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Patent 2573892 Summary

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(12) Patent Application: (11) CA 2573892
(54) English Title: IMPLANTABLE DEVICE HAVING RESERVOIR WITH CONTROLLED RELEASE OF MEDICATION AND METHOD OF MANUFACTURING THE SAME
(54) French Title: DISPOSITIF IMPLANTABLE COMPRENANT UN RESERVOIR A LIBERATION COMMANDEE DE MEDICAMENT ET PROCEDE DE FABRICATION DE CELUI-CI
Status: Dead
Bibliographic Data
(51) International Patent Classification (IPC):
  • A61K 9/22 (2006.01)
(72) Inventors :
  • PRESCOTT, ANTHONY D. (United States of America)
(73) Owners :
  • CLARITY CORPORATION (United States of America)
(71) Applicants :
  • CLARITY CORPORATION (United States of America)
(74) Agent: SMART & BIGGAR
(74) Associate agent:
(45) Issued:
(86) PCT Filing Date: 2005-07-21
(87) Open to Public Inspection: 2006-02-09
Examination requested: 2010-06-11
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2005/025998
(87) International Publication Number: WO2006/014793
(85) National Entry: 2007-01-15

(30) Application Priority Data:
Application No. Country/Territory Date
10/899,416 United States of America 2004-07-26
10/899,417 United States of America 2004-07-26

Abstracts

English Abstract




An implantable device (10) includes a body (12) defining a reservoir (14), and
a head (24) provided at an end of the body (12) and closing the reservoir. The
body (12) is made from a material impermeable to the medication while the head
(24) is made from a permeable material adapted to release the medication from
the reservoir to an implant site at a determinable rate. In one manufacture,
the body (12) of the device is molded and includes a hole at a tip end; the
head (24) is molded onto the body (12); the medication is injected into the
device through the tip end hole; and the tip end is sealed. The portion of the
device at which the medication is released is precisely fabricated in order to
control release of the medication, and the reservoir is filled and then closed
away from the area of medication permeability.


French Abstract

L'invention concerne un dispositif implantable (10) comprenant un corps (12) définissant un réservoir (14) et une tête (24) placée au niveau d'une extrémité du corps (12) et fermant le réservoir. Le corps (12) est conçu dans un matériau imperméable au médicament alors que la tête (24) est conçue dans un matériau perméable conçu pour libérer le médicament du réservoir dans un site d'implant à une vitesse pouvant être déterminée. Selon une fabrication, le corps (12) du dispositif est moulé et comprend un trou au niveau d'une extrémité en pointe; la tête (24) est moulée sur le corps (12); le médicament est injecté dans le dispositif par le biais du trou de l'extrémité en pointe; et l'extrémité en pointe est scellée. La partie du dispositif au niveau de laquelle le médicament est libéré est fabriquée de manière précise afin de commander la libération du médicament et le réservoir est rempli, puis fermé à distance de la zone de perméabilité au médicament.

Claims

Note: Claims are shown in the official language in which they were submitted.




9


What is claimed is:


1. An implantable device for insertion into a mammal and for storing and
releasing a
medication, comprising:
a) a body portion made of a first material having a first permeability
relative to the medication
and defining a reservoir for said medication,
b) said medication in said reservoir; and
c) a non-porous head portion enclosing said reservoir and made of a second
material having a
second relatively greater permeability to said medication.

2. A device according to claim 1, wherein:
said first permeability is substantially impermeability.
3. A device according to claim 1, further comprising:
d) a stopper element,
wherein said body portion defines a hole at a location spaced apart from said
head
portion, and said stopper element is provided in said hole.

4. A device according to claim 1, wherein:
said head portion does not include said first material.
5. A device according to claim 1, wherein:
said first and second materials are silicones.
6. A device according to claim 1, wherein:
said body portion is self-anchoring.
7. A device according to claim 1, wherein:
said device is a lacrimal insert sized for insertion into a portion of the
lacrimal
canaliculus of an eye.




