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
Non-patent literature reference Levy, L.M, et.al., J. Comp. Asst. Tomog. 1998, Vol 22, pg760-770 in the information disclosure statement filed 7/12/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference.
Non-patent literature reference Agarwal, et. al., Bio. Tr. Elm. Res., 1985, Vol. 7, pgs. 199-208 in the information disclosure statement filed 7/12/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference. The reference is not compliant because there is no copy provided.
Non-patent literature reference MWV Healthcare MK Sprayer in the information disclosure statement filed 7/12/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference. The reference is not compliant because the entirety of the reference is not provided.
Non-patent literature reference Maitra, et. al., The pancreas in Pathological Basis of Disease, 7th Edition, Elsevier, 2004, p1155-1207 in the information disclosure statement filed 7/12/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference. The reference is not compliant because the cited relevant pages are not included in the copy provided.
Non-patent literature reference Doerty, A.E. et. al., J. Invest. Med. 1997, Vol. 45, 237A in the information disclosure statement filed 7/12/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference. The reference is not compliant because the copy provided is illegible.
Non-patent literature reference number 3 in the information disclosure statement filed 11/12/2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered because it appears that the entire contents of the reference have not been included in the supplied reference. The reference is not compliant because there is no copy provided.
Priority
The instant application is a continuation application of PCT/US2023/060168 which claims priority to provisional application 63/297,060 with a filing date of 1/6/2022, provisional application 63/404,227 with a priority date of 9/7/2022, and provisional application 63/418,663 with a priority date of 10/24/2022. The instant claims are examined with an effective priority date of 1/6/2022.
Status of the Claims
Claims 1, 3-13, 15, 18-20, 22, 24-25, 31, 35-36, 41, and 43-45 are pending and under current examination.
Claim Rejections - 35 USC § 112
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 1, 3-13, 15, 18-20, 22, 24-25, 31, 35-36, 41, and 43-45 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.
Claims 1, 3-4, 8-9,15, 25, 31, 35-36, 41, and 43-45 recite the limitation “about”. The instant specification defines “about” to mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art (instant specification at [33]). However, this definition does not provide a clear definition as to what about may mean for a particular value in the claim, therefore it is impossible to discern the metes and bounds of the claims.
Claim 5 recites the limitation “wherein a droplet size is measured by laser diffraction”. This renders the claim indefinite because it is not clear if all of the droplets of the independent claim 1 are measured by laser diffraction.
Regarding claim 9, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “10µL to about 200µL”, and the claim also recites “20µL to about 80µL” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 15, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 15 recites the broad recitation “5% to about 100%”, and the claim also recites “15% to about 50%, about 10% to about 80%, about 5% to about 90%” which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 20 recites the limitation “wherein the second therapeutic is administered concurrently or consecutively with the administering”. This renders the claim indefinite because it is not clear if the phrase “with the administering” refers to the refers to the administration of a PDE inhibitor as recited in the independent claim 1.
Regarding claim 35, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 35 recites the broad recitation “5µm”, and the claim also recites “3µm” and “4µm” which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claims 6-7, 10-13, 18-19, 22, and 24, claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-7, 10-13, 15, 19-20, 22, 24-25, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Henkin (U.S. Patent Application No. 2015/0297601, publication year: 2015, cited in the IDS filed 7/12/2024) in view of Malvern Panalytical (available 2020).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1 and 7, Henkin teaches multi-dose nasal spray devices for delivery of theophylline to a human’s nasal epithelium that delivers a dosage unit in a plume upon actuation. The dosage unit comprises theophylline in a pharmaceutically acceptable carrier comprising one or more excipients. The plume is characterized by a D90 of less than 200µm, wherein 90% of the droplets in the plume have a size less than the D90 [0004]. The pharmaceutically acceptable carrier may be a liquid carrier [0039]. The composition may be used in a method to prevent or treat diseases associated with or caused by the increased metabolism of cAMP, such as Parkinson’s disease [0140]. The pharmaceutical dosage unit comprises an effective amount of theophylline for treating anosmia, hyposmia, dysosmia, ageusia, hypogeusia, or dysgeusia in a human in need thereof [0155].
Regarding claims 3 and 4, Henkin teaches that the droplets have a D50 of from 30 to 70µm, wherein 50% of the droplets in the plume have a size less than D50 [0004].
Regarding claim 5, Henkin teaches the relevant limitations of claim 1 above.
Regarding claims 6 and 7, Henkin teaches multi-dose nasal spray devices for delivery of theophylline to a human’s nasal epithelium that delivers a dosage unit in a plume upon actuation [0004]. Theophylline is a non-selective PDE inhibitor [0056].
