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Exhibit 4.6    
    

 
 

EMPLOYMENT AGREEMENT (translation from Dutch)    
    

Between:

Introgene
B.V. (now Crucell Holland B.V.) a private limited liability company, hereinafter referred to as Introgene; 

And:

R.H.P.
Brus; 

Whereas:

        Introgene
is a starting biotechnology company with a focus on growth; 

        Introgene
requires an executive who is capable now and in the future to sell and acquire technology; 

        Mr. Brus
has the commercial skills and is willing to make his skills available for Introgene; 

        Mr. Brus
is available to dedicate himself on a national and international level for Introgene and is not affiliated to any other third party in that respect; 

        Mr. Brus
acknowledges that Introgene operates in a highly confidential environment, with regard to research, development as well as from an organizational, corporate and
scientific point of view; 

        Mr. Brus
has agreed to relocate as soon as possible to the vicinity of Leiden, the Netherlands. 

Have agreed as follows:  

	1.
	Function: 

        Mr. Brus
will be employed by Introgene as Director Business Development. He is responsible for any and all Business Development activities the design and execution thereof. He
reports to the managing director. The function includes frequent travel and staying abroad. 

	2.
	Duration:

        The
employment agreement commences on 15 January 1997, or the sooner as may be agreed upon between the parties, for an indefinite period of time. The first two months are
considered as a probation period. 

	3.
	Labor
times; 

        The
function requires full dedication above and beyond ordinary office hours. 

	4.
	Salary
and holiday allowance: 

        The
salary of Mr. Brus is [deleted] gross per annum. Inclusive holiday allowance, and shall be made payable to a designated account by Mr. Brus in
twelve equal installments. 

	5.
	Other
benefits: 

        Introgene
is in preparation of a collective pension arrangement in line with current standards. 

        Introgene
shall pay DFL [deleted] to Mr. Brus for a sickness insurance to be taken out by Mr. Brus. 

        Mr. Brus
is eligible to participate in Introgene's option plan. He will be granted 50,000 options with an exercise price to be determined against the value of the share price on
15 January 1997. 

        Introgene
will provide Mr. Brus with a loan in the amount of DFL [deleted] to be repaid within one year. The loan will be immediately repaid at first call
of Introgene at their sole discretion. 

	6.
	Expenses:

        Introgene
shall provide for a monthly fixed expense payment in the amount of DFL [deleted] to reimburse Mr. Brus for ordinary small business expenses.
Introgene shall refund all other expenses incurred in the ordinary course of business, subject to properly recording of such expenses in accordance with Company policy. 

        Mr. Brus
shall be compensated for business travel with his own car in the amount of DFL [deleted] per kilometer. 

        As
long Mr. Brus has not found a new home in the vicinity of Leiden, Introgene shall compensate, with a maximum of three months, for housing expenses with a maximum amount of DFL
[deleted]. 

        Reasonable
relocation expenses shall be reimbursed by Introgene, including travel expenses of Mr. Brus' family on economy class level. 

        All
other relocation expenses shall be reimbursed with a maximum of DFL [deleted]. 

        All
expenses have a gross nature. At Introgene's sole discretion payments shall be made on a gross or net basis. 

	7.
	Holidays:

        Mr. Brus
is eligible to take 25 holidays per annum. 

	8.
	Sickness
and Disability; 

        Notwithstanding
article 7A:1638c Dutch Civil Code, Introgene continues to pay Mr. Brus' salary for a period of 52 weeks during sickness. Regarding the calculation of the
periods of sickness they are deemed to be aggregate and with an interruption of less thane 4 weeks. 

        Introgene
shall be liable for the conclusion of employment disability insurance, on terms to be mutual agreed upon. 

	9.
	Other
activities: 

        Mr. Brus
shall not have during his employment other business activities, regardless whether they are paid or not, without express prior written permission. 

        Notwithstanding
the foregoing Mr. Brus shall not, during his employment and for a period of one year thereafter, without prior written permission, apply or have any involvement
directly or indirectly with the application of patents or other intellectual property in the areas that Introgene is active in. In case of breach by Mr. Brus he will be held liable for a
penalty of DFL [deleted]. 

