EXHIBIT 10.6.6
EMPLOYMENT AGREEMENT
AGREEMENT made as of the 3rd day of August, 1998, by and between
Sheffield Pharmaceuticals, Inc., a Delaware corporation (the "Corporation"), and
Xxxxxx X. Xxxxx, who currently resides at 0000 Xxxxxxxxx, Xxx Xxxxx, XX 00000
("Employee").
WITNESSETH:
WHEREAS, in July 1998, the Corporation, through a wholly-owned
subsidiary acquired from Aeroquip Corporation certain intellectual property
relating to an aerosol enhancement technology (the ADDS Technology");
WHEREAS, Employee was employed by Aeroquip Corporation in the
development of the ADDS Technology;
WHEREAS, the Corporation desires to employ and retain Employee as
Vice President - Pulmonary Delivery Systems. upon the terms and subject to the
conditions of this Agreement;
and
NOW, THEREFORE, in consideration of the premises and the mutual
covenants hereinafter set forth, the parties hereto agree as follows:
1. Employment of Employee. The Corporation hereby employs Employee
as Vice President - Pulmonary Delivery Systems to perform the duties and
responsibilities incidental to such office, subject at all times to the control
and direction of the Board of Directors of the Corporation.
2. Acceptance of Employment; Time and Attention, Etc. (a) Employee
hereby accepts such employment and agrees that throughout the period of his
employment hereunder, except as hereinafter provided, he will devote his full
business and professional time in utilizing his business and professional
expertise, with proper attention, knowledge and skills faithfully, diligently
and to the best of his ability in furtherance of the business of the Corporation
and its subsidiaries and will perform the duties assigned to his pursuant to
Paragraph 1 hereof. As Vice President - Pulmonary Delivery Systems, Employee
shall also perform such specific duties and shall exercise such specific
authority related to the business and operations of the Corporation and its
subsidiaries as may be reasonably assigned to Employee from time to time by the
Chief Executive Officer or his designee.
(b) Employee shall at all times be subject to, observe and carry out
such rules, regulations, policies, directions and restrictions as the Board of
Directors of the Corporation shall from time to time establish. During the
period of his employment hereunder, Employee shall not, directly or indirectly,
accept employment or compensation from, or perform services of any nature for,
any business enterprise other than the Corporation and its subsidiaries.
Notwithstanding the foregoing in this Paragraph 2, Employee shall not be
precluded from engaging in recreational, educational (including, but not limited
to, teaching or attending educational classes, seminars or other educational
endeavors) and other activities, which activities do not materially interfere
with his duties hereunder and shall occur during vacations, holidays and other
periods outside of business hours.
3. Term. Except as otherwise provided herein, the term of Employee's
employment hereunder shall commence on the date hereof and shall continue to and
including July 31, 2000. Unless terminated earlier in accordance with the terms
hereof, this Agreement shall automatically be extended for one or more
additional consecutive one year terms unless either party notifies the other
party in writing at least 60 days before the end of the then current term
(including the initial term) of its or his desire to terminate this Agreement.
The last day of the term of this Agreement pursuant to this Paragraph 3
(including any early termination pursuant to the terms hereof) is referred to
herein as the "Termination Date."
4. Compensation. (a) As compensation for his services hereunder, the
Corporation shall pay to Employee (i) a base annual salary at the rate of
$120,000, payable in equal installments in accordance with the normal payroll
practices of the Corporation but in no event less frequently than semi-monthly,
and (ii) such bonuses based on performance criteria relating to the development
of the Corporation's pulmonary development program as may he agreed to between
the Employee and the Corporation. All compensation paid to Employee shall be
subject to withholding and other employment taxes imposed by applicable law.
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(b) During the period of Employee's employment hereunder, Employee
shall not be entitled to any additional compensation (other than as to stock
options granted pursuant to this Agreement) for rendering employment services to
subsidiaries of the Corporation or for serving in any office of the Corporation
or any of its subsidiaries to which he is elected or appointed.
5. Stock Options. (a) As additional compensation for his services
hereunder, the Corporation shall grant to Employee an option to acquire a total
of 125,000 shares of Sheffield Pharmaceuticals, Inc. common stock at an exercise
price per share equal to the closing sale price of the Corporation's common
stock as reported by the American Stock Exchange on the date hereof, with the
terms of such option to be evidenced by an option letter agreement in the form
annexed as Exhibit "A" hereto.
(b) On the date that the Corporation receives market approval from
the U.S. Food and Drug Administration (FDA) for its initial product based on the
ADDS Technology (the "Market Approval Date"), the Corporation shall grant to
Employee an option to acquire an additional 40,000 shares of Sheffield
Pharmaceuticals, Inc. common stock, with the terms of such option to be
evidenced by an option letter agreement in the form annexed as Exhibit "A"
containing such modification to such form as are set forth in the following
sentence. Such option shall (i) have an exercise price per share equal to the
closing sale price of the Corporation's common stock as reported by the American
Stock Exchange (or another exchange that constitutes the principal exchange for
the Corporation's common stock) on the Market Approval Date, (ii) be first
exercisable on the first anniversary of the Market Approval Date and (iii)
expire on the fifth anniversary of the Market Approval Date. "ADDS Technology"
means the aerosol enhancing technology purchased by the Corporation from
Aeroquip Corporation.
