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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 23, 2024 has been considered by the examiner.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference signs mentioned in the description:
Second inlet 8
Pores 9
Gas guide channel 10
Host module 11
The drawings are objected to under 37 CFR 1.83(a) because they fail to clearly depict and identify the aforementioned reference signs as described in the specification. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d).
The drawings are not of sufficient quality to permit examination. Accordingly, replacement drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to this Office action. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Applicant is given a shortened statutory period of TWO (2) MONTHS to submit new drawings in compliance with 37 CFR 1.81. Extensions of time may be obtained under the provisions of 37 CFR 1.136(a) but in no case can any extension carry the date for reply to this letter beyond the maximum period of SIX MONTHS set by statute (35 U.S.C. 133). Failure to timely submit replacement drawing sheets will result in ABANDONMENT of the application.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Specification fails to provide sufficient details regarding the tracheal arrangement and the pores. It is devoid of any explanation as to the intended structure, as it simply provides a general reiteration of what is recited in these claims (Paragraphs 007-008, 0046-0047). The Drawings do not identify or depict the pores and tracheal arrangement in a way that would facilitate the construction or configuration of the device. These issues also extend to the claims dependent on Claim 3, for example:
Claim 4 recites the limitation “second end [of the trachea] is sealed and inserted in the pores”, but this is not properly depicted in the Drawings and the Specification provides no further details regarding how this structure is intended to be interpreted (Paragraphs 0008, 0046)
Claim 5 recites the limitation “the trachea is threaded on the first pipe body”, but this is not properly depicted in the Drawings and the Specification provides no further details regarding how this structure is intended to be interpreted (Paragraph 0009).
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-6, 9, 15, 17, 19, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitations “the inner cavity of the trachea is the first channel” and “the inner cavity of the pores is a second channel”. It is unclear what the metes and bounds of these phrases entail, as the structural arrangement of the trachea and pores are not clearly defined. The Applicant has not defined “trachea” or its intended functionality in the Specification or the Claims, and has not depicted the element in the Drawings in a way that clarifies the overall arrangement. The structure which goes to make up the device must be clearly and positively specified. The structure must be organized and correlated in such a manner as to present a complete operative device.
Claim 4 recites the limitations “can be integrally formed” and “can be installed in the nozzle”. It is unclear what the metes and bounds of these phrases entail, as the structural arrangement of the trachea is not clearly defined. The use of the phrase “can be” is not a positive recitation, and it is unclear whether the hose is intended to be integrally formed with the nozzle or not. The structure which goes to make up the device must be clearly and positively specified. The structure must be organized and correlated in such a manner as to present a complete operative device. For examination purposes, the examiner has interpreted the trachea broadly as any channel or conduit within the nozzle that is in communication with pores or mesh-like perforations or openings.
Claim 5 recites the limitation “the trachea is threaded on the first pipe body”. It is unclear what the metes and bounds of this phrase entails, as the structural arrangement of the trachea is not clearly defined in relation to the pipe bodies. The Applicant has not defined “trachea” or its intended functionality in the Specification or the Claims, and has not depicted the element in the Drawings in a way that clarifies the overall arrangement. The structure which goes to make up the device must be clearly and positively specified. The structure must be organized and correlated in such a manner as to present a complete operative device. For examination purposes, the examiner has interpreted this claim to broadly encompass any pipe fittings arrangements within a nozzle that have any threaded or screwed features.
Claims 9, 15, 17, 19, and 21 recite the limitation "the active pharmaceutical ingredient". There is insufficient antecedent basis for this limitation in the claims. Appropriate correction is required.
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.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (CN 109331302 A, hereinafter "Hu") in view of Denyer et al. (US 6584971 B1, hereinafter "Denyer")
Regarding Claim 1, Hu discloses: An atomization trigger structure (Paragraph 0002, This invention relates to the field of medical device technology, specifically to a nebulizer that controls nebulization by detecting breathing using a differential pressure sensor), wherein it comprises:
a main body, comprising an atomization module (Paragraph 0010, A nebulizer that controls nebulization by detecting breathing using a differential pressure sensor includes a collection tubing, a differential pressure sensor, a microcontroller, a nebulization drive unit, and nebulization accessories)
the atomization module is provided with atomization driver (Paragraph 0010, the microcontroller, which is connected to the nebulization drive unit via a microcontroller control circuit. The microcontroller controls the on/off state of the nebulization process via the control circuit and the nebulization drive unit. The nebulization drive unit is connected to the nebulization accessories);
an air pressure sensor, the air pressure sensor is arranged in the atomization module and is electrically connected with the atomization driver (Paragraph 0013, The differential pressure sensor is used to collect different pressure values during exhalation and inhalation);
a gas guide channel (Paragraph 0059, Connect the collection hose to the differential pressure sensor interface on the outer shell and the atomizing accessory, so that the atomizing accessory and the differential pressure sensor are connected into one air channel),
the gas guide channel is arranged in the atomization module (Paragraph 0012, The collection hose is a channel that directly connects to the nebulizer accessory mask and the differential pressure sensor, and is used to collect the different air pressures generated during the human body's exhalation and inhalation processes), and the first end of the gas guide channel is placed between a first inlet and a second outlet, and the second end is arranged at a monitoring end of the air pressure sensor (Paragraph 0051, The collection tubing is connected to both the tubing interface of the nebulization accessories and the differential pressure sensor);
the atomization trigger structure is a net atomizer trigger structure, which solves the hand-mouth coordination problem of patients when using (Paragraph 0067, The differential pressure sensor collects human exhalation and inhalation data and transmits them to the microcontroller control circuit), (Paragraph 0055, The microcontroller is used to receive data collected by the differential pressure sensor and compare different pressure values during inhalation and exhalation. It also controls the nebulization drive unit to turn on and off, thereby achieving the function of nebulization during inhalation and stopping nebulization during exhalation).
