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 34-53 are pending and under current examination.
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 34-51 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.
Regarding claim 34, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 36 and 38, the claims currently recite the phrases “the immunoregulator comprises…”, “the chemokine comprises…”, “the antibody comprises…”, and “the anti-inflammatory agent comprises…”. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. and MPEP 2173.05(h). Please refer to MPEP 2173.05(h) for examples of proper Markush language: When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper. Amending the claims to recite “the group consisting of” would obviate the rejection.
Claim 39 recites the limitation “wherein releasing the immunosuppressor and/or the immunoregulator beneath the skin does not elicit a systemic response”. This renders the claim indefinite because it is not clear which systemic response is excluded by the claim (i.e. immune system, nervous system, etc.). It is also not clear how a drug that modulates an immune response does not elicit at least an immune system response.
Claim 48 recites “…a ratio of about 0:100 to about 100:0”. This renders the claim indefinite because it is not clear what property is compared in the ratio (i.e. weight, moles, volume, etc.).
Regarding claims 35, 37, 40-47, and 49-51, 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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 34, 36, 40, 42-44, and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023) and Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 34, Prausnitz teaches a microneedle device for sustained release of drug across or into a biological barrier. The biological barrier may be a biological tissue of a patient in need of the drug, including the skin or parts thereof (pg. 6 lines 20-26). The method for delivering a drug across or into a biological carrier includes providing a device that includes a base substrate which comprises a drug dispersed in a polymeric matrix material and one or more microneedles extending from the base substrate and inserting the one or more microneedles into a biological barrier to create one or more holes in the biological barrier. The microneedles dissolve and/or swell in the biological barrier and allow the drug to pass from the base substrate through the holed and into the biological barrier (pg. 13 line 26-pg. 14 line 2). The water-soluble or swellable material of the microneedles may include hyaluronic acid (pg. 3 line 29) and may be crosslinked (pg. 9 line 13). Suitable drugs include immunomodulators (pg. 13 line 8). The Examiner considers the term “inserting” to read on the “applying pressure” limitation of the instant claim.
Regarding claim 35, Prausnitz teaches the relevant limitations of claim 34.
Regarding claim 36, Prausnitz teaching that suitable drugs include immunomodulators and anti-inflammatory agents (pg. 13 lines 8-10).
Regarding claim 39, it is noted that Prausnitz is silent with regards to a systemic response rendered by the microneedle assembly and therefore reads on the “does not elicit a systemic response” limitations of instant claim 39.
Regarding claim 40, Prausnitz teaches that the microneedle device may be used for fluid extraction from the skin and may be used to collect interstitial fluid and its solutes from a patient (pg. 16 line 9). The Examiner considers the phrase “its solutes” to read on the “biomarker” limitation of the instant claim.
Regarding claims 42-44, Prausnitz teaches the relevant limitations of claim 34 above.
Regarding claim 49, Prausnitz teaches that the microneedle may have a length of about 50 to about 2000µm and that the base portion has a maximum width 20 to 500µm with an aperture diameter of about 5 to about 100µm (pg. 11 line 32-pg. 12 line 8). The water-soluble or swellable material becomes a hydrogel upon insertion into the biological barrier (pg. 3 line 1). The microneedles may be solid or hollow (pg. 3 line 9).
Regarding claim 50, Prausnitz teaches that the base substrate may include a biodegradable polymer such as poly(lactide-co-glycolide)s (pg. 10 line 9).
Regarding claim 51, Prausnitz teaches that the polymeric microneedle devices have sufficient mechanical strength to penetrate the biological barrier while also being capable of rapidly degrading for dissolving within the biological barrier in less than an hour, 30 minutes, or less than 15 minutes (pg. 16 line 33-pg. 17 line 2). Prausnitz do not disclose the swelling ratio properties as recited in claim 51. However, the invention as claimed is not structurally distinguishable from the disclosure of Prausnitz and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 34 and 42-44, Prausnitz does not teach that the hyaluronic acid polymer comprises a disulfide bond or comprises the disclosed chemical structure. However, this deficiency is cured by Li.