6. Additional Benefits; Vacation. (a) In addition to such base
salary, Employee shall receive and be entitled to participate, to the extent he
is eligible under the terms and conditions thereof, in any profit sharing,
pension, retirement, hospitalization, disability, medical service, insurance or
other employee benefit plan generally available to employees of the Corporation
that may be in effect from time to time during the period of Employee's
employment hereunder.
(b) Employee shall be entitled to two (2) weeks' paid vacation in
respect of each 12-month period during the term of his employment hereunder,
such vacation to be taken at times mutually agreeable to Employee and the Chief
Executive Officer or his designee.
(c) Employee shall be entitled to recognize as holidays all days
recognized as such by the Corporation.
7. Reimbursement of Expenses. The Corporation shall reimburse
Employee in accordance with applicable policies of the Corporation for all
expenses reasonably incurred by his in connection with the performance of his
duties hereunder and the business of the Corporation, upon the submission to the
Corporation of appropriate receipts or vouchers.
8. Restrictive Covenant. (a) In consideration of the Corporation's
entering into this Agreement, Employee agrees that during the period of his
employment hereunder and, in the event of termination of this Agreement (i) by
the Corporation upon Employee becoming Disabled (as such term is defined in
Paragraph 13), (ii) by the Corporation for Cause (as that term is defined in
Paragraph 13 hereof) or (iii) by Employee otherwise than for Employer Breach (as
that term is defined in Paragraph 14 hereof), for a further period of six (6)
months thereafter, he will not (x) directly or indirectly own, manage, operate,
join, control, participate in, invest in, whether as an officer, director,
employee, partner, investor or otherwise, any business entity that is engaged in
a directly competitive business (as hereinafter defined) to that of the
Corporation or any of its subsidiaries within the United States of America (or
any of its territories or possessions), any country located in the Caribbean,
the United Kingdom, the Republic of Ireland or Italy, (y) for himself or on
behalf of any other person, partnership, corporation or entity, call on any
customer of the Corporation or any of its subsidiaries for the purpose of
soliciting away, diverting or taking away any customer from the Corporation or
its subsidiaries, or (z) solicit any person then engaged as an employee,
representative, agent, independent contractor or otherwise by the Corporation or
any of its subsidiaries, to terminate his or her relationship with the
Corporation or any of its subsidiaries. For purposes of this Agreement, the term
"directly competitive business" shall mean any business that is then involved in
the research, development, manufacturing or commercialization in any way of any
product, compound, device or method that is or becomes a part of the
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Corporation's business or the business of any of its subsidiaries during
Employee's employment by the Corporation or any of its subsidiaries, including
such products, compounds, devices, methods or other intellectual property which
constitute the Predisclosed Technologies (as defined in Paragraph 10 below).
Nothing contained in this Agreement shall be deemed to prohibit Employee from
investing his funds in securities of an issuer if the securities of such issuer
are listed for trading on a national securities exchange or are traded in the
over-the-counter market and Employee's holdings therein represent less than 10%
of the total number of shares or principal amount of the securities of such
issuer outstanding.
(b) Employee acknowledges that the provisions of this Paragraph 8
are reasonable and necessary for the protection of the Corporation, and that
each provision, and the period or periods of time, geographic areas and types
and scope of restrictions on the activities specified herein are, and are
intended to be, divisible. In the event that any provision of this Paragraph 8,
including any sentence, clause or part hereof, shall be deemed contrary to law
or invalid or unenforceable in any respect by a court of competent jurisdiction,
the remaining provisions shall not be affected, but shall, subject to the
discretion of such court, remain in full force and effect.
9. Confidential Information.
(a) Employee shall hold in a fiduciary capacity for the benefit of
the Corporation and its subsidiaries all confidential information, knowledge and
data relating to or concerned with its research, development, information and
projects, as well as its operations, sales, business and affairs, and he shall
not, at any time during his employment hereunder and for two years thereafter,
use, disclose or divulge any such information, knowledge or data to any person,
firm or corporation other than to the Corporation and its subsidiaries or their
respective designees or except as may otherwise be reasonably required or
desirable in connection with the business and affairs of the Corporation and its
subsidiaries.
(b) Notwithstanding anything to the contrary contained herein,
Employee's obligations under Paragraph 9(a) hereof shall not apply to any
information which:
(i) becomes rightfully known to Employee subsequent or prior to his
employment by the Corporation;
(ii) is or becomes available to the public other than as a result of
wrongful disclosure by Employee;
(iii) becomes available to Employee subsequent to his employment by
the Corporation on a confidential basis from a source other than the
Corporation or its agents which source has a right to disclose such
information; or
(iv) results from research and development and/or commercial
operations at any time by or on behalf of any person, company or
other entity with which or with whom Employee shall become
associated (in a manner consistent with the terms of this Agreement)
subsequent to his employment by the Corporation or its agents
totally independent from any disclosure from the Corporation or its
agents.
