Note: Confidential treatment requested. Exhibit omits information that has
been filed separately with the Securities and Exchange Commission.
RESEARCH AGREEMENT
THIS RESEARCH AGREEMENT is effective this 1st day of July, 1996, by and
between OSTEX INTERNATIONAL, INC., a Washington corporation, having its
principal place of business at 2203 Airport Way South, Suite 400, Seattle,
Washington 98134 ("Ostex"), and the UNIVERSITY OF WASHINGTON, having its
principal office at Seattle, Washington 98195 ("University").
RECITALS
A. Ostex has an ongoing interest in research technology (including
inventions, processes, formulae and the like, whether or not patentable, and
property eligible for copyright protection) for measuring the rate of human
tissue resorption based on the quantitation of specific marker peptides derived
from cross-linking sequences in collagen, entitled "Molecular Markers of
Connective Tissue Degradation," as more particularly described in that certain
proposal attached as EXHIBIT A (the "Technology");
B. The Technology has been assigned by the University to the Washington
Research Foundation ("WRF") pursuant to Section 3.3 of that certain Technology
Administration Agreement, dated January 1, 1985, between the University and WRF,
as amended (the "UW Agreement"). Pursuant to that certain Restated Exclusive
License Agreement between Ostex and WRF, effective June 29, 1992, as amended
(the "Exclusive License Agreement"), WRF granted Ostex an exclusive, worldwide
license to make, have made, assign, sublicense, lease, develop, enhance, modify,
produce, reproduce, demonstrate, market, promote, sell, distribute, use, exploit
and otherwise commercialize and prepare derivations of the Technology;
C. Ostex entered into a Research Agreement dated July 26,
1989 and amended November 1, 1992 pursuant to which initial funding was
provided by Ostex for research with respect to the Technology;
D. It is in the mutual interest of Ostex and University
that research be continued with respect to the Technology, in accordance
with a research program to be conducted and funded pursuant to this Agreement
(the "Research Program"); and
E. Ostex is willing to fund the conduct of the Research Program, at and
through the University of Washington, Department of Biological Structure, and
the University desires to obtain such funding, all subject to and in accordance
with the terms of conditions set forth in this Agreement.
AGREEMENTS
In consideration of the covenants and promises contained herein and for
good and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:
1. SCOPE/SCHEDULE
The Research Program shall be conducted in accordance with the Research
Proposal attached hereto as EXHIBIT A and made a part hereof, or mutually
agreeable written modifications thereof. The Research Program shall be carried
out during the Program Period (as defined below), unless sooner terminated or
extended as herein provided.
2. PROGRAM PERIOD
The Program Period shall be from XXXXXXXXXXXXXXXXX, and it may be
extended
by mutual written consent of the parties not less than thirty (30) days prior to
the termination of the then current Program Period.
3. OSTEX'S PRINCIPAL OBLIGATIONS
Ostex shall pay University a total of XXXXXXXXXXXXXXX to cover all
direct and indirect costs of the Research Program asset forth in the Budget
included in the Research Proposal attached hereto as
EXHIBIT A and incorporated herein.
4. PAYMENT
Ostex will provide University funds for the costs of the research
performed under this Agreement as specified in the Budget. Ostex shall pay
University as follows upon receipt of invoices from University:
PAYMENT DATE AMOUNT
1 XXXX XXXX
2 XXXX XXXX
3 XXXX XXXX
4 XXXX XXXX
5 XXXX XXXX
6 XXXX XXXX
7 XXXX XXXX
8 XXXX XXXX
9 XXXX XXXX
10 XXXX XXXX
11 XXXX XXXX
12 XXXX XXXX
Total XXXX
University will submit its customary statement of expenses incurred under this
Agreement within thirty (30) days after the end of each six-month period.
5. PRINCIPAL INVESTIGATOR
For the purpose of this Agreement and pursuant to University policy,
David R. Eyre is designated the Principal Investigator ("Principal
Investigator") who shall be responsible for direction and content of the
Research Program, including budgeting and revisions to the Budget necessary to
accomplish the Research Program. Should the Principal Investigator leave the
University or otherwise become unavailable during the Program Period, University
may nominate a replacement. If Ostex does not accept the replacement, the
Research Program and Budget may be modified to reflect a reduced scope of work
or terminated on sixty (60) days' notice at the option of Ostex unless an
arrangement acceptable to Ostex can be made to subcontract with the departed
Principal Investigator or his new institution to continue the work on the
Research Program.
6. CONFIDENTIALITY
Neither party shall furnish any confidential and/or proprietary
information of a third party to the other party in connection with this
Agreement. Any such information which either party wishes to furnish to the
other party shall be the subject of a separate confidentiality agreement between
the parties.
