DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on September 07, 2023 and September 26, 2024 have been received and considered by the Examiner.
Response to Amendment
The following section is in reference to the Applicant’s Amendments, filed March 09, 2026
The Applicant’s election of Group I, Claims 1-6 and 11-19, has been acknowledged.
The Applicant’s cancellation of Claims 7-10 has been acknowledged.
The Applicant’s addition of Claims 20-24 has been acknowledged
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Roy et al. (US 20030055354 A1, hereinafter “Roy”).
Regarding Claim 1, Roy discloses: An inhalation exposure system (Figure 3, Paragraph 0004, The present application relates, in general, to multi-animal inhalation exposure systems), comprising:
a set of inhalation exposure chambers (Figure 3, animal restraint cartridge 210) in fluid communication with a gas delivery manifold (Figure 2, inner manifold 202), (Paragraph 0028, With reference now to FIG. 2, depicted is a pictographic representation of exposure tower 100. Shown are cutaway drawings of input module 102, exposure module 104, and exhaust module 106. Exposure module 104 is composed of three concentric manifolds all composed of nonporous, autoclavable, non-reactive materials: inner manifold 202, middle manifold 204, and outer manifold 206. A plurality of annular shaped apertured connectors 208 are housed in outer manifold 206. Each apertured connector is designed to support and mate with animal restraint cartridge 210 inserted from outside the outer manifold. A plurality of identical exposure modules 104 can be stacked between input module 102 and exhaust module 106 as necessary to accommodate the number of animals to be included in any particular study),
wherein each respective inhalation exposure chamber is configured to house a test subject for inhalation of a first gas (Paragraph 0033, With reference now to FIG. 4, depicted is a drawing of animal restraint cartridge 210 and associated hardware. Shown is opening 400 through which the nose of animal 402 extends into the chamber formed in apertured connector 208. Further demonstrated is end cap 404 which is sealed after animal 402 is positioned in restraint cartridge 210 with its nose extending through opening 400);
one or more sensors (Paragraph 0043, control program 124 initiates monitoring of the environmental conditions (temperature, relative humidity, pressure, inhalent concentration, etc.) in inner manifold 202 via a plurality of sensors housed in interface box 118 and in inner manifold 202) coupled to each respective inhalation exposure chamber to sense a characteristic of the first gas flowing from the gas delivery manifold into the respective inhalation exposure chamber (Paragraph 0033, pneumotachograph 406 is operably coupled to pressure transducer 408 by tubes 410. […] The pneumotachograph/ pressure transducer combination measures the flow of air to and from restraint cartridge 210 in real-time as animal 402's thoracic cage expands and contracts with respiratory function. These flow measurements are processed by control program 124 to calculate respiratory tidal volume, respiratory rate, respiratory minute volume, and cumulative tidal volume in near-real time for each animal simultaneously and independently);
and a controller (Figure 1, control program 124) configured to simultaneously deliver the first gas from the gas delivery manifold into the set of inhalation exposure chambers (Paragraph 0044, Once all of the environmental conditions entered by the user are achieved in inner manifold 202, control program 124 initiates the animal exposure by electronically switching all valve pairs 300a and 300b to the expose condition. Additionally, control program 124 initiates the comprehensive respiratory monitoring algorithm for each animal utilizing the electronic signals generated by pressure transducers 408. The algorithm simultaneously monitors the cumulative tidal volume for every animal being exposed in near real-time. Control program 124 uses this cumulative tidal volume measurement in conjunction with the inhalent concentration measurement acquired by environmental monitoring devices to calculate the actual inhaled dose of the inhalent for each animal in near real-time)
and, in response to a sensed condition at one inhalation exposure chamber of the set of inhalation exposure chambers, terminate delivery of the first gas into said one inhalation exposure chamber while other inhalation exposure chambers of the set of inhalation exposure chambers continue to receive delivery of the first gas (Paragraph 0045, When an individual animal's inhaled dose as measured by the respiratory monitoring algorithm of control program 124 equals that called for by the dose schedule recalled via the animal identification system, control program 124 switches valve pair 300a and 300b corresponding to that animal from the expose to the bypass condition. Meanwhile, valve pairs 300a and 300b corresponding to other animals remain in the expose condition. Other animals continue to be exposed until the respiratory monitoring algorithm of control program 124 indicates that they have inhaled the dose required by the dose schedule/identification algorithm).
