exv10w81



 






Exhibit 10.81




SUPPLY AND PURCHASE AGREEMENT




     This Supply and Purchase Agreement (“Agreement”), effective as of the 15th day of
February, 2005 (the “Effective Date”), is by and between F. HOFFMANN-LA ROCHE LTD., a Swiss limited
liability company with a place of business at Grenzacherstrasse 124, CH-4070 Basle, Switzerland and
ROCHE MOLECULAR SYSTEMS, INC., a Delaware corporation with a place of business at 4300 Hacienda
Drive, Pleasanton, CA 94588 (collectively, “ROCHE”), and GEN-PROBE INCORPORATED, a Delaware
corporation with a place of business at 10210 Genetic Center Drive, San Diego, CA 92121 and its
Affiliates (as such term is defined below) (collectively, “GPRO”).



BACKGROUND




     GPRO requests that ROCHE supply all of GPRO’s requirements for HPV Products (as such term is
defined below) solely for use with or in HPV TMA Test Kits (as such term is defined below), and
ROCHE is willing to supply those requirements all on the terms and subject to the conditions
specified in this Agreement.



          NOW, THEREFORE, the parties agree as follows:





	1.  	Definitions.
	 
	   	When used in this Agreement, the following terms shall have the meanings set forth below.






	 	1.1  	“Affiliates” means, with respect to any Person, any other Person that, directly
or indirectly, controls, is controlled by or is under common control with, that Person,
provided however, that in each case any such other Person shall be considered to be an
Affiliate only during the time period during which such control exists. For purposes
of this definition, “control” (including, with correlative meaning, the terms
“controlled by” and “under common control with”), as used with respect to any Person,
shall mean the possession, directly or indirectly, of the power to direct and/or cause
the direction of the management and policies of such Person, whether through the
ownership of voting securities, by contract or otherwise. With regard to ROCHE, the
term Affiliate shall not include Genentech, Inc., 1 DNA Way, South San Francisco,
California 94080-4990, U.S.A. (“Genentech”) or Chugai Pharmaceutical Co., Ltd, 1-9
Kyobashi 2-chome, Chuo-ku, Tokyo, 104-8301, Japan (“Chugai”).
	 
	 	1.2  	“Certificate of Analysis” means the documentation that accompanies the HPV
Products and confirms that such products meet the Specifications.
	 
	 	1.3  	“Confidential Information” means: (i) any information designated in writing by
either party as proprietary or confidential, or if orally disclosed, identified at the
time of disclosure as proprietary or confidential and confirmed in writing to be
proprietary and confidential within thirty (30) days of disclosure; (ii) ROCHE’s
business and marketing plans with respect to the HPV Patent Rights and any other




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	 	   	intellectual property rights owned by or licensed to ROCHE; and (iii) the terms and
conditions of this Agreement and the negotiations between the parties with respect
to this Agreement.
	 
	 	1.4  	“Days” means calendar days.
	 
	 	1.5  	“HPV” means the human papilloma virus.
	 
	 	1.6  	“HPV Products” means the HPV Reagent Products and the HPV RNA Transcript and
HPV DNA Products.
	 
	 	1.7  	“HPV Reagent Products” means certain oligonucleotide reagents manufactured by
ROCHE under this Agreement pursuant to the applicable Specifications (as such term is
defined below) for use by GPRO in developing the HPV TMA Test Kits and for
incorporation by GPRO into the HPV TMA Test Kits (as such term is defined below) all
for use only with TMA (as defined below).
	 
	 	1.8  	“HPV RNA Transcript and HPV DNA Products” means certain HPV transcripts and/or
HPV DNA manufactured by or on behalf of ROCHE under this Agreement pursuant to the
applicable Specifications (as such term is defined below) for use by GPRO solely for
development, formulation and quality control of the HPV TMA Test Kits (as such term is
defined below).
	 
	 	1.9  	“HPV TMA Test Kits” means the diagnostic test kits for HPV (inclusive of ASR
reagent products) developed and sold by GPRO for use only with TMA, which are designed
to run on any current or future instrument appropriate for such purpose.
	 
	 	1.10  	“Individual HPV Test Quantity” means that quantity of HPV Reagent Product(s)
necessary to generate a diagnostic result for a single patient with respect to one or
more types of HPV, as described in the Specifications. Individual HPV Test Quantities
shall be reported in appropriate mass units as calculated from the individually
measured [...***...] provided to ROCHE by GPRO.
	 
	 	1.11  	“Manufacturing Cost” shall mean the fully-burdened cost to ROCHE (expressed on
a per unit basis) of manufacturing or having manufactured the HPV Products, together
with the packaging thereof, including the cost of materials, direct labor, quality
control, and overhead (including royalties paid to Third Parties), all as determined in
accordance with ROCHE’s standard accounting practices for other products manufactured.
For the avoidance of doubt, Manufacturing Cost shall not include any cost component
attributable to excess or idle manufacturing capacity.
	 
	 	1.12  	“Person” shall mean an individual or any legally recognized entity, including
any corporation, partnership, limited partnership, limited liability company,
association or trust.





***Confidential Treatment Requested




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	 	1.13  	“ROCHE HPV Patents” means certain patent rights owned by or licensed to ROCHE,
covering the HPV Products, as further specified in Exhibit A of this Agreement,
including all divisionals, continuations, continuations-in-part applications,
substitutes, reissues, renewals, re-examinations and extensions of any of the said
patent rights, and all patents worldwide issuing on any of the patent applications
included within the said patent rights. Additional patent rights developed by ROCHE
and, to the extent permitted under the applicable license or acquisition agreement of
ROCHE with a third Person, additional patent rights licensed or acquired by ROCHE,
directed solely to oligonucleotide probes and methods for their use for the detection
of HPV shall also be included within the ROCHE HPV Patents. ROCHE HPV Patents licensed
by ROCHE shall be subject to the terms, conditions, limitations and restrictions
contained in the applicable license agreement of ROCHE with the third Person.
	 
	 	1.14  	“Specifications” means the specifications set forth in Exhibit B of
this Agreement, pursuant to which ROCHE shall manufacture the HPV Products under this
Agreement, which specifications may be modified from time to time upon request of GPRO,
subject to the written consent of ROCHE, such consent not to be unreasonably withheld,
conditioned or delayed. ROCHE acknowledges that it is aware that GPRO is likely to
request modification of the Specifications from time-to-time in connection with GPRO’s
development of the HPV TMA Test Kits and prior to any First Commercial Sale thereof.
	 
	 	1.15  	“TMA” means “Transcription-Mediated Amplification”, a transcription-based
process for amplifying a DNA or RNA target source. TMA comprises a substantially
continuous and isothermal process of generating multiple RNA copies of the target
sequence or its complement. It is expressly understood that the heating of target RNA
to relax the molecule prior to the transcription-based process can comprise a step in
“TMA.” Further, it is expressly understood that a transcription-based process, as
described herein, that begins with a single stranded DNA or RNA target sequence or a
double stranded DNA target sequence includes no more than two cycles of heat
denaturation and primer extension, employs only one primer in the first primer
extension step, and produces a double stranded promoter sequence is included within the
meaning of “TMA.” Finally, it is expressly understood and agreed that the TMA process
is not polymerase chain reaction (“PCR”) amplification, namely the amplification of a
nucleic acid sequence and the complement of that sequence by more than two cycles of
denaturation of a double stranded nucleic acid, annealing and extension of two primers,
wherein the sequence and its complement are repeatedly separated, each separated strand
serves as a template for primer extension and the resulting double stranded nucleic
acid is used in further cycles of denaturation, annealing and extension of primers.
	 
	 	1.16  	“Transfer Fee” shall have the meaning provided in Section 3.2, 3.3 or 3.4, as
applicable.




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	2.  	Supply and Purchase of HPV Products.






	 	2.1  	Obligation to Purchase. GPRO shall purchase from ROCHE, upon GPRO’s
request as provided in this Agreement, all of its requirements of HPV Reagent Products
for use in HPV TMA Test Kits and all of its requirements of HPV RNA Transcript and HPV
DNA Products for use in connection with HPV TMA Test Kits. GPRO’s obligation under
this Section 2.1 shall terminate upon any termination of this Agreement pursuant to
Section 9.
	 
	 	2.2  	Obligation to Supply. ROCHE shall supply all of GPRO’s requirements of
HPV Reagent Products for use in HPV TMA Test Kits and all of GPRO’s requirements of HPV
RNA Transcript and HPV DNA Products for use in connection with HPV TMA Test Kits, as
requested by GPRO under Section 2.1. ROCHE will manufacture, or have manufactured, the
HPV Products in accordance with the Specifications and appropriate Quality Systems
Regulations and then current Good Manufacturing Practices (cGMP) controls. Any
material deviations from the prescribed ROCHE manufacturing process shall be
communicated to GPRO prior to ROCHE’s release of the HPV Products. Manufacturing
records for the HPV Products will be kept at the facility where such HPV Products were
manufactured and will be available for necessary regulatory inspections as provided in
Section 6.2.1.
	 
	 	2.3  	Scope of GPRO’s Rights for HPV Products. GPRO shall utilize HPV
Reagent Products purchased under this Agreement solely for development of and
incorporation into HPV TMA Test Kits, and for no other purpose. GPRO shall utilize HPV
RNA Transcript and HPV DNA Products purchased under this Agreement solely for its own
internal development, formulation and quality control of HPV TMA Test Kits, and for no
other purpose. GPRO shall not have the right to resell the HPV Products on a standalone
basis or as incorporated into any other product, but only as incorporated into HPV TMA
Test Kits (including as one component of ASR reagent products). GPRO shall have the
unrestricted and unconditional right to incorporate the HPV Reagent Products into the
HPV TMA Test Kits and GPRO shall have the unrestricted and unconditional right to use
and sell the HPV TMA Test Kits (including to its distributors).
	 
	 	2.4  	Restriction on Supply by ROCHE. ROCHE shall not sell or supply the HPV
Products manufactured by it under this Agreement to any third Person.
	 
	 	2.5  	Failure a Material Breach. Failure by a party to comply with Sections
2.1, 2.2, 2.3 and 2.4 shall constitute a material breach of this Agreement by such
party.






	3.  	Fees.






	 	3.1  	Manufacturing Access Fee and Additional Charge for Patented Products.
In consideration of ROCHE’s agreement to manufacture and supply the HPV Products to
GPRO under the ROCHE HPV Patents pursuant to this Agreement, GPRO shall pay to ROCHE a
non-refundable manufacturing access fee and




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	 	   	additional charge for the HPV Products of
Thirty Million United States Dollars (US$30,000,000), payable in two installments as
follows: (i) Twenty Million United States Dollars (US$20,000,000) within ninety (90)
days after the Effective Date; and (ii) Ten Million United States Dollars
(US$10,000,000) within the earlier of (A) [...***...] ([...***...])[...***...], or (B)
[...***...]. As used in this Agreement, a “First Commercial Sale” shall mean the first
commercial sale by GPRO of any HPV TMA Test Kit (not including any use or transfer for
Non-Commercial Use (as defined below) or Clinical Trial Use (as defined below)).
	 
	 	3.2  	Transfer Fees for HPV Reagent Products. As additional consideration
for ROCHE’s agreement to manufacture and supply the HPV Reagent Products to GPRO under
this Agreement, GPRO shall pay to ROCHE, for the supply of bulk quantities of the HPV
Reagent Products during the term of this Agreement, transfer fees (the “Reagent
Transfer Fee”) as follows:






	 	3.2.1  	Each purchase order submitted by GPRO will ordinarily include
each of the HPV Reagent Products to be incorporated into the HPV TMA Test Kits.
As to each such order, GPRO shall pay to ROCHE in respect of each Individual
HPV Test Quantity of HPV Reagent Products manufactured and sold by ROCHE to
GPRO as follows: (i) from the Effective Date until [...***...]
([...***...])[...***...] after GPRO achieves the First Commercial Sale of a HPV
TMA Test Kit, US$[...***...] per Individual HPV Test Quantity; (ii) for
[...***...] ([...***...]) to [...***...] ([...***...]) after GPRO achieves the
First Commercial Sale of a HPV TMA Test Kit, US$[...***...] per Individual HPV
Test Quantity; (iii) for [...***...] ([...***...]) to [...***...] ([...***...])
after GPRO achieves the First Commercial Sale of a HPV TMA Test Kits,
US$[...***...] per Individual HPV Test Quantity; (iv) for [...***...]
([...***...]) to [...***...] ([...***...]) after GPRO achieves the First
Commercial Sale of a HPV TMA Test Kit, US$[...***...] per Individual HPV Test
Quantity; and (iv) for the remainder of the term of this Agreement, the greater
of (A) US$[...***...] per Individual HPV Test Quantity, or (B) the
Manufacturing Cost thereof (or ROCHE’s actual incurred cost if manufactured for
ROCHE by a third Person), plus a margin of [...***...] percent ([...***...]%),
provided however, that for individual orders of GPRO made during such remainder
of the term of the Agreement for a lot size of at least [...***...]
([...***...]) Individual HPV Test Quantities per order, such Transfer Fee shall
not exceed US$[...***...] per Individual HPV Test Quantity.
	 
