RESEARCH SERVICES AGREEMENT
This
Research Services Agreement (“Agreement”) is entered into this 4th day of May,
2007, (the “Effective Date”) by and between Rosetta Genomics, Ltd., an Israeli
corporation, having its principal place of business at 00 Xxxxx Xxxxxx, Xxxxxxx,
Xxxxxx 00000 (“Rosetta”), and The Trustees of Columbia University in the City of
New York, having a principal place of business at x/x Xxxxxxx & Xxxxxxxxxx
Xxxxxxxx, Xxxxxxxx University, 630 West 168th
Street,
PH 0000 Xxxx, Xxx Xxxx, Xxx Xxxx 00000 (“University”). Rosetta and University
may be referred to individually as a “Party” or collectively as
“Parties.”
RECITALS
WHEREAS,
Rosetta is engaged in the research and development of in vitro diagnostic tests
and has developed an algorithm based on a large number of microRNA in different
tumor types to identify Cancer of Unknown Primer (the “Test”); and
WHEREAS,
Rosetta requires the assistance of a CLIA and CAP (as such terms are hereinafter
defined) certified laboratory to validate, approve and perform the Test and
provide other research services (the “Research”); and
WHEREAS,
University is a research teaching institution and is interested in the
advancement of science and medicine; and
WHEREAS,
University provides CLIA and CAP certified laboratory testing services,
validates analytical methods and possesses the necessary technical capabilities,
equipment and facilities for the provision of the Services; and
WHEREAS,
Rosetta desires University to provide the Research; and
WHEREAS,
University is willing to provide the Research on the terms and conditions set
forth below.
NOW,
THEREFORE, in consideration of the mutual promises contained herein, and for
other good and valuable consideration, the receipt and adequacy of which each
of
the Parties does hereby acknowledge, the Parties, intending to be legally bound,
agree as follows:
ARTICLE
I.
ENGAGEMENT
OF UNIVERSITY
Rosetta
hereby engages University to perform the Research in accordance with the terms
and conditions set forth herein, and University hereby accepts such
engagement.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
1 of
19
ARTICLE
II.
ROSETTA
OBLIGATIONS
2.1.
Rosetta shall provide University with information about its proprietary Test,
and the Parties shall mutually agree to the validation procedure included in
Exhibit A, attached hereto and incorporated by reference, as amended from time
to time by mutual agreement of the Parties (the “Protocol”). The Protocol sets
out the roles of and obligations undertaken by Rosetta and University under
this
Agreement. In the event of any inconsistency between this Agreement and the
exhibits thereto, the terms of the Agreement shall control.
2.2.
Rosetta, in its sole discretion, may purchase and make available to University
equipment that will be used solely by the University during the term of this
Agreement to perform the Research and University may, in its sole discretion,
accept such equipment. Upon termination or expiration of the Agreement, or
if
sooner requested in writing by Rosetta, University shall return such equipment
to Rosetta.
2.3.
Rosetta shall assist University to obtain the biological samples required to
validate the Test, in the event that University does not obtain the number
of
biological samples as required under the Protocol.
ARTICLE
III.
UNIVERSITY
OBLIGATIONS
3.1.
University will conduct the Research in a laboratory located at its Health
Sciences campus, under the direction of Xx. Xxxxxx Xxxxxxxxxx (the
“Laboratory”), in accordance with the Protocol.
3.2.
University will use reasonable efforts to validate the Test according to the
Protocol and shall provide the results in a form specified by Rosetta and agreed
to by the parties.
3.3.
University will use its reasonable efforts to obtain the number and type of
biological samples needed to validate the Test as specified in
Protocol.
3.4.
Upon
Rosetta’s written request, the University shall use reasonable efforts to
prepare its laboratory to perform the Test, including obtaining all required
reviews and approvals. University shall provide prompt written notice to Rosetta
as soon as it has completed the preparations and obtained the
approvals.
3.5.
University acknowledges that Rosetta intends to market the validated Test to
third parties. For a period of at least [***] months following Rosetta’s receipt
of the notice required in Section 3.4. (the “Trial Period”), the University
shall on a non-exclusive basis perform the Test.
