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Exhibit 4.15




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CONTENTS
 CONTENTS
 CLAUSE
    
    
    
    PAGE1.
    
    DEFINITIONS AND INTERPRETATION
    
    
    12.
    
    COLLABORATION
    
    
    73.
    
    ESCROW ACCOUNT
    
    
    84.
    
    JOINT PROJECT TEAM
    
    
    105.
    
    STEERING COMMITTEE
    
    
    126.
    
    GENERAL MATTERS CONCERNING THE JOINT PROJECT TEAM AND THE STEERING COMMITTEE
    
    
    147.
    
    LICENCE
    
    
    158.
    
    DELIVERY OF KNOW-HOW
    
    
    159.
    
    ROYALTIES AND MILESTONES
    
    
    1610.
    
    CONFIDENTIALITY
    
    
    1811.
    
    OWNERSHIP OF THE PATENTS AND KNOW-HOW
    
    
    1912.
    
    INFRINGEMENT
    
    
    2013.
    
    LIABILITY/INDEMNITY
    
    
    2214.
    
    WARRANTIES
    
    
    2315.
    
    TERM
    
    
    2416.
    
    TERMINATION
    
    
    2417.
    
    RIGHTS ON TERMINATION
    
    
    2718.
    
    FORCE MAJEURE
    
    
    2719.
    
    FURTHER ASSURANCE
    
    
    2820.
    
    ASSIGNMENT AND SUB-LICENSING
    
    
    2821.
    
    MISCELLANEOUS
    
    
    2822.
    
    NOTICES
    
    
    3023.
    
    DISPUTE RESOLUTION
    
    
    3024.
    
    GOVERNING LAW AND JURISDICTION
    
    
    3125.
    
    SUPPLY AGREEMENT
    
    
    31SCHEDULE
    
    
    33Patent
    
    
    33




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THIS
AGREEMENT
 BETWEEN:
 (1)
    
    PROTHERICS MEDICINES DEVELOPMENT LIMITED(No. 19396431) whose registered office is at The
Heath Business and Technical Park, Runcorn, Cheshire WA7 4QF (Protherics"); and
 (2)
    
    ADVANCED IN VITRO CELL TECHNOLOGIES S.L.(No. ESB62520877) whose registered office is at the
Barcelona Scientific Park, Baldiri Reixac 10-12, Barcelona 08028 Barcelona, Spain
(Advancell").
 RECITAL
 (A)
    
    Protherics is an integrated biopharmaceutical company focused on developing, manufacturing
and marketing critical care and medicinal products, seeking to use industry collaboration to
achieve its business goals and long-term growth.
 (B)
    
    Protherics considers that it has the scientific, technical , personal, material and logistic
means necessary to assume and comply with its commitments in this agreement.
 (C)
    
    Advancell is a biotechnology company, whose main activities are advanced research and the
commercialisation of products from cellular-growing systems and through tissue-engineering;
and the development of new therapies based on technologies acquired from the Spanish Academia.
 (D)
    
    Advancell owns the Patents (as defined below) and other Intellectual Property Rights
pertaining to the use of the Product for the Indication (all as also defined below).
 (E)
    
    The parties wish to undertake, or have undertaken, the Development Programme (as defined
below) to obtain relevant Health Registration Approvals (as defined below) for the
commercialisation by of for Protherics of the Product, throughout the world, for the
Indication.
 (F)
    
    The parties wish for Protherics to have all rights it may require for the purpose of
developing, commercialising and otherwise exploiting the Product, world-wide, as so described,
to which end Advancell will grant to Protherics all necessary licences.
 THE PARTIES AGREE AS FOLLOWS:
 1.
    
    DEFINITIONS AND INTERPRETATION
 1.1
    
    DefinitionsIn this agreement, unless the context otherwise requires:Acadesinemeans
5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside, CAS number:
2627-69-2;Affiliatemeans any business entity which, from time to time, controls, is controlled by,
or is under common control of either party; and, for the purposes of this definition, a
business entity will be deemed to control another business entity if it owns, directly or
indirectly, in excess of fifty (50) per cent. of the outstanding voting securities or
capital stock of such business entity and has the right, directly or indirectly, to appoint
more than half of the members of the board of directors of such business entity, or owns,
directly or indirectly, any other comparable equity or ownership interest with respect to a
business entity other than a corporation;Claimmeans any claim, counterclaim, suit, action or proceedings;
 1




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Claiming Party
 Clinical Studies Clinical Study
 Confidential Information
 Cost
 Deductions
 Development Programme
 Disclosing Party
 Dispute
 Drug Product
 Effective Date
 Encumbrance Encumber
 Entire Agreement
 Escrow Account
 Escrow Account Bank
 Event of Force Majeure
 Export Control Laws
 Field of Use
 First Clinical Study
 First Commercial Sale
 2




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Good Clinical Practice
 Good Manufacturing Practice
 Good Industry Practice
 Good Laboratory Practice
 Health Authority
 Health Registration Approval
 (a)
    
    distribute, sell and market the Product for the Indication in such country
or territory, including, where applicable, post-approval marketing authorisations,
labelling approvals and technical, medical and scientific licences and pricing or
reimbursement approvals; or(b)
    
    undertake clinical studies;
 Indemnify
 Indication
 Independent Valuer
 Indirect Loss Hadley -v- Baxendale
 Intellectual Property Rights
 3




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Joint Project Team
 Know-how
 Law
 Liable Party
 Licence
 Licensor Information
 Loss
 (a)
    
    Indirect Loss; and(b)
    
    any loss which under English law would properly be considered as direct loss
or which does not constitute Indirect Loss;
 Marketing Authorisation
 Named Patient Sale
 Net Selling Price
 Non-claiming Party
 Non-clinical Studies Non-clinical Study
 Notifying Party Notified Party
 Orphan Drug
 4




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Orphan Drug Designation
 Patents
 (a)
    
    the patents and patent applications specified in schedule 1 and any patent
which may be granted pursuant to any such application;(b)
    
    any patent or application corresponding to any such patent or application
which may be granted or made; and(c)
    
    any re-issue, extension or restoration of any such patent, and any division
or continuation of any such application;
 Personnel
 Phase IIb Study
 Phase III Study
 Pricing Approvals
 Product
 Project Manager
 Quality Assurance
 Quarter Quarterly
 Receiving Party
 Regulatory Documentation
 Relevant Technology or Products
 Retention
 Royalty Event
 (a)
    
    if the third party is an Affiliate of Protherics, Royalty Event means the
first such sale of the Product to a third party which is not an Affiliate of
Protherics; and
 5




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(b)
    
    if, at the time of the sale by or on behalf of Protherics, its Sub-Licensee
or its Affiliate (as the case may be), the Product is not in the form of a Drug
Product, Royalty Event means the first such sale of the Product which is a Drug
Product;
 Senior Executives
 Shared Costs
 Steering Committee
 Study
 Sub-licence Sub-license
 Sub-licensee
 Term
 Termination
 Valid Claim
 (a)
    
    has not been held permanently revoked, unenforceable or invalid by a decision
of a court or governmental agency of competent jurisdiction, which decision is
unappealable or unappealed within the time allowed for appeal;(b)
    
    has not been abandoned, disclaimed, denied or admitted to be invalid or
unenforceable through re-issue, disclaimer or otherwise; and(c)
    
    with respect to a Patent which is a pending patent application, has not been
abandoned or finally disallowed without the possibility of appeal or re-filing of the
application; and
 Value Added Tax
 Interpretation
  (a)
    
    agreedmeans agreed by the parties in writing;(b)
    
    includemeans include without limitation; and(c)
    
    a third partymeans any person other than the parties.
 1.3
    
    Further InterpretationIn this agreement, unless otherwise expressly specified:
 (a)
    
    the index to, and the headings in, this agreement are for information only
and are to be ignored in construing it;
 6




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(b)
    
    a reference to a statute or statutory instrument, or any of their
provisions, is to be construed as a reference to that statute or statutory
instrument, or such provision, as the same may have been or may after the Effective
Date be amended or re-enacted;(c)
    
    grammatical variants of terms defined in this clause 1 will bear their
corresponding meanings;(d)
    
    references to recitals, clauses, paragraphs or the schedule are to
recitals, clauses and paragraphs of, and the schedule to, this agreement. The
schedule forms part of the operative provisions of this agreement and references to
this agreement will, unless the context otherwise requires, include references to the
recitals and the schedule;(e)
    
    where a clause refers to a matter coming to a partys awarenessor
attentionor to a similar effect, this will be taken as a reference to the state of
mind of the executive directors and officers holding such positions at the relevant
time;(f)
    
    where, in any provision or provisions, a general concept is followed by a
specific one, there will be no implication that the scope of the general concept is
to be narrowed as a result; and(g)
    
    words denoting the singular will include the plural and vice versa and
words denoting any gender will include all genders.
 2.
    
