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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/21/2026 has been entered.
Status of the Claims
Claims 1, 4-10, 12-13, and 16-21 are pending and under current examination. Claims 3, 11, and 15 are canceled.
Withdrawn Claim Rejections
All rejections pertaining to claims 3, 11, and 15 are moot because the claims are cancelled in the amendments to the clams filed 5/21/2026.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s amendments to the claims filed 5/21/2026 have necessitated the new grounds of rejection.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 4-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Lakhani (U.S. Patent Application No. 2020/0155475, publication date: 5/21/2020, of record) in view of Miranda (U.S. Patent No. 5,656,286, issue date: 08/12/1997, of record) and Sindhu et. al. (Research Journal of Pharmacy and Technology, pg. 1809-1815, publication year: 2017).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 1, Lakhani teaches a monolithic TDDS (TDDS) comprising a bioadhesive polymer, a film-forming agent, a plasticizer, a naturally occurring polysaccharide, a keratolytic agent and one or more active agents [0005]. The active agent may be present from 1-60% w/w [0005]. The active agent may include lenalidomide ([0009], [0019], and [0118]). Polyvinylpyrrolidone may be present as a bioadhesive polymer and film forming agent [0099]. Lakhani defines a bioadhesive polymer to be a polymer that exhibits a pressure-sensitive character of adhesion toward highly hydrated biological surfaces such as the hydrated skin [0053]. The Examiner therefore interprets the bioadhesive polymer of Lakhani to read on the "pressure sensitive adhesive" limitation of the instant claim. The TDDS may be made by first adding a film-forming agent and a plasticizer to water and stirring. A bioadhesive polymer and polysaccharide are added and stirred until the polymer is dissolved and the viscosity is reduced. The film forming agent and a keratolytic agent are added, followed by one or more active agents and stirred to obtain a formulation [0113]. The drug is dispersed in an adhesive polymer matrix [0028]. The active ingredient is dissolved into the polymer matrix [0033]. The Examiner interprets this to mean that the drug present in the transdermal delivery system taught by Lakhani must be solubilized and homogenously dispersed in the adhesive layer. Lakhani also teaches that methacrylate block copolymers may be present in a circular adhesive backing layer [0007] and that the TDDS may include a penetration enhancer [0109].
Regarding claim 5, Lakhani teaches a monolithic TDDS comprising a bioadhesive polymer, a film-forming agent, a plasticizer, a naturally occurring polysaccharide, a keratolytic agent and one or more active agents [0005]. The active agent may be present from 1-60% w/w [0005]. The active agent may include lenalidomide ([0009], [0019], and [0118]). Polyvinylpyrrolidone may be present as a bioadhesive polymer and film forming agent [0099].
Regarding claims 6 and 7, Lakhani teaches that the bioadhesive polymer of the TDDS may include hydroxypropylmethyl cellulose [0006]. The TDDS may also include methylcellulose as an emulsifying agent [0063].
Regarding claim 8, Lakhani teaches that the TDDS may include a penetration enhancer [0109].
Regarding claim 9, Lakhani teaches that the penetration enhancer may be glycerol monolaurate [0109]. The TDDS may also include fatty acids [0017], a surfactant [0063], a plasticizer [0005], and pH buffering agents [0079].
Regarding claim 10, Lakhani teaches that the TDDS may contain ascorbic acid and ascorbyl esters of fatty acids as antioxidants [0110] and lactic acid and salicylic acid as keratolytic agents [0006].
Regarding claim 12, Lakhani teaches that a transdermal drug delivery device may contain a matrix, in which one or more drugs or active agents are dispersed, a backing layer, a rate-controlling membrane, and an adhesive means for affixing the system to a body surface [0091]. Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 1 and 4, Lakhani does not teach an acrylate copolymer, polyisobutylene, or silicone as a pressure sensitive adhesive in the drug-in-adhesive layer of the TDDS or the inclusion of a polar aprotic solvent in the TDDS. However, this deficiency is cured by Miranda and Sindhu.
Miranda teaches a TDDS comprised of a pressure-sensitive adhesive, a drug in the adhesive composition and polyvinylpyrrolidone present as a crystallization inhibitor (Col. 4 lines 15-27 and Col. 36 lines 23-25). Miranda further teaches a pressure sensitive adhesive blend of an acrylic polymer and a silicone polymer. Other embodiments of the pressure sensitive adhesive taught by Miranda can include polyisobutylene (Col. 9 lines 34-54). Sindhu teaches that DMF and N-methyl-2-pyrrolidone are suitable penetration enhancers for transdermal drug delivery systems (pg. 6, Classification of Chemical Penetration Enhancers).
