Document:

Exhibit 10.2

 

Research Agreement dated January 28,
2004

between Medlyte, Inc.

and San Diego State University

together with Amendments No. 1
and No.2

 

 

AMENDMENT NO. 2 TO

RESEARCH AGREEMENT BETWEEN

SAN DIEGO STATE UNIVERSITY AND MEDLYTE, INC.

SDSU AGREEMENT # 40031030

 

Original
agreement dated January 28, 2004, and amended By Amendment #1, dated January 28,
2005, is hereby further amended as follows:

 

Effective August 25, 2004 — Change – Name of Company from Medlyte, Inc. to Lpath Therapeutics, Inc.

 

Extend
the term of the lease to December 31, 2005.

 

Delete
Exhibit A Budget dated 1/1/04 to 12/31/04

 

Add
Revised Exhibit A Budgeted dated 1/1/05 to 12/31/05

 

Change
authorized representative for the University from Joe Vasquez, Associate Vice
President of Business Enterprises to Scott Burns, Associate Vice President,
Enterprise Operations.

 

Delete
– University and Sponsor each agree to indemnify and to hold harmless the other
party from damage to person or property resulting from any act or omission on
the part of itself, its employees, its agents, or its officers. For purposes of
this section, any person employed by University who is also an officer,
director or shareholder of Sponsor shall be considered only an employee of
University.

 

Add
- Sponsor shall hold harmless, indemnify and defend the State of California,
the Trustees of the California State University, the San Diego State University
and the officers, employees, volunteers and agents of each of them from and
against any and all liability, loss, damage, expense, costs of every nature,
and causes of actions arising out of or in connection with the use by the
Sponsor of said property. For purposes of this section, any person employed by
University who is also an officer, director or shareholder of Sponsor shall be
considered only an employee of University.

 

All
other terms and conditions of the original agreement shall remain the same.

 

Agreement
of University and Sponsor in the terms stated above is indicated by signatures
affixed below.

 

	
  For University: SAN DIEGO
  STATE UNIVERSITY

  	
  For Sponsor: Lpath
  Therapeutics, Inc.

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Scott Burns

  	
  2/4/05

  	
  By:

  	
  /s/ Scott Pancoast

  	
   

  
	
   

  	
  Scott
  Burns

  	
   

  	
   

  
	
   

  	
  Associate
  VP, Enterprise Operations

  	
  Title:

  	
  Secretary

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/
  Thomas R. Scott

  	
  2/28/05

  	
   

  	
   

  
	
   

  	
  Thomas
  Scott

  	
   

  	
   

  
	
   

  	
  Dean,
  College of Sciences

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Christopher Glembostki

  	
   

  	
   

  	
   

  
	
   

  	
  Christopher Glembostki

  	
   

  	
   

  
	
   

  	
  Chair, Department of Biology

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Roger Sabbadini

  	
   

  	
   

  	
   

  
	
   

  	
  Roger Sabbadini

  	
   

  	
   

  
	
   

  	
  Principal Investigator

  	
   

  	
   

  
							

 

 

Exhibit A

 

	
  SDSU
  DETAILED BUDGET FOR INITIAL BUDGET PERIOD

  DIRECT COSTS ONLY

  	
   

  	
  FROM

  01/01/05

  	
   

  	
  THROUGH 12/31/05

  	
   

  
	
  PERSONNEL

  	
   

  	
  TYPE

  	
   

  	
  %

  	
   

  	
   

  	
   

  	
  DOLLAR AMOUNT REQUESTED (omit cents)

  	
   

  
	
  NAME
  (RT or salary)

  	
   

  	
  ROLE ON

  PROJECT

  	
   

  	
  APPT.

  (months)

  	
   

  	
  EFFORT PROJ.

  	
   

  	
  INST. BASE

  Annual SALARY

  	
   

  	
  SALARY

  REQUESTED

  	
   

  	
  FRINGE

  BENEFITS

  	
   

  	
  TOTALS

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  No Employees

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  SUBTOTALS

  	
   

  	
   

  	
   

  	
  $

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  
																			

 

	
  CONSULTANT COSTS Note: Forcasted expenditures for
  Sabbadini Laboratory Only (not 7993 acct) student stipends to reimburse SDSU
  Biology Department (e.g., Nicole Gellings)

  	
   

  	
  $

  	
  24,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  EQUIPMENT (Itemize) Note: Forcasted expenditures for
  Sabbadini Laboratory Only (not 7993 acct) no equipment may be purchased
  through SDSU

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  SUPPLIES (Itemize) Note: Forcasted expenditures for
  Sabbadini Laboratory Only (not 7993 acct) appoximately $10k per month

  	
   

  	
  $

  	
  120,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  TRAVEL Note:
  Forcasted expenditures for Sabbadini Laboratory Only (not 7993 acct)

  	
   

  	
  $

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  PATIENT COSTS 

  	
  INPATIENT

  	
   

  	
  $

  	
  0

  	
   

  
	
  (includes
  patient payment) 

  	
  OUTPATIENT

  	
   

  	
  $

  	
  0

  	
   

  
	
  BIOLOGY DEPARTMENT RENTAL AND SERVICES FEE
  (biosafety, radiation safety, etc.)