(c) Notwithstanding anything to the contrary contained herein, in
the event that Employee becomes legally compelled to disclose any confidential
information, Employee will provide the Corporation with prompt notice so that
the Corporation may seek a protective order or other appropriate remedy. In the
event that such protective order or other remedy is not obtained, Employee shall
furnish only such confidential information which is legally required to be
disclosed.
10. Intellectual Property/Assignment. (a) Any idea, invention,
design, written material, manual, system, procedure, improvement, development or
discovery conceived, developed, created or made by Employee alone or with
others, during the period of his employment hereunder and applicable to the
business of the Corporation or any of its subsidiaries, whether or not
patentable or registrable, shall become the sole and exclusive property of the
Corporation or such subsidiary. Employee shall disclose the same promptly and
completely to the Corporation and shall, during the period of his employment
hereunder and at any time and from time to time hereafter at no cost to Employee
(i) execute all documents reasonably requested by the Corporation for vesting in
the Corporation or any of its subsidiaries the entire right, title and interest
in and to the same, (ii) execute all documents reasonably requested by the
Corporation for filing and prosecuting such applications for patents,
trademarks, service marks and/or copyrights the Corporation, in its sole
discretion, may desire to prosecute, and (iii) give the Corporation all
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assistance it reasonably requires, including the giving of testimony in any
suit, action or proceeding, in order to obtain, maintain and protect the
Corporation's right therein and thereto.
(b) The Corporation will consider existing intellectual property developed
collaboratively by Employee, Xx. Xxxxx Xxxxxx and Xx. Xxxxxxx Xxxxxx and
disclosed to the Corporation prior to employment and set forth in Schedule A
hereto, provided such intellectual property is unencumbered (the "Predisclosed
Technologies"). At the Corporation's discretion, the Corporation may choose to
progress, to patent, and to commercialize any such Predisclosed Technology. Such
technology shall be the property of the Corporation. Employee agrees to execute
all necessary assignments to transfer any of the Predisclosed Technologies to
Corporation ownership. In the event that the Corporation commercializes this
technology, Xx. Xxxxx, Xx. Xxxxxx, and Xx. Xxxxxx shall, collectively, be
granted a single royalty of two percent (2%) of the sales or revenue received by
the Corporation for such commercialization and payable for the life of the
applicable patent from the Predisclosed Technologies as a finders fee. The
allocation of the two percent (2%) royalty shall be equally divided amongst
Employee, Xx. Xxxxxx, and Xx. Xxxxxx.
11. Equitable Relief. The parties hereto acknowledge that Employee's
services are unique and that, in the event of a breach or a threatened breach by
Employee of any of his obligations under Paragraphs 8, 9 or 10 this Agreement,
the Corporation shall not have an adequate remedy at law. Accordingly, in the
event of any such breach or threatened breach by Employee, the Corporation shall
be entitled to such equitable and injunctive relief as may be available to
restrain Employee and any business, firm, partnership, individual, corporation
or entity participating in such breach or threatened breach from the violation
of the provisions of Paragraph 8, 9 or 10 hereof. Nothing herein shall be
construed as prohibiting the Corporation from pursuing any other remedies
available at law or in equity for such breach or threatened breach, including
the recovery of damages and the immediate termination of the employment of
Employee hereunder, if and to the extent permitted hereunder.
12. Termination of Agreement; Termination of Employment; Severance;
Survival. (a) This Agreement and Employee's employment hereunder shall terminate
upon the first to occur of the following: (i) Employee becoming Disabled (as
such term is defined in Paragraph 13); (ii) Employee's death; (iii) termination
of Employee's employment by the Corporation for Cause or pursuant to
subparagraph (b) of this Paragraph 12; (iv) termination of Employee's employment
for Employer Breach; and (v) the termination of this Agreement at the end of the
term of this Agreement on the Termination Date pursuant to Paragraph 3.
(b) Notwithstanding anything to the contrary contained in this
Agreement, in the event of the termination of the Employee's employment by the
Corporation for any reason (other than for Cause or by reason of Employee
becoming Disabled), Employee shall be paid a severance payment in an amount
equal to $5,000 multiplied by the number of full months that Employee has been
employed by the Corporation prior to such termination, with such amount not to
exceed $60,000, payable in six equal monthly installments, with the first
installment being payable on the date falling two weeks after the date of such
termination and each additional installment being paid every month after such
date until such severance is paid in full.
(c) Paragraphs 7-12 of this Agreement shall survive the termination
of Employee's employment hereunder, except in the case of termination pursuant
to Paragraph 15. Notwithstanding anything contained in this Agreement to the
contrary, the royalty payable pursuant to Paragraph 10 (b) shall be payable to
Employee regardless of any termination of this Agreement.
