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 .
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 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.
Priority
The instant application 18/162,387, filed 01/31/2023, claims domestic benefit of U.S. Provisional Patent Application No. 63/304,800, filed 01/31/2022.
Status of Application and Claims
Claims 1-20 are currently pending.
Election/Restrictions
Applicant’s election of Group I, claims 1-11 and 16-20 in the reply filed on 08/11/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The restriction requirement is deemed proper and is therefore made FINAL.
Claims 12-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/11/2025.
Claims 1-11 and 16-20 are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/28/2025 and 05/08/2025 are in compliance with the provisions of 37 CFR 1.97Accordingly, the information disclosure statement has been considered by the examiner, excepted where noted. It is noted that both IDS documents 04/28 and 05/08 appear to be duplicates. The Foreign Patent Documents citations CN 113248736 A and CN 112587500 A (cited in both IDS submissions) were not considered by the Examiner because no original copy of each foreign patent document was provided, only English translations were provided.
Claim Interpretation
Claims 7 and 19 recite that the ROS-scavenging hydrogel comprises copolymerized NIPAAm, HEMA, and “4-(acryloyloxymethyl)-phenylboronic acid pinacol ester.” This broad recitation is going to be interpreted to mean that the hydrogel comprises any copolymer containing copolymerized NIPAAm, HEMA, and “4-(acryloyloxymethyl)- phenylboronic acid pinacol ester” units. “4-(acryloyloxymethyl)-phenylboronic acid pinacol ester” is not a compound name commonly recited in prior art literature. The instant specification makes reference to figure 3B of its disclosure when referring to copolymerization of NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester (see instant specification p. 33 lines 7-9). Figure 3B of the instant disclosure depicts a synthetic scheme as follows (drawings submitted on 01/31/2023, p. 18/48):
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The Examiner interprets the rightmost molecule before the reaction arrow depicted in the scheme to be the structure for the molecule that the Applicants are attempting to name “4-(acryloyloxymethyl)-phenylboronic acid pinacol ester.” The Examiner will interpret any claim recitation of “4-(acryloyloxymethyl)-phenylboronic acid pinacol ester” to mean any compound having the chemical structure of the compound closest to the reaction arrow depicted in Figure 3B above.
Claims 9-11 are ultimately dependent on claim 1, which recites “a composition for sustained release of oxygen to a tissue” in its preamble before reciting all limitations of the claimed composition in the body of the claim. Claims 9-11 describe the tissue recited in claim 1’s preamble in further detail, saying the tissue comprises an ischemic tissue (claim 9), the ischemic tissue comprises a tissue associated with an ischemic condition selected from diabetes, peripheral artery disease, and coronary heart disease (claim 10), and the ischemic tissue comprises a chronic diabetic wound bed (claim 11). Per MPEP 2111.02 (II), if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020; emphasis added). The body of claim 1 fully and intrinsically sets forth all of the limitations of the claimed composition, and therefore the preamble of claim 1 is being interpreted as an intended use recitation of the composition being claimed which is not considered a limitation of significance to the claim. Because claims 9-11 continue to merely recite the intended use of the composition of claim 1, the recitations of claims 9-11 are being interpreted as intended uses which are not limitations and do not provide significance to the claim.
Claims 16-20 are written towards a kit comprising a composition of at least one core-shell oxygen release microsphere (ORM), wherein the core comprises a water-soluble polymer-reactive oxygen species (ROS) complex and the shell comprises a biodegradable polymer conjugated to a ROS-scavenging enzyme. The instant specification does not specifically define the term “kit,” therefore the broadest reasonable interpretation for the term “kit” will be applied when interpreting the preamble of instant claims 16-20; as defined by Merriam Webster, a kit is defined as a packaged collection of related material; therefore, the preamble of claims 16-20’s recitation of a “kit” will be interpreted to mean any packaged or contained collection comprising the composition. Additionally, because the kit is recited in the preamble of the claim, and the body of the claim fully and intrinsically sets forth all of the limitations of the claimed invention while not providing any substantial information about the “kit” itself, then the preamble is not considered a limitation and is of no significance to claim construction.
Claim 20 is dependent upon claim 16, and recites the “kit of claim 16, wherein the kit is used to treat a diabetic wound.” This recitation is being interpreted as an intended use of the kit claimed in claim 16.