7. DATA REPORTS AND FACILITIES
7.1 University shall, in accordance with established
University practice, keep complete, accurate, and authentic accounts, notes,
data, and records of the work performed under this Agreement and shall provide
Ostex with semi-annual reports within thirty (30) days following the end of each
six-month period commencing on the date of this Agreement. University shall also
submit to Ostex a written comprehensive final report within ninety (90) days of
termination of the Research Program.
7.2 At the discretion and convenience of the Principal
Investigator, during the course of the Research Program, Ostex's representatives
and others designated by Ostex may be present as observers while various tests,
inspections and other aspects of the Research Program are being conducted.
Ostex's representatives may consult informally with the Principal Investigator
regarding the Research Program both personally and by telephone. Further, Ostex,
at its expense, shall have the right to send one Ostex employee to work and be
trained at the Department of Orthopedics at the University. University
acknowledges and agrees that the Principal Investigator may serve as a member of
the board of directors and/or as a consultant (but not an officer) of Ostex
during the term of this Agreement.
7.3 From its own resources and those provided under this
Agreement, University agrees to make available laboratory facilities and
equipment for the Research Program.
8. INVENTION RIGHTS
8.1 University acknowledges and agrees that (i) all Technology
made, developed or conceived on or before the date of this Agreement has been
assigned to WRF pursuant to Section 3.3 of the UW Agreement, and no commitments
have been made with respect to such Technology pursuant to Section 3.2 of the UW
Agreement, (ii) all Technology made, developed or conceived after the date of
this Agreement will be submitted to WRF pursuant to Section 3.1 of the UW
Agreement, (iii) no commitment will be made pursuant to Section 3.1 of the UW
Agreement with respect to Technology made, developed or conceived after the date
of this Agreement unless Ostex agrees to such commitment in writing, and (iv)
University shall not terminate, amend, waive or enforce the UW Agreement (or any
rights or obligations thereunder) in any manner that could adversely affect
Ostex's rights under this Agreement unless Ostex agrees in writing to such
termination, amendment, waiver or enforcement.
8.2 University shall have no right, title or interest in any
Technology made, developed or conceived by employees or consultants of Ostex
entirely without use of University facilities.
9. PUBLICATION
University will be free to publish the results of research conducted
under this Agreement within a reasonable period of time. University will provide
copies of manuscripts to Ostex prior to their submission for publication or
their presentation. In order to full protect the rights of University and Ostex,
any contemplated publication or other dissemination containing details of an
invention, whether or not patentable, will be withheld until a patent
application is filed or other appropriate steps to protect commercial value have
been completed. Such withholding shall be kept to a minimum and will not exceed
six (6) months, except by mutual agreement between Ostex and University.
10. INDEMNIFICATION
University and Ostex each agree to indemnify and to hold harmless the
other party from damage to persons or property resulting from any act or
omission on the part of itself, its employees, its agents, or its officers.
11. NOTICES
Whenever any notice is to be given hereunder, it shall be in writing
and shall be deemed received, if delivered by courier on a business day, on the
day delivered, or on the fifth business day following mailing, if sent by
first-class, certified or registered mail, postage prepaid, to the following
addresses:
University: Director, Grant and Contract Services
3935 University Way N.E., JM-24
Seattle, Washington 98195
Ostex: Ostex International, Inc.
2203 Airport Way South, Suite 301
Seattle, Washington 98134
12. TERMINATION
12.1 This Agreement may be terminated by University at any
time or by Ostex at any time on or after XXXXXXXX. Sixty (60) days' prior
written notice is needed from one party to the other if either party
determines, in its discretion, that the Research Program is no longer
academically, technically or commercially feasible. Upon receipt or delivery of
such notice of termination, University shall exert its best efforts to limit or
terminate any outstanding financial commitments for which Ostex is to be liable,
and Ostex shall reimburse University (to the extent not previously paid) for all
costs incurred by it for the Research Program, including, without limitation,
all uncancellable obligations. University shall furnish, within sixty (60) days
of the effective date of termination, a final report of all costs incurred and
all funds received and shall reimburse Ostex for payments which may have been
advanced in excess of total costs incurred with no further obligations to Ostex.
12.2 Notwithstanding paragraph 12.1, in the event that either
party shall be in default of any of its obligations under this Agreement and
shall fail to remedy such default within thirty (30) days after written notice
thereof, the party not in default shall have the option of terminating this
Agreement by giving written notice of termination to the defaulting party.
12.3 Termination of this Agreement shall not affect the rights
and obligations of the parties accrued prior to termination or the rights and
obligations set forth in Article 8.
