EXHIBIT 10.39
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
ASTERISKS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 UNDER THE SECURITIES ACT OF 1933, AS
AMENDED.
AGREEMENT
between
LONZA BIOLOGICS PLC
and
INHIBITEX INC
THIS AGREEMENT is made the 5th day of November 2004
BETWEEN
1. LONZA BIOLOGICS PLC, the registered office of which is at 000 Xxxx Xxxx,
Xxxxxx, Xxxxxxxxx XX0 0XX, Xxxxxxx ("LB") and
2. INHIBITEX INC of 0000 Xxxxxxxxx Xxxxxxx, Xxxxx 000, Xxxxxxxxxx, XX 00000,
("Customer").
WHEREAS
A. Customer has created the Cell Line as defined herein; and
B. LB has expertise in the evaluation and production of monoclonal antibodies
for therapeutic use using such Cell Lines; and
C. Customer wishes to contract LB for Services relating to the Cell Line as
described in this Agreement, and
D. LB is prepared to perform such Services for Customer on the terms and
conditions set out herein.
NOW IT IS AGREED AS FOLLOWS:
1. The following terms shall have the following meanings unless the context
requires otherwise:
"Affiliate" means any Company, partnership or other entity which
directly or indirectly Controls, is Controlled by or is
under common Control with the relevant party to this
Agreement. "Control" means the ownership of more than
fifty per cent (50%) of the issued share capital or the
legal power to direct or cause the direction of the
general management and policies of the party in
question;
"Agreement" means this agreement incorporating Schedules 1 (Product
Specification), 2 (Services), 3 (Price and Terms of
Payment) and Schedule 4 (Inhibitex Patents) as amended
or varied from time to time by written agreement of the
parties;
"Batch" means the total Product obtained from one fermentation
and associated purification using the Process and
carried out in accordance with cGMP;
"Cell Line" means the cell line, particulars of which are set out in
Schedule 1;
"cGMP" means Good Manufacturing Practices and General Biologics
Products Standards as promulgated under
2
the US Federal Food Drug and Cosmetic Act at 21CFR
(Chapters 210, 211, 600 and 610) and the Guide to Good
Manufacturing Practices for Medicinal Products as
promulgated under European Directive 91/356/EEC. For the
avoidance of doubt, LB's operational quality standards
are defined in internal GMP policy documents;
"cGMP Product" means Product which is required under Schedule 2 to be
manufactured in accordance with cGMP;
cGMP run(s) means the 2000 (two thousand) liter fermentation run(s)
to be performed under this Agreement
"Customer" means Inhibitex Inc and its successors in title and
lawful assigns;
"Customer
Information" means all technical and other information not known to
LB or not in the public domain relating to the Cell
Line, the Process (including for the avoidance of doubt
improvements or modifications thereto from time to time)
and the Product, from time to time supplied by the
Customer to LB;
"Customer
Materials" means the Materials supplied by Customer to LB (if any)
and identified as such by Schedule 1 hereto;
"Customer Patent
Rights" means all patents and patent applications of any kind
throughout the world owned by or licensed to Customer
that are necessary or useful in performance of the
Services excluding the LB Patent Rights;
"Deliver",
"Delivered" or
"Delivery" has the meaning given to it in Clause 4.1;
"FDA" means the United States Food and Drug Administration;
"LB" means Lonza Biologics plc and its Affiliates and
successors in title and lawful assigns;
"LB Know-How" means all technical and other information relating
directly or indirectly to the Process known to LB from
time to time other than Customer Information and
information in the public domain;
"LB Patent
Rights" means all patents and patent applications of any kind
throughout the world relating to the Process which from
time to time LB is the owner of or is entitled to use;
"Price" means the price specified in Schedule 3 for the
Services;
"Process" means the process for the production of the Product from
the Cell Line, including any improvements or
modifications thereto from time to time;
3
"Product" means all or any part of the product manufactured using
the Process (including any sample thereof), particulars
of which are set out in Schedule 1 and includes all
derivatives thereof made by LB;
"Services" means all or any part of the services which are the
subject of the Agreement (including, without limitation,
cell culture evaluation, purification evaluation, assay
evaluation and qualification, a 130 liter pilot run,
master, working and extended cell bank creation, sample
and bulk production, and characterization, cGMP
manufacture), particulars of which are set out in
Schedule 2;
"Specification" means the specification for Product, particulars of
which are set out in Schedule 1;
"Terms of
Payment" means the terms of payment specified in Schedule 3;
"Testing
Laboratories" means any third party instructed by LB to carry out
tests on the Cell Line or the Product.
References to the singular number include the plural and vice versa,
references to Clauses and Schedules are references to clauses and
schedules to this Agreement.
2 CUSTOMER OBLIGATIONS, WARRANTIES AND INDEMNITIES
2.1 Customer shall pay the Price set out in Schedule 3 for provision of the
Services together with any additional costs and expenses that fall due
under this Agreement in accordance with the Terms of Payment, provided
that any such additional costs and expenses are agreed to in advance by
Customer. Resin for the cGMP run shall be procured by LB and billed to
Customer at LB's cost with no xxxx up or premium added. Customer shall pay
for the Resins prior to the start of the cGMP run. LB shall use the Resins
only in the performance of the Services. The Resins shall at all times
remain the property of Customer, and at the Customer's request and option,
LB shall destroy or return to the Customer all of the Resins at the
termination of this Agreement.
2.2 Immediately following the date of the Agreement the Customer shall supply
to LB the Customer Information, together with full details of any hazards
relating to the Cell Line and/or the Customer Materials, their storage and
use. On review of this Customer Information, the Cell Line and/or the
Customer Materials shall be provided to LB at LB's request. Property in
the Cell Line and/or the Customer Materials and/or the Customer
Information supplied to LB shall remain vested in the Customer.
2.3 The Customer hereby grants LB the non-exclusive right to use the Cell
Line, the Customer Materials and the Customer Information only for the
purpose of the Agreement.
2.4 The Customer warrants to LB that:
2.4.1 Customer has the right to enter into this Agreement;
2.4.2 Customer has and shall at all times throughout the term of this
Agreement have the right to supply the Cell Line, the other Customer
Materials and the Customer Information to LB and the necessary
rights to licence or permit LB to use the same only for the purpose
of the Services;
4
2.4.3 To the best of the Customer's knowledge and belief as of the date of
this Agreement the patents and patent applications and corresponding
international applications and patents listed on Schedule 4 relating
to any of the Cell Line, the other Customer Materials, Customer
Information and Customer Patent Rights not owned by Customer are
licensed to Customer under a licence which will permit their use by
LB to perform the Services;
2.4.4 to the best of Customer's knowledge and belief as of the date of
this Agreement, the use by LB of the Cell Line, other Customer
Materials, Customer Information and Customer Patent Rights for the
Services (including without limitation the manufacture of the
Product) will not infringe any intellectual property rights of any
third party other than third parties from whom customer is a
sublicensee through LB (provided, however, that LB shall waive any
breach of this warranty which arises if a court of competent
jurisdiction determines that the use by LB of the Cell Line, other
Customer Materials, Customer Information or Customer Patent Rights
for the Services infringes the intellectual property rights of a
third party, provided that and for so long as Customer actually
indemnifies LB pursuant to Clauses 2.5 and 2.6); this warranty is
limited to the Cell Line, other Customer Materials, Customer
Information and Customer Patent Rights; Customer makes no warranty
as to the Process or the Services; and
2.4.5 Customer will promptly notify LB in writing if it receives or is
notified of a claim from a third party that the Cell Line, other
Customer Materials, Customer Information or the Customer Patent
Rights or that the use by LB thereof for the provision of the
Services infringes any intellectual property rights of such third
party.
Clause 2.4 is in lieu of all conditions, warranties and statements in respect of
the Cell Line, Customer Information, Customer Patent Rights and/or Customer
Materials whether expressed or implied by statute, custom of the trade or
otherwise (including but without limitation any such condition, warranty or
statement relating to the description or quality of the Cell Line, Customer
Patent Rights, Customer Materials and Customer Information, their fitness or
suitability for a particular purpose or use under any conditions whether or not
known to Customer) and any such condition, warranty or statement is hereby
excluded.
2.5 The Customer undertakes to indemnify and to maintain LB promptly
indemnified against any direct loss, damage, costs and expenses (including
court costs and legal fees), that LB may suffer arising directly out of
any breach of the warranties given by the Customer under Clause 2.4 above
or any claims alleging LB's use of the Cell Line, the Customer Materials
or the Customer Information infringes any rights (including, without
limitation, any intellectual or industrial property rights) vested in any
third party (other than third parties from whom Customer is a sublicense
through LB) (whether or not the Customer knows or ought to have known
about the same).
