DETAILED ACTION
This action is in response to papers filed on 01/23/2026. Claims 1-20 of Joshi et al., 17/775,269 (05/06/2022) are pending examination on the merits: claims 1-2, and 19-20 are amended. This action supersedes the Non-Final Office Action mailed on 02/19/2026. Claims 1-20 are rejected.
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 .
Priority
This application is a 371 of PCT/US2020/059580 (11/07/2020) which claims benefit of 62/933,300 (11/08/2019).
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/23/2026 has been entered.
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.
Claims 1-5 and 7-20 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. US PG-PUB 2012/0258976 A1 (“Murphy”), in view of Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”).
Regarding claim 1, Murphy teaches methods of delivering tofacitinib (Murphy, p. 2, para. [0017]), and discloses wherein the pharmaceutical composition comprises about 0.010% to about 10% of tofacitinib or a pharmaceutically acceptable salt thereof. As disclosed by Murphy, topical formulations contain 3-((3R,4R)-4-methyl-3-methyl-(7H-pyrrolo-2,3-dipyrimidin-4-yl)amino-piperidin-1-yl)-3-oxopropionitrile in therapeutically effective amounts that can be given in daily or twice daily doses to patients in need. These amounts range from about 0.1 % to about 5.0% (w/v). (Murphy, p. 13, para. [0130]).
Murphy however, does not teach a pharmaceutical composition comprising tofacitinib or a pharmaceutically acceptable salt thereof, and an ionic liquid …wherein the ionic liquid comprises a choline cation and a fatty acid anion.
Tanner teaches design principles of ionic liquids for transdermal drug delivery. Tanner teaches choline-based ionic liquids (ILs), in particular, choline and geranic acid (CAGE) in a molar ratio of 1:2 of choline to geranic acid (Abstract). According to Tanner, this molar ratio yields the highest delivery and represents a framework for enhancing skin permeability of drugs administered topically. Tanner discloses that “This work represents the first systematic structural study of ILs in transdermal drug delivery, and provides a paradigm for designing new, effective topical formulations.” (p. 8). In this skin penetration study, Tanner teaches that the drug tested using said ionic liquid drug delivery system, had penetrated well beyond the dermis as well. (p. 9, “Skin Penetration Studies”) and also had the greatest result when choline and geranic acid (CAGE) was used in a molar ratio of 1:2 of choline to geranic acid (Fig. 3):
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Moreover, while Tanner does not expressly teach the recited amounts of about 5% to about 40% of an ionic liquid as claimed, the ratio disclosed by Tanner can be routinely optimized to obtain a desirable range that is contingent upon on the total volume of the formulation. This is well within the technical skill of a person of ordinary skill in the art. As disclosed in MPEP § 2144.05, it is within the skill of an artisan to routinely optimize and formulate the claimed range in order to arrive at the claimed invention with reasonable expectation of success. See In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) which states, "where 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." See MPEP § 2144.05. Furthermore, Applicant has not demonstrated any criticality of the claimed range.
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 modify Murphy’s method of delivery tofacitinib topically, to further include ionic liquids, as taught by Tanner, and arrive at the claimed method of delivery tofacitinib to or through the skin, the method comprising administering to the skin a pharmaceutical composition comprising tofacitinib or a pharmaceutically acceptable salt thereof, and an ionic liquid in an amount sufficient to allow a therapeutically effective amount of tofacitinib to reach a target depth within or beyond the skin, wherein the ionic liquid comprises a choline cation and a fatty acid anion.” The motivation for doing so would be to optimize the delivery of tofacitinib using ionic liquids comprising CAGE in the disclosed molar ratios; thus, enhancing and optimizing the effectiveness of the treatment of dermatological issues beneath the skin’s surface using tofacitinib.
Regarding the method of claim 1 wherein the pharmaceutical composition further comprises “about 1% to about 20% of 2-(2-ethoxyethoxy)ethanol…”, Murphy in view of Tanner does not expressly disclose that the pharmaceutical further comprises 2-(2-ethoxyethoxy)ethanol.
