*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 .
Applicant’s response dated December 10, 2025 is acknowledged.
Priority
This application is a 371 of PCT/US2020/048429 filed on 08/28/2020, and claims benefit
in provisional application 62/892,679 filed on 08/28/2019.
Claim Status
Claims 1-3, 7, 8, 10, 12-14, 19, 20, 23-27, 30, 31, 36, and 38 are pending. Claims 4-6, 9, 11, 15-18, 21, 22, 28, 29, 32-35, and 37 were canceled. Newly added claim 38 reads on the elected invention of Group I. Claims 1-3, 14, and 36 were amended. Claims 13, 14, 19, 20, 23-27, 30, and 31 remain withdrawn. Claims 1-3, 7, 8, 10, 12, 36, and 38 are examined.
Withdrawn Claim Rejections — 35 USC § 112(d)
Rejections of claims 2 and 36 are withdrawn because rejections were obviated with claim amendments.
Maintained and New Claim Rejections — 35 USC § 103
Necessitated by Amendment
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 7, 8, 10, 12, 36, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Van Den Mooter (WO 2005/117834 Al Published December 15, 2005 - of record in IDS dated 02/16/2022), Staric (US 2016/0256433 Al Published September 8, 2016 - of record in IDS dated 02/16/2022).
The claims encompass an amorphous solid dispersion.
Van Den Mooter teaches solid dispersions of a basic drug and a polymer containing acidic groups (Title). These compositions comprise solid dispersions comprising (a) at least one basic drug compounds and (b) at least one pharmaceutically acceptable water-soluble polymer containing acidic groups (Abstract). Solid dispersions are an approach to enhance the dissolution behavior of drugs, especially sparingly water soluble drugs. By forming a solid dispersion the
substance crystallinity may be decreased since the substance may be present in an amorphous state and this might be desirable since dissolution of an amorphous substance does not require energy to break up the crystalline lattice (page | lines 26-30). The term "a solid dispersion" also comprises dispersions which are less homogenous throughout than solid solutions. Such dispersions are not chemically and physically uniform throughout or comprise more than one phase. For example, the term "a solid dispersion” also relates to particles having domains or small regions wherein amorphous, microcrystalline or crystalline (a), or amorphous, microcrystalline or crystalline (b), or both, are dispersed more or less evenly in another phase comprising (b), or (a) (page 3 lines 8-14). The drug is a basic drug compound with a relative inability to be dissolved into aqueous media (page 3 lines 23-28). Preferably, the basic drug compound is a compound with a relative inability to be dissolved into aqueous media (page 3 lines 23-28). The polymer is a water soluble acidic polymer having an apparent viscosity of 1- 5000 mPa.s when dissolved at 20°C in an aqueous solution of 2 % (w/v) (page 4 lines 31-34). Most preferred polymer is polyacrylic acid (page 5 lines 13-14). Example on pages 14-15 teaches solid dispersions comprising 5, 10, 20, 30, 40, 50, 60, and 80 wt. % of drug (loperamide) relative to the total amount of solids (drug plus polymer), which were spray dried. PAA was the carrier. Since the dispersion only contained the drug and the PAA, the PAA is necessarily present in a concentration of 95, 90, 80, 70, 60, 50, 40, and 20 wt. %, respectively.
Van Den Mooter does not teach a suitable range of molecular weights of polyacrylic acid.
The teachings of Staric are related to an amorphous solid dispersion comprising a polymer and a specific drug (Abstract). The polymer comprises polyacrylic acid, among others (paragraph 0024). The polymer is preferably a linear polymer (paragraph 0030). The polymer has an average molecule weight between 10,000 Da and 3,000,000 Da (paragraph 0138).
The teachings of Van Den Mooter and Staric are related to amorphous solid dispersions comprising polyacrylic acid and a drug, and it would have been obvious to have combined their teachings because they are in the same field of endeavor.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed an amorphous solid dispersion comprising 80 wt. % of polyacrylic acid and a basic drug, wherein the polyacrylic has a viscosity of 1-5000 mPa.s when dissolved at 20°C in an aqueous solution of 2 % (w/v), and wherein the polyacrylic acid and the basic drug are the only components of the dispersion, with a reasonable expectation of success because Van Den Mooter teaches a solid dispersion comprising polyacrylic acid and a basic drug wherein the polyacrylic acid and the basic drug are both amorphous, and wherein the polyacrylic acid has a viscosity of 1-5000 mPa.s when dissolved at 20°C in an aqueous solution of 2 % (w/v). It would have been obvious to have formed the dispersion comprising polyacrylic acid in a concentration of 80 wt. % and the basic drug in the concentration of 20 wt. % because Van Den Mooter teaches an example of a solid dispersion comprising polyacrylic acid in a concentration of 80 wt. % and the basic drug in the concentration of 20 wt. %. The claimed concentration range of polyacrylic acid is obvious because it encompasses 80 wt. %.
