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5.2.1 The Role oftheTechnology Transfer Office (TTO)
In the broadest sense, technology transfer in the academic context is the process of
transferring knowledge, discoveries, technologies, inventions, and authored works
to others, generally for the purpose of enabling further research and development of
new commercial products and services. This is accomplished by various means,
including publication of research results, presentations and discussions at confer-
ences, and exchange of students or personnel between academia and industry. From
the perspective of the university technology transfer ofce (TTO), however, the
focus is on the formal transfer of IP and other technology rights, usually to a com-
pany, to translate the fruits of university research into products and services that
benet the public.
The services offered by university TTOs vary somewhat, depending on the aca-
demic institution’s size, research budget, culture, and local ecosystem. The common
thread throughout is managing the institution’s IP rights, mostly in the form of pat-
ents and copyrights; marketing and licensing those rights to industry to develop and
commercialize useful products; and managing the distribution of income resulting
from those licenses. More recently, many TTOs, particularly those of mid- to large
size universities, have expanded their offerings to include one of more of the follow-
ing: industry relations and industry sponsored research contracting, alliance man-
agement functions, entrepreneurship training, funds for translational research and
proof of concept testing, startup services and seed funds, and accelerators and incu-
bators. Many non-US institutions also offer to manage their researchers’ outside
consulting activities. The services offered by the TTO are especially important for
therapeutic discoveries, considering 55% of FDA-approved NMEs originate from
academia (Kim etal. 2017).
5.2.2 The Licensing Process
The invention management and licensing process generally begins with disclosure
to the TTO of a detailed description of the invention and any relevant facts and cir-
cumstances, such as the list of inventors and any research sponsors. It is important
for the inventors and the TTO to engage each other early in the process to make sure
that everyone understands the various options for further development and commer-
cialization, and the inventors and the TTO are aligned on the best path forward. If
the invention does not need further maturation within the academic environment,
the process will likely be fairly linear. More recently, as research teams move their
biomedical inventions through various funding sources, translational programs,
and/or industry collaborations, the process may have several touchpoints and can
become more complex as some funders may impose IP or other obligations. The
TTO will assess the commercial potential of the invention and may conduct an IP
landscape analysis, after which a decision can be made whether to le for patent
protection. While some software and digital-health inventions, as well as most bio-
logical research tools, will not require patenting in order to be commercialized,
5 Technology Transfer andCommercialization
192
most inventions focused on therapeutics require patent protection in order to incen-
tivize a company to develop and bring them to market.
Many TTOs have a technology marketing team that can help identify potential
licensees and startup investors, although licensees are often identied through the
inventors’ own networks. If the technology requires further development and de-
risking to attract external investment, an inventor-founded startup that initially
makes use of a university accelerator or incubator and non-dilutive funding, such as
government grants, may represent the best and possibly only avenue to bring a tech-
nology to market.
Once one or more appropriate licensees have been identied, the TTO will nego-
tiate the nancial and legal terms and conditions with the candidate licensee(s) or
the startup entrepreneurs or investors. For startups, time-limited option agreements
are generally less expensive and time-consuming than negotiating a full license
agreement to secure the rights sufcient to get investors and management teams on
board, after which a full license agreement makes sense. To mitigate conict of
interest concerns (see Sect. 5.3 for more on conicts of interest), most universities
will not negotiate license terms with a faculty member or student. Therefore, another
entrepreneur or a lawyer should represent the startup company in the negotiations.
The research sponsors and all of the university stakeholders are strongly aligned
in their desire to see new therapeutic technologies developed as rapidly as possible
and in a manner that will lead to the greatest patient benet. One of the functions of
the TTO is to enforce licensee compliance with diligent development requirements,
nancial obligations, and other terms of the license. The TTO also manages the
accounting and distribution of licensing income to various university stakeholders.
Most academic institutions have policies that allow for a specied share of licensing
income to be distributed back to the institution to support further research, as well
as a personal share to the academic inventors.
5.2.3 Research Sponsor Rights
Biomedical research and development is an expensive proposition. Even within the
university setting, millions of dollars in research funding may be needed in order to
mature a therapeutic technology to the point at which it can attract external invest-
ment for the purpose of commercialization. With limited government funding avail-
able for the translational stage of research, universities rely more heavily on funding
grants from non-prot foundations and charities, as well as from industry. These
funding sources frequently seek some form of rights with respect to the resulting
Box 5.2: What Surprised an Academic?