Li teaches a hyaluronic acid-ss-DOCA conjugate with the structure:
PNG
media_image1.png
230
277
media_image1.png
Greyscale
The disulfide bond is stable in the mildly oxidizing extracellular milieu and may be prone to rapid cleavage through the thiol-disulfide exchange reactions with intracellular reducing molecules, especially glutathione (GSH) (pg. 2310 Introduction and Scheme 1).
Regarding claims 34 and 35, Prausnitz does not teach a method of treating a skin disorder. However, this deficiency is cured by Takada.
Takada teaches a method of administering an effective substance for the prevention or treatment of skin aging or treatment of skin scar comprising frit contacting an area affected area with a microneedle assembly then applying a given pressure to insert the microneedles through the skin into the body [0090]. The thread forming polysaccharide of the microneedle assembly may include hyaluronic acid and salts thereof [0072]. The active substance includes all proteins falling within a fibroblast growth factor (FGF) subfamily, including basic fibroblast growth factors with can be used in combination with compounds such as TGFβ [0076]. A target symptom for prevention or treatment using the microneedle assembly includes a burn wound [0020].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 34 and 42-44, it would have been prima facie obvious to one of ordinary skill in the art of filing to utilize a hyaluronic acid polymer comprising a disulfide linkage and a terminal amine in the microneedle device taught by Prausnitz. One would have understood in view of Li that a hyaluronic acid modified with a disulfide linkage and terminal amine is susceptible to intercellular cleavage via redox reaction with native glutathione. It would have been obvious that a microneedle comprising the same modified hyaluronic acid polymer would also be subject to intercellular cleavage. One of ordinary skill in the art of filing would have been motivated to include such a modified hyaluronic acid polymer in the microneedle assembly in order to target intercellular dissolution of the microneedle assembly. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Prausnitz teaches that microneedles may comprise crosslinked hyaluronic acid and are self-dissolving and/or swellable.
Regarding the method of treating a skin disorder recited by claims 34 and 35, it would have been prima facie obvious to one of ordinary skill in the art of filing to utilize the microneedle device of Prausnitz in a method of treating a skin disorder. One would have understood in view of Takada that a microneedle assembly comprising hyaluronic acid and an immune modulator may be used in a method of treating a burn wound. It would have been obvious that the microneedle device of Prausnitz may also be used in a method of treating a burn wound. One of ordinary skill in the art of filing would have understood that a microneedle assembly comprising hyaluronic acid and an immune modulatory drug is suitable for use in a method of treating a burn wound. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Takada teaches that a microneedle device nearly identical to the microneedle device taught by Prausnitz may be used in a method of treating a burn wound. See MPEP 2144.07.
Claims 37 and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023) and Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023), as applied to claims 34, 36, 40, 42-44, and 49-51 above, and further in view of Pathak (WO 2018/017674, publication year: 2018, cited in the IDS filed 11/29/2023).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Prausnitz, in view of Li and Takada, renders obvious the relevant limitations as described above.
Regarding claim 37, Prausnitz also teaches that suitable drugs for inclusion in the microneedle device include interleukin inhibitors, immunomodulators, and anti-inflammatory agents (pg. 13 lines 6-10).
Regarding claims 46-48, Prausnitz teaches that the water-soluble or swellable material of the microneedles may include hyaluronic acid (pg. 3 line 29) and may be crosslinked (pg. 9 line 13).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 37, Prausnitz does not teach the inclusion of a cell as the immunomodulator present in the microneedle assembly. However, this deficiency is cured by Pathak.
Pathak teaches sustained drug and cell delivery using a microneedle array (pg. 1 line 22). The cells for delivery with the microneedle array include mammalian cells such as T cells and other immune cells (pg. 19 line 32). The encapsulated cells provide local or systemic therapeutic benefit (Abstract).
Regarding claims 46 and 48, Prausnitz does not teach a crosslinking agent for crosslinking the hyaluronic acid polymer. However, this deficiency is cured by Pathak.