	 	3.2.2  	Notwithstanding the fact that each purchase order submitted by GPRO will ordinarily
include each of the HPV Reagent Products to be incorporated into the HPV TMA
Test Kits, GPRO shall have the right to
separately order and purchase from ROCHE one or more individual
oligonucleotide reagents included within the HPV Reagent Products. As to
each such order, GPRO shall pay to ROCHE a Transfer Fee per Individual HPV
Test Quantity of each individual oligonucleotide reagent.





***Confidential Treatment Requested




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	 	   	Such Transfer Fee
shall be equal to the Transfer Fee set forth in Section 3.2.1, above,
multiplied by [...***...], where “[...***...]” is the [...***...] of
[...***...] then [...***...] within the [...***...] and [...***...] by
[...***...] into the [...***...]. Nothing contained in this Section 3.2.2
shall diminish GPRO’s obligation under Section 2.1 to purchase from ROCHE
all of GPRO’s requirements of HPV Reagent Products for use in HPV TMA Test
Kits.






	 	3.3  	Transfer Fees for HPV RNA Transcript and HPV DNA Products. As
additional consideration for ROCHE’s agreement to manufacture and/or supply the HPV RNA
Transcript and HPV DNA Products to GPRO under this Agreement, GPRO shall pay to ROCHE,
for the supply of bulk quantities of the HPV RNA Transcript and HPV DNA Products during
the term of this Agreement, a transfer fee in respect of such HPV RNA Transcript and
HPV DNA Products sold by ROCHE to GPRO (the “Transcript Transfer Fee”) equal to ROCHE’s
Manufacturing Cost, plus a margin of [...***...] percent ([...***...]%), or ROCHE’s
actual incurred cost if manufactured for ROCHE by a third Person, plus a margin of
[...***...] percent ([...***...]%), provided however, that if HPV RNA Transcript and
HPV DNA Products are manufactured by ROCHE and sold to GPRO, the Transcript Transfer
Fee shall not exceed [...***...] percent ([...***...]%) of the Transcript Transfer Fee
that GPRO can reasonably demonstrate would have been charged if ROCHE had alternatively
had such HPV Transcript Product manufactured by a third Person for ROCHE for sale to
GPRO.
	 
	 	3.4  	HPV Reagent Products for Non-Commercial Use. Notwithstanding Section
3.2 of this Agreement, GPRO shall be entitled to purchase a limited quantity of the HPV
Reagent Products for “Non-Commercial Use”. For the purpose of this Section 3.4,
“Non-Commercial Use” shall mean that the intended use of such HPV Reagent Products, as
demonstrated by GPRO to ROCHE’s reasonable satisfaction, shall be solely for GPRO’s
internal research and development and not for transfer or sale by GPRO to any third
Person. GPRO currently estimates that it will require approximately [...***...]
Individual HPV Test Quantities for Non-Commercial Use.
	 
	 	3.5  	HPV Reagent Products for Clinical Trials. Notwithstanding Section 3.2
of this Agreement, GPRO shall be entitled to purchase a limited quantity of the HPV
Reagent Products for use only in those clinical trials required to obtain applicable
governmental regulatory approvals (“Clinical Trial Use”), provided that GPRO shall
furnish such HPV Reagent Products (and/or corresponding HPV TMA Test Kits) to the
clinical trial researchers or governmental agencies at no charge and shall not sell
such HPV Reagent Products (and/or corresponding HPV TMA Test Kits) to any third Person
and, provided further, that GPRO may only purchase up to [...***...] Individual HPV
Test Quantities of the HPV Reagent Products for use
for such purposes, and provided finally, that if GPRO can demonstrate to ROCHE’s
reasonable satisfaction that additional HPV Test Quantities are reasonably needed by
GPRO for such purposes, GPRO may purchase an





***Confidential Treatment Requested




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	 	   	additional amount of HPV Test
Quantities up to a maximum of [...***...] additional Individual HPV Test Quantities
for use only for such purposes.
	 
	 	3.6  	Transfer Fee and Order Size for Non-Commercial Use and Clinical Trial
Use. The Transfer Fee and order size for GPRO’s purchase of HPV Reagent Products
for Non-Commercial Use and Clinical Trial Use shall be in accordance with Exhibit
C to this Agreement. With respect to any Individual HPV Test Quantities ordered by
GPRO pursuant to this Section 3.6 that are not used by GPRO for Non-Commercial Use or
Clinical Trial Use as provided in Sections 3.4 and 3.5 and are instead reclassified by
GPRO for commercial use and incorporation by GPRO into HPV TMA Test Kits, upon the
earlier of such reclassification or incorporation into HPV TMA Test Kits, GPRO shall
immediately notify ROCHE. GPRO shall concurrently pay ROCHE the difference between the
applicable Transfer Fees in effect pursuant to Section 3.2 as of the date of original
delivery thereof for such Individual HPV Test Quantities and the applicable price
previously paid by GPRO for such Individual HPV Test Quantities as provided in
Exhibit C.
	 
	 	3.7  	Third Party Royalties. Any royalties or other fees owed by ROCHE to
any third Person for the practice of the ROCHE HPV Patents shall be borne exclusively
by ROCHE. Any royalties or other fees owed to any third Person for or in connection
with the HPV TMA Test Kits or the practice of TMA shall be borne exclusively by GPRO.
	 
	 	3.8  	Replacement of Scrapped HPV Reagent Products. During the term of this
Agreement, if GPRO demonstrates to ROCHE’s reasonable satisfaction that any HPV Reagent
Products, ordered by GPRO for incorporation into HPV TMA Test Kits and paid for
pursuant to Section 3.2, have been fully and finally scrapped by GPRO due to GPRO
internal accidental damage or loss, then ROCHE shall supply replacement HPV Reagent
Products and GPRO shall pay ROCHE [...***...] percent ([...***...]%) of the Transfer
Fee then in effect but in no event less than the greater of (a) US$[...***...] per
Individual HPV Test Quantity, or (b) the Manufacturing Cost thereof plus a margin of
[...***...] percent ([...***...]%). For the avoidance of doubt, this Section 3.8 shall
not apply to HPV Reagent Products ordered by GPRO for Non-Commercial Use or Clinical
Trial Use.






	4.  	Forecasts and Orders.






	 	4.1  	Forecast. Each calendar quarter, on or about the first day of each
quarter, GPRO will provide to ROCHE a rolling forecast of its requirements for HPV
Products for the next ([...***...])[...***...], based on GPRO’s good faith estimates of
anticipated sales of HPV TMA Test Kits. Such forecast shall include good faith
estimates of anticipated delivery dates. Failure to provide such information may
result in product shortages or delays. GPRO’s forecasts shall not be binding.
	 
	 	4.2  	Purchase Orders. GPRO shall purchase HPV Products hereunder by issuing a written
purchase order identifying the HPV Products to be purchased, the





***Confidential Treatment Requested




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	 	   	quantity, total order
purchase price based on the then applicable Transfer Fees, delivery instructions,
delivery dates and any other special information. The delivery date specified in each
purchase order shall be at least sixty (60) days after the date of the purchase order
when ordering [...***...] to [...***...] lots of HPV Reagent Products, ninety (90) days
after the date of the purchase order when ordering [...***...] to [...***...] lots of
HPV Reagent Products and one hundred twenty (120) days after the date of the purchase
order when ordering [...***...] to [...***...] lots of HPV Reagent Products, provided
however, that GPRO recognizes that delivery dates for initial shipments of HPV Products
may be longer than the periods set forth in this Section 4.2 and the parties agree to
confer and reasonably agree upon reasonable lead times for the delivery of initial
shipments of the HPV Products with the goal and intention of achieving lead times as
close to one hundred twenty (120) days as possible with commercially reasonable
efforts. Except as otherwise provided in Exhibit C, a “lot” of HPV Reagent Product
shall be the equivalent of one million Individual HPV Test Quantities and the minimum
order for a purchase order shall be one (1) lot and the maximum order for a purchase
order shall be [...***...] lots. Each purchase order shall specifically reference this
Agreement. Within seven (7) days of the delivery of each purchase order, as partial
pre-payment for the applicable HPV Products, GPRO shall deposit with ROCHE
US$[...***...] per Individual HPV Test Quantity for the HPV Reagent Products that were
the subject of the purchase order and the Transfer Fee pursuant to Section 3.3 for the
HPV RNA Transcript and HPV DNA Products that were the subject of the purchase order.
	 
	 	4.3  	Acceptance of Purchase Orders. ROCHE may accept or reject purchase
orders within seven (7) working days of ROCHE’s receipt of written purchase orders.
Provided that a purchase order does not request lot quantities of HPV Products greater
than [...***...]% of previously forecasted quantities, ROCHE shall accept all purchase
orders that are issued in conformance with the provisions of this Agreement. ROCHE
shall use commercially reasonable efforts to accommodate lot quantities of HPV Products
greater than [...***...]% of previously forecasted quantities. Upon acceptance of a
purchase order, such purchase order and acceptance shall constitute a binding contract
between GPRO and ROCHE (subject to the terms and conditions of this Agreement).
	 
	 	4.4  	Deferral and Cancellation. Prior to the scheduled delivery date
specified on a purchase order, GPRO may defer delivery of HPV Products specified in
such purchase order for a period not to exceed [...***...] ([...***...]) days, provided
however, that in all cases upon the expiration of such [...***...] ([...***...]) days,
ROCHE may deliver the HPV Products and invoice for the applicable amount due.
Deferrals related to that purchase order must be by written notice, and shall be
subject to a charge of [...***...]% of the unpaid purchase price for the deferred
HPV Products for each thirty (30) days deferred based on the Transfer Fee in effect
on the date of the purchase order.





***Confidential Treatment Requested




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	 	4.5  	Acceptance or Rejection. GPRO shall inspect all HPV Products within
[...***...] ([...***...]) Days of receipt thereof, and may reject any HPV Product that
does not conform to the Specifications, provided that it has not been used, abused or
damaged by GPRO or GPRO’s agents. Any HPV Product not properly and timely rejected by
GPRO shall be deemed accepted. To reject an HPV Product, GPRO shall notify ROCHE in
writing within sixty (60) Days of receipt of the HPV Product of its rejection and shall
promptly return the rejected HPV Product to ROCHE. All returned HPV Products shall be
accompanied by suitable documentation, as specified by ROCHE in response to GPRO’s
notification of rejection. GPRO shall also provide all reasonable assistance to ROCHE
to facilitate ROCHE’s investigation and confirmation of the non-conformance basis for
rejection. After confirmation of the non-conformance basis for rejection, ROCHE shall
replace the rejected HPV Product with conforming HPV Product as promptly as reasonably
possible and within the periods set forth in Section 4.2. Notwithstanding the
foregoing, if GPRO first discovers any non-conforming condition in HPV Products as
manufactured by or for ROCHE after the aforementioned 60-day period and such condition
would not have been detected in an initial inspection using commercially reasonable
inspection methods (a “Latent Defect”) and GPRO immediately notifies ROCHE of such
non-conforming condition, then such HPV Product shall be deemed to be non-conforming
under this Agreement and GPRO shall have all remedies originally available to it under
this Section 4.5 with respect to such non-conforming HPV Products.
	 
	 	4.6  	Inconsistencies. Notwithstanding the content of GPRO’s purchase order.
ROCHE’s invoice, or any other document submitted by one party to the other, this
Agreement shall take precedence over such purchase order or other document, and this
Agreement shall govern and control over any conflicting or inconsistent terms of such
purchase order(s), invoices(s) or other documents, and all terms which are inconsistent
with those provided in this Agreement shall be null and void.
	 
