California (USC) since 1979,

as a clinical professor of medicine.

After several years serving as an adjunct, Rothfeld

became a professor of practice at KGI this year. In many

ways, he says, teaching here is more fun in that it allows for

more flexibility. “Medical students have a pretty narrow

focus in that they are very concerned with what they have

to know to pass the test,” he said. “In my classes at KGI,

I get to show the whole spectrum of pharmacological

and medical science. It’s more about providing a broad

framework for (my students) to understand how to deal

with new situations, new drugs and new information—

and to be able to weigh benefits and risks.”

In fact, one of the consistent themes in Rothfeld’s classes

is that “unassailable truths” often have a shelf-life. As an

example, he points to the fact that conventional medical

wisdom used to hold that it was necessary to prescribe

drugs to suppress cardiac ventricular arrhythmias.

However, when outcomes were studied it was found

that, by and large, when you didn’t suppress arrhythmias

patients did much better.

Similarly, conventional medical wisdom used to hold

that it was necessary to raise the hemoglobin levels of

sick people. Actually, as Rothfeld points out, there is less

mortality in sick people with lower hemoglobin.

That’s why he stresses the importance of clinical trials.

“You don’t have to explain something for it to be true,

what works is what works,” he said. “The practice of

medicine is really about constantly translating findings

and putting them into practice.”

That’s why Rothfeld is such a strong proponent of

“rational medicine,” in which, as he describes it, you

have “some consideration of the

benefits and risks” associated

with a treatment, drug, or course

of action.

“You don’t seize on a small

benefit or potential benefit at the

cost of ignoring a huge risk. You

have to measure the overall benefit

to society and not be blinded by the idea of a miracle

treatment or miracle drug, which is, to some degree, the

paradigm of modern pharmacology.”

Often lost in the “miracle approach” to health care and

pharmacology is the fact that adverse drug reactions—

combined with errors and unnecessary therapies—cost

more lives than cancer and AIDS combined. “The truth

is we could cure cancer and not have as much impact on

the overall mortality rate as we would by cutting in half

deaths due to medical care. Why not put research into

how to decrease medical care-associated deaths and use

drugs more rationally?”

In addition to teaching KGI students about truly

modern medical practice, Rothfeld also serves as the

medical director and an adjunct professor of respiratory

therapy at Los Angeles Valley College, as well as the

director of translational research at COPE Health

Solutions, a leading healthcare corporation based in Los

Angeles. There, he is engaged, among other projects, in

research on the “Use of Behavioral Economics to Improve

Treatment of Acute Respiratory Infections.” The long-term

objective of which is to develop a set of applied behavioral

economic tools that are effective in promoting rational

choices among providers in infection treatment, a model

which could eventually be applied in other areas of health

care delivery and to other diseases and problems.

“We know that economic factors have a profound

effect on both patients and healthcare providers so

why not put effort into understanding them and then

incorporating them in to an applied model that will allow

you to improve patient outcomes?” he added.

Why not? It sounds pretty rational to us.

‘Post-modern’ Medicine ManAn advocate of rational medicine, Dr. Alan Rothfeld teaches his students how to deal with the unexpected

The practice of medicine is really about constantly translating findings and putting them into practice.

FAC

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Advisory Council (AC) Chair Brenda Mann was

working as a post-doc in Houston when Larry

McIntire, then chair of the Bioengineering

Department at Rice University, first brought KGI to

her attention. He thought

that the brand new graduate

school taking shape in

California might be a good

fit given Mann’s postdoc

work in bioengineering and

biomaterials.

“It seemed l ike a

comple t e ly d i f f e r en t

environment. It wasn’t the

same as working in industry,

but it wasn’t the classical

academic track either,”

Mann said. “I was attracted by the idea of training

students to work in industry through innovative teaching

methods, including a cross-disciplinary approach that

would allow science and business faculty to work

together to a much greater degree and in a different

way than I’d seen.”

As one of the first faculty to be hired at KGI in 2000,

Mann jokes that VP of Academic Affairs and Dean of

Faculty Jim Sterling beat her to an actual start date, just

slightly, as least as far as bioengineering faculty was

concerned. “It wasn’t just a great teaching opportunity;

my time at KGI was also a great learning experience for

me. I learned so much about management, networking

and business development. Since the faculty was so small

and the school was so new, you were able to step outside

of your comfort zone.”

