DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Status of Claims
The amendment, filed on 13 May 2026, is acknowledged.
Claims 34-36, 55, 59, and 64 have been amended.
Claims 37 and 43 have been cancelled.
Claims 34-36, 38-42, and 44-63 are pending and under consideration in the instant Office Action, to the extent of the following previously elected species:
the therapeutic agent is allopregnanolone;
the one or more lipophilic compounds are caprylic/capric mono- and diglycerides;
the solubilizer is 2-hydroxypropyl b-cyclodextrin;
the surfactant is sorbitan monooleate;
the co-surfactant is diethylene glycol monoethyl ether; and
the transdermal penetration enhancer is ethanol.
Objections Withdrawn
Objections to Specification and Title
Applicant’s amendment to pg. 1, lines 18-29 of the instant spec. and the title, submitted on 13 May 2026, have overcome the relevant objections set forth in the Office Action mailed on 13 November 2025. Accordingly, the relevant objections are withdrawn.
Objections to Claims
Applicant’s amendment to claim 36 has overcome the objection to the claim set forth in the Office Action mailed on 13 November 2025. Accordingly, the relevant objection is withdrawn.
Rejections Withdrawn
Rejections pursuant to 35 U.S.C. § 112
The rejections of claims 49 and 59 under 35 U.S.C. § 112 are withdrawn in view of Applicant’s amendments to the claims. The rejection of claim 55 under 35 U.S.C. § 112 is withdrawn and made anew in view of Applicant’s amendment to the claim.
Rejections pursuant to 35 U.S.C. § 102
The rejection of claims 34-35 and 44 under 35 U.S.C. § 102 is withdrawn in view of Applicant’s amendment to claim 34.
Rejections pursuant to 35 U.S.C. § 103
The rejection of claims 37 and 43 under 35 U.S.C. § 103 are rendered moot in view of Applicant’s cancellation of the claims. The rejections of claims 34-36, 38-42, and 44-63 under 35 U.S.C. § 103 are withdrawn and made anew below.
Double patenting rejections
The nonstatutory double patenting rejection of claims 34-36, 38-42, and 44-63 is withdrawn and made anew below.
New Grounds of Objection
Claim Objections
Claim 59 is objected to because it recites “at a weight ratio of about 1 in the combination of sorbitan monooleate and Polysorbate 80”. Applicant’s amendment to overcome the rejection under 35 U.S.C. § 112 removes the indefiniteness in the claim, but clarity would be improved if Applicant moved the limitation regarding the weight ratio to a new dependent claim. For example, a new claim depending from claim 59 reciting “The method of claim 59, wherein the surfactant is a combination of sorbitan monooleate and Polysorbate 80, optionally at a weight ratio of about 1”.
Appropriate correction is required.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 55-56 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 55 has been amended to recite “the one or more lipophilic compounds originally belonged to the oil before forming the microemulsion” in lines 1-3. The meaning of this limitation is unclear, the instant specification does not provide a definition of the phrase “belonged to the oil”, and the amendment does not clarify the phrase, rendering the claim indefinite. Claim 56 depends from claim 55, incorporates all of its limitations and does not resolve the issue of indefiniteness, and is therefore also rejected as being indefinite.
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 34-36, 38-42, 44-49, and 51-63 are rejected under 35 U.S.C. 103 as being unpatentable over Brinton (U.S. Patent Application Publication No. US 2017/0258810 A1, published on 14 September 2017) in view of Sintov et al. (J. Controlled Release 2010, 148, 168., provided by Applicant in the IDS filed on 13 May 2023, hereafter referred to as Sintov), Yao et al. (J. Exp. Med. 2012, 209 (13), 2501., hereafter referred to as Yao), and Prajapati et al. (Pharm. Res. 2012, 29, 285., hereafter referred to as Prajapati).
