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 .
Claim Status
Claims 1-20 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-12) in the reply filed 6/8/2026 is acknowledged. Applicant’s species election without traverse of i) hydroxypropyl methyl phthalate (HPMCP) (the polymer) ii) sodium cation (the counterion) and iii) miconazole (the API) in the reply filed 6/8/2026 is acknowledged.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim. Election was made without traverse in the reply filed 6/8/2026.
Claim 5 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed 6/8/2026.
Claims 1-4 and 6-12 are under consideration to the extent of the elected species, e.g. the polymer is HPMCP, the counterion is sodium cation, and the API is miconazole.
Claim Objections
Claim 2 is objected to for failing to correctly recite “hydroxypropyl methylcellulose phthalate (HPMCP)”. Claim 2 currently recites “hydroxypropyl methyl phthalate (HPMCP)”. While it is clear what applicant means, appropriate correction is required.
Specification Objections
The specification is objected to for failing to correctly disclose “hydroxypropyl methylcellulose phthalate”. The specification currently discloses “hydroxypropyl methyl phthalate”. While it is clear what applicant means, 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 1-4, 6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Williams et al. (US20200206139A1, published 7/2/2020) as evidenced by Bhujbal et al. (Acta Pharmaceutica Sinica B 2021:11(8):2505-2536, Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies) in view of Xu et al. (Radiation effects on hydroxypropyl methylcellulose phthalate in aqueous system, published 9/8/2007).
Williams teaches pharmaceutical composition comprising a therapeutic agent embedded within a pharmaceutically acceptable polymer and a spontaneously emulsifying component (abstract). This spontaneously emulsifying component comprises a lipid, solvent, or oil, and a surfactant or hydrophilic solvent. This component allows for the composition to overcome limited dissolution and increases the overall solubility (par. [0003]). Williams teaches that this composition mostly comprises the pharmaceutically acceptable polymer as the main drug delivery vehicle, wherein the polymer comprises from about 20 wt% to about 80 wt% of the overall composition (par. [0031]). The polymer can be a number of acceptable polymers, including hydroxypropylmethylcellulose phthalate (HPMCP) (par. [0093]) (cf. claim 2). Williams continues to teach that the composition comprises an active pharmaceutical ingredient (API) and that the API may be selected from a group including miconazole (par. [0081]) (cf. claim 11). Miconazole is an antifungal imidazole agent (par. [0082]) (cf. claim 10). The API, such as miconazole, comprises from about 10 wt% to about 60 wt% (par. [0016]) (cf. claim 9). As evidenced by Bhujbal, an amorphous solid dispersion (ASD) is “a solid dispersion in which the active ingredient is dispersed within an excipient matrix in a substantially amorphous form” (pg. 2506, sec. 1.1). Thus, Williams composition comprising a therapeutic agent (i.e.., miconazole), a pharmaceutically acceptable polymer (i.e., HPMCP), and a spontaneously emulsifying component comprising a lipid, solvent, or oil, and a surfactant or hydrophilic solvent is necessarily an ASD. .
However, Williams does not teach the use of the polymer HPMCP in its salt form, wherein the counterion for the polymer’s negative charge is sodium cation.
This deficiency is made up for by the teachings of Xu et al.
