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 .
Election/Restrictions
Applicant's election with traverse of the invention of Group I, drawn to a pharmaceutical composition and an oral dosage form comprising the pharmaceutical composition in the reply filed on 07/14/2026 is acknowledged. Applicant's further election with traverse of the species of aprepitant as the PSD, a composition where the optional pharmaceutical excipient is present, and an immediate release profile in the reply filed on 07/14/2026 is acknowledged.
The traversal is on the grounds that the application’s claims are drawn to only one combination of categories (product and process specially adapted for manufacture of that product), and unity of invention should be found on that categorical basis alone. Applicant further argues that the prior art comparison to Shelton (WO 2007/056205 A2) lacks merit, as the Examples of Shelton only provide the charge weights of the starting material, and SAIB was not detectable in the isolated solid dispersion by the LC method utilized. Applicant further argues that SAIB is only an interchangeable plasticizer in a cellulose-ester matrix and is not the drug’s carrier, while CMCAB is the primary component that constitutes 85-99% of the charge weight; Shelton’s findings suggest that the ibuprofen is not molecularly or amorphously dispersed within the SAIB itself, but rather within the CMCAB matrix with SAIB, to the extent it remains, is simply co-located within that matrix.
This is not found persuasive because PCT Rule 13.2 states (emphasis added), “Where a group of inventions is claimed in one and the same international application, the requirement of unity of invention referred to in Rule 13.1 shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.” (see also MPEP 1850), and the Examiner maintains that shared technical feature between the claimed inventions does not rise to the level of special technical feature, in view of the prior art of Shelton. Thus, the inventions do not fulfill the requirement of unity of invention.
Regarding Shelton, while Shelton could not detect SAIB in the solid dispersion by the liquid chromatography method utilized, one of ordinary skill in the art would understand that not every chemical compound can be detected by a particular LC method. Shelton clearly envisions that SAIB is, in fact, present in the solid dispersions; see particularly pg. 54, lines 12-18, “These Examples describe the preparation of…ibuprofen/CMCAB/SAIB solid dispersions” and claim 4 “further comprising at least one of the additive chosen from…sucrose acetate isobutyrate”. Shelton further suggests that the amounts (and thus corresponding ratios) of carboxyalkylcellulose ester, pharmaceutically active ingredient, and additives can be adjusted to reach ratios consistent with those of instant claim 1 (pg. 28, line 5-pg. 29, line 15). Per MPEP 2144.05 II. A., “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)”. No evidence of the criticality of the claimed ratio is currently found on the record.
The argument that CMCAB is the primary component and SAIB is not the drug’s carrier is unpersuasive. Instant claim 1 recites that the mass ratio of excipient to SAIB can range from 0:1 up to 100:1; that is, the claim is inclusive of situations where the excipient is the primary component. Further, Shelton teaches that compositions can be made by various techniques such as melt extrusion and high shear granulation (pg. 9, lines 18-22, and pg. 28, lines 1-4), substantially identical to those of the instant invention (see paragraph [0094] of the instant specification). Absence evidence to the contrary, the methods of Shelton will result in the poorly water-soluble drug present in the molecular or amorphous state in the matrix comprising SAIB and excipient CMCAB.
The requirement is still deemed proper and is therefore made FINAL.
Upon further search and consideration, the elected poorly water-soluble drug of aprepitant is being rejoined with carbamazepine.
Claims 10-15 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 07/14/2026.
Claims 2 and 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the election requirement in the reply filed on 07/14/2026.
Claims 1, 3-9, and 19 are under current examination.
Priority
This application is a national stage entry of PCT/US2022/028570, filed 05/10/2022. Priority has
been claimed to US PRO 63/192,374, filed 05/24/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/21/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The drawings are objected to because Figs. 2 and 3 are blurry and the axis and legend labels cannot be read. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 5 is objected to because of the following informalities: it is suggested that “(C) a total number of donor hydrogen” should read “(C) a total number of donor hydrogens”.
Appropriate correction is required.
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, 3-9, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Shelton et al. (WO 2007/056205 A2, published May 18th, 2007; included on IDS submitted 11/21/2023); hereafter “Shelton”, as evidenced by NIH (“Carbamazepine”, National Library of Medicine, PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Carbamazepine).
