Patent Review

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Nanoparticles applied to antineoplastic

agents: a patent landscape

Recently, research in the field of cancer nanotechnology has made notable progress, Iolanda M Fierro*,1, Maria
and, with the fast development of nanomaterials, new treatment strategies using Simone de Menezes Alencar2,
nanoparticles are being explored that have the potential to overcome existing Flavia Maria Lins Mendes3,
problems. The present review focuses on patenting as a key indicator of trends in Cristina d’Urso de Souza
Mendes1, Bernardo Furtado
nanoparticles with applications in the treatment of cancer. The impact of cancer on
Nunes1 & Adelaide Maria
health and the use of nanoparticles are briefly described. Next, a survey of patents
de Souza Antunes1,3
filed in the last 14 years is presented, the patents granted in the last four years are 1
National Institute of Industrial Property
identified, and the focus areas of the main applicants are analyzed. The mix of targets (INPI-Brazil), Mayrink Veiga, 9 Centro,
identified for patented nanoparticles systems suggests that polymers and proteins are 20090-910, Rio de Janeiro, Brazil
the main focus of the innovative efforts in this field.
2
Federal University of the State of Rio de
Janeiro (Unirio), Av. Pasteur, 296, Urca,
22290-240, Rio de Janeiro, Brazil
Cancer remains one of the leading causes of Although successful in many instances, these 3
Federal University of Rio de Janeiro
mortality worldwide, affecting over 10 mil- treatments are responsible for significant dam- (UFRJ), School of Chemistry, Centro de
Tecnologia. Av. Athos da Silveira Ramos,
lion new patients every year [1] . Its incidence age to healthy tissue, with concomitant health-
149 Bloco E - Sala E-200, Ilha do Fundão,
has risen in recent years, making it now related issues. These issues arise in part from 21949-909, Rio de Janeiro, Brazil
one of the biggest public health problems the ‘whole-body’ approach of these therapies. *Author for correspondence:
worldwide. To minimize the damage of non-cancerous Tel.: +55 21 3037 3935
The Union for International Cancer Con- tissue, treatments could be applied directly to Fax: +55 21 3037 3529
ifierro@inpi.gov.br
trol has promoted a number of initiatives the tumor, leaving neighboring tissue unaf-
designed to prevent the death of around 80 fected. Two types of targeting can be used to
million individuals in the coming 10 years. enhance the efficiency of tumor therapy. First,
According to the WHO, cancer kills more the tumor can be targeted spatially, with the
than AIDS, malaria and tuberculosis com- toxic effect of the therapeutic agent localized
bined. It is most common in developed to the tumor site. The second type of targeting
countries, but over 70% of cancer-related is on the cellular level. By directly targeting
deaths occur in countries where there is tumor cells, the treatment will not damage
restricted access to resources and actions for healthy tissues in the vicinity of the tumor [3] .
its prevention, diagnosis and treatment. The Hersm describes nanotechnology as mov-
economic impact of the disease is huge, and ing into a ‘posthype era’ in which its applica-
only in 2008 the global cost associated with tions are widely pervasive throughout scien-
premature death and disability came close tific and industrial sectors [4,5] . Over the last
to US$ 1 trillion – 1.5% of the world’s gross two decades, nanotechnology has developed
domestic product [2] . extensively, and investing in nanotechnology
Cancer treatment is still a challenge due is now standard practice by governments,
to the numerous adverse effects of the medi- research centers and companies. Nanotech-
cations available, which represent a true nology products are already on the mar-
limitation in their clinical use. ket in emerging markets as well as in more
A combination of surgery, chemotherapy developed countries.
and radiation therapy constitutes the con- According to the Freedonia Group, Inc.,
part of
ventional treatment regime for most cancers. an international business research company,

