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 Claims
Claims 4-8, 14 and 18-19 are cancelled. Claims 27 is new. Claims 1-3, 9-13, 15-17, 20-26 and 27 are pending and under exam.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 102
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).
The rejection is withdrawn following claim amendments.
Claim Rejections - 35 USC § 103
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).
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).
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).
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).
The rejection is withdrawn following claim amendments
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
Claims 1-2, 10, 12-13, 15-16 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Clark et al (Bioprinting 16 (2019); hereinafter "Clark;" See PTO-892) in view of Murata et al (Sci Rep. 2018 Oct 4; hereinafter "Murata;" See PTO-892 of 10/01/2025.
Regarding claims 1, 2, 12, 27: Clark is directed to use of “a novel thixotropic bioink made from methacrylated collagen I, thiolated hyaluronic acid, and gelatin nanoparticles which is self-supporting and capable of creating large hollow structures through bioprinting.” (See Clark Abstract). The base material of Clark is “made from methacrylated collagen” (See Clark, p.2, col.2, para 2). Clark used a gelatin nanoparticle (GNP) powder and added at 100mg/mL, 125mg/mL and 150mg/mL, concentration to the methacrylated collagen (ColMA). Clark specifically stated that “collagen fibers intermolecularly bonding to the GNP surfaces” enhances mechanical stability. (See Clark Sec 3.1, last para). Clark further disclosed gelatin nanoparticles at ~300nm in diameter (See Clark Sec 3.1, first para). Clark also indicated a method to disperse the GNPs in the hydrogel. (See Clark Sec 2.4, first para). As such Clark taught a collagen containing cell-supporting hydrogel incorporating gelatin nanoparticles having particle size within the claimed range. Clark did not teach gelatin nanoparticles carrying an agent as required by the claim.
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 to have modified the gelatin nanoparticle of Clark to carry a reagent or agent taught by Murata as both references employ gelatin nanoparticles in cell-based biomedical applications and Murata demonstrated that nanospheres can be used as carriers for functional biological agents. Murata taught that cationized gelatin nanospheres provide a nanoparticle based delivery system capable of protecting and delivering the molecular beacon to cells. Applying this known cargo-loading capability to the gelatin nanoparticles of Clark would have provided the nanoparticles with an additional known function, namely delivery of a reagent with a collagen-based cell supporting bioink.
Regarding claim 10: Clark indicated that bioprinting “allows for 3D tissue constructs to be fabricated on demand in a variety of shapes and sizes with multiple combinations of cells by extruding cellularized hydrogels, or “bioinks”, out of syringes, which can be fit with nozzles of different diameters, to create cellularized constructs. These living constructs can be used for 1) therapeutic applications, or 2) novel in vitro models of tissues that more accurately represent the in vivo pathology” (See Clark sec 1, para 1).
Regarding claim 13: Clark taught a method to make a base bioink composition made from methacrylated collagen, gelatin nanoparticle preparation, and GNP-bioink preparation. (See Clark section 2). Clark taught that “[t]he GNP powder was sterilized by dry heating the powder at 100 C for 30min. They were then added, at 100mg/mL, 125mg/mL and 150mg/mL, to the ColMA while it was still in acetic acid solution.” (See Clark 2.4). As such, Clark taught the claimed method.
Regarding claim 15-16: Clark taught culturing HepG2 cells and preparing organoids using their bioink. (See Clark Abstract).
Claims 3, 17, 21-25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Clark et al (Bioprinting 16 (2019); hereinafter "Clark;" See PTO-892) in view of Murata et al (Sci Rep. 2018 Oct 4; hereinafter "Murata;" See PTO-892 of 10/01/2025 and Yamashita et al (US20160121025A1; Published May 5, 2016; hereinafter " Yamashita;" See PTO-892 of 06/16/2026).
Regarding claim 3, 17 and 21-24 and 26: The teachings of Clark in view of Murata are set forth above. Clark in view of Murata 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 to a person of ordinary skill in the art to modify the formed collagen/GNP cell supporting structure of Clark to provide the biocompatible collagen or gelatin material at a surface of a formed body as taught by Yamashita. Both Clark and Yamashita are directed to cell supporting biomaterials employing collagen/gelatin to provide suitable cellular environments. It is also noted that Fig. 3 of Clark discloses a cell-supporting body comprising a base material including collagen and gelatin particles. Clark prepared a bioink comprising methacrylated collagen and gelatin nanoparticles, which is subsequently printed and UV-crosslinked to form three-dimensional cell supporting structures, including structures supporting HepG2 cells. Clark reported that the completed printed structures are sufficiently strong to be removed from the print surface and manipulated by hand and remain intact when submerged under culture conditions. As such, Clark itself taught a cell-supporting body comprising a formed body. A person of ordinary skill in the art would have had a reasonable expectation of success in providing collagen or gelatin containing material at the surface of the formed Clark structure.
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 Clark onto PVA hydrogel substrates.
Claim 9 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Clark et al (Bioprinting 16 (2019); hereinafter "Clark;" See PTO-892) in view of Murata et al (Sci Rep. 2018 Oct 4; hereinafter "Murata;" See PTO-892 of 10/01/2025 and Lu et al (Biomaterials. 2007 Mar; hereinafter “Lu;” See PTO-892).
The teachings of Clark in view of Murata are set forth above. Clark in view of Murata did not specifically teach a 2D shape of a base material. Lu was directed to collagen films “manufactured on a Teflon support to a thickness of 2.470.2mm, comparable to that of native Bruch’s membrane.” (See Lu Abstract). As such Lu demonstrated that collagen can be provided as a thin planar film serving as a cell-supporting substrate. A skilled artisan would have had reason to provide the collagen/GNP composition of Clark in the known planar film configuration of Lu when a planar cell-supporting substrate was desired. Such modification would have been predictable and would not have required a change in the underlying materials or their respective functions.
Conclusion
No claim is free of art.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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, Christopher M. Babic can be reached at 571-272-8507. 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.
/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