Hu does not explicitly disclose a nozzle connected to the atomization module, however, this is a common structure known in the art of inspirators.
Denyer does disclose: An atomization trigger structure (Column 5, lines 46-56, This invention applies, amongst other things, to nebulizers of the type which generate pulses of atomization, as in the prior art nebulizer described above. The invention is not, however, limited to the exact nebulizer described above, but may be applied to other nebulizers. For convenience, the description below of the present invention will refer to components of the prior art device shown in FIGS. 2 and 3, and because many of the components, for example, the manifold, may be used in the present invention. The nebulizer may be one of a jet nebulizer, ultrasonic nebulizer or a pressure mesh nebulizer), wherein it comprises
a main body, comprising an atomization module (Column 2, lines 25-33, Reference is made to our co-pending International Patent Publication No. WO 97/48431, the disclosure of which is incorporated by reference herein in its entirety as if set forth at length. FIGS. 2 and 3 of this application show the nebulizer which is disclosed in the above co-pending Patent application. Referring to FIG. 2, a mouthpiece 1 is shown through which a patient inhales in the direction of arrow 2. Below the mouthpiece 1 is a removable atomizing section 3 which, in turn, rests on a base 4) and a nozzle connected to the atomization module (Column 2, lines 43-48, Referring again to FIG. 2, air under pressure passes through the air outlet 8 of the base 4 and is conducted through a tubular post 11 to an atomizer nozzle 12 out of which the air issues under pressure. A deflector 13 is located in the path of the pressurised air issuing from the nozzle 12 so that the pressurized air is deflected laterally so as to pass beneath a baffle 14);
a gas guide channel is arranged in the atomization module (Column 2, lines 37-39, the pressurized air is led via a tube 6 to a manifold 7 which controls the flow of pressurized air to an air outlet 8 which directs air into the atomizing section 3 shown in FIG. 2), and the first end of the gas guide channel is placed between a first inlet and a second outlet, the first end is located in the nozzle (Column 2, lines 43-54, Referring again to FIG. 2, air under pressure passes through the air outlet 8 of the base 4 and is conducted through a tubular post 11 to an atomizer nozzle 12 out of which the air issues under pressure. A deflector 13 is located in the path of the pressurised air issuing from the nozzle 12 so that the pressurized air is deflected laterally so as to pass beneath a baffle 14. The passage of the pressurized air across the top of the tubular post 11 causes medication 15 to be drawn up between the outer surface of the tubular post 11 and the inner surface of a sleeve 16 which surrounds the tubular post 11. The medication 15 is atomized in the stream of air, and carried away in the stream of air below the rim of the baffle 14 and up through the mouthpiece 1 to a patient), and the second end is arranged at a monitoring end of the air pressure sensor (Column 2, lines 39-42, The base 4 also includes a pressure sensor 9 which detects the pressure within the atomizing section 3 via a port 10), (Column 2, lines 56-60, The pressure sensor 9 in the base 4 monitors the breathing pattern of a patient, and on the basis of the breathing pattern, the manifold 7 is controlled to supply pressurized air to the atomizing section 3 only during the first 50% of an inhalation phase);
Both Denyer and Hu teach nebulizer devices with control systems for adjusting drug delivery and activation based on inspiratory measures. Thus, it would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Denyer’s nozzle structure with the nebulizer system disclosed by Hu, so as to provide an art-recognized alternative interface for a patient utilizing the nebulizer; the nozzle allows for atomization and delivery of aerosols and/or powders, similar to the face mask element described by Hu.