2.6 The Customer shall further indemnify and maintain LB promptly indemnified
against all claims, actions, costs, expenses (including court costs and
legal fees on a full indemnity basis) or other liabilities whatsoever in
respect of:
2.6.1 any product liability in respect of Product, except to the extent
such liability is caused by (1) the negligent or willful act or
omission of LB in the production and/or supply of Product or
provision of Services, or (2) breach of any warranty by LB, or (3)
breach of a term of this Agreement by LB; and
2.6.2 any negligent or willful act or omission of the Customer in relation
to the use, processing, storage or sale of the Product.
2.7 Customer shall not be liable for the following loss or damage howsoever
caused (even if foreseeable or in the contemplation of LB or the Customer):
5
2.7.1 loss of profits, business or revenue whether suffered by LB or any
other person; or
2.7.2 special, indirect or consequential loss, whether suffered by LB or
any other person; and
2.7.3 any loss arising from any claim made against LB by any other person.
2.8 Customer shall obtain and maintain clinical trial insurance with a
reputable and solvent insurance provider in the amount of five million dollars
per event or linked events. Customer shall supply LB with a copy of such
insurance policy on reasonable request and shall not terminate or amend (other
than amending to increase the level of cover) such policy without prior written
notice to LB.
2.9 The obligations of the Customer under this Clause 2 shall survive the
termination for whatever reason of the Agreement.
3 PROVISION OF THE SERVICES
3.1.1 LB shall diligently carry out the Services as provided in Schedule
2, shall initiate the first cGMP run prior to the end of March 2005,
and shall use all reasonable efforts to achieve the estimated
timescales and Specifications set out in that Schedule, with the aim
of ensuring that the Product is accepted by the FDA for use in a
Phase III clinical trial.
3.1.2 If due to the negligence or willful misconduct of LB:
(i) the Product does not meet the Specification; or
(ii) the Product meets the Specification but for other reasons
cannot be used in a clinical trial;
then the Customer shall be under no obligation to pay for the cGMP
batch that produced such Product (in which case LB shall refund
amounts already paid by Customer in respect of such batch), and
shall at its discretion have the option of terminating this
Agreement in accordance with the principles of Clause 8.1 below
(including making a pro-rata payment in respect of Services
performed other than the cGMP batch that produced such Product) or
requiring LB to repeat the appropriate cGMP batch, for which the
Customer shall pay LB in accordance with the payment terms set out
in Schedule 3 applicable to a cGMP batch. In the event Customer
requires LB to replace such Product, LB shall use all reasonable
efforts to do so with the minimum delay having regard to its
commitments to third parties in the timing of such replacement.
If failure to meet Specification is due to acts or omissions of both
LB and Customer, then the cost to replace Product shall be
apportioned to the extent fault lies with each party.
3.1.3 If for reasons related to the inherent qualities of the Cell Line or
Product:
(i) the Product does not meet the Specification; or
(ii) the Product meets the Specification but for other reasons
cannot be used in a clinical trial;
then the Customer shall pay to LB the sum of [ * * * ] for the cGMP
batch that produced such Product.
6
If the Services cannot be completed for scientific or technical
reasons not the fault of either party then the provisions of section
8.1 (termination) shall apply.
3.1.4 For the cGMP runs (Stages 8 and 16) Customer shall perform the
potency testing as set forth in Schedule 1 within thirty (30) days
of sample receipt from LB. LB shall perform the remaining tests as
set forth in Schedule 1 within thirty (30) days of completion of the
run. Each party is entitled to audit the other party's test
procedures. Prior to the start of the cGMP run the parties shall
agree on the tests to be run and on the test results necessary for
the Product to meet Specification. Costs incurred by Customer in
auditing LB's tests shall be born by Customer. Costs incurred by LB
in auditing Customer's test shall be born by LB. The Price shall
include the actual costs incurred by LB in auditing Customer's test.
3.1.5 LB shall commence the first cGMP batch (Stage 8) within 15 weeks of
the completion of Stage 6 (bulk fill of 130L pilot batch) but in no
event later than March 31, 2005. If due to any delays or actions or
inactions caused solely by LB and not specifically related to
Customer's Material this first cGMP batch is not commenced by such
date, then the Customer shall be entitled to terminate this
Agreement in accordance with Clause 8.1.
3.1.6 If LB is unable to perform any or all of the Services for a period
of at least thirty (30) days due to restrictions placed upon LB by
the FDA or any other regulatory authority, Customer may terminate
this Agreement in accordance with Clause 8.1 below.
3.1.7 Prior to the start of the cGMP run each party shall designate in
writing a Project Manager who shall be the primary contact for each
party during the provision of the Services. Prior to the start of
the cGMP Run the parties shall enter into a written Quality
Agreement which shall be attached as an appendix hereto and
incorporated by reference as a part of this agreement.
3.1.8 In accordance with the Quality Agreement, LB shall make available to
Customer such data and documentation as may be necessary for
Customer to include in its regulatory filings with the FDA. LB shall
cooperate as reasonably requested by Customer, at Customer's
expense, in support of Customer's regulatory filings. Any such
filings shall be the sole and exclusive property of Customer.
3.1.9 The parties shall comply with all terms of the Quality Agreement.
3.2 LB shall comply with the International Committee for Harmonisation
regulatory requirements and all applicable local, state and federal
regulatory requirements including but not limited to FDA regulations from
time to time applicable to the Services as set out in Schedule 2.
3.3 LB hereby undertakes not to use the Cell Line, the Customer Materials or
the Customer Information (or any part thereof) for any purpose except as
set forth in this Agreement.
3.4 LB shall:
3.4.1 at all times keep the Cell Line and/or the Customer Materials secure
and safe from loss and damage in such manner as LB stores its own
material of similar nature;
3.4.2 not part with possession of the Cell Line and/or the Customer
Materials or the Product, save for the purpose of tests at the
Testing Laboratories; and
7
3.4.3 procure that all Testing Laboratories are subject to obligations of
confidence substantially in the form of those obligations of
confidence imposed on LB under this Agreement.
3.5 In providing the Services LB shall employ its most current, most efficient
and best available LB Know How and LB Patent Rights.
4 DELIVERY, TRANSPORTATION OF PRODUCT AND CUSTOMER TESTS
4.1 Product shall be Delivered EXW (ex-works) LB premises (as defined by
Incoterms 2000) which means (a) when LB places Product at the disposal of
Customer at LB's premises not cleared for export and not loaded onto any
collecting vehicle and (b) risk and title to Product pass to Customer upon
Delivery ("Deliver," "Delivery," or "Delivered," as appropriate). Subject
to Clause 4.2, unless otherwise instructed by Customer, LB shall not
Deliver Product to Customer or place Product at the disposal of Customer
until after Customer has received the Certificate of Analysis and approved
(in writing) Product for Delivery. Transportation of Product, whether or
not under any arrangements made by LB on behalf of Customer, shall be made
at the sole risk and expense of the Customer. Notwithstanding the
forgoing, Delivery by LB shall not be interpreted as the agreement by
Customer that the Product meets the Specification.
4.2 At Customer's request, LB will Deliver Product in quarantine prior to
delivery of the Certificate of Analysis. Such request shall be accompanied
by Customer's written acknowledgement that the Product has been Delivered
without the transmittal to Customer of a Certificate of Analysis and, that
accordingly the Product cannot be administered to humans until transmittal
of the Certificate of Analysis, and that Customer nevertheless accepts
full risk of loss, title and ownership of the Product. The Delivery of
Product in quarantine shall be subject to such testing requirements as LB
may reasonably require.
4.3 Unless otherwise agreed in writing, LB shall package and label Product for
Delivery in accordance with its standard operating procedures. It shall be
the responsibility of the Customer to inform LB in writing in advance of
any special packaging and labeling requirements for Product. Customer
shall be responsible for validating any special packaging or vessels
requested by Customer. All actual additional costs and expenses of
whatever nature incurred by LB in complying with such special written
requirements shall be charged to the Customer in addition to the Price.
4.4 If requested in writing by the Customer, LB will (acting as agent for
Customer) arrange for insurance of Product whilst held by LB after
Delivery (awaiting transportation) for a maximum of thirty (30) days on
terms equivalent to those under which LB insures product prior to
Delivery. All actual additional costs and expenses of whatever nature
incurred by LB in arranging such insurance shall be charged to the
Customer in addition to the Price.
4.5 If requested in writing by the Customer, LB will (acting as agent of the
Customer for such purpose) arrange the transportation of Product from LB's
premises to the destination indicated by the Customer together with
insurance cover for Product in transit at its invoiced value. All actual
additional costs and expenses of whatever nature incurred by LB in
arranging such transportation and insurance shall be charged to the
Customer in addition to the Price.