Mura teaches penetration enhancers, including 2-(2-ethoxyethoxy)ethanol (Transcutol®) as carriers for cutaneous delivery of a drug. Mura at Abstract. Mura also teaches “Transcutol (diethylene glycol monoethylether) is a well-known non-toxic, biocompatible with skin, penetration enhancer. It is known to act by swelling of stratum corneum intercellular lipids without alteration of their multiple bilayer structure…”. Mura at page 74. Mura also teaches in Fig. 3, that “Moreover, in comparison with the control, all PE solutions showed an improved drug permeation that was particularly evident when labrasol and transcutol were employed…”.
Regarding the amount from about 1% to about 20% of the 2-(2-ethoxyethoxy)ethanol, to one of ordinary skill in the art, adjusting the parameter of an amount of a penetration enhancer, present in a composition, is recognized in the art as a result-effective variables (i.e., a variable which achieves a recognized result), and thus the determination of the optimum or workable ranges of said variables are characterized as routine experimentation. MPEP § 2144.05.
Nonetheless, Mura 2011 in the Abstract teaches the preparation of Transcutol (Trc) containing vesicles for topical delivery of a drug. In the experiment, Mura 2011 prepared penetration enhancer-containing vesicles (PEVs) using Trc aqueous solutions (5–10–20–30% v/v). Mura 2011 experimental results showed that using Trc facilitated the delivery of the drug to deeper layers of the dermis in the amounts disclosed.
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 modify Murphy in view of Tanner, and Mura teachings to use of 2-(2-ethoxyethoxy)ethanol (Transcutol®) as a carrier for cutaneous delivery of a drug, with improved drug permeation properties, in further view of the teachings of Mura 2011 of the claimed amount, and arrive at the claim as recited. The motivation for doing so would have been to provide a stable composition with desired percutaneous flux of tofacitinib to deeper layers of the dermis, thus improving drug delivery using the claimed amounts. Mura states that 2-(2-ethoxyethoxy)ethanol “… It is known to act by swelling of stratum corneum intercellular lipids without alteration of their multiple bilayer structure…”. Mura at page 74. That is, the motivation for doing so would have been to provide a stable composition with desired percutaneous flux. Additionally, obviousness does not require absolute predictability, but a reasonable expectation of success. See MPEP 2143.02. Mura 2011 teaches the claimed amounts as discussed that encompasses the claimed amounts. Applicant has not demonstrated any criticality of the ranges. Claim 1 is therefore obvious over Murphy in view of Tanner, Mura and Mura 2011.
Regarding claim 2, Murphy in view of Tanner and Mura teach the method of claim 1. Murphy teaches a PEG-based ointment comprising 2% (w/w) oleyl alcohol, whereas the claimed compositions include an alternative penetration enhancer (i.e., Transcutol®) and ionic liquid components. However, Tanner and Mura teach that skin permeation can be enhanced through the use of various penetration enhancers and delivery vehicles, including vesicles and solvent systems capable of improving drug transport through the dermal barrier. These references collectively demonstrate that it was known in the art that altering penetration enhancers and solvent systems could affect drug permeation and that practitioners routinely evaluate alternative enhancers to improve delivery efficiency. Accordingly, the substitution or modification of penetration enhancers as claimed would have been an obvious design choice for one of ordinary skill in the art seeking to optimize topical drug delivery.
Regarding claim 3, Murphy in view of Tanner and Mura teach the method of claim 1. Murphy teaches as discussed above, the limitation “wherein the pharmaceutical composition comprises about 0.1% to about 8% of tofacitinib or a pharmaceutically acceptable salt thereof.” Murphy on p. 13, para. [0130] teaches that the topical formulations contain 3-((3R,4R)-4-methyl-3-methyl-(7H-pyrrolo-2,3-dipyrimidin-4-yl)amino-piperidin-1-yl)-3-oxopropionitrile in therapeutically effective amounts that can be given in daily or twice daily doses to patients in need. These amounts range from about 0.1 % to about 5.0% (w/v). (Murphy, p. 13, para. [0130]). 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). Claim 3 is therefore also obvious.
