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 .
Status of the Application
Claims 4-5, 9, 17-18, and 20-25 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 02/10/2026 are acknowledged. Claims under consideration in the instant office action are claims 4-5, 9, 17-18, and 20-25.
Applicants' arguments, filed 02/10/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 4 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Inhaled formulations and pulmonary drug delivery systems for respiratory infections, Advanced Drug Delivery Reviews, 2015, 85, pp. 83-99) in view of Ernst (US 2015/0246015) and McPhail et al. (Stability and bioavailability of a flucytosine suspension, International Journal of Pharmacy Practice, 1993, 2(4), pp. 235-239).
Zhou et al. is drawn towards inhaled formulations for respiratory infections (see abstract). Zhou et al. teaches “Dry powder inhaler (DPI) devices are generally small and portable. The duration of treatment for DPIs is also short [18–20] and this results in improved patient compliance [21]. Dry powder mixtures of drugs and/or excipients may also be chemically more stable and less susceptible to microbial contamination than corresponding liquid formulations.” (pg. 84, right column, third paragraph). Zhou et al. teaches “Immunocompromised patients with malignancy, hematologic disease, HIV, cancer and organ transplantation are highly susceptible to invasive pulmonary fungal infections. These infections cause unacceptably high mortality and morbidity rates (40–90%) and become an alarming healthcare problem [209,210]. A vast majority of the infected cases are caused by Candida spp. and Aspergillus spp. [211]. Oral and/or intravenous administrations of anti-fungal drugs, such as amphotericin B, flucytosine and a handful of clinically available azole agents, are the mainstay in the treatment of pulmonary fungal infections [212].” (pg. 92, right column, third paragraph).
Zhou et al. does not teach flucytosine in a powder form. Zhou et al. does not teach treating a fungal infection wherein the powder composition further comprises corn starch, lactose, and talc.
Ernst is drawn towards compositions for the treatment of immunogenic disorders (see abstract). Ernst teaches “In the methods of the invention the animal can be a rodent, primate, human or other animal with a nasal cavity. Examples of suitable pharmaceutical carriers, excipients and/or diluents are well known in the art and include, but are not limited to, a gum, a starch ( e.g. corn starch, pregeletanized starch), a sugar ( e.g., lactose, mannitol, sucrose, dextrose), a cellulosic material (e.g. microcrystalline cellulose), an acrylate (e.g. polymethylacrylate), calcium carbonate, magnesium oxide, talc, or mixtures thereof.” (paragraph 0239). Ernst teaches such compositions in the form of a powder suitable for intranasal administration (paragraph 0227).
McPhail et al. is drawn towards the stability and bioavailability of flucytosine suspensions (see abstract). McPhail et al. teaches that suspensions comprising powdered flucytosine (pg. 236, left column, second paragraph).
It would have been obvious to one of ordinary skill in the art to formulate flucytosine in a powdered form, as suggested by McPhail et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since suspensions comprising flucytosine in powdered form provides suitability stability and bioavailability while allowing for increased dosing as taught by McPhail et al. (see Conslusions), with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to formulate a powder composition further comprising corn starch, lactose, and talc, as suggested by Ernst, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since corn starch, lactose, and talc are common excipients in powders suitable for intranasal administration as taught by Ernst, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claims 5, 9, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Inhaled formulations and pulmonary drug delivery systems for respiratory infections, Advanced Drug Delivery Reviews, 2015, 85, pp. 83-99), McPhail et al. (Stability and bioavailability of a flucytosine suspension, International Journal of Pharmacy Practice, 1993, 2(4), pp. 235-239), and Ernst (US 2015/0246015) as applied to claim 4 and 21 above, and further in view of Welsh et al. (US 2009/0068287, already of record).
The teachings of Zhou et al., McPhail et al., and Ernst are presented above.
Zhou et al., McPhail et al., and Ernst do not teach flucytosine in an amount between about 250 mg and about 1500 mg.
Welsh et al. teaches topical formulations and methods of use of flucytosine in the treatment of fungal infections (see abstract). Welsh et al. teaches a therapeutically effective amount of the formulation comprises 0.3 g (300 mg) of flucytosine (paragraph 0045). Welsh et al. teaches the topical composition comprising a powder, ointment, solution, spray, or suspension, which can be applied to the skin, mucous membranes (e.g. nasal mucosa), vagina, oral cavity, and the like (paragraphs 0014, 0029). Welsh et al. teaches such compositions comprising a preservative such as sodium citrate or urea (paragraph 0050).
It would have been obvious to one of ordinary skill in the art to formulate flucytosine in an amount between about 250 mg and about 1500 mg, as suggested by Welsh et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Welsh et al. teaches 300 mg of flucytosine as a therapeutically active amount for the treatment of fungal infections, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Inhaled formulations and pulmonary drug delivery systems for respiratory infections, Advanced Drug Delivery Reviews, 2015, 85, pp. 83-99), McPhail et al. (Stability and bioavailability of a flucytosine suspension, International Journal of Pharmacy Practice, 1993, 2(4), pp. 235-239), and Ernst (US 2015/0246015) as applied to claim 4 and 21 above, and further in view of Simmons (US 2014/0348787, already of record).
The teachings of Zhou et al., McPhail et al., and Ernst are presented above.
