DETAILED ACTION
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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a) based on application CHINA 2022115611214 filed 12/06/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of the Claims
Claims 1, 3 and 5-13 are pending. Claims 5-13 are withdrawn. Claim 1 is amended. Claims 2 and 4 are cancelled.
Claims 1 and 3 (claim set filed 03/03/2026) are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 03/03/2026 are acknowledged. All of the amendment and arguments have been thoroughly reviewed and considered.
For the purposes of clarity of the record, the reasons for the Examiner's withdrawal and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner's response to arguments section.
The previous claims 2-4 rejection under 35 U.S.C. 112(b) have been withdrawn necessitated by amendment of claim 1 and cancellation of claims 2 and 4.
New Rejection
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.
Claims 1 and 3 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: “PS and PN are uniformly mixed and each crosslinked to form an IPN by sonication to obtain a sonicated IPN hydrogels”. It is not clear whether PS and PN are mixed by sonication, crosslinked by sonication or form IPN by sonication. The scope and boundaries of claim 1 are not certain making claim 1 indefinite.
Claim 3, dependent on claim 1, does not resolve the issue mentioned above and is rejected.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Vorwald (Vorwald et al. Acta Biomater., 2020, 108, 142-152) in view of Fu (Fu et al. ACS Biomater. Sci. Eng., 2021, 7, 2734- 2744), Silva (Silva et al. Intern. J. Biol. Macromol., 2016, 93, 1420-1431) and Zhang (Zhang et al. Adv. Eng, Mater., 2022, 24, 2100663, 1-13).
Regarding claim 1, Vorwald teaches tunable fibrin-alginate interpenetrating network (IPN) hydrogels composed of natural polymers, fibrin (protein) and alginate (polysaccharide) (Abstract). Vorwald describes that IPN combines “the desirable adhesion and stimulatory characteristics of fibrin with the tunable mechanical properties of alginate” (Abstract). Vorwald discloses that in IPN networks are interlaced with each other but not chemically bonded and each hydrogel system is crosslinked through distinct mechanisms (p. 143, left column, 3rd paragraph). Vorwald mentions that alginate and fibrinogen are mixed followed by crosslinking of fibrin by incubation for 45 min at 37°C and crosslinking of alginate with CaC2 for 30 min at 37°C (p. 143, right column 3rd paragraph). Vorwald describes encapsulation of mesenchymal stromal cells and endothelial cells at concentration 3 x 106 cells/ml in the IPN by suspension of cells in fibrin-alginate solution (p. 144, left column, last paragraph). Vorwald discloses that the IPN hydrogel supported viability and function of cells co-culture (p. 149, left column, last paragraph). Vorwald showed formation of IPN hydrogels in square mold to demonstrate that the IPN constructs can be molded into desirable morphologies (p. 145, right column, last paragraph).
Vorwald does not teach suspension of bacteria or microalgae cells in IPN and does not teach sonication of hydrogel and preparation of hydrogel through a bioprinting device.
Fu teaches microalgae immobilized in hydrogels prepared by mixing microalgae with silk fibroin (SF) followed by gelation via sonication (Abstract). Silk fibroin is a natural protein polymer purified from silkworm cocoons (p. 2735, right column, 1st paragraph). The amount of microalgae cells in hydrogel was up-to 7.8 x 107 cells/ml (p. 2736, left column, 3rd paragraph) that reads on claim 1 limitation. Fu describes that microalgae are used for carbon fixation, wastewater treatment, hydrogen production and to generate oxygen (p. 2734). Fu mentions that efficiency of oxygen generation is low when microalgae is in suspension culture (p. 2735, left column, 2nd paragraph). Fu showed that silk fibroin hydrogels with microalgae generated oxygen continuously for 7 days and when suspended in a sealed flask filled with CO2 gas, continuously produced oxygen for at least 60 days and the oxygen production was 6 times that of suspension cultures (Abstract). Fu mentioned that silk gels provided mechanical strength and stability in comparison with alginate hydrogel commonly used for microalgal immobilization (Abstract). Fu discloses that microalgae embedded in the sonication-induced silk hydrogels exhibited slow proliferation with high and sustained photosynthetic activity, with the release of significant oxygen to the medium and air. “ (p. 2735, right column, 2nd paragraph).
Silva teaches hydrogels based on the blend between alginate and silk fibroin (Abstract). The hydrogel is prepared by mixing alginate and silk fibroin protein and subjecting the mixture to ultrasound treatment followed by incubation with CaCl2 to crosslink alginate and complete the gelation (p. 1421, right column, 2nd paragraph). Silva mentions that sonication treatment accelerates the silk fibroin protein hydrophobic physical cross-linking such as intra and inter-chain interactions related to β-sheet formation (p. 1424, left column, 1st paragraph). Silva performed water uptake studies and showed decrease in the water uptake by sonicated alginate/silk fibroin hydrogels compared to alginate hydrogels. Silva describes that electrostatic and hydrophobic interactions between protein chains and also with alginate molecules decrease the diffusion of the medium inside the network (p. 1425, left column, 2nd paragraph, Figure 3A). Silva mentions that alginate/SF hydrogels significantly increased viability, attachment and proliferation of endothelial cells (Abstract).