Because the TTO is sensitive to the academic mission to share knowledge,
ling for a patent rarely slows down publication, submission of an abstract, or
giving a talk. Filing a disclosure with the TTO can be as simple as attaching
your planned talk or draft manuscript to get the process going.—DM-R
D. Mochly-Rosen et al.
193
inventions. Industry sponsors will generally receive some sort of rights to IP devel-
oped under the funded project, often in the form of a time-limited option. It is help-
ful to note, however, that even non-prot funding grants sometimes come with legal
obligations that cede some level of control over the IP rights and/or grant a specied
nancial return back to the funder. It is of utmost importance to fully understand and
carefully consider the terms and conditions attached to both for- and non-prot
research funding sources before accepting the funding so that any obligations under
those grants are aligned with the development and commercialization goals for the
technology. For example, some terms and conditions may adversely affect an aca-
demic inventor’s ability to obtain future funding from other sources to further
develop the technology or to form a new company to commercialize the IP.
5.2.4 Patent Management
Inventors should disclose inventions to the TTO as soon as there is data to support
the conception, and in any case, several weeks before any public disclosures, includ-
ing any publications in journals, conference abstracts, laboratory websites, and oral
presentations in non-condential settings. This will give both the TTO and patent
attorneys time to work collaboratively with the inventors on when to le and what
subject matter to include in order to best meet business needs and to prepare the
application accordingly (see Sect. 5.1 for more on intellectual property). Many aca-
demic inventors are not aware of the high level of strategic thinking that goes into a
patent ling, particularly for patents related to drug discovery. Timing and what
information to include in the patent application are important considerations when
determining the right balance between need to publish, meeting the rst-to-le
requirement, and ensuring that there is enough data in support of the desired claims
to meet patentability requirements. Once the patent application is drafted, the inven-
tors must work closely with the patent attorney to ensure that the full extent of the
invention and its applications in terms of potential commercial products are cap-
tured in the patent.
The patent prosecution process leading to issuance of a US patent in the bio-
medical space generally takes three to ve years, but sometimes longer. Patent l-
ings can also become very costly, particularly if broad foreign rights are pursued,
which can cost hundreds of thousands of dollars. Most TTOs have limited patent
budgets and must carefully consider at various timepoints during the ling and pros-
ecution processes which inventions warrant investment of funds for patentprotec-
tion and in which countries.
5.2.5 University Gap Funds, Accelerators andStartup Services
The ongoing challenges of obtaining seed funding for startups have increased the
importance of further developing and de-risking new therapeutic technologies
before exiting them out of the academic setting. Many academic institutions now
5 Technology Transfer andCommercialization
194
offer gap funds, accelerator programs, and/or incubators to move novel, cutting
edge technologies across the applied science stage that is often referred to as “the
valley of death”.
Gap funds and accelerator programs generally offer translational research fund-
ing, often in milestone-driven tranches, in combination with access to mentors and
advisors who have expertise in drug development, and are familiar with current
regulatory issues and other market forces (like SPARK!). Many of these programs
also offer shared access to highly valuable drug discovery tools and equipment not
generally available within academic laboratories. Incubators can also play an impor-
tant role by providing cost-efcient access to quality wet lab space and shared busi-
ness resources. Many incubators also have advisors on staff with expertise in drug
development. Academics should familiarize themselves with and take advantage of
the programs and services offered within their local ecosystem.
5.2.6 Conflict ofInterest Considerations
Whenever university faculty found and take an ownership stake in a company to
license and commercialize the university-owned IP that they invented, conict of
interest concerns will naturally arise. For example, is the faculty founder putting
students on projects that will benet the faculty member’s startup rather than proj-
ects that will advance the students’ academic goals? Is follow-on research being
driven by the potential for personal gain (see Sect. 5.3 for more on conicts of inter-
est)? Faculty founders will often wish to negotiate the IP license on their own, but
from a legal perspective, it may be difcult to determine whether they negotiated on
behalf of the university as a university employee, or solely on behalf of the indepen-
dent company.
With these and other questions in mind, most institutions with medical schools
or academic medical centers have established mitigation mechanisms to maintain
academic freedom, ensure that all research is conducted with utmost integrity, and
protect students’ academic goals and careers. Mitigation plans can include actions
such as minimizing the personal equity holdings of the startup founders, providing
full transparency to all affected lab members as to the existing nancial conicts,
and creating oversight committees that track student progress and publications,
among other things.