    COLLABORATION2.1
    
    The parties will undertake, or have undertaken, the Development Programme, on the terms and
subject to the conditions of this agreement and as provided in the Development Programme.2.2
    
    In performance of their obligations pursuant to clause 2.1:
 (a)
    
    Advancell will undertake, or have undertaken, the Non-clinical Studies
required to enable the proper conduct of the First Clinical Study of the Product for
the Indication, in accordance with the Development Programme;(b)
    
    Advancell will manufacture, or have manufactured, those quantities of the
Product required to enable the proper conduct, in accordance with the Development
Programme, of the First Clinical Study of the Product for the Indication; and(c)
    
    Protherics and Advancell will jointly undertake, or have undertaken, the
remainder of the Development Programme.
 2.3
    
    The party responsible for the undertaking of any part of the Development Programme will
undertake it, or procure that it is undertaken:
 (a)
    
    in accordance with
 (i)
    
    all applicable Laws;(i)
    
    Good Industry Practice; and(ii)
    
    the requirements of all applicable Health Authorities; and
 (b)
    
    otherwise with reasonable skill, care and attention,
 7




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having regard to the objective of the Development Programme to obtain relevant Health
Registration Approvals for the commercialisation by or for Protherics of the Product,
throughout the world, for the Indication.2.4
    
    Subject to clause 2.6, Advancell will pay all Costs attributable to the undertaking of those
matters described in clause 2.2(a) and 2.2(b).2.5
    
    Subject to clause 2.6, the parties will share equally all third party Costs attributable to
the undertaking of those matters described in clause 2.2(c), including the costs of the
Acadesine required to manufacture the Product used in the Clinical Studies.2.6
    
    Where any Product manufactured to enable the First Clinical Study is not used in such
Clinical Study, the same shall be made available, where appropriate, for use otherwise in the
Development Programme, and Protherics shall not be liable for any of the Costs of, or
attributable to, manufacturing it or having it manufactured, which Costs shall be for
Advancell in accordance with clause 2.4.2.7
    
    Each party will, subject to any limits approved by the Steering Committee, provide such
assistance as the other reasonably requests in that others performance of its obligations
pursuant to this clause 2, and the reasonable Costs of such assistance will be borne as
provided in clauses 2.4 and 2.5.2.8
    
    Only Protherics will apply for, or hold, any Health Registration Approvals relating to the
use of the Product for the Indication, or any Regulatory Documentation, save:
 (a)
    
    where Advancell is required by Law in the course of the Development
Programme to apply for and/or hold any of them; or(b)
    
    where the Development Programme provides that Advancell is to do so,
 in which case Advancell will assign the same to Protherics (or procure their assignment to
Protherics), including in accordance with clause 8.6, where applicable.3.
    
    ESCROW ACCOUNT3.1
    
    The parties will, as soon as reasonably practicable following the Effective Date, open the
Escrow Account as a joint account in their joint names for the sole purpose of receiving and
holding the Retention.3.2
    
    The debt owed to the parties by the Escrow Account Bank by virtue of its receipt and holding
of the Retention will be held by them on trust in equal shares on the terms set out in this
clause 3, and the parties will use all reasonable endeavours to procure that the Escrow
Account Bank designates the Escrow Account as a trustee account.3.3
    
    The monies making up the Retention will be kept separate from, and not co-mingled with, any
other monies (save for interest on the Retention).3.4
    
    All interest accruing on the Retention credited to the Escrow Account will belong to the
parties jointly and any sum of such interest to be paid to either party will be subject to
deduction of tax thereon or other amounts (if any) required by Law to be deducted in respect
of such sum.3.5
    
    Subject to clause 3.6, the division of Costs provided by clause 2.5 will be achieved by use
of the Escrow Account as follows:
 (a)
    
    each party will notify the other, from time to time, of the anticipated,
applicable up-coming Costs attributable to the undertaking of any part of the
Development Programme for which it proposes to contract with any third party to pay
(including the Costs of purchasing relevant quantities of the Product and of
manufacturing
 8




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the drug substance from which it is made), in advance of incurring them, and, in
each case, at the same time, will provide that other with its calculations or other
reasonable evidence thereof;(b)
    
    following any such notice, the parties will use their reasonable endeavours
to agree, as quickly as reasonably practicable, the appropriateness and acceptability
of such Costs;(c)
    
    within fifteen (15) days of reaching any such agreement, each party will
pay into the Escrow Account a sum equal to one-half of that specified in the relevant
notice given pursuant to clause 3.5(a) or as otherwise agreed pursuant to clause
3.5(b);(d)
    
    subject to clause 3.11, the notifying party will pay from the Retention
such of those Costs as arise;(e)
    
    the notified party will, from time to time, sign and deliver to the Escrow
Account Bank or the notifying party, as the notifying party directs, such bank
mandates as the notifying party may require for such purpose; and(f)
    
    the notified party will not unreasonably withhold or delay any signature
and/or action required to facilitate the making of any such payment.
 3.6
    
    If Protherics grants any Sub-licence between the completion of the First Clinical Study
undertaken in the course of the Development Programme and the filing of the first application
for a Marketing Authorisation for the Product for the Indication, and Protherics receives from
its Sub-licensee thereunder any payment of any of its Costs of undertaking any of the matters
described in clause 2.2(c):
 (a)
    
    Protherics shall pay the same into the Escrow Account;(b)
    
    such payment will belong to the parties in equal shares;(c)
    
    the parties shall, subject to clause 3.12, use such payment only to pay
Costs actually incurred in undertaking any of the matters described in clause 2.2(c);
and(d)
    
    the parties shall not so use, or commit so to use, the same in advance of
agreeing such Costs pursuant to clause 3.5(b).
 3.7
    
    Each party will act reasonably in trying to minimise (having regard to its obligations
hereunder) and in calculating any Costs notified by it to the other pursuant to clause 3.5(a)
and will, where appropriate and practicable, base such calculations on estimates provided to
it by such third parties (including clinical research organisations) as it may be considering
contracting to conduct the relevant part(s) of the Development Programme or purchase Product.3.8
    
    Without limitation, any Dispute between the parties concerning the calculation,
appropriateness or acceptability of any anticipated up-coming Cost notified by either party to
the other pursuant to clause 3.5(a) shall be referred for resolution as provided in clause 23.3.9
    
    Should either party, acting reasonably, consider that the Retention may fall to zero, or be
overdrawn, or should the Retention fall to zero or be overdrawn, it may notify the other of
the amount it reasonably considers each party will have to pay into the Escrow Account to
avoid, or rectify, such situation, as applicable (which amount may be greater than the
difference between the then balance of the Retention and the agreed budgeted Costs of the then
remaining portion of the Development Programme), and at the same time provide that other with
its calculations of such amount.
 9




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3.10
    
    Within five (5) days of any notice given pursuant to clause 3.9, each party will pay into the
Escrow Account a sum equal to one-half of the amount notified pursuant to that clause.3.11
    
    Should either party, at any time, be unable to fund from the Escrow Account any of the Costs
referred to in clauses 2.5 or 2.6 for which it has properly contracted, or will properly
contract, with any third party to pay, it may:
 (a)
    
    fund them itself, in which case it will be entitled to reclaim from the
other party one-half thereof by invoicing that other the relevant sum; and that other
party will pay any such invoice within five (5) days; or(b)
    
    postpone entering into, or making any payment under, any such third party
contract until sufficient sums are available in the Escrow Account, without liability
to the other under this agreement for any resulting delays to the Development
Programme; provided that it alone will be liable to any third party affected by the
postponement.
 3.12
    
    As soon as reasonably practicable following the earlier of Termination and the payment of the
last Cost to which clause 2.5 relates, the parties will pay half the Retention to each of them
and then close the Escrow Account.3.13
    
    No payment out of the Escrow Account will be made, authorised or requested, except as set out
herein.4.
    
