NanoGagliato 2011
Nanotech Solutions
to Translational Challenges
- SCIENTIFIC REPORT The 2011 invitational NanoGagliato conference was held in Gagliato and Guardavalle,
Italy from July 23rd to 27th. This year's theme was Nanotech Solutions to Translational
Challenges, a challenge to define the most pressings issues in healthcare and research
commercialization, propose innovative nanotechnology solutions to address the issues,
and design implementation strategies that will expedite improvements in current clinical
technologies.
The format of the sessions fostered collaborative brainstorming by clinicians, research
scientists, and entrepreneurs. Fast paced challenge sessions began with the introduction
and analysis of the session topic by the moderator, continued with presentation of
additional perspectives and proposed solutions by the respondents, and concluded with
open discussions by the panel participants.
Scientific program:
Session I: Musculoskeletal Disorders: Early Detection, Early Intervention, Tissue Engineering, and Hints for All of Medicine
Session II: Targeted/Directed/Tropic Therapy: Needs, Realities, & Myths
Session III: Surgical and Non-Surgical Surgery
Session IV: The Key to Therapy: Crossing Biological Barrier
Session V: Transplantation and Regeneration
Session VI: Opportunities and Challenges in Bed-to-Bedside NanoMed.... The Commercialization Imperative
Attendees:
Barbara L. Bass, M.D., USA ● Elvin Blanco, Ph.D, USA ● Steve Conlan, Ph.D, UK ● Mauro Ferrari, Ph.D., USA ● R.
Mark Ghobrial, M.D., USA ● Douglass Given, M.D., Ph.D., M.B.A., USA ● Rebecca Hall, Ph.D., USA ● Tim Harris,
M.B.A., USA ● Andreas Jordan, Ph.D., Germany ● Ali Khademhosseini, Ph.D., USA ● King C. Li, M.D., M.B.A., USA
● Lorenzo Pradella, Ph.D., Italy ● Jason Sakamoto, Ph.D., USA ● Rita Serda, Ph.D., USA ● Haifa Shen M.D., Ph.D.,
USA ● Tong Sun, M.S., M.B.A., USA ● Ennio Tasciotti, Ph.D., USA ● Bradley K. Weiner, M.D., USA
Organization: Accademia di Gagliato delle Nanoscienze (Academy of Gagliato of Nanosciences), Italy
Rapporteurs : Rebecca Hall, Elvin Blanco, Aleksandra Bogdanovic-Guillon
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1 Detailed list of participants:
Barbara L. Bass, M.D., Chair of Surgery, Director, Methodist Institute for Technology, Innovation and Education
(MITIE), The Methodist Hospital Research Institute, Houston, TX, USA
Elvin Blanco, Ph.D, Postdoctoral Fellow, The Department of Nanomedicine, The Methodist Hospital Research
Institute, Houston, TX, USA
Steve Conlan, Ph.D, Director, Centre for NanoHealth, Institute of Life Science College of Medicine, Swansea
University, Wales, UK
Mauro Ferrari, Ph.D., President and CEO, Chair, The Methodist Hospital Research Institute, President The Alliance
for NanoHealth, Houston, TX, USA
R. Mark Ghobrial, M.D., Ph.D., F.A.C.S., F.R.C.S. (Ed.), The Methodist Hospital Research Institute, Director, Center
for Liver Disease & Transplantation, Chief, Liver Transplantation Surgery, Director, Immunobiology Research Center,
The Methodist Hospital, Houston, TX, USA
Douglass Given, M.D., Ph.D., M.B.A., Partner Bay City Capital, San Francisco, CA, USA
Rebecca Hall, Ph.D., Scientific Communications, The Methodist Hospital Research Institute, Houston, TX, USA
Tim Harris, M.B.A., Entrepreneur & Consultant, Houston, TX, USA
Andreas Jordan, Ph.D., CEO, MagForce Nanotechnologies, AG Berlin, Germany
Ali Khademhosseini, Ph.D., Associate Professor, Harvard-MIT Division of Health Sciences and Technology, Wyss
Institute for Biologically Inspired Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard
Medical School, Cambridge, MA, USA
King C. Li, M.D., M.B.A., Senior Member, Director, Department of Translational Imaging, The Methodist Hospital
Research Institute, Chair, Department of Radiology The Methodist Hospital, Director, Molecular Imaging Program,
Professor of Radiology, Weill Medical College of Cornell University, Houston, TX, USA
Lorenzo Pradella, Ph.D., Director, Zcube, Milan, Italy
Jason Sakamoto, Ph.D., Assistant Member, The Methodist Hospital Research Institute, Interim Co-Chair, The
Department of Nanomedicine, Center Manager, Center for Transport Oncophysics, NCI Physical Science and
Oncology Center, Center Manager, Texas Center for Cancer Nanomedicine, NCI Center of Cancer Nanotechnology
Excellence, Chief Operating Officer, Alliance for NanoHealth, Houston, TX, USA
