*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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on August 5, 2025 has been entered.
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, and 36 are pending. Claims 4-6, 9, 11, 15-18, 21, 22, 28, 29, 32-35, and 37 were canceled. Claims 1 and 14 were amended. Claims 13, 14, 19, 20, 23-27, 30, and 31 remain withdrawn. Claims 1-3, 7, 8, 10, 12, and 36 are examined.
Claim Rejections — 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [1.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 36 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 2 and 36 recite a ratio of up to 5:1 and at least 4:1, respectively. The claims do not further limit claim 1 which recites a range of weight ratios from at least 3:1 and up to 6:1. The limitations of “up to 5:1” and “at least 4:1” are ranges which include ratios that extend outside the range required by claim 1, therefore claims 2 and 36 do not further limit claim 1. The range in claim 1 has two end points, and extends from 3:1 to 6:1. The “at least 3:1” requires the ranges to start at 3:1 and “up to 6:1” requires the range to end at 6:1. A range of “up to 5:1” has the end point 5:1 as the upper limit and includes all the ranges that are less than 5:1. Similarly, a range of “at least 4:1” includes 4:1 as the lower end point and includes all the ranges greater than 4:1 without an upper limit. Therefore, “up to 5:1” and “at least 4:1” are ranges of ratios that extend below 3:1 and greater than 6:1.
In the remarks dated August 5, 2025, the applicant traversed the rejections because “up to 5:1” excludes ratios of more than 5:1 such as 6:1; and a ratio of “at least 4:1” excludes ratios less than 4:1 such as 3:1.
This argument is not persuasive because “up to 5:1” includes ratios that are less than 3:1, which is outside the range in claim 1; and “at least 4:1” includes ratios that are greater than 6:1 which is outside the range in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections — 35 USC § 103
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, and 36 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 1 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, at least 100 cP and at least 200 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 claimed range is broad, at least 200,000 Da, and there is no evidence in the specification that claimed range is critical.
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, up to 5:1 in claim 2, and at least 4:1 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.
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
In the remarks dated August 5, 2025, applicant traversed the rejections.
Applicant’s arguments were fully considered but are not persuasive for the following reasons.
Applicant reiterated the arguments made in the prior response.
In response, applicant’s arguments in the prior response are not persuasive for reasons of record.
Applicant argued that the examiner provided no reason for selecting polyacrylic acid having a molecular weight of at least 200,000 Da.
Argument is not persuasive because the claims are rejected as obvious over the cited references. The prior art range renders the claimed range obvious because the ranges overlap. In an obviousness rejection, the prior art is not required to teach the same range as claimed and the examiner is not required to provide a reason as to why the skilled artisan would have selected the exact range as claimed.
Applicant argued that Staric is concerned with improving stability of BCS Class III drug. The skilled artisan would not have had a reason to look to the teaching of Staric to find a solution for improving the drug loading levels and stability. Staric teaches a list of suitable polymers where polyacrylic acid is listed. Staric provides no suggestion to specifically select linear polyacrylic acid. Staric teaches other polymers as preferred. Staric’s molecular weight range is broad and not enabled in any examples. Staric does not teach that selecting a high molecular weight of at least 200,000 Da could improve drug loading for drugs in BCS class II and IV.
Arguments against Staric are not persuasive because Van Den Mooter teaches that a linear polyacrylic acid is suitable for making a dispersion with a drug selected from a BCS class II and IV drugs. Thus, it is irrelevant that Staric does not teach using a linear polyacrylic acid for making a dispersion of a drug selected from a BCS class II and IV drugs. It is also irrelevant that Staric teaches a list of suitable polymers.
Staric teaches a range of molecular weights of from 10,000 to 3,000,000 Da, which is a limited range of molecular weights. Staric is not required to provide examples of compositions having polymers within said molecular weight range for the obviousness rejection to be proper.
In response to applicant's argument that references do not teach selecting a high molecular weight of at least 200,000 Da could improve drug loading for drugs in BCS class II or IV, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Prior art does not have to teach the same reason as applicant’s reason for selecting claimed elements.
In the instant case, Van Den Mooter does not limit the molecular weight of the linear polyacrylic acid, and the skilled artisan would have been motivated to look to a secondary reference such as Staric for suitable molecular weights of polymers such as polyacrylic acid for making solid drug dispersions.
Conclusion
No claims are allowed.
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/ALMA PIPIC/
Primary Examiner, Art Unit 1617