EXHIBIT 10.56
[CONFIDENTIAL TREATMENT REQUESTED]
[Certain confidential information has been omitted from the Agreement and filed
separately with the Securities and Exchange Commission pursuant to a request by
Registrant for confidential treatment pursuant to Rule 24b-2. The omitted
confidential information has been identified by the following statement:
"CONFIDENTIAL TREATMENT REQUESTED".]
AMENDED AND RESTATED LICENSE AGREEMENT
This AMENDED AND RESTATED LICENSE AGREEMENT effective as of April 1, 1996
(this "Agreement") between CIBA CORNING DIAGNOSTICS CORP., a corporation
organized under the laws of the State of Delaware, U.S.A., that intends to
change its name to Chiron Diagnostics Corp. effective on or about November 1,
1996 (hereinafter "Chiron") and BIOANALYSIS LIMITED, a corporation organized
under the laws of the United Kingdom of Great Britain and Northern Ireland
(hereinafter "Bioanalysis").
WHEREAS, Chiron (as assignee of Corning Glass Works) and Bioanalysis are
parties to an agreement dated as of December 6, 1984 (the "Original Agreement")
relating to the sublicense to Chiron by Bioanalysis of certain technology
licensed by Bioanalysis from the University of Wales College of Medicine
(formerly known as the Welsh National School of Medicine and hereinafter
referred to as "UWCM"); and
WHEREAS, certain disputes have arisen between Chiron and Bioanalysis under
the Original Agreement, which disputes the parties wish to resolve pursuant to a
Settlement Agreement of even date herewith (the "Settlement Agreement"); and
WHEREAS, the terms of the Settlement Agreement provide for the amendment
and restatement of the Original Agreement as set forth herein;
NOW, THEREFORE, Chiron and Bioanalysis agree to amend and restate the
Original Agreement to read in its entirety as follows:
1.DEFINITIONS
When used in this Agreement with initial capitals, the terms defined in
this Section 1 shall have the respective meanings set forth below:
a."ADDITIONAL ROYALTY ACCOUNT" shall have the meaning specified in Section
3(c).
b."AE" shall mean any chemiluminescent aryl acridinium esters.
c."AFFILIATE" of a party shall mean a corporation or any other business
entity, in whatever country organized, which, directly or indirectly, controls,
is controlled by or is under common control with such party. For this purpose,
control shall mean the ownership of more than 50% of the issued share capital or
the legal power to direct or cause the direction of the general management and
policies of the party in question. Notwithstanding the foregoing, in the case
of Chiron, "Affiliate" shall (i) include Ciba Corning Diagnostics de Mexico S.A.
(which intends to change its name on or about November 1, 1996 to Chiron S.A. de
C.V.), so long as Chiron continues to own at least 49% of the voting stock of
that corporation, and (ii) exclude Ciba-Geigy Limited, a Switzerland corporation
("Ciba"), and any subsidiaries of Ciba, unless and until such time as Ciba and
Chiron Corporation may mutually agree upon the terms and conditions upon which
Ciba may be deemed an Affiliate of Chiron for purposes of this Agreement.
d."BAYER AGREEMENT" means the Licensing Agreement dated as of December 18,
1986 between Bayer Corporation (formerly known as Miles Laboratories, Inc.) and
Chiron.
e."BAYER OFFSET ACCOUNT" shall have the meaning specified in Section 3(b).
f."BIOANALYSIS PRODUCTS" shall mean the products identified in Schedule A.
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g."CAMPBELL PATENTS" shall mean U.S. Patent No. 4,946,958, any foreign
counterpart patent of U.S. Patent No. 4,946,958 or any continuation, division,
re-issue or re-examination either the U.S. patent above named or its foreign
counterpart.
h."CLAIM" shall mean an issued patent claim which defines an invention
which the patentee has been granted the right to exclude others from making,
using, or selling throughout the granting country. The term does not include
any patent claim which has been disclaimed, canceled, or finally adjudicated to
be invalid.
i."CLOSING DATE" shall mean July 1, 1996.
j."IMMUNOASSAY" shall mean any assay wherein the analyte of interest is an
antibody or protein or is determined by the binding thereto of an antibody or
other specific binding protein.
k."LICENSED PATENTS" shall mean all patents relating to Immunoassays
employing AE labels now or hereafter legally or beneficially owned or controlled
by Bioanalysis ("Bioanalysis Patents") or UWCM ("UWCM Patents"), including all
of the Xxxxxxxx Patents, provided that "Licensed Patents" shall not include any
patent arising out of an invention first conceived on or after, and with an
earliest claimed priority date on or after, April 1, 1996. The list of the
Licensed Patents and the pending applications which may result in the issuance
of Licensed Patents ("Licensed Patent Applications") is attached hereto as
Schedule B, provided that any omission from such list shall not affect the
status of a patent which would otherwise be a Licensed Patent hereunder.
l."LICENSED PRODUCTS" shall mean Immunoassays or components for
Immunoassays for use in (i) human healthcare and (ii) pre-clinical and
laboratory research whether or not directed to human healthcare, the
manufacture, use or sale of which would, in the absence of a license, infringe a
Claim of a Licensed Patent.
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m."NET SALES REVENUE" shall mean the amount billed by Chiron or its
Affiliates or sublicensees to third parties for the sale of Royalty Products or
performance of assays using Royalty Products, less discounts allowed; less
credits for customers' returns and allowances; less the value of the instrument
and service components of an operating or capital lease for which the charges
are included in the price of Royalty Products purchased by the lessee; less
charges for freight handling and transportation paid by Chiron; and less sales
and use taxes and other similar taxes incurred, all to the extent reasonable and
as determined in accordance with generally accepted accounting practices and
industry practices. Notwithstanding the foregoing, if Chiron or its Affiliates
or sublicensees bills a third party for performance of an assay using a Royalty
Product, the amount of Net Sales Revenue shall be equal to the average Net Sales
Revenue for sales of such Royalty Product in the country in which such assay is
performed during the quarter in which such assay is performed, or, if such
Royalty Product is not sold for commercial use in such country during such
quarter, the worldwide average Net Sales Revenue for sales of such Royalty
Product for such quarter, or, if such Royalty Product is not sold commercially
in any country, a reasonable apportionment shall be made of the gross amount
invoices for performance of the assay between the value of the assay and the
value of the laboratory services associated therewith, taking into account the
average selling prices of similar products, such apportionment to be negotiated
in good faith between the parties and arbitrated if they are unable to agree.