Regarding Claim 2, Roy discloses all of the limitations of Claim 1. Roy further discloses: wherein the controller is configured to deliver a second gas (Paragraph 0032, This assembly of valves 300a and 300b allows each pair to be electronically switched via control program 124 into either a "bypass" condition or an "expose" condition. In the bypass condition, valve 300a is set so that clean air from middle manifold 204 flows into inlet 306a, out of outlet 302a, through apertured connector 208, and into outer manifold 206. In the bypass condition valve 300b is set so that the inhalent atmosphere in inner manifold 202 flows into inlet 304b, out of outlet 302b, and directly into outer manifold 206.) to the one inhalation exposure chamber contemporaneously with the termination of the delivery of the first gas (Paragraph 0045, When the required doses are achieved for all animals and all valve pairs 300a and 300b are in the bypass condition, control program 124 deactivates aerosol dissemination device 114, and terminates the flows through inhalent air input tube 108, clean air input tube 106, and output air tube 110. Control program 124 notifies the user via an audible signal and a visible indication on the graphical user interface of data processing system 122 that the exposures for all animals are complete).
Regarding Claim 3, Roy discloses all of the limitations of Claim 2. Roy further discloses: wherein the second gas is breathable air (Paragraph 0029, Also provided with input module 102 is coupler fitting 216, designed to be operably coupled with clean input air hose 110 (not shown in FIG. 2) and providing the mechanism for introducing clean, filtered air into clean air intake plenum 218 and, hence, into middle manifold 204 of exposure module 104).
Regarding Claim 4, Roy discloses all of the limitations of Claim 1. Roy further discloses: at least one respective valve between the gas delivery manifold and each respective inhalation exposure chamber of the set of inhalation exposure chambers (Paragraph 0031, Depicted in FIG. 3 is a top view drawing of exposure module 104. Shown in FIG. 3 is that housed in middle manifold 204 are electronically controlled three-way valves 300a and 300b, each associated with an apertured connector 208. Valve 300a is oriented such that outlet 302a is plumbed to apertured connector 208, inlet 304a is plumbed to inner manifold 202, and inlet 306a is open to middle manifold 204. Valve 300b is oriented such that outlet 302b is plumbed to outer manifold 206, but not into apertured connector 208, inlet 304b is plumbed to inner manifold 202, and inlet 306b is open to middle manifold 204. Valves 300a and 300b are coupled to interface box 118 via wire bundle 116 and controlled by means of control program 124 running on data processing system 122).
Regarding Claim 5, Roy discloses all of the limitations of Claim 4. Roy further discloses: wherein the least one respective valve comprises a pinch valve, a pneumatically actuated valve, or an electronically actuated valve (Paragraph 0044, Once all of the environmental conditions entered by the user are achieved in inner manifold 202, control program 124 initiates the animal exposure by electronically switching all valve pairs 300a and 300b to the expose condition).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Alston et al. (WO 03000329 A2, hereinafter “Alston”), further in view of Molgaard-Neilsen (US 20090125103 A1, hereinafter “Molgaard”).
Regarding Claim 6, Roy discloses all of the limitations of Claim 5. Roy discloses valves (Figure 3, valve pairs 300a and 300b), but does not disclose said valves comprising pinch valves.
Alston does disclose: wherein the least one respective valve comprises the pinch valves (Pages 14-15, lines 31-5, Referring now to Figs. 5 and 6, one embodiment of a flow regulating valve 32 will be described. Valve 32 may be used in device 10 along with any of the other systems described herein. Valve 32 comprises a valve body 34 having an inlet end 36, an outlet end 38 and a gas flow passage 40 between the inlet end 36 and the outlet end 38. Valve body 34 is constructed of a resilient material, such as a silicone rubber. Valve body 34 at outlet end 38 has a central region 42 and a plurality of extending regions 44 that extend outwardly from central region 42. In operation, extending regions 44 are drawn together to limit the flow of gases through gas flow passage 40 as the vacuum level downstream of outlet end 38 increases) that includes
an outer wall which defines an inner lumen, wherein the outer wall is reversibly collapsible along a plurality of foldable wall portions (Pages 14-15, lines 35-6, Valve body 34 is constructed of a resilient material, such as a silicone rubber. Valve body 34 at outlet end 38 has a central region 42 and a plurality of extending regions 44 that extend outwardly from central region 42. In operation, extending regions 44 are drawn together to limit the flow of gases through gas flow passage 40 as the vacuum level downstream of outlet end 38 increases)
such that, when the outer wall is adjusted to a collapsed configuration, the inner lumen is sealed against gaseous flow between the input end and the output end (Page 15, lines 14-18, When used in an aerosolization device, valve 32 may be used to increase flow resistance and thereby limit the flow rate to be within certain limits. At low vacuum levels, valve 32 remains fully open so that adequate flow rates may be achieved. At higher vacuum levels, extending regions 44 close to limit and eventually stop the flow through valve 32).
Both Roy and Alston teach controlled aerosolized drug delivery devices, with valve arrangements that function similarly to regulate the flow of inhalants in the systems. Thus, it would have been obvious to one skilled in the art before the effective filing date to incorporate the art-recognized, alternative valve arrangement as disclosed by Alston to provide a pneumatically regulated inhalation system.