Claim Objections
Claims 9-11 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1, because their intended use limitations only serve to limit the preamble of claim 1, and the composition of the claims is not substantially different from the composition of claim 1. Claim 16 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1, because the “kit” recited in the preamble is not considered a limitation and is of no significance to claim construction, whereas the composition in the body of the claim is identical to the composition of claim 1. For the same reasons, claim 17 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 5, claim 18 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 6, and claim 19 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. Claim 20 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 16, because the kit’s intended use limitation provides no substantial difference compared to the kit of claim 16. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 16 is objected to because of the following informalities: claim 16 line 1 recites “a kit comprising the composition of at least one core-shell oxygen release microsphere…” (emphasis added). Because claim 16 is an independent claim, this should instead recite “a kit comprising a composition of at least one core-shell oxygen release microsphere…” in line 1 (emphasis added). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 16 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention.
The specification discloses a specific core-shell ORM with a core comprising a hydrogen peroxide-PVP complex and a shell comprising poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-co-acrylate- oligolactide-co-Nacryloxysuccinimide) conjugated to catalase, and further discloses that the ORM is contained within a hydrogel comprising copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester; these disclosures satisfy the written description and enablement provisions of 35 USC 112, first paragraph: However, claims 1 and 16 are directed to encompass a core-shell ORM comprising any water-soluble polymer and any reactive oxygen species complexed in the core, as well as any biodegradable polymer conjugated to any ROS-scavenging enzyme in the shell, and claims 6 and 18 are directed to encompass any ROS-scavenging hydrogel (absent any further descriptors); these broad genera only correspond in some undefined way to the specifically instantly disclosed core-shell ORM with a core comprising a hydrogen peroxide-PVP complex and a shell comprising poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-co-acrylate- oligolactide-co-Nacryloxysuccinimide) conjugated to catalase, as well as the specifically instantly disclosed hydrogel comprising copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester. Only the specifically disclosed core-shell ORM comprising a PVP, H2O-2, poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-co-acrylate- oligolactide-co-Nacryloxysuccinimide), and catalase, and only the specifically disclosed hydrogel comprising copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester meet the written description provision of 35 USC § 112, first paragraph. The broad genera of “water-soluble polymer,” “reactive oxygen species,” “biodegradable polymer,” “ROS-scavenging enzyme,” and “ROS-scavenging hydrogel” however, do not meet the written description and enablement provisions due to a lack of specific chemical structural information for these components. Each genus of “water-soluble polymer,” “reactive oxygen species,” “biodegradable polymer,” “ROS-scavenging enzyme,” and “ROS-scavenging hydrogel” are highly variable and encompass a myriad of possibilities. The specification provides no guidance as to determine specific examples, besides the PVP, H2O-2, poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-co-acrylate- oligolactide-co-Nacryloxysuccinimide), catalase, and copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester which, respectively, fulfill each genus description. The specification provides insufficient written description to support each genus encompassed by the claims.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of the above specifically disclosed species, the skilled artisan cannot envision the detailed chemical structures of the encompassed species for each genus. Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Therefore, only the above chemically and structurally defined species, but not the full breadth of the claimed genera in claims 1, 6, 16, and 18 meet the written description provision of 35 USC § 112, first paragraph. The species specifically disclosed are not representative of the genera because the genera are highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9-11 and 20 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As addressed in the Claim Interpretation section supra, claims 9-11 serve only to further limit the preamble of claim 1, which is an intended use limitation of the composition of claim 1. Because claims 9-11 merely recite further limitations of the intended use of the composition of claim 1, the limitations of claims 9-11 are being interpreted as intended use limitations. These claims provide no further structural or functional limitations regarding the composition claimed in the body of instant claim 1, and therefore, these claims fail to further limit the subject matter of the claim(s) upon which they depend. Similarly, claim 20 is dependent upon claim 16, and recites the “kit of claim 16, wherein the kit is used to treat a diabetic wound.” This recitation is being interpreted as an intended use of the kit claimed in claim 16. Because claim 20 recites only an intended use of the kit of claim 16, claim 20 fails to provide further structural or functional limitations for the kit, and therefore, claim 20 fails to further limit the subject matter of claim 16. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 9-11, 16-17 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guan, Y. et al. (2020). "Photoluminescent oxygen-release microspheres to image the oxygen release process in vivo." Acta Biomaterialia, 115, 333-342 (cited in PTO-892 accompanying this action).