    JOINT PROJECT TEAM4.1
    
    Within thirty (30) days following the Effective Date the parties will establish the Joint
Project Team.4.2
    
    The membership of the Joint Project Team will be comprised of an equal number of
representatives of each party, and initially no more than four (4) representatives of each
party.4.3
    
    Without prejudice to clause 6.3, the parties may, by agreement from time to time, increase or
decrease the number of members of the Joint Project Team, and each may replace those members
appointed by it at will by notice to the other.4.4
    
    Each party will:
 (a)
    
    promptly notify the other of its appointments to, replacements for or
removals from, the Joint Project Team of its representatives thereon;(b)
    
    ensure that the members thereof appointed by it and present on the Joint
Project Team are at all times suitably skilled, willing, available and qualified to
undertake their roles as members thereof, as such roles may change over time; and(c)
    
    remove from the Joint Project Team, and promptly replace, any of them who
is not, or otherwise provide them with such training or other assistance as may be
required such that they are so skilled, willing, available and qualified, as soon as
reasonably practicable.
 4.5
    
    Notwithstanding clause 4.4, if the members of the Joint Project Team reasonably object to the
inclusion in the membership of the Joint Project Team of any person, they may remove him with
immediate effect if a majority of the members decide that he should be removed and they first
give their reasons for that decision to the parties.
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4.6
    
    The Joint Project Team will be responsible for overseeing the proper undertaking of the
Development Programme and, where relevant, for making decisions with respect thereto,
including with respect to:
 (a)
    
    the quality and quantity of Product required for the Non-clinical Studies
and Clinical Studies undertaken in the course of the Development Programme;(b)
    
    the design of the Non-clinical Studies and Clinical Studies undertaken in
the course of the Development Programme; and(c)
    
    the selection of third party contractors to be involved in the Development
Programme,
 but will not be responsible for any matter specified in this agreement as the
responsibility of the Steering Committee, and, for the avoidance of doubt, shall not be
entitled to amend this agreement.4.7
    
    The Joint Project Team will meet where and when it determines, provided that:
 (a)
    
    each of its meetings will be at a location reasonably accessible to all its
members, which will alternate with each meeting between the United Kingdom and Spain;(b)
    
    its members will be entitled to attend its meetings by telephone and that
suitable telephone facilities are present at its meetings to enable this; and(c)
    
    it will meet on no less than one weeks notice to all its members sent to
each member in such manner as he may have reasonably specified or otherwise by fax or
first class post (and for the purposes of this clause 4 the provisions of clause 22
will apply mutadis mutandis).
 4.8
    
    The parties Project Managers will take turns, alternating at each meeting of the Joint
Project Team, as the chairman of such meeting, and Protherics Project Manager will chair its
first meeting.4.9
    
    The Joint Project Team will discharge its functions in such manner as it reasonably sees fit.4.10
    
    The Joint Project Team will determine its own quorum, provided that this will always include
equal numbers of representatives of each of Protherics and Advancell.4.11
    
    The Joint Project Team will only decide any matter if quorate and, if any member of the Joint
Project Team wishes any decision to be voted upon, each of its members will have one vote,
with the chairman not having a casting vote.4.12
    
    All decisions, and actions, of the Joint Project Team made at any of its meetings will be
minuted, and the minutes provided to the members of the Steering Committee for the time being
within seven (7) days of the relevant meeting (and for these purposes the provisions of clause
22 will apply mutadis mutandis; provided that minutes may also be provided by email to such
relevant addresses as are provided in advance, in which case they will be deemed to be
received upon sending).4.13
    
    The parties will use their reasonable endeavours to bring about agreement of the members of
the Joint Project Team with respect to all matters addressed by it as quickly as reasonably
practicable but if the Joint Project Team is unable to reach a decision on any matter within a
reasonable time, the Joint Project Team will, and any of its members may, refer the matter in
writing to the Steering Committee with:
 (a)
    
    such information as the Steering Committee may reasonably require to decide
the matter; and
 11




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(b)
    
    details of the date by which the matter must be decided,
 and from the time of such reference, the matter will be for the Steering Committee, and not
the Joint Project Team, to decide.4.14
    
    The chairman of the relevant meeting of the Joint Project Team will oversee its compliance
with clauses 4.6 to 4.7 and 4.9 to 4.13, and such compliance will be the responsibility of the
party of which such person is the Project Manager.5.
    
    STEERING COMMITTEE5.1
    
    Within thirty (30) days following the Effective Date the parties will establish the Steering
Committee.5.2
    
    Without prejudice to clause 6.3, the membership of the Steering Committee will be comprised
of three (3) representatives of each party, including the Project Managers of each party.5.3
    
    Each party may, from time to time, replace those members appointed by it to the Steering
Committee at will and upon notice to the other party.5.4
    
    The parties, beginning with Protherics, will take turns to appoint, on each occasion for a
one-year term, a member of the Steering Committee as chairman of the Steering Committee, the
first appointment to take effect from the first meeting of the Steering Committee; and the
party which does not appoint the then appointed chairman of the Steering Committee shall, at
the same time, appoint the secretary of the Steering Committee, for such one-year term, from
amongst its other members. Should any chairman or secretary of the Steering Committee cease
to be a member of the Steering Committee, the party which appointed him/her as chairman or
secretary, as applicable, shall appoint another member thereof to such position from his/her
ceasing to be a member until the end of what would have been his/her term.5.5
    
    Each party will ensure that the members of the Steering Committee appointed by it, and
present on the Steering Committee, are at all times suitably skilled, willing, available and
qualified to undertake their roles as members thereof, as such roles may change over time, and
will remove from the Steering Committee, and promptly replace, any of them who is not, or
otherwise provide them with such training or other assistance as may be required such that
they are so skilled, willing, available and qualified as soon as reasonably practicable.5.6
    
    Notwithstanding clause 5.5, if the members of the Steering Committee reasonably object to the
inclusion in the membership of the Steering Committee of any person, they may remove him with
immediate effect if a majority of the members decide that he/she should be removed and they
first give their reasons for that decision to the parties.5.7
    
    The Steering Committee will be responsible for overseeing the general working relationships
under this agreement and the Joint Project Team. In particular, the responsibilities of the
Steering Committee will include:
 (a)
    
    resolving disputes arising from the Joint Project Team;(b)
    
    appointing additional committees and/or working groups from time to time as
may be agreed by the Steering Committee as necessary to facilitate the Development
Programme;(c)
    
    maintaining a good working relationship between the parties;(d)
    
    overseeing the operation of the Escrow Account in accordance with clause 3;
 12




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(e)
    
    agreeing the terms of the Development Programme, and any amendments to the
Development Programme;(f)
    
    agreeing the budget for the Development Programme and any amendments to it
which will, or may, increase the total cost of the Development Programme by more than
£100,000; and(g)
    
    any other matters which this agreement requires to be resolved or managed
by the Steering Committee,
 but, for the avoidance of doubt, the Steering Committee shall not be entitled to amend this agreement.5.8
    
    The Steering Committee will meet where and when it determines, provided that:
 (a)
    
    each of its meetings will be at a location reasonably accessible to all its
members, which will alternate with each meeting between the United Kingdom and Spain;(b)
    
    its members will be entitled to attend its meetings by telephone and that
suitable telephone facilities are present at its meetings to enable this;(c)
    
    it will meet no less than once every six (6) months, the first meeting to
be within three (3) months of the Effective Date, and otherwise within a reasonable
time to determine any matter referred to it; and(d)
    
    it will meet on no less than one weeks notice to all its members sent to
each member in such manner as he/she may have reasonably specified or otherwise by
fax or first class post (and for the purposes of this clause 5 the provisions of
clause 22 will apply mutadis mutandis).
 5.9
    
    The Steering Committee will determine its own quorum, provided that this will always include
at least one representative of each of Protherics and Advancell.5.10
    
    The Steering Committee will discharge its functions in such manner as it reasonably sees fit.5.11
    
    The Steering Committee will only decide any matter if quorate and, if any member of the
Steering Committee wishes any decision to be voted upon, each of its members will have one
vote.5.12
    
    If any vote of the Steering Committee is tied, whichever of its then chairman and secretary
has been appointed by Protherics shall have the casting vote, provided that such casting vote:
 (a)
    
    is exercised to further the objectives of the Development Programme;(b)
    
    does not change the budget of the Development Programme; and(c)
    
    does not require either party to incur expenditure additional to any as has
previously been agreed (by the parties, the Joint Project Team or the Steering
Committee),
 and if, because of such proviso, any vote remains tied notwithstanding this clause 5.12,
the vote shall be deemed not to have passed, and any purported casting vote cast contrary
to such proviso shall be void.5.13
    
    If any vote of the Steering Committee concerning agreeing the terms of the Development
Programme, or any amendment to the Development Programme, is tied, the matter shall be
resolved as follows:
 13




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(a)
    
    the matter shall, from the time of such vote, be referred to the Chief
Executive Officer for the time being of Protherics and the President for the time
being of Advancell, who may decide the matter on behalf of the parties;(b)
    
    if the matter is not so decided within a period of ten (10) Business Days,
either such person may require it to be referred to a third party expert in matters
of that nature agreed between them and:
 (i)
    
    the parties which they represent shall use their reasonable
endeavours to procure that such persons agree the identity of such expert as
quickly as reasonably practicable;(ii)
    
    the parties shall afford such expert all reasonable assistance
in deciding the matter, and shall use their reasonable endeavours to procure
that he decides it as quickly as practicable and with the intention of
furthering the objective of the parties set out in the recitals;(iii)
    
    such experts decision shall be binding on the parties and the
parties shall procure that he records it, together with his reasons for
reaching it, and delivers such record to the parties as quickly as reasonably
practicable; and(iv)
    
    the parties shall share equally the costs of such expert.
 5.14
    
    The secretary of the Steering Committee will oversee its compliance with clauses 5.8 to 5.13,
and such compliance will be the responsibility of the party which appointed to the Steering
Committee the member who is its secretary.5.15
    
    The secretary will minute all actions and decisions of the Steering Committee, and provide
copies of the minutes to its members within seven (7) days of the relevant meeting (and for
these purposes the provisions of clause 22 will apply mutadis mutandis; provided that minutes
may also be provided by email to such relevant address as are provided in advance, in which
case they will be deemed to be received upon sending).5.16
    
    Minutes of the actions and decisions of the Steering Committee will not be considered
definitive until signed by the Chairman of the Steering Committee with the approval of the
Steering Committee.6.
    