Regarding claims 10-13, Henkin teaches that the pharmaceutically acceptable liquid carrier comprises water, a viscosity adjusting agent, a buffering agent, a flavoring agent, a humectant, a penetration enhancer, a pH adjusting agent, a present , a solvent or co-solvent, a surfactant, a tonicity adjusting agent, or a combination thereof [0173].
Regarding claim 15, Henkin does not disclose the nasal cavity coverage properties as recited in claim 15. However, the invention as claimed is not structurally distinguishable from the disclosure of Henkin and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Regarding claim 19, Henkin teaches that a subject receiving treatment experiences a clinically detectable improvement in taste or small function [0023]. The instant specification defines treatment of chemosensory dysfunction in Parkinson’s disease to include Parkinson’s associated taste and/or smell loss [115 of instant specification], therefore the Examiner considers the teachings of Henkin to read on the “chemosensory disorder” limitation of the instant claim 19.
Regarding claims 20 and 22, Henkin teaches that the patient may be administered a therapeutically effective amount of a PDE inhibitor and a vasoactive agent such as apomorphine [0139].
Regarding claim 24, Henkin teaches that the theophylline formulations and dosage units provided can be used in a nasal spray and be delivered in a plume [0158].
Regarding claim 25, Henkin teaches that individual or single intranasal dose of the PDE inhibitors ranges from 1µg to 10 mg [0149].
Regarding claim 31, Henkin teaches that the plume is characterized by a D10 of greater than 12.5µm, wherein 10% of the droplets in the plume have a size less than the D10.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 1, 3, and 4, Henkin does not teach a D90 or D50 within the range embraced by the instant claims. However, this deficiency is cured by Malvern Panalytical.
Malvern Panalytical teaches that most nasal spray pumps produce droplet in the range from 20µm to around 120µm. The droplet size should be such that the droplets deposit within the nasal passages. If the droplet size is too fine there is a possibility that the particles will pass through the nasal passages and deposit in the lungs. This could lead to the deposition of drug particles and excipients that are not approved for pulmonary absorption. On the other hand, if the droplet size is too large, the spray may be trapped in the nostrils (pg. 2, Droplet Size Characterization).
Regarding claim 5, Henkin does not teach that the droplet size is measured by laser diffraction. However, this deficiency is cured by Malvern Panalytical.
Malvern Panalytical teaches that the FDA’s draft guidance recommends the use of laser diffraction to determine the droplet size produced for a given device and formulation. Laser diffraction systems allows the changes in droplet size during pump actuation to be followed in real-time, enabling the atomization dynamics to be assessed (pg. 2, Droplet Size Characterization).
Regarding claim 25, Henkin does not teach a number of unit doses per nasal spray device.
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding the droplet size of the spray as specified in claims 1, 3, and 4, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Malvern Panalytical teaches that the droplet size of a nasal spray has a direct effect on the deposition of the droplets within the nasal passages and the absorption of the drug into the nasal passages. The Applicants' specification provides no evidence that the selected droplet size ranges in claims 1, 3, and 4 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the direct effect droplet size has on the deposition of absorption of a drug contained within a nasal spray, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the droplet size of the spray embraced by Henkin. One of ordinary skill in the art would have been motivated to change the droplet size as this could be expected to be advantageous for achieving the desired deposition and absorption profile of the drug.
Regarding claim 5, it would have been prima facie obvious to one of ordinary skill in the art of filing to utilize laser diffraction to measure droplet size. One would have understood in view of Malvern Panalytical that laser diffraction is the FDA-recommended method of measuring droplet size of nasal spray formulations. It would have been obvious to utilize laser diffraction to measure the droplet size of the nasal spray taught by Henkin. One of ordinary skill in the art of filing would have been motivated to utilize laser diffraction to measure droplet size in order to utilize the real-time analysis of droplet size offered by the method. The artisan of ordinary skill in the art would have had reasonable expectation of success because Malvern Panalytical teaches that laser diffraction is the FDA-recommended method to measure droplet size in nasal spray formulations.
Regarding claim 25, the number of unit doses present in the nasal delivery device is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal number of doses present in the nasal delivery device in order to best achieve the desired results as such would provide an advantageous amount of unit doses available to the user. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Henkin teaches multi-dose nasal spray devices for delivery of theophylline to a human’s nasal epithelium that delivers a dosage unit in a plume upon actuation. The dosage unit comprises theophylline in a pharmaceutically acceptable carrier comprising one or more excipients [0004]. The Examiner considers it prima facie obvious to optimize the number of doses present in a nasal spray device, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the number of unit doses present in the nasal spray device would have a direct effect on the number of doses available to the patient and therefore be an optimizable variable.
Claims 8-9 and 35-36 are rejected under 35 U.S.C. 103 as being unpatentable over Henkin (U.S. Patent Application No. 2015/0297601, publication year: 2015, cited in the IDS filed 7/12/2024) in view of Malvern Panalytical (available 2020), as applied to claims 1, 3-7, 10-13, 15, 19-20, 22, 24-25, and 31 above, and further in view of Medspray (Ultra-soft Nasal Sprays, available 2019, cited in the IDS filed 7/1/2026).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 8, 35, and 36, Henkin teaches the relevant limitations of claim 1 above.