Regarding Claim 2, Hu in view of Denyer discloses all of the limitations of Claim 1. Denyer further discloses: wherein the gas guide channel comprises a first channel and a second channel that are connected, the first channel is arranged in the nozzle, and the second channel is arranged in the atomization module (Column 2, lines 43-54, Referring again to FIG. 2, air under pressure passes through the air outlet 8 of the base 4 and is conducted through a tubular post 11 to an atomizer nozzle 12 out of which the air issues under pressure. A deflector 13 is located in the path of the pressurised air issuing from the nozzle 12 so that the pressurized air is deflected laterally so as to pass beneath a baffle 14. The passage of the pressurized air across the top of the tubular post 11 causes medication 15 to be drawn up between the outer surface of the tubular post 11 and the inner surface of a sleeve 16 which surrounds the tubular post 11. The medication 15 is atomized in the stream of air, and carried away in the stream of air below the rim of the baffle 14 and up through the mouthpiece 1 to a patient).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Rubsamen et al. (US 5735263 A, hereinafter “Rubsamen”).
Regarding Claim 3, as best understood based on the 35 U.S.C. 112(a) and (b) issues identified above, Hu in view of Denyer discloses all of the limitations of Claim 2. Denyer further discloses wherein a trachea is arranged in the nozzle, and the inner cavity of the trachea is the first channel (Column 2, lines 43-48, Referring again to FIG. 2, air under pressure passes through the air outlet 8 of the base 4 and is conducted through a tubular post 11 to an atomizer nozzle 12 out of which the air issues under pressure. A deflector 13 is located in the path of the pressurised air issuing from the nozzle 12 so that the pressurized air is deflected laterally so as to pass beneath a baffle 14). However, Hu in view of Denyer is silent regarding the inclusion of pores in the atomization module.
Rubsamen further discloses: the atomization module is provided with a pores, and the inner cavity of the pores is a second channel (Column 15, lines 50-59, An aerosol may be created by forcing drug through pores of a membrane which pores have a size in the range of about 0.25 to 2.5 microns. When the pores have this size the particles which escape through the pores to create the aerosol will have a diameter in the range of 0.5 to 5 microns. Drug particles may be released with an air flow intended to keep the particles within this size range. The creation of small particles may be facilitated by the use of the vibration device which provides a vibration frequency in the range about 800 to about 4000 kilohertz).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the pore element taught by Robertson to provide an additional means for distributing the aerosol in different particle sizes for more effective inhalation and absorption of the aerosol solution.
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), in view of Rubsamen (US 5735263 A), further in view Robertson et al. (US 5487378 A, hereinafter “Robertson”).
Regarding Claim 4, as best understood based on the 35 U.S.C. 112(a) and (b) issues identified above, Hu in view of Denyer and Rubsamen discloses all of the limitations of Claim 3. Rubsamen describes the pore element in communication with the nozzle of the device (Column 31, lines 9-16, Vibration is applied while the formulation 56 is being forced from the pores of the polycarbonate membrane 59. The formulation can be aerosolized with only vibration i.e., without applying pressure. Alternatively, when vibration is applied in certain conditions the pressure required for forcing the liquid out can be varied depending on the liquid, the size of the pores and the shape of the pores). Denyer discloses wherein the trachea can be integrally formed with the nozzle, and can be installed in the nozzle in the depiction a pipe-like passage way within the nozzle in Figure 2, but does not explicitly describe the structure of the trachea.
Robertson more clearly disclose: wherein the trachea may be a hose or a hard pipe, can be integrally formed with the nozzle, and can be installed in the nozzle, the first end of the hose is located in the inner cavity of the nozzle, and the second end is sealed and inserted in the pores (Columns 17-18, lines 63-6, It has been found that efficient aerosol generation is achieved if the nozzle arrangement and vibrating element are constructed and arranged to ensure radial transfer of energy. Thus, it is preferred that the nozzle array (700) and/or tube (702) is a tight fit within the disc (710) in order to optimise the transfer of ultrasonic energy between the vibrating element and nozzle array. This may be achieved by the arrangement as illustrated in FIG. 20, although other configurations are readily possible, for example, the end of the tube (702) may be provided with a conical surface which fits within a complementary aperture on the metal disc), (Column 6, lines 34-40, Such materials are commercially available, e.g., from 3M, and are typically polymers such as polypropylene or high density polyethylene containing a network of pores of typical diameter <1 mµ. The area of such material in contact with the liquid is generally at a point along the feed tubing between the reservoir and aerosol generator)
Robertson discloses an aerosol drug delivery apparatus, similar to Hu, Denyer, and Rubsamen. It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Robertson’s nozzle array with the existing nebulizer and atomizer structure disclosed by the aforementioned combination, so as to provide an alternative arrangement that can optimize the transfer of energy between elements
Regarding Claim 5, as best understood based on the 35 U.S.C. 112(a) and (b) issues identified above, Hu in view of Denyer, Rubsamen, and Roberston discloses all of the limitations of Claim 3. Rubsamen further discloses: wherein the nozzle further comprises:
a first pipe body, the first pipe body is provided with a first inlet, a first outlet and a first guide channel connecting the first inlet and the first outlet; a second pipe body, the second pipe body is provided with a second inlet, a second outlet and a second guide channel connecting the second inlet and the second outlet; the end of the second pipe body is inserted in the first pipe body, and the second outlet is located between the first inlet and the first outlet (Column 32, lines 6-14, (115) The device shown within FIG. 2 is designed to be reusable. More specifically, the drug delivery device can be "loaded" with a cassette of the type shown within either of FIGS. 3 and 4. The cassette is comprised of an outer cover 30, a canister 3 and top nozzle piece 31. The components are shown in a disassembled state in FIG. 3. A different embodiment of such components are shown in an assembled state within FIG. 4);
the trachea is threaded on the first pipe body, and the first end is located in the first guide channel, and the second end is located at the outer side of the second pipe body (Column 32, lines 14-18, In essence, the cassette shown in FIG. 3 is somewhat less secure than the cassette shown within FIG. 4. As indicated, the top portion of the cover 30 is open within FIG. 3. This allows one to force the canister 3 downward and open the valve 5 to allow release of drug), (Column 24, lines 12-21, FIG. 1 shows a cross-sectional view of a hand-held, portable, electronic breath-actuated inhaler device which can be used in connection with the present invention. The device is shown with a holder 1 having cylindrical side walls and a removable cap. The holder 1 is "loaded" in that it includes the pressurized canister 3. The canister 3 includes a non-metering valve 5 which is held down in the open position when the cap 2 is screwed down, thus setting the valve 5 into a seat 6 which is in connection with a flow path 8).
Regarding Claim 6, as best understood based on the 35 U.S.C. 112(a) and (b) issues identified above, Hu in view of Denyer, Rubsamen, and Roberston discloses all of the limitations of Claim 5. Rubsamen further discloses: wherein the angle between the central axis of the second inlet and the second outlet is 100°- 160° the trachea comprises a first section and a second section that are connected, and the first section and the second section are parallel to the central axis of the second inlet and the second outlet respectively (Figure 2, Paragraphs 0024-0025, lines 62-5, The formulation 4 contained within canister 3 is released into the atmosphere ultimately via nozzle 13 which opens into inspiratory flow path 11. It is at this point that the low boiling point propellant within formulation 4 flashes, i.e. rapidly evaporates, thus providing particles of analgesic drug in an aerosol which is introduced into the mouth and ultimately into the lungs of the patient. In order to allow for ease of use, it is possible to form inspiratory flow path 11 into a mouth piece which can be specifically designed to fit the mouth of a particular patient using the device)
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Sur (US 20190082736 A1).
Regarding Claim 7, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer is silent regarding whether the air pressure sensor is waterproof.
Sur does disclose: wherein the air pressure sensor (Paragraph 0005, a sensor configured to produce measurements of differential pressure between an ambient atmospheric pressure and a pressure caused by airflow through at least a portion of the aerosol delivery device) is a waterproof air pressure sensor (Paragraph 0008, In some example implementations of the aerosol delivery device of any preceding or any subsequent example implementation, or any combination thereof, the sensor and the microprocessor are potted in a waterproof material to thereby make the sensor and the microprocessor waterproof or resistant to water, aerosol precursor composition or vaporize components of the aerosol precursor composition).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Sur’s waterproof material so as to provide an additional degree of protection for the electrical components of the nebulizer assembly disclosed by Hu in view of Denyer.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Rocci et al. (US 5676129 A, hereinafter “Rocci”).
Regarding Claim 8, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer is silent regarding the response time or accuracy range of the air pressure sensor.
Rocci does disclose: wherein the response time range of the air pressure sensor is 1ms~ 1000 ms; the pressure accuracy range of the air pressure sensor is 1Pa~100 hPa (Column 5, lines 19-25, Pressure sensors are available to measure different pressure ranges, the dynamic pressure range of the sensor in the preferred embodiment being -0.58 psi to +5.8 psi, with a sensor response time of 0.8 millisecond. The sensor is electronically connected by a connector 13 to circuitry, as shown in FIG. 4, that includes a microprocessor 14, a Liquid Crystal Display (LCD) 15, and an operational amplifier 16).
It is common in the art of electrical devices and circuitry to have a range of adjustable response times and accuracy ranges. Thus, it would have been obvious to one skilled in the art before the effective filing date to incorporate this art recognized feature with the pressure sensor arrangements disclosed by Hu in view of Denyer.
Claims 9-10 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Stein (US 20120272951 A1).
Regarding Claim 9, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer discloses drug delivery apparatuses, but does not explicitly disclose what medicament or active pharmaceutical ingredient is utilized in said apparatus.
