**3. Intellectual property landscape in drug repurposing**

The drugs may either be on-market (ONM) or off-market (OFM) drugs. Further, the ONM drugs may be on-patent (ONP) or off-patent (OFP) drugs. As per the latest version of the United States Food and Drug Administration-Orange Book (US FDA-OB), 1577 drugs are ONM drugs and 1543 drugs are OFM drugs. Out of 1577 ONM drugs, 1142 drugs lack patent/exclusivity claims and could be utilized for drug repositioning projects [10]. Nevertheless, obtaining patent protection for known drugs can be a challenging task. The repurposed drug can be patented in the United States if the drug constitutes patentable subject matter under 35 U.S.C. § 101. According to 35 U.S.C. §, 101 repurposed drugs may be patented provided its new indication or use has not been published before. Nevertheless, the eligibility of patentability of "therapeutic use" varies between jurisdictions from country to country [11]. While the patent based on "therapeutic use" is possible in the United States and some other countries, it is not permitted in India. Therefore, another approach to obtain a patent for previously known drugs in India is to draft claims for novel pharmaceutical formulations. On the contrary, if a drug to be repurposed is still under patent protection, then that drug can either be acquired or in-licensed from the patentee. Hence, patent protection of repurposed drugs for new indications is possible. However, initial experimentation should establish the usefulness of the drugs along with robust invention disclosures and detailed formulation applications may be directed to the patent office [12].

### **4. Strategies involved in drug repurposing**

Drug repurposing in infectious diseases involves different strategies by integrating both vHTS and HTS methodologies to identify a drug molecule, a microbial target, and an immunopathological pathway to fight against an infectious pathogen. The various strategies involved are (i) computer-aided (structure-based [13] and ligand-based pharmacophoric [14]) repurposing, (ii) phenotype-based HTS aided repurposing [15], (iii) 'omics-based drug repurposing [16], (iv) drug-disease biological pathway analysis [17, 18], (v) poly-pharmacology-based drug repurposing [19, 20], and (vi) serendipity [21], which are summarized in **Figure 2**.

**Figure 2.** *Strategies involved in drug repurposing.*

However, the plausible drugs for anti-microbial repurposing may fall into three different evaluating scenarios and two different approaches, namely, "on-target repurposing" and "off-target repurposing" [22] as shown in **Figure 3**.

#### **4.1 Computer-aided drug repurposing**

vHTS is an efficient approach to identify compounds for drug repurposing. Where vHTS is a generalized term for different screening filters, it is categorized under two broad classes of virtual screening for drug repurposing, that is, (i) structure-based drug repurposing and (ii) ligand-based pharmacophoric repurposing.

#### *4.1.1 Structure-based drug repurposing*

Protein data bank (PDB) is the largest compilation of structural data on microbial target proteins. Presently, there are 62,402 structural deposits related to bacterial target proteins and 9653 structural deposits related to viral target proteins in PDB.

Further, nearly 60% of these proteins are complexed with a biologically relevant ligand, which provides information about the shared binding sites and amino acids of the target site involved in intramolecular interactions with the ligand. These proteins are utilized for structure-based drug repurposing by virtual screening (docking studies) the drugs for repurposing in comparison to the ligand. The ligand in comparison could either be the one that is already complexed at the target site or any other approved drugs available as a particular modulator of the target site. The selection of screened drugs for repurposing is completely based on scoring and drug interactions. To complement the structures available in the PDB, another method used for structure-based screening is called homology modeling. Homology *Trends in Molecular Aspects and Therapeutic Applications of Drug Repurposing for Infectious… DOI: http://dx.doi.org/10.5772/intechopen.100858*

**Figure 3.** *Various scenarios and approaches in drug repurposing.*

modeling can generate 3D structures of even those proteins whose structures are difficult to obtain through X-ray crystallography. Apart from these sources, there are other databases of high-quality 3D protein models, such as SWISS-MODEL Repository (SMR) to support structure-based drug repositioning pipelines [13].
