DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The present application, filed December 28, 2021, is a national stage application of PCT/EP2020/068355, filed June 30, 2020, which claims priority to foreign priority application BE2019/5421, filed July 1, 2019.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 8, 2025 has been entered.
Status of the Application
Applicant’s communication, received December 8, 2025, wherein claims 1, 3, 4, 8, 9, 13, 14, 15, and 20 are amended, is acknowledged.
Claims 1-20 are pending and examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, received December 8, 2025, with respect to the rejection of claim 20 under 35 U.S.C. 112(a) for lacking enablement for the prevention of nasal inflammations has been fully considered and found to be persuasive to remove the rejection because the claims are amended to recite a topical method of treatment for decreasing nasal inflammation. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the rejection of claims 1, 3-11, 15-18, and 20 under 35 U.S.C. 103 as unpatentable over Cataldo in view of Mygind and Durham, has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the rejection of claim 2 under 35 U.S.C. 103 as unpatentable over Cataldo in view of Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the rejection of claims 12-14 and 19 under 35 U.S.C. 103 as unpatentable over Cataldo in view of Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 1, 3-11, 15-18, and 20 as unpatentable over the claims of U.S. Patent No. 7,829,550 in view of Cataldo Mygind, and Durham, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘550 and embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claim 2 as unpatentable over the claims of U.S. Patent No. 7,829,550 in view of Cataldo Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘550 and embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 12-14 and 19 as unpatentable over the claims of U.S. Patent No. 7,829,550 in view of Cataldo Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘550 and embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 1, 4-11, 15-18, and 20 as unpatentable over the claims of U.S. Patent No. 8,772,265 in view of Cataldo Mygind, and Durham, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘265 and embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claim 2 as unpatentable over the claims of U.S. Patent No. 8,772,265 in view of Cataldo Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘265 and embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 19 as unpatentable over the claims of U.S. Patent No. 8,772,265 in view of Cataldo, Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘265 and embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 1, 3-11, 15-18, and 20 as unpatentable over the claims of U.S. Patent No. 9,034,846 in view of Cataldo Mygind, and Durham, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘846 and embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claim 2 as unpatentable over the claims of U.S. Patent No. 9,034,846 in view of Cataldo Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘846 and embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 12-14 and 19 as unpatentable over the claims of U.S. Patent No. 9,034,846 in view of Cataldo, Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘846 and embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claims 1, 4-11, 15-18, and 20 as unpatentable over the claims of U.S. Patent No. 9,993,487 in view of Cataldo Mygind, and Durham, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘487 and embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claim 2 as unpatentable over the claims of U.S. Patent No. 9,993,487 in view of Cataldo Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘487 and embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the nonstatutory double patenting rejection of claim 19 as unpatentable over the claims of U.S. Patent No. 9,993,487 in view of Cataldo, Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘487 and embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the provisional nonstatutory double patenting rejection of claims 1, 3-11, 15-18, and 20 as unpatentable over the claims of co-pending U.S. patent application 17/641,416 in view of Cataldo Mygind, and Durham, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘416 and embodiments of Cataldo, Mygind, and Durham cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the provisional nonstatutory double patenting rejection of claim 2 as unpatentable over the claims of co-pending U.S. patent application 17/641,416 in view of Cataldo, Mygind, Durham, and Vitins, has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘416 and embodiments of Cataldo, Mygind, Durham, and Vitins cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received December 8, 2025, with respect to the provisional nonstatutory double patenting rejection of claim 19 as unpatentable over the claims of co-pending U.S. patent application 17/641,416 in view of Cataldo, Mygind, Durham, and Cataldo (2001), has been fully considered and found to be persuasive to remove the rejection because the present independent claims are amended to recite a topical method of treatment for decreasing nasal inflammation requiring administration of a nasal composition, which the claims of ‘416 and embodiments of Cataldo, Mygind, Durham, and Cataldo (2001) cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
The following are new and/or modified grounds of rejection in response to Applicant’s amendments received December 8, 2025.
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 5 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 depends from claim 41. However, the current claims do not include a claim 41. Claim 5 is interpreted as depending from claim 4, consistent with the claims received April 17, 2025.
Claim 10 recites “wherein the concentration of cyclodextrins is from 0.5 1 mM to 50 mM.” It is unclear if the range of cyclodextrins has a lower limit of 0.5 mM, 1 mM, or a lower limit of 0.5 to 1 mM.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 6, 10, and 15-18 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Namburi (U.S. pre-grant publication no. US 20060045850 A1; cited in PTO-892), as evidenced by Lin (Lin, R. Y.; et al. Journal of Allergy and Clinical Immunology 1997, vol. 99, pp. 265-266; cited in PTO-892) and Suman (Suman, J. D.; et al. Pharmaceutical Research 1999, vol. 16, pp. 1648-1652; cited in PTO-892).
Namburi teaches aqueous, anti-inflammatory steroid compositions in solution form suitable for nasal administration and having a reduced stinging sensation as well as a method for treating inflammation of the nasal mucosa by intranasal administration of anti-inflammatory steroid compositions (cover page, Abstract, lines 1-5).
Namburi teaches Example 1, which is a nasal solution comprising 0.025% Flunisolide, 1.5% hydroxypropyl-beta-cyclodextrin, water, and citric acid, among other ingredients (p. 4, Example 1, [0040], see table).
As evidenced by the MP Bio catalog entry for hydroxypropyl-beta-cyclodextrin (cited in PTO-892), hydroxypropyl-beta cyclodextrin has a molecular weight of 1375 g/mol (p. 2). Given this molecular weight, the concentration of hydroxypropyl-beta-cyclodextrin is approximately 10.9 mM.
Namburi further teaches Example 3, which is a nasal solution comprising 0.005% fluticasone propionate, 2.0% sulfobutylether-beta-cyclodextrin, water, and citric acid, among other ingredients (p. 4, Example 3, [0044], see table).
As evidenced by the PubChem entry for sulfobutylether-beta-cyclodextrin (cited in PTO-892), sulfobutylether-beta-cyclodextrin has a molecular weight of 2088.2 g/mol (p. 1). Given this molecular weight, the concentration of sulfobutylether-beta-cyclodextrin is approximately 9.6 mM.
Namburi further teaches administering these nasal compositions to volunteers by spraying the composition in each nostril (p. 5, Example, 5, [0050], lines 1-6). This is interpreted as topical administration to the nasal mucosa, absent evidence to the contrary. In addition, a nasal spray is interpreted as an inhalable composition, as recited in claims 17 and 18.
Finally Namburi teaches and claims a method of treating inflammation of the nasal mucosa, which method comprises intranasally administering to a subject in need thereof an anti-inflammatory steroid composition comprising: an anti-inflammatory steroid in an amount of from about 0.0001% to about 2.0% (w/v); a cyclodextrin in an amount of from about 0.1% to about 20% (w/v); additional reagents recited in the claim, and a pH adjusting agent to adjust the pH of the composition to between 5 and 7 (p. 6, claim 18). In this instance, because Namburi teaches this composition comprising cyclodextrins for treating inflammation of the nasal mucosa, the cyclodextrins are interpreted as present in a therapeutically effective amount.
Thus the method of Namburi, practiced with, for example, the composition of Example 1 or Example 3, anticipates claims 1, 4, 6, 10, and 15-18.
Regarding the limitation that the method reduces the number of goblet cells in the subject's nasal mucosa, this is believed to be inherent to the method of Namburi, as evidenced by Lin. Lin teaches a study in which patients with rhinitis, asthma, or both used nasal corticosteroids, which was associated with a significantly lower number and percent of goblet cells (p. 265, right column, results section, lines 1-8; data shown on p. 266, Table 1). Therefore, the method of Namburi, wherein anti-inflammatory corticosteroids are administered to patients for treating inflammation, is believed to inherently reduce the number of goblet cells in the subject's nasal mucosa tissue, absent evidence to the contrary.
Regarding the method as using an aerosol-generating device for the delivery of the nasal composition to the subject as recited in claim 15, because Namburi teaches these compositions as being applied by one spray to each nostril of a subject, the examiner believes this necessitates an aerosol generating device for spraying the composition, which would necessarily generate aerosols, absent evidence to the contrary. Moreover, Suman teaches a comparison of nasal deposition and clearance of aerosol generated by a nebulizer and an aqueous spray pump (p. 1648, Title), further establishing that aqueous spray formulations, when sprayed, are expected to generate aerosols.
Regarding claim 16, as evidenced by the present specification teaching that goblet cells are simple columnar epithelial cells that secrete gel-forming mucins and are typically found in the respiratory tracts (p. 12, lines 19-20), the method of Namburi, wherein their composition comprising cyclodextrin is administered by spray to the nasal mucosa, is interpreted as satisfying the limitations of claim 16, because delivery of this spray would necessarily involve topical application of the cyclodextrin directly onto goblet cells in the inflamed nasal mucosa, absent evidence to the contrary.
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.
Claims 1, 4-7, 10-11, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Namburi (U.S. pre-grant publication no. US 20060045850 A1; cited in PTO-892) in view of Lin (Lin, R. Y.; et al. Journal of Allergy and Clinical Immunology 1997, vol. 99, pp. 265-266; cited in PTO-892).
The examiner believes that Namburi anticipates claims 1, 4, 6, 10, and 15-18, as described in the above rejection under 35 U.S.C. 102. However, for the sake of argument, if the reduction in goblet cell numbers is not inherent to the method of Namburi, then claims 1, 4-7, 10-11, and 15-18 would have been obvious over Namburi in view of Lin.
Namburi teaches as described in the above rejection under 35 U.S.C. 102. In addition, Namburi teaches and claims the cyclodextrin of their composition may be 2-hydroxypropyl-β-cyclodextrin (p. 5, claim 2, lines 7-8).
Namburi does not teach the reduction in goblet cell numbers in nasal mucosa, as recited in independent claims 1 and 16. Moreover, Namburi does not teach a specific example of a composition with pH between 6.5 and 7 as recited in claim 5, a specific example with 2-hydroxypropyl-beta-cyclodextrin as recited in claims 6 and 7, or an example of the concentration of cyclodextrins between 20 mM and 30 mM as recited in claim 11.
Lin teaches as described in the above rejection under 35 U.S.C. 102.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to practice the method of Namburi for reducing nasal inflammation, which satisfies the requirements of independent claims 1 and 16, with an expectation that said method will reduce the number of goblet cells in nasal mucosa. One of ordinary skill in the art would have been motivated to practice the method of Namburi for reducing nasal inflammation, which satisfies the requirements of independent claims 1 and 16, with an expectation that said method will reduce the number of goblet cells in nasal mucosa because the method of Namburi requires administration of a composition comprising cyclodextrin and an anti-inflammatory steroid, such as a corticosteroid, to the nasal mucosa for the purposes of treating inflammation, and because Lin teaches the use of topical nasal corticosteroids reduces the number of goblet cells in patients with asthma and/or rhinitis. Therefore, one of ordinary skill in the art would have reasonably expected a reduction in goblet cells of the nasal mucosa following administration of the composition of Namburi.
Regarding the pH between 6.5 and 7 as required by claim 5, because Namburi teaches and claims their composition with a pH between 5 and 7, one of ordinary skill in the art would have reasonably considered compositions with pH values throughout this range, including compositions with pH between 6.5 and 7.