8. An implantable device for insertion into a mammal and for storing and
releasing a
medication, comprising:
a) a first portion made of a first material having a first permeability
relative to the medication,
said first portion defining a head, a neck, a body and an internal space;
b) a tip portion coupled to first portion at an end opposite said head of said
first portion, said
tip portion enclosing said internal space so as to define a reservoir and made
of a second
material having a second relatively greater permeability to said medication;
and
c) a medication provided within said reservoir,
wherein said insert is sized for insertion into the lacrimal punctum.
9. A device according to claim 8, wherein:
said first permeability is substantially impermeability.
10. A device according to claim 9, further comprising:
d) a seal element,
wherein said body portion defines a hole at a location spaced apart from said
tip portion,
and said seal element is provided in said hole.

11. A device according to claim 8, wherein:
said first and second materials are silicones.
12. A device according to claim 8, wherein:
said body portion is self-anchoring.
13. A device according to claim 8, wherein:
said device is a lacrimal insert sized for insertion into a portion of the
lacrimal
canaliculus of an eye.

14. A method of manufacturing an implantable device for insertion into a
mammal and for
storing and releasing a medication, comprising:
a) molding an insert having an internal medication-storing reservoir, and
having portions
which are relatively permeable and impermeable to the medication; and



11


b) injecting the medication into the reservoir at a location spaced apart from
the permeable
portion.

15. A method according to claim 14, further comprising:
sealing the insert at the location at which the medication is injected.
16. A method according to claim 14, wherein:
said molding includes molding the insert from two different silicones, one of
which is
permeable to the medication and the other of which is relatively impermeable
to the
medication.

17. A method according to claim 14, wherein:
said molding includes molding the insert to a size for insertion into a
portion of the
lacrimal canaliculus of an eye.

18. A method of manufacturing an implantable device for insertion into a
mammal and for
storing and releasing a medication, comprising:
a) providing a body of the device, the body having neck and tip ends, and
defining an internal
space which is open at both the neck and tip ends, the body including
structure to anchor the
device within an opening of the mammal, the body being made from a first
material;
b) providing a head of the device onto the neck end of the body to partially
enclose the
internal space and define a reservoir, the head being made from a second
material;
c) injecting medication into the reservoir of the device through the tip end
of the body; and
d) sealing the tip end of the body closed,
wherein the first material is relatively impermeable to the medication and the
second
material is relatively permeable to the medication so as to release the
medication through the
head of the device at a determinable rate.

19. A method according to claim 18, wherein:
said providing the head of the device onto the neck end of the body includes
molding
the head of the insert onto the neck end of the body.



12


20. A method according to claim 18, wherein:
said first and second materials are different silicones.
21. A method according to claim 18, wherein:
said sealing includes providing a stopper element in the open tip end.
22. A method according to claim 18, wherein:
said providing a body of the device includes providing a body sized for
insertion into a
portion of the lacrimal canaliculus of an eye.

23. A method of manufacturing an implantable device for insertion into a
mammal and for
storing and releasing a medication, comprising:
a) providing a body of the device, the body having head, neck and open end,
and defining an
internal space and an opening in the head, the body made from a first
material;
b) providing a tip of the device onto the open end of the body to partially
enclose the internal
space and define a reservoir, the tip made from a second material, wherein one
of the body and
tip include structure to anchor the device within an opening of the mammal;
c) injecting medication into the reservoir of the device through the opening
in the head of the
body; and
d) sealing the opening in the head of the body closed,
wherein the first material is relatively impermeable to the medication and the
second
material is relatively permeable to the medication so as to release the
medication through the
head of the device at a determinable rate.

24. A method according to claim 23, wherein:
said providing the tip of the device onto the open end of the body includes
molding the
tip of the device onto the open end of the body.

25. A method according to claim 23, wherein:
said first and second materials are different silicones.



13


26. A method according to claim 23, wherein:
said sealing includes providing a stopper element in the opening in the head.
27. A method according to claim 23, wherein:
said providing a body of the device includes providing a body sized for
insertion into a
portion of the lacrimal canaliculus of an eye.

28. A method of administering medication to a mammal, comprising:
a) providing an implantable container including a body comprised of a first
material, the body
defining a reservoir with a medication provided therein, and a medication
release portion
comprised of a second material and coupled to the body to close the reservoir,
wherein the first
material is relatively impermeable to the medication and the second material
is more permeable
than the first material to the medication, and
b) implanting the device at least partially within an opening in the mammal so
as to release the
medication through the medication release portion of the container at a
determinable rate

29. A method according to claim 28, wherein:
said implanting includes implanting the device at least partially within a
naturally
occurring opening in the mammal.