Regarding instant claims 1, 3, and 6, Shelton teaches pharmaceutical compositions for delivery of pharmaceutically active substances having low solubility in a medium such as water, the compositions comprising said pharmaceutically active agent and at least one carboxyalkylcellulose ester (pharmaceutically acceptable excipient) (see entire document, particularly abstract and claim 1). The compositions are taught to comprise a solid dispersion and, in an embodiment, the pharmaceutically active agent is amorphous (pg. 7, line 24-pg. 8, line 13). Shelton further teaches that the pharmaceutically active agent is chosen from those including carbamazepine (pg. 20, lines 10-11). Shelton further teaches the inclusion of at least one additive chosen from those including sucrose acetate isobutyrate (SAIB) (claim 4; pg. 24, line 24-pg. 25, line 2). Shelton teaches that solid dispersions can be prepared by methods such as co-evaporation, in which the solvent is removed, and solvent-free processes (see pg. 9, lines 18-22 and pg. 51, lines 9-19), and thus contemplates compositions which are free from solvent.
Shelton exemplifies a solid dispersion comprising carbamazepine, CMCAB, and SAIB where 0% of the drug is crystalline, indicating that the solid dispersion is amorphous (pg. 56, lines 5-13 and Example 93 at Table 8 at pg. 73). Shelton exemplifies a ratio of CMCAB (excipient) to SAIB of 25.12 g to 1.52 g, or 16.5:1, consistent with the recited mass ratio of claim 1 (iii). Shelton further teaches that compositions can comprise: (a) at least one carboxyalkylcellulose ester in an amount ranging from 0.1 to 99 weight percent, based on the total weight (a) and (b) in said composition; (b) the at least one pharmaceutically active agent in an amount ranging from 0.1 to 99 weight percent, based on the total weight (a) and (b) in said composition; and (c) at least one additive in an amount ranging from 0 to 50 weight percent, based on the total weight of (a), (b),and (c) in the composition (pg. 28, line 5-pg. 29, line 15). Shelton therefore suggests that component ratios consistent with the instant claims are suitable for use in the solid dispersions.
Regarding instant claim 4, as noted above, Shelton exemplifies a ratio of CMCAB (excipient) to SAIB of 25.12 g to 1.52 g, or 16.5:1, consistent with the recited mass ratio of the instant claim. Shelton further teaches that in an embodiment, the compositions exhibit a near zero-order release profile wherein the pharmaceutically active agent releases almost immediately (pg. 13, lines 7-9).
Regarding instant claim 5, as evidenced by NIH, carbamazepine is reported to have a melting point of 190.2 °C, or less than 250 °C (pg. 10, “3.2.4 Melting Point”). Further, the structure of carbamazepine (reproduced below from NIH) demonstrates two donor hydrogens on the C(=O)NH2 functional group.
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Regarding instant claim 7, as noted above, Shelton teaches that solid dispersions can be prepared by methods such as co-evaporation, in which the solvent is removed, and solvent-free processes (see pg. 9, lines 18-22 and pg. 51, lines 9-19), and thus contemplates compositions which are free from solvent.
Regarding instant claim 8, Shelton teaches that the pharmaceutical composition can be formulated into an oral dosage form (pg. 27, lines 12-18).
Regarding instant claim 9, Shelton teaches that the pharmaceutical composition can take a variety of forms including tablets and capsules (pg. 27, lines 12-24).
Regarding instant claim 19, as noted above, Shelton teaches that solid dispersions can be prepared by methods such as co-evaporation, in which the solvent is removed, and solvent-free processes (see pg. 9, lines 18-22 and pg. 51, lines 9-19), and thus contemplates compositions which are free from solvent.
Shelton does not exemplify the carbamazepine to SAIB ratio of claim 1 (ii) with sufficient specificity to anticipate, but rather renders obvious the instant claims.
As noted above, Shelton teaches that compositions can comprise: (a) at least one carboxyalkylcellulose ester in an amount ranging from 0.1 to 99 weight percent, based on the total weight (a) and (b) in said composition; (b) the at least one pharmaceutically active agent in an amount ranging from 0.1 to 99 weight percent, based on the total weight (a) and (b) in said composition; and (c) at least one additive in an amount ranging from 0 to 50 weight percent, based on the total weight of (a), (b),and (c) in the composition (pg. 28, line 5-pg. 29, line 15). Shelton therefore suggests that component ratios consistent with the instant claims are suitable for use in the solid dispersions. Per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Shelton further suggests that the amount of active ingredients can be adjusted to achieve the desired therapeutic response (pg. 33, lines 7-23), and that the inclusion of additives affects the release profile of active ingredients (pg. 61, lines 9-18; Tables 17 and 17A-C at pgs. 78-80). Thus, it would have been prima facie obvious to one of ordinary skill in the art to routinely optimize the amounts of active agent and SAIB, and their corresponding ratio, in the compositions of Shelton in order to achieve a dosage form with a desired therapeutic effect and release profile. Per MPEP 2144.05 II. A., “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)”.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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