3.6.
University shall perform the Research in accordance with all applicable laws
and
regulations, including the provisions of the Health Insurance Portability and
Accountability Act, that may apply to Research provided during the term of
this
Agreement.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
2 of
19
3.7.
University represents and warrants that as of the Effective Date, the Laboratory
is certified as a laboratory capable of performing the laboratory procedures
indicated on the CLIA and CAP certifications attached hereto as Exhibit B under
the Clinical Laboratory Improvement Amendments of 1988 (“CLIA”) and that it is
also certified by the College of American Pathologists (“CAP”). University shall
use best efforts to maintain the Laboratory’s CLIA and CAP certifications during
the term of this Agreement and shall notify Rosetta immediately if it loses
or
learns that it is about to lose either certification.
3.8.
In
situations when Rosetta provides material or equipment to University, University
shall use such material and equipment only for providing the Research.
University shall take due care to protect the equipment from damage, vandalism,
and theft and to prevent the use of the equipment for uses not outlined in
the
equipment operating manual.
3.9.
Upon
reasonable advance written notice, University shall permit representatives
of
Rosetta to have access at reasonable times to the facilities of University
where
the Research is performed for the sole purpose of observing the performance
of
the Research and/or reviewing the records, documentation or other data relating
to the Research. This provision shall survive termination or expiration of
this
Agreement for a period of [***] years.
ARTICLE
IV.
COMPENSATION
4.1.
Rosetta shall make payment to University for the support of the Research in
accordance with the fee and payment schedule included in Exhibit C, attached
hereto and incorporated by reference. University shall not xxxx any person
other
than Rosetta for the Research performed hereunder.
4.2.
Unless otherwise agreed to by the Parties, upon the occurrence of each payment
milestone University shall provide Rosetta with a separate invoice that
summarizes the Research performed during that relevant period. Rosetta shall
pay
University by check or wire transfer to a bank account designated in writing
by
University within fourteen (14) days of Rosetta’s receipt of an
invoice.
4.3.
Checks shall be drawn to the account of The Trustees of Columbia University
in
the City of New York, and mailed to the following address:
THE
TRUSTEES OF COLUMBIA UNIVERSITY
IN
THE
CITY OF NEW YORK
Columbia
University - Restricted Funds/STV
X.X.
Xxx
0000
Xxx
Xxxx,
XX 00000-0000
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
3 of
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ARTICLE
V.
TERM
AND TERMINATION
5.1.
This
Agreement shall commence on the Effective Date and shall expire the sooner
of a
period of two (2) years or through at the end of the Trial Period, unless
terminated earlier as provided herein or extended by mutual written consent
of
the Parties (“Research Period”). The parties may elect, upon mutual written
agreement, to lengthen the Trial Period for a period of additional six (6)
months (altogether twelve (12) months. If the Parties desire to extend their
relationship beyond the Trial Period and have University serve as a contract
laboratory to perform the Test on behalf of Rosetta, they will negotiate a
new
agreement for such services. University does not warrant that the Research
shall
be completed by the end of the Research Period.
5.2.
This
Agreement may be terminated:
(a)
by
Rosetta for any reason upon [***] days written notice to University;
provided that, Rosetta pays University all amounts due for the support of the
Research and any noncancellable commitments incurred by University as of the
date University receives Rosetta’s notification of its intent to terminate the
Agreement.
(b)
by
either Party if the other Party breaches a material provision of this Agreement
and fails to cure such breach to the reasonable satisfaction of the
non-breaching Party within thirty (30) days following written notification
of
such breach.
5.3.
In
the event of termination, University shall be compensated for Research performed
up to the date of termination.
5.4.
Effect of Expiration or Termination.