Pathak teaches sustained drug and cell delivery using a microneedle array (pg. 1 line 22) comprising crosslinked polyethylene glycol based synthetic biodegradable crosslinked gels (pg. 9 lines 23-24). The biodegradable polymers include hyaluronic acid (pg. 16 line 24). The crosslinked polyethylene glycol based crosslinked hydrogels are made using a PEG derivative with a degradable glutarate group and a terminal n-hydroxysuccinimide group reacted with equimolar quantities of a PEG derivative with terminal amine groups (pg. 76 lines 21-30). The preferred average molecular weight of polymer may range from 1000 to 200,000g/mol (pg. 60 line 11).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 37, the idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional immunoregulator cells used in microneedle devices. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
Regarding claims 46 and 48, the idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional PEG crosslinkers used in the production of crosslinked hyaluronic acid for microneedle assemblies. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023) and Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023), as applied to claims 34, 36, 40, 42-44, and 49-51 above, and further in view of Lunyak (U.S. Patent Application No. 2018/0161373, publication year: 2018) and Yantasee (WO 2021/011496, publication date: 1/21/2021, cited in the IDS filed 11/29/2023).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Prausnitz, in view of Li and Takada, renders obvious the relevant limitations as described above. Prausnitz also teaches that suitable drugs for inclusion in the microneedle device include interleukin inhibitors, immunomodulators, and anti-inflammatory agents (pg. 13 lines 6-10).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Prausnitz does not teach the inclusion of the chemokines, cytokines, antibodies, or anti-inflammatory agents embraced by the instant claim. However, these deficiencies are cured by Takada, Lunyak, and Yantasee.
Takada teaches a method of administering an effective substance for the prevention or treatment of skin aging or treatment of skin scar comprising frit contacting an area affected area with a microneedle assembly then applying a given pressure to insert the microneedles through the skin into the body [0090]. The active substance includes all proteins falling within a fibroblast growth factor (FGF) subfamily, including basic fibroblast growth factors with can be used in combination with compounds such as TGFβ [0076]. Lunyak teaches a microneedle-based system that may be utilized to deliver one or more factors produced by a population of stem cells [0006]. In an embodiment of the invention, any skin disorder may be treated by a composition of factors produced by the factor production units of the invention [0189]. The factors can include CCL22 [0187] and TGF-beta 1 and TGF-beta 2 [0186]. The factors may be delivered in combination with other active agents and treatment modalities, including corticosteroids and non-steroidal anti-inflammatory compounds [0177]. Yantasee teaches an immunotherapeutic construct that can be formulated into a microneedle formulation [0013]. The administration of an immunotherapeutic construct may be combined with a treatment for cancer [0086], including anti-CD52 antibodies ([0109], pg. 26 line 2). The compositions may be used to treat cancer of the skin [0267].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the drugs of Prausnitz and the therapeutics of Takada, Lunyak, and Yanatasee for the treatment of skin disorders via microneedle assembly). See MPEP 2144.06 (II).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023) and Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023), as applied to claims 34, 36, 40, 42-44, and 49-51 above, and further in view of Martell (European Medical Journal, pg. 14-21, publication year: 2017).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Prausnitz, in view of Li and Takada, renders obvious the relevant limitations as described above. Prausnitz also teaches that suitable drugs for inclusion in the microneedle device include interleukin inhibitors, immunomodulators, and anti-inflammatory agents (pg. 13 lines 6-10).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Prausnitz does not teach that depleting an unwanted immune cell by recruiting the unwanted cells. However, this deficiency is cured by Martell.
