DETAILED ACTION
Claims 10, 14-15, 22-24, 27-30, 35-43 are currently pending. Claims 10, 14, 22, 24, 27-30, 35-36, 38-39 and 41 are currently under examination.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/22/2025 has been entered.
Election/Restrictions
Claims 42-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/11/2022. Newly added claims 42-43 are directed to other than the elected capsaicin, hypertonic saline and non-cystic fibrosis bronchiectasis.
Withdrawn Rejections
The prior rejection of claim(s) 10, 14, 21-22, 24, 27-30, 32, 35-36, 38-39 and 41 under 35 U.S.C. 103 as being unpatentable over US 2008/0260863 in view of US 2001/0024801 and US 2015/0065539 as evidenced by NIH is withdrawn in light of Applicant amended the instant claim to specify wherein the subject does not have cystic fibrosis that the ‘863 publication, the ‘801 publication and the ‘539 publication does not teach.
Examiner’s Note
Applicant's amendments and arguments filed 09/22/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 09/22/2025, it is noted that claims 10 and 30 have been amended. No new matter or claims have been added.
New Rejections:
The following rejections are newly applied based on Applicant’s claim amendments.
Claim Rejections - 35 USC § 112 (b)
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 10, 14, 22, 24, 27-30, 35-36, 38-39 and 41 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 10 and 30 are directed to “wherein the duration and/or intensity of treatment effects of HTS or ITS treatment is increased in comparison to the duration and/or intensity of treatment effects of HTS or ITS treatment when administered alone”. The limitation of treatment effect is not defined and thus it is unclear what effect is increased, e.g. mucociliary clearance. Additionally, it appears Applicant is comparing HTS/ITS treatment to itself, as the first recitation does not clearly recite in combination with the neuronal agonist. Thus the instant claim has unclear metes an bounds. Claims 14, 22, 24, 27-29, 35-36, 38-39 and 41 are further rejection as being dependent on claims 10 and 30 and not clarifying the ambiguity of the claims.
Modified Rejections:
The following rejections are modified based on Applicant’s claim amendments.
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.
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.
Claim(s) 10, 14, 22, 24, 27-30, 35-36, 38-39 and 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over McShane (previously applied) in view of US 2015/0065539 (previously applied).
Regarding claim 10, 24, 27, 30, 35 and 41, the limitation of a method of increasing mucociliary clearance in a subject in need thereof comprising administering hypertonic saline (HTS) treatment or isotonic saline (ITS) treatment, wherein the subject has one or more non-cystic fibrosis respiratory diseases, disorder or conditions treatable by increasing mucociliary clearance, wherein the subject does not have cystic fibrosis is met by McShane teaches non-cystic fibrosis bronchiectasis (abstract). The goal of airway clearance is to mobilize bronchopulmonary secretion and interrupt the vicious cycle of inflammation and infection. Airway clearance employs an inhaled agent (e.g. 7% hypertonic saline) in conjunction with chest physiotherapy have significant improvements in quality-of-life scores and exercise capacity were achieved in patients using the PEP device twice daily for 3 months (page 650, second column, third paragraph). Nebulized hypertonic saline improved clearance of mucus by reducing osmolality and making it easier to clear (pgs. 651, first column, second paragraph).
Regarding claims 14 and 38-39, the limitation of wherein the one or more non-cystic fibrosis respiratory diseases include bronchiectasis is met by McShane teaching non-cystic fibrosis bronchiectasis (abstract, title).
Regarding claim 28 wherein the HTS treatment has a NaCl concentration of about 1% to 40% w/v is met by McShane teaching nebulized hypertonic saline improved clearance of mucus by reducing osmolality and making it easier to clear (pgs. 651, first column, second paragraph). NIH evidences hypertonic saline is any solution of sodium chloride (NaCl) in water at a concentration of higher than 0.9% w/v (page 1).
McShane does not specifically teach administering an effective amount of one or more neuronal agonists selected from capsaicin (claim 10, 22, 27, 35-36).
The ‘539 publication teaches increasing mucociliary clearance in a subject. The compounds are effective in increasing the depth of ASL, thereby increasing mucociliary clearance in the subject (abstract). Mucous stasis and increased mucous production are common problems that impact a variety of human conditions. A number of diseases and/or conditions may lead to suboptimal mucous clearance and/or excess mucous production [0002]. The compounds useful include any known activators of cellular mucociliary clearance including capsaicin [0032]. Increasing mucociliary clearance in a subject is taught including administering to a subject an amount of activator compound capable of enhancing the ability of the cellular mucociliary clearance apparatus [0046]. The active agent can be administered as a liquid dosage form or by inhalation via the pulmonary system [0073]. Formulations are taught to include saline solutions [0083]. Hypertonic saltine is taught to be used [0110]. Increased ASL is taught (abstract, reading on claim 29).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of HTS and capsaicin to improve mucociliary clearance as McShane teaches HTS being used to mobilize bronchopulmonary secretions to treat non-CF bronchiectasis and the ‘539 publication teaches capsaicin being used for mucociliary clearance to treat non-CF diseases. It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of two ingredients, HTS and capsaicin, both known to improve mucous clearance to treat non-CF diseases. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success in using the combination of HTS and capsaicin for inhalation as the ‘539 publication teaches inhalable compositions including capsaicin and saline solutions.
