DETAILED ACTION
Claims 1-2, 4-11, 13-24 are pending. Of these, claims 13-23 are withdrawn as directed to a nonelected invention. Therefore, claims 1-2, 4-11, and 24 are under consideration on the merits.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/23/26 was filed prior to the mailing date of a Final Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, it was considered by the Examiner.
Status of the Rejections
The 112(b) rejection is withdrawn in view of the amendment.
The 103 rejections are withdrawn in view of the amendment and new rejections are set forth below.
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 and 24 are newly rejected necessitated by Applicant’s amendment under 35 U.S.C. 103 as unpatentable over Frank et al. (Pharmaceutics 2021, 13, 2017; of record in IDS) in view of Balakrishnan et al. (US Pat. Pub. 2017/0190763; of record).
As to claims 1 and 24, Frank et al. shares common inventors with the present application and was published on 11.26.21, which is within the one year grace period prior to the filing date of the present application. The inventive entity of Frank et al., however, is not identical to the present inventive entity nor is it a subset of the present inventive entity, and there is no evidence of record that the relevant disclosure of Frank et al. was obtained from the present inventors. Therefore, the 102(b)(1) exception does not apply based upon the evidence of record, and Frank et al. is currently treated as prior art to the present application.
Frank et al. discloses a process for densifying a co-precipitated material comprising posaconazole (an “API”) comprising introducing a solvent stream containing dissolved API and HPMCAS_M (the elected species of “stabilizing excipient”) into an anti-solvent comprising acidified water to form a coprecipitated amorphous dispersion of claim 1, followed by drying and annealing at a temperature above the wetted glass transition temperature of the coprecipitated material in order to density the material (Section 2.2.3. on page 4 and Section 3 on page 5 and last paragraph of page 10). Frank teaches that the process is notable for its ability to enable the production of amorphous solid dispersions containing pharmaceutical actives that have thermal instability and limited solubility.
As to claims 1 and 24, Frank does not further expressly disclose that the API is ulonivirine as recited by claim 1, nor that the HPMCAS excipient is HPMCAS-L (i.e., lower substituted) as opposed to the HPMCAS-M (i.e., medium substituted) excipient disclosed by Frank.
Balakrishnan discloses that MK-8507 (synonymous with “ulonivirine”) as a known anti-HIV compound (paragraph 259).
As to claims 1 and 24, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the process of Frank by selecting ulonivirine as the API, because Balakrishnan discloses that ulonivirine was a known API at the time of the effective filing date of the present invention, such that the skilled artisan would have been motivated to select ulonivirine in with a reasonable expectation of success in generating co-precipitated particles of ulonivirine stabilized with an excipient having improved stability and solubility and that could be used to formulate the ulonivirine as a tablet for oral administration.
Regarding claim 24, it further would have been prima facie obvious to select a lower substituted HPMCAS-L as the excipient because these compounds vary only by the degree of substitution and the skilled artisan would have been optimizing the compound for the same purpose in the Frank method as in the present invention, i.e., to serve as a stabilizing excipient for the production of a coprecipitated amorphous dispersion of a pharmaceutical. Discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 2, 4-5, and 7-11 are rejected under 35 U.S.C. 103 as unpatentable over Frank et al. (Pharmaceutics 2021, 13, 2017) in view of Balakrishnan et al. (US Pat. Pub. 2017/0190763) as applied to claims 1 and 24 above, and further in view of Schenck et al. (US Pat. Pub. 2020/0261365; of record in IDS).
The teachings of Frank are relied upon as discussed above. Frank teaches the use of HPMCAS_M as discussed above, which is a “stabilizing excipient” of claim 5 that is a polymer of claim 8 and that is a hydroxypropyl methylcellulose acetate succinate of claims 9-10), and further teaches annealing via removal of solvent and increased temperature as discussed above (claim 7). Frank further teaches that the amorphous dispersion can be compressed into tablets as recited by claim 11 (last paragraph of page 8).