Regarding claim 4, Murphy in view of Tanner and Mura teach the method of claim 1. Murphy teaches as discussed above, the limitation “wherein the pharmaceutical composition comprises about 0.1% to about 5% of tofacitinib or a pharmaceutically acceptable salt thereof.” Murphy on p. 13, para. [0130] teaches that the topical formulations contain 3-((3R,4R)-4-methyl-3-methyl-(7H-pyrrolo-2,3-dipyrimidin-4-yl)amino-piperidin-1-yl)-3-oxopropionitrile in therapeutically effective amounts that can be given in daily or twice daily doses to patients in need. These amounts range from about 0.1 % to about 5.0% (w/v). (Murphy, p. 13, para. [0130]). 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). Claim 4 is therefore also obvious.
Regarding claim 5, Murphy in view of Tanner and Mura teach the method of claim 1. Tanner discloses in Fig. 9, that the use of CAGE allowed for the drug being tested to be delivered beyond the dermis and into the acceptor fluid (p. 8):
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Therefore, as discussed above, it would have been obvious to one of ordinary skill in the art to select and use CAGE ionic liquid, in the disclosed molar ratio, to deliver tofacitinib to beyond the dermis and arrive at the claimed method. Tanner demonstrates the effectiveness of this drug delivery system in delivery a drug beyond the epidermis or dermis layer, thus improving the drug’s delivery to target areas beneath the dermis and epidermis, and would be expected to enhance the effectiveness of treating diseases or condition beyond the epidermis and dermis. Claim 5 is therefore also obvious.
Regarding claim 7, Murphy in view of Tanner and Mura teach the method of claim 5. Tanner teaches in Fig. 9, a study whereby the drug being assessed for optimized delivery were tested using four different combinations: drug + citronellic acid, drug + geranic acid, drug + CAGE, and drug + choline:citronellic acid. The amount of the drug reaching the epidermis, dermis and acceptor fluid were assessed. The citronellic acid transport at the dermis is disclosed to be about 37 ug/cm2; while the CAGE transport resulted in about 55 ug/cm2. This is about 1.5 times the total amount of tofacitinib reaching at least the dermis layer, provided by a control composition replacing the ionic liquid with the same amount of citronellic acid. While Murphy in view of Tanner do not compare the composition to -(2-ethoxyethoxy)ethanol, a permeation enhancer, it is noted that the structural features of the claim have been met and thus the properties would necessarily follow.
Regarding claim 8, Murphy in view of Tanner and Mura teaches the method of claim 5.
Tanner teaches in Fig. 9, a study whereby the drug being assessed for optimized delivery were tested using four different combinations: drug + citronellic acid as a control, drug + geranic acid, drug + CAGE, and drug + choline:citronellic acid. The amount of the drug reaching the epidermis, dermis and acceptor fluid were assessed. The choline: citronellic acid control transport at the dermis is disclosed to be about 20 ug/cm2; while the CAGE transport resulted in about 55 ug/cm2. This is at least 2 times the total amount of tofacitinib reaching at least the dermis layer, provided by a control composition replacing the ionic liquid with the same amount of choline:citronellic acid.
While Murphy in view of Tanner and Mura does not show a comparison to a PEG-based ointment and 2% of oleyl alcohol it is noted that the structural features of the claim have been met and thus the properties would necessarily follow.
Regarding claim 9, Murphy in view of Tanner and Mura teach the method of claim 5. As discussed above, Murphy in view of Tanner teaches the limitation “wherein the pharmaceutical composition allows therapeutically effective amount of tofacitinib to reach at least an epidermis layer” (Tanner: Fig. 9). Moreover, "where 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." See In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955). MPEP § 2144.05. Claim 9 is therefore also obvious.