30. A method according to claim 28, wherein:
said implantable container is sized for insertion into a portion of the
lacrimal canaliculus
of an eye.

Description

Note: Descriptions are shown in the official language in which they were submitted.



CA 02573892 2007-01-15
WO 2006/014793 PCT/US2005/025998
IMPLANTABLE DEVICE HAVING RESERVOIR WITH
CONTROLLED RELEASE OF MEDICATION
AND METHOD OF MANUFACTURING THE SAME
BACKGROUND OF THE INVENTION

1. Field of the Invention
This invention relates broadly to medical devices. More particularly, this
invention
relates to medical device adapted to store and release medication.

2. State of the Art
In order to treat various conditions, drugs are administered to the eye. The
most
common form of drug delivery is by topical application to the eye's surface,
e.g., by drops. The
eye is uniquely suited to surface administration because drugs can penetrate
through the cornea,
rise to therapeutic concentration levels inside the eye, and exert their
beneficial effects. In fact,
ninety five percent of drugs delivered to the eye are currently administered
through eye drops.
Rarely are drugs for the eye administered orally or by injection, either
because they reach the
eye in too low a concentration to have the desired pharmacological effect, or
because their use
is complicated by significant systemic side effects.

Topical eye drops, though effective, are inefficient. When an eye drop is
instilled in the
eye, it overfills the conjunctival sac, the pocket between the eye and the
lids, causing a
substantial portion of the drop to be lost due to overflow of the lid margin
onto the cheek. In
addition, a substantial portion of the drop remaining on the ocular surface is
washed away into
the nasolacrimal duct, thereby diluting the concentration of the drug. Not
only is this portion of
the drug dose lost before it can cross the cornea, but this excess drug may be
undesirably
carried into the nose and throat where it is absorbed into the local or
general circulation,
sometimes leading to serious systemic side effects. The small portion of the
drug in the eye
drop which does penetrate the cornea results in an initial peak tissue
concentration, a higher
level than is required for the initial pharmacological effect. The tissue
concentration then
gradually decreases, such that by the time the next eye drop is due, the
tissue concentration and
the intended pharmacological effect may be too low.


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2

To compound the problems described above, patients often do not use their eye
drops as
prescribed. Often, this poor compliance is due to an initial stinging or
burning sensation caused
by the eye drop. Certainly, instilling eye drops in one's own eye can be
difficult, in part
because of the normal reflex to protect the eye. Therefore, sometimes one or
more drops miss
the eye. Older patients may have additional problems instilling drops due to
arthritis,
unsteadiness, and decreased vision, and pediatric and psychiatric patient
populations pose
difficulties as well.

As a result of the above problems, there have been efforts to use a punctum
plug in a
manner which optimizes topical administration to take advantage of the
benefits of topical
administration but overcomes its drawbacks. U.S. Pat. No. 3,949,750 to Freeman
describes a
punctum plug manufactured of a porous material which stores and slowly
dispenses an
ophthalmic medication to the eye. The Freeman plug overcomes many of the
negative of
topical administration, as a large proportion of the slowly dispensed
medication is subject to a
level rate of uptake at the eye without overflow of the conjunctival sac. If
there is any
drawback to the Freeman plug, it is that the dose of medication which can be
stored in a solid
porous plug is relatively small.

U.S. Pat. No. 6,196,993 to Cohan et al. describes a punctum plug having a
reservoir
within the body of the plug adapted for storing a larger quantity of
medication, and a collarette
having a pore in communication with the reservoir. The reservoir has a closed
lower end and
an upper portion open to the pore. The medication stored in the reservoir is
released through
the pore to the surface of the eye over time, with pore size adapted to
control release rate of the
medication. In one embodiment, a medication-permeable material is provided
over the pore.
The plug itself is shown manufactured in the patent in one piece from silicone
or another
material that is impermeable to the medication. However, with the reservoir
being larger than
the upper pore, the Cohan device cannot be manufactured as a one-piece plug.
In fact, early
versions of the Cohan device were manufactured with the collarette being glued
or otherwise
fused to a neck portion of the plug and the medication then inserted into the
reservoir through
the pore. This construction has serious drawbacks. Drug release or
permeability is affected by
locating the gluing site of the collarette to the body adjacent the pore site,
as the pore may
become clogged with glue or otherwise impede movement of the medication so as
to affect


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3

drug release. In addition, if the permeable membrane is desired to be used
over the pore, it
must be placed over the collarette after filling the reservoir through the
pore, which creates
difficulties in product handling as the placement of such membrane may cause
inadvertent
premature release of medication during handling. Furthermore, any adhesive
used to attach the
permeable membrane to the collarette may affect the release rate of medication
during
implantation.