Brinton teaches methods of reversing or preventing neurological disease or defects associated with neural loss or degeneration via administration of compositions containing 3a-hydroxy-5a-pregnan-20-one (allopregnanolone) (Abstract and para. [0002]). The method for treating or preventing neurological deficits due to neurodegenerative disease, such as Parkinson’s disease (para. [0010] and claim 22), is taught to comprise administration of a composition comprising allopregnanolone (claim 1). This method of treating or preventing neurological deficits due to a disease that may be Parkinson’s disease is considered analogous to the method “for treating or preventing neuronal damage caused by Parkinson’s disease” recited in instant claim 34. The composition is further taught to comprise a dextrin (claim 2), ethanol (claim 7), diglycol monoethyl ether (para. [0082]), which is interpreted as equivalent to the elected diethylene glycol monoethyl ether, and sorbitan monooleate (para. [0084]). The composition is taught to be capable of being formed as a stable microemulsion (para. [0095]) and is taught to have a carrier, in which the API is dissolved (para. [0062-0063]) at an amount from 0.5-100% w/w of the composition (para. [0074]). Further, Brinton teaches that their composition may comprise the lipophilic compounds capric/caprylic triglycerides and that the method may be administered via a route which may be transdermal, injection (subcutaneous or intravenous), or pulmonary (claim 1).
Allopregnanolone is taught to be administered “at dosages and for periods of time effective to stimulate or induce neural proliferation and/or to protect against neural loss in an individual” (para. [0052]). Brinton teaches that this may be achieved by administering the composition comprising allopregnanolone in a single dose or over several doses, with the several doses being administered daily, every other day, weekly, or monthly (para. [0012]). When administered using multiple doses, the range of API is taught to be about 0.1-1,000 mg, but the dose and administration frequency can be “readily determined by the treating physician” (para. [0052]). The time period of administration is taught to range from one month to 72 weeks (para. [0012] and claims 16-18). The instant specification does not define the manner in which the formulation comprising allopregnanolone “provides a dose of 4 mg” and it is therefore interpreted as being administered at a concentration of 4 mg allopregnanolone, which falls within the range taught by Brinton.
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the dose of allopregnanolone recited in instant claims 34, 39-42, and 45-48 and the frequency of administration recited in instant claims 39-42 and 45-48. The teachings of Brinton encompass the claimed dose of 4 mg and the frequency of once weekly administration over the time span of 12 weeks or 3 months, rendering them obvious.
Brinton does not teach the quantity of the surfactant and co-surfactant, the dextrin to be 2-hydroxypropyl b-cyclodextrin, nor the lipophilic compounds caprylic/capric mono- and diglycerides. These deficiencies are offset by the teachings of Sintov, Yao, and Prajapati.
Sintov teaches the development and performance of a new microemulsion nasal spray (Abstract). Microemulsions are taught to have improved absorption of low-molecular-weight drugs following nasal administration, but the mechanism is poorly understood (pg. 169, left column, para. 1). Sintov hypothesized that a non-irritating microemulsion system is the source of this desirable effect and studied the impact of different microemulsion systems on nasal sprays containing lispro insulin (pg. 169, left column, para. 2).
In Figure 1, Sintov demonstrated that in microemulsions comprising more than 10% w/w oil, the maximum water solubilization capacity was 50% w/w, and that the optimally stable co-surfactant: surfactant ratio was 1:5 (pg. 171, 3.1. Characterization of the microemulsion system). Analysis of Fig. 1 demonstrates that that the microemulsion remains stable across a surfactant/co-surfactant weight percentage range, from as low as ~50% w/w of the surfactant/co-surfactant-water-oil mixture to as high as ~90% w/w, and that an optimal ratio contains ~87% w/w of the surfactant/co-surfactant mixture (pg. 172, left column, para. 2 - pg. 173, left column, para. 2).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the quantity of surfactant and co-surfactant in instant claim 36. The teachings of Sintov significantly overlap with the claimed range, rendering it obvious.
