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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments with respect to claim(s) 45-63 under 35 U.S.C. 103 and double patenting have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Status
Claims 45-63 are new and pending under examination. Claims 1-44 are cancelled. Claims 45, 48, 54, 57 are currently amended.
Priority
The instant Application claims priority to the provisional application 63/084,211, filed 9/28/2020. The date of 9/28/2020 is acknowledged.
Specification
The disclosure is objected to because of the following informalities: [0020], line 2, discusses “sustained release from date 0-1434, 38”. It is unclear if this date “0-1434, 38” is a typographical error. Appropriate correction is required.
The use of the terms Voltaren, Capsaisin, Arthricream (all [0004]) and Tewameter ([0069]), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include proper symbols indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim 45 recites “the core of the first plurality of microneedles releasing the small molecule drug into the skin of the subject without delay, said small molecule drug released at a first substantially constant rate over a first period of time and the shell and cap of the second plurality of microneedles degrading in the skin to release the small molecule drug at a second substantially constant rate after a delay period with the small molecule drug released from the second plurality of microneedles at a substantially constant rate over a second period of time extending beyond said first period of time, the second substantially constant rate being independent of the delay period.”
Claim 54 recites similar language: “the shall and cap of the first plurality of microneedles degrading in the skin to release the small molecule drug at a first release rate after a first delay period, and the shell and cap of the second plurality of microneedles degrading into the skin to release the small molecule drug at a second release rate after a second delay period greater than the first delay period, said first release rate being independent of the first delay period and said second release rate being independent of the second delay period.”
The above limitations of these claims describe functional rather than a structural elements of the instant inventions. As such, the claim is being interpreted based upon the structural limitations (i.e., regarding claim 45, a substrate comprising a plurality of projections, a first group of projections supporting a first plurality of microneedles, a second group of projections supporting a second plurality of microneedles; the first plurality of microneedles comprising a PLGA core with a small molecule drug mixed therein, the second plurality of microneedles comprising a PLGA core with the small molecule drug mixed therein further comprising a PLGA shell and cap, wherein the PLGA cap is secured to the substrate by a water-soluble material; and, regarding claim 54, wherein the first and second plurality of microneedles are made of PLGA of a first and a second molecular weight, respectively), where the functional limitation is a property endowed by the structure.
The functional limitations of claims 48-50 and 57-59 are being interpreted in the same manner.
Claim Rejections - 35 USC § 103
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.
Claim(s) 45-51 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Polymer Microneedles for Controlled-Release Drug Delivery. Pharm Res 23, 1008–1019 (2006).) in view of Nguyen et al. (US 2019/0269895 A1, filed 3/5/2019, published 9/5/2019, on IDS filed 10/14/2022).
Park et al. teaches poly-lactide-co-glycolide (PLGA) microneedle arrays (transdermal microneedle system) and methods of making thereof (Abstract; Introduction, Pg 1008-1009).
Park teaches that the study goal was to develop a minimally invasive polymeric controlled-release system suitable for self-administration without the pain or complexity of current controlled-release devices. Park proposes redesigning the microparticles to have the shape of microneedles to give the polymeric particles the functionality of both needles and drug matrices for controlled release. By integrally forming these microscopic needles onto a patch substrate (substrate), arrays of drug-loaded microneedles could be inserted into the skin and worn like a transdermal patch for slow release over time; or, an alternative approach would involve intentionally separating the patch base from the needles after insertion into the skin, thereby leaving the drug-filled needles invisibly buried in the skin for slow release. Because these microneedles are made of FDA-approved, biodegradable polymer, they should safely disappear after drug delivery is complete, and previous studies have shown that microneedles are painless (Pg 1008, right column, second paragraph).
Microneedles of this size can penetrate past the skin's outer barrier of stratum corneum and deliver drug to the epidermis and superficial dermis, where drug can diffuse rapidly for local delivery to skin or systemic distribution via uptake by dermal capillaries. Through the use of biodegradable polymers such as poly-lactide-co-glycolide (PLGA), well-established controlled-release mechanisms can be exploited to control release from microneedles (Pg 1009, left column, second paragraph).