4.6 Where LB has made arrangements for the transportation of Product, the
Customer shall diligently examine the Product as soon as practicable after
receipt. Notice of all claims (time being of the essence) arising out of:
4.6.1 visible damage to or total or partial loss of Product in transit
shall be given in writing to LB and the carrier within five (5)
working days of receipt by Customer; or
8
4.6.2 non-Delivery shall be given in writing to LB within ten (10) days
after Customer's receipt of LB's dispatch notice.
4.7 The Customer shall make damaged Product and associated packaging materials
available for inspection and shall comply with the requirements of any
insurance policy covering the Product notified by LB to the Customer. LB
shall offer the Customer all reasonable assistance (at the cost and
expense of the Customer) in pursuing any claims arising out of the
transportation of Product.
4.8 If there is any dispute concerning whether Product returned to LB fails to
meet Specification or whether such failure is due (in whole or in part) to
acts or omissions of LB, the Customer, or any third party after Delivery,
or if there is any dispute in relation to clauses 3.1.2 and/or 3.1.3, such
dispute shall be referred for decision to an independent expert (acting as
an expert and not as an arbitrator) to be appointed by agreement between
LB and the Customer or, in the absence of agreement by the President for
the time being of Biotechnology Industry Organization. The costs of such
independent expert shall be borne equally between LB and the Customer. The
decision of such independent expert shall be in writing and, save for
manifest error on the face of the decision, shall be binding on both LB
and the Customer.
4.9 The provisions of clauses 3.1.2, 3.1.3 and 4.8 shall be the sole remedy
available to the Customer in respect of Product that fails to meet
Specification. This limitation of remedy applies only to Customer's remedy
with respect to its procurement of such Product and the provisions of
Article 6 shall nevertheless apply.
5 PRICE AND TERMS OF PAYMENT
5.1 Unless otherwise indicated in writing by LB, all prices and charges are
exclusive of Value Added Tax or of any other applicable taxes, levies,
imposts, duties and fees of whatever nature imposed by or under the
authority of any government or public authority, which shall be paid by
the Customer (other than taxes on LB's income). All invoices are strictly
net and payment must be made within thirty (30) days of date of invoice.
Payment shall be made without deduction, deferment, set-off, lien or
counterclaim of any nature.
5.2 In default of payment on due date:
5.2.1 interest shall accrue on any amount overdue at the prime lending
rate in the United States, interest to accrue on a day to day basis
both before and after judgment; and
5.2.2 LB shall, at its sole discretion, and without prejudice to any other
of its accrued rights, be entitled to suspend the provision of the
Services or to treat this Agreement as repudiated on not less than
thirty (30) days' prior notice in writing to Customer given at any
time thereafter.
6 LB WARRANTIES AND INDEMNITY
6.1 LB warrants that:
6.1.1 the Services shall be performed in accordance with the terms of
section 3 and the Quality Agreement and schedule 1 of this
Agreement, and the cGMP batch (Stages 8 and 16) shall in addition be
performed in accordance with LB's standard operating procedures and
cGMP.
9
6.1.2 unencumbered title (save for any unlicensed third party intellectual
property rights which may exist) to Product will be conveyed to
Customer upon Delivery;
6.1.3 as of the date of this Agreement the LB Know How and LB Patent
Rights are owned by LB or LB is otherwise entitled to use them for
the purposes of providing Services under this Agreement and during
the term of this Agreement LB shall not do or cause anything to be
done which would adversely affect their ownership or entitlement to
use the same for those purposes;
6.1.4 LB has the necessary corporate authorisations to enter into this
Agreement;
6.1.5 as of the date of this Agreement to the best of LB's knowledge and
belief, the use by LB of the Process (excluding any modifications or
steps made or developed by Customer, the Customer Materials,
Customer Information and Customer Patent Rights) and LB Patent
Rights and LB Know How for the performance of the Services as
provided herein will not infringe any rights (including without
limitation any intellectual or industrial property rights) vested in
any third party; and
6.1.6 LB will notify Customer in writing immediately if it receives or is
notified of a claim from a third party that the use by LB of the
Process and/or the LB Know How or the LB Patent Rights for Services
infringes any intellectual property rights vested in such third
party.
6.2 This Agreement including but not limited to Clause 6.1 is in lieu of all
conditions, warranties and statements in respect of the Services and/or
the Product whether expressed or implied by statute, custom of the trade
or otherwise (including but without limitation any such condition,
warranty or statement relating to the description or quality of the
Product, its fitness or suitability for a particular purpose or use under
any conditions whether or not known to LB) and any such condition,
warranty or statement is hereby excluded.
6.3 LB undertakes to indemnify and to maintain Customer promptly indemnified
against any direct loss, damage, costs and expenses (including court costs
and legal fees) that Customer may suffer arising directly out of any
breach of the warranties given by LB in Clause 6.1 or any claims alleging
that LB's use of LB Know-How (excluding use of LB Know-How with Customer
Materials or Customer Information) infringes any rights (including without
limitation any intellectual or industrial rights) vested in a third party
(whether or not LB knows or ought to have known the same).
6.4 LB shall further indemnify and maintain Customer promptly indemnified
against all claims, actions, costs, expenses (including court costs and
legal fees on a full indemnity basis) or other liabilities whatsoever in
respect of:
6.4.1 any clinical trial liability or product liability in respect of
Product, except to the extent such liability is caused by the
negligent or willful act or omission of Customer in the provision of
the Customer Materials or Customer Information to LB; and
6.4.2 any negligent or willful act or omission of LB in relation to the
processing, or storage of the Product or provision of the Services.
6.5 LB's aggregate liability for direct damages arising out of or in
connection with this Agreement or the transactions contemplated hereby
shall not exceed the total maximum aggregate sum payable under this
Agreement for the Services, in accordance with Schedule 3 (Price and Terms
of Payment), except that the foregoing limitation shall not apply in the
case of (a) breach of Clause 7 (Confidentiality) by LB, (b) personal
injury or death caused by the negligence of LB, or (c) grossly negligent
or intentionally wrongful acts or omissions of LB. The foregoing
limitation shall also not apply to claims arising under, or LB's breach
of, Clause 6.1 (LB Warranties and Indemnity); provided, however, that LB's
aggregate liability for direct damages arising out of or in connection
with claims arising
10
under, or LB's breach of, Clause 6.1 (LB Warranties and Indemnity), shall
not exceed an amount equivalent to twice the total maximum aggregate sum
payable under this Agreement for the Services, in accordance with Schedule
3 (Price and Terms of Payment).
6.6 NEITHER PARTY SHALL BE LIABLE TO THE OTHER FOR ANY INCIDENTAL, PUNITIVE,
INDIRECT, OR CONSEQUENTIAL DAMAGES OF ANY KIND, INCLUDING LOST PROFITS,
LOST DATA, LOST REVENUES, AND LOSS OF BUSINESS OPPORTUNITY, WHETHER OR NOT
THE OTHER PARTY WAS AWARE OR SHOULD HAVE BEEN AWARE OF THE POSSIBILITY OF
THESE DAMAGES, EXCEPT THAT THE FOREGOING LIMIATION SHALL NOT APPLY IN THE
CASE OF (a) BREACH OF CLAUSE 7 (CONFIDENTIALITY) BY EITHER PARTY, (b)
PERSONAL INJURY OR DEATH, OR (c) NEGLIGENT OR INTENTIONALLY WRONGFUL ACTS
OR OMISSIONS.
6.7 LB shall obtain and maintain product liability insurance with a reputable
and solvent insurance provider in the amount of not less than five million
dollars per event or linked. LB shall supply Customer with a copy of such
insurance policy on reasonable request and shall not terminate or amend (other
than amending to increase the level of cover) such policy without prior written
notice to Customer.
6.8 Nothing contained in this Agreement shall purport to exclude or restrict
any liability for death or personal injury resulting directly from negligence by
LB in carrying out the Services or any liability for breach of the implied
undertakings of LB as to title.
6.9 The obligations of LB and of the Customer under this Clause 6 shall
survive the termination for whatever reason of the Agreement.
7. CONFIDENTIALITY
7.1 The Customer acknowledges that LB Know-How and LB acknowledges that
Customer Information with which it is supplied by the other pursuant to
the Agreement is supplied, subject to Clause 7.5, in circumstances
imparting an obligation of confidence and each agrees to keep such LB
Know-How or such Customer Information secret and confidential and to
respect the other's proprietary rights therein and not at any time for any
reason whatsoever to disclose or permit such LB Know-How or LB Information
or such Customer Information to be disclosed to any third party save as
expressly provided herein.
