A jury found in 2002 that RIM infringed on NTP-owned patents that cover an email system on its BlackBerry mobile devices.
Appeals were thrown out and settlement talks failed. NTP ended up seeking an injunction against RIM that would force the vendor to shut down its service in North America.
Wednesday's rejection was based in part on information that had not been considered in the 2002 trial.
The Patent Office ruling leaves only one of the disputed NTP patents in place. The remaining patent has already been rejected twice and a final ruling is expected soon.
NTP still has the opportunity to appeal against the decision and has indicated in the past that it plans to do so. The overall process is expected to be dragged out for years.
RIM said in a statement that it was confident that the invalidation would withstand the appeal process.
While the invalidation is an important victory for RIM, the two firms are still scheduled to appear before a judge this Friday.
The judge is expected to rule on NTP's demand for an injunction against RIM that would force the vendor to discontinue its service in North America.
RIM unveiled a contingency plan earlier this month which it claims will allow the company to continue operating if the judge rules in NTP's favour. But analysts have questioned the stability and feasibility of the workaround.
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