A well-written white paper builds credibility, creates free exposure
in the press, attracts new customers, and can even push new technology
into traditionally conservative markets. Whether you’re selling
technology, a complex service or a sophisticated product, Copywriter Connection
can help educate your customers about that technology in a way that not
only excites them—but also drives action.
Habeas Inc.
Email is broken.
In a June 2003 statement to Congress, the head of the Federal Trade
Commission, Orson Swindle, testified that “spam is about to kill
the ‘killer app’ of the internet –specifically, consumer
use of email and e-commerce.” The commissioner was not exaggerating.
For businesses and individuals alike, email has become an essential
communication tool. Studies suggest that 30 billion electronic messages
traverse the internet every day. But the same characteristics that make
email so valuable for personal and corporate communication—its
low cost and ease of use—have also made email an irresistible
tool for unsolicited marketing activities. Because email has been a
decentralized and virtually unregulated system, there have been few
obstacles keeping spammers from swamping inboxes with billions of junk-mail
messages. According to a February 2004 Internet News article, spam will
likely account for 80% of all email sent around the world by the end
of 2004.
As a result of the proliferation of spam (and the spam-filtering industry
that sprung up to fight it) email has become an increasingly unreliable
method of communication. The cost to business of fighting spam has become
enormous. Radicati Group, a market-research firm, estimates that corporations
will spend $635 million on anti-spam products and services in 2004.
One of the biggest issues businesses face is that the technology they’ve
purchased to thwart spam is frequently preventing legitimate messages
such as transaction confirmations and financial statements from getting
through. And the problem is getting worse.
As Commissioner Swindle argued, the scourge of unwanted email threatens
to undermine the entire system. Corporations sending legitimate email
face difficulties in getting their messages past the ever-increasing
spam-filtering processes of internet service providers (ISPs), as well
as the lost-opportunity costs of their messages not reaching customers.
ISPs face the increasingly difficult and costly task of protecting their
subscribers’ privacy and the integrity of their inboxes. At the
same time, if ISPs erroneously flag legitimate messages as spam, they
can incur large complaint-resolution costs. Additionally, the viruses
often contained in unsolicited emails can threaten recipients’
computers and even disrupt the entire network to which those computers
are linked. Finally, many users are becoming so disgusted with unwanted
junk-mail messages that they are reducing their use of email.
Worse, these dangerous trends are emerging just as more businesses
than ever are incorporating email into their business processes.
To preserve the integrity of this invaluable communication tool, for
corporations and consumers, for business and personal use, we must establish
a system to make email reliable again. The good news: It can be done.
This paper will examine the major problems threatening email today,
the current approaches to address these problems, and discuss ‘best
practices’ that volume email senders must adopt to ensure the
delivery of their messages and to maintain their good standing with
customers, vendors and partners.
Dendritic NanoTechnologies, Inc.:
The Answer to the Physical Limitations of Nanotechnology
ROBERT BERRY, PH.D.*
ABSTRACT
Nanotechnology is one of those rare advancements whose impact it is
impossible to overestimate.
This emerging technology has the potential to change how we work
and play, the ways we fight disease, even our life expectancies. Nanotechnology’s
move into practical use, however, has been slow because the very nanostructures
that hold such promise are neither precise nor physically predictable
enough for low-cost mass production. In this article, Dr. Robert Berry
discusses a solution–dendritic polymers, or “dendrimers”–nanostructures
with the precision and predictable physical properties necessary for
commercialization. Dr. Berry also discusses the leading developer of
dendrimers, Dendritic NanoTechnologies, Inc. (DNT), which has the intellectual
property and strategic relationships to bring nanotech to the applications
sure to change our world.
INTRODUCTION
Imagine a world where nanoscopic probes travel constantly through our
bodies, monitoring our health at all times and alerting us at the first
sign of danger. Imagine a world where disease is cured safely and painlessly,
where invasive surgeries and painful treatments are replaced with nanoparticles
sent into our bodies to find diseased cells and destroy them. Of all
the areas of our lives in which nanotechnology will soon make an impact,
perhaps the most exciting is in the field of medicine–because
in this area, nanotechnology will literally be the difference between
life and death.