  $2.50/ft2 x 820 ft2 = $2,050/mo x12 mo = $24,605

  	
   

  	
  $

  	
  24,605

  	
   

  
	
  SUBTOTAL
  DIRECT COSTS FOR INITIAL BUDGET PERIOD

  	
   

  	
  $

  	
  168,605

  	
   

  
	
  FACILITIES
  FEES TO UNIVERSITY (Business Affairs)

  	
   

  	
  $

  	
  7,400

  	
   

  
	
  CONSORTIUM/CONTRACTUAL
  

  	
  CONTRACTUAL:

  	
   

  	
   

  	
   

  
	
  ATTORNEY FEES 

  	
  ATTORNEY:

  	
   

  	
   

  	
   

  
	
  TOTAL
  DIRECT COSTS FOR INITIAL BUDGET PERIOD

  	
   

  	
  $

  	
  176,005

  	
   

  
	
  INDIRECT
  COSTS FOR INITIAL BUDGET PERIOD (6% DC)

  	
   

  	
  10,560

  	
   

  
	
  TOTAL
  COSTS FOR INIITIAL BUDGET PERIOD

  	
   

  	
  $

  	
  186,565

  	
   

  

 

 

RESEARCH
AGREEMENT BETWEEN SAN DIEGO STATE UNIVERSITY AND MEDLYTE, INC.

 

This Agreement dated January 28, 2004 is by and between San Diego
State University, a public institution of higher education (hereinafter
referred to as “University”), and Medlyte, Inc., a Delaware corporation
with offices in San Diego County, California (hereinafter referred to as “Sponsor”).

 

Whereas, Sponsor is interested in sponsoring research at University
concerning the role of sphingolipids in human disease in the form of a
fee-for-service research agreement;

 

Therefore, University and Sponsor hereby agree to the terms stated
below.

 

1.             Scope of Work. The scope of work (“Project”) shall be as
described in the research proposal entitled “Role of Sphingolipids in Human
Disease” (the “Proposal”), by Dr. Roger Sabbadini, Ph.D. of Department of
Biology. It is understood that the Proposal is an “instructional research
project” whereby undergraduate and graduate students may have the opportunity
to use this project as an “incubator” for gaining practical laboratory
experience in the industry-related biotechnology arena.

 

2.             Services. University will provide facilities for use by University volunteers,
adjunct faculty associated with Medlyte (Life Sciences Rooms 308 and 308B and other
space totaling at least 820 ft2), as well as equipment, accounting
and other services described in the Proposal and related budget that are
necessary or appropriate to perform and complete the work contemplated in the
Proposal. Sponsor shall have the right to purchase, or direct University to
purchase on its behalf, equipment (defined as non-disposable items costing more
than $500) and to place such equipment at University. However, Sponsor will own
all right, title and interest to such equipment and will have the right to
remove such equipment at any time.

 

3.             Key Personnel. The project director/principal investigator
will be Dr. Roger Sabbadini, Ph.D., who may select, supervise and
terminate project staff as needed. No other person will be substituted for the
project director except with Sponsor’s approval. Sponsor may exercise the
Termination provision of this Agreement if a satisfactory substitute is not identified.
Any employees conducting research at SDSU will receive direct salary
compensation by the Sponsor only and will be recognized by the university
either as ‘volunteer workers’ or ‘adjunct faculty’ members under special
appointment by the Biology Department.

 

4.             Control of Research. Control of the research will rest entirely
with University. However, it is agreed that University, through the project
director, will maintain continuing communication with Sponsor. University’s
project director and Sponsor will mutually define the frequency and nature of
these communications.

 

5.             Funding and Payment. Sponsor will pay a monthly administrative
fee for

 

1

 

utilities
and maintenance and a fee equal to 6% of overhead costs to the University, as
well as a fee to the Biology Department for rental and services, as set forth
in the budget (“Budget”) attached as Exhibit A.  Sponsor will pay the amounts on the schedule as
set forth in the Budget on the condition that the Project Director submits a
written Progress Report to the Sponsor on a quarterly basis. The Project
Director may transfer funds from one category to another on the Budget after
written notice to Sponsor of such reallocation. Any amounts not spent on the
Project shall be refunded to Sponsor at the end of the Project.

 

6.             Project Period. The Agreement will be effective for twelve
(12) months beginning January 1, 2004 and ending December 31, 2004.
This period may be amended by mutual written agreement by authorized
representatives of University and Sponsor.

 

7.             Invention Rights. Title to any discovery, invention, finding,
data or conclusion, whether or not patentable, derived from the Project or
research under this Agreement will be owned solely by Sponsor. University
agrees to take all actions necessary or appropriate, at Sponsor’s request and
cost, to effectuate such sole ownership.

 

8.             Publication. University will be free to publish the results of research conducted
under this Agreement within a reasonable time. Prior to submission for
publication of a manuscript or outline/notes for a symposium, the University
agrees to send the Sponsor a copy of the manuscript/outline to be submitted,
and shall allow the Company thirty (30) days from receipt to determine whether
the manuscript/outline contains subject matter for which patent protection
should be sought prior to publication or public disclosure. Should the Sponsor
believe the subject matter of the manuscript contains a patentable invention to
which it may have rights under this Agreement, the Sponsor shall have until the
end of such 30-day period to notify the University that it wishes to either
seek to obtain patent protection or that it wishes to keep the information
non-public, and University agrees to provide reasonable cooperation to the
Sponsor and to take no action inconsistent with the Sponsor’s decision
(including withholding publication for a reasonable period of time upon request
in order to file for patent protection). In order to fully protect the rights
of University and Sponsor, any contemplated publication 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.

 

9.             Hold Harmless. University and Sponsor 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. For purposes of this section, any
person employed by University who is also an officer, director or shareholder
of Sponsor shall be considered only an employee of University.

 

10.           Use of Names. University and Sponsor each agree that they
will not use the name, trademark, or other identifier of the other for any
advertising, promotion, or other commercially related purpose except with
advance written approval.

 

11.           Assignment. Sponsor shall have the right to assign or transfer any rights

 

2

 

or
obligations arising from this Agreement without the prior written notice to the
University.

 

12.           Disclaimer of Warranties. All information received from or technology
developed with the University is experimental in nature and the University
makes no express or implied warranties or representations with respect to its
utility, safety, merchantability, or fitness for a particular purpose. All
warranties, express or implied arising out of or in connection with the
furnishing, performance, or use of any University technology are hereby
disclaimed.