Martell teaches that cytokines can recruit cytotoxic T cells, IgG-bearing B cells, macrophages, mast cells, and B cells bearing IgG, IgA and IgE (pg. 17, Adaptive Immune System).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing that the immunomodulator taught by Prausnitz may recruit immune cells. One would have understood in view of Martell that an immunomodulator such as a cytokine is able to recruit a wide variety of immune cells. It would have been obvious that the inclusion of such a cytokine in the microneedle assembly taught by Prausnitz may also recruit immune cells. One of ordinary skill in the art of filing would have been motivated to recruit unwanted immune cells in order to enhance or ameliorate a local immune response. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Prausnitz teaches that immunomodulators may be included in the microneedle assembly.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023) and Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023), as applied to claims 34, 36, 40, 42-44, and 49-51 above, and further in view of Zhang et. al. (Chem. Commun. (Camb), pg. 1-10, publication year: 2016).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Prausnitz, in view of Li and Takada, renders obvious the relevant limitations as described above.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Prausnitz, in view of Li and Takada, does not teach a reducing agent for the disulfide bond present in the hyaluronic acid polymer. However, this deficiency is cured by Zhang.
Zhang teaches that 20mM tricarboxyethylphosphine (TCEP) may be used to reduced intermolecular disulfide bonds in Cys-HA conjugate and PEG thioester hydrogels (pg. 3, fourth paragraph).
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing to utilize TCEP as a reducing agent to cleave a disulfide bond present in a hyaluronic acid polymer. One would have understood in view of Zhang that TCEP is a suitable reducing agent for the cleavage of intermolecular disulfide bonds present in a hyaluronic acid hydrogel. The artisan of ordinary skill in the art would have had reasonable expectation of success because Zhang teaches that 20mM TCEP may be used to reduce intermolecular disulfide bonds in a crosslinked hyaluronic acid hydrogel. See MPEP 2144.07.
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Prausnitz (WO2008/011625, publication year: 2008, cited in the IDS filed 11/29/2023) in view of Li et. al. (Biomaterials, pg. 2310-2320, publication year: 2012, cited in the IDS filed 11/29/2023), Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023) and Pathak (WO 2018/017674, publication year: 2018, cited in the IDS filed 11/29/2023), as applied to claims 37 and 46-48 above, and further in view of Bennett (U.S. Patent Application No. 2009/0227689, publication year: 2009).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Prausnitz, in view of Li, Takada, and Pathak, renders obvious the relevant limitations as described above. Prausnitz teaches that the water-soluble or swellable material of the microneedles may include hyaluronic acid (pg. 3 line 29) and may be crosslinked (pg. 9 line 13).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Prausnitz does not teach a crosslinking agent for crosslinking the hyaluronic acid polymer. However, this deficiency is cured by Bennett.
Bennett teaches an 8-arm PEG functionalized with succinimidyl glutarate. The combined molecular weight of the 8 arms may be about 20,000 g/mol [0064]. The that may be used to crosslink hyaluronic acid in the formation of hydrogels [0024].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional PEG crosslinkers used in the production of crosslinked hyaluronic acid hydrogels. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Francis (U.S. Patent Application No. 2018/0161252, publication year: 2018, cited in the IDS filed 11/29/2023).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Francis teaches a microneedle device for application to the skin and may contain and deliver to the skin one or more therapeutic agents [0027]. The microneedles may be formed from or include disulfide crosslinked hyaluronic acid [0038]. The active ingredients delivered to the skin include anti-inflammatory drugs [0058]. In use, the microneedle device is placed against the skin in the target location for which treatment is desired. The microneedles are caused to penetrate the stratum corneum by the application of pressure to the backing layer [0050]. The instant specification defines immunomodulators to include anti-inflammatory drugs (pg. 30 lines 3-5), therefore the Examiner considers the anti-inflammatory drugs taught by Francis to read on the “immunoregulator” limitation of the instant claim. With regards to the “locally regulating an immune response” limitations of instant claim 52, the prior art teaches the same method of contacting a microneedle array comprising a biodegradable hyaluronic acid polymer and an immunoregulator with the skin as claimed and therefore, the application of the microneedle array must also regulate an immune response; the Examiner directs attention to MPEP 2112.01 (I) which states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, a prima facie case of either anticipation or obviousness has been established.”