13. Disability. In the event that during the term of his employment
by the Corporation Employee shall become Disabled (as that term is hereinafter
defined) he shall continue to receive the full amount of the base salary to
which he was theretofore entitled for a period of six months after he shall be
deemed to have become Disabled (the "First Disability Payment Period"). If the
First Disability Payment Period shall end prior to the Termination Date,
Employee thereafter shall be entitled to receive salary at an annual rate equal
to 80% of his then current base salary for a further period ending on the
earlier of (i) six months thereafter or (ii) the Termination Date (the "Second
Disability Payment Period"). Upon the expiration of the Second Disability
Payment Period, Employee shall not be entitled to receive any further payments
on account of his base salary until he shall cease to be Disabled and shall have
resumed his duties hereunder and provided that the Corporation shall not have
theretofore terminated this Agreement as hereinafter provided. The Corporation
may terminate Employee's employment hereunder at any time after Employee is
Disabled, upon at least 10 days' prior written notice; provided, however, that
such termination shall not relieve the Corporation from its obligation to make
the payments to Employee described above in this Paragraph 13. For the purposes
of this Agreement, Employee shall be deemed to have become Disabled when (x) by
reason of
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physical or mental incapacity, Employee is not able to perform his duties
hereunder for a period of 90 consecutive days or for 120 days in any consecutive
180-day period and (y) Employee's physician or a physician designated by the
Corporation shall have determined that it is unlikely that Employee will be
able, by reason of physical or mental incapacity, to perform a substantial
portion of his duties hereunder for the following 120 days. In the event that
Employee shall dispute any determination of his disability pursuant to clauses
(x) or (y) above, the matter shall be resolved by the determination of three
physicians qualified to practice medicine in the United States of America, one
to be selected by each of the Corporation and Employee and the third to be
selected by the designated physicians. If Employee shall receive benefits under
any disability policy maintained by the Corporation, the Corporation shall be
entitled to deduct the amount equal to the benefits so received from base salary
that it otherwise would have been required to pay to Employee as provided above.
14. Termination for Cause. The Corporation may at any time upon
written notice to Employee terminate Employee's employment for Cause. For
purposes of this Agreement, the following shall constitute Cause: (i) the
willful and repeated failure of Employee to perform any material duties
hereunder or gross negligence of Employee in the performance of such duties, and
if such failure or gross negligence is susceptible to cure by Employee, the
failure to effect such cure within twenty (20) days after written notice of such
failure or gross negligence is given to Employee; (ii) except as permitted
hereunder, unexplained, willful and regular absences of Employee from the
Corporation; (iii) excessive use of alcohol or illegal drugs, interfering with
the performance of Employees duties hereunder; (iv) indictment for a crime of
theft, embezzlement, fraud, misappropriation of funds, other acts of dishonesty
or the violation of any law or ethical rule relating to Employee's employment;
(v) indicted for any other felony or other crime involving moral turpitude by
Employee; or (vi) the breach by Employee of any of the provisions of paragraphs
8, 9 or 10 and if such breach is susceptible of cure by Employee, the failure to
effect such cure within twenty (20) days after written notice of such breach is
given to Employee. For purposes of this Agreement, an action shall be considered
"willful" if it is done intentionally, purposely or knowingly, distinguished
from an act done carelessly, thoughtlessly or inadvertently. In any such event,
Employee shall be entitled to receive his base salary to and including the date
of termination.
15. Termination for Employer Breach. Employee may upon written
notice to the Corporation terminate this Agreement in the event of the breach by
the Corporation of any material provision of this Agreement, and if such breach
is susceptible of cure, the failure to effect such cure within 20 days after
written notice of such breach is given to the Corporation (an "Employer
Breach"). Employee's right to terminate this Agreement under this Paragraph 14
shall be in addition to any other remedies Employee may have under law or
equity.
16. Insurance Policies. The Corporation shall have the right from
time to time to purchase, increase, modify or terminate insurance policies on
the life of Employee for the benefit of the Corporation, in such amounts as the
Corporation shall determine in its sole discretion. In connection therewith,
Employee shall, at such time or times and at such place or places as the
Corporation may reasonably direct, submit himself to such physical examinations
and execute and deliver such documents as the Corporation may reasonably deem
necessary or desirable; provided that such examinations shall be performed by,
and that such documents shall be delivered only to, qualified physicians and/or
medical representatives of licensed insurance companies. At Employee's written
request upon the termination of Employee's employment under this Agreement
(other than for Cause or as result of Employee's death), the Corporation shall
assign to Employee the Corporation's interest in such life insurance policies
(to the extent such policies are so assignable by their terms), whereupon
Employee shall assume all obligations of the Corporation in respect thereof.
17. Entire Agreement; Amendment. This Agreement constitutes the
entire agreement of the parties hereto relating to the subject matter hereof and
any prior agreement between the Corporation and Employee is hereby superseded
and terminated effective immediately and shall be without further force or
effect. No amendment or modification himself shall be valid or binding unless
made in writing and signed by the party against whom enforcement thereof is
sought.
18. Notices. Any notice required, permitted or desired to be given
pursuant to any of the provisions of this Agreement shall be delivered in person
or sent by responsible overnight delivery service or sent by certified mail,
return receipt requested, postage and fees prepaid, if to the Corporation, at
its address set forth above to the attention of the Corporation's Chief
Executive Officer and, if to Employee, at his address set forth above. Either of
the parties hereto may at any time and from time to time change the address to
which notice shall be sent hereunder by notice to the other party given under
this Paragraph 18. Notices shall be deemed effective upon receipt.
