Barely nine hours after Pfizer made its fourth and “final” takeover offer, raising it to $118 billion, AstraZeneca rejected it today, ending the U.S. pharma giant’s plan to create the world’s largest biopharmaceutical company.

In holding steadfast against higher offers, which included increasing the cash portion from 32% to 45%, Pfizer said its “improved proposal is final and cannot be increased,” adding it will not pursue a hostile takeover directly to shareholders and would proceed only with an offer that has the recommendation of AZ’s board of directors.

Reaction to Pfizer’s latest bid was emphatic, with AZ chairman Leif Johansson releasing a statement saying, “the Final Proposal is a minor improvement that continues to fall short of the board’s view of value and has been rejected.”

He said Pfizer’s takeover pursuit was driven largely by corporate financial benefits to its shareholders and tax minimization.

“From our first meeting in January to our latest discussion yesterday, and in the numerous phone calls in between, Pfizer has failed to make a compelling strategic business or value cause,” said Johansson. “We have rejected Pfizer’s Final Proposal because it is inadequate and would present significant risks for shareholders, while also having serious consequences for the company, our employees and the life sciences sector in the U.K., Sweden and the U.S.”

Ian Read, Pfizer’s CEO, said in a statement Sunday he did not believe AZ was prepared to recommend a deal at a reasonable price. “We remain ready to engage in a meaningful dialogue, but time for constructive engagement is running out,” said Read, referring to the May 26 deadline set by U.K. takeover law for Pfizer to walk away rather than sweeten the bid. The law also stipulates Pfizer wait six months before making another bid.

Reaction to AZ’s rejection of the final Pfizer offer was mixed.

“We are disappointed the board of AstraZeneca has rejected Pfizer’s latest offer so categorically,” Alastair Gunn, co-manager of Britain’s Jupiter Distribution Fund and Jupiter High Income Fund, said in a statement. “They should have at least engaged in a constructive conversation with Pfizer on the details of the offer to assess the opportunities that a combined entity could bring.”

Anne Richards, chief investment officer of Aberdeen Asset Management, which holds a 2.39% stake in AZ, told the London Telegraph she thought Pfizer “could do better.”

Still, other analysts cited AZ’s failures in drug development in recent years. The company’s forecasts should be “heavily discounted” because many pharma companies have made wrong long-term forecasts, Timothy Anderson, an analyst at Sanford C. Bernstein, wrote in his report.

“Is AZ realistic in what it believes ‘fair value’ is?”  he wrote. “Projecting the worth of new drug pipelines is notoriously difficult, and drug companies and financial analysts alike are often wrong to the tune of billions of dollars, especially when going out five to 10 years.”

The merger possibility had raised concerns of potential job loss in the U.K., Sweden and the U.S. Wellcome Trust, a medical research charity, has said previous major acquisitions have led to substantial R&D reductions, and Pfizer could ship AZ’s oncology research from the U.K. to the west coast of the U.S. where Pfizer has a cancer research center.  

On the east coast, the governors of Maryland and Delaware have sought assurances that AZ jobs and facilities in their states would be protected. Concerns over closing a tax loophole if Pfizer acquired AZ prompted Michigan Sen. Carl Levin, chairman of the Permanent Subcommittee on Investigation, which targets corporate tax avoidance, to say he would “act fast” to close the  loophole, which allows companies to reduce overseas taxes it pays the U.S. by redomiciling or shifting headquarters to the U.K., a process known as inversion.

“It’s becoming increasingly clear that the loophole in our tax laws allowing these inversions threatens to devastate federal tax receipts,” Levin told the London Telegraph.  

The potential takeover also had raised concerns in the U.K., including calls for new governmental powers that would prevent takeovers by foreign companies in the interest of national security. AZ accounts for about 2% of British exports.