Lifecycle management of orphan drugs approved in Japan.

BACKGROUND: The development of orphan drugs (ODs) is challenging from both development and business perspectives because of their small patient populations. To overcome such business challenges, lifecycle management (LCM), which maximizes profits by increasing sales and extending product lifetimes, is important to overcome the business challenges arising from their small patient populations. To clarify the activities of the LCM of ODs, we investigated additional indications that contribute to market expansion and marketing exclusivity using the patent extension and re-examination system of ODs approved in Japan between 2004 and 2019. RESULTS: The 203 ODs consisting of 173 active ingredients were approved in Japan between 2004 and 2019. Sixty-eight (39%) of the 173 active ingredients have additional indications, of which 57 have at least one non-OD indication. Three-fourths of the 203 ODs had patent rights, and most of them included substance or use claims. Although the re-examination period for most ODs was 10 years after the approval, most patents had a longer duration than the re-examination period. CONCLUSIONS: Pharmaceutical companies were actively adding non-OD indications and were emphasizing the use of patent rights by registering extensions of substance or use patents for exclusive marketing periods. These results indicate that LCM through the addition of indications and registration of patent extensions is carried out as a strategy for many ODs in Japan, similar to the LCM of general non-ODs.

Patent production is a prerequisite for successful exit of a biopharmaceutical company.

Patents are especially important for the business of drug discovery; however, their importance for biopharmaceutical companies has not been revealed quantitatively yet. To examine the correlation between patents and long-term business outcome of biopharmaceutical companies we analyze annual number of patent families and business conditions of 123 public-listed biopharmaceutical companies established from 1990 to 1995 in the USA. Our results show the number of patent families per year correlates well with the business condition: average of the bankruptcy group is significantly smaller than those of the continuing and the merger and acquisitions (M&A) groups. In the M&A by big pharma group, the acquisition cost correlates with the number of annual patent families. However, patentability and strategy of foreign patent application are not different among the groups. Therefore, the productivity of invention is the key factor for success of biopharmaceutical companies.

Analysis of 10 years drug lifecycle management (LCM) activities in the Japanese market.

We investigated drug lifecycle management (LCM) activities in the Japanese market by examining new and updated approvals by the Pharmaceuticals and Medical Devices Agency (PMDA) between 2001 and 2010. PMDA gave a total of 726 approvals, of which 263 and 463 were new and updated approvals, respectively. Approvals for new indication comprised of more than 60% of updated approvals regardless of chemical or biological entities, therapeutic area and the company nationality. The case study on anti-rheumatoid arthritis biologics showed that the addition of new indications accelerated their sales exponentially. Thus, the development of new indications is an effective LCM approach for creation of new values of existing drugs.

Ion-trap mass spectrometry unveils the presence of isomeric oligosaccharides in an analyte: stage-discriminated correlation of energy-resolved mass spectrometry.

Mass spectrometry, especially tandem mass spectrometry, has been widely used in the field of analytical sciences for handling biological and chemical samples. The technique resolves molecular and fragment ions based on the mass to charge ratio. Energy-resolved mass spectrometry (ERMS) further provides an activation energy-related factor in the dissociation reaction. Therefore, it is a very powerful technique that can discriminate isomeric compounds. Despite the power of ERMS, useful information cannot be obtained when an analyte contains structural isomers. Carbohydrates carry multiple chiral centers, thus oligomers of monosaccharides can form a vast number of structural isomers. We decided to use such species in our endeavors to establish a method of identifying the 'purity' of an analyte solely based on mass spectrometry. In the present paper, we describe a stage-discriminated spectral correlation of ERMS, which not only enables identification of the presence of contaminants in an analyte, but also provides information regarding the 'purity' of fragment ions.