Rita Serda, Ph.D., Assistant Member, The Methodist Hospital Research Institute, Interim Co-Chair, The Department
of Nanomedicine, Director, Scanning Electron Microscopy Core, Faculty Director, The Methodist Hospital Research
Institute Academy for Medical Science and Technology, Houston, TX, USA
Haifa Shen M.D., Ph.D., Assistant Member, The Methodist Hospital Research Institute, Houston, TX, USA
Tong Sun, M.S., M.B.A., Director of Central Operations, The Methodist Hospital Research Institute, Houston, TX,
USA
Ennio Tasciotti, Ph.D., The Methodist Hospital Research Institute, Interim Co-Chair, Regenerative Medicine, The
Department of Nanomedicine, Director, Spine Advanced Technology Lab, Houston, TX, USA
Bradley K. Weiner, M.D., Associate Member, The Methodist Hospital Research Institute, Chief of Spinal Surgery,
Medical Director, Orthopedic/Spine Nanotechnology Laboratory, The Methodist Hospital, Professor and Vice
Chairman of Orthopaedics, Weill Cornell Medical College of Cornell University, Houston, TX, USA
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2 Challenge Session I:
Musculoskeletal Disorders: Early Detection, Early Intervention, Tissue Engineering, and Hints for All of
Medicine
Moderator: Brad Weiner
First Respondent: Ali Khademhosseini
Second Respondent: Ennio Tasciotti
This session began with an analysis of the current challenges in orthopedic medicine and research. There is limited
funding for this research, despite the fact that musculoskeletal morbidity is 50 times higher than funding for cancer
and heart disease. In addition to accidental injury, musculoskeletal injuries result from common conditions including
osteoarthritis, osteoporosis, and degeneration of the spine. The traditional approach to treating musculoskeletal
disorders is to assess, diagnose, treat, and evaluate patient outcome. However, the diagnostic process is ‘crude’,
because it relies on tools like x-ray, MRI, and CT, which can assess the mechanical defects and pathology, but not
the pathophysiology. The available treatments are also ‘crude’ and the outcomes are less than ideal. Patients
recover movement, but not to pre-injury or pre-disease levels. Physicians are looking to nanotechnology for solutions
that allow them to diagnose and treat patients before the damage/degeneration is so extensive that it requires
surgical replacements with bone and metal. It was noted that the pathophysiology of spinal degeneration is unique
from other causes of musculoskeletal disorders, making early diagnosis especially relevant for this clinical area.
Some of the proposed areas of nanotechnology developments for these applications include:
• Microenvironmental control- introducing stem cells into the body in the correct spatial relationship to regenerate
tissue architecture and intercellular interactions in the area of injury
• Microfabrication of vasculature- creating artificial vessels such as capillaries to encourage revascularization, or
using nanovectors to deliver angiogenic factors
• Material development- developing materials like carbon nanotubes that can be used to increase the mechanical
strength, host tolerance, and other properties of prostheses and implants.
• Biomarker detection-minimally invasive, inexpensive methods to detect minute early diagnostic markers in the
peripheral blood, such as rare peptide and microsomal markers
The field of orthopedic medicine is turning to ‘theranostics’ to support early intervention strategies. Theranostics
refers to diagnostic tests that predict patient responses to therapeutic regimens based on analysis of patient
information with informatics systems. These systems use biochemical, spatial, and temporal information to diagnose
a disease and give a comprehensive and personalized assessment of how a therapeutic regimen with affect disease
progression in an individual patient. A major limitation to the development of theranostics is the lack of information
about the biological mechanisms which underly the development of the disease. By identifying the major driving
factor of the pathophysiology, the clinician gains information about how fast the disease will progress that helps
predict patient outcome. Examples of markers suited to theranostics are cytokines, which are present at varying
levels in the peripheral blood and at areas of injury like degenerating discs.