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19. No Assignment; Binding Effect. Neither this Agreement, nor the
right to receive any payments hereunder, may be assigned by either party without
the other party's prior written consent. This Agreement shall be binding upon
Employee, his heirs, executors and administrators and upon the Corporation, its
successors and assigns.
20. Waivers. No course of dealing nor any delay on the part of
either party in exercising any rights hereunder shall operate as a waiver of any
such rights. No waiver of any default or breach of this Agreement shall be
deemed a continuing waiver or a waiver of any other breach or default.
21. Governing Law. This Agreement shall be governed by and construed
in accordance with the laws of the State of Delaware, except that body of law
relating to choice of laws.
22. Invalidity. If any clause, paragraph, section or part of this
Agreement shall be held or declared to be void, invalid or illegal, for any
reason, by any court of competent jurisdiction, such provision shall be
ineffective but shall not in any way invalidate or affect any other clause,
paragraph, section or part of this Agreement.
23. Further Assurances. Each of the parties shall execute such
documents and take such other actions as may be reasonably requested by the
other party to carry out the provisions and purposes of this Agreement in
accordance with its terms.
24. Headings. The headings contained in this Agreement have been
inserted for convenience only and shall not affect in any way the meaning or
interpretation of this Agreement.
25. Publicity. The Corporation and Employee agree that they will not
make any press releases or other announcements prior to or at the time of
execution of this Agreement with respect to the terms contemplated hereby,
except as required by applicable law, without the prior approval of the other
party, which approval will not be unreasonably withheld.
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to
be duly executed as of the day and year first above written.
SHEFFIELD PHARMACEUTICALS, INC.
BY: /s/ Xxxx X. Xxxxxxxx
----------------------------
Name: Xxxx X. Xxxxxxxx
Title: Executive VP
/s/ Xxxxxx X. Xxxxx
----------------------------------
Xxxxxx X. Xxxxx
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Schedule A to
Employment Agreement
Intellectual Property
7
INVENTION DESCRIPTION
METHOD AND APPARATUS FOR PRECISELY METERING
AND GENERATING DRY POWDER AEROSOLS
HISTORY:
Xxxxxx Xxxxxxxxxxx (Univ. of Michigan), Xxxxxxx Xxxxxx, Xxxxx
Xxxxxx, June 1997 - request for proposal describes apparatus
metering and actuation method.
Xxxxx Xxxxxx, Xxxxxxx Xxxxxx, Xxxx Xxx, Xxx Xxxxxx, Xxx Xxxxx,
September 1997 - aerosol generation and actuation method.
Xxx Xxxxx, Xxxxx Xxxxxx, December 1997 - method for deposition of
precisely metered powders.
Xxx Xxxx (Wood, Herron & Xxxxx) and Xxx Xxxxx - May 1998,
prosecution strategy.
DESCRIPTION:
This invention teaches a method to precisely meter unit-doses of a
dry, powdered compound and to disperse it as an aerosol into an air stream. It
also describes the apparatus and a method to load powdered doses into the
apparatus.
Unit doses are defined as individual powder caches, precisely measured to
contain a specific amount of the powder compound. The amount can range from 5
micrograms up to 500 milligrams. The dose precision ranges from 1 microgram for
the smallest dose size, to 50 micrograms for the largest dose size.
The dry powder is composed of finely disperse compound(s) with median diameters
ranging from 0.5 micron to 20 microns. The powder is loaded into precisely
partitioned cells on a substrate by electrostatic deposition (such as the
commercial system from Delsys). Each cell in the partitioned zones constitutes a
unit dose. The cells are separated from each other by a finite distance or a
physical barrier to avoid overlap and intermixing. For example the partitioned
cells can be an array of cylindrical, rhombohedral, tetrahedral or pyramidal
mounds or bumps. Alternatively they can be rectangular or circular, octagonal,
hexagonal or other polygonal-perimeter walled-cells. The substrate can be a flat
surface or it can be preformed into shallow-walled lattice. The volume of the
partitions and deposit density control the mass of powder in each partition. The
deposit packing density is sufficiently low to minimize irreversible
agglomeration of the powder particles, but high enough to minimize settling.
Ideally the packing density corresponds to a level just at the threshold of the
critical packing fraction characteristic of the powder shape and size
distribution.
One (1) to several thousand cells could be formed on the substrate. The
substrate can be formed into three-dimensional shapes. For example it could be
cylindrical with the cells on the internal surface or on the external surface.
The substrate can be polymer, metallic or compose of silicon, alumina or other
ceramic material. The cells can be etched, pressed, stamped or machined
(optically or mechanically) into the surface. In certain embodiment it may be
desirable to render the substrate porous so that air may flow, under the
influence of an applied pressure gradient, through the cell to aid in evacuating
the deposited powder.
After deposition the cells are sealed with a thin foil of plastic and/or metal.
The foil can be applied by lamination, vapor deposition, gas phase
polymerization or by spraying. The foil serves to protect the powder deposit
from spilling, contamination, and mechanical or environmental disruption due to
the effects of handling, humidity, temperature and exposure to uncontrolled
environments. In preferred embodiments a polymer foil, coated with a vapor
deposited metal can practically package the powder cell array for up to several
years of storage.