No royalty shall be due upon a sale of a Royalty Product by Chiron to an
Affiliate. Instead, royalty shall be due when such Royalty Product is re-sold
to or used to perform an assay for a third party, and Net Sales Revenue shall be
calculated based on the invoiced price to such party. Royalty shall accrue only
once as to any Royalty Product.
n."PRIME RATE" shall mean, as to each of Chiron's fiscal quarters, the
prime rate of interest as published on the last business day of such quarter in
the Wall Street Journal, provided that Chiron may substitute for the Wall Street
Journal any comparable print or electronic publication, provided that such
substitute publication is used generally by Chiron for such purposes in its
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accounting operations. Chiron agrees to notify Bioanalysis of any change in the
source it uses for the Prime Rate.
o."PROPRIETARY INFORMATION" - Information of any kind, including without
limitation, inventions, technology, disclosures, processes, systems, methods,
formulae, patent applications, machinery, materials, research activities and
plans, costs of production, contract forms, prices, volume of sales, promotional
methods, and lists of names or classes of customers, know-how and trade secrets,
owned or controlled by a party which such party regards as valuable and holds
confidentially other than information which (i) was known by the receiving party
prior to its disclosure by the disclosing party; (ii) is or becomes public
knowledge without fault of the receiving party; (iii) is obtained or derived by
the receiving party from a third party which, to the best knowledge of the
receiving party after appropriate inquiry, is lawfully in possession of such
information and has the right to disclose the information to the receiving party
on a non-confidential basis; or (iv) is developed or derived by the receiving
party, prior or subsequent to its disclosure by the disclosing party,
independently and without resort to the information which was disclosed by the
disclosing party.
p."ROYALTY ADVANCE" shall have the meaning specified in Section 3(a)(ii).
q."ROYALTY PRODUCTS" shall have the following meanings at the respective
times specified below:
i.Until the earlier of August 7, 2007 or depletion of the Bayer Offset
Account, "Royalty Products" shall mean (A) so long as at least one Claim of a
Xxxxxxxx Patent remains in force anywhere in the world, Immunoassays or
components for Immunoassays that use an AE label, regardless of whether such
products constitute Licensed Products hereunder, except as to any product which
is an Independent Sublicensee Product referred to in clause (ii) of this
Paragraph 1(q); or (B) if no Claim of a Xxxxxxxx Patent remains in force,
Immunoassays or components of Immunoassays, the manufacture, use or sale of
which would, in the absence of a license, infringe a
5
Claim of a Licensed Patent in force in country in which such manufacture, use or
sale occurs, as determined by applicable principles of patent law.
ii.Thereafter, and at all times with respect to any products of a
sublicensee which are not designed for use on a Chiron instrument and are not
labelled with a Chiron trademark ("Independent Sublicensee Products"), "Royalty
Products" shall mean Immunoassays or components for Immunoassays the
manufacturer, use or sale of which would, in the absence of a license, infringe
a Claim of a Xxxxxxxx Patent in force in a country in which such manufacture,
use or sale occurs, as determined by applicable principles of patent law.
r."UWCM LICENSE" shall mean the Agreement dated as of July 12, 1984 between
UWCM and Bioanalysis pursuant to which UWCM licensed the UWCM Patents to
Bioanalysis.
2.GRANT OF LICENSE; LIMITATIONS
x.XXXXX. Bioanalysis hereby grants to Chiron a world-wide sublicense under
the UWCM Patents and a world-wide license under the Bioanalysis Patents to
develop, make, have made, import, use, offer to sell and sell Licensed Products.
Such sublicense and license (i) shall be exclusive as to Licensed Products for
use in human healthcare and pre-clinical and laboratory research directed to
human healthcare and non-exclusive as to Licensed Products for use in
pre-clinical and laboratory research not directed to human health care and (ii)
shall include the right to grant sublicenses in accordance with the terms of
Section 5 hereof; provided, however, that pre-clinical and laboratory research
conducted by Bioanalysis with application to human healthcare shall not infringe
Chiron's exclusive license so long as that research has potential application to
fields other than human healthcare.
b.RESERVATION OF RIGHTS IN GRANTOR. Notwithstanding the exclusive licenses
granted to Chiron hereunder, Bioanalysis reserves to itself the non-exclusive
right (with right of sublicense to
6
third parties or Affiliates with whom Bioanalysis enters into collaborative
arrangements for the development, manufacture and marketing of Bioanalysis
Products) to make, have made, import, use, offer to sell and sell the
Bioanalysis Products.
c.RIGHTS LIMITED TO LICENSED PRODUCTS. Nothing herein grants to Chiron any
rights under the Licensed Patents with respect to the manufacture, use or sale
of any products other than Licensed Products. Without limiting the generality
of the foregoing, nothing herein shall be construed as a grant to Chiron of any
rights under the Licensed Patents to develop, make, have made, import, use,
offer to sell or sell nucleic acid hybridization assays or any other assays for
which rights are not specifically granted to Chiron herein.
x.XX LIMITATIONS EXCEPT UNDER PATENTS. As between the parties to this
Agreement, the field of use restrictions contained herein prohibit the
manufacture, use or sale of any product by either party only to the extent that
such manufacture, use or sale constitutes infringement of a Claim of a patent in
force in the jurisdiction in which such activity occurs.
e.PROPRIETARY INFORMATION. Bioanalysis and UWCM have provided Chiron with
information relating to the use of acridinium esters in immunoassays and binding
protein assays. To the extent that any information provided to Chiron by
Bioanalysis or UWCM constitutes Proprietary Information, Bioanalysis and UWCM
covenant not to assert any restriction on the use or communication of such
Proprietary Information, including publication, except at the direction of
Chiron. To the extent that any Proprietary Information provided to Chiron by
UWCM or Bioanalysis has entered the public domain, it has done so without the
fault of Chiron. Bioanalysis has not provided Chiron with Proprietary
Information useful in the field of nucleic acid hybridization assays.
f.OPTION. In the event that Bioanalysis obtains during the term of this
Agreement any patent rights either as owner or licensee, which relate to an AE
technology, Bioanalysis will grant to
7
Chiron an option to receive a non-exclusive license at a reasonable royalty for
the Licensed Products (as defined to include such patent rights as Licensed
Patents). The terms of the license will include a most favored licensee clause
and rights to grant sublicenses to third parties with whom Chiron enters into
collaborative arrangements for the development, manufacture and marketing of the
Licensed Products, and will not include license fees or minimum royalties. The
royalty rate and other terms of the license not specified herein will be
negotiated in good faith and resolved in accordance with the dispute resolution
procedures set forth in Section 9(c) if the parties cannot agree. The option
will be exercisable no later than six months after Chiron's receipt of
Bioanalysis' written request to either exercise or waive its rights with respect
to a particular patent or patent application. Bioanalysis agrees that it will
not, without Chiron's written consent, waive its rights to a license under any
of the Patents as defined in the UWCM License.
3.LICENSE FEES AND ROYALTIES
a.RESTRUCTURING FEE AND ROYALTY ADVANCE. Chiron shall make the following
non-refundable payments to Bioanalysis on the Closing Date:
i.A license restructuring fee in the amount of [CONFIDENTIAL TREATMENT
REQUESTED], which shall not be creditable against royalties, and
ii.An advance upon future royalties in the amount of [CONFIDENTIAL
TREATMENT REQUESTED] (the "Royalty Advance").