Park further describes and tests tapered-cone microneedles (having a height and shape selected to penetrate a skin of a subject; Pg 1009, right column, “Fabrication of Biodegradable Microneedles: Fabrication of Microneedle Master Structures and Molds, third paragraph).
Park teaches encapsulating calcein or BSA in multiple layers of polymers; for fastest release, calcein or BSA is encapsulated in PLGA; for slower release, calcein or BSA is encapsulated in microparticles composed of CMC and then PLGA; for even slower release, calcein or BSA is encapsulated in microparticles composed of PLA and then PLGA (Pg 1010, left column, paragraphs 2-4).
Park teaches that a single encapsulation formula (calcein directly entrapped within the PLGA matrix of the microneedles) showed a zero-order kinetics over a period of 4h; BSA showed the same release kinetics over 5 days (Pg 1013, left column, “Release from Microneedles Using a Single-Encapsulation Formulation,” first paragraph; Figure 4A).
Park does not teach:
A plurality of projections that support a plurality of microneedles;
a plurality of microneedles comprising a shell, a cap, and a drug matrix therein, wherein the drug is a small molecule drug; nor
the pluralities of microneedles are attached to the plurality of projections via a water-soluble material.
Nguyen teaches a core-shell microneedle system, and a method of manufacturing thereof, that provides a pulsatile drug delivery system programmed to release drugs/vaccines at predictable times using biodegradable polymers with controlled dosages. The microneedle system can be fully embedded into the skin and then release drugs/vaccines as sharp bursts in a timely manner, similar to multiple bolus injections (Abstract).
Nguyen teaches the following:
The microneedles attach to a supporting array that can be applied to skin, which comprise a plurality of projections to support a plurality of microneedles (Figure 4; [0030]);
The microneedles are fabricated from FDA approved materials (e.g., Poly(D,L-lactide-co-glycolide) (PLGA), poly-lactide acid (PLA) - biodegradable) that are commonly used for drug delivery, medical devices, etc. ([0026]; claim 8);
The core-drugs include therapeutic agents (e.g., drugs or vaccines such as Prevnar-13, pain medicine, allergic drugs (small molecule), etc.) dissolved or dispersed in suitable polymer solutions ([0032]);
A drug-core is made via a mold into conical shapes, comprising a polymeric carrier such as PLGA (Figure 3 and 5-7; [0029]; claims 1 and 8);
The drug-cores are aligned and transferred on to a cap-layer of PLGA; then the cap layer is aligned and pressed on the microneedle shell under a slightly-increased temperature to simultaneously load drugs and seal the microneedles (Figure 3 and 5-7; [0029]);
The drug-cores are inserted into shells (Figure 6; [0029]);
The supporting array is then coated with a water-soluble polymer (i.e., PVP, PVA) and aligned with the coreshell microneedles and sufficient heat for bonding with the PLGA caps is supplied ([0047]);
The microneedles detach from the supporting array upon insertion into the skin to release the drug (Figure 4).
Thus, regarding claims 45 and 48, Park teaches:
A transdermal microneedle system comprising a substrate for application to skin of a patient, the substrate comprising a plurality of microneedles and can be designed to intentionally detach from the substrate upon insertion into the skin;
each of the microneedles has a height and shape designed to penetrate the skin of a subject;
the microneedles are made of PLGA, which exhibit zero-order release kinetics over an extended period of time.
Nguyen teaches:
A transdermal microneedle system comprising a substrate comprising a plurality of projections that support a plurality of microneedles;
a plurality of microneedles comprising a shell, a cap, and a drug matrix therein, wherein the drug is a small molecule drug; and
the pluralities of microneedles are attached to the plurality of projections via a water-soluble material.
Therefore, regarding claims 45 and 48, it would be prima facie obvious to combine the
PLGA coreshell features taught by Nguyen (the plurality of projections to support the plurality of microneedles; the shell and cap surrounding the coredrug matrix; and attaching the cap of the coreshell microneedles to the projections via a water-soluble material) with the transdermal microneedle system taught by Park. One would be motivated to do so in order to design a substrate comprising multiple pluralities of microneedles with different drug release properties, wherein one plurality of microneedles has a delay period, which would allow for a single substrate to release drugs over an extended period of time. One would have a reasonable expectation of success as Park established the release kinetics of drugs encapsulated in PLGA microneedles and Nguyen taught that such release dynamics were possible with PLGA coreshells.