Xu teaches the conversion of typical HPMCP to Na type (i.e. the sodium salt form) to form a hydrogel in paste-like status by radiation crosslinking (abstract). This was done to investigate the mechanism for gel formation and evaluate the resulting polymer gels to guide future HPMCP-based controlled release systems for APIs (intro par. 4). Xu teaches that it is possible to form Na type HPMCP polymer, wherein the polymer has sodium cation counterions. Xu teaches that the Na salt of HPMCP is soluble in water (3.1 par. 1). This property is increased when the salt form of the polymer is used, as HPMCP alone is more hydrophobic on its own and conversion to the salt form causes it to become more hydrophilic (3.1 par. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instantly claimed invention to modify Williams to produce a pharmaceutical composition comprising from about 10 wt% to about 60 wt% of an amorphous therapeutic agent, including miconazole, from about 20 wt% to about 80 wt% of a pharmaceutically acceptable polymer, including HPMCP, and a spontaneously emulsifying component comprising a lipid, solvent, or oil, and a surfactant or hydrophilic solvent, wherein the HPMC is the Na salt of HPMCP as taught by Xu because Xu teaches that Na salt of HPMCP has increased solubility and the pharmaceutical compositions of Williams are for improving the solubility and dissociation of poorly soluble drugs for the improved delivery of drugs. One of ordinary skill in the art looking to develop a composition with increased solubility for low-solubility drugs or dispersions would reasonably combine the teachings of Williams and Xu, since Williams and Xu both teach increasing drug solubility for improved delivery. One of ordinary skill in the art would have had a reasonable expectation of success in forming the Na salt form of HPMCP as Xu outlines the method of preparation using the same HPMCP polymer as Williams. The teachings of Xu to form the salt form of the HPMCP polymer would result in a composition as taught by Williams comprising the salt form of the polymer (for greater solubility) along with an amorphous therapeutic agent, including miconazole. This resulting composition would comprise a main chain polymer of HPMCP with negatively charged carboxylic groups that are quenched by the sodium cations (cf. claims 1-4). This composition is necessarily an ASD comprising the Na salt form of HPMCP and an amorphous therapeutic agent, including miconazole and a spontaneously emulsifying component comprising a lipid, solvent, or oil, and a surfactant or hydrophilic solvent (cf. claim 6).
With respect to claims 8-9 and 12 directed to relative contents of various components in the compositions of the inventive compositions, the Examiner notes that the loadings taught in the cited references are not exactly congruent with the claim limitations. However, it is the Examiner's position that the cited art teaches a range of loadings of these components that significantly overlap with the claimed loadings and, as such, would render the claimed invention obvious. See MPEP § 2144.05. "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)."
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (US20200206139A1, published 7/2/2020) as evidenced by Bhujbal et al. (Acta Pharmaceutica Sinica B 2021:11(8):2505-2536, Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies) in view of Xu (Radiation effects on hydroxypropyl methylcellulose phthalate in aqueous system, published 9/8/2007) as applied to claims 1-4, 6, and 8-12 above, and further in view of Appel (US20020015731A1, published 2/7/2002, cited in IDS filed 11/12/2024).
Williams and Xu have been described supra.
However, neither Williams or Xu teach the inclusion of an amino acid or amino sulfonic acid.
This deficiency is made up for by the teachings of Appel.
Appel teaches a controlled release dosage form comprising a drug-containing composition and a water-swellable composition (abstract). Appel teaches that in one embodiment, the drug is present in the form of a solid, amorphous dispersion wherein the drug is dispersed in a pharmaceutically acceptable polymer selected from a group including hydroxypropyl methyl cellulose phthalate (HPMCP) (par. [0038]). Appel’s composition further comprises a fluidizing agent. This fluidizing agent is responsible for increasing the fluidity of the composition when the composition imbibes a given quantity of water, aiding in delivery of the drug (par. [0047]). Appel teaches that the fluidizing agent is beneficial for the overall delivery of the active ingredient from the amorphous solid dispersion that comprises a polymer such as HPMCP. Appel names amino acids as one such exemplary fluidizing agent (par. [0047]).
It would have been prima facie obvious to one of ordinary skill in the artbefore the effective filing date of the instant invention to modify the pharmaceutical composition as taught by Williams and Xu comprising from about 10 wt% to about 60 wt% of an amorphous therapeutic agent, including miconazole, from about 20 wt% to about 80 wt% of a pharmaceutically acceptable polymer, including HPMCP, and a spontaneously emulsifying component comprising a lipid, solvent, or oil, and a surfactant or hydrophilic solvent to further include a fluidizing agent, such as amino acids in order to increase the fluidity of the composition when the composition imbibes a given quantity of water, aiding in delivery of the drug according to Appel. The resulting pharmaceutical composition would comprise the HPMCP sodium salt-form polymer interspersed with an amorphous therapeutic agent, including miconazole, a spontaneously emulsifying component comprising a lipid, solvent, or oil, and a surfactant or hydrophilic solvent as well as amino acids to increase the fluidity of the composition in aqueous environments and aid in the delivery of miconazole. One would have reasonable expectation of success in modifying Williams and Xu with the teachings of Appel as all teachings rely on the same polymer, HPMCP, which is the major component of the composition.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW RYAN BURKE whose telephone number is (571)272-8949. The examiner can normally be reached Mon-Fri. 8am-5pm.
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, David Blanchard can be reached at 5712720827. 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.
/MATTHEW RYAN BURKE/Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
Prosecution Insights