The U.S. Patent and Trademark Office has ordered a re-examination of the patent for the blockbuster anti-clotting drug Plavix, citing new questions about the drug's patentability.

A lawyer for Canadian generics manufacturer Apotex Inc. had requested the re-exam in June, saying that certain drug research conducted prior to the Plavix patent's 1989 issuance should render the patent invalid.

Sanofi-Aventis SA (SNY) of Paris and New York-based Bristol-Myers Squibb Co. (BMY) co-market Plavix, which last year had about $8.6 billion in global sales, ranking it as the second best-selling prescription drug in the world behind Pfizer Inc.'s (PFE) Lipitor cholesterol pills. Sanofi, which discovered the drug, owns the patent.

Spokespeople for Bristol and Apotex declined immediate comment, and a Sanofi spokesman couldn't immediately be reached.

It's the latest attempt by Apotex to overturn the Plavix patent to clear the way for it to sell cheaper generic copies of the drug before the patent expires in 2011 (market exclusivity is scheduled to last into 2012 due to an extension for having studied the drug in children).

Previous attempts by Apotex to overturn the Plavix patent in federal court have been unsuccessful; Apotex has appealed its most recent loss to the U.S. Supreme Court.

Historically, the patent office has granted most requests for patent re-exams, but a minority of such exams result in all of a patent's claims being canceled. The re-exam process can take up to two years. Recently, the patent office also ordered the re-exam of the U.S. patent for Merck & Co.'s (MRK) blockbuster allergy and asthma drug Singulair.

Apotex briefly sold generic Plavix in the U.S. in 2006, flooding the market with enough pills to hurt sales of branded Plavix for months, but was ordered to stop by the U.S. judge overseeing the patent dispute. A proposed settlement of the patent litigation in 2006 had fallen apart, and eventually led to U.S. criminal charges against Bristol and a former executive due to a side deal in the proposed settlement. The fiasco led to the ouster of Peter Dolan as Bristol's chief executive in 2006.

Bristol shares fell 4 cents to $21.63; Sanofi's American depositary shares fell 3 cents to $31.69.

-Peter Loftus; Dow Jones Newswires; 215-656-8289; peter.loftus@dowjones.com