Guan teaches oxygen-release microspheres (ORMs) wherein a complex of polyvinylpyrrolidone (PVP), H2O2 and a fluorescent drug hypericin (HYP) are used as core, and poly(N-isopropylacrylamide-co-acrylate-oligolactide-co-hydroxyethyl methacrylate-co-N-acryloxysuccinimide) conjugated with catalase is used as shell (Abstract). Guan teaches the abbreviation for this shell polymer is poly(NIPAAm-co-AOLA-co-HEMA-co-NAS) (abbreviated as PNAHN) (p. 335 “2.2. Polymer synthesis” lines 7-9). Guan teaches the hydrogel poly(NIPAAm-co-AOLA-co-HEMA) (abbreviated PNAH) is used to deliver the microspheres into tissues (p. 335 “2.2. Polymer synthesis” lines 16-20). Guan teaches 50 mg/mL of microspheres and 2 million/mL of MSCs are mixed with 6 wt % PNAH hydrogel to generate a gel, and 100 μL of 6 wt% PNAH hydrogel solution with 50 mg/mL microspheres are injected into thigh muscles of 8-week-old nude mice (p. 336 “2.7. Effect of oxygen release on cell survival under hypoxia;” “2.8. Injection of oxygen-release microspheres, MSCs, and hydrogel into thigh muscles”). Guan teaches sustained oxygen release is achieved during the gradual degradation of the shell of the ORM (p. 340 R. Col. final para). Guan teaches future delivery of the oxygen-release microspheres in combination with mesenchymal stem cells (MSCs) into ischemic tissues such as ischemic limb and heart in order to evaluate in vivo oxygen release, MSC survival, and tissue regeneration (p. 341 L. Col. 1st para). The gel composition comprising the PNAH hydrogel and the ORM having a core comprising a complex of H2O2 and PVP and a shell comprising poly(NIPAAm-co-AOLA-co-HEMA-co-NAS) conjugated to catalase reads on a composition for sustained release of oxygen to a tissue comprising ischemic tissue, wherein the composition comprises at least one core-shell ORM wherein the core comprises a water-soluble polymer-reactive oxygen species (ROS) complex and the shell comprises a biodegradable polymer conjugated to a ROS- scavenging enzyme, more specifically wherein the ROS comprises H2O2, the water-soluble polymer comprises PVP, the biodegradable polymer comprises poly(NIPAAm-co-HEMA-co-AOLA-co-NAS), and the ROS-scavenging enzyme comprises catalase, as recited in instant claims 1-5 and 9.
Furthermore, as addressed in the Claim Interpretation section supra, the intended use recitations in the preamble of claim 1 and claims 9-11 provide no further limitations to the claimed composition and do not provide significance to the claimed composition, and thus the composition of Guan reads on the composition of claims 9-11. Similarly, as addressed in the Claim Interpretation section, the preamble of claim 16 recites a kit comprising a composition of at least one core-shell oxygen release microsphere (ORM), wherein the core comprises a water-soluble polymer-reactive oxygen species (ROS) complex and the shell comprises a biodegradable polymer conjugated to a ROS-scavenging enzyme. Because Guan fully teaches the claimed ORM-containing composition, and because the recitation of “kit” in the preamble of the claims 16-17 provide no further limitations to the claimed composition and the recitation of the intended use in claim 20 does not further limit the claimed composition, Guan also reads on claims 16, 17 and 20.
Therefore, Guan anticipates claims 1-5, 9-11, 16-17 and 20.
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.
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 1-11 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Guan, Y. et al. (2020). "Photoluminescent oxygen-release microspheres to image the oxygen release process in vivo." Acta Biomaterialia, 115, 333-342 (cited in PTO-892 accompanying this action) in view of Niu, H. (2018). "Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis." The Ohio State University, PhD Dissertation. OhioLink, https://etd.ohiolink.edu/acprod/odb_etd/ws/send_file/send?accession=osu1543406270126261&disposition=inline (cited in PTO-892 accompanying this action).