Additionally, it would have been prima facie obvious to combine prior art elements according to known methods to yield predictable results (MPEP 2143(I)(A)). Park teaches a plurality of PLGA microneedles encapsulating a drug, and Nguyen teaches a plurality of PLGA coreshell microneedles comprising a PLGA drug core surrounded by a PLGA shell and cap. The only difference between the teachings of the prior art and the instant claim 45 is that the two different pluralities of microneedles are not actually combined onto the same substrate. However, one skilled in the art would have recognize that microneedles made entirely of PLGA implanted in the skin would degrade at the same rate because they are made of the same material; more specifically, the PLGA of microneedles comprising a PLGA encapsulating a drug and the PLGA microneedles comprising a PLGA shell and cap surrounding a PLGA drug matrix would degrade at the same rate. Without the inclusion of said drug in the shell and cap of the second plurality of microneedles, drug release would happen from only the first plurality of microneedles while the second plurality of microneedles continued to degrade at a similar rate without releasing any drug; after a delay period, then the second plurality of microneedles would begin to release the drug. One skilled in the art would recognize that such a dynamic is ideal to create a long-acting drug release system, wherein one subset of microneedles degrades to release a desired drug immediately without delay and a second subset degrades at approximately the same rate over time and releases its drug from its drug core matrix after a second period of time. Therefore, combining the two pluralities of microneedles into the same substrate would yield predictable results readily recognized by one skilled in the art, thereby producing the instant invention of claims 45 and 48.
Additionally, it would have been prima facie obvious to try combining the plurality of microneedles taught by Park and the plurality of microneedles taught by Nguyen (MPEP 2143(I)(E)). At the time of filing, the art recognized a desire to create a long-acting, tunable drug delivery system that utilized microneedles as a means to administer such compounds in a painless way. As stated above, Park and Nguyen each respectively teach PLGA-based microneedles with different drug release profiles. Therefore, it would have been obvious to try to combine the two populations of microneedles, thereby leading to the instant invention.
Regarding claim 46, Nguyen teaches that the microneedle shape is conical in nature to pierce or penetrate the skin, thus resulting in a tapered configuration extending from a base adjacent the first and second groups of projections (Abstract; Figure 4; [0007], [0009], [0026], [0030], [0048]). Moreover, the dimensions of the microneedles are shown in Figure 4, wherein the core has a diameter of 200µm at the base and a height of 300µm. Nguyen further teaches that the core-shell microneedles comprise a cap that is adjacent to the base of the drug-core (Figure 3 and 5-7; [0029]).
Regarding claim 47, Nguyen teaches that the core-shell microneedle cap and shell have a diameter of 300µm at the cap and a height of 600µm (Figure 4).
Regarding claims 49 and 50, Nguyen teaches a microneedle device comprising a plurality of microneedles comprised of drug-cores made of PLGA matrices containing drugs such as pain medicine ([0012]; claim 8), wherein all the microneedles in the microneedle patch are comprised of the same PLGA matrix drug-core.
Regarding claim 51, Nguyen teaches that microneedles can administer versatile drugs (e.g., growth hormone, allergic drugs, pain medicine, etc. (non-steroidal anti-inflammatory)) ([0012]).
Claim(s) 45-53 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Polymer Microneedles for Controlled-Release Drug Delivery. Pharm Res 23, 1008–1019 (2006).) and Nguyen et al. (US 2019/0269895 A1, filed 3/5/2019, published 9/5/2019, on IDS filed 10/14/2022), as applied to claims 45-51 above, and further in view of Prausnitz et al. (CA-3115572-A1, published 4/18/2019).
The teachings of Park and Nguyen have been set forth above. Park and Nguyen do not teach that the small molecule drug in the microneedles is curcumin or an antiviral.
Prausnitz teaches separable microneedles and microneedle patches composed of biodegradable polymers such as PLGA (Abstract; Pg 9, second paragraph, lines 9-13). Prausnitz teaches that a variety of substances can be formulated for delivery with microneedles, including antivirals and turmeric (curcumin; Pg 23, lines 20-22; Pg 24, line 3; and Pg 26, line 3).