Chiron shall not be required to make any further payments until the
Royalty Advance has been fully depleted by application to royalties earned under
Paragraph 3(d).
x.XXXXX OFFSET ACCOUNT. An account (the "Bayer Offset Account") shall be
established as an accounting mechanism for the purpose of determining when
Chiron has been fully compensated for its royalty payments under the Bayer
Agreement, plus interest thereon, through reductions in the
8
rate of royalty that would otherwise have been payable hereunder. The amount of
the Bayer Offset Account as of April 1, 1996 is agreed to be [CONFIDENTIAL
TREATMENT REQUESTED]. Effective as of the end of each of Chiron's fiscal
quarters, (i) there shall be added to the Bayer Offset Account (A) an amount
equal to the interest that would have accrued on the balance of the Bayer Offset
Account during such quarter if such balance earned interest at the Prime Rate
(provided that for the quarter ending June 30, 1996, such hypothetical interest
shall be deemed to accrue only from and after the Closing Date) and (B) the
amount of royalties paid by Chiron to Bayer under the Bayer Agreement for such
quarter, and (ii) there shall be subtracted from the Bayer Offset Account an
amount equal to the difference between the amount of royalties paid to
Bioanalysis for such quarter (including royalties paid by means of an
application of credit for the Royalty Advance) and the amount of royalties that
would have been payable at a royalty rate of [CONFIDENTIAL TREATMENT REQUESTED].
Nothing herein shall be construed to require Bioanalysis to make any actual
deposit or payment of funds to cover any amount of the Bayer Offset Account.
c.ADDITIONAL ROYALTY ACCOUNT. A second account (the "Additional Royalty
Account") shall be established for the purpose of determining the time at which
the rate of royalty payable hereunder shall be reduced to zero until Chiron has
been fully compensated for its royalty payments under the Bayer Agreement, plus
interest thereon. The amount of the Additional Royalty Account as of the
Closing Date shall be [CONFIDENTIAL TREATMENT REQUESTED]. Effective as
of the end of each of Chiron's fiscal quarters, (i) there shall be added to the
Additional Royalty Account an amount equal to the interest that would have
accrued on the balance of the Additional Royalty Account during such quarter if
such balance earned interest at the Prime Rate (provided that for the quarter
ending June 30, 1996, such interest shall be deemed to accrue only from and
after the Closing Date and provided further that no such interest shall accrue
after August 7, 2007) and (ii) there shall be subtracted from the Additional
Royalty Account an amount equal to the amount of royalties paid to Bioanalysis
for such quarter, other than royalties paid through application of the Royalty
Advance. The Additional Royalty Account is an accounting mechanism only, and
except
9
as provided in Section 9(b), nothing herein shall require Chiron to make any
actual deposit of funds to cover the amount of the Additional Royalty Account.
d.ROYALTY RATES AND APPLICATION OF ADVANCE. Chiron shall pay Bioanalysis
royalties on its sales of Royalty Products at the rates of (i)[CONFIDENTIAL
TREATMENT REQUESTED]. All royalties shall first be credited against the Royalty
Advance and no additional cash payments in respect of royalties shall be payable
until the Royalty Advance has been fully depleted. Thereafter, royalties shall
be due and payable as provided in Paragraph 3(d), 3(e) and 4(b). Chiron will
not be liable to pay more than actual accrued royalties even if they do not
deplete the Additional Royalty Account during the term of this Agreement, and
Bioanalysis will not be responsible for any shortfall if Chiron does not recover
the amount of the Bayer Offset Account during the term hereof.
e.EFFECT OF INVALIDITY/UNENFORCEABILITY. Chiron will make all payments
provided for in this Agreement, notwithstanding that any of the Licensed Patents
may be held invalid and/or unenforceable in any proceeding at a later date, so
long as at least one Claim of a Licensed Patent remains in force and has not
been finally adjudicated to be invalid, provided, that (i) after the earlier of
August 7, 2007 or depletion of the Bayer Offset Account, royalties shall be
payable only with respect to Royalty Products as defined in Paragraph 1(q)(ii)
hereof, (ii) no royalties shall be payable after August 7, 2007 except to the
extent, if any, necessary to deplete the Additional Royalty Account; and (iii)
if no Claim of any Xxxxxxxx Patent remains valid, royalties shall be payable
only with respect to Royalty Products as defined in Clause (B) of Paragraph
1(q)(i).
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4.RECORD KEEPING, PAYMENT AND REPORTS
a.RECORDS. Chiron shall maintain records of sales of Royalty Products in
sufficient detail to enable royalties payable hereunder to be determined and
shall cause its Affiliates and sublicensees to do likewise. Such records shall
be maintained for a period of at least five years after the end of quarter to
which they relate.
b.REPORTS AND PAYMENTS. Within sixty (60) days after the end of each
fiscal quarter (as Chiron may establish from time to time for its corporate
operations) Chiron shall provide Bioanalysis with a written statement of Net
Sales Revenue of Royalty Products by Chiron and its Affiliates and sublicensees,
a calculation of royalties owed, and a payment of the total amount then due.
Quarterly royalty reports will separately identify sales by Chiron and its
sublicensees and will also include a report on the value of the Royalty Advance,
the Additional Royalty Account and the Bayer Offset Account and a report of any
pending disputes under Section 6(b).
c.PRO-RATION WITHIN QUARTERS. With respect to changes in royalty rates
occurring other than at the end of a fiscal quarter, the amount of Net Sales
Revenue occurring prior to the change in rate shall be deemed to be equal to the
Net Sales Revenue for the entire quarter, times a fraction, the numerator of
which shall be the number of days from the first day of the quarter to the date
of the rate change and the denominator of which shall be the number of days in
the quarter.
d.CURRENCY. All payments hereunder shall be made in U.S. currency.
Non-US$ denominated sales will be converted into dollar sales in accordance with
the standard accounting procedure used by Chiron with respect to its sales
generally as of the Closing Date. In the event that Chiron changes its method
of converting foreign currency sales into U.S. dollars, Chiron will notify
Bioanalysis of the change. If during the first accounting period that such
change is in effect, the Net Sales Revenue determined using the new method of
currency conversion is at least 95% of the Net Sales Revenue determined using
the previous method of currency conversion, Bioanalysis'
11
approval of the change in conversion method shall not be required. If the new
method of currency conversion results during such initial accounting period in a
reduction of Net Sales Revenue to less than 95% of Net Sales Revenue under the
previous method, Chiron shall continue to use its previous method of currency
conversion for purposes of this Agreement unless and until Chiron and
Bioanalysis agree on implementation of the new method. Notwithstanding the
foregoing, non-US dollar sales of sublicensees may be converted to U.S. dollars
in accordance with the method used by the sublicensee in question in its
financial statements generally.
e.TAXES. No taxes or deductions of any kind shall be made or taken from
the payments due under Section 3(a). All taxes which Chiron is required to
withhold from royalty payments shall be deducted from such payments and evidence
of actual payment to the relevant taxing authority shall be delivered to
Bioanalysis at the time the accounting for the payment is made to Bioanalysis.