	 	4.7  	Product Modifications. Each party will notify the other party promptly
(and, in any case, no later than thirty (30) Days) after it receives information that
the processes, Specifications or materials used to manufacture the HPV Products will be
changed. Without pre-approval by GPRO, which shall not be unreasonably withheld,
conditioned or delayed, ROCHE shall not make any change in the manufacturing process
for the HPV Products that would cause the HPV Products not to meet the Specifications.
The parties shall discuss any such changes and agree on their acceptability and any
potential financial impact the changes may have on the Transfer Fee. Any such
agreement shall be in the form of a signed amendment to this Agreement.






	5.  	Packing and Delivery.






	 	5.1  	Delivery. ROCHE will use commercially reasonable efforts to effect
delivery on or before the date indicated in GPRO’s purchase order, provided that date
is in





***Confidential Treatment Requested




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	 	   	conformance with the terms and conditions of this Agreement. ROCHE shall not be
liable for any delay or failure in performance or delivery where such delay or failure
arises or results from any cause beyond ROCHE’s reasonable control, including, but not
limited to, strike, boycott, or other labor disputes, failures or delays by common
carriers, embargo, governmental regulation, or delay in obtaining materials,
earthquakes, storms, power outages or acts of God. In the event of any such delay or
failure in performance due to a cause beyond ROCHE’s reasonable control, ROCHE shall
have such additional time within which to perform its obligations hereunder as may
reasonably be necessary in ROCHE’s reasonable judgment.
	 
	 	5.2  	Delivery Terms. Delivery of HPV Products shall be made by Roche to
GPRO at GPRO’s designated facility or facilities as is specified in GPRO’s purchase
order. ROCHE shall invoice GPRO for all transportation charges.
	 
	 	5.3  	Packaging. All HPV Products delivered pursuant to this Agreement shall
be suitably packed in ROCHE’s standard transportation cartons, marked for delivery to
the relevant delivery address, and delivered to GPRO as provided herein. ROCHE shall
comply with any special packaging requirements set forth in the Specifications. ROCHE
shall select the carrier.
	 
	 	5.4  	Custody, Control, Title, Risk of Loss and Location of Sale. Control,
custody, title and risk of loss with respect to all HPV Products shall pass from ROCHE
to GPRO upon delivery of the HPV Products to GPRO at its designated facility.
Accordingly, the sale of HPV Products by ROCHE to GPRO shall occur for all purposes of
this Agreement upon delivery to GPRO’s designated facility. The parties further
acknowledge, intend and agree that upon ROCHE’s sale of the HPV Products for use in or
with the HPV TMA Test Kits that the doctrine of patent exhaustion will apply with
respect to such use and as to all claims of the ROCHE HPV Patents. GPRO acknowledges
and agrees that following the sale of the HPV Products hereunder GPRO will not
transport such HPV Products (including as incorporated into HPV TMA Test Kits) from the
jurisdiction in which they were delivered and purchased to any other jurisdiction in
which the doctrine of patent exhaustion would not apply to the importation, offer for
sale, sale or use thereof based on the original sale and delivery in the first
jurisdiction. (By way of example and not of limitation, under current law GPRO
acknowledges and agrees that HPV Reagent Products sold to it in the United States will
not be transported to, or sold by GPRO in HPV TMA Test Kits in, Europe and GPRO will
purchase and take delivery in Europe of all HPV Products to be used in or with HPV TMA
Test Kits to be sold in Europe.)
	 
	 	5.5  	Disclaimer of Patent Exhaustion or Implied Licenses as to Other ROCHE
Patents. In connection with the delivery and sale of HPV Products pursuant to this
Agreement, ROCHE hereby disclaims any applicability of the doctrine of patent
exhaustion with respect to, or any grant of implied license rights under, any patent
rights of ROCHE or its Affiliates other than the ROCHE HPV Patents, and GPRO




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	 	   	acknowledges and agrees that it obtains no benefit of the doctrine of patent
exhaustion or implied license rights under any other patent rights of ROCHE or its
Affiliates.
	 
	 	5.6  	Certificate of Analysis. ROCHE shall provide a Certificate of Analysis
with each delivery of HPV Products.






	6.  	Invoicing and Payment; Inspections and Audits, Etc.






	 	6.1  	Invoicing and Payment. ROCHE will invoice GPRO for the Transfer Fees
after ROCHE has delivered the HPV Products. The Transfer Fee to be charged shall be
the Transfer Fee in effect pursuant to Section 3.2 on the date the subject HPV Products
were delivered to GPRO, less the deposit made by GPRO pursuant to Section 4.2. GPRO
shall pay all applicable amounts due in respect of each purchase order within thirty
(30) days after receipt of ROCHE’s invoice therefor. Payment terms are net thirty (30)
Days from receipt of ROCHE’s invoice to GPRO. GPRO shall be liable for the invoiced
price of all HPV Products substantially conforming to a GPRO purchase order, unless
GPRO properly rejected the HPV Products in a timely manner. If payment is not received
by the due date, a service charge may be added at the rate of [...***...]% per
[...***...] ([...***...]% per [...***...]) or the maximum legal rate, whichever is
less, to unpaid invoices from the due date thereof, and GPRO agrees to pay such charge.
If GPRO consistently fails to make payments when due, ROCHE reserves the right to
require alternative payment terms, including, without limitation, sight draft, letter
of credit, or payment in advance. Upon making such demand, ROCHE may suspend
production and/or deliveries. If, within the period stated in such demand, but in no
event longer than thirty (30) Days, GPRO fails to give adequate assurance of due
performance, ROCHE may make deliveries under reservation of a security interest and
demand payment against tender of documents of title. GPRO hereby represents to ROCHE
that GPRO is now solvent and agrees that each acceptance of delivery of HPV Product
sold hereunder shall constitute reaffirmation of this representation at such time.
	 
	 	6.2  	Inspections and Audits.






6.2.1 GPRO Audits. ROCHE shall permit and assure GPRO access during
reasonable business hours and upon thirty (30) days written notice to conduct an
audit (i) of those areas of all facilities where the HPV Products are manufactured,
tested, filled, released, packaged, labeled, stored and/or handled, as applicable,
and (ii) all quality control records, test records and manufacturing records for the
HPV Products, each in order for GPRO to perform a quality assurance audit of such
facilities and activities, (iii) ROCHE’s qualification policies and procedures for
third Person manufacturers and suppliers, and (iv) in the event the Transfer Fee for
HPV Products is determined based upon ROCHE’s Manufacturing Cost
thereof; the cost basis for such Manufacturing Cost, provided, however, that GPRO
shall not cause such an audit to occur more than once in any given



***Confidential Treatment Requested




11









 








[...***...]
([...***...])[...***...] period, except as may be required by cGMP or any other
applicable law or regulation, and, provided, further, that all such audits shall be
conducted in such a manner as to not unreasonably interfere with the conduct of
regular business activities at the audited facility. ROCHE shall permit GPRO or a
third Person designated by GPRO to copy, under reasonable confidentiality
obligations, such documents as GPRO can reasonably establish are required to be
copied for regulatory purposes.



6.2.2 GPRO Books and Records. GPRO shall maintain regular and complete
records for a period of [...***...] ([...***...]) years after the expiration of the
calendar quarter to which they pertain, sufficient to enable verification of GPRO’s
compliance with the terms and conditions of this Agreement and the accuracy of all
statements and payments made by GPRO. Such records shall be maintained at GPRO’s
regular place of business and, on thirty (30) days notice, shall be available for
inspection and audit by ROCHE’s outside accountants, acting in confidence, during
normal business hours, for [...***...] ([...***...]) years immediately following the
end of the calendar quarter to which they pertain; provided, however, that ROCHE
shall not cause such an inspection and audit to occur more than once in any given
[...***...] ([...***...])[...***...] period or with respect to any records after the
expiration of [...***...] ([...***...]) years after the end of the calendar quarter
to which such records pertain and, provided, further, that all such inspections and
audits shall be conducted in such a manner as to not unreasonably interfere with the
conduct of the GPRO’s regular business activities. Should any such audit reveal a
payment short fall by GPRO, the amount of the short fall shall be paid promptly by
GPRO after the discovery thereof, together with interest thereon calculated at the
lower of (i) the prime rate of the Bank of America plus [...***...] percent
([...***...]%), or (ii) the maximum rate provided under applicable law, until paid.
If the payment shortfall revealed in any audit is greater than [...***...] percent
([...***...]%), GPRO shall also pay all costs and expenses of the audit, including
all charges of ROCHE’s outside accountants.




	 	6.3  	Taxes and Duties. The purchase price of all HPV Products is exclusive
of any taxes, fees, duties, licenses or levies now or hereinafter imposed upon the
production, storage, sale, transportation or use of the HPV Products, and such taxes
and items shall be paid by GPRO (other than a tax measured by ROCHE’s net income). In
lieu of payment, GPRO shall provide an exemption certificate acceptable to the taxing
authorities.






	7.  	Label Statement; Patent Marking; Trademarks.






	 	7.1  	Label Statement. GPRO shall include on and with each HPV TMA Test Kit
a statement to the effect that the product is sold and intended for use only in Human
In Vitro Diagnostics and that all other implied licenses are expressly disclaimed.
The location of such label disclaimer shall be on the outside of the packaging for
each HPV TMA Test Kit and on any product insert included with the product or





***Confidential Treatment Requested




12









 









	 	  	otherwise published by GPRO, or such other reasonably prominent location(s) as shall
be specified by ROCHE from time to time.
	 
	 	7.2  	Patent Marking. ROCHE will mark all HPV Products as appropriate under
statutory patent provisions with respect to the ROCHE HPV Patents. GPRO will also mark
all HPV TMA Test Kits as appropriate under statutory patent provisions with respect to
the ROCHE HPV Patents on both the outside packaging and any product insert included
with the product or otherwise published by GPRO as reasonably directed by ROCHE from
time to time. With respect to containers of HPV Products included in the HPV TMA Test
Kits, if it is reasonably feasible to mark such containers as appropriate under
statutory patent provisions, GPRO shall so mark such containers as reasonably directed
by ROCHE from time to time, provided, however, that if it is not reasonably feasible to
so mark such containers because of the size of the containers or other limiting
considerations, GPRO shall include the following statement on the outside of each such
container as reasonably directed by ROCHE from time to time: “Patented. See Product
Packaging and Insert for Patent Numbers.”
	 
	 	7.3  	No Trademark Rights. Neither party shall have any license or right to
use any trademark owned by or licensed to the other party.






	8.  	Warranties; Exclusions, Disclaimers, Indemnification; Limitation of Liability.






	 	8.1  	ROCHE Warranties.






	 	8.1.1  	With respect to any HPV Product purchased by GPRO under this
Agreement ROCHE warrants that the HPV Product will conform to the applicable
Specifications and will be free from defects in materials or workmanship when
delivered to GPRO pursuant to the provisions of Section 5 above. ROCHE shall
promptly replace all HPV Products that do not conform to this warranty at no
charge to GPRO. HPV Products are temperature sensitive, as fully set forth in
the Specifications. Subject to the inspection and rejection procedures and
remedies set forth in Section 4.5, once HPV Products have been removed from
original containers and/or incorporated into the HPV TMA Test Kits, the
foregoing warranty no longer applies.
	 
	 	8.1.2  	Subject to the provisions and limitations of Section 9.3
below, ROCHE warrants that the execution, delivery and performance of this
Agreement by ROCHE (including the manufacture, use, sale, or offer for sale and
importation of the HPV Products by ROCHE pursuant to this Agreement) will not
violate or breach any agreement to which ROCHE is a party or is otherwise bound
or subject and that the sale of the HPV Products by
ROCHE to GPRO is an authorized sale pursuant to any and all such agreements.




13









 












	 	8.2  	Mutual Warranties. Each party warrants to the other that (i) it is a
validly existing corporation in good standing under its jurisdiction of incorporation
and has all requisite corporate power and authority to enter into this Agreement and
perform its obligations set forth herein, (ii) this Agreement has been duly authorized
by all necessary corporate action of such party, and has been duly executed and
delivered by it, and (iii) there is no action, suit or governmental, administrative,
arbitration or regulatory proceeding pending as of the Effective Date which could
prevent such party from carrying out its obligations under this Agreement.
	 