13. WARRANTS AND COVENANTS BY UNIVERSITY
13.1 University hereby warrants that it has the right and
authority to enter into this Agreement and that the representatives whose
signatures appear hereunder are duly authorized by University to enter into this
Agreement on behalf of University.
13.2 University covenants that it will not knowingly enter
into agreements with any industrial and/or commercial funding source other than
Ostex inconsistent with its obligations under this Agreement.
14. APPLICABLE LAW
This Agreement shall be governed by the laws of the State of
Washington.
15. ARBITRATION AND JURISDICTION
15.1 At the request of either party, any controversy, claim,
or dispute arising out of or relating to any provision of this Agreement shall
be settled by arbitration to be conducted in Seattle, Washington. Such
arbitration shall be in accordance with the rules applied by the American
Arbitration Association. Judgment upon any award rendered through arbitration
may be entered into any court of competent jurisdiction.
15.2 Ostex and University agree to submit to jurisdiction
in Seattle, Washington.
16. PARTIES BOUND
This Agreement, including the indemnification provisions, shall be
binding upon and inure to the benefit of the parties hereto, their respective
successors, assigns, legal representatives and heirs. Ostex may assign this
Agreement to any successor to all or substantially all of the assets and
business of Ostex. This Agreement shall not otherwise be assignable by either
party without the prior written consent of the other party.
17. NO ORAL MODIFICATION
No change, modification, extension, termination or waiver of this
Agreement, or any of the provisions herein contained, shall be valid unless made
in writing and signed by duly authorized representatives of the parties hereto.
18. SURVIVORSHIP
Sections 8 and 9 of this Agreement shall survive any expiration or
termination of this Agreement.
19. USE OF NAMES
Neither party will use the name of the other party or its employees in
any advertisement, press release or publicity with respect to the Technology
without the prior written approval of the other party. University shall have the
right to acknowledge Osteonix's support of the research performed under this
Agreement in scientific publications and other scientific communications.
IN WITNESS WHEREOF, the undersigned have entered into this Agreement as
of the date first set forth above.
UNIVERSITY: OSTEX:
By /S/ DONALD W. ALLEN By ROBERT J. GLASER
------------------------------- ----------------
Donald W. Allen, Director Robert J. Glaser, COO
Grant and Contract Services
Date: 11/21/96 Date: 10/23/96
University of Washington
Seattle, Washington 98105
To: Ostex International, Inc.
Type of Support Requested: Research Grant (continuation)
Title of Project: Molecular Markers of Connective Tissue
Degredation
Principal Investigator: David R. Eyre
Amount Requested: XXXXXX (including indirect costs)
Funding Period; XXXXXXXXXX
University office to be Grant & Contract Services
contacted regarding 3935 University Way NE, Box 355754
negotiation of award: Seattle, Wa 98195
Tel: 206-543-4043
Official authorized to
give University approval: /S/ DONALD W. ALLEN
-------------------------
Donald W. Allen, Director
Grant & Contract Services
RESEARCH PROPOSAL
Title: Molecular Markers of Connective Tissue Degradation
Funding Period: XXXXXXXXXXXXXXXXXX
PI: David R. Eyre
Orthopaedic Research Laboratories
University of Washington
Box 356500
Seattle, WA 98195-6500
Sponsor: Ostex International, Inc.
H. Raymond Cairncross
Chairman and CEO
2203 Airport Way South
Seattle, WA 98134
SUMMARY
This is a continuation research proposal for an existing project,
"Molecular Markers of Connective Tissue Degredation", funded from July 1, 1989
to the present.XXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX.