The Bottom Line
Technology transfer is essential for commercialization of discoveries and
inventions from academia. The process can be complex and requires balanc-
ing the interests of numerous constituents, including inventors, licensees, the
university, the government, and the public. The end result can be satisfying to
all parties when university technology is successfully translated to industry
for society’s benet.
D. Mochly-Rosen et al.
195
5.3 Navigating Conflicts ofInterest
EmilyEgeler
As university faculty members get more involved in the drug development process,
it is essential that academic institutions maintain their high-quality unbiased
research and education missions. Faculty owe their primary allegiance to their insti-
tution and its core values. Investigators are also responsible to government agencies
and the public who fund the research and ultimately to the patients who are treated
by these new therapeutics.
The potential for nancial conicts of interest is common and sometimes
unavoidable as academic investigators work to translate their discoveries. An
increase in collaborations across academia and industry has arisen due to the push
to move technology forward faster. The goal should not be to shun all interactions
with for-prot entities, but rather to manage and report these interactions in a trans-
parent way to protect the public.
5.3.1 Identifying Conflicts ofInterest
The Sunshine Act, which elicits transparency of physician payments or ownership
interests made by all pharmaceutical, medical device, biotechnology, and medical
supply manufacturers doing business in the US, went into effect March 31, 2013, as
part of the Patient Protection and Affordable Care Act. Each institution has local
policies for reporting nancial interests and determining if the interests could have
a direct and signicant effect on the research. Currently, the Public Health Service,
which encompasses many federal agencies including the National Institutes of
Health (NIH), FDA, and Centers for Disease Control and Prevention (CDC), denes
a signicant nancial interest as (a) income greater than $5000 per year, (b) equity
or ownership in a non-publicly traded company, or (c) personal income from IP
outside of any university paid royalties.
A conict of interest (COI) depends on the situation and does not necessarily
reect on the character or actions of the individual. If a reasonable person might
conclude that relationships or interests could inuence academic responsibilities,
investigators should disclose the nancial interests following institutional protocols.
Box 5.3: What Surprised an Academic?
It is not against most university and funding agency policies for academics to
nancially benet from their research and clinical work. On the contrary,
institutions should encourage faculty to work long and hard to make new
therapeutics a reality. It is, however, essential that the public trust the impar-
tiality of the research and clinical trial data generated in publicly funded insti-
tutions and that the independence of trainee education and mentorship be
maintained. This is why it is so important to properly manage conicts of
interest.—DM-R
5 Technology Transfer andCommercialization
196
Disclosing a potential COI does not imply that the research or clinical work is actu-
ally biased; maintaining integrity of research ndings is still a personal responsibil-
ity. Instead, disclosure of conicts of interest is an avenue to increase transparency
between nancial interests related to the research and clinical outcomes in drug
development. Managing a COI may be as simple as adding language to an informed
consent form, hiring an outside statistician, or blinding the data to the investigator.
Some nancial interests are unmanageable COIs and will prevent participation in
running or analyzing a clinical trial.
5.3.2 Conflicts ofInterest toAvoid
Some industry relationships are almost never appropriate. Most importantly, clini-
cal investigators should not hold primary responsibility for a clinical trial in which
they stand to nancially benet from the outcome. Clinicians should attempt to
minimize the possibility that industry relationships inuence discussion of treat-
ment options for patients who consider participation in the clinical study. For
instance, clinicians should not accept personal payment for each patient they enroll
or refer to a clinical trial.
On the laboratory research side, it is important that academics keep their univer-
sity role and responsibilities separate from any for-prot ventures. For instance,
graduate students or postdoctoral scholars should not be coerced into performing
research that will benet a faculty startup company or otherwise have their research
topic areas restricted. Education must include openness in research with free
exchange of scholarly information and opportunities to present work at seminars
Box 5.4: Guide to Identifying Conicts of Interest
1. Do any nancial interests or relationships, including items without current
value like stock options, relate directly to my responsibilities and role as
an academic investigator?
2. Could my research ndings impact the success of these interests, or appear
to affect the success?
3. Could a reasonable person conclude that my research or role at the univer-
sity might be inuenced by my nancial ties?
4. Does my institution have requirements to report interests for spouses, part-
ners or dependent children?
Box 5.5: What Surprised an Academic?
Federal regulations and institutional policies may require us to report nan-
cial interests for our spouse, partner or dependents in addition to our own
industry connections. Usually this is only necessary if their connections relate
to our area of research or clinical practice.—DM-R
D. Mochly-Rosen et al.
197
and in papers or dissertations without delay. An academic researcher should not
accept corporate funding or in-kind gifts that require a delay in publication or that
use university resources to preferentially benet a particular company.