	10.
	Confidentiality:

        Mr. Brus
shall, both during his employment as after termination of this agreement, keep confidential any and all information that came in his possession as a result of his
employment. 

        In
case of breach Mr. Brus will be held liable for an amount of DFL [deleted], multiplied with DFL [deleted] per day that the
violation continues. 

	11.
	Non-Compete

        Mr. Brus
shall for a period of one year after termination of this agreement not be active whatsoever in the field of Introgene's business, regardless whether these activities are
current or in preparation. 

Signed
in two original copies: 

	

 Introgene B.V.	
 	

 R.H.P. Brus	
 	

 

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Exhibit 4.6

EMPLOYMENT AGREEMENT (translation from Dutch)QuickLinks
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Exhibit 4.7    
    

 
 

EMPLOYMENT AGREEMENT    
    

The
undersigned, 

CRUCELL HOLLAND BV, having its offices at Archimedesweg 4, 2333 CN, Leiden, (hereinafter referred to as "Crucell"), 

and 

Prof. Dr. J. Goudsmit, now residing at Koninginneweg 4, 1075 CX Amsterdam, (hereinafter referred to as Employee), 

WHEREAS  

        Crucell is a leading biotechnology company, principally engaged in the discovery and development of biopharmaceutical products that utilize the immune system to
combat diseases. 

        Crucell
is a subsidiary of Crucell N.V., a public limited liability company according to the laws of the Netherlands with a public listing on Amsterdam stock exchange Euronext N.V. and
Nasdaq, New York. 

        Crucell
has previously employed Employee as Senior Vice-President Vaccine Research as per September1, 2002 and now wishes to employ the Employee as Executive Vice
President & Chief Scientific Officer as per the Effective Date. 

        Employee
has stated that he is fully entitled and available to serve Crucell nationally and internationally and that he has, in that respect, no restrictions or obligations with respect
to anybody; 

        Employee
is fully aware that the business of Crucell requires extreme confidentiality as to everything that is created, developed, prepared, investigated scientifically organisationally,
economically, as well as commercially; 

        Employee
and Crucell wish to ratify and confirm the Employee's new position and associated employee benefits. The underlying employment agreement will replace the former employment
agreement with Crucell. The number of years of service of Employee ("the seniority") at Crucell will be respected under this new employment agreement; 

        HAVE AGREED AS FOLLOWS:

DUTIES  

	1.1.
	Employee
will be employed by Crucell as Executive Vice-President & Chief Scientific Officer. The Employee will report to the President & Chief Executive
Officer of Crucell and will be a member of the Executive Committee. The function may include travelling and staying abroad. Employee is expected to use his particular knowledge in medical research,
including but not limited to vaccine research and if possible, for the creation of industrial or intellectual property rights such as rights attached to inventions.

	1.2.
	Employee
accepts that he shall also perform duties other than the ones which are considered his usual duties if such performance may be reasonably expected from him. 

COMMENCEMENT, DURATION AND TERMINATION  

	2.1
	The
employment shall commence on September 1, 2002, and will be entered into for an indefinite term. For the avoidance of doubt, this employment contract cancels and supersedes
all previous employment contracts, between Crucell and the Employee, including but not limited to the employment contract dated August 29, 2001. However it is agreed that the number of years of
service of the Employee since September 1, 2001 ("the seniority") at Crucell will be respected under this employment agreement. 

	2.3.
	The
employment agreement shall in any event and without prior notice expire at the end of the month in which Employee reaches the age of sixty-five.

	2.4
	Notice
will be given by both parties in writing, with effect as per the end of a calendar month. The term of notice is six months for Crucell and three months for Employee. 

HOURS OF WORK  

	3.1
	The
function requires total dedication during and beyond office hours. 

REMUNERATION AND HOLIDAY ALLOWANCE  

	4.1.
	Employee
shall receive a gross annual salary of Euro 320,000. The gross salary includes statutory holiday allowance of 8%, to be paid in the month of May each year. The salary, net
of the statutory holiday allowance, is payable in equal instalments, at the end of each month, to the bank account which will be indicated by Employee. The holiday allowance shall be accrued on a
monthly basis by reserving a sum equal to 8% of the monthly income received by the Employee. 

