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 Claims
Claims 1-2 and 4-24 are pending. Claim 3 is canceled.
Claims 18-24 are withdrawn as being drawn to a non-elected invention or species, there being no linking or generic claim.
Claims 1-2 and 4-17 are examined on their merits in light of the elected species of Compound I.
Previous Rejections
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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, and constitute the complete set presently being applied to the instant application.
Rejections Withdrawn
Claim Rejections - 35 USC § 103
In light of the cancelation of the claim, the rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over CN 105726488 (7/6/2016)(“CN”) in view of Zhang et al. WO 2017/009316 (1/19/2017) as evidenced by https://www.reference.com/science-technology/density-sugar-6b6c05ee13db5c32(accessed 7/24/2025) is withdrawn as moot.
Rejections Maintained
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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/e 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.
The rejection of claims 1-2 and 4-17 under 35 U.S.C. 103 as being unpatentable over CN 105726488 (7/6/2016)(“CN”) in view of Zhang et al. WO 2017/009316 (1/19/2017) as evidenced by https://www.reference.com/science-technology/density-sugar-6b6c05ee13db5c32(accessed 7/24/2025) is maintained.
CN discloses enteric coated micro pellets comprising a core bead; a first sealing layer, a drug loaded layer comprising RSV inhibitor and adhesive agent, a second sealing layer, and an enteric coating layer. (See CN claim 1). The core bead with a diameter of 0.2 to 2 mm is selected from a sucrose sphere and an enteric coating layer. (See claim 2). The core bead with a diameter of 0.1 to 2 mm is selected from a sucrose sphere, a microcrystalline cellulose sphere and a starch sphere. (See CN claim 1). The first and the second sealing layer includes Opadry. (See Abstract). The enteric coating material is selected from acrylic resin, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate. (See CN claim 8). Acrylic resin is selected from Eudragit L30D-55 and Eudragit L100. (See [0019]). Eudragit L100 is called for in instant claim 14. CN teaches a capsule as called for in instant claim 4.
The binding and adhesive agent can be hydroxypropyl methylcellulose. (See claim 4). Hydroxymethylcellulose is called for in instant claims 9 and 13.
A core bead is called for in instant claim 1 and a first sealing layer is called for in instant claim 1. A core bead that comprises a sucrose sphere is called for in instant claim 5. A core bead of 0.2 to 2 mm overlaps with the diameter of 0.2 to 2 mm called for in instant claim 5. With a diameter of 0.2 mm, the weight of a sugar sphere is (Volume=4/3 π radius3= 0.000004188 cm3; Weight = 0.000004188 cm3 x 1.59 g/cm3 = 0.007 mg. (The density of sugar is 1.59 g/cm3 as evidenced by https://www.reference.com/science-technology/density-sugar-6b6c05ee13db5c32) 0.007 mg falls within the 0.05 to 0.5 mg.
The enteric coating layer includes 50-90 wt% of an enteric coating material, 1-40 wt% of a plasticizer, 1-20 wt% of an anti-caking agent, and 1-20 wt% of an emulsifier. The first sealing layer has a weight gain of 2-10% and the drug-loaded layer has a weight gain of 10-200 wt%. 50-90 wt% of an enteric coating material overlaps with the 30-95 wt% called for in claim 13. 1-40 wt% of a plasticizer overlaps with the 1-40% of a plasticizer called for in instant claim 13, and 1-20 wt% of an anti-caking agent is called for in claim 13 as well. (See [0015-20]). 1-20 wt% of an emulsifier overlaps with the 0.5 -20 wt% of an emulsifier called for in instant claim 13. CN teaches that the enteric coating layer provides steady supply of RSV discharged in the intestine and optimizes the RSV inhibitor and as such the enteric coating layer is taught to be a results-effective variable. (See [0005]). Therefore, it would be no more than routine experimentation to experiment to arrive at the optimal weight of the enteric coating layer as called for in instant claims 13, 14 and 15.
CN teaches that its invention will not disintegrate or dissolve in stomach acid but will dissolve in the small bowel and enter the bloodstream. CN teaches that its invention allows for the optimization of the pharmacokinetic profile of the RSV inhibitor API and improves the safety window of the medicine as well as its anti-RSV activity. (See [0004]). CN also teaches that the sealing coats, the first sealing coat and the second sealing coat prevent the API from contacting the core bead and reacting with it and reacting with it chemically possibly degrading it, so the sealing coats are taught to be a results-effective variable. Therefore, it would be no more than routine experimentation to experiment to arrive at the optimal weight of the first sealing layer as called for in instant claim 6, 7. Therefore, it would be no more than routine experimentation to experiment to arrive at the optimal weight of the second sealing layer as called for in instant claim 10, 12.