Regarding claim 12, Lakhani does not teach a specific weight percentage for the solubilized drug-in-adhesive layer of the TDDS.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 1, based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the bioadhesives of Lakhani and a blend of an acrylic polymer and a silicone polymer the for the purpose of a pressure sensitive adhesive in a TDDS). See MPEP 2144.06-II.
Furthermore, with regard to the “polar aprotic solvent” limitation of the instant claim 1, the idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional skin permeation enhancers used in TDDS. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
With regards to the “crystallization inhibitor” limitations of instant claims 1 and 5, the prior art teaches the same polyvinylpyrrolidone as claimed and therefore, the crystallization inhibitor properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
With regards to the “thickener” limitations of instant claims 6 and 7, the prior art teaches the same cellulose derivative thickeners as claimed and therefore, the thickener properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
With regards to the “skin permeation enhancer” limitations of instant claim 9, the prior art teaches the same compounds as claimed and therefore, the skin permeation enhancer properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
Regarding claim 12, the weight percentage of solubilized drug-in-adhesive layer in the TDDS is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight percentage in order to best achieve the desired results as such would provide advantageous dosage effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005]. The Examiner considers it prima facie obvious to optimize the thickness, and therefore the weight percentage, of the drug-in-adhesive layer absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight percentage of drug-in-adhesive layer would directly affect the dose of drug present in the TDDS and therefore be an optimizable variable.
Claims 13 and 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Lakhani (U.S. Patent Application No. 2020/0155475, publication date: 5/21/2020, of record), in view of Tang et al. (WO2009/158120, publication date 12/30/2009; of record) and Miranda (U.S. Patent No. 5,656,286, issue date: 08/12/1997, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 13, Lakhani teaches a monolithic TDDS comprising a bioadhesive polymer, a film-forming agent, a plasticizer, a naturally occurring polysaccharide, a keratolytic agent and one or more active agents [0005]. The active agent may be present from 1-60% w/w [0005]. The active agent may include lenalidomide ([0009], [0019], and [0118]). Lakhani defines a bioadhesive polymer to be a polymer that exhibits a pressure-sensitive character of adhesion toward highly hydrated biological surfaces such as the hydrated skin [0053]. The Examiner therefore interprets the bioadhesive polymer of Lakhani to read on the "pressure sensitive adhesive" limitation of the instant claim. The TDDS may contain a surfactant [0063]. The film forming agent and a keratolytic agent are added, followed by one or more active agents and stirred to obtain a formulation [0113]. The drug is dispersed in an adhesive polymer matrix [0028]. The active ingredient is dissolved into the polymer matrix [0033]. The Examiner interprets this to mean that the drug present in the transdermal delivery system taught by Lakhani must be homogenously dispersed in the adhesive layer. Lakhani also teaches that the patch sustainably delivers one or more active agents for 8-24 hours [0005] and that methacrylate block copolymers may be present in a circular adhesive backing layer [0007].
Regarding claims 16 and 17, Lakhani teaches the relevant limitations of claim 13 above.
Regarding claim 18, Lakhani teaches that the penetration enhancer in the TDDS may be glycerol monolaurate [0109]. The TDDS may also include fatty acids [0017], a surfactant [0063], a plasticizer [0005], and pH buffering agents [0079].
Regarding claims 19 and 20, Lakhani teaches that the emulsifying agent present in the TDDS may be surfactant such as a poloxamer [0063].
Regarding claim 21, Lakhani teaches that a transdermal drug delivery device may contain a matrix, in which one or more drugs or active agents are dispersed, a backing layer, a rate-controlling membrane, and an adhesive means for affixing the system to a body surface [0091]. Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 13, Lakhani does not teach a solid dispersion of a drug in adhesive layer or crosslinked polyvinylpyrrolidone present in the TDDS or an acrylate copolymer, polyisobutylene, or silicone as a pressure sensitive adhesive in the drug-in-adhesive layer of the TDDS. However, this deficiency is cured by Tang and Miranda.