Alston discloses the valve being in fluid communication between an output end connected to a respective inhalation exposure chamber and an input end opposite from the inhalation exposure chamber (Page 13, lines 1-9, Disposed in flow path 22 is a flow regulating valve 26, and coupled to flow path 24 is a receptacle 28 containing a powder to be aerosolized. Flow paths 22 and 24 join together into a fourth flow path 30 that leads to outlet end 16. The flow rate through each flow path 22 and 24 is controlled by the resistance of receptacle 28 and the configuration of flow regulating valve 26. The resistance of receptacle 28 is generally constant and is based on the configuration of the receptacle, while the resistance of valve 26 is highly variable. More specifically, valve 26 is configured to remain fully open (and thus provide little or no resistance) at low vacuums and to progressively provide greater resistances at higher vacuums).
However, the combination does not explicitly disclose said valve including the inner lumen extending between an output end connected to a respective inhalation exposure chamber and an input end opposite from the inhalation exposure chamber.
Molgaard does disclose: an outer wall which defines an inner lumen, the inner lumen extending between an output end and an input end (Paragraph 0063, Turning now to FIG. 7, there is shown an embodiment of valve assembly 200 including therewithin a tri-leaflet valve element 100 of the type shown in FIGS. 3 and 4 or of the type shown in FIGS. 5 and 6. The assembly 200, in this embodiment, includes a casing 202 having openings 204, 206 at either end. The valve 100 is sealed to the casing 202 so that each end of the valve 100 envelops one of the openings 204, 206, so as to provide a channel passing through the centre of the assembly 200, for the passage of an element 16 of the type shown in FIG. 2 and discussed in connection therewith), (Paragraph 0064, The casing 202 is provided with a port 208 for the supply of pressured fluid 210 into the chamber 212 which surrounds the outside of the valve element 100. Application of pressurized fluid into the chamber 212 causes the valve leaflets of the valve 100 to be pressed towards the centre of the casing 202 and thereby to constrict the passage between the two openings 204, 206, in other words to compress the central aperture 108 of FIG. 4. This has the effect of closing the valve element 100 into a sealing configuration)
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Molgaard’s valve arrangement with the system disclosed by Roy in view of Alston, so as to provide a more resilient and adjustable sealing means (Paragraphs 0004-0005, A difficulty arises with the use of such a series of seals, however, in that in order to have good sealing characteristics they also tend to create a significant resistance to movement of an insert therein, which can substantially impair the operability of the insert by making it too hard to slide within the sheath. This can in some instances lead to damage of the insert, for example by kinking. […] This [valve] has the advantage that an element can be inserted into the sheath and moved there along with relative ease while the controllable haemostatic valve is in an open configuration. Once the insert is in place the valve can be tightened to seal. Such tightening is also advantageous during the procedure of insertion of the device into the sheath assembly. In practice, it is often necessary for such a solution also to include a valve which self-seals, such as one or more of the disk-shaped valves mentioned above to secure sealing during handling)
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Vincent et al. (US 5626130 A, hereinafter “Vincent”).
Regarding Claim 20, Roy discloses all of the limitations of Claim 1. Roy further discloses: wherein the controller configured to simultaneously deliver the first gas comprising an aerosol (Paragraph 0027, Integral with inhalent air input hose 108 is inhalent dissemination device 112. Inhalent dissemination device 112 is meant to be indicative of a variety of different devices for dispersing organic or inorganic substances in an aerosol, gas, fume, dry powder, or other suitable form)
However, Roy does not explictly disclose whether said aerosol includes suspended liquid or solid. Vincent does disclose a first gas comprising an aerosol including suspended liquid or solid (Column 4, lines 5-19, Exemplary combinations of test substances are (binary mixtures): air/ozone, air/solid particles suspended in air, air/carbon dioxide […]. It is an advantage of the invention that the apparatus enables the delivery of various combinations of two or more different gaseous or vaporous substances, also relatively unstable mixtures or compounds, since the mixtures/ compounds can be formed at the time of, or directly before, reaching the animal).
Similar to Roy, Vincent also teaches an inhalation system for controlled administration of gases to animal test subjects (Column 1, lines 4-9, This invention relates to respiratory devices for laboratory animals, particularly to such devices which enable a controlled delivery of a gaseous or vaporous substance to the nose and lungs of a laboratory animal without exposing the entire head or whole body of the animal to the substance). It would have been obvious to one of ordinary skill in the art to incorporate a variety of combinations of aerosols in accordance with the particular experimentations being conducted on said animal subjects. It is common and well-known in the art of inhalation systems to have suspended liquids and solids in aerosols.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Vincent (US 5626130 A), further in view of Van Der Mark et al. (US 20150020804 A1 hereinafter “Mark”).