Regarding claim 10, Murphy in view of Tanner and Mura teach the method of claim 5. As discussed above, Murphy in view of Tanner teaches the limitation “wherein the pharmaceutical composition allows therapeutically effective amount of tofacitinib to reach at least a dermis layer” (Tanner: Fig. 9). Moreover, "where 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." See In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955). MPEP § 2144.05. Claim 10 is therefore also obvious.
Regarding claim 11, Murphy in view of Tanner and Mura teach the method of claim 1. As discussed above, Murphy in view of Tanner teaches the limitation “wherein the pharmaceutical composition allows therapeutically effective amount of tofacitinib to reach beyond the dermis layer” (Tanner: Fig. 9). Moreover, "where 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." See In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955). MPEP § 2144.05. Claim 10 is therefore also obvious.
Regarding claims 12-13, Murphy in view of Tanner and Mura teach the method of claim 1. Tanner, as disclosed above, teaches wherein the fatty acid is geranic acid (Abstract). Claims 12-13 are therefore also obvious.
Regarding claim 14, Murphy in view of Tanner and Mura teach the method of claim 1. Tanner further teaches wherein the ionic liquid is a deep eutectic solvent (DES) (Abstract, and p. 1). Claim 14 is obvious.
Regarding claims 15-16, Murphy in view of Tanner and Mura teach the method of claim 1. Tanner teaches in Fig. 3, that the molar ratio of choline cation and fatty acid (i.e., geranic acid) is present in a range from about 2:1 to 1:4. Tanner also discloses that the most optimal molar ratio is 1:2 (Abstract: “First, the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE, which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery”). 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). Claims 15-16 are also obvious.
Regarding claims 17-18, Murphy in view of Tanner and Mura teach the method of claim 1. Murphy discloses methods of delivering tofacitinib (Murphy, p. 2, para. [0017]), and teaches wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier (Murphy, p. 2, para. [0015], pharmaceutical composition comprising 3-((3R,4R)-4-methyl-3-methyl-(7H-pyrrolo2,3-dipyrimidin-4-yl)-amino-piperidin-1-yl)-3-oxopropionitrile; one or more penetration enhancers; and a pharmaceutically acceptable carrier; p. 14, para. [0131], wherein the pharmaceutically acceptable carrier is at least 30% by weight PEG).
Regarding claim 19, Murphy in view of Tanner and Mura teach the method of claim 1— the use of 2-(2-ethoxyethoxy)ethanol (Transcutol®) as a carrier for cutaneous delivery of a drug, with improved drug permeation properties, teaches the method of the instant claim 1.
Murphy in view of Tanner, and Mura however does not expressly disclose “wherein the pharmaceutical composition comprises from about 5% to about 15% of the 2-(2-ethoxyethoxy)ethanol.”
However, to one of ordinary skill in the art, adjusting the parameter of an amount of a penetration enhancer, present in a composition, is recognized in the art as a result-effective variables (i.e., a variable which achieves a recognized result), and thus the determination of the optimum or workable ranges of said variables are characterized as routine experimentation. MPEP § 2144.05.
Nonetheless, Mura 2011 in the Abstract teaches the preparation of Transcutol (Trc) containing vesicles for topical delivery of a drug. In the experiment, Mura 2011 prepared penetration enhancer-containing vesicles (PEVs) using Trc aqueous solutions (5–10–20–30% v/v). Mura 2011 experimental results showed that using Trc facilitated the delivery of the drug to deeper layers of the dermis in the amounts disclosed.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Murphy in view of Tanner, and Mura teachings as applied above to claim 1, in further view of the teachings of Mura 2011, and arrive at the claim as recited. The motivation for doing so would have been to provide a stable composition with desired percutaneous flux of tofacitinib to deeper layers of the dermis, thus improving drug delivery. Moreover, Applicant has not disclosed any criticality for the claimed range. Claim 19 is also obvious.
Regarding claim 20, and as discussed and applied above, Murphy in view of Tanner and Mura teaches a topical composition, comprising tofacitinib or a pharmaceutically acceptable salt thereof, and an ionic liquid in an amount sufficient to allow a therapeutically effective amount of tofacitinib to reach a target depth within or beyond the skin, wherein the ionic liquid comprises a choline cation and a fatty acid anion all in the claimed amounts. Claim 20, as is claims 1-19, is also obvious.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. US PG-PUB 2012/0258976 A1 (“Murphy”), in view of Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”).