10.4155/PPA.14.47 © 2014 Future Science Ltd Pharm. Pat. Anal. (2014) 3(6), 613–623 ISSN 2046-8954 613
Patent Review  Fierro, de Menezes Alencar, Lins Mendes et al.
Key terms
Bionanotechnology: Biomedical applications of
nanotechnology.
Nanomedicine: The application of nanotechnology to the
screening, diagnosis, prevention and treatment of several
diseases.
Liposomes: Colloidal carriers, often composed of
phosphatidylcholine-enriched phospholipids, formed
spontaneously when certain lipids are hydrated in
aqueous media.
in the USA alone, demand for bionanotechnology
products is increasing over 17% annually. It is esti-
mated to reach US$ 110 billion by 2016, including
nanomedicines, nanodiagnostics and nanotechnol-
ogy-based medical supplies and devices. This report
predicts that the greatest short-term impact of nano-
medicine will be in therapies and diagnostics for cancer
and central nervous system disorders [6] .
Likewise, there has been rapid growth in nanotech-
nology publications and patent production [7,8] . The
share of nanotechnology papers oriented toward bio-
medical and clinical medicine applications has risen
from just over 5% to more than 11% [5] .
The application of nanotechnology to the screening,
diagnosis, prevention and treatment of several diseases
is an emerging field that has the potential to revolu-
tionize individual and collective healthcare in the 21st
century. At the beginning of this century, health, sci-
ence and technology were identified as prerequisites
for social and economic development, as set out in the
United Nations Millennium Development Goals [9] .
Biomedical nanotechnology is the fastest growing
field in nanotechnology, and has enormous poten-
tial to positively impact the healthcare system. Some
important biomedical applications of nanotechnology
that may have potential clinical applications include
targeted drug delivery, especially in the oncology sec-
tor, detection/diagnosis and imaging [3] , not to men-
tion the probable increased understanding of complex
underlying disease mechanisms.
Nanotechnology involves the manipulation of materi-
als on a nanometric scale, by reducing bulk materials into
nanoparticles (NPs). The size of nanomaterials provides
a large surface area-to-volume ratio; as the particle size
decreases, the amount (or number) of surface atoms rap-
idly increases [3] . Working on a nanoscale offers several
advantages, since nano-sized materials possess unique
physical, chemical, electronic and biological character-
istics compared with larger particles. For applications in
medicine, nanosystems can be designed to be active on a
molecular level with a high degree of specificity.
For this review, we will take the definition of NP as
a sub-classification of ultrafine particle with lengths in
614 Pharm. Pat. Anal. (2014) 3(6)
two or three dimensions greater than 0.001 μm (1 nm)
and smaller than about 0.1 μm (100 nm) and which may
or may not exhibit a size-related intensive property [10] .
According to numerous authors, the main classes
of NPs employed for biomedical applications include
dendrimers, fullerenes, liposomes, magnetic par-
ticles, metals, polymers, semiconductors, solid lipids,
carbon-based materials, peptide/protein particles and
virus-mediated particles [10–12] .
NPs can have many different shapes and composi-
tions, which means that their properties – size, shape,
surface charge – can be engineered to make them suit-
able for a specific biomedical application [13] . NPs have
proven to be the most versatile and widely used constit-
uents with broad applications such as delivery vectors,
imaging agents, synthetic inhibitors and sensors [3] .
Presently, diverse NPs are being investigated for can-
cer therapeutics and diagnostics. The properties of some
of these systems can be improved to enhance their deliv-
ery directly to the tumor, and targeted therapy represents
a stimulating approach toward cancer treatment. Besides
site specificity and efficient delivery, some of the other
improvements include higher efficacy, fewer side effects
and overcoming multidrug resistance by tumor cells [14] .
Nanostructured carriers have been developed to pro-
tect drugs from enzymatic degradation, enhance drug
absorption by improving their penetration across the
mucosal epithelium and to modulate drug pharmacoki-
netics, therefore improving efficacy and reducing drug
toxicity [15] .
The analysis of scientific publications and above all
patent documents can help to understand the dynamics
of bionanotechnology research and innovation systems.
Patent documents are the most important source of
technological information, as they contain about 70% of
all the technology developed around the world, as well
as having the advantage of being globally standardized.
Statistics on patents have been used as indicators of the
results of invention-related activities [16] . Furthermore,
patents are the most commonly used indicator in land-
scapes [17] . This is corroborated by the Organization for
Economic Cooperation and Development, which states
that patent data can be used as a source of information
in order to measure science and technology activities [16] .
The use of patent analysis as a method for technologi-
cal foresight yields strategic intelligence on technologies
and can reveal competitive advantages derived from lead-
ership in technological development. It gives an under-
standing of who the leading patent applicants/holders
for a given technology are, enabling comparisons to
be made among companies, countries or technological
areas, as well as areas where patenting is intensive [9] .
This review analyzes the main trends in the
patenting of NPs with oncology applications.
future science group
 Nanoparticles applied to antineoplastic agents  Patent Review