The amounts deducted on account of such taxes shall be deemed to have been paid
to Bioanalysis for purposes of depleting the Additional Royalty Account.
f.AUDIT. Upon Bioanalysis' request (but not more than once per year) and on
reasonable notice, Chiron will, and will cause its Affiliates and sublicensees
to, permit, at the expense of Bioanalysis, independent certified public
accountants, reasonably acceptable to both parties, to have access during
reasonable business hours to inspect and make extracts from such records as may
be reasonably necessary to determine, in respect of any quarterly period, the
correctness of any royalty statements and payments under this Agreement,
provided that Chiron will bear any such reasonable audit expense if the review
or audit shows an underpayment of more than 10% for the applicable period,
unless the conclusions of such review or audit are determined to be incorrect by
agreement of the parties or pursuant to the dispute resolution procedures set
forth in Paragraph 9. The independent certified public accountants must sign
non-disclosure agreements prohibiting them from revealing any information to any
third party and allowing them to disclose to Bioanalysis only information
reasonably necessary to be communicated in order to carry out the purpose of the
audit.
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5.SUBLICENSES
a.RIGHT TO GRANT SUBLICENSES. Chiron shall have the right to grant
sublicenses under the rights granted in Paragraph 2(a) to Affiliates and to
third parties. Royalties shall be payable to Bioanalysis by Chiron with respect
to its sublicensees' Net Sales Revenue (determined in the same manner as Net
Sales Revenue of Chiron) for Royalty Products at the same rates and in the same
manner as provided in Paragraphs 3(d) and 4(b). If Chiron does not receive a
royalty report or payment from a sublicensee prior to the date when Chiron's
report and payment are due to Bioanalysis, Chiron shall make the royalty report
and payment to Bioanalysis based on its best estimate of the amount of royalty
due with respect to the sublicense and shall make an appropriate adjustment in
the next quarter's report and payment. If so agreed by Chiron with a
sublicensee, royalties with respect to a sublicense may be paid semi-annually
rather than quarterly and on the basis of the sublicensee's fiscal periods
rather than Chiron's fiscal periods.
b.Arrangements Not Sublicenses. As used herein, the term "sublicense"
shall not include (i) the right of [CONFIDENTIAL TREATMENT REQUESTED] or a
[CONFIDENTIAL TREATMENT REQUESTED] or (ii) any arrangement whereby a
[CONFIDENTIAL TREATMENT REQUESTED], whether or not such party also
[CONFIDENTIAL TREATMENT REQUESTED] or a combination of Chiron [CONFIDENTIAL]
TREATMENT REQUESTED]. Chiron's royalty payments to Bioanalysis with respect
to products [CONFIDENTIAL TREATMENT REQUESTED] who also
[CONFIDENTIAL TREATMENT REQUESTED] shall be based on the
[CONFIDENTIAL TREATMENT REQUESTED] by such [CONFIDENTIAL TREATMENT REQUESTED]
and not on [CONFIDENTIAL TREATMENT REQUESTED].
c.IN-KIND SUBLICENSES. In the event that Chiron receives any right
benefit, advantage, concession other than money (including, without limitation
any licenses to any patents of any Affiliate or third party or any business
discount from or any equity of any Affiliate or third party) in consideration
for a grant by Chiron of a sublicense under the licenses granted to it pursuant
to this Agreement, Chiron shall (i) nonetheless be obligated to pay Bioanalysis
royalties pursuant to
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this Agreement based on such third party's or Affiliate's sales or revenues in
connection with Royalty Products or (ii) if no such sales or revenues are to be
received from such third party or Affiliates, inform Bioanalysis of such event
and provide Bioanalysis with all reasonable documentation and information
necessary or appropriate for the parties to negotiate in good faith with respect
to the proper valuation of any such right, benefit, advantage or concession and
the corresponding amounts owing to Bioanalysis in connection therewith, which
shall be determined by allocating the total value received by Chiron between the
sublicense granted hereunder and all other items of value provided by Chiron and
dividing the value allocable to the sublicense granted hereunder equally between
Chiron and Bioanalysis. In the event that the parties do not agree on the
proper valuation or the amounts owing, such issues will be resolved in
accordance with the parties' dispute resolution procedures pursuant to Section
9.
6.PROSECUTION, MAINTENANCE AND ENFORCEMENT OF PATENTS
a.PROSECUTION AND MAINTENANCE. Bioanalysis shall pay for all expenses in
prosecuting the Licensed Patent Applications and maintaining the Licensed
Patents. Bioanalysis shall maintain the Licensed Patents listed in Schedule B.
Bioanalysis shall provide Chiron with copies of all pending Licensed Patent
Applications and inform Chiron concerning the progress of all relevant patent
prosecutions on a semi-annual basis.
b.ENFORCEMENT OF PATENTS BY CHIRON. Chiron shall have the sole,
unrestricted right to enforce the Licensed Patents against all infringers whose
products would constitute Licensed Products if sold by Chiron hereunder, without
regard to whether the infringing products compete with Chiron's products.
Chiron shall pay all costs and keep all recoveries with respect to such
enforcement. Bioanalysis shall assist Chiron as reasonably requested by Chiron,
including by making its officers and employees available as witnesses, and
providing full access to all relevant documents and records, provided that
Chiron shall reimburse all of Bioanalysis out-of-pocket costs
14
in connection therewith. Bioanalysis shall join an enforcement action as party
plaintiff if required by law. Chiron will have no right to offset against any
payments otherwise due under this Agreement, any costs, expenses or damages
relating to such infringement or infringement litigation. Chiron agrees to
defend, indemnify and hold Bioanalysis and UWCM harmless from any liability
arising out of actions taken by Chiron pursuant to this sub-section, as well as
attorneys fees arising out of any failure to defend.
c.ENFORCEMENT BY BIOANALYSIS. Notwithstanding the provisions of Paragraph
6(b), if Bioanalysis notifies Chiron of activities which Bioanalysis believes
constitute infringement of the Licensed Patents within the scope of Chiron's
right to enforce as specified in Paragraph 6(b), and if Chiron does not within
12 months thereafter commence patent enforcement proceedings against the alleged
infringer or conclude licensing negotiations with the alleged infringer
(provided that such period shall be extended to the extent of any period during
which Chiron is engaged in proceedings against or negotiations with another
infringer), Bioanalysis shall thereafter have the right, but not the obligation,
to enforce the Licensed Patents against such alleged infringer at Bioanalysis'
own expense and with all recoveries of damages being for Bioanalysis' sole
benefit. Such right of Bioanalysis to enforce the Licensed Patents shall lapse
unless Bioanalysis institutes enforcement proceedings within six months of the
date Bioanalysis is first permitted to institute such proceedings in accordance
with this Paragraph. Except with respect to enforcement actions against
Ciba-Geigy or its subsidiaries, nothing herein shall be deemed to permit
Bioanalysis to grant any license under the Licensed Patents within the scope of
the exclusive license granted to Chiron hereunder.
