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 .
Detailed Action
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 14 October 2025 and 18 November 2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. See attached copy of PTO-1449.
Status of Application
2. Applicants’ arguments/remarks filed 14 October 2025 are acknowledged. Claims 1-3, 6, 24-25, 27-28, 31-34, 36-37, 41, and 45 are currently pending. Claims 4-5, 7-23, 26, 29-30, 35, 38-40, 42-44, and 46-130 are cancelled. Claims 1-3, 6, 24-25, 27-28, 31-32, and 36 are currently amended. Claims 1-3, 6, 24-25, 27-28, 31-34, 36-37, 41, and 45 are examined on the merits within.
Withdrawn Rejections
3. Applicants’ arguments, filed 14 October 2025, with respect to the 35 U.S.C. 102(a)(1) Rejections have been fully considered and are persuasive. The 35 U.S.C. 102(a)(1) Rejections of claims 1-4, 6, 20-22, 24-25, and 27-28 have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Appel et al. (U.S. Patent Application Publication No. 2009/0142404) in view of Pieper (U.S. Patent Application Publication No. 2006/0204450).
New Rejections
Claim Rejections – 35 U.S.C. 103
4. 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.
5. Claim(s) 1-3, 6, 24-25, 27-28, 31-32, 34, 36-37, 41, and 45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Appel et al. (U.S. Patent Application Publication No. 2009/0142404) in view of Pieper (U.S. Patent Application Publication No. 2006/0204450).
Regarding instant claims 1-3, 25, and 27-28, Appel et al. teach using a spray drying process to form particles of sildenafil citrate coated with HPMCAS. See paragraph [0132]. The particles are in the size from 0.1 to 500 µm. See paragraph [0015]. The drug and polymer are mixed with excipients. See paragraph [0010]. Fillers and diluents include sucrose, xylitol, lactose, mannitol, microcrystalline cellulose, dextran, maltodextrin, sorbitol, etc. See paragraph [0089].
Regarding instant claim 6, the drug and polymer can be formulated into capsules. See paragraph [0085].
Regarding instant claim 24, in vitro dissolution tests were conducted on 2.542 mg of sildenafil citrate alone or 3.276 mg of coated crystals. See paragraph [0135].
Appel et al. do not teach lactose with an average particle diameter of 60 to 80 micrometers.
Pieper teaches novel compositions comprising anticholinergics and PDE 5-inhibitors. See abstract. PDE-5 inhibitors include sildenafil. See paragraph [0021]. The inhalable powders may include the actives with excipients. Excipients include lactose. See paragraphs [0040-0041]. The excipients have a particle size between 15 and 80 µm. The active substances have an average particle size of 0.5 to 10 µm. See paragraph [0042]. Examples include sildenafil and lactose combined in an inhalable formulation. See paragraph [0094]. The capsules comprise 25,000 micrograms (25 mg) of sildenafil citrate. The pharmaceutical composition can be used to treat pulmonary hypertension: unexplained pulmonary hypertension, primary plexogenic pulmonary hypertension, thrombotic pulmonary hypertension, embolic pulmonary hypertension, pulmonary hypertension secondary to congenital heart disease, pulmonary venous occlusive disease (PVOD), pulmonary venous hypertension, pulmonary hypertension in parenchymal lung disease, pulmonary hypertension in lung transplantation, as well as pulmonary hypertension due to hypoxic arteriopathy, pulmonary capillary haemangiomatosis, liver disease, medial defects of lung vessels, misalignment of pulmonary vessels, tumor emboli, drug abuser's lung, pulmonary schistosomiasis, and human immunodeficiency virus (HIV). See paragraph [0032]. The formulation suitable for inhalation can be inhalable powders, propellant-containing metered-dose aerosols and propellant-free inhalable solutions or suspensions. See claim 7.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to formulate the composition of Appel et al. into an inhalable composition because Pieper teach sildenafil can effectively be administered by inhalation. One would have been motivated, with a reasonable expectation of success, to provide a different effective route of administration. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the sizes of lactose between 15 and 80 µm since these are known effective excipient sizes when in combination with sildenafil active ingredients having an average particle size of 0.5 to 10 µm used for inhalation. It would have been well within the purview of the skilled artisan to modify the amount of active ingredient within known effective amounts taught by Pieper. It would have been well within the purview of the skilled artisan to formulate the composition as a metered dose inhaler (i.e., package) because Pieper teaches inhalers are an effective form of administration. It would have been well within the purview of the skilled artisan to add additional active ingredients to optimize the formulation to provide additional therapeutic benefits. It would have been obvious to administer the formulation to treat HIV or pulmonary diseases because Pieper teaches the effectiveness of the combination of sildenafil and lactose in treating these diseases when administered in an inhalable form.
6. Claim(s) 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Appel et al. (U.S. Patent Application Publication No. 2009/0142404) in view of Pieper (U.S. Patent Application Publication No. 2006/0204450) as applied to claims 1-3, 6, 24-25, 27-28, 31-32, 34, 36-37, 41, and 45 above and further in view of Beck-Broichsitter et al. (U.S. Patent Application Publication No. 2014/0127311).
Appel and Pieper do not teach administration 1, 2, 3 or 4 times a day.
Beck-Broichsitter et al. teach biocompatible nano-polymer particles for treatment of pulmonary hypertension. See abstract. Sildenafil citrate is an active agent of the group of phosphodiesterase-5 inhibitors administered to a patient orally three times daily. See paragraph [0005]. The aim of the invention is to provide an aerosilizable and inhalable preparation allowing a long-lasting and controlled release of active agent. See paragraph [0016]. Prior art knows of inhalations as a more selective route of administration by which undesired systemic side effects can be avoided. The direct administration of the drug to the lung facilitates the targeted treatment of respiratory diseases as already demonstrated for the prostacyclin-analogue iloprost in the treatment of pulmonary hypertension. See paragraph [0011]. The formulation can be administered in metered dose inhalers or dry powder inhalers. See paragraph [0035].
It would have been obvious to modify the daily administration based on known effective parameters taught by Beck-Broichsitter et al., such as three times a day, dependent on the desired effect needed.
Conclusion
7. Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
8. No claims are allowed at this time.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615