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 .
Election/Restrictions
Receipt is acknowledged of a reply filed on 09/17/25, which includes Amendments to claims in response to the restriction requirement filed on 07/17/25. Applicant has amended claims in such a way that the restriction and Species election requirements are moot. As such the restriction requirement and Species election are withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 5-15, 43-47 are amended, claims 1-4, 16-42 and 48-49 are canceled and new claim 50 is added. Accordingly, claims 5-15, 43-47 and 50 are pending and under examination on the merits.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed on 03/13/23.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/13/23 has been considered by the examiner.
Objections to the Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01 (o).
Correction of the following is required:
Claims 44-45 recite a mass median aerodynamic diameter (MMAD) range or value that are not disclosed in the Specification.
Claims 46-47 recite a mean fine particle fraction (FPF) range of value that are not disclosed in the Specification.
The claims as filed in the original specification are part of the disclosure and therefore, if an application as originally filed contains a claim disclosing material not disclosed in the remainder of the specification, the applicant may amend the specification to include the claimed subject matter. In re Benno, 768 F.2d 1340, 226 USPQ 683 (Fed. Cir. 1985). See MPEP § 2163.06(III) and MPEP § 608.01(o).
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 5-15, 43-47 and 50 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) and In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. See In re Wands, 858 F.2d 731, 737, 8 USPQ 2d 1400, 1404 (Fed. Cir. 1998). The court set forth the eight factors to consider when assessing if a disclosure would require undue experimentation. Citing Ex parte Forman, 230 USPQ 546, the court recited eight factors.
These factors include, but are not limited to:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples,
8) The quantity of experimentation needed to male or use the invention based on the content of the disclosure.
(1 and 2) The breadth of the claims and the nature of the invention: The claims are broad. The claims are drawn to a method of treating a viral lung disease by administering a composition as an aerosol comprising favipiravir, mannitol, hydroxychloroquine, umifenovir, molnupiravir, pimodivir, and/or remdesivir, and/or their water-soluble salt ….. dissolved in a carrier solution.
(3 and 5) The state of the prior art and the level of predictability in the art: The art teaches methods of treating a viral lung disease by inhalation of one or more antiviral agents by inhalation or other routes of delivery. It is known in the art that mannitol is not an antiviral agent or effective in treating a viral lung disease. It is known and disclosed that mannitol is an excipient and is added to formulations as a taste masking agent (See CN 111297838 or the instant Specification). Accordingly, the level of predictability of "viral lung disease" being treatable with a composition comprising mannitol, in the art is very very low.
(6 and 7) The amount of direction provided by the inventors and the existence of working examples: Applicants have provided in the specification disclosure regarding treating a viral lung disease by a composition comprising favipiravir and possibly other antiviral agents disclosed (no examples, test or data provided for other antiviral agents). In view of the lack of any guidance or disclosure on mannitol being effective in treating viral lung disease, further testing would be necessary to use the invention as broadly as claimed.
(8) The quantity of experimentation needed to make or use the invention bases on the content of the disclosure: The quantity of experimentation needed to make and use the invention based on the contents of the disclosure and the unpredictability asserted by the Applicant, is very high and not enabled by the specification.
Conclusion
For the forgoing reasons, the specification is not enabling for the scope of the claims.
In view of the unpredictability in the art, the lack of working examples, the excessive breadth of the claims and lack of guidance in the specification, it would require undue experimentation on the part of the person of skill in the art to practice the full scope of the invention.
Claims 5-15, 43-47 and 50 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) and In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. See In re Wands, 858 F.2d 731, 737, 8 USPQ 2d 1400, 1404 (Fed. Cir. 1998). The court set forth the eight factors to consider when assessing if a disclosure would require undue experimentation. Citing Ex parte Forman, 230 USPQ 546, the court recited eight factors.
These factors include, but are not limited to:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples,
8) The quantity of experimentation needed to male or use the invention based on the content of the disclosure.