SUMMARY OF THE INVENTION

It is therefore an object of the invention to provide an ophthalmological
device for
lacrimal insertion which includes a reservoir for a medication, which is
adapted to release the
medication over a period of time, and which is relatively easy to manufacture.

In accord with these objects, which will be discussed in detail below, a
lacrimal insert is
provided with a reservoir for storing a medication, such as a glaucoma,
antimicrobial, anti-
inflammatory, dry-eye syndrome medication and which, for purposes herein,
shall also include
a therapeutic such as a mydriatic or a cycloplegic. In one embodiment, the
lacrimal insert is a
punctum plug comprising a body having a neck end, a tip end and a centrally
defined reservoir,
and a head provided at the neck end of the body and enclosing the reservoir.
The body is made
from a first material which is substantially impermeable to the medication
while the head is
made from a second material which is permeable to the medication and adapted
to release the
medication from the reservoir to the eye at a determinable rate.

In accord with a preferred method of manufacturing the lacrimal insert of the
invention,
in a first step, the body is molded from the first material to define the
reservoir. The internal
space defining the reservoir is molded open at both the neck and tip ends. In
a second step, the
head is molded from the second material onto the neck end of the body. In a
third step, the
medication is injected into the reservoir of the plug through the tip end
opening of the body. In
a fourth step, the open tip end of the body is provided with a cork-like seal
to close the
reservoir. Thus, in accord with the invention, the reservoir is sealed at a
location away from the
area of medication permeability.


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In accord with another embodiment of manufacture, where a self-healing
material is
used to mold the body, the body is molded with an internal space open only at
the neck end.
The head is then attached to the body prior to filing with medication.
Thereafter, a needle is
punctured through the body to inject the medication and then withdrawn, with
the body self-
healing to retain the medication.

In accord with yet another embodiment of the invention, a lacrimal insert
design is
provided which is adapted to release medication into the lacrimal duct, e.g.,
sinus or throat
medications as opposed to at the ocular surface. The body is molded of a first
relatively
impermeable material with head, neck and a flared portions. The head portion
defines an
opening for injecting a medication. A tip molded of a second relatively more
permeable
material is then provided at the end of the flared portion. Medication is
injected into the body
to fill a reservoir defined between the body and tip, and a seal is then
provided in the opening in
the head portion to close the reservoir.

In accord with all embodiments of the invention, the first and second
materials are
preferably two types of silicone, one relatively impermeable to the
medication, and the other
having a suitable rate of permeability for the medication.

It will be appreciated that in accord with the invention, the portion of the
insert at which
the medication is released is precisely fabricated in order to control release
of the medication,
and the reservoir is filled and then closed away from the area of
permeability.

Additional objects and advantages of the invention will become apparent to
those
skilled in the art upon reference to the detailed description taken in
conjunction with the
provided figures.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic section view of a punctum plug according to a first
embodiment of
the invention;


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Figs. 2 through 5 illustrate a method of manufacturing the punctum plug of
Fig. 1;
Figs. 6 and 7 illustrate a method of manufacturing a second embodiment of a
punctum
plug according to the invention;

Figs. 8 through 10 illustrate a method of manufacturing a third embodiment of
a
punctum plug according to the invention; and

