intent to deceive - sandoz case
i guess one can construe indirect, clear and convincing evidence of intent to deceive the PTO to get a false patent issued
"YEDA and, on information and belief, TEVA’s assertions to the PTO regarding
the higher toxicity of higher molecular weight copolymer-1 compositions were so directly
contradictory to their statements to the FDA and the assertions made in the Bornstein et al. paper
that the contradiction cannot reasonably be interpreted as an error, but instead as an intentional
effort to deceive the PTO."
The Summary Basis of Approval for TEVA’s NDA reveals that TEVA, working
with YEDA, conducted numerous studies showing that copolymer-1 compositions having an
average molecular weight from 4.7 kDa to 13.0 kDa did not produce a statistically significant
toxic effect in rats and humans. These studies reported that copolymer-1 compositions with a
molecular weight above 10 kDa were not toxic to animals or humans. See Review and
Evaluation of Pharmacology Toxicology Data from Teva’s NDA #20-622, undated, and Review
and Evaluation of Clinical Data: Safety, from Teva’s NDA #20-622, dated January 30, 1996,
Appendix 7.b.1 and 7.b.2
YEDA and, on information and belief, TEVA also made material omissions by
failing to highlight adequately the significance of the Johnson et al. and Bornstein et al. papers to
the PTO. This is evidenced, as just one example, by YEDA and, on information and belief,
TEVA’s failure to cite the Johnson et al. and Bornstein et al. papers as references for the ’430
patent, the application for which was filed on February 27, 1998. Similarly, YEDA and, on
information and belief, TEVA failed to cite those papers as references for the ’847 patent, the
application for which was filed on December 14, 2001. The Bornstein et al. and Johnson et al.
papers were finally cited as references for the ’539 patent, the application for which was filed on
July 10, 2003. However, the two papers are listed near the end of nearly three pages of
references and their titles were not included in the listing. Both listings contained errors: the
journal for the Johnson et al. paper was listed as Neurobiology rather than Neurology, and the
Bornstein et al. paper was listed as authored by “Borenstein.”
The results presented by TEVA and YEDA to the FDA, that higher molecular
weight (i.e., 10.0 to 13.0 kDa) copolymer-1 compositions are not toxic, or no more toxic than
lower molecular weight copolymer-1 compositions (4.7 to 10.0 kDa), were consistent with a
paper published in the New England Journal of Medicine and co-authored by three individuals—
Ruth Arnon, Michael Sela, and Dvora Teitelbaum—listed on the four patents asserted by
Plaintiffs in the current case. In that paper, Murray B. Bornstein et al., A Pilot Trial of Cop-1 in Exacerbating-Remitting Multiple Sclerosis, 317 New Eng.J. Med. 408 (1987), the authors
reported that copolymer-1, with a molecular weight between 14 and 23 kDa (unspecified metric),
was well tolerated by patients, showing that copolymer-1 compositions with an average
molecular weight above 10 kDa were not toxic to humans. Bornstein et al. also reported that
administration of 14-23 kDa copolymer-1 was non-toxic during short-term and long-term
administration in mice, rabbits, and dogs.
In order to avoid certain prior art objections and to obtain its patents, YEDA and,
on information and belief, TEVA intentionally made false representations to the PTO regarding
the toxicity of copolymer-1 compositions. The false representations were directly contrary to
TEVA and YEDA’s own findings in its clinical trials, contradicted what TEVA and YEDA had
told the FDA, and were contrary to the published research findings of three of the listed
individuals on TEVA and YEDA’s patents.
