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 .
Status of the Claims
Claims 12-13, and 15 have been cancelled.
Claims 11, 14, and 16-22 are pending and currently under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received and placed in the file.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS) filed on 10/31/2024 is attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 14, and 16-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the microneedle" in lines 4 and 11. There is insufficient antecedent basis for this limitation in the claim.
Claim 19-21 recites “a middle end portion”. This language is indefinite because it is unclear what middle end means, as it can be the middle of the microneedle or the end of the microneedle or the portion the closer to the end of the microneedle.
Claims depending from rejected claims have also been rejected because they incorporate
all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness
concerns outlined above.
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 11, 14, 16-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US20180161252A1, Published 06/14/2016) in view of Zhuang et al. (CN110897996A, Published 03/24/2020).
Applicant’s Invention
The claims are drawn to a local anesthesia patch comprising:(i) a2 wherein the amide-based local anesthetic is one or more selected from the group consisting of lidocaine, mepivacaine, prilocaine, articaine, bupivacaine, etidocaine, and salts thereof, wherein the amide-based local anesthetic, the hyaluronic acid, and the polyvinylpyrrolidone are included at a weight ratio ranging from 1:1.5:0.05 to 1:2.5:0.3, wherein the support layer has a thickness ranging from 150 to 500 m wherein the microneedle has a height ranging from 500 to 1,000 um, wherein the support layer is a polymer film and is: (i) a plastic sheet or film selected from the group consisting of polyethylene, polyurethane, polyvinyl alcohol, polypropylene, polyethylene terephthalate, polystyrene (GPPS), polylactide, polyglycolide, polycaprolactone, polyethylene glycol, polyanhydride, polyamide, polyesteramide, polyorthoester, polydioxanone, polyacetal, polyketal, polycarbonate, polyorthocarbonate, polyphosphazene, polyhydroxybutyrate, polyhydroxyvalerate, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acid), poly(methylvinyl ether), chitin, chitosan and its copolymer, terpolymer, carboxymethylcellulose, hyaluronic acid, polyvinylpyrrolidone, and an ethylene vinyl acetate (EVA) copolymer;(ii) a paper sheet selected from the group consisting of sterilization paper, cellophane, non-woven fabric, and woven fabric;(iii) a silicone resin thin film formed by spraying or spreading; or (iv) a fluorine oil thin film formed by spraying or spreading.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 11, Francis teaches a microneedle device suitable for application to the skin and methods for using the same, wherein the microneedles also may be used to deliver active ingredients to the skin (abstract). Francis also teaches that the active ingredients include local anesthetics, and anesthetics such as lidocaine (i.e., amide-based local anesthetic)(paragraph [0058]). Francis further teaches the devices generally provide an array of dissolvable microneedles which deliver polymeric compositions beneath the skin surface (paragraph [0027]). Francis continues to teaches microneedles may be formed from any suitable biocompatible and biodegradable polymer such as hyaluronic acid and polyvinylpyrrolidone and mixtures thereof (paragraph [0037]). Francis also teaches polymer carriers which have compatibility with the active ingredient such as hyaluronic acid and polyvinylpyrrolidone (paragraph [0058]). Francis further teaches the intermediate substrate layer (i.e., support layer) is adapted to support the microneedles and provide sufficient structural rigidity, in combination with backing layer, wherein substantially all of the intermediate substrate layer 200 is formed from a water-soluble polymer or mixtures thereof (paragraph [0042]), wherein suitable water-soluble polymers include, for example pullulan, PVP (i.e., polyvinylpyrrolidone), PGA (i.e., polyglycolide), PLGA, PLA (i.e., polylactide) (paragraph [0044]). Francis continues to teach the intermediate layer may have any suitable thickness, depending upon the structural properties of the polymer used and those of the backing layer 300 to which the intermediate substrate layer 200 is attached. Conveniently, the thickness of the intermediate substrate layer is about 5-30 mils (i.e., 127μm – 762μm)(paragraph [0043]). Francis also teaches by “microneedles” is meant a plurality of protrusions and have a height (h), 100μm-1,500μm (paragraph [0018]).
Regarding claim 17, Francis teaches the microneedle device may be applied to the skin on any part of the body for which treatment is desired including, for example, the face (cheeks, forehead, and/or periorbital region) neck, dëcolletage, back of hands, armpits, arms, and legs (paragraph [0027]). The examiner points out that the limitation wherein the local anesthesia patch is for local anesthesia for treating dental or dermatological diseases does not limit the anesthesia patch and is an intended use of the patch.
Regarding claim 18, Francis teaches the individual microneedles may have any appropriate shape and dimension. For example, the microneedles may be shaped as pyramids, prongs, diamonds, and cones (i.e. conical) (paragraph [0033]).
Regarding claims 19-20, Francis teaches as illustrated in FIG. 3, the microneedle is characterized by an upper body portion (i.e., sharp end portion) and a lower body portion (i.e., middle end portion) that may or may not be symmetrical. The base (i.e., support portion) may be the intermediate substrate layer, as illustrated in FIG. 3, or a contiguous substrate layer joining the microneedles in the base region which is itself affixed to the intermediate substrate layer.