 

13.           Applicable Law and Venue. This Agreement shall be governed by and enforced
according to the laws of the State of California without giving effect to the
conflict of laws provisions thereof. Exclusive jurisdiction and venue of any
dispute under this Agreement shall lie with the United States District Court
for the Southern District of California or the Superior Court of California for
San Diego County.

 

14.           Nonperformance. Nonperformance by the University shall not
operate as a breach of the terms of this Agreement if due to strikes or other
labor disputes or to prevention or prohibition by law, the loss or injury to
products in transit, an act of God, or war or other cause beyond the control of
the University.

 

15.           Severability. If any of the provisions of this Agreement
shall be determined to be illegal or unenforceable by a court of competent
jurisdiction, the other provisions shall remain in full force and effect.

 

16.           Notices. Unless otherwise indicated elsewhere in this Agreement, all notices
and communications in connection with this Agreement will be addressed to University/Sponsor
officials who sign this Agreement.

 

17.           Termination. Either University or Sponsor may terminate this Agreement by giving
thirty (30) days written notice to the other. In the event of such termination,
University will cease further obligation of project funds and will take all
reasonable steps to cancel or otherwise reduce outstanding obligations. Sponsor
will be obligated to pay actual costs and firm obligations as reduced by
diligent efforts of University. In the event of a termination by the University,
the Sponsor shall have the right to technology pursuant to Section 7
resulting from the research as defined in Section 1.

 

18.           Amendments. Any amendment to this Agreement must be in writing and signed by
authorized representatives of University and Sponsor. No waiver of this
Agreement shall be valid and enforceable unless in writing and signed by the
authorized representative for the party granting the waiver. The waiver by any
party of a breach of any of the provisions of this Agreement shall not operate
or be construed as a waiver of any subsequent breach by any party or a breach
of the entire Agreement. The authorized representative for the University is Joseph
Vasquez, Associate Vice President of Business Enterprises, San Diego State
University. Faculty members and other research personnel are not authorized to
bind the University.

 

19.           Entire Agreement. This Agreement expresses the entire
agreement

 

3

 

between
the parties. All prior negotiations, understandings, promises and agreements,
oral or written, are superseded hereby.

 

Agreement of University and Sponsor in the terms stated above is
indicated by signatures affixed below.

 

	
  For
  University:

  	
  For
  Sponsor:

  
	
  SAN
  DIEGO STATE UNIVERSITY

  	
  MEDLYTE,
  INC.

  
	
   

  	
   

  
	
  By:

  	
   

  	
  /s/
  Joseph W Vasquez

  	
   

  	
  By:

  	
   

  	
  /s/
  Scott Pancoast

  
	
   

  	
  (signature)

  	
   

  	
   

  	
  (signature)

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
  Joseph Vasquez

  	
   

  	
  Name:

  	
  Scott Pancoast

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Assoc.
  VP for Business Enterprises

  	
   

  	
  Title:

  	
  Director of the Company

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
  /s/
  Thomas R. Scott

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (signature)

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
  Thomas Scott

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Dean,
  College of Sciences

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
  /s/
  Christopher Glembostki

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (signature)

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
    Christopher
  Glembostki

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
    Chair,
  Department of Biology

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
  /s/
  Roger Sabbadini

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (signature)

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
    Roger
  Sabbadini

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
    Principal
  Investigator

  	
   

  	
   

  	
   

  
									

 

4

 

Exhibit A

 

	
  SDSU
  DETAILED BUDGET FOR INITIAL BUDGET PERIOD

  DIRECT COSTS ONLY

  	
   

  	
  FROM

  01/01/04

  	
   

  	
  THROUGH 12/31/04

  	
   

  
	
  PERSONNEL

  	
   

  	
  TYPE

  	
   

  	
  %

  	
   

  	
   

  	
   

  	
  DOLLAR AMOUNT REQUESTED (omit cents)

  	
   

  
	
  NAME
  (RT or salary)

  	
   

  	
  ROLE ON

  PROJECT

  	
   

  	
  APPT.

  (months)

  	
   

  	
  EFFORT

  PROJ.

  	
   

  	
  INST. BASE

  Annual SALARY

  	
   

  	
  SALARY

  REQUESTED

  	
   

  	
  FRINGE

  BENEFITS

  	
   

  	
  TOTALS

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Nicole
  Gellings, PhD student

  	
   

  	
  student

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  18,962

  	
   

  	
  $

  	
  18,962

  	
   

  	
  $

  	
  5,689

  	
   

  	
  $

  	
  24,651

  	
   

  
	
  John Vekich, MS student

  	
   

  	
  student

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  8,696

  	
   

  	
  $

  	
  9,600

  	
   

  	
  $

  	
  0

  	
   

  	
  $

  	
  8,696

  	
   

  
	
  PhD student TBN

  	
   

  	
  student

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  18,962

  	
   

  	
  $

  	
  13,552

  	
   

  	
  $

  	
  0

  	
   

  	
  $

  	
  13,552

  	
   

  
	
  Brad Sibald, MS
  students

  	
   

  	
  student

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  8,696

  	
   

  	
  $

  	
  9,600

  	
   

  	
  $

  	
  0

  	
   

  	
  $

  	
  8,696

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  SUBTOTALS

  	
   

  	
   

  	
   

  	
  $

  	
  51,714

  	
   

  	
  $

  	
  5,689

  	
   

  	
  $

  	
  55,595

  	
   

  

 

	
  CONSULTANT
  COSTS Note: Forcasted expenditures for Sabbadini Laboratory Only (not 7993
  acct) 

  Miscellaneous Consulting and external services conducted at SDSU

  	
   

  	
  $

  	
  30,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  EQUIPMENT
  (Itemize) Note: Forcasted expenditures for Sabbadini Laboratory Only (not
  7993 acct)

  Misc. small equip., columns, etc.