Regarding Claim 21, Roy in view of Vincent discloses all of the limitations of Claim 20. Roy discloses one or more sensors coupled to each respective inhalation exposure chamber to sense the characteristic of the first gas (Claim 91, The system of claim 89, wherein said inhalent manifold comprises: at least one environmental-condition sensor integral with said inhalent manifold, said at least one environmental condition sensor selected from an environmental-condition-sensor group including a temperature sensor, a relative humidity sensor, a pressure sensor, and an inhalent concentration sensor; and said exposure control system operably coupled to said at least one environmental-condition sensor), but does not disclose an optical sensor.
Mark does disclose an optical sensor (Paragraph 0010, The optical beam crosses the aerosol beam, and falls on an optical sensor (optionally through a diaphragm and optionally focused using one or more lenses)) to determine an aerosol content of the first gas delivered to the respective inhalation exposure chamber (Paragraph 0009, A system has been proposed that estimates the aerosol output rate by measuring the density of the aerosol beam, which is then used in a feedback control loop to adjust the electrical power. The aerosol density can be measured by means of an optical beam perpendicular to the aerosol beam).
Being that Roy already teaches a variety of sensors for detecting changes in the inhalation system, incorporating an optical sensor would be an obvious modification to one of ordinary skill in the art before the effective filing date. The optical sensor taught by Van der Mark allows for more accurate control and assessment of the delivery of the aerosols to the test subjects.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Vincent (US 5626130 A), view of Mark (US 20150020804 A1), further in view of Lomask (US 5379777 A).
Regarding Claim 22, Roy in view of Vincent and Mark discloses all of the limitations of Claim 21. Roy further discloses: wherein said one or more sensors coupled to each respective inhalation exposure chamber to sense the characteristic of the first gas comprise a pneumotachograph to measure variation in a volume of a part of the test subject (Paragraph 0033, Pneumotachograph 406 is operably coupled to pressure transducer 408 by tubes 410. Pressure transducer 408 is coupled to interface box 118 via wire bundle 116 and monitored by control program 124 running on data processing system 122 (not shown in FIG. 4). […] The pneumotachograph/pressure transducer combination measures the flow of air to and from restraint cartridge 210 in real-time as animal 402's thoracic cage expands and contracts with respiratory function. These flow measurements are processed by control program 124 to calculate respiratory tidal volume, respiratory rate, respiratory minute volume, and cumulative tidal volume in near-real time for each animal simultaneously and independently).
However, Roy does not disclose a plethysmograph. Lomask does disclose: wherein said one or more sensors coupled to each respective inhalation exposure chamber to sense the characteristic of the first gas comprise a plethysmograph to measure variation in a volume of a part of the test subject (Columns 1-2, lines 64-3, The plethysmograph still further includes two pneumotachographs in the top of the animal chamber for creating a pressure drop in the animal chamber during respirations. The plethysmograph may be used either in a volume mode of operation by plugging the pneumotachographs, or in a flow mode of operation by leaving the pneumotachographs unplugged).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Lomask’s plethysmograph in an animal inhalation chamber with the existing pneumotachograph disclosed by Roy, so as to provide an art-recognized means of assessing the lung capacity and overall changes in volume of the test subject.
Claims 23 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Vincent (US 5626130 A), view of Mark (US 20150020804 A1),in view of LaBauve (US 4520808 A).
Regarding Claim 23, Roy in view of Vincent and Mark discloses all of the limitations of Claim 21. Roy further discloses: wherein each respective inhalation exposure chamber of the set of inhalation exposure chambers defines a cylindrical inner volume sized to enclose the test subject so that a head of the test subject is oriented nearest the gas delivery manifold (Paragraph 0033, With reference now to FIG. 4, depicted is a drawing of animal restraint cartridge 210 and associated hardware. Shown is opening 400 through which the nose of animal 402 extends into the chamber formed in apertured connector 208).
The shape of the inhalation exposure chambers are generally cylindrical, however, if the Applicant is not convinced, LaBauve demonstrates a cylindrical inner volume (Columns 3-4, lines 59-2, FIG. 2 illustrates animal holding tube means 12 that can employed in accordance with this invention. In this embodiment, animal positioning means 42, which can also be referred to as plunger 42, is used to adjust the space within the tube means 12 so that the nose of the test animal is positioned at a fixed point within said tube means 12, i.e., directly adjacent to test atmosphere inlet means 40. Test atmosphere inlet means 40 allows test atmosphere to communicate with the interior of tube means 12)
LaBauve discloses both a cylindrical and a partially conical inner volume, both capable of effectively functioning as an inhalation chamber and holding means for a test subject. It would have been obvious to one skilled in the art before the effective filing date to modify the shape of inhalation chamber disclosed by Roy to provide an alternative arrangement that minimizes the stress of an animal test subject (Column 4, lines 4-17, Test atmosphere inlet means 40 is depicted in FIG. 2 as a flat, mesh structure. In FIG. 3, the test atmosphere inlet means is depicted in an alternative embodiment as conical nose-piece 41. The flat mesh structure design allows the test animal more head room decreasing stress levels; however the conical nose-piece positions the nose of the test animal more fixedly. The animals tend to gnaw the conical nose-pieces making them rough and sharp inside. This roughened, rasp-like surface tends to lacerate the animal's lips and thereby increase their stress levels. The flat wire mesh structure cannot be chewed as easily thereby eliminating this problem. However, both designs are capable of adequately functioning as test atmosphere inlet means)
Regarding Claim 24, Roy in view of Vincent and Mark discloses all of the limitations of Claim 21. Roy discloses communicat[ing] the aerosol into a gas inlet of the gas delivery manifold (Paragraph 0027, Integral with inhalent air input hose 108 is inhalent dissemination device 112. Inhalent dissemination device 112 is meant to be indicative of a variety of different devices for dispersing organic or inorganic substances in an aerosol, gas, fume, dry powder, or other suitable form), but does not disclose a nebulizer.