FRINGE BENEFITS  

	5.1.
	Employee
is allowed to participate in the corporate pension plan of Crucell. Crucell warrants that the terms and conditions of Employees' pension plan shall in all material aspects
be equal to and therefore not less advantageous than the current pension plan(s) of Crucell's Chief Executive Officer. Main terms of the pension plan shall consist of an agreed maximum pensionable
salary of Euro 226,890, inclusive the yearly indexation and Employee contribution of 6% of the applicable pension basis ("pensioengrondslag"). The advisory costs with respect to such pension plan
shall also be borne by Crucell. Crucell shall assist the Employee in terminating or transferring accrued pension rights with his current pension plan.

	5.2.
	Crucell
shall reimburse 75 percent of health care insurance premiums to Employee.

	5.3.
	Employee
is granted the right to participate in Crucell's applicable option plan. As evidence of the Employee's promotion to Executive Vice-President & Chief
Scientific Officer, the Employee receives as at September 20, 2002 (the "Date of Grant") 100,000 additional options (the "Grant") Crucell N.V. at the Stock Exchange of Euronext N.V. and NASDAQ
and associated Stock Appreciation Rights. The option exercise price will be established in euro's, based on 117% of the average price of the share Crucell N.V. at the close of market on the three
trading days on the official market of the stock market of Euronext N.V. in Amsterdam (EAX) prior to the Date of Grant. The option grant will exclusively be governed by Crucell's applicable option
plan. The Stock Appreciation Rights grant will be exclusively governed by Crucell's applicable SAR plan.

	5.4.
	For
greater certainty the Employee accepts that any compulsory tax withholdings related to or as a result of his rights under this section are for his account.

	5.5.
	To
the extent permitted by Dutch or US security laws is the Employee entitled to a director's loan, bearing the same interest rate, and under the same terms and conditions of other
director's loans, equal to the amount of taxes to paid by Employee in connection with the Grant. 

EXPENSES  

	6.1.
	Crucell
shall reimburse Employee necessary reasonable business expenses after approval of the specifications. Each month, the Employee will receive a minimum net fixed expense
allowance in accordance with Crucell Holland's expense allowance policy.

	6.2.
	The
Employee is entitled to a company car in accordance with Crucell's applicable company car policy. 

	6.3.
	All
reimbursements are subject to the right of Crucell to restrict to the amount(s) that is or will be allowed by tax regulations or, at the choice of Crucell, to withhold possible
premiums and taxes due, at Employee's expense. 

HOLIDAYS  

	7.1
	Employee
shall be entitled to paid holidays with pay in each calendar year at a rate of 30 working days. Employee shall be obliged to take these holidays in consultation with, and
after approval of, Crucell. Holiday leave which has not been taken by the Employee can be transferred to a following year, but shall lapse in accordance with the statutory five-year term
of prescription after expiry of the calendar year in which the entitlement arose. 

ILLNESS AND DISABILITY  

	8.1.
	If
the Employee is unable to perform his duties agreed owing to illness, Crucell shall pay 100% of his agreed wage for a period of 52 weeks. In this provision, wage is understood to
mean the wages referred to in article 4 plus the allowances referred to in article 5. Periods of illness are calculated together if intervals are shorter than four weeks.

	8.2.
	Employee
will participate in Crucell's corporate disability insurance plan. The premiums are for the account of Crucell. 

NO SIDELINES  

	9.1.
	Except
for:

	(i)
	the
duties related to the Employee's chair at the "Amsterdam Medisch Centrum" on a "nul aanstelling" basis for which duties Employee
will be granted a paid absence leave for a maximum of 24 days per year, assuming these days will be divided proportionally over the year.

	(ii)
	his
involvement with the International AIDS Vaccine Initiative ("IAVI"), for which involvement the Employee will receive a paid absence leave of 12 days per year, excluding
travelling days.

	(iii)
	the
involvement of Employee as member of de Council of Scientific Advise of Prima Gen, a company based in Amsterdam,

	(iv)
	the
involvement in reviewing scientific papers, 

Employee
shall during the employment refrain from having any interest in, or conducting of any outside commercial, outside business or outside scientific activities, with or without remuneration,
without the prior written consent of Crucell, such consent not unreasonably to be withheld. 