(1 and 2) The breadth of the claims and the nature of the invention: The claims are broad. The claims are drawn to a method of treating a viral lung disease by administering a composition as an aerosol comprising favipiravir, mannitol, hydroxychloroquine, umifenovir, molnupiravir, pimodivir, and/or remdesivir, and/or their water-soluble salt ….. dissolved in a carrier solution.
(3 and 5) The state of the prior art and the level of predictability in the art: The art teaches methods of treating viral lung diseases including influenza or COVID-19 by inhalation of active agents such as favipiravir, hydroxychloroquine, umifenovir, molnupiravir, pimodivir, or remdesivir. It is known in the art that not all antiviral active agents can effectively treat ALL viral lung diseases. Accordingly, the level of predictability of "all" viral lung diseases being treatable with the said method, in the art is very low.
(6 and 7) The amount of direction provided by the inventors and the existence of working examples: Applicants have provided in the specification disclosure regarding treating COVID-19 caused by SARS-CoV-2) and influenza. In fact, these are the only two disorders that are named in the specification. In view of the various different disorders known (and not yet known) which may or may not be treatable with favipiravir further testing would be necessary to use the invention as broadly as claimed.
(8) The quantity of experimentation needed to make or use the invention bases on the content of the disclosure: The quantity of experimentation needed to make and use the invention based on the contents of the disclosure and the unpredictability asserted by the Applicant, is very high and not enabled by the specification.
Conclusion
For the forgoing reasons, the specification is not enabling for the scope of the claims.
In view of the unpredictability in the art, the lack of working examples, the excessive breadth of the claims and lack of guidance in the specification, it would require undue experimentation on the part of the person of skill in the art to practice the full scope of the invention.
Claims 5-15, 43-47 and 50 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating a viral lung disease by inhalation of a composition comprising favipiravir, does not reasonably provide enablement for derivatives thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. See In re Wands, 858 F.2d 731, 737, 8 USPQ 2d 1400, 1404 (Fed. Cir. 1998). The court set forth the eight factors to consider when assessing if a disclosure would require undue experimentation. Citing Ex parte Forman, 230 USPQ 546, the court recited eight factors.
These factors include, but are not limited to:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples
8) The quantity of experimentation needed to male or use the invention based on the content of the disclosure.
(1-5) The breadth of the claims, the nature of the invention, the state of the prior art and the level of predictability in the art. The claim is broad. The claim is drawn to a method of treating a viral lung disease by inhalation of a composition comprising favipiravir, mannitol, hydroxychloroquine, … or derivatives thereof. The art teaches favipiravir for use in inhalable pharmaceutical formulations for treating viral lung diseases. However, it is not clear how far the said favipiravir or hydroxychloroquine, … can be derivatized and still maintain their function. Accordingly, the level of predictability of suitability of any derivative of the recited agents in the art is very low.
(6-7) The amount of direction provided by the inventors and the existence of working examples: Applicants have provided in the specification disclosure regarding use of favipiravir formulations for treating viral lung disease.
(8) The quantity of experimentation needed to make or use the invention bases on the content of the disclosure: The quantity of experimentation needed to make and use the invention based on the contents of the disclosure and the unpredictability asserted by the Applicant, is very high and not enabled by the specification.
Summary and conclusion
The term "derivatives" implies a group of favipiravir, …. derivative compounds that, although finite, is large and potentially diverse enough to render the claim indefinite. The term "derivatives" is not defined by the claim, and the specification does not cite examples of specific derivative compounds. It is unclear if these are functional derivatives or structural derivatives and it is unclear how far one may derivatize the said agents/compounds but still retain function. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Examiner suggests removing the term “derivatives”.
For the forgoing reasons, the specification is not enabling for the scope of the claims.
In view of the unpredictability in the art, the lack of working examples, the excessive breadth of the claims and lack of guidance in the specification, it would require undue experimentation on the part of the person of skill in the art to practice the full scope of the invention.
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 8-11 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 8-11 are directed to a composition comprising from 0.01 to 20 mg favipiravir, 0.01-20 mg of mannitol, …. (in claim 8), 0.01-10 mg (in claim 9), 1-10 mg (in claim 10) and 1-5 mg (in claim 11). It is not clear if the dosage range is for a dose on the composition, a dose per mL of the composition (as in claims14-15) or the total amount in the composition for multi-dose (as in claim 43).