7.2 The Customer and LB shall each procure that all their respective
employees, consultants, contractors and persons for whom it is responsible
having access to confidential LB Know-How or LB Information or
confidential Customer Information shall be subject to the same obligations
of confidence as the principals pursuant to Clauses 7.1 and 7.3 and shall
be bound by secrecy agreements in support of such obligations.
7.3 LB and the Customer each undertake not to disclose or permit to be
disclosed to any third party (including any contractors or consultants not
previously approved in writing by LB, such approval not to be unreasonably
withheld or delayed), or otherwise make use of or permit to be made use of
(a) any trade secrets or confidential information relating to the
technology, business affairs or finances of the other, any subsidiary,
holding company or subsidiary or any such holding company of the other, or
of any suppliers, agents, distributors, licensees or other customers of
the other which comes into its possession under this Agreement. or (b) the
commercial terms of this Agreement except to the extent that the same is
required to be disclosed pursuant to subpoena, court order, judicial
process or otherwise by law, provided the Receiving Party provides prompt
notice to the Disclosing Party of such requirement in order to give the
Disclosing Party an opportunity to timely seek a protective order or other
appropriate judicial relief. In the event the Disclosing Party is unable
to obtain a protective order or other appropriate judicial relief, the
Receiving Party shall disclose only that portion of the Disclosing Party's
Confidential Information
11
which is legally required to be disclosed, and ensure that all such
Confidential Information of the Disclosing Party shall be redacted to the
fullest extent permitted by law prior to such disclosure and that the
Disclosing Party shall be given an opportunity to review the Confidential
Information prior to its disclosure.
7.4 The obligations of confidence referred to in this Clause 7 shall not
extend to any information which:
7.4.1 is or becomes generally available to the public otherwise than by
reason of a breach by the Receiving Party of the provisions of this
Clause 7;
7.4.2 is known to the Receiving Party and is at its free disposal prior to
its receipt from the Disclosing Party;
7.4.3 is subsequently disclosed to the Receiving Party without being made
subject to an obligation of confidence by a third party;
7.4.4 LB or the Customer may be required to disclose under any statutory,
regulatory or similar legislative requirement including but not
limited to the U.S. Securities and Exchange Commission requirements
for registrations to sell securities to the public , subject to the
imposition of obligations of secrecy wherever possible in that
relation; or
7.4.5 is developed by any servant or agent of the Receiving Party without
access to or use or knowledge of the information by the Disclosing
Party.
7.5 The Customer and LB acknowledge that:
7.5.1 without prejudice to any other rights and remedies that the parties
may have, the parties agree that the Confidential Information is
valuable and that damages may not be an adequate remedy for any
breach of the provisions of Clauses 7.1, 7.2, 7.3 and 7.4. The
parties agree that the relevant party will be entitled without proof
of special damage to the remedies of an injunction and other
equitable relief for any actual or threatened breach by the other
party;
7.5.2 the Customer shall not at any time have any right, title, licence or
interest in or to LB Know-How, the LB Patent Rights or any other
intellectual property rights relating to the Process which are
vested in LB or to which LB is otherwise entitled except as
otherwise agreed in writing by the parties; and
7.5.3 LB acknowledges that save as provided herein LB shall not at any
time have any right, title, licence or interest in or to the
Customer Information, Customer Patent Rights or any other
intellectual property rights vested in Customer or to which the
Customer is entitled.
7.6 Ownership of any technique, process, apparatus, material, product, data,
formula, software, design, trade secret, Confidential Information,
improvement, know-how, or invention, whether patentable or not, made in
performing the services will, save as set out in this section 7.6 follow
the United States laws of inventorship, and inventors shall be the owners.
7.6.1 In the event that LB develops an invention which relates exclusively to
the LB Process, Know-how or Patent Rights, and not to Customer Material,
Information or Patent Rights, LB shall own all right, title and interest
in and to such invention.
7.6.2 In the event that LB develops an invention which relates exclusively to
the Customer Material, Information or Patent Rights, and not to the LB
Process, Know-how or Patent Rights, LB shall promptly provide written
notice to Customer of such invention and will,
12
upon request of Customer, assign such invention to Customer on
commercially reasonable terms to be negotiated in good faith between the
parties. For the avoidance of doubt an invention shall not relate
exclusively to the Customer material if such invention is capable of
application by LB to materials other than Customer Material.
7.6.3 In the event that LB develops an invention using the Customer Material for
which no Customer employee is an inventor and which is an invention not
described in either section 7.6.1 or 7.6.2 above, then LB shall, upon
request by Customer, grant a nonexclusive license to Customer of such
invention on commercially reasonable terms to be negotiated in good faith
by the parties.
7.6.4 In the event that Customer develops an invention relating to the LB
Process, Know-how or Information during its interaction with LB in the
performance of the Services, then Customer shall, upon request by LB,
grant a nonexclusive license to LB of such invention on commercially
reasonable terms to be negotiated in good faith by the parties.
7.6.5 All notices described in this section 7.6 shall include a detailed
description of the invention.
7.7 The obligations of LB and the Customer under this Clause 7 shall survive
the termination for whatever reason of the Agreement.
8. TERMINATION
8.1 If the parties agree at any stage in the provision of the Services that it
will not be possible to successfully complete the Services for scientific
or technical reasons not the fault of either party, a thirty (30) day
period shall be allowed for good faith discussion and attempts to resolve
such problems. If such problems are not resolved within such period, or if
the parties do not agree that scientific or technical reasons prohibit
successful completion of the Services, LB and the Customer shall each have
the right to terminate the Agreement forthwith by notice in writing. In
the event of such termination, the Customer shall pay to LB a termination
sum calculated by reference to all the Services performed by LB prior to
such termination including a pro rata proportion of the Price for any
stage of the Services which is in process at the date of termination
including the costs of terminating any third party commitments entered
into pursuant to the Agreement, such sum not to exceed the Price.
8.2 Customer may in its sole discretion terminate the Services at any time for
any reason by giving not less than (thirty) 30 days' notice in writing to
LB. In the event of termination pursuant to this Clause 8.2 and subject to
Clauses 8.3 and 8.4 the Customer shall pay LB a termination sum calculated
by reference to the Services actually performed by LB prior to termination
including a pro rata proportion of the Price for any stage of the Services
which is in process at the date of termination including costs of
terminating any third party commitments entered into pursuant to this
Agreement, such sum not to exceed the Price. plus:
8.2.1 in the event notice to terminate Services pursuant to this Clause
8.2 is issued to LB six (6) months or less before LB's then
estimated start date for Stage 8 or Stage 16, or at any time during
such Stages, Customer shall pay LB a sum equal to the full price of
that stage or those stages in question, which payment shall fall due
to LB thirty days from the date of termination of such Services.
(For the avoidance of doubt, per Schedule 3 the first cGMP run, i.e.
Stage 8, is already planned to start no later than the end of March
2005; therefore this clause will require full payment if the first
cGMP run is cancelled) ; or
8.2.2 in the event notice to terminate Services pursuant to this Clause
8.2 is issued to LB more than six (6) months but not more than
twelve (12) months before LB's then estimated start date for Stage
8, Customer shall pay LB a sum equal to 85%
13
(eighty-five percent) of the full price of Stage 8, which payment
shall fall due to LB thirty days from the date of termination of
such Services; or
8.2.3 in the event notice to terminate Services pursuant to this Clause
8.2 is issued to LB more than six (6) but not more than nine (9)
months before LB's then estimated start date for Stage 16, Customer
shall pay LB a sum equal to twenty five percent (25%) of the full
price of that stage or those stages in question; which payment shall
fall due to LB thirty days from the date of termination of such
Services.
8.2.4 in the event notice to terminate Services pursuant to this Clause
8.2 is issued to LB more than nine (9) months before LB's then
estimated start date for Stage 16 then no payment shall be due to LB
(For the avoidance of doubt, per Schedule 3, the second cGMP run,
i.e. Stage 16 is now planned to start by the end of December 2005;
therefore if Customer cancels this run prior to the end of March
2005 then no payment shall be owed to LB for the second cGMP run) .
LB shall use reasonable efforts to mitigate loss and the obligation to
make payment under Clause 8.1 or clause 8.2 shall be reduced
(retrospectively, and hence LB shall make an appropriate refund to
Customer) to the extent that LB mitigates its loss in this regard (and LB
shall promptly notify the Customer of any such mitigation). This provision
shall not entitle the Customer to be refunded an amount greater than that
paid by customer to LB pursuant to this Clause 8.
8.3 For the avoidance of doubt activities relating to the start or
commencement of a run shall be deemed to commence with the date of removal
of the vial of cells for the performance of the fermentation from frozen
storage.