Tang teaches a TDDS that utilizes an acrylic adhesive [00044] and also includes a solid dispersion drug-in-adhesive comprised of a stable amorphous form of a therapeutic agent and polymeric stabilizer which is also a dispersant capable of forming hydrogen bonding with the therapeutic agent [00019]. Tang teaches that the therapeutic agent may include anti-inflammatory substances [00051-52] and that the TDDS may contain crospovidone as a cohesion-promoting agent [00071]. Tang also teaches that the solid dispersion TDDS has an improved stability and absorption rate from the skin [00019]. Miranda teaches a TDDS comprised of a pressure-sensitive adhesive, a drug in the adhesive composition and polyvinylpyrrolidone present as a crystallization inhibitor (Col. 4 lines 15-27 and Col. 36 lines 23-25). Miranda further teaches a pressure sensitive adhesive blend of an acrylic polymer and a silicone polymer. Other embodiments of the pressure sensitive adhesive taught by Miranda can include polyisobutylene (Col. 9 lines 34-54).
Regarding claim 16, Lakhani does not teach a weight percentage range of crosslinked polyvinylpyrrolidone. However, this deficiency is cured by Tang.
Tang teaches that crosslinked polyvinylpyrrolidone may be present in the TDDS as a cohesion promoting agent and that the amount of stabilizing agent present in the composition may generally be in the range of 0-15% by weight of the adhesive [00072].
Regarding claim 17, Lakhani does not specify the ratio of therapeutic agent to crospovidone that may be present in the TDDS.
Regarding claim 21, Lakhani does not teach a specific weight percentage for the solubilized drug-in-adhesive layer of the TDDS.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 13 and 16, it would have been prima facie obvious to one of ordinary skill in the art of filing to employ a solid dispersion of lenalidomide and crospovidone in the TDDS embraced by Lakhani. One would have understood in view of Tang that a solid dispersion of an amorphous form of a therapeutic agent would render improved stability and absorption through the skin and that crospovidone present in the TDDS would help to promote cohesion. It would have been obvious to include such a solid dispersion and crospovidone in the TDDS embraced by Lakhani. One of ordinary skill in the art of filing would have been motivated to include a solid dispersion of lenalidomide and crospovidone in the TDDS embraced by Lakhani in order to improve cohesion, stability, and absorption through the skin. The artisan of ordinary skill would have had reasonable expectation of success because Tang teaches that a solid dispersion may be used for anti-inflammatory agents.
Regarding the pressure sensitive adhesive limitation of the instant claim 13, based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the bioadhesives of Lakhani and a blend of an acrylic polymer and a silicone polymer the for the purpose of a pressure sensitive adhesive in a TDDS). See MPEP 2144.06-II.
With regards to the “skin permeation enhancer” limitations of instant claim 13, the prior art teaches the same surfactants as claimed and therefore, the skin permeation enhancer properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
Regarding the weight ratio of immunomodulatory agent to crosslinked polyvinylpyrrolidone as specified in claim 17, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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).
Furthermore, Lakhani teaches that lenalidomide may be present from 1-60% w/w [0005]. Tang also teaches that crospovidone may be present as a cohesion promoting agent in amounts ranging from 0-15% by weight of the adhesive layer [00072]. The Applicants' specification provides no evidence that the selected weight ratio in claim 17 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the cohesion promoting properties of crospovidone, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the weight ratio. One of ordinary skill in the art would have been motivated to change the weight ratio as this could be expected to be advantageous for optimizing the cohesion of the TDDS.
Regarding claim 21, the weight percentage of solubilized drug-in-adhesive layer in the TDDS is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight percentage in order to best achieve the desired results as such would provide advantageous dosage effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005]. The Examiner considers it prima facie obvious to optimize the thickness, and therefore the weight percentage, of the drug-in-adhesive layer absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight percentage of drug-in-adhesive layer would directly affect the dose of drug present in the TDDS and therefore be an optimizable variable.
Response to Arguments
Applicant's arguments filed 5/21/2026 have been fully considered but they are not persuasive.
On page 8, Applicant argues that the Advisory Action and Final Office Action reiterate that the bioadhesives of Lakhani and the pressure sensitive adhesives of Miranda are functional equivalents without recognizing any place were the equivalency is recognized in the prior art. This is not found persuasive. In response, please refer to MPEP 2141.03(I) regarding the factors to consider when determining level of ordinary skill: "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. In the instant case, based on the teachings of Lakhani and Miranda, one of ordinary skill in the art would have recognized that both the bioadhesives of Lakhani and the pressure sensitive adhesives of Miranda may serve as the adhesive in a transdermal drug delivery system and therefore would have recognized that the adhesives are functional equivalents. Therefore, the argument is not persuasive and the rejection is maintained.