	 	8.3  	Exclusion and Disclaimer of Other Warranties.
	 
	 	   	THE WARRANTIES SET OUT IN SECTIONS 8.1.1, 8.1.2 and 8.2 ARE IN LIEU OF ALL OTHER
REPRESENTATIONS OR WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING THOSE OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR NON-INFRINGEMENT. ROCHE
DISCLAIMS ANY REPRESENTATION OR WARRANTY, EXPRESS OR IMPLIED, AS TO THE VALIDITY OF
THE ROCHE HPV PATENTS OR AS TO WHETHER THE HPV PRODUCTS OR THE HPV TMA TEST KITS
WILL BE FREE FROM ANY INFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF ANY THIRD
PERSON.
	 
	 	8.4  	Indemnification.






	 	8.4.1  	ROCHE shall indemnify, hold harmless and defend GPRO, its
directors, officers, shareholders, employees, representatives, attorneys,
Affiliates, licensors and agents (each such Person an “GPRO Indemnitee”) from
and against any and all claims, suits and damages asserted by any third Person,
and all related costs, fees and expenses (including reasonable attorneys’ and
experts’ fees and court costs) suffered or incurred by any GPRO Indemnitee
arising out of, resulting from or otherwise concerning any breach of the
warranties provided by ROCHE in Section 8.1.2 and 8.2.
	 
	 	8.4.2  	GPRO shall indemnify, hold harmless and defend ROCHE, its
directors, officers, shareholders, employees, representatives, attorneys,
Affiliates, licensors and agents (each such Person an “ROCHE Indemnitee”) from
and against any and all claims, suits and damages asserted by any third Person,
and all related costs, fees and expenses (including reasonable attorneys’ and
experts’ fees and court costs) suffered or incurred by any ROCHE Indemnitee
arising out of, resulting from or otherwise concerning (i) any breach by GPRO
of its warranties set forth in Section 8.2, or (ii) the HPV TMA Test Kits,
including, without limitation, the manufacture, use or sale of the HPV TMA Test
Kits, except to the extent that any such claim, suit or damages asserted by any
third Person arises out of, results
from or otherwise concerns any breach of the warranties provided by ROCHE in
Section 8.1.2 or 8.2. For the avoidance of doubt, GPRO’s




14









 






	 	   	indemnity
obligations under this Section 8.4.2 shall extend to all claims by any third
Person(s) for infringement of any patent other than those included within
the ROCHE HPV Patents.
	 
	 	8.4.3  	A party indemnifying and holding an Indemnitee harmless under
Section 8.4.1 or Section 8.4.2 above (an “Indemnitor”) shall defend any such
claim or suit asserted by the third Person and shall be entitled to control the
defense and settlement thereof, provided that the Indemnitee may participate in
such defense at its sole cost and expense and, provided, further, that the
Indemnitee shall cooperate fully in such defense (such as by providing
documents and giving testimony, as appropriate) as reasonably requested by the
Indemnitor.






	 	8.5  	Limitation of Liability.
	 
	 	   	NOTWITHSTANDING ANY OTHER PROVISION OF THIS AGREEMENT, IN NO EVENT SHALL ROCHE OR
GPRO BE LIABLE, WHETHER IN CONTRACT, TORT, WARRANTY, INDEMNITY OR UNDER ANY STATUTE
OR ON ANY OTHER BASIS WHATSOEVER FOR SPECIAL, INCIDENTAL, INDIRECT, PUNITIVE,
MULTIPLE OR CONSEQUENTIAL DAMAGES SUSTAINED BY THE OTHER PARTY OR ANY OTHER PERSON
OR ENTITY ARISING OUT OF SUCH PARTY’S RESPECTIVE PERFORMANCE OR FAILURE TO PERFORM
ITS OBLIGATIONS UNDER THIS AGREEMENT INCLUDING THOSE RELATING TO THE MANUFACTURE OR
SALE OF HPV PRODUCTS OR HPV TMA TEST KITS OR THE PERFORMANCE OF SERVICES, OR THE
POSSESSION OR USE OF ANY HPV PRODUCT OR HPV TMA TEST KITS, WHETHER OR NOT
FORESEEABLE AND WHETHER OR NOT ROCHE OR GPRO, AS APPLICABLE, IS ADVISED OF THE
POSSIBILITY OF SUCH DAMAGES, INCLUDING, WITHOUT LIMITATION, DAMAGES ARISING FROM OR
RELATING TO LOSS OF USE, DOWNTIME, OR LOSS OF REVENUE, PROFITS, GOODWILL, OR
BUSINESS OR OTHER FINANCIAL LOSS. NOTHING CONTAINED IN THIS SECTION 8.5 SHALL LIMIT
OR WAIVE A PARTY’S RIGHT TO SEEK SPECIFIC PERFORMANCE OF THIS AGREEMENT OR ANY
REMEDY OTHER THAN SPECIAL, INCIDENTAL, INDIRECT, PUNITIVE, MULTIPLE OR CONSEQUENTIAL
DAMAGES.






	9.  	Term and Termination.






	 	9.1  	Term. This Agreement shall become effective as of the Effective Date
and shall continue in effect until the expiration of the last to expire of the ROCHE
HPV Patents or unless terminated earlier in accordance with the terms and conditions of
this Section 9. Upon any such termination, GPRO will have no further obligation
to purchase the HPV Products from ROCHE and ROCHE will have no further obligation to
manufacture and supply the HPV Products to GPRO.




15









 






	 	9.2  	Termination for Breach. Either party may terminate this Agreement at
any time, in response to a material breach by the other party by giving the other party
notice of such intention to terminate and sixty (60) Days to cure the material breach.
If the other party fails to cure the material breach within such sixty (60) day period,
such party may terminate this Agreement by further written notice of termination to the
other party. Such termination shall not affect any other legal or equitable remedies
for breach which the terminating party may have.
	 
	 	9.3  	Other Termination Rights.






[...***...]




	 	9.4  	Termination in the Event of Bankruptcy. Either party shall have the right to
terminate this Agreement effective immediately upon written notice to the other party
if such other party (i) files in any court or agency pursuant to any bankruptcy or
insolvency law a case or petition in bankruptcy or insolvency or for





***Confidential Treatment Requested




16









 









	 	   	reorganization or
similar arrangement or for the appointment of a receiver or trustee of such party or
its assets, (ii) is served with an involuntary case or petition against it in any
insolvency proceeding, which case or petition has not been stayed or dismissed within
60 days after service upon such party, or (iii) makes an assignment for the benefit of
its creditors.
	 
	 	9.5  	Effect of Termination. Upon the termination of this Agreement, except
with regard to accepted purchase orders which shall remain in full force and effect and
be performed by the parties in accordance with their respective terms and conditions,
the respective obligations of the parties hereunder shall concurrently terminate,
provided however, that the provisions of Sections 6.2, 6.3, 8, 11 and 12 shall survive
and remain in full force and effect in accordance with their terms, conditions and
limitations and all other provisions hereof which would reasonably be expected to
survive termination shall so survive.






	10.  	Alternative Manufacturing Site.






	 	10.1  	Alternative Manufacturing Site. ROCHE may manufacture the HPV Products
at its manufacturing facilities in New Jersey, U.S.A. or in Germany, or at any ROCHE
approved third-Person supplier manufacturing site (each an “Alternative Manufacturing
Site”); provided, however, that GPRO shall not have the right, and ROCHE shall not
grant to GPRO the right, to manufacture the HPV Products on ROCHE’s behalf or
otherwise. ROCHE agrees to qualify one Alternative Manufacturing Site, to be selected
in ROCHE’s sole discretion, as a secondary site for the manufacture of HPV Products for
ROCHE for sale to GPRO hereunder. Upon commencement of manufacturing at any site other
than ROCHE’s manufacturing facilities in New Jersey, U.S.A., the parties shall
reasonably agree upon a reasonable process to establish the equivalency, as determined
by performance testing, of the HPV Products manufactured at such site to the HPV
Products manufactured at the New Jersey facilities.






	11.  	Confidentiality.






	 	11.1  	Confidentiality Obligations. Except as expressly authorized in
writing, neither ROCHE nor GPRO shall disclose to any third Person or use any
Confidential Information of the other party except as reasonably necessary to exercise
its rights and perform its obligations hereunder. Neither ROCHE nor GPRO shall
disclose any Confidential Information of the other party to any third Person that has
not agreed in writing to keep such information confidential. Any reproduction or copy
of Confidential Information shall carry the same proprietary and/or confidential
notices and legends that appear on the original. The parties agree that any breach of
the restrictions contained in this Section 11.1 will cause irreparable
harm to the non-breaching party, entitling such party to injunctive relief in
addition to all other legal remedies.




17









 






	 	11.2  	Exceptions. The recipient of any Confidential Information of the other
party shall be relieved of this obligation of confidentiality and restriction on use to
the extent that: (i) such information was in the public domain at the time it was
disclosed or has become in the public domain through no fault of the recipient; (ii)
the recipient can prove such information was known to it, without restriction, at the
time of disclosure as shown by the files of the recipient in existence at the time of
disclosure; (iii) such information is disclosed by the recipient with the prior written
approval of the other party; (iv) the recipient can prove such information was
independently developed by it without any use of the other party’s Confidential
Information; (v) such information becomes known to the recipient, without restriction,
from a source other than the other party without breach of this Agreement, or (vi) the
recipient is required to disclose such Confidential Information by the rules of a
securities exchange to which a party is subject, applicable law, regulation or order of
a governmental agency or a court of competent jurisdiction, provided that the recipient
shall provide written notice thereof to the other party and sufficient opportunity to
object to any such disclosure or to request confidential treatment thereof.






	12.  	General.






	 	12.1  	Force Majeure. Neither party shall be liable for any failure or delay
in its performance, other than the payment of funds due under this Agreement, due to
causes, including, but not limited to, acts of God, acts of civil or military
authority, fires, epidemics, floods, earthquakes, riots, wars, sabotage, labor
shortages or disputes, governmental actions or any other events, which are beyond its
reasonable control. The delayed party shall: (i) give the other party written notice
of such cause promptly, and in any event within fifteen (15) Days of discovery thereof,
and (ii) use its reasonable efforts to correct such failure or delay in its
performance. The delayed party’s time for performance or cure under this Section shall
be extended for a period equal to the duration of the cause.
	 
	 	12.2  	Relationship of Parties. GPRO is an independent contractor. Neither
GPRO nor GPRO’s employees, consultants, contractors or agents are agents, fiduciaries,
employees or joint venturers of ROCHE, nor do they have any authority to bind ROCHE by
contract or otherwise to any obligation. They will not represent to the contrary,
either expressly, implicitly, by appearance or otherwise.
	 
	 	12.3  	Assignment. Neither GPRO nor ROCHE may assign or transfer (whether by
merger, operation of law or in any other manner) any of its rights or delegate any of
its obligations under this Agreement without the express prior written consent of the
other party; provided that, without limitation of or breaching this Section 12.3: (i) a
party may assign or transfer any of its rights or delegate any of its obligations under
this Agreement, in whole or in part, to any of its Affiliates, without the consent of
the other party, but without relieving the delegating party
from the responsibility for performance of any of such obligations, and (ii) a party
may assign or transfer its rights or delegate its duties and obligations (in whole
and not in part) under this Agreement to any Person which acquires all, or




18









 






	 	   	substantially all, of its assets and/or business, provided that such assignee or
transferee duly and effectively assumes all of the obligations of the assigning or
transferring party hereby by an instrument reasonably satisfactory to the other
party, and provided further, that in the case of GPRO’s assignee or transferee, such
assignee or transferee shall be approved in writing by ROCHE prior to such
assignment or transfer, provided that ROCHE’s approval shall not be unreasonably
withheld. If ROCHE reasonably withholds consent as to any proposed assignee or
transferee, then GPRO may validly effect such assignment or transfer by paying ROCHE
(i) if the proposed assignment or transfer is to occur at anytime prior to
[...***...], the sum of US$[...***...], and (ii) if the proposed assignment or
transfer is to occur at anytime on or after [...***...], the sum of US$[...***...].
Any assignment or transfer in violation of the provisions of this section shall be
void and shall constitute a material breach of this Agreement. Subject to the
foregoing, this Agreement shall be binding upon and shall inure to the benefit of
each party’s respective permitted successors and permitted assigns.
	 