Yao teaches the neuroprotective properties of cyclodextrins in cells and mouse models (Abstract). Cyclodextrins, cyclic polysaccharide compounds, are taught to extract cholesterol from cultured cells (pg. 2502, right column, para. 1). Cholesterol plays an important role in neurodegenerative diseases, for example increasing the risk factors of Alzheimer Disease when present in high concentrations, and the ability of cyclodextrins to regulate cholesterol has been observed to correct “abnormal cholesterol metabolism, and [prevent] neurodegenerative changes” in mice models of the lipid storage disease Niemann-Pick type C1 (pg. 2501, left column, para. 1 - pg. 2503, left column, para. 1).
Hydroxypropyl b-cyclodextrin (HP-b-CD) was administered to mice models which overexpress human amyloid precursor protein (APP), a protein associated with neurons (pg. 2503, left column, para. 2), and found to “enhance cholesterol efflux through increased expression of cholesterol transporters” (pg. 2509, left column, penultimate para.). Further, administration of HP-b-CD was observed to significantly increase expression of ABCA1, which reduces amyloid deposition, and to decrease deposition of plaques in the brains of the mouse models (pg. 2509, right column, para. 1). Yao concludes that administration of HP-b-CD “significantly improved memory deficits and reduced amyloid deposition” and could have therapeutic potential in the treatment of neurodegenerative diseases such as Alzheimer Disease (pg. 2509, right column, final para.).
Prajapati teaches a comparative evaluation of mono-, di-, and triglycerides for applications in pharmaceutical dosage formulations (Title and Abstract). Medium chain lipids are taught to be popular in drug formulations due to being liquid at room temperature and their ability to exist in different phases when mixed with water (pg. 299, left column). When using Capmul® MCM EP, a mixture of 60% caprylic/capric monoglycerides and 35% caprylic/capric diglycerides, Prajapati found that, when used in combination with a surfactant and water, the mono- and diglyceride mixture was capable of forming microemulsions and did not form a gel phase, which may be desirable as the gel may trap the API in the formulation, thereby delaying or impeding its release (pg. 292-293, Effect of Monoglyceride/Diglyceride Combination). Further, the mixture can be optimized to suit desired formulation characteristics by adjusting component ratios according to the phase diagram in Fig. 4 and data in Table III (pg. 293, Effect of Monoglyceride/Diglyceride Combination). Prajapati concludes that, for many lipid/surfactant mixtures, undesirable gel or liquid crystalline phases can be produced, but are “practically eliminated” when combining “monoglyceride with diglyceride or triglyceride at 1:1 ratios” (pg. 304, Conclusion).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Sintov, Yao, and Prajapati with the method of Brinton to arrive at the method of claims 34-36, 38-42, 44-49, and 51-63 because combining or substituting elements known in the prior art in related methods produces predictable results. Brinton teaches a method of treating, reversing, or preventing neurological disease or defects associated with neurodegenerative disease, such as Parkinson’s disease, comprising administration of a composition comprising allopregnanolone at doses and frequencies that render obvious those recited in instant claims 34, 39-42, and 45-48. Brinton further taught their composition to comprise a dextrin, ethanol diglycol monoethyl, capric/caprylic triglycerides, and sorbitan monooleate, to be in the form of a stable microemulsion, and to contain the API in a carrier at an amount from 0.5-100% w/w of the composition.
In view of the teachings of Sintov, a person of ordinary skill would be motivated to make the quantity of surfactant and co-surfactant in their composition be ~50-90% w/w because Brinton does not teach a quantity of surfactant and/or surfactant+co-surfactant to use and the teachings of Sintov provide missing information an ordinary artisan would need to practice the complete method of Brinton. In addition, Sintov teaches the above range to produce a stable microemulsion, which would be desirable to an artisan utilizing the above composition in a method of treatment.
