Medytox and Daewoong Pharmaceutical continued to brawl over the origin of the latter's Nabota strains, as each company yielded different analysis results.
The two companies had conducted an appraisal test by providing the strains of their botulinum toxin (BTX) to experts selected by each company as part of an ITC order since July.
In line with the ITC submission schedule, Medytox submitted its report to the ITC on Sep. 20, and Daewoong submitted its report on Oct. 11.
While the reports were not available to anyone other than a legal representative separately designated by the ITC's order, the representatives of the two companies have agreed to disclose the conclusions of the report in a separate agreement.
Medytox said the results of the analysis proved that Daewoong stole its BTX strain.
"Professor Paul Keim at Northern Arizona University, who analyzed Daewoong's BTX strains, submitted a report to the ITC, which confirmed that that the botulinum strain of Daewoong was derived from the Medytox," the company said. "The professor further stressed that it is virtually impossible to identify and isolate the botulinum bacteria of Daewoong in the natural environment of Korea."
While Daewoong submitted a rebuttal report from Professor David Sherman of the University of Michigan, the report did not support Daewoong's argument that the company managed to isolate and identify the BTX strains from Korea's soil, Medytox added.
Medytox said it had consistently insisted on the full disclosure of Professor Keim's report, but Daewoong only agreed to disclose a part of the report.
"We urge Daewoong to agree on unveiling Medytox's full report," the company said.
In response, Daewoong said that its investigation into Nabota's strain demonstrated that the two strains are genetically different.
"Medytox's report is riddled with errors," Daewoong said. "Professor David Sherman, Daewoong's designated expert, said in a rebuttal report that the method of genetic analysis on the Medytox side was inappropriate."
Instead of Medytox's method, which can produce only partial results, Daewoong also confirmed that the strains of the two companies differed in various areas through a direct comparison of whole-genome sequencing (WGS), the company added.
Notably, Sherman found that the 16s rRNA gene sequences of the two strains are different from each other.
"Since 16s rRNA genes evolve very slowly, it is common to assume that the two BTX come from different strains," the company said.
Professor Kleim, Medytox’s expert, rebutted Daewoong’s argument, saying that some of the differences in the two strains' genes were mutations in the growth of the strain.
Sherman also refuted such claims and said that the numerous differences in direct comparative analysis of the entire gene sequence are not because of mutations in the simple passaging process but because the strains of the two companies originate from separate sources.
The recent squabble between the two companies is an extension from their previous dispute over the results of spore formation tests of both strains.
Medytox had claimed that its strains are the only ones in the world known not to form spores under any conditions and that Daewoong can't isolate and identify the same strains from the soil.
The company made such comments official as it professed that its strains do not form spores under any conditions, including those for appraisal testing, at a court hearing in January of this year.
However, a report by Dr. Andrew Pickett, an investigator for Medytox, showed that its strains also formed spores when tested under the same conditions as Daewoong's test.
While the spore formation contradicted the company's previous statement, Medytox said that Daewoong's test that confirmed spore formation was unconventional.
"Daewoong had submitted to Health Canada that its strains do not form spores," Medytox said. "However, the company tried to sway public opinion by selecting and disclosing only favorable information that its strain forms spores under unusual experimental conditions."
After Medytox submitted the result that its strains also form spores when using Daewoong's unusual experimental condition, Daewoong has failed to refute such claims during the ITC litigation process, the company added.
Regarding such accusations, Daewoong quoted their investigator Professor Brenda Wilson, who pointed out that there were various errors in the contents of Dr. Pickett's test, which questioned the validity of the test.
"Even if there are no errors in Medytox's test, the spore-forming properties of the two strains were different," Daewoong said. "The two strains showed the same results in only eight combinations under 18 test conditions, including heat treatment, anaerobic, aerobic, and incubation periods, and mismatched in the other conditions."
Based on such reports, Daewoong has confirmed that the strains of the two companies clearly showed that the genotypes of the two strains were different from each other, the company added.
Amid the prolonged dispute between the two companies, all eyes are now on the ruling from the ITC. The ITC decision is likely to come out no later than next June, as the U.S. customs act mandates that all ICT procedures be finalized within 15 months, industry watchers said.
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