Claims are given their broadest reasonable interpretation and herein, the dosage amount is interpretate as encompassing both a single doe or the total amount of the composition (multi-dose).
Claim Interpretations
Claims are directed to a method of treating viral lung diseases comprising administering a composition comprising as an aerosol comprising favipiravir, mannitol, hydroxychloroquine, umifenovir, molnupiravir, pimodivir, and/or remdesivir, and/or their water-soluble salt ….. dissolved in a carrier solution. That is, the claims encompass a composition comprising favipiravir or mannitol or remdesivir, etc.
Claims 8-11 recite an amount range by weight in mg of each component in the composition. It is not disclosed if the said amount range is per dose, per puff (inhalation) or per total weight of the composition as a multi-dose unit.
Claims are given their broadest reasonable interpretation.
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 5-7 are rejected under 35 U.S.C. 102(a)(1) (a)(2) as being anticipated by CN 111297838. (Recitations from attached English translation by Google patents).
CN ‘838 teaches an antiviral drug inhalation spray comprising components in percentage by mass: 0-30% of antiviral active agent, 0-30% of adjuvant, 0-30% of taste masking agent and the balance of solvent, inhaled into the respiratory tract of a patient treating the severe respiratory tract and lung infection caused by the virus. In particular embodiment, the mass percentage of the antiviral active agent is 0.1-10%, preferably 1-5%; the mass percentage of the auxiliary agent is 0.1-10%, preferably 1-5%; the mass percentage of the taste masking agent is 0.1-10%, preferably 1-5% (See Abstract, page 4 and claims 1-2).
Regarding claims 5-6, CN ‘838 teaches the method of administering by inhalation (aerosol) to a subject to treat viral lung infections, comprising 1-10% by mass of an antiviral active and 0.1-10% by mass of a taste masking active and a solvent.
Additionally, CN ‘838 teaches that the said antiviral active agent is an active agent against the novel coronavirus COVID-19, and is selected from one or more of hydroxychloroquine sulfate, chloroquine phosphate, favipiravir, oseltamivir phosphate, ribavirin, rimantadine hydrochloride, etc, (See page 4, 1st, 5th and 11th full para and claim 3).
Regarding claims 5 and 7, it is disclosed that the said antiviral medicinal inhalation spray is filled in an atomizer, preferably an air compression atomizer, a heating atomizer, a vibrating screen micropore atomizer or an ultrasonic atomizer and wherein the said taste masking agent is a sugar alcohol compound selected from one or more of xylitol, sorbitol or mannitol, and the solvent is water, ethanol, etc. The antiviral active is completely dissolved in the solvent (See claims 6-7 and page 5, 4th-7th and 11th para).
Further regarding claim 5, CN ‘838 teaches that the medicine spray (liquid spray) is a preparation which is filled with medicine-containing solution, in a special device, and when in use, the content is released in the form of mist by means of pressure of a manual pump heating and ultrasonic vibration, and the medicine spray (liquid spray) is used for lung inhalation (See page 5, last para).
Example 1 discloses the preparation method comprising the following steps:
(1) taking water, mannitol, propylene glycol, hydroxychloroquine sulfate and essence according to the prescription amount; (2) after complete dissolution, filtering; (3) quantitative filling; (4) and (6) packaging. The medicine spray is put into a proper atomization device, the atomized particle size formed by atomization is 1-5 µm, and the medicine is mainly deposited in the pulmonary tail end alveolus (in the final 5-6 level bronchi) (See Example 1 on pages 7-8).
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.
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.
Claims 5-15, 43-46 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over CN 111297838 (Recitations from attached English translation by Google patents), in view of Dalby et al (A review of the development of Respimat® Soft Mist TM Inhaler) and Coomes et al (Favipiravir, an antiviral for COVID-19?).
