definiens: means a change, circumstance or effect that, individually or in the aggregate with all such other changes, circumstances or effects, has a material adverse effect on either ( i ) the Conveyed Assets taken as a whole, or ( ii ) the Product business, taken as a whole, that in either case would be reasonably estimated or quantified, individually or collectively with any such other adverse effects ; provided, however, for purposes of determining whether a Material Adverse Effect has occurred, changes, circumstances and effects caused by or 5 EXECUTION COPY relating to the following shall be disregarded ( provided, further, that the underlying facts, circumstances and causes of the following, in and of themselves, shall not be excluded from such determination ) if and to the extent they do not disproportionately affect the Conveyed Assets or the Product business when compared to similarly situated businesses : ( i ) changes in conditions generally affecting ( A ) the healthcare or biotechnology industry or ( B ) the United States or world economy or securities markets ; ( ii ) the execution or announcement of this Agreement or the other Transaction Documents or the consummation of the transactions contemplated hereby and thereby, including any loss of employees, suppliers or customers resulting therefrom ; ( iii ) changes in any Governmental Rule or generally accepted accounting principles or interpretations thereof ; or ( iv ) any act of civil unrest, war or terrorism