  	
   

  	
  $

  	
  20,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  SUPPLIES (Itemize)
  Note: Forcasted expenditures for Sabbadini Laboratory Only (not 7993 acct)

  	
   

  	
  $

  	
  120,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TRAVEL Note: Forcasted
  expenditures for Sabbadini Laboratory Only (not 7993 acct)

  	
   

  	
  $

  	
  5,000

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  PATIENT COSTS

  	
  INPATIENT

  	
   

  	
  $

  	
  0

  	
   

  
	
  (includes patient payment)

  	
  OUTPATIENT

  	
   

  	
  $

  	
  0

  	
   

  
	
  BIOLOGY
  DEPARTMENT RENTAL AND SERVICES FEE (biosafety, radiation safety, etc.)

  $2.50/ft2 x 820 ft2 = $2,050/mo x12 mo = $24,605 + $5,000 in fees

  	
   

  	
  $

  	
  29,605

  	
   

  
	
  SUBTOTAL DIRECT COSTS FOR
  INITIAL BUDGET PERIOD

  	
   

  	
  $

  	
  260,200

  	
   

  
	
  FACILITIES FEES TO UNIVERSITY
  (Business Enterprises)

  	
   

  	
  $

  	
  7,400

  	
   

  
	
  CONSORTIUM/CONTRACTUAL 

  	
  CONTRACTUAL:

  	
   

  	
   

  	
   

  
	
  ATTORNEY FEES 

  	
  ATTORNEY:

  	
   

  	
   

  	
   

  
	
  TOTAL DIRECT COSTS FOR INITIAL
  BUDGET PERIOD

  	
   

  	
  $

  	
  267,600

  	
   

  
	
  INDIRECT COSTS FOR INITIAL
  BUDGET PERIOD (6% DC)

  	
   

  	
  16,056

  	
   

  
	
  TOTAL COSTS FOR INIITIAL BUDGET
  PERIOD

  	
   

  	
  $

  	
  283,656

  	
   

  

 

 

Explanation of EXHIBIT A

 

Rental
fees: The Sponsor agrees to reimburse the Department of Biology for occupied
space at a fee of $2.50 ft2.

 

Facilities
fees: The Sponsor agrees to reimburse SDSU for utilities, janitorial and other
services at a fixed cost of $7,400 to be paid to the Office of Business
Enterprises. These fees include $200 per month for utilities plus a blanket
$5,000 in compensation for other services such as janitorial, landscaping, etc.

 

Other
fees: The Sponsor agrees to pay for other services on a fee-for-service basis,
including fees for vivarium use, health and safety issues, protection of human
subjects, etc at a commercially acceptable rates with the exception of services
provided to students performing thesis work at the university under the
sponsorship of the Sponsor.

 

Student
stipends: The Sponsor agrees to support PhD and MS students according to
Biology Department reimbursement policies.

 

5

 

EXHIBIT B:
‘THE PROPOSAL’

THE ROLE OF SPHINGOLIPIDS IN HUMAN DISEASE

 

RESEARCH
PLAN PROJECT I: The Role of Sphingolipids in Cardiac Ischemia

 

A.            SPECIFIC AIMS

 

The
identification of signaling components involved in cardiac ischemia reperfusion
(IR) injury is a critical step toward discovering therapeutic interventions for
reducing the size of cardiac infarcts and improving patient outcomes. Research
has demonstrated sphingolipid signaling molecules are key components that
participate in the cell death and loss of function associated with cardiac IR
injury, and furthermore, that induction of this pathway is one of the earliest
events during this process. Preliminary studies in our laboratory have
suggested that activation of the sphingolipid-signaling pathway by IR occurs
through the neutral form of sphingomyelinase (nSMase1) and its adaptor protein,
FAN (factor associated with neutral SMase activation).

 

With
this in mind, we have the following project
goal: The development of a small molecule inhibitor of the
sphingomyelinase signaling system that will provide protection from cardiac
cell death and loss of inotropy during acute ischemic insults such as during an
acute myocardial infarction (AMI).

 

•                 PHASE I: Validation of FAN and nSMase1 as targets for
therapeutics intervention. This validation is required before embarking on a
drug discovery program (Phase II).

 

•                 PHASE II: Demonstration in pre-clinical trials that
drug candidates against nSMase1 and/or FAN are effective in preventing cardiac
cell death and loss of inotropy associated with IR injury.

 

The
proposed Phase I research plan will include preliminary studies that reveal,
for the first time, that FAN is a critical mediator in the cardiomyocyte cell
death process induced by IR. These studies will additionally provide evidence
that nSMasel is the specific isoform of nSMase involved in this process.

 

Accordingly, the Phase I validation of nSMase1 and FAN as targets for
therapeutic intervention will include the following specific aims:

 

•                 Specific aim 1: Determine whether infarct sizes are reduced
and left ventricular pressure improved after an acute ischemic event in the
absence of the FAN/nSMase signaling system by producing reversible cardiac
infarcts using our in-house FAN knockout mouse model.

 

•                   Milestone 1: Completion of surgeries and measurements of infarct size
and left ventricular developed pressure (LVDP). Expectation of 20 – 50%
decrease in infarct size and significant increase in LVDP.

 

•                 Specific aim 2: Determine
whether infarct sizes are reduced and left ventricular pressure improved after
an acute ischemic event in the absence of the FAN/nSMase signaling system by
producing reversible cardiac infarcts using a currently available nSMase1
knockout mouse model.

 

6

 

•                   Milestone 1: Establishment of breeding
colony.

 

•                   Milestone 2: Completion of surgeries and
measurements of infarct size and left ventricular developed pressure (LVDP).
Expectation of 20 – 50% decrease in infarct size and a significant increase in
LVDP.