Patent search methodology As nanotechnology involves a variety of different

The database selected for the retrieval of patent docu-
ments was the Derwent Innovations Index, which con-
tains over 11 million patent documents that have been
filed, published and sometimes granted in more than
40 countries since 1963. This database contains patent
applications in the areas of chemistry, electricity and
electronics and engineering, and its main advantage is
the fact that all the patent documents in it are indexed,
and their abstracts were written by specialists in the
area. As such, the abstracts are full of key words and
are available in English, together with their titles, no
matter where the patent application was filed and pub-
lished, which facilitates the recovery of the documents
using defined search strategies [16] .
The main reasons for the choice of this patent
database were:
• The possibility of exporting the patent documents
recovered in the search in their entirety using soft-
ware designed to work with this type of informa-
tion, such as the commercial software package
VantagePoint®, for the treatment of the patent data
included in this article;
• The availability of Manual Codes for classifying all
the patent documents indexed in the database. This
classification has a hierarchical structure similar to
that of the International Classification of Patents
(IPC), although in less detail. The Manual Codes
divide the technological knowledge contained in
the patent documents into 21 sections [16] .
For the search of patent documents related to NPs
with oncology applications, terms and classifications
relating to two concepts were identified: antineoplas-
tics and NPs. The related IPC classes and Derwent
Manual Codes were used.
technologies and is relatively recent from the perspec-
tive of intellectual property, the IPC does not yet have a
full set of classifications to represent it. In version 7 the
IPC did include class B82Y, referring to specific uses
or applications of nanostructures, the measurement
or analysis of nano-structures and the manufacture or
treatment of nanostructures. Other classes used were
A61K 9/15, for medicinal preparations characterized
by special physical form nanocapsules, and A61P 35
(antineoplastic agents), in order to restrict the search
to the use of NPs for cancer treatment.
The Derwent Manual Codes listed in Table 1 were
selected because they are specific to drugs used to treat
cancer or to nanotechnologies/NPs applied to the
pharmaceutical sector.
Given that the existing classifications encompass-
ing NPs may not fully cover the scope of patenting in
this area, the titles and/or abstracts of the patent docu-
ments were also searched using certain keywords, such
as ‘nanoparticle’ and variations thereof.
Combined searches were then undertaken using the
chosen classifications and key words. The raw data were
retrieved and the patent documents published between
2000 and 2014 were selected and treated using Van-
tagePoint, developed and sold by Search Technology.
This data mining tool can process large quantities of
data by automating tasks like the standardization and
production of reports and maps to make them easier to
visualize for analysis purposes [9] .
Results
Patent applications
The search results yielded a total of 4235 patent docu-
ments. The historical profile of the patent applications
filed is shown in Figure 1, with the left axis showing the
number of priority patent applications filed per year

Table 1. Selected Derwent Manual Codes.

Code Title
B14-H Cancer-related drugs
B05-U Fullerene type cage structures
B11-C12 Nanotechnology (general) – covers nanoswitches made of DNA
B12-M10A7 Nanotechnology devices: use of nanotechnology to deliver drugs to specific sites an
control their release at that point
B12-M11Q Nanoparticles: tablets, capsules, etc. (general)
E05-U05A Nanoparticles, nanopowder: other carbon nano 3D structures (general)
E31-U01 Inorganic nanostructures
J04-F02A Nanoparticles (process)
J04-F02A1 Composite particles: nanostructure production
J04-F02C Nanofilms (process)

