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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/15/2025 has been entered.
Status of Application
Applicants' arguments/remarks filed 10/15/2025 are acknowledged. Claims 1 and 8 are amended. Claim 2 is canceled. Claims 9-10 are newly added. Claims 1-10 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicant’s amendment filed 10/15/2025 and with respect to applicant’s arguments/ remarks
the rejection of Claim 2, under 35 U.S.C. 103 over Grunsteiner et al. and Ogino et al. is withdrawn due to the cancelation of the claim.
the rejection of Claims 1-8, under 35 U.S.C. 103 as being unpatentable over Grunsteiner et al. and Ogino et al. is withdrawn due to the amendment of the claims.
Modified Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 5-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grunsteiner et al. (WO 2012/084969 Al).
Claims 1 and 9,
Grunsteiner et al. teach
The transdermal therapeutic system (TTS) comprising the adhesive composition, containing rotigotine (Title). Transdermal delivery systems (TTS), such as transdermal patches (pg. 1, lines 22-23) which has a high adhesive strength against patient's skin and maintains the stable active ingredient. (pg. 3, lines 22-25), rotigotine or a pharmaceutically acceptable salt thereof (pg. 4, line 26) and optionally, a backing layer, (pg. 4, line 33).
An adhesive composition for a TTS comprising a styrenic polymer and/or polyisobutylene, rotigotine or a pharmaceutically acceptable salt thereof, and at least one specific vinyl pyrrolidone (co)polymer. (pg. 4, lines 8-11). The adhesive composition containing a pressure sensitive adhesive (PSA) selected from the group consisting of a styrenic polymer, rotigotine or a pharmaceutically acceptable salt thereof as the active ingredient, and at least one crosslinked polyvinylpyrrolidone (Abs).
The term "rotigotine" in the context of the present invention comprises rotigotine and analogues thereof such as a pharmaceutically acceptable rotigotine salt or rotigotine in its basic form (pg. 7, line 1-4). Rotigotine can be contained in the drug containing adhesive composition of the present invention in an amount of 1 to 30 % by weight, preferably in an amount of 5 to 20 % by weight, more preferably in an amount of 7 to 15 % by weight, based on the total weight of the adhesive composition. (pg. 7, lines 15-18).
The pressure sensitive adhesive (PSA) contained in the composition of the present invention is selected from the group consisting of a styrenic polymer, a polyisobutylene, or any kind of mixtures thereof. (pg. 7, lines 26-28). The amount of PSA in the adhesive composition preferably ranges from 40 to 98 % by weight, more preferably from 50 to 90 % by weight, even more preferably from 55 to 86 % by weight, most preferably from 60 to 86 % by weight, based upon the total weight of the composition. (pg. 8, lines 4-7).
In a preferred embodiment of the invention the styrenic copolymer is an A-B-A triblock
copolymer. More preferably, the A-B-A copolymer comprises at least one styrenic polymer (pg. 8, lines 33-34), block A, preferably polystyrene, and at least one polymer block B obtained from monomers isoprene. (pg. 9, lines 1-2). The styrenic polymer adhesive preferably comprises a tackifier. (pg. 11, line 15).
The crosslinked polyvinyl pyrrolidone is preferably present in the polyisobutylene containing adhesive composition of the invention in an amount of 1 to 30 % by weight, preferably from 1 to 30 % by weight, based upon the total weight of the adhesive composition (pg. 33, lines 10-17).
The drug containing adhesive composition may further comprise one or more tackifiers. Such tackifiers increase the adhesiveness of the adhesive layer. Tackifiers which may be used in the drug containing adhesive composition according to the present invention include but are not limited to any compatible resins or mixtures thereof. (pg. 17, lines 10-16), such as: alicyclic petroleum hydrocarbon resins; such as styrene resins (pg. 17, lines 30-33). The one or more tackifier(s) are preferably contained in the drug containing adhesive composition in an amount of 10 to 70 % by weight, preferably 25 to 65 % by weight, more preferably 40 to 55 % by weight, based upon the total weight of the drug containing adhesive composition, (pg. 18, lines 13-16).
Durotak® 87-608A (PSA) (Example 3, pg. 29) and Styrenic rubber (PSA) (Example 4, and 5, pg. 30, and 31): these pressure sensitive adhesive compositions without drug(s) and cross-linked polyvinylryrrolidone in the adhesive layer, comprise 20-50% Block copolymer, 40-60% Tackifer, 10-30% Plasticizer (oil) and Antioxidant <1%). (slide 10, Choi, Drug Delivery Polymers, Henkel Corporation, (https://20039547.s21i.faiusr.com/61/ABUIABA9GAAg3LGg6wUoz4eHrgE.pdf).
