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 .
Claim Objections
Claims 4-5 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 18 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “the solubilizer has a solubility of 30 mg/ml or more in memantine enanthate”. The disclosure notes that memantine enanthate is solid a room temperature (see page 10 sections 57-58). Thus the expression of the solubility of another compound in memantine enanthate in units of milligrams per milliliter implies that the memantine enanthate is in liquid form. The specification details the opposite dissolution process and dissolves memantine free base or one of its salt forms in a solubilizer, where 1 ml of solubilizer is combined with 50 mg of the memantine compound to test for solubility (see page 18 sections 160-161). Another assessment of solubility of memantine enanthate or memantine levulinate in various solvents again combines 1 ml of the potential solubilizer with the memantine salt (see page 21 section 177-page 22 section 180). The result is a solubility of at maximum 500 mg memantine compound per gram of solubilizer (see figure 1). In the case of peanut oil, which displayed the lowest tested memantine enanthate solubility in figure 1, its value was reported as about 50 mg memantine per milliliter solubilizer. For a combination of liquids, the parameter of solubility would convert to miscibility when the solubilizer is also a liquid. Presuming the density of memantine enanthate is about the same as that of memantine free base (1.365 g/ml), expressing its solubility in peanut oil as milligrams solubilizer per milliliter memantine enanthate converts to a solubility (miscibility) of 27,027 milligrams peanut oil per milliliter memantine enanthate (see Puchkov et al. RU-2483715 English translation paragraph 6). The more memantine enanthate is soluble in a solubilizer, the smaller its amount relative to that of the solubilizer. The instant claims recite the opposite scheme where combinations of solubilizer and memantine enanthate with lesser memantine enanthate solubilities are claimed. Thus solubilizers, such as peanut oil, are well within the claimed range as are those that dissolve memantine enanthate to a minuscule degree.
The layering of additional functional limitations onto the broad collection of possible solvents that meet the limitations of instant claim 1, yields a scope of claimed preparations that are not adequately described. Claim 18 requires that no crystallization occur in the preparation and claim 19 requires a cumulative skin permeation of memantine of at least 1500 mg/cm2 over 7 days. There is no discussion of a structure-function correlation that connects particular chemical structures of solubilizers to the combination of functions. A portion of the scope of solubilizers that were deemed to solubilize memantine enanthate at 30 mg memantine enanthate per milliliter of solubilizer or more were shown to also avoid crystallization after one month of storage (see instant table 17). The claim scope embraces far more solubilizers that are much less able to solubilize memantine enanthate. As poorer solubilizers of memantine enanthate, a number of the embraced solubilizers will not be able to maintain the compound in solubilized form. However, there is no discussion pointing to which of these solubilizers will yield a preparation that does not crystallize . Similarly in regard to claim 19, a portion of the scope of solubilizers that were deemed to solubilize memantine enanthate at 30 mg memantine enanthate per milliliter of solubilizer or more were shown to also able to yield achieve at least 1500 mg/cm2 over 7 days. Here again the claimed scope of solubilizers in the instant preparation is far broader than this set and embraces solubilizers that solubilize memantine enanthate to a far lesser degree. No guidance was provided connecting which of these solubilizers are able to attain the claim skin permeation, in spite of the lower capabilities of solubilization. As a result the artisan of ordinary skill would not have deemed the applicant to be in possession of the invention as currently claimed at the time of filing.
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.
Claim18 is 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.
The duration of time over which crystallization is inhibited is not clear. Specifically, it is unclear if a precipitation that crystallizes after any brief period of time of maintaining solubility is embraced or if the preparation can never crystallize in order to be embraced. For the sake of application of prior art, a composition that can solubilize the memantine enanthate for any period of time will be deemed sufficient to meet the claim limitations. Clarification is still required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 10-13, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US PGPub No. 2019/0183810 – see IDS) in view of Vepachedu (previously cited).