It would have been obvious to have selected the basic drug from compounds belonging to BCS class II and IV, with a reasonable expectation of success because Van Den Mooter teaches that the term basic drug compound includes drug compounds belonging to BCS class II and IV (paragraph bridging pages 3 and 4).
Regarding claims 1 and 7, the polyacrylic acid and the drug together comprise 100% of the amorphous solid dispersion, which meets the limitation that requires the polyacrylic acid and the drug to be present together in a concentration of at least 80 wt. % and at least 90 wt. %. Viscosity ranges in claims 1 and 3, from 100 cP to 1000 cP and from 200 cP to 1000 cP, are obvious over 1-5000 mPas (equivalent to 1-5000 cP) because claimed ranges overlap with Van Den Mooter’s range. The examiner acknowledges that viscosity in Van Den Mooter was measured differently than the claimed viscosity ranges. However, the Office does not have the means to test properties of prior art compositions for the purpose of comparing to properties of claimed compositions. Additionally, the specification was reviewed and there is no evidence that claimed ranges are critical.
Regarding the limitation that requires a linear polyacrylic acid, it is apparent from the chemical structure of polyacrylic acid on page 13 of Van Den Mooter that polyacrylic acid is linear. Additionally, Staric teaches using linear polyacrylic acid to make amorphous solid dispersions of active pharmaceutical agents.
Van Den Mooter does not teach a molecular weight range of polyacrylic acid. It would have been obvious to have used polyacrylic acid having an average molecule weight between 10,000 Da and 3,000,000 Da, with a reasonable expectation of success because it was known from Staric that polyacrylic acid having an average molecule weight between 10,000 Da and 3,000,000 Da is suitable for making amorphous solid dispersions comprising polyacrylic acid and a drug. Staric does not teach how the molecular weight range was measured. However, the Office does not have the means to measure properties of prior art products in order to compare to properties of claimed products. The specification was reviewed and there is no evidence that claimed range is critical. The claimed molecular weight ranges of between 200,000 Da and 1,500,000 Da in claim 1 and from 500,000 Da to 1,500,000 Da are obvious because the ranges overlap with 10,000 Da and 3,000,000 Da.
Regarding claims 1, 2, and 36, it would have been obvious to have varied the amount of drug to polymer (a:b) in a range of weight ratios from 5:95 to 80:20, with a reasonable expectation of success because Van Den Mooter teaches examples of dispersions on page 14 formed by spray drying solutions containing 5, 10, 20, 30, 40, 50, 60, 70, and 80 % w/w of drug relative to the total amount of solids (drug plus polymer). The dispersion only contains the drug and the polymer, therefore the dispersion would have contained 95, 90, 80, 70, 60, 50, 40, 30, and 20 % w/w of polymer. The weight ratio of drug:polymer are 5:95, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, and 80:20. Claimed ranges of at least 3:1 and up to 6:1 in claim 1, at least 3:1 and up to 5:1 in claim 2, and at least 4:1 and up to 5:1 in claim 36 are obvious because prior art teaches 80:20 or 4:1, which is encompassed by claimed ranges. Additionally, claimed ranges overlap with Van Den Mooter’s range. Furthermore, Van Den Mooter teaches varying the drug to polymer, in a wt. by wt. ratio, from 5:1 to 1:899, preferably 5:1 to 1:100, more preferably from 2:1 to 1:100, even more preferably from 1:1 to 1:100, still more preferably from 1:1 to 1:5, or from 2:1 to 1:5, or from 1:1 to 1:3 (page 5 lines 18-22).
Regarding claim 8, Van Den Mooter does not teach presence of water in the solid dispersion, which renders the claim obvious when water concentration is 0 wt. %.
Regarding claims 10 and 12, it would have been obvious to have formed a tablet comprising up to 90 wt. % of the solid dispersion, with a reasonable expectation of success because Van Den Mooter teaches an embodiment of a tablet comprising the solid dispersion in a maximum amount of 90 wt. % (paragraph bridging pages 5 and 6). It would have been obvious to have formed the tablet comprising excipients, with a reasonable expectation of success because Van Den Mooter teaches forming the tablet by conventional tableting techniques with conventional excipients (page 9 lines 20-28).
Combining prior art elements according to known methods to obtain predictable results supports obviousness, and the selection of a known material suitable for its intended purpose supports obviousness.
Response to Arguments
Applicant’s arguments submitted in the remarks dated December 10, 2025, were fully considered but are not persuasive for the following reasons.
Argument that claims now exclude linear poly(acrylic acid) products referred to as high molecular weight is not persuasive because the claims recite the transitional phrase “comprising” and do not recite a negative limitation excluding said high molecular weight linear poly(acrylic acid).