BUDGET
Molecular Markers of Connective Tissue Degradation
(continuation project, XXXX)
XXXXXXXXXXXX
Personnel Position Effort Salary Fringe Total
- -------------- ----------- ------- ------ ------ ------
Lynne Atley, Ph.D. Post-doctoral fellow 100% XXX XXX XXX
Michael Harkey, Ph.D. Research Associate 50% XXX XXX XXX
MaryAnn Weis, B.S. Manager-Research 25% XXX XXX XXX
Ping Shao, B.S. Res. Technologist 100% XXX XXX XXX
Kristin Vosberg, B.S. Res. Technologist 100% XXX XXX XXX
Layne Norland, D.V.M. Graduate Student 100% XXX XXX XXX
Secretary 30% XXX XXX XXX
------
XXX
EQUIPMENT
Micro-titer plate washer, XXXX; water baths, XXXX; Microcentrifuge, XXXX;
Pulsed power supply, XXXX; Controlled environment shaker XXXX; Gel
electophoresis system XXXX; Purchase of HPLC system for peptide
fractionation, XXXX XXXX
SUPPLIES
XXXXXXXXXXXXXXXX
XXXXXXXXXXX and supplies
XXXXXXXXXXX and supplies
General chemicals and biochemicals
Plasticware, glassware and disposable XXXX
TRAVEL
Investigators to acedemic scientific meetings XXXX
DISCRETIONARY BUDGET(64 series, separate account)
To sponsor research seminars, conferences, meals, travel and
entertainment expenses for visiting scientists, seminar speakers
and visitors to the University on Ostex-related business XXXX
OTHER
XXXXXXXXXXXX
XXXXXXXXXXXX. Shared
Costs of service contracts on major equipment, equipment
repairs and replacement, photographic services, publication
costs, computer charges, copying, postage, courier services
and telephone charges. XXXX
------
Total Direct XXXX
(XX of modified total direct costs) UW indirect costs XXXX
--------
XXX Total XXXX
BUDGET FOR ENTIRE PROPOSED PROJECT-PERIOD
XXXX XXXX XXXX
XXXX XXXX XXXX
XXXX XXXX XXXX
XXXX XXXX XXXX
-------- ----- ---------
Salaries (+fringe benefits) XXXX XXXX XXXX
Equipment XXXX XXXX XXXX
Supplies XXXX XXXX XXXX
Travel XXXX XXXX XXXX
Discretionary XXXX XXXX XXXX
Other XXXX XXXX XXXX
-------- ------ ---------
Total direct costs XXXX XXXX XXXX
UW indirect costs XXXX XXXX XXXX
(XX of MTDC) --------- ------ ---------
Total XXXX XXXX XXXX
BUDGET JUSTIFICATION
The principal investigator, David Eyre, Ph.D., will direct the work
scientifically. Lynne Atley, who spent 6 months with us in 1994 as a visiting
scholar, will complete her Ph.D. requirements in Melbourne (University of
Melbourne) by April 1996 and join us as a post-doctoral fellow. She trained
under Drs. John Wark and Peter Ebeling with her thesis research on bone turnover
markers, and is keen to expand her knowledge of collagen biochemistry and work
on novel markers of skeletal metabolism. Working 100% on this project, her
efforts will focus on XXXXXXXXXXXXXXXXXXXXXas well as the application of the new
collagen-based markers (types II and III) in clinical XXXXXXX. Michael Harkey,
Ph.D. is a molecular biologist studying the XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX.
MaryAnn Weis, B.S. the laboratory's chief technician and research manager, runs
the gas-phase protein sequencer (a core resource for all the scientific aims)
and also has taken over project duties on O-CSF from Patricia Woods, B.S., who
left the laboratory in December 1995. Ping Shao, B.S., has worked full time on
the project for over four years. She has considerable experience in
XXXXXXXXXXXXX and in the running of immunoassays, including responsibility for
all NTx assays that we run in collaboration with outside investigators. Her
responsibility going forward will be the XXXXXXXXXXXXXXXX. Kristin Vosberg,
B.S., has worked full time on the project for over two years. Her experience is
in preparing antisera, running immunoassays including Western blots and in the
preparation and analysis of XXXXXXXXX. Her responsibility going forward will be
the development and XXXXXXXXXXXX. Layne Norland, D.V.M., is studying for a
Masters degree in the Dept. of Comparative Medicine. His research project is a
collaboration with our laboratory, to investigate whether XXXXXXXXXXXXXXXXX.
A. SPECIFIC AIMS
The primary focus of this project will continue to be...
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B. PROGRESS REPORT
The aims for the last three years in summary were to:
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PROGRESS
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C. RESEARCH PLAN
The scientific strategy is to ...
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D. PUBLICATIONS
The following papers and abstracts of meeting presentations from the Orthopedic
Research Laboratories have resulted from or are related to this project.
Articles
1. Niyibizi C, Bonadio J, Byers PH, Eyre DR. Incorporation of type I collagen
molecules that contain a mutant a2(l) chain (Gly580-greater than Asp) into
bone matrix in a lethal case of osteogenesis imperfecta. J ' Bioi.
Chem. 267:23108-23112,1992.
2. Bogaert R, Tiller GE, Weis MA, Gruber HE, Rimoin DL, Cohn DH, Eyre DR.
Substitution of glutamate for glycine 853 of the triple helical domain of type
11 collagen produces hypochondrogenesis. J. Biol. Chem. 267:22522-22526, 1992.
3. Harris ST, Gertz BJ, Eyre DR, Genant HK, Chesnut CH Ill. The effect of
short-term treatment with alendronate upon vertebral density and biochemical
markers of bone remodeling. J. Clin. Endocrinol. Meth. 76:1399-1407, 1993.
4. Ezzat S, Melmed S, Endrew D, Eyre DR, Singer FR. Biochemical assessment of
bone formation and resorption in acromegaly. J. Clin. Endocrinol. Metab.