After three and half years as a member of the KGI

faculty, Mann moved to Salt Lake City with her husband

Jordan Gerton, who had been doing postdoc work at

Caltech and who was growing tired of the infamous

SoCal commutes. “I was happy at KGI, but sometimes

you have to make decisions based on what’s best for

both of you.”

Post-KGI, Mann had a choice between accepting a

traditional faculty position or working for a startup,

SentrX Surgical—a biotech company with an initial

market focus on therapeutic medical devices and

combination products to prevent post-surgical adhesions.

She decided to take a chance and work for the startup—a

bold move she would not have made, she says, if it were

not for her experience at KGI. “I was the third person

hired after the CEO and an administrative assistant. I

absolutely don’t think I would have done it if KGI hadn’t

made me comfortable with the business side,” she said.

“Before KGI, I had never seen a business plan; I didn’t

really know much about starting a company.”

In 2006, after serving as the director of pre-clinical

R&D for SentrX (now Carbylan BioSurgery), Mann

co-founded a spinoff company SentrX Animal Care,

which focuses on wound treatment products developed

specifically for horses and small animals. At first, as

the new company’s chief operating officer, she was

responsible for both manufacturing and research

and development, but as it grew she turned over her

manufacturing responsibilities to others and now

concentrates solely on R&D.

Yet, despite finding such success in industry, Mann

has never lost her connection with KGI. “I’ve served

on the AC since I left the faculty,” she said. Coming

from the animal health perspective, I think I provide

a different standpoint from other AC members, and,

in turn, have this incredible network of professionals

available to me from all areas of the life sciences. Most

importantly, I have the opportunity to get to know the

next-generation of industry professionals and stay on

top of how they think.”

In fact, Mann says the chance to interact with students

and colleagues face-to-face is why she particularly looks

forward to coming back to campus for biannual AC

meetings. “Occasionally, I think it may be time for

me to step off the AC but, since I’ve been here from

the beginning, I hope I provide a certain institutional

memory. It’s been very rewarding to watch and hopefully,

in some way, contribute to KGI’s growth over the years.

It’s fascinating to observe all the changes.”

ADV

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IL ‘Manning’ UpCurrent AC chair and former faculty member Dr. Brenda Mann talks about her long history with KGI, why she stays involved

Robert Baltera Jr., MS, MBA, was elected to the KGI Board of Trustees in September. A seasoned

pharmaceutical industry executive, Baltera acquired a wealth of business and product management

experience during 17 years with biotech pioneer Amgen and four years as CEO of Amira Pharmaceuticals,

which was acquired by Bristol-Meyers Squibb Company for $475M. While at Amira, Baltera was

instrumental in focusing Amira’s clinical development efforts and forging key collaborations with partners

such as GlaxoSmithKline. Before becoming Amira’s CEO, he held a number of senior management

positions at Amgen, the last being vice president of corporate and contract manufacturing. Baltera

also successfully used his collective experience to serve as team leader responsible for the approval

of Kineret™ in rheumatoid arthritis, a highlight of his many accomplishments while at Amgen. He

holds an MBA from UCLA Anderson School of Management and earned a Bachelor of Science in microbiology and a Master

of Science in genetics from The Pennsylvania State University.

Baltera Brings Experience, Insight to BOT

In September, the Board of Trustees

unanimously approved awarding a

Doctor of Applied Life Sciences honoris

causa to Marsh Cooper. In addition

to being one of the longest-serving

and most active members of the KGI

Board, Cooper is also a member of the

Board of Directors of the W. M. Keck

Foundation. Soon after the approval,

KGI President Sheldon Schuster and

Chair of the Board of Trustees Robert

Curry traveled to Toronto to present

Cooper with the degree and wish him

a Happy 100th Birthday!

Quite an Honor

In fact, business savvy, global thinking and an in-depth

understanding of science and technology are exactly what’s

needed in the industry leaders of tomorrow, and exactly why

he remains so committed to KGI’s mission: “We are entering

an exciting time for the life science and healthcare industries

with the emergence of personalized medicine and better

understanding of the human genome. But the best discoveries

are of little use to the world if they cannot be commercialized

and developed for people’s use. This requires both technical

and business expertise, which is a hallmark of KGI graduates.”

continued from page 3

STU

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For most people in the United

States, rabies is low on the

potential threat level. The number

of rabies-related human deaths averages

two or three each year and more than

90 percent of all animal cases reported

annually to the CDC occur in wildlife,

principally in wild carnivores and bats.