 

The
anticipated success of accomplishing these aims will demonstrate that the
sphingomyelinase signaling system is a major participant in
ischemia/reperfusion injury by validating nSMase1 and FAN as targets for drug
discovery. This target validation will enable us to identifying small molecule
inhibitors of this signaling system that can used in pre-clinical trials that
we will propose in PHASE II. The ultimate goal of the research is to develop
lead compounds that can be taken to Phase 1 Clinical Trials. The proposed work
will form the basis of discovering novel medical therapeutics that will reduce
the cell death associated with AMI and other acute ischemic events in the
clinical setting.

 

RESEARCH
PLAN PROJECT II: Sphingolipids as Markers of Cardiac Ischemia

 

A.            SPECIFIC AIMS

 

The
over all project goal is to
develop a sphingolipid-based diagnostic for cardiac ischemia that can be used
to evaluate patients suffering from acute cardiac ischemia.

 

PHASE I: Validation that sphingolipids are sensitive
and specific markers of cardiac ischemia in a trial designed to provoke
ischemia in stable angina patients. This validation is required before
embarking on a chest pain Emergency Department trial (Phase II).

 

PHASE II: Conduct a follow-on clinical trial using sphingolipids
as biomarkers for the evaluation of acute coronary syndrome (ACS) in the
Emergency Department. Develop a simple antibody-based test platform that would
be used in clinical laboratory instruments and point-of-care triage (POCT)
determinations of cardiac ischemia.

 

It
is now known that coronary artery disease is aggravated by inflammation. It has
been suggested that sphingolipid signaling molecules are mediators of
inflammation, particularly in response to pre-inflammatory cytokines such as
TNFa and IL2. In
addition to release by these molecules as part of the inflammatory response,
sphingolipids are possibly produced as a direct result of ischemia. In this
case, one may expect to observe increased sphingolipid production either as a
consequence of the TNFa produced by ischemic cardiac tissue or directly from heart cells. It
is also possible that the sphingolipids are responsible for the poor outcomes
observed in acute coronary syndrome patients who have elevated serum levels of
TNFa. Thus, we reasoned
that sphingolipids produced either by inflammation or ischemia would correlate
with coronary disease. Consequently, we initiated a clinical study designed to
test the hypothesis that blood levels of key sphingolipids are predictive of
obstructive CAD.  In an open trial of all patients sent to the catheterization lab for
angiography, serum sphingosine-1-phosphate (S1P) was found to be a robust predictor of coronary
disease. Subsequent subgroup analyses demonstrated that the predictive power of
serum S1P was dramatically improved for patients hospitalized for evaluation of
cardiac ischemia. Animal and cell culture experiments demonstrated that
ischemic hearts produce significant amounts of sphingolipids and release it
into the extracellular compartment. These recently published studies suggest
that serum sphingolipids could be used

 

7

 

to
predict cardiac ischemia independent of the inflammatory response. A clinical
trial is required with clear ischemia endpoints to determine the predictive
power of serum sphingolipids as ischemic markers.

 

Accordingly, we have designed a trial with the following PHASE I specific aims:

 

1)              Conduct a clinical trial designed to provoke
active ischemic in patients presenting with angina who undergo exercise
treadmill testing (ETT). Serial blood samples will be obtained before and
several times after treadmill testing for the determination of serum sphingolipid
levels.

 

Milestone: Consent 200 patients into the trial

 

2)              Compare serum sphingolipid levels with
inflammatory biomarkers, CRP and TNFa, MI markers (TnI) and standard assessments
of CHD, including stress ECG, stress echo, nuclear myocardial scanning and
coronary angiography

 

Milestone 1: Establish the specificity and sensitivity of
the putative ischemic markers with a yes/no evaluation of active ischemia

 

Milestone 2: Confirm yes/no for ischemia based on positive
stress ECGs, stress echos and nuclear myocardial scans with CAD determined by
coronary angiography. Ischemia-negative patients are those with a negative
stress ECGs, stress echos and nuclear myocardial scans.

 

Milestone 3: Serum sphingolipids as putative ischemic
markers should better correlate with clinicial endpoints than other serum
analytes used in the study (inflammatory markers and TnI) in patents not
experiencing MI

 

3)              Develop monoclonal antibodies suitable for
developing a serum assay for testing of patients suspected of cardiac ischemia

 

Milestone 1: Obtain stable hybridoma cell lines with high
titers (>100,000 dilution)

 

Milestone 2: Purify antibodies and determine Kds for each
hybridoma culture

 

The anticipated success of
accomplishing these aims will demonstrate that serum sphingolipids are ischemic
biomarkers that can form the basis of a simple blood test for ischemia that
will be developed in PHASE II. Thus, the overall
goal of this work is to develop a test for active ischemia suitable
for clinical laboratory instruments and point-of-care triage (POCT)
applications. This test could be used to improve the sensitivity and
specificity of ETT and could be used as a point of care triage in the emergency
department to demonstrate non-cardiac causes of chest pain. Patients presenting
with potential cardiac complaints could be screened initially with sphingolipid
analyte testing in addition to standard assays. A second use for sphingolipid
ischemic markers may be as an additional component of risk stratification.
Given that published work from our laboratory indicates that elevated serum S1P
levels are independent of traditional factors, it may improve the accuracy of
algorithms designed to identify patients who need more aggressive diagnostic
evaluations or medical interventions (12).

 

The proposed studies will demonstrate for the first time that serum
sphingolipids are powerful and novel markers of cardiac ischemia. Positive
results from the proposed work will suggest additional clinical trials and
laboratory investigations needed to elucidate the underlying mechanisms linking
sphingolipids with ischemia and provide guidance on how sphingolipids can be
best used to improve patient care and outcomes.