	 	12.4  	Rights of and Performance by Affiliates. To the extent that any term
or provision of this Agreement grants rights to or contemplates, permits or requires
performance by any Affiliate of a party, such Affiliate shall be considered to be an
intended third party beneficiary of this Agreement, and such party shall cause such
Affiliate to perform each and every obligation of such party under this Agreement in
accordance with the terms and conditions hereof.
	 
	 	12.5  	Applicable Law; Arbitration. This Agreement shall be governed by and
construed in accordance with the laws of the State of California, excluding its
conflict of laws principles. Any dispute, controversy or claim by or between ROCHE and
GPRO arising out of or relating to this Agreement or the matters or transactions
contemplated herein shall be settled by binding arbitration in San Francisco,
California if initiated by GPRO and in San Diego, California if initiated by ROCHE,
conducted in accordance with the Commercial Arbitration Rules of the American
Arbitration Association, and judgment on any award rendered in any such arbitration may
be entered in any court having jurisdiction over a party or its property.
	 
	 	12.6  	Severability. If for any reason an arbitration panel finds any
provision of this Agreement, or portion thereof, to be unenforceable, that provision of
the Agreement shall be enforced to the maximum extent permissible so as to effect the
intent of the parties, and the remainder of this Agreement shall continue in full force
and effect.
	 
	 	12.7  	No Waiver. Failure by either party to enforce any provision of this
Agreement shall not be deemed a waiver of future enforcement of that or any other
provision.
	 
	 	12.8  	Complete Agreement. This Agreement, including all attachments and
exhibits, constitutes the entire agreement between the parties with respect to the
subject matter hereof, and supersedes and replaces all prior or contemporaneous





***Confidential Treatment Requested




19









 









	 	   	understandings or agreements, written or oral, regarding such subject matter. No
amendment to or modification of this Agreement shall be binding unless in writing and
signed by a duly authorized representative of both parties.
	 
	 	12.9  	Benefit; No Third Party Beneficiaries. Except as expressly
contemplated herein, this Agreement is entered into solely for the benefit of the
parties hereto, and the provisions of this Agreement will be for the sole and exclusive
benefit of such parties. Except as expressly contemplated herein, nothing herein
contained will be deemed to create any third party beneficiaries or confer any benefit
or rights on or to any third Person, and no third Person will be entitled to enforce
any provisions hereof or exercise any rights hereunder, except as expressly
contemplated herein.
	 
	 	12.10  	Headings; Sections and Exhibits. Headings contained in this Agreement
are for convenience only and will not be used in the interpretation of this Agreement.
References herein to sections, schedules and exhibits are to the sections, schedules
and exhibits, respectively, of this Agreement. The schedules and exhibits are hereby
incorporated herein by reference and made a part of this Agreement. Should any
inconsistency exist or arise between a provision of this Agreement and a provision of
any exhibit, schedule, or other incorporated writing, the provision of this Agreement
will prevail.
	 
	 	12.11  	No Construction Against Drafter. Each party and its counsel have
participated fully in the review and preparation of this Agreement. Any rule of
construction to the effect that ambiguities are to be resolved against the drafting
party will not apply in interpreting this Agreement.
	 
	 	12.12  	Certain Words and Terms. Unless the context clearly requires
otherwise: (i) the plural and singular numbers will each be deemed to include the
other; (ii) “shall”, “will,” “will agree,” or “agrees” are mandatory, and “may” is
permissive; (iii) “or” is not exclusive; and (iv) “includes” and “including” are not
limiting.
	 
	 	12.13  	Counterparts. This Agreement may be executed in any number of
counterparts, and each counterpart will be deemed an original instrument, but all
counterparts together will constitute but one agreement.
	 
	 	12.14  	Notices. All notices, requests, demands, or other communications
under this Agreement will be in writing. Notice will be sufficiently given for all
purposes as follows: (i) when personally delivered to the recipient, notice is
effective on delivery; (ii) when mailed certified mail, return receipt requested,
notice is effective on receipt, if delivery is confirmed by a return receipt; (iii)
when delivered by Federal Express/Airborne/United Parcel Service/DHL WorldWide, or
United States Express Mail, charges prepaid or charged to the sender’s account,
notice is effective on delivery, if delivery is confirmed by the delivery service;
and (iv) when sent by fax to the last fax number of the recipient known to the party
giving notice, notice is effective on receipt, provided that: (a) a duplicate




20









 






	 	   	copy
of the notice is promptly given by first-class or certified mail or by overnight
delivery, or (b) the receiving party delivers a written confirmation of receipt.
Any notice given by fax will be deemed received on the next business day if it is
received after 5:00 p.m. (recipient’s time) or on a non-business day.
	 
	 	12.15  	Notice Refused, Unclaimed, Or Undeliverable. Any correctly addressed
notice that is refused, unclaimed, or undeliverable because of an act or omission of
the party to be notified will be deemed effective as of the first date that said notice
was refused, unclaimed, or deemed undeliverable by the postal authorities, messenger,
or overnight delivery service.
	 
	 	12.16  	Addresses. Addresses for purpose of giving notice are as set forth
immediately below, or such other addresses as may be designated in writing by the
parties from time to time during the term of this Agreement:





	 	 	 	 	 
	

	 	If to ROCHE:
	 	Roche Molecular Systems, Inc.
	

	 	 	 	4300 Hacienda Drive
	

	 	 	 	Pleasanton, CA 94588
	

	 	 	 	FAX No.: (510) 814-2956
	

	 	 	 	Attn.: General Counsel
	 
	 	 	 	 
	

	 	If to GPRO:
	 	Gen-Probe Incorporated
	

	 	 	 	10210 Genetic Center Drive
	

	 	 	 	San Diego, CA 92121
	

	 	 	 	FAX No.: 858-410-8637
	

	 	 	 	Attn.: General Counsel







	 	12.17  	Publicity and Confidentiality of Agreement. Each party and its
Affiliates shall maintain the confidentiality of all provisions of this Agreement and
neither party nor any of its Affiliates shall make any public announcement of or
otherwise disclose to any third Person this Agreement or any of its terms without the
prior written consent of the other party, except that a party may disclose such
information as may have entered into the public domain through no fault of such party
or as required by the rules of a securities exchange to which a party is subject or any
applicable law or regulation based upon the written advice of counsel and then only
with prior notice to the other party as far in advance as reasonably possible and with
reasonable consideration to the advice of the other party as to how such disclosure
could be modified to conform with applicable rules, laws and regulations and still
protect the confidentiality interests of the other party. The parties further agree
that in the event that either party wishes to prepare and publicly disseminate a press
release announcing the product purchase
and supply relationship provided herein, such party shall provide the other party a
written draft of such release at least seven (7) days prior to the intended date of




21









 






	 	   	release, and the other party shall have the right to make reasonable modifications
to such draft press release during such seven (7) day review period.





          IN WITNESS WHEREOF, the parties hereto have duly executed this Agreement to be effective as of
the Effective Date.




	 	 	 	 	 	 	 	 	 
	ROCHE MOLECULAR SYSTEMS, INC.	 	 	 	GEN-PROBE INCORPORATED
	 
	 	 	 	 	 	 	 	 
	By:

	 	/s/ H. Dreismann
	 	 	 	By:
	 	/s/ Henry L. Nordhoff
	

	 	 
	 	 	 	
	 	 
	

	 	H. Dreismann
	 	 	 	
	 	Henry L. Nordhoff
	 
	 	 	 	
	 	 
	Printed Name	 	 	 	
	 
	 	 	 	 	 	 	 	 
	President & CEO	 	 	 	President and Chief Executive Officer
	Title

	 	 	 	 	 	Title	 	 
	 
	 	 	 	 	 	 	 	 
	Date:

	 	2-15-2005
	 	 	 	Date:
	 	2-15-2005
	 
	 	 	 	 	 	 	 	 
	By:

	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 
	Printed Name	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 
	Title
	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	Date:

	 	 	 	 	 	 	 	 






(Signatures Continued on Next Page)




22









 









F. HOFFMANN-LA ROCHE LTD.




	 	 	 	 	 
	By:

	 	/s/ Stephen Arnold
	 	 
	

	 	 
	 	 
	 
	 	 	 	 
	Stephen Arnold	 	 
	 	 	 
	Printed Name	 	 
	 
	 	 	 	 
	Deputy Director	 	 
	 	 	 
	Title
	 	 	 	 
	 
	 	 	 	 
	Date:

	 	Feb
15, 2005
	 	 
	

	 	 
	 	 
	 
	 	 	 	 
	By:

	 	/s/ C. J. Ruetseh
	 	 
	

	 	 
	 	 
	 
	 	 	 	 
	Claus-Joerg Ruetseh	 	 
	 	 	 
	Printed Name	 	 
	 
	 	 	 	 
	Deputy Director	 	 
	 	 	 
	Title
	 	 	 	 
	 
	 	 	 	 
	Date:

	 	Feb
15, 2005
	 	 
	

	 	 
	 	 






23









 






EXHIBIT A




LICENSED ROCHE HPV PATENTS




The following patents and patent applications are included within the scope of the April 1, 1990
Cross License Agreement originally entered into between Life Technologies, Inc. and Institut
Pasteur and are subject to the terms, conditions, restrictions and limitations therein. ROCHE
represents and warrants that, as of the Effective Date, it is the assignee by written agreement to
the rights of Institut Pasteur under the said Cross License Agreement.



     United States Patent Application:



	 	 	 	 	 	 	 
	

	 	Application for [...***...]
	 	[...***...]
	 	Applic     [...***...]
	 
	 	 	 	 	 	 
	Issued United States Patents:	 	 	 	 
	 
	 	 	 	 	 	 
	

	 	Patent for [...***...]
	 	No. [...***...]
	 	Applic     [...***...]
	

	 	 	 	 	 	            

Issued [...***...]
	 
	 	 	 	 	 	 
	

	 	Patent for [...***...]
	 	No. [...***...]
	 	Applic     [...***...]
	

	 	 	 	 	 	            

Issued [...***...]
	 
	 	 	 	 	 	 
	

	 	Patent for [...***...]
	 	No. [...***...]
	 	Applic     [...***...]
	

	 	(formerly [...***...])
	 	 	 	            
Issued [...***...]
	 
	 	 	 	 	 	 
	Other Patent Applications (All Types Except [...***...];[...***...])
	 
	 	 	 	 	 	 
	

	 	[...***...]
	 	No. [...***...]	 	 
	

	 	[...***...]
	 	No. [...***...]	 	 
	

	 	[...***...]
	 	No. [...***...]	 	 






OWNED ROCHE HPV PATENTS




The patents and patent applications listed on Attachment “1” to this Exhibit “A”
were originally owned by Institut Pasteur or co-owned by Institut Pasteur and Centre National de la
Recherche Scientifique (“CNRS”). ROCHE represents and warrants that, as of the Effective Date, it
is the successor-in-interest, by written assignment, to the rights of Institut Pasteur and CNRS
therein.



***Confidential Treatment Requested


 









 










GPRO acknowledges that Roche has informed GPRO that U.S. patent no. 5,981,173 and its foreign
counterparts were acquired by Roche from Institut Pasteur subject to an exclusive license in favor
of Digene Corporation. Until such time as the said exclusive license terminates or expires,
Roche’s rights in this U.S. patent and its foreign counterparts are subject to the terms,
conditions, limitations and restrictions of the said exclusive license.




INTERNALLY DEVELOPED/OWNED 

ROCHE HPV PATENTS




[...***...] – directed to various [...***...] and [...***...]




[...***...] – directed to various [...***...]




[...***...] – directed to various [...***...]




[...***...] – directed to methods of [...***...]




[...***...] – directed to various [...***...]




[...***...] – directed to methods of [...***...] with [...***...] and to [...***...]




Pending ROCHE HPV-Related Patent Applications:




[...***...] – “[...***...]” – directed to [...***...] including [...***...].




***Confidential Treatment Requested





 









 






Attachment 1 to Exhibit A

To Supply and Purchase Agreement




Owned Roche Patents






 









 








DETERMINED [...***...] DERIVED FROM A [...***...], THEIR USES FOR [...***...] AND THE PRODUCTION OF
[...***...]