(a)
On
and as of the effective date of any termination or expiration, University shall
(i) promptly transfer all information in its possession used in providing the
Research including without limitation, all technical information and know-how
related to the validation of the Test, and all other information relating to
the
Research, including the results of the validation, that is useful to enable
Rosetta or a third party to perform the Test, make any regulatory submission,
or
provide Test results to medical professionals; and (ii) promptly return any
materials or equipment provided to it by Rosetta.; provided that, in the event
that the Agreement is terminated by University in accordance with Section
5.2(b), University will not be obligated to comply with Section 5.4(a)(i) and
all rights granted to Rosetta herein shall automatically terminate on the date
of termination of this Agreement.
(b)
Articles 2.2, 3.8, 4.l, 5.3, 5.4, VI, VII , IX, X and XI shall survive the
expiration or termination of this Agreement. In addition, University hereby
acknowledges that neither expiration nor termination of this Agreement shall
affect in any manner Rosetta’s right to perform or have the Test performed by
Rosetta or a third party.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
4 of
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ARTICLE
VI.
RESERCH
REPORTS AND INVENTIONS
(a)
All
data, reports, information, discoveries, or improvements developed by University
in the performance of the Research hereunder shall be provided to the Company
in
research reports (“Research Reports Information”). The Company may use the
Research Report Information for any purpose whatsoever, and the University
may
use the Research Report Information for non-commercial, internal and academic
purposes and in accordance with the publication provisions set forth in Sections
10.3
and
10.4.
(b)
Inventorship of any inventions shall be determined according to U.S. patent
laws
and ownership shall follow inventorship. University hereby grants to Rosetta
an
option to obtain an exclusive or a non-exclusive license, at Rosetta’s election,
through good faith negotiation and on commercially reasonable terms, to any
and
all of University’s rights in any invention developed by University under this
Agreement. This option to obtain the license shall extend for a period of six
(6)
months
following formal written disclosure of the invention to Rosetta.
ARTICLE
VII.
CONFIDENTIALITY
7.1.
As
of the Effective Date, University agrees to use its best efforts to treat all
Confidential Information (as described herein) disclosed by Rosetta under this
Agreement as being secret and confidential. For the purposes of this Agreement,
“Confidential Information” shall mean all confidential or proprietary materials
or information disclosed by an officer of Rosetta not generally available to
the
public that is confidential and proprietary to Rosetta, including, but not
limited to, all information regarding the Test, any analytical procedures,
processes, know-how, the Protocol and other information related to any test
that
may or will be under development. The parties agree that any information
disclosed by Rosetta to a non-officer of University shall only be considered
to
be Confidential Information under this Agreement if that non-officer executes
a
non-disclosure agreement with Rosetta. University shall not disclose the
Confidential Information nor use it for any purposes other than as required
in
the performance of its duties under this Agreement.
7.2.
The
provisions of Article 7.1 shall not apply to any information disclosed hereunder
that:
(a)
was
known to University prior to its date of disclosure by Rosetta as evidenced
by
University’s written records;
(b)
is
disclosed lawfully to University either before or after the date of the
disclosure by Rosetta, by a third party rightfully in possession of the
Confidential Information without an obligation of confidentiality;
(c)
is
published or generally known to the public, either before or after the date
of
disclosure through no fault or omission on the part of University;
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
5 of
19
(d)
is
independently developed by University without reference to or in reliance upon
the Confidential Information; and
(e)
is
required to be disclosed by University to comply with applicable laws, to defend
or prosecute litigation or to comply with governmental regulations, provided
that University provides prior written notice of such disclosure to Rosetta
and
takes reasonable and lawful actions to avoid and/or minimize the degree of
such
disclosure.
7.3.
The
obligations of confidentiality set forth in this Agreement shall survive its
termination or expiration for a period of [***].
ARTICLE
VIII.
INSURANCE
University
shall obtain and maintain during the term of this Agreement and for a reasonable
period thereafter insurance as is necessary to cover its employees and any
liability that might arise out of the Research performed under this
Agreement.
ARTICLE
IX.
INDEMNIFICATION;
NO WARRANTIES
9.1
Each
Party agrees to assume any and all risks of personal injury and property damage
attributable to the negligent acts or omissions of that Party or its officers,
employees and agents.