However, in areas of the developing

world, particularly in rural India, Asia

and Africa, rabies—an infectious disease

caused by a group of viruses from the

Lyssavirus genus — remains a pernicious

problem.

The World Health Organization (WHO) estimates that

more than 55,000 people die of rabies every year, with

roughly 36 percent of those deaths occurring in India.

Additionally, more than four million people are bitten

by dogs suspected to be rabid and thus should receive

treatment. A WHO report also stated that the paralytic

form of rabies is often misdiagnosed, contributing to the

underreporting of the disease.

If not treated after a bite from a rabid animal,

symptoms will usually develop between four to six weeks

and almost always lead to death. Current treatments

(cell culture vaccine plus antibodies from a previously

vaccinated human or horse) are effective but are often

unavailable, expensive, or inconveniently distant from

disease-burdened areas. More specifically, cell culture

vaccines may cost up to $40 to $50 for a full 4-5 shot

regimen delivered over the course of four weeks. The

cost of treatment along with the large number of shots

over time is not ideal for people living in rural areas who

must travel significant distances multiple times to receive

treatment.

That’s where KGI PhD candidate Ryan McComb

comes in. Working under Adjunct Professor Dr. Larry

Grill, McComb is conducting research that could lead to

the development of a more potent, less costly and locally

produced plant-made rabies vaccine. By increasing both

vaccine availability (through lowered production costs)

and reducing the number of times an exposed person

needs to receive a booster shot, the vaccine would have the

potential to greatly ease the rabies burden in developing

countries. Using cutting-edge bioscience research to help

develop (plant made) vaccines that can be produced locally

and cost-effectively is the focus of Dr. Grill’s work. In

addition to serving as an adjunct faculty member at KGI,

Grill is also a professor at Pitzer College, where he directs

The Ferre/Marquet Vaccine Research Center, which is

dedicated to developing cost-effective vaccine production

and addressing urgent health issues in southern Africa.

“With our goal of developing and providing

inexpensive vaccines that will be produced in developing

countries, the rabies vaccine could be the accomplishment

of the decade,” Grill said.

A modified plant virus vaccine is essentially a plant

virus that has been re-engineered to mimic the physical

structures and properties of a disease-causing pathogen,

such as virus, bacteria or parasite, McComb explains.

Plant-made rabies vaccines work by using plant virus

nanoparticles as antigen presentation scaffolds for eliciting

protective antibodies from the immune system.

PhD Candidate’s Research Could Help Ease Rabies Burden in Developing World

Ryan McComb gives his Thesis Scope presentation at KGI on Oct. 30.

With our goal of developing and providing inexpensive vaccines that will be produced in developing countries, the rabies vaccine could be the accomplishment of the decade.

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continued from page 1

Although his work has found broad-

based application in industry and Caltech

has one of the best university tech

transfer offices in the country, Grubbs

is well acquainted with the difficulties

and frustrations associated with moving

fundamental discovery into industry.

“I think traditionally there’s been

some frustration in academic labs

that when you license discovery to big

companies, it often tended to die on the

vine, and that transition into widespread

application just never happened, he

said.”

Such challenges are one of the reasons

that he’s particularly interested in the

KGI model.

“I have always liked the CUC

(Claremont University Consortium)

system,” Grubbs added. “And, I think

KGI’s model of collaborating closely

with industry to advance training and

education is a very interesting one. I

also think it’s important to give young

researchers and scientists a framework

for understanding how discovery

transitions into product in a commercial

environment.”

In order to facilitate that transition,

Grubbs helped to establish a company,

Materia, Inc., where many of the

commercial applications for metathesis-

based products have been developed.

Although not without a learning curve,

Grubb says the company has done

extremely well in acting as pipeline from

academics to commercial application.

In the meantime, Grubbs, who

spent his early life in rural Kentucky

and attributes much of his intellectual

curiosity to his grandmother’s influence,

is anxious to continuing following his

research path in olefin metathesis, where

he says there are “many problems of

catalysis yet to be solved.”