Regarding claim 22, Francis teaches the microneedle device may be applied to the skin on any part of the body for which treatment is desired including, for example, the face (cheeks, forehead, and/or periorbital region) neck, dëcolletage, back of hands, armpits, arms, and legs (paragraph [0027]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Francis does not teach wherein the local anesthesia patch comprises the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone weight ratio ranging from 1:1.5:0.05 to 1:2.5:0.3 (instant claim 11); lidocaine in an amount of 1mg to 5mg (instant claim 14); and the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone are included 32wt%, 63wt%, and 5wt% respectively (instant claim 16). However these deficiencies are cured by Zhuang et al.
In the analogous art of drug administration using microneedles, Zhuang teaches the present invention provides a method for preparing polymer microneedles that not only saves the cycle time, guarantees the molding rate, but is also simple and easy to operate, and does not affect the drug loading. A single material will make the microneedle strength insufficient or easy to break, so the polymer is selected to prepare the microneedle array, and the preparation cycle is reduced by changing the preparation method. PVA has high strength, high bio-solubility, and good water-containing effect of HA. The advantages of these two materials are combined to achieve better results. Using separate drying and re-bonding preparation methods not only reduces the preparation cycle, but also improves the microneedle forming effect. Mix HA, PVP, PVA and lidocaine in proportion to obtain microneedle mixture. A small amount of methine blue was added to observe the drug distribution in the microneedles (paragraph 6). Zhuang also teaches the preparation method of the above-mentioned soluble lidocaine polymer microneedles: 1) Mix HA solution, PVA solution, lidocaine solution, PVP solution and methine blue in a ratio of 1: 1: 4: 1: 1 to obtain a mixture solution (paragraph 12), wherein the configured solutions are: 10% PVA aqueous solution, 5% HA aqueous solution, 10% lidocaine ethanol solution and 5% PVP ethanol solution and the HA solution, the PVA solution, the lidocaine solution and the PVP solution are mixed at a ratio of 1: 1: 4: 1 to obtain a mixed solution (paragraphs 31-32).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to optimize the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone weight ratio ranging from 1:1.5:0.05 to 1:2.5:0.3, lidocaine in an amount of 1mg to 5mg, and the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone at 32wt%, 63wt%, and 5wt% respectively in Francis’ microneedle. Francis teaches the active ingredients include local anesthetics, and anesthetics such as lidocaine (i.e., amide-based local anesthetic)(paragraph [0058]). Francis continues to teaches microneedles may be formed from any suitable biocompatible and biodegradable polymer such as hyaluronic acid and polyvinylpyrrolidone and mixtures thereof (paragraph [0037]). One would have understood in view of Zhuang the preparation method of the above-mentioned soluble lidocaine polymer microneedles: 1) Mix HA solution, PVA solution, lidocaine solution, PVP solution and methine blue in a ratio of 1: 1: 4: 1: 1 to obtain a mixture solution (paragraph 12), wherein the configured solutions are: 10% PVA aqueous solution, 5% HA aqueous solution, 10% lidocaine ethanol solution and 5% PVP ethanol solution and the HA solution, the PVA solution, the lidocaine solution and the PVP solution are mixed at a ratio of 1: 1: 4: 1 to obtain a mixed solution (paragraphs 31-32). Therefore it would have been obvious to optimize the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone weight ratio ranging from 1:1.5:0.05 to 1:2.5:0.3, lidocaine in an amount of 1mg to 5mg, and the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone at 32wt%, 63wt%, and 5wt% respectively in Francis’ microneedle because Zhuang teaches making soluble lidocaine polymer microneedles ) Mix HA solution, PVA solution, lidocaine solution, PVP solution and methine blue in a ratio of 1: 1: 4: 1: 1 to obtain a mixture solution (paragraph 12), wherein the configured solutions are: 10% PVA aqueous solution, 5% HA aqueous solution, 10% lidocaine ethanol solution and 5% PVP ethanol solution and the HA solution, the PVA solution, which one of ordinary skill can use as a starting point using routine experimentation to optimize the amounts of the amide based local anesthetic, hyaluronic acid and the polyvinylpyrrolidone for desired 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 addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
With regards to the limitation wherein the amide-based local anesthetic, the hyaluronic acid and the polyvinylpyrrolidone are included in the middle end portion and constitute an entire layer of the middle end portion, it would have been obvious to one of ordinary skill in the art to have the ingredients present in the middle end portion of Francis’ microneedles. One would have understood that Francis teaches an aqueous polymeric solution is then prepared and placed into the mold, preferably as a viscous gel. The filled mold is then centrifuged under conditions that promote filling of the microneedle mold cavities. The filled mold is then dried. Optionally, the mold may be partially filled several times with the same or different polymeric solutions to allow for customization of the microneedles over their length and/or for the incorporation of active ingredients in specific portions/layers of the microneedles (paragraph [0054]), wherein microneedles may be formed from any suitable biocompatible and biodegradable polymer such as hyaluronic acid and polyvinylpyrrolidone and mixtures thereof (paragraph [0037]). It would have been obvious to one of ordinary skill to have the ingredients present in the middle end portion of Francis’ microneedle because Francis teaches that the microneedles can be made from hyaluronic acid and polyvinylpyrrolidone which are soluble polymers, wherein the active ingredients can be incorporated in specific portions/layers of the microneedles which reads to hyaluronic acid, polyvinylpyrrolidone, and amide-based local anesthetic being present in the middle end portion of the microneedle.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US20180161252A1, Published 06/14/2016) in view of Zhuang et al. (CN110897996A, Published 03/24/2020) as applied to claims 11, 14, 16-20, and 22 above, and further in view of Jung et al. (WO2022003653A1, Published 01/06/2026).