	9.2
	The
remuneration for the duties/involvement of/in the activities mentioned under (i), (ii), (iii)and (iv), if any, shall be for the Employee and discussed and reported to Crucell's
Chief Executive Officer.

	9.3
	For
avoidance of doubt the activities referred to under (iii) and (iv) shall be performed in the Employees spare time. 

CONFIDENTIALITY  

	10.1.
	Except
as required by law or to the extent applicable to information that is in the public domain otherwise than through unauthorised disclosure by the Employee. Employee is fully
aware and acknowledges that, during the employment as well as thereafter, strict secrecy in respect of all matters relating to Crucell, organisational, commercial, and scientific, all in the broadest
sense, is necessary. This obligation is not restricted to relations with third parties but includes other employees of Crucell in so far the proper performance of the duties of employee does not
require disclosure. 

	10.2.
	Notwithstanding
Clause 13.1, every material violation of section 10.1. may be referred to a competent Dutch court and appropriate damages and/or legal action
requested. 

NON COMPETITION  

	11.1
	Employee
shall for a period of one year after the end of the employment fully refrain from any business wise activity, including any (whether or not for payment) involvement with
business wise activities, directly or indirectly, relating to the commercial application of discovery and development of biopharmaceutical products that utilize the immune system to combat diseases
within the fields Crucell acts, has acted or prepares to act on at the moment the employment ends.

	11.2
	Furthermore
Employee shall strictly refrain, during the employment as well as during one year thereafter, without the prior written consent of Crucell, from any involvement with the
creation, the application for and the recording of intellectual property rights beyond his proper performance under the employment or, after the end thereof, the creation, the application for and the
recording of intellectual property rights concerning the existing or future field of activities of Crucell.

	11.3
	Notwithstanding
Clause 13.1, every material violation of sections 11.1 and 11.2 may be referred to a competent Dutch court and appropriate damages and/or legal action
requested. 

INTELLECTUAL AND INDUSTRIAL PROPERTY RIGHTS  

	12.1.
	Employee
shall inform Crucell forthwith of every invention, procedure, publication, design, model and in general every creative result in the field of industrial or intellectual
property attained by employee, if and to the extent that it relates to Crucell's business activities both in the Netherlands and abroad. If the industrial and intellectual property rights attaching to
the invention, etc. do not automatically accrue to Crucell by virtue of the employment relationship, Employee shall at Crucell's first request transfer such rights to Crucell and
co-operate fully in recording such rights in the name of Crucell as exclusive owner, all at the expense of Crucell.

	12.2.
	Employee
hereby irrevocably appoints Crucell as his agent for the purpose of in his name preparing all documents and performing all other acts necessary for the implementation of
the provisions of this article and Crucell is hereby authorised to appoint a sub-agent for the implementation of the foregoing.

	12.3.
	Employee
acknowledges that his salary includes reasonable compensation for (his contribution to) the creation of intellectual and industrial property rights. 

SEVERANCE PAY UPON TERMINATION OF EMPLOYMENT CONTRACT  

	13.1
	If
the Employee is dismissed by Crucell, parties will leave it to the decision of the competent court as to what the amount of severance pay shall be. However, In any case the
severance pay granted by the court shall be increased with the amount of salary that the Employee would have received, should the notice period of article 2.4 have been observed by Crucell.

	13.2
	Without
prejudice to the provision referred to in the previous paragraph, the minimum severance pay shall be at least equal to a year salary excluding holiday allowance, if the
dismissal of the Employee is due to a merger or a take over of Crucell, either directly or indirectly. 

LAW  

	14.1
	This
agreement shall be governed by and construed in accordance with the laws of the Netherlands. All disputes arising out of or in connection to this Agreement shall be referred to
the competent Dutch court. 

EXECUTED
on October 25, 2002, in Leiden, the Netherlands and effective as per the Effective Date in duplicate, 

	For and on behalf of

Crucell Holland B.V.	 	

Employee
	

By: Crucell N.V.
 Title: Director	
 	

By:
 Name: J. Goudsmit
	

By:
	
 	

 
	Name: Domenico Valerio

Title: President & Chief Executive Officer

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Exhibit 4.7

EMPLOYMENT AGREEMENT

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