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7.REPRESENTATIONS AND WARRANTIES.
a.Bioanalysis represents and warrants that:
i.OWNERSHIP. Bioanalysis is the sole owner of the UWCM License, a
true, complete and correct copy of which, including all amendments through the
date hereof, has been provided to Chiron, and is the sole owner or exclusive
licensee of each of the Licensed Patents and Licensed Patent Applications.
ii.THIRD PARTY RIGHTS. Bioanalysis has not granted any rights to any
third party that are inconsistent with the terms of this Agreement, no third
party has made any claim to have been granted such rights, and Bioanalysis is
not aware of any grounds for any such claim.
iii.COMPLETE LIST. To the best of Bioanalysis' knowledge after due
inquiry, Schedule B is a complete list of patents and patent applications
relating to Immunoassays using AE labels that is now or at any time since
December 6, 1984 has been legally or beneficially owned or controlled by
Bioanalysis or UWCM, except for Woodhead ET AL. EP 478,626, and the related
applications and counterparts thereof.
iv.Nothing in this Agreement shall be construed as a warranty or
representation by Bioanalysis as to the validity of any Licensed Patent.
Nothing in this Agreement shall be construed as a warranty or representation by
Bioanalysis that any product made, used, sold or imported under any Licensed
Patent is or will be free from infringement of patents not licensed hereunder or
patents of third parties. Nothing in this Agreement shall be construed as
conferring by implication, estoppel or otherwise any license or rights under any
patents belonging to Bioanalysis other than the Licensed Patents as defined in
this Agreement.
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b.Chiron represents and warrants that Net Sales Revenue for the period
January 1, 1995 - December 31, 1995 was not less than [CONFIDENTIAL TREATMENT
REQUESTED].
8.TERM AND TERMINATION
a.TERM. Except as provided in Paragraph 8(b), the licenses granted to
Chiron hereunder shall continue until the expiration of the last to expire of
the Licensed Patents. Notwithstanding the foregoing, Chiron's obligations to
pay royalties hereunder shall continue only so long as provided in accordance
with Paragraphs 3(d) and 3(e).
b.CHALLENGE TO VALIDITY. The initiation of any legal proceeding
challenging the validity of a Xxxxxxxx Patent by Chiron or any party acting
under the direction and control of Chiron shall give Bioanalysis an immediate
right to terminate the license upon written notice to Chiron, such termination
to be effective thirty (30) days after notice of termination unless such
challenge to validity is dismissed with prejudice within the thirty day period.
Notwithstanding the foregoing, if the challenge to validity is asserted by a
party other than Chiron or an Affiliate and Chiron disputes whether such party
is under its direction and control, no termination shall occur unless a final
decision of an arbitral panel in a proceeding conducted in accordance with
Paragraph 9 hereof determines that such party is under the direction and control
of Chiron. If the arbitrators determine that the party challenging validity was
acting under the direction or control of Chiron, Chiron will have a period of
thirty (30) days to cause such challenge to be withdrawn and thereby avoid
termination, unless the arbitrators conclude that Chiron's contention as to
direction or control was made in bad faith, in which case the Agreement shall
terminate immediately upon such determination. Nothing herein shall prevent
Chiron from presenting evidence of prior art in connection with a dispute
regarding the proper interpretation of the scope of any Claim of any patent.
17
9.DISPUTES AND REMEDIES FOR BREACH.
a.DAMAGES SOLE REMEDY. Except as provided in paragraphs 8(b) and 9(b),
Bioanalysis' sole remedy for breach of the license agreement by Chiron shall be
the recovery of an award of damages in an arbitration proceeding, which award
shall include interest at the Prime Rate compounded quarterly from the date the
damages were incurred. In any arbitration proceeding, the arbitrators shall
have authority to award attorneys' fees to the prevailing party. Nothing herein
is intended to limit Bioanalysis right to seek injunctive relief with respect to
infringement of the Licensed Patents by activities outside the scope of the
license and sublicense granted hereunder.
b.EXTRAORDINARY REMEDY. If Bioanalysis, after initiating and prevailing in
an arbitration with respect to non-payment of royalties in which the recovery
exceeds 10% of the amount of royalties due for the period with respect to which
the determination of royalties is in dispute (which period shall be a period of
at least two quarters), again initiates and prevails in such an arbitration and
recovers such an amount, and provided that Chiron has not theretofore been the
prevailing party in an arbitration between the parties, the unrecovered balance,
if any, of the Additional Royalty Account shall become immediately due and
payable as a non-refundable advance on future royalties.
c.RESOLUTION OF DISPUTES. Chiron and Bioanalysis agree that the following
procedure will govern the resolution of any dispute between or among them
arising out of or relating to this Agreement:
i.the parties will use all reasonable efforts for a period of at least
90 days to resolve the dispute through negotiation;
ii.if the dispute cannot be settled through negotiation, Chiron and
Bioanalysis agree to try in good faith to settle the dispute by mediation
administered by the American Arbitration Association under its Commercial
Mediation Rules; and
18
iii.if the dispute cannot be resolved by mediation Chiron and
Bioanalysis agree that the dispute will be resolved by mandatory, binding
arbitration. The arbitration will take place in San Francisco, CA, at the
offices of the American Arbitration Association ("AAA"), pursuant to the AAA
International Commercial Rules. The dispute will be resolved by the majority
decision of three arbitrators of whom one will be nominated by the Claimant(s)
and one by Respondent(s), and a third nominated by the two party-appointed
arbitrators, unless Claimant(s) and Respondent(s) agree in any given dispute to
have it settled by a single arbitrator acceptable to both Claimant(s) and
Respondent(s). If a party fails to nominate its arbitrator to a three arbitrator
panel within 30 days after the other party has appointed its arbitrators and
served written notice of such appointment on the other party, or if within 30
days after both party-appointed arbitrators are appointed, the party appointed
arbitrators have not agreed upon the appointment of a third arbitrator, then the
missing arbitrator will be appointed by the AAA in accordance with the governing
rules. The decision of the arbitrators, or of the single arbitrator, as the
case may be, will be final and binding. Judgment on the award may be entered in
any Court of competent jurisdiction.
iv.The parties agree that, prior to the formation of the arbitral
panel, a party may apply to a state or federal court in California for
provisional or interim relief. After the arbitration panel is empaneled, it
shall have sole jurisdiction to hear such application, except that the parties
agree that any relief ordered by the arbitrators may be enforced by a California
state court.
v.If Chiron or Bioanalysis desire to join Gen-Probe as a party to an
arbitration commenced or to be commenced under this Section, then each of the
parties shall use their best efforts to convince Gen-Probe to join the
arbitration. If Gen-Probe will not agree to join the arbitration, then each of
Chiron and Bioanalysis agrees that, notwithstanding this Section, the
complaining party shall bring its dispute in federal court in California, or in
the event that the federal court does not have jurisdiction over the subject
matter of the dispute, in state court in California.
vi.Each of the parties submits to the jurisdiction of the federal
courts in California, or in the event that the federal court does not have
jurisdiction over the subject matter of the
19
dispute, to the jurisdiction of the state courts in California, for purposes of
Section 9(c)(iv) and 9(c)(v) of this Agreement.