future science group www.future-science.com 615

Patent Review  Fierro, de Menezes Alencar, Lins Mendes et al.
and the right the total number of applications accumu-
lated in the period. A clear increase can be observed in
the global interest in NPs with oncology applications
in recent years, shown by the significant growth in the
number of patent applications.
This initial set of patents was then treated in a num-
ber of different stages which included grouping the
patents according to the type of assignee: companies,
government (including national institutes and fund-
ing agencies), universities, hospitals and individual
inventors (individual researchers or other individual
assignees). Most of the patent applications were filed
by universities (41.9%) and companies (36.7%), while
individual inventors (10.5%), government (8.0%) and
hospitals (3.0%) accounted for a smaller proportion.
The 4235 patent documents were filed by over
2500 applicants and were widely dispersed: the largest
made 85 patent applications while the smallest made
just one. The main patent applicants, with 25 or more
applications filed, accounting for around 15% of all the
documents encountered, are listed in Table 2.
Granted patents
In order to identify which patent applications were suc-
cessful in the search period, from 2000 to 2014, a semi-
automated procedure was used via VantagePoint in
order to identify the kind codes for the patents granted
by each country. Of the original 4235 applications filed,
it was found that around a third (1335) were granted.
Priority year
700
600
500
Number of filings per year
400
300
200
100
0 0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Figure 1. Profile of patenting of nanoparticles with oncology applications over time.
Data taken from [18] .
616 Pharm. Pat. Anal. (2014) 3(6)
In this study, only the patents granted in the last 4
years according to the Derwent Innovations Index were
investigated, which summed 761 patents granted in all,
but 508 distinct patents. Patents are granted by indi-
vidual countries according to their specific legislation, so
the same patent may be granted in more than one coun-
try. The countries in which the patents were granted,
followed by the respective number of patents, were USA
(216), China (173), South Korea (79), Australia (51),
South Africa (49), European Patent Office (42), Japan
(30), New Zealand (30), Mexico (25), Russia (22),
Canada (19), Hong Kong (10), Israel (5), France (3),
Philippines (3), UK (2), Netherlands (1) and Norway
(1). Interestingly, just over 60% of all the patents were
granted in just three countries: the USA (28%), China
(23%) and South Korea (10%).
The 508 patents were selected for analysis and their
assignees were classified according to their type, that
is, whether they were a company, university, govern-
ment, individual inventor or hospital. At this stage, any
partnerships between the different types of assignees
were also identified. The result of this analysis can be
seen visually in Figure 2 in percentage terms, showing
that research and development of NPs for use in oncol-
ogy takes place mainly at universities and companies,
since combined they account for almost 70% of all
the patents granted. The most significant partnerships
are between universities and companies and between
different companies.
4500
4000
3500
Accumulated number of filings
3000
2500
2000
1500
1000
500
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 Nanoparticles applied to antineoplastic agents  Patent Review

Table 2. Main patent applicants and respective countries of origin.

Patent applicants Number of patent Country of origin
applications filed
University of California 85 USA
University of Texas System 61 USA
MIT 56 USA
Abraxis Bioscience LLC 46 USA
Centre National de la Recherche Scientifique 44 France
Elan Pharma International Ltd 38 Ireland
Johns Hopkins University 34 USA
Fudan University 32 China
Brigham & Women’s Hospital 31 USA
Nanjing University 31 China
Yonsei Industry-Academic Cooperation Foundation 28 South Korea
Abbott Cardiovascular Systems Inc. 26 USA
Searete LLC 26 USA
US Department of Health & Human Services 26 USA
Tsinghua University 25 Taiwan
Shanghai Jiao Tong University 25 China
Data taken from [18].

The analysis of these same 508 patents granted for
the treatment, prevention and diagnosis of cancer also
revealed that they often included claims for other dis-
eases as well. We therefore analyzed the section ‘use’
of each document and found that they mainly con-
tained claims for the following diseases: diabetes (9%),
inflammatory diseases (6%), Alzheimer’s disease
(5.5%), psoriasis (5.3%) and arthritis (5.1%).
In order to analyze these patents qualitatively, the
assignees with most patents granted in the last 4 years
and the respective countries of protection were identi-
fied. As can be seen from Table 3, four countries stand
out for the number of applicants with six or more
granted patents each: the USA, China, South Korea
and South Africa, summing a total of 86.
Analysis of granted patents
The analysis of the granted patents [19–90] showed that
the most common classes of NPs are claimed (Figure 3)
although not all of them are exclusively related with
technologies for cancer, including several other diseases
such as Alzheimer’s disease, diabetes, anemia, differ-
ent types of infections, rheumatoid arthritis and other
inflammatory diseases. Nonetheless, a number of docu-
ments protect cancer-related uses comprising treatment,
prevention, detection/diagnosis and imaging.
It is well known that polymer-drug conjugates,
liposomes and inorganic particulates prolong blood
circulation times, reduce toxicity to healthy tissue and
improve anti-tumor efficacy [16] . Magnetic NPs have
potential for noninvasive tumor treatment, since the
application of a magnetic field will selectively heat
the NPs rapidly and efficiently, allowing for the selec-
tive destruction of tumor cells [3] . The only magnetic
NPs with a history of clinical approval and use are
iron-oxide-based NPs.
New techniques involving molecular images allow
the understanding of physiological processes of the
human body on the nanoscale, thus leading to the
development of methods to diagnose and treat diseases
more accurately and sensitively. One example in par-
ticular is superparamagnetic NPs using proteins for the
molecular imaging of cancer [16] .
The literature draws attention to the need for reducing
metallic NPs’ toxicity, since these NPs could accumulate
in the biological medium due to the highly ionic envi-
ronment, affecting the dynamic interactions between
NPs and cells [3] . The distinctive properties acquired by
particles when they are formulated at the nanoscale can
have a significant impact on their bioreactivity, making
predictive toxicology very difficult.
We next summarize by country of protection the
main findings analyzing the 86 granted patents.
USA
In the USA, the country where most patents in
this area have been granted, the main assignees are
universities.