Regarding the composition with 2-hydroxypropyl-beta-cyclodextrin as recited in claim 6 and required by claim 7, because Namburi teaches embodiments with hydroxypropyl-beta-cyclodextrin and additionally teaches and claims the cyclodextrin may be 2-hydroxypropyl-beta-cyclodextrin, one of ordinary skill in the art would have considered specifically 2-hydroxypropyl-beta-cyclodextrin as the hydroxypropyl-beta-cyclodextrin that may be used as the cyclodextrin in the method of Namburi.
Regarding the concentration of cyclodextrins between 20 mM and 30 mM as recited in claim 11, although Namburi teaches lower compositions with lower concentrations of cyclodextrin than 20-30 mM, because Namburi claims their composition may contain from about 0.1 to 20% cyclodextrin, one of ordinary skill in the art would have considered concentrations of cyclodextrins within the range disclosed by Namburi, absent a showing of the criticality of the range of 20-30 mM recited in claim 11, because said concentrations may be more effective in treating inflammation than the specific Example compositions taught by Namburi.
Regarding claim 16, as evidenced by the present specification teaching that goblet cells are simple columnar epithelial cells that secrete gel-forming mucins and are typically found in the respiratory tracts (p. 12, lines 19-20), the method of Namburi, wherein their composition comprising cyclodextrin is administered by spray to the nasal mucosa, is interpreted as satisfying the limitations of claims 16, because delivery of this spray would necessarily involve topical application of the cyclodextrin directly onto goblet cells in the inflamed nasal mucosa, absent evidence to the contrary. Moreover, the spray delivered to the nose is interpreted as an inhalable composition formulated as an aerosolizable aqueous composition or a topical nasal spray, as required by claims 17 and 18.
Therefore the invention taken as a whole is prima facie obvious.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Namburi in view of Lin as applied to claims 1, 4-7, 10-11, and 16-18 above, and further in view of Vitins (U.S. pre-grant publication no. US 20100111883 A1; of record).
Namburi teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
Namburi does not teach wherein the nasal inflammation is a viral nasal inflammation, as required by claim 2.
Vitins teaches formulations comprising one or more cyclodextrins, said formulations
being particularly useful to treating or preventing viral infections (cover page, Abstract, lines 1-4). Vitins teaches and claims a sprayable composition comprising: (a) about 0.1% to about 50% by weight of one or more cyclodextrins or salts or derivatives thereof; (b) one or more polyols; and (c) water. Vitins claims this composition may include α-cyclodextrins (p. 10, claim 11), β-cyclodextrins (p. 10, claim 12), and γ-cyclodextrins (p. 11, claim 13).
Vitins further claims this sprayable composition as a nose spray (p. 11, claim 14) that does not include any additional active ingredients (p. 11, claim 16). Vitins teaches the compositions are particularly useful for topical administration (p. 2, [0019], lines 10-12), which includes the nasal passages (p. 2, [0019], lines 15-16). Vitins teaches that in one preferred embodiment, the compositions comprise hydroxypropyl-β-cyclodextrin (p. 3, [0025], lines 18-19).
In addition, Vitins teaches and claims an aqueous, sprayable composition of a cyclodextrin that does not include any additional active ingredients (p. 10, claim 8; p. 11, claim 16), and Vitins teaches and claims a pharmaceutical or cosmetic composition of cyclodextrin for application to a site where a primary viral infection actively exists (p. 11, claim 28).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to practice the method of Namburi for the purposes of treating a viral nasal inflammation. One of ordinary skill in the art would have been motivated to practice the method of Namburi for the purposes of treating a viral nasal inflammation because Namburi teaches the application of a composition comprising cyclodextrin formulated as an aqueous nasal spray composition, as discussed above, for the purposes of treating inflammation of nasal mucosa, and because Vitins teaches their composition of cyclodextrin for treating viral infections in the form of a nasal spray. Thus one of ordinary skill in the art would have recognized that, in view of Vitins teaching the antiviral effect of a cyclodextrin composition with no additional active ingredients formulated for administration to the nose, the method obvious over Namburi may be used to treat a viral nasal inflammation, because in addition to treating nasal inflammation, the method would also be expected to treat a nasal viral infection.
One of ordinary skill in the art would have had a reasonable expectation of success administering the composition taught by Namburi for the purposes of treating viral nasal inflammation because Namburi teaches said composition for treating inflammation of nasal mucosa, and because Vitins teaches their composition of cyclodextrin for treating viral infections in the form of a nasal spray. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success administering the composition taught by Namburi for the purposes of treating nasal inflammation associated with a viral infection, because administration of said composition for treating nasal inflammation is obvious over Namburi, and because Vitins teaches the antiviral activity of a composition comprising cyclodextrins. Thus the method of Namburi would have reasonably treated both nasal inflammation and a nasal viral infection, and thus would have been expected to treat any nasal inflammation associated with said viral infection as well.
Therefore the invention taken as a whole is prima facie obvious.
Claims 9, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Namburi in view of Lin as applied to claims 1, 4-7, 10-11, and 16-18 above, and further in view of Wei (Wei, C. C.; et al. Laryngoscope 2013, vol. 123, pp. 2347-2359; cited in PTO-892).
As described in the above rejection under 35 U.S.C. 102, claim 16 is anticipated by Namburi. Claim 16 is included in this rejection because claim 19 depends from claim 16, and therefore claim 16 is also obvious over Namburi in view of Lin, and further in view of Wei.
Namburi teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
Namburi does not teach the nasal composition as isotonic or hypertonic, as recited in claims 9, 19, and 20.
Wei teaches the use of topical nasal therapies in the management of chronic rhinosinusitis. Wei teaches that in patients delivered hypertonic or isotonic nasal sprays, although both solutions improved mucociliary clearance as measured by saccharine clearance times, buffered normal saline significantly improved nasal airway patency, while hypertonic saline
did not. In addition, Wei teaches that hypertonic saline caused increased nasal burning and irritation compared with isotonic saline (p. 2348, right column, second full paragraph, lines 10-18).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to formulate the nasal spray of Namburi as an isotonic solution. One of ordinary skill in the art would have been motivated to formulate the nasal spray of Namburi as an isotonic solution because Namburi teaches their nasal spray for reducing nasal inflammation, and because Wei teaches that nasal sprays formulated as isotonic solutions improved nasal airway patency and caused less nasal burning compared with hypertonic saline solutions. Accordingly, one of ordinary skill in the art would have considered preparing the formulation of Namburi as an isotonic solution, because the composition of Namburi as an isotonic solution may also reduce nasal airway patency and caused less nasal burning than alternative formulations, and thus may be a more effective composition for treating nasal inflammation.
Regarding the salt recited in claim 19, each example disclosed by Namburi (e.g., Example 1, p. 4, [0040]) includes 40 mg (0.04 g) per 200 mL solution of edetate disodium, which is herein interpreted as a salt, for a concentration of 0.2 mg/mL.
Therefore the invention taken as a whole is prima facie obvious.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Namburi in view of Lin as applied to claims 1, 4-7, 10-11, and 16-18 above, and further in view of Suman (Suman, J. D.; et al. Pharmaceutical Research 1999, vol. 16, pp. 1648-1652; cited in PTO-892).
As described in the above rejection under 35 U.S.C. 102, the examiner believes that Namburi teaching spraying their composition to the nasal mucosa would require an aerosol generating device, as required by claim 15. However, for the sake of argument, if a “spray” can be generated without an aerosol-generating device, then claim 15 would have been obvious over Namburi in view Lin, and further in view of Suman.
Namburi teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
Namburi does not teach the method of claim 1, wherein said topical method further comprises the step of using an aerosol-generating device for the delivery of the nasal composition to the subject, as recited in claim 15.
Suman teaches a comparison of nasal deposition and clearance of aerosol generated by a nebulizer and an aqueous spray pump (p. 1648, Title), establishing that aqueous spray formulations generate aerosols. In addition, Suman teaches that after comparing a nebulizer used to deliver an aerosol with a spray pump, a nebulizer that is adapted to deliver aerosol into the nose can deposit droplets in areas that a spray pump cannot reach (p. 1651, right column, Conclusions section, first paragraph, lines 1-3), and that extended coverage to all surfaces of the nasal epithelium by a drug could maximize topical exposure or increase absorption (p. 1651, right column, Conclusions section, second paragraph, lines 1-3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to practice the method obvious over Namburi in view of Lin using an aerosol generating device, such as a nebulizer that is adapted to deliver aerosol into the nose. One of ordinary skill in the art would have been motivated to practice the method obvious over Namburi in view of Lin using an aerosol generating device, such as a nebulizer that is adapted to deliver aerosol into the nose, because Namburi teaches administration of their composition using a spray, and because Suman teaches nebulizers adapted to deliver aerosol into the nose can deposit droplets in areas that a spray pump cannot reach, thus extending the coverage to all surfaces of the nasal epithelium. Therefore, one of ordinary skill in the art would have considered practicing the method obvious over Namburi in view of Lin with a nebulizer adapted to deliver aerosol to the nose, because said nebulizer may extend coverage of the aerosol to more surfaces of the nasal epithelium, maximizing topical exposure of the therapeutic.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1, 3-11, 15-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Cataldo (U.S. pre-grant publication no. US 20090012041 Al; of record) in view of Mygind (Mygind, N.; et al. Respiratory Medicine 1998, vol. 92, pp. 547-549; of record), Durham (Durham, S. R. Clinical and Experimental Allergy 1998, vol. 28, Supplement 2, pp. 11-16; of record), and Keller (Publication no. EP 1894559 A1; cited in PTO-892).
Cataldo teaches compositions and medicaments with cyclodextrin for the treatment and prevention of bronchial inflammatory diseases, particularly asthma (cover page, Abstract, lines 1-4).
Cataldo teaches an example where mice were administered α-cyclodextrin and hydroxypropyl-β-cyclodextrin at concentrations of 1, 7.5, and 50 mM and to hydroxypropyl-γ-cyclodextrin at a concentration of 50 mM by inhalation after being sensitized to allergens by exposure to ovalbumin (p. 4, [0057], lines 6-11). Cataldo teaches that aerosol was produced using an ultrasonic nebulizer (p. 4, [0053]), and that aerosol size distribution emitted from solutions of cyclodextrins was determined using a laser size analyzer (p. 4, [0055], lines 1-3). Cataldo teaches that after allergen exposure, mice treated with placebo displayed a significant increase in peribronchial inflammation as quantified by the peribronchial inflammation score and reduced levels of eosinophils (p. 5, [0070], lines 1-3; document p. 2, Figure 1), and that mice treated with hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin had decreased inflammation scores when compared to placebo treated mice (p. 5, [0071], lines 1-6; document p. 3, Figure 2).
Cataldo further teaches that the cyclodextrin may be administered via oral, parenteral, or topical administration (p. 3, [0032], lines 1-3), and recites a preferable route of administration is topical administration with an aerosol composition (p. 3, [0032], lines 4-6). Cataldo teaches the aerosol composition may be a solution, a suspension, or a micronised powder mixture, and that the composition may be administered using a nebulizer, a metered dose inhaler or a dry powder inhaler (p. 3, [0032], lines 6-11). Cataldo teaches that an appropriate amount of a pharmaceutically acceptable salt is typically used to render the composition isotonic (p. 3, [0034], lines 4-6).
Cataldo teaches a large number of cyclodextrins may be used in their method, including hydroxypropylated cyclodextrins preferably substituted randomly mainly in position 2 and 3 (p. 2, [0019]). This is interpreted as an express teaching that the hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin may be 2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin.
Cataldo teaches that the pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7.5 (p. 3, [0034], lines 8-9).