9.2
NOTHING
IN THIS AGREEMENT WILL BE CONSTRUED AS A PROMISE OR REPRESENTATION BY UNIVERSITY
TO ACHIEVE ANY SPECIFIC OR USABLE RESEARCH RESULT OR THAT THE RESEARCH WILL
BE
COMPLETED BY THE END OF THE RESEARCH PERIOD.
9.3
UNIVERSITY IS PROVIDING THE RESEARCH REPORT INFORMATION ON AN “AS IS” BASIS.
UNIVERSITY MAKES NO WARRANTIES EITHER EXPRESS OR IMPLIED OF ANY KIND, AND HEREBY
EXPRESSLY DISCLAIMS ANY WARRANTIES, REPRESENTATIONS OR GUARANTEES OF ANY KIND
AS
TO THE RESEARCH REPORT INFORMATION.
9.4
The
University will use best efforts to select Samples that will meet the criteria
set forth in the Protocol. The parties acknowledge that any biological samples
utilized by the parties and exchanged between the parties during the course
of
performing the Research are provided “AS IS” AND WITHOUT WARRANTY OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR ANY OTHER WARRANTY,
EXPRESS OR IMPLIED. THE PARTIES MAKE NO REPRESENTATION OR WARRANTY THAT THE
USE
OF
THE
BIOLOGICAL MATERIALS WILL NOT INFRINGE ANY PATENT OR OTHER PROPRIETARY RIGHT
OR
THAT THE BIOLOGICAL MATERIALS WILL NOT POSE A HEALTH OR SAFETY RISK
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
6 of
19
9.5
In no
event shall University’s liability to Rosetta exceed the payments made to
University by Rosetta under this Agreement.
9.6
The
parties hereto acknowledge that the limitations and exclusions of liability
and
disclaimers of warranty set forth in this Agreement form an essential basis
of
the bargain between the parties.
9.7
Rosetta
will indemnify, defend and hold University, its trustees, officers, faculty
members, students, employees and agents (“Indemnities”) harmless from and
against any and all actions, suits, claims, demands, prosecutions, liabilities,
costs, expenses, damages, deficiencies, losses or obligations brought by a
third
party (including reasonable attorneys fees) (“Claims”) based on or arising out
of its use of the Research Report Information except to the extent that any
Claim is caused by the gross negligence or malfeasance of one or more
Indemnity.
ARTICLE
X.
PUBLICITY
AND PUBLICATIONS
10.1.
Neither Rosetta nor University shall make any news release or other public
statement, whether to the press or otherwise, disclosing the existence of this
Agreement or the terms thereof without the prior written approval of the other
Party, except as required by law.
10.2.
Rosetta will not use the name, insignia, or symbols of University, its faculties
or departments, or any variation or combination thereof, or the name of any
trustee, faculty member, other employee, or student of University for any
purpose whatsoever, except those required by law, without University’s prior
written consent.
10.3.
Subject to Section 10.4, University shall have the right, consistent with
academic standards, to publish or present the results of the Research provided
that the manuscript, abstract or other material proposed to be published or
presented (“Proposed Publication”) shall be submitted to Rosetta at
least [***] days prior to submission for publication or presentation
to permit Rosetta to request removal of any Confidential Information contained
therein and to patentable invention disclosed therein. Rosetta shall complete
its review within [***] days after receipt of the Proposed Publication. If
Rosetta believes that any Proposed Publication contains any information relating
to any patentable invention the disclosure of such Proposed Publication shall
be
delayed for [***] days from the date of receipt of the Proposed Publication
to
permit the filing of a patent application. If Rosetta believes that any Proposed
Publication contains confidential information, Rosetta shall so notify
University and University shall remove any such Confidential Information prior
to publication or presentation.
10.4.
If
the Research is part of a multi-center study, the University agrees that it
will
not publish until after the data from the multi-center study is published in
a
combined paper that identifies all the sites, including Rosetta, that
participated in that in the event that the multi-center publication has not
been
completed within [***] years from the date of the expiration or termination
of
this Agreement, University may publish or present its individual results of
the
Research hereunder, provided further that the Proposed Publication is first
reviewed by Rosetta in accordance with Section 10.3.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
7 of
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10.5.