Regarding claim 9, Henkin teaches that the volume of the dosage unit is from about 50-750µL [0078].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 8, 35, and 36, Henkin does not teach a duration of the plume, a nozzle pore size, or a number of nozzle pores. However, this deficiency is cured by Medspray.
Medspray teaches spray nozzles providing a slow-moving, ultra-fine mist without using fast evaporating propellants or excipients (pg. 2). The sprays may deliver a dose volume of 25-100µL, a droplet size of from 20 to 100µm, and a spray time of 1 to 3 seconds (pg. 2). Engineering the size (1-30µm), number of pores (1-200), vectors and geometric pattern means the industry can tailor the spray application (pg. 2). These nozzle pores with low flow resistance enable nasal spray devices to create an ultra-soft, slow-moving mist that limits dripping and flow into consumers’ throat, is preservative-free, completely silent, and avoids the need for a specific head positioning or propellants (pg. 1).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 8, 35, and 36, it would have been prima facie obvious to one of ordinary skill in the art of filing to utilize a nasal spray with the spray duration, nozzle pore size, and number of pores taught by Medspray. One would have understood in view of Medspray that a spray nozzle with a dose volume of 25-100µL, a droplet size of from 20 to 100µm, and a spray time of 1 to 3 seconds (pg. 2) have low-flow resistance that enables nasal spray devices to create an ultra-soft, slow-moving mist that limits dripping and flow into consumers’ throat, is preservative-free, completely silent, and avoids the need for a specific head positioning or propellants (pg. 1). It would have been obvious to utilize such a spray nozzle in the nasal spray device of Henkin. One of ordinary skill in the art of filing would have been motivated to utilize the spray nozzle of Medspray in order to utilize the ultra-soft, slow-moving mist that limits dripping and flow into consumers’ throat, is preservative-free, completely silent, and avoids the need for a specific head positioning or propellants (pg. 1). The artisan of ordinary skill in the art would have had reasonable expectation of success because Medspray teaches that their spray nozzles are compatible with nasal sprays.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Henkin (U.S. Patent Application No. 2015/0297601, publication year: 2015, cited in the IDS filed 7/12/2024) in view of Malvern Panalytical (available 2020), as applied to claims 1, 3-7, 10-13, 15, 19-20, 22, 24-25, and 31 above, and further in view of Haehner et. al. (Movement Disorders, pg. 839-842, publication year: 2007).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Henkin teaches that the composition may be used in a method to prevent or treat diseases associated with or caused by the increased metabolism of cAMP, such as Parkinson’s disease [0140]. In some embodiments, the subject experiences a clinically detectable improvement in taste or smell function within 1-4 weeks of starting treatment [0023].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Henkin does not teach that the Parkinson’s disease may be any of the Parkinson’s diseases embraced by the instant claim. However, this deficiency is cured by Haehner.
Haehner teaches that olfactory dysfunction is a very early sign of idiopathic Parkinson’s disease (pg. 839, Abstract).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing to utilize the treatment of Henkin to treat idiopathic Parkinson’s disease. One would have understood in view of Haehner that olfactory dysfunction is a very early sign of idiopathic Parkinson’s disease. It would have been obvious that a composition that increases taste or smell function in patients with Parkinson’s disease may be used to treat the olfactory dysfunction associated with idiopathic Parkinson’s disease. One of ordinary skill in the art of filing would have been motivated to utilize the composition of Henkin to treat idiopathic Parkinson’s disease in order to improve taste and smell function in the patient. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Haehner teaches that olfactory dysfunction is a very early sign of idiopathic Parkinson’s disease.
Claims 41 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Hoekman (U.S. Patent Application No. 2022/0296504, filing date: 10/11/2021) in view of Malvern Panalytical (available 2020).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 41 and 44, Hoekman teaches a method for treating off episodes in a patient with Parkinson’s disease comprising administering to a subject an effective intranasal dose of levodopa [0005]. The composition further comprises hydroxypropyl methyl cellulose [0007]. In the method, the dose is administered by an intranasal delivery device that delivers a powder to the nasal cavity [0082]. The compound contained within the nasal spray device may be a liquid or a powder [0096]. The nasal spray device targets a specific region of the nasal cavity utilizing a narrow, targeted delivery plume [0095]. The median diameter of levodopa particle size distribution (D50) is 5µm-500µm [0126].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 41 and 44, Hoekman does not teach a D90 of the particles produced by the nasal delivery device. However, this deficiency is cured by Malvern Panalytical.