Fig. 11 is a schematic section view of a monocanalicular insert according to
another
embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Turning now to Fig. 1, a first embodiment of a lacrimal insert in the shape of
a punctum
plug 10 for' insertion into a lacrimal puncta is shown. The punctum plug 10
includes a body 12
defining a reservoir 14, a neck portion 16, a flared portion 18, and a tapered
portion 20
terminating in a tip 22. A non-porous head 24 is provided over the neck
portion 16 of the body
12 and encloses the reservoir. A medication 26 is provided in the reservoir.
In accord with one
aspect of the invention, the body 12 and head 24 are made of different
materials, with the body
12 being made from a biocompatible, preferably soft and flexible first
material which is
relatively impermeable to the medication, and the head 24 being made from a
biocompatible,
preferably soft and flexible second material which is permeable to the
medication. Most
preferably, both materials are silicones. Such silicones of selective
permeability are available
from NuSil Technology of Carpinteria, CA. Other suitable materials may also be
used.
Materials may be selected to affect the rate of release of medication through
the head 24 of the
plug 10 (or other plug location, as discussed below with respect to Figs. 8
through 10). Thus,
the second material is preferably chosen for its desired rate of release with
respect to a
particular medication.

Referring to Fig. 2, in accord with a preferred method of manufacturing the
plug 10, in a
first step, the body 12 is molded from the first material to define the
reservoir 14 having a larger
diameter neck end 30, a tapered portion 32 and an open tip 34. Thus, the
internal space


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6

defining the reservoir is molded open at both the neck and tip ends. Referring
to Fig. 2, once
the body has solidified, the head 24 is molded from the second material onto
the neck portion
16 of the body 12. The end of the neck portion 16 may be provided with a flare
36 to facilitate
molded engagement with the head 24. Referring to Fig. 3, after the head 24 has
solidified onto
the body 12 such that the body and head are integrated, the medication 26 is
injected with a
needle 38 or other suitable device into the reservoir 14 of the plug 10
through the open tip 34.
Referring to Fig. 4, in a final step, the open tip 34 of the body 12 is
sealed. In a preferred
embodiment, a medication impermeable stopper 40 is provided to close the
reservoir 14. The
stopper 40 is preferably made of silicone or PTFE, though other suitable
materials can be used.
Alternatively, or additionally, a sealant may be 'painted' onto the plug at
the site of the opening
to provide the seal. Therefore, in accord with the invention, the reservoir 14
is sealed at a
location away from the area of medication permeability, and most preferably at
a location
opposite the head 24. Thus, the portion of the plug at which the medication is
released is
precisely fabricated in order to control medication release, and the
medication reservoir is
closed away from the area of permeability so as not to interfere with such
permeability.

The plug 10 is sized for insertion into a portion of the lacrimal canaliculus
of a human
eye, with the head and body anchored by the punctum. When so inserted (in
accord with
technique well known in the art), the medication is released from the plug to
the ocular surface
over time at the predetermined rate to provide medicinal or therapeutic
benefit.

Turning now to Figs. 6 and 7, a second method of manufacturing a plug 110
according
to the invention is shown. The body 112 of the plug is made from a self-
healing material, with
an internal space 114 open only at the neck end 136. The head 124 is then
attached to the body
112 prior to filing the reservoir space 114 with medication. A needle 138 or
similar device is
punctured through the body 112 to inject the medication 126. After injecting
the medication
126, the needle 138 is withdrawn, with the body self-healing to retain the
medication 126.

In accord with yet another embodiment of the invention a plug 210 (Fig. 10) is
provided
adapted to release medication into the lacrimal duct, e.g., allergy, sinus or
throat medications,
rather than to the surface of the eye. Referring to Fig. 8, the body 212 is
molded of the first
relatively impermeable material with head 224, neck 216 and a flared open end
218. The head


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7

portion 224 defines an opening 242. Referring to Fig. 9, a tip 244 of a second
relatively more
permeable material is molded onto the flared open end 218 to define a
reservoir within the body
212 and preferably a portion of the tip 244. Medication 226 is injected
through the opening 242
into the reservoir 214. Referring to Fig. 10, finally, a stopper 240 is
provided in the opening in
the head portion to close the reservoir 214. This embodiment may also be
designed without a
seal; i.e., in the manner of using a self-healing body material, as described
above.