On page 9, Applicant argues that the present inventors have found that the use of a polar aprotic solvent ensures that the immunomodulatory agent is solubilized and homogenously distributed within the solubilized drug in adhesive layer. This is not found persuasive. In response to applicant's argument that the use of a polar aprotic solvent ensures that the immunomodulatory agent is solubilized and homogenously distributed within the drug in adhesive layer, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
On page 9, Applicant argues that there is no teaching or suggestion in Lakhani that would motivate a person of ordinary skill to modify Lakhani to include a solvent-borne adhesive system, particularly when Lakhani deploys water-borne polymer systems. This is not found persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have recognized that both the bioadhesives of Lakhani and the pressure sensitive adhesives of Miranda may serve as the adhesive in a transdermal drug delivery system and therefore would have recognized that the adhesives are functional equivalents. Therefore, the argument is not persuasive and the rejection is maintained.
On page 9, Applicant argues that lenalidomide would not be stable in a water-borne system of Lakhani and as such, one of skill in the art would know that the adhesives of Lakhani and Miranda are not functional equivalents given their differing impacts on the hydrolyzation of lenalidomide. This is not found persuasive. In response, please refer to MPEP 2141.03(I) regarding the factors to consider when determining level of ordinary skill: “A person of ordinary skill in the art is also a person of ordinary creativity, not an automation.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. The Examiner also respectfully directs attention to MPEP 2123 (I), which states “a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments”. Lakhani teaches that the water-based TDDS may include lenalidomide and that the TDDS may provide sustained release of the drug for 24 hours. One of ordinary skill in the art would have therefore concluded that the water-based polymer adhesive of Lakhani would not hydrolyze the lenalidomide within 24 hours and would therefore conclude that the biopolymer adhesive and Lakhani and the polyacrylate adhesive of Miranda are functional equivalents.
On page 10, Applicant argues that the TDDS of the instant invention are capable of continuous delivery of an immunomodulatory agent for much longer periods of time than those taught by Lakhani. This is not found persuasive. In response, the Examiner draws attention to MPEP 2144.05(I), which states: “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 the instant case, the TDDS of Lakhani teaches sustained delivery of the drug for up to 24 hours which overlaps with the lower limit of the claimed range of the instant claim 13. Therefore, the Examiner considers the teachings of Lakhani to read on the limitations of the instant claim 13.
Double Patenting
Applicant’s amendments to the claims filed 5/21/2026 have necessitated the new grounds of rejection.
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, 4-10, and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,201,622, in view of Lakhani (U.S. Patent Application No. 2020/0155475, publication date: 5/21/2020, of record), Miranda (U.S. Patent No. 5,656,286, issue date: 08/12/1997; of record) and Sindhu et. al. (Research Journal of Pharmacy and Technology, pg. 1809-1815, publication year: 2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘622 patent embrace a transdermal delivery system for delivery of lenalidomide. The transdermal delivery system is an occlusive formulation comprising a liquid, a semi-solid, a dispersion, a suspension, a polymer film, a transdermal patch, a drug-in-adhesive, a matrix or a combination. The Examiner interprets the various formulations embraced by the claims of the ‘622 patent to encompass the “single, double, or multi-layered structure” limitation of the instant claim 1. The transdermal patch may be a pressure sensitive adhesive patch. The claims of the ‘622 patent also embrace a penetration enhancer, a surfactant, a solvent, and a solubilizer.
The claims of the ‘622 patent teach a stabilizer but do not teach a crystallization inhibitor or the amount of drug that may be present in the adhesive layer. The claims of the ‘622 patent also do not teach a thickener or a skin modifier. The claims of the ‘622 patent also do not embrace a backing layer or release liner nor does it embrace a specific weight percentage of the drug-in-adhesive layer relative to the total weight of the TDDS. The claims of the ‘622 patent also do not teach a specific pressure sensitive adhesive or polar aprotic solvent. However, this deficiency is cured by Lakhani, Miranda, and Sindhu.
