AstraZeneca has rejected a final £69 billion takeover offer from US drugs giant Pfizer, saying it undervalued the company.
The UK-based pharmaceuticals firm spurned the latest advance from the Viagra maker after it upped the price it was prepared to pay over the weekend.
AstraZeneca said the deal would bring "uncertainty and risk" for its shareholders and "undervalues the company and its attractive prospects".
Chairman Leif Johansson said: "Pfizer's approach throughout its pursuit of AstraZeneca appears to have been fundamentally driven by the corporate financial benefits to its shareholders of cost savings and tax minimisation."
He said that from the time of initial talks in January, the US company had "failed to make a compelling strategic, business or value case".
Astra for the first time placed a figure on a value it might have been able to consider putting to its shareholders to recommend a sale - of about £74.3 billion, nearly £5 billion above the £69.4 billion final offer from Pfizer.
It came after a weekend of talks involving Mr Johannson, his chief executive Pascal Soriot and finance director Marc Dunoyer after Pfizer made an offer of £53.50 a share for the UK-based group.
Mr Johansson said that in response to the Friday offer, it had indicated that "even assuming that other key aspects of the proposal had been satisfactory" that the price at which it would have been prepared to recommend a sale would be more than 10% higher.
He added: "The final proposal is a minor improvement which continues to fall short of the board's view of value and has been rejected."
Mr Johansson said Astra had created a "culture of innovation, with science at the heart of its operations".
He reiterated widely expressed concerns that a deal would have "serious consequences for the company, our employees and the life sciences sector in the UK, Sweden and the US".
Astra outlined four key points underlying its rejection of the deal, starting with planned cost-cutting which would "imply a meaningful reduction in research and development potential and capabilities".
It also said the integration of the two companies would risk "significant disruption" to the delivery of its new drugs - echoing Mr Soriot's claim before MPs last week that life-saving medicines could be delayed by the distraction caused by a mega-merger.
The UK firm pointed as well to Pfizer's past record, saying its previous large-scale takeovers had "highlighted the challenges around the negative impact of integration on research and development productivity and output".
Finally, Astra expressed concerns about the impact of plans by the US firm to separate out its operations into three business units.
In addition, the rejection statement repeated the concern expressed about the "tax-driven inversion structure" of the deal.
This refers to the controversial proposal to re-domicile the newly merged giant to the UK for tax purposes while maintaining corporate headquarters in the US and a listing on the New York Stock Exchange.
Astra noted in its statement that this had "already been the subject of intense public and governmental scrutiny" and brought "increased uncertainty" for shareholders.
The company also pointed to the fact that the majority of the offer was still in the form of shares - which many Astra investors would have to sell.
"The board believes that Pfizer's final proposal, in relation to price, form of consideration and the four particular points that are central to the board's concerns around value, remains inadequate," the firm said.
"Accordingly, the board has rejected the final proposal."
Astra's shares plunged by as much as 14% in early trading, driving its market value down to £52.1 billion, £17 billion less than the value Pfizer had put on the company.
Asked when the saga would be over, Mr Johansson told BBC Radio 4's Today programme: "I have no idea.
"This has been going on for quite some time and we have been in very deep engagement over the whole of the weekend, if Pfizer now says this is the final offer I have to believe what they say."
It comes after the announcement last night from the US giant which it said represented a fourth and final approach, and was 15% higher than a previous proposal on May 2.
Pfizer also said that it would not make a hostile offer direct to Astra shareholders, instead urging them to press the company's board to begin substantive engagement over a deal.
Without further discussions or an extension of the deadline for making a firm offer, Pfizer's proposal will expire at 5pm on May 26.
Pfizer chief executive Ian Read said last night that it did not believe Astra 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.
"We have said from the beginning that we will remain disciplined in the price we are willing to pay and we will not depart from that guiding principle.
"We believe that our proposal represents compelling and full value for AstraZeneca and that other issues that have been raised by AstraZeneca do not represent material difficulties."
The company's final offer increased the cash element from 33% to 45%. It said the proposal was 34% higher than Astra's all-time high closing share price prior to the bid speculation.
It has already pledged in a letter to Prime Minister David Cameron that any deal would not stop the building of Astra's planned research and development (R&D) hub in Cambridge and that 20% of the combined company's R&D workforce will be in the UK.
But the pledges have been criticised by the president of the Royal Society, who said they were "vague, come with caveats and have an inappropriate timescale".
Allan Black, national officer at the GMB union, said: "We call upon the Astra Zeneca board to continue to reject Pfizer's approach and we call upon the institutional investors to break the habit of a lifetime and look beyond a quick buck."
Edison Investment Research analyst Dr Mick Cooper said Pfizer's statement that it would not "go hostile" suggested that Astra had succeeded in shoring up the support of key institutional shareholders.
"These investors are clearly banking that they are more likely to get £55 per share growth and above in returns from a standalone AstraZeneca rather than £24.76 in cash now and taking the risk that a 26% stake in an enlarged Pfizer will deliver higher long-term returns," he said.