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 .
DETAILED ACTION
A request for continued examination under 37 C.F.R. 1.114, including the fee set forth in 37 C.F.R. 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 C.F.R. 1.114, and the fee set forth in 37 C.F.R. 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 C.F.R. 1.114. Applicant’s submission filed July 29, 2025 has been received and entered into the present application.
Status of claims
The amendment filed on July 29, 2025 is acknowledged. Claims 2-7 and 10-15 have been canceled. New claims 17-27 have been added. Claims 1, 8-9, and 16-27 are under examination in the instant office action.
Applicants' arguments, filed on July 29, 2025, have been fully considered but they are moot in view of new grounds of rejection necessitated by the amendments (adding new limitations in claim 1 and new claims). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 27 is objected to because of the following informalities: typographical errors. The word “and” before “combination thereof” in line 2 should be corrected to --or--.
Claim Rejections - 35 USC § 112 (b)
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 17-20 and 22-25 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 pre-AIA the applicant regards as the invention.
New claims 17-20 recite that the composition further comprises: an estrogen (claim 17); a progesterone, a progestin, or a combination thereof (claim 18); nutritional supplements, vitamins, or a combination thereof (claim 19); and a compound useful for treating a central nervous disorder (claim 20), respectively.
New claims 22-25 recites that the transdermal patch further comprises: an estrogen (claim 22); a progesterone, a progestin, or a combination thereof (claim 23); nutritional supplements, vitamins, or a combination thereof (claim 24); and a compound useful for treating a central nervous disorder (claim 25), respectively.
The recitation of “further comprising” renders the scope of the claims indefinite because it is unclear whether 1) the composition or the transdermal patch also contains those recited ingredients in additional to a therapeutic agent recited in claim 1, or 2) they are the therapeutic agent recited in claim 1.
If the first interpretation is right, the new claims may raise new matter issues because the original disclosure do not support adding an estrogen; a progesterone, a progestin, or a combination thereof; nutritional supplements, vitamins, or a combination thereof; and a compound useful for treating a central nervous disorder in addition to another therapeutic agent.
For the examination purpose, the second interpretation will be used in light of the specification.
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 of this title, 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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 8-9, and 16-27 are rejected under 35 U.S.C. 103 as being unpatentable over US 2004/0081685 (hereafter, Wright) in view of US 2010/0256174 (hereafter, Yamaguchi; cited in the IDS filed on 11/22/2021).
Wright teaches a transdermal delivery system such as transdermal patch for delivering a therapeutic agent or drug through the skin or mucosa (abstract). Wright further teaches that certain preferred transdermal delivery system includes a softening agent such as levulinic acid and a penetration enhancer such as oleic acid, which is one of more preferred penetration enhancers ([0045], [0061], and claims 10-11).
Wright discloses that suitable therapeutic agents include estrogenic steroids such as estrone, 17-beta-estradiol and ethinyl estradiol and progesterone ([0051]).
Wright further discloses that suitable therapeutic agents include potent narcotics and analgesics such as fentanyl and etorphine; and local anaesthetics such as buprenorphine, penzocaine, morphine and morphine derivatives, lidocaine, prilocaine, mepivacaine or non-steroidal antirheumatics/anti-inflammatories such as indometnacin, diclofenac or etopenamate; sedatives such as pentabarbital sodium, phenobarbital, secobarbital sodium, codeine, (a-bromoisovaleryl) urea, carbromal, and sodium phenobarbital, psychis energizers such a 3-(2-aminopropyl) indole acetate and 3-(2-aminobutyl) indole acetate; tranquilizers such as reserpine, chlorpromazine hydrochloride, and thiopropazate hydrochloride ([0051]), which are compounds for treating CNS disorders.
Wright further discloses that suitable therapeutic agents include potent nutritional agents such as vitamins, essential amino acids, and essential fats ([0051]).
Wright discloses that the above drugs and other drugs can be present in the therapeutic patch of the invention alone or in combination form with pharmaceutical carriers wherein the carriers include, water, glycol, polymers, adjuvants such as preserving, stabilizing, wetting, emulsifying agents, and the like ([0058]).
Yamaguchi teaches an external preparation composition having good transdermal absorbability wherein the external preparation composition having excellent transdermal absorbability can be produced by dissolving a medicinal substance or a salt thereof in a fatty acid-based ionic liquid to form a composite ionic composition of the medicinal substance (abstract). Yamaguchi teaches the external preparation composition further comprises an organic acid in addition to the fatty acid-based ionic liquid and preferable examples of the organic acid can include levulinic acid, acetic acid, and oleic acid wherein the amount of the organic acid used is 1 to 10% by weight, preferably 1 to 5% by weight, of the whole amount ([0016], [0049]. [0052], Tables 26-27, [0176], and claims 7-8). Yamaguchi further teaches the transdermal absorbability is improved at an increased content of fatty acid such as levulinic acid or isostearic acid ([0191]), [0203], and [0215]). Yamaguchi also discloses an external preparation composition comprising 2 w/w % oleic acid ([0244]).