76:1452- 1457, 1993.
5. Bolien AM, Eyre DR. Direct extraction of gelatinases
from rat bone. Connect. Tiss. Res. 29:223-230, 1993.
6. Gerstenfeld LC, Riva A, Hodgens K, Eyre DR, Landis WJ. Post-translational
control of collagen fibrillogenesis in a mineralizing chick osteoblast culture
system. Bone Miner. Res. 8:1031-1043, 1993.
7. Gertz BJ, Shao P, Hanson DA, Quan H, Harris ST, Genant HK, Chesnut CH 111,
Eyre DR. Monitoring bone resorption in early postmenopausal women by an
immunoassay for cross-linked collagen peptides in urine. J. Bone Miner Res.
9:135- 142, 1994.
8. Eyre, DR. New Molecular Markers of Bone Metabolism. Ther. Res. 15:1 00-1 1 1,
1994.
9. Bollen A-M, Eyre DR. Bone resorption rates in children monitored by the
urinary assay of collagen type I cross-linked peptides. Bone 15:31-34, 1994.
10. Bell NH, Hollis BW, Shary J, Eyre DR, Eastell R, Colwell A, Russell GRG.
Diclofenac sodium is as effective as premarin in inhibiting bone resorption in
postmenopausal women. Am. J. Med. 96:349-353, 1994.
11. Brenner RE, Vetter U, Bollen A-M, Mike M, Eyre DR. Bone resorption
assessed by immunoassay of urinary cross-linked collagen peptides in patients
with osteogenesis imperfecta. J. Bone Miner. Res. 9:933-937, 1994.
12. Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R. The effect
of calcium supplementation on the circadian rhythm of bone collagen degradation.
J. Clin. Endocrinol. Metab. 79:730-735, 1994.
13. Niyibizi C, Eyre DR. Structural characteristics of cross-linking sites in
type V collagen of bone: Chain specificity's and heterotypic links to type I
collagen. Eur. J. Biochem. 224:934-950, 1994.
14. Bogaert R, Wilkin D, Wilcox WR, Lachman R, Rimoin D, Cohn DH, Eyre DR.
Expression in cartilage of a 7-amino acid deletion in type 11 collagen from two
unrelated individuals with Kniest dysplasia. Am. J. Hum. Genet. 55:1128-1136,
1994.
15. Bockman RS, Wilhelm F, Siris E, Singer F, Chausmer A, Sitton R, Kotier J,
Bosco BJ, Eyre DR, Levenson D. A multicenter trial of low-dose gallium nitrate
in patients with advanced Paget's disease of bone. J. Clin. Endocrincl. Metab-
80:595-602, 1995.
16. Eyre DR, Wu J-J. Collagen structure and cartilage matrix integrity. J.
Rheumatol. 22(Suppl. 43):82-85, 1995.
17. Eyre DR. The specificity of collagen cross-links as markers of bone and
connective tissue degradation. Acta Orthop. Scand. 66(Suppi. 266):166-170, 1995.
18. Key Jr. LL, Rodriguez RM, Willi SM, Wright NM, Hatcher HC, Eyre DR, Cure JK,
Griffin PP, Ries WL. Long term treatment of osteopetrosis with recombinant human
interferon gamma: An 18 month clinical trial. N. Engl. J. Med.
332(24):1594-1599, 1995.
19. Wu J-J, Eyre DR. Structural analysis of cross-linking domains in cartilage
type Xi collagen: Insights on polymeric assembly. J. Biol. Chem.
270(32):18865-18870, 1995.
20. Tiller GE, Polumbo PA, Weis MA, Lachman RS, Cohn DH, Rimoin DL, Eyre DR.
Dominant mutations in the type 11 collagen gene (COL2Al) produce
spondyloepimetaphyseal dysplasia (SEMD), Strudwick type. Nature Genet.
11(l):87-89, 1995.
21. Steinmann B, Eyre DR, Shao P. Urinary pyridincline cross-links in
Ehlers-Danlos Syndrome type VI. Am. J. Hum. Genet. 1995; 57:1505-1508.
22. Bolien A-M, Martin MD, Leroux BG, Eyre DR. Circadian variation in urinary
excretion of bone collagen cross-links. J. Bone Miner. Res. 1995; 10(12):1885-
1890.
23. Diab M, Wu J-J, Eyre DR. Collagen type IX from human cartilage: A structural
profile of intermolecular cross-linking sites. Biochem. J. 3 14:327-332, 1996.
Abstracts
1 . Diab M, Shapiro F, Eyre DR. Abnormality of type IX collagen in diastrophic
dysplasia. Trans. Ortho. Res. Cos. (San Francisco (1 8)S 1): 1 20, 1993.