 

8

 

RESEARCH
PLAN PROJECT III: Anti-sphingolipid Antibodies in the Treatment of Cancer

 

A.            SPECIFIC AIMS

 

The identification of
signaling components that promote tumor growth is a critical step toward
discovering therapeutic interventions for reducing cancer’s morbidity and
mortality and generally improving patient outcomes. Research has demonstrated
that sphingosine kinase (SPHK) is a recently validated oncogene that produces
an extracellular sphingolipid signaling molecule, sphingosine-1-phosphate (S1P), that
promotes tumor growth. Tumor growth is promoted both directly and indirectly by
S1P’s growth factor actions related to tumor cell proliferation and metastasis,
as well as S1P’s pro-angiogenic effects. Medlyte has produced a biospecific monoclonal anti-S1P antibody (anti-S1P Mab) that
could be used as a therapeutic molecular sponge to selectively absorb S1P, thus
lowering extracellular concentrations of this tumor growth factor with the
anticipated reduction in tumor volume and metastatic potential as well as
simultaneously blocking new blood vessel formation that would, otherwise, feed
the growing tumor. The anticipated success of the molecular absorption concept
will represent an innovative approach to the treatment of cancer.

 

Accordingly in Phase I of the proposed work, our project goal is to evaluate the therapeutic
potential of our anti-S1P monoclonal antibodies. In accomplishing this goal, we
have the following Specific Aims:

 

•                  Specific Aim 1: In vitro
testing of anti-S1P Mab’s ability to reduce S1P-dependent cell
proliferation and metastatic potential.

 

•                 Milestone 1: Test ability of anti-S1P Mab to reduce
S1P-dependent proliferation in selected tumor cell lines. Determine if
Mab-reduced cell count is due to removal of S1P’s anti-apoptotic protective
effects.

 

•                  Milestone 2: Test ability of anti-S1P Mab to reduce
S1P-dependent cell migration in an in vitro Matrigel
assay for metastatic potential.

 

•                  Milestone 3: Test ability of anti-S1P Mab to reduce
S1P-dependent angiogenesis in an in vitro Matrigel
angiogenesis assay using HUVECs.

 

•                  Specific Aim 2: In vivo testing of anti-S1P Mab’s ability to reduce tumor
growth and associated angiogenesis.

 

•                  Milestone 1: Test Mab’s ability to reduce volume of
Xenografted tumors in SCID mice.

 

•                  Milestone 2: Use Matrigel plugs implanted subcutaneously
in C57B1/6N mice to test the anti-angiogenic effects of the anti-S1P Mab.

 

By
successfully accomplishing these aims, we will demonstrate that Medlyte’s
anti-S1P Mab is an effective therapeutic in the treatment of cancer in animal
models. The anticipated success of the proposed initial pre-clinical work will
lead to more intensive pre-clinical testing for safety and efficacy planned for
Phase II. The ultimate goal of the Phase II research is to develop humanized
anti-S1P Mabs that can be taken to Phase 1 Clinical Trials for comparison with
the

 

9

 

anthracycline
anti-neoplastic agents. Further, the anti-S1P Mab will be developed as an in vitro diagnostic tool to define the
minimum dosage for optimum efficacy. While therapeutic antibodies are not
generally regarded as toxic, the theranostics approach will improve patient
safety in our planned clinical trials. Importantly, the pathway for getting our
putative therapeutic antibody to market will be much shorter than the
conventional small molecule approach.

 

10Exhibit 10.3

 

Assignment Agreement dated June 9,
2005

between Lpath Therapeutics Inc.

and LPL Technologies, Inc.

 

 

ASSIGNMENT AGREEMENT

 

This
ASSIGNMENT AGREEMENT (the “Agreement”) is entered as of the 9th day of June 2005
by and between Lpath Therapeutics, Inc., a Delaware corporation (“Buyer”),
and LPL Technologies, Inc., a Delaware corporation (“Seller”).

 

WHEREAS,
Seller owns by way of assignment the entire right, title, and interest in and
to the patent rights, as defined on Exhibit A appended hereto (the “Patent
Rights”).

 

WHEREAS,
Buyer wishes to purchase from Seller, and Seller wishes to sell to Buyer,
Seller’s entire right, title, and interest in and to the Patent Rights upon the
following terms and conditions:

 

1.                                       Assignment; Documentation; Exclusion of
Liabilities.

 

1.1                                 Seller hereby assigns to Buyer exclusively
throughout the world all right, title, and interest (choate or inchoate) in the
Patent Rights (the “Assignment”), and Buyer hereby accepts the Assignment.

 

1.2                                 Within twenty-five (25) days after the
Effective Date (as defined below) of this Agreement, Seller shall deliver to
Buyer (or Buyer’s designee) all documentation (whether in written or electronic
form) then in the possession of Seller’s patent counsel, Baker &
Hosteller LLP, related to the Patents Rights (the “Documentation”). Without
limiting the generality of the foregoing, such documentation may include such
items as patent application file wrappers, docket and patent and patent
application status information, invention disclosures, the complete name and
current address of any inventor or applicant listed on any patent or patent
application within the Patent Rights or on any invention disclosure related
thereto, laboratory notebooks, manuscripts and publications, published abstracts,
posters presented at scientific symposia, business and scientific presentations
(whether made in academic or commercial settings), and the like. Upon delivery,
the Documentation shall become the sole and exclusive property of Buyer, and
Buyer shall thereafter have the unrestricted right to make, use, reproduce,
sell, display, create derivatives of, modify, distribute, perform, or otherwise
exploit the Documentation.

 

1.3                                 Seller shall retain no right, license, or
interest whatsoever in or to the Patent Rights or Documentation, or to any
discovery, invention, or work of authorship disclosed or described therein.

 

1.4                                 Buyer shall not assume, shall not take
subject to, and shall not be liable for, any liabilities or obligations of any
kind or nature, whether absolute, contingent, accrued, known, or unknown, of
Seller or any affiliate of Seller as a result of the Assignment or the delivery
of the Documentation.