Styrenic rubber (PSA) Example 4 (pg. 30) and Example 5 (pg. 31) comprise 61-86% of total adhesive layers when Rotigotine (9%) and cross-linked polyvinylryrrolidone (30% Example 4, 5% in Example 5). Percentages of Styrenic polymer are readjusted and recalculated when including Rotigotine (9%) and cross-linked polyvinylryrrolidone are 17-43%, which are overlapping with the applicant’s limitation of the Styrenic rubber (PSA) 5-30%.
The drug containing adhesive composition may further comprise one or more of a liquid diluent. The liquid diluent may have the function of a plasticizer for reducing the glass transition temperature (T g) of the adhesive polymers in particular of the mid-block polymer (B-block), if present. (pg. 16, lines 8-11). The liquid diluent is generally contained in the adhesive composition in an amount of less than 60 wt.%, preferably 15 to 50 % by weight, based on the total amount of the drug containing adhesive composition. (pg. 17, lines 4-6).
With regard to claim 3,
Grunsteiner et al. teach with the rotigotine stabilization method applied to claim 1, the term "rotigotine" m the context of the present invention comprises rotigotine and analogues thereof such as a pharmaceutically acceptable rotigotine salt or rotigotine in its basic form (pg. 7, line 1-4). In the Example 2, the content of the rotigotine and/or the pharmaceutically acceptable salt thereof in terms of rotigotine free form: the content of the cross-linked polyvinylpyrrolidone or crospovidone) are 9: 0, 15 and 25 by weight (pg. 29) or in the Example 5, 9:5 (pg. 31)
With regard to claim 5,
Grunsteiner et al. teach with the rotigotine stabilization method applied to claim 1, further incorporating an imidazole-based antioxidant in the adhesive agent layer applied to claim 4, and one or more antioxidants in an amount of from 0.001 to 2% by weight based upon the total weight of the adhesive composition (pg. 35, line 16-17).
With regard to claim 6,
Grunsteiner et al. teach the adhesive layer comprise solvent (pg. 5, line 16). Suitable solvents include, but are not limited to, organic solvents such as ethanol, 2-propanol, isopropyl alcohol, methanol, (pg. 25, lines 24-25), which are aliphatic alcohols.
With regard to claim 7,
Grunsteiner et al. teach with the rotigotine stabilization method applied to claim 1, tackifiers which may be used in the drug containing adhesive composition include but are not limited to any compatible resins or mixtures thereof such (pg. 17, lines 10-14): as polyterpene resins (pg. 17, line 21) or the hydrogenated polyterpene resins; phenolic modified terpene resins and hydrogenated derivatives thereof. (pg. 17, lines 25-26).
With regard to claim 8,
Grunsteiner et al. teach the pressure sensitive adhesive (PSA) contained in the composition of the present invention is selected from the group consisting of a styrenic polymer, a polyisobutylene, or any kind of mixtures thereof. (pg. 7, line 26-28). Other than the styrene-based thermoplastic elastomer, another high molecular weight polymer such as polyisobutylene and/or polyisoprene, the high molecular weight polymer may be used in amounts of 1 to 15 wt.%, preferably 2 to 10 wt.% based on the total weight of the drug containing adhesive composition. (pg. 11, lines 6-9).
With regard to claim 9,
Grunsteiner et al. teach the drug containing adhesive composition may further comprise one or more of a liquid diluent. The liquid diluent may have the function of a plasticizer for reducing the glass transition temperature (T g) of the adhesive polymers in particular of the mid-block polymer (B-block), if present. (pg. 16, lines 8-11). The liquid diluent is generally contained in the adhesive composition in an amount of less than 60 wt.%, preferably 15 to 50 % by weight, based on the total amount of the drug containing adhesive composition. (pg. 17, lines 4-6). The liquid diluent is an oil component such as mineral oil, preferably paraffinic mineral oil, naphthenic mineral oil, aromatic mineral oil, synthetic liquid oligomers of polybutene, polypropene and polyterpene, isoparaffin oil, paraffin oil, or mixtures thereof. Most preferably, the liquid diluent is white petroleum mineral oil. (pg. 16, lines 15-18).
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 non-obviousness.