Lee et al. teach a transdermal system composed of an adhesive matrix with memantine salt, solubilizer, and adhesive polymer (see claim 1). The memantine salt is composed of memantine and counter ions that may be selected from aliphatic carboxylic acids (see claim 1). Lee et al. teach the solubilizer at 1 to 15 wt% of the adhesive matrix, memantine salt at 5 to 20 wt% of the adhesive matrix, and adhesive polymer at 45-90 wt% of the adhesive matrix (see paragraph 48, 54, and 63 and claims 4, 7, and 10). Adhesive polymer options include polyisobutylene as well as acrylic polymers (see claim 8). They teach a double adhesive layer configuration where a pair of memantine salt loaded adhesive layers are between a backing layer and release layer (see paragraph 35). A high performing example of this configuration includes memantine salt, propylene glycol as the solubilizer, and polyisobutylene adhesive (pressure sensitive adhesive) (see examples 3 and 6). An additional embodiment composed of a single memantine adhesive layer is also detailed that is prepared by dissolving its components in ethyl acetate and isopropyl alcohol that is then spread on a release paper, dried, and laminated to a support (see examples 1 and 4 sample 365; instant claims 15-17). The 365 sample also had a high skin flux and included memantine salt, propylene glycol as the solubilizer, and polyisobutylene adhesive (pressure sensitive adhesive) (see instant claims 10-11). An enanthate salt of memantine is not explicitly detailed.
Vepachedu teaches various acid addition salts for memantine that may be employed to treat dementia (see paragraph 3 and claims 1-3). Enanthate is named amongst the named salts (see claim 3). Heptanoic acid is an aliphatic carboxylic acid and its synonymous with enanthoic acid (see paragraph 526).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make a version of the example 3 percutaneous drug delivery layer of Lee et al. with a release liner or of sample 365 of example 4 with memantine enanthate as the aliphatic carboxylic acid salt, in light of Vepachedu. The modification is obvious as the simple substitution of one known element for another in order to yield the same improvement (e.g. heptanoic acid salt vs generic carboxylic acid salt). The application of the exemplified proportions and generally taught proportions for memantine, solubilizer, and adhesive polymer would follow and meets or yields overlapping ranges with the instantly claimed ranges, thereby rendering the instantly claimed ranges obvious. “In the case where the claimed ranges ‘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)” (see MPEP 2144.05). Additionally would follow to make the layered constructs, where a solution of the adhesive layer is made employing an envisioned solvent and combined with a release and liner layer. It is the position of the examine that this process yields a preparation that does not crystallize over some period of time, even if brief (see instant claim 18). It also would have been obvious to exchange an adhesive acrylic polymer for the polyisobutylene as the simple substitution of one known element for another in order to yield a predictable outcome. In light of instant example 12, it appears that propylene glycol solubilizes memantine enanthate less than propylene glycol monocaprylate (memantine enanthate solubility 500 mg/g solubilizer detailed in figure 1, converts to 2777 mg solubilizer per ml memantine enanthate – as calculated by the examiner) and is therefore within the scope of claimed solubilizers, absent evidence to the contrary (see instant examples 1 and 12 and instant figure 10). Further the preparation also appears to meet the functional limitation of instant claim 19 based upon instant figure 10. Therefore claims 1-2, 10-13, and 15-19 are obvious over Lee et al. in view of Vepachedu.
Claims 1-2 and 8-18 are rejected under 35 U.S.C. 103 as being unpatentable over Terehara et al. (previously cited) in view of Ito (previously cited) and Vepachedu as evidenced by Fuller (US PGPub No. 2010/024944), Mochizuki et al. (US Patent No. 6,187,763), Nielson et al. (US PGPub No. 2004/0258654), and Glinka et al. (US PGPub No. 2008/0146640).
Terehara et al. teach a percutaneous absorption preparation for treating dementia composed of an adhesive drug containing a layer, a support, and cover/liner/release layer (see abstract, paragraph 34, and claim 1). The adhesive layer includes a hydrophobic polymer and may also include a plasticizer (see paragraphs 9, 17, 22, and 54; instant claim 14). The hydrophobic polymer is envisioned as polyisobutylene, styrene-isoprene-styrene block copolymer, or a (meth)acrylic polymer that is present at 5 to 90 wt% (see paragraphs 17-21 and 47; instant claims 7-13). The plasticizer is envisioned and exemplified as paraffin oil (solubilizer) as well as other non-polar liquids that include squalane (solubilizer) (see page 54 and example 1; Mochizuki et al. column 1 lines 42-48; Nielson et al. paragraph 69; Fuller paragraph 101). They teach the plasticizer at 10 to 50 wt% of the adhesive layer and paraffin oil is exemplified at about 30 wt% (see paragraph 55 and examples). Preparation of the adhesive layer occurs by dissolving its components in a solvent, envisioned as toluene, hexane, or ethyl acetate that is then spread on a release paper, dried, and laminated to a support (see paragraph 60; instant claim 15). An enanthate salt of memantine is not explicitly detailed.
Ito teaches a percutaneous absorption preparation for treating dementia composed of a drug containing a layer, a support, and cover/liner/release layer (see abstract, paragraph 65, and example 1). The dementia drug is envisioned as memantine that may be present in an addition salt form at 0.5 to 20 mass% (see paragraphs 28-30; instant claims 1-2).