 

1

 

2.                                       Further Assurances.

 

2.1                                 Seller agrees to execute, acknowledge and
deliver such further instruments and to do all such other acts as may be
necessary or appropriate in order to carry out the express provisions of this
Agreement. If Buyer is unable for any reason whatsoever to secure Seller’s
signature to any document it is entitled to under this Agreement, Seller hereby
irrevocably designates and appoints Buyer and its duly authorized officers and
agents, as its agent and attorney-in-fact with full power of substitution to
act for and on behalf of and instead of Seller, to execute and file any such
document or documents and to do all other lawfully permitted acts to further
the purposes of the foregoing with the same legal force and effect as if
executed by Seller.

 

2.2                                 To the extent allowed by law, the Assignment
includes all rights of paternity, integrity, disclosure and withdrawal and any
other rights that may be known as or referred to as “moral rights” or the like
(collectively, “Moral Rights”). To the extent Seller retains any such Moral Rights
under applicable law, Seller hereby ratifies and consents to, and provides all
necessary ratifications and consents to, any action that may be taken with
respect to such Moral Rights by or authorized by Buyer, and Seller agrees not
to assert any Moral Rights with respect thereto. Seller shall confirm any such
ratifications, consents, and agreements from time to time as requested by Buyer.

 

3.                                       Consideration. Subject to the fulfillment of Seller’s
obligations under this Agreement, as full and complete consideration for the
Assignment, delivery of Documentation, and the other rights conveyed pursuant
to this Agreement, the sufficiency of which Seller hereby acknowledges, Buyer
shall pay to Seller within twenty-five (25) days after the Effective Date:

 

3.1                                 Twelve Thousand Five Hundred Dollars
(US$12,500);

 

3.2                                 Twelve Thousand Five Hundred shares of common
stock of Buyer, as evidenced by Buyer’s issuance of a stock certificate naming
Seller as the owner of such number of shares of Buyer’s common stock; and

 

3.3                                 The total ground shipping charges for
delivery of the Documentation referred to in Section 1.2 hereof.

 

4.                                       Confidential Information. Seller shall not use or disclose anything
assigned to Buyer hereunder or any other technical or business information or
plans of Buyer to any third party. Seller recognizes and agrees that there is
no adequate remedy at law for a breach of this Section 4, that such a
breach would irreparably harm Buyer, and that Buyer is entitled to equitable
relief (including, without limitation, issuance of any injunction) with respect
to any such breach or potential breach in addition to any other remedies.

 

5.                                      Representations and Warranties. Seller represents and warrants to Buyer
that: (i) Seller is the sole owner (other than Buyer) of all rights,
title, and interest in the Patent Rights and Documentation in the countries in
which they have been issued or pending, that Seller holds good and marketable
title to the Documentation and in all of the patents and patent applications within
the Patent Rights, that Seller has the complete and unrestricted power and the
unqualified

 

2

 

right
to sell, assign, and deliver the Patent Rights and Documentation to Buyer, and
that, except for Documentation in the possession of Seller’s outside patent
counsel, Seller does not otherwise possess, control, or have access to
Documentation; (ii) Seller has not assigned, transferred, licensed,
pledged, or otherwise encumbered any patent or patent application within the
Patent Rights or any discovery, invention, or work of authorship disclosed in
the Patent Rights or Documentation, or agreed to do so; (iii) Seller is duly
organized and in good standing in the state of its incorporation; (iv) the
execution, delivery, and performance of this Agreement, nor the consummation of
the transaction contemplated hereby, shall, with or without the passage of time
or the delivery of notice or both, (a) conflict with, violate, or result
in any breach of the terms, conditions, or provisions of the certificate of
incorporation or bylaws of Seller, or (b) conflict with or result in a
violation or breach of, or constitute a default or require consent of any third
party (or give rise to any right of termination, cancellation, or acceleration)
under any of the terms, conditions, or provisions of any contract or other
instrument or obligation to which Seller is a party or by which Seller or any
patent or patent application within the Patent Rights may be bound; (v) Seller
has full power and authority to enter into this Agreement and to make the
Assignment and to deliver the Documentation; (vi) the execution and
delivery of this Agreement by Seller and the performance by Seller of its
obligations hereunder have been duly authorized by all necessary action by the
board of directors, and, if necessary, shareholders, of Seller, and no other
act or proceeding on the part of or on behalf of Seller or its board of
directors or shareholders is necessary to approve the execution and delivery of
this Agreement; (vii) the signatory officer(s) of Seller have the power
and authority to execute and deliver this Agreement and to take all other
actions required to be taken by Seller pursuant to the provisions of this
Agreement; (viii) Seller is not aware of any violation, infringement, or
misappropriation of any third party’s intellectual property rights (or any
claim thereof) by or through the practice of any discovery, invention, or work
of authorship disclosed, claimed, or otherwise provided in the Patent Rights or
Documentation; (ix) Seller is not aware of any questions or challenges
with respect to the validity of any claims of any issued patents or of any
pending patent application within the Patent Rights; (x) this Agreement has
been duly and validly executed and delivered by Seller and constitutes a legal,
valid, and binding agreement, enforceable against Seller in accordance with its
terms; and (xi) following execution of this Agreement, no restriction shall
exist on Buyer’s right to sell, resell, license, sublicense, or transfer in
whole or in part (a) the Documentation or (b) any patent or patent
application within the Patent Rights.

 

6.                                     Fair Consideration; No Fraudulent Conveyance.  The
sale of the Patent Rights and Documentation pursuant to this Agreement is made
in exchange for fair and equivalent consideration. Seller is not now insolvent
and shall not be rendered insolvent by the sale, transfer, and assignment of
the Patent Rights or Documentation pursuant to the terms of this Agreement.
Seller is not entering into this Agreement or any of the other agreements
referenced in this Agreement with the intent to defraud, delay, or hinder its
creditors and the consummation of the transactions contemplated by this
Agreement shall not have any such effect. This Agreement and the Assignment
shall not constitute a fraudulent conveyance or otherwise give rise to any
right of any creditor of Seller to any portion of the Documentation or any
patent or patent application within the Patent Rights after the Effective Date.

 

7.                                     Post-Closing Cooperation. Seller agrees that, if reasonably requested
by Buyer, it shall cooperate with Buyer, at Buyer’s expense, in enforcing the
terms of any agreement between

 

3

 

Seller and any third party involving the Patent Rights or any portion
thereof, including, without limitation, terms relating to confidentiality and
the protection of intellectual property rights. In the event that Buyer is
unable to enforce its intellectual property rights against a third party as a
result of a rule or law barring enforcement of such rights by a transferee
of such rights, Seller agrees to initiate proceedings against such third party
in Seller’s name, provided that Buyer shall be entitled to participate in such
proceedings and provided further that Buyer shall be responsible for the
expenses of such proceedings.

 

8.                                      Taxes. Seller shall be responsible for paying and shall promptly discharge
when due any sales, use, transfer, income, or other tax or other governmental
charge, fee, or obligation payable by Seller arising from or attributable to
the Assignment, delivery of Documentation, or this Agreement.

 

9.                                      Miscellaneous.

 

9.1                                 Any notice, report, approval, or consent
required or permitted hereunder shall be in writing and will be deemed to have
been duly given if delivered personally or mailed by first-class, registered or
certified U.S. mail, postage prepaid to the respective addresses of the parties
as set below (or such other address as a party may designate in writing by ten (10) days
notice).

 

9.2                                 No failure to exercise, and no delay in
exercising, on the part of either party, any privilege, any power or any rights
hereunder shall operate as a waiver thereof, nor shall any single or partial
exercise of any right or power hereunder preclude further exercise of any other
right hereunder. If any provision of this Agreement shall be adjudged by any
court of competent jurisdiction to be unenforceable or invalid, that provision
shall be limited or eliminated to the minimum extent necessary so that this
Agreement shall otherwise remain in full force and effect and enforceable.

 

9.3                                 This Agreement shall be deemed to have been
made in, and shall be construed pursuant to the laws of the State of California
and the United States without regard to conflicts of laws provisions thereof.
Each of the parties to this Agreement consents to the exclusive jurisdiction and
venue of the state and federal courts located in San Diego County, California.
The prevailing party in any action to enforce this Agreement shall be entitled
to recover costs and expenses including, without limitation, attorneys’ fees.

 

9.4                                 The terms of this Agreement are confidential
to Buyer and no press release or other written or oral disclosure of any nature
regarding the compensation terms of this Agreement shall be made by Seller
without Buyer’s prior written approval; provided, however, approval for such disclosure
shall be deemed given to the extent such disclosure is required to comply with applicable
laws or governmental rules and regulations.

 

9.5                                 Any waiver or amendment of this Agreement
shall be effective only if made in writing and signed by a representative of
the respective parties authorized to bind the parties.

 

9.6                                 Both parties agree that this Agreement
(including the first three paragraphs and appended Exhibit A) represents
the complete and exclusive statement of the mutual

 

4

 

understanding of the parties with respect to, and supersedes and
cancels all previous written and oral agreements and communications relating
to, the subject matter of this Agreement.

 

9.7                                This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original and all of which
together shall constitute one instrument.

 

9.8                                Each party acknowledges and represents that,
in executing this Agreement, it has had the opportunity to seek advice as to
its legal rights from legal counsel and that the person signing on its behalf
has read and understood all of the terms and provisions of this Agreement. Each
party shall be responsible for payment of any legal fees it incurs with respect
to the drafting, negotiation, and execution of this Agreement. This Agreement
shall not be construed against any party by reason of the drafting or
preparation thereof.

 

IN WITNESS WHEREOF, the parties have executed this Agreement on the day
and year first indicated above.

 

	
  SELLER – LPL TECHNOLOGIES,
  INC.

  
	
   

  
	
  By:

  	
  /s/ Aarun M. Goldman

  	
   

  
	
   

  	
   

  	
   

  
	
  Name:

  	
  AARUN M. GOLDMAN

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
  ACTING CFO

  	
   

  
	
   

  	
   

  	
   

  
	
  Address:

  	
  7740 METRIC DRIVE

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  MENTOR, OHIO 44060

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  
	
  BUYER – LPATH
  THERAPEUTICS, INC.

  
	
   

  
	
  By:

  	
  /s/ Scott Pancoast

  	
   

  
	
   

  	
   

  	
   

  
	
  Name:

  	
  SCOTT PANCOAST

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
  President

  	
   

  
	
   

  	
   

  	
   

  
	
  Address:

  	
  9191 Towne Centre Dr.

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  San Diego, CA 92122

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  

 

5

 

Exhibit A

 

Patent Rights

 

For
purposes of this Agreement, “Patent Rights” shall be defined as the United
States patents scheduled below, together with any United States provisional
and/or non-provisional patent application from which any such patent issued or
claims priority, as well as any divisional, continuation (including any
continuation-in-part), reissue, or reexamination of any such patent or patent
application, and any international or foreign counterpart of any such patent
application or patent.

 

U.S.
patents

 

1.                U.S. patent number 6,248,553

2.                U.S. patent number 6,255,063

3.                U.S. patent number 6,380,177

4.                U.S. patent number 6,448,023

5.                U.S. patent number 6,461,830

6.                U.S. patent number 6,485,922

7.                U.S. patent number 6,500,633

8.                U.S. patent number 6,716,595

 

6

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