“I’ve been very fortunate to have been

able to follow my intellectual interests

and have it ultimately result in products

that have biomedical applications or

that can be found in products under the

hood of your car,” said Grubbs, adding

that potential new applications currently

under the company’s banner include three

drugs to treat Hepatitis C that are in

clinical trials.

Asked if things have changed for him

in the years since he won the Nobel Prize,

his reply is, “not really, I just have to say

no a little more often.”

Luckily, for KGI and President

Schuster, when asked to serve on the

newly formed President’s Council Dr.

Grubbs’ answer was yes.

“I can’t think of a better example of

a scientist whose work embodies KGI’s

mission to translate the power and

potential of science for the benefit of

society,” President Schuster said. “We

are very grateful that he has agreed to

take this active role in support of KGI.”

I think KGI’s model of collaborating closely with industry to advance training and education is a very interesting one. I also think it’s important to give young researchers and scientists a framework for understanding how discovery transitions into product in a commercial environment.

“Introducing what ‘looks like’ the dangerous pathogen

into the body gives the immune system the ability to prime the

body’s defenses for the real disease threat without causing the

disease,” he said. “Plant viruses are safe since they don’t infect

and replicate in animal cells but still act as a potent activator of

the body’s immune system.”

Furthermore, he adds, plant-made vaccines using modified

plant viruses are inexpensive to manufacture, compared to cell

culture vaccines, since they only require water, sunlight, and

fertilizer as opposed to cell culture media and large stainless steel

fermenting tanks. The infrastructure for producing plant-made

vaccines is much smaller and can be scaled up to meet demand

by simply increasing the number of acres of plant vaccine crops.

In addition, modified plant virus vaccines can be easily purified

by using alternative methods that are less costly than purifying

vaccine material produced in cell culture. And finally, modified

plant virus vaccines are very safe since they do not require the

use of animal products as found in cell culture media.

“I think these advantages provide a compelling case for

modified plant virus vaccines so long as they prove to be potent and

effective against the pathogen they are meant to protect against,”

McComb said.

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RESE

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H Proprietary technology for manufacturing antibodies is an early KGI success story

Most of the KGI community is familiar with Dr. Jim

Cregg’s passion for Pichia pastoris (or Pichia p as it’s

known around here). The focus of his research has been

on developing the yeast as a system for the production

of recombinant proteins, and he is the lead inventor on

many of the seminal Pichia protein expression patents.

Several of those patents resulted from an interesting

collaboration between KGI and the Seattle-based biotech

company, Alder Biopharmaceuticals. And, the story of

how this particular patent came about speaks to the early

success of the KGI’s institutional model, which is built on

close collaboration with industry.

A crucial player in the story is former KGI Vice

President of Academic Affairs and Chief Scientific Officer

David Galas. Alder CEO Randy Schatzman happened to

mention to friend and former Celltech colleague, Galas,

how he and his partners (in what was then not even a

startup) were looking for an alternative way to produce

commercial antibodies for use in antibody therapeutics.

“Antibody manufacturing capacity is generally held

by a limited number of companies,” Cregg explained.

“They wanted to find a way to do it themselves and they

wanted an alternative to (typical) cell culture production.”

In other words, he says, they wanted a way to produce

them better, faster and cheaper.

And, that’s when Cregg and KGI Senior Research

Scientist (now Research Professor) Dr. Ilya Tolstorukov

entered the picture. Galas was familiar with the work

they had been doing with yeast and thought it might be

a good fit. While Cregg had been working with Pichia

since the ’80s, Tolstorukov’s PhD research project,

defended in 1973, was related to discovery of genes

involved in mating and “mating–type switching” in

classical yeast model Saccharomyces cerevisiae. In 1974,

he began working with methylotrophic yeast similar to

Pichia pastoris, particularly as it related to methods of

mating and genetic analysis. In fact, Cregg had studied

Tolstorukov’s publications when he first began working

with and learning how to manipulate Pichia P.

“When we first considered the idea of making

antibodies in the Pichia pastoris expression system, Ilya

spent several weeks analyzing the landscape and designing

the material to work with,” Cregg said, adding that

although he thought it was a possibility he still remained

somewhat skeptical that they could pull it off. “No one

had ever made full-length, multi-chain antibodies in Pichia

before, and I wasn’t sure we were going to be successful.

