Sanofi-Aventis is doing everything possible to cajole, pressure and manipulate Genzyme Corp into entering acquisition talks based on its opening offer of $69 a share.

Genzyme on Monday rejected Sanofi's offer, which is worth about $18.5 billion, saying it undervalues the company, and shareholders say they will back the board if Sanofi attempts a hostile offer.

The French drugmaker's advisors have promoted the idea in the media that Sanofi will not significantly raise its bid, and have hinted the company will walk away if the Cambridge, Massachusetts-based biotech company refuses to come to the table.

But Genzyme's shareholders are unimpressed by the rhetoric, and won't accept anything under $75 a share, according to feedback from 13 Genzyme shareholders on Monday, with some saying they will hold out, in the event of a tender offer, for at least $80.

I think, with what they are offering, Sanofi will get as far with Genzyme's investors as they did with its board, said Michael Obuchowski, chief investment officer at First Empire Asset Management, who said that if Sanofi goes hostile he would not tender his shares for much under $80 a piece.

If an acquisition doesn't happen I would not be heartbroken, he said. But at about $80 a share it might make sense to sell.

Shares of Genzyme, which is one of the world's leading makers of drugs for rare genetic disorders, rose nearly 4 percent to $70.13 in afternoon trading.

On Monday, Sanofi Chief Executive Chris Viehbacher attempted to throw water on hopes among Genzyme investors that a second pharmaceutical company bidder might emerge.

The number of players who can mobilize $18.5 billion in cash for Genzyme is pretty limited, he said on a conference call with analysts.

So far, no other bidder has emerged, but that is not to say one won't, especially given the indirect presence of billionaire activist Carl Icahn on the company's board.

In June, Icahn abandoned a threatened proxy fight at Genzyme in return for the acceptance of two of his representatives.

Icahn has a history of pulling other players into the mix when he is involved in the sale of a company, even against expectations.

In July, 2008, for example, Bristol-Myers Squibb Co offered to acquire ImClone Systems, maker of the cancer drug Erbitux, for $60 a share, an offer it subsequently increased to $62. Icahn, who was ImClone's chairman at the time, rejected both offers.

Conventional wisdom held that Bristol, which owned a 17 percent stake in ImClone, was the only logical buyer, and though a rival bidder could emerge, it was unlikely.

Icahn, however, announced in September that he had received a takeover offer of $70 a share from a large pharmaceutical company, and in October that year, Eli Lilly & Co agreed to acquire ImClone for $6.5 billion, or $70 a share -- a 51 percent premium over ImClone's closing price on July 30, the day before Bristol made its first offer.

Carl is like a human calculator with a great radar, said Mark Stevens, author of an unauthorized biography of Icahn called King Icahn and chief executive officer of management consulting firm MSCO. He's a great chess player and he's always thinking 12 moves ahead, whereas the senior management he's in contest with, they are thinking three moves ahead.

While Icahn is ultimately a pragmatist, he is driven as much as anything by the desire to torture his opponents, Stevens said.

Having people twist in the wind, having people not know what's coming next, having people caught in a Kafka-like experience is what his joy is, he said. Nobody is as good at is as he is.

While Icahn, and the investors who followed him into Genzyme, might be willing to accept somewhat less than the company's longer-term investors, Sanofi will have to cough up at least $5 a share more than is currently on offer, they say.

Genzyme and its investors see Sanofi's offer as an opportunistic one based on a decline in Genzyme's share price sparked by a manufacturing crisis.

Last year Genzyme was forced to temporarily close its manufacturing plant in Boston due to a viral contamination.

The shut-down lead to a shortage of two of the company's biggest-selling products and sent Genzyme's shares plummeting.

Before the manufacturing problems, Genzyme's shares peaked at almost $84 in 2008. They hit $45.39 in May, the lowest since July 2004.

Genzyme has since taken extensive steps to address its manufacturing problems and says it is on track to restore patients to full dosages of their medications by the end of the year.

Some investors would, however, like Genzyme to start the negotiation process sooner rather than later.

I think the board's mandate should be to enter discussions now, with a focus on maximizing shareholder value, said David Katz, chief investment officer at Matrix Asset Advisors.