future science group www.future-science.com 617

Patent Review  Fierro, de Menezes Alencar, Lins Mendes et al.
Companies Individual inventors
29.1% 3.5%
8.3 ent
Hospitals
m
1.0%
%
ern
Gov
Partnerships
19.1%
Universities
39.0%
Figure 2. Breakdown of patent assignees.
Com: Companies; Gov: Government; Hosp: Hospitals; Univ: Universities.
Data taken from [18].
The partnership between National Tsinghua Univer-
sity and GP Medical, Inc. is the top assignee, with 14
granted patents. Twelve of these patents claim composi-
tions of NPs comprising chitosan. Polymeric NPs are
generally synthesized from natural or synthetic polymers
and are available in different types with specific prop-
erties for each particular application [91] . Chitosan is a
cationic biopolymer that can be used as a nanocarrier.
There are several advantages in using biopolymeric NPs
of chitosan, including biocompatibility and good bio-
degradability, low immunogenicity and toxicity, as well
as immunostimulating and high mucoadhesive prop-
erties [92] . These specific properties could explain the
great interest of many researchers and industries for new
applications of chitosan and its derivatives.
One of the patents retrieved [19] described imaging
NPs comprising positively charged chitosan, useful for
managing a tumor of an animal subject and for treat-
ing cancerous tumors. The advantage claimed is that
the NPs enhance imaging contrast quality or property
during an imaging procedure and enhance epithelial
permeation or intestinal paracellular transport. An
important application of nanotechnology is the prepa-
ration of dual-purpose NPs used simultaneously for
diagnosis and therapy. The term ‘theranostics’ was
coined to define agents that combine diagnostic and
therapeutic capabilities at the same time, allowing
imaging to be performed not only before or after, but
also during a treatment regimen.
Another patent [20] claimed a composition of NPs,
where each NP comprises N-palmitoyl chitosan,
adapted for sensing a change of an environmental pH
intracellularly or extracellularly; discriminating var-
ied acidity of cellular organelles and for treating dif-
ferent types of tumors, with enhanced intracellular
localization and anticancer agent release.
618 Pharm. Pat. Anal. (2014) 3(6)
Univ-Univ
Gov-Univ 1.6%
1.4%
2.4% -Com
Gov
Com-Com Hosp-Univ 0.8%
5.3% Gov-Univ-Com 0.6%
Univ-Hosp-Com 0.6%
Univ-Com Hosp-Com 0.2%
6.1%
Univ-Hosp-Gov 0.2%
Upon entering the tumor site, it is desirable that the
therapeutic agent be released in a controlled fashion in
order to reach cytotoxic levels. To achieve this, several
strategies are used that include pH-, temperature- and
ultrasound-stimulated release [1] .
The Massachusetts Institute of Technology and
the University of California have been granted nine
and eight patents, respectively, for distinct types of
nano-sized carriers, such as polymeric NPs, magnetic
NPs, liposomes and protein-based NPs for various
drug-delivery applications.
A pharmaceutical composition useful for the treat-
ment of prostate cancer and solid tumors expressing
prostate specific membrane antigen comprising NPs
containing a therapeutic agent and targeting moiety
which is prostate specific membrane antigen ligand is
claimed [21] . The main advantages claimed are that the
NPs exhibit highly controlled properties and deliver
the drug while reducing side effects. A big obstacle
in the efficacy of existing therapies is the inability of
the chemotherapy agents to achieve high concentra-
tions in the tumor without causing severe side effects.
Formulations using NPs try to overcome this target-
ing tumor cells specifically, thereby avoiding systemic
side effects.
The patent [22] claimed a composition comprising
one or more NPs, each one modified with ligands, for
delivery of a therapeutic agent to a target expressing a
receptor and where each NP is conjugated to the sur-
face of the carrier. The method is useful for treating a
disease state selected from breast cancer, ovarian can-
cer, lung cancer and lymphoma, among others. Sev-
eral studies have investigated the possibility of active
accumulation of drugs in tumors, by coating NPs
with ligands that target receptors highly expressed on
tumor cells.
future science group