LaBauve does disclose: a nebulizer configured to communicate the aerosol into a gas inlet of the gas delivery manifold (Column 3, lines 16-32, Test atmosphere enters first plenum duct 14 by means of inlet 20. The test atmosphere can be supplied by various means, e.g., nebulizers which generate liquid drop aerosols; dust generators; gas generators; gas cylinders; and by exposure to ambient atmospheres occurring either naturally or artificially such as an automobile exhaust or smoke stack emissions. The source of the test atmosphere is preferably an aerosol generator (not shown) which incorporates a test material, usually a toxic chemical, into an aerosol. The aerosol generator can be any of several types, so that a detailed discussion thereof is not believed necessary to a complete understanding of the present invention. In a typical aerosol generator, e.g, the Babbington neubilizer, purified, dry, filtered, compressed air flows through a jet contacting the test material thereby entraining the test material as an aerosol).
Similar to Roy, LaBauve also teaches an inhalation system for controlled administration of gases to animal test subjects (Column 3, lines 8-15, FIG. 1 illustrates an animal inhalation exposure system 10 comprising a plurality of animal holding tube means 12, first plenum duct 14, and second plenum duct 16. Exposure system 10 actively draws test atmosphere into animal holding tube means 12, past the nose of the test animal and out through exhaust outlet means 18 into second plenum duct 16. The path of the test atmosphere is outlined in FIG. 1 by the arrows). Nebulizers are an art-recognized means of aerosol distribution and are commonly used for respiratory drug delivery. It would have been obvious to one of ordinary skill in the art to incorporate a nebulizer as taught by LaBauve into the system disclosed by Roy to provide a controlled administration of aerosolized gases to a test subject.
Claims 11-12 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Molgaard (US 20090125103 A1), in view of Alston (WO 03000329 A2), further in view of Butsch (DE 102006048454 B3).
Regarding Claim 11, Roy discloses: An inhalation exposure system (Figure 3, Paragraph 0004, The present application relates, in general, to multi-animal inhalation exposure systems), comprising:
a valve (Figure 3, valve pairs 300a and 300b) extending between an output end connected to an aerosol exposure chamber and an input end opposite from the aerosol exposure chamber (Paragraph 0031, Depicted in FIG. 3 is a top view drawing of exposure module 104. Shown in FIG. 3 is that housed in middle manifold 204 are electronically controlled three-way valves 300a and 300b, each associated with an apertured connector 208),
a housing that radially surrounds an outer wall of the valve, the housing having a port (Paragraph 0031, Valve 300a is oriented such that outlet 302a is plumbed to apertured connector 208, inlet 304a is plumbed to inner manifold 202, and inlet 306a is open to middle manifold 204. Valve 300b is oriented such that outlet 302b is plumbed to outer manifold 206, but not into apertured connector 208, inlet 304b is plumbed to inner manifold 202, and inlet 306b is open to middle manifold 204. Valves 300a and 300b are coupled to interface box 118 via wire bundle 116 and controlled by means of control program 124 running on data processing system 122)
a second gas source configured to supply to the input end a second gas comprising an aerosol (Paragraph 0027, Integral with inhalent air input hose 108 is inhalent dissemination device 112. Inhalent dissemination device 112 is meant to be indicative of a variety of different devices for dispersing organic or inorganic substances in an aerosol, gas, fume, dry powder, or other suitable form);
a sensor that communicates information indicative of an amount of the aerosol delivered to the aerosol exposure chamber (Paragraph 0043, control program 124 initiates monitoring of the environmental conditions (temperature, relative humidity, pressure, inhalent concentration, etc.) in inner manifold 202 via a plurality of sensors housed in interface box 118 and in inner manifold 202);
and a controller (Figure 1, control program 124) in communication with the sensor so that in response to a determination that an exposure parameter of the aerosol delivered to the aerosol exposure chamber exceeds a threshold value (Paragraph 0044, Once all of the environmental conditions entered by the user are achieved in inner manifold 202, control program 124 initiates the animal exposure by electronically switching all valve pairs 300a and 300b to the expose condition. Additionally, control program 124 initiates the comprehensive respiratory monitoring algorithm for each animal utilizing the electronic signals generated by pressure transducers 408. The algorithm simultaneously monitors the cumulative tidal volume for every animal being exposed in near real-time. Control program 124 uses this cumulative tidal volume measurement in conjunction with the inhalent concentration measurement acquired by environmental monitoring devices to calculate the actual inhaled dose of the inhalent for each animal in near real-time).