Stein does disclose: A spray assembly, comprising a spray and the atomization trigger structure of claim 1 (Paragraph 0002, Metered Dose Inhalers (MDIs) are widely used for the treatment of respiratory diseases such as asthma, COPD, and allergic rhinitis. MDIs use high-pressure liquefied propellants to atomize the formulation into small droplets capable of delivering drug into the regions of the respiratory tract via oral or nasal inhalation. The drug(s) may be suspended in the formulation or may be dissolved to form a homogeneous solution),
and the active pharmaceutical ingredient in the spray comprises at least one of β2 receptor agonist, glucocorticoid, muscarinic receptor antagonist and phosphodiesterase 4 inhibitor (Paragraph 0033, The pharmaceutical formulations according to the invention may contain one or more drugs (therapeutically or prophylactically active compounds), for example selected from anti-inflammatory agents, anticholinergic agents (particularly an M1, M2, M1/M2 or M3 receptor antagonist), β2 -adrenoreceptor agonists, antiinfective agents (e.g. antibiotics, antivirals), antihistamines, as well as vaccines and vaccine adjuvants).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Stein’s pharmaceutical aerosol formulations with the drug delivery assembly disclosed by Hu in view of Denyer, so as to provide effective administration of medicament for the treatment of various respiratory conditions (Stein, Paragraphs 0003-0005, The size distribution of the delivered drug particles in terms of MMAD and GSD is thus a key factor influencing the therapeutic effectiveness of MDI aerosols. However, it is often difficult to control the MMAD and/or GSD for drugs in solution delivered from an MDI. Moreover, some MDIs contain a combination of drugs where one drug is in solution and the other is in suspension. […] For such suspension-solution combination products it can be even more challenging to achieve delivery of the drugs to a desired location in the respiratory tract)
Regarding Claim 10, Hu in view of Denyer and Stein discloses all of the limitations of Claim 9. Stein further discloses: wherein at least one of:
the β2 receptor agonist comprises at one least of salbutamol or pharmaceutically acceptable salts thereof, fenoterol or pharmaceutically acceptable salts thereof, terbutaline or pharmaceutically acceptable salts thereof, formoterol or pharmaceutically acceptable salts thereof, olodaterol or pharmaceutically acceptable salts thereof, arformoterol or pharmaceutically acceptable salts thereof, indacaterol or pharmaceutically acceptable salts thereof, vilanterol or pharmaceutically acceptable salts thereof (Paragraph 0032, Examples of β2 -adrenoreceptor agonists include salmeterol (e.g. as racemate or a single enantiomer such as the R-enantiomer or the S-enantiomer), salbutamol (e.g. as racemate or a single enantiomer such as the R-enantiomer), formoterol (e.g. as racemate or a single enantiomer such as the R,R-enantiomer), fenoterol, carmoterol, etanterol, naminterol, clenbuterol, pirbuterol, flerbuterol, reproterol, bambuterol, terbutaline salmefamol, indacaterol and salts thereof, for example the xinafoate (1-hydroxy-2-naphthalenecarboxylate) salt of salmeterol, the sulphate salt of salbutamol or the fumarate salt of formoterol).
the glucocorticoids (Paragraph 0047, Non-steroidal compounds having glucocorticoid agonism that may possess selectivity for transrepression over transactivation and that may be useful in combination therapy) comprise at one least of fluticasone or pharmacologically acceptable salts or esters thereof, mometasone or pharmacologically acceptable salts or esters thereof, ciclesonide or pharmacologically acceptable salts or esters thereof, beclomethasone or pharmacologically acceptable salts or esters thereof, flunisolide or pharmacologically acceptable salts or esters thereof, budesonide or pharmacologically acceptable salts or esters thereof, triamcinolone or pharmacologically acceptable salts or esters thereof, dexamethasone or pharmacologically acceptable salts or esters thereof (Paragraph 0046,Suitable anti-inflammatory agents include corticosteroids. Suitable corticosteroids which may be used in combination with the compounds of the invention are those oral and inhaled corticosteroids and their pro-drugs which have anti-inflammatory activity. Examples include methyl prednisolone, prednisolone, dexamethasone, fluticasone propionate, […] beclomethasone esters (eg. the 17-propionate ester or the 17,21-dipropionate ester), budesonide, flunisolide, mometasone esters (eg. the furoate ester), triamcinolone acetonide, rofleponide, ciclesonide […] Preferred corticosteroids include fluticasone propionate).