Malvern Panalytical teaches that most nasal spray pumps produce droplet in the range from 20µm to around 120µm. The droplet size should be such that the droplets deposit within the nasal passages. If the droplet size is too fine there is a possibility that the particles will pass through the nasal passages and deposit in the lungs. This could lead to the deposition of drug particles and excipients that are not approved for pulmonary absorption. On the other hand, if the droplet size is too large, the spray may be trapped in the nostrils (pg. 2, Droplet Size Characterization).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding the droplet size of the spray as specified in claims 41 and 44, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Malvern Panalytical teaches that the droplet size of a nasal spray has a direct effect on the deposition of the droplets within the nasal passages and the absorption of the drug into the nasal passages. The Applicants' specification provides no evidence that the selected droplet size range in claims 41 and 44 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the direct effect droplet size has on the deposition of absorption of a drug contained within a nasal spray, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the droplet size of the spray embraced by Hoekman. One of ordinary skill in the art would have been motivated to change the droplet size as this could be expected to be advantageous for achieving the desired deposition and absorption profile of the drug.
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Illum (U.S. Patent No. 6,342,251, issue date: 1/29/2002) in view of Malvern Panalytical (available 2020).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Illum teaches a method for treating Parkinson’s disease comprising the nasal administration of a liquid composition comprising apomorphine and at least one or more excipients (Claims 1, 23, and 24). The formulation in the form of a liquid can be administered using a nasal spray device (col. 9 lines 46-47). With regards to the “plume” and “plurality of droplets” limitations of instant claim 43, the prior art teaches the same nasal spray device as claimed and therefore, the plume and plurality of droplets properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (I) which states: “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established”
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Illum does not teach a D90 of the particles produced by the nasal delivery device. However, this deficiency is cured by Malvern Panalytical.
Malvern Panalytical teaches that most nasal spray pumps produce droplet in the range from 20µm to around 120µm. The droplet size should be such that the droplets deposit within the nasal passages. If the droplet size is too fine there is a possibility that the particles will pass through the nasal passages and deposit in the lungs. This could lead to the deposition of drug particles and excipients that are not approved for pulmonary absorption. On the other hand, if the droplet size is too large, the spray may be trapped in the nostrils (pg. 2, Droplet Size Characterization).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding the droplet size of the spray as specified in claim 43, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Malvern Panalytical teaches that the droplet size of a nasal spray has a direct effect on the deposition of the droplets within the nasal passages and the absorption of the drug into the nasal passages. The Applicants' specification provides no evidence that the selected droplet size range in claim 43 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the direct effect droplet size has on the deposition of absorption of a drug contained within a nasal spray, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the droplet size of the spray embraced by Illum. One of ordinary skill in the art would have been motivated to change the droplet size as this could be expected to be advantageous for achieving the desired deposition and absorption profile of the drug.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Farmer (U.S. Patent No. 12,059,447, filing date: 8/8/2020) in view of Malvern Panalytical (available 2020).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Farmer teaches a method for treating neurological conditions comprising administration of a composition comprising donepezil, rivastigmine, galanthamine, tacrine, memantine, riluzole, edaravone, tetrabenzine, and amantadine (col. 12 lines 26-34). In preferred embodiments, the composition is administered to the subject nasally (col. 4 line 31) and may be made into aerosol formulations so that it can be sprayed (col. 12 line 47). Formulations for nasal aerosol administration may also be formulated with illustrative carriers (col. 12 line 51). With regards to the “plume” and “plurality of droplets” limitations of instant claim 45, the prior art teaches the same nasal spray device as claimed and therefore, the plume and plurality of droplets properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (I) which states: “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established”
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Farmer does not teach a D90 of the particles produced by the nasal delivery device. However, this deficiency is cured by Malvern Panalytical.
Malvern Panalytical teaches that most nasal spray pumps produce droplet in the range from 20µm to around 120µm. The droplet size should be such that the droplets deposit within the nasal passages. If the droplet size is too fine there is a possibility that the particles will pass through the nasal passages and deposit in the lungs. This could lead to the deposition of drug particles and excipients that are not approved for pulmonary absorption. On the other hand, if the droplet size is too large, the spray may be trapped in the nostrils (pg. 2, Droplet Size Characterization).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding the droplet size of the spray as specified in claim 45, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Malvern Panalytical teaches that the droplet size of a nasal spray has a direct effect on the deposition of the droplets within the nasal passages and the absorption of the drug into the nasal passages. The Applicants' specification provides no evidence that the selected droplet size range in claim 45 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the direct effect droplet size has on the deposition of absorption of a drug contained within a nasal spray, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the droplet size of the spray embraced by Farmer. One of ordinary skill in the art would have been motivated to change the droplet size as this could be expected to be advantageous for achieving the desired deposition and absorption profile of the drug.
Conclusion
No claims are allowed.
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/ELIZABETH ANNE MEYERS/Examiner, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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