2. Caulfield MP, Morgan C, Carlton E, Brickman AS, Clemens JD, Eyre DR, Pandian
MR. Comparison of an immunoassay for cross-linked N-telopeptide of bone collagen
with HPLC detection of pyridinolines. The Endocrine Society, 1993.
3. Dickson IR, Arora MK, Coombes RC, Shao P, Eyre D. Pyridinolines and cross-
linked type 1 collagen N-telopeptides as markers of bone metastases in breast
cancer. J. Bone Miner. Res. 8(Sl):S288, 1993.
4. Lee MY, Woods PE, Lottsfeldt JL, Ramesh N, Osborne WRA, Eyre DR. Isolation
and molecular characterization of a murine osteoclast colony stimulating factor
(0- CSF). J. Bone Miner. Res. 8(Sl):Sl44, 1993.
5. Blumsohn A, Al-Dehaimi AW, Herrington K, Shao P, Eyre DR, Eastell R. Effect
of timing of calcium supplementation on the circadian rhythm of bone collagen
degradation. J. Bone Miner. Res. 8(Sl):Sl58, 1993.
6. Rodriguez RR, Ries WL, Eyre DR, Key LL. Type I collagen cross-linked N-
telopeptide excretion by osteopetrotic patients during interferon gamma therapy:
A correlation with bone biochemical and densitometric markers. J. Bone Miner.
Res. 8(Sl):S291, 1993.
7. Ebeling PR, Atley LM, Eyre DR, Guthrie J, Dennerstein L, Wark JD. Sensitivity
of type I collagen N-telopeptide cross-links in detecting early menopausal
changes in bone tumover. Proc. ANZ Bone Miner. Soc. A2, 1993.
8. Ebeling PR, Atley LM, Eyre DR, Shao P, Guthrie J, Dennerstein L, Wark JD.
Sensitivity of collagen N-telopeptide cross-links and osteocalcin in detecting
early menopausal changes in bone tumover. Abstract presented at the 4th
lntemational symposoium on Osteoporosis in Hong Kong, March 1993.
9. Fiedelius C, Eyre DR, Christiansen C. Urinary type I collagen cross-linked N-
telopetides: A new marker for bone resorption. Poster presented at the 4th
International Symposium on Osteoporosis in Hong Kong, March 1993.
10. Eyre DR, Bogaert R, Diab M, Hanson D, Knigge P, Niyibizi C, Weis MA, Wu ii.
Studies on the molecular structure of collagen heteropolymers in bone and
cartilage. Presented at the 5th International Conference on Osteogenesis
Imperfecta, September 27-30, 1993, Oxford, England.
11. Kanthawatana S, Eyre DR, Hendeles L. The effect of short course of oral
prednisone on a biochemical marker of bone resorption. Xllth Intemational
Congress of Pharmacology. Montr6al, Qu6bec, July 1994.
12. Apone S, Fevold K, Lee M, Eyre D. A rapid method for quantifying osteoclast
activity in vitro. J. Bone Miner. Res. 9(Sl):Al2O, p. S178, 1994.
13. Clemens JD, Herrick- M, Singer FR, Rosen HN, Shao P, Eyre DR. Cross-linked
N- telopeptides of type I collagen in human serum as a biochemical marker of
bone resorption. J. Bone Miner. Res. 9(Sl):A5-72, p. S228, 1994.
14. Prior JC, Eyre Dr, Ebeling PR, Wark, JD. Trabecular bone loss after
premenopausal oophorectomy is not prevented by con'ugated estrogen or
medroxyprogesterone--a double-blind, randomized 1-year study. J. Bone Miner.
Res. 9(Sl):C294, p. S394, 1994.
15. Key LL, Rodriguez RM, Hatcher H, Eyre DR, Ries WL. Long term treatment of
osteopetrotic patients with interferon gamma. J. Bone Miner. Res. 9(Sl):72, p.
S138, 1994.
16. Sowers M-F, Eyre, D, Hollis, BW. Changes in bone tumover markers and bone
density with lactation. J. Bone Miner. Res. g(Sl):A512, p. S2p7, 1994.
17. Jackson G, Hollis BW, Eyre DR, Baylink DJ, Bell NH. Effects of race and
calcium intake on bone markers and calcium metabolism in young adult men. J.
Bone Miner. Res. 9(S 1):Al 78, p. S 1 85, 1994.
18. Ebeling PR, Eyre DR, Gurthrie J, Dennerstein L, Wark JDF. Prediction of
early menopausal bone loss by biochemical markers of bone turnover. Amer. Soc.
Bone Miner. Res., Kansas City, MO, September 1994.