Vepachedu teaches various acid addition salts for memantine that may be employed to treat dementia (see paragraph 3 and claims 1-3). Enanthate is named amongst the named salts (see claim 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the percutaneous drug delivery layer with a liner and support on either side of Terehara et al. with memantine enanthate as the dementia treating drug. This choice would have been obvious in light of Ito because they detail memantine salt delivery percutaneously via a similar preparation and in light of Vepachedu who point to this particular variety of addition salt for memantine that was known. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. It additionally would have been obvious to select a hydrophobic polymer envisioned by Terehara et al., namely polyisobutylene, styrene-isoprene-styrene block copolymer, or a (meth)acrylic polymer as well as a plasticizer such as the exemplified paraffin oil and/or squalane. These choices would have been obvious due to their suggestion and meet the instant limitations for pressure sensitive adhesive and solubilizer/ solubilizer + plasticizer, respectively. The application of the taught proportions for memantine, hydrophobic polymer, and plasticizer (solubilizer) would follow and yields overlapping ranges with the instantly claimed ranges, thereby rendering the instantly claimed ranges obvious (see MPEP 2144.05). It additionally would have been obvious to make the layered construct as Terehara et al. suggest, where a solution of the adhesive layer is made employing an envisioned solvent and combined with a release and liner layer. It is the position of the examine that this process yields a preparation that does not crystallize over some period of time, even if brief (see instant claim 18). As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith. In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Thus there is no mechanism to directly ascertain the solubility of the memantine enanthate in the paraffin oil or squalane. However, the peanut oil solubilizer, a non-polar solvent, had the least ability to solubilize memantine enanthate as compared to the other better solubilizers instantly assessed (see instant figure 1). The other tested solubilizers were predominantly oxygen containing (polar) glycerides and fatty acid esters (see instant figure 1; Glinka et al. paragraph 83). Paraffin oil is less polar than peanut oil due to it being composed purely of hydrocarbons. It is the view of the examiner that it would likely solubilize memantine enanthate to a lesser degree than peanut oil and place it within the claimed scope of a being a solubilizer that has 30 mg/ml solubility or more in memantine enanthate, absent evidence to the contrary. Therefore claims 1-2 and 8-18 are obvious over Terehara et al. in view of Ito and Vepachedu as evidenced by Fuller, Mochizuki et al., Nielson et al., and Glinka et al.
Response to Arguments
Applicant's arguments filed July 2, 2026 have been fully considered, but they are not fully persuasive. The rejection over Ito in view of others is withdrawn. New grounds of rejection are detailed to address the new claim limitations.
The applicant argues that solubilizers that dissolve 30 mg or more of memantine enanthate per milliliter of the solubilizer yield an unexpectedly superior performance. The specification details that a sampling of these solubilizers produced a degree of skin permeation that approaches or matches that of the free base, while yielding reduced skin irritation as compared to the free base. While the hydrochloride salt of memantine also yielded lower skin irritation than the free base when included in some of these same solubilizers, it also produced considerably less skin permeation than the enanthate salt. The claim scope is not limited to this set of solubilizer-memantine enanthate pairs, but instead reverses the recitation of the solubility and claims a scope with an array of solvents that also dissolve far less than 30 mg memantine enanthate per milliliter of solubilizer. Thus the applicant’s arguments are not directed to the claims as currently recited. As a result the showing is not commensurate in scope with the claims.
It is noted that the reversal in solubility recitation, noted above, is also recited in the specification (see specification page 5 section 21). One would expect solubility expressed as a quantity of solute in a quantity of solubilizer. The specification also seems to imply this view of solubility as it details dispersing 50 mg of memantine enanthate in 1 ml of propylene glycol monocaprylate on page 18. The figure 1 description describes it as showing “solubility of memantine enanthate and memantine levulinate depending on the type of solubilizer” and shows propylene glycol monocaprylate as one of the best performing of the solubilizers that solubilized about 450 mg memantine enanthate per gram of propylene glycol monocaprylate (see specification page 9 section 40). Thus it appears that there may be an error in the claim recitation stating “the solubilizer has a solubility of 30 mg/ml or more in memantine enanthate” in the claims and the specification, where instead a recitation that memantine enanthate has a solubility of 30 mg/ml or more in the solubilizer may have been intended. The applicant is encouraged to review the disclosure and specification and ensure the intended claim scope is recited and reflected in the specification.
Conclusion
No claim is 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 CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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, Robert Wax can be reached at (571) 272-0623. 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.
/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615