As an example composition comprising cyclodextrins, Cataldo teaches a 200 mL composition comprising 10-50 g cyclodextrin (abbreviated CD therein), preferably 20 g cyclodextrin, preferably hydroxypropyl-beta-cyclodextrin (abbreviated HP-β-CD therein), 1.2-1.5 g of sodium chloride, and water (p. 3, [0037]). Practicing the method of Cataldo with this composition is interpreted as satisfying the limitations of claim 4, wherein no further anti-inflammatory active pharmaceutical ingredient is present in the inhalable composition.
As described in the above example, Cataldo teaches administering to mice an inhalable composition of cyclodextrin using an ultrasonic nebulizer (p. 4, [0053]).
In addition, Cataldo teaches compositions comprising 2-O-methylcyclodextrin at concentrations of 10, 20, 50 and 75 mM (p.5, [0077], lines 1-2) with NaCl (p. 5, [0077], lines 5-8). These compositions with 10 or 20 mM cyclodextrin, when administered to mice using the method described in the other example taught by Cataldo, reduce the peribronchial inflammation score compared with mice administered placebo (pp. 5-6, [0081], lines 1-8; document p. 9, Figure 9).
Regarding claims 16-18, as evidenced by the present specification teaching that goblet cells are simple columnar epithelial cells that secrete gel-forming mucins and are typically found in the respiratory tracts (p. 12, lines 19-20), the method of Cataldo, wherein hydroxypropyl-γ-cyclodextrin is administered to mice via inhalation of an aerosolized solution, is interpreted as satisfying the limitations of claims 16-18, because delivery of this aerosol would necessarily involve topical application of the cyclodextrin directly onto goblet cells in the inflamed nasal mucosa, absent evidence to the contrary. In addition, because the composition administered by Cataldo comprises hydroxypropyl-γ-cyclodextrin diluted in PBS and administered by inhalation, it satisfies the limitations of an inhalable composition as recited in claim 17 and an aerosolizable aqueous composition as recited in claim 18.
Cataldo does not specifically teach a method for treatment for decreasing nasal inflammations by topically administering to the tissue a nasal composition, as required by claims 1, 16, and 20. In addition, Cataldo does not teach the composition for reducing or decreasing the number of goblet cells in the subject's nasal mucosa tissue following said topical administration, as recited in claims 1, 16, and 20.
Mygind teaches that nasal inflammation can aggravate asthma symptoms. Mygind teaches that inhaled allergens are predominantly deposited in the nose, whether a patient suffers from rhinitis, asthma or both, and offers four rationale for treating nasal inflammation that may aggravate asthma symptoms p. 547, Abstract, lines 3-9).
Inhaled allergens are predominantly deposited in the nose, whether a patient suffers from rhinitis, asthma or both.
Antigen presentation consequently takes place in the nose, and the response of the airway immune system is thus initiated in the nasal mucous membrane.
Antigen presentation in the nose may possibly induce cell recruitment and activation not only in the nasal mucosa but also in the lower airways.
Suppression of nasal inflammation may therefore be necessary for optimal management of asthma.
Mygind concludes by stating: “If the nose is not treated, potentially harmful inflammatory reactions will continue in asthmatic patients.” (p. 548, right column, final paragraph, lines 9-11).
Durham teaches the involvement of eosinophils during inflammation in both nasal and bronchial tissue. Durham teaches that the allergic response can be biphasic, irrespective of
whether it occurs in the nose, the lungs or the skin (p. 12, left column, lines 1-2). Durham teaches that the early phase response occurs within 0–60 min following allergen exposure, and results directly from IgE-dependent activation of mast cells by a Type I hypersensitivity reaction. Durham teaches that in allergic rhinitis this is characterized by the classic nasal symptoms of sneezing, itching, congestion and mucus discharge, and increased numbers of eosinophils are found in nasal secretions together with histamine and other inflammatory mediators (p. 12, left column, lines 2-10).
In addition, Durham teaches that examination of bronchoalveolar lavage fluid for activated CD4+ cells by flow cytometry after allergen challenge in 15 patients indicated that the number of cells was increased in patients with asthma, and that a further increase in CD25 expression accompanied house dust mite challenge. Durham teaches that the number of eosinophils present in the first 60 mL of bronchial wash and the following 120 mL of bronchoalveolar lavage was increased in patients following allergen challenge, when compared to a control challenge in the same individual on a separate occasion (p. 14, left column, lines 8-21).
Durham concludes by stating that the inflammatory changes which occur in the lower and the upper airways in response to seasonal and perennial allergens, whether by provocation in the laboratory or natural seasonal exposure, have therefore been demonstrated to involve the recruitment and activation of T cells, the expression of TH2-type cytokines and tissue eosinophilia (p. 14, left column, first full paragraph, liens 1-6).
Keller teaches compositions for administration as aerosols that include a corticosteroid and cyclodextrin and are suitable for oral or nasal administration (cover page, Abstract, lines 1-6).
Keller teaches that infants breath through the nose, which is why nebulizing systems with a nasal mask should be used for the administration of active agents by inhalation, and that restriction also applies in the case of other species such as rodents (p. 2, [0003], lines 2-4). Keller further teaches that like infants, rodents breath through the nose, which is why in this case the aerosol should be applied by means of a nasal mask in order to achieve a high pulmonary deposition (p. 3, [0012]).
Keller teaches that oral inhalation is usually preferred if the target region where the aerosol is to be deposited is the lower respiratory tract, such as the bronchi or the alveolar region, and in contract, nasal inhalation through one or both nostrils is usually more suitable if the aerosol is administered for the prevention or treatment of a symptom or disease affecting a
region of the upper respiratory tract, such as the nasal mucosa or the paranasal sinuses (p. 6, [0036]). A composition administered to the nose is herein interpreted as a nasal composition.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer the method taught by Cataldo to a subject for the purposes of treating nasal inflammation. One of ordinary skill in the art would have been motivated to administer the method taught by Cataldo for the purposes of treating nasal inflammation because Cataldo teaches the application of a composition comprising a cyclodextrin compound, including the compositions discussed above, for the treatment or prevention of bronchial inflammatory diseases, particularly asthma, that reduces the levels of eosinophils in bronchial tissue, because Mygind teaches that suppression of nasal inflammation may be required for optimal management of asthma given the nose as a place where allergens accumulate and where the immune system is active, and because Durham teaches that infiltration of eosinophils occurs during the inflammatory response in both bronchial and nasal tissues. Therefore, one of ordinary skill in the art would have recognized that administration of an asthma treatment which reduces bronchial inflammation and eosinophils in bronchial tissue may be reasonably administered to a patient for the purposes of treating nasal inflammation associated with asthma.
Regarding the administration of this composition to nasal tissue, because Mygind recognizes that nasal inflammation can aggravate asthma symptoms and suggests treating nasal inflammation, because potentially harmful inflammatory reactions will continue in asthmatic patients, and because Keller teaches that nasal inhalation is the preferred route of administration for treating a symptom or disease affecting a region of the upper respiratory tract, such as the nasal mucosa. Accordingly, one of ordinary skill in the art would have considered practicing the method of Cataldo using nasal administration.
Moreover, because Keller teaches that some subjects breath through the nose, such as infants and rodents, one of ordinary skill in the art would have recognized that practicing the method of Cataldo, such as for treating asthma, on subjects such as infants or rodents should involve nasal administration of the composition of Cataldo.
One of ordinary skill in the art would have had a reasonable expectation of success administering the composition taught by Cataldo for the purposes of treating nasal inflammation because Cataldo teaches said composition for treatment or prevention of bronchial inflammatory diseases, particularly asthma, Mygind teaches that suppression of nasal inflammation may be required for optimal management of asthma, and Durham teaches infiltration of eosinophils during the inflammatory response in both bronchial and nasal tissue. Therefore one of ordinary skill in the art would have had a reasonable expectation of success administering the composition of Cataldo for the purposes of treating nasal inflammation in patients with asthma, because the inflammatory response in both bronchial and nasal tissues are characterized by an increase in the number of eosinophils in said tissue.
Regarding the requirement of the present claims that the topical administration of the nasal composition is for reducing the number of goblet cells in the subject's nasal mucosa tissue following said topical administration, this limitation is not acknowledged by any of Cataldo, Mygind, Durham, or Keller. However, the reduction in goblet cells is believed to be necessarily present when administering a composition comprising cyclodextrin to nasal tissue.
As stated above, Cataldo teaches an example where mice were administered α-cyclodextrin and hydroxypropyl-β-cyclodextrin at concentrations of 1, 7.5, and 50 mM and to hydroxypropyl-γ-cyclodextrin at a concentration of 50 mM by inhalation after being sensitized to allergens by exposure to ovalbumin (p. 4, [0057], lines 6-11). Cataldo teaches that after allergen exposure, mice treated with placebo displayed a significant increase in peribronchial inflammation as quantified by the peribronchial inflammation score and reduced levels of eosinophils (p. 5, [0070], lines 1-3; document p. 2, Figure 1), and that mice treated with hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin had decreased inflammation scores when compared to placebo treated mice (p. 5, [0071], lines 1-6; document p. 3, Figure 2).
Cataldo does not teach that their method is for reducing the number of goblet cells in the subject's nasal mucosa tissue following said topical administration. However, as evidenced by the present specification, this reduction in the number of goblet cells in the nasal mucosa tissue is believed to be necessarily present when practicing the method of Cataldo described above. The specification provides a working example where BALB/c mice were sensitized with Ovalbulmin (OVA) on days 1 and 11 by intraperitoneal injection, followed by administration of OVA aerosols. The specification provides that mice were treated from Day 22 to Day 98 with PBS (8 mice in control group) or with hydroxypropyl-γ-cyclodextrin 50 mM diluted in PBS (8 mice in treated group) by aerosolization. The specification provides that on day 99, the animals were sacrificed, nasal cavity was removed, and number of goblet cells determined (p. 14, lines 4-17). The specification provides that hydroxypropyl-γ-cyclodextrin as shown in the second black column leads to a reduction from 50% (control group, white column) to 20% of goblet cells (p. 14, lines 28 to p. 15, line 4).
Therefore, as evidenced by the present specification, the method of Cataldo, wherein mice were administered 50 mM hydroxypropyl-γ-cyclodextrin by inhalation of aerosols for the purposes of reducing bronchial inflammation from exposure to OVA would necessarily have the effect of reducing goblet cells in nasal mucosa tissue.
MPEP 2112.01 (especially at I) citing In re Best, 562 F.2d 1252, 195 USPQ 430 (C.C.P.A. 1977) and In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe necessarily includes functions or characteristics that are newly recited or
identical to an invention as instantly claimed. In such a situation the burden is shifted to the applicants to show the invention of the applicant and the prior art are not the same or that the prior art invention does not necessarily possess the characteristics of the claimed invention.
In this case, because the method taught by Cataldo involves administering to mice 50 mM hydroxypropyl-γ-cyclodextrin by inhalation of aerosols for the purposes of reducing bronchial inflammation, and because the instant specification provides that administration to mice of 50 mM hydroxypropyl-gamma-cyclodextrin by aerosolization leads to a reduction in goblet cell count in nasal mucosa, this reduction in goblet cell count in nasal mucosa is believed to be necessarily present when performing the method taught by Cataldo.
Therefore, because Cataldo, Mygind, Durham, and Keller provide motivation to administer the composition comprising cyclodextrin to nasal tissue for the purposes of treating inflammation, such as inflammation associated with asthma, a reduction in goblet cells in nasal tissue is believed to be necessarily present when practicing the method obvious over Cataldo in view of Mygind, Durham, and Keller.