Thus, regarding claims 52 and 53, Park and Nguyen teach a transdermal microneedle system wherein a small molecule drug is encapsulated within pluralities of PLGA microneedles. Prausnitz teaches PLGA microneedles can encapsulate a variety of substances including antivirals and curcumin. Based on these teachings, it would be prima facie obvious to encapsulate antivirals or curcumin into the microneedle system taught by Park and Nguyen in order to treat a variety of conditions or diseases. One would have a reasonable expectation of success as Prausnitz had previously taught that similar PLGA-based microneedles could encapsulate these therapeutics.
Claim(s) 54-61 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Polymer Microneedles for Controlled-Release Drug Delivery. Pharm Res 23, 1008–1019 (2006).) and Nguyen et al. (US 2019/0269895 A1, filed 3/5/2019, published 9/5/2019, on IDS filed 10/14/2022) in view of Makadia et al. (Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel). 2011 Sep 1;3(3):1377-1397.).
The teachings of Park and Nguyen have been set forth above. Park and Nguyen do not teach:
The first plurality of microneedles comprises a PLGA of a first molecular weight; nor
The second plurality of microneedles comprises a PLGA of a second molecular weight.
Makadia teaches that PLGA has been among the most attractive polymeric candidates
used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and is FDA approved (Abstract).
Makadia teaches that polymers with higher molecular weight have generally exhibited lower degradation rates. Molecular weight has a direct relation with the polymer chain size. Polymers having higher molecular weight have longer polymer chains, which require more time to degrade than small polymer chains (Pg 9, “4.2.3. Effect of Weight Average molecular Weight (Mw)”).
Therefore, regarding claims 54 and 57, it would be prima facie obvious to generate
PLGA coreshell microneedles of different molecular weights. One would be motivated to do so in order to design multiple pluralities of microneedles with different release rates and kinetics that release drugs over an extended period of time. One would have a reasonable expectation of success as Makadia taught that the biodegradation of PLGA is dependent upon the molecular weight, wherein a higher molecular weight results in slower degradation.
Additionally, it would have been prima facie obvious to apply a known technique to a known device ready for improvement to yield predictable results (MPEP 2143(I)(D)). Park and Nguyen teach PLGA coreshell microneedles comprising a drug core surrounded by a PLGA shell and cap. The prior art teaches that the biodegradation of PLGA can be tunable based upon the molecular weight of the PLGA used, as taught by Makadia. One of ordinary skill in the art would recognize that using a PLGA of one molecular weight for one plurality of microneedles and another PLGA of a different molecular weight for another plurality of microneedles would be a simple way to alter the biodegradation rate of the shell and cap of the microneedles, and, thus, by having a different molecular weight for each plurality of microneedles, one would be able to tune the biodegradation rates such that there would be a delay prior to the degradation and drug release at a first release rate from the first plurality of microneedles followed by release of the drug from the second plurality of microneedles at a second release rate after a second delay longer than the first delay period. Thus, applying the known technique of modulating the molecular weight of PLGA for different populations of microneedles would yield predictable results, thereby resulting in the instant invention of claims 54 and 57.
Additionally, it would have been prima facie obvious to try incorporating multiple pluralities of microneedles composed of PLGA of different molecular weights into the same substrate for drug delivery (MPEP 2143(I)(E)). At the time of filing, the art recognized a desire to create a long-acting, tunable drug delivery system that utilized microneedles as a means to administer such compounds in a painless way, as taught by Park and Nguyen. As stated above, Makadia teaches that the biodegradation rate of PLGA is dependent upon its molecular weight, with higher molecular weights resulting in slower degradation. Therefore, it would have been obvious to try to create a substrate with two pluralities of microneedles, each with a different molecular weight, in order to take advantage of the differences in biodegradation.
Regarding claim 55, Nguyen teaches that the microneedle shape is conical in nature to pierce or penetrate the skin, thus resulting in a tapered configuration extending from a base adjacent the first and second groups of projections (Abstract; Figure 4; [0007], [0009], [0026], [0030], [0048]). Moreover, the dimensions of the microneedles are shown in Figure 4, wherein the core has a diameter of 200µm at the base and a height of 300µm. Nguyen further teaches that the core-shell microneedles comprise a cap that is adjacent to the base of the drug-core (Figure 3 and 5-7; [0029]).