19. Wu JJ, Murray J, Eyre DR. Evidence foi copolymeric cross-linking between
types 11 and Ill collagens in human articular cartilage. ORS, Atlanta, 1996.
20. lchimura S, Wu JJ, Eyre DR. A sensitive method for collagen type IX peptide-
mapping in human cartilage. ORS, Atlanta, 1996.
21. Wang C, Eyre DR, Clark R, Kleinberg D, lranmanesh A, Dudley RE, Berman N,
Swerdloff RS. Sublingual testosterone replacement decreases bone resorption and
increase bone formation markers in hypogonadal men. Int. Congress of
Endocrinol., 1996.
University of Washington Hazardous Materials Use
Complete and Return to
Environmental Health and Safety GS-05
A. Principal Investigator: David R. Eyre. Ph.D.
B. Department: Orthopaedics
C. Building: Health Sciences Room #: BB1052
D. Phone No.: 543-4700
E. Mail Stop: Box 356500
F. Co-investigator(s) _________________________ ______________________
========================= ======================
G Title of Project or Proposal.
Molecular Markers of Connective Tissue Degradation
Yes No
1. Will Hazardous Materials be used or stored in your laboratory? x
2. Have you and your employees received Hazard Communication training? x
3. Will your research include the use of substances of high acute toxicity, x
reproductive toxins, carcinogens, mutagens, or teratogens?
4. Is there a chemical inventory available for your laboratory? x
5. Do you have access to a computer that is in or near your laboratory for the
purpose of accessing networked safety information? x
6. Are you familiar with the UW's Hazardous Waste Disposal Guidelines? x
7. Doe your laboratory contain the following?
A. X FIRE EXTINGUISHERS?
B. X FLAMMABLE LIQUID STORAGE CABINETS?
C. X BIOLOGICAL SAFETY CABINETS?
D. X FUME HOODS (ANY TYPE)?
E. _ RESPIRATORS AND REPLACEMENT CARTRIDGES?
F. X PROTECTIVE GLOVES (LATEX, NITRILE, VINYL, ETC.)?
G. X COMPRESSED GASES?
H. X EYE WASHES?
I. X EMERGENCY SHOWER WITHIN 100 FT. OF THE LAB?
J. X ROOM WINDOWS THAT OPEN?
8. Please list on the back of this form any special hazards or precautions
associated with the use of chemicals in your research?
University of Washington Biohazard Activity Review
Complete and Return to
Environmental Heath and Safety Box 354400
A. Principal Investigator: David R. Eyre. Ph.D.
B. Department: Orthopaedics
C. Building: Health Sciences LAB Room #: BB1052, 1054, 1032
D. Phone No.: 543-4700
E. Box: 356500 E-Mail: ntx@u.washington.edu
F. Co-investigator(s) _________________________ ______________________
========================= ======================
G Title of Project or Proposal.
Molecular Markers of Connective Tissue Degradation
__ Check here if project is non-competitive renewal and skip to Section M
Yes No
H. Is your lab engaged in the following areas of biohazard activity?
1. Activities involving non-human primates, including blood, tissues and/or
body fluids from non-human primates. __ x
2. Activities involving other animals or animal blood and tissues:
Animal Type: XXXXXX
a. Commercially raised laboratory animals. x __
b. Feral (wild caught) animals. __ x
3. Activities involving human blood, tissues, body fluids and excreta.
a. Have all personnel received Hepatitis B vaccinations?
(See UW Exposure Control Plan or call 543-7278 for
more information.) x __
b. Does the laboratory have an exposure control plan?
(if yes, answer Section I. below.) x __
4. Activities involving contact with cultures or specimens which may contain
microorganisms (including viruses). Culture Type: ___________ __ x
5. Activities involving recombinant DNA. (All projects involving recombinant
DNA must be registered with the UW Recombinant DNA Committee,
regardless of containment level. See Section III., pages 2-5 of the
"University
Biohazard Safety Manual" or call EH&S at 543-7278 regarding non-competitive
grant renewals.) __ x
I. Does your laboratory exposure control plan cover:
1. Procedures on use of personal protective equipment and
clothing? x __
2. Procedures for handling hypodermic needles, glass, pipettes
and biological wastes? x __
3. Immunization and medical surveillance program(s)? x __
4. Personnel training? x __
If the answer to any or part of section H. is "Yes" , please complete the next
page.
University of Washington
Biohazard Activity Review
Page 2 of 2
Another
J. Does this project require the use of? In Lab* Location
1. Laminar flow biological safety cabinets. x __
2. Centrifuge x __
3. Autoclave x __
4. Sonication Equipment x __
*equipment located in rooms listed on first page.
K. Submit the following with this form.
1 . A copy of the GC-1 form.