CN ‘838 teaches an antiviral drug inhalation spray comprising components in percentage by mass: 0-30% of antiviral active agent, 0-30% of adjuvant, 0-30% of taste masking agent and the balance of solvent, inhaled into the respiratory tract of a patient treating the severe respiratory tract and lung infection caused by the virus. In particular embodiment, the mass percentage of the antiviral active agent is 0.1-10%, preferably 1-5%; the mass percentage of the auxiliary agent is 0.1-10%, preferably 1-5%; the mass percentage of the taste masking agent is 0.1-10%, preferably 1-5% (See Abstract, page 4 and claims 1-2).
Regarding claims 5-6, CN ‘838 teaches the method of administering by inhalation (aerosol) to a subject to treat viral lung infections, comprising 1-10% by mass of an antiviral active and 0.1-10% by mass of a taste masking active and a solvent.
Additionally, CN ‘838 teaches that the said antiviral active agent is an active agent against the novel coronavirus COVID-19, and is selected from one or more of hydroxychloroquine sulfate, chloroquine phosphate, favipiravir, oseltamivir phosphate, ribavirin, rimantadine hydrochloride, etc, (See page 4, 1st, 5th and 11th full para and claim 3).
Regarding claims 5 and 7, it is disclosed that the said antiviral medicinal inhalation spray is filled in an atomizer, preferably an air compression atomizer, a heating atomizer, a vibrating screen micropore atomizer or an ultrasonic atomizer and wherein the said taste masking agent is a sugar alcohol compound selected from one or more of xylitol, sorbitol or mannitol, and the solvent is water, ethanol, etc. The antiviral active is completely dissolved in the solvent (See claims 6-7 and page 5, 4th-7th and 11th para).
Further regarding claim 5, CN ‘838 teaches that the medicine spray (liquid spray) is a preparation which is filled with medicine-containing solution, in a special device, and when in use, the content is released in the form of mist by means of pressure of a manual pump heating and ultrasonic vibration, and the medicine spray (liquid spray) is used for lung inhalation (See page 5, last para).
Example 1 discloses the preparation method comprising the following steps:
(1) taking water, mannitol, propylene glycol, hydroxychloroquine sulfate and essence according to the prescription amount; (2) after complete dissolution, filtering; (3) quantitative filling; (4) and (6) packaging. The medicine spray is put into a proper atomization device, the atomized particle size formed by atomization is 1-5 µm, and the medicine is mainly deposited in the pulmonary tail end alveolus (in the final 5-6 level bronchi) (See Example 1 on pages 7-8).
Regarding claims 8-15, CN ‘838 teaches that the said antiviral drug inhalation spray has a concentration specification of said antiviral active agent and adjuvant of 1 mg-300 mg/ml, preferably 1mg/ml, 5mg/ml, 10mg/ml. The dosage of the drug administered is significantly reduced compared to oral and injection administration, and the actual dose to be taken depends on the concentration of the nebulizer and the frequency of administration, and if the required dose is higher, the concentration of the nebulizer and the frequency of use can be appropriately increased, and vice versa (See page 5, 9th and 10th paras and claim 9).
Regarding claims 44-45 and 50, CN ‘838 teaches that the new coronavirus infection is mainly in nasal cavity and upper respiratory tract in early stage, and develops pneumonia in later stage to burst the whole respiratory system. When the atomized particle size is larger than 15 microns and larger than 10 microns, the medicine stays in the oral cavity and the nasal cavity; when the particle size of the atomized particles is larger than 10 mum and larger than 5 mu m, the medicine can reach the inner part of the first 6-grade branch trachea of the lower respiratory tract; when the atomized particle size is larger than 5 microns and larger than 1 micron, the medicine can reach the pulmonary alveolus at the tail end (in the final 5-6 grade bronchi) (See page 5, 8th para), and that a medicinal inhalation spray for resisting new coronavirus is provided, which is applied to treat novel coronavirus (COVID-19), other coronaviruses, syncytial virus, nipah virus, Hendra virus infection, atypical pneumonia (SARS-CoV), middle east respiratory syndrome (MERS-CoV), and influenza (See page 12, Example 6).