Lakhani teaches a monolithic TDDS comprising a bioadhesive polymer, a film-forming agent, a plasticizer, a naturally occurring polysaccharide, a keratolytic agent and one or more active agents [0005]. The active agent may be present from 1-60% w/w [0005]. The active agent may include lenalidomide ([0009], [0019], and [0118]). Polyvinylpyrrolidone may be present as a bioadhesive polymer and film forming agent [0099]. Lakhani defines a bioadhesive polymer to be a polymer that exhibits a pressure-sensitive character of adhesion toward highly hydrated biological surfaces such as the hydrated skin [0053]. The Examiner therefore interprets the bioadhesive polymer of Lakhani to read on the "pressure sensitive adhesive" limitation of the instant claim. The TDDS may be made by first adding a film-forming agent and a plasticizer to water and stirring. A bioadhesive polymer and polysaccharide are added and stirred until the polymer is dissolved and the viscosity is reduced. The film forming agent and a keratolytic agent are added, followed by one or more active agents and stirred to obtain a formulation [0113]. The drug is dispersed in an adhesive polymer matrix [0028]. The active ingredient is dissolved into the polymer matrix [0033]. The Examiner interprets this to mean that the drug present in the transdermal delivery system taught by Lakhani must be solubilized and homogenously dispersed in the adhesive layer. Lakhani teaches that the bioadhesive polymer of the TDDS may include hydroxypropylmethyl cellulose [0006]. The TDDS may also include methylcellulose as an emulsifying agent [0063]. Lakhani teaches that the TDDS may contain ascorbic acid and ascorbyl esters of fatty acids as antioxidants [0110] and lactic acid and salicylic acid as keratolytic agents [0006]. Miranda teaches a TDDS comprised of a pressure-sensitive adhesive, a drug in the adhesive composition and polyvinylpyrrolidone present as a crystallization inhibitor (Col. 4 lines 15-27 and Col. 36 lines 23-25). Miranda further teaches a pressure sensitive adhesive blend of an acrylic polymer and a silicone polymer. Other embodiments of the pressure sensitive adhesive taught by Miranda can include polyisobutylene (Col. 9 lines 34-54). Miranda also teaches the inclusion of DMSO, a polar aprotic solvent, as a skin permeation enhancer (Col. 33 line 27).
Furthermore, Lakhani teaches that a transdermal drug delivery device may contain a matrix, in which one or more drugs or active agents are dispersed, a backing layer, a rate-controlling membrane, and an adhesive means for affixing the system to a body surface [0091]. Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005].
The idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional crystallization inhibitors, thickeners, and skin modifiers used in TDDS. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
With regards to the “crystallization inhibitor” limitations of instant claims 1 and 5, the prior art teaches the same polyvinylpyrrolidone as claimed and therefore, the crystallization inhibitor properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
With regards to the “thickener” limitations of instant claims 6 and 7, the prior art teaches the same cellulose derivative thickeners as claimed and therefore, the thickener properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
With regards to the “skin permeation enhancer” limitations of instant claim 9, the prior art teaches the same compounds as claimed and therefore, the skin permeation enhancer properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
The weight percentage of solubilized drug-in-adhesive layer in the TDDS is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight percentage in order to best achieve the desired results as such would provide advantageous dosage effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Lakhani teaches that the monolithic layer is about 1 to 5mm in width and that the patch has a diameter between 4 and 8 cm2 [0005]. The Examiner considers it prima facie obvious to optimize the thickness, and therefore the weight percentage, of the drug-in-adhesive layer absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight percentage of drug-in-adhesive layer would directly affect the dose of drug present in the TDDS and therefore be an optimizable variable.
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (pressure sensitive adhesive of the claims of the ‘622 patent and a blend of an acrylic polymer and a silicone polymer the for the purpose of a pressure sensitive adhesive in a TDDS). See MPEP 2144.06-II.
The idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional skin permeation enhancers used in TDDS. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
Claims 13 and 16-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,201,622, in view of Lakhani (U.S. Patent Application No. 2020/0155475, publication date: 5/21/2020, of record), Tang et al. (WO2009/158120, publication date 12/30/2009; of record), and Miranda (U.S. Patent No. 5,656,286, issue date: 08/12/1997; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘622 patent embrace the relevant limitations as described in the double patenting rejection of claims 1, 5-10, and 12 above. The relevant limitations of claims 1, 5-10, and 12 are rendered obvious in view of Lakhani in the double patenting rejection of claims 1, 5-10 and 12 above. The claims of the ‘622 patent also teach that the transdermal delivery system is for continuous administration of the immunomodulatory imide for one to twenty-eight days. The claims of the ‘622 patent do not embrace solid dispersion or crosslinked polyvinyl pyrrolidone. The claims of the ‘622 patent do not embrace an acrylate copolymer, polyisobutylene, or silicone as a pressure sensitive adhesive in the drug-in-adhesive layer of the TDDS. However, this deficiency is cured by Tang and Miranda.