Regarding the limitation of wherein the duration and/or intensity of treatment effects of HTS or ITS treatment is increased in comparison to the duration and/or intensity of treatment effects of HTS or ITS treatment when administered alone is met by the ‘539 publication teaching increasing mucociliary clearance in a subject (abstract) thus it would be obvious that the addition of capsaicin, a known mucociliary clearing ingredient, would lead to increased intensity of treatment effects of HTS or ITS in comparison to HTS or ITS used alone, as adding an ingredient known to increase mucociliary clearance would result in increased mucociliary clearance.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
Applicant argues in the previous response of March 10, 2025 they have surprisingly found that HTS or ITS treatment causes airway surface layer production in part through stimulation of the nervous system. Mention and/or capsaicin can be used in combination with HTS or ITS to surprisingly increase ASL secretion, increase mucociliary clearance and also increase the intensity and/or duration of treatment effects of the HTS or ITS or the treatment compared to when the HTS or ITS treatment is administered alone.
In response, the ‘539 publication teaches the use of capsaicin to improve mucociliary clearance, thus the addition of capsaicin to HTS leading to improve mucociliary clearance is not considered unexpected.
Applicant argues Example 2 demonstrates HTS or ITS treatment along with exemplary neuronal agonists and other nervous system modulators in wild type and CF swine. It was surprisingly found that ASL secretion in response to HTS treatment was different between wild and cystic fibrosis pigs. It was found that adding exemplary neuronal agonists capsaicin and menthol to HTS or ITS increases the volume of fluid produced and prolongs duration of action of HTS or ITS in vivo and also increased the duration of HTS-triggered mucociliary clearance in wild-type swine (Figure 14).
In response, the ‘539 publication teaches increasing mucociliary clearance in a subject. The compounds are effective in increasing the depth of ASL, thereby increasing mucociliary clearance in the subject (abstract). Mucous stasis and increased mucous production are common problems that impact a variety of human conditions. A number of diseases and/or conditions may lead to suboptimal mucous clearance and/or excess mucous production [0002]. The compounds useful include any known activators of cellular mucociliary clearance including capsaicin [0032]. Increasing mucociliary clearance in a subject is taught including administering to a subject an amount of activator compound capable of enhancing the ability of the cellular mucociliary clearance apparatus [0046]. The active agent can be administered as a liquid dosage form or by inhalation via the pulmonary system [0073]. Formulations are taught to include saline solutions [0083]. Thus the ‘539 publication teaches that it is known to use capsaicin to be inhaled in saline solutions to increase mucociliary clearance in patient which do not have CF, and thus is not unexpected. It is further noted the results are not commensurate in scope as they do not require the administration via inhalation and additionally the results pointed to are the combination of HTS, CAP and Menthol wherein the instant claims require HTS or ITS and the active agent is mention, capsaicin or a combination thereof.
Applicant argues the TAM declaration provided shows further evidence that adding neuronal agonist to HTS and ITS treatments in WT swine evidences both airway hydration and MCC and further that addition of capsaicin and menthol to the ITS or HTS treatment extended the effects on MCC. Adding neuronal agonists to HTS or ITS treatment will have beneficial therapeutic effects in non-cystic fibrosis respiratory diseases, disorders or conditions.
In response, TAM declaration states that the addition of capsaicin or menthol did to HTS did not further increase HTS-triggered mucociliary clearance and that adding capsaicin or menthol to ITS treatment stimulated MCC to about the same level as HTS-treated preparation at 30 minutes after treatment (Figures 1A-C, 2A-C) and the addition of capsaicin and menthol to the ITS treatment of HTS treatment extended the effects n MCC. Thus, Applicant has demonstrated ITS and HTS do not have the same superior treatments and the combination of menthol and capsaicin is needed to show the increased duration in wild-type swine airways. Thus, the results presented are not commensurate in scope with the instant claims. It is likewise noted the instant claims do not contain the mode/area of administration wherein the results demonstrate the need for administration to the trachea.
Applicant argues McShane generally teaches HTS can be used in the airway clearance process to mobilize bronchopulmonary secretions. Airway clearance and mucociliary clearance are distinct but related concepts. MCC is specifically the movement and/or removal of particles form airway secretion through the action of cilia. Applicant argues McShane is silent to neuronal agonists.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The ‘539 publication teaches increasing mucociliary clearance in a subject. The compounds are effective in increasing the depth of ASL, thereby increasing mucociliary clearance in the subject (abstract).
Applicant argues the office has provided no reason why a person of ordinary skill in the art would have been motivated to select capsaicin form the broad list of mucociliary clearance activators from the ‘539 publication and combine it with McShane. Such argument relies on the knowledge capsaicin as a neuronal agonist of the present inventions to arrive at the asserted combination, rather than the teaching or suggestion in the prior art itself.
In response, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of HTS and capsaicin to improve mucociliary clearance as McShane teaches HTS being used to mobilize bronchopulmonary secretions to treat non-CF bronchiectasis and the ‘539 publication teaches capsaicin being used for mucociliary clearance to treat non-CF diseases. It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of two ingredients, HTS and capsaicin, both known to improve mucous clearance to treat non-CF diseases. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success in using the combination of HTS and capsaicin for inhalation as the ‘539 publication teaches inhalable compositions including capsaicin and saline solutions. Thus the motivation to improve mucous clearance is found in the prior art.
Applicant argues McShane also does not address the concerns associated with combining two agents known to irritate the airway and cause coughing. There is not reasoning provided in the Office Action as to how the cited art would overcome the skilled person’s expectation that such a combination would be detrimental.
In response, the ‘539 publication teaches the combination of capsaicin in saline for mucociliary clearance (abstract, [0002], [0032], [0083]), and thus the combination of saline and capsaicin was known in the art to treat diseases. Further it is noted that instant claim contains no limitations directed to irritation of the airway and coughing, thus Applicant is arguing limitations not present in the instant claims.
Conclusion
No claims are allowed.
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/LYNDSEY M BECKHARDT/ Examiner, Art Unit 1613