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 .
Change of Examiner
The examiner assigned to this case has changed since the previous office correspondence. Examiner Toriana Vigil will now be examining this application. Contact information can be found at the end of this document.
Claim Status
Claims 1 – 30 are examined here-in.
Claim Rejections - 35 USC § 103 (New, Necessitated by Amendment)
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 non-obviousness.
Claims 1 – 30 are rejected under 35 U.S.C. 103 as being unpatentable over Brinton (US 2021/0085692 A1) in view of Reddy (WO 2013/112605 A2, of record).
Brinton teaches compositions containing allopregnanolone and methods of use for treating Alzheimer’s or dementia (abstract). Allopregnanolone is also known as 3α-hydroxy-5α-pregnan-20-one or tetrahydroprogesterone (paragraphs 0039 – 0041).
Brinton teaches allopregnanolone is a therapeutic that targets neural stem cells, promotes neural stem cell regeneration, and restores cognitive function (paragraphs 0008 - 0009). Brinton teaches that allopregnanolone also induces the generation of new neurons, protects against neuronal loss, stimulates neurite outgrowth and organization, and protects against loss of neurites and neural networks, which improves or restores neurological function (paragraph 0017).
Brinton teaches that the dosage amount of allopregnanolone will vary depending on the specific disease being targeted, however, generally a dose between 2 and 10 mg is suitable (paragraphs 0012, 0044). Brinton teaches that the administration and dosage schedule of allopregnanolone also depends on the specific disease being targeted (paragraph 0014). In some cases, the drug is administered once a week for 6 months (paragraph 0014).
Brinton teaches allopregnanolone compositions also include additional active agents, such as steroids (paragraphs 0047 – 0048).
Brinton teaches allopregnanolone compositions may be formulated as solid oral dosage forms, including as tablets and capsules (paragraphs 0050 – 0051, 0087).
Brinton teaches formulations containing allopregnanolone can include diluents, binders, lubricants, disintegrators, fillers, pH modifying agents, preservatives, antioxidants, solubility enhancers, and coating compositions (paragraph 0054 – 0058, 0087). Brinton teaches surfactants are pharmaceutically acceptable excipients suitable for inclusion in tablets, including anionic, cationic, amphoteric and nonionic surfactants (paragraphs 0058, 0063). Brinton teaches sodium lauryl sulfate is a suitable anionic surfactant for the composition (paragraph 0063).
Brinton teaches that the formulation will contain between 5 and 100 % by weight of the active material, and suggests that the remaining amount will be carrier and other substances (paragraph 0065).
Brinton does not teach a treated crystalline form of allopregnanolone.
Reddy teaches the missing element of Brinton.
Reddy teaches formulations comprising neuroactive steroid, allopregnanolone, for treating CNS disorders (abstract, page 6, lines 15-32).
Reddy teaches that the lipophilic nature of allopregnanolone makes it different to formulate for in vivo administration, noting that allopregnanolone can be chemically modified to improve solubility (page 62, lines 13 - 20). Reddy teaches that particle size reduction of neuroactive steroid compounds also increases drug solubility (page 83 lines 2 – 4). Reddy teaches particle size reduction via micronization techniques including grinding, milling, coacervation, and spray drying, among others (page 83 lines 5 – 13). Reddy teaches the drug particles may be crystalline or amorphous in a size range from 10 nm to 100 microns (page 83 lines 14 – 19).
Claims 1 – 30 are rendered prima facie obvious over the combination of Brinton and Reddy as combining prior art elements according to known methods to yield predictable results. A person of ordinary skill in the art would be motivated to modify Brinton’s teachings for a composition with allopregnanolone to include chemically or physically treated crystalline allopregnanolone particles because Reddy teaches chemical or physical treatment of allopregnanolone particles increases the drug’s solubility (page 62, lines 13 – 20, page 83 lines 2 – 19). Therefore, the combination of Brinton and Reddy’s teachings for prior art elements according to known methods would be expected to yield predictable results (e.g., an oral table composition with allopregnanolone and additives, wherein allopregnanolone has increased solubility because it is treated) to one of ordinary skill in the art, which is prima facie obvious according to MPEP 2143(i)(a).