The discussion turned to funding sources for musculoskelatal disorder research and development. It was noted that
this decision is strongly influenced by the perspectives of market analysts, and whether they considered the market
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3 based on the number of patients with a particular injury or clustered all injuries that would benefit from a particular
technology. The factors that market analysts consider when determining whether to invest in the development of
these technologies include: time to market, market size, cost of treatment, market need, and source of payment for
the treatment (patient, or public or private insurance programs). The source of payments for healthcare was
discussed in detail because it is a major factor that defines the market. For example, in the UK, a maximum of 40 k₤
was recently set per year of life gained by treatment. Factors like this significantly alter and complicate the markets,
making them dependent on cultural, political, and socioeconomic fluctuations. However, it was noted that as the
mean age of the world population continues to increase, so will the potential increase in lifespan and quality of life
from treatments for musculoskeletal disorders, thereby further strengthening the demand for research and
development of new treatments for musculoskeletal disorders.
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Challenge Session II:
Targeted/Directed/Tropic Therapy: Needs, Realities, & Myths
Moderator: Doug Given
First Respondent: Lorenzo Pradella
Second Respondent: Mauro Ferrari
Tropic therapy refers to the delivery of the right molecule to the right site at the right time. A major R&D focus right
now is nanotechnology developments for the tropic delivery of siRNA, but it suffers from a lack of financial
investments in this area. Early on, this research had two major unknowns: the mechanism of action of siRNA at the
time was not known, and the choice/dosage/design of the siRNA delivery system was not known. Without the
mechanism of action, it was difficult to make informed hypotheses about how potential delivery systems would work.
This created issues with the delivery systems interfering with the mechanisms of siRNA action, which led companies
and/or investors to decide that the research was too risky for investment. Combined, the two unknowns created a
daunting challenge for development and regulatory approval. The decision that the risk was too high for investment
in this area, was based in part on of the requirement for a 5-7 year turnaround on investments by venture capitalists.
However, early translational research takes longer than this, leaving a hole in the commercialization pipeline for
translational technologies.
Panelists discussed the urgent need for new financial instruments or diversified funding strategies that address this
need. They also discussed the need to change the culture of investment in tropic therapies, beginning with a
continuation of the discussion of market analysis as a driving force. Analysis of short term gain requires how quickly
a company can sell a product, recover their investment, and produce a profit by satisfying an unmet need. Analysis
of long term gain takes into account the total profit that would be gained from an ‘improvement’ technology that
changes the standard of care, thus realizing majority market share.
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4 Panelists explored this issues further by outlining the traditional Pharma approach to commercialization of late stage
drugs, that focuses mostly on identifying ‘blockbuster’ deliverables and ‘low hanging fruit’ that can be most rapidly
profitable. In order to change this culture, especially in the current economic environment, companies must accept a
low profit margin. However, this does not necessarily mean that the company must accept a smaller net profit, if the
companies can selectively invest in technologies that will change the standard of care. To move outside the Pharma
comfort zone of ‘rapid profit from deliverables’, the investment culture must be changed to embrace the market
potential of diagnostics that support early intervention strategies. This holistic approach to healthcare and
commercialization can result in lower cost of treatment, higher benefit to patients, and higher profits for investors.
The conversation moved on to types of nanotechnologies that are in development to address the need for tropic
delivery. Technologies can be broken down into three types: self-driven by inherent properties, targeted delivery by
engineered properties, and local delivery. Local delivery was characterized as a first line approach, while systemic
delivery is the hallmark of successful approved applications. Developing molecular targeting is necessary for the
new era of personalizing delivery. The optimal approach will also be determined by the pathophysiology of the
disease and the biological barriers that must be crossed to reach the disease sites. Albumin chaperoned
nanoparticles (Abraxane®) were discussed as an example of a successful self driven delivery strategy to cross the
vascular endothelium. Multistage delivery systems were discussed as an approach to therapies that require more
than one type of delivery mechanism, for example, across the vascular endothelium and targeting to a disease site
within tissue.
Speakers noted that private companies repeatedly mention that the lack of molecular knowledge is a major limitation
for targeting, but don’t want to invest in this research, so they compensate with brute force approaches based on
engineering the physical and chemical properties of nanoparticles.