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Francis doesn’t teach a single embodiment or example meeting all limitation of the invention of claim 52.
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Within the broader scope of Francis all of the limitations of the invention of claim 52 are met. It would have been prima facie obvious for one having ordinary skill in the art to choose the limitations in the instant claims from those disclosed by Francis and arrive at this conclusion because such was contemplated by Francis.
Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Francis (U.S. Patent Application No. 2018/0161252, publication year: 2018, cited in the IDS filed 11/29/2023), as applied to claim 52 above, and further in view of Lunyak (U.S. Patent Application No. 2018/0161373, publication year: 2018).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Francis renders obvious the relevant limitations as described above.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Francis does not teach that the tissue may be the tissues or grafts embraced by the instant claim. However, this deficiency is cured by Lunyak.
Lunyak teaches a microneedle-based system that may be utilized to deliver one or more factors produced by a population of stem cells [0006]. In an embodiment of the invention, any skin disorder may be treated by a composition of factors produced by the factor production units of the invention [0189], including a burn or a condition in need of a skin graft [0006]. The factors can include CCL22 [0187] and TGF-beta 1 and TGF-beta 2 [0186]. The factors may be delivered in combination with other active agents and treatment modalities, including corticosteroids and non-steroidal anti-inflammatory compounds [0177]. The substrate for the factors and compounds may include hyaluronic acid [0230].
Finding of a Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art of filing to apply the microneedle assembly taught by Francis to burned tissue for a skin in need of a skin graft. One would have understood in view of Lunyak that a microneedle assembly comprising hyaluronic acid and an anti-inflammatory compound may be used to treat a burn. It would have been obvious to use the microneedle assembly taught by Francis to treat a burn. One of ordinary skill in the art of filing would have been motivated to utilize the microneedle assembly taught by Francis to treat a burn in order to provide the benefits of the immunomodulatory compounds contained within the assembly to the burned tissue. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Lunyak teaches that a microneedle assembly comprising an anti-inflammatory compound may be used to treat burned skin tissue.
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 34, 36, 40, 42-46, 48-50, and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907.
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace a method of transdermally delivering a therapeutic agent to a subject in need thereof comprising contacting a microneedle array comprising a plurality of microneedles projecting from a substrate with a skin surface of the subject and applying pressure on the microneedle array such that the penetrating tip of each microneedle penetrates the skin surface, thereby releasing the therapeutic agent. The microneedle is a porous microneedle composed of a degradable hyaluronic acid polymer comprising the structure:
PNG
media_image2.png
259
177
media_image2.png
Greyscale
The method further comprises sampling a skin interstitial fluid of the subject wherein the interstitial fluid comprises a biomarker and/or a cell. The therapeutic agent may comprise a cell, a chemokine, a chemotherapeutic, a nucleic acid, a protein, a macromolecule, a nanoparticle, an exosome, a chemical-based drug, or any combination thereof. The disulfide bond of a degradable hyaluronic acid polymer is configured to be cleaved upon exposure to a reducing agent. The reducing agent may include 1mM to 100mM TCEP, glutathione, dithiothreitol, or beta-mercaptoethanol. The claims of the ‘907 application also embrace a PEG crosslinker for crosslinking hyaluronic acid wherein the PEG comprises a succinimidyl functional group. The crosslinker may also comprise a first PEG having a molecular weight of about 40kDa and a second PEG having a molecular weight of about 10kDa, wherein the first PEG and second PEG are at a ratio of about 0:100 wt.% to about 100:0 wt. %. The claims of the ‘907 application also embrace a microneedle array comprising a hyaluronic acid polymer in which each microneedle has a height of about 100-1500µm and a base radius of about 100-1500µm. The claims of the ‘907 application also embrace a microneedle array in which the hyaluronic acid polymer is crosslinked to form a hydrogel. The microneedle array may also comprise a biodegradable substrate comprising a poly(D,L-lactide-co-glycolide) polymer. It is noted that the claims of the ‘907 application are silent with regards to a systemic response rendered by the microneedle assembly and therefore reads on the “does not elicit a systemic response” limitations of instant claim 39.