Table 3. Main applicants with over six patents granted.
Country Assignees with six or more patents
USA GP Medical Inc. and Tsinghua University partnership (14) Polymer, liposome
  MIT (9)
  University of California (8)
China Shandong University (8)
  Southeast University (6)
  Fudan University (6)
  Nanjing University (6)
South Korea Korea Inst. Sci & Technology (8)
  Yonsei Industry-Academic Cooperation Foundation (6)
  Snu R & DB Foundation (6)
South Africa Abraxis Bioscience LLC (9)
NP: Nanoparticle.
China
As shown in Table 3, four applicants, all universities,
stand out for having been granted six or more patents
in China.
Shandong University has been granted eight patents,
four of which are for the preparation of NPs involving
polymers (polyethyleneglycol-poly(L-lactide), chito-
san, block copolymer based on ethylene oxide and pro-
pylene oxide as a drug carrier), one is for a lipid carrier,
and three are for nano-preparations of a drug, [23] for
adriamycinone derivative nanocrystallization, [24] for
etoposide nanosuspension and [25] for N3-O-toluoyl
uracil nanosuspension.
Southeast University has six patents, two of which
are for polymer-based NPs. The NP in [26] comprises
chitosan and micromolecular chemotherapeutics with
core shell structures, while [27] describes a drug-carried
microsphere containing hydroxypropyl β-cyclodextrin
and paclitaxel, which enhances the anticancer effect
of paclitaxel. Similar to other anticancer drugs, pacli-
taxel is inherently water insoluble, given its lipophilic
nature. While this degree of hydrophobicity is favor-
able for drug permeation through cell membranes,
intravenous administration would result in rapid drug
aggregation and formation of capillary embolisms. By
encapsulating the drug within the NP, the apparent
solubility of the drug can be significantly increased [1] .
This university also has two patents that employ
magnetic NPs. The innovation protected by [28] is a
magnetic NP polyethylenimine-manganese zinc iron
oxide with transfection efficiency and reduced cyto-
toxicity, while [29] protects a method for preparing dau-
norubicin and 5-bromotetrandrine-carrying magnetic
nano ferroferric oxide particles. Magnetic NPs comprise
an important class of nanomaterials commonly inves-
tigated for their potential use in medicine. Iron-based
future science group
Nanoparticles applied to antineoplastic agents  Patent Review
Class of nanoparticle in the patent
Polymer, magnetic NPs
Polymer, magnetic NPs, liposome, protein
Polymer, lipids
Polymer, magnetic NP, liposome, metallic NP
Polymer, protein, dendrimer
Polymer, protein, dendrimer
Polymer, magnetic NP, protein
Protein, polymer, metallic NP, dendrimer, magnetic NP
Lipids, polymer, magnetic NP, liposome, metallic NP
Protein
NPs as well as other elements, including cobalt and
nickel, are the most studied. New treatment strategies
should be explored, such as the use of noble-metal NPs,
since these metals are inert. As an example, gold NPs
have been used without any significant side effects being
observed. Another strategy would be to increase the
hydrophobicity of the metallic NP surface, since this is
directly related to toxic effects in living systems [3] .
Another university with six patents is Fudan, most of
which claim polymeric NPs. The patent [30] is for a drug
delivery system that comprises high polymer material,
polyethylene glycol, polypeptide, therapeutic genes and
chemotherapy medicine. This system specifically deliv-
ers the drug to tumor cells. Meanwhile, [31] describes a
preparation of amphiphilic NPs with excellent stabil-
ity used for the delivery of the active ingredient, such
as chitosan and 5-fluorouracil methotrexate. Reference
[32] uses polyethylene glycol-polylactic acid to build
into micelle, with KC2S-biotin-streptavidin for treat-
ing brain disease. The nanocarrier system crosses the
blood–brain barrier. For the biological action of mag-
netic NPs, it is necessary their functionalization with
biomolecules. This strategy allows these NPs to circu-
late for a prolonged period of time and target a particu-
lar organ. Polyethylene glycol and other polymers are
widely used to prolong nanocarriers half-life, increasing
their stabilization and biodistribution.
Most of Nanjing University’s patents use polymer NPs
as drug carriers. The patent [33] provides protection for
a preparation of glucan/polycaprolactone amphiphilic
Key term
Nanocarrier: A nanomaterial used to transport another
substance, such as a drug. Commonly used nanocarriers
include polymers, liposomes, solid lipids, magnetic particles
and metallic particles.
www.future-science.com 619
Patent Review  Fierro, de Menezes Alencar, Lins Mendes et al.