The medicinal inhalation spray of the present application enters the lung in the form of aerosol, which refers to small particles of solid or liquid, a colloidal system dispersed and suspended in a gaseous medium. In medical treatment, the medicine is atomized into aerosol for a patient to inhale to a respiratory system, so that the aim of treating diseases locally and systemically is fulfilled.
CN ‘838 lacks a specific disclosure on the device being soft mist inhaler the concentration in mg or the FPF of the particles. These are either obvious from CN ‘838 or in view of Dalby et al and Coomes et al.
Specifically, CN ‘838 teaches that the inhalation can be via mist, but does not expressly disclose a soft mist inhaler is used. Dalby et al renders this feature obvious.
Regarding claims 5, 46 and 47, Dalby et al teach that the Respimat® Soft Mist™ Inhaler (SMI) Respimat® Soft Mist™ Inhaler (SMI) is a new generation inhaler from Boehringer Ingelheim developed for use with respiratory drugs. The device functions by forcing a metered dose of drug solution through a unique and precisely engineered nozzle (the uniblock), producing two fine jets of liquid that converge at a pre-set angle. The collision of these two jets generates the soft mist. The soft mist contains a high fine particle fraction (FPF) of approximately 65 to 80%. The features of the soft mist, result in larger amounts of the drug reaching the lungs and less being deposited in the oropharynx compared with either pMDIs or DPIs. Generation of the soft mist from Respimat® SMI is purely mechanical, so propellants are not necessary. The innovative design of Respimat® SMI, using water-based drug formulations, ensures patients receive consistent and reliable doses of the drug with each actuation. Clinical studies have confirmed that Respimat® SMI is effective and safe in delivering bronchodilators to patients with asthma or chronic obstructive pulmonary disease (See abstract).
Regarding claim 43, it is disclosed that Respimat® SMI is a new generation, propellant-free, multi-dose inhaler developed by Boehringer Ingelheim. The term ‘soft mist’ is used to describe both the mechanism of aerosol generation and the qualities of the aerosol cloud, and represents an innovative approach to patient-oriented inhalation therapy (See page 2, 2nd col, 2.).
Regarding claims 44-45, CN ‘838 teach the different size ranges for deposition in each part of the respiratory system and that particles from 5 to 10 microns deposit in the lower and upper part of the respiratory system. Dalby et al also teach that the efficacy of an inhaled drug is largely dependent on the amount of the drug deposited in the lungs and its topographical anatomical distribution. It may be possible to deliver drugs more precisely by using aerosols with a defined particle size distribution; for example, particles with a diameter of 2–5 μm are generally deposited in the smaller bronchioles and peripheral airways. Larger particles tend to be deposited in the upper airways, whereas those smaller than 2 μm are, to a large extent, breathed in and out of the alveoli with minimal actual deposition (See page 2, 1st col). Dalby et al also disclose in Fig. 5, typical aerodynamic particle size distribution for the aerosol generated by Respimat® Soft Mist™ Inhaler, using an aqueous drug solution and an Andersen cascade impactor (See page 6, 2nd col).
Dalby et al conclude that “Respimat® SMI has been shown to allow a reduction in the dose of a combination bronchodilator compared with delivery via CFC-MDI, while offering the same level of therapeutic efficacy and safety. Therefore, the development of Respimat® SMI represents a significant step forward in pulmonary drug delivery (See Conclusion on page 8).
Regarding claims 8-15, CN ‘838 teaches that the concentration specification of said antiviral active agent and adjuvant is from 1mg-300 mg/ml, preferably 1mg/ml, 5mg/ml, 10mg/ml. The dosage of the drug administered is significantly reduced compared to oral and injection administration, and the actual dose to be taken depends on the concentration of the nebulizer and the frequency of administration, and if the required dose is higher, the concentration of the nebulizer and the frequency of use can be appropriately increased, and vice versa (See page 5, 9th and 10th paras and claim 9).
