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 .
Status of Claims
The amendments and arguments filed on 12/16/2025 are acknowledged and have been fully considered. Claims 1 has been amended. Claims 14-20,27, and 37 have been withdrawn. Claims 4,8-10, 21-26, 28-36, and 38-46 have been canceled. Applicants’ amendments are supported by the originally filed disclosure.
No new matter has been added.
Thus, claims 1-3,5-7,11-13 and 47-54 will be examined on the merits herein.
Rejections Maintained and Made Again in view of Applicant’s Amendments
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 1-3,5-7,11-13, 50 and 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (ACS Nano 2018; as submitted on IDS of 01/31/2024) in view of BAEK (US 20170189660).
The instantly claimed invention is directed to composition comprising: (a) a biocompatible polymeric network comprising a crosslinked hydrophilic polymer, wherein said crosslinked hydrophilic polymer comprises a hydrophilic polymer crosslinked via a plurality of reactive oxygen species (ROS)-responsive linkages; and (b) an antibiotic or antibiotic-loaded carrier embedded in the biocompatible polymeric network.
Regarding instant claims 1,5-6, 11 and 52, Wang et al disclose a core−shell microneedle (MN) array patch, consisting of degradable cross-linked poly(vinylalcohol) (PVA) (page 2467). The shell component is designed to mimic the complementary function in peroxisome where catalase nanogel (CAT-NG) is formed and embedded inside a cross-linked PVA layer covering the surface of PVA-TSPBA MN core. Collectively, the design of the core and shell components offers: (1) sufficient catalysis with GOx to perform the glucose-responsive action in the core and (2) efficient elimination of H2O2 to alleviate inflammation affecting the surrounding tissues and mitigate systemic toxicity (page 2467). As depicted below Wang teaches TSPBA was synthesized using quaternization reaction of N1,N1,N3,N3-tetramethylpropane-1,3-diamine in the presence of excess 4-(bromomethyl)phenylboronic acid (page 2467). Wang discloses core–shell microneedle (MN) array patch consisting of degradable cross-linked poly (vinyl alcohol) (PVA) gel for self-regulated insulin delivery with rapid responsiveness to elevated BGLs (page 2467). Wang discloses insulin and the microneedle array is a platform for transdermal drug delivery. Wang teaches bioresponsive core−shell MN array patch offers a platform technique for transdermal drug delivery in a physiological factor-controlled manner (sustained release) and enhanced biocompatibility (page 2471, Conclusion).
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Regarding instant claims 11 and 54, Instant specification disclose " the crosslinked hydrophilic polymeric network is prepared by crosslinking PVA or a copolymer thereof with N-(4-bromobenzyl)-N3-(4-bromophenyl)-N1, N1, N3, N3, -tetramethylpropane-1,3-diaminium (TSPBA) in the presence of the antibiotic (page9, lines 20-23). In some embodiments, the crosslinking is performed by mixing the PVA with the TSPBA in a molar ratio of between about 20:1 to about 1:5, optionally about 3:1(page 9, lines 23-25" … and the “Synthesis of ROS-Responsive Crosslinker 4-(Bromomethyl) phenylboronic acid (1 g, 4.6 mmol) and N, N, N′, N′-tetramethyl-1,3-propanediamine (0.2 g, 1.5 mmol) were dissolved in dimethylformamide (DMF; 40 mL) and the solution was stirred at 60° C. for 24 h (example 1 page 43-44). Afterward, the mixture was poured into tetrahydrofuran (THF, 100 mL), filtrated, and washed with THF (3×20 mL). After drying under vacuum overnight, pure TSPBA (0.6 g, yield 70%) was obtained " (example 1 page 43-44). Wang discloses "Synthesis of TSPBA. 4-(Bromomethyl) phenylboronic acid (1 g, 4.6 mmol) and N, N, N’, N’-tetramethyl-1,3-propanediamine (0.2 g, 1.5 mmol) mixed in DMF (40 mL) was stirred at 60 o C for 24 h. Then, the clear solution was precipitated in THF (100 mL) and filtrated, and the white solid was further washed with THF (3×20 mL). After placed under vacuum overnight, pure TSPBA (0.6 g, yield 70%) " (methods, page2). Therefore, it would yield the same ratio as in instant claim.
However, it a does not expressly disclose that antibiotics are used/loaded. BAEK et al remedy this deficiency.