Applicant argued that present invention unexpectedly exhibits a uniform, single amorphous phase and does not show drug phase separation despite the low solubility of class II and class IV drugs. Applicant cited passages from the instant specification to support the argument that claimed invention has unexpected properties.
Arguments related to unexpected results are not persuasive because the applicant has not met the requirements of MPEP 716.02. Van Den Mooter recognized that crystallization of a basic drug compound in a solid dispersion can be significantly suppressed when the basic drug compound is incorporated into a solid dispersion of a polymer containing acidic groups. Van Den Mooter further stated that solid dispersions described in the reference have an increased physical stability (paragraph bridging pages 1-2 and the rest of page 2).
Results for examples F10, F11, F13, F14, and F15 in Table 8 are not sufficient to overcome the rejections because the claimed composition is not commensurate in scope with the four examples (F10, F13, F14, and F15) that exhibited the asserted unexpected amorphous characteristics. The applicant did not show with data that said unexpected properties would have occurred over the entire breadth of the claims. Applicant tested itraconzole, whereas the claims broadly recite a drug in BCS classes II and IV. The viscosity and the molecular weight of the polyacrylic acid used in the examples is unknown. According to Table 1, LMW PAA-1 synthesized in EA solvent has a viscosity of 200, there are three MMW polyacrylic acids each having a different viscosity, and one HMW having a viscosity of 2075. The only description of the polyacrylic acid in Table 8 is LMW-EA, MMW-EA, and HMW. It is unknown which MMW-EA was used in the examples, and it cannot be determined if the claimed viscosity range of 100-1000 is commensurate in scope with the tested compositions that have the asserted unexpected properties. Table 1 does not provide a range of molecular weights for the LMW-EA, MMW-EA, and HMW-EA and it cannot be determined if the claimed range is commensurate in scope with the tested examples. The tested compositions have a drug:PAA weight ratio of 80:20, whereas the claims require a range.
The applicant did not compare the claimed invention to the closest prior art of record, which is Van Den Mooter. Van Den Mooter on pages 13-14 teaches a method of making a solid dispersion by spray drying using loperamide and polyacrylic acid that is not crosslinked and having a Mw of 100,000, where the drug to polymer weight ratio includes 80:20.
Arguments against Staric’s molecular weight range are not persuasive because applicant did not show that claimed molecular weight range is critical. Additionally, Van Den Mooter limits the polymer by a viscosity range of 1-5000, 1-700, or 1-100 mPa.s (page 4 lines 31-34), and exemplifies a solid drug dispersion comprising uncrosslinked poly(acrylic acid) of molecular weight 100,000 Da. In view of these teachings, it is apparent that Van Den Mooter considered molecular weight of the polymer and preferred lower molecular weights as evidenced by the example and the narrower viscosity ranges of 1-700 and 1-100 mPa.s which are at the lower end of the 1-5000 mPa.s range. The purpose of relying on Staric was to show that 10,000-3,000,000 Da was a suitable range of molecular weights for making amorphous drug/polymer dispersions according to the state of the art. Van Der Mooter’s exemplified molecular weight of 100,000 is encompassed by Staric’s range, therefore there is an overlap in molecular weights between Staric and Van Der Mooter which shows that molecular weights taught by Staric would have been suitable for making solid dispersions of Van Der Mooter. It would have been obvious to the skilled artisan to form Van Der Mooter’s drug/polymer dispersion using a range of molecular weights of poly(acrylic acids) and the skilled artisan would have been capable of determining the range that is suitable for making a stable dispersion because the purpose of Van Der Mooter is to form a stable solid dispersion. It is apparent from Van Der Mooter that linear poly(acrylic acid) may be used in a range of molecular weights because Van Der Mooter teaches ranges of viscosities and a viscosity is affected by molecular weight. The claimed viscosity and molecular weight ranges are obvious because they overlap with their corresponding ranges in the prior art. The prior art does not teach measuring said parameters in the same manner as claimed, however the Office does not have the means to test prior art products according to claims to determine if the prior art product meets the claimed properties.
Arguments against Staric’s objective are not persuasive because it is irrelevant that Staric teaches drugs different from claimed drugs. Van Den Mooter teaches the claimed drugs and teaches forming a stable drug dispersion. A person skilled in the art would have been motivated to vary the variables, such as drug to polymer weight ratio and the polymer molecular weight, in order to form a stable solid dispersion because the purpose of Van Der Mooter is to form a stable solid dispersion.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). All limitations and motivation to combine are present in the cited references as described in the office action.
Conclusion
No claims are allowed.
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 Alma - Pipic whose telephone number is (571)270-7459. The examiner can normally be reached M-F 9:00am-5:00pm. 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.
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/ALMA PIPIC/
Primary Examiner, Art Unit 1617
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