In view of the teachings of Yao, one of ordinary skill would be motivated select 2-hydroxypropyl b-cyclodextrin as the dextrin to use in the composition taught by Brinton because Yao teaches the particular molecule to have use in neuroprotection, which the ordinary artisan would desire in the method taught by Brinton of treating, reversing, or preventing neurological disease or defects associated with neurodegenerative disease. Further, Brinton teaches the genus of dextrin, but does not teach a specific dextrin, and the teachings of Yao would provide missing information and allow the ordinary artisan to practice the complete method of Brinton.
Finally, in view of the teachings of Prajapati, a person of ordinary skill would be motivated to use caprylic/capric mono- and diglycerides from Capmul® MCM EP in the composition administered as part of the method of Brinton because Prajapati teaches the mixture, when used alongside a surfactant and co-surfactant, was capable of forming a stable microemulsion without forming an undesirable gel. Brinton and Sintov both taught the utility of forming compositions as microemulsions and the ordinary artisan would desire the use of components that further aid the stability of the compositions.
Instant claims 40, 42, 46, and 48 recite the method of administration of a composition comprising allopregnanolone “improves one or more motor skills in the subject” and instant claim 51 recites the solubility of allopregnanolone to be higher in the presence of caprylic/capric mono- and diglycerides, 2-hydroxypropyl b-cyclodextrin, sorbitan monooleate, and diethylene glycol monoethyl ether than in the absence of those components. The teachings of Brinton, Sintov, Yao, and Prajapati have rendered obvious a method of treating Parkinson’s’ disease comprising administering a composition comprising allopregnanolone, caprylic/capric mono- and diglycerides, sorbitan monooleate, ethanol, and diethylene glycol monoethyl ether in the quantities recited and with the frequency recited (vide supra). Brinton, Sintov, Yao, and Prajapati are silent regarding the motor skills of subjects following administration of the above method and the solubility of allopregnanolone.
"[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP § 2112.01. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Therefore, because Brinton, Sintov, Yao, and Prajapati render obvious the method recited in instant claims 34-36, 38-39, 41, 44-45, 47, 49, and 52-63, the method would necessarily also improve “one or more motor skill in the subject” and instant claims 40, 42, 46, and 48 are also rendered obvious. Further, the solubility of allopregnanolone is an inherent property of the molecule, and its presence in the composition rendered obvious above would have the same solubility properties as recited in instant claim 51. As a result, there is a reasonable expectation of success in arriving at the method of instant claims 34-36, 38-42, 44-49, and 51-63 in view of the teachings of Brinton, Sintov, Yao, and Prajapati.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Brinton (U.S. Patent Application Publication No. US 2017/0258810 A1, published on 14 September 2017) in view of Sintov (J. Controlled Release 2010, 148, 168., provided by Applicant in the IDS filed on 13 May 2023), Yao (J. Exp. Med. 2012, 209 (13), 2501.), and Prajapati (Pharm. Res. 2012, 29, 285.) as applied above to claims 34-36, 38-42, 44-49, and 51-63 and further in view of Henry et al. (Proceedings MEMS 98. IEEE. Eleventh Annual International Workshop on Micro Electro Mechanical Systems., 1998, 494., provided by Applicant in the IDS filed on 15 May 2023, hereafter referred to as Henry).
Brinton, Sintov, Yao, and Prajapati teach the above and particularly relevant to claim 50 Brinton teaches that their method may administer the composition comprising allopregnanolone intravenously.
Brinton, Sintov, Yao, and Prajapati do not teach their method to administer their composition using a microneedle device. This deficiency is offset by the teachings of Henry.