Regarding claim 56, Nguyen teaches that the core-shell microneedle cap and shell have a diameter of 300µm at the cap and a height of 600µm (Figure 4).
Regarding claims 58-60, Nguyen teaches a microneedle device comprising a plurality of microneedles comprised of drug-cores made of PLGA matrices containing drugs such as pain medicine ([0012]; claim 8), wherein all the microneedles in the microneedle patch are comprised of the same PLGA matrix drug-core.
Regarding claim 61, Nguyen teaches that microneedles can administer versatile drugs (e.g., growth hormone, allergic drugs, pain medicine, etc. (non-steroidal anti-inflammatory)) ([0012]).
Claim(s) 54-63 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Polymer Microneedles for Controlled-Release Drug Delivery. Pharm Res 23, 1008–1019 (2006).), Nguyen et al. (US 2019/0269895 A1, filed 3/5/2019, published 9/5/2019, on IDS filed 10/14/2022), and Makadia et al. (Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel). 2011 Sep 1;3(3):1377-1397.), as applied to claims 54-61 above, and further in view of Prausnitz et al. (CA-3115572-A1, published 4/18/2019).
The teachings of Park, Nguyen, and Makadia have been set forth above. Park, Nguyen, and Makadia do not teach that the small molecule drug in the microneedles is curcumin or an antiviral.
Prausnitz teaches separable microneedles and microneedle patches composed of biodegradable polymers such as PLGA (Abstract; Pg 9, second paragraph, lines 9-13). Prausnitz teaches that a variety of substances can be formulated for delivery with microneedles, including antivirals and turmeric (curcumin; Pg 23, lines 20-22; Pg 24, line 3; and Pg 26, line 3).
Thus, regarding claims 62 and 63, Park, Nguyen, and Makadia teach a transdermal microneedle system wherein a small molecule drug is encapsulated within the pluralities of PLGA microneedles. Prausnitz teaches PLGA microneedles can encapsulate a variety of substances including antivirals and curcumin. Based on these teachings, it would be prima facie obvious to encapsulate antivirals or curcumin into the microneedle system taught by Park, Nguyen, and Makadia in order to treat a variety of conditions or diseases. One would have a reasonable expectation of success as Prausnitz had previously taught that similar PLGA-based microneedles could encapsulate these therapeutics.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 54-56 and 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-25, 27, 29, and 31-33 of copending Application No. 17/871,490 (‘490, reference application; claim set filed 12/22/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 23 of copending Application No. ‘490 recites a drug delivery system comprising: an assembly including a substrate, and a plurality of microneedles extending from the substrate, each microneedle including: a shell including a biodegradable polymer, said shell having a tapered shape from a distal tip to a proximal base having a diameter larger than the distal tip, a core including a mixture of a therapeutic agent and a polymeric carrier, and a cap including a biodegradable polymer, the cap bonded to the base of the shell and enclosing the core within the shell, said cap and shell not including any therapeutic agent, and said assembly comprising a water-soluble polymer layer between the cap and the substrate, said water-soluble polymer layer connecting the microneedles to the substrate with the tips of the microneedles directed away from the substrate, wherein the water-soluble polymer layer is configured to dissolve to release the microneedles from the substrate when the microneedles are inserted into the skin of a patient, leaving the microneedles embedded in the skin where the cap and shell of each of the plurality of microneedles degrade at a predetermined time to release the therapeutic agent into the skin of the patient.