Regarding the pH of 6.5-7 required by claim 5, although Cataldo does not teach the pH of the composition used in their example, because Cataldo teaches that the pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7.5, one of ordinary skill in the art would have considered adjusting the pH of the inhalable composition to a pH of 7, which would satisfy the limitations of claim 5.
Regarding the cyclodextrin as 2-hydroxypropyl-β-cyclodextrin as required by claim 7, because Cataldo teaches examples wherein both hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin are administered for the purposes of reducing bronchial inflammation, and further teaches that the hydroxypropyl-cyclodextrins may be substituted at the 2-position, one of ordinary skill in the art would have reasonably considered substituting the 50 mM hydroxypropyl-γ-cyclodextrin in the example of Cataldo described above with 2- hydroxypropyl-β-cyclodextrin.
Regarding the requirement that there is no corticosteroid or oil present in the inhalable composition in effective amounts as recited in claim 8, because Cataldo does not expressly teach a corticosteroid or oil present in their composition in effective amounts, the method of Cataldo is interpreted as satisfying claim 8.
Regarding the requirement of claim 9 wherein the composition is isotonic or hypertonic, because Cataldo teaches that their preferred compositions comprising cyclodextrins are isotonic (see, for example, p. 3, [0037]), one of ordinary skill in the art would have reasonably contemplated formulating said composition as isotonic.
Regarding the specific concentration of cyclodextrins required by claim 11, because Cataldo teaches an example administering 50 mM hydroxypropyl-γ-cyclodextrin, and further teaches additional examples administering 10, 20, 50, 100, or 200 mM 2-O-methyl cyclodextrin for the purposes of reducing bronchial inflammation, one of ordinary skill in the art would have reasonably considered that concentrations of cyclodextrin in the range of 20-30 mM that may be used in the method of Cataldo, as required by claim 11.
Regarding the method of claim 20, because Cataldo teaches an aqueous inhalable composition with 50 mM hydroxypropyl-γ-cyclodextrin which may be substituted at the 2 position, teaches the composition may be isotonic or hypertonic, and suggests the pH of the composition is from 7-7.5, which includes pH 7, the method of claim 20 with the specific requirements of the composition comprising cyclodextrin that are recited in claim 20 also would have been obvious over Cataldo in view of Mygind, Durham, and Keller.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: Regarding the previous rejection of claims 1, 3-11, 15-18, and 20 under 35 U.S.C. 103 as unpatentable over Cataldo in view of Mygind and Durham, Applicant provides the following arguments.
1. Applicant argues that Cataldo discloses a treatment for bronchial inflammatory diseases with cyclodextrin compounds and methods of administration, including aerosolization for optimal delivery, and that such treatments are bronchodilators. Applicant argues that Cataldo does not teach intranasal administration, Cataldo does not suggest intranasal administration, Cataldo is not at all concerned with nasal inflammation, and Mygind teaches that intranasal administration would not be effective in treating bronchial inflammatory diseases. Therefore, Applicant argues that Cataldo teaches away from using intranasal administration for treating pulmonary inflammation. Applicant argues that given Cataldo's silence with respect to intranasal administration and nasal inflammation, it is respectfully submitted that Cataldo, when considered appropriately, constitutes non-analogous art. (Applicant’s remarks, pp. 7-8).
2. Applicant argues that the claimed intranasal inventions are distinct from Cataldo, Mygind and/or Durham with respect to several key aspects, namely, (1) the claimed inventions are specific for "intranasal" treatments of "nasal inflammations" by the topical application of a cyclodextrin compound onto inflamed nasal mucosa tissue to decrease the number of goblet cells, (2) there is a novel, unobvious and unpredictable decrease in the number of the goblet cells in a subject's inflamed nasal mucosa tissue sufficient in decreased numbers to reduce some level of a subject's nasal inflammation when the subject is intranasally treated in accordance with the
claimed inventions 1-20, and (3) there is a novel, unobvious, and unpredictable therapeutic
effect when treating nasal inflammations in accordance with the claimed intranasal inventions.
Applicant argues that the claimed intranasal inventions are directed to the intranasal treatment of nasal inflammations, such as sinusitis or rhinitis, which is neither taught, suggested, disclosed nor claimed by Cataldo. Rather, Cataldo teaches the treatment of bronchial inflammatory diseases, particularly asthma, and does not address nasal inflammations.
Applicant argues that there is an unexpected reduction in the number of goblet cells in the nasal inflamed mucosa tissue following intranasal administration in accordance with the claimed
Inventions, embodied by example 2 in the specification. This unexpected result is a specific, novel, unobvious and unpredictable effect of the claimed inventions, which is neither taught, suggested, disclosed or claimed by Cataldo, especially in connection with intranasal administration of a cyclodextrin compound to treat nasal inflammations.
Applicant argues that the distinction between the claimed "intranasal" inventions and Cataldo, the reduction in peribronchial inflammation scores about which Cataldo references concerns "bronchial inflammation," whereas the reduction in the number of goblet cells in the inflamed nasal mucosa tissue about which claims 1-20 claim, concern inflammation in the nose, not bronchial inflammation. They are two very distinct and unrelated medical effects from two
very distinct and unrelated medical treatments further supporting that Cataldo is non-analogous art.
Applicant argues that the treatment approaches for inflammation in the nose (rhinitis/sinusitis) and the treatment approaches for inflammation in the bronchial tubes (bronchitis) differ significantly, primarily due to the different locations and specific functions of the affected airways. Treatment for nasal inflammations concerns topical application through the nose. In contrast, treatment for bronchial inflammation concerns inhalation and tube treatment generally administered through the mouth, as this mouth method maximizes drug delivery to the lungs, not the nose. Indeed, if you inhale the composition through the nose, most of the aerosols will deposit inside the nose and sinuses and not reach the lungs effectively.
Applicant argues that a sufficient decrease in the number of goblet cells in the subject's inflamed nasal mucosa tissue would result to effectively reduce some level of nasal inflammation in the subject suffering with nasal inflammation when the topical methods, as claimed in claims 1-20, are practiced. Applicant argues that goblet cells are specialized epithelial cells that secrete gel-forming mucins and that are found in the respiratory tracts. Differentiation of epithelial cells into goblet cells plays a key role in excessive mucus production, and thus the number of goblet cells in nasal mucosa tissue is indicative of the state of the inflammation. A decrease in the number of goblet cells in inflamed nasal mucosa tissue reflects a decrease in the level of nasal inflammation. (Applicant’s remarks, pp. 8-11).
3. Applicant argues that Cataldo's method is directed to bronchial inflammation (bronchitis, asthma, COPD), and for bronchial inflammation the medication needs to reach the lower airways, so the aerosol should be inhaled through the mouth. Applicant argues that if you inhale through the nose, most of the aerosol will deposit inside the nose and sinuses and not reach the lungs effectively, and thus any topical method of administration of a nasal composition would destroy the teachings of Cataldo. Applicant argues this is confirmed by Mygind, who teaches that "the nose acts as a filter for inhaled air, thereby protecting the delicate structures in the lower airways.” Finally, Applicant argues that Durham discusses the mechanisms of mucosal inflammation in the nose and lungs, particularly in the context of allergic rhinitis and asthma, and even if the article highlights the similarities in inflammatory responses between these two conditions, Durham does not concern the decrease in the number of goblet cells in the nose. (Applicant’s remarks, pp. 17-18).
Applicant’s arguments have been fully considered but they are not found persuasive.
Regarding Applicant’s first argument that Cataldo is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Cataldo is concerned with treating bronchial inflammatory diseases such as asthma and COPD. As taught by Mygind, inflammation in nasal tissue can affect asthma symptoms, and thus one of ordinary skill in the art would have recognized that treatment of nasal inflammation may benefit a subject with asthma. Moreover, as shown by Durham, bronchial inflammation and nasal inflammation share similar mechanisms. Therefore, one of ordinary skill in the art would have considered methods of treating bronchial inflammation, such as bronchial inflammation associated with asthma, as reasonably pertinent to methods of treating nasal inflammation.
In addition, because Keller teaches that some subjects breath through the nose, such as infants and rodents, one of ordinary skill in the art would have recognized that practicing the method of Cataldo on subjects such as infants or rodents should involve nasal administration of the composition of Cataldo, which would thus involve topical administration of the composition comprising cyclodextrin to nasal tissue in the form of an aerosol. Therefore, the teachings of Cataldo are considered as reasonably pertinent to the claimed invention.
Regarding Applicant’s second argument, as described above, Cataldo is concerned with treating bronchial inflammatory diseases such as asthma. Mygind teaches inflammation in nasal tissue can affect asthma symptoms, and Durham teaches bronchial inflammation and nasal inflammation share similar mechanisms. Therefore, one of ordinary skill in the art would have reasonably considered methods of treating bronchial inflammation, such as bronchial inflammation associated with asthma, as relevant to methods of treating nasal inflammation, because nasal inflammation may affect asthma symptoms and inflammation in bronchial and nasal tissue share similar mechanisms. Accordingly, one of ordinary skill in the art would have considered that administration of the composition comprising cyclodextrin taught by Cataldo may be effective for treating nasal inflammation.
Regarding Applicant’s argument that there is an unexpected reduction in the number of goblet cells in the nasal inflamed mucosa tissue following intranasal administration in accordance with the claimed invention, the examiner agrees with Applicant that the claimed method shows a reduction in goblet cells. However, Applicant’s arguments that these results are novel and unexpected are not persuasive evidence of nonobviousness to overcome the present rejection.
As stated, the examiner agrees with Applicant that the claimed method shows a reduction in goblet cells. However, this reduction in goblet cells is believed to be necessarily present when administering the composition comprising cyclodextrin taught by Cataldo to the nasal tissue for treating nasal inflammation associated with asthma, as rendered obvious by Cataldo, Mygind, Durham, and Keller.
Moreover, Ordoñez (Ordoñez, C. L.; et al. American Journal of Respiratory and Critical Care Medicine 2001, vol. 163, pp. 517-523; cited in PTO-892) teaches that mild and moderative asthma is associated with airway goblet cell hyperplasia (p. 517, Title). Ordoñez concludes from their studies that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma is associated with increased stored mucin and secreted mucin. These findings suggest that acute degranulation of hyperplastic goblet cells may represent a mechanism for asthma exacerbations in mild and moderate asthma and that chronic degranulation of goblet cells may contribute to chronic airway narrowing in moderate asthma (p. 517, Abstract, lines 22-29). Therefore, in view of Ordoñez, one of ordinary skill in the art would have recognized goblet cells as contributing to asthma symptoms.
In this instance, because goblet cells are well known to be involved in inflammation (such as inflammation associated with asthma), a reduction in goblet cells using a method known to be effective for treating inflammation would not be unexpected, absent evidence that this reduction in goblet cells is specific for goblet cells in nasal tissue. Discovering the mechanism (i.e., a reduction in number of goblet cells) of an anti-inflammatory treatment already recognized by the prior art would not render an invention patentable, because such a treatment recognized by the prior art would necessarily act by that mechanism of action, absent evidence to the contrary. As described in the above rejection, the present claims are obvious over Cataldo in view of Mygind, Durham, and Keller, because the administration of a method for treating bronchial inflammation would be reasonably considered as effective for treating nasal inflammation, and recognition of the mechanism of this method for treating inflammation does not constitute persuasive evidence of nonobviousness to overcome this rejection.