10.NOTICES.
Any notice or report required or permitted to be given under this Agreement
shall be in writing and shall be delivered by hand or overnight courier or
mailed postage prepaid by recorded, registered or certified mail return receipt
requested, addressed as set forth below unless changed by notice so given:
If to Chiron:
Ciba Corning Diagnostics Corp.
000 Xxxxx Xxxxxx
Xxxx Xxxxxxx, XX 00000
Attention: President
Copy to: General Counsel
If to Bioanalysis:
Bioanalysis Limited
Cardiff Business Technology Centre
Xxxxxxxxxx Xxxx
Xxxxxxx XX0 0XX, Xxxxxx Xxxxxxx
Attention: Managing Director
Any such notice or report shall be deemed delivered on the date received,
provided that no such notice or report shall be deemed delinquent if deposited
in the mails or delivered to a courier service on or before the date such notice
or report is required to be given.
20
11.MISCELLANEOUS.
a.CONFIDENTIALITY. Bioanalysis agrees to hold in confidence all
information it may receive hereunder concerning royalty payments and sales by
Chiron and its Affiliates and sublicensees, except that Bioanalysis may disclose
such information (i) to the extent such information has previously been publicly
disclosed by Chiron, (ii) to the extent required to be disclosed by applicable
law and after using all reasonable efforts to obtain confidential treatment of
the required disclosure, (iii) to its legal counsel and accountants, or (iv) to
the arbitrators in any arbitral proceeding pursuant to Paragraph 9 hereof.
This obligation shall survive termination of this Agreement.
x.XX JOINT VENTURE. This Agreement does not constitute and shall not be
construed as an agency, joint venture or partnership between the parties.
c.BENEFIT AND ASSIGNMENT. This Agreement shall be binding upon and inure
to the benefit of the successors and assigns of the parties hereto, provided,
however, that neither party may assign or transfer its rights and obligations
without the written consent of the other party, which consent shall not be
unreasonably withheld, except that Chiron may assign its rights and obligations
without such consent to a purchaser or other transferee of Chiron's
immunodiagnostics business, and Bioanalysis may assign its rights and
obligations without such consent to UWCM and Affiliates of Bioanalysis.
d.ENTIRE AGREEMENT; AMENDMENT. This Agreement is the entire agreement
between the parties with respect to the matters set forth herein and supersedes
all other prior agreements or understandings, whether written or oral. No
representations, oral or otherwise, express or implied, other than those
expressly set forth herein or in the Settlement Agreement have been made by
either party to the other concerning the subject matter of this Agreement. This
Agreement may not be
21
modified or amended other than in writing signed by the party whose rights or
obligations are modified or amended.
e.WAIVER. The failure of party to insist upon another party's strict
adherence to any term of this Agreement on any occasion will not be construed as
a waiver or deprive that party of the right to insist upon strict adherence to
that term or any other term of this Agreement.
f.GOVERNING LAW. This Agreement shall be governed and construed in
accordance with the laws of the State of California, U.S.A., without giving
effect to that state's conflict of law rules.
g.SEVERABILITY. If any provision or sub-provision of this Agreement is
found invalid or unenforceable, the balance of the Agreement, and all provisions
thereof shall continue in full force and effect.
h.INTERPRETATION. References to any gender include the other gender and to
the singular number the plural number and vice versa. All headings throughout
this Agreement have been inserted for the purpose of ease of reference only and
do not define, limit or affect the meaning or interpretation of this Agreement
or of any instrument created pursuant hereto or in accordance herewith. Each
party has been provided with an opportunity to participate in the drafting and
preparation of this Agreement. Therefore, in any construction to be made of
this Agreement, the same shall not be construed against any party.
i.GEN-PROBE AGREEMENT - This Agreement does not diminish, alter, or affect
in any way, the rights of Gen-Probe under the Gen-Probe Agreement.
[REMAINDER OF THE PAGE LEFT INTENTIONALLY BLANK]
22
IN WITNESS WHEREOF, the parties hereto have executed this Agreement or
caused their duly authorized representatives to execute this Agreement as of the
date first above written.
CIBA CORNING DIAGNOSTICS CORP. BIOANALYSIS LIMITED
By: /s/ Xxxxxxx X. Xxxxxx By: /s/ J.L.D. Xxxx
-------------------------- ----------------------------
Xxxxxxx X. Xxxxxx Director
Senior Vice President,
Immuno/Chemistry
Date: 7/2/96 Date:
-------------------------
21
SCHEDULE A
PAGE 1 OF 8
SCHEDULE A
BIOANALYSIS PRODUCTS
1. HIV 1/2 per attached description (and all reasonable improvements thereto
which do not substantially change the nature of the product).
2. Hepatitis B per attached description (and all reasonable improvements
thereto which do not substantially change the nature of the product).
3. Anti-Thyroglobulin per attached description (and all reasonable
improvements thereto which do not substantially change the nature of the
product).
4. Anti-Thyroid Peroxidase per attached description (and all reasonable
improvements thereto which do not substantially change the nature of the
product).
5. Thyrotrophin Receptor Antibodies per attached description (and all
reasonable improvements thereto which do not substantially change the nature of
the product).
6. Insulin (manual microtiter plate format).
7. Proinsulin (manual microtiter plate format).
Reasonable improvements do not include modifications to enable use on automated
instruments.
1
SCHEDULE A
Page ____
IMMUNOASSAY FOR HIV 1/2 ANTIBODIES IN SERUM
BACKGROUND
HIV is regarded as the causative agent of AIDS. It is difficult to detect
circulating viral protein or cDNA/RNA by routine methods. Thus screening tests
for HIV rely on the detection of circulating (anti-HIV) antibodies.
Since the discovery of HIV, a number of such assays have been described.
There are three main HIV antigenic gene products: GAG (viral core proteins:
p55, p24, p17, p9, p7), POL (regulatory proteins including reverse
transcriptase p66 and p51, protease p10, integrase/endonuclease p31) and ENV
(envelope glycoproteins gp160, gp120 and gp41). Of these, the gene products
of ENV and GAG are of most interest with regard to the detection of anti-HIV
antibodies in serum. All these proteins and their fragments are capable of
generating a host immune response and will yield positive bands in western
blot and radioimmuno-precipitation detection systems. These two testing
methods offer high levels of specificity and sensitivity but are too labor
intensive and time consuming for routine laboratory use. They thus form a
body of confirmatory tests for samples screened positive for HIV antibodies
by ELISA.
Early tests used viral lysates as antigen though this invariably resulted in an
unacceptably high false positive rate. More recently developed tests have
involved the use of synthetic or recombinant proteins as antigen to minimize
unwanted cross-reactions.