Henry teaches the utility of microneedle devices in the transdermal delivery of drugs (Abstract). Transdermal delivery of drugs is taught to overcome limitations due to the size, charge, and sensitivity of drugs as well as limitations from other methods of administration such as GI tract degradation of orally administered drugs (pg. 1, left column, final para. - right column, para. 1). However, human skin poses “an extremely good barrier to most drugs, resulting in low drug delivery rates that are not therapeutically effective” (pg. 1, right column, para. 1). Using a microneedle device, Henry administered drugs across the skin barrier “without causing any pain” (pg. 1, right column, final para.). Henry concluded that microneedles are simple to produce, suitable for many applications, capable of “increasing skin permeability by up to more than four orders of magnitude”, and have “the potential to significantly increase the number and type of drugs which can be delivered across the skin” (pg. 5, left column, Conclusions).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to utilize microneedles to practice the method rendered obvious by the teachings of Brinton, Sintov, Yao, and Prajapati in view of the teachings of Henry because using a known device to apply a known technique yields predictable results. Brinton, Sintov, Yao, and Prajapati rendered obvious a method of treating, reversing, or preventing neurological disease or defects associated with neurodegenerative disease, such as Parkinson’s disease, comprising administration of a composition comprising allopregnanolone, caprylic/capric mono- and diglycerides, sorbitan monooleate, ethanol, and diethylene glycol monoethyl ether in the quantities recited and with the frequency recited. In view of the teachings of Henry, one of ordinary skill would be motivated to use a microneedle to administer the composition rendered obvious above because Henry teaches this administration method to cross the skin barrier without inducing pain and increase the API skin permeability, which the ordinary artisan would desire in a method that requires the delivery of an API to a user. As a result, there is a reasonable expectation of success in arriving at the method of claim 50 in view of the teachings of Brinton, Sintov, Yao, and Prajapati and further in view of the teachings of Henry.
Response to Arguments
The Applicant’s arguments, filed on 13 May 2026, have been fully considered but are not persuasive.
In para. 1 of pg. 11, Applicant states that “The Office Action acknowledges that the cited references—including Brinton—do not disclose the subject matter of claim 37 by virtue of not rejecting claim 37 under 35 U.S.C. § 102.” Applicant is advised that this is an incorrect interpretation of the rejection – the omission of claim 37 from the rejection under 35 U.S.C. § 102 was an acknowledgement that the Brinton reference did not anticipate the subject matter of claim 37. However, as noted in the rejection under 35 U.S.C. § 103 (vide supra), the subject matter of claim 37 is obvious in view of the teachings of Brinton. See MPEP § 2131 and 2141 for discussions of examination guidelines regarding anticipation and obviousness, respectively.
From pg. 13-14, Applicant argues that they have found unexpected results. Guidelines on determining whether results are expected or unexpected are provided in MPEP § 716.02. To demonstrate that results are unexpected and significant, the Applicant has the responsibility of presenting evidence that establishes “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). “Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims”. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e).
Applicant provided two NPL documents (Hernandez et al. Alzheimer’s Dement. 2020, 6, e12107., hereafter referred to as Hernandez and Raikes et al. Alzheimer’s Dement. 2022, 8, e12258., hereafter referred to as Raikes) to support their demonstration of unexpected results. First is argued that following 12-13 weeks of weekly administration of allopregnanolone at 2, 4, or 6-18 mg, patients presented with the largest gains in hippocampal volume when administered 4 mg doses weekly. Applicant directs the reader to Table 5 of Hernandez, noting that the largest gains in hippocampal volumes were observed in the group that received 4 mg weekly doses, and to Fig. 1 of Raikes, which they argue shows that 4 mg weekly doses produced “the greatest overall positive gains” in hippocampal volume. Applicant further argued that 2 and 6-18 mg weekly administration demonstrated an inhibitory effect and that “[t]he record contains no evidence that these results would have been expected from the broad ranges of [allopregnanolone] described in Brinton”.