Regarding Applicant’s third argument, as stated above, although Cataldo is concerned with treating bronchial inflammatory diseases such as asthma and COPD, because Mygind teaches inflammation in nasal tissue can affect asthma symptoms and Durham teaches bronchial inflammation and nasal inflammation share similar mechanisms, one of ordinary skill in the art would have reasonably considered methods of treating bronchial inflammation, such as bronchial inflammation associated with asthma, as relevant to the claimed method.
Moreover, because Keller teaches that some subjects breath through the nose, such as infants and rodents, one of ordinary skill in the art would have recognized that practicing the method of Cataldo, such as for treating the bronchial inflammatory asthma, on subjects such as infants or rodents should involve nasal administration of the composition of Cataldo.
Regarding the reduction in goblet cells, as evidenced by the present specification and described above, this reduction is believed to be necessarily present when cyclodextrins are administered to nasal mucosa, absent evidence to the contrary.
Therefore, for the reasons described in the above, the rejection of claims 1, 3-11, 15-18, and 20 under 35 U.S.C. 103 as unpatentable over Cataldo in view of Mygind, Durham, and Keller, is maintained.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Cataldo in view of Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Vitins (U.S. pre-grant publication no. US 20100111883 A1; of record).
Claim 2 depends from claim 1 and requires the nasal inflammation is a viral nasal inflammation.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections 35 U.S.C. 103.
Cataldo, Mygind, Durham, and Keller do not teach wherein the nasal inflammation is a viral nasal inflammation, as required by claim 2.
Vitins teaches formulations comprising one or more cyclodextrins, said formulations
being particularly useful to treating or preventing viral infections (cover page, Abstract, lines 1-4). Vitins teaches and claims a sprayable composition comprising: (a) about 0.1% to about 50% by weight of one or more cyclodextrins or salts or derivatives thereof; (b) one or more polyols; and (c) water. Vitins claims this composition may include α-cyclodextrins (p. 10, claim 11), β-cyclodextrins (p. 10, claim 12), and γ-cyclodextrins (p. 11, claim 13).
Vitins further claims this sprayable composition as a nose spray (p. 11, claim 14) that does not include any additional active ingredients (p. 11, claim 16). Vitins teaches the compositions are particularly useful for topical administration (p. 2, [0019], lines 10-12), which includes the nasal passages (p. 2, [0019], lines 15-16). Vitins teaches that in one preferred embodiment, the compositions comprise hydroxypropyl-β-cyclodextrin (p. 3, [0025], lines 18-19).
In addition, Vitins teaches and claims an aqueous, sprayable composition of a cyclodextrin that does not include any additional active ingredients (p. 10, claim 8; p. 11, claim 16), and Vitins teaches and claims a pharmaceutical or cosmetic composition of cyclodextrin for application to a site where a primary viral infection actively exists (p. 11, claim 28).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to practice the method of Cataldo for the purposes of treating a viral nasal inflammation. One of ordinary skill in the art would have been motivated to practice the method of Cataldo for the purposes of treating a viral nasal inflammation because Cataldo teaches the application of a cyclodextrin formulated as an inhalable aqueous composition, as discussed above, for the treatment or prevention of bronchial inflammatory diseases, particularly asthma, Mygind teaches that suppression of nasal inflammation may be required for optimal management of asthma given the nose as a place where allergens accumulate and where the immune system is active, Keller teaches nasal administration as preferred for treating nasal tissue, Durham teaches infiltration of eosinophils during inflammation in both bronchial and nasal tissues, and because Vitins teaches their composition of cyclodextrin for treating viral infections in the form of a nasal spray. Thus one of ordinary skill in the art would have recognized that, in view of Vitins teaching the antiviral effect of a cyclodextrin composition with no additional active ingredients formulated for administration to the nose, the method obvious over Cataldo, Mygind, Durham, and Keller may be used to treat viral nasal inflammation, because in addition to treating nasal inflammation, the method would also be expected to treat a nasal viral infection.
One of ordinary skill in the art would have had a reasonable expectation of success administering the composition taught by Cataldo for the purposes of treating viral nasal inflammation because Cataldo teaches said composition for treatment or prevention of bronchial inflammatory diseases, particularly asthma, Mygind teaches that suppression of nasal inflammation may be required for optimal management of asthma, because Durham teaches infiltration of eosinophils during inflammation in both bronchial and nasal tissues, Keller teaches nasal administration as preferred for treating nasal tissue, and because Vitins teaches their composition of cyclodextrin for treating viral infections in the form of a nasal spray. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success administering the composition taught by Cataldo for the purposes of treating nasal inflammation associated with a viral infection, because administration of said composition for treating nasal inflammation is obvious over Cataldo in view of Mygind, Durham, and Keller, and because Vitins teaches the antiviral activity of said composition. Thus the method of Cataldo would have reasonably treated both nasal inflammation and a nasal viral infection, which would have been expected to treat any nasal inflammation associated with said viral infection.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection over Cataldo in view of Mygind, Durham, and Vitins, Applicant argues that claim 2 depends from claim 1, and thus all arguments presented above regarding claim 1 apply to claim 2. In addition, Applicant argues that Vitins does not disclose a method of treating nasal inflammation caused by
viral nasal infection. Vitins rather describes cyclodextrins as possessing antiviral activity, but antiviral activity and treatment of nasal inflammation involve entirely different mechanisms. (Applicant’s remarks, pp. 18-19).
For the same reasons described in the above response to Applicant’s arguments as applying to claim 1, the rejection of claim 2 over Cataldo in view of Mygind, Durham, Keller, and Vitins is maintained. In addition, although Vitins does not disclose specifically treating nasal inflammation caused by viral nasal infection, because Cataldo, Mygind, Durham, and Keller render obvious the administration of cyclodextrin for treating inflammation, and because Vitins teaches the antiviral activity of compositions comprising cyclodextrins, because in addition to treating nasal inflammation, the method would also be expected to treat a nasal viral infection.
Claims 12-14 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Cataldo in view of Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Cataldo (Cataldo, D.; et al. Chest 2001, vol. 120, pp. 1815-1821; cited in previous office action), hereinafter Cataldo (2001).
Claims 12-14 and 19 depend from claims 1 and 16 and require the composition consists of the components recited in the claims.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. In addition, Mygind teaches that it is logical to look upon the nose and the bronchi as integrated parts of one ‘united airway’ and that optimal management of airway disease, caused by inhaled allergens, may necessitate control of inflammation in all parts of the airways (p. 547, Abstract, lines 1-3).
Cataldo, Mygind, Durham, and Keller do not teach the specific compositions of claims 12-14 and 19. Specifically, the range of 1.2-1.5 g sodium chloride in 200 mL of solution, as taught by Cataldo, corresponds to a concentration of sodium chloride of 6-7.5 mg/mL, which is higher than the concentration of salt in the presently claimed compositions.
Cataldo (2001) teaches that hypertonic saline solution is a potent indirect bronchoconstrictor (p. 1815, Abstract, Background section, lines 2-3). Cataldo (2001) teaches a study in which 16 patients with severe asthma underwent sputum induction by inhaling hypertonic (4.5%) or isotonic (0.9%) saline solutions (p.1815, Abstract, Study Objectives and Patients sections). Cataldo (2001) teaches that the maximal fall in peak expiratory flow (PEF) during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p.1815, Abstract, Results section, lines 1-2; p. 1817, Figure 1). Cataldo (2001) teaches that when compared to sputum induced by hypertonic saline solution, sputum induced by isotonic saline solution inhalation yields comparable results regarding the eosinophil and neutrophil cell counts and fluid phase mediators/ proteins in subjects with moderate-to-severe asthma reporting a clinical history of bronchial hypersecretion (p. 1820, right column, lines 1-8). However, Cataldo (2001) concludes by stating that isotonic saline solution causes much less bronchoconstriction than hypertonic saline solution in those patients, and thus recommends performing sputum induction with isotonic saline solution (p. 1820, right column, lines 8-12).
It would have been prima facie obvious to one of ordinary skill in the art to administer a composition comprising 20-30 mM cyclodextrin, 0.5 to 3 mg/ml of a pharmaceutically acceptable salt, and water for treating nasal inflammation. One of ordinary skill in the art would have been motivated to administer a composition comprising 20-30 mM cyclodextrin, 0.5 to 3 mg/ml of a pharmaceutically acceptable salt, and water for treating nasal inflammation because Cataldo teaches the application of a cyclodextrin compound, including the compositions discussed above, for the treatment or prevention of bronchial inflammatory diseases, particularly asthma, because Mygind suggests that suppression of nasal inflammation may be required for optimal management of asthma given the nose as a place where allergens accumulate and where the immune system is active, Keller teaches nasal administration as preferred route of administration for treating nasal tissue, and because Durham teaches infiltration of eosinophils during the inflammatory response in both bronchial and nasal tissue. In addition, because Cataldo (2001) teaches that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommends isotonic solutions for inhalation to reduce bronchoconstriction, and because Mygind teaching that the one may view the nose and the bronchi as integrated parts of one ‘united airway’, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution instead.
Regarding the specific concentration of salt present in the composition, in view of Cataldo (2001) teaching the effects of bronchoconstriction depends on salt concentration (e.g., a hypertonic or isotonic solution), one of ordinary skill in the art would have recognized that the concentration of salt may be adjusted to reduce bronchoconstriction, and thus would have considered a range of salt concentrations depending on symptoms of bronchoconstriction experienced by the patient when practicing the method obvious over Cataldo in view of Mygind, Durham, and Keller.
MPEP 2144.05 II at A 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).” In this instance, one of ordinary skill in the art would have considered the guidance of Cataldo and Cataldo (2001) when selecting a salt concentration, and would have adjusted said salt concentration if any symptoms of bronchoconstriction were observed.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection over Cataldo in view of Mygind, Durham, and Cataldo (2001), Applicant argues that claims 12-14 and 19 depend from claims 1 and 16, and therefore, all arguments apply to claims 12-14 and 19. (Applicant’s remarks, p. 19)
Therefore, for the same reasons described in the above response to Applicant’s arguments, the present rejection of claims 12-14 and 19 over Cataldo in view of Mygind, Durham, Keller, and Cataldo (2001) is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-11, 15-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-6 of U.S. Patent No. 7,829,550 (reference patent, hereinafter ‘550) in view of Cataldo (cited above), Mygind (cited above), Durham (cited above), and Keller (cited above).
Didier Cataldo is included as an inventor on the present application and on ‘550.
Claim 1 of ‘550 claims a method for the treatment of asthma in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of those cyclodextrins recited therein, and claim 3 requires the cyclodextrin compound is hydroxypropyl β-cyclodextrin. Claim 5 claims a method for treatment of asthma comprising the administration to a patient in need of such treatment of an effective dose of cyclodextrin compound alone, and claim 6 requires the mode of administration is inhalation.
The claims of ‘550 do not teach a topical method of treatment for decreasing nasal inflammation by topically administering to the subject nasal mucosa tissue an inhalable
composition comprising one or more cyclodextrins or pharmaceutically acceptable
derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa
tissue, whereby said topical method of treatment decreases the subject's nasal
inflammation; and wherein the one or more cyclodextrins or pharmaceutically acceptable derivatives thereof are in a therapeutically effective amount and wherein, the therapeutically effective amount is a cyclodextrin concentration in the range of from 1 mM to 75 mM, as required by independent claims 1 and 16.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. Specifically, Cataldo teaches the example wherein 50 mM 2-hydroxypropyl-gamma-cyclodextrin is administered to mice by inhalation to reduce bronchial inflammation, which as evidenced by the present specification and described in the above rejection under 35 U.S.C. 103, necessarily has the effect of reducing the number of goblet cells in the subject's nasal mucosa.