Brinton’s teaching for compositions containing allopregnanolone, additional active agents, and various pharmaceutically acceptable excipients for the treatment of Alzheimer’s or dementia in a solid oral dosage form such as a tablet, wherein allopregnanolone is in an amount ranging from 5 to 100% by weight of the composition (abstract, paragraphs 0047 – 0048, 0050 – 0051, 0054 – 0058, 0065, 0087), in combination with Reddy’s teaching for chemically or physically treated crystalline allopregnanolone particles (page 62, lines 13 – 20, page 83 lines 2 – 19) reads on instant claims 1, 9, 19, and 26.
Brinton’s teaching that allopregnanolone treats Alzheimer’s and dementia (abstract, paragraphs 0008 – 0009, 0017) and Reddy’s teaching for allopregnanolone to treating CNS disorders (abstract, page 6, lines 15 – 32) each read on the intended use recitation of “for use in treating a CNS disorder” as recited in the preamble of claims 1, 9, 19, and 26.
Reddy’s teaching for the chemical or physical modification of crystalline allopregnanolone particles to improve solubility, including particle size reduction via micronization techniques including grinding, milling, coacervation, and spray drying, among others (page 62, lines 13 – 20, page 83 lines 2 – 19) reads on the recitation for “treated crystalline form” of allopregnanolone as recited in claims 1, 9, 19, and 26.
Brinton’s teaching that the formulations containing allopregnanolone can include diluents, binders, lubricants, disintegrators, fillers, pH modifying agents, preservatives, antioxidants, solubility enhancers, coating compositions, and surfactants (paragraph 0054 – 0058, 0063, 0087) reads on the claimed “plurality of additives comprising at least one non-surfactant and at least one hydrophilic surfactant” recited in instant claims 1 and 26 and the “at least one hydrophilic surfactant” recited in instant claims 9 and 19. Notably, sodium lauryl sulfate (as well as several other examples named by Brinton) meets the criteria for “hydrophilic” as described in the instant specification as having an HLB value greater than 10 (paragraph 0096 of instant specification). Sodium lauryl sulfate is also named in paragraph 0100 of the instant specification as a suitable hydrophilic surfactant.
Brinton’s teaching that the formulation contains between 5 and 100 % by weight of the active material, and suggestion that the remaining amount will be carrier and other substances (paragraph 0065) reads on the requirement of no more than 50% allopregnanolone and 0.5 to 31% hydrophilic surfactant as recited in claims 1, 9, 19, and 26. Brinton’s teaching for 5 to 100% by weight allopregnanolone overlaps on the instantly claimed range of no more than 50%, and Brinton’s teaching that the remaining amount will be carrier and other substances overlaps on the instantly claimed amount of 0.5 to 31% hydrophilic surfactant. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Reddy’s teaching that allopregnanolone particles may be crystalline with a size range from 10 nm to 100 microns (page 83 lines 14 – 19) reads on the particle size range recitation of claims 19 and 26. Reddy’s teaching for a size range from 10 nm to 100 microns overlaps on the instantly claimed “particle size distribution of at least one of a D90 of less than at least one of 20 µm, 15 µm, 10 µm, 5 µm, and 2 µm, and a D50 of about 0.3 µm to about 8 µm” because the particle size range of 0.3 to 20 µm falls within Reddy’s taught range of 10 nm to 100 microns. Claimed ranges that overlap or fall within prior art teachings are prima facie obvious according to MPEP 2144.05(i)(a).