    GENERAL MATTERS CONCERNING THE JOINT PROJECT TEAM AND THE STEERING COMMITTEE6.1
    
    The parties will ensure that neither the Joint Project Team nor the Steering Committee acts
contrary to this agreement, and clauses 4 and 5 will be interpreted accordingly.6.2
    
    The parties will use their reasonable endeavours to ensure that the Joint Project Team and
the Steering Committee discharge their functions with all due diligence and expeditiously.6.3
    
    The Joint Project Team and the Steering Committee may each co-opt such persons as they decide
to attend their meetings in order to assist them in discharging their functions and/or as
additional members, provided that all such persons are bound by obligations of confidentiality
at least as protective of each of the parties, and their interests, as those of this
agreement.6.4
    
    The agenda of each meeting of each of the Joint Project Team and the Steering Committee will
include a resolution for the approval of the minutes of the previous meeting.6.5
    
    The meetings of the Joint Project Team and the Steering Committee, and the minutes of their
decisions and actions, will be in the English language.
 14




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6.6
    
    The chairman of each of the Joint Project Team and the Steering Committee, from time to time,
will oversee its compliance with this clause 6, and such oversight will be the responsibility
of the party which appointed the chairman.7.
    
    LICENCE7.1
    
    Subject to clause 7.2, Advancell grants to Protherics, as of the Effective Date, an
exclusive, sub-licensable licence in the Field of Use under:
 (a)
    
    the Patents; and(b)
    
    such Intellectual Property Rights as subsist, or come into subsistence, in
the Know-how,
 to develop, make, dispose of, offer to dispose of, use, import and keep the Product, and
any product derived from or incorporating the Product, including by way of the Development
Programme.7.2
    
    The exclusivity of the licence granted by clause 7.1 will be subject only to Advancell being
entitled to undertake, or have undertaken, the Development Programme as provided by this
agreement.7.3
    
    Subject to clause 7.2, any development, making, disposal of, offer to dispose of, use,
importation or keeping of the Product, or any product derived from or incorporating the
Product, in the Field of Use, will require the prior written agreement of, and the grant of a
sub-license from, Protherics.7.4
    
    Advancell will, from time to time, assist Protherics, as Protherics may request (including by
signing any necessary documents), to record the interest of Protherics and any Sub-licensees
under the Patents (including such as are filed and/or granted during the Term) on any relevant
patent register.7.5
    
    Without prejudice to the exclusivity of the Licence (subject to clause 7.2), Advancell will
not, at any time, do anything to lessen its entitlement to, or Encumber or grant any third
party any right in or to, any of the Intellectual Property Rights licensed hereby, save as
permitted by clause 11.5.7.6
    
    Protherics shall use its reasonable endeavours to commercialise the Product for the
Indication, bearing in mind the potential market therefor.8.
    
    DELIVERY OF KNOW-HOW8.1
    
    Advancell will deliver to Protherics all of the Know-how which Protherics reasonably requires
to perform, or enjoy the benefit of, this agreement, but Advancell will retain copies thereof
for the purposes of its own performance of this agreement.8.2
    
    Advancell will deliver to Protherics all of the Know-how referred to in clause 8.1 as soon as
reasonably practicable following the Effective Date or its creation or its coming into
Advancells possession or under its control, as applicable.8.3
    
    Advancell will provide such assistance as Protherics may request to transfer the Know-how to
Protherics or to assist in the use thereof in Protherics undertaking of, or having
undertaken, the Development Programme and/or the commercialisation of the Product for the
Indication.8.4
    
    The assistance referred to in clause 8.3 may include:
 (a)
    
    preparing for, or attending, meetings with any Health Authority;
 15




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(b)
    
    dealing with requests or enquiries from any Health Authority;(c)
    
    and preparing and filing applications for Health Registration Approvals.
 8.5
    
    If at any time Advancell becomes aware of any defect or insufficiency in any Know-how it will
immediately notify Protherics with full details.8.6
    
    To the extent permitted by Law, Advancell hereby assigns to Protherics, or will procure the
assignment to Protherics, in each case with effect from the Effective Date or the same coming
into existence, whichever is the sooner, all right, title and interest in and to the Orphan
Drug designation of the Product for the Indication in the European Union, and the pending
Orphan Drug designation of the Product for the Indication in the United States of America, in
the name of Advancell.9.
    
    ROYALTIES AND MILESTONES9.1
    
    In consideration of the rights granted by this agreement, Protherics will make the payments
specified in this clause 9.9.2
    
    Protherics will pay Advancell five hundred thousand pounds (£500,000) within five (5) days
following the Effective Date.9.3
    
    Protherics will pay to Advancell a royalty at the rate of twelve point eight per cent.
(12.8%) of:
 (a)
    
    the Net Selling Price in respect of each Royalty Event concluded in the
European Union or the United States of America; and(b)
    
    the Net Selling Price of Protherics in respect of each other Royalty Event,
 as provided in clause 9.4.9.4
    
    Protherics shall pay royalties in accordance with clause 9.3 from the first disposal for
value of the Product for the Indication until, on a country-by-country, or
territory-by-territory basis, the later to occur of:
 (a)
    
    the * anniversary of the First Commercial Sale of the Product in such
country or territory; and(b)
    
    the expiry of the last Valid Claim of any Patent in such country or
territory claiming the use of the Product for the Indication,
 and, following such cessation of the obligation to pay royalties in a country or territory,
the Licence will continue in effect in such country or territory on a fully paid-up basis
for the remainder of the Term. .9.5
    
    If Protherics grants any Sub-licence before filing its first application for the grant of a
Marketing Authorisation for the Product for the Indication anywhere in the European Union or
in the United States of America, Protherics will pay Advancell * per
cent. (*%) of
Protherics receipts in the form of development or commercialisation milestones, whether cash
or otherwise (other than any Net Selling Price and any sum the subject of clause 3.6),
pursuant to such Sub-licence, received by Protherics prior to the grant of the first such
Marketing Authorisation, including any development-related milestones.9.6
    
    Payments pursuant to clauses 9.3 or 9.5 will be made Quarterly thirty (30) days after the end
of the Quarter in which Protherics (or in the case of clause 9.3(a), its relevant
Sub-licensee) receives the Net Selling Price or other receipt on which they are calculated.
 * confidential treatment
requested 16




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9.7
    
    Subject to clause 9.9, Protherics will pay Advancell milestone payments as follows (and no
such milestone will be payable more than once):
 (a)
    
    £3,500,000 at the start of the first Phase IIb Study;(b)
    
    £* at the start of the *;(c)
    
    £* upon *;(d)
    
    £* upon *;(e)
    
    £* upon the *;
and(f)
    
    £* upon the *.
 9.8
    
    For the purposes of this agreement, a Phase IIb Study or Phase III Study will be considered
to start when the first patient involved therein is dosed in the course thereof.9.9
    
    If Protherics files any application for a Marketing Authorisation for the Product for the
Indication without having first completed a Phase IIb Study and/or Phase III Study, the sums
specified in clauses 9.7(a) and (b) shall become payable at the time of such filing.9.10
    
    Protherics will, within thirty (30) days of the occurrence of each such event, notify
Advancell of the occurrence of each of the events referred to in any of clauses 9.7(a) to (d)
and, within thirty (30) days following receipt of any such notification, Advancell will
deliver to Protherics an invoice for the amount payable in respect of such event pursuant to
the relevant such clause.9.11
    
    Protherics will pay the sums properly specified in the invoices issues pursuant to clause
9.10 within thirty (30) days following the end of the month in which the relevant invoice is
received by Protherics.9.12
    
    All payments pursuant to this clause 9 will be made in Euros to Advancells account no.
*, or as otherwise specified
by Advancell in advance from time to time.9.13
    
    For the purpose of calculating payments due hereunder, conversions from the currency in which
the relevant sale of the Product is made into Euros will, where applicable, be calculated at
the actual average rate of exchange for the year to date as used by Protherics in producing
its accounts.9.14
    
    Protherics will keep at its usual place of business true and accurate books of account
containing all information necessary for the determination of all royalties due under this
agreement, and will procure that its relevant Sub-licensees do likewise.9.15
    
    Protherics will permit Advancells external representatives a right of access, once per year,
during normal business hours upon reasonable notice, to the books of account kept pursuant to
clause 9.14, and to take copies of them.9.16
    
    Advancell will keep confidential any information which it may acquire in the exercise of its
rights under this clause 9.15, in accordance with clause 10.9.17
    
    All sums paid hereunder will be exclusive of any applicable Value Added Tax due.9.18
    
    Any overdue sum payable under this agreement will bear interest, accruing from the due date
until the date of actual payment, whether before or after judgment, calculated at a
 * confidential treatment
requested 17




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daily rate equivalent to one (1) per cent. above the United Kingdom base rate for the time
being of Barclays Bank plc and compounded annually at the end of year, and, if this
agreement is terminated other than at the end of a year, on the date of Termination.
 9.19
    
    Payments hereunder will be made without set-off or deduction, other than such amount as the
paying party is required to deduct or withhold by law. If requested, evidence as to the
payment of such tax or sum withheld will be given by the paying party to the other and the
parties will co-operate reasonably to claim recovery or exemption under any double taxation or
similar agreement with respect to any such deduction.10.
    