CN102406949, KR1267318

CN102813915, US8318198, US8198246,

US8304408
Dendrimer
(2.3%) Liposome
Li CN101804021, CN102240267, CN101889983, CN101982168, CN102397554,
(4.6%) CN102406949, CN102504290, CN102885785, CN10110665, CN102127231, CN101879427,
CN101856432, CN102600082, CN102389399, KR1263732, KR1286059, KR1367940,
KR1223484, KR1184928, KR1308746, KR1267313, KR1267318, KR993024, US8257740,
US8187570, US8221795, US8361439, US8449915, US8048404, US8283317, US8226928,
Polymer US8114380, US8574544, US8187571, US8287905, US8062668, US8591905, US8246968,
(45.3%) US8580253
Main classes of
nanoparticles
claimed in CN102294035, CN102772809,
S N
the granted CN102225209, CN102302503,
Patents KR1209266, KR1230384, US8445021
Magnetic
particle
(8%)

CN10058386, KR1085203, KR1000358,

KR993024
Lipid
(4.6%)
Peptides CN103007290, KR1349360, KR1233850,
KR1276180
Protein Metal
(4.6%)
Protein/peptide
(15%)
CN102397554, KR1223484, KR1254726, KR1332621,
ZA201107556, ZA201201531, ZA201206959, ZA201108999,
ZA201207329, ZA201106659, ZA201206960, ZA200707491,
US8263133

Figure 3. Main classes of nanoparticles claimed in the granted patents.

block polymer medicine carrying NPs. The amphiphilic
block polymer has good hydrophilic, biological degrada-
tion and biological compatibility. The patent [34] is for
tea polyphenol/chitosan NPs used as drug carriers.
South Korea
Three institutions from South Korea count amongst
the top recipients of patent protection for their innova-
tions in the last 4 years. The Korea Institute of S&T has
eight patents, six of which are for polymeric NPs, such
as polyoxyalkylene derivatives of fatty acid esters, poly-
oxyethylene sorbitan monooleate as a nanocarrier with
high water solubility, and excellent biocompatibility and
specificity.
SNU R & DB Foundation was granted six patents
in the period under study. Their focus tends to be on
the use of lipid NPs for drug delivery, either for cancer
treatment [35] , prevention [36] or diagnosis [37] . The char-
acteristics of the patented NPs are the absence of side
effects and reduced toxicity.
The Yonsei Industry-Academic Cooperation had six
patents granted in South Korea in the study period.
They are for a variety of NPs: two for polymers [38,39] ,
two for peptides [40,41] , one for a magnetic NP [42] and
one for a metallic NP [43] . There was also found to be a
trend toward photothermal therapy for treating cancer.
South Africa
Abraxis BioScience LLC (currently a subsidiary of Cel-
gene Corporation) is a biopharmaceutical company
whose portfolio includes eight patents granted in South
Africa for protein-based NP compounds, the greater
part of them being NPs comprising albumin and a
water-insoluble active agent that are useful for treat-
ing several types of cancer, for example, squamous cell
cancer and gastric or stomach cancer [44] .
The patent [45] claimed a composition comprising
NPs having a taxane and an albumin useful for assess-
ing the responsiveness of an individual to treatment and
for treating a cancer that is highly fibrotic and/or has a
dense stroma.
Protein-based NPs for delivering drugs are particu-
larly interesting as they hold certain advantages, such
as greater stability during storage and in vivo, as well
as being nontoxic and non-antigenic. Albumin is an
attractive candidate for NP preparation, since besides