5.3.3 Managing Conflicts ofInterest: Clinical Investigators
Disclosing conicts of interest in the clinical research setting is intended to solidify
public condence in the results of clinical trials and to ensure that clinicians are act-
ing in the best interest of their patients. Areas of concern include intentional or,
more likely, unconscious bias in interpretation of study results, reporting of adverse
events, or selection of a course of treatment. Accepting gifts from companies,
including things like free drug samples or even pens with the company logo, is not
allowed in some universities as such practices may potentially inuence the open,
independent environment of the academic institution or affect the university’s tax-
exempt status.
Clinical investigators should be able to partner with industry to improve patient
care, but it is important to be aware of university policies and to avoid situations that
might impact the impartiality of the study design, data collection, or ndings.
Expect to disclose conicts of interest in relation to human subject research proto-
col submissions to the Institutional Review Board (or Ethics Committee), grant
applications, or Material and Human Tissue Transfer Agreements. An institutional
COI may arise when a university or hospital stands to benet monetarily from clini-
cal research results because of a nancial relationship with a company. The poten-
tial for institutional COI should be considered when an institution is deciding
whether to participate as a clinical site for a trial. A hospital or academic medical
center may decline to participate if the institution would benet nancially (e.g.,
through future royalty streams, milestone payments, or equity ownership) from
positive study results.
5.3.4 Managing Conflicts ofInterest: Laboratory Researchers
The public relies on researchers from universities and other academic institutions to
be impartial and comprehensive when reporting their ndings. Not only is the pub-
lic the end recipient of any drugs developed based on the research, but also the
funders of research supported by federal grants. The most common nancial
Box 5.6: What Surprised an Academic?
Faculty who serve on a scientic advisory board (SAB) or medical advisory
board (MAB) may be compensated with stock or stock options (equity) in lieu of
payment for services. Avoid accepting equity as payment if you are an investiga-
tor in related human subject research studies. Holding any equity can be con-
strued as having the ability to compromise the objectivity of the research study.
This includes stock options whose value cannot readily be determined.—DM-R
5 Technology Transfer andCommercialization
198
conicts of interest for researchers arise from paid consulting, accepting monetary
or in-kind support from an industry partner, or having equity ownership in a startup
company that holds IP licenses from the university.
It is important that nancial ties do not affect or appear to affect the design, con-
duct, interpretation, or reporting of research. Nor should industry afliations inter-
fere with the selection of research topics. Importantly, we must also protect the
integrity of our educational mission. Our teaching and mentorship must not be
biased by nancial considerations. Agreements cannot restrict students’ ability to
publish or present results, and trainee work should be independent from any men-
toring faculty’s COI.Within the academic setting, all meetings should be educa-
tional and not for marketing purposes.
5.4 Working withtheUniversity Compliance Office
JenniferSwantonBrown and NicholasGaich
This section focuses on academic institutional requirements for conducting human
research, using Stanford University as an example. While each institution’s compli-
ance infrastructure and policies will vary to some degree, the guiding principles are
the same: to protect human research subjects, to ensure high quality design and
execution of research protocols, and to ensure that government regulatory require-
ments are met. We highly recommend that you consult your institution’s policies
before conducting human research.
Regulatory compliance at Stanford for research involving human subjects is
denedin the Human Research Protection Program (HRPP) and administered by
the Research Compliance Ofce (RCO) in the Ofce of the Vice Provost and Dean
of Research. The RCO administers Stanford’s Administrative Panels for Human
Subjects in Research, the formal name for the Stanford Institutional Review Board
(IRB). Panels for Human Subjects in Research committees in other countries have
different names, such as Independent Ethics Committee (IEC) in Europe; Human
Research Ethic Committee (HREC) in Australia, etc. Additionally, and based on
allocation of funding for an investigator-initiated project, there may be university
sponsored project and research compliance requirements administered by the
Research Management Group (RMG).
The Bottom Line
Conicts of interest include any industry connections that could appear to
inuence the design, conduct, or interpretation of research or clinical trials.
Disclosing a COI does not imply that the results are biased. Accurate disclo-
sure of a COI is essential to maintain transparency and public trust in research.
Consult university policies for specic guidance on what and how to report.