Applicant’s Invention
Francis renders obvious all the limitations of instant claim 11. Applicant’s claim 21 further adds the limitation wherein the amide-based local anesthetic, the hyaluronic acid, and the polyvinylpyrrolidone are located in a core layer of the middle end portion and the core layer is formed to be covered by a shell layer.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 21, Francis teaches the active ingredients include local anesthetics, and anesthetics such as lidocaine (i.e., amide-based local anesthetic)(paragraph [0058]). Francis continues to teaches microneedles may be formed from any suitable biocompatible and biodegradable polymer such as hyaluronic acid and polyvinylpyrrolidone and mixtures thereof (paragraph [0037]). Francis also teaches as illustrated in FIG. 3, the microneedle is characterized by an upper body portion (i.e., sharp end portion) and a lower body portion (i.e., middle end portion) that may or may not be symmetrical. The base (i.e., support portion) may be the intermediate substrate layer, as illustrated in FIG. 3, or a contiguous substrate layer joining the microneedles in the base region which is itself affixed to the intermediate substrate layer.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Francis does not teach wherein the amide-based local anesthetic, the hyaluronic acid, and the polyvinylpyrrolidone are located in a core layer of the middle end portion and the core layer is formed to be covered by a shell layer. However this deficiency is cured by Jung et al.
In the analogous art of drug administration using microneedles, Jung teaches the loss of drugs, particularly biopharmaceuticals or oxygen-sensitive drugs, during the manufacturing and storage process of the microneedle structure causes a significant obstacle in replacing the conventional drug delivery system with the microneedle structure (second paragraph). Jung also teaches the multi-layer microneedle structure and the method for manufacturing the same according to an embodiment of the present invention are provided to cover the core layer including the drug by the shell layer as a multi-layer structure, so that the exposure and release of the drug can be blocked by the shell layer, so the manufacturing process to prevent drug loss (paragraph 26). Jung further teaches as shown in Figure 5, in the case of the droplets before the formation of the microstructure, the activity rate of ascorbic acid is 100% in both cases with a shell layer and without a shell layer, but in the microneedle structure after the preparation is completed, it has a shell layer. The ascorbic acid activity rate of the case was 91%, and the ascorbic acid activity rate of the case without the shell layer was 65%. As a result, it can be seen that the loss of the drug is effectively prevented by the shell layer (section 5, third paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have the amide-based local anesthetic, the hyaluronic acid, and the polyvinylpyrrolidone located in a core layer of the middle end portion and the core layer is formed to be covered by a shell layer in Francis’ microneedle. Francis teaches as illustrated in FIG. 3, the microneedle is characterized by an upper body portion (i.e., sharp end portion) and a lower body portion (i.e., middle end portion) that may or may not be symmetrical. The base (i.e., support portion) may be the intermediate substrate layer, as illustrated in FIG. 3, or a contiguous substrate layer joining the microneedles in the base region which is itself affixed to the intermediate substrate layer. The artisan of ordinary skill would have been motivated to have the amide-based local anesthetic, the hyaluronic acid, and the polyvinylpyrrolidone located in a core layer of the middle end portion and the core layer is formed to be covered by a shell layer in Francis’ microneedle because Jung teaches the multi-layer microneedle structure and the method for manufacturing the same according to an embodiment of the present invention are provided to cover the core layer including the drug by the shell layer as a multi-layer structure, so that the exposure and release of the drug can be blocked by the shell layer, so the manufacturing process to prevent drug loss (paragraph 26). Jung further teaches as shown in Figure 5, in the case of the droplets before the formation of the microstructure, the activity rate of ascorbic acid is 100% in both cases with a shell layer and without a shell layer, but in the microneedle structure after the preparation is completed, it has a shell layer. The ascorbic acid activity rate of the case was 91%, and the ascorbic acid activity rate of the case without the shell layer was 65%. As a result, it can be seen that the loss of the drug is effectively prevented by the shell layer (section 5, third paragraph). The skill artisan would have had a reasonable expectation of success because Francis teaches microneedles for the administration of active ingredients to the skin wherein the active ingredients are present in the microneedle and Jung also teaches microneedles for the administration of active ingredients to the skin wherein the active ingredients are present in the microneedle.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
Prosecution Insights