Among nanotechnology’s most highly anticipated–and lucrative–applications
are disease diagnostics and drug delivery. Engineered nanostructures,
however, lack the precision and reproducibility for the vital yet highly
delicate art of probing the body to search for disease and unleashing
the precise dosage of the required drugs to fight it. The most promising
development to overcome this obstacle is a new class of nanostructure
called the dendritic polymer, or “dendrimer.” With their
low-cost, scalable and precision architecture, dendrimers are the ideal
agents for targeting disease and delivering the drugs to wipe them out.
I. DENDRIMERS
Dendrimers are nanoparticles that can be precisely designed and manufactured
for a wide variety of applications. They are formed by the addition
of shells of branched molecules to a central core.
Figure 1: Poly(amidoamine) Dendrimer Structure
Sample dendrimer with a core of 12-diaminododecane, a Poly(amidoamine)
or PAMAM branch and an Amidoethanol surface.
Adjusting the chemical properties of their core, shells,
and surface layer can tailor dendrimers to fit the needs of specific
applications. Because of their precise architecture and construction,
dendrimers possess inherently valuable physical, chemical and biological
properties, uniquely suited to drug diagnostics and drug delivery. These
properties include:
• Efficient membrane transport
Dendrimers have demonstrated rapid transport capabilities across biological
membranes.
• Precise architecture, size and shape control
Dendrimers branch out in a highly predictable fashion to form amplified
three-dimensional structures with highly ordered architectures.
• High loading capacity
Dendrimer structures can be used to carry and store a wide range of
metals, organic or inorganic molecules by encapsulation and absorption.
• High uniformity and purity
The synthetic process used produces dendrimers with uniform sizes, precisely
defined surface functionality, and very low impurity levels.
• Low toxicity
Most dendrimer systems display very low cytotoxicity levels.
• Low immunogenicity
Dendrimers commonly manifest a very low or negligible immunogenic response
when injected or used topically.
Figure 2: Targeted drug delivery
The high level of control over the dendrimer architecture makes
this class of polymers ideal carriers for the active pharmaceutical
ingredients in areas such as drug delivery, diagnostic/imaging and gene
transfection.
Figure 3: MRI Reagents
Dendrimers have demonstrated excellent potential as metal chelates
for MRI. Analysis of dendrimer-chelate structure on retention and distribution
has led to the discovery of the unique ability to control pharmacokinetic
behavior by tuning dendrimer size and surface functionality.
Figure 4: Transfection Agents
Poly(amidoamine) (PAMAM) dendrimers, which have been used to deliver
nucleic acids have characteristic novelties associated with a superior,
next-generation transfection agent–characteristics such as an
amenability to nucleic acid complexation, chemical modification and
targeting, transfection enhancing, and/or fluorescent molecule conjugation.
Dendrimers provide the necessary interface between chemistry
and biology, possessing the unique traits to act as safe and effective
drug-delivery vehicles as well as highly sophisticated diagnostic imaging
agents. In the biotechnology and drug fields, these highly adaptable
structures have finally taken nanotechnology from the theoretical into
the practical. In fact, dendrimers have already been commercialized
in products designed for HIV prevention, anthrax detection, cardiac-marker
diagnostics and gene transfection.
II. COMPANY BACKGROUND
Dendrimers were actually discovered by Dendritic NanoTechnologies,
Inc. (DNT) founder Donald A. Tomalia, Ph.D. In 1979, Dr. Tomalia, then
a senior scientist with The Dow Chemical Company, discovered the fourth
major class of macromolecular architecture, dendritic polymers. Because
of their unique physical properties, these new nanostructures–which
Dr. Tomalia would later coin “dendrimers”–heralded
great promise for a wide range of real-world applications, most notably
in biotechnology and pharmaceuticals. As a result of Dr. Tomalia’s
work, Dow Chemical was awarded the world’s first dendrimer patents.
Two decades later, Dr. Tomalia, serving as co-director of the National
Center for Dendrimer-Based Nanotechnology at Central Michigan University,
launched DNT in the Applied Research and Technology Center on the CMU
campus.
Incorporated in 2003, DNT has quickly established itself as the world’s
leading developer and provider of dendrimer-based technologies:
• DNT holds the most extensive portfolio of dendrimer-based intellectual
property in the world, with over 200 patents in 41 patent families.
• The company has secured more than $9 million in investment
capital.