D. Mochly-Rosen et al.
199
For industry-funded clinical trials, a Stanford investigator may initiate all three
phases of research oversight in parallel: IRB (human subject) approval, contract
negotiation, and budget development. IRB approval is required for all human sub-
ject research and is not contingent on the other two processes. Detailed budgets are
required for sponsored projects and strongly encouraged for department-funded
projects. Contracts are contingent on meeting all sponsored project compliance
requirements and IRB approval and are needed if drug, device, biologic, or funding
is received from, or data, publication rights, or IP is shared with an entity outside
Stanford, for example, from an industry collaborator or as a subaward from another
academic institution.
5.4.1 IND Requirements
An Investigational New Drug application (IND) must be led with FDA before any
unapproved drug can be used in research with human subjects in the US. The
Stanford IRB requires written evidence of FDA concurrence with the IND if the
compound being studied has never received FDA approval for any use in the US.
If the drug being studied has prior approval by FDA for use in the US, the study
may require a new IND or be IND-exempt. For instance, Stanford’s IRB application
walks the investigator through the regulatory questions that assist an investigator in
making this determination. Clinical trials are typically IND exempt if the researcher
studies the drug according to its legally marketed labeling. Trials typically require a
new IND if the research involves a “route of administration or dosage level or use in
a patient population or other factor that signicantly increases the risks (or decreases
the acceptability of the risks) associated with the use of the drug product” (Code of
Federal Regulations 21 CFR 312.2(b)(iii)).
Box 5.7: What Surprised an Academic?
Clinical research with foods or nutritional supplements is an area that requires
a nuanced understanding of regulatory affairs. An academic might reasonably
expect that studying the effects of vitamins or herbal supplements to treat
disease or alleviate symptoms is nothing like studying a new cell therapy or
small molecule. FDA, however, considers foods and supplements to be drugs,
if their research meets the regulatory denition of a clinical investigation.
Navigating this regulatory landscape is complicated by the fact that such
products are often commercially available, and their manufacturers may not
fully understand the IND regulations. One investigator, following a nutraceu-
tical manufacturer’s advice, would have begun a clinical trial without an
FDA-required IND but for the quick action of the IRB and expert knowledge
in the Clinical Research Quality (CRQ) regulatory affairs team.—JSB
5 Technology Transfer andCommercialization
200
5.4.2 IRB Oversight
At Stanford, applications to the IRB are submitted via an electronic submission
process, called eProtocol. For studies that are not IND-exempt, the IRB requires
documentation of an FDA-approved IND.Acceptable documentation includes a let-
ter issued by FDA indicating the IND number.
Informed Consent templates are available from Stanford’s IRB website. The
investigator needs to provide any advertisements or recruitment materials to the IRB
at the time of application. Guidance on Data and Safety Monitoring or special regu-
lations for research with children are also available among the IRB’s comprehensive
guidance documents. By carefully following the Informed Consent templates and
fully answering the eProtocol questions prior to IRB application submission, a
researcher can expect an approval from the IRB within 4–6weeks. The Stanford
IRB also reviews and approves Health Insurance Portability and Accountability Act
of 1996 (HIPAA) authorizations for research.
There are additional requirements and approvals for research conducted at indi-
vidual units within Stanford, such as the Veterans Administration Palo Alto Health
Care System. Additional requirements and approvals may also be needed for certain
indications, such as cancer, or for particular therapeutic modalities, such as stem
cell research.
In the era of precision health and real-world data, additional reviews on data use,
privacy or security domains, when needed, are integrated into the IRB system.
5.4.3 Sponsor–Investigator Research Training andSupport
Sponsor–investigator research (SIR) is dened as research conducted by a Stanford
investigator who holds an IND from FDA.The Stanford IRB requires protocol-
specic sponsor–investigator research training for the Principal Investigator (and/or
Protocol Director) and research team prior to initial IRB approval. This training is
provided by regulatory staff from the Cancer Clinical Trials Ofce (CCTO) or
Spectrum’s Workforce Development program. Training includes review of required
regulatory documentation and reporting to FDA and IRB. Prior to continuing
approval of an ongoing project, RCO requires investigator self-assessments and
conducts consent reviews. Individual departments and centers also provide over-
sight. Sample training and review documents can be found on Stanford’s IRB
website.
Training and regulatory consultation are available for any aspect of investigator-
initiated research at Stanford (see Sect. 5.4 Resources for relevant websites).
• Sample templates, logs, and standard operating procedures (SOPs) are available
through CCTO, Spectrum, and CRQ.
• Good Clinical Practice training is available upon request or when required.
D. Mochly-Rosen et al.