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Challenge Session III:
Surgical and Non-Surgical Surgery
Moderator: Barbara Bass
First Respondent: Andreas Jordan
Second Respondent: Jason Sakamoto
Despite the enormous progress in surgical techniques, surgeons still treat disease by taking more tissue than they
need, balancing the chance of removing all diseased tissue with taking too much normal tissue. However, if
resection margins are set too wide, the surgery can do more harm than good. The critical needs in tumor resection
surgery are more accurate assessment of tumor margins with imaging modalities, better tools to determine the extent
of disease (i.e. nodal and metastatic spread), and improvement of the regenerative wound healing process.
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5 Non-surgical surgery for cancer therapy was discussed, with the specific example of targeted NanoTherm® Therapy
from MagForce for the treatment of glioblastoma multiforme (GBM). This technology is the first nanotechnology
medical product to receive the European CM mark, after 25 years of intensive research. In clinical trials of this
technology, 15 nm iron oxide nanoparticles coated with aminosilane were directly injected into brain tumors
(glioblastoma multiforme). Alternating magnetic fields were used to force the particles into cells, where they were
found to rapidly aggregate and define a stable treatment zone. The magnetic fields cause oscillation of the
aggregated particles, heating the tumor cells to 40-80 C, which destroys the tumor tissue in the area. Interestingly,
the glioblastoma tumors had a natural outer barrier, which combined with the stable treatment zone created by
particle aggregation, protected the surrounding healthy tissue from damage. The persistence of the nanoparticles in
the treatment zone allowed for up to six rounds of treatment without repeating the injection. It was noted that patients
are not eligible for this therapy if they have metal implants (such as dental implants) within 40 cm of the treatment
site. Also, MRI can no longer be used to screen for recurrence after therapy and must be replaced with PET.
NanoTherm® therapy extended the life expectancy and doubled the mean survival time of the glioblastoma patients.
An additional benefit of this approach is that this targeted thermoablation is more accurate in targeting the therapy
within the tumor margins, thereby reducing damage to healthy tissue, and from the inflammatory encapsulation
during the wound healing response. MagForce is now pursuing second generation conjugated nanoparticles with
enhanced anti-tumor properties. Conjugations in development include isotopes/radiopharamceuticals, antibodies,
and temperature sensitive release moieties.
The future challenges for nanotechnology in the area of nonsurgical-surgery is targeting to metastases and
accurately defining margins at the microscopic scale. The general consensus was that nanotechnology is in
development, but is not yet available to address these challenges. Several developing technologies were discussed
including the use of fiber optic needles to define tumor margins, self-tying sutures, and gel materials for
encapsulating tumors.
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Challenge Session IV:
The Key to Therapy: Crossing Biological Barriers
Moderator: King Li
First Respondent: Rita Serda
Second Respondent: Steve Conlan
This session addressed the impact that nanotechnology has had on drug delivery, and the current challenges in
crossing biological barriers. Speakers highlighted several examples of clinically-approved nanoplatforms.
Nanoparticle-based drug delivery platforms such as liposomal doxorubicin (DOXIL®) and albumin-bound paclitaxel
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6 (Abraxane®) are now commonplace in prescribed chemotherapeutic regimens, having shown distinct advantages
over their free-drug counterparts. While these technologies use the advantages of nanoscale delivery systems to
enhance blood residence times and tumor accumulation, biological barriers still hinder efficacious drug delivery.
Examples of biological barriers include the blood brain barrier, tissue fibrosis, tumor capsularization, fluid pressure
differentials, the reticuloendothelial system (RES), enzymatic degradation, and biological membranes. The
development of nanoscale shuttling vectors that can transverse these barriers in a controlled manner is a huge
opportunity for nanomedicine to improve the efficacy of therapy or to limit negative side effects.
One of the most pronounced and insurmountable biological barriers to drug delivery is the blood brain barrier (BBB).
The BBB is such an obstacle to drug delivery for the treatment of conditions ranging from Alzheimer’s disease to
glioblastoma multiforme (GBM), that local delivery by direct injection to the brain is currently the only viable delivery
option for many treatments in development for these conditions. Direct olfactory access to the brain was discussed
as a possible alternative port of entry into the brain. The importance of considering the tumor microenvironment
when designing delivery technologies was also highlighted. It is possible to target brain tumors using fenestrations of
newly formed vessels as entry points. Regarding direct local delivery, panelists discussed the work of Robert Langer
and coworkers on drug-eluting polymer wafers (Gliadel®) that were implanted following surgical excision of GBM.