, as applied to claim 1-5, and 7-20, and in further view of Christiano et al., WO 2013/149194A1 (“Christiano”).
Regarding claim 6, Murphy in view of Tanner teaches the method of claim 5.
Murphy in view of Tanner however, does not expressly disclose “wherein the amount of tofacitinib in the at least one of an epidermis layer and a dermis layer is sufficient to inhibit activity of at least one of JAK-1, JAK-2, TYK-2, and JAK-3 in the at least one of an epidermis layer and a dermis layer.”
Christiano, also in the field of delivering tofacitinib (p. 2, para. [0006]), teaches wherein the amount of tofacitinib in the at least one of an epidermis layer and a dermis layer is sufficient to inhibit activity of at least one of JAK-1, JAK2, TYK-2, and JAK-3 in the at least one of an epidermis layer and a dermis layer (Christiano, p. 2, para. [0006]: method of treating a hair-loss disorder in a mammalian subject in need thereof, the method comprising administering to the subject an inhibitor of a protein tyrosine kinase (PTK) involved in cytokine signaling. In one embodiment, the inhibitor is a Jak3 inhibitor. In one embodiment, the inhibitor is tofacitinib). On p. 66, para. (00215], Jak3 proteins and Jak3 modulating compounds (e.g., a Jak3 inhibitor) can be administered to a subject by any means suitable for delivering the Jak3 proteins and Jak3 modulating compounds to cells of the subject, such as the dermis, epidermis. Christiano also teaches on p. 80, para. [00269]: To activate a Jak protein target in the skin, the skin should be penetrated at about 0.5 mm, about 1mm, about 1.5 mm, about 2mm, about 2.5 mm, about 3 mm, about 3.5 mm, or at about 4 mm. Depending on the depth of penetration, the concentration of a JAK inhibitor, such as a JAK 1/2 inhibitor or a JAK3 inhibitor, can range from about 25 nM to about 5000 nM. At the higher concentration ranges, one JAK inhibitor can elicit an inhibitory effect not only of its target but also of other JAK proteins).
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 modify Murphy in view of Tanner teachings, with the teachings of Christiano and arrive at the claim as recited successfully. The motivation for doing so would have been to allow for the treatment of skin disorders by delivering to the skin an effective amount of an inhibitor of a protein tyrosine kinase involved in cytokine signaling (Christiano, p. 19, para. [0092]). Claim 6 is therefore obvious over Murphy in view of Tanner, and in further view of Christiano.
Examiner’s Response
Applicant argues the amendments made to claims 1-2, and 19-20 to specify the amounts of each component of the pharmaceutical composition. Applicant also argues that as a whole, the references do not teach the claimed invention as currently recited because Murphy teaches a PEG-based ointment formulation that comprises 2% (w/w) oleyl alcohol. Applicant argues that they prepared the same composition (c.f., Example 9, para [0098] of Specification), along with a composition comprising 40% (w/w) 2-(2-ethoxyethoxy)ethanol. Applicant argues unexpected results based on the data in Fig. 1 of the Specification. Applicant argues that “…compositions containing ionic liquid according to… embodiments of the present disclosure resulted in a significantly increase permeation of tofacitinib compared to the two control compositions that includes oleyl alcohol and Transcutol® as penetration enhancers…”. Applicant’s Remarks at page 6. Applicant then argues the Tanner reference citing unpredictability in the art, and argues the Mura reference citing that Mura teaches the use of vesicles to enhance skin permeation. Applicant then argues that the claimed invention which includes a different penetration enhancer Transcutol® showed surprisingly results that could not have been predicted by one of ordinary skill in the art.