the muscarinic receptor antagonist comprises at one least of tiotropium or pharmaceutically acceptable salts thereof, glycopyrronium or pharmaceutically acceptable salts thereof, umeclidinium or pharmaceutically acceptable salts thereof, aclidinium or pharmaceutically acceptable salts thereof, ipratropium or pharmaceutically acceptable salts thereof, oxitropium or pharmaceutically acceptable salts thereof, revefenacin or pharmaceutically acceptable salts thereof (Paragraph 0053, Suitable anticholinergic agents are those compounds that act as antagonists at the muscarinic receptors, in particular those compounds which are antagonists of the M1 or M3 receptors, dual antagonists of the M1/M3 or M2/M3, receptors or pan-antagonists of the M1/M2/M3 receptors. Exemplary compounds for administration via inhalation include ipratropium (e.g. as the bromide, CAS 22254-24-6, sold under the name Atrovent), oxitropium (e.g. as the bromide, CAS 30286-75-0) and tiotropium (e.g. as the bromide, CAS136310-93-5, sold under the name Spiriva)).
Regarding Claim 13, Hu in view of Denyer and Stein discloses all of the limitations of Claim 9. Stein further discloses: the phosphodiesterase 4 inhibitor (Paragraph 0049, Combinations including a phosphodiesterase 4 (PDE4) inhibitor may be used. The PDE4-specific inhibitor useful in this aspect of the invention may be any compound that is known to inhibit the PDE4 enzyme or which is discovered to act as a PDE4 inhibitor, and which are only PDE4 inhibitors, not compounds which inhibit other members of the PDE family, such as PDE3 and PDE5, as well as PDE4) comprises at least one of roflumilast or pharmacologically acceptable derivatives thereof, and apremilast or pharmacologically acceptable derivatives thereof (Paragraph 0051. Other compounds of interest include […] roflumilast (CAS reference No 162401-32-3) and a pthalazinone (WO99/47505) from Byk-Gulden).
Regarding Claim 14, Hu in view of Denyer and Stein discloses all of the limitations of Claim 9. Stein further discloses: A method for treating COPD (chronic obstructive pulmonary disease) and/or asthma in a human in need thereof, wherein the method comprises administering to the human a spray assembly of claims 9 (Paragraph 0002, Metered Dose Inhalers (MDIs) are widely used for the treatment of respiratory diseases such as asthma, COPD, and allergic rhinitis. MDIs use high-pressure liquefied propellants to atomize the formulation into small droplets capable of delivering drug into the regions of the respiratory tract via oral or nasal inhalation. The drug(s) may be suspended in the formulation or may be dissolved to form a homogeneous solution).
Claims 15-16 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Jauernig et al. (EP 1712220 A1, hereinafter “Jauernig”).
Regarding Claim 15, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer discloses drug delivery apparatuses, but does not explicitly disclose what medicament or active pharmaceutical ingredient is utilized in said apparatus.
Jauernig does disclose: A spray assembly, comprising a spray and the atomization trigger structure of claim 1 (Paragraph 0129, In this case of application, very simple devices for the generation of the aerosol can, in principle, also be used, for example, mechanical atomizers such as those commonly used for oral or nasal sprays. Alternatively, jet, ultrasonic or piezoelectric vibrating membrane nebulizers can also be used for this purpose which may have to be adapted in the case of nasal application) the active pharmaceutical ingredient in the spray comprises at least one of prostacyclin , treprostinil and iloprost (Paragraph 0103, According to one of the embodiments comprising more than only one active agent, at least one of these compounds is selected from the group consisting of anti-inflammatory drugs, such as corticosteroids, non steroidal anti-inflammatory drugs (NSAIDs), Leukotriene-Antagonists, Betasympathomimetics, Anticholinergics, Phosphodiesterase-inhibitors, potassium channel openers, Tachikinin and kinin antagonists, IgE-synthesis inhibitors, endothelin-receptor antagonists, anesthetics, immunomodulators, antiinfectives, interferones, Vasodilatators, Angiotension Converting Enzyme (ACE) inhibitors, Cytostatics in particular: […] prostacyclins, beraprost, Iloprost).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Jauernig’s pharmaceutical aerosol formulations with the drug delivery assembly disclosed by Hu in view of Denyer, so as to provide effective administration of medicament for the treatment of various respiratory conditions (Jauernig, Paragraph 0032, Another preferred use of the medicament of the invention is for a management of a disease, symptom or condition affecting the bronchial system or the lung. Such diseases include inflammatory processes of the lungs and connecting tissue, such as, asthma, pediatric asthma, obstructive bronchitis, chronic obstructive bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, lung infections, vascular, parenchymal lung disease, such as sarcosidosis, pulmonary fibrosis, or cystic fibrosis, or bronchiolitis obliterans caused e.g. after lung transplantation, or pulmonary hypertension and lung cancer. A particularly preferred condition whose treatment can be substantially improved with the invention is pediatric asthma. The invention allows the highly efficient administration of aerosols comprising poorly soluble glucocorticoids such as budesonide to pediatric patients)
Regarding Claim 16, Hu in view of Denyer and Friedrich discloses all of the limitations of Claim 15. Jauernig further discloses: A method for treating pulmonary arterial hypertension in a human in need thereof, wherein the method comprises administering to the human a spray assembly of claim 15 (Paragraph 0132, Another preferred use of the medicament of the invention is for a management of a disease, symptom or condition affecting the bronchial system or the lung. Such diseases include inflammatory processes of the lungs and connecting tissue, such as, asthma, pediatric asthma, obstructive bronchitis, chronic obstructive bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, lung infections, vascular, parenchymal lung disease, such as sarcosidosis, pulmonary fibrosis, or cystic fibrosis, or bronchiolitis obliterans caused e.g. after lung transplantation, or pulmonary hypertension and lung cancer).