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Grunsteiner et al. (WO 2012/084969 Al), as described in claim 1 above, in view of Ahmad et al. (Ahmad, Synthesis, spectroscopic, computational (DFT/B3L YP), AChE inhibition and antioxidant studies of imidazole derivative, Journal of Molecular Structure 1151 (2018) 327e342).
The teachings of Grunsteiner et al. are described in claim 1 above.
Grunsteiner et al. teach with the rotigotine stabilization method applied to claim 1, the adhesive composition may further comprise optional components (additives/excipients) antioxidants. (pg. 14, line 26-28).
Grunsteiner et al. do not teach antioxidants imidazole.
Ahmad et al. teach imidazole derivatives are antioxidants. (Title).
It would have been obvious to one of ordinary skill in the art before effective filing date of the invention to add one of imidazole derivative as an antioxidant since Ahmad et al. have proven that it is one.
Claims 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Grunsteiner et al. (WO 2012/084969 Al), as described in claim 1 above.
The teachings of Grunsteiner et al. are described in claim 1 above.
Grunsteiner et al. teach the stability of rotigostine in long-term storage at various temperatures and humidities.
60°C for 2 weeks is generally a more aggressive accelerated stability test than 40°C for 2 months and is often used to predict a shorter shelf life. The specific equivalence depends on the product's activation energy, which describes how sensitive its degradation rate is to temperature.
60°C for 2 weeks provides Faster results: Provides a quicker indication of potential issues.
Higher-stress test: Provides a more aggressive challenge to the product and packaging.
Regulatory acceptance: Often a standard condition for accelerated testing, especially when used with other data.
Potential for different degradation pathways: Very high temperatures may trigger different chemical or physical changes that would not occur in normal storage conditions.
Less conservative prediction: If the degradation pathway is different, the shelf-life prediction could be inaccurate.
40°C for 2 months is More conservative: Conditions are less extreme, so they are more likely to represent the degradation pathway that occurs in real-time.
Better for extrapolation: The lower temperature is closer to ambient storage, which can make predictions more reliable.
Better for temperature-sensitive products: Avoids creating unrealistic conditions that can occur at very high temperatures, such as glass transition or protein unfolding.
Takes more time: The longer duration delays obtaining initial stability data.
Use 60°C for 2 weeks for a quick, aggressive stress test to identify major stability problems early in development.
Use 40°C for 2 months for a more reliable prediction of long-term stability, especially if the product is sensitive to very high temperatures.
Grunsteiner et al. teach the stability was determined by visual inspection based on the amount of rotigotine crystals in the matrix of the TTS after different storage times and temperatures 40°C for 2 and 4 months. (pg. 28, line 25-26). The results are that no rotigotine crystals in the matrix is found in different storage conditions in the table below (pg. 29).
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It would have been obvious to one of ordinary skills in the art before the effective filing date of the invention to know the stability of rotigotine and/or a pharmaceutically acceptable salt thereof in a rotigotine-containing patch since Grunsteiner et al. has proven it is, especially in longer time for up to 4 months.
Response to Arguments
Regarding 35 USC 103 rejection
Applicants argue that in all points 1-2, and 4-6 about "better adhesion" at less than 30% styrenic copolymer, the strong adhesion observed in Applicant's data, Applicant's probe tack values with the peel force values reported in Grunsteiner, specify the content of rotigotine (5-15% by mass), and Applicant concurrently submits a Declaration under 37 C.F.R. § 1.132 executed by Mr. Takao Kurokawa.
All Applicant's arguments have been fully considered and they are not persuasive since Grunsteiner teaches the styrenic copolymer is an A-B-A triblock copolymer. More preferably, the A-B-A copolymer comprises at least one styrenic polymer, (pg. 8, lines 33-34), block A, preferably polystyrene, and at least one polymer block B obtained from monomers isoprene. (pg. 9, lines 1-2). The content of the styrene-based thermoplastic elastomer is 17-43% by mass in the adhesive agent layer. Thus, applicant’s limitations are the same with what Grunsteiner teaches, so there are no different advantages between applicant’s claims and prior arts’ teachings. Please see the details of the rejection of claim 1 above.
Applicants argue that Applicant's stability data-measured at 60 °C for 2 weeks-are not comparable to Grunsteiner' s long-term storage data at various temperatures and humidities.
Applicant's arguments have been fully considered and they are not persuasive. Please see the details of the rejection of claim 10 above. Especially, the stability test was carried out at 40°C for longer times up to 4 months, while the higher temperature for a short time are usually for quicker results, but the stability for longer time is proving product stability.
Conclusion
No claim is allowed.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615