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Examiner’s Response
Applicant’s arguments are acknowledged, but are not found to be persuasive in view of the rejections the rejection of claims 1-5 and 7-20 under 35 U.S.C. 103 as being unpatentable over Murphy et al. US20120258976A1 (“Murphy”), in view of Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”), and claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Murphy in view of Tanner and Mura, as applied to claim 5, and in further view of Christiano et al., WO2013149194A1 (“Christiano”).
Applicant asserts that the amendments to claims 1-2, and 19-20 specifying the amounts of the components distinguish over the cited prior art. However, Applicant has not adequately demonstrated that the amended ranges or amounts result in a composition that is structurally or functionally distinct from those taught the cited references. Furthermore, as discussed above, the adjustment of component concentrations (c.f., the ionic liquid amount) within known formulation parameters would have been within the routine skill of a person of ordinary skill in the art seeking to optimize drug permeation. Regarding tofacitinib and 2-(2-ethoxyethoxy)ethanol, the prior art teaches the claimed ranges that overall in scope as discussed above. 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).
Applicant further argues that Murphy teaches a PEG-based ointment comprising 2% (w/w) oleyl alcohol, whereas the claimed compositions include an alternative penetration enhancer (i.e., Transcutol® ) and ionic liquid components. However, Tanner and Mura teach that skin permeation can be enhanced through the use of various penetration enhancers and delivery vehicles, including vesicles and solvent systems capable of improving drug transport through the dermal barrier. These references collectively demonstrate that it was known in the art that altering penetration enhancers and solvent systems would affect drug permeation and that practitioners routinely evaluate alternative enhancers to improve delivery efficiency. Accordingly, the substitution or modification of penetration enhancers as claimed would have been an obvious design choice for one of ordinary skill in the art seeking to optimize topical drug delivery.
Applicant also argues that the data in Fig. 1 demonstrate unexpected results because compositions containing the ionic liquid allegedly provide a significantly increased permeation of tofacitinib compared to the control compositions containing oleyl alcohol and Transcutol®. However, the evidence provided is not commensurate in scope with the claims and does not persuasively establish that the observed results are unexpected relative to the closest prior art. As shown in Fig. 1, the control compositions themselves exhibit differing baseline permeation values, indicating that the underlying vehicle composition already influences drug delivery. The observed increase in permeation for the claimed compositions therefore appears attributable, at least in part, to inherent differences in the formulation vehicles rather than to an unexpected synergistic effect arising from the claimed features. Moreover, the data presented do not demonstrate that the magnitude of improvement would have been surprising to one of ordinary skill in the art in view of the teachings of Tanner and Mura, which describe the unpredictable yet often enhanced permeation associated with alternative delivery systems, vesicular carriers, and modified solvent environments. While applicant asserts unpredictability in the art, such unpredictability does not render obvious variations patentable where the prior art provides motivation to explore known alternatives for improving drug delivery.
Applicant further relies on Mura for the proposition that vesicle-based systems enhance permeation; however, this teaching actually supports the examiner’s position that the art recognized multiple strategies for improving dermal drug delivery, including altering the delivery vehicle, solvent systems, or enhancer composition. One of ordinary skill in the art would therefore have been motivated to modify the Murphy formulation by incorporating alternative penetration enhancers or solvent systems such as those suggested by Tanner and Mura in order to improve permeation performance.
Accordingly, the evidence of record does not demonstrate that the claimed compositions exhibit results that are unexpected or superior relative to the closest prior art in a manner sufficient to overcome the prima facie case of obviousness. Therefore, applicant’s arguments regarding unexpected results and non-obviousness are not persuasive, and the rejection under 35 U.S.C. §103 is maintained.
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 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-9, 11, 13, 15-17, and 23 of copending Application No. 18030177 (reference application), in view of Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”), Murphy et al., US20120258976A1 (“Murphy”), Zakrewsky et al., US 20160263225 A1 (“Zakrewsky”), and Christiano et al., WO2013149194A1 (“Christiano”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application recite a gel composition comprising an ionic liquid, having a cationic and anionic component, for use as a topical composition in methods treating skin diseases and conditions.