Dependent claims include the drug delivery system of claim 23, wherein the biodegradable polymer includes Poly(D,L-lactide-co-glycolide) (“PLGA”) or poly-lactide acid (“PLA”) (claim 24); the drug delivery system of claim 24, wherein the cap includes PLGA or PLA (claim 25); the drug delivery system of claim 23, wherein the shell of a first subset of the plurality of microneedles is selected to degrade at a first time to release the therapeutic agent therein into skin of a patient, and wherein the shell of a second subset of the plurality of microneedles is selected to degrade at a second time to release the therapeutic agent therein into the skin of the patient (claim 27); the drug delivery system of claim 28, wherein the shell of a first subset of the plurality of microneedles is selected to degrade at a first time to release a first dose of the vaccine therein into skin of a patient, and wherein the shell of a second subset of the plurality of microneedles is selected to degrade at a second time to release a second dose of the vaccine therein into the skin of the patient (claim 29); the drug delivery system of claim 23, wherein the therapeutic agent treats pain or allergy symptoms of a patient (claim 31); the drug delivery system of claim 23, wherein the core of at least one of the microneedles includes a maximum diameter of 200µm and a maximum height of 300µm (claim 32); and the drug delivery system of claim 32, wherein at least one of the microneedles in the plurality of microneedles includes a maximum height of 600µm (claim 33).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 45 and 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 8, 10, and 12 of U.S. Patent No. 11,426,570 B2 (‘570) in view of Park et al. (Polymer Microneedles for Controlled-Release Drug Delivery. Pharm Res 23, 1008–1019 (2006).), Nguyen et al. (US 2019/0269895 A1, filed 3/5/2019, published 9/5/2019, on IDS filed 10/14/2022), and Makadia et al. (Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel). 2011 Sep 1;3(3):1377-1397.).
Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
Claim 1 of U.S. Patent No. ‘570 recites a method of manufacturing a microneedle assembly, the method comprising: generating a core microneedle assembly by:
filling a plurality of microneedle cavities in a first silicone mold with a copolymer, and generating a core from the copolymer in each of the copolymer-filled cavities;
generating a therapeutic agent assembly by: filling a plurality of cavities in a second silicone mold with a therapeutic agent, spinning the second silicone mold to remove a scum layer of the therapeutic agent on the second silicone mold, and removing molded portions of the therapeutic agent from the cavities of the second mold and transferring the molded portions of the molded therapeutic agent to a substrate;
aligning the therapeutic agent assembly with the core microneedle assembly to thereby fill cavities of the cores in the core microneedle assembly with respective ones of the molded portions of the therapeutic agent;
and spinning the first silicone mold having the molded portions of the therapeutic agent filled into the core cavities to remove a scum layer of the copolymer on the first silicone mold.
Dependent claims include the method of claim 1, wherein the cavities in each of the first silicone mold and the second silicone mold are conical shaped (claim 2); the method of claim 1, wherein the copolymer is Poly(D,L-lactide-co-glycolide) (PLGA) (claim 3); the method of claim 1, wherein the therapeutic agent is mixed with a polymeric carrier of biocompatible or biodegradable polymers (claim 8); the method of claim 1, further comprising generating a cap assembly by: filling a plurality of cavities in a third silicone mold with a copolymer to form a plurality of caps, spinning the third silicone mold to remove a scum layer of the copolymer on the third silicone mold, removing the molded caps from the third mold and transferring the molded caps onto the core microneedle assembly, and aligning the cap assembly with the core microneedle assembly to thereby cover the cores in the core microneedle assembly with the caps (claim 10); and the method of claim 10, further comprising coating a supporting array with a water soluble polymer and contacting the supporting array with the cap assembly (claim 12).
U.S. Patent ‘570 does not teach the presence of two distinct pluralities of microneedles on the supporting array that exhibit different release kinetics, wherein the first plurality of microneedles release immediately at a near constant rate over a first period of time and the second plurality of microneedles exhibits a delay period before releasing at a near constant rate over a second period of time that extends beyond the first period of time. U.S. Patent ‘570 also does not teach that the multiple pluralities of microneedles each comprise polymers of different molecular weights that impact their degradation rates.
Park, Nguyen, and Makadia teach a transdermal microneedle system wherein 1) a plurality of microneedles wherein a subset of said microneedles immediately release at a near constant order over a first period time and a second subset exhibits a delay period before releasing at a near constant rate over a second period of time that extends beyond the first and 2) each plurality of microneedles comprises a polymer with a different molecular weight that impacts their degradation rates.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Park, Nguyen, and Makadia into US ‘570, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Park, Nguyen, and Makadia teach transdermal microneedle systems comprised of different pluralities of microneedles with different delays and release kinetics. Thus, the claims are obvious in view of US ‘570.
Prior Art Cited but not Referenced
McHugh et al. (Fabrication of fillable microparticles and other complex 3D microstructures. Science. 2017 Sep 15;357(6356):1138-1142.) teaches generating 3D microstructures from polymers such as PLGA and release kinetics.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658