[...***...]


***Confidential Treatment Requested


 









 








	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	(11	)	 	Publication number: [...***...]
	 
	 	 	 	 	 	 	 	 
	(12)	 	EUROPEAN PATENT SPECIFICATION

	 
	 	 	 	 	 	 	 	 
	(15)

	 	Date of publication of patent specification: [...***...]
	 	 	(51	)	 	Int. Cl5: [...***...],
	

	 	 	 	 	 	 	 	                [...***...]
	 
	 	 	 	 	 	 	 	 
	(21)

	 	Application number: [...***...]	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	(22)

	 	Date of filing: [...***...]	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	 
	 
	 	 	 	 	 	 	 	 
	(54)	 	Determined [...***...] derived from a [...***...], their [...***...] for In [...***...] and the [...***...]of [...***...].






	 	 	 	 	 	 	 	 	 	 
	 	 	 	 
	 	 	 	 	 	 	(73	)	 	Proprietor: [...***...]
	(30)

	 	Priority: [...***...]
	 	 	 	 	 	 	[...***...] Roux
	(43)

	 	Date of publication of application:

[...***...]
	 	 	 	 	 	 	[...***...] (FR)
	(45)

	 	Publication of the grant of the patent:

[...***...]
	 	 	 	(72	)	 	Inventor: [...***...]

[...***...]
	(64)

	 	Designated Contracting States:

[...***...]
	 	 	 	(74	)	 	Representative: [...***...]

[...***...]
	(58)

	 	[...***...]	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	 	 	 	 





	 	 	 
	Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the
European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned
statement. It shall not be deemed to have been filed until the opposition fee has been paid (Art. 99(1) European patent convention).
	 
	 	 
	 






***Confidential Treatment Requested


 









 






[...***...] OF THE [...***...], AND [...***...]THEREOF




[...***...]



***Confidential Treatment Requested



 









 








	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	(11	)	 	Publication No: [...***...]
	

	 	FRENCH REPUBLIC


	 	 	 	 	 	(use only to order

a reproduction)
	 
	 	 	 	 	 	 	 	 
	(19)

	 	NATIONAL INSTITUTE FOR
	 	 	(21	)	 	National file no.: [...***...]
	

	 	PATENT RIGHTS

	 	 	 	 	 	 
	

	 	 	 	 	(51	)	 	Int. Cl.6: [...***...]
	

	 	PARIS	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	(12)	 	PATENT                           
	 	                                                               B1






	 	 	 
	 
	 
	 	 
	(54)	 	 [...***...] FROM THE [...***...] APPLICATION OF THESE SEQUENCES FOR THE
[...***...] BY THE [...***...] AND FOR THE PRODUCTION OF [...***...].





	 	 	 	 	 	 	 	 	 	 
	 	 	 	 
	 
	 	 	 	 	 	(60	)	 	References to other
related national documents:
	(22)

	 	Filing date: [...***...].
	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:
	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...].
	 	 	 	(72	)	 	Inventor(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(45)

	 	Publication date of the patent:
	 	 	 	(73	)	 	Owner(s):
	

	 	[...***...].	 	 	 	 	 	 	 
	 
	 	 	 	 	 	(74	)	 	Agent(s): [...***...]
	(56)

	 	List of documents cited in the search report:
	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of this publication

	 	 	 	 	 	 	 
	 	 	 	 






***Confidential Treatment Requested


 









 






[...***...] AND [...***...] FOR THE [...***...] OF [...***...].




[...***...]




***Confidential Treatment Requested


 









 








	 	 	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	 	 	(11) Publication number: [...***...]	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	(12)	 	EUROPEAN PATENT SPECIFICATION

	 
	 	 	 	 	 	 	 	 	 	 
	(45)

	 	Publication date of the paten specification: [...***...]
	 	 	(51	)	 	 Int. Cl5: [...***...]	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	(31)

	 	File number: [...***...]	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	(33)

	 	Filing date: [...***...]	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] with and method of [...***...] diagnosis of [...***...]	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 





	 	 	 	 	 	 	 	 	 	 
	 	 	 	 
	(30)

	 	Priority: [...***...]

	 	 	 	(72	)	 	Owner: INSTITUTE PASTEUR
	

	 	 	 	 	 	 	 	 	[...***...]

	(43)

	 	Publication date of the application:	 	 	 	 	 	 	 
	

	 	[...***...]
	 	 	 	 	 	 	Owner: [...***...]
	

	 	 	 	 	 	 	 	 	[...***...]


	(45)

	 	Notice of the patent grant:

[...***...] 

	 	 	 	(73	)	 	Inventor: [...***...]

[...***...]


	(54)

	 	Designated contracting states:

[...***...]

	 	 	 	 	 	 	F-75013 Paris (FR)

Inventor: [...***...]
	

	 	 	 	 	 	 	 	 	[...***...]
	(56)

	 	Documents cited:
	 	 	 	 	 	 	Inventor[...***...]
	

	 	[...***...]
	 	 	 	 	 	 	[...***...]
	

	 	 	 	 	 	 	 	 	Inventor: [...***...]
	

	 	 	 	 	 	 	 	 	[...***...] 


	

	 	 	 	 	 	(74	)	 	Agent: [...***...]
	

	 	 	 	 	 	 	 	 	[...***...]


	 	 	 	 





	 	 	 
	Note: Within nine months from the publication of the mention of the grant of the
European patent, any person may give notice to the European Patent Office of
opposition to the European patent granted. Notice of opposition shall be filed in
a written reasoned statement. It shall not be deemed to have been filed until the
opposition fee has been paid (Art. 99(1) European patent convention).
	 
	 	 
	 





***Confidential Treatment Requested


 









 






[...***...]FOR [...***...]CONTAINING AT LEAST [...***...] OF THE [...***...] PARTICULARLY OF THE
[...***...]AND [...***...]




[...***...]



***Confidential Treatment Requested



 









 








	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	(11	)	 	Publication No:                [...***...]
	

	 	FRENCH REPUBLIC


	 	 	 	 	 	(use only to order

a reproduction)
	 
	 	 	 	 	 	 	 	 
	

	 	NATIONAL INSTITUTE FOR
	 	 	(21	)	 	National file no.:                [...***...]
	

	 	PATENT RIGHTS 

	 	 	 	 	 	 
	

	 	 	 	 	(51	)	 	Int. Cl.3:
[...***...].
	

	 	PARIS	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	CERTIFIED
COPY

	 	 	 	 	 	 
	Paragraph 3a of article 57 of the decree 79 822 of 9/9/1979


	(12)	 	PATENT
	 	 	 	 	 	                                                                        B1






	 	 	 
	 
	 
	 	 
	(54) [...***...] that code for [...***...] containing [...***...] one [...***...] of the [...***...], in particular of type [...***...] and the [...***...].





	 	 	 	 	 	 	 	 	 	 
	 	 	 	 
	

	 	 	 	 	 	(60	)	 	References to other related national documents:
	[...***.

	 	..] April 5, 1982	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:
	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

	 	 	 	(72	)	 	Inventor(s): [...***...]
	 
	 	[...***...].	 	 	 	 	 	 	 
	


	 	 	 	 	 	(73	)	 	Owner(s):
	 
	 	 	 	 	 	 	 	 	 
	


	 	 	 	 	 	(74	)	 	Agent(s): [...***...]
	(45)

	 	Publication date of the patent: 	 	 	 	 	 	 	 
	 
	 	[...***...]

	 	 	 	 	 	 	 
	[...***...] List of documents cited in the search report:	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of this publication	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested


 









 






[...***...] AND [...***...] FOR THE [...***...]OF [...***...]


[...***...]




***Confidential Treatment Requested





 









 








	 	 	 	 	 	 	 	 	 
	FRENCH REPUBLIC




	 	 	(11	)	 	Publication Number :

(use only to order
a reproduction)
	 	[...***...]
	NATIONAL INSTITUTE FOR

PATENT RIGHTS

	 	 	(21	)	 	National file no.:

	 	[...***...]
	

PARIS

	 	 	(51	)	 	Int. Cl.4: [...***...].	 	 






CERTIFIED COPY

Paragraph 3a of article 57 of the decree 79 822 of 9/9/1979



	 	 	 	 	 
	(12)

	 	PATENT
	 	B1






	 	 	 
	   





	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] and [...***...] of [...***...].
	 
	 	 	 	 
	

	 	 	 	 	 	(60	)	 	References to other related national documents:
	(22)

	 	Filing date: [...***...]	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:
	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	72	)	 	Inventor(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...].
	 	 	 	(73	)	 	Owner(s):
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(74	)	 	Agent(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(45)

	 	Publication date of the patent:

[...***...]	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(56)

	 	List of documents cited in the search report:	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of
this publication

	 	 	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested




 









 








	 	 	 	 	 	 	 	 	 
	FRENCH REPUBLIC




	 	 	(11	)	 	Publication Number :

(use only to order
a reproduction)
	 	[...***...]
	NATIONAL INSTITUTE FOR

PATENT RIGHTS

	 	 	
(21	
)	 	
National file no.:

	 	
[...***...]
	

PARIS

	 	 	
(51	
)	 	
Int. Cl.4: [...***...].	 	 






CERTIFIED COPY

Paragraph 3a of article 57 of the decree 79 822 of 9/9/1979



	 	 	 	 	 
	(12)

	 	CERTIFICATE OF ADDITION

TO A PATENT
	 	B2






	 	 	 
	   





	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] and method of [...***...] of [...***...].
	 
	 	 	 	 
	

	 	 	 	 	 	(60	)	 	References to other related national documents: [...***...]
	(22)

	 	Filing date: [...***...].	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:	 	 	 	 	 	 	 
	

	 	 	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...].
	 	 	 	72	)	 	Inventor(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(73	)	 	Owner(s):
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(74	)	 	Agent(s): [...***...]
	(45)

	 	Publication date of the patent:

[...***...].	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(56)

	 	List of documents cited in the search report:	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of
this publication

	 	 	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested





 









 








[...***...]AND [...***...] OF THE[...***...],[...***...]OF [...***...]AND [...***...]IN WHICH THEY ARE USED.


[...***...]




***Confidential Treatment Requested




 









 








(11) Publication number: [...***...]




	 	 	 
	(12)

	 	EUROPEAN PATENT SPECIFICATION






	 	 	 	 	 
	(45)

	 	Publication date of the paten specification:

[...***...]
	 	(51) Int. Cl.5: [...***...]
	 
	 	 	 	 
	(31)

	 	File number: [...***...]	 	 
	 
	 	 	 	 
	(33)

	 	Filing date: [...***...]	 	 
	 
	 	 	 	 
	(86)

	 	International file number: [...***...]	 	 
	 
	 	 	 	 
	(87)

	 	International publication number:

[...***...]	 	 






	 	 	 
	   





	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] AND [...***...] THAT ARE [...***...] OF THE [...***...],[...***...] AND [...***...].
	 
	 	 	 	 
	

	 	 	 	 	 	(56	)	 	Documents cited:
	(30)

	 	Priority: [...***...]
	 	 	 	 	 	 	[...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...]
	 	 	 	(73	)	 	Owner: [...***...]

[...***...]
	 
	 	 	 	 	 	 	 	 	 
	(45)

	 	Date of notice of the patent grant:

[...***...]
	 	 	 	(72	)	 	Inventor: [...***...]

[...***...]
	 
	 	 	 	 	 	 	 	 	 
	(54)

	 	Designated contracting states:

[...***...]
	 	 	 	(74	)	 	Agent: [...***...]

[...***...]
	 
	 	 	 	 	 	 	 	 	 
	(56)

	 	Documents cited:	 	 	 	 	 	 	 
	

	 	[...***...]	 	 	 	 	 	 	 
	

	 	[...***...]	 	 	 	 	 	 	 
	

	 	[...***...]	 	 	 	 	 	 	 
	

	 	[...***...], summary in entirety, p. 1323, lines 6-	 	 	 	 	 	 	 
	

	 	17

	 	 	 	 	 	 	 
	 	 	 	 
	 
	Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the
European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned
statement. It shall not be deemed to have been filed until the opposition fee has been paid (Art. 99(1) European patent convention).
	 	 	 	 