It would therefore have been prima facie obvious to topically administer to a subject’s nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof to decrease nasal inflammation and reduce the number of goblet cells in the subject's nasal mucosa tissue in view of ‘550 claiming a method for the treatment of asthma in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of cyclodextrin compound to the mammal by inhalation, Cataldo teaching a method of reducing bronchial inflammation using the method claimed by ‘550, and as evidenced by the specification, this method of Cataldo having the effect of reducing goblet cells in a subject’s nasal mucosa. In addition, in view of Mygind specifically teaching nasal inflammation associated with asthma, Keller teaching nasal administration as preferred route of administration for treating nasal tissue, and Durham teaching infiltration of eosinophils during inflammation in both bronchial and nasal tissues, one of ordinary skill in the art would have recognized that the method of ’550 may reasonably be used to decrease nasal inflammation as well.
Regarding claims 3-11, 15, and 17-18, in view of ‘550 claiming administration of cyclodextrin alone for treating asthma, one of ordinary skill in the art would have contemplated administering compositions comprising cyclodextrin that satisfy the limitations of present claims 1, 3-11, and 17-18, as well as using a device for aerosolization as required by claim 15, because Cataldo, Mygind, Keller, and Durham render obvious said compositions and methods for reducing nasal inflammation, as described in the above rejections under 35 U.S.C. 103.
Regarding claim 20, because the methods of claims 1 and 16 are obvious over the claims of ‘550 in view of Cataldo, Mygind, Durham, and Keller, and the inhalable aqueous composition and specific requirements of the composition of claim 20 are obvious over Cataldo, Mygind, Durham, and Keller, as described above, the method of claim 20 would also have been obvious over the claims of ‘550 in view of Cataldo, Mygind, Durham, and Keller.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-6 of ‘550 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Vitins (cited above).
Claim 1 of ‘550 claims a method for the treatment of asthma in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of those cyclodextrins recited therein, and claim 3 requires the cyclodextrin compound is hydroxypropyl β-cyclodextrin. Claim 5 claims a method for treatment of asthma comprising the administration to a patient in need of such treatment of an effective dose of cyclodextrin compound alone, and claim 6 requires the mode of administration is inhalation.
The claims of ‘550 do not claim the method of present claim 1, wherein the nasal inflammation is a viral nasal inflammation, as required by present claim 2.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejection.
Vitins teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 1, wherein the subject has a viral nasal inflammation, in view of the claims of ‘550, Cataldo, Mygind, Durham, and Keller rendering obvious the present claim 1, as described in the above non-statutory double patenting rejection, and Vitins further teaching the antiviral activity of a cyclodextrin composition with no additional active ingredients formulated for administration to the nose. Therefore one of ordinary skill in the art would have recognized, in view of Vitins, that nasal inflammation resulting from viral nasal inflammation may be reasonably treated using the method obvious over the claims of ‘550, Cataldo, Mygind, Durham, and Keller.
Claims 12-14 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5-6 of ‘550 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Cataldo (2001) (cited above).
Claim 1 of ‘550 claims a method for the treatment of asthma in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of those cyclodextrins recited therein, and claim 3 requires the cyclodextrin compound is hydroxypropyl β-cyclodextrin. Claim 5 claims a method for treatment of asthma comprising the administration to a patient in need of such treatment of an effective dose of cyclodextrin compound alone, and claim 6 requires the mode of administration is inhalation.
The claims of ‘550 do not claim the method of claim 1 or 16, wherein the composition comprising cyclodextrin has the specific properties recited in present claims 12-14 and 19.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Cataldo (2001) teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claims 1 and 16 with the compositions recited in present claims 12-14 and 19 in view of the claims of ‘550, Cataldo, Mygind, Durham and Keller rendering obvious present claims 1 and 16, as described in the above non-statutory double patenting rejection, and Cataldo (2001) further teaching that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommending isotonic solutions for inhalation to reduce bronchoconstriction. Therefore, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution to reduce symptoms of bronchoconstriction. In addition, one would have considered Cataldo and Cataldo (2001) for guidance on the specific salt concentration in the composition, and would have further adjusted said salt concentration in response to any symptoms of bronchoconstriction.
Claims 1, 4-11, 15-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 6-7 of U.S. Patent No. 8,772,265 B2 (reference patent, hereafter ‘265) in view of Cataldo, Mygind, Durham, and Keller.
Didier Cataldo is an inventor on the present application and on ‘265.
Claim 1 of ‘265 claims a water soluble curcumin compound for treating proliferative and/or inflammatory disorders, characterized in that the compound is a hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27). Claim 2 claims a pharmaceutical composition comprising at least a therapeutically sufficient amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1 as active ingredient and a pharmaceutically acceptable vehicle or carrier. Claim 4 claims a pharmaceutical composition according to claim 2, said pharmaceutical composition having a pharmaceutically acceptable administration form selected from the group consisting of tablets, pills, capsules, suppositories, syrups, solutions, creams, inhalator liquid or powder and sprays.
Claim 6 of ‘265 claims a method of treating proliferative and/or inflammatory disorders in a subject in need thereof, comprising administering a pharmaceutically acceptable amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1, and claim 7 claims the inflammatory disorder may be asthma.
The claims of ‘265 do not teach a topical method of treatment for decreasing nasal inflammation by topically administering to the subject nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa tissue, whereby said topical method of treatment decreases the subject's nasal inflammation; and wherein the one or more cyclodextrins or pharmaceutically acceptable derivatives thereof are in a therapeutically effective amount and wherein, the therapeutically effective amount is a cyclodextrin concentration in the range of from 1 mM to 75 mM, as required by independent claims 1 and 16.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. Specifically, Cataldo teaches the example wherein 50 mM 2-hydroxypropyl-gamma-cyclodextrin is administered by inhalation to reduce bronchial inflammation, which as evidenced by the present specification and described in the above rejection under 35 U.S.C. 103, necessarily has the effect of reducing the number of goblet cells in the subject's nasal mucosa.
It would therefore have been prima facie obvious to topically administer to a subject’s nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa tissue and to decrease nasal inflammation in view of ‘265 claiming a method for reducing inflammatory cells in lung tissue by administering to a human a composition comprising hydroxypropyl-β-cyclodextrin via inhalation, Cataldo teaching a method of reducing bronchial inflammation by administering via inhalation of either hydroxypropyl-β-cyclodextrin or hydroxypropyl-γ-cyclodextrin, and as evidenced by the specification and described above, this method of Cataldo necessarily having the effect of reducing goblet cells in a subject’s nasal mucosa. In addition, in view of Mygind specifically teaching nasal inflammation associated with asthma, Keller teaching nasal administration as preferred route of administration for treating nasal tissue, and Durham teaching infiltration of eosinophils during inflammation in both bronchial and nasal tissues, one of ordinary skill in the art would have recognized that the method of ‘265 may reasonably be used to decrease nasal inflammation as well. Regarding administration by inhalation, because ‘265 claims the pharmaceutical composition formulated as an inhalator liquid, powder, or spray, one of ordinary skill in the art would have contemplated administration of said composition by inhalation.
Regarding claims 4-11, 15, and 17-18, in view of ‘265 claiming administration of a composition comprising cyclodextrin for treating asthma, one of ordinary skill in the art would have contemplated administering compositions comprising cyclodextrin that satisfy the limitations of present claims 1, 4-11, and 17-18, as well as using a device for aerosolization as required by claim 15, because Cataldo, Mygind, Durham, and Keller render obvious said compositions and methods for treating nasal inflammation, including nasal inflammation associated with asthma, as described in the above rejections under 35 U.S.C. 103.
Regarding claim 20, because the methods of claims 1 and 16 are obvious over the claims of ‘265 in view of Cataldo, Mygind, Durham, and Keller and the inhalable aqueous composition and the specific requirements of this composition recited in claim 20 are obvious over Cataldo, Mygind, Durham, and Keller as described above, the method of claim 20 would also have been obvious over the claims of ‘265 in view of Cataldo, Mygind, Durham, and Keller.
In this instance, because the claims of ‘265 claim administration of a composition comprising hydroxypropyl-beta-cyclodextrin, Cataldo teaches reducing bronchial inflammation by administering via administration by inhalation of either hydroxypropyl-β-cyclodextrin or hydroxypropyl-γ-cyclodextrin, which, as evidenced by the instant specification, reduces goblet cell counts, the method obvious over the claims of ‘265 in view Cataldo, Mygind, Durham, and Keller would also reduce goblet cell counts, absent evidence to the contrary.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 6-7 of ‘265 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 4-11, 15-18, and 20 above, and further in view of Vitins.
Claim 1 of ‘265 claims a water soluble curcumin compound for treating proliferative and/or inflammatory disorders, characterized in that the compound is a hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27). Claim 2 claims a pharmaceutical composition comprising at least a therapeutically sufficient amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1 as active ingredient and a pharmaceutically acceptable vehicle or carrier. Claim 4 claims a pharmaceutical composition according to claim 2, said pharmaceutical composition having a pharmaceutically acceptable administration form selected from the group consisting of tablets, pills, capsules, suppositories, syrups, solutions, creams, inhalator liquid or powder and sprays.
Claim 6 of ‘265 claims a method of treating proliferative and/or inflammatory disorders in a subject in need thereof, comprising administering a pharmaceutically acceptable amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1, and claim 7 claims the inflammatory disorder may be asthma.
The claims of ‘265 do not claim the method of present claim 1, wherein the nasal inflammation is a viral nasal inflammation, as required by present claim 2.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Vitins teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 1, wherein the subject has a viral nasal inflammation, in view of the claims of ‘265, Cataldo, Mygind, Durham, and Keller rendering obvious the present claim 1, as described in the above non-statutory double patenting rejections, and Vitins further teaching the antiviral activity of a cyclodextrin composition formulated for administration to the nose. Therefore one of ordinary skill in the art would have recognized, in view of Vitins, that nasal inflammation resulting from viral nasal inflammation may be reasonably treated using the method obvious over the claims of ‘265, Cataldo, Mygind, Durham, and Keller.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, and 6-7 of ‘265 in view of Cataldo, Mygind, and Durham as applied to claims 1, 4-11, 15-18, and 20 above, and further in view of Cataldo (2001).
Claim 1 of ‘265 claims a water soluble curcumin compound for treating proliferative and/or inflammatory disorders, characterized in that the compound is a hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27). Claim 2 claims a pharmaceutical composition comprising at least a therapeutically sufficient amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1 as active ingredient and a pharmaceutically acceptable vehicle or carrier. Claim 4 claims a pharmaceutical composition according to claim 2, said pharmaceutical composition having a pharmaceutically acceptable administration form selected from the group consisting of tablets, pills, capsules, suppositories, syrups, solutions, creams, inhalator liquid or powder and sprays.
Claim 6 of ‘265 claims a method of treating proliferative and/or inflammatory disorders in a subject in need thereof, comprising administering a pharmaceutically acceptable amount of the water soluble hydroxypropyl-beta-cyclodextrin complex of curcumin lysinate (NDS27) according to claim 1, and claim 7 claims the inflammatory disorder may be asthma.