Targeted nanoparticle-based thermal ablation (NanoTherm®) also requires direct injection of magnetic nanoparticles
to destroy GBM tumors – an inside-out approach to therapy. Remote-controlled delivery by laser activated release of
gold nanoparticles from endosomal delivery systems was also addressed. Despite these and other advances,
getting drugs past barriers such as the BBB remains a major problem in nanobased drug delivery.
Tumor fibrosis, capsule formation, reduced vascularization, and fluid pressure differentials are common barriers that
reduce the efficacy of cancer treatments. Pancreatic cancer is particularly resistant to drug permeability because the
tumors are highly fibrotic and poorly vascularized. They are also surrounded by a thickened extracellular matrix
coating that acts as a barrier. They are therefore difficult to treat with stand-alone chemotherapy, resulting in poor
prognosis for patients. If biological barriers like this can be transversed, and sequestration of particles avoided,
patient prognosis following chemotherapy can be vastly improved. Alternative approaches to transversing barriers
were discussed including exploitation of physical force (mechanical, magnetic, ultrasound), chemical properties (pH,
redox reactions, enzymatic activity), and active transport mechanisms.
Protein opsonization and subsequent particle clearance by the RES is also a major barrier to delivery. Panelists
postulated patient specific approaches may be necessary to avoid this clearance mechanism. For example,
sampling the protein repertoire from the patient and using this to coat nanoparticles with native moieties may render
the particle unrecognizable as ‘non-self’. This point introduced the concept of ‘look-alike’ humanization of
nanoparticles for drug delivery. Leukocytes were discussed as possible shuttles to increase nanoparticle dispersion,
extravasation, and targeting because they are specifically designed to navigate the blood stream for prolonged
periods of time and home-in on disease sites. The challenge for the future of drug delivery is how to incorporate
biological components like these in the design of nanoparticles for systemic drug delivery.
Panelists discussed the nanoparticle design principle KISS in drug delivery technology, an acronym for “Keep It
Simple and Stupid.” This refers to taking a conservative and step-wise approach to modifying delivery systems for
targeting to disease sites. The theory is based on experimental evidence that repeatedly demonstrates that
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7 modifications to nanoparticles enhance aggregation, sequestration, and clearance from the peripheral blood and
tissue. Properties that influence clearance rates and targeting include size, surface charge, and shape. Even simple
modifications of these properties can dramatically alter the in vivo fate of injectables. Thus, in order to cross the
numerous biological barriers to drug delivery, one may have to find unique and innovative particle enhancements that
result in increased pathology targeting and site-specific accumulation, but which avoid clearance mechanisms.
Discussions concerning physical barriers as ways of keeping drugs out led way to discussions of creating and
manipulating nanomaterial barriers or other nanotechnology based strategies to keep drugs in the tumor or target
zone, thereby maximizing drug delivery through a sustained release of drug over time. An idea was presented that
involved the use of stabilized peri-tumor biological barriers or material coatings as a means to physically constrain
therapies, tumor growth, and access to nutrients. Strategies like this that are aimed at creating physical barriers to
provide confinement would potentially cut off nutrients to the tumor, while also preventing the tumor from
metastasizing, which is the primary reason for cancer patient morbidity and mortality.
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Challenge Session V:
Transplantation and Regeneration
Moderator: Mark Ghobrial
First Respondent: Ennio Tasciotti
Second Respondent: Elvin Blanco
This discussion centered on organ regeneration, which is often considered highly revolutionary and theoretical, yet
was inspired by ground-breaking transplant biology work conducted in the 1960’s and 1980’s. Organ transplantation
is now commonplace, with heart and kidney transplants now standard practice. The next frontier in transplantation is
the prevention of organ transplant failure due to rejection of the organ by its new host, by improving existing
immunsuppressive/tolerance strategies and developing more tailored and personalized tolerance mechanisms. This
is the area where several nanotechnology strategies can make the greatest impact in the field of transplant biology.