620 Pharm. Pat. Anal. (2014) 3(6) future science group

 Nanoparticles applied to antineoplastic agents  Patent Review

being easy to purify and soluble in water, it has been Conclusion

shown to be biodegradable, nontoxic and metabolized
in vivo to produce innocuous degradation products [93] .
Although early predictions for commercialization
are promising, there are some difficulties that challenge
the future of nanomedicine. Its success is dependent
upon the effective protection of intellectual property
rights, an essential tool in a modern economy [94] .
Future perspective
The analysis of the granted patents within the past
4 years identified a mix of NP classes with the majority
of patent interest focused on few of them. Although
polymers and proteins engendered the largest patent
count, it is not possible yet to say whether this inter-
est will translate into more drug candidates entering
clinical development, since at the moment, despite
massive research on NP systems for cancer detection
and therapy, there are not many in the market. Even
though NP-based imaging and treatment are striv-
ing to advance into clinical trials, the call for a per-
sonalized medicine has made NP-based theranostics a
research hotspot. A combined technique can lead to
the acceleration of drug development, enhanced dis-
ease management, reduced risks and costs. Further-
more the same properties that make NPs a desired
technology for therapeutic intervention may also cause
adverse effects. It is thus important that new formula-
tions take into account the fine balance between the
efficacy and toxicity of these particles.
In our opinion, future patenting activities in the
NPs field will persist to represent a mix of targets, and
significant innovation will occur as key challenges
in cancer treatment can be overcome by these NP
formulations.
Nanotechnology and nanomedicine are awakening
increasing interest on the part of the scientific commu-
nity, industry professionals and governments because
of the countless potential new ways they can be used
in health.
Landscape analysis can be a powerful tool for devel-
oping policy and business strategy, and this analysis of
patents granted around the world shows that the main
actors in industry and/or academia are focusing on devel-
oping polymeric and protein NPs with the clear purpose
of maximizing therapeutic efficacy and reducing toxicity
in cancer treatment, diagnosis and prevention.
The application of NPs in medicine is an emerg-
ing field with the potential to have a positive effect on
human healthcare. Nanotherapeutics will cross new
frontiers in the understanding and practice of medi-
cine, improving clinical outcomes and significantly
enhancing patients’ quality of life.
Acknowledgements
The authors thank CAPES (Coordenação de Aperfeiçoamento
de Pessoal de Nível Superior) for the access to the Derwent
Innovation Index database [18] , available at the CAPES Journal
Portal (www.periodicos.capes.gov.br/).
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial inter-
est in or financial conflict with the subject matter or mate-
rials discussed in the manuscript. This includes employment,
consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this
manuscript.

Executive summary
Background
• Currently there is a diversity of nanoparticles being investigated for cancer therapeutics and diagnostics. The
present review describes the results of a survey of patent applications between 2000 and 2014, and analyzes
the patents granted within the last 4 years in the field of nanoparticles applied to antineoplastic agents.
Patent applications
• There is a clear rise in the global interest along the last years, shown by a significant growth in the number of
applications, with a total of 4235 documents filed and more than 2500 assignees.
Granted patents
• Of the original 4235 applications filed, it was found that around a third (1335) were granted, being 761 in the
last 4 years, corresponding to 508 distinct patents.
• The analysis of these 508 documents showed that research and development of nanoparticles for use in
oncology takes place mainly at universities and companies, since combined they account for almost 70% of all
the patents granted.
• The USA, China, South Korea and South Africa stand out for the number of applicants with six or more
granted patents each, summing a total of 86.
• The most common classes of nanoparticles are claimed, with polymers and proteins generating the largest
patent count and a number of documents protecting cancer-related uses comprising treatment, prevention,
detection/diagnosis and imaging.

future science group www.future-science.com 621

Patent Review  Fierro, de Menezes Alencar, Lins Mendes et al.
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