definiens: shall meanEe total of all costs incurred by VERTEX associated with the development of a panicular Refused Candidate, including all direct and indirect costs associated with clinical studies, manufacturing of drug substance and drug product, scale - up and fonnulation research, regulatory activities, pre - marketing activities and market research, as well as an allocation of corporate overheads reasonable and appropriate under the circumstances and not at variance with U.S. generally accepted accounting principles and VERTEX 's usual practices . Where appropriate, allocation of manufacturing costs will be based on the share of capacity actually dedicated to a Drug Candidate as a percentage of the total capacity that is practically available for use, such that cost will not include an undue burden or overhead related to other projects and to ex.cess capaci~ 1.42 shall mean either ( a ) a claim of an issued and unexpired Patent which has not been revoked or held pennanently unenforceable or invalid hy a decision of a court or other governmental agency of competent jurisdiction, unappealable or unappeaJed within the time allowed for appeal, and which has not been admitted to be invalid or unenforceable through reissue or disclaimer or otherwise, or ( b ) a claim of a pending patent application which claim was filed in good faith and has not been abandoned or finally disallowed without the possibility of appeal or refiling of said application