The difference between the instant application and the reference application, is that while the instant claims detail tofacitinib with said ionic liquid base for topical administration, the reference application focuses primarily on the base ionic liquid component itself, and formulating it as a gel composition, which includes the presence of antioxidants, water, and cellulose. However, the instant application’s comprising language does not preclude the presence of antioxidants, water, and cellulose, or gel formulation based on desirability. Moreover, regarding the amount of ionic liquid, the ranges overlap in scope with the claimed invention. 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).
While the reference claims do not disclose tofacitinib, the secondary references teach said tofacitinib as part of an ionic liquid composition for treating skin conditions and diseases as disclosed above.
It would have therefore been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and modify the claims of the reference application, in view of the secondary references of tofacitinib and the cited secondary references, and arrive at the claimed invention successfully. One would have been motivated to create a formulation that allows treatment to penetrate deep within the dermis and beyond in order to treat deep skin issues and conditions per the teachings of the reference application, in view of Murphy et al. US20120258976A1 (“Murphy”), Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”) as discussed above. The claims are obvious over the reference claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49, 62, 65, 73, and 75-76 of copending Application No. 16981956 (reference application), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”), Murphy et al., US20120258976A1 (“Murphy”), Zakrewsky et al., US 20160263225 A1 (“Zakrewsky”). and Christiano et al., WO2013149194A1 (“Christiano”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application recite a composition comprising an ionic liquid, having a cationic and anionic component, for use as a topical composition in treating skin diseases and conditions.
Independent claim 49 of the reference application recites:
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Instant independent claim 1, for example, recites:
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The difference between the instant application and the reference application, is that while the instant claims detail the tofacitinib with said ionic liquid base for topical administration, the reference application focuses primarily on the base ionic liquid component itself, and its formulation, which includes the presence of fragrance agents, citric acid, and other routine components for formulating a composition based on desirability and route of administration. However, it must be noted that the instant application recites comprising language that does not preclude the presence of said fragrance agents, citric acid, and other routine components for formulating the composition based on desirability. Moreover, regarding the amount of ionic liquid, the ranges overlap in scope with the claimed invention. 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).
While the reference claims do not disclose tofacitinib, the secondary references teach said tofacitinib as part of an ionic liquid composition for treating skin conditions and diseases as disclosed above.
It would have therefore been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and modify the claims of the reference application, in view of the secondary references of tofacitinib and the cited secondary references, and arrive at the claimed invention successfully. One would have been motivated to create a formulation that allows treatment to penetrate deep within the dermis and beyond in order to treat deep skin issues and conditions per the teachings of the reference application, in view of Murphy et al. US20120258976A1 (“Murphy”), Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”) as discussed above. The claims are obvious over the reference claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments/Examiner’s Response
Applicant contends that both independent claims in the respective nonstatutory double patenting rejections recite, among other features, that the ionic liquid comprises a choline cation and fatty acid anion, and that the pharmaceutical composition further comprises 2-(2-ethoxyethoxy)ethanol, present in the composition based on the claimed amounts. Applicant argues that none of the prior art disclose 2-(2-ethoxyethoxy)ethanol. Applicant’s Remarks at page 5.
Examiner’s Response
Applicant’s arguments are acknowledged but are not found to be persuasive in view of the teachings presented in the rejection of claims 1-5, and 7-20 under 35 U.S.C. 103 as being unpatentable over Murphy et al. US20120258976A1 (“Murphy”), in view of Tanner et al., Adv. Mater. 2019, 31, 1901103, pp. 1-10 (“Tanner”), Mura et al., Int. J. Pharm., 380 (2009), pp. 72-79, (“Mura”), and Mura et al., (2011), Journal of Drug Targeting, 19(3), 189–196 (“Mura 2011”), and claim 6 under 35 U.S.C. 103 as being unpatentable over Murphy in view of Tanner and Mura, as applied to claim 5, and in further view of Christiano et al., WO2013149194A1 (“Christiano”) discussed above.
Conclusion
No claims are allowed.
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/C A/Examiner, Art Unit 1622 March 7, 2026
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622