Some of my Foolish colleagues and I have expounded on the problems with large pharma mergers and acquisitions -- and history is on our side -- but as we get closer to Pfizer (NYSE:PFE) and Merck (NYSE:MRK) wrapping up their deals, it looks like a new group is voicing their displeasure: external partners.

The acquisitions may make the drug companies bigger, but they may lose a few drugs in the process.

In-house competition
Japanese drugmaker Eisai said last week that it plans to end its partnership with Pfizer to market its Alzheimer's drug, Aricept, after Pfizer buys Wyeth. Pfizer recorded nearly half a billion dollars in sales of the drug last year, so the loss wouldn't be huge, but it's not trivial either.

The acquisition of Wyeth includes its phase 3 Alzheimer's drug, bapineuzumab, which Wyeth is developing with Elan. Eisai is surely worried that, if bapineuzumab is approved, Pfizer will give bapineuzumab more attention than Aricept.

Pfizer says that Eisai has no basis for terminating the partnership, so this one looks destined for court or perhaps a renegotiation of the partnership if the two sides can agree on a compromise. Pfizer could, for instance, agree to give Eisai a small royalty on bapineuzumab if Aricept sales fall below a certain level.

An excuse to terminate
Johnson & Johnson (NYSE:JNJ) doesn't really need Schering-Plough to market Remicade and its follow-on anti-inflammatory, Simponi, overseas. Nearly half of the health care giant's sales came from overseas last quarter; its sales force could certainly handle it. But Johnson & Johnson is stuck with Schering because Schering inked a deal with Remicade's developer, Centocor, before J&J bought it.

I'm sure that Johnson & Johnson would love to get out of the contract, and Merck's acquisition of Schering might just be the window of opportunity. A change of control allows Johnson & Johnson to terminate the contract.

Management at Merck is no dummy -- $2.1 billion in revenue from that drug last year will keep you on your toes -- so Merck set up the acquisition as a reverse merger where Schering is technically acquiring Merck and then changing its name to Merck. Sneaky? Yes. Will Johnson & Johnson go for it? I think it's likely we'll see Johnson & Johnson force a compromise or maybe it'll play out in court, but Johnson & Johnson is playing it close to its chest.

Best of both worlds
For partners, mergers are great because they often get to make a decision about whether the acquisition is in the best interest of their respective companies. For instance, I haven't heard any complaints from Amgen (NASDAQ:AMGN) about Pfizer becoming its new marketing partner for Enbrel. Why would Amgen complain? It's getting a company that's pretty good at increasing the sales of blockbusters -- insert your favorite Lipitor ad here -- and it appears that Amgen might be able to get a piece of any competing product that Pfizer might develop.

We also didn't hear many complaints from Bristol-Myers Squibb (NYSE:BMY) when it was outbid by Eli Lilly (NYSE:LLY) for ImClone Systems. After all, Bristol-Myers got a larger marketing partner for Erbitux. However, Bristol-Myers is likely to go to court, if necessary, to get a hold of the follow-up to Erbitux that Eli Lilly is developing, but that would have been the case whether Eli Lilly acquired ImClone or not.

The acquisitions that could have been
Sometimes external partnerships just drive away would-be acquirers altogether. This may have been what happened to Biogen Idec (NASDAQ:BIIB) at the end of 2007. The company put itself up for sale, but change of control provisions in its partnerships with Genentech and Elan gave the partners the option to buy out Biogen's half of their partnerships for Rituxan and Tysabri, respectively. The thought of losing two major drugs was probably enough to scare many potential acquirers away.

For better or worse, the same fate is likely to befall many development-stage drugmakers that have taken on multiple partners to fund the development of their drug pipelines, such as Alnylam.

Lesson for investors
Many aspects of partnership agreements are kept secret, but that doesn't mean investors should ignore them altogether. There's usually some information about the terms of the agreements nestled inside the 10-Ks -- yes, you actually do have to read them. Keep in mind that many have change in control clauses, which may lower the value to any potential acquirer.

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Elan is a Rule Breakers pick. Biogen Idec is a Stock Advisor recommendation. Pfizer is an Inside Value selection. Johnson & Johnson is an Income Investor recommendation. Got that? Want to find out why? Try any of these newsletters today, free for 30 days.

Fool contributor Brian Orelli, Ph.D., doesn't own shares of any company mentioned in this article. The Fool has a disclosure policy.