***Confidential Treatment Requested






 









 








[...***...],[...***...] AND [...***...]TO THIS [...***...]AND [...***...] FOR THE [...***...]OF [...***...]AND FOR THE
[...***...]OF [...***...]THESE [...***...].




[...***...]




***Confidential Treatment Requested





 









 








	 	 	 	 	 	 	 	 	 
	FRENCH REPUBLIC




	 	 	(11	)	 	Publication No :

(use only to order
a reproduction)
	 	[...***...]
	 
	 	 	 	 	 	 	 	 
	(19)  NATIONAL INSTITUTE FOR
PATENT RIGHTS

	 	 	(21	)	 	 National file no.:

	 	[...***...]
	

	 	 	 	 	 	 	 	 
	

	 	 	(51	)	 	 Int. Cl.4: [...***...]	 	 
	PARIS



	 	 	 	 	 	 	 	 






	 	 	 	 	 
	(12)

	 	PATENT
	 	B1






	 	 	 
	   





	 	 	 	 	 	 	 	 
	(54)	 	[...***...] FOR [...***...] AND PRODUCTS THAT ARE [...***...] RELATED TO THESE [...***...],[...***...],[...***...],[...***...] AND METHOD OF [...***...] OF [...***...] AND IN VIVO [...***...]
	 
	 	 	 	 
	 
	 	 	 	 	 	 	 
	(22)

	 	Filing date: [...***...].
	 	 	 	 	(60) References to other related national documents:
	 
	 	 	 	 	 	 	 
	(30)

	 	Priority:	 	 	 	 	 
	

	 	 	 	 	 	 	(71) Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...]
	 	 	 	 	(72) Inventor(s): [...***...]
	 
	 	 	 	 	 	 	 
	

	 	 	 	 	 	 	(73) Owner(s):
	 
	 	 	 	 	 	 	 
	

	 	 	 	 	 	 	(74) Agent(s): [...***...]
	 
	 	 	 	 	 	 	 
	(45)

	 	Publication date of the patent:

[...***...]	 	 	 	 	 
	 
	 	 	 	 	 	 	 
	(56)

	 	List of documents cited in the search report:	 	 	 	 	 
	 
	 	 	 	 	 	 	 
	Refer to the end of
this publication

	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested





 









 








	 	 	 	 	 	 	 	 	 
	FRENCH REPUBLIC




	 	 	(11	)	 	Publication Number:

(use only to order
a reproduction)
	 	[...***...]
	 
	 	 	 	 	 	 	 	 
	(19)  NATIONAL INSTITUTE FOR
PATENT RIGHTS

	 	 	(21	)	 	 National file no.:

	 	[...***...]
	

	 	 	 	 	 	 	 	 
	

	 	 	(51	)	 	 Int. Cl.6: [...***...]	 	 
	PARIS
	 	 	 	 	 	 	 	 






	 	 	 	 	 
	(12)

	 	CERTIFICATE OF ADDITION 

TO A PATENT
	 	B1






	 	 	 
	   





	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] FOR [...***...] PRODUCTS THAT ARE [...***...] RELATED TO THESE [...***...] METHOD OF [...***...] OF [...***...] AND [...***...]
	 
	 	 	 	 
	

	 	 	 	 	 	(60	)	 	References to other related national documents: [...***...]
	(22)

	 	Filing date: [...***...]	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:	 	 	 	 	 	 	 
	

	 	 	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...]
	 	 	 	72	)	 	Inventor(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(73	)	 	Owner(s):
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(74	)	 	Agent(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(45)

	 	Publication date of the patent:

[...***...].	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(56)

	 	List of documents cited in the search report:	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of
this publication

	 	 	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested





 









 








[...***...], THEIR [...***...]TO [...***...] AND [...***...]OF [...***...].


[...***...]



***Confidential Treatment Requested





 









 








	 	 	 	 	 	 	 	 	 
	FRENCH REPUBLIC




	 	 	(11	)	 	Publication No:

(use only to order
a reproduction)
	 	[...***...]
	 
	 	 	 	 	 	 	 	 
	(19)  NATIONAL INSTITUTE FOR
PATENT RIGHTS

	 	 	(21	)	 	 National file no.:

	 	[...***...]
	

	 	 	 	 	 	 	 	 
	

	 	 	(51	)	 	 Int. Cl.6: [...***...]	 	 
	PARIS



	 	 	 	 	 	 	 	 






	 	 	 	 	 
	(12)



	 	PATENT


	 	B1


	   






	 	 	 	 	 	 	 	 	 	 
	(54)	 	[...***...] FROM THE [...***...] FOR [...***...] OF [...***...] BY THIS [...***...]
	 
	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(22)

	 	Filing date: [...***...]
	 	 	 	(60	)	 	References to other related national documents:
	 
	 	 	 	 	 	 	 	 	 
	(30)

	 	Priority:	 	 	 	 	 	 	 
	

	 	 	 	 	 	(71	)	 	Applicant(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(43)

	 	Publication date of the application:

[...***...]
	 	 	 	(72	)	 	Inventor(s): [...***...]
	

	 	 	 	 	 	(73	)	 	 Owner(s):
	 
	 	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	(74	)	 	 Agent(s): [...***...]
	 
	 	 	 	 	 	 	 	 	 
	(45)

	 	Publication date of the patent:

[...***...]	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	(56)

	 	List of documents cited in the search report:	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 
	Refer to the end of
this publication

	 	 	 	 	 	 	 
	 	 	 	 





***Confidential Treatment Requested





 









 








	 	 	 	 	 	 	 
	United States Patent [19]

	 	[11]
	 	Patent Number:
	 	          [...***...]
	Orth et al.

	 	[45]
	 	Date of Patent:
	 	[...***...]
	 





	 	 	 	 	 	 	 	 	 
	[54]

	 	[...***...],[...***...]TO THE
[...***...]
	 	[56]
	 	 	 	Refernces Cited
	

	 	 	 	 	 	 	 	 
	[75]

	 	Inventors: [...***...]
	 	 	 	[...***...]	 	PUBLICATIONS
	

	 	 	 	 	 	[...***...]	 	 
	[73]

	 	Assignees: [...***...]
	 	 	 	[...***...]	 	 
	 
	 	 	 	 	 	 	 	 
	[21]

	 	Appl. No.: [...***...]
	 	[57]
	 	 	 	ABSTRACT
	 
	 	 	 	 	 	 	 	 
	

	 	 	 	 	 	[...***...]	 	 
	[22]

	 	Filed: [...***...]	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	

	 	Related U.S. Application Data	 	 	 	 	 	 
	[60]

	 	[...***...]; and

[...***...]	 	 	 	 	 	 
	[51]

	 	Int.
Cl.6
.............................................................[...***...]		 	 	 	 	 
	[52]

	 	U.S. Cl............	 	 	 	 	 	 
	[58]

	 	Field of Search.............	 	 	 	 	 	 
	

	 	 	 	 	 	 	 	[...***...]






***Confidential Treatment Requested





 









 






EXHIBIT B-1




Product Specification, Analytical Method Transfer and GMP Manufacture of HPV Reagent Products.





	   	The product specifications detailed in this Exhibit (as of the Effective Date) are
general in nature. During the period when ROCHE is supplying Notebook and Draft Production
lots of HPV Reagent Products, specifications for the HPV Products will become more detailed.
The Parties will from time to time amend this Exhibit to reflect the more detailed product
specification.
	 
	1.  	Overview
	 
	   	This purchase and supply arrangement will consist of two phases:






	 	(a)  	Technology Transfer
	 
	 	(b)  	Manufacture and Supply of HPV Reagent Products






	   	Prior to initiation of manufacture of the first Notebook lot, GPRO and ROCHE will meet to
review the manufacturing plan and the analytical methods to be employed. Thereafter and
throughout the period when ROCHE is supplying and delivering the HPV Reagent Products for
non-commercial use, GPRO and ROCHE will meet regularly as reasonably needed to review
timelines, manufacturing processes, QC methods and product specifications.
	 
	2.  	GPRO’s HPV Reagent Products Requirements
	 
	   	Total Number of Oligonucleotides per Individual HPV Test Quantity: Approx [...***...]
different oligonucleotides:





	 	 	 
	Oligonucleotide Classification:
	 	 
	

	 	Group 1 – oligonucleotides containing up to [...***...]
	

	 	Group 2 – oligonucleotides containing up to [...***...]
	

	 	Group 3 – oligonucleotides containing up to [...***...]
	

	 	Group 4 – oligonucleotides containing up to [...***...]
	 
	 	 
	General Specifications:

	 	All phosphodiester, DNA, some oligos require [...***...]
	 
	 	 
	Amounts of Oligonucleotide

	 	Group 1 – Approx [...***...] per lot of [...***...] tests
	 
	 	 
	

	 	Group 2 – Approx [...***...] per lot of [...***...] tests
	 
	 	 
	

	 	Group 3 – Approx [...***...] for lots up to [...***...] tests
	 
	 	 
	

	 	Group 4 – Approx [...***...] per lot of [...***...] tests






*** Confidential Treatment Requested




 









 









	   	Oligonucleotide Sequences: The specific sequences for each of the oligonucleotides for
the HPV Reagent Products to be included in the HPV TMA Test Kits for use with TMA will be
transferred to ROCHE during technology transfer.
	 
	3.  	Technology Transfer
	 
	   	The Technology Transfer phase may require site visits by personnel to ROCHE.
Topics to be covered could include but are not limited to raw material vendor specific
requirements, synthesis method development, purity methods, and analytical methods.
Completion of technology transfer is estimated at 6-8 weeks.
	 
	   	The following table lists the proposed analytical methods to be transferred to ROCHE for use
in release testing of GMP material, as well as the approximate quantity of material required
to perform these release tests. The analytical methods included in the following table have
or will be validated by GPRO. For Notebook and Draft Production Lots, sequencing of the
oligonucleotides for identification will be required.





	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 	Sample Volume	 
	 	 	 	 	Analytical	 	 	Method Transfer	 	 	required for	 
	 	Parameter	 	 	Method	 	 	Required	 	 	Analytical Test	 
	 	Purity

	 	 	HPLC
	 	 	ü	 	 	 	 
	 	Concentration

	 	 	UV
	 	 	ü
	 	 	TBD	 
	 	Molecular Weight

	 	 	MALDI-Tof
	 	 	ü	 	 	 	 
	 






	4.  	GMP Manufacture
	 
	   	ROCHE will provide GMP manufactured HPV Reagent Products (termed “Notebook ”, “Draft
Production” and “Production” lots) made to the agreed upon specifications and batch sizes,
using the process description as provided by ROCHE and approved by GPRO. (Notebook lots may
not include all required GMP documentation.) During Notebook Lot manufacturing, it is
expected that ROCHE will concurrently develop GMP compliant systems and processes for the
manufacturing of Production Lot oligonucleotides. GPRO may initiate ordering of Draft
Production or Production Lot materials prior to the conclusion of Notebook Lot production.
Subject to Section 4.2 of the Agreement, GPRO will allow a maximum of 120 calendar days from
the time of order placement to receipt of Draft Production or Production Lot material.
	 
	   	If and to the extent that GPRO specifies or provides to ROCHE any method for oligonucleotide
synthesis and/or oligonucleotide purification processes, GPRO shall provide to ROCHE any
existing validation or verification of such methods. If and to the extent that ROCHE uses
ROCHE’s methods for oligonucleotide synthesis and/or oligonucleotide purification processes,
ROCHE will provide a validation or verification plan for the oligonucleotide synthesis and
oligonucleotide purification processes before initiating the manufacture of the first
Notebook lot. These ROCHE validation and/or verification plans must be agreed upon by GPRO
and ROCHE. HPV Reagent Products manufactured by ROCHE shall be delivered in accordance with
the terms and conditions of the Agreement and, unless GPRO requests deferral of delivery
pursuant to Section 4.4 of the Agreement, shall be delivered no more than four (4) months
following the date of manufacture.
	 
	5.  	Packaging and Delivery




 









 






	   	The packaging method will be by [...***...] aliquots in [...***...] (Fisher [...***...]).
The HPV oligonucleotides will be diluted in PCR Grade water. The use of PCR grade water as
diluent is subject to GPRO review of ROCHE’s water systems to be completed during the
technology transfer process and prior to the initiation of the manufacture of the first
Notebook Lot. Product must be labeled with applicable patent markings pursuant to Section
7.2 of the Agreement, oligonucleotide description, part number, batch number, manufacturing
date, purity and concentration. Product must be stored at -[...***...] prior to delivery.
Product will be delivered over night on dry ice. Product must be delivered to GPRO in a
frozen state.
	 