    CONFIDENTIALITY10.1
    
    At all times during the Term, and for a period of five (5) years following Termination, each
party (the Receiving Party) will, and will cause its officers, directors, employees, agents
and Affiliates to, keep confidential, and not publish or otherwise disclose, and not use,
directly or indirectly, for any purpose, any Confidential Information provided to it by or on
behalf of the other party (the Disclosing Party), except to the extent such disclosure or
use is expressly permitted by the terms of this agreement or is reasonably necessary for the
performance of the Development Programme or otherwise for the purposes envisaged by this
agreement.10.2
    
    Advancell recognises that, by reason of Protherics status as an exclusive licensee pursuant
to clause 7, Protherics has an interest in Advancells retention in confidence of certain
confidential information of Advancell. Accordingly, Advancell will, and will cause its
Affiliates and their respective officers, directors, employees and agents to, keep
confidential, and not publish or otherwise disclose, any confidential information in its
possession, or under its control, relating to the Product, including the Know-How (the
Licensor Information). The disclosure by Advancell to Protherics of Licensor Information
will not, in itself, cause such information to cease to be confidential.10.3
    
    Notwithstanding clause 10.1, each party may disclose, and permit the disclosure of,
Confidential Information to the extent that such disclosure is:
 (a)
    
    made in response to a valid order of a court of competent jurisdiction or
other competent authority (including any Health Authority), provided, however, that
the Receiving Party will, subject to Law, first have given notice to the Disclosing
Party and given the Disclosing Party a reasonable opportunity to seek to overturn any
such order or obtain a protective order requiring that the Confidential Information
subject of such order be held in confidence by such court or authority or, if
disclosed, be used only for the purpose for which the order was issued; and provided
further that if such order is not overturned or a protective order is not obtained,
the relevant Confidential Information disclosed in response to such court or
governmental order will be limited to that which is legally required to be disclosed
in response to such court or governmental order;(b)
    
    made by the Receiving Party to a Health Authority as may be necessary or
reasonably useful in connection with any filing, application or request for a Health
Registration Approval; provided, however, that reasonable measures will first be
taken to assure confidential treatment of such Confidential Information, to the
extent such protection is available;(c)
    
    made by the Receiving Party to a relevant authority, as required and/or
permitted hereby, where necessary or reasonably useful for the purposes of obtaining
or enforcing a Patent or any Intellectual Property Right in the Know-How, as required
and/or permitted hereby, provided, however, that the Receiving Party will take
reasonable measures to assure confidential treatment of such information, to the
extent such protection is available; or
 18




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(d)
    
    otherwise required by Law, provided, however, that the Receiving Party
will, subject to Law:
 (i)
    
    provide the Disclosing Party with reasonable advance notice of,
and an opportunity to comment on, any such required disclosure;(ii)
    
    if requested by the Disclosing Party, seek confidential
treatment with respect to any such disclosure to the extent available; and(iii)
    
    use its reasonable endeavours to act upon the comments of the
Disclosing Party in making any such disclosure.
 10.4
    
    Protherics may disclose, and otherwise use, Confidential Information as necessary in
developing, studying and commercialising the Product, provided that Protherics takes such
steps as are reasonable in the circumstances to protect the confidentiality of such
Confidential Information, to the extent not incompatible with its legitimate interests.10.5
    
    Notwithstanding the foregoing, Confidential Information will not include any information
that:
 (a)
    
    is or hereafter becomes part of the public domain by or through no wrongful
act, fault or negligence on the part of the Receiving Party;(b)
    
    can be demonstrated by documentation, or other competent proof, to have
been in the Receiving Partys possession prior to disclosure by the Disclosing Party,
free of any obligation of confidence owed to any third party;(c)
    
    is subsequently received by the Receiving Party from a third party who is
not bound by any obligation of confidentiality with respect to said information;(d)
    
    is generally made available to third parties by the Disclosing Party
without restriction on use or disclosure; or(e)
    
    can be demonstrated by documentation, or other competent proof, to have
been independently developed by or for the Receiving Party without reference to the
Disclosing Partys Confidential Information.
 10.6
    
    Specific aspects or details of Confidential Information will not be deemed to be within the
public domain, or in the possession of the Receiving Party, merely because the Confidential
Information is embraced by more general information in the public domain or in the possession
of the Receiving Party, and any combination of Confidential Information will not be considered
in the public domain or in the possession of the Receiving Party merely because individual
elements of such Confidential Information are in the public domain or in the possession of the
Receiving Party unless the combination and its principles are in the public domain or in the
possession of the Receiving Party.10.7
    
    This clause 10 will not be construed to prohibit either party from identifying the other
party in its internal business communications, provided that any Confidential Information in
such communications remains subject to this clause 10.10.8
    
    Clauses 10.3 and 10.5 to 10.7(with the exception of clauses 10.5 (b)) will apply, mutatis
mutandis, to Licensor Information as they do to Confidential Information and, for these
purposes, Advancell will be deemed to be the Receiving Party, and Protherics the Disclosing
Party, thereof.10.9
    
    The text of any press release or other communication to be published by or in the media
concerning the subject matter of this agreement will require the approval of both parties.11.
    
    OWNERSHIP OF THE PATENTS AND KNOW-HOW
 19




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11.1
    
    Advancell will, with all reasonable skill, care and attention:
 (a)
    
    file applications for Patents;(b)
    
    prosecute all those Patents that are patent applications (including those
filed hereafter), and(c)
    
    maintain all those Patents that are granted patents,
 so as to acquire and maintain the broadest patent protection practicable for the inventions
claimed by the Patents listed in schedule 1, throughout the world, for the longest term
practicable (including by defending any claim, counter-claim, objection or opposition
concerning validity or entitlement).11.2
    
    Advancell will:
 (a)
    
    give serious consideration to any proposals of Protherics concerning
Advancells performance of its obligations further to clause 11.1;(b)
    
    keep Protherics informed of progress, and of objections raised, in respect
of such matters; and(c)
    
    otherwise provide Protherics with evidence of its compliance with those
obligations.
 11.3
    
    Without prejudice to clause 11.1, if Advancell wishes to abandon any application comprised in
the Patents, or not to renew or maintain any particular Patent, Advancell will give Protherics
sixty (60) days notice and will, if requested by Protherics, assign such Patent to
Protherics, for nominal consideration, free of Encumbrances.
 11.4
    
    Other than pursuant to clause 11.3, Advancell will not assign any Patent, or any Intellectual
Property Right in any Know-How, in the Field of Use, nor will Advancell Encumber any of them.
 11.5
    
    Advancell shall only assign or Encumber any Patent or any Intellectual Property in any
Know-How if it does so on terms that:
 (a)
    
    protect Protherics benefit hereunder; and(b)
    
    ensure that each person to whom any such assignment or Encumbrance is
granted imposes:
 (i)
    
    such obligation; and(ii)
    
    the obligation imposed by this clause 11.5(b),
  in each case which are directly enforceable by Protherics.12.
    