The claims of ‘265 do not claim the method of present claim 16, wherein the composition comprising cyclodextrin has the specific properties recited in present claim 19.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Cataldo (2001) teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 16 with the compositions recited in present claim 19 in view of the claims of ‘265, Cataldo, Mygind, Durham, and Keller rendering obvious claim 16, as described in the above non-statutory double patenting rejection, and Cataldo (2001) further teaching that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommending isotonic solutions for inhalation to reduce bronchoconstriction. Therefore, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution to reduce symptoms of bronchoconstriction. In addition, one would have considered Cataldo and Cataldo (2001) for guidance on the specific salt concentration in the composition, and would have further adjusted said salt concentration in response to any symptoms of bronchoconstriction.
Claims 1, 3-11, 15-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9,034,846 B2 (reference patent, hereafter ‘846) in view of Cataldo, Mygind, Durham, and Keller.
Didier Cataldo is included as an inventor on the present application and on ‘846.
Claim 1 of ‘846 recites a method for the treatment of COPD (chronic obstruction pulmonary disease) in a host mammal in need of such treatment, comprising the step of administering a composition consisting essentially of an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, random methylated-β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxybutyl-β-cyclodextrin, glucosyl-β-cyclodextrin, maltosyl-β-cyclodextrin, 2-O-methyl-β-cyclodextrin or a combination thereof and their pharmaceutically acceptable salts. Claim 2 claims the cyclodextrin compound is hydroxypropyl-β-cyclodextrin, and claim 3 claims the mode of administration is inhalation.
The claims of ‘846 do not teach a topical method of treatment for decreasing nasal inflammation by topically administering to the subject nasal mucosa tissue an inhalable
composition comprising one or more cyclodextrins or pharmaceutically acceptable
derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa
tissue, whereby said topical method of treatment decreases the subject's nasal
inflammation; and wherein the one or more cyclodextrins or pharmaceutically acceptable derivatives thereof are in a therapeutically effective amount and wherein, the therapeutically effective amount is a cyclodextrin concentration in the range of from 1 mM to 75 mM, as required by independent claims 1 and 16.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. Specifically, Cataldo teaches the example wherein 50 mM 2-hydroxypropyl-gamma-cyclodextrin is administered by inhalation to reduce bronchial inflammation, which as evidenced by the present specification and described in the above rejection under 35 U.S.C. 103, necessarily has the effect of reducing the number of goblet cells in the subject's nasal mucosa. In addition, Cataldo teaches that their invention relates to a method used for treating bronchial inflammatory diseases, preferably asthma and chronic obstructive pulmonary disease (COPD) (p. 2, [0025], lines 1-3) (emphasis added).
It would therefore have been prima facie obvious to topically administer to a subject’s nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa tissue and to decrease nasal inflammation in view of ‘846 claiming a method for the treatment of COPD in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of a cyclodextrin compound recited therein to the mammal by inhalation, Cataldo teaching a method of reducing bronchial inflammation using the method claimed by ‘846 related to asthma and COPD, and as evidenced by the specification, this method of Cataldo having the effect of reducing goblet cells in a subject’s nasal mucosa. Finally, in view of Mygind specifically teaching nasal inflammation associated with asthma, Keller teaching nasal administration as preferred route of administration for treating nasal tissue, and Durham teaching infiltration of eosinophils during inflammation in both bronchial and nasal tissues, one of ordinary skill in the art would have recognized that the method claimed by ‘846 may reasonably be used to decrease nasal inflammation as well.
Regarding claims 3-11, 15, 17-18, in view of ‘846 claiming administration of cyclodextrin alone for treating COPD, one of ordinary skill in the art would have contemplated administering compositions comprising cyclodextrin that satisfy the limitations of present claims 1, 3-11, and 17-18, and 20, as well as using a device for aerosolization as required by claim 15, because Cataldo, Mygind, Durham, and Keller render obvious said compositions and methods for treating nasal inflammation, including nasal inflammation, as described in the above rejections under 35 U.S.C. 103.
Regarding claim 20, because the methods of claims 1 and 16 are obvious over the claims ‘846 in view of Cataldo, Mygind, Durham, and Keller, and the inhalable aqueous composition and the specific requirements of this composition are obvious over Cataldo, Mygind, Durham, and Keller, as described above, the method of claim 20 would also have been obvious over the claims of ‘846 in view of Cataldo, Mygind, Durham, and Keller.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of ‘846 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Vitins.
Claim 1 of ‘846 recites a method for the treatment of COPD (chronic obstruction pulmonary disease) in a host mammal in need of such treatment, comprising the step of administering a composition consisting essentially of an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of β-cyclodextrin, hydroxypropyl- β-cyclodextrin, sulfobutylether-β-cyclodextrin, random methylated-β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, hydroxypropyl β-cyclodextrin, hydroxybutyl-β-cyclodextrin, glucosyl- βcyclodextrin, maltosyl-β-cyclodextrin, 2-O-methyl-β-cyclodextrin or a combination thereof and their pharmaceutically acceptable salts. Claim 2 claims the cyclodextrin compound is hydroxypropyl-β-cyclodextrin, and claim 3 claims the mode of administration is inhalation.
The claims of ‘846 do not claim the method of present claim 1, wherein the nasal inflammation is a viral nasal inflammation, as required by present claim 2.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Vitins teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 1, wherein the subject has a viral nasal inflammation, in view of the claims of ‘846, Cataldo, Mygind, Durham, and Keller rendering obvious the present claim 1, as described in the above rejection, and Vitins further teaching the antiviral activity of a cyclodextrin composition with no additional active ingredients formulated for administration to the nose. Therefore one of ordinary skill in the art would have recognized, in view of Vitins, that nasal inflammation resulting from viral nasal inflammation may be reasonably treated using the method obvious over the claims of ‘846, Cataldo, Mygind, Durham, and Keller.
Claims 12-14 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of ‘846 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Cataldo (2001).
Claim 1 of ‘846 recites a method for the treatment of COPD (Chronic obstruction pulmonary disease) in a host mammal in need of such treatment, comprising the step of administering a composition consisting essentially of an effective amount of cyclodextrin compound to the mammal, wherein the cyclodextrin compound is selected from the group consisting of β-cyclodextrin, hydroxypropyl- β-cyclodextrin, sulfobutylether-β-cyclodextrin, random methylated-β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, hydroxypropyl β-cyclodextrin, hydroxybutyl-β-cyclodextrin, glucosyl-β-cyclodextrin, maltosyl-β-cyclodextrin, 2-O-methyl-β-cyclodextrin or a combination thereof and their pharmaceutically acceptable salts. Claim 2 claims the cyclodextrin compound is hydroxypropyl-β-cyclodextrin, and claim 3 claims the mode of administration is inhalation.
The claims of ‘846 do not claim the method of claim 1 or 16, wherein the composition comprising cyclodextrin has the specific properties recited in present claims 12-14 and 19.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Cataldo (2001) teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claims 1 and 16 with the compositions recited in present claims 12-14 and 19 in view of the claims of ‘846, Cataldo, Mygind, Durham, and Keller rendering obvious the present claims 1 and 16, as described in the above non-statutory double patenting rejections, and Cataldo (2001) further teaching that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommending isotonic solutions for inhalation to reduce bronchoconstriction. Therefore, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution to reduce symptoms of bronchoconstriction. In addition, one would have considered Cataldo and Cataldo (2001) for guidance on the specific salt concentration in the composition, and would have further adjusted said salt concentration in response to any symptoms of bronchoconstriction.
Claims 1, 4-11, 15-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. 9,993,487 B2 (reference patent, hereafter ‘487) in view of Cataldo, Mygind, Durham, and Keller.
Didier Cataldo is an inventor on the present application and on ‘487.
Claim 1 of ‘487 recites a method of reducing inflammatory cells in lung tissue in a human wherein the human is in need of such treatment, said method comprising administering to the human a pharmaceutical composition consisting essentially of budesonide, or a pharmaceutically acceptable salt or ester thereof, and hydroxypropyl-β cyclodextrin (HP-β-CD), wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, and the HP-β-CD are in a stoichiometric ratio of from about 1:1 to about 2:1, wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, is present in the pharmaceutical composition in an effective amount, and wherein the effective amount of the budesonide, or a pharmaceutically acceptable salt or ester thereof, is in a range of from about 0.05 mcg to about 1000 mcg, and claim 7 requires the composition is an inhalation solution.
The claims of ‘487 do not teach a topical method of treatment for decreasing nasal inflammation by topically administering to the subject nasal mucosa tissue an inhalable
composition comprising one or more cyclodextrins or pharmaceutically acceptable
derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa
tissue, whereby said topical method of treatment decreases the subject's nasal
inflammation; and wherein the one or more cyclodextrins or pharmaceutically acceptable derivatives thereof are in a therapeutically effective amount and wherein, the therapeutically effective amount is a cyclodextrin concentration in the range of from 1 mM to 75 mM, as required by independent claims 1 and 16.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. Specifically, Cataldo teaches the example wherein 50 mM 2-hydroxypropyl-gamma-cyclodextrin is administered by inhalation to reduce bronchial inflammation, which as evidenced by the present specification and described in the above rejection under 35 U.S.C. 103, necessarily has the effect of reducing the number of goblet cells in the subject's nasal mucosa.
It would therefore have been prima facie obvious to topically administer to a subject’s nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa tissue and to decrease nasal inflammation in view of ‘487 claiming a method for reducing inflammatory cells in lung tissue by administering to a human a composition comprising hydroxypropyl-β cyclodextrin via inhalation, Cataldo teaching a method of reducing bronchial inflammation by administering via inhalation a composition comprising either hydroxypropyl-β-cyclodextrin or hydroxypropyl-γ-cyclodextrin, and as evidenced by the specification and described above, this method of Cataldo necessarily having the effect of reducing goblet cells in a subject’s nasal mucosa. In addition, in view of Mygind specifically teaching nasal inflammation associated with asthma, Keller teaching nasal administration as preferred route of administration for treating nasal tissue, and Durham teaching infiltration of eosinophils during inflammation in both bronchial and nasal tissues, one of ordinary skill in the art would have recognized that the method of ‘487, which is directed to reducing inflammatory cells in lung tissue, may reasonably be used to decrease nasal inflammation as well, because this composition, when administered via inhalation, would be expected to contact the human’s nasal mucosa.
Regarding claims 4-11, 15, and 17-18, in view of ‘487 claiming administration of cyclodextrin alone for treating inflammation in lung tissue, one of ordinary skill in the art would have contemplated administering compositions comprising cyclodextrin that satisfy the limitations of present claims 1, 4-11, and 17-18, as well as using a device for aerosolization as required by claim 15, because Cataldo, Mygind, Durham, and Keller render obvious said compositions and methods for treating nasal inflammation, as described in the above rejections under 35 U.S.C. 103.
Regarding claim 20, because the methods of claims 1 and 16 are obvious over the claims ‘487 in view of Cataldo, Mygind, Durham, and Keller, and the inhalable aqueous composition and the specific requirements of this composition recited in claim 20 are obvious over Cataldo, Mygind, Durham, and Keller, as described above, the method of claim 20 would also have been obvious over the claims of ‘487 in view of Cataldo, Mygind, Durham, and Keller
In this instance, because the claims of ‘487 claim administration of a composition comprising hydroxypropyl-β-cyclodextrin, Cataldo teaches reducing bronchial inflammation by administering via administration by inhalation of either hydroxypropyl-β-cyclodextrin or hydroxypropyl-γ-cyclodextrin, which, as evidenced by the instant specification, reduces goblet cell counts, the method obvious over the claims of ‘487 in view Cataldo, Mygind, Durham and Keller would also reduce goblet cell counts, absent evidence to the contrary.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of ’487 in view of Cataldo, Mygind, Durham Keller as applied to claims 1, 4-11, 15-18, and 20 above, and further in view of Vitins.