The teachings of Guan, as they pertain to instant claims 1-5, 9-11, 16-17 and 20, are addressed in the 35 U.S.C. 102 anticipation rejection supra. It is reiterated that Guan teaches a hydrogel of its gel composition which comprises poly(NIPAAm-co-AOLA-co-HEMA) (abbreviated PNAH) (p. 335 “2.2. Polymer synthesis” lines 16-20). Guan teaches that in general, when delivering transplanted cells, long-term survival of the transplanted cells remains a problem, because the low oxygen environment compromises normal cell metabolism; to address the above hurdles, one of the strategies is to use hydrogels capable of releasing oxygen and will enhance cell-matrix interaction to increase cell survival (p. 334 L. Col. 1st para).
Guan differs from the instantly claimed invention in that it fails to teach the hydrogel of its composition is a ROS-scavenging hydrogel, as recited in claims 6 and 18; thus, Guan fails to teach the ROS-scavenging hydrogel comprises copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester, and recited in claims 7 and 19, and further fails to claim the hydrogel comprises at least one of a thermosensitive hydrogel, an injectable hydrogel, and any combination thereof, as recited in instant claim 8. Additionally, despite the lack of patentable weight given to the following claim recitations (see Claim Interpretation section supra), for the purposes of compact prosecution the following also applies: Guan fails to explicitly teach that the composition is used for sustained release of oxygen to ischemic tissue comprising a tissue associated with an ischemic condition selected from diabetes, peripheral artery disease, and coronary heart disease, more specifically a chronic diabetic wound bed, as recited in instant claims 10-11. Guan also fails to explicitly teach a “kit” (interpreted as packaged collection) comprising the composition of the core-shell ORM, and a ROS-scavenging hydrogel, as recited in instant claims 16-19, and that the kit is used to treat diabetic wound, as recited in instant claim 20.
Niu teaches a dual-responsive hydrogel system for application in tissue engineering which is injectable and capable of ROS sensitivity, thermosensitivity, and growth and proliferation of MSCs (pp. 134-135 “3.5 Conclusion”). Niu teaches the hydrogel is used in wound healing for diabetes and improves cell survival by scavenging ROS content under ischemia; furthermore, the hydrogel is biocompatible and non-toxic in vivo (p. 30 final para). Niu teaches the hydrogels provide as a reliable carrier for treating the remodeling phase of chronic wounds (p. 133-134 bridging para).
Niu teaches the hydrogel contains poly(NIPAAm-co-HEMA-co-NAS-co-AAcPB) (abbreviated PNHNA), which is copolymerized NIPAAm, HEMA, AAcPB, and NAS (p. 111 “3.2.3 Synthesis of poly(NIPAAm-co-HEMA-co-NAS-co-AAcPB”; p. 113 “3.2.5 Characterization and physical properties of PNHNA hydrogels”; p. 115 1st sentence). Niu teaches that “AAcPB” has the following chemical structure (p. 111 Figure 3.1):
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The Examiner notes that Niu’s AAcPB has the same chemical structure as the instantly claimed “4-(acryloyloxymethyl)-phenylboronic acid pinacol ester” (see Claim Interpretation section supra). Therefore, Niu’s hydrogel containing copolymer of NIPAAm, HEMA, AAcPB and NAS reads on a ROS-scavenging hydrogel comprising copolymerized NIPAAm, HEMA, and 4-(acryloyloxymethyl)-phenylboronic acid pinacol ester.
Niu teaches MSCs encapsulated in the PNHNA hydrogel with H2O2 are formed by adding a total of 200 μL PNHNA hydrogel solution to a tube, mixing with 8 million/mL MSCs and incubating to form a gel, before further addition of cell culture medium containing H2O2 (100 μM) (p. 120 “3.2.9 MSCs encapsulated in APLA and PNHNA hydrogels with H2O2”). Niu teaches that more MSC cell death occurs in hydrogel without the presence of AAcPB in the copolymer of the hydrogel, whereas MSCs continue to proliferate after 7 days when encapsulated in PNHNA hydrogels under H2O2 (pp. 127-128 bridging para).
