**4.1. Research and technology developments related to rabies control were diverse and polyspecific**

Given that the major research areas were veterinary sciences, virology, and immunology (Figure 4), and that the two most cited articles related to rabies control belonged to interdis‐ ciplinary research regions, i.e., agent-based modeling and economic analysis (Table 2), it is apparent that rabies research has diversified from classical to novel research areas. In partic‐ ular, new research is prospective and aims to accelerate the development of domestic and international management frameworks for rabies.

However, the methods used for rabies diagnosis and vaccine development are progressing if we take patent US 5332567 and US 6019978 as examples of the top 10 most cited patent applications (Table 5). These methods were characterized as being applicable to various other pathogens and were polyspecific. Given that current rabies vaccines aim to introduce new functions, e.g., animal rabies vaccines combined with other antigens [3], these polyspecific methods would contribute to further vaccine development.

## **4.2. Gap between research and technology development for rabies control**

We found that the number of articles related to rabies increased throughout the world, but the number of patent applications directed at rabies control was stable according to PCT and in each country. Given that only two of the top 10 most cited articles were directly related to rabies control, as shown in Table 2, and that none of the top 10 patent applications were specifically for rabies control, as shown in Table 5, it was not clear whether the articles were directly linked to the patent applications for rabies. Thus, it is not necessarily that research on rabies leads to technological developments related to rabies control.

## **4.3. The US, France, and the UK are the leading countries for rabies research**

Table 5. Top 10 most cited patent applications related to rabies control during 2001–2011

linkage

**Table 5.** Top 10 most cited patent applications related to rabies control during 2001–2011

exogenous DNA

mycoplasma, whereas none were specifically applicable to the rabies virus.

to rabies control during 2001–2011.

**Rank Cited number**

Recombinant virus

174 Trends in Infectious Diseases

(e.g. replication-defective adenovirus recombinant as a rabies vaccine carrier)

Organic active ingredient (e.g.

red bean-derived antiviral agent)

virus mutant for live vaccines)

infections caused by virus )

rabies vaccine)

organophosphorous compound for producing medicaments for therapeutic treatment of

Natural product, Chinese herbal extract (e.g.

Fabrication method (e.g. preparation method of

Mutant (e.g. attenuated recombinant rabies

237.

**2** 57 WO200366005 CONFORMA

**4** 40 WO200476677 INSTITUTE FOR

**6** 32 US6019978 WISTAR INSTITUTE

**8** 31 US6180111 MARYLAND

**10** 29 WO200454622 IMMUNOMEDICS

**9** 29 WO200775270 IBC

**5** 37 US20060228300 IBC

**control were diverse and polyspecific**

and international management frameworks for rabies.

**4. General overview of research and technology development related to rabies control based on bibliometric and patent analyses**

Immunoconjugates with an intracellularly-cleavable

**patent number applicants Title Contribution to rabies control**

The number of patent applications was calculated by patent family. In some cases, a patent belonged to two or more technology fields, so the total number of applications exceeded

Ansamycins having improved pharmacological and

**<sup>3</sup>** <sup>45</sup> WO200464759 CHIRON Use of tryptanthrin compounds for immune potentiation Yes (enhancement of the immune response to infections

Monoclonal antibody production by EBV transformation

Stably tethered structures of defined compositions with multiple functions or binding specificities

Table 5 shows the top 10 most cited patent applications related to rabies. All the patent applications were related to diagnostic or therapeutic methods for rabies, such as immunoconjugates (US 5332567, WO200454622), a vaccine carrier (US 6019978), and a monoclonal antibody production system (WO200476677). It was interesting that all the patent applications were applicable to various pathogens, such as bacteria, viruses, and

Replication-defective adenovirus human type 5 recombinant as a vaccine carrier

Yes (method of targeting a polyspecific diagnostic agent

Yes (method of treating or preventing infection

Yes (providing a neutralizing monoclonal human antibodies that recognizes antigens from various pathogens including rabies virus)

Yes (useful for treating subjects infected with various

Yes (more efficacious method in comparison with the currently used vaccinia rabies vaccine)

Yes (vector for cloning heterologous DNA encodes epitopes of interests from antigens of veterinary

for virus infection including rabies)

pathogens including rabies virus)

pathogens including rabies)

pathogens including rabies virus)

Yes (useful for therapeutic conjugates against pathogens including rabies virus)

Vaccine delivery system Yes (useful for the diagnosis of viral diseases including rabies)

Multivalent immunoglobulin-based bioactive assemblies Yes (useful for treating infection with various

including rabies)

including rabies)

immunoconjugates

Table 4. Technology fields of patent applications related to rabies control during 2001–2011