2. An assessment of the possible risks from biohazards and a
brief summary of the biosafety
precautions followed.
3. Any comments received from departmental review of the project.
4. A summary of the proposed project written in lay terms and/or
a copy of the application
being submitted for grant support
L. If Class III agents* are involved submit the following additional information
with this form:
1. A resume of the training and experience of each person who
will participate in the project
2. A description of laboratory facilities available including
containment equipment such as biological safety cabinets, etc.
Include a statement by Environmental Heath and Safety
assessing the adequacy of containment facilities.
+ Consult UW Biosafety Manual for classification of agents.
Note: Work with Class IV agents will not be approved at the
University of Washington as appropriate facilities are not
available.
M. If this is a non-competitive renewal of funded grant and there are no
significant changes in the project from
the original submittal, submit the following:
a. A copy of the new GC-1 form.
b. a brief summary of the new year's proposed activity.
For more information contact
EH&S Biosafety Specialist at 543-7278
Form HS SR-1 trev
BOX FOR COMMITTEE USE ONLY
MASTER ___
COMMITTEE ___
REVIEWER ___
INVESTIGATOR X
25-763-E
APPLICATION NUMBER
UNIVERSITY OF WASHINGTON
HUMAN SUBJECTS DIVISION BOX 355752
STATUS REPORT: Application no. 24-112-E
__ DO NOT RENEW. Complete items 1-6 of Status Report and return form.
XX RENEW WITH MINOR OR NO CHANGES. Complete items 1-10 of Status Report;
- -- submit one original plus three (3) copies of this form.
RENEW WITH CHANGES IN PROCEDURES, POPULATION, OR PURPOSE: Complete
and submit nine (9) copies of a new HSRC application (UW 13-11) and
this Status Report (items 1-10).
Investigator's name, position, division and department, mail stop and telephone
number:
David R. Eyre, Ph.D., Professor, Dept. of Orthopaedics, Box 356500, 543-4700
Title of Human Subjects Application:
Connective Tissue Research XXXXXXXXXXXXXXXXXXXXXXXXXXXX
Brief summary of findings to date (add sheets if necessary):
SEE ATTACHED
4. Number and types of adverse events. complaints, and withdrawals and
how they were handled (add sheets if necessary):
NONE.
5. No. of subjects enrolled in study to date:
XX Normals/Controls XX Patients/Cases
6. No. of subjects added during past year of approval:
XX Normals/Controls XX Patients/Cases
7. No. of subjects continuing participation: N/A See attached.
XX Normals/Controls XX Patients/Cases
8. How many new subjects will join the study over the next year?
XX Normals/Controls XX Patients/Cases
9. Do you propose any minor changes in this study or consent form?
X No. ___ Yes. If yes, describe (add sheets if necessary).
Submit 4 copies of revised consent form and other materials, if appropriate.
10. Provide information for all funding, awarded or proposed for this activity
(add sheets if necessary).
Type: XX research grant, __ contract, __ fellowship, __training grant,
__ other, explain:
Name of principal investigator: David R. Eyre, Ph.D.
Name of agency: SEE ATTACHED. Agency's no. (if assigned):
Title of proposal: SEE ATTACHED SEE ATTACHED
Inclusive dates: from SEE ATTACHED, through ________________
Submitted through Grant and Contract Services? __ No XX Yes __ VAMC __Other:
HSRC Chair's signature: ____________________ Date June 08, 1995 Approve XX
Disapprove __
Subject to the following conditions:
Period of approval is one year, from 06-08-95 through 06-07-96.
* VALID ONLY AS LONG AS APPROVED PROCEDURES ARE FOLLOWED *
Washington, Comparative Medic 01/30/1996
- - Protocol Description
Eyre, David R. BOX 356500
PROTOCOL: 2547-03 Last Update: 01/30/1996
Immunoassay Assessment of Type I and Type II Collagen Degradation in the
Received: 11/15/1995 Approved: 11/16/1995 Sig. Chg.: 01/25/1996
Expires: 11/15/1996 Vet Appr.: 01/25/1996
Funding sources: Ostex International
PI: Eyre, David R. Mail: BOX 356500 S/D: / Orthopaedics
Contacts: Function Phone Emergency
Norlund, Layne C 543-0474/ 685-8932
Species: 11 XXXXXXXXXXX Strain: XXXXXXX
Vivarium: 01 Lab Room: 01 G609,D604 Oper. Room:
1 2 3 4 Total
Approved: X X X X XXX
Ordered: XXX X X X XXX
Adjusted: XX X X X XX
Remaining: XX X X X XX
Y-Drug administration Y-Blood sampling Y-Euthanasia
Y-Collection of tissue Y-Withhold meds
NO CONDITIONS
Protocol Summary:
21. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX