<PAGE>
AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON MAY 23, 1996
REGISTRATION NO. 333-3374
- - -------------------------------------------------------------------------------
- - -------------------------------------------------------------------------------
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
----------------
POST-EFFECTIVE AMENDMENT NO. 1
TO
FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
NOVOSTE CORPORATION
(EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)
FLORIDA 5047 59-2787476
(STATE OR OTHER (PRIMARY STANDARD (I.R.S. EMPLOYER
JURISDICTION OF INDUSTRIAL CLASSIFICATION IDENTIFICATION NO.)
INCORPORATION OR CODE NUMBER)
ORGANIZATION)
4350-C INTERNATIONAL BLVD.
NORCROSS, GEORGIA 30093
(770) 717-0904
(ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER, INCLUDING AREA CODE, OF
REGISTRANT'S PRINCIPAL EXECUTIVE OFFICES)
THOMAS D. WELDON
NOVOSTE CORPORATION
4350-C INTERNATIONAL BLVD.
NORCROSS, GEORGIA 30093
(770) 717-0904
(NAME, ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER, INCLUDING AREA CODE,
OF AGENT FOR SERVICE)
COPIES TO:
SETH I. TRUWIT, ESQ. LAWRENCE S. WITTENBERG, ESQ.
EPSTEIN BECKER & GREEN, P.C. TESTA, HURWITZ & THIBEAULT, LLP
250 PARK AVENUE HIGH STREET TOWER
NEW YORK, NEW YORK 10177 125 HIGH STREET
(212) 351-4500 BOSTON, MASSACHUSETTS 02110
(617) 248-7000
APPROXIMATE DATE OF COMMENCEMENT OF PROPOSED SALE TO PUBLIC: As soon as
practicable after this Registration Statement becomes effective.
If any of the securities being registered on this Form are to be offered on
a delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, check the following box. [_]
If this Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, please check the following
box and list the Securities Act registration statement number of the earlier
effective registration statement for the same offering. [X] File No. 333-3374
If this Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [_]
If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box. [_]
----------------
CALCULATION OF REGISTRATION FEE
- - -------------------------------------------------------------------------------
- - -------------------------------------------------------------------------------
<TABLE>
<CAPTION>
PROPOSED PROPOSED
MAXIMUM MAXIMUM
TITLE OF SECURITIES AMOUNT BEING OFFERING PRICE AGGREGATE AMOUNT OF
BEING REGISTERED REGISTERED(1) PER SHARE(2) OFFERING PRICE REGISTRATION FEE
- - -------------------------------------------------------------------------------------
<S> <C> <C> <C> <C>
Common Stock, $.01 par
value................. 460,000 $14.00 $6,440,000 $2,221
</TABLE>
- - -------------------------------------------------------------------------------
- - -------------------------------------------------------------------------------
(1) Includes 60,000 shares that the Underwriters have the option to purchase
to cover over-allotments, if any.
(2) Estimated solely for purposes of calculating the registration fee pursuant
to Rule 457(c) under the Securities Act.
----------------
THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT
SHALL FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS
REGISTRATION STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH
SECTION 8(a) OF THE SECURITIES ACT OF 1933 OR UNTIL THIS REGISTRATION
STATEMENT SHALL BECOME EFFECTIVE ON SUCH DATE AS THE COMMISSION, ACTING
PURSUANT TO SAID SECTION 8(a), MAY DETERMINE.
- - -------------------------------------------------------------------------------
- - -------------------------------------------------------------------------------
<PAGE>
INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
The information included in Part I of the Registration Statement filed by
Novoste Corporation with the Securities and Exchange Commission (File No. 333-
3374) pursuant to the Securities Act of 1933, as amended, is incorporated by
reference into this Registration Statement. This registration statement is
being filed pursuant to Rule 462(b) to register an additional 460,000 shares
of Common Stock.
<PAGE>
PART II
INFORMATION NOT REQUIRED IN PROSPECTUS
ITEM 13. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION.
The estimated expenses of this offering are as follows:
<TABLE>
<S> <C>
S.E.C. Registration Fee............................................ $ 13,325
N.A.S.D. Filing Fee................................................ 4,364
Nasdaq National Market Qualification Fee........................... 37,616
Accounting Fees.................................................... 80,000
Legal Fees and Expenses............................................ 180,000
Blue Sky Qualification Fees and Expenses........................... 25,000
Printing and Engraving............................................. 90,000
Transfer Agent's Fees and Expenses................................. 10,000
Miscellaneous Expenses............................................. 34,695
--------
Total............................................................ $475,000
========
</TABLE>
ITEM 14. INDEMNIFICATION OF DIRECTORS AND OFFICERS.
Section 607.0850 of the Florida Business Corporation Act grants corporations
the power to indemnify their directors, officers, employees and agents in
accordance with the provisions thereof, Article VI of Registrant's Amended and
Restated Articles of Incorporation and Article VIII of Registrant's By-laws
provide for indemnification of Registrant's directors, officers, agents and
employees to the full extent permissible under Section 607.0850 of the Florida
Business Corporation Act.
See also Section 6 of the Purchase Agreement.
ITEM 15. RECENT SALES OF UNREGISTERED SECURITIES.
From April 8, 1993 to June 9, 1993, Registrant issued an aggregate of 26,862
shares of Common Stock to four consultants for services valued at an aggregate
of $80,586 (or $3.00 per share) as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF CONSULTANT NO. OF SHARES
---------------- ------------------ -------------
<S> <C> <C>
4/8/93 Towey & Associates 8,000
5/18/93 Longbow Partners 18,000
6/9/93 William Mack 431
6/9/93 Jack Snoke 431
</TABLE>
On July 7, 1993, Registrant issued three Senior Secured Promissory Notes,
each in the principal amount of $100,000, payable with interest accruing
thereon at 8% per annum to Thomas Weldon, Norman Weldon and Charles Larsen,
such promissory notes being convertible into one share of Common Stock at a
conversion price equal to the greater of $3.20 or the fair market value of the
Common Stock on the date of conversion. In December 1995, the holder of each
promissory note converted in full his promissory note into, and was issued,
31,250 shares of Common Stock.
On October 16, 1993, Registrant granted to Thomas Weldon, Norman Weldon and
Charles Larsen the right to convert, at any time on or prior to December 31,
1998, their respective accrued salaries through December 31, 1993, which
aggregated $320,629, into shares of Common Stock at $3.20 per share.
Simultaneously with the consummation of this offering, the accrued salaries
will be converted into 100,195 shares of Common Stock, with Thomas Weldon,
Norman Weldon and Charles Larsen receiving 56,394, 5,312 and 38,489 shares,
respectively.
In September 1993, Registrant issued 312,500 shares of Common Stock to
Venhill Limited Partnership, Henry L. Hillman, Elsie Hilliard and C.G.
Grefenstette, Trustees, and C.G. Grefenstette and Edward A. Craig, III
(predecessor trustee to Thomas G. Bigley), Trustees, which together are
principal shareholders of Registrant
II-1
<PAGE>
(collectively, the "Hillman Related Shareholders"), for $1,000,000 (or $3.20
per share) and, for no additional consideration, warrants to purchase an
additional 750,000 shares of Class B Common Stock (at $3.75 per share).
Concurrently therewith, as a finder's fee for securing the investment by the
Hillman Related Shareholders, Registrant issued The Kriegsman Group warrants
to purchase 31,250 shares of Common Stock at $3.20 per share.
In November 1993, two private investors were issued an aggregate of 18,750
shares of Common Stock for $60,000 (or $3.20 per share) and, for no additional
consideration, warrants to purchase an aggregate of 22,500 shares of Common
Stock at $4.00 per share as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF PURCHASER NO. OF SHARES
---------------- --------------------- -------------
<S> <C> <C>
11/8/93 G&G Diagnostics LP II 15,625
11/8/93 Irwin Gruverman 3,125
</TABLE>
In December 1993, Registrant issued 13,000 shares of Common Stock to two
consultants for services valued at $39,000 (or $3.00 per share) as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF CONSULTANT NO. OF SHARES
---------------- ------------------ -------------
<S> <C> <C>
12/27/93 Longbow Partners 12,000
12/28/93 Raphael Meloul 1,000
</TABLE>
On each of February 23, 1994 and July 8, 1994, Registrant issued 7,500
shares of Common Stock to Towey & Associates for consulting services valued at
$24,000 (or $3.20 per share).
In March 1994, the Hillman Related Shareholders purchased 312,500 shares of
Common Stock from Registrant for $1,000,000 (or $3.20 per share). Concurrently
therewith, in payment of finder's fee for securing the investment by the
Hillman Related Shareholders, Registrant issued The Kriegsman Group warrants
to purchase 31,250 shares of Common Stock at $3.20 per share.
In November 1994, the Registrant received a bridge loan from an affiliate of
the Hillman Related Shareholders in the amount of $250,000. The note was
payable on demand at any time after January 1, 1995, with accrued interest at
10% per annum. The loan was repaid on January 27, 1995.
On December 29, 1994, Registrant issued an aggregate of 21,563 shares of
Common Stock to two consultants for an aggregate of $69,002 (or $3.20 per
share) as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF CONSULTANT NO. OF SHARES
---------------- ------------------ -------------
<S> <C> <C>
12/29/94 Towey & Associates 7,500
12/29/94 Longbow Partners 14,063
</TABLE>
In January 1995, Registrant issued 266,667 shares of Class B Common Stock to
Noro-Moseley Partners III, L.P. ("Noro-Moseley"), a principal shareholder, for
$1,000,000 (or $3.75 per share) and, for no additional consideration, warrants
to purchase an additional 266,667 shares of Class B Common Stock at $4.50 per
share. Concurrently therewith, in payment of a finder's fee for securing the
Noro-Moseley investment, Registrant issued The Kriegsman Group warrants to
purchase 26,667 shares of Common Stock at $3.75 per share. Also in January
1995, the Hillman Related Shareholders exercised warrants to purchase 266,664
shares of Class B Common Stock, with Registrant receiving proceeds therefrom
of $999,990.
On April 25, 1995, Registrant issued to ABS Employees' Venture Fund Limited
Partnership 39,604 shares of Class B Common Stock for $148,515 (or $3.75 per
share) and, for no additional consideration, warrants to purchase an
additional 39,604 shares of Class B Common Stock at $4.50 per share.
In July 1995, Registrant issued 400,000 shares of Class B Common Stock to
Advanced Technology Ventures IV, L.P. ("ATV") for $1,500,000 (or $3.75 per
share) and, for no additional consideration, warrants to purchase an
additional 400,000 shares of Class B Common Stock (at $4.50 per share). As
part of the ATV
II-2
<PAGE>
financing, the Hillman Related Shareholders and Noro-Moseley exchanged their
shares of Common Stock for an equivalent number of shares of Class B Common
Stock and their warrants to purchase an aggregate of 750,000 shares of Class B
Common Stock for new warrants adding a cashless exercise provision and
extending the expiration date to December 31, 1999, but otherwise containing
substantially similar terms, including the right to purchase the identical
number of shares of Class B Common Stock.
On September 18, 1995, Registrant issued to Karen Vinjamuri 13,334 shares of
Class B Common Stock for $50,003 (or $3.75 per share) and warrants to purchase
13,334 shares of Class B Common Stock at $4.50 per share.
On December 6, 1995, Registrant issued 27,813 shares of Common Stock to two
consultants for services valued at $89,002 (or $3.20 per share) as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF CONSULTANT NO. OF SHARES
---------------- ------------------ -------------
<S> <C> <C>
12/6/95 Longbow Partners 25,313
12/6/95 Herbert Kontges 2,500
</TABLE>
In December 1995 and January 1996, Registrant issued a series of Fixed Rate
Convertible Promissory Notes to Noro-Moseley, the Hillman Related
Shareholders, ATV and Cynthia Weldon, in the principal amounts of $295,380,
$761,550, $443,070 and $300,000, respectively. Each of these notes had a
maturity date of June 1, 1996 and accrued interest at a rate of 8% compounded
annually on the unpaid principal amount, and provided that the holder thereof
may convert all or a portion of the outstanding principal amount plus accrued
interest into one share of Class B Common Stock for each $3.75 in principal
amount plus accrued interest of such note being converted. As part of the
Recapitalization, offering, the holders are converting the principal of and
accrued interest on such notes into 495,766 shares of Class B Common Stock,
assuming a closing date of this Offering of May 15, 1996. As part of the
December 1995 debt financing, in payment of a finder's fee, Registrant issued
The Kriegsman Group warrants to purchase 9,395 shares of Common Stock at $3.75
per share.
On January 30, 1996, Registrant issued 2,433 shares of Common Stock to Ian
Crocker, M.D., for consulting services rendered in the fourth quarter of 1995
valued at $14,598 (or $6.00 per share).
On January 30, 1996, Registrant issued 3,800 shares of Common Stock to Emory
University valued at $24,244 (or $6.38 per share) as partial consideration for
the rights granted under the license agreement between Emory University and
Registrant of even date. Registrant also issued 6,200 shares of Common Stock
to two physicians employed by Emory University valued at $39,556 (or $6.38 per
share) as consideration for services rendered under the license agreement of
even date as follows:
<TABLE>
<CAPTION>
DATE OF ISSUANCE NAME OF CONSULTANT NO. OF SHARES
---------------- ------------------ -------------
<S> <C> <C>
1/30/96 Ian Crocker, M.D. 1,800
1/30/96 Ron Waksman, M.D. 4,400
</TABLE>
On February 5, 1996, the Company granted 15,000 shares of Common Stock to
Spencer B. King, III, M.D., for consulting services valued at $95,700 (or
$6.38 per share).
On March 31, 1996, Registrant issued 1,010 shares of Common Stock to Ian
Crocker, M.D., for consulting services rendered in the first quarter of 1996
valued at $6,450 ( or $6.38 per share).
On March 31, 1996, Registrant issued 7,523 shares of Common Stock to Towey &
Associates for consulting services valued at $48,000 (or $6.38 per share).
See "Management--Executive Compensation" of the Prospectus for shares issued
in 1995 and 1996 to one executive officer as compensation for services
rendered in 1995.
From April 1, 1993 through April 1, 1994, Registrant granted under its Stock
Option Plan 182,000 options at $3.20 per share to 8 holders.
II-3
<PAGE>
From April 1, 1994 through April 1, 1995, Registrant granted under its Stock
Option Plan 294,000 options at $3.20 per share to 9 holders.
From April 1, 1995 through December 31, 1995, Registrant granted under its
Stock Option Plan 224,750 options at $3.20 per share to 24 holders.
From January 1, 1996 through May 10, 1996, Registrant granted under its
Stock Option Plan 36,500 options at the greater of $12.00 per share or the
initial public offering price per share in the offering covered by this
Registration Statement.
In March and April 1996, Registrant received bridge loans in the aggregate
amount of $1,500,150 from the Hillman Related Shareholders, Noro-Moseley and
ATV in exchange for Fixed Rate Promissory Notes in the aggregate principal
amount of the loan, due June 30, 1996 with interest at the rate of 8.0%
compounded annually.
The foregoing transactions of Registrant were exempt from registration under
the Securities Act of 1933, as amended, under Sections 3(a)(9) and 4(2)
thereunder, and all stock certificates issued in connection therewith were
legended to reflect their restricted status.
ITEM 16. EXHIBITS
(a) EXHIBITS:
<TABLE>
<C> <S>
*1 --Form of Underwriting Agreement.
*3.1 --Articles of Incorporation of Registrant, as amended.
*3.2 --Form of Amended and Restated Articles of Incorporation of
Registrant to be filed prior to the closing of this offering.
*3.3 --Form of Amended and Restated By-Laws of Registrant to be adopted
prior to the closing of this Offering.
*4.1 --Form of Specimen Common Stock Certificate of Registrant.
*4.2 --Registration Rights Agreement, dated July 28, 1995, by and among
Registrant, Norman R. Weldon, Thomas D. Weldon, Charles E.
Larsen, the Hillman Investors (as defined therein), Noro-Moseley
Partners-III, L.P. and Advanced Technology Ventures IV, L.P.
*4.3 --Registration Rights Agreement, dated April 26, 1995, between
Registrant and ABS Employees' Venture Fund Limited Partnership.
*4.4 --Registration Rights Agreement, dated September 20, 1995, between
Registrant and Karen C. Vinjamuri.
*4.5 --Stock Purchase Warrant, dated September 24, 1993, between
Registrant and The Kriegsman Group.
*4.6 --Stock Purchase Warrant, dated March 24, 1994, between Registrant
and The Kriegsman Group.
*4.7 --Stock Purchase Warrant, dated August 1995, between Registrant
and The Kriegsman Group.
*4.8 --Stock Purchase Warrant, dated December 1, 1995, between
Registrant and The Kriegsman Group.
*4.9 --Consulting Agreement, dated July 30, 1992, between Registrant
and Spencer B. King III, M.D.
*4.10 --Consulting Agreement, dated February 1, 1996, between Registrant
and Spencer B. King III, M.D.
*4.11 --Consulting Agreement, dated February 1, 1993, between Registrant
and Harry A. Kopelman, M.D.
</TABLE>
II-4
<PAGE>
<TABLE>
<C> <S>
*4.12 --Consulting Agreement, dated October 4, 1992, between
Registrant and Robert Langer.
*4.13 --Consulting Agreement, dated July 30, 1992, between Registrant
and John B. Martin.
*4.14 --Consulting Agreement, dated November 4, 1992, between
Registrant and Raphael Meloul.
*4.15 --Consulting Agreement, dated June 30, 1992, between Registrant
and David O. Williams, M.D.
*4.16 --Form of Fixed Rate Promissory Notes by Registrant, in the
aggregate principal amount of $1,500,150, at the interest rate
of 8.0% compounded annually.
5 --Opinion by Epstein Becker & Green, P.C., as to legality.
*10.1 --Form of Stock Option Plan of Registrant, as amended.
+10.2 --License Agreement, dated January 30, 1996, between Emory
University and Registrant.
+10.3 --Clinical Research Study Agreement, dated January 30, 1996, by
Emory University and Registrant.
+10.4 --License Agreement, dated January 31, 1996, between Spencer B.
King III, M.D. and Registrant.
+10.5 --Restenosis Therapy Project Development and Supply Agreement,
dated November 28, 1994, with Registrant, relating to the
supply of radioactive beta isotopes.
*10.6 --Option to Purchase Assets Agreement dated August 22, 1995,
with Registrant relating to the purchase of assets of
Registrant's supplier of radioactive beta isotopes.
*10.7 --License/Product Supply Agreement, dated as of May 11, 1992,
by and among Sumitomo Bakelite Co., Ltd., Sumitomo Plastics
America, Inc., Norman R. Weldon,
Thomas D. Weldon, Charles E. Larsen and Registrant.
*10.8 --Lease, dated July 9, 1992, between Weeks Master Partnership,
L.P. and Registrant, as amended.
*10.9(a) --Agreement, dated June 15, 1995, between NationsBank of
Georgia, N.A. and Registrant, superseding the indebtedness
originally evidenced by documents dated September 1994.
*10.9(b) --Continuing and Unconditional Guaranty dated September 15,
1994, by Charles Larsen.
*10.9(c) --Continuing and Unconditional Guaranty dated September 15,
1994, by
Thomas D. Weldon.
*10.9(d) --Continuing and Unconditional Guaranty, dated June 15, 1995,
by Norman R. Weldon.
*11 --Computation of Per Share Earnings.
23.1 --Consent of Ernst & Young LLP (contained on page II-9).
*23.2 --Consent of Epstein Becker & Green, P.C. (included in Exhibit
5).
*24 --Power of Attorney.
</TABLE>
- - --------
* Previously filed.
+ Portions have been omitted and filed separately with the Securities and
Exchange Commission pursuant to a request for confidential treatment.
(B) FINANCIAL STATEMENT SCHEDULES:
Schedules have been omitted for the reason that they are not required or are
not applicable or because the required information is included in the financial
statements or the notes thereto.
II-5
<PAGE>
ITEM 17. UNDERTAKINGS.
Registrant hereby undertakes to provide to the Underwriters at the closing
specified in the Purchase Agreement certificates in such denominations and
registered in such names as required by the Underwriters to permit prompt
delivery to each purchaser.
Insofar as indemnification for liabilities arising under the Securities Act
of 1993, as amended (the "Act") may be permitted to directors, officers and
controlling persons of Registrant pursuant to the provisions of its Amended
and Restated Certificate of Incorporation, its By-Laws, or otherwise,
Registrant has been advised that in the opinion of the Securities and Exchange
Commission such indemnification is against public policy as expressed in the
Act and is, therefore, unenforceable. In the event that a claim for
indemnification against such liabilities (other than the payment by Registrant
for expenses incurred or paid by a director, officer or controlling person of
Registrant in the successful defense of any action, suit or proceeding) is
asserted by such director, officer or controlling person in connection with
the securities being registered, Registrant will, unless in the opinion of its
counsel the matter has been settled by controlling precedent, submit to a
court of appropriate jurisdiction the question whether such indemnification by
it is against public policy as expressed in the Act and will be governed by
the final adjudication of such issue.
Registrant hereby further undertakes that:
(1) For purposes of determining any liability under the Act, the
information omitted from the form of prospectus filed as part of this
Registration Statement in reliance upon Rule 430A and contained in a form
of prospectus filed by Registrant pursuant to Rule 424(b)(1) or (4) or
497(h) under the Act shall be deemed to be part of this Registration
Statement as of the time it was declared effective.
(2) For purposes of determining any liability under the Act, each post-
effective amendment that contains a form of prospectus shall be deemed to
be a new registration statement relating to the securities offered therein,
and the offering of such securities at that time shall be deemed to be the
initial bona fide offering thereof.
II-6
<PAGE>
SIGNATURES
PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, REGISTRANT HAS
DULY CAUSED THIS POST-EFFECTIVE AMENDMENT TO THE REGISTRATION STATEMENT TO BE
SIGNED ON ITS BEHALF BY THE UNDERSIGNED, THEREUNTO DULY AUTHORIZED, IN THE
CITY OF ATLANTA, STATE OF GEORGIA, ON THE 22ND DAY OF MAY, 1996.
Novoste Corporation
* Norman R. Weldon, Ph.D.
By: _________________________________
Norman R. Weldon, Ph.D.
Chairman of the Board
PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, THIS POST-
EFFECTIVE AMENDMENT TO THE REGISTRATION STATEMENT HAS BEEN SIGNED BELOW BY THE
FOLLOWING PERSONS IN THE CAPACITIES AND ON THE DATES INDICATED.
SIGNATURE TITLE DATE
* Norman R. Weldon, Ph.D. Chairman of the
- - ------------------------------------- Board and Director May 22, 1996
NORMAN R. WELDON, PH.D.
* Thomas D. Weldon President, Chief
- - ------------------------------------- Executive Officer May 22, 1996
THOMAS D. WELDON and Director
(Principal
Executive Officer)
* William P. Lane Vice President,
- - ------------------------------------- Finance and Chief May 22, 1996
WILLIAM P. LANE Financial Officer
(Principal
Financial and
Accounting Officer)
* Charles E. Larsen Director
- - ------------------------------------- May 22, 1996
CHARLES E. LARSEN
* J. Stephen Holmes Director
- - ------------------------------------- May 22, 1996
J. STEPHEN HOLMES
* Richard M. Johnston Director
- - ------------------------------------- May 22, 1996
RICHARD M. JOHNSTON
II-7
<PAGE>
SIGNATURE TITLE DATE
* Pieter J. Schiller Director
- - ------------------------------------- May 22, 1996
PIETER J. SCHILLER
* Jack R. Kelly, Jr. Director
- - ------------------------------------- May 22, 1996
JACK R. KELLY, JR.
* William E. Whitmer Director
- - ------------------------------------- May 22, 1996
WILLIAM E. WHITMER
/s/ Norman R. Weldon, Ph.D.
*By: ________________________________
NORMAN R. WELDON, PH.D.,
ATTORNEY-IN-FACT
II-8
<PAGE>
CONSENT OF INDEPENDENT AUDITORS
We consent to the reference to our firm under the captions "Selected
Financial Data" and "Experts" and to the use of our report dated February 9,
1996 in Post-Effective Amendment No. 1 to the Registration Statement (Form S-1
No. 333-3374) and related Prospectus of Novoste Corporation for the
Registration of 2,400,000 shares of its Common Stock.
Ernst & Young LLP
Atlanta, Georgia
May 22, 1996
II-9
<PAGE>
EXHIBIT INDEX
<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION PAGE NO.
------- ----------- --------
<C> <S> <C>
*1 --Form of Underwriting Agreement.
*3.1 --Articles of Incorporation of Registrant, as amended.
*3.2 --Form of Amended and Restated Articles of Incorporation of
Registrant to be filed prior to the closing of this
offering.
*3.3 --Form of Amended and Restated By-Laws of Registrant to be
adopted prior to the closing of this Offering.
*4.1 --Form of Specimen Common Stock Certificate of Registrant.
*4.2 --Registration Rights Agreement, dated July 28, 1995, by
and among Registrant, Norman R. Weldon, Thomas D. Weldon,
Charles E. Larsen, the Hillman Investors (as defined
therein), Noro-Moseley Partners-III, L.P. and Advanced
Technology Ventures IV, L.P.
*4.3 --Registration Rights Agreement, dated April 26, 1995,
between Registrant and ABS Employees' Venture Fund Limited
Partnership.
*4.4 --Registration Rights Agreement, dated September 20, 1995,
between Registrant and Karen C. Vinjamuri.
*4.5 --Stock Purchase Warrant, dated September 24, 1993, between
Registrant and The Kriegsman Group.
*4.6 --Stock Purchase Warrant, dated March 24, 1994, between
Registrant and The Kriegsman Group.
*4.7 --Stock Purchase Warrant, dated August 1995, between
Registrant and The Kriegsman Group.
*4.8 --Stock Purchase Warrant, dated December 1, 1995, between
Registrant and The Kriegsman Group.
*4.9 --Consulting Agreement, dated July 30, 1992, between
Registrant and Spencer B. King III, M.D.
*4.10 --Consulting Agreement, dated February 1, 1996, between
Registrant and Spencer B.
King III, M.D.
*4.11 --Consulting Agreement, dated February 1, 1993, between
Registrant and Harry A. Kopelman, M.D.
*4.12 --Consulting Agreement, dated October 4, 1992, between
Registrant and Robert Langer.
*4.13 --Consulting Agreement, dated July 30, 1992, between
Registrant and John B. Martin.
*4.14 --Consulting Agreement, dated November 4, 1992, between
Registrant and Raphael Meloul.
*4.15 --Consulting Agreement, dated June 30, 1992, between
Registrant and David O. Williams, M.D.
*4.16 --Form of Fixed Rate Promissory Notes by Registrant, in the
aggregate principal amount of $1,500,150, at the interest
rate of 8.0% compounded annually.
*5 --Opinion by Epstein Becker & Green, P.C., as to legality.
*10.1 --Form of Stock Option Plan of Registrant, as amended.
+10.2 --License Agreement, dated January 30, 1996, between Emory
University and Registrant.
+10.3 --Clinical Research Study Agreement, dated January 30,
1996, by Emory University and Registrant.
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION PAGE NO.
------- ----------- --------
<C> <S> <C>
+10.4 --License Agreement, dated January 31, 1996, between
Spencer B. King III, M.D. and Registrant.
+10.5 --Restenosis Therapy Project Development and Supply
Agreement, dated November 28, 1994, with Registrant,
relating to the supply of radioactive beta isotopes.
*10.6 --Option to Purchase Assets Agreement dated August 22,
1995, with Registrant relating to the purchase of assets
of Registrant's supplier of radioactive beta isotopes.
*10.7 --License/Product Supply Agreement, dated as of May 11,
1992, by and among Sumitomo Bakelite Co., Ltd., Sumitomo
Plastics America, Inc., Norman R. Weldon,
Thomas D. Weldon, Charles E. Larsen and Registrant.
*10.8 --Lease, dated July 9, 1992, between Weeks Master
Partnership, L.P. and Registrant, as amended.
*10.9(a) --Agreement, dated June 15, 1995, between NationsBank of
Georgia, N.A. and Registrant, superseding the
indebtedness originally evidenced by documents dated
September 1994.
*10.9(b) --Continuing and Unconditional Guaranty dated September
15, 1994, by Charles Larsen.
*10.9(c) --Continuing and Unconditional Guaranty dated September
15, 1994, by
Thomas D. Weldon.
*10.9(d) --Continuing and Unconditional Guaranty, dated June 15,
1995, by Norman R. Weldon.
*11 --Computation of Per Share Earnings.
23.1 --Consent of Ernst & Young LLP (contained on page II-9).
*23.2 --Consent of Epstein Becker & Green, P.C. (included in
Exhibit 5).
*24 --Power of Attorney.
</TABLE>
- - --------
* Previously filed.
+ Portions have been omitted and filed separately with the Securities and
Exchange Commission pursuant to a request for confidential treatment.
<PAGE>
EXHIBIT 5
[LETTERHEAD OF EPSTEIN BECKER & GREEN, P.C.]
May 22, 1996
Novoste Corporation
4350-C International Blvd.
Norcross, Georgia 30093
Ladies and Gentlemen:
We have acted as counsel to Novoste Corporation (the "Company") in
connection with its filing of post-effective amendment no. 1 to a registration
statement on Form S-1 (File No. 333-3374, such post-effective amendment to the
registration statement, at the time of its effectiveness, hereinafter the
"Registration Statement") covering shares of the Company's authorized and
unissued shares of Common Stock, $.01 par value, including shares subject to an
over-allotment option (collectively, the "Shares").
As such counsel, we have examined original copies, or copies certified
to our satisfaction, of the corporate records of the Company, agreements and
other instruments, certificates of public officials and such other documents as
we deemed necessary as a basis for the opinion hereinafter set forth.
On the basis of the foregoing, we are of the opinion that the Shares
have been validly authorized and, when sold as contemplated by the Registration
Statement, will be legally issued, fully paid and nonassessable.
<PAGE>
Novoste Corporation
May 22, 1996
Page 2
We hereby consent to the filing of this opinion as an exhibit to
post-effective amendment no. 1 to the Registration Statement and to the
reference made to us under the caption "Legal Matters" in the prospectus
constituting part of the Registration Statement.
Very truly yours,
EPSTEIN BECKER & GREEN, P.C.
By: /s/ Seth I. Truwit
--------------------------------
Seth I. Truwit, Esq.
<PAGE>
EXHIBIT 10.2
EXCLUSIVE AGREEMENT
between
EMORY UNIVERSITY
and
NOVOSTE CORPORATION
<PAGE>
TABLE OF CONTENTS
ARTICLE 1. DEFINITIONS...................................... 2
ARTICLE 2. ASSIGNMENT AND GRANT OF LICENSE.................. 8
ARTICLE 3. ROYALTIES AND OTHER PAYMENTS..................... 11
ARTICLE 4. REPORTS AND ACCOUNTING........................... 14
ARTICLE 5. PAYMENTS......................................... 17
ARTICLE 6. DEVELOPMENT AND MARKETING PROGRAM................ 19
ARTICLE 7. PATENT PROSECUTION............................... 22
ARTICLE 8. INFRINGEMENT AND THIRD PARTY RIGHTS.............. 25
ARTICLE 9. WARRANTIES AND INDEMNIFICATION................... 28
ARTICLE 10. CONFIDENTIALITY.................................. 33
ARTICLE 11. TERM AND TERMINATION............................. 36
ARTICLE 12. ASSIGNMENT....................................... 42
ARTICLE 13. MISCELLANEOUS.................................... 43
ARTICLE 14. NOTICES.......................................... 51
EXHIBIT A.................................................... 54
EXHIBIT B.................................................... 58
<PAGE>
THIS LICENSE AGREEMENT is made and entered into as of this day of
January, 1996 by and between EMORY UNIVERSITY, a nonprofit Georgia corporation
with offices located at 1380 South Oxford Road, N.E., Atlanta, Georgia 30322,
(hereinafter referred to as "EMORY") and NOVOSTE CORPORATION, a Florida
corporation with its principal place of business located at 4350 International
Boulevard, Suite C, Norcross, Georgia 30093 (hereinafter referred to as
"NOVOSTE").
WITNESSETH
WHEREAS, EMORY asserts that it is the rightful owner of all right, title,
and interest in inventions developed by employees of EMORY and is responsible
for the protection and promotion of commercial development of such inventions;
and
WHEREAS, Ron Waksman, M.D. ("Waksman") and Ian R. Crocker, M.D. ("Crocker")
have, during their course of employment with EMORY, collaborated with NOVOSTE
employees to jointly invent certain novel devices and methods useful for the
treatment of restenosis; and
WHEREAS, Waksman and Crocker have executed an assignment of certain
inventions and the patent rights therein to NOVOSTE and there is, accordingly, a
dispute regarding title to such invention and patent rights; and
<PAGE>
WHEREAS, NOVOSTE represents that it has the necessary expertise and
resources to fully develop and commercialize such methods and devices; and
WHEREAS, EMORY wishes to have such methods and devices developed and
commercialized and made available in commerce for use by the public; and
WHEREAS, the parties desire to develop and commercialize such devices and
methods to their mutual benefit and to resolve all disputes as to title to such
inventions and the patent rights therein.
NOW, THEREFORE, for and in consideration of the mutual covenants and the
premises herein contained, the parties, intending to be legally bound, hereby
agree as follows.
ARTICLE 1. DEFINITIONS
-----------------------
The following terms as used herein shall have the following meaning:
1.1 "Affiliate" shall mean any corporation or non-corporate business entity
which controls, is controlled by, or is under common control with a party to
this Agreement. A corporation or non-corporate business entity shall be
regarded as in control of another corporation if it owns directly, or indirectly
controls, at
- 2 -
<PAGE>
least forty (40%) percent of the voting stock of the other corporation, or (i)
in the absence of the ownership of at least forty (40%) percent of the voting
stock of a corporation or (ii) in the case of a non-corporate business entity,
or non-profit corporation, if it possesses, directly or indirectly, the power to
direct or cause the direction of the management and policies of such corporation
or non-corporate business entity, as applicable.
1.2 "Agreement" shall mean this Agreement, including all Exhibits attached to
this Agreement.
1.3 "Assigned Patent" shall mean United States patent application serial number
08/330,327 and any reissues, renewals, extensions., divisionals, continuations,
which issue thereon, including reexamined and reissued patents, and any foreign
counterparts of such patent applications and issued patents.
1.4 "Dollars" shall mean United States dollars.
1.5 "FDA" shall mean the United States Food and Drug
Administration or successor entity.
1.6 "FDA Approval Application" shall mean, a PMA application or any other
application required to be filed with the FDA in order to obtain approval for
the sale of a Licensed Product in the United States.
- 3 -
<PAGE>
1.7 "Indemnitees" shall mean EMORY, its trustees, employees, students, and
their heirs, executors, administrators, successors and legal representatives.
1.8 "Licensed Patents" shall mean the prepared and unfiled patent
application attached as a part of Exhibit B hereto and any other patent
application, now or hereafter filed, which claims Licensed Technology (filed by
NOVOSTE in accordance with Section 7.2 hereof) together with any reissues,
renewals, extensions, divisionals, continuations, continuations-in-part, and
patents which issue thereon including reexamined and reissued patents, and any
foreign counterparts of such patent applications and issued patents.
1.9 "Licensed Product(s)" shall mean any catheter, transfer device or other
device, or other accessories sold with the catheter and/or the transfer device,
the manufacture, use, offer to sell or sale of which is covered by a Licensed
Patent, or uses or incorporates Licensed Technology.
1.10 "Licensed Technology" shall mean know how, devices, instruments,
technical data, trade secrets, designs, plans, specifications, methods,
processes, systems, all improvements, discoveries, developments, modifications,
formulae, concepts, techniques, ideas, manufacturing procedures, marketing
strategies
- 4 -
<PAGE>
and expertise, and any other information and documentation, whether or not
patented, which is conceived, learned, invented, or developed before or after
the date of this Agreement by Waksman, Crocker, and any other investigator
carrying out medical research sponsored by NOVOSTE during their course of
employment by EMORY or other employees of EMORY working under their direction to
the extent that: (i) such Licensed Technology is useful for the manufacture, use
or sale of any Licensed Product covered by the Assigned Patent or any Licensed
Patent and; (ii) EMORY possesses the right to license the use of such Licensed
Technology to NOVOSTE for commercial purposes without incurring financial or
other obligations to any non-employee third party or breaching any obligation of
confidentiality identiality with any such third party. "Licensed Technology
shall not include the subject matter claimed in the Assigned Patent.
1.11 "Territory" means the world.
1.12 "Net Selling Price" of Royalty-bearing Products shall mean the gross
invoice price actually paid by a purchaser of a Royalty-bearing Product to
NOVOSTE, an Affiliate of NOVOSTE, a sublicensee of NOVOSTE, or any other party
authorized by NOVOSTE to sell or lease Royalty-bearing Products (net of rebates,
refunds, replacements or credits allowed to purchasers for return of
- 5 -
<PAGE>
Royalty-bearing Products or as reimbursement for damaged Royalty-bearing
Products, discounts, sales, use or value-added taxes, duties, shipping and
transportation charges, insurance and allowances, commissions paid to non-
employee outside salesmen or distributors, import and custom duties, and any
separately itemized cost or expense for handling or disposing of radiation
contaminated catheters, transfer devices or other accessories sold with the
catheter and/or transfer device which shall not exceed NOVOSTE's costs for such
handling and disposal) and, if applicable, the value of all properties and
services received in consideration of a Sale of Royalty-bearing Products, by
NOVOSTE or Affiliates or sublicensees or authorized agents to Sell, from
unrelated purchasers in accordance with NOVOSTE's or sublicensee's or authorized
agents to Sell's normal practice and for which NOVOSTE, sublicensees or
authorized agents to Sell give credit to such purchasers for the value of such
properties and services. Where a Sale is deemed consummated by a gift, lease,
use or other disposition of products for other than a selling price stated in
cash, the term "Net Selling Price" shall mean the average gross selling price
billed by NOVOSTE in consideration of the Sale of comparable Royalty-bearing
Products during the three (3) month period immediately preceding such Sale, as
calculated above. if
- 6 -
<PAGE>
there are no such comparable Royalty-bearing products, "Net Sales Price" shall
be negotiated in good faith between the parties based on a commercially
reasonable fair market-value of the Royalty-bearing Product.
Notwithstanding anything set forth in this Paragraph 1.12, "Net Sales
Price" shall not in any event include any consideration paid to NOVOSTE, its
Affiliates, sublicensees or authorized agents for the sale, lease, use, service,
acquisition, handling, or disposal of radioactive isotopes or other radiation
sources.
1.13 "Registration" shall mean, in relation to any Licensed Product, such
approvals or marketing clearances by United States and other federal
authorities, such as the FDA and the Nuclear Regulatory Commission (NRC), and
state authorities as may be legally required before such Licensed Product may be
commercialized or Sold in the United States.
1.14 "Royalty-bearing Product" shall mean any catheter, transfer device or
other device, (excluding the isotope) or accessories sold with the catheter or
transfer device, the manufacture, use or sale of which is covered by the
Assigned Patent or a Licensed Patent, or which uses or incorporates Licensed
Technology. In no event shall "Royalty-bearing Product" include any service or
other act relating to the acquisition, handling,
- 7 -
<PAGE>
disposal or service of radioactive isotopes or other radiation sources.
1.15 "Sale" or "Sold" shall mean the sale, transfer, exchange for inventory
or services of comparable value, or other disposition of Royalty-bearing
Products whether by gift, lease or otherwise by NOVOSTE, an Affiliate of NOVOSTE
or NOVOSTE's sublicensees or any third party authorized by NOVOSTE to make such
sale, transfer, exchange or disposition including, but not limited to, the use
of Royalty-bearing Products by NOVOSTE, or any other person or entity authorized
to use Royalty-bearing Products by NOVOSTE. Sales of Royalty-bearing Products
shall be deemed consummated upon the first to occur of: (a) receipt of payment
from the purchaser; (b) if deemed Sold by use, when first put to such use; or
(c) if otherwise transferred, exchanged for inventory or services of comparable
value, or disposed of, by gift, lease or otherwise, when such transfer, exchange
for inventory or services of comparable value (not for returns of defective
Royalty-bearing Products) gift, lease or other disposition occurs.
ARTICLE 2. ASSIGNMENT AND GRANT OF LICENSE
------------------------------------------
2.1 Assignment. Emory shall, contemporaneous with the execution of this
----------
Agreement, execute and deliver to NOVOSTE the Quitclaim Assignment of the
Assigned Patent attached as Exhibit A.
- 8 -
<PAGE>
2.2 License. EMORY hereby grants NOVOSTE and its Affiliates an exclusive
-------
right and license to make, have made, use, offer to sell, sell Licensed Products
and to perform any other acts that without this license would be an act of
infringement, inducing infringement or contributory infringement and to grant
sublicenses to others to, make, use, offer to sell and sell Licensed Products
and to perform such acts in the Licensed Territory during the term of this
Agreement. EMORY further grants NOVOSTE and its Affiliates an exclusive right
and license to practice Licensed Technology and to grant sublicenses to others
to practice Licensed Technology, to make, have made, use, and sell Royalty-
bearing Products in the Territory during the term of this Agreement.
2.3 Retained License and Rights. EMORY retains on behalf of itself and its
---------------------------
employees, a royalty-free, non-exclusive right and license to use Licensed
Technology and subject matter claimed in any Licensed Patents for Emory's
research and educational purposes only. To the extent necessary for EMORY's
research and educational purposes only, NOVOSTE grants to EMORY a royalty-free,
non-exclusive license (without the right to grant sublicenses) to use the
subject matter covered by the Assigned Patent. EMORY reserves the right to grant
third parties rights to practice Licensed Technology for any purpose other than
to make, use, offer to sell,
- 9 -
<PAGE>
and sell products that come within the claims of the Licensed Patents. NOVOSTE
may supply Royalty-bearing Products at cost, to EMORY for Emory's research and
educational purposes, provided that such Royalty-bearing Products are not used
in studies sponsored by competitors of NOVOSTE and that EMORY shall not,
pursuant to this Section, supply any competitor of NOVOSTE with any samples of
any Royalty-bearing Products provided by NOVOSTE. However, EMORY shall be
authorized to accept research funding from NOVOSTE's competitors.
2.4 Sublicenses. NOVOSTE shall have the right to grant sublicenses
-----------
consistent with this Agreement, provided that NOVOSTE shall remain responsible
to EMORY for the operations of its sublicensees relevant to this Agreement, as
if such operations were carried out by NOVOSTE. NOVOSTE shall provide EMORY
with copies of any sublicenses within ninety (90) days of their execution date.
Such sublicense agreements shall be treated as NOVOSTE confidential information
in accordance with Article 10 of this Agreement.
2.5 No Implied License. The license and right granted in this Agreement
-------------------
shall not be construed to confer any rights upon NOVOSTE by implication,
estoppel, or otherwise as to any technology not specifically identified in this
Agreement, the Assigned Patent, Licensed Patents or Licensed Technology.
- 10 -
<PAGE>
ARTICLE 3. ROYALTIES AND OTHER PAYMENTS
---------------------------------------
3.1 Earned Royalties. NOVOSTE shall pay EMORY a royalty equal to XXXXX
----------------
percent of the Net Selling Price of Royalty-bearing Products Sold in the
Territory, except as provided for in Sections 3.2 and 3.3 of this Agreement.
3.2 Reduced Royalties.
-----------------
(a) No Issued Patents. If no Assigned Patent or Licensed Patent issues in the
-----------------
United States with claims covering a Royalty-bearing Product within three (3)
years of the filing date of U.S. Patent Application No. 08/330,327, NOVOSTE
shall, commencing with the first calendar quarter after such third year, pay
EMORY a reduced royalty rate of XXXXX percent of the Net Selling Price of
Royalty-bearing Products in the Territory. NOVOSTE's obligation to pay royalties
pursuant to this Section shall terminate ten (10) years after the first royalty
bearing commercial Sale of a Royalty-bearing Product, unless after such third
year a Licensed Patent or Assigned Patent issues in the United States with
claims covering a Royalty-bearing Product, at which time the applicable royalty
rate shall revert to XXXXX percent and shall remain in effect until the last to
expire of all Licensed Patents and Assigned Patent with claims covering a
Royalty-bearing Product in the United States.
- 11 -
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
(b) Adverse Claims Regarding the Assigned Patent.
---------------------------------------------
If any claim or action is filed against NOVOSTE by EMORY, Waksman, Crocker,
or other EMORY employee or former employee, relating to the ownership, title,
license or other claim of rights to the Assigned Patent, NOVOSTE shall,
commencing with the first calendar quarter after any such claim or action is
filed, pay EMORY a reduced royalty of XXXXX percent of the Net Selling Price
of Royalty-Bearing products in the Territory, and the Minimum Annual Royalties
set forth below shall be reduced by fifty (50%) percent. If such claim or
action is successfully defeated by NOVOSTE, the applicable royalty rate shall
revert to XXXXX percent and the Minimum Annual Royalties shall revert to those
amounts set forth below. NOVOSTE shall provide EMORY with a full and complete
accounting of all withheld royalties and NOVOSTE's costs and expenses associated
with such litigation, in reports provided to EMORY pursuant to Article 4 of this
Agreement. If the amount of withheld royalties exceeds the costs and expenses
incurred by NOVOSTE in defeating such claim or action, such amount shall be paid
to EMORY at the end of the first quarter following the termination of the claim
or action. If NOVOSTE fails to prevail in such action, NOVOSTE shall be
entitled to pay the reduced royalties
- 12 -
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
prescribed under this Section to the extent required to satisfy any NOVOSTE
obligations to the prevailing party.
(c) Under no circumstances shall (i) reduced running royalties payable to
EMORY under this Agreement fall below XXXXX percent; (ii) nor shall minimum
annual royalties fall below fifty (50%) percent of those prescribed in Section
3.4.
3.3 Royalty-Free Products Notwithstanding anything to the contrary in this
---------------------
Agreement, no royalty shall be due or payable for Royalty-bearing Products that
are made, used, or Sold for use in (i) clinical trials, (ii) training or
demonstration procedures, (iii) research or development relating to improving
Royalty-bearing Products, or (iv) Licensed Products sold at cost to EMORY.
3.4 Additional Consideration.
------------------------
(a) NOVOSTE shall pay EMORY XXXXX percent of any signing fees, minimum
royalties, milestone or up-front payments received by NOVOSTE from any
sublicensee (excluding advanced earned royalty payments). NOVOSTE shall not be
required to pay EMORY any portion of any fees received from sublicensees to be
used by NOVOSTE solely for the purpose of conducting clinical trials, research
and development or for tooling. Such XXXXX percent payment shall be in addition
to running royalties payable to EMORY based on Sales
- 13 -
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
by NOVOSTE sublicensees in accordance with Sections 1.12, 1.15, 3.1 and 3.2 of
this Agreement.
(b) Commencing upon one year after the first commercial (for purposes other
than clinical trial, research or development, or training or demonstration) Sale
of any Royalty-bearing Product in any major country (U.S., U.K., France,
Germany, Japan or Canada), NOVOSTE shall.11 pay EMORY minimum annual royalties
in accordance with the following schedule:
Year Amount
- - ---- ------
Year 2 After First Commercial Sale $ XXXXX
Year 3 After First Commercial Sale $ XXXXX
Year 4 After First Commercial Sale $ XXXXX
Years 5-10 After First Commercial Sale $ XXXXX
(c) NOVOSTE shall, within thirty (30) days after execution of this
Agreement, issue shares of NOVOSTE Common Stock as indicated below:
(a) Forty-four Hundred (4,400) shares to XXXXX. **
(b) Eighteen Hundred (1,800) shares to Ian Crocker, M.D.
(c) Thirty Eight Hundred (3,800) shares to Emory University
ARTICLE 4. REPORTS AND ACCOUNTING
---------------------------------
4.1 Royalty Reports and Records. Commencing with the first calendar quarter
---------------------------
during which NOVOSTE makes its first commercial
- 14 -
** EMORY or any party designated by EMORY.
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
sale of a Royalty-bearing Product, NOVOSTE shall furnish, or cause to be
furnished to EMORY, on a quarterly basis, and within sixty (60) days of the end
of each quarter a written report or reports governing each of NOVOSTE, NOVOSTE's
Affiliates and sublicensees fiscal quarters showing:
(i) the Sales of all Royalty-bearing Products in the Territory during the
reporting period (including the number of units shipped, sold and the value of
any payments due or received) together with calculations of Net Selling Prices
and royalties payable to EMORY in Dollars in accordance with Sections 1.12,
1.14, 3.1, 3.2 and 3.4 of this Agreement; and
(ii) the exchange rates, used, if any, in determining the
amount of Dollars; and
(iii) any other consideration payable to EMORY in accordance with Article 3,
including but not limited to, fees received by NOVOSTE from sublicensees.
To the extent that the "Net Selling Price" is calculated by making deductions
in accordance with Section 1.12 of this Agreement, the written royalty report
shall separately itemize such deductions and the basis therefore, including but
not limited to, deductions for actual costs or expenses incurred for handling or
disposing of radiation contaminated catheters, transfer devices and
- 15 -
<PAGE>
accessories of such devices (excluding isotopes) and shall further indicate
NOVOSTE's costs on either a per catheter or transfer device basis, or a periodic
basis, or both.
4.2 Right to Audit. EMORY shall have the right, upon prior notice to
--------------
NOVOSTE, not more than once in each NOVOSTE fiscal year, through an independent
public accountant selected by EMORY and acceptable to NOVOSTE, which acceptance
shall not be unreasonably refused, to have access during normal business hours
of NOVOSTE, as may be reasonably necessary, related to the Sale of Licensed
Products to verify the accuracy of the royalty reports furnished by NOVOSTE
pursuant to Section 4.1 of this Agreement. NOVOSTE shall include in any
sublicenses granted pursuant to this Agreement, a provision requiring the
sublicensee to keep and maintain a record of Sales made pursuant to such
sublicense and to grant similar access to such records by EMORY's independent
public accountant. If such independent public accountant's reports show any
underpayment of royalties, within sixty (60) days after NOVOSTE's receipt of
such report, and NOVOSTE accepts the accuracy of such report, NOVOSTE shall
remit or shall cause its sublicensees to remit to EMORY:
(i) the amount of such underpayment; and
- 16 -
<PAGE>
(ii) if such underpayment exceeds five (5%) percent of the total
royalties owned for the fiscal year then being reviewed, the reasonably
necessary fees and expenses of such independent public accountant performing the
audit. Otherwise, EMORY's accountant's fees and expenses shall be borne by
EMORY. Any overpayment of royalties shall be fully creditable against future
royalties payable in any subsequent royalty periods. If NOVOSTE does not accept
the accuracy of the independent public accountant's report, then NOVOSTE may
invoke its options to mediate and arbitrate in accordance with Section 13.11 of
this Agreement.
4.3 Confidentiality of Records. All information subject to review under
--------------------------
this Article 4 or any sublicense shall be confidential. Except where provided by
law, EMORY and its accountant shall retain all such information in confidence.
ARTICLE 5. PAYMENTS
-------------------
5.1 Payment Due Dates. Royalties and amounts payable to EMORY from any
-----------------
other consideration paid to NOVOSTE during the period covered by each royalty
report provided for under Article 4 of this Agreement, shall be due and payable
on the date such royalty report is due. Minimum annual royalties shall be due
on or before February 28th of the calendar year following the year for which the
minimum annual royalties are due. Payments of royalties
- 17 -
<PAGE>
in whole or in part may be made in advance of such due date. Any payment in
excess of One Hundred Thousand ($100,000.00) Dollars shall be made by wire or
transferred to the account of EMORY designated by EMORY from time to time;
provided, however, that in the event that EMORY fails to designate such account,
NOVOSTE may remit payment to EMORY to the address applicable for the receipt of
notices hereunder; providing, further, that any notice by EMORY of such
account or change in such account, shall not be effective until fifteen (15)
days after receipt thereof by NOVOSTE.
5.2 Currency Restrictions. Except as hereinafter provided in this Section
---------------------
5.2, all royalties shall be paid in Dollars. If, at any time, legal
restrictions prevent the prompt remittance of part of or all royalties with
respect to any country of the Territory where Royalty-bearing Products are sold,
NOVOSTE or its sublicensee shall have the right and option to make such payments
by depositing the amount thereof in local currency to EMORY's account in a bank
or depository in such country.
5.3 Interest. Royalties and other payments required to be paid by NOVOSTE
--------
pursuant to this Agreement shall, if overdue, bear interest of ten (10%)
percent until paid. The payment of such interest shall not foreclose EMORY from
exercising any other rights it may have because any payment is overdue.
- 18 -
<PAGE>
ARTICLE 6. DEVELOPMENT AND MARKETING PROGRAM
--------------------------------------------
6.1 Diligence obligations. NOVOSTE shall directly, or in collaboration with
---------------------
Affiliates and sublicensees, use commercially reasonable efforts:
(i) to conduct a product development program relating to the commercial
use of Royalty-bearing Products for the prophylaxis or treatment of restenosis,
and
(ii) if, in NOVOSTE's opinion, the results of the development program
so justify, to seek Registration in the United States. For purposes of this
Agreement "commercially reasonable efforts" shall mean NOVOSTE shall use
commercially reasonable efforts, including seeking to establish alliances, with
other device companies where deemed appropriate and beneficial to NOVOSTE,
consistent with those used by medical device companies of similar size and with
comparable resources in the United States in research and development projects
for technology deemed to have commercial value comparable to the Royalty-bearing
Products and Licensed Technology. The development program shall include such
product development work as NOVOSTE may, in its sole discretion, consider
necessary for such Registrations or approvals.
6.2 Fulfillment, Conversion. NOVOSTE's commercially reasonable efforts
-----------------------
obligations set forth in Section 6.1 shall be
- 19 -
<PAGE>
deemed to have been fulfilled if (a) NOVOSTE uses commercially reasonable
efforts in filing an application with appropriate regulatory agencies to market
one or more Royalty-bearing Products in any major market country (France, U.K.,
Canada, U.S. or Japan) within forty-eight (48) months of the effective date of
this Agreement; and
(b) NOVOSTE uses commercially reasonable efforts to diligently pursue
reasonable regulatory requirements necessary for achieving approval or
Registration in any such major market countries.
If NOVOSTE fails to meet either deadline set forth in subsection 6.2 above,
EMORY may, upon at least sixty (60) days, prior written notice, grant third
parties identical or lesser rights in the Licensed Patents as granted to NOVOSTE
hereunder (in which case the license granted under Article 2 shall become
non-exclusive and EMORY shall be authorized to provide potential and actual
licensees with information pertaining to the Licensed Patents and Licensed
Technology in the same manner as if this Agreement were terminated in accordance
with Section 11.5(c)), and such termination has the effect described in
Paragraph 2 of Section 11.7, unless within such sixty (60) day period, NOVOSTE
meets such deadline. NOVOSTE shall further use commercially reasonable
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<PAGE>
efforts to bring Licensed Products to market in major markets outside the United
States such as France, the United Kingdom, Canada, and Japan. NOVOSTE shall
have the right to pursue mediation or arbitration pursuant to Article 13.11 if
NOVOSTE disputes EMORY's right to exercise any remedy under this paragraph.
6.3 Progress Reports. During the term of this Agreement, NOVOSTE shall
----------------
provide semi-annual reports to EMORY, summarizing in reasonable detail,
NOVOSTE's activities related to the development of Royalty-bearing Products, and
securing Registrations or approvals. At a minimum, such reports shall include a
summary of correspondence or other communications between NOVOSTE or NOVOSTE's
affiliates and sublicensees and foreign or domestic agencies pertaining to any
regulatory application for a Royalty-bearing Product. Where such correspondence
or communication indicates a request for additional data from any government
agency, NOVOSTE or NOVOSTE's Affiliates and sublicensee shall inform EMORY at
the time progress reports are due of NOVOSTE or NOVOSTE's Affiliates or
sublicensees schedules with respect to responding to such requirements.
6.4 NOVOSTE Not Restricted. Nothing in this Agreement is intended to
----------------------
inhibit or prohibit NOVOSTE from exploring, making,
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<PAGE>
using or selling other technologies useful for treating restenosis, even if
deemed competitive to Royalty-bearing Products.
ARTICLE 7. PATENT PROSECUTION
-----------------------------
7.1 NOVOSTE shall have full and complete responsibility for all patent
prosecution activities with respect to the Assigned Patent and shall be
primarily responsible for all patent prosecution activities pertaining to the
Licensed Patents. NOVOSTE shall, either directly, or through its outside
counsel, provide EMORY with copies of all filings and patent office
correspondence pertaining to such patent prosecution activities, in a timely
manner, so as to give EMORY an opportunity to comment thereon. EMORY shall
have authority to maintain or add claims supported by any Licensed Patents
provided it does so in a timely manner after notice to NOVOSTE. NOVOSTE shall
diligently pursue prosecution, issuance and maintenance of the Assigned Patent
and Licensed Patents in the United States, the United Kingdom, Germany, France,
Japan and Canada. NOVOSTE may use the PCT or European Patent Convention as
NOVOSTE sees fit for the above identified countries. NOVOSTE may further
exercise its discretion to pursue prosecution, issuance and maintenance of the
Assigned Patent and Licensed Patents in other foreign countries. Any patent
counsel retained to prosecute or maintain any Licensed Patents shall be put on
written
- 22 -
<PAGE>
notice that such counsel represents NOVOSTE and EMORY for the purpose of such
patent prosecution and maintenance activities.
If NOVOSTE fails to diligently pursue prosecution in the United States,
United Kingdom, France, Germany or Japan of any Licensed Patent application or
maintain any issued Licensed Patent under this Agreement, such application or
issued patent shall no longer be subject to this Agreement and EMORY shall be
free, at its discretion, to assume the prosecution and maintenance of such
patent applications or issued patents and grant rights to third parties
pertaining to such Licensed Patent applications or issued Licensed Patents.
7.2 To enable NOVOSTE to prepare and file Licensed Patent applications,
EMORY shall promptly disclose to NOVOSTE in written form ("invention
disclosure") any Licensed Technology that may conceivably be patentable made
during the course of any research or clinical trials sponsored by NOVOSTE
pertaining to NOVOSTE'S Beta System to treat restenosis.
7.3 Upon receipt of EMORY'S invention disclosure, NOVOSTE shall have an
initial six-month period to evaluate the disclosure to determine if it wishes to
file a patent application on the subject matter of such disclosure. If NOVOSTE
is unable to complete its evaluation within the first six month period, it may
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<PAGE>
request permission from EMORY for a second six-month evaluation period to
continue such evaluation, which permission shall not be unreasonably withheld by
EMORY. In no event shall NOVOSTE'S evaluation period exceed a total of twelve
months.
7.4. (a) Licensed Patents for any inventions made or conceived jointly by
NOVOSTE and EMORY personnel shall be owned jointly by NOVOSTE and EMORY (not
including any inventions claimed in the Assigned Patent). The parties agree to
cooperate in the preparation and prosecution of any patent applications for such
joint inventions. NOVOSTE shall have the same responsibility for filing patent
applications directed to joint inventions as for inventions made solely by EMORY
employees.
7.4. (b) NOVOSTE shall promptly notify EMORY if, after receiving an
invention disclosure, it believes that the invention was made by NOVOSTE
employees, either alone or jointly with EMORY employees. If, after receiving
notice from NOVOSTE that an invention was jointly made, EMORY believes that the
invention claimed was invented solely by employees of EMORY, the parties each
agree to promptly investigate, in good faith, the making of such invention and
to share the results of such investigation with one another. If unable to agree
on inventorship after such investigation, the parties agree to submit the issue
of
- 24 -
<PAGE>
inventorship for decision to an experienced patent attorney, who has represented
neither NOVOSTE nor EMORY, and who is agreeable to both parties. Each party
will cooperate fully with such attorney, and the attorney's fee shall be borne
equally by both parties. The decision of "inventorship" by the attorney shall
be binding, and the parties agree to cooperate in any necessary steps to change
inventorship, if required by the attorney's decision.
ARTICLE 8. INFRINGEMENT AND THIRD PARTY RIGHTS
----------------------------------------------
8.1 Infringement. If either NOVOSTE or EMORY becomes aware of a product or
service, the manufacture, use or Sale of which appears to infringe the Assigned
Patent or any Licensed Patent, the party obtaining such knowledge shall promptly
advise the other party of all relevant facts and circumstances pertaining to the
potential infringement. NOVOSTE shall have the right to enforce any Licensed
Patent. NOVOSTE shall exercise full control over any such action with respect
to the infringement or protection of the Assigned Patent or any Licensed
Patents; provided that EMORY shall have the opportunity to be represented in
such action at EMORY's sole option and expense. EMORY shall cooperate with
NOVOSTE in any such effort, at NOVOSTE's expense, including being joined as a
party to such action, if necessary. Any damages or costs recovered in
connection with any action filed by NOVOSTE hereunder, which
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<PAGE>
exceed NOVOSTE's out-of-pocket costs and expenses of litigation, shall be deemed
to be Net Sales of Licensed Products in the fiscal year received by NOVOSTE, and
royalties shall be payable by NOVOSTE to EMORY thereon in accordance with the
terms of this Agreement.
If NOVOSTE shall fail, within sixty (60) days after receiving notice from
EMORY of a potential infringement, or providing EMORY with notice of such
infringement, to either (a) terminate such infringement or (b) institute an
action to prevent continuation thereof and, thereafter to prosecute such action
diligently, or if NOVOSTE notifies EMORY that it does not plan to terminate the
infringement or institute such action, then EMORY shall have the right to do so
at its own expense. NOVOSTE shall cooperate with EMORY in such effort, at
EMORY's expense, including being joined as a party to such action as necessary.
Any damages or costs recovered by EMORY in connection with any action shall be
retained by EMORY.
8.2 Third Party-Rights. If the manufacture, use or Sale of a Royalty-
-------------------
bearing Product is objected to as infringing a patent issued as of the date of
this Agreement from the date of such objection until the objection is finally
resolved, NOVOSTE shall have the right to retain as a reserve 12.5% of any
royalties coming due to EMORY under Article 3 and to apply such reserve against:
its
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<PAGE>
legal expenses; any settlement costs or license fees; any court ordered
recovery; and any loss suffered by NOVOSTE, including any loss as a result of
any court-ordered injunction. NOVOSTE shall exercise full control over the
settlement or resolution of any such objection and full control over any related
litigation, and shall have full and complete authority to settle and resolve
such objection on such terms as NOVOSTE, in its sole discretion, sees fit.
EMORY shall have the right to be represented in any proceeding regarding such
objection by counsel of its own choice and at its own expense. Within thirty
(30) days of a final resolution of all such matters, NOVOSTE shall pay any
balance of said reserve to EMORY and provide EMORY an accounting of the amounts
held in reserve and amounts offset by NOVOSTE against the reserve. If the final
resolution of the matter requires NOVOSTE to make royalty or other payments to
the other party, and such payments result in NOVOSTE's cumulative royalty
obligation on the Sale of Royalty-bearing Products exceeding five (5%) percent
of the Net Selling Price, NOVOSTE shall be authorized to retain up to 12.5% of
any future royalties, (excluding minimum annual royalties) due under this
Agreement to meet such obligations of NOVOSTE.
- 27 -
<PAGE>
ARTICLE 9. WARRANTIES AND INDEMNIFICATION
----------------------------------------
9.1 Merchantability and Exclusion of Warranties. NOVOSTE possesses the
-------------------------------------------
necessary expertise and skill in the technical areas pertaining to the Licensed
Patents and Licensed Technology to make and has made its own evaluation of the
capabilities, safety, utility and commercial application of the Licensed Patents
and Licensed Technology. ACCORDINGLY, EXCEPT AS SET FORTH IN SECTION 9.7, EMORY
DOES NOT MAKE ANY REPRESENTATION OR WARRANTY OF ANY KIND WITH RESPECT TO THE
LICENSED PATENTS OR LICENSED TECHNOLOGY AND EXPRESSLY DISCLAIMS ANY WARRANTIES
OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE AND ANY OTHER IMPLIED
WARRANTIES WITH RESPECT TO THE CAPABILITIES, SAFETY, UTILITY, OR COMMERCIAL
APPLICATION OF THE LICENSED PATENTS OR LICENSED TECHNOLOGY.
9.2 No Liability. EMORY shall not be liable to NOVOSTE or NOVOSTE's
------------
Affiliates, customers or sublicensees for special incidental, indirect, or
consequential damages resulting from the manufacture, testing, design, labeling,
use or Sale of Royalty bearing Products.
9.3 Indemnification.
---------------
(a) NOVOSTE shall defend, indemnify, and hold harmless the Indemnitees, from
and against any and all claims, demands, loss, liability, expense, or damage
(including investigative costs, court
- 28 -
<PAGE>
costs and attorneys, fees) Indemnitees may suffer, pay, or incur as a result of
claims, demands or actions against any of the Indemnitees arising or alleged to
arise by reason of, or in connection with, any and all personal injury
(including death) and property damage caused or contributed to in whole or in
part by NOVOSTE's or NOVOSTE's Affiliates', contractors', agents', or
sublicensees' manufacture, testing, design, use, Sale, or labeling of any
Royalty-bearing or Licensed Products except where such claim, demand, loss,
liability, expense or damage results solely from EMORY's negligence or
misconduct or misrepresentation implied or direct. NOVOSTE's obligations under
this Article shall survive the expiration or termination of this Agreement for
any reason.
(b) EMORY shall notify NOVOSTE promptly and in writing of any claim, suit or
proceeding relating to the Licensed Patents or the Licensed Technology of which
EMORY becomes aware, and for which EMORY intends to seek indemnification in
accordance with Section 9.3(a). EMORY shall furnish NOVOSTE with full
information concerning any such claim, suit or proceeding and shall render
NOVOSTE full cooperation to facilitate a settlement or defense of any such
claim. EMORY shall have the opportunity to be represented by counsel at its
sole option and expense.
- 29 -
<PAGE>
9.4 Insurance. Without limiting NOVOSTE's indemnity obligations under the
---------
preceding paragraph NOVOSTE shall, to the extent available at commercially
reasonable rates and prior to the Sale of any Royalty-bearing Product, cause to
be in force, an "occurrence based type" liability insurance policy which:
(a) insures Indemnitees for all claims, damages, and actions mentioned
in Section 9.3 of this Agreement, including but not limited to, damages caused
by radioactive substances; and
(b) includes a contractual endorsement providing coverage for all
liability which may be incurred by Indemnitees in connection with the Agreement;
and
(c) requires the insurance carrier to provide EMORY with no less than
thirty (30) days' written notice of any change in the terms or coverage of the
policy or its cancellation; and
(d) provides Indemnitees product liability coverage in an amount no
less than Two Million Dollars ($2,000,000.00) per occurrence for bodily injury
and One Million Dollars ($1,000,000.00) per occurrence for property damage,
subject to a reasonable aggregate amount.
9.5 Occurrence Based Coverage Not Available. If NOVOSTE is unable to obtain
---------------------------------------
"occurrence based type" liability insurance at commercially reasonable rates,
NOVOSTE shall procure "claims made
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<PAGE>
type" liability coverage to be effective throughout the term of this Agreement
and "tail coverage", extending at least five (5) years after termination of this
Agreement. NOVOSTE shall notify EMORY prior to its first commercial Sale of any
Licensed Product, of all insurance coverage and other assets available to
NOVOSTE to meet NOVOSTE's obligations under Sections 9.3 and 9.4 of this
Agreement.
9.6 Notice of Claims. NOVOSTE shall promptly notify EMORY of all claims
----------------
involving the Indemnitees and shall advise EMORY of the policy amounts that
might be needed to defend and pay any such claims.
9.7 Warranties of EMORY. EMORY represents and warrants that it is the
-------------------
lawful assignee of all intellectual property rights, including patent rights,
possessed by Ian Crocker, M.D. and Ron Waksman, M.D. pertaining to the Licensed
Patents and Licensed Technology and has the right and authority to grant the
rights and licenses provided for in Article 2 of this Agreement.
9.8 Indemnification by EMORY. EMORY shall indemnify and hold NOVOSTE, its
------------------------
Affiliates, authorized agents and sublicensees, harmless from and against any
liability or damages or expenses resulting from any claim or action by EMORY,
Waksman, Crocker or other EMORY employee or former employee relating to
ownership,
- 31 -
<PAGE>
title, license or other claim of rights to any Licensed Patent, or in or to any
inventions claimed therein. NOVOSTE shall promptly inform EMORY in writing of
any action, claim or liability in respect of which NOVOSTE intends to claim such
indemnification. NOVOSTE shall permit EMORY, at its discretion, to settle any
such action, claim or liability and agrees to the complete control of such
defense or settlement by EMORY; provided, however that such settlement does not
adversely affect NOVOSTE's rights hereunder or impose any obligations financial
or otherwise on NOVOSTE in addition to those set forth herein in order for
NOVOSTE to exercise the rights granted to it under this Agreement. NOVOSTE
shall not be responsible for any legal fees or other costs incurred other than
as provided herein. NOVOSTE, its employees and agents shall cooperate fully
with Emory and its legal representatives, at EMORY's expense, in the
investigation and defense of any action, claim or liability covered by this
indemnification. The amount of such indemnification shall be limited to the
total consideration received by EMORY from NOVOSTE under this agreement,
including cash royalty payments and the value of any NOVOSTE stock issued to
EMORY hereunder. The value of such stock shall be determined as follows: (i) if
shares or other units of NOVOSTE equity are publicly traded on a recognized
securities market, the publicly traded price shall
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<PAGE>
apply; or (ii) if such shares are not publicly traded, the value shall be equal
to the per share price obtained by NOVOSTE in its most recent round of preferred
equity financing, unless since such round, NOVOSTE's Board of Directors has
established a new per share price in good faith, in which case, such Board
determined price shall apply. EMORY shall, under all circumstances, be entitled
to satisfy any obligations to NOVOSTE under this Section respecting such stock
by returning the stock to NOVOSTE. If NOVOSTE incurs costs or damages for which
it is entitled to indemnification in an amount which exceeds the total
consideration received by EMORY at the time such costs or damages are incurred,
NOVOSTE may retain one hundred (100%) percent of future royalties payable to
EMORY hereunder, including any minimum royalties, and apply it as a credit
against such unpaid costs or damages until such amounts are recouped in full by
NOVOSTE. NOVOSTE shall provide EMORY with a complete and full accounting of any
such royalty credits in reports provided to EMORY pursuant to Article 4 of this
Agreement.
ARTICLE 10. CONFIDENTIALITY
---------------------------
10.1 Treatment of Confidential Information. Except as otherwise provided
-------------------------------------
hereunder, during the term of this Agreement and for a period of five (5) years
thereafter;
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<PAGE>
(i) NOVOSTE and its Affiliates, sublicensees and alliance partners
shall retain in confidence and use only for purposes of this Agreement any
information or data designated confidential and pertaining to the Licensed
Technology supplied by EMORY to NOVOSTE under this Agreement;
(ii) EMORY shall retain in confidence and use only for purposes of
this Agreement any information and data designated confidential and supplied by
NOVOSTE or on behalf of NOVOSTE to EMORY under this Agreement.
For purposes of this Agreement, all such information and data which a party
is obligated to retain in confidence shall be called "Information."
10.2 Right to Disclose. To the extent that it is reasonably necessary to
-----------------
fulfill its obligations or exercise its rights under this Agreement or any
rights which survive termination or expiration hereof, each party may disclose
Information to its Affiliates, sublicensees, consultants, alliance partners,
outside contractors, and clinical investigators on condition that such entities
or person agree:
(i) to keep the Information confidential for at least the same time
periods and to the same extent as each party is required to keep the Information
confidential;
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<PAGE>
(ii) to use the Information only for such purposes as such parties are
authorized to use the Information.
Each party or its Affiliates or sublicensees may disclose Information to the
government or other regulatory authorities or qualified independent consultants
to the extent that such disclosure (a) is reasonably necessary to obtain patents
or authorizations to conduct clinical trials and to market commercially Licensed
Products, provided that such party is otherwise entitled to engage in such
activities under this Agreement or (b) is otherwise legally required to make
such disclosure.
10.3 Release from Restrictions. The obligation not to disclose Information
-------------------------
shall not apply to any part of such Information that:
(i) is or becomes patented, published or otherwise part of the public
domain, other than by acts of the party obligated not to disclose such
Information; (for purposes of this Article 10 the "receiving party") or its
Affiliates or sublicensees in contravention of this Agreement;
(ii) is disclosed to the receiving party or its Affiliates or
sublicensees by a third party provided that such Information was not obtained by
such third party directly or
- 35 -
<PAGE>
indirectly from the other party under this Agreement pursuant to an obligation
of confidentiality; or
(iii) prior to disclosure under this Agreement, was already in the
possession of the receiving party, its Affiliates or sublicensees, provided that
such Information was not obtained directly or indirectly from the other party
under this Agreement; or
(iv) results from research and development by the receiving party or
its Affiliates or sublicensees independent of disclosures from the other party
of this Agreement, provided that the persons developing such information have
not had exposure to the information received from the disclosing party; or
(v) is required by law to be disclosed by the receiving party, provided
that the other party is notified and given reasonable opportunity to oppose such
requirement; or
(vi) NOVOSTE and EMORY agree in writing may be disclosed.
ARTICLE 11. TERM AND TERMINATION
--------------------------------
11.1 Term. Unless sooner terminated as otherwise provided in this
----
Agreement, the term of this Agreement shall commence on the effective date
hereof and shall continue in full force and effect until the later of (a) the
expiration of the last Assigned Patent
- 36 -
<PAGE>
or Licensed Patent to expire or (b) twenty (20) years after the date hereof.
11.2 Termination. EMORY shall have the right to terminate this Agreement,
-----------
in accordance with the procedures set forth in Section 11.3, upon the occurrence
of any one or more of the following events;
(a) failure of NOVOSTE to make any payment required pursuant to this
Agreement when due; or
(b) failure of NOVOSTE to render reports to EMORY as required by this
Agreement; or
(c) the insolvency of NOVOSTE; or
(d) the institution of any proceeding by NOVOSTE under any bankruptcy,
insolvency, or moratorium law; or
(e) any assignment by NOVOSTE of substantially all of its assets for
the benefit of creditors; or
(f) placement of NOVOSTE's assets in the hands of a trustee or a
receiver unless the receivership or trust is dissolved within thirty (30) days
thereafter; or
(g) a decision by NOVOSTE (except through the sale of NOVOSTE or the
business of NOVOSTE per Article 12) or NOVOSTE's assignee of rights under this
Agreement to quit the business of developing or selling Licensed Products; or
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<PAGE>
(h) the breach of any other material term of this Agreement; or
(i) the cessation of the business of developing and marketing catheters
by NOVOSTE, or an assignee of NOVOSTE's interests under this Agreement.
11.3 Exercise. EMORY may exercise its right of termination by giving
--------
NOVOSTE, its trustees, receivers or assigns, thirty (30) days' prior written
notice of EMORY's election to terminate. Such notice shall be sixty (60) days
if the basis of exercising EMORY's right of termination is the failure of
NOVOSTE to provide a progress report as required under Section 6.3 of this
Agreement. Such notice shall include the basis for such termination. Upon the
expiration of such period, this Agreement shall automatically terminate unless
NOVOSTE has cured the breach. Such notice and termination shall not prejudice
EMORY's right to receive royalties or other sums due hereunder and shall not
prejudice any cause of action or claim of EMORY accrued or to accrue on account
of any breach or default by NOVOSTE.
11.4 Failure to Enforce. The failure of EMORY or NOVOSTE, at
------------------
any time or for any period of time, to enforce any of the provisions of this
Agreement shall not be construed as a waiver of
- 38 -
<PAGE>
such provisions or as a waiver of the right of EMORY or NOVOSTE thereafter to
enforce each and every such provision.
11.5 Termination by NOVOSTE. NOVOSTE shall have the right to terminate this
----------------------
Agreement upon the occurrence of any of the following events:
(a) The breach of a material term of this Agreement by EMORY; or
(b) If the manufacture, use or Sale of Royalty-bearing Products is
determined by a court to infringe third party rights; or
(c) if the Sale of Licensed Products requires approval by any
government agency, and after using commercially reasonable efforts to gain such
approval, including but not limited to: performing alternative tests or analyses
as requested by any agency; submitting relevant data to such agency; and after
pursuing available and commercially reasonable administrative procedures and
appeal processes permitted by such agency NOVOSTE is unable to obtain such
approval in such territory; or
(d) NOVOSTE determines in its sole discretion that it is not
commercially practicable to proceed with such manufacture, use or Sale of
Royalty-bearing Products due to litigation costs or costs required for obtaining
licenses, or due to changes in the
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<PAGE>
market resulting from the emergence of competitive technologies and rights from
such third parties.
11.6 Exercise. NOVOSTE may exercise its right of termination pursuant to
--------
Section 11(5) (a), by giving EMORY sixty (60) days prior written notice of
NOVOSTE's election to terminate. The notice shall include the basis for such
termination. Upon the expiration of such period, this Agreement shall
automatically terminate unless EMORY has cured the breach. Such notice of
termination shall not prejudice any cause of action or claim of NOVOSTE accrued
or to accrue on account of any breach or default by EMORY.
NOVOSTE may exercise its right of termination pursuant to section 11.5(b),
(c) or (d) , or if the license hereunder becomes nonexclusive pursuant to 6.2,
by giving EMORY thirty (30) days prior written notice of NOVOSTE's election to
terminate. This agreement shall be terminated upon the expiration of such
thirty (30) days.
11.7 Effect. In the event this Agreement is terminated for any reason
------
whatsoever, other than by NOVOSTE under Paragraph 11.5(a) , NOVOSTE shall
return, or at EMORY Is direction destroy, all data, writings and other documents
and tangible materials such as cell lines, supplied to NOVOSTE by EMORY provided
that such items
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<PAGE>
consist of Licensed Technology or Licensed Patents. NOVOSTE shall provide EMORY
with full and complete copies of all toxicity, efficacy, and other data
generated by NOVOSTE or NOVOSTE's sublicensees, contractors and agents in the
course of NOVOSTE's efforts to develop Licensed Products, to the extent NOVOSTE
controls such data and information. NOVOSTE shall be authorized to retain one
(1) archival copy of confidential information received from EMORY under this
Agreement in its corporate offices to be used solely for the purpose of NOVOSTE
monitoring compliance with this Agreement.
If the Agreement is terminated as a result of NOVOSTE's breach pursuant to
Section 11.2 or in accordance with 11.5 (b), (c) or (d), EMORY shall be
authorized to provide full and complete copies of all information provided to
EMORY by NOVOSTE pertinent to the Licensed Patents and Licensed Technology to
any third party with a bona fide interest in licensing any technology licensed
to NOVOSTE hereunder. Such information shall be provided on a confidential
basis, provided, however, that if such third party signs a license agreement
with EMORY, such third party shall be free to use such information for all
purposes including to obtain government approvals to sell Licensed Products.
NOVOSTE shall cooperate with EMORY in granting any third parties data or patent
rights (such as
- 41 -
<PAGE>
under the Assigned Patent) needed to proceed with commercializing, including the
IDE, or other approval applications filed by NOVOSTE, any Licensed Products upon
reasonable terms and conditions acceptable to NOVOSTE in its complete and
absolute discretion. If EMORY or its licensee are unable, after good faith
negotiations with NOVOSTE, to conclude terms allowing for the commercial
development or Sale of Licensed Products, EMORY or its licensee may refer the
matter to mediation and arbitration pursuant to Section 13.11 of this Agreement.
11.8 NOVOSTE Rights Upon Termination. Upon termination of this Agreement
--------------------------------
pursuant to Section 11.5(a), or upon the expiration of any obligations of
NOVOSTE to pay royalties pursuant to Article 3 of this Agreement, NOVOSTE shall
have a perpetual, royalty free, worldwide exclusive, license to make, have made,
use and sell Licensed Products covered by the Licensed Patents and practice
Licensed Technology.
ARTICLE 12. ASSIGNMENT
----------------------
Neither party shall assign this Agreement or any part thereof without the
prior written consent of the other party, which consent shall not be
unreasonably withheld. Either party may, however, without consent, assign or
sell their rights under this Agreement in connection with the transfer or sale
of substantially their
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<PAGE>
entire business to which this Agreement pertains, or in the event of their
merger or consolidation with another company. Any permitted assignee shall
assume all obligations of its assignor under this Agreement. No assignment
shall relieve any party of responsibility for the performance of any accrued
obligation which such party has under this Agreement. Any assignee of this
Agreement shall assume all accrued and prospective obligations including but not
limited to those set forth in Articles 6 and 7. Any such assignee shall further,
within sixty (60) days of becoming the assignee of rights hereunder, meet with
representatives of EMORY, to discuss such assignee's plans for the future
development of the Licensed Patents and Licensed Technology. If such assignee
determines that it does not wish to continue the development or marketing
obligations required under this Agreement, then such assignee shall
immediately terminate this Agreement. Any such termination shall be treated in
accordance with the second paragraph of Section 11.7 as if the termination
resulted from a breach of this Agreement.
ARTICLE 13. MISCELLANEOUS
-------------------------
13.1 Export Controls. NOVOSTE acknowledges that EMORY is subject to
---------------
United States laws and regulations controlling the export of technical data,
biological materials, chemical
- 43 -
<PAGE>
compositions and other commodities and that EMORY's obligations under this
Agreement are contingent upon compliance with applicable United States export
laws and regulations. The transfer of technical data, biological materials,
chemical compositions and commodities may require a license from a cognizant
agency of the United States government or written assurances by NOVOSTE that
NOVOSTE shall not export data or commodities to certain foreign countries
without the prior approval of certain United States agencies. EMORY neither
represents that an export license shall not be required nor that, if required,
such export license shall issue.
13.2 Legal Compliance. NOVOSTE shall comply with all laws and regulations
----------------
relating to its manufacture, use, Sale, labeling or distribution of Licensed
Products and shall not take any action which would cause EMORY or NOVOSTE to
violate any laws and regulations.
13.3 Independent Contractor. NOVOSTE's relationship to EMORY shall be that
----------------------
of a licensee or assignee only. NOVOSTE shall not be the agent of EMORY and
shall have no authority to act for, or on behalf of, EMORY in any matter.
Persons retained by NOVOSTE as employees or agents shall not, by reason thereof,
be deemed to be employees or agents of EMORY.
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<PAGE>
13.4 Patent Marking. NOVOSTE shall mark Licensed Products Sold in the
--------------
United States with United States patent numbers. Licensed Products
manufactured or Sold in other countries shall be marked in compliance with the
intellectual property laws in force in such foreign countries.
13.5 Use of Names. EMORY acknowledges that Spencer B. King, III, M.D., Ron
------------
Waksman, M.D. and Ian Crocker, M.D. are authorized to license the use of their
names to NOVOSTE for the purposes of promoting the Royalty-bearing Products.
Any such License Agreement shall be subject to EMORY's consulting and conflict
of interest policies. NOVOSTE shall obtain the prior written approval of EMORY
prior to making use of EMORY's name for any commercial purpose. NOVOSTE shall
be permitted to disclose EMORY's name and the names of the inventors of the
Licensed Products in any document used in connection with NOVOSTE's financing
activities to the extent that NOVOSTE is advised by counsel that such disclosure
is required by law.
13.6 Place of Execution. This Agreement and any subsequent modifications
------------------
or amendments hereto shall be deemed to have been executed in the State of
Georgia, U.S.A. This Agreement shall not become effective or binding upon EMORY
until signed on its behalf
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<PAGE>
by its Executive Vice President or Vice President and General Counsel
in the State of Georgia, U.S.A.
13.7 Governing Law. This Agreement and all agreements, modifications,
-------------
alterations, or supplements hereto, and the rights of the parties hereunder
shall be construed under and governed by the laws of the State of Georgia and
the United States of America. Only courts in the State of Georgia, U.S.A., shall
have jurisdiction to hear and decide any controversy or claim between the
parties arising under or relating to this Agreement.
13.8 Entire Agreement. This Agreement constitutes the entire agreement
----------------
between EMORY and NOVOSTE with respect to the subject matter hereof and shall
not be modified, amended or terminated, except as herein provided or except by
another agreement in writing executed by the parties hereto.
13.9 Severability. All rights and restrictions contained herein may be
------------
exercised and shall be applicable and binding only to the extent that they do
not violate any applicable laws and are intended to be limited to the extent
necessary so that they will not render this Agreement illegal, invalid or
unenforceable. if any provision or portion of any provision of this Agreement,
not essential to the commercial purpose of this Agreement, shall be held to be
illegal, invalid or unenforceable by a court of
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<PAGE>
competent jurisdiction, it is the intention of the parties that the remaining
provisions or portions thereof shall constitute their agreement with respect to
the subject matter hereof, and all such remaining provisions or portions thereof
shall remain in full force and effect. To the extent legally permissible, any
illegal, invalid or unenforceable provision of this Agreement shall be replaced
by a valid provision which shall implement the commercial purpose of the
illegal, invalid or unenforceable provision. In the event that any provision
essential to the commercial purpose of this Agreement is held to be illegal,
invalid or unenforceable and cannot be replaced by a valid provision which will
implement the commercial purpose of this Agreement, this Agreement and the
rights granted herein shall terminate.
13.10 Force Majeure. Any delays in, or failure of performance of any party
-------------
to this Agreement, shall not constitute a default hereunder, or give rise to any
claim for damages, if and to the extent caused by occurrences beyond the control
of the party affected, including, but not limited to, acts of God, strikes or
other concerted acts of workmen, civil disturbances, fires, floods, explosions,
riots, war, rebellion, sabotage, acts of governmental authority or failure of
governmental authority to issue licenses or approvals which may be required.
- 47 -
<PAGE>
13.11 Mediation. Except for the right of either party to apply to a court
---------
of competent jurisdiction for a temporary restraining order, a preliminary
injunction, or other equitable relief to preserve the status quo or prevent
irreparable harm, any and all claims, disputes or controversies arising under,
out of, or in connection with the Agreement, including any dispute relating to
patent validity or infringement, which the parties shall be unable to resolve
within sixty (60) days shall be mediated in good faith. The party raising such
dispute shall promptly advise the other party of such claim, dispute or
controversy in a writing which describes in reasonable detail the nature of such
dispute. By not later than five (5) business days after the recipient has
received such notice of dispute, each party shall have selected for itself a
representative who shall have the authority to bind such party, and shall
additionally have advised the other party in writing of the name and title of
such representative. By not later than ten (10) business days after the date of
such notice of dispute, the party against whom the dispute shall be raised
shall select a mediation firm in the Atlanta area and such representatives shall
schedule a date with such firm for a mediation hearing. The parties shall enter
into good faith mediation and shall share the costs equally. If the
representatives of the parties have not been
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<PAGE>
able to resolve the dispute within fifteen (15) business days after such
mediation hearing, the parties shall have the right to pursue any other remedies
legally available to resolve such dispute. If the dispute is not successfully
resolved through mediation, either party shall have the option to pursue binding
arbitration. Any such arbitration shall be held in Atlanta, Georgia and shall
be performed in accordance with all relevant guidelines and rules of the
American Arbitration Association before a panel of three independent
arbitrators.
13.12 Publications. NOVOSTE acknowledges EMORY's obligation to disseminate
------------
new knowledge and research findings. However, notwithstanding any other
provisions of this Agreement, EMORY acknowledges that NOVOSTE may have
proprietary interests and agrees to submit any manuscript which discloses data
or other information pertaining to any Licensed Technology, to NOVOSTE for
review sixty (60) days prior to submission for any oral presentation or written
publication. NOVOSTE shall then have forty-five (45) days to respond to EMORY
with any requested revisions. NOVOSTE shall have the right to edit such proposed
disclosure to remove any NOVOSTE confidential or proprietary information and to
delay the publication of any manuscript which first discloses an invention for a
reasonable period of time, to
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<PAGE>
enable NOVOSTE to file, or have filed, a patent application to protect any
invention disclosed therein.
13.13 Data Ownership. EMORY shall retain ownership of any medical records,
--------------
patient specimens, x-rays, angiograms, EKG'S, ultrasonic images and recordings,
and other patient medical data generated during clinical studies sponsored by
NOVOSTE and conducted at EMORY.
EMORY shall retain ownership of all scientific data, photos, selected
tissues, histology slides, microscope preparations, angiograms, ultrasonic
images and other primary information sources obtained as a result of conducting
in vitro and animal experimental procedures sponsored by NOVOSTE at EMORY under
approved protocols and using EMORY facilities.
NOVOSTE shall retain ownership of all completed case medical record forms,
research notebooks, prototypes, devices, supplies, radiation sources, and
equipment provided by NOVOSTE. EMORY shall be entitled to retain a confidential
copy of the case medical record forms, without duplication, subject to the
Confidentiality provisions for all clinical studies conducted at EMORY.
EMORY shall, within the bounds of legal requirements, make such medical
records, patient specimens, x-rays, angiograms, EKG'S, ultrasonic images and
recordings, and other patient medical data
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<PAGE>
generated under this Agreement available for audit, review and copying by
NOVOSTE.
EMORY agrees to promptly provide NOVOSTE with copies of all data, codes,
photographs and other recorded scientific information obtained as a result of
conducting in vitro and animal experimental procedures at EMORY.
NOVOSTE shall have free, clear, and unencumbered access to all data subject
to the provisions of this Agreement and may use such data in connection with any
of its research, development, marketing or promotional activities and may be
disclosed by NOVOSTE to other clinical centers, consultants, the Food and Drug
Administration and other Federal, State and/or local regulatory agencies.
ARTICLE 14. NOTICES
-------------------
All notices, statements, and reports required to be given by one party to
the other shall be in writing and shall be deemed to have been given upon
delivery in person or upon the expiration of five (5) days after deposit in a
lawful mail depository in the country of residence of the party giving the
notice, registered or certified airmail postage prepaid, and addressed as
follows:
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<PAGE>
EMORY NOVOSTE
Vincent La Terza President
Director of Licensing Novoste Corporation
and Patent Counsel 4350 International Boulevard
2009 Ridgewood Drive Suite C
Atlanta, Georgia 30322 Norcross, Georgia 30093
Either party hereto may change the address to which notices to such party
are to be sent by giving notice to the other party at the address and in the
manner provided above. Any notice may be given, in addition to the manner set
forth above, by telex, facsimile or cable, provided that the party giving such
notice obtains acknowledgment by telex, facsimile or cable that such notice has
been received by the party to be notified. Notice made in this manner shall be
deemed to have been given when such acknowledgment has been transmitted.
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<PAGE>
IN WITNESS WHEREOF, EMORY and NOVOSTE have caused this Agreement to be
signed by their duly authorized representatives, under seal,'as of the day and
year indicated below.
EMORY UNIVERSITY: NOVOSTE CORPORATION
By: /s/ By: /s/
---------------------------- ----------------------------
Name: John Temple Name: Thomas D. Weldon
--------------------------
Title: Executive Vice President Title: President & CEO
-------------------------
Date: 1/30/96 Date: 1/30/96
-------------------------- --------------------------
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<PAGE>
EXHIBIT A
QuitClaim Assignment
For good and valuable consideration, the receipt and sufficiency of which is
hereby acknowledged, Emory University, a nonprofit Georgia corporation, with
offices at 1380 South Oxford Road, N.E., Atlanta, Georgia 30322 ("EMORY") hereby
irrevocably and unconditionally quitclaims and assigns to Novoste Collporation,
a Florida Corporation, with offices at 4350-C International Boulevard, Norcross,
Georgia 30093-3037 ("NOVOSTE"), its successors, legal representatives and
assigns, any and all right, title and interest throughout the world that EMORY
may now or hereafter have in:
(1) U.S. Patent Application entitled "Method and Apparatus For Treating a
Desired Area in the Vascular System of a Patient" filed on October 27, 1994, and
assigned Serial No. 08/330,327 and in any United States division or continuation
application or reexamination, reissue or extension of any U.S. Patent issuing
therefrom.
EMORY agrees to assist NOVOSTE in such manner as may be reasonably required
to obtain the cooperation of EMORY employees in the execution, filing and
prosecution of the above-identified
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<PAGE>
patent applications, and any division, continuation, reexamination, reissue or
extension thereof, in the United States and to vest title to the above-
identified patent applications in the United States.
EMORY further agrees upon the request of NOVOSTE, its successors, legal
representatives and assigns, in the event of said application or any
continuation or division thereof, or Letters Patent issued thereon, or any
reissue or application for the reissue thereof becoming involved in Interference
or any other contested matter, to cooperate to the best of its ability with
NOVOSTE, its successors, legal representatives and assigns in the matters of
preparing and executing the preliminary statement or other such document and
giving and producing evidence in support thereof. EMORY further agrees to
perform, upon such request, any and all affirmative acts to obtain said Letters
Patent, and vest all rights therein hereby conveyed in NOVOSTE, its successors,
legal representatives and assigns whereby said Letters Patent will be held and
enjoyed by NOVOSTE, its successors, legal representatives and assigns to the end
of the term for which said Letters Patent may be granted as fully and entirely
as the same would have been held and enjoyed by EMORY if this assignment and
sale had not been made.
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<PAGE>
NOVOSTE acknowledges that activities required to perfect NOVOSTE's patent
rights shall be undertaken at NOVOSTE's expense. NOVOSTE further acknowledges
that EMORY has no authority to compel the cooperation of any individuals not
employed by EMORY.
EMORY also assigns to NOVOSTE, its successors, legal representatives and
assigns the entire right, title and interest in foreign patent applications
corresponding to U.S. Patent Application No. 08/330,327 or any divisional or
continuation thereof and the right of priority for patent and utility model
applications in all countries arising under any applicable international
convention for the protection of industrial property and/or any internal
priority legislation of such countries, and EMORY agrees upon the request of
NOVOSTE, its successors, legal representatives and assigns to execute any and
all documents that shall be required to be executed in connection with any and
all applications for foreign Letters Patent thereof, including the prosecution
thereof, and to execute any and all documents necessary to invest title in said
foreign applications and patents in said Assignee, and to assist NOVOSTE in such
manner as may be reasonably required to obtain the cooperation of EMORY
employees in the execution, filing and prosecution of the above-identified
foreign patent applications.
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<PAGE>
EMORY UNIVERSITY
By:
/s/ John L. Fengler 1/30/96
- - ----------------------- ------------------
Name:
Title: Exec V. Pres. Date
SUBSCRIBED and SWORN to before me this 30th day of
-----
January, 1996.
- - ------- --
- - ---------------------------
NOTARY PUBLIC
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<PAGE>
EXHIBIT B
PATENT APPLICATION
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<PAGE>
January 3, 1996
Attorney Docket No. WELD-111-CIP
TITLE:
METHOD AND APPARATUS FOR RADIATION TREATMENT OF A DESIRED
AREA IN THE VASCULAR SYSTEM OF A PATIENT
INVENTORS:
RON WAKSMAN, M.D.
THOMAS D. WELDON
RICHARD A. HILLSTEAD
JONATHAN J. ROSEN
CHARLES E. LARSEN
IAN R. CROCKER, M.D.
RAPHAEL F. MELOUL
GEORGE K. BONNOITT, JR.
DAVID S. HALPERN
FIELD OF THE INVENTION
The present invention relates generally to the delivery of treating
elements by a catheter to a selected site within the vascular system of a
patient. More particuarly, the present invention relates to method and apparatus
for the delivery of a treating element, such as a radiation source, through a
catheter to a desired site, such as a coronary artery, for inhibiting wound
healing response, such as restenosis following balloon angioplasty.
RELATED APPLICATIONS
This application is a continuation-in-part of application Ser. No.
08/330,327 filed October 27, 1994.
BACKGROUND OF THE INVENTION
It is known that the human body's healing response to wounds typically
includes the formation of what is commonly called scar tissue. This response
also occurs within the vascular system of a person following injury to a blood
vessel. An injury that provokes the formation of scar tissue may occur in
various locations within the vascular system, such as in the carotid artery or
in coronary bypasses, or in various ways, such as trauma from surgical or
diagnostic procedures.
EXHIBIT B
<PAGE>
2
One area of the vascular system of particular concern with respect to such
injuries is coronary arteries that are subjected to procedures for removing or
reducing blockages due to plaque within the arteries. Partial and even complete
blockage of coronary arteries by the formation of an atherosclerotic plaque is
a well known and frequent medical problem. Such blockages may be treated using
atherectomy devices, which mechanically remove the plaque; hot or cold lasers,
which vaporize the plaque; stents, which hold the artery open; and other devices
and procedures which have the objective of allowing increased blood flow through
the artery. The most common such procedure is the percutaneous transluminal
coronary angioplasty (PTCA) procedures -- more commonly referred to as balloon
angioplasty. In this procedure, a catheter having an inflatable balloon at its
distal end is introduced into the coronary artery, the uninflated balloon is
positioned at the stenotic site and the balloon is inflated. Inflation of the
balloon disrupts and flattens the plaque against the arterial wall, and
stretches the arterial wall, resulting in enlargement of the intraluminal
passageway and increased blood flow. After such expansion, the balloon is
deflated and the balloon catheter removed.
PTCA is a widely used procedure and has an initial success rate of between
90 and 95 percent. However, long term success of PTCA (as well as the other
artery-opening procedures referred to above) is much more limited, due largely
to restenosis, or reclosing of the intraluminal passageway through the artery.
Restenosis, wherein the vessel passageway narrows to approximately 50% or less
of the enlarged size, is experienced in approximately 30 to 50 percent of the
patients within six months after PTCA. Restenosis may occur for various reasons,
but it is now believed that restenosis is, in significant part, a natural
healing response to the vessel injury caused by inflation of the angioplasty
balloon.
Vessel injury may occur in several ways during PTCA, including: denudation
(stripping) of the endothelium (the layer of flat cells that line the blood
vessels); cracking, splitting and/or disruption of the atherosclerotic plaque
and intima
<PAGE>
3
(innermost lining of the blood vessel); dehiscence (bursting) of the intima and
the plaque from the underlying media; stretching and tearing of the media and
adventitia (outside covering of the artery) which may result in aneurysmal
expansion; and injury to the vessel smooth muscle. Such injury to the vessel
typically initiates the body's own natural repair and healing process. During
this healing process, fibrin and platelets rapidly accumulate in the
endothelium, and vascular smooth muscle cells proliferate and migrate into the
intima. The formation of scar tissue by smooth muscle proliferation, also known
as intimal hyperplasia, is believed to be a major contributor to restenosis
following balloon angioplasty of the coronary artery.
Prior attempts to inhibit restenosis of coronary arteries have included,
among other things, the use of various light is therapies, chemotherapeutic
agents, stents, atherectomy devices, hot and cold lasers, as well as exposure of
the stenotic site to radiation. These therapies have had varying degrees of
success, and certain disadvantages are associated with each of these therapies.
Although radiation therapy has shown promise, particularly in inhibiting intimal
hyperplasia, the devices available for delivery of radiation sources to a
stenotic site have been limited and have tended to suffer from drawbacks which
limit their usefulness. Typical of the devices using radiation to treat
restenosis are those shown or described in U.S. Patents 25 Nos. 5,059,166 to
Fischell; 5,213,561 to Weinstein; 5,302,168 to Hess, 5,199,939 to Dake;
5,084,002 to Liprie; and 3,324,847 to Zoumboulis.
<PAGE>
4
SUMMARY OF THE INVENTION
The present invention is directed to apparatus and methods for delivering
one or more treating elements, such as a radiation source, through a catheter to
a desired location in the vascular system of a human patient and to retrieving
the treating element(s) through the catheter, if so desired. The present
invention is particularly applicable, but not limited, to the treatment of
coronary arteries that have been or will be subjected to PTCA or other artery-
opening procedures, in order to inhibit intimal hyperplasia and reduce the risk
of restenosis. The present invention is also useful in other areas of the
vascular system, such as in the carotid artery or in coronary bypasses.
More specifically, as set forth in the appended claims, the
present invention comprises an elongated flexible catheter tube having a
proximal end portion adapted to remain outside the patient's body, a distal end
portion adapted to be positioned at a selected location within the vascular
system of the patient and a lumen extending therebetween, with the diameter of
the catheter tube being sufficiently small for insertion into the patient's
vascular system. The catheter tube is preferably but not necessarily adapted
for positioning the distal end of the tube at the desired site by advancement
over a guide wire. A port is provided at the proximal end portion of the tube,
through which blood-compatible liquid may be introduced from a source of such
liquid into the lumen. One or more treating elements, which may be in the form
of a solid capsule, pellet or the like, such as a capsule or pellet containing
radioactive material, is positionable within the lumen and is movable between
the proximal and the distal end portions of the tube under the motive force
exerted by the liquid flowing through the lumen.
In accordance with the present invention, a method is also provided for
treating a selected area in the vascular system of a patient wherein an
elongated flexible catheter tube having a distal end portion adapted to be
positioned at a selected location within the vascular system of the patient, a
proximal
<PAGE>
5
end portion adapted to remain outside the patient's body, a lumen extending
therebetween, and a diameter sufficiently small for insertion into the patient's
vascular system is introduced into the vascular system of a patient. The
catheter is preferably but not necessarily introduced over a guide wire until
the distal end portion of the tube is within the selected area of the vascular
system. A port communicating with the first lumen is adapted for introduction of
blood-compatible liquid into the lumen. One or more treating elements, such as a
capsule or pellet containing radioactive material, is introduced into the lumen
at the proximal end portion of the tube and is moved from the tube's proximal
end portion through the lumen to the distal end portion within the selected area
by flowing the blood-compatible liquid through the lumen to generate a motive
force on the element so as to move it from the proximal end to the desired
location at the distal end portion. There, the treating element is allowed to
remain a sufficient time for treatment of the selected area, during which time
the remaining portion of the catheter is free of treating elements so as to not
unnecessarily expose other tissue to such treatment. After the treatment is
completed, the catheter tube is removed from the patient.
In another embodiment, the present invention is embodied in an angioplasty
balloon catheter having proximal and distal end portions, with a lumen extending
therebetween. The lumen communicates with an inflatable balloon located on the
distal end portion. In accordance with the present invention, one or more
treating elements, such as a radiation source, is either carried fixedly at the
balloon or moved through a lumen from the proximal end portion to the distal end
portion, for delivery of radiation to the stenotic site as the angioplasty
procedure is actually carried out -- therefore allowing what may otherwise be
a two-step process to be carried out in a single step. From this summary, it
should be apparent that the method of the present invention may be carried out
before, during or after an angioplasty or other artery-opening procedure,
whichever is deemed most desirable by the treating physician.
<PAGE>
6
DRAWINGS
Figure 1 is a diagrammatic representation of a catheter-based treatment
delivery system embodying the present invention.
Figure 2A is cross-sectional view of one embodiment of the proximal end
portion of the treatment delivery system of the present invention.
Figure 2B is a cross-sectional view of another embodiment of the treatment
delivery system of the present invention.
Figure 2C is a cross-sectional view of still another embodiment of the
treatment delivery system of the present invention.
Figure 3 is a cross-sectional view of one embodiment of the treating
elements of the present invention.
Figure 4 is a partial cross-sectional view of one embodiment of the
elongated catheter tube of the present invention, showing the treating elements
disposed in the distal end portion of the tube.
Figure 5 is a partial cross-sectional view of a second embodiment of the
elongated catheter tube of the present invention, showing the treating elements
in the distal end portion of the tube.
Figure 6A is a partial cross-sectional view of a third embodiment of the
elongated catheter tube of the present invention, showing the treating elements
in the distal end portion of the tube.
Figure 6B is a partial cross-sectional view of the Figure 6A embodiment of
the elongated catheter tube of the present invention, disposed within an outer
guiding catheter which may be used to position the catheter tube of the present
invention within the body of a patient.
Figure 7A is a partial cross-sectional view of a fourth embodiment of the
elongated catheter tube of the present invention, showing the treating elements
disposed in the distal end portion of the tube.
Figure 7B is a partial cross-sectional view of the elongated catheter tube
of Figure 7A taken along line 7-7B.
<PAGE>
7
Figure 8A is a partial cross-sectional view of a fifth embodiment of the
elongated catheter tube of the present invention, showing the treating elements
in the distal end portion of the tube.
Figure 8B is a partial cross-sectional view of a modified
version of the embodiment of the elongated catheter tube of Figure 8A, showing
the treating elements in the distal end portion of the tube.
Figure 9 is a partial cross-sectional view of a sixth embodiment of the
elongated catheter tube of the present invention showing toroidal or ring-shaped
treating elements in the distal end portion of the tube.
Figure 10 is a partial cross-sectional view of an alternative embodiment of
the present invention having an inflatable balloon and treating elements
fixedly positioned on the distal end portion.
Figure 11 is a partial cross-sectional view of an alternative embodiment of
the present invention having an inflatable balloon, with the treating elements
disposed therein.
Figure 12 is a partial cross-sectional view of another alternative
embodiment of the present invention having an inflatable balloon, with the
treating elements movable along the catheter.
Figure 13 is a partial cross-sectional view of a further alternative
embodiment of the present invention having an inflatable balloon, with the
treating elements movable along the catheter.
Figure 14 is a partial cross-sectional view of another embodiment of the
treatment delivery system of the present invention.
Figure 15A is a partial cross-sectional view of a further embodiment of the
treatment delivery system of the present invention.
Figure 15B is an elevational view of part of the proximal end portion of
the treating system shown in Figure 15A.
Figure 15C is a cross-sectional view taken along lines 15c=15c of Figure
15A.
<PAGE>
8
Figure 16 is a partial cross-sectional view of various parts of a further
embodiment of the treatment delivery system of the present invention.
Figure 17 is a partial cross-sectional view of another alternative
embodiment of the present invention having an inflatable balloon, with the
treating elements movable along the catheter.
Figure 18 is a partial cross-sectional view of still another alternative
embodiment of the present invention having an inflatable balloon, with the
treating elements movable along the catheter.
Figure 19 is a partial cross-sectional view of still another alternative
embodiment of the present invention having an inflatable balloon, with treating
elements movable along the catheter.
- - -------------------
Confidential treatment has been requested for portions of this page and for
all of pages 9 and 10 of this exhibit. The copy filed herewith omits the
information subject to the confidentiality request. Omissions are designated as
"XXXXX". The portions omitted have been filed separately with the Securities
and Exchange Commission pursuant to said request for confidential information.
<PAGE>
9
XXXXX
<PAGE>
10
XXXXX
<PAGE>
11
DETAILED DESCRIPTION
Figure 1 depicts one embodiment of the present invention in general
diagrammatic form for ease of initial understanding. Shown in Figure 1 is an
elongated catheter 2 having a proximal end portion 4, a distal end portion 6,
and at least one lumen 8 extending therebetween. The catheter is sized for
insertion of the distal end portion through the vascular system of a patient to
a selected area to be treated, such as the site of a balloon angioplasty
procedure or other opening procedure, such as an atherectomy, in a coronary
artery. This may be carried out, for example, by inserting the catheter
percutaneously into a femoral artery and advancing the catheter over a typical
guide wire 10 upwardly through the descending aorta, over the aortic arch,
downwardly through the ascending aorta and into the particular coronary artery
that has been selected for treatment, such as a coronary artery that has been
subjected to PTCA or other artery-opening procedure. Guide wires and procedures
used in advancing such a catheter to the point of the angioplasty procedure are
well known and will not be discussed in detail.
At the proximal end of the catheter, which is located outside the patient
in a percutaneous procedure such as described above, a transporting and/or
loading device 12 is provided for loading a treating element, such as a pellet
or capsule comprising or containing radioactive material, into the lumen 8 of
the catheter 2. Additional treating elements may also be loaded such that the
total length of the combined treating elements corresponds to at least the
length of the stenotic area of the vasculature to be treated. The total length
of the combined treating elements also could be longer than the stenotic area in
order to assure that the end edges of the stenotic area are also treated. This
loading procedure may also be performed manually, but a mechanical loader as
described in more detail later is preferred to provide better user protection
against radiation.
After the treating element is loaded into the lumen 8, pressurized blood-
compatible liquid, such as sterile saline
<PAGE>
12
solution or sterile water, is introduced via liquid source 14 through a port 16
in the proximal end of the lumen behind the treating element. Flow of liquid
through the lumen pushes the treating element along the lumen to the distal end
portion, which is located at the site to be treated. The liquid which provides
the motive force for moving the treating element may be allowed to exit from the
distal end of the catheter or may be returned in a parallel lumen provided in
the catheter or may be returned via suction through the same lumen in which the
treating element travels.
After the treating element is located at the desired site, the
treating element is allowed to remain for a time sufficient to treat the tissue.
For radiation treatment of a stenotic site, the treating element preferably are
beta-emitting radiation sources, and the residence time period will be
relatively short, on the order of minutes as discussed in more detail below.
After the treatment is complete, the catheter may be removed with the
treating element remaining at the distal end or, alternatively, liquid may be
forced through the lumen in a reverse direction to return the treating element
to the proximal end and into the loading device, if desired, before removal of
the catheter. The reverse flow of fluid may be achieved by forcing liquid under
positive pressure through the lumen in a reverse direction or by applying a
suction, such as by withdrawing the piston of a syringe attached at the proximal
end of the lumen, to the lumen.
The transporting/loading device 12 need not be connected directly to the
proximal end of the catheter 2 if such direct connection would result in
possible kinking of the catheter or would restrict maneuverability. In that
case, an additional length of tubing (which may have the same number of lumens
as the catheter) could be provided between the transporting/loading device 12
and the proximal end portion 4 of the catheter. In such event, the additional
length of tubing (as well as the proximal end portion of the catheter located
outside the patient) may be shielded to protect the user and/or the patient from
unnecessary radiation exposure.
<PAGE>
13
Figure 2A shows one actual embodiment of the proximal end of the catheter
system depicted in Figure 1. Although not limited to use with radioactive
treating elements, the device shown in Figure 2A is particularly adapted for
that application.
Specifically, Figure 2A depicts a three-lumen catheter system 18 with a
loading device 20 containing treating elements 22 and connected to the proximal
end of a three lumen catheter tube 24. The loading device comprises a rigid body
26 preferably of a suitable rigid polymer, having a proximal end 28, a distal
end 30 and a first, a second and a third bore, 32, 34 and 36 respectively,
extending therebetween. A fitting 38 located at the distal end of the body
connects the first, second and third bores, respectively, with one of the three
lumens 33, 35 and 37 of the catheter tube 24.
At the proximal end of the housing member, ports, such as luer connector
ports, are provided for communication with bores 32, 34 and 36. A first port 40
is aligned with the first bore 32 of the body and is adapted for the entry or
exit of a liquid, such as sterile saline. A second port 42 is in communication
with the second bore 34 of the housing member and is likewise adapted to
permit the entry or exit of liquid into the body. The third port 44 opens into
the third bore of the body and is adapted to receive a guide wire 46 to aid in
positioning the distal end of the catheter tube within a patient. A valve (not
shown), such as a Touhy-Borst valve, may be attached to the third port to
prevent leakage of fluid around the guide wire during or after insertion of the
device into the patient.
For loading and/or unloading of the treating elements 22, a retaining
device such as a magazine, carrier or carriage 48 is slidably positioned within
a slot 50 defined in the body 26 intermediate the proximal and distal ends. The
carriage is preferably constructed of the same material as the rigid body 26 and
has a first through bore 52 and a second through bore 54. The first and second
through bores of the carriage may be selectively aligned with the first bore 32
of the body, depending upon the lateral position of the carriage relative to the
body. A carriage with only a single through bore may also be used.
<PAGE>
14
By pre-loading the treating elements into the carriage, they may be
conveniently handled, shipped and stored separate from the rest of the loading
device. When the user is ready for the procedure, the carriage may be simply
inserted into the body, thereby minimizing handling of the treating elements by
and exposure to the user. The carriage is preferably made of a material and has
sufficient thickness to protect the user against unnecessary exposure to
radiation when the treating elements are radioactive. As shown in Figure 2A,
carriage 48 is fully inserted into the body 26, with the first bore 52 of the
carriage aligned with the first bore 32 of the body. In this position, second
bore 54 of the carriage contains the treating elements 22 and is positioned
within the body, thereby providing protection of the user from radiation emitted
by the treating elements. In this first position, fluid, such as sterile saline,
may be introduced through the first port to prime the body and catheter and
remove any air contained therein, if so desired.
By sliding the carriage 48 outwardly from the body 26, the carriage is
moved into a second position wherein second bore 54 of the carriage is coaxially
aligned with first bore 32 of the body, and the treating elements 22 are ready
for introduction into the catheter 24. In this second position, pressurized
liquid, such as sterile saline, may be introduced via pump 14
through first port 40 to supply the motive force against the treating
elements 22, ejecting them from second through bore of the carriage, distally
through the first bore 32 of the body, and into a lumen of the catheter.
The specific design of the pump 14 may be chosen from various alternatives.
For example, the pump 14 may be a simple saline-filled piston syringe attached
via luer lock connector to port 40 of body 26. Manual depression of the syringe
plunger would provide sufficient force to eject the treating elements and move
them to the desired position in the catheter (and withdrawal of the plunger may
assist in returning the treating elements to the proximal end portion after the
treatment is complete).
Alternatively, the motive force may be provided by a column of
<PAGE>
15
liquid from a suspended container of sterile saline or water, controlled by a
simple roller clamp or stopcock.
Alternative configurations for the carriage (not shown) also may be used
without departing from the scope of the present invention. For example, the
carriage may be cylindrical and/or rotatably mountable within the body. Through
bores or chambers within the carriage may be selectively brought into alignment
with the bores of the body by rotating the carriage. The treating elements may
be pre-loaded in the cylinder to minimize user contact and to protect the user
from radiation when a radioactive treating element is employed. By providing the
treating elements 22 pre-loaded into a loading device 20 or pre-loaded into a
carriage 48 that may be inserted into a loading device, user contact with the
treating elements is minimized, and for radioactive treating elements, the user
may be shielded from radiation.
Figure 2B shows a further alternative embodiment of a catheter system of
the present invention. Catheter system 56 includes a combination loading device
and pump 58 and a multi-lumen catheter 60. The combination pump and loading
device comprises a body portion 62 having a distal end portion 64 attached to
the elongated catheter tube and a proximal end portion 66 mounting connectors
for fluid communication with passageways defined in the body.
The body portion 62 has a central bore or passageway 68 in which treating
elements 22 are located prior to the treatment and after the treatment is
completed. The central bore 68 communicates directly with one of the lumens of
multi-lumen catheter 60. Discharge of the treating elements from the bore 68 is
controlled by gate 70, which may be moved between positions blocking flow or
allowing flow through central bore. Alternatively, the gate may contain openings
of sufficiently small size to permit fluid to pass therethrough, while
preventing passage of the treating elements while the gate blocks the central
bore. This aids in priming the system with the treating elements in position
in bore 68, if so desired.
<PAGE>
16
For providing the pressurized flow of liquid to transport treating elements
to and from the distal end of catheter 60, a pair of piston-cylinder
arrangements are provided on opposite sides of the body portion 62. Piston-
cylinder arrangement 72 provides the liquid flow for dispatching the treating
elements to the distal end of the catheter and piston-cylinder arrangement 74
provides the reverse liquid flow for retrieving the treating elements therefrom.
Interior passageway 76 in the body 62 communicates between liquid inlet
port 78, central bore 68 and the cylinder of dispatch piston-cylinder
arrangement 72, which provides the fluid flow for moving the treating elements
into and along a principal lumen of the catheter 60. One-way, spring loaded ball
valve 80 within passageway permits liquid to enter through the inlet port
but blocks liquid from exiting from the port. Vent 79 allows displacement
air to exit from the passageway 76 when liquid is added, for priming purposes
and the like, and a pressure relief valve 81 may be provided to prevent
overpressurization of the catheter.
Interior passageway 82 in the body 62 communicates between the cylinder of
the retrieval piston-cylinder arrangement 74 and a return lumen of the catheter
60. At the distal end portion of the catheter, the return lumen communicates
with the principal lumen to provide a closed circulation path for the liquid
that dispatches and retrieves the treating elements.
In addition, the body 62 has a third interior passageway 84 that
communicates between guide wire inlet 86 and a guide wire lumen of the catheter
60. By itself, the catheter 30 may not have sufficient strength or torsional
rigidity for insertion along a lengthy serpentine vascular path -- in typical
angioplasty procedures, the distance between the percutaneous entry point and
the coronary artery may be approximately 3-4 feet (90-120 cm). To assist in
positioning the distal end of the catheter at the desired location, the catheter
may be advanced over a guide wire that is pre-inserted to the desired location
in a manner well known to those skilled in performing angioplasty and similar
procedures. The guide wire inlet preferably includes
<PAGE>
17
a Touhy-Borst valve or similar known device to close the guide wire inlet around
the guide wire to restrict leakage of blood or other fluid from the guide wire
lumen.
In use, the interior passageways, piston-cylinder arrangements, and catheter
principal and return lumen are filled with sterile water or saline through the
liquid inlet port 78 and one-way valve 80. In the initial position, the dispatch
and retrieval piston-cylinders are oppositely positioned, with the piston of the
dispatch piston-cylinder 72 in a withdrawn position, as shown in Figure 2B, and
the piston of the retrieval piston-cylinder 74 in an advanced position, also as
shown in Figure 2B. Before the treating elements can be moved to the desired
position, gate 70 controlling the central bore must be opened.
By advancing the dispatch piston, the liquid in the dispatch
cylinder is forced through the interior flow path 76 and into the central bore
68 containing the treating elements 22. The pressurized liquid flow ejects the
treating elements from the central bore and forces the treating elements along
the principal lumen of the catheter to the distal end portion located at the
site to be treated. As liquid moves along the principal lumen in a distal
direction, it displaces an equal amount of liquid that returns along the return
lumen and enters the cylinder of the retrieval piston-cylinder arrangement 74,
pushing the retrieval piston outwardly.
Retrieval of the treating elements may be accomplished by reversing the
steps described above. The retrieval piston is advanced, forcing liquid in a
reverse or distal direction along the return lumen and returning the fluid to
the body along the principal lumen. The liquid flow moves the treating elements
in a proximal or return direction along the principal lumen, returning them to
the central bore of the body 62. The returning liquid enters the cylinder of the
dispatch piston-cylinder arrangement 72.
With the catheter system as shown in Figure 2B, a completely closed system
is provided, and no liquid that contacts the treating elements is allowed to
enter the patient's body.
<PAGE>
18
This may be particularly important when the treating agent is radioactive. The
closed system arrangement also allows the treating elements, whether a single
element or a train of treating elements, to be shifted back and forth slightly
while in the distal portion of the catheter by alternately slightly depressing
the dispatch and retrieval pistons. This technique may be used to provide a more
uniform exposure of the selected vessel area, particularly where there is dead
space between or at the ends of the treating elements.
A variation on the catheter system of Figure 2B is depicted in Figure 2C.
The catheter system 88 shown there similarly includes a combination pump and
loading device 90 and a multilumen catheter 92. The combination pump and loading
device 90 also has a body portion 94 with a distal end portion 96 attached to
the catheter 92, and a proximal end portion 98. In this embodiment, however,
liquid inlet port 100, guide wire inlet 102 and dispatch and retrieval bellows
104 and 106, respectively, are located on one side of the body 94. This
arrangement permits a large cylindrical chamber 108 to be provided, extending
inwardly from the proximal end of the body, for receiving a carrier or insert
110 which is pre-loaded with treating elements 22. Alternatively, the body 94
and insert 110 could be of one piece or integral construction.
Insert 110 has a central bore 112 in which the treating elements are
located, a gate 114 controlling passage of the treating elements from the
central bore, and a laterally extending branch 116 of the central bore. When
inserted into the chamber 108 of the body 94, central bore 112 of the insert 110
is aligned with central passageway 118 of the body 94, which communicates
directly with a principal lumen of the catheter 92, and branch 116 communicates
with internal passageway 120 of the body, which connects to the liquid inlet
port 100 and the dispatch bellows 104.
Alternatively, the insert 110 could have a plurality of bores and be
rotatably mounted in the body for selective alignment of the bores with inlet
port 100 and central passageway 118. In this arrangement, one bore could be
empty for fast
<PAGE>
19
priming of the system and another bore could contain the treating elements.
As with the embodiment in Figure 2B, an internal liquid flow passageway
122 is provided in the body 94, communicating between the retrieval bellows and
a return lumen of the catheter 92, and a guide wire passageway 124 is provided
between a guide wire lumen of the catheter and guide wire inlet 102. Also
similarly, a vent 126 is provided in communication with the passageway that
connects with the liquid inlet port l00.
In operation, the catheter system of Figure 2C is essentially identical to
that discussed regarding Figure 2B. The embodiment of Figure 2C allows the
treating elements to be conveniently stored separately from the remainder of the
catheter system, for example in special radiation-proof containers.
It should be clear that in each of the embodiments discussed above, the
body, carrier (insert or carriage) and catheter may be provided in various
combinations of assemblage, as a matter of choice. For example, the body and
carrier could be preassembled or even of one piece construction. Similarly, the
body could be preassembled with the catheter tube, with the carrier separate for
convenient storage and transportation of the treating elements. Alternatively
all three elements could be separate and assembled in the desired configuration
on site -- this would permit the physician to select the appropriate combination
depending on the desired procedure.
For radiation exposure of the desired site, the treating elements 22
contain radioactive material, preferably betaemitting. In the preferred
embodiment shown in Figure 3, the treating elements are elongated hollow
cylinders 128 which are preferably constructed of stainless steel, silver,
titanium or other suitable material, and are ideally in the range of 2.5 to 5.5
mm in length. The cylindrical treating elements have rounded first and second
ends with a chamber 130 extending therebetween. The inner diameter of chamber
130 is preferably in the range of 0.4 to 0.6 mm. A first end plug 132 closes the
first end of the cylinder, while a second end plug 134 closes the second end.
The
<PAGE>
20
end plugs are preferably less than about 1 mm in width and are affixed to
cylinder 128, for example, by welding.
The outer diameter of the treating elements is preferably between
approximately 0.6 and 0.8 mm, being sized, of course, to slidably fit into the
respective receiving bores of the carriages, bodies and catheter lumen described
above. To permit maximum mobility through the loading devices and catheters
described above, the inner diameter of each of the bores or lumens the treating
elements pass through should preferably be less than twice the outer diameter
of the cylindrical treating elements and the outer surface of the treating
elements may be coated with Teflon material or similar low-friction material to
reduce friction between the treating element and the wall of the lumen in which
it moves. This allows the treating elements to move quickly through the
lumen, minimizes unnecessary exposure of other tissue to the treating elements
and in particular minimizes radiation exposure to other tissue. Additionally, to
increase the surface area of the treating elements subject to the motive force
provided by fluid being passed through the system, the treating elements may
also be provided with one or more annular ridges which extend outwardly about
the circumference of the treating elements.
To treat a length of vascular tissue, a plurality of treating elements,
joined together to form a train of treating elements, as illustrated in the
attached figures, may be used. To keep the treating elements uniformly spaced
from each other, and, more importantly, to prevent the treating elements from
becoming too spaced apart while moving through the catheter, the individual
treating elements may be connected by several lengths of hard tempered spring
wire 136, as is shown in Figure 3.
Each treating element 22, as constructed above, encapsulates a therapeutic
agent, such as a radiation emitting substance 138. Radiation emitting substance
138 is contained within interior chamber 130 of the treating element and may be
composed of any alpha, beta or gamma particle emitting substance. Preferably,
however, the radioactive source is a pure beta-particle emitter,
<PAGE>
21
or beta and gamma emitter. Examples of such substances include
Strontium/90/, Ruthenium/106/, Phosphorus/32/, Iridium/192/, and/or Iodine/125/.
The amount and strength of the radioactive material contained in the
combined number of treating elements 22 should be sufficient to deliver a
desired dosage of from 100 to about 10,000 rads, preferably about 700 to 5,000
rads, in about 2-10 minutes. Radioactivity is generally measured in units of
"Curie" (Ci), and the radioactivity of the material for the present invention is
selected to provide the above dosage. For the preferred dosage, the radioactive
material may have a radioactivity of approximately 0.45 and 25,000 mCi per
centimeter of vessel to be treated, depending on the radiation source used. As
described briefly earlier, when a train of treating elements is used which have
dead space (non-radioactive) between adjacent elements, the train may be
oscillated by moving the catheter slightly back and forth or by briefly
repeatedly reversing the flow of liquid, resulting in a shifting back and forth
of the treating elements to provide a more uniform radiation exposure of the
selected area of the vessel.
The selected radioactive material may be contained within glass, foil, or
ceramics, or, alternatively, within a powder or liquid medium, such as
microparticles in liquid suspension. When solid materials are used, the
preferred outer diameter of the material is approximately 0.5 mm, allowing it to
be inserted into the central chamber 130 of the treating element cylinder 128.
Such radioactive materials may be formed into pellets, spheres, and/or rods in
order to be placed into the chamber of the treating element.
Various alternative treating elements may also be used to
contain the radioactive material without departing from the present
invention. For example, the treating elements may be toroidal, spherical, or in
the form of elongated rings, and in such configurations, the radioactive
material may be actually impregnated in a metal and formed into the desired
shape. Alternatively, a radioactive powder may be fired to fuse the material so
that it may be formed into the desired shape, which may then be encapsulated in
metal, such as titanium, stainless
<PAGE>
22
steel or silver, or in plastic, as by dipping in molten or uncured plastic. In
still another embodiment, the treating elements may be formed from a ceramic
material which has been dipped in a radioactive solution. In a still further
alternative, the treating elements 22 may be constructed in the form of two
piece hollow cylindrical capsules having a larger-diameter half with a central
cavity and a smaller-diameter half also having a central cavity, the smaller
half slidably received within the larger half and bonded or welded to form the
capsule structure.
Turning now to a more detailed description of the catheters of the present
invention, as stated previously, catheters of the present invention may be pre-
attached to the loading device or, as discussed with regard to Figure 2, a
fitting such as 38 may be provided for attaching an elongated catheter tube to
the loading device. Although catheters of the present invention may vary in the
number of lumens or the specific construction of such lumens, those catheters
have in common, a proximal end attachable to a body member such as body 26, a
distal end opposite the body which is adapted to be positioned at a selected
site in the body, and an elongated tubular portion therebetween. For those
catheters that are not pre-attached to the loading device, the proximal end may
be provided with a keyed fitting to allow attachment of only certain catheters
to the fitting on the loading device. Such fittings may include those generally
known in the art which will not be discussed herein, but also may include
specially designed fittings which would be peculiar to this device. A specially
keyed fitting would prevent the inadvertent attachment of the fitting or body to
other catheters on the market which are not specifically designed to receive the
treating elements and/or to prevent the treating elements from being released
into the body.
As used herein, the terms "elongated tube," "elongated catheter tube" and
similar phrases are intended to include a catheter possessing one or more lumens
produced from a single extrusion and catheters of multiple lumens wherein the
catheter is made up of several separate tubes bundled together.
<PAGE>
23
Figure 4 depicts the distal end portion of one catheter of the present
invention, generally at 140, with the treating elements located in the distal
end portion. In this embodiment, the catheter comprises a single tubular member
142 having a proximal end portion (not shown), a distal end portion and a lumen
144 extending therebetween. The tubular member is preferably extruded from Nylon
11 material, although other suitable plastic materials may be used. The outer
diameter of the tubular member is sized according to the intended application --
for example 5 French or smaller for use in treating the stenotic site of a
coronary artery. The inner diameter of the lumen is correspondingly sized to
receive the treating elements 22.
To prevent treating elements 22 from exiting the distal end of the tubular
member, a retention projection may be provided in the lumen to block passage of
the treating elements, such as an end barrier 146. Barrier 146 is a separate
molded tip adhered or bonded to the distal end portion of tubular member 142.
Barrier 146 preferably has a smooth rounded external surface to minimize
possible abrasion to a vessel or other tissue and a central opening 148 to allow
liquid flow therethrough.
To aid in placement of the catheter at the desired location, a marker band
150 is attached to the outer surface of tubular member 142 at the distal end
portion. To provide a continuous smooth outer surface, a slight undercut may be
provided in the surface of the catheter tube, in which the marker band resides.
Although shown on the exterior surface of the catheter, the marker band may also
be provided internally as well. Preferably the barrier 146 and marker band 150
are constructed from barium, a platinum-iridium compound, or like substance,
which is visible by fluoroscope during placement of the catheter.
In use, still referring to Figure 4, the distal end portion of the tubular
portion is introduced into the body of a patient into a selected site, such as
the coronary artery 152 following balloon angioplasty. In such instances, a
guide wire will typically be pre-positioned in the patient, although a guiding
catheter could also be used. The distal end of the catheter is
<PAGE>
24
then advanced over the guide wire, through lumen 144. The positioning of the
device is made more precise due to the ability to fluoroscopically observe the
barrier 146 and marker band 150 at the distal end portion of the catheter tube.
After the distal end portion of the catheter is positioned such that the
previously stenosed area, generally at 154, of the coronary artery is located
between the barrier 146 and marker band 150, the guide wire can be removed, and
the proximal end of the catheter can be connected to a treating element loading
device and/or pump, as described earlier with reference to the Figure 2-2B
embodiments.
So connected, the treating elements 22 are in direct communication with
lumen 144 of the catheter and a flow path is formed therebetween. Pressurized
liquid, such as from a fluid, syringe or other piston-cylinder arrangement,
plunger, or pump, elevated saline solution container, is then directed against
the treating elements, causing them to advance along the catheter lumen until
stopped by the end barrier 146.
Referring to the Figure 2A embodiment of a loading device as an example, to
move the treating elements 22 from the body 26 to the selected site in the
patient, the carriage 48 is moved from the first position to the second
position. This releases the treating elements into the flow path where they are
carried rapidly by the motive force of the fluid therein into and through the
lumen of the catheter to the distal end portion, which is located at the
stenotic site. The rapid transportation of the treating elements reduces the
amount of radiation which is transmitted to tissues in the body through which
the elongated catheter tube extends. In this embodiment, the liquid transporting
the treating elements exits through the central opening 148 in the end barrier
146.
As noted above, upon reaching the distal end portion of the elongated
tube, the treating elements are prohibited from being ejected into the patient
by the barrier 146. Once more, the barrier and marker band may be used to
fluoroscopically visualize the released radioactive elements, and account for
their location. The barrier and marker band may be specifically spaced
<PAGE>
25
to cover the distance of the lumen occupied by the total length of the
radioactive treating elements, and the location of the elements may be confirmed
by viewing a solid image between the barrier and marker band on the fluoroscope.
To maintain the treating elements within the distal end portion of the
elongated tube, a constant fluid pressure through the lumen and against the
treating elements may be required to counteract the effects of external blood
pressure and/or gravitational forces exerted upon the treating elements,
depending on the angle at which the distal end portion of the elongated tube is
placed and on the specific location in the patient.
Preferably, in order to sufficiently irradiate the stenotic site of a
coronary artery that has been subjected to PTCA to inhibit intimal hyperplasia,
the treating elements should remain at the selected site for a sufficient time
to deliver a therapeutically effective amount of radiation, which is preferably
between about 100 and 10,000 rads, preferably about 700 to 5,000. The length of
time required to deliver this dosage of radiation depends primarily on the
strength of the radioactive source used in the treating elements and the number
of treating elements employed. The radioactivity needed will depend on the
strength of the source used and the emission, and may be in the range of 0.45 to
25,000 mCi depending on the source. After sufficient time, such as 2 to 10
minutes, has been allowed for treatment, the treating elements may be removed by
withdrawing the catheter from the patient or by applying suction (such as by a
syringe) to the proximal end of the lumen in which the treating element travels.
Another embodiment of an elongated catheter tube 156 of the present
invention is shown in Figure 5. The proximal end of the catheter tube may be
pre-attached to a loading device/pump or employ a fitting for keyed attachment
to such a device, as described in detail earlier. Accordingly, only the distal
end portion of the catheter is depicted in Figure 5.
As shown in Figure 5, the elongated tube 156 comprises co-axial inner and
outer tubes 158 and 160 respectively. Inner tube
<PAGE>
26
158 defines an inner bore or lumen 162, through which the treating elements 22
are advanced. Inner and outer tubes are spaced apart to define to define a
return lumen 164 therebetween for return of the liquid used to advance the
treating elements.
The distal end of the outer tube 160 tapers to a narrow, flexible and
atraumatic tip 166 bonded to the outer tube. A radiopaque barrier 168 located
slightly beyond the end of the inner tube 158 closes the outer tube 160 and
blocks further proximal movement of the treating elements 22. Similarly to
marker band 150 of the previous embodiment, a marker band 170 may be provided in
an undercut area on the surface of outer tube 160 at a location spaced
proximally from the barrier 168 to enhance placement of the distal end portion
and the treating elements at the desired location.
When used to treat the site of a coronary artery where a balloon
angioplasty procedure has been carried out, this catheter 156 is positioned in
the previously stenosed site by a guide tube or similar device. Positioning of
the distal end portion of the catheter may be viewed fluoroscopically due to the
radiopaque barrier 168 and marker band 170.
If not pre-attached to a loading device/pump, the proximal end of the
catheter is attached to such a device as described earlier. Without
unnecessarily repeating earlier description, the treating elements 22 are
advanced along the inner lumen 162 of the catheter under the force of liquid
flowing therethrough. With this embodiment, instead of exiting from the distal
end of the catheter, the liquid exits from the distal end of the inner lumen (or
through a side aperture 172 in the wall of the inner tube), and returns through
the return lumen 164 provided between the inner tube and the outer tube. The
return liquid may be allowed to exit through the loading device/pump or may be
collected therein, as described earlier, for alternative disposal.
Unlike the first embodiment, this embodiment is a completely
closed system, in that the fluid is not released into the patient
and the treating elements 22 do not contact the blood. While this eliminates
the effects of blood pressure in moving the
<PAGE>
27
treating elements, a small but constant fluid flow may be required to maintain
the treating elements in the distal end portion of the elongated catheter tube
due to the gravitational effects in the event the treatment site is at a higher
elevation than the proximal end of the catheter. By oscillating the liquid flow
between the dispatch and retrieval pistons, the train of treating elements 22
may be shifted slightly back and forth to make the exposure along the desired
area more uniform.
The radioactive treating elements remain in the distal end portion of the
elongated tube for a sufficient period of time to deliver a therapeutically
affective amount of radiation. As was previously discussed, this is preferably
about 100-10,000 rads, in the case of inhibiting the development of intimal
hyperplasia.
After a sufficient amount of radiation is delivered, the treating elements
22 may be retrieved from the distal end portion of the elongated catheter tube
and returned to the loading device by introducing pressurized fluid into the
return lumen. This reverses the flow of liquid and creates an oppositely
directed motive force on the treating elements forcing them proximally through
the inner lumen 162 for return to the loading device. The elongated catheter
tube may then be removed from the patient and the procedure concluded.
Alternatively, the treating elements may be removed by withdrawing the catheter
from the patient.
In a third alternative embodiment of the present invention
shown in Figures 6A and 6B, the catheter is constructed and operates
similarly to that described for the Figure 5 embodiment. Elongated catheter
tube 174 comprises co-axial inner and outer tubes 176 and 178 respectively.
Inner tube 176 defines an inner bore or lumen 180, through which the treating
elements 22 are advanced. Inner and outer tubes are spaced apart to define a
return lumen 182 therebetween for return of the liquid used to advance the
treating elements.
The distal end of the outer tube 178 is not tapered, but is
closed by radiopaque solid tip 184, which also serves as a barrier to the
treating elements as they move along the inner lumen 180. Also similarly, a
marker band 186 is provided on the surface of outer tube 178 at a location
spaced proximally from
<PAGE>
28
the tip 174 to enhance placement of the distal end portion and the treating
elements at the desired location.
The initial placement of the distal end portion of elongated catheter tube
174 is facilitated by the use of a third or guide tube 188, as is shown in FIG
6B. As shown therein, the separate third tube 188 has a proximal end portion
(not shown), a tapered distal end portion and a lumen 190 extending
therebetween.
In use, the guide tube has sufficient strength or rigidity
for placement or is placed into the body of a patient over a pre-positioned
guide wire, so that the distal end portion of the third tubular member is
located at a specific selected site within the body at which treatment is
desired. Once the guide tube is positioned at the selected site, and the guide
wire at least partially pulled back, the elongated catheter tube 174 shown in
Figure 6A may be inserted into lumen 190 of the guide tube.
As in the Figure 5 embodiment, the embodiment shown in Figures 6A and 6B
allows treating elements 22 to be hydraulically moved between the proximal and
distal end portions of the elongated tube, with the direction of the hydraulic
flow being determined by the pressure gradient existing between the delivery and
retrieval lumens. Thus, after maintaining the treating elements at the distal
end portion of the elongated catheter tube for a desired period of time, the
treating elements may be retrieved by reversing the flow of fluid through the
elongated tube. Following this the catheter and third or guide tube may be
removed from the patient and the procedure concluded.
Another embodiment of the catheter of the present invention, particularly
intended for placement at a desired location by advancement over a guide wire,
is shown in Figures 7A and 7B. The elongated catheter tube 192 comprises a pair
of inner tubes 194 and 196 that extend in a parallel side-by-side arrangement
within an outer tube 198. Inner tube 194, which is of smaller diameter than tube
196, defines an inner lumen 200 for receiving a guide wire used for placement of
the catheter at the desired location within the patient. Inner tube 196, which
is of larger
<PAGE>
29
diameter, provides inner lumen 202 along which the treating elements 22 travel.
Return lumen 204 is provided by the space between the inner surface of the
outer tube 198 and the outer surfaces of the inner tubes 194 and 196 for return
flow of liquid used to transport the treating elements.
As seen in Figure 7A, the outer tube 198 has an open tapered distal end. An
interluminal wall 206 is provided within the outer tube at the beginning of the
taper and at the distal end of the inner tubes 194 and 196. The wall 206
includes an aperture in sealed communication with lumen 200 of inner tube 194,
through a guide wire may pass. The wall 206 is preferably slightly
spaced from the distal end of the other inner tube 196, through which the
treating elements pass, to allow liquid to exit from the end of tube 196 for
return through the return lumen 206. The wall also provides a barrier to prevent
the treating elements from exiting the end of tube 196.
As in the earlier embodiments, the elongated catheter tube 192 has first
and second radiopaque marker bands, 208 and 210 on the outer tube to aid in
placing the distal end portion at the desired location in the patient. As noted
earlier, although generally depicted on the outer tube in many of the
embodiments, the markers may be provided inside the catheter at any convenient
location, such as on an inner tube or surface, without departing from the
present invention.
In use for treating a stenotic site in a coronary artery with radiation,
the proximal end of the elongated catheter 192 tube may be pre-connected to a
loading device/pump or separately connected to such a device by a keyed fitting
or similar arrangement, as discussed earlier. The distal end portion of the
elongated catheter tube is then positioned at the selected site within the
body of the patient by advancing the catheter over a pre-positioned guide wire.
In this embodiment, the guide wire may be allowed to remain in position. This
has the significant advantage that it is unnecessary to insert the guide wire a
second time if a further catheter or device needs to be inserted after the
treatment is completed.
<PAGE>
30
The radiopaque marker bands 208 and 210 are visible on a fluoroscope and
aid in the placement of the device. When the distal end portion of the elongated
tube is positioned such that the selected site is located between marker bands
208 and 210, liquid may be pumped through the lumen 202 to move the treating
elements to the distal end portion of the elongated catheter tube, where they
are accounted for by the positioning of the marker bands. After sufficient
irradiation has occurred, the flow through the device is reversed by reversing
the flow of pressurized fluid through the return lumen causing return of the
treating elements to the loading device. The elongated catheter tube may then be
removed from the patient and the procedure completed.
A further alternative embodiment of the catheter of the present invention,
preferably intended for placement over a guide wire, is shown in Figures 8A and
8B. The elongated catheter tube 212 comprises a pair of inner tubes 214 and 216
that extend in a parallel side-by-side arrangement within an outer tube 218. As
in the Figure 7 embodiment, inner tube 214, which is of smaller diameter than
tube 216, defines an inner lumen 220 for receiving a guide wire used for
placement of the catheter at the desired location within the patient. Inner tube
216, which is of larger diameter, provides inner lumen 222 along which the
treating elements 22 travel. A return lumen 224 is provided by the space between
the inner surface of the outer tube 218 and the outer surfaces of the inner
tubes 214 and 216 for return flow of liquid used to transport the treating
elements, in the very same manner as depicted in Figure 7B. In the Figure 8
embodiment, however, inner tube 214 (for the guide wire) extends fully along the
length of the outer tube 218, and is bonded to the outer tube at the distal-most
location, where the outer tube is tapered.
In Figure 8A, an internal barrier 226 is provided at the end of the inner
tube 216, through which the treating elements are carried, to block the passage
of treating elements from the distal end of the tube 216. A center opening in
the barrier 226 allows liquid to pass from the lumen 222 of the inner tube 216
to the return lumen. Alternatively, the barrier may be solid as
<PAGE>
31
depicted with barrier 228 in Figure 8B (which is otherwise the same as Figure
8A), and an aperture 230 may be provided in the wall of inner tube 216 to permit
liquid to flow between the treating element lumen 222 and the return lumen.
Although not depicted in Figures 8A or 8B, it should be understood that the
elongated catheter tube may also include a series of marker bands appropriately
placed along the length of the tube to aid in accurate placement in the patient.
Another embodiment of the catheter of the present invention
is shown in Figure 9. As shown there, catheter 232 has three coaxial tubes,
inner tube 234, outer tube 236 and intermediate tube 238, which all extend the
full length of the catheter. Inner tube 234 has a lumen 240 for receiving a
guide wire for placement of the catheter at the desired location in the patient.
Inner tube 234 is spaced from intermediate tube 238 to define an annular
treating element passageway 242 therebetween. In this embodiment, the treating
elements are preferably ring shaped, as at 244, or donut shaped, as at 246, to
allow them to slide over the inner tube 234 and along the passageway 242. To
provide a return flow channel, the inner diameter of the outer tube 236 is
slightly larger than the intermediate tube 238 to provide a return flow path 248
therebetween.
The end of the catheter is closed by a molded tip plug 250, preferably of
radiopaque material, bonded to the ends of the inner and outer tubes 234 and
236. Center passageway 252 through the tip plug allows for the passage of a
guide wire or the like for placement of the catheter at the desired location.
The distal end of the intermediate tube 238 stops short of the tip plug, thereby
allowing the treating element passageway 242 to communicate directly with the
return flow path 248. Radiopaque marker bands, although not shown, may also be
incorporated on the distal end portion of the elongated catheter tube to aid in
placing the elongated tube within the body at the selected site.
After the distal end portion of the elongated tube is
positioned at the desired location in the patient, a liquid, such as saline,
is forced through the treating element passageway 242 and directed against the
ring-shaped treating elements, moving
<PAGE>
32
the treating elements along the passageway over the inner tube 234 until they
abut the distal tip plug 250. The radioactive elements are retained at the
distal end portion of the elongated catheter tube for a sufficient time to
deliver the therapeutically effective amount of radiation to the selected site.
To retrieve the treating elements, the fluid flow is reversed through the flow
path by forcing liquid in a distal direction through the return lumen. Following
this the elongated tube can be removed over the guide wire and the procedure
completed.
In a still further embodiment of the present invention, shown in Figure 10,
a catheter 254 is provided which includes both an inflatable balloon membrane
256 for carrying out a balloon angioplasty procedure and treating elements 22
fixed in the distal end of the catheter for simultaneous treatment. The catheter
of Figure 10 includes an elongated tubular portion 258, typically of extruded
construction, with a guide wire lumen 260 and an inflation lumen 262. A balloon
membrane is located at the distal end of the catheter tube and sealed to the
exterior surface to form an inflatable balloon. Port 264 communicates between
the inflation lumen and the inside of the balloon for inflating the balloon by
pressurized liquid. Only the distal end portion of the catheter is shown -- the
proximal end of the catheter being typical of angioplasty catheter construction
as is well known to those skilled in the field.
To perform radiation treatment simultaneously with a balloon angioplasty
procedure, radioactive treating elements 22 are located within the balloon,
between coaxial walls 266 and 268 of the distal end portion of the catheter. The
treating elements are ring-shaped or donut-shaped, as described earlier, and
positioned over the inner wall 266. Stop rings 270, preferably of radiopaque
material, are positioned at each end of the string of treatment elements to
maintain the treatment elements at a fixed location within the balloon and aid
in locating the catheter at the desired location.
The strength and other characteristics of the radioactive treating elements
are essentially as described earlier and will
<PAGE>
33
not be repeated. With this construction, the balloon angioplasty procedure and
the radiation treatment of the stenotic site may be carried out simultaneously
instead of sequentially, thereby further reducing the time, cost and risk
associated with such procedures.
In use, catheter 254 is positioned into the stenosed area of the artery
over a pre-positioned guide wire. Using the radioactive treating elements alone
or in conjunction with the radiopaque end rings, the distal end portion of the
catheter is positioned such that the balloon portion is located at the stenosed
site. Pressurized fluid introduced into the proximal end of the inflation lumen,
as with a syringe, enters through port 264, inflating the balloon. The expanding
balloon membrane 256 compresses the sclerotic plaque and increases the diameter
of the blood vessel. The balloon may be deflated and the distal tip retained in
this position for the desired period of time to deliver an effective amount of
radiation to the previously stenosed area. The device may then be removed from
the patient and the procedure completed.
Figure 11 shows a variation of the radiation delivery system of Figure 10.
In the Figure 11 embodiment, the basic operation and construction of the
catheter are the same as described with respect to that shown in Figure 10,
except that in Figure 11, the radioactive treating elements are located on inner
tube 272 and directly below balloon membrane 274. Balloon membrane may be
inflated by the introduction of pressurized fluid through inflation lumen 276
defined between inner tube 272 and co-axial outer tube 278.
Figure 12 shows the distal end portion of another balloon catheter 280
embodying the present invention. The catheter 280 employs three coaxial tubes,
inner tube 282, outer tube 284 and intermediate tube 286. Inner tube 282 defines
an inner lumen 288 through which a guide wire may extend for placement of the
catheter at the desired location. The space between the inner tube and the
intermediate tube 286 defines an annular lumen 290, through which ring-shaped or
donut-shaped treating elements may pass. The space between the intermediate tube
and the outer tube
<PAGE>
33
not be repeated. With this construction, the balloon angioplasty procedure and
the radiation treatment of the stenotic site may be carried out simultaneously
instead of sequentially, thereby further reducing the time, cost and risk
associated with such procedures.
In use, catheter 254 is positioned into the stenosed area of the artery
over a pre-positioned guide wire. Using the radioactive treating elements alone
or in conjunction with the radiopaque end rings, the distal end portion of the
catheter is positioned such that the balloon portion is located at the stenosed
site. Pressurized fluid introduced into the proximal end of the inflation lumen,
as with a syringe, enters through port 264, inflating the balloon. The expanding
balloon membrane 256 compresses the sclerotic plaque and increases the diameter
of the blood vessel. The balloon may be deflated and the distal tip retained in
this position for the desired period of time to deliver an effective amount of
radiation to the previously stenosed area. The device may then be removed from
the patient and the procedure completed.
Figure 11 shows a variation of the radiation delivery system of Figure 10.
In the Figure 11 embodiment, the basic operation and construction of the
catheter are the same as described with respect to that shown in Figure 10,
except that in Figure 11, the radioactive treating elements are located on inner
tube 272 and directly below balloon membrane 274. Balloon membrane may be
inflated by the introduction of pressurized fluid through inflation lumen 276
defined between inner tube 272 and co-axial outer tube 278.
Figure 12 shows the distal end portion of another balloon catheter 280
embodying the present invention. The catheter 280 employs three coaxial tubes,
inner tube 282, outer tube 284 and intermediate tube 286. Inner tube 282 defines
an inner lumen 288 through which a guide wire may extend for placement of the
catheter at the desired location. The space between the inner tube and the
intermediate tube 286 defines an annular lumen 290, through which ring-shaped or
donut-shaped treating elements may pass. The space between the intermediate tube
and the outer tube
<PAGE>
34
284 forms a return lurnen 292 for return of liquid used to transport the
treating elements.
The catheter 280 also includes a balloon membrane 294 bonded at one end to
the exterior surface of the outer tube 284 and bonded to the exterior surface of
the inner tube 282 (which extends beyond the distal ends of the intermediate and
outer tubes) at the other end. The distal end of the outer tube is closed by a
barrier 296, which may be radiopaque, to block the exit of the treating elements
from the distal end of lumen 290. In this embodiment, the same liquid used to
transport the treating elements is also used to inflate the balloon membrane,
although that is not required if a separate inflation lumen were provided. To
inflate the balloon membrane, a side opening 298 or port is provided in the wall
of the outer tube 284 and also in the intermediate tube 286 if desired. With
this construction, pressurized blood-compatible liquid, such as sterile saline,
may be used to advance the treating elements while simultaneously advancing the
treating elements to the distal end portion of the catheter. The treating
elements may be retrieved by reversing the flow of the liquid through the return
and treating element lumen 292 and 290, respectively. Further release of
pressure exerted upon the liquid will allow the balloon to deflate and the
catheter to be removed.
Figure 13 illustrates a still further embodiment of a balloon catheter 300
which has a pair of adjacent parallel inner tubes, 302 and 304, forming guide
wire lumen 306 and a treating element lumen 308. In a manner similar to Figures
7 and 8, the inner tubes are contained within an outer tube, and the interior
space therebetween forms a return lumen. A balloon membrane 310 is bonded to the
outer surface of the outer tube, forming an inflatable balloon. The balloon
membrane may be inflated, through side port 312 in the wall of inner tube 304,
by the same blood-compatible liquid that is used to propel the treating elements
along the lumen 308. As in Figure 12, this catheter permits expansion of the
balloon membrane to carry out an angioplasty procedure within a blood vessel at
the same time the treating elements are being moved to the distal end portion of
<PAGE>
35
the catheter (where the balloon is located) to effect radiation treatment of the
tissue being subjected to the balloon angioplasty procedure.
Figure 14 shows a device that is essentially identical to that shown in
Figure 2C and described in detail earlier, except that the body member 94
includes a latch 314, such as spring loaded pin, to retain insert 110 within
chamber of cavity 108. A release mechanism 316 may also be provided to release
the insert.
Figures 15A-15C show another embodiment of treatment delivery system that
is similar in many respects to the embodiment shown in Figure 2C. In this
embodiment, however, the gate 114 is in the form of a disc 318 pivotally mounted
at the distal end of the insert 110. The disc includes a pair of spaced-apart
apertures 320 and 322, of different sizes, therethrough, which may be moved into
alignment with the center bore 112 of the insert. One of the apertures 320 is
smaller in diameter than the treating elements 22, and when aligned with the
bore 112 blocks the passage of treating elements from the bore while allowing
liquid to pass therethrough for priming and the like. Alternatively, the disc
may be pivoted to a position where the larger aperture 322 is aligned with the
center bore 112, which allows the treating elements to be ejected from the
insert by liquid flow pressure and advanced into and through the catheter. For
shipment and storage, the disc may be positioned to fully cover the bore 112 of
the insert.
In this embodiment, the body 94 includes a pair of opposed side access
openings 324 for accessing the disc 318 to pivot it between the desired
positions, and a pair of opposed viewing access openings 326 for visually
verifying the location of the treating elements. In this embodiment, the
catheter 92 has a proximal fitting 328 for attachment to the distal end of the
body 94. This fitting may be keyed to assure that it is attached in the proper
relationship to the body and the correct lumen of the catheter are aligned with
the proper passageways of the body.
Figure 16 shows a simplified version of the treating system of the present
invention. As shown there, the treating elements
<PAGE>
36
22 are contained in a central passageway 330 of a solid body 332. Female luer
lock connector 334 is provided at the inlet end of the passageway and male luer
lock connector 336 is provided at the outlet end of the passageway, although a
keyed fitting as described above also may be used.
During travel and storage a temporary female luer lock connector 338 is
attached to the outlet connector 336. The connector 338 includes a pin 340 that
extends from the connector into the passageway to hold the treating elements in
place and provide a barrier against the escape of radiation. The inlet end of
the passageway is smaller than the treating elements, thereby keeping the
treating elements located in generally the center of the body 332.
To use this embodiment, the temporary connector 338 is removed and a female
luer lock connector (or keyed connector, as discussed above) connector 342 at
the proximal end of single lumen catheter 344 is attached to the outlet
connector 336. A source, such as a syringe or suspended container, of
blood-compatible liquid, such as saline, is attached to the inlet connector 334,
and liquid is allowed to flow through the center passageway, ejecting the
treating elements 22 and forcing them along the length of the catheter from the
proximal to the distal end portion, which is presumable located at the site in
the vascular system where treatment is desired. After the treatment is complete,
the treating elements are removed by withdrawing the catheter from the patient's
body or by applying a suction to the proximal end to return the treating
elements by the force of reversed liquid flow.
Figure 17 is identical to Figure 12, except that a fourth co-axial outer
tube 346 is provided over tube 284, and the end of the balloon membrane 294 is
bonded to the outer tube 346 instead of the tube 284. The distal end of the
outermost tube 346 terminates just inside the balloon membrane, and the space
between the outermost tube 346 and the tube 284 provides an inflation lumen 348
through which pressurized fluid may flow directly into the area beneath the
membrane to inflate the balloon. This construction allows a separate source of
<PAGE>
37
pressurized fluid to be used to inflate the balloon membrane, and inflation of
the balloon membrane is not dependent on the pressure of the liquid used to move
the treating elements to the distal end portion of the catheter.
Similarly, Figure 18 is identical to Figure 13, except that an additional
tube 350 is provided over the other tubes described in connection with Figure
13, and one end of the balloon membrane 310 is bonded to surface of the tube
350. As with Figure 17, the space between the additional tube 350 and the tubes
described earlier provides an inflation lumen 352, the distal end of which lumen
opens directly in the area beneath the balloon membrane. This construction also
allows a source of fluid, independent of the liquid used to move the treating
elements, to be used to inflate the membrane in carrying out an angioplasty
procedure.
Figure 19 shows a still further embodiment of the distal end portion of a
catheter 354 having an elongated inner tube 356 (which extends from a proximal
end portion, not shown) defining an inner lumen 358. The inner tube 356 extends
co-axially within an outer tube 360, the distal end of which stops short of the
distal end of the inner tube. Balloon membrane 362 is attached at one end to the
surface of outer tube 360 and is attached at the other end to the surface of the
inner tube 356. The space between the inner and outer tubes forms an inflation
lumen 364, through which liquid may be introduced to inflate the balloon.
A separate elongated catheter tube 364 is insertable into inner
lumen 358 such that the distal end portion of the separate tube lies within the
area of the balloon. The separate tube also has a lumen 366 extending from the
proximal end (not shown) through which treating elements 22 are movable under
the force of flowing liquid from the proximal to the distal end portion of the
catheter (the liquid in this embodiment exits through the distal end of the
lumen 358).
XXXXXX
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for portions of this page and for all
of pages 38 through 62 of this Exhibit B. The copy filed herewith omits the
information subject to the confidentiality request. The portions omitted have
been filed separately with the Securities and Exchange Commission pursuant to
such request for confidential information.
<PAGE>
FIG.1
FIG.2A
<PAGE>
FIG. 2B
<PAGE>
FIG.2C
<PAGE>
FIG.3
FIG.4
FIG.5
<PAGE>
FIG.6A
FIG.6B
FIG.7A
FIG.7B
<PAGE>
FIG. 8A
FIG. 8B
<PAGE>
FIG. 9
FIG. 10
<PAGE>
FIG. 11
FIG. 12
<PAGE>
FIG. 13
FIG. 14
<PAGE>
FIG. 15A
FIG. 15B
FIG. 15C
<PAGE>
FIG. 16
FIG. 17
<PAGE>
FIG. 18
FIG. 19
<PAGE>
FIG. 20-37a
- - --------------------------------------------------------------------------------
Confidential treatment has been requested for figures 20 through 37a of this
Exhibit B. The copy filed herewith omits the information subject to the
confidentiality request. The portions omitted have been filed separately with
the Securities and Exchange Commission pursuant to such request for confidential
information.
<PAGE>
38-62
XXXXX
<PAGE>
EXHIBIT 10.3
CLINICAL RESEARCH STUDY AGREEMENT
This Agreement is entered into as of the 30th day of January, 1996, by and
between Novoste Corporation, located at 4350-C INTERNATIONAL BLVD., Norcross,
Georgia 30093 (hereinafter referred to as "Novoste") and Emory University at
1784 North Decatur Road, Suite 510, Atlanta, GA 30322 (hereinafter referred to
as "University").
WITNESSETH THAT:
The University agrees to conduct a clinical research study (the "STUDY")
entitled "Beta Energy Restenosis Trial" according to the protocol attached as
Exhibit A. In this undertaking, the University agrees to devote reasonable
efforts in order to perform efficiently the work required under this Agreement.
The University agrees that it will comply with all applicable laws, rules and
regulations relating to the conduct of such STUDY, particularly such laws, rules
and regulations concerning or promulgated by the Food and Drug Administration.
To the extent any portions of Exhibit A are inconsistent with this Agreement,
the terms of this Agreement shall govern.
NOW THEREFORE, in consideration of the foregoing and the mutual covenants herein
below set forth, the parties hereto agree as follows:
(1) PRINCIPAL INVESTIGATOR.
----------------------
The STUDY performed under this Agreement will be under the direction of Spencer
B. King III, M.D. (hereinafter referred to as "INVESTIGATOR"). All University
employees involved in the clinical research study (hereinafter referred to as
INVESTIGATORs).
(2) HUMAN SUBJECTS.
--------------
This protocol has been approved by the University's Institutional Review Board
(Exhibit B) and NOVOSTE. The University shall obtain from each of the patients
participating in this STUDY, advance informed consent in compliance with 21 CFR
50.1 through 50.27 and any modifications thereof as may be adopted. Novoste will
reimburse the University and/or the patient for reasonable costs and expenses
incurred in diagnosing and treating unanticipated adverse effects, injuries,
illnesses, or reactions that result from the use or application of Novoste's
investigations, drugs or devices in the course of this STUDY.
1
<PAGE>
(3) INDEMNIFICATION.
---------------
An "Indemnification Agreement for Clinical STUDY" is attached as Exhibit C and
is incorporated for reference.
(4) UNIVERSITY AND NOVOSTE CONTACTS.
-------------------------------
The University's scientific contact for this Agreement will be Dr. King at (404)
712-4467. The University's administrative contact for this Agreement will be
Nancy Wilkinson, at (404) 727-2503. Novoste's scientific contact will be Dr.
Joan Macdonald, at (770) 717-0904. Novoste's administrative contact will be Dr.
Jonathan Rosen at (770) 717-0904.
(5) PERIOD OF PERFORMANCE.
---------------------
The term of this Agreement shall be from the date this Agreement is mutually
executed until the STUDY is either completed or terminated. It is anticipated
that the STUDY will begin on or about January 22, 1996 and be completed on or
about December 31, 1996.
(6) PAYMENT SCHEDULE.
----------------
(A) Payments shall be made payable to EMORY UNIVERSITY and forwarded to the
following address:
Ms. Marilyn Surbey
Assistant Vice President for Finance
Office of Grants and Contracts Accounting
Emory University
1784 N. Decatur Road
Suite 530
Atlanta, GA 30322
(404) 727-4240
It is agreed that Novoste will reimburse the University on a per patient
basis and for the total amount of the study not to exceed one hundred
ninety-five thousand nine hundred forty-five dollars ($195,945) in
accordance with the approved budget and payment schedule attached as Exhibit
D. Novoste acknowledges that the University has included its indirect costs
for this clinical STUDY. For purposes of identification, payments will
include the title of the STUDY and the name of the INVESTIGATOR.
(B) In the event of termination, the sum for professional services and
expenses payable under this Agreement shall be limited to the prorated fees
based on actual work performed and actual expenses
2
<PAGE>
committed pursuant to the protocol. Any unexpended funds not due under this
calculation but already paid shall be returned to Novoste.
(7) INDEPENDENT CONTRACTOR.
----------------------
Each party to this Agreement shall act as an independent contractor and shall
not be construed for any purpose as the agent, employee, servant or
representative of the other party, and neither party shall enter into any
contract or agreement with a third party which purports to obligate or bind the
other party. Neither party shall be liable for any obligation incurred by the
other except as expressly provided for herein.
(8) PUBLICATIONS.
------------
Novoste acknowledges the University, INVESTIGATOR and INVESTIGATORs publication
privileges under the Agreement. However, notwithstanding the confidentiality
provisions or any other provision, the University, INVESTIGATOR and
INVESTIGATORs acknowledge that Novoste may have proprietary interests and agree
to submit a manuscript to Novoste for review sixty (60) days prior to submission
for any oral presentation or written publication. Novoste shall then have forty-
five (45) days to respond to the University, INVESTIGATOR and INVESTIGATORs with
any requested revisions. Novoste shall have the right to edit such proposed
disclosure to remove any Novoste PROPRIETARY INFORMATION or information
reasonably necessary to protect Novoste's competitive position and to delay the
publication of any invention for a reasonable period of time(not to exceed 4
months), to enable Novoste to file or have filed a Patent application to protect
any invention disclosed therein.
(9) CONFIDENTIALITY.
---------------
(a) Novoste acknowledges that the INVESTIGATOR and INVESTIGATORs are
currently employed in Emory University's Department of Cardiology and Radiation
Oncology and as such have full time academic, service and research
responsibilities to Emory. In connection with such Emory employment, the
INVESTIGATOR and INVESTIGATORs have entered into certain Agreements with Emory
relating to the ownership of intellectual property rights, conflicts of interest
and other matters and is subject to certain policy statements of Emory
(collectively defined as the Emory Agreements). If any provision of this
Agreement is in conflict with any Emory Agreement, then the Emory agreement
shall govern to the extent of such conflict and the conflicting provisions of
this Agreement shall not apply. The INVESTIGATOR and INVESTIGATORs agree to
furnish Novoste with copies of any Emory Agreements with the INVESTIGATOR and
INVESTIGATORs.
3
<PAGE>
(b) PROPRIETARY INFORMATION.
-----------------------
(i) INVESTIGATOR and INVESTIGATORs acknowledge that during the course of
performing services hereunder, Novoste may disclose information to the
INVESTIGATOR and INVESTIGATORs which Novoste considers proprietary trade secret
information. Any such information, shall be disclosed to the INVESTIGATOR and
INVESTIGATORs in written or oral form and marked as Novoste PROPRIETARY
INFORMATION. If Novoste is unable to first disclose such information in written
form, Novoste shall, within sixty (60) days of first disclosing such information
provide the INVESTIGATOR and INVESTIGATORs with a copy of such information in
written form and marked as Novoste PROPRIETARY INFORMATION.
(ii) The INVESTIGATOR and INVESTIGATORs shall not disclose any Novoste
PROPRIETARY INFORMATION to any third person or entity, other than
representatives or agents of Novoste. The INVESTIGATOR and INVESTIGATORs shall
treat all such information as confidential and proprietary property of Novoste.
(iii) The term "PROPRIETARY INFORMATION" shall not include information
that: (i) is or becomes generally available to the public other than by
disclosure in violation of this Agreement; (ii) was within the INVESTIGATOR and
INVESTIGATORs possession prior to being furnished to INVESTIGATOR and
INVESTIGATORs by Novoste hereunder; (iii) becomes available to INVESTIGATOR and
INVESTIGATORs on a nonconfidential basis from a party which does not have a
confidential obligation to Novoste respecting such information; or (iv) is
independently developed by INVESTIGATOR and INVESTIGATORs without reference to
any information received from Novoste by INVESTIGATOR and INVESTIGATORs.
(iv) The INVESTIGATOR and INVESTIGATORs may disclose any PROPRIETARY
INFORMATION that is required to be disclosed by law, government or court order.
If disclosure is required, the INVESTIGATOR and INVESTIGATORs shall give Novoste
advance notice so that Novoste may seek a protective order or take other action
reasonable in light of the circumstances.
(v) Upon termination of this Agreement, the INVESTIGATOR and
INVESTIGATORs shall promptly return to Novoste all materials containing
PROPRIETARY INFORMATION as well as data, reports, records and other property
furnished by Novoste to the INVESTIGATOR and INVESTIGATORs, together with all
copies of any of the foregoing. Notwithstanding such return, the INVESTIGATOR
and INVESTIGATORs shall continue to be bound by the terms of the confidentiality
provisions
4
<PAGE>
contained in this Agreement for a period of five (5) years after the termination
of this Agreement.
(10) INVENTIONS AND PATENTS RIGHTS.
-----------------------------
10.1 The University understands and acknowledges that Novoste has been engaged
in a continuous research, design development and marketing program with respect
to the Beta Energy Restenosis Project ("THE SYSTEM") and that Novoste has filed
United States patent application, Serial No.: 08/330,327, which names Drs.
Waksman and Crocker, both employees of the University, and certain Novoste
employees as inventors entitled "Method and Apparatus for Treating a Desired
Area in the Vascular System of a Patient". The University acknowledges and
agrees that Novoste shall have a worldwide Exclusive Agreement to make, use and
sell devices, methods or services claimed in such patent application and any
reissues, renewals, extensions, divisionals, continuations, continuations-in-
part, and patents which issue thereon, including reexamined and reissued patents
and any foreign counterparts of such patent applications and issued patents, in
accordance with the Worldwide Exclusive Agreement of even date herewith
("Exclusive Agreement"). Such Exclusive Agreement shall cover any inventions or
discoveries made by University employees during the course of this and any other
research or clinical trials regarding THE SYSTEM sponsored by Novoste
("University Study Inventions").
10.2 The University shall promptly disclose all University Study Inventions to
Novoste in written form. Any such University Study Inventions for which Novoste
pursues patent protection shall be considered a Licensed Patent under the
Exclusive Agreement. Any such University Study Inventions for which Novoste
declines to pursue patent protection shall be considered Licensed Technology
under the Exclusive Agreement. The University shall delay any public disclosure
of any University Study Inventions for at least ninety (90) days from the date
the University discloses it to Novoste to enable Novoste to pursue patent
protection. Such delay may be extended upon the agreement of both parties.
(11) DATA OWNERSHIP.
--------------
The University shall retain ownership of any medical records, including but not
limited to, patient specimens, x-rays, angiograms, EKG's, ultrasonic images and
recording, and other patient medical data generated during clinical studies
conducted at Emory University under this Agreement. The University shall, within
the bounds of legal requirements, make such medical records, patient specimens,
x-rays, angiograms, EKG's, ultrasonic images and recording, and other patient
medical data generated under this Agreement available for audit, review and
copying by Novoste.
5
<PAGE>
Novoste shall retain ownership of all completed case medical record forms,
research notebooks prototypes, devices, supplies, radiation sources, and
equipment provided by Novoste. The University shall be entitled to retain a
confidential copy of the case medical record forms, without duplication, subject
to sections 8, 9, 10 of this Agreement.
Subject to the Publications and Intellectual Property provisions of this
Agreement, Novoste shall have access to all clinical data and may freely use
such data in connection with any of its research, development, marketing or
promotional activities and may be disclosed by Novoste to other clinical
centers, consultants, the Food and Drug Administration and other Federal, State
and/or local regulatory agencies.
(12) PUBLICITY. Novoste will not include the University in any advertising,
---------
sales promotion or other publicity material without the prior written approval
of the University. Likewise, the University will not name Novoste in any
advertising, sales promotion, or publicity without the express written consent
of Novoste. The University will reference Novoste in all scientific and clinical
publications related to the STUDY if Novoste so requests and if Novoste provides
prior written approval.
(13) TERMINATION.
-----------
The STUDY may be terminated prior to completion by written notice from Novoste
to the University or by the University to Novoste for any of the following
reasons:
(A) Notification to Novoste or the University from federal or state regulatory
authorities to terminate said STUDY;
(B) Determination by Novoste or the University that the University, after a
reasonable opportunity, is unable for any reason to perform the STUDY
satisfactorily as required in the protocol; or
(C) Inability of the INVESTIGATOR to continue the STUDY at the University and a
successor acceptable to both the University and Novoste is not available.
Written notice of the decision to exercise such termination right shall be given
to the University by Novoste or to Novoste by the University by certified mail,
delivered ten (10) days before said termination of the STUDY. Immediately upon
receipt of a notice of termination by either Novoste or the University, the
University shall stop entering patients into the STUDY and
6
<PAGE>
shall cease conducting procedures, to the extent medically permissible, on
patients already entered into the Study protocol. In the event of termination,
expenses payable to the University shall be as stated in paragraph 6B.
Termination or completion of this Agreement, however, shall not relieve the
obligations undertaken by the parties in paragraphs 3, 8, 9, 10, 12 and 13.
(14) MODIFICATIONS.
-------------
Any alteration in or amendment to this Agreement must be approved in writing by
the University and Novoste prior to such alteration or amendment becoming
effective.
(15) GOVERNING LAW.
-------------
This Agreement shall be governed by and construed in accordance with the laws of
the state of Georgia.
(16) ARBITRATION.
-----------
In the event that there is any dispute between the parties hereto, the parties
agree to submit the matter to binding arbitration in Atlanta, Georgia in
accordance with the commercial rules of the American Arbitration Association
then applicable before a panel of three arbitrators. The decision of the panel
of arbitrators shall be final, binding and conclusive upon the parties hereto
and judgment thereon may be entered in any court having jurisdiction. The costs
of such arbitration shall be paid or reimbursed by the non-prevailing party.
(17) SEVERABILITY.
------------
In the event that any provision of this Agreement is held to be invalid,
prohibited or unenforceable for any reason, such provision shall be ineffective
without invalidating the remaining provisions of this Agreement. Notwithstanding
the foregoing, if such provision could be more narrowly drawn so as not to be
invalid, prohibited or unenforceable, it shall be so narrowly drawn without
invalidating the remaining provisions of the Agreement.
7
<PAGE>
IN WITNESS WHEREOF, the undersigned Parties have caused this Agreement to be
executed by their duty authorized representatives.
EMORY UNIVERSITY
By: /s/ 1/30/96
------------------------------------- ------------------
Authorized Official Date
By: /s/ 1-30-96
------------------------------------- ------------------
Principal Investigator Date
/s/
-------------------------------------
Title
NOVOSTE
By: /s/
-------------------------------------
Date: 1/30/96
------------------
Title: President & CEO
----------------------------------
Witness:
--------------------------------
Date:
----------------------------------
8
<PAGE>
Exhibit A/(1)/
Clinical Study Protocol
Pages 1-29
- - --------------------------------------------------------------------------------
(1) Confidential treatment has been requested for this entire Exhibit A,
consisting of 29 pages. The copy filed herewith omits the information
subject to the confidentiality request. The portions omitted have been filed
separately with the Securities and Exchange Commission pursuant to such
request for confidential information.
<PAGE>
Exhibit B
Emory HIC Study Approval
Emory Committee I Approval
<PAGE>
[LETTERHEAD OF EMORY UNIVERSITY SCHOOL OF MEDICINE]
February 16, 1995
Spencer King, M.D.
Andreas Gruentzig Cardiovascular Center
F606, Emory University Hospital
RE: HIC Protocol No: 809-94
Dear Dr. King:
Your research proposal entitled "Beta Energy Restenosis Trial" and informed
consent form have been approved by the Human Investigations Committee.
This approval is valid for one year. Any serious reactions resulting reaction
from this study should be reported immediately to the Committee, to the
Departmental Chairperson, and to any sponsoring agency or company. Approval is
contingent upon your agreement to obtain informed consent from your subjects, to
abide by the policies and procedures of Emory University School of Medicine with
regard to use of human subjects in investigation in keeping with the University
Assurance Document, and to keep appropriate records concerning your subjects.
Brochures or manuals describing the study which are given to volunteers or
patients and advertisements for the study must be submitted to the Committee for
approval.
Projects which are being submitted to agencies or other sponsors for external
funding must also be approved through the Office of Sponsored Programs prior to
initiation of the study.
Please note that this protocol has been assigned the above referenced HIC
protocol number. All inquiries and correspondence concerning this protocol must
include this number.
Sincerely,
/s/ T. Hersh
Theodore Hersh, M.D.
Chairman
Human Investigations Committee
cc: Department Chair
Office of Sponsored Programs
THE ROBERT W. WOODRUFF HEALTH SCIENCES CENTER
<PAGE>
[LETTERHEAD OF EMORY UNIVERSITY SCHOOL OF MEDICINE]
TO: File
FROM: Stan Wilson, M.M.Sc.
Deputy RSO
DATE: March 16, 1995
RE: New Authorization
The purpose of this note is to announce the issuance of a new authorization for
Human Use of radioactive materials. Committee I, the Human Use Radioisotope
committee has approved ballots for the application for Radiation Oncology
Research Protocols submitted by Dr. Ian Crocker. Current allowed materials are:
/90/Sr - 2000 mCi in the form of sealed sources and
/125/I - 1000 mCi in the form of sealed sources.
The file number for this authorization is RH045.
The signed authorization including significant conditions will be prepared soon.
Please call if I may be of any further assistance.
cc: Dr. Lisella
Betty Goetz
Application file
Reading file
<PAGE>
Exhibit C
Indemnification Agreement
<PAGE>
EXHIBIT C
INDEMNIFICATION AGREEMENT FOR CLINICAL STUDY
---------------------------------------------
Beta Energy Restenosis Trial ("BERT") designed to evaluate the safety and
efficacy of low dose beta radiation in the inhibition and prevention of intimal
hyperplasia following balloon angioplasty.
This Agreement is by and between Emory University, hereinafter referred to
as "UNIVERSITY", and Novoste Corporation, hereinafter referred to as "NOVOSTE".
It shall become effective on or about the 22nd day of January, 1996.
WITNESSETH THAT:
WHEREAS, NOVOSTE has planned to conduct certain studies as described in the
protocol attached hereto and made a part hereof, which protocol shall be signed
by the physicians responsible for conducting the studies; and
WHEREAS, the UNIVERSITY is willing to perform said studies and recognizes
the need for medical professional liability indemnification;
NOW, THEREFORE, IT IS UNDERSTOOD AND AGREED UPON by the parties hereto, as
follows:
1. NOVOSTE agrees to defend, indemnify and hold harmless the UNIVERSITY, its
trustees, its employees, and its affiliated hospitals and The Emory Clinic,
its partners and employees, and the UNIVERSITY agrees to defend, indemnify
and hold harmless NOVOSTE, its executive management and authorized agents,
from and against any and all liabilities, suits, proceedings, claims,
demands, debts, costs (including legal costs), obligations and actions of
any kind by anyone for any loss, damage, injury or loss of life which
results from the performance of this clinical STUDY and attributable to or
arising from (a) negligence, wrongful act(s), or wrongful failure to act on
the part of the indemnifying party, (b) the indemnifying party's violations
of any federal or state law, rule or regulation, (c) the indemnifying
party's
9
<PAGE>
actions or inactions in furtherance of the STUDY, (d) the indemnifying
party's breach or default in the performance of the obligations to be
performed in connection with the STUDY, (e) the indemnifying party's
activities or operations, or (f) any material deviation by the indemnifying
party from the protocol or other written recommendations or instructions
furnished by NOVOSTE for the STUDY.
2. NOVOSTE shall provide evidence to the UNIVERSITY, within thirty (30) days
after the effective date of this Agreement, that it has sufficient liability
insurance or such other adequate forms of protection, as satisfactory to the
UNIVERSITY, to satisfy its indemnification obligation.
3. The UNIVERSITY shall, at the request of NOVOSTE, provide evidence to NOVOSTE
that it has such liability insurance or other forms of protection as is
necessary and proper, against negligence, wrongful act(s), or wrongful
failure to act on the part of the UNIVERSITY, its trustees, its employees,
or its affiliated hospitals and The Emory Clinic, its partners and
employees.
4. The UNIVERSITY shall obtain from each of the patients participating
in the STUDY, advance informed consent in compliance with 21 CFR
50.1 through 50.27 and any modifications thereof as may be adopted by
the U.S. Government.
5. The Indemnifying Party shall notify the Indemnified Party in writing of any
claims of loss, damage, injury or loss of life arising from this clinical
STUDY within thirty (30) days after the Indemnified Party has knowledge of
the claim.
6. The Indemnifying Party shall allow the Indemnified Party and/or its insurer
the right to assume direction and control of the defense against such claims
or suits thereon, including without limitation the right to select defense
counsel and the right to settle such claims or suits at the sole discretion
of the Indemnified Party or its insurer.
10
<PAGE>
7. The Indemnifed Party shall in all ways cooperate fully with the Indemnifed
Party and its insurer in defending against, and disposing of, any such
claims or suits.
8. The UNIVERSITY shall have kept and make available to NOVOSTE all records
concerning the STUDY.
In Witness Whereof, the undersigned Parties do hereby agree to the terms and
conditions of this Agreement, as evidenced by the authorized signatures
below.
UNIVERSITY: By: /s/ Charles Hatcher Date: 2/6/96
----------------------------- ---------------
Dr. Charles Hatcher
Vice President for Health Affairs
NOVOSTE: By: /s/ Date: 1/30/96
----------------------------- ---------------
Witness: By: /s/ Date: 1/30/96
----------------------------- ---------------
<PAGE>
Exhibit D
Proposed Budget
Payment Schedule
<PAGE>
Preliminary Budget
NOVOSTE
Radiation charges (beginning of study - $400/patient) $ 400
6 month follow up cath (outpatient cath lab) 1,500
Angiography core lab 500
------
40 patient @ $2,400/patient $96,000
Research Nurse @ 50% $30,631
Coordinator @ 50% 24,727
-------
$54,727 54,727
-------
$150,727
Overhead @ 30% 45,218
TOTAL $195,945
4/25/95
<PAGE>
[LETTERHEAD OF NOVOSTE]
Payments will bc made to the University on the following basis:
Start of Trial $ 20,800.00 100% Radiation charges + OH
Start of Trial $ l7,787.00 25% Admin. Support + OH
Quarterly (3) $ 17,786.00 25% Admin. Support + OH
Start of F/U $ 39,000.00 50% Outpatient Cath + OH
End of F/U $ 39.000.00 50% Outpatient Cath + OH
End of Core $ 26.000.00 l00% Core Lab Analysis + OH
- - --------------------------------------------------------------------
Totals $195,945.00
Definitions:
- - -----------
Start of Trial: Procedure performed on first patient
Quarterly: Admin support paid over twelve months in four payments starting
with "Start of Trial".
Start of FIU First Patient Receives Follow-up Angio at 6 months from "Start
of Trial".
End of F/U 40th Patient Receives 6 month Angio
End of Core Novoste Receives Final Report on Core Lab Analysis
OH Emory University Overhead Rate of 30.0%
All Payments to be received within l0 days of scheduled events.
All Payments assume completion of Study Protocol with 40 patients.
<PAGE>
EXHIBIT 10.4
LICENSE AGREEMENT
LICENSE AGREEMENT made this 31st day of January, 1996 by and between Novoste
Corporation, a Florida Corporation located at 4350-C International Blvd.
Norcross, GA 30093 ("Novoste"), and Spencer B. King III, M.D. ("Dr. King").
RECITALS:
A. Novoste, a highly-reputed medical technology development company with a
successful track record of proprietary innovative devices, is developing a
system to treat restenosis with radiation ("Project Beta System") as defined
hereunder.
B. Novoste anticipates that the Project Beta System will yield a commercially
viable catheter system, Transfer Device and accessories to be used in the
field of Interventional Cardiology (the "Product").
C. Dr. King has agreed to allow Novoste to use his name in connection with the
Sales and Marketing of the Product, all in the terms hereinafter set forth.
Now Therefore, based on the foregoing recitals and other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the
parties agree as follows:
1. License. Dr. King hereby grants with Dr. King's consent not
-------
unreasonably withheld Novoste the exclusive right but not the obligation to
utilize his name (the "Name") in connection with the marketing, advertising,
sales and distribution of the Product in the field of Interventional Cardiology,
and, to sublicense others to do so. Dr. King represents and covenants that such
grant does not conflict with any other license rights heretofore granted any
entity or person and that he will not in the future license any entity or person
in any manner that may conflict with the rights hereby licensed to Novoste. Dr.
King further represents and warrants that this agreement does not conflict with
any agreements with Emory University or its policy.
2. Term. This agreement shall run for the greater of the life of the patent
----
or ten (10) years from the date hereof (the "Term"), unless terminated earlier
pursuant to Section 7 hereinbelow. The license granted hereunder is subject to
Novoste's obtaining Dr. King's written approval prior to Novoste's initial use
of Dr. King's name.
3. Royalties. Novoste agrees to pay Dr. King a sum equal to the greater of (a)
---------
XXXXX (XXXXX%) of all Net Sales (defined below) of the Product or (b) in the
event that Novoste sells the Product at a unit price less than five hundred
- - ---------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
1
<PAGE>
dollars ($500.00), XXXXX (XXXXX%) of Net Sales will be calculated as though the
sales price of each unit of the Product sold were five hundred dollars
($500.00). The royalty payment shall be paid to Dr. King within sixty (60) days
of the last day of each calendar quarter during the Term based on Net Sales for
the Calendar quarter then recently ended. Net Sales shall mean the gross invoice
price actually paid by a purchaser of a Royalty-bearing Product to Novoste, an
affiliate of Novoste, a sublicensee of Novoste, or any other party authorized by
Novoste to sell Royalty-bearing Products (net of rebates, refunds, replacements
or credits allowed to purchasers for return of Royaltybearing Products or as
reimbursement for damaged Royalty-bearing Products, discounts, sales, use or
value-added taxes, duties, shipping and transportation charges, insurance and
allowances, commissions paid to non-employee outside salesmen or distributors,
import and custom duties, and any separately itemized cost or expense for
handling or disposing of radioactive catheters, transfer devices or other
materials).
Notwithstanding "Net Sales Price" shall not in any event include any
consideration paid to Novoste, its Affiliates, sublicensees or authorized agents
for the sale, lease, use, service, acquisition, handling, or disposal of
radioactive isotopes or other radiation sources.
The royalty obligations described in this Section 3 shall apply even if Novoste
does not use Dr. King's name in association with the sale, marketing,
advertising and distribution of the Product, and shall be assumed by any
purchaser or licensee of the Project Beta System so that any sales of the
Product made by such purchaser or licensee shall result in the payment of
royalties to Dr. King. Unless Dr. King does not allow Novoste or asks Novoste
to remove his name from the Product, then Novoste will not be obligated to pay
any royalty on Products sold without the use of Dr. King's name. Novoste hereby
covenants that any purchase, sale or license agreement with respect to the
Project Beta System shall require the third party purchaser to assume all of
Novoste's royalty payment obligations under this Agreement. Royalties shall be
payable for the time period of the greater of the life of any patent issued on
the Product or ten (10) years from the date hereof (the Term).
4. Statements and Payments. Novoste agrees to keep complete and accurate
-----------------------
records and books of accounts relating to sales of the Product for five years
and, within sixty (60) days after the end of each calendar quarter, to furnish
Dr. King at his address designated in Section 18 hereinbelow, a statement in
writing showing in reasonable detail: (a) the gross sales of the Product, if
any, for such calendar quarter and, on a cumulative basis, (b) a computation of
Net Sales showing the amount of each allowable deduction from the gross sales of
the Product; and (c) the payment, if any due to Dr. King at such time. The
foregoing statement shall accompany the royalty payment payable pursuant to
Section 3 hereinabove.
- - ---------------
Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
2
<PAGE>
5. Audit. Novoste hereby grants Dr. King the right, exerciseable once per year
-----
(non-cumulatively), to inspect, audit, investigate accounts and records of
Novoste relating only to the sale and/or distribution of the Product for the
purpose of determining the sufficiency and accuracy thereof and the correctness
of the statements and payments made by Novoste. Such inspection, investigation
and/or audit of such books, accounts and records shall be at Dr. King's expense
and take place during normal business hours upon reasonable notice by Dr. King,
provided, however, that if such audit indicates that Novoste underpaid Dr. King
by five percent (5%) or more for any quarter, Novoste shall be responsible for
the cost of such audit. All books and records relating to the sales of the
Product shall be kept available by Novoste for at least five (5) years after the
date of sale.
6. Lifetime Cap. The maximum total royalty payment payable to Dr. King
------------
hereunder shall be five million dollars ($5,000,000.00) cumulatively. Once all
royalty payments reach the maximum amount, the provisions of Sections 3, 4 and 5
shall terminate and no further royalties are due on the sale of the Product.
7. Termination. Dr. King may terminate this agreement upon the occurrence of
-----------
any one of the following events:
(a) if Novoste shall have failed to make any payment due hereunder on the
date such payment is due;
(b) if Novoste shall fail to deliver any of the statements required to be
delivered hereunder or to make available for inspection, investigation
and/or audit its books and records pursuant to the provisions hereof;
(c) if upon one or more inspections, investigations and/or audits, it is
determined that for each of two (2) consecutive calendar quarters, the
royalty amounts paid by Novoste were less than ninety percent (90%) of the
amounts due to Dr. King in such periods; or
(d) if Novoste shall:
(i) file a petition in bankruptcy or for reorganization or for the
adoption of the arrangement under any bankruptcy or insolvency act, or
an answer or other pleading admittance of failing to deny the material
allegations of such a petition or seeking, consenting to or acquiescing
in the relief therein provided;
(ii) make an assignment for the benefit of its creditors;
3
<PAGE>
(iii) consent to the appointment of a receiver or trustee or
custodian for all or a substantial part of its property or to the
filing of a petition against it under any bankruptcy or insolvency
act; or
(iv) be adjudicated a bankrupt organization.
In the event any of such events occur, Dr. King, if he desires to terminate this
agreement, shall give notice of termination in writing to Novoste as provided
hereunder. If Novoste shall fail to cure such event of default within ninety
(90) days of receipt of such notice, then this agreement shall terminate.
Novoste may terminate this Agreement for "cause". Cause means (a) willful
misconduct on the part of Dr. King with respect to the business and affairs of
Novoste, (b) Dr. King's conviction of any felony or any act involving fraud or
moral turpitude, or (c) the suspension, revocation or cancellation of Dr. King's
right to practice his profession in Georgia. If Novoste terminates for any of
the above reasons, the provisions of Sections 3, 4, and 5 shall also terminate.
8. Rights of Novoste Upon Termination or Expiration. Upon the expiration or
--------------------------------------------------
termination of this agreement for any reason, neither Novoste nor its receivers,
representatives, trustees, agents, successors and/or assignees shall have any
right to exploit or in any way use the Name in connection with the advertising,
marketing, promotion, sales or distribution of the Product except in connection
with the distribution and sale of remaining inventory, for which Novoste shall
be responsible for the payment of all royalties in accordance with the terms
hereof.
9. Confidentiality Covenant. Dr. King acknowledges that the trade secrets,
------------------------
information, ideas, research, methods, improvements and materials owned,
licensed or developed by Novoste are and shall remain the sole and exclusive
strictly confidential property of Novoste. All information and knowledge about
Novoste and its products, services, methods, standards, specifications,
procedures and techniques which are not public knowledge and such other data as
Novoste may designate as confidential shall be kept strictly confidential by Dr.
King, used only for the purposes authorized by Novoste. Dr. King covenants and
agrees that during and after the termination of this Agreement (for five 5
years) neither he nor anyone associated with him shall copy or disclose to
anyone or use for any purposes other than as authorized by Novoste any such
confidential information.
10. Assignment. This agreement shall be binding upon and shall inure to the
----------
benefit of the parties hereto and their respective successors and assignees.
4
<PAGE>
No assignment shall relieve any party from the responsibility for the
performance of any accrued obligations which such party then has hereunder.
11. Relationship of the Parties. The parties hereto agree that the status
---------------------------
of Dr. King is that of an independent contractor and that Dr. King is not a
partner or legal representative of Novoste. Dr. King shall have no right or
authority to assume or create any obligation or responsibility, express or
implied, on behalf of or in the name of Novoste, or to bind Novoste in any
manner.
12. No Waiver of Rights. The failure of either party to enforce at any
-------------------
time any of the provisions of this agreement, or any rights in respect
thereto, or to exercise any election herein provided, shall in no way be
considered to be a waiver of said provisions, rights or election, or in any
way to affect the validity of this agreement.
13. Governing Law. This agreement shall be governed by and construed and
-------------
enforced in accordance with the laws of the State of Georgia.
14. Legal Counsel. The parties hereto agree that they each have been
-------------
represented by independent legal counsel in connection with the review and
negotiation of this Agreement and the subject matter contained herein.
15. Attorneys' Fees. In the event that either of the parties to this
---------------
agreement commence arbitration against the other party to this Agreement to
enforce any of its or his rights hereunder, the prevailing party in such
action shall be entitled to recover from the other party all reasonable
costs thereof, including reasonable attorneys' fees.
16. Arbitration. In the event that there is any dispute between the parties
-----------
hereto, the parties agree to submit the matter to binding arbitration in
Atlanta, Georgia in accordance with the commercial rules of the American
Arbitration Association then applicable before a panel of three arbitrators.
The decision of the panel of arbitrators shall be final, binding and
conclusive upon the parties hereto and judgment thereon may be entered in
any court having jurisdiction. The costs of such arbitration shall be paid
or reimbursed by the non-prevailing party.
17. Indemnification. Dr. King and Novoste shall indemnify, defend and
---------------
hold the other harmless from and against any and all liabilities, suits,
proceedings, claims, demands, debts, costs (including legal costs),
obligations and actions of any kind by anyone allegedly arising from or
connected with (a) the indemnifying party's violations of any federal or
state law, rule or regulation, (b) the indemnifying party's actions or
inaction's in furtherance of this Agreement, (c) the indemnifying party's
breach or default in the performance of the obligations to be performed
under this Agreement, (d) the indemnifying party's negligence, or (e) the
indemnifying party's activities or
5
<PAGE>
operations. The provisions of this paragraph in the case of Novoste shall
extend to its executive management and authorized agents.
18. Communications. All notices under this agreement shall be in writing
--------------
and (unless otherwise specifically provided for herein) shall be deemed to
have been given at the time when mailed, by registered mail, postage prepaid,
addressed to either party hereto at the following addresses:
Spencer B. King III, M.D.
------------------------
------------------------
Novoste Corporation
4350-C International Blvd.
Norcross, GA 30093-3027
Attn: President
or to such changed address as such parties may have fixed by notice; provided,
however, that any notice of any change of address shall be effective only upon
receipt thereof.
19. Severability. If any provisions of this agreement shall be held to be
------------
invalid or unenforceable, such invalidity or unenforceability shall attach only
to such provision and shall not in any way affect or render invalid or
unenforceable any other provision of this agreement, and this agreement shall be
carried out as if such invalid or unenforceable provision were not contained
herein.
20. Further Assurances. The parties each agree to execute any and all
------------------
documents and perform any and all acts which may be reasonably requested by the
other in furtherance of any of the provisions herein.
21. Entire Agreement. This agreement constitutes the entire final agreement
----------------
between the parties with respect to, and supersedes any and all prior agreements
between the parties hereto both oral and written concerning the subject matter
hereof and may not be amended, modified or terminated except by a writing signed
by the parties hereto.
IN WITNESS WHEREOF, the parties have hereunto set their hands as of the date
first above written.
6
<PAGE>
NOVOSTE CORPORATION
By: /s/ Spencer B. King III M.D. By: /s/ Thomas D. Weldon
------------------------------ ---------------------------
Spencer B. King III M.D. Thomas D. Weldon, President
Date: 1-31-96 Date: 1/31/96
---------------------------- -------------------------
Witness: /s/ Date: 1/31/96
------------------------- -------------------------
7
<PAGE>
EXHIBIT 10.5
RESTENOSIS THERAPY PROJECT
DEVELOPMENT AND SUPPLY AGREEMENT
DEVELOPMENT AND SUPPLY AGREEMENT made this 28th day of November, 1994 by and
between NOVOSTE CORPORATION, a Florida corporation ("NOVOSTE") and BEBIG
ISOTOPENTECHNIK UND UMWELTDIAGNOSTIK GMBH, a German corporation ("BEBIG").
1. BACKGROUND AND RECITALS
NOVOSTE Corporation (NOVOSTE) forwarded to BEBIG Isotopentechnik (BEBIG) a
Purchase Order on 5 October 1994 for 12 radioactive sealed sources applicable
to a catheter developed by NOVOSTE designed to inhibit or prevent the
proliferative responses of a vessel or duct to interventional therapy
("Restenosis Therapy").
NOVOSTE and BEBIG intend to work on a number of development, manufacturing,
recycling, and regulatory activities for which certain terms, parameters and
specifications can not yet be fully established.
THE PARTIES wish to describe the general nature of their collaboration, and,
where possible, define certain specific terms and conditions which apply to
the current and planned co-operation.
NOVOSTE and BEBIG now wish to enter into the following
Development and Supply Agreement wherein NOVOSTE and BEBIG agree to work
exclusively with each other to develop and manufacture a radioactive sealed
source for use in Restenosis Therapy.
NOW THEREFORE, based on the foregoing and the mutual promises and other
consideration hereinafter describes, the parties hereto agree as
follows:
2. GENERAL PRINCIPLES
a) BEBIG and NOVOSTE agree to work together beginning immediately and
continuing over the balance of 1994 to develop and refine engineering
and performance specifications, explore U.S. and international
regulatory issues, test early-stage restenosis devices and share test
results. BEBIG shall make available to NOVOSTE its engineering
expertise and manpower in the field of encapsulation of radioactive
materials and the fabrication of sealed sources.
b) Any patentable innovation, improvement, modification or new application
to, of, or for any medical device used to store, transfer, deliver or
provide interventional therapy related to Restenosis
<PAGE>
Therapy ("Restenosis Therapy Device") discovered or invented by BEBIG
during the entire term of this Agreement shall be promptly disclosed to
NOVOSTE and in connection therewith, BEBIG shall grant to NOVOSTE an
exclusive, world-wide fully-paid license to use such inventions or
discoveries.
c) Any patentable innovation, improvement, modification or new application
to, of or for any sealed radioactive source ("Radioactive Component")
discovered or invented by NOVOSTE during the entire term of this Agreement
shall be promptly disclosed to BEBIG and in connection therewith, NOVOSTE
shall grant to BEBIG an exclusive, world-wide fully-paid license to use
such inventions or discoveries for uses other than in the general field of
Restenosis Therapy.
d) BEBIG agrees not to sell, lease, license or otherwise transfer, directly
or indirectly, radioactive sources of like isotope to any other buyer or
party for use in the treatment of restenosis. NOVOSTE in turn agrees not
to purchase, lease, or otherwise acquire directly or indirectly a
radioactive source of like isotope for use in the treatment of restenosis
from any other supplier or party.
3. PROTOTYPE MANUFACTURING
a) BEBIG agrees to manufacture prototype radiation source "trains" with
similar specifications to the Purchase Order referenced above at a base
price of XXXXX each.
b) The base price of XXXXX may be adjusted to accommodate for significant
changes in design specifications, materials costs, labor costs, and
currency exchange rates from the date of execution of this Agreement.
c) To facilitate the design and development of prototypes during the six
month period beginning with execution of this Agreement:
i) BEBIG agrees to make available to NOVOSTE upon request the
professional services of a suitable senior design engineer on an "as
needed" basis up to fifteen (15) hours per week for a fixed cost of
US$16,500.00 to be paid as follows:
. $5,000 on execution of this Agreement
. $5,000 within 90 days of execution
. $6,500 within 180 days of execution
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Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
ii) NOVOSTE agrees to pay for coach air travel and accommodations for
the BEBIG engineer to attend technical review meetings as requested by
NOVOSTE.
d) NOVOSTE agrees to pay direct costs for engineering, materials, or
regulatory testing conducted by independent testing laboratories under
BEBIG direction only when such testing is approved in advance in writing
by NOVOSTE.
e) Upon execution of this Agreement, NOVOSTE will prepare an open purchase
order for fifty (50) prototype radiation source "trains" at a base price
of XXXXX each. Specifications are to be determined as a result of the
ongoing development program, but all sources are to be delivered and
payment completed within the six month period described in Section 3.c
above.
Within one (1) year of execution of this Agreement, NOVOSTE agrees to
purchase and BEBIG agrees to provide a quantity of between fifty (50) and
two hundred (200) radiation source "trains" suitable for human trials at
the base price.
g) NOVOSTE will schedule delivery of shipments at its convenience and agrees
to cover any additional shipping costs associated with staggered
deliveries.
h) BEBIG agrees to accept return shipments of prototype radiation sources
from NOVOSTE and to arrange for the permanent disposal of said material
for a fee not to exceed XXXXX per train plus shipping. NOVOSTE agrees to
return all prototypes it wishes to dispose of in this way by year end
1997.
4. COMMERCIAL MANUFACTURING
a) By approximately year end 1995, NOVOSTE intends to complete the
preliminary phase of its human clinical evaluation. If NOVOSTE chooses to
continue the program based on the success of these trials, then NOVOSTE
agrees to purchase and BEBIG agrees to provide a quantity of between one
hundred (100) and four hundred (400) "trains" suitable for human clinical
trials at base price to be delivered during the following twelve (12) month
period.
b) At the time of the Purchase Order described in Section 4(a) above, the
parties agree to work together in good faith to complete the negotiation of
a more detailed a Supply/Requirement Agreement pursuant to which NOVOSTE
shall fill its commercial requirements for radioactive
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Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
components and BEBIG shall supply NOVOSTE's needs for same on a mutually
exclusive basis.
c) Under the terms of said Supply/Requirement Agreement, BEBIG will provide
commercial grade sources with specifications similar to the prototypes
purchased under the original Purchase Order described in the Recital to
NOVOSTE for the base price of XXXXX per "train" on the understanding
that a volume of 100,000 source "trains" will be purchased during the
first five (5) years of the Supply Agreement.
i. The base price may be adjusted to accommodate significant changes
in design specifications, materials specifications, supply costs,
labor costs and currency exchange rate changes from the date of
execution of this Agreement.
ii. BEBIG agrees provide documented justifications for any
anticipated change in the base price.
d) Should BEBIG be unable to supply a given Purchase Order within ninety
(90) days of any date of promised delivery, NOVOSTE may purchase it's
radioactive components elsewhere until BEBIG can once again provide
required materials. When BEBIG is able to supply the material as
required by NOVOSTE, the parties will resume their exclusive supply and
purchase relation at the next Purchase Order opportunity.
e) NOVOSTE agrees to work with BEBIG in its best efforts to identify, apply
for, maintain and certify all required licenses, approvals and
authorizations.
5. GENERAL PROVISIONS
a) This Agreement is based on the assumption that NOVOSTE shall develop a
disposable restenosis device for one-time use. If the product concept is
changed in such a way that customers return used restenosis devices to
NOVOSTE, NOVOSTE agrees to negotiate in good faith with BEBIG in an attempt
to reach an agreement to reprocess the radioactive components as returned.
b) If NOVOSTE's customers may retain the radioactive components for multiple
uses, then NOVOSTE agrees to negotiate in good faith with BEBIG an
agreement to share a portion of the revenues earned from such reuse.
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Confidential treatment has been requested for portions of this page of this
exhibit. The copy filed herewith omits the information subject to the
confidentiality request. Omissions are designated as "XXXXX". The portions
omitted have been filed separately with the Securities and Exchange Commission
pursuant to such request for confidential information.
<PAGE>
c) This Agreement is based further on the assumption that NOVOSTE develops a
restenosis device for commercial distribution within a reasonable time. It
shall be void if NOVOSTE discontinues its efforts or if no formal FDA
application for the device has been filed by 31 October 1997.
d) The provisions of the Confidentiality Agreement between the parties date 12
August 1994 shall survive the execution and delivery of this Agreement.
e) The laws of the State of Florida shall govern this Agreement. Disputes
arising hereunder shall be submitted for resolution to binding arbitration
in Chicago.
f) NOVOSTE agrees to acknowledge BEBIG as the supplier of the radioactive
component on the packaging of its restenosis device and in related
promotional and product literature as long as NOVOSTE controls the means of
product distribution.
g) The term of the Agreement shall be for a period of six (6) years from the
date of first execution. The Agreement will be automatically extended for
three (3) year periods unless a written cancellation is given by either
party at least two (2) years in advance of a renewal date.
In Witness Whereof, the undersigned have hereunto set their hands as
of the date first above written.
NOVOSTE CORPORATION BEBIG ISOTOPENTECHNIK
By: /s/ Jonathan Jay Rosen By: /s/ Andreas Eckert /s/ Jurgen Ziegler
-------------------------------- --------------------------------------
Name: Jonathan Jay Rosen, Ph.D. Name: Andreas Eckert Jurgen Ziegler
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Title: Vice President, Product Dev. Title:
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