Thus the above description discloses a method to precisely meter, package and
store unit doses of powdered compound(s). The method of aerosol actuation and
generation is next described.
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The partitioned cells and foil covering incorporate features which allow each
partition to be individually opened. For example the foil can be embossed with a
grid of conductors such as aluminum, graphite, nichrome. Alternatively the grid
can be incorporated into the shallow-walled partitions, or into the surface of
the substrate. The grid pattern is correspondent to the perimeters or a portion
or the perimeters of the cells. Electrical current passed selectively through
the grid on the partition perimeters heats sufficiently to melt or degrade the
foil to that the covering disintegrates, melts, or otherwise fails mechanically
to rupture the cell cover. The heating is sufficiently localized to avoid
degradation of the physical, chemical or biological properties of the powder
inside the cell. Simultaneously, a force field is applied to the deposit so that
as the cell ruptures the powder is ejected into the media above the substrate.
This force field can be: an electrostatic field, a mechanical force such as
vibrations from an electromechanical or an acoustic generator, or a convective
gradient such as a fluid flowing through the cell or tangentially above the
cell. The force field is sufficient to disperse the powder into the media
adjacent to the substrate. Thus each cell can individually ruptured and the
contents discharged into the media. The medium into which the cells are
discharged is typically gaseous, but it could be vapor or liquid state fluid.
Multiple partitions could be discharged simultaneously or in a specific
combinatorial sequence. Different compounds can be deposited into different
cells in the same array and discharged in a specific sequence or combination.
ADVANTAGES:
Existing dry powder dispersing technology relies either on a propellant or a
carrier powder to disperse the target compound into a carrier media. The
described invention eliminates the need for the propellant by using
electromechanical or other fluid propulsion mechanisms. This can increase the
precision and consistency of dispersion, while reducing cost, size and
complexity of the dispersing device.
The elimination of the powder carrier increases the dispersion efficiency and
affords more precise control of dose metering and particle size distribution. It
can also eliminate the presence of unnecessary species in the dispersed aerosol.
The partitioning and deposition method provides a highly accurate, pre-metering
system to generate precise dose sizes. It eliminates problems with typical unit
dose packages (e.g. blister packages or capsules) such as retention of powder in
the package, while providing the same packaging and storage stability. The
multiplicity of cells provides the equivalent to a reservoir of powder, but
provides an accuracy of measurement not available in existing reservoir devices.
The ability to discharge cells in specific sequences and combinations enables
the ability to customize dosing quantity and composition, while using a single
apparatus or powder supply.
Because the production of the substrate and filling with powder is comparable to
existing blister or capsule packaging, there should be no cost penalty.
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INVENTION DESCRIPTION
METHOD AND APPARATUS FOR USING POROUS PLASTICS TO DISPERSE
AND DISPENSE DRUGS FOR INHALATION
HISTORY:
Disclosed 2/27/98: Xxxxxx Xxxxx, Xxxxxxx Xxxxxx
DESCRIPTION:
Porous material used to control airflow through a conduit thus creating a
laminar flow across the cross sectional area of a conduit. Due to the nature of
the porous material, it can be molded and machined into numerous shapes allowing
for various air flow boundary conditions, i.e. pipes, baffles, frits, plugs,
etc. Depending on the shape of the material, the air flow boundary, created by
the air moving through the pores, can be used to inhibit deposition on the inner
surfaces of a medical device such as a metered dose inhaler (MDI), dry powder
inhaler (DPI), nebulizer, etc. The airflow through the material can also be used
to displace the momentum of an aerosol burst, such as the bolus of an MDI, to
promote dispersion and/or evaporation.
Description of Material:
Porous plastic consisting of various polymers with a range of pore diameters:
o High-density polyethylene (HDPE)
Pore size: 35 - 250um
o Ultra high molecular weight Polyethylene (UHMW)
Pore size: 7 - 40um
o Polypropylene (PP)
Pore size: 125 - 350um
o Polyvinylidene fluoride (PVDF)
Pore size: 25um average size
o Polytetrafluoroethylene (PTFE)
Pore size: 25um average size
o Nylon 6 (N6)
Pore size: 200um average size
o Polyethersulfone (PES)
Pore size: 100um average size
ADVANTAGES:
o Dispersion of air flow
o Material creates a boundary of air flow extending from material surface
thus allowing counteraction of opposing flows
o Molded plastics shapes
o Chemical resistant
o Machinable
o Low cost
o Various pore sizes for controlled air flow
o Minimizes drug deposition due to surface characteristics
10
OTHER APPLICATIONS:
Impregnation of a suitable geometrical shape of the porous plastic with a dry
powder drug, such as albuterol. Impregnated plastic is then loaded into a device
for dispensing of the drug. Once air is pushed or pulled through the porous
plastic the entrapped drug would be carried out by the air flow. Due to the
nature of the porous plastic, the drug dose will dispense as a function of the
porosity, air flow, time of inhalation, and bulk of the material. The most
practical design of this dispensing method would be for single use dosage with a
disposable device. The design embodiment would be that of a pack of cigarettes
in which each single use device is sealed until the desired time of need. This
would be ideal for third world applications (low cost) and for conditions with
high humidity since the devices would be sealed until used.