Addressing the Hernandez reference, the authors state in para. 2, right col. of pg. 8 that their trial was “powered for safety and [pharmacokinetics], thus given the small sample size and duration of treatment, the efficacy of [allopregnanolone] could not be determined” (bold added for emphasis). The authors also cautioned the reader that their assessments were exploratory and that their analysis of hippocampal volume change “suggested a potential signal in the 4 mg [allopregnanolone] dose that will be investigated further in an appropriately powered phase 2 trial”. The Applicant’s argument that Hernandez provides evidence of unexpected results is undermined by the limitations stated in the reference, specifically that the small sample size prevents conclusions regarding the efficacy of allopregnanolone and that the 4 mg dose suggests a potential signal that requires further investigation. In addition, using Applicant’s reasoning that hippocampal volume change is correlated to neurogenesis and therefore successful treatment, Applicant’s argument that a 6-18 mg weekly dose demonstrates an inhibitory effect is undermined by Table 5 of Hernandez. Table 5 provides data showing that volume loss in the 6-18 mg group is less severe than in the placebo group, which would lead the reader to conclude that a 6-18 mg weekly dose of allopregnanolone successfully treated patients by mitigating hippocampal volume loss when compared to untreated patients.
Addressing the Raikes reference, the authors similarly cautioned the reader that the purpose of their trial was “to determine safety and establish maximally tolerated dose in the target [Alzheimer’s Disease] population and thus not specifically powered for these exploratory outcomes. The small sample size is an important consideration in interpreting the present findings” (bold added for emphasis) (pg. 9, 4.5 Limitations, para. 1). Also in this para. Raikes notes that the purpose of their study was “not to provide conclusive evidence of [allopregnanolone] effect but rather to identify mechanistic and regenerative-relevant candidate endpoints for future trials and to determine target effect sizes on which to power such trials” (pg. 9, 4.5 Limitations, para. 1). Applicant relied on Fig. 1 of Raikes, which presents an analysis of MRI imaging, to support their argument that the 4 mg weekly dose produced “the greatest overall positive gains” in hippocampal volume. However, Raikes states in para. 2 of section 4.5 that the “imaging sequences used for the present analyses were not fully optimized” and had limitations.
Applicant’s argument citing the Hernandez and Raikes references is not considered to be a persuasive demonstration of unexpected and surprising results. The Hernandez and Raikes references used in Applicant’s arguments state that their data have limitations and could not be used to determine the efficacy of allopregnanolone, in addition to warning against conclusions based upon the small sample size.
In addition, the Applicant has not demonstrated unexpected results commensurate in scope with the claimed invention. “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).” See MPEP § 716.02(d). Instant claim 34 recites a method comprising the step of administering a formulation which provides 4 mg of allopregnanolone and comprises a pharmaceutically acceptable carrier which Applicant elected to comprise caprylic/capric mono- and diglycerides, 2-hydroxypropyl b-cyclodextrin, sorbitan monooleate, diethylene glycol monoethyl ether, and ethanol. The Raikes reference states that the trial design was previously described in the Hernandez reference (Raikes, 2.1 Trial design), which in turn teaches that allopregnanolone was administered in a “clear aqueous solution packaged in an IV bag with non-di(2-ethylhexyl)phthalate”, sulfobutylether-b-cyclodextrin, and NaCl (Hernandez, 2.3 Interventions and study drug). The formulations in the Hernandez and Raikes references are not the same as the formulation recited in the method of instant claim 34 and therefore are not commensurate in scope with the instant invention.
In addition, Hernandez teaches that the above formulation was administered “once weekly for 12 consecutive weeks” (Hernandez, 2.3 Interventions and study drug). Instant claim 34 recites the method “treating or preventing neuronal damage caused by Parkinson’s disease” comprising administering the recited formulation, but does not recite administration once weekly for 12 consecutive weeks – this administration frequency is recited in instant claim 39. Finally, both the Hernandez and Raikes references are drawn to the treatment of Alzheimer’s disease and neither mentions the treatment or prevention of Parkinson’s disease or other neurodegenerative diseases.