    INFRINGEMENT12.1
    
    Each party will, as soon as it becomes aware, give the other full written particulars of any
conduct or proposed conduct by any third party which amounts, or might amount, either to
infringement of any Patent or unauthorised use of any Know-how.12.2
    
    Each party will, as soon as it becomes aware, notify the other of any allegation by any third
party that:
 20




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(a)
    
    any Patent is invalid;(b)
    
    that the undertaking of the Development Programme, or exploitation of the
Product for the Indication, infringes, or will infringe, any rights of another
person; or(c)
    
    that the Patents are otherwise attacked or attackable,
 and will give the other full written particulars thereof, and make no comment or admission
with respect thereto, to any third party.12.3
    
    Subject to clause 12.7, Advancell will bring and conduct, with all reasonable skill, care and
attention, all Claims and other action for infringement of any Patent, or with respect to the
unauthorised use of any Know-how, which it or Protherics considers appropriate.12.4
    
    Advancell will give Protherics reasonable opportunity to comment on material issues regarding
any action to which clause 12.3 relates, and will comply with Protherics reasonable
directions with respect thereto.12.5
    
    Protherics will, at Advancells Cost, provide all reasonable assistance requested by
Advancell for the purposes of Advancells performance of its obligations further to clause
12.3.12.6
    
    Any damages, or account of profits, awarded further to any action taken pursuant to clause
12.3 will be divided equitably between the parties having regard to their respective losses
resulting from the relevant infringement or unauthorised use.12.7
    
    Without prejudice to Advancells obligations pursuant to clause 12.3, where:
 (a)
    
    Protherics gives Advancell thirty (30) days notice requesting any action
of any type referred to in clause 12.3, and Advancell does not commence such action
within this time period; or(b)
    
    prompt action is reasonably necessary regarding the relevant matter,
Protherics gives Advancell notice to this effect and Advancell does not commence such
action within the time specified in the notice,
  (i)
    
    may commence, and conduct, such action;(ii)
    
    will be entitled to all of any damages, or account of profits,
awarded in respect thereof; and(iii)
    
    may, and at Advancells cost, require Advancell to join,
either as a co-plaintiff or as defendant (such choice, if available under the
applicable Law, to be made by Advancell, in its discretion), in, and assist
regarding, such action.
 12.8
    
    Protherics may deduct its Costs in taking, conducting and settling any action further to
clause 12.7 from any sums payable pursuant to clause 9 in such manner as Protherics
determines, provided that Protherics may only so deduct any third party costs award made in
respect of any such action after it is made.12.9
    
    The Costs referred to in clause 12.8 shall be net of any award of costs made to Protherics in
the action to which they relate.12.10
    
    If any costs award is made to Protherics in any action further to clause 12.7 and Protherics
has, by the time of such award, deducted any of its Costs in taking,
 21




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conducting and settling such action from any sums payable by it pursuant to clause 9,
Protherics shall pay Advancell a sum equal to such deduction at the same time as
Protherics makes its next payment to Advancell pursuant to clause 9.13.
    
    LIABILITY/INDEMNITY13.1
    
    The following provisions govern the entire liability of each party (including any liability
for the acts and omissions of its Personnel) to the other in respect of:
 (a)
    
    any breach of its contractual obligations arising under this agreement; and(b)
    
    any representation, statement or tortious act or omission including
negligence arising under or in connection with this agreement.
 13.2
    
    Except as is expressly stated in this agreement, no representation, condition or warranty
whatsoever is made or given by or on behalf of Protherics, and, to the greatest extent
permissible by Law, any such conditions and warranties, whether arising by operation of Law or
otherwise, are expressly excluded.
 13.3
    
    No exclusion or limitation set out in this clause 13 will apply in the case of:
 (a)
    
    fraud or fraudulent concealment;(b)
    
    death or personal injury resulting from the negligence of either party; or(c)
    
    any other liability which cannot lawfully be excluded or limited.
 13.4
    
    Subject to clause 13.6, neither party will be liable to the other in respect of any act or
omission to the extent that the same arises as a result of a failure by that other, or any
third party, to fulfil its obligations under this agreement.
 13.5
    
    Neither party will be liable to the other for any Indirect Loss or any related Claims and
Costs arising from any act or omission, provided that this clause will not exclude any
liability either party may have to the other in respect of any Costs incurred in connection
with repeating any part of the Development Programme.
 13.6
    
    The following provisions shall apply to any liability of either or both of the parties to any
third party arising out of any act or omission of either or both of them in the course of, or
connected with, the Development Programme, and their reasonable Costs incurred in respect of
any Claim made, threatened or reasonably contemplated with respect to such matter (together,
Shared Costs"):
 (a)
    
    subject to clauses 13.6(b) and (c), the parties shall be jointly and
severally liable, in equal shares, as between each other for all Shared Costs;(b)
    
    each partys liability pursuant to clause 13.6(a) shall be conditional on
the other:
 (i)
    
    giving notice in writing to such party (the Liable Party") of
such act or omission, setting out reasonable details thereof including, as far
as reasonably practicable, details of the maximum potential Shared Costs with
respect thereto;(ii)
    
    at all reasonable times, consulting with, and providing
reasonable information, assistance (including reasonable access to premises,
personnel and documentation) and co-operation to, the Liable Party, in a timely
manner, with respect thereto, and to the progress, conduct and settlement
thereof;
 22




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(iii)
    
    taking such action in relation to the matter as the Liable
Party may agree in writing to its taking (such agreement not to be unreasonably
withheld or delayed);(iv)
    
    from first giving notice pursuant to clause 13.6(b)(i), only
using advisers agreed with the Liable Party (such agreement not to be
unreasonably withheld or delayed) in respect of such matter;(v)
    
    at all times using its reasonable endeavours to keep to such
Shared Costs to a minimum and otherwise mitigating them;(vi)
    
    not encouraging or promoting any relevant Claim;(vii)
    
    not admitting any liability in respect of, or settling, any
such Claim, or agreeing to do either of the foregoing, without first obtaining
the Liable Partys written consent (not to be unreasonably withheld or
delayed);(viii)
    
    if (and when) any such Claim is made, notifying the Liable Party within
reasonably sufficient time to enable the Liable Party properly to contest the
same before final judgment; and(ix)
    
    not waiving or otherwise compromising, and using its reasonable
endeavours to enforce against any relevant third party, the parties rights in
relation to or in connection with the matter, save where the parties agree
otherwise (such agreement not to be unreasonably withheld or delayed); and
 (c)
    
    this clause 13.6 is:
 (i)
    
    subject to clauses 2.4 to 2.7, inclusive; and(ii)
    
    without prejudice to clause 14.
 13.7
    
    Advancell will not be liable for Protherics exploitation of the Product outside the
Development Programme, save to the extent that Advancell is at fault.13.8
    
    The parties will each obtain, and maintain for the Term and six (6) years thereafter,
insurance against their liabilities hereunder, in such amounts as shall be sufficient to cover
all such liabilities, with one or more reputable insurers, and will provide one another with
evidence of such insurance upon request from time to time.14.
    
    WARRANTIES14.1
    
    Each party warrants and represents to the other that:
 (a)
    
    it has authority to enter into, and perform, this agreement and that its
entry into, and performance of, this agreement does not, and will not, conflict with
any of its other obligations; and(b)
    
    it will undertake, or have undertaken, the Development Programme:
 (i)
    
    in accordance with:
 (A)
    
    all applicable Laws;(B)
    
    Good Industry Practice; and(C)
    
    the requirements of all applicable Health
Authorities; and
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(ii)
    
    otherwise with reasonable skill, care and attention.
 14.2
    
    Advancell warrants and represents to Protherics that:
 (a)
    
    it is the exclusive legal and beneficial owner of the patents and patent
applications specified in schedule 1, which is a complete and accurate list of all
subsisting Patents, and of all Intellectual Property Rights as subsist in the
Know-how;(b)
    
    it is not aware of any current or proposed Claim, valid or otherwise, to
the ownership or other interest in any Patent or any Intellectual Property Rights as
subsists in any of the Know-how, nor of any reasonable basis for the assertion of any
such Claim;(c)
    
    it is not aware of any current or proposed Claim, valid or otherwise, that
the undertaking of the Development Programme or any other exercise of any of the
Intellectual Property Rights licensed, or purported to be licensed, by the Licence
will or might infringe any third party rights;(d)
    
    the Know-how was generated in the course of the normal duties of
Advancells employees;(e)
    
    it is free to disclose and deliver the Know-how to Protherics;(f)
    
    except as expressly permitted by this agreement, it will take no action in
derogation of the Licence;(g)
    
    it has not supplied or permitted the supply of any Know-how to any person,
except under binding obligations of confidentiality, and that it is not aware of any
breach of any such obligations; and(h)
    
    it is not aware of any use by any third party of any of any of the
inventions claimed by any of the Patents which will, or might, amount to an
infringement, or of any unauthorised use of any of the Know-how.
 14.3
    
    Protherics warrants and represents to Advancell that it intends to perform its obligations
hereunder.14.4
    
    Save for those warranties expressly given in this clause 14, neither party makes any
warranty, express or implied, and, to the extent permitted by Law, each party specifically
disclaims any warranties not expressly given in this clause 14.15.
    
    TERM15.1
    
    This agreement will commence on the Effective Date.15.2
    
    The Licence will continue in force until all of the Patents, and all Intellectual Property
Rights subsisting in any Know-how, have expired, or until the earlier termination of this
agreement.16.
    