Niu teaches injectability of the PNHNA hydrogel is excellent via 26G needle with 1 mL syringe commonly used for animal surgeries (pp. 125-126 bridging para). Niu teaches injection of the PNHNA hydrogel into wounds of diabetic mice models, and demonstrates accelerated healing with wound closure rates reaching 60% after 10 days, which is significantly higher than groups without treatment (p. 129 “3.3.9 In vivo wound healing using db/+ and db/db mice”).
Regarding claims 6-8 and 18-19, it would have been prima facie obvious, before the effective filing date of the instantly claimed invention, to substitute Guan’s poly(NIPAAm-co-AOLA-co-HEMA) (PNAH) hydrogel (used to deliver the ORMs and MSCs to ischemic tissue) with Niu’s ROS-scavenging, injectable hydrogel containing poly(NIPAAm-co-HEMA-co-NAS-co-AAcPB) (PNHNA), and arrive at the instantly claimed invention. The ordinarily skilled artisan would have been motivated to perform this substitution based on the many disclosed benefits of the hydrogel taught by Niu, which include its ROS sensitivity, thermosensitivity, capabilities toward growth and proliferation of MSCs, improval of cell survival under ischemic conditions, biocompatibility, non-toxicity, and acceleration of wound healing rates. The ordinarily skilled artisan would have a reasonable expectation of success performing this substitution because Guan teaches the PNAH hydrogel for carrying the ORMs and MSCs comprises a similar copolymer to the copolymer of Niu PNHNA, including at least its NIPAAm and HEMA units; additionally, the hydrogels are formed using similar gelation methods when incorporating MSCs; therefore, the ordinarily skilled artisan would expect successful gel formation using the PNHNA hydrogel when encapsulating at least the MSCs taught by Guan. Additionally, there is no indication in the prior art that the ORMs of Guan would be incompatible with Niu’s PNHNA, which is a highly similar hydrogel to the PNAH hydrogel that is demonstrably compatible with Guan’s ORMs.
Regarding claims 10-11, it would have been prima facie obvious, before the effective filing date of the instantly claimed invention, for a person having ordinary skill in the art to use the ORM- and MSC-containing hydrogel rendered obvious by the combined teachings of Guan and Niu to supply oxygen to chronic diabetic wound bed ischemic tissue, and arrive at the instantly claimed invention. The ordinarily skilled artisan would have been motivated to do so because Guan directly suggests delivery of the ORMs and MSCs encapsulated by hydrogel into ischemic tissues for oxygen release and wound healing, and Niu teaches that diabetic wounds, particularly chronic ones, are ischemic tissues treatable by its hydrogel. The ordinarily skilled artisan would have a reasonable expectation of success using the ORM- and MSC-containing hydrogel rendered obvious by the combination of Guan and Niu to supply oxygen to chronic diabetic wound bed ischemic tissue because both teachings are used for ischemic wound treatment, and a simple combination of elements from each teaching would not appear to the ordinarily skilled artisan to hinder their effects on ischemic diabetic wound treatment.
Regarding claims 16-20, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the claimed invention, to use a syringe to contain the ORM- and MSC-containing hydrogel rendered obvious by the combined teachings of Guan and Niu, and use the syringe containing the obvious ORM- and MSC-containing hydrogel to treat a diabetic wound, and arrive at the instantly claimed invention (see Claim Interpretation supra regarding the interpretation of the term “kit” meaning any package or container). The ordinarily skilled artisan would have been motivated to do so because Niu teaches its hydrogel is injectable for facilitating diabetic wound healing in mice, and injects the hydrogel using syringe; therefore, in order to facilitate diabetic wound healing using the obvious ORM- and MSC-containing hydrogel, the ordinarily skilled artisan would seek to follow Niu’s syringe injection method for the treatment of diabetic wounds using the ORM- and MSC-containing hydrogel. The ordinarily skilled artisan would have a reasonable expectation of success because Niu teaches its hydrogel is injectable, and Guan also teaches its combination of ORM and MSC within hydrogel to be injectable into mice; therefore, all individual components are injectable and the ordinarily skilled artisan would find no reason to doubt the combination of the ORM, MSC and hydrogel in a syringe for injection would result in an uninjectable composition.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia Marie Taylor whose telephone number is (571)272-5239. The examiner can normally be reached Monday-Friday 8 am - 4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at (571) 272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SOPHIA MARIE TAYLOR/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616