Regarding the functional limitations recited for claims 1, 9, 19, and 26 regarding Cmax and dissolution (i.e. “wherein administration of said tablet form to a recipient provides in said recipient a Cmax of 3α-OH-5α-pregnan-20-one of at least 4 ng/ml when administered in a recipient fed state and a Cmax of 3α-OH-5α -pregnan-20-one of at least 9 ng/ml when administered in a recipient fasted state” and “wherein when measured using a USP Type II dissolution apparatus in 900 mL of deionized water with 0.5% (w/v) of sodium lauryl sulfate at 75 rpm at 37 0C and having a sink condition of said 3α-OH-5α-pregnan-20-one, said composition comprises at least one of: at least 50% of said 3α-OH-5α-pregnan-20-one released at about 30 minutes post in vitro release test initiation, at least 40% of said 3α-OH-5α-pregnan-20-one released at about 15 minutes post in vitro release test initiation, a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate release of at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a first comparison composition consisting essentially of a surfactant-free formulation, when said composition comprises a surfactant, at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a second comparison composition consisting essentially of crystalline 3α-OH-5α-pregnan-20-one suspension in canola oil, and at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a third comparison composition comprising crystalline 3α-OH-5α-pregnan-20-one suspension in polysorbate 80”): these functional limitations appear to be the result of a composition containing treated crystalline allopregnanolone with various additives and a surfactant as taught by the combination of Brinton and Reddy since it does not appear from the instant disclosure that additional elements are required to cause the functional limitations (paragraphs 0009, 0120, example 2 of the instant specification). According to MPEP 2112(III) and 2163.07(a), an inherent feature of a composition or method does not need to be explicitly recognized in the prior art for the prior art to be applied. Said differently, “By disclosing in a patent application a device that inherently performs a function or has a property, operates according to a theory or has an advantage, a patent application necessarily discloses that function, theory or advantage, even though it says nothing explicit concerning it” MPEP 2163.07(a).
Since a composition containing treated crystalline allopregnanolone with various additives and a surfactant as taught by the combination of Brinton and Reddy appears to overlap with the instantly claimed composition, the skilled artisan would have expected that the composition of Brinton and Reddy would have the same properties regarding Cmax and dissolution as that which is instantly claimed. Something which is old (e.g., the composition of Brinton and Reddy) does not become patentable upon the discovery of a new property and this feature need not have been recognized at the time of the invention. See MPEP 2112(I) and 2112(II). Put another way, "When the claimed compositions are not novel they are not rendered patentable by recitation of properties, whether or not these properties are shown or suggested in the prior art." In re Spada, 911 F .2d 705, 709, (Fed. Cir. 1990). Therefore, since the combination of Brinton and Reddy’s prior art teachings recite a composition containing treated crystalline allopregnanolone with various additives and a surfactant, the functional limitations of claims 1, 9, 19, and 26 are obvious.
Brinton’s teaching that the formulation contains between 5 and 100 % by weight of the active material, and suggestion that the remaining amount will be carrier and other substances (paragraph 0065) reads on the requirement of hydrophilic surfactant in an amount of 1 to 25% as recited in claims 2, 11, 14, 22, and 27. Brinton’s teaching that the amount of composition that is not allopregnanolone will be carrier and other substances overlaps on the instantly claimed range of 1 to 25% hydrophilic surfactant. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Brinton’s teaching that the allopregnanolone composition can also include additional active agents, such as steroids (paragraphs 0047 – 0048) reads on the requirement for at least one lipophilic additive as recited in instant claims 3, 15, 23, and 28, because steroids are lipophilic molecules.
Reddy’s teaching that allopregnanolone particles are processed via micronization techniques including grinding, milling, coacervation, and spray drying (page 83 lines 2 – 19) reads on instant claims 4, 12, and 20.