Yamaguchi further teaches that the drug or the drug can be transdermally absorbed more easily by dissolving a salt of the drug or the drug in an ionic liquid form (room temperature molten salt) in a fatty acid-based ionic liquid having 5 to 20 carbon atoms to form a cluster ion composition, which is then solvated in an appropriate organic solvent (mixed solvent of a proton-donor solvent and a proton-acceptor solvent) and the addition of a few % of fatty acid as a transdermal absorption accelerator further improve the transdermal absorption ([0013]). In addition, Yamaguchi teaches that a matrix-type patch comprising the composition formulated therein can also be prepared to provide a pharmaceutical product that exhibits favorable transdermal absorbability ([0018]). Yamaguchi further teaches that an adhesive is used as a base in patches wherein the adhesive is composed mainly of an elastomer (polymer) with a tackifier, a softener, a filler, an antioxidant (BHT), and the like ([0059] and [0064]).
The specific combination of features claimed is disclosed within the broad genera of taught by Wright, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any motivation to select this specific combination of variables, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected oleic acid as a permeation enhancer and levulinic acid as a softening agent for their transdermal system comprising claimed therapeutic agents as taught and suggested by Wright to arrive at compositions “yielding no more than one would expect from such an arrangement”. While it does not disclose a specific example of a transdermal patch comprising a therapeutic agent, oleic acid, and levulinic acid, the prior art explicitly teaches the addition of oleic acid as permeation enhancer and levulinic acid as softening agent for improving transdermal delivery. Thus, one of ordinary skill in the art would have been motivated to add those since such combination has been suggested by prior art. In addition, Yamaguchi already teaches the addition of a few % of fatty acid as a transdermal absorption accelerator further improve the transdermal absorption and suggests the combinational use of one or more fatty acids including levulinic acid and oleic acid. Thus, one of ordinary skill in the art would have been motivated to do so on the reasonable expectation that the combination of oleic acid and levulinic acid would further improve transdermal absorption of the therapeutic agent through human skin.
As to the concentration of oleic acid and levulinic acid, Yamaguchi teaches the range of oleic acid and levulinic acid which overlaps those claimed as stated above. “A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379,1382-83 (Fed. Cir. 2003). Also, it would have been prima facie obvious to optimize the concentration of oleic acid and levulinic acid depending on a specific therapeutic agent to be used for obtaining best results based on the range disclosed in the prior art. In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Applicant did not show the criticality of the claimed concentration.
Claims 1, 8-9, 16, 20-21, and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over US 6264980 (hereafter, Hille) in view of US 2010/0256174 (hereafter, Yamaguchi; cited in the IDS filed on 11/22/2021) as evidenced by US 2395446.
Hille teaches the transdermal application of medicinal agents (therapeutic agent) with the aid of inactive ingredients forming subcooled melts, wherein the inactive ingredient having an absorption-increasing effect is levulic acid (abstract, col 2, lines 15-20 and lines 27-35 and claim 1). Levulinic acid is also known as levulic acid as evidenced by US 2395446 (p1, col2, lines 34-38).
Hille discloses suitable medicinal agent for their invention includes hormone, psychotropic drugs, migraine analgesics, anticholinergics, sympathicolytics, sympathicomimetics (compound for treating CNS disorder) (col 2, lines 15-20).
Hille further teaches a transdermal therapeutic system is applied on the skin of a patient (human) and the medicinal agent is to be released to take a topical or systemic effect in the patient (col 2, lines 7-20). Hille further teaches that administration forms have a layered structure; in the simplest case they consist of a backing layer, a self-adhesive active substance reservoir, and a removable protective layer to be removed prior to application (transdermal patch) (col 2, lines 7-20).
Hille discloses the use of 10% levulic acid with oleyl oleate in an example (Table 1 and column 2, Example 1, lines 1-6).
Hille does not specifically disclose oleic acid.
Yamaguchi teaches an external preparation composition having good transdermal absorbability wherein the external preparation composition having excellent transdermal absorbability can be produced by dissolving a medicinal substance or a salt thereof in a fatty acid-based ionic liquid to form a composite ionic composition of the medicinal substance (abstract). Yamaguchi teaches the external preparation composition further comprises an organic acid in addition to the fatty acid-based ionic liquid and preferable examples of the organic acid can include levulinic acid, acetic acid, and oleic acid wherein the amount of the organic acid used is 1 to 10% by weight, preferably 1 to 5% by weight, of the whole amount ([0016], [0049]. [0052], Tables 26-27, [0176], and claims 7-8). Yamaguchi further teaches the transdermal absorbability is improved at a increased content of fatty acid such as levulinic acid or isostearic acid ([0191]), [0203], and [0215]). Yamaguchi also discloses a external preparation composition comprising 2 w/w % oleic acid ([0244]).