Tang teaches a TDDS that utilizes an acrylic adhesive [00044] and also includes a solid dispersion drug-in-adhesive comprised of a stable amorphous form of a therapeutic agent and polymeric stabilizer which is also a dispersant capable of forming hydrogen bonding with the therapeutic agent [00019]. Tang teaches that the therapeutic agent may include anti-inflammatory substances [00051-52] and that the TDDS may contain crospovidone as a cohesion-promoting agent [00071]. Tang also teaches that the solid dispersion TDDS has an improved stability and absorption rate from the skin [00019]. Tang teaches that crosslinked polyvinylpyrrolidone may be present in the TDDS as a cohesion promoting agent and that the amount of stabilizing agent present in the composition may generally be in the range of 0-15% by weight of the adhesive [00072]. Miranda teaches a TDDS comprised of a pressure-sensitive adhesive, a drug in the adhesive composition and polyvinylpyrrolidone present as a crystallization inhibitor (Col. 4 lines 15-27 and Col. 36 lines 23-25). Miranda further teaches a pressure sensitive adhesive blend of an acrylic polymer and a silicone polymer. Other embodiments of the pressure sensitive adhesive taught by Miranda can include polyisobutylene (Col. 9 lines 34-54).
It would have been prima facie obvious to one of ordinary skill in the art of filing to employ a solid dispersion of lenalidomide and crospovidone in the TDDS embraced by the claims of the ‘622 patent. One would have understood in view of Tang that a solid dispersion of an amorphous form of a therapeutic agent would render improved stability and absorption through the skin and that crospovidone present in the TDDS would help to promote cohesion. It would have been obvious to include such a solid dispersion and crospovidone in the TDDS embraced by the claims of the ‘622 patent. One of ordinary skill in the art of filing would have been motivated to include a solid dispersion of lenalidomide and crospovidone in the TDDS embraced by the claims of the ‘622 patent in order to improve cohesion, stability, and absorption through the skin. The artisan of ordinary skill would have had reasonable expectation of success because Tang teaches that a solid dispersion may be used for anti-inflammatory agents.
With regards to the “skin permeation enhancer” limitations of instant claim 13, the prior art teaches the same surfactants as claimed and therefore, the skin permeation enhancer properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
Regarding the weight ratio of immunomodulatory agent to crosslinked polyvinylpyrrolidone as specified in claim 17, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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).
Furthermore, Lakhani teaches that lenalidomide may be present from 1-60% w/w [0005]. Tang also teaches that crospovidone may be present as a cohesion promoting agent in amounts ranging from 0-15% by weight of the adhesive layer [00072]. The Applicants' specification provides no evidence that the selected weight ratio in claim 17 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to the cohesion promoting properties of crospovidone, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the weight ratio. One of ordinary skill in the art would have been motivated to change the weight ratio as this could be expected to be advantageous for optimizing the cohesion of the TDDS.
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the pressure sensitive adhesive of the claims of the ‘622 patent and a blend of an acrylic polymer and a silicone polymer the for the purpose of a pressure sensitive adhesive in a TDDS). See MPEP 2144.06-II.
Claims 1, 4-10, 12-13 and 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of copending Application No. 18/933,332, in view of PubChem (Lenalidomide, available 8/12/2020, of record) and Sindhu et. al. (Research Journal of Pharmacy and Technology, pg. 1809-1815, publication year: 2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims.
Inter alia, the claims of the ‘332 application embrace a TDDS comprising a molecular solid suspension of a drug in adhesive layer of an active pharmaceutical ingredient which may be an immunomodulatory agent with a logP value ranging from -2 to about 8. The TDDS also includes an adhesive polymer, an insoluble carrier excipient, and at least one nonionic surfactant. The insoluble carrier excipient may be a crosslinked polyvinylpyrrolidone and the adhesive polymer comprises an acrylate copolymer, a polyisobutylene polymer, and a silicone polymer. The weight ratio of the active pharmaceutical ingredients to the insoluble carrier excipient ranges from 1:0.4 to about 1:5. The non-ionic surfactant may be chosen from an ethoxylated alcohol and a poloxamer. The TDDS further comprises an occlusive backing layer forming an exterior facing-surface of the TDDS, and a release liner, wherein the release liner is positioned adjacent a skin contacting surface of the TDDS. The Examiner interprets this to mean that the TDDS of the ‘332 application is at least a single-layered structure.