Roy does not disclose a cylindrical valve comprising an outer wall which defines an inner lumen. Molgaard does disclose a cylindrical valve (Paragraph 0044, The shape of the valve 10 can take a variety of forms, the preferred of which is shown in FIGS. 3 and 4 and described in further detail below. In one embodiment, the three leaflets 14 are substantially rectangular along their lengths such that the valve element 10 is substantially cylindrical throughout its length) comprising
an outer wall which defines an inner lumen (Paragraph 0050, Referring now to FIGS. 3 and 4, there is shown a preferred embodiment of valve 100 to be used as a haemostatic valve in a deployment or delivery device of the type discussed above. In this embodiment, the valve 100 has three elongate leaflets 102 which are connected to one another in sealed manner along their adjacent edges 104), the inner lumen extending between an output end connected to an aerosol exposure chamber and an input end opposite from the aerosol exposure chamber (Paragraph 0063, Turning now to FIG. 7, there is shown an embodiment of valve assembly 200 including therewithin a tri-leaflet valve element 100 of the type shown in FIGS. 3 and 4 or of the type shown in FIGS. 5 and 6. The assembly 200, in this embodiment, includes a casing 202 having openings 204, 206 at either end. The valve 100 is sealed to the casing 202 so that each end of the valve 100 envelops one of the openings 204, 206, so as to provide a channel passing through the centre of the assembly 200, for the passage of an element 16 of the type shown in FIG. 2 and discussed in connection therewith),
and wherein the outer wall is reversibly collapsible along a plurality of foldable wall portions (Paragraph 0018, According to an aspect of the present invention, there is provided a valve element formed of at least three elongate flexible leaflets arranged so as to provide a polygonal passage therebetween when the valve element is in an open configuration, the leaflets being able to close in on one another along at least a portion thereof, thereby to provide a seal);
a housing (Figure 7, casing 202) that radially surrounds the outer wall of the cylindrical valve (Paragraph 0063, Turning now to FIG. 7, there is shown an embodiment of valve assembly 200 including therewithin a tri-leaflet valve element 100 of the type shown in FIGS. 3 and 4 or of the type shown in FIGS. 5 and 6. The assembly 200, in this embodiment, includes a casing 202 having openings 204, 206 at either end. The valve 100 is sealed to the casing 202 so that each end of the valve 100 envelops one of the openings 204, 206, so as to provide a channel passing through the centre of the assembly 200, for the passage of an element 16 of the type shown in FIG. 2 and discussed in connection therewith), the housing having a port (Figure 7, port 208);
a first gas source in fluid connection with the port and configured to supply a first gas to the port (Paragraph 0064, The casing 202 is provided with a port 208 for the supply of pressured fluid 210 into the chamber 212 which surrounds the outside of the valve element 100);
Molgaard teaches a variety of valve structures and shapes that provide similar functionality (Paragraph 0043, It is not ruled out that the valve 10 could have more than three leaflets, such as 4, 5 or 6), (Paragraph 0044, The shape of the valve 10 can take a variety of forms, the preferred of which is shown in FIGS. 3 and 4 and described in further detail below). It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Molgaard’s various valve arrangements with the system disclosed by Roy, so as to provide a more resilient and adjustable sealing means (Paragraph 0005, In practice, it is often necessary for such a solution also to include a valve which self-seals, such as one or more of the disk-shaped valves mentioned above to secure sealing during handling).
The valve disclosed by Molgaard is fluid-tight when an insert is placed within the valve (Abstract, An element (16) inserted in the tri-leaflet valve (100) can be sealed by closure of the valve (100), for example by pressurization or twisting). However, Molgaard does not explicitly disclose a seal against gaseous flow when there is not an insert present.
Alston does disclose: when the outer wall is adjusted to a collapsed configuration, the inner lumen is sealed against gaseous flow between the input end and the output end (Page 15, lines 14-18, When used in an aerosolization device, valve 32 may be used to increase flow resistance and thereby limit the flow rate to be within certain limits. At low vacuum levels, valve 32 remains fully open so that adequate flow rates may be achieved. At higher vacuum levels, extending regions 44 close to limit and eventually stop the flow through valve 32).
Both Roy in view of Molgaard and Alston teach controlled aerosolized drug delivery devices, with valve arrangements that function similarly to regulate the flow of inhalants in the systems. Thus, it would have been obvious to one skilled in the art before the effective filing date to incorporate the art-recognized, alternative valve arrangement as disclosed by Alston to provide a pneumatically regulated inhalation system.