• DNT has established key relationships with Dow Chemical, Australia-based
Starpharma Holdings and other firms that provide the company a broad
range of licensing opportunities and other revenue sources.
• The company has been awarded over $3.5 million in research
contracts from the U.S. Department of Defense, the National Institutes
of Health, Pfizer and others.
• DNT is selling and licensing its more than 200 dendrimer products,
has several revenue-generating licensing agreements in place, and has
achieved positive cash flow.
III. MARKET OPPORTUNITY
Nano-enabled polymeric delivery systems represent the biggest opportunity
for nanotechnology companies, according to market-research firm NanoMarkets.1
The company’s recently released report, “Nano Drug Delivery,”
notes that nanotechnology-enabled drug-delivery systems will generate
over $1.7 billion in 2009 and $4.8 billion in 2012. Additionally, NanoMarkets
finds imaging agents and nano-enabled cancer drugs will become the most
lucrative applications in the nanotechnology field.
IV. BUSINESS STRATEGY
The NanoMarkets recent findings, corroborated by countless other market-research
studies of most promising applications for dendrimer-based nanotechnology,
speak directly to the value of DNT’s uniquely comprehensive portfolio
of intellectual property and the soundness of the company’s business
strategy. DNT’s initial market focus is on providing dendrimer
technology for imaging diagnostics and drug delivery–likely the
two most lucrative opportunities in the field. DNT’s two-phase
business strategy enables the company to take the lead in delivering
these new solutions.
Phase I: Transfection Reagents
DNT’s Phase I business objective is to capture early licensing
opportunities in (1) imaging contrast agents for new diagnostic solutions
for enhancing the findings of MRIs, (2)transfection reagents for RNA-i
delivery with improved gene silencing with less toxicity, and (3) encapsulation
and release of platinate based anti-cancer drugs to reduce the toxicity
and side effects of their use. DNT has existing IP that will be leveraged
and licensed in all three areas.
For example, one of the greatest challenges for the use of RNA-i based
medicine and conventional therapeutics is finding the appropriate delivery
vehicle to transport active pharmaceutical ingredients into the desired
area Using the knowledge of genomics and proteomics, researchers are
now on the edge of identifying where, when and how diseases are triggered
at the molecular level. RNA interference technology offers an extremely
efficient tool for identifying and confirming drug targets and for understanding
how cells respond when selected genes are shut off. DNT’s initial
research has indicated that dendritic structures are the ideal delivery
vehicle for RNA-i based drug delivery technologies.
As these and other new scientific breakthroughs occur, DNT’s
dendritic technology will be the key to solving the targeting or delivery
components required to bring these technologies to the market.
For an idea of the size of the market opportunity for this initial
phase, consider that 40 million MRI imaging procedures were conducted
in 2003, with 120 million using contrast agents. Consider also that
MRI agents in the U.S. alone generate $365 million in revenue each year.
Phase II: Technology to extend IP and accelerate commercialization
PAMAM and PPI dendrimers, the original gold standards of dendrimer
architectures, have been incorporated in thousands of studies by third
parties that illustrate the application potential of dendrimers. The
cost of synthesizing these precise structures, however, has limited
their use in commercial applications.
New technology pioneered by DNT will reduce the cost of synthesis by
orders of magnitude and address key limitations of the current PAMAM
manufacturing process. DNT has developed a new low cost, scalable class
of dendrimer structures and has established an aggressive research agenda
that is addressing the synthesis, scalability, and rapid manufacturing
of the new dendrimers. The new class of dendrimer structures will set
an industry benchmark for precision scalable architecture and will position
DNT in the enviable position of controlling a technology that has application
in multiple billion dollar markets in multiple industries.
V. CONCLUSION
The medical community is increasingly demanding nanotechnology solutions
to improve the detection, treatment and prevention of disease. Dendrimers
have emerged as the ideal nanostructures to serve these demands–and
are, in fact, expected to become a multibillion-dollar industry in their
own right within just the next few years.
At the forefront of this new technology is DNT. The company enjoys
an unrivaled intellectual-property portfolio, a strong customer base,
a broad range of key partnerships and positive cash-flow. The discoverer
of dendrimers himself serves as the company’s president and chief
technology officer. With a significant competitive advantage as the
world’s leading developer and provider of dendritic polymers,
DNT is poised to continue to drive this industry-changing technology.