I had my doubts.”

And, the process of making them, which took about

a year, didn’t exactly go smoothly. “We had our lumps

and bumps along the way,” Cregg said. For example,

Tolstorukov had a “heck of a time” cloning the genes

that they needed to use in the R&D phase of the project

because commercial DNA libraries didn’t have anything

that would suit their purposes. “We basically had to design

and build our own,” Cregg noted.

Additionally, since Alder wanted to avoid having to

license technology (for the manufacturing of antibodies)

that was already patent-protected, the duo had to come

It was the first time I was involved to such a degree with a company making a product from yeast. It was a great experience for me to see a company come out of nothing using our ideas.

up with a novel approach to bringing together two cassettes

expressing heavy and light chains in one cell.

“The key element of our technology and what allowed us

to make it novel was an idea to mate (hybridize) haploid cells

expressing two different chains to create a diploid expressing

two chains capable of assembling into one tetrapeptide antibody

molecule,” Tolstorukov explained.

KGI, which had been fronting Alder the cost of this research

through use of its facilities and Cregg’s and Tolstorukov’s time

and talents, then licensed the technology to Alder. On its website,

Alder, which has grown from a startup company to one with more

than $100 million of investment in their antibody development

technology and portfolio of therapeutics, touts the Pichia system’s

ability to make “fully functional whole antibodies at a fraction

of the time and cost of other technologies.”

Its advantages, among others, include scalability (scales

reliably from 1 Liter to 50,000 Litersc); speed (each strain doubles

in 90 minutes) and cost-effectiveness (ramps to production with

minimal investment). Overall, it takes 12 months on average to

generate a commercial antibody strain using mammalian cell

cultures, while Alder’s Pichia-based “Mab Xpress® Antibody

Production System” takes about five weeks.

“The use of MabXpress has allowed us to progress our

therapeutics very rapidly from discovery into clinical studies,”

Schatzman said. “Another advantage of this technology is that

it has allowed us to consider entering disease markets where

antibodies have not previously played a role as therapeutics

and where pricing constraints have previously been a barrier

to therapeutic antibodies; an example of one such market is the

treatment of chronic migraine.”

Alder has long since repaid the research costs of developing

the Pichia system as well as an annual licensing fee. In addition,

KGI has stock in Alder which would yield a profit if the company

goes public. But, for Cregg and Tolstorukov, the benefits go

beyond the financial. “It was the first time I was involved to such

a degree with a company making a product from yeast. It was a

great experience for me to see a company come out of nothing

using our ideas,” Cregg said.

And while the circumstances that resulted in this proprietary

technology may have been unique, Cregg and Tolstorukov say

they are two of the strongest proponents of the KGI model of

collaboration with industry.

“I don’t think it would happen exactly same way today, with

one person (Galas) basically making the decision to fund the

research. Today, there would be committees to evaluate it,” Cregg

said. “That said, I do think it’s very exciting to see the work

going on here today—all the contributions that KGI is making in

rare diseases, in biomarkers, in medical devices, in many areas.”

Welcoming fellowship donors and student fellowship recipients

At the Sheraton Fairplex Hotel and Conference Center in Pomona

Wednesday, January 30, 2013

For An Italian Dinner – Buon Appetito!

KGI’s 5th Annual Fellowship DinnerSAVE THE DATE

This fall, KGI and the Jonas Salk Legacy Foundation hosted an exclusive screening of “The Shot Felt ’Round

the World” at the Huntington Library in San Marino. The documentary film about Dr. Jonas Salk and the nation’s

crusade to develop a polio vaccine includes interviews with Salk’s sons, Drs. Peter and Jonathan Salk, and those

who were part of his research team at the University of Pittsburgh. More than 150 people attended the event on

September 9, which included a panel discussion featuring Peter and Jonathan Salk, Tjardus Greidanus, the film’s

director-editor, and producer Laura Davis. KGI was able to grant complimentary admission to current students

thanks to the generosity of several anonymous donors.

The Shot Felt ’Round the World

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535 Watson Drive • Claremont, California 91711 www.kgi.edu