BAEK discloses a microneedle, the microneedle including a needle body portion formed using a water-soluble material; an active ingredient coating portion configured to coat the surface of the needle body portion, and including an active ingredient transferred to the biological tissue (Abstract). BAEK teaches the needle body portion may include at least one of a viscous material and the active ingredient transferred to the biological tissue ([0018]; claim 2).
Regarding instant claims 1-2 and 50, BAEK discloses the needle body portion may be formed using biodegradable polymer resin ([0020]; claim 4). BAEK discloses that the needle body portion may include at least one of a viscous material and the active ingredient transferred to the biological tissue ([0018]; claim 2). The viscous material included in the needle body portion may include at least one of carboxymethyl cellulose (CMC), hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate), chitosan, polylysine, collagen, gelatin... ethylcellulose (EC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, cyclodextrin, copolymer of monomers constituting the polymer, and cellulose ([0019]; claim 3). BAEK teaches an active ingredient coating portion configured to coat the surface of the needle body portion ([0017]; claims). The active ingredient included in the needle body portion and the active ingredient coating portion may include insulin, tetracycline, oxytetracycline, doxycycline, minocycline ([0023], [0071]; claim 8).
Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the composition as described by Wang et al with the composition of BAEK. One would be motivated to do so with a reasonable expectation of success in simple substitution of one known element for another to obtain predictable results. In the instant case to increase penetration of antibiotic.
Regarding instant claims 7, Wang et al disclose PVA (89-98KDa, 99% hydrolysis) (Materials, page 3).
Regarding instant claims 3, 13, and 53, BAEK discloses that the active ingredient included in the needle body portion and the active ingredient coating portion may include at least one of α-interferon, β-interferon for multiple sclerosis (MS), erythropoietin, follitropin β, follitropin α, G-CSF, GM-CSF, human chorionic gonadotropin, luteinizing hormone, salmon calcitonin, glucagon, GNRH antagonist, insulin (a non-antibiotic therapeutic agents) , vitamin and vitamin derivatives (wound-healing agents. ([0023]; claim 8).
Regarding instant claim 12, BAEK teaches active ingredient may be within the range of 9:1 to 1:9, desirably, within the range of 1:1 to 1:2 ([0079]). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Therefore, instant claims are prima facie obvious over the combination above with the addition of a known transport device (microneedle), art-recognized within the field of use, for standard use of treating/preventing acne. Thus, the claimed invention is prima facie obvious over the combination above.
Claims 1-3,5-7,11-13, 47-50 and 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (ACS Nano 2018; as submitted on IDS of 01/31/2024) in view of BAEK (US 20170189660) as applied to claims 1-3,5-7,11-13, 50 and 52-54 above, and further in view of Yu et al (US 20090068255 A1).
The teachings of Wang et al and BAEK have been set forth above. However, they do not expressly disclose including an absorbent additive or the specific type of non-antibiotic therapeutic agent. Yu et al remedies this deficiency.
Regarding instant claims 47-49, Yu discloses application of matrix metalloproteinase (MMP) inhibitors to the skin inhibits the degradation of proteins found in the skin including collagen, elastin, and other basement membrane and extracellular matrix protein (see entire document, for instance, abstract). Yu teaches, the inventive MMP inhibitor compositions may also be applied to the skin to treat or prevent a skin disease (e.g., proliferative disease, inflammatory disease (such as Acne)) (see entire document, for instance, abstract). Yu teaches the MMP inhibitors may be administered using techniques specifically designed to deliver pharmaceutical agents to the skin, for example, microneedle systems ([0012]). Yu teaches polyvinyl alcohol ([0112], [0126]- [0128]). Yu discloses absorbents such as diatomaceous earth ([0138]). Yu teaches cosmetic composition may in addition to an MMP inhibitor also include another active ingredient such as a vitamin, anti-inflammatory agent, retinoid, anti-oxidant (see entire document, for instance, [0085], claim 10).
It would have been obvious to utilize an absorbent additive such as diatomaceous earth and a non-antibiotic therapeutic agent such as retinoid as taught in Yu in the composition of Wang et al and BAEK. One would have been motivated to do so since Yu teaches that application of matrix metalloproteinase (MMP) inhibitors to the skin inhibit the degradation of proteins found in the skin including collagen, elastin, and other basement membrane and extracellular matrix protein and MMP inhibitors may be administered using microneedle systems. There would be a reasonable expectation of success since Yu et al and Wang et al and BAEK are all drawn to compositions for microneedles and methods of treating acne or other inflammatory/infectious skin diseases. One would be motivated to do so with a reasonable expectation of success in use of known techniques to improve similar devices (methods or products).