It is noted that the Applicant also has not compared their invention with the closest prior art. See MPEP § 716.02(e). In summary, the references Applicant has used to support their claim of unexpected results are not commensurate in scope with the claimed invention and the argument is not found to be persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 34-36, 38-42, and 44-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 10-12, 15-20, and 22 of U.S. Patent No. 11,207,331 B2 in view of Sintov (J. Controlled Release 2010, 148, 168., provided by Applicant in the IDS filed on 13 May 2023), Gupta et al. (Sci. Pharm. 2012, 80 (4), 1061., hereafter referred to as Gupta), Yao (J. Exp. Med. 2012, 209 (13), 2501.), Prajapati (Pharm. Res. 2012, 29, 285.), and Henry (Proceedings MEMS 98. IEEE. Eleventh Annual International Workshop on Micro Electro Mechanical Systems., 1998, 494.).
Commonly assigned U.S. Patent No. 11,207,331 B2 recites a method of treating or preventing neurological deficits in a person suffering from a neurodegenerative disease, which in one embodiment is Parkinson’s disease, comprising the administration of a composition comprising allopregnanolone (claims 11-12, 15, and 22). The route of administration in the method is recited to be transdermal, injection, or pulmonary (claim 1) and may be administered weekly or less frequently over a span of time from 1-6 months (claims 16-19). The composition is further recited to comprise a dextrin, ethanol, and diglycol monoethyl ether (claims 2-3, 7, and 10). Finally, ‘331 recites the dose of allopregnanolone to be from 0.1-100 mg (claim 20).
Commonly assigned U.S. Patent ‘331 does not recite the composition of their method to comprise caprylic/capric mono- and diglycerides or sorbitan monooleate, the dextrin to be 2-hydroxypropyl b-cyclodextrin, the weight percent of the surfactant/co-surfactant, nor the composition to be administered via microneedle. These deficiencies are offset by the teachings of Sintov, Gupta, Yao, Prajapati, and Henry.
Sintov, Yao, Prajapati, and Henry have been described above.
Gupta teaches formulations for overcoming solubility issues with the drug sertraline for transdermal delivery (Abstract). To deliver sertraline across the skin barrier, Gupta employed transfersomes, metastable vesicles that can “squeeze” through pores in the skin and non-invasively deliver the API (pg. 1062, para. (2-4). The study sought to optimize the formulation for in vitro release and utilized the non-ionic surfactant Span® 80, which is a trade name for sorbitan monooleate, as evidenced by the instant specification (Abstract and pg. 1063, para. 1). Span® 80 is taught to be biocompatible, pharmaceutically acceptable, and capable of efficiently entrapping the API and excipients in vesicles (pg. 1067, para. 4-6). Gupta concluded that the vesicle comprising sorbitan monooleate possessed “excellent release and permeation” properties, did not irritate subject skin following administration, and could be a promising carrier for a variety of APIs (pg. 1077, Conclusion).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Sintov, Gupta, Yao, Prajapati, and Henry with the method recited in U.S. Patent ‘331 to arrive at the claimed invention because combining prior art elements from related inventions to impart known benefits yields predictable results. Commonly assigned patent ‘331 recites a method for treating or preventing neurological deficits from neurodegenerative disease, which in one embodiment is Parkinson’s disease, comprising the administration of a composition comprising allopregnanolone in the amount and frequency recited in the instant application. The route of administration in the method is recited to be transdermal, injection, or pulmonary, and the composition is recited to comprise a dextrin, ethanol, and diglycol monoethyl ether.
In view of the teachings of Sintov, a person of ordinary skill would be motivated to add a surfactant and co-surfactant to their composition in the amount of ~50-90% w/w because Patent ‘331 does not recite the inclusion of nor a quantity of surfactant and/or surfactant+co-surfactant to use and Sintov teaches the above range to produce a stable microemulsion, which would be desirable to an artisan utilizing the above composition in a method of treatment. In view of the teachings of Gupta, an ordinary artisan would be motivated to select the surfactant sorbitan monooleate because Gupta teaches the surfactant to provide a stable vesicle for delivering APIs, to be biocompatible and pharmaceutically acceptable, and to produce no skin irritation to users following administration.