Turning now to Fig. 11, another design of a lacrimal insert 310 is shown. The
insert
310 shown may be manufactured in accord with any of the methods described
above to release
medication at the head end or tip end. By of example, as shown, the insert 310
is manufactured
with a body 312 having an elongate distal tubular portion 360 preferably
angled relative to a
neck 316 of the body. The body 312 and tubing portion 360 define a reservoir
314 of
substantially greater volume than in the other embodiments. After molding the
body 312 of a
first relatively impermeable material, the head 324 is molded onto the neck
316 of the body 312
of a second relatively permeable material. Medication 326 is provided in the
reservoir through
the open end 362 of the tubular portion 360 and a preferably medication-
impermeable stopper
element 340 is used to close the reservoir 314.

It will be appreciated that in accord with the invention, the portion of the
insert at which
the medication is released is precisely fabricated in order to control release
of the medication,
and the reservoir is filled and then closed away from the area of
permeability.

While thus far the invention has been described with respect to lacrimal
applications, it
is appreciated that implantable devices having medication-storing reservoirs
made in accord
with the above principles and methodology can have other application. For
example, the insert
can be adapted in size and shape for insertion into an opening in a cochlea to
deliver a
medication to the inner ear. By way of another example, the insert can be
implanted into a hole
drilled in bone to deliver into the medullary canal a medication or
therapeutic, including a gene-
therapeutic agent. In accord with yet another example, an insert can be
implanted into a hole
drilled into the skull to deliver neurological medications to the brain. In
yet another example,
an insert can be anchored at a surgical opening to deliver a medication such
as an antibiotic
directly to a surgical site. The inserts may also be implanted within the
nasal cavity. Such


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inserts may be of various shapes, sizes and first and second materials, each
suitable for its
particular application. Furthermore, the devices may be adapted in size and
shape for
veterinary applications, particularly for, though not limited to, mammals. In
each application,
the insert preferably includes a flared or barbed structure or other means for
anchoring the
insert in the body opening.

There have been described and illustrated herein several embodiments of
inserts, and
particularly several lacrimal inserts, adapted to release medication over time
and methods of
manufacturing such inserts. While particular embodiments of the invention have
been
described, it is not intended that the invention be limited thereto, as it is
intended that the
invention be as broad in scope as the art will allow and that the
specification be read likewise.
Thus, while exemplar shapes have been shown with respect to the inserts, it
will be appreciated
that other suitable shapes for the inserts, particularly those known in the
art for similar inserts
which do not release medications in a manner as described or which are not
formed in a manner
as described, may be used as well. It will therefore be appreciated by those
skilled in the art
that yet other modifications could be made to the provided invention without
deviating from its
scope as claimed.

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Administrative Status , Maintenance Fee  and Payment History  should be consulted.

Administrative Status

Title Date
Forecasted Issue Date Unavailable
(86) PCT Filing Date 2005-07-21
(87) PCT Publication Date 2006-02-09
(85) National Entry 2007-01-15
Examination Requested 2010-06-11
Dead Application 2013-06-07

Abandonment History

Abandonment Date Reason Reinstatement Date
2012-06-07 R30(2) - Failure to Respond

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Registration of a document - section 124 $100.00 2007-01-15
Application Fee $400.00 2007-01-15
Maintenance Fee - Application - New Act 2 2007-07-23 $100.00 2007-01-15
Maintenance Fee - Application - New Act 3 2008-07-21 $100.00 2008-04-18
Maintenance Fee - Application - New Act 4 2009-07-21 $100.00 2009-04-23
Request for Examination $800.00 2010-06-11
Maintenance Fee - Application - New Act 5 2010-07-21 $200.00 2010-06-11
Maintenance Fee - Application - New Act 6 2011-07-21 $200.00 2011-04-13
Maintenance Fee - Application - New Act 7 2012-07-23 $200.00 2012-04-26
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
CLARITY CORPORATION
Past Owners on Record
PRESCOTT, ANTHONY D.
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
Documents

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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Abstract 2007-01-15 2 71
Claims 2007-01-15 5 167
Drawings 2007-01-15 5 65
Description 2007-01-15 8 388
Representative Drawing 2007-03-20 1 5
Cover Page 2007-03-21 1 42
Claims 2007-01-16 6 476
Prosecution-Amendment 2010-06-30 1 41
PCT 2007-01-15 2 71
Assignment 2007-01-15 4 190
PCT 2007-01-16 9 800
Prosecution-Amendment 2010-06-11 1 49
Fees 2010-06-11 1 34
Prosecution-Amendment 2011-12-07 3 131