11
INVENTION DESCRIPTION
A METHOD TO GENERATE DROPLETS OF PRECISE SIZE AND PRECISE EJECTION
VELOCITY
HISTORY:
Xxxxx Xxxxxx, Xxx Xxxxx, Xxxx Xxxxxx, Xxxxxxx Xxxxxxxxx, March 1997- discussion
of potential application for acoustic radiation pressure.
Xxxxx Xxxxxx, Xxx Xxxxx, Xxxx Xxxxxx, Xxxxxxx Xxxxxxxxx and Xxx Xxxxxxxx (NASA
Xxxxx Research Center), June 1997 - Discussion of experimental design and
protocols to generate droplets of insulin.
DESCRIPTION:
This is a disclosure of a method to generate droplets of precise size and
precise ejection velocity.
This invention teaches a method to generate precisely uniform size of droplets
at a controlled velocity. The method uses acoustic radiation pressure to
generate droplets for any liquid medicament. The generator consists of an
acoustic transducer that emits a focused tone burst from below a pool of liquid
directed at the pools' surface. The burst causes the surface to erupt and form a
droplet, which is ejected with an initial velocity. The droplet size can vary
over a wide range, since the generator is nozzleless and is not bound strictly
to a fixed nozzle diameter. The droplet size can be controlled, since it is
proportional to the acoustic wavelength, thus, varying the input frequency
varies the droplet size inversely. The droplet size produced can range from 1um
to 50um. For finer droplet size, multiple transducer may be used. The acoustic
radiation pressure droplet generator can create droplets from liquid solution as
well as from liquid suspension systems without clogging since the generator is
nozzleless. In addition, the particles in the suspension system would cross the
ejection point and would either get ejected along with the liquid or swept a way
from the ejection point, thus creating a self cleaning system.
The droplet generator consists of a piezoelectric transducer mounted on the end
of a buffer rod (sapphire). A spherical focusing lens is positioned at the
opposite end of the rod. The lens of the device is submerged below the surface
of a liquid pool. The transducer generates a high frequency acoustic tone burst
which propagates down the length of the sapphire rod. When it reaches the
opposing end, the acoustic waves encounter a spherical focusing lens that
transmits the acoustic energy into the liquid pool. The lens causes the acoustic
waves to be focused at a small point at the pool surface. The device relies on
the acoustic pressure to propel droplets from a small pool of liquid. The
pressure is greatest in the beam's focal region, particularly, at the pool
surface where the wave reflection occurs. The pressure acts to lift a small
column of liquid which appears initially as a small mound. When enough energy is
applied to overcome the liquid surface tension, the mound becomes a momentary
liquid fountain where each short tone burst emits a single droplet. As one
increases the energy level, the droplets begin to form tails, which then break
off into satellite droplets. Further increases in the energy causes the process
to transition to a continuous fountain.
ADVANTAGES:
The advantages of the acoustic pressure droplet generator:
1. It produces uniform droplet size distribution,
2. It produces a wide range of droplet size,
3. It can control the ejection velocity of the droplets,
4. It can atomize liquid as well as suspension systems,
5. It can atomize polypeptides and proteins without any molecular chains
denaturation,
6. It does not clog, self cleaning system
12
EXHIBIT A TO
EMPLOYMENT AGREEMENT
SHEFFIELD PHARMACEUTICALS, INC.
000 XXXXXXXXX XXXX
XX. XXXXX, XXXXXXXX 00000-0000
--------------, 1998
To: [Insert Name & Address
of Employee]
At a meeting of the Compensation Committee of the Board of Directors
of Sheffield Pharmaceuticals, Inc. (the "Company") held on July 15, 1998, the
Company authorized the grant to you of an option (the "Option") to purchase
_____________________ (___,000) shares (the "Shares") of Common Stock, par value
$.01 per share, of the Company. The Option is being granted in connection with
your employment by the Company.
Except as provided below, the option may be exercised at anytime and
from time after ________________, 199__ and on or prior to _______________,
200__ (on which date the Option will, to the extent not previously exercised,
expire).(1) The purchase price per Share payable by you is $______.(2)
Unless at the time of the exercise of the Option a registration statement under
the Securities Act of 1933, as amended (the "Act") , is in effect as to the
Shares, any Shares purchased by you upon the exercise of the Option shall be
acquired for investment and not for sale or distribution, and if the Company so
requests, upon any exercise of the Option, in whole or in part, you will execute
and deliver to the Company a certificate to such effect. The Company shall not
be obligated to issue any Shares pursuant to the Option if, in the opinion of
counsel to the Company, the Shares to be so issued are required to be registered
or otherwise qualified under the Act or under any other applicable statute,
regulation or ordinance affecting the sale of securities, unless and until such
Shares have been so registered or otherwise qualified.