The claims of the ‘332 application also teach a method of forming a molecular solid suspension of drug-in-adhesive layer in which the active pharmaceutical ingredient is solubilized in a polar aprotic solvent. The Examiner considers this to read on the “solubilized” limitation of the instant claim 1.
The claims of the ‘332 application do not embrace lenalidomide as the immunomodulatory agent, a weight percentage range of the active pharmaceutical ingredient, a weight percentage range of the crosslinked polyvinylpyrrolidone, or a weight percentage range of the drug-in-adhesive layer with respect to the weight of the TDDS. The claims of the ‘332 application also do not embrace a specific polar aprotic solvent. However, this deficiency is cured by PubChem and Sindhu. PubChem teaches that lenalidomide is an immunomodulatory agent (pg. 1 Compound Summary) with a logP of -0.4 (pg. 6 LogP). Sindhu teaches that DMF and N-methyl-2-pyrrolidone are suitable penetration enhancers for transdermal drug delivery systems (pg. 6, Classification of Chemical Penetration Enhancers).
It would have been prima facie obvious to one of ordinary skill in the art of filing to include lenalidomide as the immunomodulatory drug in the TDDS embraced by the claims of the ‘332 application. One would have understood in view of PubChem that lenalidomide is an immunomodulatory drug with a logP of -0.4. It would have been obvious to use lenalidomide as the immunomodulatory agent in the TDDS embraced by the claims of the ‘332 application. One would have understood that lenalidomide is suitable for inclusion in the TDDS because it’s logP value falls within the acceptable range embraced by the claims of the ‘322 application. The artisan of ordinary skill would have had reasonable expectation of success because the claims of the ‘322 broadly embrace immunomodulatory agents with a logP ranging from -2 to about 8. See MPEP 2144.07.
The weight percentage range of active pharmaceutical agent and crosslinked polyvinyl pyrrolidone is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight percentage in order to best achieve the desired results as such would provide advantageous dosing effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, the claims of the ‘322 application embrace crosslinked polyvinyl pyrrolidone an insoluble carrier excipient for the active pharmaceutical ingredient. The Examiner considers it prima facie obvious to optimize the weight percentage of active ingredient and carrier excipient, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight percentage of active ingredient and carrier excipient would have a direct effect on the dosage and delivery of the drug from the TDDS and therefore be an optimizable variable.
The weight percentage of solubilized drug-in-adhesive layer in the TDDS is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal weight percentage in order to best achieve the desired results as such would provide advantageous dosage effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, the claims of the ‘322 application embrace a drug contained in the adhesive layer of the TDDS. The Examiner considers it prima facie obvious to optimize amount of drug-in-adhesive layer present in a TDDS absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the weight percentage of drug-in-adhesive layer would directly affect the dose of drug present in the TDDS and therefore be an optimizable variable.
With regards to the “pressure-sensitive adhesive” limitations of instant claims 13 and 15, the prior art teaches the same adhesives as claimed and therefore, the pressure-sensitive properties are necessarily present; the Examiner directs attention to MPEP 2112.01 (II) which states: “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.”
It would have been prima facie obvious to one of ordinary skill in the art of filing to include DMF or NMP as the polar aprotic solvent embraced by the claims of the ‘322 application. One would have understood in view of Sindhu that DMF and NMP are polar aprotic solvents suitable for inclusion in pharmaceutical formulations as a penetration enhancer. The artisan of ordinary skill would have had reasonable expectation of success because the claims of the ‘322 application broadly embrace polar aprotic solvents without limitation. See MPEP 2144.07.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 5/21/2026 have been fully considered but they are not persuasive.
Applicants’ request for the double patenting rejection of record to be held in abeyance is acknowledged. However, this request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Accordingly, the rejection will be maintained until a terminal disclaimer is filed or claims are amended to obviate the rejection.
Conclusion
No claims are allowed.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
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