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 .
Claim Status
1. The amendment filed 07/03/2025 has been entered. Claims 1, 3, 5, 6, and 9 remain pending and are under consideration. Claim 1 has been amended to delete “glycine-arginine-glycine-aspartate”.
Priority
2. This application claims the benefit of priority to Taiwan Patent Application No. 109130694, filed on September 8, 2020.
3. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Withdrawn Claim Rejections
4. The rejection of claims 1 and 3 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to delete “glycine-arginine-glycine-aspartate”.
5. The rejection of claim 6 is rejected under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to the claim.
6. The rejection of claims 1, 5, 6, and 9 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to delete “glycine-arginine-glycine-aspartate”.
Rejections Necessitated by Amendments
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.
7. Claim(s) 1, 3, 5, 6, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Han (WO2007064152A1; Filed 11/29/2006; Published 06/07/2007), hereinafter Han which is cited on the IDS filed 08/27/2021 in view of Liu (CN102626521A; previously cited), in view of Choi (Choi BG, et. al. Macromolecules 2011, 44, 7, 2269–2275; previously cited), hereinafter Choi. A machine translation of CN102626521A has been provided. The translation was performed on April 10, 2024 of pages 1 - 11 of the original document.
Regarding “a cell culture auxiliary agent comprising a structural formula” of P-L-S-L-P of claims 1 and 5, Han teaches a hydrogel comprising Formula 1:
PNG
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341
1019
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Greyscale
where PEO-PPO-PEO is the substrate(“polyoxyethylene polyoxypropylene ether block copolymer” of claim 1 and 5), the linker is an anhydride META, and R is a biologically active material that is the peptide YIGSR or IKVAV or REDV or RNIAEIIKDA or LDV or PDSGR (“peptide” of claim 1 and 5) (page 3, line 1; page 5, lines 11 – 18; page 6, lines 5 – 15; page 12, Example 3; page 13 – 14; page 22, lines 15 - 20). Han teaches in Reaction Scheme 1 on page 9 that the anhydride META is a linker between the substrate F127 and the peptides represented as R and thus the hydrogel has the generic formula Peptide-META-F127-META-Peptide. Han does not teach “maleic anhydride” of claims 1 and 5. Han teaches cell culture with the hydrogel at 20% by weight (“cell culture medium” of claim 5) (page 10, lines 18 – 20) but does not teach 0.05 – 0.5 wt% of claim 5.
Han does not teach “maleic anhydride” of claims 1, 3, 5, and 9 or a cell culture medium comprising “0.05 – 0.5 wt%” of hydrogel of claim 5 or “99.5 – 99.95 wt%” of a cell culture solution of claim 6. However, Han teaches the hydrogel comprising the peptide YIGSR exhibited an improvement of approximately 80% in cell affinity for proliferation of vascular cells compared to conventional F127 (page 13, lines 10 – 12); the hydrogel comprising the peptide IKVAV exhibited an improvement of approximately 90% in cell affinity of nerve cells compared to F127 (page 14, lines 2 – 5); the hydrogel comprising the peptide REDV exhibited an improvement of approximately 80% in cell affinity for intravascular cells compared to F127 (page 14, lines 8 – 22). Han teaches tissue engineering techniques using hydrogels include culturing cells separated from a tissue extracted from a patient’s body in a hydrogel and then injecting the cell-hydrogel into the human body (page 2, lines 4 – 5). Han teaches for studying tissue engineering, it is important to prepare thermosensitive hydrogels that can be converted to a gel at around the body temperature and that are similar to tissues of a living body (page 2, lines 17 – 19). Han teaches F127 of Pluronics are approved by the U.S. FDA as materials that can be injected into the human body but there has been no example of chemically coupling biologically active materials to F127 (page 3, lines 11 – 13; page 4, lines 4 – 6). Han teaches a biologically active material includes a ligand peptide having cell affinity including RGD, REDV, LDV, YIGSR, PDSGR, IKVAV, RNIAEIIKDA (page 4, lines 6 – 15). Han teaches it has been known that RGD and PDSGR enhance adhesion of almost all cells, REDV and LDV enhance proliferation of vascular endotheliocytes, YIGSR enhances proliferation of vascular cells, and IKVAV and RNIAEIIKDA enhance proliferation of nerve cells (page 4, lines 15 – 18). Han also teaches the “R” in Formula 1 can be growth factors such as TGF-β or EGF or NGF or VEGF (page 15 – 18). Han teaches 4-META has been used as a dental adhesive and has no toxicity and a relatively excellent mechanical property (page 7, lines 5 – 7). Han teaches 4-META or 2-META has a double bond at one end so as to enable polymerization and an anhydride group at the other end capable of being converted to a carboxyl group which can be used to couple a biologically active material (page 7, lines 7 – 10).
