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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/22/2025 has been entered.
Response to Amendments
Applicant's amendments filed 10/22/2025 to claim 1 have been entered. Claims 2-4, 7-10, and 15 are canceled. Claims 1, 5, 6, 11-14, and 16-22 remain pending, of which claims 1, 5, 6, 11-13, 21, and 22 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 Claims 14 and 16-20 remain withdrawn from consideration.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. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
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 1, 5, 6, 11-13, 21, and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “wherein the fungal derived protein forms particles” (emphasis added). Claim 6 depends from claim 1 and recites “wherein the fungal derived protein extract forms a gel and/or coating” (emphasis added). Claim 12 depends from claim 1 and recites “wherein the cell culture matrix extract forms a coating…” (emphasis added). The recitation of “forms” blurs the metes and bounds of these claims, as there are at least two reasonable but mutually exclusive interpretations of the scope of these claims when read in light of the specification: 1) “forms” would be synonymous for “capable of forming” and so a formulation of particles for claim 1, a gel and/or coating for claim 12, and a coating for claim 12 is not required by the claims and their respective dependent claims, or 2) “forms” would be synonymous for “formulated as” and so a formulation of particles for claim 1, a gel and/or coating for claim 12, and a coating for claim 12 is required by the claims and their respective dependent claims. Correction and/or clarification is required.
Claim 6 depends from claim 1 and recites the limitation "extract”. There is insufficient antecedent basis for this limitation in the claim, as claim 1 does not require any extract.
Claim 21 depends from claim 1 and recites the limitation "biomaterial". There is insufficient antecedent basis for this limitation in the claim, because claim 1 recites a “biomaterial component”.
Because claims 5, 6, 11-13, 21, and 22 depend from claim 1 and do not resolve the point of confusion, these claims must be rejected with claim 1 as indefinite.
Claim 21 is 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.
In this case, claim 21 depends from canceled claim 10, and so claim 21 does not further limit any currently pending claim under consideration on the merits at this time.
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 § 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, 5, 6, 11, and 13 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 on the embodiment of a crosslinked or the embodiment of a crosslinked and boiled/denatured protein hydrogel for 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 1, Bodenberger does not teach fungi selected from the group consisting of Flammulina velutipes and Lentinus edodes. Claim 1 is 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 particles having an average diameter of about 500 nm to about 1600 nm. Regarding claim 5, 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) nanoparticles 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. 1b; 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 5. Yu teaches that bovine serum albumin (BSA) nanoparticles are capable of acting as a cell culture matrix for culturing cells (Figure 4), reading on claims 1 and 5. 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 claims 1 and 5.
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 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, 10, 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 4-7 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
In response to applicant's argument over Yu on page 4 of the reply, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this case, Applicant appears to be bodily incorporating the teachings of Yu into the teachings of Bodenberger, which is not the proper test for obviousness. Furthermore, Applicant has not provided any factual evidence that the methods of Yu could not generate the claimed particle diameter range; see M.P.E.P. § 2121.
On pages 4-5 of the reply, Applicant alleges that Bodenberger is deficient by not teaching the claimed product being obtained from the group consisting of Flammulina velutipes and Lentinus edodes. This is not found persuasive because claim 1 is product-by-process claim which only further limits 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.
On pages 5-7 of the reply, Applicant alleges the claimed composition possesses unexpected properties. See M.P.E.P. § 716 for general guidance with respect to unexpected properties/results. In this case, the arguments are not persuasive of error because 1) Applicant is relying on unclaimed product-by-process limitations to boiling; although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993), and 2) even if a step of boiling was claimed, Bodenberger as cited above teaches a step of boiling and Applicant has not shown by any preponderance of evidence that the combination of the product-by-process limitations of both boiling and obtaining the claimed composition from the group consisting of Flammulina velutipes and Lentinus edodes otherwise yields any unexpected result and/or property compared to the composition of Bodenberger.
Conclusion
No claims are allowed. No claims are free of the art.
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