The importance of immunology in this area was emphasized, in particular the role of the three most important cells
that mediate organ acceptance or failure: T-cells, B-cells, and hematopoetic stem cells. When the delicate interplay
between the immune system and the new organ is better understood, then one can begin to engineer nanodevices
that deliver immunosuppressants and other agents in a site-specific, personalized, and sustained fashion. These
nanoplatforms would facilitate the establishment of the immune tolerance that is required for successful organ
transplantation.
The panel discussed tissue/organ genesis and regeneration, highlighting the current push in research involving
generation of organs like the heart and lungs. Current research suggests that organ and tissue regeneration may
one day become a widely applicable and accepted reality in medicine (beyond what is currently possible with tissues
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8 like bone marrow, skin, and liver). The field of tissue engineering has progressed to a point where technologies now
exist to create scaffolds and support structures for artificial organ growth using starter cells and tissues. However,
while the ex vivo growth of less complex 3D organs like skin grafts for burn patients is commonplace, the production
of more complex organs like the heart and lungs is not yet a reality. Visions for expanded stem cell and organ ‘starter
tissue explant’ banks were discussed. These banks would provide the starting material that tissue engineers would
use to create customized transplant organs. Tissue engineers are also working on bone regeneration in hopes of
creating new bone in situ. The critical role of developmental biology in this field was noted, as an understanding of
organogenesis during stem cell differentiation and embryonic development may be modelled by nanotechnology to
produce artificial organs.
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Challenge Session VI:
Opportunities and Challenges in Bed-to-Bedside NanoMed.... The Commercialization Imperative
Moderator: Tim Harris
First Respondent: Rebecca Hall
Second Respondent: Tong Sun
This session focused on the challenge of commercializing research innovations so that we can achieve our
translational objectives of making real changes in the clinical care of patients. A major barrier to translation is the
lack of funding for the early high-risk steps in the R&D pipeline, referred to as the ‘black hole’. This area used to be
funded mostly by venture capitalists, with low level investment by Pharma and IPO’s. The recent economic slowdown has created a more conservative investment culture, and as a result, this area now relies on funds from
government grants, philanthropic investors, and early seed funding mechanisms.
The conservative investment culture comes from several core principles that Pharma relies on to assess risk.
Pharma considers proof of concept to ne the completion of Phase II clinical trials, whereas research labs consider it
fulfilled by successful preclinical trials. Thus, there is a gap of funding for the Phase I and II trials. This ‘black hole’ is
considered too risky based on SWOT analysis (assessment of strengths, weaknesses, opportunities, and threats)
because of the nature of the research (variables associated with moving from animal to humans), issues with
securing legal rights to the intellectual property in the various markets, and the difficulty of assuring proper trial
design to expedite and ensure regulatory approval.
Examples of challenges that researchers without business and commercialization experience face in bridging the gap
to translation via commercialization were discussed in regards to three areas: securing legal rights, market analysis,
and building relationships with industry partners. The ‘commercialization imperative’ refers to the absolute necessity
of integrating the commercialization process into our concept of translational research as a foundation principle.
Researchers must be educated on the steps of the commercialization process, and advised on how to design their
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9 projects with this process in mind, beginning from the moment of conceptualization and integrated with their
development of applications for funding of early stage bench research. This will form a stronger basis for
relationships with industry when the research progresses to preclinical and early phase clinical trials.
Policy makers at research institutions and in funding agencies should be taking this ‘commercialization imperative’
approach when developing their platforms and goals. Translational RFAs should require sections on future plans for
translation of the research, as they often do, including a clearly defined plan for the next step in the
commercialization process. Institutions may be able foster support for this by requiring these plans/justifications that
can be aided by commercialization offices, before submitting applications on behalf of investigators. Industry
partners are key resources for requirements and guidelines that would aid researchers in the project design with a
commercial/ translational objective in mind.
The diversity of the panelist comments clearly illustrated the disconnect that exists between the different perspectives
of researchers, tech transfer/commercialization specialists, and industry partners on what technologies have
sufficient value for investment in legal protection and commercial development. The gap is caused not only by
researchers not understanding the requirements for legal protection of intellectual property, regulatory approval
processes, and market analysis, but also by business professionals not understanding the scope of the utility of the
invention, not being able to conceptualize the potential applications for clinical use, or not accurately assessing the
potential an invention has for changing standards of care and thereby realizing significant profit.