Frank does not further expressly disclose that the drying and annealing step is carried out using thin film evaporation as recited by claim 2, or that the co-precipitated amorphous dispersion undergoes densification and at a higher level relative to a process that does not anneal above the wetted glass transition temperature as recited by claim 4.
Schenck discloses a process for preparing a pharmaceutical composition comprising particles comprising an active (API) and a stabilizing excipient, the process comprising introducing a solvent stream containing the API dissolved in a solvent along with a stabilizing excipient into anti-solvent to form a co-precipitated material, wherein the stabilizing excipient may be hydroxypropyl methyl cellulose acetate succinate, which is the elected species of stabilizing excipient (paragraphs 25, 33). Schenck further teaches drying the co-precipitated material as recited by claim 1 by evaporating the solvent using thin film evaporation as recited by claim 2 (paragraphs 21 and 35-41). The thin film evaporation removes the solvent as recited by claim 7, and the process also is carried out at increased temperature as recited by claim 7 (see the working examples which use a temperature of 60 degrees Celsius).
As to claims 2, 4-5, 7-11, and 21, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to use thin film evaporation to perform the drying and annealing step, because Schenck expressly teaches that the drying of a coprecipitated material comprising an API and hydroxypropyl methyl cellulose acetate succinate may be carried out via a thin film freezing step, such that the skilled artisan reasonably would have expected that thin film evaporation could be used for the annealing step in the Frank process of coprecipitating a material comprising an API and hydroxypropyl methyl cellulose acetate succinate. Such a modification is merely the simple substitution of one known element for another according to known methods to yield predictable results, which is prima facie obvious. MPEP 2143.
The resulting process will result in the co-precipitated amorphous dispersion undergoing densification and at a higher level relative to a process that does not anneal above the wetted glass transition temperature as recited by claim 4 because it is made by a process comprising the same steps recited by the claims. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When, as here, the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01.
Claim 6 is rejected under 35 U.S.C. 103 as unpatentable over Frank et al. (Pharmaceutics 2021, 13, 2017) in view of Balakrishnan et al. (US Pat. Pub. 2017/0190763) and Schenck et al. (US Pat. Pub. 2020/0261365) as applied to claims 2, 4-5, 8-11, and 21 above, and further in view of McClain (WO2012/092504).
The teachings of Frank, Balakrishnan, and Schenck are relied upon as discussed above, and Frank further teaches that the solvent and anti-solvent are mixed using a rotor stator device (see Figure 1), but Frank does not further expressly specify that the rotor stator device is in-line as recited by claim 6.
McClain discloses that high shear mixers disperse one phase such as a liquid into another phase such as another liquid with which it normally would be immiscible, and that such mixers can be used to create granular products (paragraph 374). McClain further teaches that one example of a high shear mixer is an inline rotor-stator mixer, and that ultra high shear inline mixers can produce particles of an exceptionally narrow particle size distribution (paragraphs 378-382)
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the process of Frank, Balakrishnan, and Schenck as combined supra by selecting an in-line rotor stator as the type of rotor stator mixer used to produce the co-precipitated particles, because Frank discloses that a rotor stator mixer is suitable for use in the method taught therein and McClain teaches that inline rotor-stator mixers are a type of rotor-stator mixer that are known to be useful in generating particles and that an ultra high shear inline mixer advantageously allows for exceptional control over the size distribution of the particles, such that the skilled artisan reasonably would have expected that said inline rotor stator mixers could be used as the type of rotor stator mixer in the Frank process. Such a modification is merely the simple substitution of one known element for another according to known methods to yield predictable results, which is prima facie obvious. MPEP 2143.
Response to Arguments
Applicant’s arguments have been considered carefully but are moot in light of the new grounds of rejection.
Conclusion
Applicant's 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAREN GOTFREDSON whose telephone number is (571)270-3468. The examiner can normally be reached on M-F 9AM-6PM.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600
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