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-Myers and Sanofi-Aventis said the patent is valid and enforceable. A Sanofi spokesman said a court injunction barring generic Plavix remains in effect, and Sanofi will respond to the patent office re-exam "in due course."

An Apotex spokesman declined comment.

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. In December, the U.S. Court of Appeals for the Federal Circuit upheld a lower court's ruling that the patent is valid and enforceable. Apotex has appealed to the U.S. Supreme Court.

In its request for a re-exam, Apotex said claims in the U.S. Plavix patent should be reconsidered because so-called "prior art" anticipated the claims, including information in Sanofi's application for a Canadian drug patent. This prior art would have taught anyone skilled in the art of drug development how to invent Plavix, Apotex claims.

The patent office mailed its decision to re-examine the Plavix patent to Sanofi on Monday, according to the patent office's Website.

Historically, the patent office has granted most requests for patent re-exams, but a minority of such exams result in the cancellation of all of a patent's claims. 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 rose 10 cents to $21.77; Sanofi's American depositary shares fell 2 cents to $31.70.

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