In view of the teachings of Yao, one of ordinary skill would be motivated select 2-hydroxypropyl b-cyclodextrin as the dextrin to use in the composition recited in ‘331 because Yao teaches the particular molecule to have use in neuroprotection, which the ordinary artisan would desire in the method recited by commonly assigned patent ‘331 of treating or preventing neurological disease or defects associated with neurodegenerative disease. Further, ‘331 recites the genus of dextrin, but does not teach a specific dextrin, and the teachings of Yao would provide missing information and allow the ordinary artisan to practice the complete method of ‘331.
In view of the teachings of Prajapati, a person of ordinary skill would be motivated to use caprylic/capric mono- and diglycerides from Capmul® MCM EP in the composition administered as part of the method of ‘331 because Prajapati teaches the mixture, when used alongside a surfactant and co-surfactant, was capable of forming a stable microemulsion without forming an undesirable gel. Sintov taught the utility of forming compositions as microemulsions and the ordinary artisan would desire the use of components that further aid the stability of the compositions. Finally, in view of the teachings of Henry, one of ordinary skill would be motivated to use a microneedle to administer the composition recited in the method of ‘331 because Henry teaches this administration method to cross the skin barrier without inducing pain and increase the API skin permeability, which the ordinary artisan would desire in a method that requires the delivery of an API to a user.
Instant claims 40, 42, 46, and 48 recite the method of administration of a composition comprising allopregnanolone “improves one or more motor skills in the subject” and instant claim 51 recites the solubility of allopregnanolone to be higher in the presence of caprylic/capric mono- and diglycerides, 2-hydroxypropyl b-cyclodextrin, sorbitan monooleate, and diethylene glycol monoethyl ether than in the absence of those components. The invention of Patent ‘331 in view of the teachings of Brinton, Sintov, Yao, and Prajapati have rendered obvious a method of treating Parkinson’s’ disease comprising administering a composition comprising allopregnanolone, caprylic/capric mono- and diglycerides, sorbitan monooleate, ethanol, and diethylene glycol monoethyl ether in the quantities recited and with the frequency recited (vide supra). Patent ‘331, Brinton, Sintov, Yao, and Prajapati are silent regarding the motor skills of subjects following administration of the above method and the solubility of allopregnanolone.
"[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP § 2112.01. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Because the method recited by ‘331 and the teachings of Sintov, Gupta, Yao, and Prajapati render obvious the method recited in instant claims 34-36, 38-39, 41, 44-45, 47, 49, and 52-63, the method would necessarily also improve “one or more motor skill in the subject” and instant claims 40, 42, 46, and 48 are also rendered obvious. Further, the solubility of allopregnanolone is an inherent property of the molecule, and its presence in the composition rendered obvious above would have the same solubility properties as recited in instant claim 51. As a result, there is a reasonable expectation of success in arriving at the method of instant claims 34-36, 38-42, and 44-63 in view of the method recited in commonly assigned U.S. Patent No. 11,207,331 B2 and in view of the teachings of Brinton, Gupta, Sintov, Yao, and Prajapati.
Claims 34-36, 38-42, and 44-63 are directed to an invention not patentably distinct from claims 1-3, 7, 10-12, 15-20, and 22 of commonly assigned U.S. Patent No. 11,207,331 B2 in view of the teachings of Sintov, Gupta, Yao, Prajapati, and Henry. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 11,207,331 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Response to Arguments
The Applicant’s statement regarding the nonstatutory double patenting rejection, filed on 13 May 2026, are acknowledged.
In the section titled “Rejection under Obviousness-type Double Patenting” on pg. 15 of the remarks, Applicant “respectfully requests for this rejection to be held in abeyance until the claims are otherwise determined to be allowable”. A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by the Applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
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.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
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