	6.  	Product Contact Surfaces:
	 
	   	GPRO requires all final oligonucleotide contact surfaces to be single-use to prevent
any contamination. Examples of final oligonucleotide contact surfaces include but are not
limited to laboratory glassware, purification columns, tubing, and diafiltration cassettes.
GPRO reserves the right to designate such contact surfaces. GPRO will require a designated
freezer for the storage of completed HPV Reagent Products.
	 
	7.  	Specifications
	 
	   	The following table outlines preliminary analytical tests and specifications that will
be used for testing Notebook Lots of HPV Reagent Products. Specifications are set for each
of the 4 different oligonucleotide groups. This testing will be conducted on Notebook lots
for information purposes only. Also, a joint study will be conducted by ROCHE and GPRO on
initial Notebook lots to determine the equivalency of the purity levels of the
oligonucleotides as measured by ROCHE’s QC methods compared with the purity levels as
measured by GPRO’s QC methods.
	 
	   	Final sequence and purity specifications will be set for each type of oligonucleotide
manufactured in the Production lots. These final specifications will be based on
information collected from Notebook and Draft Production manufacturing lots for each type of
oligonucleotide.





	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 	Oligonucleoti	 	 	GPRO Target	 	 	 	 	 	Concentration	 
	 	de Group 	 	 	Purity*	 	 	Mass Specification**	 	 	Specification***	 
	 	Group 1

	 	 	3  [...***...]%
	 	 	+/- 0.1%
theoretical mass
g/M
	 	 	ROCHE QC value
within
[...***...]
% of ROCHE Mfg
Value	 
	 	Group 2

	 	 	3  [...***...]%
	 	 	+/- 0.1%
theoretical mass
g/M
	 	 	ROCHE QC value
within
[...***...]
% of ROCHE Mfg
Value	 
	 	Group 3

	 	 	3  [...***...]%
	 	 	+/- 0.1% theoretical
mass g/M
	 	 	ROCHE QC value within
[...***...] % of ROCHE Mfg Value	 
	 





*** Confidential Treatment Requested


 









 






	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 	Oligonucleoti	 	 	GPRO Target	 	 	 	 	 	Concentration	 
	 	de Group 	 	 	Purity*	 	 	Mass Specification**	 	 	Specification***	 
	 	Group 4

	 	 	3  [...***...]%
	 	 	+/- 0.1%
theoretical mass
g/M
	 	 	ROCHE QC value
within
[...***...]
% of ROCHE Mfg
Value	 
	 











	*	 	Purity as determined by GPRO using GPRO’s standard QC testing methods for
oligonucleotides including ion exchange and HPLC
	 
	**	 	Mass Specification determined by Maldi-Tof.






	***  	ROCHE’s QC determined value for the concentration of each HPV oligonucleotide (as
determined by UV measurement in OD units/mL) must be within [...***...]% of ROCHE’s
manufacturing target value.
	 
	8.  	GMP Documentation
	 
	   	In order to ensure compliance with current GMP, and any other applicable regulatory
requirements or guidelines, compliant documentation from batch records, analytical methods,
final release testing, etc. will be generated specifically for HPV Reagent Products. GMP
documentation, including batch records, will be available for GPRO review.
	 
	9.  	Quality Assurance
	 
	   	A Certificate of Analysis (C of A) and Material Safety Data Sheet (MSDS) will be
provided for all HPV Reagent Products delivered. The Certificate of Analysis will contain
applicable patent markings pursuant to Section 7.2 of the Agreement, the oligonucleotide
description, including lot type, part number, batch number, manufacturing date, purity,
concentration, manufacturing location and storage condition. Upon the request by ROCHE,
GPRO will more specifically describe the content and form it requests for the C of A and
MSDS.





*** Confidential Treatment Requested




 









 





EXHIBIT B-2




Product Specification, Analytical Method Transfer and GMP Manufacture of HPV RNA 
Transcript and HPV
DNA Products





	   	The product specifications detailed in this Exhibit (as of the Effective Date) are
general in nature. The Parties will, from time to time, amend this Exhibit to reflect a more
detailed product specification.
	 
	1.  	Overview
	 
	   	This purchase and supply arrangement will consist of 2 phases:






	 	•  	Technology Transfer
	 
	 	•  	Manufacture and Supply of HPV Transcript Products






	2.  	RNA Transcript AND HPV DNA Description
	 
	   	ROCHE will supply GPRO HPV Transcript Products for the following HPV types:
[...***...] . In the event GPRO needs HPV Transcript Products for additional HPV
types, ROCHE will reasonably consider making such HPV Transcript Products for GPRO.
	 
	   	The transcripts will include the [...***...] and [...***...] genes and a [...***...] of the
[...***...] gene.
GPRO will supply ROCHE with the specific transcript sequences during the technology transfer
phase.
	 
	   	In the event that Gen-Probe develops a HPV TMA Test kit directed at HPV viral DNA then ROCHE
agrees to provide Gen-Probe with certain HPV DNA or fragments cloned into a suitable vector,
in lieu of HPV RNA Transcripts. Such HPV DNA should be purified from the expression vector
and be free of contaminating nucleases that could interfere with assay performance.
	 
	3.  	Technology Transfer
	 
	   	The following table lists the proposed analytical methods to be transferred to ROCHE
for use in release testing of HPV RNA Transcript and HPV DNA Products, as well as the
approximate quantity of material required to perform these release tests. The analytical
methods included in the following table have or will be validated by GPRO. Completion of
technology transfer is estimated at 6-8 weeks.





	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	Analytical	 	 	Method Transfer	 	 	Approx. Sample
Quantity required for	 
	 	Parameter	 	 	Method	 	 	Required	 	 	Analytical Test	 
	 	HPV RNA Transcripts

	 	 	 	 	 	o	 	 	 	 
	 	Gel photo

	 	 	Digital Image or

Polaroid
	 	 	ü
	 	 	4 tubes @ 5 ug / tube	 
	 




*** Confidential Treatment Requested



 









 






	 	 	 	 	 	 	 	 	 	 	 	 
	 
	 	 	 	 	Analytical	 	 	Method Transfer	 	 	Approx. Sample 
Quantity required for	 
	 	Parameter	 	 	Method	 	 	Required	 	 	Analytical Test	 
	 	Molecular Weight

	 	 	RNA Ladder Bands
	 	 	ü	 	 	 	 
	 	Purity

	 	 	PAGE

(Polyacrylamide

agarose Gel

Electrophoresis)
	 	 	ü	 	 	 	 
	 	Sequence

	 	 	RNA Sequencing
	 	 	ü	 	 	 	 
	 	HPV
DNA

	 	 	 	 	 	o	 	 	 	 
	 	Gel Photo

	 	 	Digital image or

Polaroid
	 	 	o	 	 	 	 
	 	Purity

	 	 	PAGE
	 	 	o	 	 	 	 
	 	Sequence

	 	 	DNA Sequencing
	 	 	o	 	 	 	 
	 






	   	Quantity required for analytical testing is subject to change
	 
	4.  	Manufacturing of HPV RNA Transcript and HPV DNA Products
	 
	   	The HPV RNA Transcript Products should be manufactured under GMP using the Ambion
Megascript T7 kit for transcription and termination followed by the Qiagen Rnaeasy Mini Kit
(or Ambion Megaclear kit) for purification. The yield from each lot of HPV Transcript
Product must be greater than [...***...] of transcript.
	 
	   	HPV RNA Transcript and HPV DNA Products manufactured by ROCHE shall be delivered in
accordance with the terms and conditions of the Agreement and, unless GPRO requests deferral
of delivery pursuant to Section 4.4 of the Agreement, shall be delivered no more than four
(4) months following the date of manufacture.
	 
	5.  	Packaging and Delivery
	 
	   	The packaging method will be in 0.5 ml aliquots in microcentrifuge tubes at a
concentration of 5 ug/mL. Transcripts will be diluted in Rnase free water. Product must
be labeled with applicable patent markings pursuant to Section 7.2 of the Agreement,
transcript description, part number, batch number, manufacturing date, purity and
concentration. Product must be stored at < [...***...] prior to delivery.
Product will be delivered over night on dry ice. Product must be delivered to GPRO in a
frozen state.
	 
	6.  	Specifications
	 
	   	Product specifications for transcripts and DNA will be [...***...]% agreement with
master sequence in areas specified by GPRO and fulfillment of order quantity.
	 
	   	QC analytical methods to be performed for product release will include the following
methods:






	 	•  	Photographic image of the PAGE gel for purposes including,






     o Molecular Weight by PAGE



*** Confidential Treatment Requested





 









 









	 	o  	Purity > [...***...]% by PAGE






	 	•  	Sequencing ([...***...]% agreement)






	7.  	GMP Documentation
	 
	   	In order to ensure compliance with current GMP, and any other applicable regulatory
requirements or guidelines, compliant documentation from batch records, analytical methods,
final release testing, etc. will be generated specifically for the HPV RNA Transcript and
HPV DNA Products. GMP documentation, including batch records, will be available for GPRO
review.
	 
	8.  	Quality Assurance
	 
	   	A Certificate of Analysis (C of A) and Material Safety Data Sheet (MSDS) will be
provided for all HPV RNA Transcript and HPV DNA Products delivered. The Certificate of
Analysis will contain the applicable patent markings pursuant to Section 7.2 of the
Agreement, ribonucleotide description, part number, batch number, manufacturing date,
purity, concentration, manufacturing location and storage condition. Upon the request of
ROCHE, GPRO will more specifically describe the contents and form it requests for the C of A
and MSDS.




*** Confidential Treatment Requested


 









 






EXHIBIT C




TRANSFER FEES FOR HPV REAGENT PRODUCTS FOR

NON-COMMERCIAL AND CLINICAL TRIAL USE




     The Transfer Fee and order size for GPRO’s purchase of HPV Reagent Products for Non-Commercial
Use and Clinical Trial Use shall be as follows:



	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	Price Per	 
	 	 	 	 	Overall Lot	 	 	Constituent	 	 	Individual HPV	 
	 	Manufacturing Process Designation	 	 	Size	 	 	Batch Sizes	 	 	Test Quantity	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	Notebook Lots

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$[...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	Draft Production Lots

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$[...***...]	 
	 	and Production Lots

	 	 	 	 	 	[...***...]	 	 	 	 
	 	

	 	 	 	 	 	[...***...] x	 	 	 	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$[...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	

	 	 	 	 	 	[...***...] x	 	 	 	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$ [...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$ [...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$[...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$ [...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 
	 	     “      “

	 	 	[...***...]
	 	 	[...***...] x
	 	 	$ [...***...]	 
	 	

	 	 	 	 	 	[...***...]	 	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 





“Notebook Lots” means HPV Reagent Product lots manufactured pursuant to and in accordance with
ROCHE’s Notebook Lot documentation practices for oligonucleotides intended for use solely in
product development. The specifications for process and product, identity and purity tests for
such HPV Reagent Product lots will be preliminary and subject to modification. Neither official
Quality Control testing by ROCHE nor Quality Assurance release by ROCHE will be required for
Notebook Lots. Certificate of Analysis indicating purity and identity is required.



“Draft Production Lots” means HPV Reagent Product lots manufactured pursuant to and in accordance
with ROCHE’s Draft Production Lot documentation practices. The specifications for process and
product, identity and purity tests for such HPV Reagent Product lots will be


***Confidential Treatment Requested


26









 












preliminary and subject to modification. Manufacturing may be performed with generic batch record
where redlining of manufacturing documents by the operator are acceptable. Neither official
Quality Control testing by ROCHE nor Quality Assurance release by ROCHE will be required for Draft
Production Lots. Certificate of Analysis indicating purity and identity is required.



“Production Lots” means HPV Reagent Product lots manufactured pursuant to and in accordance with
ROCHE’s GMP Production documentation practices, with full GMP manufacturing and testing with final
process and product specifications. Official Quality Control testing and Quality Assurance release
are required. All manufacturing processes and all test methods are validated and / or verified.




27