As discussed above with regards to the functional limitations, the functional limitations of dissolution as recited in instant claim 5, 6, 16, 24, and 29 (i.e. “wherein when measured using a USP Type II dissolution apparatus in 900 mL of deionized water with 0.5% (w/v) of sodium lauryl sulfate at 75 rpm at 37 °C and having a sink condition of said 3α-OH-5α-pregnan-20-one, said composition comprises at least one of: at least 50% of said 3α-OH-5α-pregnan-20-one released at about 30 minutes post in vitro release test initiation, at least 40% of said 3α-OH-5α-pregnan-20-one released at about 15 minutes post in vitro release test initiation, a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate release of at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a first comparison composition consisting essentially of a surfactant-free formulation, when said composition comprises a surfactant, at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a second comparison composition consisting essentially of crystalline 3α-OH-5α-pregnan-20-one suspension in canola oil, and at least one of 10%, 15%, 20%, and 25% greater than a 3α-OH-5α-pregnan-20-one 30-minute post in vitro test initiation release rate of a third comparison composition comprising crystalline 3α-OH-5α-pregnan-20-one suspension in polysorbate 80” and “wherein said oral pharmaceutical composition comprises a dosage form having a disintegration time of less than at least one of about 25 minutes, about 20 minutes, about 15 minutes, about 10 minutes, about 5 minutes, about 3 minutes, about 2 minutes, and about 1 minute as measured according to (701) Disintegration, USP 43”): these functional limitations appear to be the result of a composition containing treated crystalline allopregnanolone with various additives and a surfactant as taught by the combination of Brinton and Reddy since it does not appear from the instant disclosure that additional elements are required to cause the functional limitations (example 2 of the instant specification). According to MPEP 2112(III) and 2163.07(a), an inherent feature of a composition or method does not need to be explicitly recognized in the prior art for the prior art to be applied. Said differently, “By disclosing in a patent application a device that inherently performs a function or has a property, operates according to a theory or has an advantage, a patent application necessarily discloses that function, theory or advantage, even though it says nothing explicit concerning it” MPEP 2163.07(a).
Since a composition containing treated crystalline allopregnanolone with various additives and a surfactant as taught by the combination of Brinton and Reddy appears to overlap with the instantly claimed composition, the skilled artisan would have expected that the composition of Brinton and Reddy would have the same properties regarding dissolution as that which is instantly claimed. Something which is old (e.g., the composition of Brinton and Reddy) does not become patentable upon the discovery of a new property and this feature need not have been recognized at the time of the invention. See MPEP 2112(I) and 2112(II). Put another way, "When the claimed compositions are not novel they are not rendered patentable by recitation of properties, whether or not these properties are shown or suggested in the prior art." In re Spada, 911 F .2d 705, 709, (Fed. Cir. 1990). Therefore, since the combination of Brinton and Reddy’s prior art teachings recite a composition containing treated crystalline allopregnanolone with various additives and a surfactant, the functional limitations of claims 5, 6, 16, 24, and 29 are obvious.
Reddy’s teaching that allopregnanolone particles may be crystalline with a size range from 10 nm to 100 microns (page 83 lines 14 – 19) reads on the particle size range recitation of claims 7 and 17. Reddy’s teaching for a size range from 10 nm to 100 microns overlaps on the instantly claimed “particle size distribution of at least one of a D90 of less than at least one of 20 µm, 15 µm, 10 µm, 5 µm, and 2 µm, and a D50 of about 0.3 µm to about 8 µm” because the particle size range of 0.3 to 20 µm falls within Reddy’s taught range of 10 nm to 100 microns. Claimed ranges that overlap or fall within prior art teachings are prima facie obvious according to MPEP 2144.05(i)(a).
Brinton’s teaching for a dose of allopregnanolone between 2 and 10 mg (paragraphs 0012, 0044) reads on instant claims 8, 18, 25, and 30 which recite a range of 6 to 12 mg allopregnanolone in the composition. Instant contain the limitation “wherein administration of said composition provides a solubilization of…” which is interpreted to be the desired outcome of the administration. Since Brinton does not teach that allopregnanolone is lost between dosing and solubilization, Brinton’s teaching for a dose of allopregnanolone between 2 and 10 mg is interpreted to read on the instant claims limitation to “provide a solubilization of” a range of 6 to 12 mg.
Brinton’s teaching that formulations containing allopregnanolone can include diluents, binders, lubricants, disintegrators, fillers, pH modifying agents, preservatives, antioxidants, solubility enhancers, and coating compositions (paragraph 0054 – 0058, 0087) reads on “a plurality of additives” as recited in claims 13 and 21.
Examiner’s Reply to Attorney Arguments Dated December 3, 2025
Applicant’s arguments have been considered but are moot because the new grounds of rejection specifically addresses the claims as presently amended.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Toriana N. Vigil whose telephone number is (571)270-7549. The examiner can normally be reached Monday - Friday 9:00 a.m. - 5:00 p.m. EST.
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, Sahana Kaup can be reached at 571-272-6897. 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.
/TORIANA N. VIGIL/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
Prosecution Insights