Claims 1-3,5-7,11-13, 50- 54 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (ACS Nano 2018; as submitted on IDS of 01/31/2024) in view of BAEK (US 20170189660) as applied to claims 1-3,5-7,11-13, 50 and 52-54 above, and further in view of Muller et al (US 20080268514 A1).
The teachings of Wang et al and BAEK have been set forth above. Wang et al disclose PVA (89-98KDa, 99% hydrolysis) (Materials, page 3). However, they do not expressly disclose the hydrophilic polymer is PVA with a Mw of about 72 kDa. Muller et al remedies this deficiency.
Regarding instant claim 50, Muller discloses polyvinyl alcohol (PVA), a dissolvable matrix material. PVA may be obtained from a variety of commercial sources and is available in specific discrete molecular weights or, alternatively, as a polydisperse preparation of polymers within several prescribed molecular weight ranges based on variable degrees of polymerization ([0078]). For example, the Mowiol.RTM. series of PVA products may be obtained from Fluka in approximate molecular weight ranges of 16, 27, 31, 47, 55, 61, 67, 130, 145, or 195 kDa, and other PVA products are known, such as the preparation having average molecular weight of 30-70 kDa (Sigma No. P 8136) as used in the accompanying Examples. Based on the present disclosure, the skilled person will appreciate that, depending on the physicochemical properties (e.g., molecular mass, hydrophobicity, surface charge distribution, solubility, etc.) of a particular biomolecule of interest that is present in a biological sample to be stored under liquid conditions as described herein, these or other PVA products, or other suitable matrix materials that dissolve or dissociate in a solvent, can be identified readily and without undue experimentation, for use according to the present compositions and methods ([0078]).
Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the composition as described by Wang et al and BAEK with the composition of Muller et al. One would be motivated to incorporate the hydrophilic polymer (PVA) with a Mw of about 72 kDa as taught by Muller et al into the composition of Wang et al and BAEK with a reasonable expectation of success since Muller teaches particular advantages to the use of PVA with a similar molecular weight to the molecular weight instantly claimed. It is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered but they are not persuasive. Applicants argue, “the superior effect of the RR- MN is believed to be related to the sustained release provided by the ROS- responsive material”. It is noted that the Wang teaches utilizing bioresponsive core−shell MN array patch for transdermal drug delivery in a physiological factor-controlled manner (sustained release) and enhanced biocompatibility (page 2471, Conclusion). The burden is shifted to the applicant to set forth their claimed invention and the process that rendered their product not obvious over the prior art.
In response to applicant's argument that "ROS generation in the context of treating acne is very different than the ROS generated in using the composition of Wang as part of glucose-sensitive insulin delivery", a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Therefore, the rejection is maintained.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., release rate of an antibiotic from microneedles) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicants argue, "that Wang and Baek, Yu, and Muller, alone or in combination, do not teach or suggest each and every element of claim 1. "
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, Wang et al disclose a core−shell microneedle (MN) array patch, consisting of degradable cross-linked poly(vinylalcohol) (PVA) (page 2467). The shell component is designed to mimic the complementary function in peroxisome where catalase nanogel (CAT-NG) is formed and embedded inside a cross-linked PVA layer covering the surface of PVA-TSPBA MN core. Wang teaches bioresponsive core−shell MN array patch offers a platform technique for transdermal drug delivery in a physiological factor-controlled manner (sustained release) and enhanced biocompatibility (page 2471, Conclusion). However, it a does not expressly disclose that antibiotics are used/loaded. BAEK in the similar art of microneedle, teaches an active ingredient coating portion configured to coat the surface of the needle body portion ([0017]; claims). The active ingredient included in the needle body portion and the active ingredient coating portion may include insulin, tetracycline, oxytetracycline, doxycycline, minocycline ([0023], [0071]; claim 8). Thus, a skilled artisan would have a reasonable expectation of success in simple substitution of one known element for another to obtain predictable results. In the instant case to increase penetration of antibiotic.
Thus, absent of a clear showing of criticality, prior art is considered to teach and suggest the instantly recited composition.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET JOSEPH whose telephone number is (571)270-1372. The examiner can normally be reached Monday and Thursday 0730-1730 Eastern.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham, can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET JOSEPH/Patent Examiner, Art Unit 1611
/TREVOR LOVE/Primary Examiner, Art Unit 1611