This report describes a method for the detection of [Confidential Treatment
Requested] to HIV1 and HIV2 by the use of [Confidential Treatment Requested] and
[Confidential Treatment Requested] respectively.
METHOD
[Confidential Treatment Requested] are dissolved in [Confidential Treatment
Requested] buffer to give a concentration of [Confidential Treatment Requested]
and added to the xxxxx of [Confidential Treatment Requested] or [Confidential
Treatment Requested]. Following [Confidential Treatment Requested] incubation,
xxxxx are [Confidential Treatment Requested] by addition of [Confidential
Treatment Requested] in [Confidential Treatment Requested]. This is followed by
a further incubation for [Confidential Treatment Requested] at [Confidential
Treatment Requested]. Affinity purified [Confidential Treatment Requested] is
labeled with [Confidential Treatment Requested] by standard techniques and
diluted in [Confidential Treatment Requested] buffered [Confidential Treatment
Requested] containing [Confidential Treatment Requested] treated [Confidential
Treatment Requested] and [Confidential Treatment Requested]. [Confidential
Treatment Requested] of this solution yields approximately [Confidential
Treatment Requested]. Pooled HIV1 positive serum was obtained from
[Confidential Treatment Requested]. HIV2 positive serum and HIV1 seroconversion
panels were obtained from [Confidential Treatment Requested]. Control samples
were obtained from the [Confidential Treatment Requested] and [Confidential
Treatment Requested].
Sample diluent is [Confidential Treatment Requested] containing [Confidential
Treatment Requested] and [Confidential Treatment Requested].
ASSAY PROTOCOL
1. Pipette [Confidential Treatment Requested] sample diluent into each well
2. Add [Confidential Treatment Requested] sample or control
3. Mix by addition of a further [Confidential Treatment Requested] sample
diluent
4. Incubate [Confidential Treatment Requested] at [Confidential Treatment
Requested] with [Confidential Treatment Requested]
5. Wash [Confidential Treatment Requested] in [Confidential Treatment
Requested]
6. Add [Confidential Treatment Requested] labeled antibody
7. Incubate [Confidential Treatment Requested] with [Confidential Treatment
Requested]
8. Wash [Confidential Treatment Requested] in [Confidential Treatment
Requested]
9. Read each well for [Confidential Treatment Requested] in plate luminometer
SCREENING TEST FOR HEPATITIS B SURFACE ANTIGEN
INTRODUCTION
Hepatitis B represents a significant global health problem. Because of its
mode of transmission through biological fluids, it is of particular concern
to the blood transfusion services since the disease will invariably affect
those who receive infected blood.
The cause of infection is the hepatitis B virus (HBV) which, in its intact form
is known as a Dane particle. This particle is of 42 nm diameter, though
infected blood may contain large quantities of viral envelopes as 22 nm spheres
or as filaments. These particles incorporate the hepatitis B surface antigen
(HBSAg) which is a specific marker of HBV infection. HBSAg comprises a group
determinant and two sets of mutually exclusive sub-type determinants which
produce the sub-types adw, adr, ayw and ayr.
Detection of the presence of immunoreactive HBSAg in serum or plasma is
diagnostic of HBV infection.
METHOD
The method described below is a [Confidential Treatment Requested] assay in
which the solid-phase antibody comprises a mixture of [Confidential Treatment
Requested] and [Confidential Treatment Requested] antibodies [Confidential
Treatment Requested] to the xxxxx of microtitre strips or plates and the labeled
reagent is a mixture of [Confidential Treatment Requested] incorporating a
[Confidential Treatment Requested]. The serum sample is incubated in a well
together with an aliquot of [Confidential Treatment Requested] and after
reaction, the xxxxx are washed to remove unbound material. The plate carrying
the xxxxx is transferred to a [Confidential Treatment Requested] to detect the
presence of bound immune complexes. Results are analyzed by comparison with
test xxxxx containing samples of positive and negative controls.
DESCRIPTION
Microtitre plates or strips [Confidential Treatment Requested] are coated with a
mixture of [Confidential Treatment Requested] and [Confidential Treatment
Requested] antibody. Coating is carried out by [Confidential Treatment
Requested] by [Confidential Treatment Requested] reaction in [Confidential
Treatment Requested]. After washing with [Confidential Treatment Requested] the
plates are blocked with [Confidential Treatment Requested] for [Confidential
Treatment Requested] hours at [Confidential Treatment Requested]. The plates
are washed again and then vacuum dried prior to storage in sealed bags.
Two [Confidential Treatment Requested] antibodies are labeled with [Confidential
Treatment Requested] by standard methods and are used in solution in
[Confidential Treatment Requested] supplemented with [Confidential Treatment
Requested] and [Confidential Treatment Requested]. Approximately [Confidential
Treatment Requested] are added to each well in a volume of [Confidential
Treatment Requested].
PROTOCOL
1. Dispense [Confidential Treatment Requested] test sample or control into
each well
2. Add [Confidential Treatment Requested] labeled antibody and cover plate
3. Incubate at [Confidential Treatment Requested] for [Confidential Treatment
Requested] with shaking
4. Wash plate [Confidential Treatment Requested] with [Confidential Treatment
Requested]
5. Transfer plate to [Confidential Treatment Requested] and read each well for
[Confidential Treatment Requested].
IMMUNOCHEMILUMINOMETRIC ASSAY FOR
THYROGLOBULN ANTIBODIES
INTRODUCTION
Autoimmune thyroid disease is characterized by the production of antibodies to
various thyroid proteins. Thyroglobulin (Tg) is one such protein and the
detection of circulating antibodies to Tg is indicative of autoimmunity.
METHOD
The present assay for Tg antibodies involves [Confidential Treatment Requested]
of Tg onto [Confidential Treatment Requested] tubes to which the serum sample is
added. Following [Confidential Treatment Requested] and washing, anti-Tg
antibodies, if present, are detected using [Confidential Treatment Requested]
labeled [Confidential Treatment Requested] which binds to the human
Immunoglobulin.
DESCRIPTION
[Confidential Treatment Requested] tubes are coated with [Confidential Treatment
Requested] using standard conditions. [Confidential Treatment Requested] is
labeled with [Confidential Treatment Requested] in the usual manner.
Purified Tg is labeled with [Confidential Treatment Requested] Co.) according to
the Manufacturer's instructions.
The test is designed to be used with a [Confidential Treatment Requested] serum
sample.
