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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/27/2026 has been entered.
Status of Claims
Claims 4-8, 14 and 18-19 are cancelled. Claims 21-26 are new. Claims 1-3, 9-13, 15-17, and 20-26 are pending and under exam.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 112
Claim 8 and 14 were rejected for requiring an introduction rate of gelatin particle. The rejection is withdrawn following cancellation of the claims.
Claims 1-3, 8-10, 13-17, and 19-20 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hwang et al (Biomed Mater Res A. 2016 Apr; hereinafter "Hwang;" See PTO-892).
Claims 25 and 26 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al (Sci Rep (2016); hereinafter "Huang;" See PTO-892).
The rejection is withdrawn following claim amendments and cancellations.
Claim Rejections - 35 USC § 103
Claim 11 was rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al (Biomed Mater Res A. 2016 Apr; hereinafter "Hwang;" See PTO-892) as applied to claim 1 above further in view of Lee et al (Biomaterials. 2012 Oct; hereinafter "Lee;" See PTO-892).
Claim 12 was rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al (Biomed Mater Res A. 2016 Apr; hereinafter "Hwang;" See PTO-892) as applied to claim 1 above further in view of Murata et al (Sci Rep. 2018 Oct 4; hereinafter "Murata;" See PTO-892).
Claim 21 and 23 were rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al (Biomed Mater Res A. 2016 Apr; hereinafter "Hwang;" See PTO-892) as applied to claim 1 above further in view of Nyugen et al (Biomaterials Science; Jun 27, 2020; Hereinafter “Nyugen;” See PTO-892).
Claims 22 and 24 were rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al (Biomed Mater Res A. 2016 Apr; hereinafter "Hwang;" See PTO-892) as applied to claim 1 above further in view of Nakamura et al (Tissue Eng Part C Methods. 2019 Jun; Hereinafter “Nakamura;” See PTO-892).
The rejection is withdrawn following claim amendments and cancellations.
NEW REJECTIONS
Claim Rejections - 35 USC § 102
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 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 1-2, 9-10, 15-17 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Binulal et al (Biomed Mater. 2012 Dec; hereinafter "Binulal;" See PTO-892).
Regarding claim 1-2, 15-17 and 20: Binulal disclosed “[n]anofibrous semi-synthetic polymeric nanocomposite scaffolds were engineered by incorporating a maximum of 15 wt% biopolymeric gelatin nanoparticles (nGs) into the synthetic polymer poly(ε-caprolactone) (PCL) prior to electrospinning.” (See Binulal Abstract). Binulal disclosed that in their system, “gelatin is incorporated as distinct nanoparticle within the PCL nanofibers (PCL_nG) rather than blended together with PCL using a common solvent” (See Binulal p.2, col. 1, para 3). Binulal indicated regarding the gelatin particles that “[s]pherical particles of size ∼100 nm were obtained in our method, as evident from both the SEM and AFM images shown in figures 1(A) and (B), respectively. Dynamic light scattering measurements indicated that the suspended particles were in a range of 50–150 nm in size (figure 1(C)).” (See Binulal p. 4, col. 2, last para). It is also noted that Binulal noted adhesion and growth of hMSC on nanofibrous scaffolds (See Figure 9). PCL nanofibers read on the biocompatible, base material. As such every element of the claim is anticipated.
Regarding claims 9-10: Binulal disclosed that “In our experiments, PCL_nG scaffolds showed discontinuous nanofibers in the scaffolds within two to four
weeks (figure 7), but they maintained the physical dimensions and morphology of the nanofibrous scaffolds. However, as figure 6 indicates, the scaffolds had larger pore sizes after degradation, which may be beneficial for cellular infiltration into the scaffolds.” (See Binulal p. 8; col. 1-2, para 2). The physical dimensions read on 3D base material. Additionally, Figure 5 showing wettability of the nanofibrous scaffolds shows a 2D cross section of the nanofiber scaffolds. As such the technique recited in Binulal reads on generation of 2D scaffolds.