Zhou et al., McPhail et al., and Ernst do not teach a composition further comprising gentamicin, clindamycin, mupirocin, and methylprednisolone.
Simmons is drawn towards compositions and methods for treating ear infections, which may include antifungals and antibiotics (see abstract). Simmons teaches gentamicin, clindamycin, mupirocin and methylprednisolone as active agents in the treatment of such infections (claims 7, 9, 11, 17-21).
It would have been obvious to one of ordinary skill in the art to treat a fungal or bacterial infection wherein the composition further comprises gentamicin, clindamycin, mupirocin, and methylprednisolone, as suggested by Simmons, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Claims 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Inhaled formulations and pulmonary drug delivery systems for respiratory infections, Advanced Drug Delivery Reviews, 2015, 85, pp. 83-99), McPhail et al. (Stability and bioavailability of a flucytosine suspension, International Journal of Pharmacy Practice, 1993, 2(4), pp. 235-239), Ernst (US 2015/0246015), and Attaway et al. (Subacute Invasive Pulmonary Aspergillosis Associated with Ankylosing Spondylitis, Am J Respir Crit Care Med, 2016, 193(5), pp. 572, already of record) as applied to claims 4 and 21 above, and further in view of Welsh et al. (US 2009/0068287, already of record).
The teachings of Zhou et al., McPhail et al., Ernst, and Attaway et al. are presented above.
Zhou et al., McPhail et al., Ernst, and Attaway et al. do not teach flucytosine in an amount between about 250 mg and about 1500 mg.
Welsh et al. teaches topical formulations and methods of use of flucytosine in the treatment of fungal infections (see abstract). Welsh et al. teaches a therapeutically effective amount of the formulation comprises 0.3 g (300 mg) of flucytosine (paragraph 0045). Welsh et al. teaches the topical composition comprising a powder, ointment, solution, spray, or suspension, which can be applied to the skin, mucous membranes (e.g. nasal mucosa), vagina, oral cavity, and the like (paragraphs 0014, 0029). Welsh et al. teaches such compositions comprising a preservative such as sodium citrate or urea (paragraph 0050).
It would have been obvious to one of ordinary skill in the art to formulate flucytosine in an amount between about 250 mg and about 1500 mg, as suggested by Welsh et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Welsh et al. teaches 300 mg of flucytosine as a therapeutically active amount for the treatment of fungal infections, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (Inhaled formulations and pulmonary drug delivery systems for respiratory infections, Advanced Drug Delivery Reviews, 2015, 85, pp. 83-99), McPhail et al. (Stability and bioavailability of a flucytosine suspension, International Journal of Pharmacy Practice, 1993, 2(4), pp. 235-239), and Ernst (US 2015/0246015) as applied to claim 4 and 21 above, and further in view of Attaway et al. (Subacute Invasive Pulmonary Aspergillosis Associated with Ankylosing Spondylitis, Am J Respir Crit Care Med, 2016, 193(5), pp. 572, already of record).
The teachings of Zhou et al., McPhail et al., and Ernst are presented above.
Zhou et al., McPhail et al., and Ernst do not teach treating subjects with arthritis or joint diseases associated with ankylosing spondylitis and other spondyloarthmpathy.
Attaway et al. is drawn towards invasive pulmonary aspergillosis associated with ankylosing spondylitis (pg. 572). Attaway et al. teaches that “Patients with ankylosing spondylitis can develop pulmonary manifestations of their disease, including apical fibrobullous disease (1). They are more likely to develop apical superinfections with mycobacterial or fungal infections as well, the most common of which is Aspergillus (2, 3).” (pg. 572).
It would have been obvious to one of ordinary skill in the art to treat subjects with arthritis or joint diseases associated with ankylosing spondylitis and other spondyloarthmpathies, as suggested by Attaway et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since fungal infections are known to develop in patients with ankylosing spondylitis as taught by Attaway et al., with a reasonable expectation of success absent evidence of criticality of the particular steps.
Response to Arguments
Applicant's arguments filed 02/10/2026 have been fully considered but they are not persuasive.
Applicant argues that “Notably, in contrast to Zhou and Ernst, McPhail describes ultimate drug delivery for GI tract absorption via administration of the suspension orally or nasogastric tube. McPhail describes preparing the suspension by crushing flucytosine tablets in a mortar with a pestle and grinding for two minutes to a uniform amorphous white powder, suspending the powder in a methylcellulose-based liquid suspending agent containing propylene glycol, syrup, and Nipasept, and storing the suspension. Thus, the powder in McPhail is an intermediate step. McPhail does not purport to teach administration of powder, but rather a suspension for the purpose of oral or nasogastric tube administration to the GI tract. A suspension includes solid particles dispersed in liquid, but these solid particles are not the same as a powder and administration of a suspension is not the same as administration of a powder format.” The Examiner respectfully disagrees since McPhail is only relied on for the teaching that flucytosine in particular can be in a powder form in a formulation (pg. 236, left column, second paragraph), and given that Zhou already teaches formulations suitable for dry powder inhalations (pg. 84, right column, third paragraph), one of ordinary skill in the art would have been motivated to formulate a composition comprising flucytosine in a powdered format.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
Claims 4-5, 9, 17-18, and 20-25 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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