8.4 The parties may each terminate the Agreement forthwith by notice in
writing to the other party upon the occurrence of any of the following
events:
8.4.1 if the other commits a material breach of the Agreement (which shall
include a breach of the warranties set out in Clauses 2 and 6
respectively) which in the case of a breach capable of remedy is not
remedied within thirty (30) days of the receipt by the other of
written notice identifying the breach and requiring its remedy; or
8.4.2 if the other ceases for any reason to carry on business or compounds
with or convenes a meeting of its creditors or has a receiver or
manager appointed in respect of its assets to which this agreement
pertains or is the subject of an application for an administration
order or of any proposal for a voluntary arrangement or enters into
liquidation (whether compulsorily or voluntarily) or undergoes any
analogous act or proceedings under foreign law.
8.5 Upon the termination of the Agreement for whatever reason:
8.5.1 LB shall promptly return to the Customer all Customer Information
and shall dispose of or return to the Customer the Customer
Materials (and where supplied by Customer the Cell Line) and any
materials therefrom, as directed by the Customer;
8.5.2 the Customer shall promptly return to LB all LB Know-How it has
received from LB;
8.5.3 the Customer shall not thereafter use or exploit the LB Patent
Rights or the LB Know-How in any way whatsoever unless subject to a
separate written license or agreement;
8.5.4 LB and the Customer shall do all such acts and things and shall sign
and execute all such documents as necessary to evidence compliance
with this Clause 8.5.
14
8.6 Termination of this Agreement for whatever reason shall not affect the
accrued rights of either LB or the Customer arising under or out of this
Agreement and all provisions which are expressed to survive the Agreement
shall remain in full force and effect.
8.6.1 The term of this Agreement shall commence on the date first written above
and shall expire upon completion of the Services and payment therefor,
unless earlier terminated as provided herein.
8.7 During the course of this Agreement, and at any time prior to 31st
December 2007, Customer may request and if requested, LB shall provide to
Customer a license and technology transfer agreement for relevant
technical know-how related to the Process, excluding the content of LB's
proprietary feed additives, to allow Customer or its designee to duplicate
the Process, under a technology transfer agreement mutually agreed upon,
subject to commercially reasonable pricing and other terms associated with
technology transfer. The financial terms for the technology transfer shall
be negotiated in good faith by the parties, and the total fee for such
technology transfer will depend on the extent of LB's proprietary know-how
used in the Process. For the avoidance of doubt, the terms of any such
technology transfer do not include a licence to LB's proprietary glutamine
synthetase (GS) gene expression system.
8.8 If prior to 31st December 2006, LB and Customer agree that additional cGMP
product is to be produced by LB for Customer then the terms for such
further production at the 2000L scale shall include a price not to exceed
the Price under this Agreement. All other terms of that agreement will be
substantially as set forth in this Agreement.
8.9 Should the Customer seek future commercial supply of the Product at 2000L
or 5000L scale Lonza will enter into good faith negotiations in respect of
such supply. The price for such supply will be dependent upon selected
scale, total product requirements and campaign size.
9. FORCE MAJEURE
9.1 If LB is prevented or delayed in the performance of any of its obligations
under the Agreement by Force Majeure and shall give written notice thereof
to the Customer specifying the matters constituting Force Majeure together
with such evidence as LB reasonably can give and specifying the period for
which it is estimated that such prevention or delay will continue, LB
shall be excused from the performance or the punctual performance of such
obligations as the case may be from the date of such notice for so long as
such cause of prevention or delay shall continue.
9.2 The expression "Force Majeure" shall be deemed to include any cause
affecting the performance by LB of the Agreement arising from or
attributable to acts, events, acts of God, omissions or accidents beyond
the reasonable control of LB or which LB could not reasonably prevent or
mitigate; provided, however that unanticipated scientific or technical
problems shall not constitute Force Majeure. Customer shall have the right
to terminate this Agreement if a force majeure event continues for a
period longer than two months.
10. GOVERNING LAW, JURISDICTION AND ENFORCEABILITY
10.1 The construction, validity and performance of the Agreement shall be
governed by the laws of the United States and the State of New York, and
LB and the Customer submit to the non-exclusive jurisdiction of the
Courts.
10.2 No failure or delay on the part of either LB or the Customer to exercise
or enforce any rights conferred on it by the Agreement shall be construed
or operate as a waiver thereof nor shall any single or partial exercise of
any right, power or privilege or further exercise thereof operate so as to
bar the exercise or enforcement thereof at any time or times thereafter.
15
10.3 The illegality or invalidity of any provision (or any part thereof) of the
Agreement or these Standard Terms shall not affect the legality, validity
or enforceability of the remainder of its provisions or the other parts of
such provision as the case may be.
11. NOTICES
11.1 Any notice or other communication to be given under this Agreement shall
be delivered personally or sent by facsimile transmission and by first
class pre-paid post addressed as follows:
11.1.1 If to Lonza Biologics to: Lonza Biologics plc
000 Xxxx Xxxx
Xxxxxx
Xxxxxxxxx XX0 0XX
England
Facsimile: 01753 777001
For the attention of: The Head of Legal Services
11.1.2 If to the Customer to: Inhibitex Inc
0000 Xxxxxxxxx Xxxxxxx
Xxxxx 000
Xxxxxxxxxx
XX 00000, XXX
Facsimile: (000) 000 0000
For the attention of: Xxxxxx Xxxxxxxxx
or to such other destination as either party hereto may hereafter notify
to the other in accordance with the provisions of this Clause 11.
11.2 All such notices or other communications shall be deemed to have been
served as follows:
11.2.1 if delivered personally, at the time of such delivery;
11.2.2 if sent by facsimile, upon receipt of the transmission confirmation
slip showing completion of the transmission;
11.2.3 if sent by first class pre-paid post, ten (10) business days
(Saturdays, Sundays and Bank or other public holidays excluded)
after being placed in the post.
12. MISCELLANEOUS
12.1 Neither party shall be entitled to assign, transfer, charge or in any way
make over the benefit and/or the burden of this Agreement without the
prior written consent of the other which consent shall not be unreasonably
withheld or delayed, save that either party shall be entitled without the
prior written consent of the other to assign, transfer, charge,
sub-contract, deal with or in any other manner make over the benefit
and/or burden of this Agreement to any company with which such party may
merge or to any company to which such party may transfer or license its
assets and undertakings.
12.2 The text of any press release or other communication to be published by or
in the media concerning the subject matter of the Agreement shall require
the prior written approval of LB and the Customer.
12.3 The Agreement embodies the entire understanding of LB and the Customer and
there are no promises, terms, conditions or obligations, oral or written,
expressed on implied, other
16
than those contained in the Agreement. The terms of the Agreement shall
supersede all previous agreements (if any) which may exist or have existed
between LB and the Customer relating to the Services.
12.4 No variation of or addition to this Agreement or any part thereof shall be
effective unless in writing and signed on behalf of both parties.
Notwithstanding the above the parties hereby confirm that amendments to
the Specification shall be effective if reduced to writing and signed by
the quality and/or regulatory representative of both parties, which
quality and/or regulatory representative shall be nominated from time to
time by each party
AS WITNESS the hands of the duly authorised representatives of the parties
hereto the day and year first above written.
Signed for and on behalf of /s/ X.X. Xxxxxxx Nov. 5, 2004
LONZA BIOLOGICS PLC -----------------------
X.X. Xxxxxxx
Head of LBP TITLE
Signed for and on behalf of /s/ Xxxxxx Xxxxxxxxx Nov. 5, 2004
INHIBITEX INC -----------------------
Xxxxxx Xxxxxxxxx
VP Business Development TITLE
17
SCHEDULE 1
"Cell Line" shall mean the [ * * * ] Cell Line created by Customer expressing
Product.
"Product" shall mean the [ * * * ] antibody produced by the Cell Line known
as [ * * * ] that binds to ClfA of which the Customer is the proprietor.
A. SPECIFICATION FOR BULK PURIFIED DRUG SUBSTANCE
Below is a list of tests typically carried out as cGMP Specification testing for
an antibody product from LB. During the course of the Services LB and Customer
will agree the testing appropriate to a cGMP Specification for Product. All
amounts stated to be target amounts are indications only and are not binding on
LB.
