DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 5/01/2026 to claims 1, 6, 12, and 21 have been entered. Claims 2-5, 7-10, and 15 are canceled. Claim 23 has been added. Claims 1, 6, 11-14, and 16-23 remain pending, of which claims 1, 6, 11-13, and 21-23 are being considered on their merits. Claims 14 and 16-20 remain withdrawn from consideration. References not included with this Office action can be found in a prior action.
The instant amendments to claim 1 have overcome the 35 U.S.C. § 112(b) rejections of record, which are withdrawn.
Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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, 6, 11, 13, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Bodenberger et al. (Appl Microbiol Biotechnol (2017) 101:1907–1917; provided in the IDS dated 5/11/2022) in view of Yu et al. (Nanoscale Research Letters (2014), 9:343).
Bodenberger teaches a cell culture matrix comprising protein obtained from Baker’s yeast and formulated as a hydrogel (i.e. S. cerevisiae) (see the paragraph spanning p1908-1909) reading on claims 1, 6, and 13. In a separate embodiment, Bodenberger teaches a cell culture matrix comprising protein obtained from Baker’s yeast and formulated as a hydrogel and further functionalized with an RGD sequence motif (e.g. a cell-adhesive sequence) (subheading “Hydrogels are biocompatible” on p1913), reading on both the biomaterial component and cell-adhesive sequence claim 1, and alternatively reading on claims 1, 6, and 13. Bodenberger teaches crosslinking the protein obtained from Baker’s yeast with tetrakis (hydroxylmethyl) phosphonium chloride (THPC) such as form a hydrogel, wherein THPC reacts with primary and secondary amines (p1908, sentence starting “In our setup, …” through the end of that paragraph in the left column that carries over from p1907) and wherein the crosslinked yeast protein formulated as a hydrogel maintains its shape after boiling (e.g. denaturing) (p1912, subheading “Freeze-drying of gels does not influence thermal and chemical stability”), reading in-part on the product-by-process limitation to denaturing of claim 1 and reading on claim 11. Bodenberger teaches that hydrogels have utility for time-dependent drug delivery or for the encapsulation of pharmacological substances (p1907, sentence starting “Hydrogels, on the other hand…” through sentence ending “…Ashley et al. 2013).” on p1908), reading in-part on claims 1 and 5.
Regarding claim 23, Bodenberger does not teach fungi selected from the group consisting of Flammulina velutipes and Lentinus edodes. Claim 23 is a product-by-process claims, further limiting the source of claimed cell matrix product but not limiting any particular structure of the cell culture matrix composition of claim 1. See M.P.E.P. § 2113; product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See M.P.E.P. § 2113 (III). Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, the burden is shifted to Applicant to show that the fungal source imparts any novel and/or non-obvious structural characteristics to the claimed product as compared to the substantially identical composition taught by Bodenberger. Applicant must clearly set forth why any structural difference between the claimed composition and the composition of Bodenberger is non-obvious.
Regarding claim 1, Bodenberger does not teach wherein the fungal derived protein is formulated as self-aggregating precipitate with particles having an average diameter of about 500 nm to about 1600 nm and formed by denaturation and wherein wherein the protein denaturation step allows the fungal derived protein to retain its primary sequence / cell-adhesive sequence but removes its secondary and/or tertiary structure. Regarding claim 1, Bodenberger does not teach wherein the fungal derived protein is formulated as particles having a zeta potential of about -10 mV to about -50 mV.
Yu teaches bovine serum albumin (BSA) nanoparticle precipitate prepared by desolvation, either crosslinked or denatured, and having an average diameter of about 492 nm and a diameter range of about 250-850 nm (Abstract and Fig. 1; detailed methods at “Preparation of BSA-NPs and RhB-BSA-NPs” on page 2), reading on claim 1. Yu teaches a zeta potential of the BSA nanoparticles of about -15.4 mV, being advantageous to conjugate said nanoparticles to Rhodamine B (RhB) as a fluorescent tracer (page 5, paragraph starting “The BSA-NPs…”; see Figure 5 for in vivo imaging of RhB-BSA-NPs in the inner ears of treated subjects), reading on claim 1. Yu teaches that bovine serum albumin (BSA) nanoparticles are capable of acting as a cell culture matrix for culturing cells (Figure 4), reading on claim 1. Yu teaches there is a need in this art to improve methods of delivery drugs to the inner ears of subjects, as intratympanic injection is easy to perform in the clinic but the loss of drug through the Eustachian tube becomes the obstacle to treat inner ear disorders efficiently; thus, hydrogel- and particle-based vehicles (or carriers) have been investigated recently for sustained and prolonged drug supply (paragraph spanning pages 1-2), reading on claim 1.