**Table 4.** Technology fields of patent applications related to rabies control during 2001–2011

Other 10 14 5 2

**Prevention (primarily vaccine)**

Protein (e.g. chimeric rabies G protein ) 18 13 15 0

Peptide (e.g. antigenic peptide of rabies virus) 10 8 14 0

**Diagnosis (detection of virus, antibodies)**

60 12 42 9

17 2 36 0

9 0 24 2

31 7 15 8

10 1 5 0

**Treatment (medical drugs for post-exposure prophylaxis etc.)**

**Other**

biological properties

of B cells

**1** <sup>101</sup> US5332567 IMMUNOMEDICS Detection and treatment of infections with

**3.6. Top 10 most cited patent applications**

THERAPEUTICS

RESEARCH BIOMEDICINE

PHARMACEUTICALS

**7** 31 WO9800166 RHONE MERIEUX Recombinant canine adenovirus (CAV) containing

OF ANATOMY & BIOLOGY UNIVERSITY OF PENNSYLVANIA

UNIVERSITY OF

MCCALL JOHN DOUGLAS

PHARMACEUTICALS

Our bibliometric and patent analyses using the Web of Science®, DWPI, and DPCI highlighted five main features of the trends in research and technology development related

**4.1. Research and technology developments related to rabies** 

Given that the major research areas were veterinary sciences, virology, and immunology (Figure 4), and that the two most cited articles related to rabies control belonged to interdisciplinary research regions, i.e., agent-based modeling and economic analysis (Table 2), it is apparent that rabies research has diversified from classical to novel research areas. In particular, new research is prospective and aims to accelerate the development of domestic

However, the methods used for rabies diagnosis and vaccine development are progressing if we take patent US 5332567 and US 6019978 as examples of the top 10 most cited patent The survey demonstrated that the US led rabies research because it had the highest percentage of total articles related to rabies, i.e., 32.5% of the total. France ranked second (10.6%) but there was a big difference compared with the US. These two countries and the UK were also the top three producers of articles in the area of infectious diseases (Table 1). Four of the top five organizations that published articles related to rabies were also in these three countries. These results showed that the US, France, and the UK were the undisputed leaders in research on rabies and all infectious diseases.

### **4.4. Brazil was a particularly productive country for rabies research**

Like the US, France, and the UK, Brazil was considered to be a productive country for rabies research because it published the fourth highest number of articles (Table 1). The Universidade de Sao Paulo was ranked fourth among the top five organizations (Figure 3) and it played a leading role in rabies research in Brazil.

on technology development. Science linkage is an indicator of technological innovation, which is based on calculating the number of non-patent references such as articles, which are an indicator of the degree of science related to patents, i.e., the number of articles cited per patent [31]. There are technological limitations to science linkage, but many studies have aimed to measure the linkage of patents filed in the US and Europe [31]. From this perspective, meas‐ uring science linkage may be a challenge during future surveys of the trends in research and technology development related to rabies control. This challenge will also apply to zoonoses

Trends in Research and Technology Development Related to Zoonosis Control Based on Bibliometric and Patent…

http://dx.doi.org/10.5772/57566

177

The study described in this chapter was supported by a Japanese Grant-in-Aid for Scientific Research (KAKENHI) (research project number 23580435). We thank Mr. Mitsuaki Baba

[1] Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P. Global

[2] Lembo T, Hampson K, Kaare MT, Ernest E, Knobel D, Kazwala RR, Haydon DT, Cleaveland S. The feasibility of canine rabies eliminations in Africa: Dispelling doubts with data. PLOS Neglected Tropical Diseases 2010; 4 e626. http:// www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000626 (accessed

[3] Tordo N. New developments in rabies vaccines. OIE Global Conference on Rabies Control, 7-9 September 2011, Seoul, Republic of Korea. http://www.oie.int/eng/ A\_RABIES/Abstracts\_rabiesConf/abstract1-6/S2/Tordo.pdf (accessed 15 August 2013)

trends in emerging infectious diseases. Nature 2008; 451 990-994.

(Property Co., Ltd.) for his technical support to survey patents.

1 National Institute of Science and Technology Policy (NISTEP), Japan

Hiromi Takahashi-Omoe1\* and Katsuhiko Omoe2

\*Address all correspondence to: omoe@nistep.go.jp

in general.

**Acknowledgements**

**Author details**

2 Iwate University, Japan

15 August 2013)

**References**

Brazil may have a high level of rabies research because this country has initiated nationwide public campaigns to vaccinate dogs and cats against rabies, which have demanded studies to assess the antibody levels in vaccinated animals [29]. Moreover, research on rabies control has been active because the population has a serious risk of infection given the close relationships between these potential zoonosis-transmitting animals and humans [29].

#### **4.5. Development of patent applications for rabies control in China**

China exhibited a remarkable increase in patent applications (Figure 5). It was significant that China overtook the US with respect to the number of patent applications after 2007. From a technological perspective, patent applications related to natural products and Chinese herbal extracts increased greatly, as described in section 3.5.

The Chinese statistics showed that 1,633,000 patent applications (the total number of invention patents, design patents, and utility models) were filed with the State Intellectual Property Office (SIPO) by 2011, with a greater than threefold increase during 2005 alone [30]. This remarkable increase in the overall volume of patent applications in China may be attributable to the subsidization policy specified by the China Elements of Strategy for Intellectural Property Right, which facilitated the creation, application, protection, and management of intellectual property rights in 2008. Thus, the notable increase in overall patent applications after the change in China's policy may have led to the increased number of patent applications related to rabies control.