TEST METHOD
NO. CRITERION (LB SOP NUMBER) SPECIFICATION
------------------------------------------------------------------
1. Characteristics
1.1 [ * * * ] [ * * * ] [ * * * ]
1.2 [ * * * ] [ * * * ] [ * * * ]
1.3 [ * * * ] [ * * * ] [ * * * ]
1.4 [ * * * ] [ * * * ] [ * * * ]
2. Identity
1.5 [ * * * ] [ * * * ] [ * * * ]
1.6 [ * * * ] [ * * * ] [ * * * ]
1.7 [ * * * ] [ * * * ] [ * * * ]
---------
(1) [ * * * ]
18
TEST METHOD
NO. CRITERION (LB SOP NUMBER) SPECIFICATION
------------------------------------------------------------------
3. Purity
1.8 [ * * * ] [ * * * ] [ * * * ]
1.9 [ * * * ] [ * * * ] [ * * * ]
4. Impurities
TEST METHOD (LB SOP
NO. CRITERION NUMBER) SPECIFICATION
------------------------------------------------------------------
1.10 [ * * * ](1) [ * * * ] [ * * * ]
1.11 [ * * * ] [ * * * ] [ * * * ]
1.12 [ * * * ] [ * * * ] [ * * * ]
----------
(1) [ * * * ]
19
5. Excipients
TEST METHOD (LB SOP
NO. CRITERION NUMBER) SPECIFICATION
------------------------------------------------------------------
1.13 [ * * * ] [ * * * ] [ * * * ]
1.14 [ * * * ] [ * * * ] [ * * * ]
1.15 [ * * * ] [ * * * ] [ * * * ]
1.16 [ * * * ] [ * * * ]
20
TEST METHOD (LB SOP
NO. CRITERION NUMBER) SPECIFICATION
------------------------------------------------------------------
6. Safety
1.17 [ * * * ] [ * * * ] [ * * * ]
1.18 [ * * * ] [ * * * ] [ * * * ]
7. Sample from production fermenter on day of harvest (pre-clarification)
1.19 [ * * * ] [ * * * ] [ * * * ]
1.20 [ * * * ] [ * * * ] [ * * * ]
1.21 [ * * * ] [ * * * ] [ * * * ]
1.22 [ * * * ] [ * * * ] [ * * * ]
[ * * * ]
8. In-process tests (LB to identify sample points) to be agreed by project
managers and QA from both Parties.
1.23 [ * * * ] [ * * * ]
1.24 [ * * * ] [ * * * ]
1.25 [ * * * ] [ * * * ]
9. Storage and shipping information
Final Formulation Buffer: [ * * * ]
Bottling of Bulk Product:
Primary containers: [ * * * ]
Denominations:
The bulk Product will be dispensed into [ * * * ],
filling to a tolerance of [ * * * ]% of the nominal
volume of the container.
Any remaining bulk Product will be dispensed into
[ * * * ], filling to a tolerance of [ * * * ]% of the
nominal volume of the container.
Any remaining Product will be filled into one container
of the smallest size specified. If this is not filled
with a tolerance of [ * * * ]% of the nominal volume.
This will be labelled as a Customer Sample and will not
be released for clinical use.
For the calculation of the total fill volume it is
assumed that 1g of liquid ~ 1ml.
Product Storage Conditions: [ * * * ]
Shipment Temperature: Product shipped at [ * * * ]
Customer samples (removed during the middle of dispensing):
[ * * * ]
21
B. SPECIFICATION FOR A MASTER CELL BANK
STARTING MATERIAL DEFINITION
Master Cell Bank (MCB) of a cryopreserved Cell Line prepared from a pooled
culture and stored in individual ampoules in liquid nitrogen refrigerators.
GENERAL MASTER CELL BANK SPECIFICATION
1. The acceptance criteria for tests performed on ampoules from the cell bank.
TEST
NO. CRITERION METHOD SAMPLE SIZE TEST
-------------------------------------------------------------------
1.1 [ * * * ] [ * * * ] [ * * * ] [ * * * ]
1.2 [ * * * ] [ * * * ] [ * * * ] [ * * * ]
1.3 [ * * * ] [ * * * ] [ * * * ] [ * * * ]
22
SCHEDULE 2
CONTENTS
1 SUPPLY OF CUSTOMER MATERIALS AND CUSTOMER KNOW HOW
2 ACTIVITIES TO BE UNDERTAKEN BY LB
1 Stage 1 - Airlift Fermentation Process Evaluation
2 Stage 2 - Purification Process Evaluation
3 Stage 3 - Evaluation of LB's Generic Assays
4 Stage 4 - Master Cell Bank Preparation and Analysis
5 Stage 5 - [ * * * ] Master Cell Banks Testing for Adventitious Agents
6 Stage 6 - Development Pilot Batch (non- cGMP) at 130 L Scale
7 Stage 7 - Preparation of cGMP Documentation
8 Stage 8 - Production of cGMP Product at 2000 litre Scale
9 Stage 9 - Evaluation of Virus Reduction for [ * * * ]
10 Stage 10 - Product Reference Standard
11 Stage 11 - QC Testing of Vialled Product
12 Stage 12 - Stability Study of Bulk Purified Product (cGMP material)
13 Stage 13 - Vialled Product Stability Studies
14 Stage 14 - Regulatory Support
15 Stage 155 - Determination of Extinction Coefficient
16 Stage 16 - Production of cGMP Product at 2000 L Scale
23
1 SUPPLY OF CUSTOMER MATERIALS AND CUSTOMER KNOW HOW
[ * * * ]
(iv)
24
2 ACTIVITIES TO BE UNDERTAKEN BY LB
1 STAGE 1 - AIRLIFT FERMENTATION PROCESS EVALUATION
1.1 OBJECTIVES
1.1.1 To adapt [ * * * ]
1.1.2 To transfer [ * * * ]
1.1.3 To develop [ * * * ]
1.1.4 To provide [ * * * ]
1.1.5 To evaluate [ * * * ]
1.2 ACTIVITIES
Stage 1A
1.2.1 Following [ * * * ] receive [ * * * ]. Send [ * * * ].
1.2.2 [ * * * ]
1.2.3 [ * * * ]
1.2.4 Perform [ * * * ]
1.2.5 Receive from the Customer [ * * * ]
1.2.6 Perform a [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
25
1.2.16 Issue a summary report of activities completed in
Stages 1A and 1B to the Customer including the
following:
- Assessment of the [ * * * ]
- Assessment of the [ * * * ]
Note: In all reports to the Customer any techniques or
reagents used which are proprietary to LB will be described in
outline only.
1.3 TIMESCALE
This Stage may commence by agreement with the Customer and
LB. This Stage shall be complete upon issue of the report of
activities. It is estimated that this Stage will take [* * *]
to complete.
26
2 STAGE 2 - PURIFICATION PROCESS EVALUATION
2.1 OBJECTIVES
2.1.1 To consult [ * * * ]
2.1.2 To evaluate [ * * * ]
2.1.3 To provide [ * * * ]
2.2 ACTIVITIES
2.2.1 Evaluate [ * * * ]
2.2.2 Advise [ * * * ]
2.2.3 Review [ * * * ]
2.2.4 Receive [ * * * ] under Stage 1A.
2.2.5 Evaluate the [ * * * ]
2.2.6 [ * * * ]
2.2.7 Evaluate the [ * * * ]
2.2.8 Determine the [ * * * ]
2.2.9 Provide [ * * * ]
2.2.10 [ * * * ]
2.2.11 [ * * * ]
2.2.12 Provide [ * * * ]
2.2.13 Issue report of activities to Customer. This shall include:
- [ * * * ];
27
- [ * * * ]
2.3 TIMESCALE
This Stage may commence after material is available from Stage 1A.
This Stage shall be complete upon issue of the report of activities.
It is estimated that this Stage will take [ * * * ] to complete but
this duration is dependent upon sources of material from other
Stages of the services.
3 STAGE 3 - EVALUATION OF LB'S GENERIC ASSAYS
3.1 OBJECTIVES
3.1.1 To assess the performance of [ * * * ].
3.1.2 To make a recommendation about [ * * * ].
3.2 ACTIVITIES
3.2.1 Assess the performance of [ * * * ]. Determine whether
[ * * * ].
3.2.2 Make a recommendation to the Customer about [ * * * ].
3.2.3 Issue a report of activities to the Customer.
3.3 TIMESCALE
This Stage may commence as soon as Product samples are available.
This Stage shall be complete upon issue of the report. It is
estimated that this Stage will take [ * * * ] to complete. If the
results of this Stage indicate that a specific protein assay will
have to be developed for this Product, this work may be added to the
work program under terms and conditions to be agreed.
4 STAGE 4 - MASTER CELL BANK PREPARATION AND ANALYSIS
4.1 OBJECTIVES
4.1.1 To test [ * * * ].
4.1.2 To create [ * * * ].
Note: [ * * * ].
28
1.2.7 [ * * * ]
1.2.8 Perform [ * * * ]
1.2.9 Provide [ * * * ]
1.2.10 Review all [ * * * ]
Stage 1B
Note: The scope of this sub-stage may be further modified to
meet the demands of the program. Any additional
activities will be outlined in an amendment to this
agreement.