The claims of the ‘907 application do not disclose the swelling ratio properties as recited in the instant claim 51. However, the invention as claimed is not structurally distinguishable from the disclosure of the claims of the ‘907 application and therefore, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are inherent in the composition taught by the prior art. Since the Patent and Trademark Office does not have the facilities for examining and comparing the claimed composition with that of the prior art, the burden of proof is shifted to the Applicants to show an unobvious distinction between the structural and functional characteristics of the claimed composition and the composition of the prior art; i.e., to prove that the properties are not inherent. See In re Best, 562 F.2d 1252, 195 U.S.P.Q. 430 (CCPA 197) and Ex parte Gray, USPQ 2d 1922 (PTO Bd. Pat. App. & Int.). As recited in MPEP §2112.01 (II): “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
With regards to the “treating a skin disorder” and “locally regulating an immune response” limitations of instant claims 34 and 52, respectively, the prior art teaches the same method of contacting a microneedle array comprising a biodegradable hyaluronic acid polymer and an immunoregulator with the skin as claimed and therefore, the application of the microneedle array must also regulate an immune response and must also treat a skin disorder; the Examiner directs attention to MPEP 2112.01 (I) which states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, a prima facie case of either anticipation or obviousness has been established.”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 35 and 53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907, as applied to claims 34, 36, 40, 42-46, 48-50, and 52, and further in view of Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace the relevant limitations as described above. The claims of the ‘907 application do not teach a method of treating a skin disorder comprising those embraced by the instant claim 35. However, this deficiency is cured by Takada. Takada teaches a method of administering an effective substance for the prevention or treatment of skin aging or treatment of skin scar comprising frit contacting an area affected area with a microneedle assembly then applying a given pressure to insert the microneedles through the skin into the body [0090]. The thread forming polysaccharide of the microneedle assembly may include hyaluronic acid and salts thereof [0072]. The active substance includes all proteins falling within a fibroblast growth factor (FGF) subfamily, including basic fibroblast growth factors with can be used in combination with compounds such as TGFβ [0076]. A target symptom for prevention or treatment using the microneedle assembly includes a burn wound [0020].
It would have been prima facie obvious to one of ordinary skill in the art of filing to utilize the microneedle device embraced by the claims of the ‘907 application in a method of treating a skin disorder. One would have understood in view of Takada that a microneedle assembly comprising hyaluronic acid and an immune modulator may be used in a method of treating a burn wound. It would have been obvious that the microneedle device of the claims of the ‘907 application may also be used in a method of treating a burn wound. One of ordinary skill in the art of filing would have understood that a microneedle assembly comprising hyaluronic acid and an immune modulatory drug is suitable for use in a method of treating a burn wound. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Takada teaches that a microneedle device nearly identical to the microneedle device taught by the claims of the ‘907 application may be used in a method of treating a burn wound. See MPEP 2144.07.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 37 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907, as applied to claims 34, 36, 40, 42-46, 48-50, and 52, and further in view of Pathak (WO 2018/017674, publication year: 2018, cited in the IDS filed 11/29/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace the relevant limitations as described above. The claims of the ‘907 application do not embrace a microneedle assembly in which the cell is a T cell, B cell, natural killer cell, dendritic cell, or macrophage. However, this deficiency is cured by Pathak. Pathak teaches sustained drug and cell delivery using a microneedle array (pg. 1 line 22). The cells for delivery with the microneedle array include mammalian cells such as T cells and other immune cells (pg. 19 line 32). The encapsulated cells provide local or systemic therapeutic benefit (Abstract).
The idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional immunoregulator cells used in microneedle devices. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 38 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907, as applied to claims 34, 36, 40, 42-46, 48-50, and 52, and further in view of Takada (U.S. Patent Application No. 2013/0072902, publication year: 2013, cited in the IDS filed 11/29/2023), Lunyak (U.S. Patent Application No. 2018/0161373, publication year: 2018), and Yantasee (WO 2021/011496, publication date: 1/21/2021, cited in the IDS filed 11/29/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace the relevant limitations as described above. The claims of the ‘907 application do not embrace the chemokines, cytokines, antibodies, or anti-inflammatory agents embraced by the instant claim. However, this deficiency is cured by Takada, Lunyak, and Yantasee.
Takada teaches a method of administering an effective substance for the prevention or treatment of skin aging or treatment of skin scar comprising frit contacting an area affected area with a microneedle assembly then applying a given pressure to insert the microneedles through the skin into the body [0090]. The active substance includes all proteins falling within a fibroblast growth factor (FGF) subfamily, including basic fibroblast growth factors with can be used in combination with compounds such as TGFβ [0076]. Lunyak teaches a microneedle-based system that may be utilized to deliver one or more factors produced by a population of stem cells [0006]. In an embodiment of the invention, any skin disorder may be treated by a composition of factors produced by the factor production units of the invention [0189]. The factors can include CCL22 [0187] and TGF-beta 1 and TGF-beta 2 [0186]. The factors may be delivered in combination with other active agents and treatment modalities, including corticosteroids and non-steroidal anti-inflammatory compounds [0177]. Yantasee teaches an immunotherapeutic construct that can be formulated into a microneedle formulation [0013]. The administration of an immunotherapeutic construct may be combined with a treatment for cancer [0086], including anti-CD52 antibodies ([0109], pg. 26 line 2). The compositions may be used to treat cancer of the skin [0267].
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the drugs of the claims of the ‘907 application and the therapeutics of Takada, Lunyak, and Yanatasee for the treatment of skin disorders via microneedle assembly). See MPEP 2144.06 (II).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 41 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907, as applied to claims 34, 36, 40, 42-46, 48-50, and 52, and further in view of Martell (European Medical Journal, pg. 14-21, publication year: 2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace the relevant limitations as described above. The claims of the ‘907 application do not teach the depletion of an unwanted immune cell by recruiting unwanted cells. However, this deficiency is cured by Martell. Martell teaches that cytokines can recruit cytotoxic T cells, IgG-bearing B cells, macrophages, mast cells, and B cells bearing IgG, IgA and IgE (pg. 17, Adaptive Immune System).
It would have been prima facie obvious to one of ordinary skill in the art of filing that the microneedle assembly embraced by the claims of the ‘907 application may recruit immune cells. One would have understood in view of Martell that an immunomodulator such as a cytokine is able to recruit a wide variety of immune cells. It would have been obvious that the inclusion of such a cytokine in the microneedle assembly taught by the claims of the ‘907 application may also recruit immune cells. One of ordinary skill in the art of filing would have been motivated to recruit unwanted immune cells in order to enhance or ameliorate a local immune response. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because the claims of the ‘907 application teaches that chemokines may be included in the microneedle assembly.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 47 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of copending Application No. 18/278,907, as applied to claims 34, 36, 40, 42-46, 48-50, and 52, and further in view of Bennett (U.S. Patent Application No. 2009/0227689, publication year: 2009).
Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims render obvious the instant claims.
Inter alia, the claims of the ‘907 application embrace the relevant limitations as described above. The claims of the ‘907 application do not teach an 8-arm PEG crosslinking agent. However, this deficiency is cured by Bennett. Bennett teaches an 8-arm PEG functionalized with succinimidyl glutarate. The combined molecular weight of the 8 arms may be about 20,000 g/mol [0064]. The that may be used to crosslink hyaluronic acid in the formation of hydrogels [0024].
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the PEG crosslinkers embraced by the claims of the ‘907 application and the 8-arm PEG crosslinking agent taught by Bennett for the purpose of forming crosslinked hyaluronic acid hydrogels). See MPEP 2144.06 (II).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ANNE MEYERS whose telephone number is (571)272-2271. The examiner can normally be reached Monday-Friday 8am-5pm ET.
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.
ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614