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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Binulal et al (Biomed Mater. 2012 Dec; hereinafter "Binulal;" See PTO-892) in view of Attarwala et al (Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018 Mar; hereinafter "Attarwala;" See PTO-892).
Regarding claim 11: The teachings of Binulal are set forth above. Binulal disclosed gelatin nanoparticles incorporated into electrospun PCL scaffolds for structural and bioactive purposes. However, the nanoparticles are used in their native form as biomaterial components rather than as carrier for any reagents or agents. Attarwala is directed to use of gelatin nanoparticles in gene delivery systems. Attarwala taught that “nucleic acids were first encapsulated within type-B gelatin nanoparticles, followed by encapsulation of gelatin nanoparticles within poly(ε-caprolactone) (PCL) based microspheres” (See Attarwala; p. 4; first para). Attarwala demonstrated that gelatin nanoparticles-in-microsphere oral systems in which nucleic-acid-loaded-gelatin nanoparticles are incorporated into PCL-based materials.
It would have been obvious to one of ordinary skill in the art to modify the gelatin nanoparticles of Binulal to carry a reagent or agent as taught by Attarwala. Because both references employ gelatin nanoparticles in conjunction with PCL-based structures for biomedical applications, the modification would have represented the predictable use of a known carrier function of gelatin nanoparticles within the known scaffold system of Binulal.
Accordingly, the combination of Binulal and Attarwala teaches or renders obvious a cell-supporting body wherein the gelatin particles carry a reagent or an agent as recited in claim 11.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Binulal et al (Biomed Mater. 2012 Dec; hereinafter "Binulal;" See PTO-892) in view of Attarwala et al (Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018 Mar; hereinafter "Attarwala;" See PTO-892); further in view of Murata et al (Sci Rep. 2018 Oct 4; hereinafter "Murata;" See PTO-892 of 10/01/2025).
Regarding claim 12: The teachings of Binulal in view of Attarwala are set forth above. The cited prior art do not teach a molecular beacon containing gelatin nanoparticles as required by the instant claims. However, Murata taught preparation of cationized gelatin nanospheres (cGNS) incorporating a molecular beacon (MB), and visualize cellular apoptosis. (See Murata Abstract). Murata taught that the cationized gelatin and MB are electrostatically interacted to each other, and the negative charge of MB may be shielded by the positive charge of cationized gelatin. Murata indicated that cGNS is advantageous over PLGA nanoparticles because of the “simplicity of controlling degradability and the consequent controllability of nucleic acids release profile. The controlled release of nucleic acids regulated by the gelatin degradation have been applied extracellularly and intracellularly. Based on these reports, we strongly believe that cGNS enable the sustained release of MB, leading to the prolonged and controlled visualization of cellular biological functions.” (See Murata p. 7, para 2).
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the molecular beacon containing gelatin nanoparticles-containing scaffold of Binulal , as modified in view of Attarwala in order to provide the known agent carried by gelatin nanoparticles for another. The substitution of one agent carried by gelatin nanoparticles for another represents predictable use of prior-art elements according to their established functions.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Binulal et al (Biomed Mater. 2012 Dec; hereinafter "Binulal;" See PTO-892) in view of Yuan et al (Biointerphases. 2012 Dec; hereinafter "Yuan;" See PTO-892); further in view of Bohidar et al (J. Chem. Phys.; (1993); hereinafter "Bohidar;" See PTO-892 of 10/01/2025).