    TERMINATION16.1
    
    The parties may agree to terminate this agreement if they consider the results of the
Development Programme to be unsatisfactory, in which case:
 (a)
    
    the Licence will terminate;(b)
    
    Protherics will return to Advancell such Know-how as has been delivered by
Advancell to Protherics pursuant to clause 8.1; and
 24




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(c)
    
    Protherics will assign back to Advancell, or procure the assignment back to
Advancell of, the right, title and interest in Orphan Drug designations which were
assigned to Protherics pursuant to clause 8.6.
 16.2
    
    Without prejudice to clause 16.1, either party may terminate this agreement, or request that
the parties re-negotiate its terms, by giving not less than thirty (30) days notice to the
other party at any time during the sixty (60) days following the date on which the report of
the results of the First Clinical Study is signed by the relevant representative of the second
party to sign it.
 16.3
    
    If Advancell gives notice pursuant to clause 16.2:
 (a)
    
    it will, at the time of giving it, irrevocably offer to assign to
Protherics:
 (i)
    
    all right, title and interest in and to the Patents, and all
Intellectual Property Rights subsisting in the Know-how, or which has otherwise
acquired further to the Development Programme, free of Encumbrances;(ii)
    
    the benefit of all contracts to which it is party and which
relate to the Development Programme or otherwise to the Product, including any
sub-licences; and(iii)
    
    the names and contact details of its then current sales
agents, suppliers and distributors of the Product,
 in each case for such consideration as Advancell has been advised by the
Independent Valuer is a fair, open-market price therefor at that time, and will
provide Protherics with such advice, and the basis of its determination, at the
same time as making such offer;(b)
    
    clauses 7.1, 7.2, 7.4, 7.5 (excluding the reference therein to clause 7.2),
11, 12, 16.3, 16.5 and 16.6 shall, unless and until Protherics takes an assignment of
those rights and matters specified in clause 16.3(a) further to the offer made by
Advancell pursuant to that clause, survive Termination pursuant to such notice; and(c)
    
    clause 9 shall, unless and until Protherics takes an assignment of those
rights and matters specified in clause 16.3(a) further to the offer made by Advancell
pursuant to that clause, also survive such Termination, save that, from such
Termination:
 (i)
    
    the royalty rate in clause 9.3 shall be * per
cent. (*%);(ii)
    
    the reference in clause 9.5 to * per cent. (*%) shall be
replaced with a reference to * per cent. (*%);(iii)
    
    the sum of £3,500,000 referred to in clause 9.7(a) shall be
reduced to £*;(iv)
    
    the sum of £* referred to in clause 9.7(b) shall be
reduced to £*;(v)
    
    the sum of £* referred to in clause 9.7(c) shall be
reduced to £*;(vi)
    
    the sum of £* referred to in clause 9.7(d) shall be
reduced to £*;
 * confidential treatment
requested 25




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(vii)
    
    the sum of £* referred to in clause 9.7(e) shall be
reduced to £*; and(viii)
    
    the sum of £* referred to in clause 9.7(f) shall be
reduced to £*.
 16.4
    
    If Protherics gives notice pursuant to clause 16.2, it will, at the time of giving it,
irrevocably offer to assign to Advancell:
 (a)
    
    the benefit of its Health Registration Approvals relating to the Product
and all its Regulatory Documentation;(b)
    
    its reports of the results of, and the data generated in the course of, the
Studies;(c)
    
    all its right, title and interest in such Intellectual Property Rights
acquired by it further undertaking the Development Programme, and which relate
exclusively thereto, or in its Health Registration Approvals relating to the Product
or its Regulatory Documentation; and(d)
    
    the benefit of all contracts to which it is party and which relate
exclusively to the Development Programme or otherwise to the Product,
 for such consideration as Protherics has been advised by the Independent Valuer is a fair,
open-market price therefor at that time, and provide Advancell with such advice, and the
basis of its determination, at the same time as making such offer.16.5
    
    The party receiving any offer pursuant to clauses 16.3(a) or 16.4 will have sixty (60) days
in which to accept such offer in writing, after which time such offer will lapse.16.6
    
    Without prejudice to clause 7.5, the party making any offer pursuant to clauses 16.3(a) or
16.4 will, until the end of the sixty (60) days period referred to in clause 16.5, do nothing
to lessen its entitlement to, and will in no way Encumber or grant any third party any right
in or to, any of the subject matter of the offer.16.7
    
    If Protherics accepts any offer made by Advancell pursuant to clause 16.3(a), and
notwithstanding Termination, Advancell will continue to provide Protherics with all assistance
with respect to the development or exploitation of the Product in the Indication as Protherics
may reasonably request.16.8
    
    Either party (Notifying Party") may terminate this agreement, immediately, by notice to the
other party (Notified Party"), if:
 (a)
    
    the Notified Party is in material breach of this agreement and such breach
is not capable of remedy;(b)
    
    the Notified Party has a receiver or an administrative receiver or
administrator appointed of the whole, or any part, of its undertaking or assets, or
has an officer appointed to perform a function analogous to that of any such officer,
or enters into any composition with its creditors;(c)
    
    an order is made, or a resolution passed for winding-up of the Notified
Party or the Notified Party enters administration (as such term is defined in
schedule B1 of the Insolvency Act 1986), unless such order or resolution or other
appointment is part of a scheme of solvent reconstruction of the Notified Party; or(d)
    
    the equivalent of any of the foregoing occurs in any relevant jurisdiction.
 16.9
    
    If either party is in material breach of this agreement, and such breach is capable of
remedy, the other party may give the first party a notice of termination of this
 * confidential treatment
requested 26




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agreement and that notice will come into effect sixty (60) days after the date on which it
is given, unless within that period the notified party has permanently remedied the
breach.16.10
    
    For the purposes of this clause 16, a material breachmeans a breach (including an
anticipatory breach) which is serious in the widest sense of having a serious effect on the
benefit which the innocent party would otherwise derive from this agreement in accordance with
its terms and for the avoidance of doubt includes any breach of clause 10.16.11
    
    Where this agreement terminated pursuant to clause 16.8:
 (a)
    
    the Licence will terminate;(b)
    
    Protherics will return to Advancell such Know-how as has been delivered by
Advancell to Protherics pursuant to clause 8.1; and(c)
    
    Protherics will assign back to Advancell, or procure the assignment back to
Advancell of, the right, title and interest in Orphan Drug designations which were
assigned to Protherics pursuant to clause 8.6.
 17.
    
    RIGHTS ON TERMINATION17.1
    
    Termination of this agreement will be without prejudice to any rights of either party against
the other which may have accrued up to the date of Termination.17.2
    
    Without prejudice to clause 16.3, the following provisions will survive Termination:
 (a)
    
    the confidentiality obligations of clause 10;(b)
    
    the obligations of Protherics in respect of the accounting for, payment of
and verification of royalties due in respect of Royalty Events prior to Termination;
and(c)
    
    clauses 1, 3, 13, 14, 16.7, 17, 19, 21, 22 and 24.
 18.
    
    FORCE MAJEURE18.1
    
    Event of Force Majeuremeans, in relation to either party, an event or circumstance beyond
the reasonable control of that party (Claiming Party") including, strikes, lock outs and
other industrial disputes (in each case, whether or not relating to the Claiming Partys
workforce).18.2
    
    The Claiming Party will not be deemed to be in breach of this agreement or otherwise liable
to the other party (Non-claiming Party") for any delay in performance or any non-performance
of any obligations under this agreement (and the time for performance will be extended
accordingly) if and to the extent that the delay or non-performance is due to an Event of
Force Majeure provided that:
 (a)
    
    the Claiming Party could not have avoided the effect of the Event of Force
Majeure by taking precautions which, having regard to all matters known to it before
the occurrence of the Event of Force Majeure and all relevant factors, it ought
reasonably to have taken but did not take; and(b)
    
    the Claiming Party has used reasonable endeavours to mitigate the effect of
the Event of Force Majeure and to carry out its obligations under this agreement in
any other way that is reasonably practicable.
 18.3
    
    The Claiming Party will promptly notify the Non-claiming Party of the nature and extent of
the circumstances giving rise to the Event of Force Majeure.
 27




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18.4
    
    If the Event of Force Majeure in question prevails for a continuous period in excess of
ninety (90) days after the date on which it began, the Non-claiming Party may give notice to
the Claiming Party terminating this agreement. The notice to terminate must specify the
Termination date, which must be not less than thirty (30) days after the date on which the
notice to terminate is given. Once a notice to terminate has been validly given, this
agreement will terminate on the Termination date set out in the notice. Neither party will
have any liability to the other in respect of Termination due to an Event of Force Majeure.19.
    
    FURTHER ASSURANCEEach party will, at the request and Cost of the other, from time to time after the
Effective Date, sign all such deeds and documents and do all such things as that other may
reasonably require for the purpose of giving effect to this agreement.20.
    