Rosetta acknowledges that University is dedicated to free scholarly exchange
and
to public dissemination of the results of its scholarly activities. Except
for
University’s obligations set forth in Sections 10.3 and 10.4 and Article VII,
nothing in this Agreement shall restrict the right of University and its faculty
and other employees to publish, disseminate or otherwise disclose the
Research.
ARTICLE
XI.
NOTICES
All
notices or other communications that are required or permitted by this Agreement
shall be in writing and shall be delivered personally, sent by facsimile (and
promptly confirmed by personal delivery, registered or certified mail or
overnight courier), sent by internationally recognized overnight courier or
sent
by registered or certified mail, postage prepaid, return receipt requested,
addressed as follows:
Rosetta
Genomics, Ltd
|
||
00
Xxxxx Xxxxxx
|
||
Science
Park
|
||
POB
4059
|
||
Rehovot,
L3 00000
|
||
Xxxxxx
|
||
Attn:
|
||
Facsimile
No.: x000 0 000 0000
|
||
With
a copy to:
|
Rosetta
Genomics, Inc.
|
|
000
X.X. Xxxxxxx Xxx, Xxxxx X 000
|
||
Xxx
Xxxxxxxxx, XX
00000
|
||
Attn:
|
||
Facsimile
No.: 000 000 0000
|
||
If
to University:
|
Executive
Director
|
|
Science
and Technology Ventures
|
||
00
Xxxxxxxxx Xxxxxx #0X
|
||
Xxx
Xxxx, XX 00000
|
||
facsimile:
0-000-000-0000
|
||
With
a copy to:
|
General
Counsel
|
|
000
Xxx Xxxxxxx, XX 0000
|
||
000
Xxxx 000xx
Xxxxxx
|
||
Xxx
Xxxx, XX 00000
|
||
Facsimile
No.: 0-000-000-0000
|
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
8 of
19
ARTICLE
XII.
STATUS
OF THE PARTIES
This
Agreement shall not be deemed to create any partnership, joint venture, or
agency relationship between the Parties. Each Party shall act hereunder as
an
independent contractor and its agents and employees shall have no right or
authority under this Agreement to assume or create any obligation on behalf
of,
or in the name of, the other Party. All persons employed by a Party shall be
employees of such Party and not of the other Party, and all costs and
obligations incurred by reason of any such employment shall be for the account
and expense of such Party.
ARTICLE
XIII.
MISCELLANEOUS
13.1.
This Agreement, including any attachments, may not be altered, amended or
modified except by a written document signed by both Parties.
13.2.
University shall not assign any of its rights or obligations under this
Agreement without the prior written authorization of Rosetta.
13.3.
This Agreement and all rights and obligations hereunder shall not be assigned
(whether through merger or consolidation, by operation of law, or otherwise);
provided, however, that Rosetta may assign this Agreement and its rights and
obligations hereunder upon written notification to the University, to an
Affiliate in connection with the transfer or sale of all or substantially all
of
its assets related to the Test or its business in the event of its merger or
consolidation or change in control or similar transaction and provided further
that any permitted assignee shall assume all obligations of Rosetta under this
Agreement in writing. Any assignment or attempted assignment contrary to the
provisions hereof shall be null and void.
13.4.
This Agreement shall be binding upon and inure to the benefit of the Parties
hereto and each of their respective successors and assigns.
13.5.
All
agreements and covenants contained herein are severable, and in the event any
of
them shall be held to be invalid by any competent court, this Agreement shall
be
interpreted as if such invalid agreements or covenants were not contained
herein.
13.6.
This Agreement constitutes the entire agreement between the Parties and
supersedes all prior communications, representations, or agreements, either
verbal or written between the Parties. Each Party confirms that it is not
relying on any representations or warranties of the other Party except as
specifically set forth herein.
13.7.
The
waiver by either Party of any right hereunder shall not be deemed a waiver
of
any other right hereunder.
13.8.
This Agreement may be executed in two (2) or more counterparts, each of which
shall be deemed an original, but all of which together shall constitute one
and
the same instrument.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
9 of
19
13.9.