1.2.11 Assess the [ * * * ]
1.2.12 [ * * * ]
1.2.13 Provide [ * * * ]
1.2.14 Evaluate [ * * * ]
1.2.15 Provide [ * * * ]
4.2 ACTIVITIES
4.2.1 [ * * * ];
(a) [ * * * ] Testing:
(i) [ * * * ]
(ii) [ * * * ]
(b) [ * * * ]
4.2.2 Prepare[ * * * ]. Establish [ * * * ].
4.2.3 Establish [ * * * ]
Note: [ * * * ]
4.2.4 [ * * * ]:
- [ * * * ]
- [ * * * ]
Note: [ * * * ].
4.2.5 Issue a report of activities to the Customer. This report will
include:
- Details of [ * * * ].
- Details of [ * * * ].
- A description of [ * * * ].
- Summary of [ * * * ].
- A summary of [ * * * ].
4.3 TIMESCALE
29
This Stage may commence as soon as the [ * * * ]. This Stage shall
be complete with the issue of the report of activities. It is
estimated that this report will be issued [ * * * ] from the start
of this Stage.
It is estimated that [ * * * ] will be established [ * * * ] from
the start of this Stage.
5 STAGE 5 - [* * *] MASTER CELL BANKS TESTING FOR ADVENTITIOUS AGENTS
5.1 OBJECTIVES
5.1.1 To carry out additional testing [ * * * ].
5.2 ACTIVITIES
5.2.1 [ * * * ]:
[ * * * ]
[ * * * ]
[ * * * ]
GENERAL
[ * * * ]
5.2.2 Issue a copy of [ * * * ] to the Customer containing the
results of the tests carried out in this Stage
5.3 TIMESCALE
30
This Stage may commence as soon [ * * * ]. This Stage shall be
complete upon [ * * * ] from commencement of this Stage.
6 STAGE 6 - DEVELOPMENT PILOT BATCH (NON- CGMP) AT 130L SCALE
6.1 OBJECTIVES
6.1.1 To assess [ * * * ] 130L pilot scale [ * * * ].
6.1.2 To establish [ * * * ].
6.1.3 To assess [ * * * ].
6.1.4 To evaluate [ * * * ].
Note: [ * * * ].
Note: [ * * * ].
6.2 ACTIVITIES
6.2.1 [ * * * ].
6.2.2 Perform the [ * * * ].
6.2.3 [ * * * ]
6.2.4 [ * * * ].
6.2.5 [ * * * ].
6.2.6 [ * * * ].
6.2.7 [ * * * ]
6.2.8 [ * * * ]
6.2.9 [ * * * ]
6.2.10 [ * * * ]
6.2.11 [ * * * ]-
31
[ * * * ]
6.2.12 Review [ * * * ]
6.2.13 [ * * * ]
6.2.14 Issue a summary report of activities for this Stage to the
Customer. This report shall include [ * * * ] such as:
- [ * * * ];
- [ * * * ];
- [ * * * ];
- [ * * * ];
- [ * * * ].
6.3 TIMESCALE
This Stage may commence when [ * * * ] is available for use, and
sufficient information is available from previous Stages of the
Services to proceed.
This Stage shall be complete upon issue of the summary report to the
Customer. It is estimated that this report shall be issued [ * * * ]
from commencement of this Stage.
7 STAGE 7 - PREPARATION OF CGMP DOCUMENTATION
7.1 OBJECTIVE
7.1.1 To prepare cGMP documentation for use [ * * * ].
Note: [ * * * ].
7.2 ACTIVITIES
7.2.1 Prepare documentation [ * * * ]. The documentation shall
cover:
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
7.2.2 Provide copy of issued GMP Product specification to Customer.
32
7.3 TIMESCALE
This Stage may commence as soon as suitable information is available
from previous Stages of the Services. This Stage shall be complete
when the Customer is notified by LB that the documentation [ * * * ]
and the copy of the issued GMP Product specification has been sent
to the Customer. It is estimated that this Stage shall be complete
[ * * * ] from the commencement of activities of this Stage 7.
8 STAGE 8 - PRODUCTION OF CGMP PRODUCT AT 2000 LITRE SCALE
8.1 OBJECTIVE
8.1.1 To manufacture Product at 2000 litre scale
Note: The following assumptions have been made with respect to the
process [ * * * ].
8.2 ACTIVITIES
8.2.1 [ * * * ].
Note: [ * * * ].
8.2.2 at 2000 litre scale
8.2.3 [ * * * ]
8.2.4 [ * * * ]
8.2.5 [ * * * ]
8.2.6 [ * * * ]
8.2.7 [ * * * ]
8.2.8 [ * * * ]
8.2.9 [ * * * ]
33
8.2.10 Deliver Product [ * * * ] to Customer.
8.3 TIMESCALE
This Stage may commence when [ * * * ].
This Stage shall be complete upon disposition of Product by LB's
Quality department. It is estimated that Product will be delivered
[ * * * ] from commencement of this Stage. If Customer requests in
writing, the Product can be shipped [ * * * ]. It is estimated that
this shipment could occur [ * * * ] from commencement of this Stage.
9 STAGE 9 - EVALUATION OF VIRUS REDUCTION FOR [ * * * ]
9.1 OBJECTIVE
9.1.1 To obtain data for reduction of [ * * * ].
9.2 ACTIVITIES
9.2.1 Design [ * * * ].
9.2.2 Prepare a [ * * * ].
9.2.3 Collect [ * * * ].
9.2.4 Carry out the [ * * * ].
9.2.5 Repeat the [ * * * ].
9.2.6 [ * * * ]
34
9.2.7 Measure the [ * * * ]
9.2.8 Calculate [ * * * ]
9.2.9 Issue an audited report of the activities to the Customer. The
report will include [ * * * ].
9.3 TIMESCALE
This Stage may commence when [ * * * ].
This Stage shall be complete with the issue of the report of
activities. It is estimated that this report will be issued
[ * * * ] from commencement of the Stage. The final report may be
delayed to allow incorporation of data [ * * * ].
10 STAGE 10 - PRODUCT REFERENCE STANDARD
10.1 OBJECTIVES
10.1.1 To [ * * * ] a new product reference standard
10.1.2 To carry out [ * * * ].
10.1.3 To assess the [ * * * ].
10.2 ACTIVITIES
10.2.1 Provide a [ * * * ].
Note: The following activities to be carried out on all materials:
10.2.2 Test [ * * * ].
10.2.3 Analyse [ * * * ]:
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
35
Note: [ * * * ]
Note: [ * * * ]
10.2.4 Provide an audited report of activities to the Customer. This
report will be audited and will include:
- a summary of [ * * * ];
- a summary of the [ * * * ];
- an assessment of whether [ * * * ];
- a description of any [ * * * ];
- a recommendation in the report [ * * * ].
10.2.5 Timescale
This Stage will commence as soon as Product is available and
will be complete on issue of the final report of activities
and it is estimated that this will be issued [ * * * ] from
the preparation of [ * * * ]. From issue of [ * * * ] it is
estimated that the elapsed time until the Customer review of
the report is [ * * * ].
Note: The Customer shall review [ * * * ] within [ * * * ] of
receiving the document from LB. If the Customer's comments
are not returned to LB within this time LB reserves the right
to issue the [ * * * ].
11 STAGE 11 - QC TESTING OF VIALLED PRODUCT
11.1 OBJECTIVES
11.1.1 To test [ * * * ] of vialled Product, [ * * * ].
11.1.2 To provide the Customer with a summary of testing for vialled
Product.
11.2 ACTIVITIES
11.2.1 Agree with Customer [ * * * ].
Note: It is understood that the Customer will have previously
carried out an audit of the Customer's contract vialler and
is satisfied with their suitability to vial and test Product
for use in clinical trials. LB, therefore, accepts no
liability for performance of the Customer's contract vialler.
11.2.2 Prepare appropriate documentation for the vialled Product
(including Specification and QC laboratory release forms).
11.2.3 Receive vials of Product representative of [ * * * ] from the
Customer's contract vialler.
11.2.4 Test the Product from [ * * * ].
36
11.2.5 Undertake [ * * * ].
11.2.6 Issue a summary of testing for vialled Product.
11.3 TIMESCALE
This Stage may commence on receipt of vials from the Customer. This
Stage shall be complete upon issue of a summary of testing. It is
estimated that this will be available [ * * * ] from the date of
receipt of the vials.
12 STAGE 12 - STABILITY STUDY OF BULK PURIFIED PRODUCT (CGMP MATERIAL)
12.1 OBJECTIVE
12.1.1 To test the stability of bulk purified Product from [ * * * ]
produced under this Services agreement.