Regarding Claim 21, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer discloses drug delivery apparatuses, but does not explicitly disclose what medicament or active pharmaceutical ingredient is utilized in said apparatus.
Jauernig does disclose: A spray assembly, comprising a spray and the atomization trigger structure of claim 1 (Paragraph 0129, In this case of application, very simple devices for the generation of the aerosol can, in principle, also be used, for example, mechanical atomizers such as those commonly used for oral or nasal sprays. Alternatively, jet, ultrasonic or piezoelectric vibrating membrane nebulizers can also be used for this purpose which may have to be adapted in the case of nasal application), and the active pharmaceutical ingredient in the spray comprises a small molecule cytotoxic drug (Paragraph 0036, An active agent is a substance or mixture of substances which can be used for therapeutic, diagnostic, or prophylactic purposes, or for achieving or maintaining general health and well-being. The active agent can be a chemically defined synthetic ("small") molecule, a naturally derived or synthetic peptide, a protein, a polysaccharide, or a nucleic acid such as RNA or DNA. The active agent may also be referred to as active compound, drug, drug substance, medicinal substance, therapeutic agent, and the like) or a biological agent (Paragraph 0103, According to one of the embodiments comprising more than only one active agent, at least one of these compounds is selected from the group consisting of […] Cytostatics)
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Jauernig’s pharmaceutical aerosol formulations with the drug delivery assembly disclosed by Hu in view of Denyer, so as to provide effective administration of medicament for the treatment of various respiratory conditions (Jauernig, Paragraph 0032, Another preferred use of the medicament of the invention is for a management of a disease, symptom or condition affecting the bronchial system or the lung. Such diseases include inflammatory processes of the lungs and connecting tissue, such as, asthma, pediatric asthma, obstructive bronchitis, chronic obstructive bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, lung infections, vascular, parenchymal lung disease, such as sarcosidosis, pulmonary fibrosis, or cystic fibrosis, or bronchiolitis obliterans caused e.g. after lung transplantation, or pulmonary hypertension and lung cancer. A particularly preferred condition whose treatment can be substantially improved with the invention is pediatric asthma. The invention allows the highly efficient administration of aerosols comprising poorly soluble glucocorticoids such as budesonide to pediatric patients)
Regarding Claim 22, Hu in view of Denyer and Jauernig discloses all of the limitations of Claim 21. Jauernig further discloses: A method for treating lung cancer in a human in need thereof, wherein the method comprises administering to the human a spray assembly of claim 21 (Paragraph 0030, [0030] In another aspect, the invention provides methods for treating a human subject suffering from an inflammatory disease originating from the upper and lower respiratory tract including sinusitis, asthma, pediatric asthma, chronic obstructive bronchitis, bronchiectasis, lung emphysema, parenchymal and vascular lung disease, sarcosidosis, pulmonary and/or cystic fibrosis, pulmonary hypotension, lung cancer).
Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hu (CN 109331302 A) in view of Denyer (US 6584971 B1), further in view of Reinhart et al. (EP 3666315 A1, hereinafter “Reinhart”).
Regarding Claim 17, Hu in view of Denyer discloses all of the limitations of Claim 1. Hu in view of Denyer discloses drug delivery apparatuses, but does not explicitly disclose what medicament or active pharmaceutical ingredient is utilized in said apparatus.