The
headings used in this Agreement are for convenience only and are not a part
of
this Agreement.
13.10.
This Agreement shall be construed and enforced in accordance with the laws
of
the State of New York, without application of its principles of conflict of
laws.
[signatures
on following page]
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
10 of
19
IN
WITNESS WHEREOF, each of the Parties hereto has caused this Agreement to be
executed by its duly authorized representative as of the date written
above.
ROSETTA GENOMICS, LTD | THE TRUSTEES OF COLUMBIA | |||
UNIVERSITY
IN THE CITY OF NEW YORK
|
||||
![]() |
5/7/07 | |||
Name: |
Date |
Name:
XXXX
X. XXXXXXXX
|
Date | |
Title:
|
Title:
SENIOR
DIRECTOR
|
|||
SCIENCE
&
TECHNOLOGY
VENTURES
|
Read and Understood: | ||||
![]() |
5/7/07 | |||
Name: Xxxxxx Xxxxxxxxxx, MD |
Date | |||
Assoc.
Director, Molecular Pathology Laboratory
|
||||
Assistant
Professor of Clinical Pathology
|
![]() |
5/7/07 | |||
Name: Xxxxxxx Xxxxxxxxx, MD PhD |
Date | |||
Chair,
Department of Pathology
|
||||
Delafield
Professor of Pathology
|
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
11 of
19
IN
WITNESS WHEREOF, each of the Parties hereto has caused this Agreement to be
executed by its duly authorized representative as of the date written
above.
ROSETTA GENOMICS, LTD | THE TRUSTEES OF COLUMBIA | |||
UNIVERSITY IN THE CITY OF NEW YORK | ||||
![]() |
5/7/07 | |||
Name: Xxxx
Xxxxxx
|
Date |
Name:
|
Date | |
Title:
President
and CEO
Rosetta
Gcnomics
LTD.
|
Title:
|
Read and Understood: | |||
|
|||
Name: Xxxxxx Xxxxxxxxxx, MD |
Date | ||
Assoc.
Director, Molecular Pathology Laboratory
|
|||
Assistant
Professor of Clinical Pathology
|
|
|||
Name: Xxxxxxx Xxxxxxxxx, MD PhD |
Date | ||
Chair,
Department of Pathology
|
|||
Delafield
Professor of Pathology
|
Portions
of this Exhibit were omitted and have been filed separately with the
Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities
Exchange
Act of 1934.
Page
11
of 19
EXHIBIT
A
Protocol
Clinical
Validation of Rosetta Genomics’ XxXXX assay for Cancer of Unknown Primary (CUP)
with Xxxxxx Xxxxxxxxxx, Associate Director of Molecular Pathology Laboratory,
Department of Pathology, Columbia University Medical
Center
Project
Goal: The
goal
is to validate the Rosetta Genomics microRNA profiling assay to identify the
primary origin of metastatic cancers. The study will use the collection of
FFPE
samples of primary and metastatic cancers from the Department of Pathology
of
Columbia University Medical Center. MicroRNA analysis will be performed on
blinded samples at CUMC, and accuracy of microRNA profiling will be determined.
Should the accuracy be acceptable, then an additional set of blinded samples
will be tested at CUMC molecular pathology laboratory for the development of
a
clinical diagnostic assay, to identify the primary site of CUPS. The ultimate
goal is to obtain data to allow the identification of sensitivity and
specificity of the assay for various primaries, to allow submission data to
the
New York State Department of Health Clinical Laboratory Evaluation Program.
These data will be submitted from the CUMC Molecular Pathology Laboratory,
PFI7313.
Background:
MicroRNAs
(mirs) are short non-coding RNAs that regulate gene expression through
post-transcriptional suppression of mRNA. They are associated with cancer and
development, and demonstrate tissue specificity. 3%-5% of cancers present as
metastatic cancers with an unknown primary. The process of identifying the
source of the primary tumor is lengthy, expensive, and often inaccurate.