Claim 1 of ‘487 recites a method of reducing inflammatory cells in lung tissue in a human wherein the human is in need of such treatment, said method comprising administering to the human a pharmaceutical composition consisting essentially of budesonide, or a pharmaceutically acceptable salt or ester thereof, and hydroxypropyl-β cyclodextrin (HP-β-CD), wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, and the HP-β-CD are in a stoichiometric ratio of from about 1:1 to about 2:1, wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, is present in the pharmaceutical composition in an effective amount, and wherein the effective amount of the budesonide, or a pharmaceutically acceptable salt or ester thereof, is in a range of from about 0.05 mcg to about 1000 mcg, and claim 7 requires the composition is an inhalation solution.
The claims of ‘487 do not claim the method of present claim 1, wherein the nasal inflammation is a viral nasal inflammation, as required by present claim 2.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Vitins teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 1, wherein the subject has a viral nasal inflammation, in view of the claims of ‘487, Cataldo, Mygind, Durham, and Keller rendering obvious the present claim 1, as described in the above non-statutory double patenting rejection, and Vitins further teaching the antiviral activity of a cyclodextrin composition formulated for administration to the nose. Therefore one of ordinary skill in the art would have recognized, in view of Vitins, that nasal inflammation resulting from viral nasal inflammation may be reasonably treated using the method obvious over the claims of ‘487, Cataldo, Mygind, Durham, and Keller.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of ’487 in view of Cataldo, Mygind, and Durham as applied to claims 1, 4-11, 15-18, and 20 above, and further in view of Cataldo (2001).
Claim 1 of ‘487 recites a method of reducing inflammatory cells in lung tissue in a human wherein the human is in need of such treatment, said method comprising administering to the human a pharmaceutical composition consisting essentially of budesonide, or a pharmaceutically acceptable salt or ester thereof, and hydroxypropyl-β cyclodextrin (HP-β-CD), wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, and the HP-β-CD are in a stoichiometric ratio of from about 1:1 to about 2:1, wherein the budesonide, or a pharmaceutically acceptable salt or ester thereof, is present in the pharmaceutical composition in an effective amount, and wherein the effective amount of the budesonide, or a pharmaceutically acceptable salt or ester thereof, is in a range of from about 0.05 mcg to about 1000 mcg, and claim 7 requires the composition is an inhalation solution.
The claims of ‘487 do not claim the method of claim 16, wherein the composition comprising cyclodextrin has the specific properties recited in present claim 19.
Cataldo, Mygind, and Durham teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Cataldo (2001) teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 16 with the compositions recited in present claim 19 in view of the claims of ‘487, Cataldo, Mygind, and Durham rendering obvious claim 16, as described in the above non-statutory double patenting rejection, and Cataldo (2001) further teaching that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommending isotonic solutions for inhalation to reduce bronchoconstriction. Therefore, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution to reduce symptoms of bronchoconstriction. In addition, one would have considered Cataldo and Cataldo (2001) for guidance on the specific salt concentration in the composition, and would have further adjusted said salt concentration in response to any symptoms of bronchoconstriction.
Claims 1, 3-11, 15-18, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 15, and 18 of co-pending U.S. patent application 17/641,416 (reference application, hereafter ‘416) in view of Cataldo, Mygind, Durham, and Keller.
Didier Cataldo is an inventor on the present application and on ‘416.
The amended claims received August 15, 2025 are cited in this provisional non-statutory double patenting rejection.
Claim 1 of ‘416 claims a plurality of spherical or non-spherical microparticles for use in the treatment of respiratory diseases comprising one or more carriers and one or more active pharmaceutical ingredients with the properties recited therein. Claim 5 specifies the carrier is selected from the cyclodextrins shown therein, including 2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin, claim 6 specifies the carrier is hydroxypropyl-β-cyclodextrin. Claim 15 claims a method of treating a disease wherein microparticles analogous to those described in claim 1 are administered by inhalation, and claim 18 claims the disease is a respiratory disease selected from the group that includes asthma.
The claims of ‘416 do not claim a topical method of treatment for decreasing nasal inflammation by topically administering to the subject nasal mucosa tissue an inhalable
composition comprising one or more cyclodextrins or pharmaceutically acceptable
derivatives thereof for reducing the number of goblet cells in the subject's nasal mucosa
tissue, whereby said topical method of treatment decreases the subject's nasal
inflammation; and wherein the one or more cyclodextrins or pharmaceutically acceptable derivatives thereof are in a therapeutically effective amount and wherein, the therapeutically effective amount is a cyclodextrin concentration in the range of from 1 mM to 75 mM, as required by independent claims 1 and 16.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103. Specifically, Cataldo teaches the example wherein 50 mM 2-hydroxypropyl-gamma-cyclodextrin is administered by inhalation to reduce bronchial inflammation, which as evidenced by the present specification and described in the above rejection under 35 U.S.C. 103, necessarily has the effect of reducing the number of goblet cells in the subject's nasal mucosa.
It would therefore have been prima facie obvious to topically administer to a subject’s nasal mucosa tissue an inhalable composition comprising one or more cyclodextrins or pharmaceutically acceptable derivatives thereof to decrease nasal inflammation and reduce the number of goblet cells in the subject's nasal mucosa tissue in view of ‘416 claiming a method for the treatment of asthma in a host mammal in need of such treatment, consisting essentially of the step of administering an effective amount of the microparticles comprising cyclodextrin by inhalation, Cataldo teaching a method of reducing bronchial inflammation and treating asthma by administering via inhalation a composition comprising cyclodextrin, and as evidenced by the specification, this method of Cataldo having the effect of reducing goblet cells in a subject’s nasal mucosa. In addition, in view of Mygind specifically teaching nasal inflammation associated with asthma, Durham teaching infiltration of eosinophils during inflammation in both bronchial and nasal tissues, and Keller teaching nasal administration as preferred route of administration for treating nasal tissue, one of ordinary skill in the art would have recognized that the method of ‘416 may reasonably be used to decrease nasal inflammation as well.
Regarding claims 3-11, 15, and 17-18, in view of ‘416 claiming administration of cyclodextrin alone for treating asthma, one of ordinary skill in the art would have contemplated administering compositions comprising cyclodextrin that satisfy the limitations of present claims 1, 3-11, and 17-18, as well as using a device for aerosolization as required by claim 15, because Cataldo, Mygind, Durham, and Keller render obvious said compositions and methods for treating nasal inflammation, including nasal inflammation associated with asthma, as described in the above rejections under 35 U.S.C. 103.
Regarding claim 20, because the methods of claims 1 and 16 are obvious over the claims ‘416 in view of Cataldo, Mygind, Durham, and Keller, and the inhalable aqueous composition and the specific requirements of this composition recited in claim 20 are obvious over Cataldo, Mygind, Durham, and Keller as described in the above rejections under 35 U.S.C. 103, the method of claim 20 would also have been obvious over the claims of ‘416 in view of Cataldo, Mygind, Durham, and Keller.
In this instance, because the claims of ‘416 claim administration of a composition comprising hydroxypropyl-γ-cyclodextrin and hydroxypropyl-β-cyclodextrin, Cataldo teaches reducing bronchial inflammation by administering via administration by inhalation of either hydroxypropyl-β-cyclodextrin or hydroxypropyl-γ-cyclodextrin, which, as evidenced by the instant specification, reduces goblet cell counts, the method obvious over the claims of ‘416 in view Cataldo, Mygind, Durham, and Keller would also reduce goblet cell counts, absent evidence to the contrary.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 15, and 18 of co-pending U.S. patent application ‘416 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Vitins.
Claim 1 of ‘416 claims a plurality of spherical or non-spherical microparticles for use in the treatment of respiratory diseases comprising one or more carriers and one or more active pharmaceutical ingredients with the properties recited therein. Claim 5 specifies the carrier is selected from the cyclodextrins shown therein, claim 6 specifies the carrier is hydroxypropyl-beta-cyclodextrin. Claim 15 claims a method of treating a disease wherein microparticles analogous to those described in claim 1 are administered by inhalation, and claim 18 claims the disease is a respiratory disease selected from the group that includes asthma.
The claims of ‘416 do not claim the method of present claim 1, wherein the nasal inflammation is a viral nasal inflammation, as required by present claim 2.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Vitins teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of present claim 1, wherein the subject has a viral nasal inflammation, in view of the claims of ‘416, Cataldo, Mygind, Durham, and Keller rendering obvious the present claim 1, as described in the above non-statutory double patenting rejection, and Vitins further teaching the antiviral activity of a cyclodextrin composition with no additional active ingredients formulated for administration to the nose. Therefore one of ordinary skill in the art would have recognized, in view of Vitins, that nasal inflammation resulting from viral nasal inflammation may be reasonably treated using the method obvious over the claims of ‘416, Cataldo, Mygind, Durham, and Keller.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 19 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 15, and 18 of co-pending U.S. patent application ‘416 in view of Cataldo, Mygind, Durham, and Keller as applied to claims 1, 3-11, 15-18, and 20 above, and further in view of Cataldo (2001).
Claim 1 of ‘416 claims a plurality of spherical or non-spherical microparticles for use in the treatment of respiratory diseases comprising one or more carriers and one or more active pharmaceutical ingredients with the properties recited therein. Claim 5 specifies the carrier is selected from the cyclodextrins shown therein, claim 6 specifies the carrier is hydroxypropyl-beta-cyclodextrin. Claim 15 claims a method of treating a disease wherein microparticles analogous to those described in claim 1 are administered by inhalation, and claim 18 claims the disease is a respiratory disease selected from the group that includes asthma.
The claims of ‘416 do not claim the method of 16, wherein the composition comprising cyclodextrin has the specific properties recited in present claim 19.
Cataldo, Mygind, Durham, and Keller teach as described in the above rejections under 35 U.S.C. 103 and in the above non-statutory double patenting rejections.
Cataldo (2001) teaches as described in the above rejection under 35 U.S.C. 103.
It would therefore have been prima facie obvious to practice the method of claim 16 with the compositions recited in present claim 19 in view of the claims of ‘416, Cataldo, Mygind, Durham, and Keller rendering obvious claim 16, as described in the above non-statutory double patenting rejection, and Cataldo (2001) further teaching that inhalation of hypertonic solutions causes bronchoconstriction in asthma patients and recommending isotonic solutions for inhalation to reduce bronchoconstriction. Therefore, one of ordinary skill in the art would have recognized that administration of a hypertonic solution for treating nasal inflammation may have also caused bronchoconstriction, and thus would have contemplated administration of an isotonic solution to reduce symptoms of bronchoconstriction. In addition, one would have considered Cataldo and Cataldo (2001) for guidance on the specific salt concentration in the composition, and would have further adjusted said salt concentration in response to any symptoms of bronchoconstriction.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Response to Applicant’s arguments: Regarding the previous nonstatutory double patenting rejections, Applicant presents the same arguments as presented with respect to claim 1 above. Therefore, for the same reasons described above, the present nonstatutory double patenting rejections are maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN BRANDSEN whose telephone number is (703)756-4780. The examiner can normally be reached Monday - Friday from 9:00 am to 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at (571)270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693