The emulsifier can be Tween as called for in instant claim 13. The plasticizer can be polyethylene glycol as called for in claim 13. (See CN claim 8). Talc is taught as an anti-plastering or anti-caking aid. Talc is called for in instant claim 13.
Talc is taught as an anti-plastering agent and as such, CN teaches that talc is a results-effective variable and it would be no more than routine experimentation to experiment to arrive at the optimal amount of talc relative to the pellets as called for in instant claim 16.
CN teaches that the first sealing coat includes talc. (See CN claim 8). Talc in the first sealing layer is called for in instant claim 7.
CN teaches RSV inhibitors but does not teach N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine or a dosage amount of it. This deficiency is made up for with the teachings of Zhang et al.
Zhang et al. (Zhang) teaches crystalline forms of N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine for the treatment of respiratory syncytial virus infections (RSV). (See Abstract). N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine corresponds to the structure of Compound I wherein R1 is methyl and R2 is hydrogen as called for in instant claim 2. N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine is the elected species that falls with scope of Compound I in instant claim 1. Zhang teaches that its compounds show good stability and solubility, as well as good anti-RSV activity. (See page 2, lines 10-15). Zhang also states that it is teaching therapeutically effective amounts of compound (I) and is also teaching therapeutically effective amounts of compound (I) in a pharmaceutical dosage form. (See page 6).
N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine corresponds to the structure of Compound I wherein R1 is methyl and R2 is hydrogen as called for in instant claim 2. Zhang teaches 10-20 mg of N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine. (See Table 16). 10-20 mg overlaps with the 10 to 300 mg called for in instant claim 1.
Zhang teaches a size of the compound N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine as 0.1 mm which overlaps with the less than 100 micrometers called for in instant claim 17.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention making the CN formulation of a sugar sphere with 0.2 mm diameter and a first seal coat, a drug layer, an enteric coating layer including 50-90 wt% of an enteric coating material, 1-40 wt% of a plasticizer like polyethylene glycol, 1-20 wt% of an anti-caking agent like talc, and 1-20 wt% of an emulsifier like Tween, and a second seal coat to use 10-20 mg of N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine taught by Zhang in the drug layer in light of the teachings of Zhang that its compound N-[3-Amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5 H))-yl) -6- methyl-4-quiazolinamine shows good stability and solubility as well as good anti-RSV activity.
There would be a reasonable expectation of success because Zhang teaches a known RSV inhibitor that possesses good stability, solubility and anti-RSV activity and CN teaches a dosage formulation that is directed to a RSV inhibitors. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945), MPEP 2144.07.
Response to Arguments
Applicants’ comments of October 12, 2025 have been fully reviewed and are found to unpersuasive for the reasons described below.
Applicants argue that CN ‘488 fails to teach or suggest at least the element of amended claim 1 that recites “the pharmaceutical unit dosage composition includes 10 to 300 mg of the Compound (I). Applicants argue that Zhang teaches that 20 mg of compound (I) of each crystal form was placed in an aluminum pan and recorded the sample weight change under different humidity, so the 20 mg compound (I) in Zhang was used to measure dynamic vapour sorption, not in a pharmaceutical unit dosage composition, as required by claim 1.
Applicants’ arguments have been carefully reviewed and are not found to be persuasive. Applicants’ argument that Zhang’s teaching that 20 mg of compound (I) of was used to measure dynamic vapour sorption, not in a pharmaceutical unit dosage composition is not found to be persuasive because Zhang states that it is teaching therapeutically effective amounts of compound (I) and is also teaching therapeutically effective amounts of compound (I) in a pharmaceutical dosage form.
Zhang states that it is directed to therapeutically effective amounts of the crystalline form or the pharmaceutical composition it discloses. (See Zhang claim 27 and page 6, lines 5-10). Zhang is teaching and testing the attributes and properties of therapeutically effective amounts. Therefore, Zhang is testing amounts that include 100 mg (see Example 1), 44 mg (see Examples 5 and 6), 20 mg (see Example 7), and 40 mg (see Example 8). Each of these disclosed amounts overlaps with the 10 to 300 mg called for in instant claim 1.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
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SARAH CHICKOS
Examiner
Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619