Regarding claim 13: The teachings of Binulal are set forth above. Binulal did not teach a method of manufacturing a cell-supporting body by immobilizing solated gelatin particle on PCL base material. However, Yuan taught a preformed PCL substrate that is surface functionalized and subsequently incubating gelatin containing solution, resulting in immobilization of gelatin on the surface of PCL substrate. Yuan further disclosed that unbound gelatin is removed by washing, thereby retaining immobilized gelatin on the base material. (See Yuan Sec 2.5 and 3.2). Yuan thus taught post-fabrication application of gelatin to a PCL-base material and retention/immobilization of gelatin thereon for improving biological performance. It is noted that Yuan did not explicitly teach arriving at solated gelatin by heating gelatin particles. It is however known that gelatin is a thermoreversible biopolymer that undergoes sol-gel transition depending on the temperature. For example, Bohidar taught that “[g]elatin, which is denatured collagen, undergoes thermoreversible gelation in aqueous solution when the protein concentration is higher than typically 2%-3% (wlw). Usually a hot sol of gelatin is prepared at 50 ·C and is allowed to cool down to O·C by storing the preparation in a constant low temperature bath. The gelation occurs at T g-30 ·C. The gelatin monomers predominantly present in the initial preparation have a random coil conformation.” (See Bohidar p. 8970, col. 1, para 1).
In view of this known property a person of ordinary skill in the art would have recognized that thermal processing compositions on a polymeric substrate would result in predictable phase behavior and stabilization of gelatin-based coatings. As such it would have been obvious to apply heat treatment to process gelatin-containing coatings on PCL substrate to modulate physical state and enhance retention/organization of gelatin on the surface, particularly in view of Yuan’s teaching of gelatin immobilization of PCL and Binulal’s disclosure of gelatin nanoparticles.
Claims 3 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Binulal et al (Biomed Mater. 2012 Dec; hereinafter "Binulal;" See PTO-892) in view of Yamashita et al (US20160121025A1; Published May 5, 2016; hereinafter " Yamashita;" See PTO-892) and Bohidar et al (J. Chem. Phys.; (1993); hereinafter "Bohidar;" See PTO-892 of 10/01/2025).
Regarding claim 3 and 21-24 and 26: The teachings of Binulal in view of Bohidar are set forth above. Binulal did not specifically teach use of a cell-culture plate as a base material and immobilized gelatin particles in a region of the base material on which the biocompatible substance is attached, wherein the biocompatible substance is gelatin. Yamashita disclosed laminating cell sheets using gelatin hydrogel particles. (See Yamashita claim 23). Yamashita disclosed that gelatin hydrogel particles may be dispersed in physiological solutions and applied onto the surface of a cell sheet, where they remain localized and become integrated into multilayer cell constructs during incubation at 37 C. (See Yamashita [0108]). Yamashita further taught that gelatin hydrogel particles are used in amounts sufficient to uniformly or regionally coat biological surfaces and support cell adhesion and tissue formation. Additionally Yamashita expressly taught that cardiac cell sheet produced in a 24-well plate was placed and left flat on a gelatin-coated culture dish. The medium was then aspirated to settle the culture dish and the sheet. Subsequently, another cardiac cell sheet was added with the differentiation medium and layered on the cardiac cell sheet treated with the gelatin hydrogel particles. The medium was then removed. The same operations were repeated to get 5 cardiac cell sheets layered. (See Yamashita [0121]). As such the culture dish reads on the base material. The gelatin hydrogel particle is interpreted to read on the biocompatible substance.
It would have been obvious for a person of ordinary skill in the art to modify the gelatin-based particulate system of Binulal by applying gelatin particles to a conventional cell-supporting substrate such as a cell-culture plate (as required by claim 3), as taught by Yamashita. Yamashita explicitly taught the application of gelatin-hydrogel particles onto biological surfaces where they remain localized during incubation and contribute to stable multilayer constructs. Given that hydrogel particles are added between stacked cell sheets, and gelatin sheets are intentionally used to control cell sheet stacking, it is pointed out that gelatin-particles are designed to be placed at interfaces and remain in position to mediate layering. It would have been obvious that gelatin nanoparticles applied to a gelatin-coated or cell-supporting substrate would become immobilized on surface in a predictable manner.
Regarding claim 25: Yamashita suggested the use of polyvinyl alcohol as a hydrogel manufacturing material. (See Yamashita [0050]). In view of Yamashita’s disclosure of hydrogel-based substrates for biological assembly, it would have been obvious to apply gelatin nanoparticles of Binulal onto PVA hydrogel substrates.
Conclusion
No claim is free of art.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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