Rosetta
Genomics has developed a platform for profiling and characterizing all known
and
several hundred novel human microRNAs. Protocols have been developed for the
reliable extraction of RNA from formalin-fixed, paraffin-embedded (FFPE)
archival tissue samples, in a manner that retains the microRNA fraction. In
addition, the protocols also reliably extract microRNAs from fresh/frozen
tissues. For accurate, high-throughput measurement of microRNA expression
levels, a microarray platform with probes for nearly 700 microRNAs has been
developed. MicroRNA expression levels have been measured and tissue-specific
microRNAs identified with these protocols. In addition, we have constructed
and
optimized a simple algorithm to classify samples into tissue type categories.
In
addition, the design of the algorithm allows us to easily trace the strong
points in the classification, and to incorporate additional information where
required.
Using
the
above methods, protocols and algorithms, to analyze several hundred tumor and
normal tissue samples obtained from patients with 15 distinct tumor types ,
tissue source was identified using only a small number of microRNAs. Overall,
the accuracy of determining tissue origin of tumors reached ~85%, with increased
accuracy observed in subsets of tumor categories.
In
conclusion, tissue specificity of microRNAs permits the identification of tumor
origin based on a surprisingly small number of microRNA. Furthermore, the
development of a microRNA-based algorithm further enables the determination
of
the tissue origin. These findings will enable the development of an important
diagnostic assay for clinicians.
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
12
of 19
Protocol:
[***] at
Columbia. The anticipation is that [***].
Primary
Tumors:
1. |
[***]
|
2. |
[***]
|
3. |
[***]
|
4. |
[***]
|
5. |
[***]
|
6. |
[***]
|
7. |
[***]
|
8 |
[***]
|
9. |
[***]
|
10. |
[***]
|
11. |
[***]
|
12. |
[***]
|
13. |
[***]
|
14. |
[***]
|
15. |
[***]
|
16. |
[***]
|
17. |
[***]
|
18. |
[***]
|
[***]
Columbia
Study Plan:
To
identify the appropriate samples to be assayed for microRNA profiling in full
agreement with Rosetta Genomics. All relevant clinical information to allow
the
unambiguous identification of [***].
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
13
of 19
The
CUMC
molecular pathology staff will collaborate with Rosetta Genomics in data
analysis necessary for project goals. Should the analytical performance
characteristics be satisfactory, [***].
Rosetta
Genomics Study Plan:
[***].
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
14
of 19
EXHIBIT
B
CLIA
and CAP Certificates
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
15
of 19
![img1](https://www.sec.gov/Archives/edgar/data/1362959/000114420407039955/img1.jpg)
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
16
of 19
![img2](https://www.sec.gov/Archives/edgar/data/1362959/000114420407039955/img2.jpg)
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
17
of 19
EXHIBIT
C
Budget
Budget
per Validation Phase (estimated between 3 and 6 months in
duration):
Payment
|
Due
Date
|
Direct
Costs
|
Indirect
Costs (25%)
|
Total
Amount Due
|
|||||||||
1
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
2
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
3
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
4
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
|
TOTAL |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
Budget
per Laboratory Preparation Period (estimated 3 months in
duration):
Payment
|
Due
Date
|
Direct
Costs
|
Indirect
Costs (25%)
|
Total
Amount Due
|
|||||||||
1
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
2
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
3
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
41,668
|
||||||
|
TOTAL |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
18
of 19
Budget
per Trial Period (Six months in duration)*
Payment
|
Due
Date
|
Direct
Costs
|
Indirect
Costs (25%)
|
Total
Amount Due
|
|||||||||
1
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
2
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
3
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
4
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
5
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
6
|
[***] |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
||||||
|
TOTAL |
$
|
[***]
|
$
|
[***]
|
$
|
[***]
|
* In
the
event that the parties agree to extend the Trial Period for an additional [***],
then the
University
will be entitled to an additional payment of $[***].
Portions
of this Exhibit were omitted and have been filed separately with the Secretary
of the Commission pursuant to the Company's
application
requesting confidential treatment under Rule 24b-2 of the Securities Exchange
Act of 1934.
Page
19
of 19