Roy discloses the controller switching the valve condition to adjust flow into the aerosol exposure chamber (Paragraph 0045, When an individual animal's inhaled dose as measured by the respiratory monitoring algorithm of control program 124 equals that called for by the dose schedule recalled via the animal identification system, control program 124 switches valve pair 300a and 300b corresponding to that animal from the expose to the bypass condition. Meanwhile, valve pairs 300a and 300b corresponding to other animals remain in the expose condition. Other animals continue to be exposed until the respiratory monitoring algorithm of control program 124 indicates that they have inhaled the dose required by the dose schedule/identification algorithm).
Though Roy does not explicitly describe the controller supplies the first gas to adjust the outer wall of the cylindrical valve to the collapsed configuration and to flow into the aerosol exposure chamber, it would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Molgaard and Alston’s pinch valve arrangements with the controlled gas dispersal described by Roy.
If the Applicant is not convinced, Butsch explicitly discloses the controller (Paragraph 0006, The shut-off device can be a simple electrical, pneumatic, hydraulic or mechanical shut-off device) supplies the first gas to adjust the outer wall of the cylindrical valve to the collapsed configuration and to flow into the aerosol exposure chamber (Paragraph 0007, With the shut-off device closed, the pinch valve is pressurized via the Venturi nozzle from the compressed air connection, thereby compressing the rubber sleeve of the pinch valve and thus closing the pinch valve […] When the shut-off device is opened, air flows through the Venturi nozzle at the appropriate operating pressure, evacuating the area around the hose cuff and opening the hose cuff in a ring shape).
Butsch provides a clear teaching regarding the implementation and functionality of an elastically deformable pinch valve in a pneumatic system. Thus, it would have been obvious to one skilled in the art before the effective filing date to modify the controlled gas dispersal system described by Roy in view of Molgaard and Alston to include the valve control methods disclosed by Butsch, so as to provide a simple and effective means of adjusting fluidic flow in the system (Paragraph 0003, Based on this state of the art, the invention aims to provide a device for controlling a pinch valve, the design of which allows for simpler wiring, simple assembly and cost-effective manufacturing).
Regarding Claim 12, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Molgaard further discloses: wherein the port is exposed toward an exterior surface of the outer wall of the cylindrical valve (Figure 7, Paragraph 0064, The casing 202 is provided with a port 208 for the supply of pressured fluid 210 into the chamber 212 which surrounds the outside of the valve element 100).
Regarding Claim 15, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Molgaard further discloses: wherein the plurality of foldable wall portions comprises three foldable wall portions (Paragraph 0044, The shape of the valve 10 can take a variety of forms, the preferred of which is shown in FIGS. 3 and 4 and described in further detail below. In one embodiment, the three leaflets 14 are substantially rectangular along their lengths such that the valve element 10 is substantially cylindrical throughout its length).
Regarding Claim 16, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Roy further discloses: wherein the first gas and the second gas are atmospheric gas (Paragraph 0027, Shown connected to the input module are inhalent air input hose 108 and clean air input hose 110. Integral with inhalent air input hose 108 is inhalent dissemination device 112. Inhalent dissemination device 112 is meant to be indicative of a variety of different devices for dispersing organic or inorganic substances in an aerosol, gas, fume, dry powder, or other suitable form).
Regarding Claim 17, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Roy further discloses: wherein the exposure parameter is selected from a group consistent of an amount of aerosol, an exposure time, an accumulated dose, and an accumulated inhaled aerosol value (Paragraph 0043, control program 124 initiates monitoring of the environmental conditions (temperature, relative humidity, pressure, inhalent concentration, etc.) in inner manifold 202 via a plurality of sensors housed in interface box 118 and in inner manifold 202. Control program 124 also electronically manages a variety of devices (a humidification device, a heating/cooling device, an inhalent dissemination device, flow controlling devices, etc.) as necessary to achieve and maintain said environmental conditions at levels defined by the user. Since all valve pairs 300a and 300b are in the bypass condition, all animals are supplied with clean filtered air from middle manifold 204 and not exposed to the inhalent while control program 124 achieves the user defined environmental conditions in inner manifold 202), (Paragraph 0045, When an individual animal's inhaled dose as measured by the respiratory monitoring algorithm of control program 124 equals that called for by the dose schedule recalled via the animal identification system, control program 124 switches valve pair 300a and 300b corresponding to that animal from the expose to the bypass condition […] Other animals continue to be exposed until the respiratory monitoring algorithm of control program 124 indicates that they have inhaled the dose required by the dose schedule/identification algorithm), (Paragraph 0033, Pneumotachograph 406 is operably coupled to pressure transducer 408 by tubes 410. Pressure transducer 408 is coupled to interface box 118 via wire bundle 116 and monitored by control program 124 running on data processing system 122 (not shown in FIG. 4). […] The pneumotachograph/pressure transducer combination measures the flow of air to and from restraint cartridge 210 in real-time as animal 402's thoracic cage expands and contracts with respiratory function. These flow measurements are processed by control program 124 to calculate respiratory tidal volume, respiratory rate, respiratory minute volume, and cumulative tidal volume in near-real time for each animal simultaneously and independently).