    ASSIGNMENT AND SUB-LICENSING20.1
    
    Neither party may assign its rights hereunder, in whole or in part, except to any of its
Affiliates and provided that:
 (a)
    
    it notifies the other party in advance of any such assignment;(b)
    
    it shall procure the re-assignment thereof to itself upon such Affiliate
ceasing to be its Affiliate; and(c)
    
    it ensures that such Affiliates does not otherwise assign, or grant any
interest in or to, the same,
 and, notwithstanding such assignment, the assigning party shall remain fully liable for
the performance of this agreement.20.2
    
    If any assignment of a type referred to in clause 20.1 takes place, this agreement will be
binding upon the assignee and the name of the relevant party appearing in this agreement will
be deemed to include the names of such assignee.
 20.3
    
    Protherics will not Sub-license without:
 (a)
    
    first notifying Advancell of the identity of the relevant Sub-licensee and
the terms of the relevant Sub-license; and(b)
    
    including in the Sub-licence provisions granting Advancells external
representatives a right of access, once per year, during normal working hours upon
reasonable notice:
 (i)
    
    to the books of account which Protherics requires it to keep
pursuant to clause 9.14; and(ii)
    
    to such other records as are necessary to verify the royalties
due to Advancell in respect of the Net Sales of such Sub-licensee,
  21.
    
    MISCELLANEOUS21.1
    
    Save where otherwise provided herein, each party will bear its own Costs connected with the
negotiations, preparation and implementation of this agreement.
 28




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21.2
    
    Each party will, at the request and Cost of the other party, sign any further formal document
which may be necessary to give effect to this agreement in any territory.
 21.3
    
    Except in the case of fraud or fraudulent concealment, the parties acknowledge that:
 (a)
    
    the Entire Agreement constitutes the entire and only agreement between the
parties relating to the subject matter of the Entire Agreement; and(b)
    
    neither party has been induced to enter into the Entire Agreement in
reliance on, nor has it been given, any representation or other statement of any
nature whatsoever other than those set out in the Entire Agreement and expressly
described as representations.
 21.4
    
    This agreement may be varied only by a document signed by both of the parties.21.5
    
    No breach of this agreement will be waived or discharged, except with the consent of the
parties.21.6
    
    No failure or delay by a party to exercise any of its rights under this agreement will
operate as a waiver of it or them and no single or partial exercise of any such right will
prevent any other or further exercise of that or any other right.21.7
    
    If any of the terms of this agreement is or becomes (whether or not following any judgment or
otherwise) invalid, illegal or unenforceable in any respect under the law of any jurisdiction:
 (a)
    
    the validity, legality and enforceability under the law of that
jurisdiction of any other provision; and(b)
    
    the validity, legality and enforceability under the law of any other
jurisdiction of that or any other provision,
 will not be affected or impaired in any way as a result.21.8
    
    In the circumstances set out in clause 21.7, the parties will meet to discuss the relevant
provision and will substitute a lawful and enforceable provision which so far as possible
results in the same economic effects.21.9
    
    Except as provided in clause 12, the rights and remedies provided in this agreement are
cumulative and not exclusive of any rights or remedies provided by law or in equity.21.10
    
    The Contracts (Rights of Third Parties) Act 1999 will not apply to this agreement and no
rights or benefits expressly or impliedly conferred by it will be enforceable under that Act
against the parties to it by any other person, except for rights and benefits conferred on
Protherics Affiliates.21.11
    
    Nothing in this agreement will create a partnership or joint venture between the parties
and, except as expressly provided in this agreement, neither party will enter into or have
authority to enter into any engagement or make representation or warranty on behalf of, or
pledge the credit of or otherwise bind or oblige, the other party, it being intended that each
party will remain an independent contractor.21.12
    
    Save as otherwise expressly provided herein, neither party will not be liable for any debts,
torts or contracts of the other.21.13
    
    Each party undertakes to comply fully with applicable international treaties and the Laws
and regulations of the United States, the European Community, the United Kingdom and any other
applicable jurisdiction governing exports, re-exports and transfers (together the Export
Control Laws") of technology developed or disclosed as a result of this
 29




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agreement or products made using any such technology (together the Relevant Technology or
Products") and, without limitation, to obtain all necessary consents and licences from the
competent governmental authorities in all relevant jurisdictions for the purpose of
compliance with the Export Control Laws.21.14
    
    Each party undertakes contractually to oblige any third party to whom it discloses or
transfers any Relevant Technology or Products to make an undertaking to it in similar terms to
the one set out in clause 21.13.21.15
    
    The parties acknowledge that any performance under this agreement is subject to any
restrictions which may be imposed by any Export Control Laws.21.16
    
    Each party agrees, if requested, to provide the other party with any reasonable assistance,
at the reasonable Cost of the other party, to enable it to perform any activity required by
any competent governmental authority in any relevant jurisdiction for the purpose of
compliance with any Export Control Laws.21.17
    
    The official text of this agreement is in the English language and, in the event of any
dispute concerning the construction or interpretation of this agreement, reference will be
made only to this agreement as written in the English language and not to any translation into
any other language.22.
    
    NOTICES22.1
    
    Any communication, including any notice, given under or in connection with this agreement
will be in writing in the English language and will be delivered personally or sent by
pre-paid first class post (air mail if posted to or from a place outside the United Kingdom)
to the address of each party stated above, or sent by fax, in the case of Protherics to its
Senior Executive for the time being and in the case of Advancell, its Company President.22.2
    
    Any such communication will be deemed to have been duly given or made as follows:
 (a)
    
    if personally delivered, upon delivery at the address of the relevant
party;(b)
    
    if sent by post, five (5) working days after the date of posting; and(c)
    
    if sent by fax, when despatched to +44 (0)1928 518 002 (in the case of
Protherics) or +34 (0)93 403 4544 (in the case of Advancell),
 provided that if, in accordance with the above provision, any such communication would
otherwise be deemed to be given or made outside normal working hours, such notice, demand
or other communication will be deemed to be given or made at the start of normal working
hours on the next business day.23.
    
    DISPUTE RESOLUTION23.1
    
    Any Dispute which arises will first be referred to Senior Executives of the parties for
resolution. Either party may give seven (7) days notice to the other requiring that a
Dispute be referred to Senior Executives of the parties. The Senior Executives will meet
within seven (7) days of the expiry of the notice (or earlier, if agreed) and will attempt in
good faith to resolve the Dispute. The notice requesting the meeting of Senior Executives
will contain brief details of the Dispute in question.23.2
    
    If the Dispute is resolved by the Senior Executives, the resolution will be recorded in
writing and signed by duly authorised representatives of each of the parties and that
resolution will be final and binding on the parties.
 30




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23.3
    
    If any Dispute is not resolved by the Senior Executives within seven (7) days of their
meeting pursuant to clause 23.1, or within such further period as the parties may agree in
writing, the parties will attempt to settle it by mediation in accordance with the CEDR Model
Mediation Procedure and, unless otherwise agreed between the parties, the mediator will be
nominated by CEDR.23.4
    
    The mediation will take place in London in the English language and The Mediation Agreement
referred to in the CEDR Model Mediation Procedure will be governed by, and construed and take
effect in accordance with, English law.23.5
    
    If any Dispute is not resolved by mediation within fourteen (14) days of commencement of the
mediation, or within such further period as the parties may agree in writing, the dispute may
only then be referred to arbitration in accordance with clause 24, provided that this clause
23 will not prevent either party seeking interim or emergency injunctive relief.23.6
    
    The foregoing provisions of this clause 23 are without prejudice to clause 5.13.24.
    
    GOVERNING LAW AND JURISDICTION24.1
    
    This agreement, and any Dispute, will be governed by and construed in accordance with English
law.24.2
    
    Subject to clause 23, all Disputes between the parties arising out of or in connection with
this agreement or its formation shall be finally settled under the Rules of Arbitration of the
International Chamber of Commerce, by one arbitrator appointed in accordance with the said
Rules; and any such arbitration shall be held in Paris, France, and the language of the
arbitration shall be the English language.25.
    
    SUPPLY AGREEMENT25.1
    
    The parties shall endeavour, in good faith, to reach, at
least * before the expected
date of the First Commercial Sale, an agreement for the supply from Advancell to Protherics of
the quantities of the Product required by Protherics for its commercialisation, and:
 (a)
    
    the cost of supply of such Product will be limited to its cost of
manufacture, plus customary industrial margins; and(b)
    
    such supply agreement will contain provisions to grant Advancell preferred
provider status and to grant Protherics the right to contract with an alternative
supplier to be used in case Advancell cannot supply, in full, Protherics required
amount of Product for commercialisation or the cost of supply from Advancell is not
competitive compared with that of potential alternative suppliers.
 25.2
    
    All Product which Protherics may need for the implementation of the Development Programme
shall be supplied by Advancell.
 * confidential treatment
requested 31




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PROTHERICS MEDICINES DEVELOPMENT LIMITED
 /s/
Andrew Heath
 ADVANCED IN VITRO CELL TECHNOLOGIES S.L.
 /s/
Luis Antonio Ruiz Avila
 32