Reinhart does disclose: wherein the active pharmaceutical ingredient in the spray comprises an antibiotic or an antiviral drug (Paragraph 0041, Among the active compounds which may be useful for serving one of the purposes named previously and that may be used together with the present invention, are, for example, substances selected from the group consisting of anti-inflammatory compounds, anti-infective agents, […] , antibiotics, antifungals, antivirals)
the antibiotic comprises at one least of aztreonam, tobramycin, amikacin, ciprofloxacin (Paragraph 0042, Examples of anti-infective agents, whose class or therapeutic category is herein understood as comprising compounds which are effective against bacterial, fungal, and viral infections, i.e. encompassing the classes of antimicrobials, antibiotics, antifungals, antiseptics, and antivirals, are […] monobactams, including aztreonam; - aminoglycosides, such as apramycin, gentamicin, amikacin, isepamicin, arbekacin, tobramycin […] - gyrase inhibitors or fluroquinolones, including ciprofloxacin),
the antiviral drug comprises at least one of zanamivir, Laninamivir, ribavirin (Paragraph 0042, antivirals, including aciclovir, ganciclovir, birivudin, valaciclovir, zidovudine, didanosin, thiacytidin, stavudin, lamivudin, zalcitabin, ribavirin)
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Reinhart’s pharmaceutical aerosol formulations with the drug delivery assembly disclosed by Hu in view of Denyer, so as to provide effective administration of medicament for the treatment of various respiratory conditions and to provide a variety of viable ingredients that can effectively be used in combination with the aforementioned nebulizer arrangements (Reinhart, Paragraphs 50-55).
Regarding Claim 18, Hu in view of Denyer and Reinhart discloses all of the limitations of Claim 17. Reinhart further discloses: A method for treating lung infection in a human in need thereof, wherein the method comprises administering to the human a spray assembly of claim 17 (Paragraph 0040, The active compound comprised in the fluid to be nebulised or aerosolised by the aerosol generator may be a drug substance or a medicament which is useful for the prevention, management, diagnosis or treatment of any disease, symptom or condition affecting the body, skin, body cavities, the abdomen, the eyes, the ear, the intestine, the stomach, the nose, the nasal cavities, the sinuses, the osteomeatal complex, the mouth, the trachea, the lungs, upper lungs, lower lungs, central lungs, the bronchia, the bronchioles, the alveoli and/or the respiratory tract. In particular, the aerosol may comprise an active compound which is useful for the prevention, management, diagnosis or treatment of any pulmonary or respiratory disease, symptom or condition. The active compound comprised in the fluid to be nebulised or aerosolised by the aerosol generator may be used especially for clinical trials or regulatory approvals).
Regarding Claim 19, Hu in view of Denyer and Stein discloses all of the limitations of Claim 1. Hu in view of Denyer discloses drug delivery apparatuses, but does not explicitly disclose what medicament or active pharmaceutical ingredient is utilized in said apparatus.
Reinhart does disclose: the active pharmaceutical ingredient in the spray comprises at least one of pirfenidone, Nintedanib (Paragraph 0041, Examples of potentially useful anti-inflammatory compounds are glucocorticoids and non-steroidal anti-inflammatory agents such as […] pirfenidone), (Paragraph 0042, Examples of anti-infective agents, whose class or therapeutic category is herein understood as comprising compounds which are effective against bacterial, fungal, and viral infections, i.e. encompassing the classes of antimicrobials, antibiotics, antifungals, antiseptics, and antivirals, are […] wound healing compounds, including pirfenidone, dexpantenol, allantoin, vitamins, hyaluronic acid, alpha-antitrypsin, anorganic and organic zinc salts/compounds, salts of bismuth and selen; - antifibrotic compounds, for example, pirfenidone).
It would have been obvious to one skilled in the art before the effective filing date to incorporate the teachings of Reinhart’s pharmaceutical aerosol formulations with the drug delivery assembly disclosed by Hu in view of Denyer. Specifically, incorporating the teachings of the anti-inflammatory, anti-fibrotic, and wound healing compound taught by Reinhart would serve to provide an ingredient that can effectively be used in combination with the aforementioned nebulizer arrangements, and provides multiple potential benefits to a user (Reinhart, Paragraphs 50-55).
Regarding Claim 20, Hu in view of Denyer and Reinhart discloses all of the limitations of Claim 19. Reinhart further discloses: A method for treating idiopathic pulmonary fibrosis in a human in need thereof, wherein the method comprises administering to the human a spray assembly of claim 19 (Paragraph 0059, The aerosol generator, such as a nebuliser, may be used with fluids or liquids of the groups of viral gene therapy agents or non-viral gene therapy agents. The transferred nucleotide constructs may be single or double stranded DNA, RNA, or siRNA. In one study, the gene therapeutic agent carries especially the CF gene to substitute and cure the cystic fibrosis deficiency), (Paragraph 0042, Examples of anti-infective agents, whose class or therapeutic category is herein understood as comprising compounds which are effective against bacterial, fungal, and viral infections, i.e. encompassing the classes of antimicrobials, antibiotics, antifungals, antiseptics, and antivirals, are […] antifibrotic compounds, for example, pirfenidone).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
McLoughlin et al. (US 20180177959 A1) discloses a control device for a medical aerosol delivery device with multiple delivery modes dependent on inhalation data
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/MISHAL HUSSAIN/
Examiner
Art Unit 3785
/BRANDY S LEE/Supervisory Patent Examiner, Art Unit 3785
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