Regarding Claim 18, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Butsch further discloses: wherein the first gas is supplied to the port at a pressure in a range from 40 pounds per square inch gauge to 80 pounds per square inch gauge (Paragraph 0007, With the shut-off device closed, the pinch valve is pressurized via the Venturi nozzle from the compressed air connection, thereby compressing the rubber sleeve of the pinch valve and thus closing the pinch valve. Preferably, the system is operated at an operating pressure of approximately 2 to approximately 4 bar [29 to 58 PSI], particularly preferably at approximately 3 bar [43.5 PSI]).
Claims 13-14 rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Molgaard (US 20090125103 A1), in view of Alston (WO 03000329 A2), in view of Butsch (DE 102006048454 B3), further in view of Mark (US 20150020804 A1).
Regarding Claim 13, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Roy further discloses: a variety of environmental-conditon sensors (Claim 91, The system of claim 89, wherein said inhalent manifold comprises: at least one environmental-condition sensor integral with said inhalent manifold, said at least one environmental condition sensor selected from an environmental-condition-sensor group including a temperature sensor, a relative humidity sensor, a pressure sensor, and an inhalent concentration sensor; and said exposure control system operably coupled to said at least one environmental-condition sensor), but does not disclose an optical sensor.
Mark does disclose wherein the sensor is an optical sensor (Paragraph 0010, The optical beam crosses the aerosol beam, and falls on an optical sensor (optionally through a diaphragm and optionally focused using one or more lenses))
As Roy already teaches a variety of sensors for detecting changes in the inhalation system, incorporating an optical sensor would be an obvious modification to one of ordinary skill in the art before the effective filing date. The optical sensor taught by Van der Mark allows for more accurate control and assessment of the delivery of the aerosols to the test subjects (Paragraph 0009, A system has been proposed that estimates the aerosol output rate by measuring the density of the aerosol beam, which is then used in a feedback control loop to adjust the electrical power. The aerosol density can be measured by means of an optical beam perpendicular to the aerosol beam).
Regarding Claim 14, Roy in view of Molgaard, Alston, Butsch, and Mark discloses all of the limitations of Claim 13. Mark further discloses: wherein the optical sensor is a photometer (Paragraphs 0021-0022, The invention is based on the recognition that light sensing can be used to derive a particle size parameter of the aerosol flow, as well as the conventional derivation of particle density (otherwise known as the volume fraction). In particular, by providing measurement with at least two wavelengths, the extra degree of freedom enables the particle density as well as the particle size to be determined. The light detector can be for detecting light which has passed through the aerosol flow, thus measuring obscuration. In this case, a dye can be added to the aerosol liquid to increase the absorption and thereby increase the signal strength).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Roy (US 20030055354 A1), in view of Molgaard (US 20090125103 A1), in view of Alston (WO 03000329 A2), in view of Butsch (DE 102006048454 B3), further in view of Boucher et al. (US 8778383 B2, hereinafter “Boucher”).
Regarding Claim 19, Roy in view of Molgaard, Alston, and Butsch discloses all of the limitations of Claim 11. Alston describes an aerosol delivery rate (Page 4, lines 27-29, The flow regulating valve may also be configured to regulate the flow rate below about 20 liters/min and more preferably below about 16 liters/min over a wide range of vacuums, such as between about 15 cm H2O and about 80 cm H2O), but does not explicitly disclose a range from 0.5 standard liters per minute to 1 standard liters per minute.
Boucher does disclose: wherein the aerosol is delivered at a rate in a range from 0.5 standard liters per minute to 1 standard liters per minute (Column 33, lines 35-37, The flow rate entering the inlet 26 may be between 0.5 L/min to 5 L/min and more preferably between 1 and 3 L/min).
It is common practice in the art of respiratory devices to incorporate preset pressure value ranges in accordance with the needs of the user, and thus configuring the inhalation system taught by Roy to adopt a range under between 0.5 and 1 SLPM. It would have been obvious to test and incorporate different ranges of pressure values through routine experimentation.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Haefner et al (US 20110218450 A1) discloses respiratory measurement collection and assessment in inhalation testing systems
Simiele et al. (US 20220152345 A1) discloses a tubular pinch valve arrangement coupled to an airflow source for actuation
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/MISHAL HUSSAIN/
Examiner
Art Unit 3785
/BRANDY S LEE/Supervisory Patent Examiner, Art Unit 3785
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