You understand and acknowledge that, under existing law, unless at
the time of the exercise of the Option a registration statement under the Act is
in effect as to such Shares (i) any Shares purchased by you upon exercise of
this option may be required to be held indefinitely unless such Shares are
subsequently registered under the Act or an exemption from such registration is
available; (ii) any sales of such Shares made in reliance upon Rule 144
promulgated under the Act may be made only in accordance with the terms and
conditions of that Rule (which, under certain circumstances, restrict the number
of shares which may he sold and the manner in which shares may
----------
(1) The first date for exercise shall be the date six months after the
issuance date of the Option and the last date for exercise shall be
the fifth anniversary of such issuance date.
(2) Purchase price shall he the closing price of the Company's common
stock on the American Stock Exchange as of the date of commencement of
employment.
13
be sold); (iii) in the case of securities to which Rule 144 is not applicable,
compliance with Regulation A promulgated under the Act or some other disclosure
exemption will be required; (iv) certificates for Shares to be issued to you
hereunder shall bear a legend to the effect that the Shares have not been
registered under the Act and that the Shares may not be sold, hypothecated or
otherwise transferred in the absence of an effective registration statement
under the Act relating thereto or an opinion of counsel satisfactory to the
Company that such registration is not required; and (v) the Company will place
an appropriate "stop transfer" order with its transfer agent with respect to
such Shares. In addition, you understand and-acknowledge that the Company has no
obligation to you to furnish information necessary to enable you to make sales
under Rule 144.
In the event that the Company shall at any time prior to the
expiration of the Option and prior to the exercise thereof: (i) declare or pay
to the holders of the Common Stock a dividend payable in any kind of shares of
stock of the Company; or (ii) change or divide or otherwise reclassify its
Common Stock into the same or a different number of shares with or without par
value, or into shares of any class or classes; or (iii) consolidate or merge
with, or transfer its property as an entirety or substantially all of its assets
to any other corporation; or (iv) make any distribution of its assets to holders
of its Common Stock as a liquidation, or partial liquidation dividend or by way
of return of capital; then, upon the subsequent exercise of the Option, the
purchase price of the Shares issuable upon the exercise hereof shall be
appropriately adjusted by the Board of Directors of the Company so that you
shall receive for the exercise price, in addition to or in substitution for the
Shares to which you would be entitled upon such exercise, such additional shares
of stock of the Company, or such reclassified shares of stock of the Company, or
such securities or property of the Company resulting from such consolidation or
merger or transfer, of such assets of the Company, which you would have been
entitled to receive had you exercised the Option prior to the happening of any
of the foregoing events.
In the event that your employment by the Company is terminated for
cause, then the Option shall be immediately canceled upon such termination of
employment and you shall have no further rights with respect to the Option. In
the event that your employment by the Company is terminated for reasons other
than for cause, then you may, during the ninety (90) day period following the
date you cease to be employed by the Company, exercise the Option to the extent
that you were entitled to exercise it at the date of such termination. To the
extent that you were not entitled to exercise the Option at the date of such
termination, or if you do not exercise the Option (to the extent you are
entitled to exercise) within the time specified in this paragraph, the Option
shall terminate.
The Option (or installment thereof) is to be exercised by delivering
to the Company a written notice of exercise in the form attached hereto as Annex
A, specifying the number of Shares to be purchased, together with payment of the
purchase price of the Shares to be purchased. The purchase price is to be paid
in cash.
The Option does not confer upon any right whatsoever as a
stockholder of the Company. Your right to exercise the Option shall not
terminate as a result of the termination of your employment by the Company.
The Option shall be binding upon any successors or assigns of the
Company.
If the foregoing correctly sets forth our understanding, please
indicate your acceptance by signing this letter in the space provided below.
Very truly yours,
SHEFFIELD PHARMACEUTICALS, INC.
BY:
------------------------------
Name:
Title:
AGREED TO AND ACCEPTED:
-------------------------------
[Name of Employee]
14
Exhibit A
STOCK SUBSCRIPTION FORM
To: Sheffield Pharmaceuticals, Inc.
Gentlemen:
I hereby exercise my option to purchase from Sheffield
Pharmaceuticals, Inc. (the "Company"), pursuant to the Stock Option Letter
Agreement between us dated as of _____________, 1998, ______________ shares of
the Company's Common Stock, $.01 par value, and herewith tender payment therefor
at the rate of $_____ per share.
I represent and warrant that I am acquiring the said shares for my
own account for investment purposes only; that I have no present intention of
selling or otherwise disposing of such shares or any part thereof; that I will
not transfer said shares in violation of the securities laws of the United
States; that I am familiar with the business operations, management and
financial condition and affairs of the Company; that I have not relied upon any
representation of the Company with respect thereto; and that I have the personal
financial means to comply with all of said representations. I further confirm
that I have been advised that said shares will not be registered under the
Securities Act of 1933, as amended, and that I have consulted with and been
advised by counsel as to the restrictions on resale to which said shares will
thereby be subject.
The form in which I wish my name and address to appear on the
Company stock records is as follows:
Name:
---------------------------------------
Address:
--------------------------------------------
--------------------------------------------
--------------------------------------------
Very truly yours,
--------------------------------
[Name of Employee]
15