Additionally, Coomes et al teach that patients with COVID-19, SARS-CoV-2, respiratory infections have been treated with favipiravir at doses of 600-800 mg orally (See article).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Coomes et al and Dalby et al with CN ‘838 to arrive at the instant invention with a reasonable expectation of success. It would have been obvious to do so because CN ‘838 teaches a method of treating viral lung disease by administering to a subject via inhalation (aerosol) a composition comprising an antiviral active including favipiravir or hydroxychloroquine, a taste masking agent including mannitol and a solvent including water or water and ethanol. The said compositions are delivered via an ultrasonic vibration or mist. Additionally, Dalby et al teach that a soft mist inhaler can advantageously by used for delivering medicinal compositions to the respiratory system wherein the higher amount of the medicine reaches the lung and thus smaller doses can be used. This is in addition to fact that soft mist inhalers are better for environment and have other advantages. Thus, one of ordinary skill in the art is more than motivated to deliver CN ‘838’s compositions to the subject via Dalby et al’s soft mist inhaler and be able to not only reduce the dosage but achieve better results and be less harmful to the environment. In other words, the claims would have been obvious because the technique for improving a particular formulation (delivery method) was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations.
It also would have been obvious to one of ordinary skill in the art to select from or adjust the dosage amount or concentration of the said antiviral active agents of CN ‘838 because CN ‘838 discloses suitable ranges and teach that the amount of the medicament administered via inhalation is much less than its oral dosage. Dalby et al teach that using soft mist inhalers are more effective in delivering the medicinal formulation to the respiratory system and as such less of the said active agents is needed. Furthermore, Coomes et al teach that suitable oral doses of favipiravir include 600 or 800 mg. Thus, the combination of references would have led one of ordinary skill in the art to optimize and adjust the dosage and the concentration of the antiviral active agent for the desired treatment.
In this regard the courts have held that “[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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed.Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). (See MPEP 2144.05).
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 5, 43-47 are rejected under 35 U.S.C. 103 as being unpatentable over CN 111297838 (Recitations from attached English translation by Google patents), in view of Surber (US 20150044288).
Teachings of CN ‘838 are delineated above and incorporated herein.
CN ‘838 does not teach an FPF range or value for the delivered liquid formulation. This would have been known to one of ordinary skill in the art as taught by Surber.
Surber teach formulations of imatinib or a phenylaminopyrimidine derivative compound for aerosolization and use of such formulations for inhaled aerosol administration (See abstract).
Regarding claim 5, Surber teach administration of such formulation via a nebulizer including a liquid nebulizer. The said nebulizer may be an ultrasonic nebulizer, a pulsating membrane nebulizer, a nebulizer comprising a vibrating mesh or plate with multiple apertures, or a nebulizer comprising a vibration generator and an aqueous chamber.
Regarding claim 43, Surber teach that the said nebulizers contain two or more doses of the active compound. There is no limit to the total number of containers provided in a multi-dose kit (See [0434]).
Regarding claims 44-47, Surber teach a formulation having a mass median aerodynamic diameter (MMAD) of droplet size of the aqueous solution emitted with the vibration generator of about 1 μm to about 5 μm; and a fine particle fraction (FPF=%≦5 microns) of droplets emitted from the liquid nebulizer of at least about 30%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65% (See [0020]-[0021]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Surber with CN ‘838 to arrive at the instant invention with a reasonable expectation of success. It would have been obvious to do so because CN ‘838 teaches a method of treating viral lung disease by administering to a subject via inhalation (aerosol) a composition comprising an antiviral active including favipiravir or hydroxychloroquine, a taste masking agent including mannitol and a solvent including water or water and ethanol. The said compositions are delivered via an ultrasonic or vibrating mesh. However, CN ‘838 is silent with regard to the fine particle fraction of the formulation or delivered dose. One of ordinary skill in the art would have been motivated to have incorporated this feature from Surber because it is disclosed that formulations delivered via a vibrating mesh nebulizer can deliver a dose with FPF of from 30% to over 60%.
That is, the combination of references would have led one of ordinary skill in the art to the claimed invention.
Claims 5-15, 43-47 and 50 are rejected.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616