Yamaguchi further teaches that the drug or the drug can be transdermally absorbed more easily by dissolving a salt of the drug or the drug in an ionic liquid form (room temperature molten salt) in a fatty acid-based ionic liquid having 5 to 20 carbon atoms to form a cluster ion composition, which is then solvated in an appropriate organic solvent (mixed solvent of a proton-donor solvent and a proton-acceptor solvent) and the addition of a few % of fatty acid as a transdermal absorption accelerator further improve the transdermal absorption ([0013]). In addition, Yamaguchi teaches that a matrix-type patch comprising the composition formulated therein can also be prepared to provide a pharmaceutical product that exhibits favorable transdermal absorbability ([0018]). Yamaguchi further teaches that an adhesive is used as a base in patches wherein the adhesive is composed mainly of an elastomer (polymer) with a tackifier, a softener, a filler, an antioxidant (BHT), and the like ([0059] and [0064]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add oleic acid to the transdermal composition of Hille for further improving transdermal absorption of a therapeutic agent because Yamaguchi already teaches the addition of a few % of fatty acid as a transdermal absorption accelerator further improve the transdermal absorption and suggests the combinational use of one or more fatty acids including levulinic acid and oleic acid. Thus, one of ordinary skill in the art would have been motivated to do so on the reasonable expectation that the addition of oleic acid would further improve transdermal absorption of the therapeutic agent through human skin. According to M.P.E.P. § 2144.06, “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One having ordinary skill in the art would have been motivated to combine these references and make the modification because they are drawn to the same technical fields (constituted with same ingredients and share common utilities), and pertinent to the problem which applicant concerns about. MPEP 2141.01(a).
As to the concentration of oleic acid and levulinic acid, the prior art teaches the range of the transdermal absorption enhancers which overlaps those claimed as stated above. “A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379,1382-83 (Fed. Cir. 2003). Also, it would have been prima facie obvious to optimize the concentration of the transdermal absorption enhancers depending on a specific medicinal agent to be used for obtaining best results based on the range disclosed in the prior art. In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Applicant did not show the criticality of the claimed concentration.
As to new claims 21 and 26-27, Yamaguchi teaches the transdermal composition further comprises a base wherein the base for liquid preparations include mixed solutions of alcohols (e.g., isopropanol, ethanol, propylene glycol, and glycerin), fats and oils (e.g., olive oil and soybean oil), and water and an adhesive base for patches includes an elastomer such as rubber polymers with a tackifier, a softener, a filler, an antioxidant such as BHT, and the like ([0055]-[0064] and Table 47). Thus, it would have been prima facie obvious to add one or more known excipients taught by Yamaguchi for preparing the transdermal composition or patch. Generally, it is prima facie obvious to select a known material for incorporation into a composition based on its recognized suitability for its intended use. See MPEP 2144.07.
Response to Applicant’s arguments
Responses are limited to Applicants' arguments relevant to either reiterated or newly applied rejections.
As to surprising results for a much greater flux for compositions that comprise both oleic acid and levulinic acid, the examiner notes that it is applicant's burden to demonstrate unexpected results over the prior art. See MPEP 716.02, also 716.02 (a) - (g). Furthermore, the unexpected results should be demonstrated with evidence 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). Moreover, evidence as to any unexpected benefits must be "clear and convincing" In re Lohr, 137 USPQ 548 (CCPA 1963), and be of a scope reasonably commensurate with the scope of the subject matter claimed, In re Linder, 173 USPQ 356 (CCPA 1972). In the instant case, the alleged unexpected result of the claimed composition is still not commensurate in scope with the claims as amended. The results shown in the specification are limited to formulations comprising ondansetron as active agent (see Table A). However, the instant claims are directed to a formulation comprising any therapeutic agents, not limited to ondansetron. There is no adequate basis for concluding that similar effects would be obtained for formulations comprising various therapeutic agents, which have different chemical and physical properties from ondansetron. In addition, Yamaguchi discloses the addition of levulinic acid as an additive further improved the transdermal absorbability (see Table 26). Thus, alleged surprising results (improved transdermal absorption) would have been expected.
For the foregoing reasons, Applicant’s arguments have not found to be persuasive.
Double Patenting Rejections
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 8-9, 16, 20-21, and 25-27 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of US patent 9,186,352.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘352 patent are drawn to a composition or a transdermal patch for use on human skin comprising: a mixture comprising ondansetron, an ondansetron salt, or a mixture thereof (therapeutic agent for treating a central nervous disorder); from about 1% to about 5% by weight of the composition of oleic acid; and from about 1% to about 5% by weight of the composition of levulinic acid. As to claims 21 and 26-27, it would have been prima facie obvious to add one or more excipients suitable for preparing the transdermal composition.
As such, the instant claims are anticipated by or would have been obvious over the claims of ‘352 patent.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611