Regarding maleic anhydride of claims 1, 3, 5, and 9, Liu teaches F127 comprising a peptide or growth factor or drug where the peptide or growth factor are attached to F127 using an anhydride that is maleic anhydride (page 1; page 4; page 7, Example 3; page 8, para. 1 – 2). Liu does not teach cell culture medium comprising “0.05 – 0.5 wt%” of hydrogel of claim 5 or “99.5 – 99.95 wt%” of a cell culture solution of claim 6. One would have been motivated to combine the teachings of Han and Liu because both teach coupling a molecule to F127 using anhydrides.
Regarding culture medium comprising “0.05 – 0.5 wt%” of hydrogel of claim 5 or “99.5 – 99.95 wt%” of a cell culture solution of claim 6, Choi teaches a cell culture medium comprising a F127 block polymer comprising a linker and peptide where the peptide block copolymer is 0.1 wt% and the cell culture solution(DMEM) is 99% (Table 1; Figure 1; page 2270, right col. paragraph 3; 1 mg/mL of FGM-GRGD in 200 µL of DMEM, which is 0.1 wt% FGM-GRGD (0.0002 g FGM-GRGD/0.2 g solution * 100% = 0.1 wt%) and 99.9% DMEM (100% - 0.1% = 99.9%) (page 2270, right col. paragraph 3; Figure S6). Choi teaches one can design an interesting assembly as well as thermosensitive sol-to-gel transition for drug delivery and tissue regeneration by modifying the peptide attached to F127 via the linker (page 2275, left col. para. 1).
It would have been obvious prior to the effective filing of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Han regarding an F127 hydrogel with a cell affinity peptide attached to F127 via an anhydride linker with the teachings of Liu regarding maleic anhydride to attach a peptide to F127 with the teachings of Choi regarding a cell culture comprising an F127 hydrogel and a cell culture solution to arrive at the claimed cell culture auxiliary agent and cell culture medium comprising 0.05 – 0.5 wt% of the cell culture auxiliary agent with a structural formula of P-L-S-L-P where P is IKVAV, REDV, YIGSR, RNIAEIIKDA, LDV or PDSGR and the linker is maleic anhydride and the substrate is F127. One would have been motivated to combine the teachings of Han, Liu, and Choi in a cell culture hydrogel with increased cell affinity for tissue engineering as Han teaches tissue engineering techniques using hydrogels include culturing cells separated from a tissue extracted from a patient’s body in a hydrogel and then injecting the cell-hydrogel into the human body and for studying tissue engineering, it is important to prepare thermosensitive hydrogels that can be converted to a gel at around the body temperature and that are similar to tissues of a living body. One would have a reasonable expectation of success in combining the teachings as Han teaches the hydrogel comprising the peptide YIGSR exhibited an improvement of approximately 80% in cell affinity for proliferation of vascular cells compared to conventional F127; the hydrogel comprising the peptide IKVAV exhibited an improvement of approximately 90% in cell affinity of nerve cells compared to F127; the hydrogel comprising the peptide REDV exhibited an improvement of approximately 80% in cell affinity for intravascular cells compared to F127.
Applicant’s Arguments/ Response to Arguments
8. Applicant Argues: On page 5 – 6, Applicant asserts that with the removal of GRGD from claim1 and 5, neither Lee nor Choi meet the limitations of amended claim 1.
Response to Arguments: The previous rejections have been withdrawn in view of the amendments to claims 1 and 5. New rejections have been set forth above in which Han teaches a hydrogel of the formula P-L-S-L-P where the peptide is IKVAV or REDV or YIGSR or RNIAEIIKDA or LDV or PDSGR (page 3, line 1; page 5, lines 11 – 18; page 6, lines 5 – 15; page 12, Example 3; page 13 – 14; page 22, lines 15 - 20) thus meeting the amino acid sequences recited in amended claims 1 and 5.
Conclusion
No claims 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.
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/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632