PROTOCOL
1. Dispense [Confidential Treatment Requested] of sample into
[Confidential Treatment Requested] coated tube
2. Add [Confidential Treatment Requested] solution and vortex
3. Incubate for [Confidential Treatment Requested]
4. Aspirate and wash [Confidential Treatment Requested] with wash
solution
5. Add [Confidential Treatment Requested] of [Confidential Treatment
Requested] solution
6. Incubate for [Confidential Treatment Requested]
7. Aspirate and wash [Confidential Treatment Requested]
8. Measure tubes for [Confidential Treatment Requested] in [Confidential
Treatment Requested]
PERFORMANCE
Limit of detection: [Confidential Treatment Requested] TgAb activity
Precision: [Confidential Treatment Requested] CV intra-assay over range
Range: [Confidential Treatment Requested] U/ml
IMMUNOCHEMILUMINOMETRIC ASSAY FOR
THYROID PEROXIDASE ANTIBODIES
INTRODUCTION
Autoimmune thyroid disease is characterized by the production of antibodies to
various thyroid proteins. Thyroid peroxidase (TPO) is one such protein and the
detection of circulating antibodies to TPO is indicative of thyroid
autoimmunity.
METHOD
The present assay for TPO antibodies involves indirect [Confidential Treatment
Requested] of TPO onto [Confidential Treatment Requested] tubes to which the
serum sample is added. Following aspiration and washing, anti-TPO antibodies,
if present, are detected using [Confidential Treatment Requested] labelled
[Confidential Treatment Requested] which binds to the human immunoglobulin.
DESCRIPTION
[Confidential Treatment Requested] tubes are coated with [Confidential Treatment
Requested] using standard conditions. [Confidential Treatment Requested] is
labeled with [Confidential Treatment Requested] in the usual manner.
Purified TPO is labeled with [Confidential Treatment Requested] Co.) according
to the Manufacturer's instructions.
The test is designed to be used with a [Confidential Treatment Requested] serum
sample.
PROTOCOL
1. Dispense [Confidential Treatment Requested] of sample into
[Confidential Treatment Requested] coated tube
2. Add [Confidential Treatment Requested] of [Confidential Treatment
Requested] solution and vortex
3. Incubate for [Confidential Treatment Requested] at [Confidential
Treatment Requested]
4. Aspirate and wash [Confidential Treatment Requested] with wash
solution
5. Add [Confidential Treatment Requested] of [Confidential Treatment
Requested] solution
6. Incubate for [Confidential Treatment Requested] at [Confidential
Treatment Requested]
7. Aspirate and wash [Confidential Treatment Requested] times
8. Measure tubes for [Confidential Treatment Requested] in [Confidential
Treatment Requested]
PERFORMANCE
Limit of detection: [Confidential Treatment Requested]
Precision: [Confidential Treatment Requested] CV intra-assay over range
Range: [Confidential Treatment Requested] U/ml
CHEMILUMINESCENT RECEPTOR ASSAY FOR
THYROTROPHIN RECEPTOR ANTIBODIES
INTRODUCTION
Autoimmune thyroid disease is characterized by the production of antibodies to
various thyroid proteins. Thyrotrophin receptor (TR) is one such protein and
the detection of circulating antibodies to TR is important in the diagnosis and
management of autoimmune hyperthyroidism (Xxxxxx' Disease).
METHOD
The present assay for TR antibodies (TRAb) involves incubation of the serum
sample with a [Confidential Treatment Requested] preparation in the presence of
[Confidential Treatment Requested] labeled[Confidential Treatment Requested].
The presence of TRAb prevents binding of the labeled [Confidential Treatment
Requested] to the
receptor. Receptor-bound [Confidential Treatment Requested]activity is thus
[Confidential Treatment Requested] to TRAb activity. Receptor-bound
complexes are separated by [Confidential Treatment Requested]precipitation.
DESCRIPTION
[Confidential Treatment Requested] tubes are used as reaction tubes.
[Confidential Treatment Requested] is labeled with [Confidential Treatment
Requested] using established methods.
[Confidential Treatment Requested] receptors are isolated from [Confidential
Treatment Requested] using published methods.
The test is designed to be used with a [Confidential Treatment Requested] serum
sample.
PROTOCOL
1) Dispense [Confidential Treatment Requested] of serum sample into tube
2) Add [Confidential Treatment Requested] of receptor solution
3) Incubate [Confidential Treatment Requested] at [Confidential Treatment
Requested]
4) Add [Confidential Treatment Requested] of [Confidential Treatment
Requested] labeled [Confidential Treatment Requested] solution
5) Incubate [Confidential Treatment Requested]
6) Add [Confidential Treatment Requested] solution, vortex
7) Centrifuge for [Confidential Treatment Requested] at [Confidential
Treatment Requested]
8). Aspirate supernatant
9) Resuspend pellet in [Confidential Treatment Requested] deionized water
10) Measure tubes for [Confidential Treatment Requested] in [Confidential
Treatment Requested]
PERFORMANCE
Limit of detection: [Confidential Treatment Requested] TRAb activity
Precision: [Confidential Treatment Requested] intra-assay over range
Range: [Confidential Treatment Requested] U/ml
SCHEDULE B
Page ___
SCHEDULE B
UWCM PATENTS
CASE WCM 3: LUMINESCENT PROTEIN LABELING
COUNTRY PATENT # FILED PRIORITY EXPIRY
------- -------- ----- -------- ------
GB 2008247B 14/11/78 17/11/77 14/11/98
Canada 1113392 16/11/78 17/11/77 01/12/98
Germany 2849708 16/11/78 17/11/77 Lapsed
Switzerland 640061 13/11/78 17/11/77 13/11/98
France 7832459 17/11/78 17/11/77 17/11/98
USA 4478817 14/11/78 17/11/77 23/10/01
CASE WCM 3 (DIVISIONAL) HOMOGENEOUS ASSAY
COUNTRY PATENT # FILED PRIORITY EXPIRY
------- -------- ----- -------- ------
GB 2095830B 01/11/81 17/11/77 14/11/98
Germany 2858792 07/06/89 17/11/77 17/11/98
Switzerland 645725 13/12/83 17/11/77 13/11/98
Canada 1116079 27/3/81 17/11/77 12/01/99
CASE WCM 13: ACRIDINIUM LABELS
COUNTRY PATENT # FILED PRIORITY EXPIRY
------- -------- ----- -------- ------
GB 2112779B 08/12/82 11/12/81 08/12/02
Europe* 0082636 08/12/82 11/12/81 08/12/02
USA# 4946958 26/09/88 11/12/81 07/08/07
CASE WCM 16: MASS PHOTON IMMUNOASSAY
COUNTRY PATENT # FILED PRIORITY EXPIRY
------- -------- ----- -------- ------
GB 2129553B 09/09/83 10/09/82 09/09/03
Europe** 0103469 09/09/83 10/09/82 09/09/03
USA 4761382 05/02/87 10/09/82 02/08/05
Japan Pending 29/12/83 10/09/82 29/12/03
*France, Germany, Holland, Switzerland
**Belgium, France, Germany, Italy, Holland, Switzerland
UWCM PATENT APPLICATIONS
#US Continuation Applications 08/328563 filed 24/10/94 and 08/455414 filed
31/05/95 are still pending.
BIOANALYSIS PATENTS
None
BIOANALYSIS PATENT APPLICATIONS
None