12.2 ACTIVITIES
12.2.1 Provide [ * * * ].
12.2.2 Take [ * * * ]
Note: [ * * * ]
12.2.3 Assay [ * * * ]:
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
Note: [ * * * ]
12.2.4 Confirm [ * * * ].
12.2.5 Issue an interim report of activities at [ * * * ].
12.2.6 Issue an audited report at the end of the study.
12.3 TIMESCALES
37
This Stage can commence once suitable material is available. This
Stage shall be complete on issue of the final report to the
Customer. The interim report of results will be issued within
[ * * * ]. The final report will be issued within [ * * * ].
Note: The Customer shall review [ * * * ] of receiving the document
from LB. If the Customer's comments are not returned to LB
within this time, the estimated timelines for the work may be
adjusted accordingly.
13 STAGE 13 - VIALLED PRODUCT STABILITY STUDIES
13.1 OBJECTIVE
13.1.1 To test the stability of the vialled Product [ * * * ].
13.2 ACTIVITIES
13.2.1 Provide a [ * * * ].
38
13.2.2 Prepare [ * * * ].
[ * * * ]
Where:
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
Note: Additional material [ * * * ] at Customer's request
13.2.3 Analyse [ * * * ]:
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
- [ * * * ]
13.2.4 Carry out [ * * * ].
13.2.5 Provide an audited summary of results after the [ * * * ]
timepoint.
13.2.6 On completion of the study issue an audited report of the
studies to the Customer.
13.3 TIMESCALES
This Stage shall commence once vialled Product is available. Audited
summary of results will be issued at [ * * * ] timepoints.
This Stage shall be complete upon issue of the audited report of the
study. The audited summary of results will be available within [ * * * ].
The final report will be issued within [ * * * ]
14 STAGE 14 - REGULATORY SUPPORT
39
14.1 OBJECTIVE
14.1.1 To prepare regulatory documentation and provide regulatory
support as required by the Customer.
14.2 ACTIVITIES
Note: The scope of this Stage will be agreed with the Customer
before commencement. Typical activities would include the
following.
14.2.1 To provide regulatory documentation [ * * * ].
14.2.2 [ * * * ].
14.2.3 To advise [ * * * ].
14.3 TIMESCALE
This Stage can commence when the appropriate data is available. The
duration of the Stage will depend on the extent of regulatory
support requested by the Customer. LB will aim to complete the
regulatory work as soon as possible after receiving all the relevant
data from these Services, in anticipation of the Customer requiring
the earliest possible filing date. This Stage shall be complete upon
submission of the regulatory documentation.
15 STAGE 155 - DETERMINATION OF EXTINCTION COEFFICIENT
15.1 OBJECTIVES
15.1.1 To determine an extinction coefficient [ * * * ]
15.2 ACTIVITIES
15.2.1 Provide a [ * * * ].
15.2.2 Determine the [ * * * ]
15.2.3 Measure the [ * * * ].
15.2.4 [ * * * ].
15.2.5 Estimate the [ * * * ].
15.2.6 Calculate a [ * * * ].
15.2.7 Repeat Activities 15.2.3 to 15.2.6 on a further two
occasions.
15.2.8 Calculate [ * * * ].
40
15.2.9 Provide a report of activities to the Customer.
15.3 TIMESCALE
This Stage shall commence as soon as Product is available and will
be complete on issue of the final report of activities (Activity
15.2.9) and it is estimated that this will be issued [ * * * ]. From
[ * * * ] it is estimated that the elapsed time until the Customer
review of the report is [ * * * ].
Note: The Customer shall review [ * * * ] within[ * * * ]. If the
Customer's comments are not returned to LB within this time
Lonza reserves the right to issue [ * * * ].
16 STAGE 16 - PRODUCTION OF CGMP PRODUCT AT 2000 LITRE SCALE
16.1 OBJECTIVE
16.1.1 To manufacture Product at 2000 litre scale.
Note: The following assumptions have been made with respect to the
process [ * * * ]
16.2 ACTIVITIES
16.2.1 After receiving [ * * * ].
Note: [ * * * ]
16.2.2 Perform [ * * * ] at 2,000 litre scale
16.2.3 [ * * * ]
16.2.4 [ * * * ]
16.2.5 [ * * * ]
16.2.6 Test [ * * * ].
16.2.7 Review [ * * * ].
41
16.2.8 [ * * * ]
16.2.9 Review [ * * * ].
16.2.10 Deliver Product and consolidated batch record to Customer.
16.3 TIMESCALE
This Stage may commence when [ * * * ].
This Stage shall be complete upon disposition of Product
[ * * * ]. It is estimated that Product will be delivered [ * * * ]
from commencement of this Stage. [ * * * ] It is estimated that this
shipment could occur [ * * * ] from commencement of this Stage.
42
SCHEDULE 3
Price and Terms of Payment
1. Price
In consideration for LB carrying out the Services as detailed in Schedule 2 the
Customer shall pay LB as follows:
PRICE(1)
STAGE (UK (POUND) STERLING)
-------- ----------------------------
Stage 1 Airlift Fermentation Process Evaluation [ * * * ]
Individual invoice may be issued
for each sub-stage
Sub-stage A
Sub-stage B
Stage 2 Purification Process Evaluation [ * * * ]
Stage 3 Evaluation of LB's Generic Assays [ * * * ]
Stage 4 Master Banks Preparation and Analysis [ * * * ] plus testing
laboratory charges
actually incurred by
LB estimated to be [ * * * ]
Stage 5 [ * * * ] Master Cell Bank Testing for Adventitious [ * * * ] plus testing
Agents laboratory charges
estimated to be [ * * * ]
Stage 6 Development Pilot Batch (non-cGMP) at 130 L Scale [ * * * ]
Stage 7 Preparation of cGMP Documentation [ * * * ]
Stage 8 Production of cGMP Product at 2000 litre scale [ * * * ]
Stage 9 Evaluation of Virus Reduction for [ * * * ] [ * * * ] plus testing
laboratory charges actually
incurred by LB estimated
to be [ * * * ]
Stage 10 Product Reference Standard [ * * * ]
Stage 11 QC Testing and QA Review of Final Vialled Product [ * * * ] per time point
Stage 12 Stability Study of Bulk Purified Product (cGMP material)
Each timepoint [ * * * ]
Stage 13 Vialled Product Stability Studies [ * * * ] per time point
Stage 14 Regulatory Support Depending on Scope for
IND preparation
Estimated to be [ * * * ]
43
Stage 15 Determination of Extinction Coefficient [ * * * ]
Stage 16 Production of cGMP Product at 2000 litre scale [ * * * ]
Notes:
(1) [ * * * ]
(2) [ * * * ]
(3) [ * * * ].
(4) [ * * * ]
(5) [ * * * ].
(6) [ * * * ]
44
2. Payment
Payment by the Customer of the Price for each Stage shall be made against
LB's invoices as follows(1):
2.1 For Stage 1
50% upon commencement of Stage 1.
50% upon completion of Stage 1.
2.2 For Stage 2
50% upon commencement of Stage 2.
50% upon completion of Stage 2.
2.3 For Stage 3
50% upon commencement of Stage 3.
50% upon completion of Stage 3.
2.4 For Stage 4
50% upon commencement of Stage 4.
50% upon completion of Stage 4.
2.5 For Stage 5
50% upon commencement of Stage 5.
50% upon completion of Stage 5.
2.6 For Stage 6
50% upon commencement of Stage 6.
50% upon completion of Stage 6.
2.7 For Stage 7
50% upon commencement of Stage 7.
50% upon completion of Stage 7.
2.8 For Stage 8
50% upon removal of an ampoule of MCB out of freeze.
50% upon completion of Stage 8.
2.9 For Stage 9
50% upon commencement of Stage 9.
50% upon completion of Stage 9.
Testing Laboratory charges will be invoiced separately.
2.10 For Stage 10
50% upon commencement of Stage 10.
50% upon completion of Stage 10.
Testing Laboratory charges will be invoiced separately.
2.11 For Stage 11
50% upon commencement of Stage 11.
50% upon completion of Stage 11.
2.12 For Stage 12
100% payment per issued time point
2.13 For Stage 13
100% payment per issued time point
2.14 For Stage 14
Price depends on scope of work(6)
2.15 For Stage 15
50% upon commencement of Stage 15
45
50% upon completion of Stage 15
2.16 For Stage 16
50% upon removal of an ampoule of MCB out of freeze.
50% upon completion of Stage 16.
Notes: see "1 Price", above, in this Schedule 3.
46
SCHEDULE 4
Inhibitex Patents
1. U.S. 6,008,341 (ClfA DNA); U.S. 6,177,084 (ClfA protein)
2. U.S. 6,635,473 (SdrG DNA)
3. U.S. 10/056,052 (ClfA monoclonal application)
The Inhibitex Patents also include divisional and continuation applications as
well as all corresponding international applications.
47