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further prepare Bodenberger’s nanoparticles by the denaturation and desolvation methods of Yu to yield nanoparticles with a diameter range of about 250-850 nm and -15.4 zeta potential as taught by Yu. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Yu teaches detailed desolvation methods, and both Bodenberger and Yu are directed towards protein matrix compositions capable of culturing cells, and because Bodenberger teaches that hydrogels have utility for time-dependent drug delivery or for the encapsulation of pharmacological substances and so Yu is in the same field of endeavor as the claims. The skilled artisan would have been motivated to do so because Yu teaches there is a need in this art to improve methods of delivery drugs to the inner ears of subjects and particle-based vehicles would likely meet that need based on the successful delivery of nanoparticles to the inner ears of subjects taught by Yu, thus improving upon the composition of Bodenberger’s composition to be a drug delivery vehicle.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 12, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Bodenberger and Yu as applied to claims 1 and 11 above, and further in view of Cavo et al. (Scientific Reports (March 2018), 8:5333).
This rejection addresses the embodiment of a hydrogel coating cells for claim 12.
The teachings of Bodenberger and Yu are relied upon as set forth above.
Regarding claim 12, Bodenberger does not teach a calcium-crosslinked alginate coating formulation. Regarding claim 21, Bodenberger does not teach alginate. Regarding claim 22, Bodenberger does not teach calcium.
Cavo teaches a composition comprising a breast cancer cell-laden 3D alginate hydrogel (Abstract and Figure 1). Cavo teaches that alginate is a good candidate for the accomplishment of a 3D structure stable over a prolonged time, and that alginate can be easily arranged in a 3D gel-like structure and the mechanical properties of the resultant gel can be precisely tuned via calcium ions-mediated crosslinking (page 2, paragraph starting “Alginate is a good…”), reading on claims 12, 21, and 22. Cavo teaches that the cell culture matrix composition is advantageous as an in vitro model of cancer metastasis (Abstract) for measuring morphological changes in the cultured cancer cells (Fig.5 and 6 and page 3, paragraph starting “Cell morphology was firstly…” through paragraph ending “…a most regular shape.” on page 5), reading on claims 12, 21, and 22.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the alginate of Cavo and substitute the tetrakis (hydroxylmethyl) phosphonium chloride (THPC) of Bodenberger with the calcium of Cavo and Bodenberger’s cell culture matrix composition. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Cavo and Bodenberger are directed towards cell culture matrix compositions and towards the downstream culture of breast cancer cells. The skilled artisan would have been motivated to do so because Cavo teaches that the cell culture matrix composition is advantageous as an in vitro model of cancer metastasis for measuring morphological changes in the cultured cancer cells, and so the substitution would therefore improve upon the composition of Bodenberger as an in vitro model of cancer metastasis.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 5-10 of the reply have been fully considered, but not found persuasive of error for the reasons given below. Any reference to previously presented arguments are not found persuasive for the reasons given in their respective Office Action(s).
On pages 6-7 of the reply, Applicant appears to allege that it would have been unpredictable to combine Yu with Bodenberger with respect to the claimed particle diameter range. This is not persuasive because absolute predictability is not a prerequisite for a prima facie case for obviousness (see M.P.E.P. § 2143.02), and Applicant has not asserted any technical reasoning supported by any preponderance of evidence that it would have otherwise been unpredictable to further prepare Bodenberger’s nanoparticles by the desolvation methods of Yu to yield nanoparticles with a diameter range of about 250-850 nm and -15.4 zeta potential as taught by Yu to arrive at the cell culture matrix composition of independent claim 1. Applicant appears to alleges that Bodenberger is deficient by not teaching every element of claim 1, but this is not found persuasive as Bodenberger is not applied alone to anticipate the claims under 35 U.S.C. § 102 but in-combination with Yu to reject the claims as prima facie obvious under 35 U.S.C. § 103. The claimed invention becomes obvious when the references are considered together as a whole rather than each alone.
On page 8 of the reply, Applicants rely on arguments traversing the above rejection of claim 1over Bodenberger and Yu to traverse the rejection of claims 12, 21, and 21 further in view of Cavo. Therefore, the response set forth above to arguments also applies to this rejection.
Applicant’s arguments on pages 8-9 of the reply are not persuasive, as Applicant is relying on the product-by-process limitations of claim 1 to denaturing but this feature is entirely taught by Yu as cited above. Therefore, any alleged benefits of denaturation imparted to the claimed composition is expected in view of Bodenberger and Yu absent any showing to the contrary, see M.P.E.P. § 716.02.
Conclusion
No claims are allowed. No claims are free of the art.
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 SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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