The panelists called attention to the importance of communication between in house technology
assessment/commercialization professionals and researchers, so that both can make for informed decisions and
streamline translation of innovations. This concept was illustrated by a discussion of the experiences of basic
science researchers on the panel with tech transfer offices. The market would be defined by the researcher as the
number of people that are afflicted with the disease(s) in the world that would potentially benefit from their research.
Industry and tech transfer specialists are more pragmatic, understanding that availability and access are two
completely different things, and access is the bottleneck that defines the market and profit. Access depends on
factors that affect regulatory approval, manufacture, delivery, cost, and sociopolitical considerations. A firm
understanding of this distinction, and the skills to do more meaningful market analysis, would be very helpful to
researchers in both the early stages of translational research project conceptualization/planning and in the later
stages of building relationships with industry partners.
Most researchers understand the need for documentation of all experiments, but would benefit from guidance on
experimental design considerations that take into account the need to secure their intellectual property rights as well.
In order to receive a patent, the data must support the claim that their invention is novel, nonobvious, and useful.
Utility for an intended clinical use is usually the sticking point, though the legal definitions of novelty and obviousness
are also challenges for researchers. This creates a communication gap between technology transfer administrators
and researchers that can hinder the information flow and decisions about which inventions are worthy of investment
in legal protection and support for commercialization.
As evidenced by anecdotal experiences from panelists seeking venture capital and industry investment in their
projects, researchers are also often not equipped with the skills to set up their teams to transition from bench and
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10 preclinical research, to the early phase I and phase II trials. Is this necessary? The discussion appeared to support
the conclusion that it is necessary for translational research because of the ‘commercialization imperative’. This
transition stage is no longer supported by industry, which means it must be done elsewhere- most logically in the
types of translation focused research centers associated with hospitals and specialized in clinical research.
Therefore it is absolutely necessary for there to be a new mechanism for basic research labs to make this transition
to early preclinical research/Phase I clinical labs/collaborations as their research reaches this stage. This transition
will require strong guidance from business professionals to streamline the research in accordance with clear industry
requirements/regulatory pathways to maximize the efficient use of limited funding resources during early R&D
phases. In this way, the project can cross the ‘black hole’ in the R&D pipeline and move to late phase II and phase III
with industry partners or start-ups.
This transition stage will also require development of a culture and environment within and/or closely associated with
non-profit research centers. Panelists discussed different incubator models to foster commercialization. For
example, the Swansea University Institute of Life Science (ILS) was mentioned as an example of a successful
business incubator. It was initiated with $150 million in funding from the European Union Convergence Funding
Programme. The building was constructed with public and private funds from a partnership between Swansea
University, the Welsh government, the UH National Health Services, IBM, and other private business partners. The
high tech infrastructure provided by industry partners that include UBM and Siemens Healthcare, and the innovative
private/public funding mechanisms for start-ups, has made the ILS a magnet for spin-offs and start-ups throughout
Wales. Businesses are being incubated for drug discovery, medical devices, and regenerative medicine for heart
failure, cancer, arthritis, and home healthcare.
The ILS has also been successful in developing an area with a small concentration of life science and healthcare
start-ups. This observation led to a discussion about ‘The Silicon Valley model’ and the reasons why it has not been
replicated in the biomedical sector. The case of Houston was considered, where efforts to develop a local
commercial pharma and biomedical device sector are a major focus. The Texas Medical Center provides a highly
experienced and educated workforce and cutting edge innovations in healthcare, and has been supported by
business acceleration/incubator organizations like BioHouston and the Houston Technology Center (HTC) for more
than a decade. Throughout the national economic slow-down, Houston has maintained a stable economy. The HTC
recently announced plans for $100 million in venture capital funding support of early stage technologies in sectors
including life sciences and nanotechnology in the Houston area. Houston also has access to funding from the
Cancer Research Institute of Texas and the Texas Emerging Technology Fund, which support commercialization in
this sector. Despite these resources, the sector has not developed as rapidly as expected in such fertile ground. The
panel hypothesized that the critical nutrient that may be lacking is the culture of entrepreneurship in the workforce
and medical/research institutions in the area. The success of the Silicon Valley model was attributed to cultural
factors such as a pro-networking, collaborative, and entrepreneurial spirit, and the early introduction of
scientists/engineers to business practices and principles with programs like dual academic degree programs. The
concentration of business and research experiences that co-exist in such places creates a very special
entrepreneurship spirit that fosters translational projects and innovations with commercial potential.
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