Zhang teaches that 3D bioprinting is a promising technology to combine cells and biomaterials as bioinks to fabricate functional constructs (p. 7, left column, last paragraph). Zhang describes different biomaterials and discloses that polysaccharides including alginate are ideal biomaterials for construction of 3D hydrogels “due to their excellent hydrophilicity, biocompatibility, and biodegradability “ (p. 4, left column, 2nd paragraph). Zhang teaches several protein-based biomaterials for 3D bioprinting including fibrinogen of Vorwald teaching and silk fibroin of Fu teaching. Zhang discloses that “silk fibroin is an emerging biopolymer for 3D bioprinting, which has the characteristics of biocompatibility, biodegradability, mechanical strength, and the ability to stabilize unstable compounds.” (p. 3, right column, 2nd and 3rd paragraphs). Zhang mentions that single biomaterials have limitations for bioprinting: “Polysaccharides usually have no cell attachment sites and therefore are not conducive to cell adhesion and growth. Protein-based materials have good biocompatibility and favorable biological activities but their printability and mechanical properties cannot fully satisfy the needs of 3D bioprinting.” (p. 7, right column, 2nd paragraph). Zhang discloses that synthetic polymers or polysaccharides are mixed with peptides or proteins for modulation of their printability, mechanical and biological properties (p. 9, left column, 2nd paragraph).
First, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Vorwald and Fu and use IPN hydrogel composed of natural PS, alginate and PN, fibrous protein taught by Vorwald for immobilization of microalgae and use silk fibroin as fibrous protein based on Fu teaching. One would have been motivated to do so since Fu showed that microalgae immobilized on hydrogel prepared with silk fibroin sustained photosynthetic activity and had significantly increased oxygen producing activity and mentions that alginate is commonly used for microalgae hydrogel and Vorwald described advantages of combination of fibrous protein and alginate for IPN hydrogels in which fibrous protein provides adhesion and alginate provides tunability and capacity of the hydrogel to be shaped in different morphologies. A skilled artisan would have reasonably expected success in the combination because Vorwald and Fu teach hydrogels containing fibrous proteins for cell attachment.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Silva teaching and apply sonication treatment to the mixture of alginate and silk fibroin during preparation of IPN microbial hydrogel based on Vorwald and Fu teachings. One would have been motivated to do so since Fu described gelation of silk fibroin by sonication and Silva teaches that sonication accelerates cross-linking of silk fibroin and describes preparation of alginate/silk fibroin hydrogel by sonication wherein the resulting hydrogel has decreased water uptake. A skilled artisan would have reasonably expected success in the combination because Vorwald, Fu and Silva teach hydrogels for cells immobilization, Vorwald and Silva describe hydrogels with alginate and Fu and Silva – with silk fibroin protein.
Third, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare IPN hydrogel based on Vorwald, Fu and Silva teachings by bioprinting device as described by Zhang. One would have been motivated to do so since Zhang teaches application of 3D bioprinting to the components described in Vorwald, Fu and Silva teaching, i.e. polysaccharide, alginate, and fibrous proteins, fibrinogen and silk fibroin, and mentions combination of polysaccharide and protein components during bioprinting for modulation of their printability, mechanical and biological properties. A skilled artisan would have reasonably expected success in the combination because Vorwald, Fu, Silva and Zhang teach hydrogels and their preparation for cell immobilization.
Last, regarding the recitation: “a swelling rate of the sonicated IPN hydrogels is <20% within 5 days” is interpreted as a property of the IPN microbial hydrogel. Pursuant to MPEP 2112.01: “Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” Thus, given the combination of Vorwald, Fu, Silva and Zhang renders the claimed structure obvious and Silva teaches reduced water uptake by sonicated alginate/silk fibroin hydrogel, the combination would necessarily render the claimed properties obvious as well.
Therefore, the teachings of Vorwald, Fu, Silva and Zhang render claim 1 obvious.
Regarding claim 3, Vorwald teaches IPN as described above comprising natural polysaccharide, alginate, crosslinked with CaCl2, and hence undergoing ionic crosslinking (p. 143, right column 3rd paragraph). Fu teaches microalgae hydrogels composed of silk fibroin (SF) (Abstract). Fu discloses physical crosslinking of SF between the hydrophobic domains of SF, leading to the formation of β-sheet domains (p. 2735, right column, 1st paragraph) and that crosslinking is performed by self-assembly of SF and does not require additional reagents. Silva teaches alginate ionic crosslinking with CaCl2 (p. 1424, left column, 1st paragraph) and the silk fibroin protein hydrophobic physical cross-linking such as intra and inter-chain interactions related to β-sheet formation (p. 1424, left column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make IPN hydrogel for microalgae immobilization composed of alginate and SF based on Vorwald, Fu and Silva teachings and follow instructions of Vorwald, Fu and Silva for cross-linking of alginate and SF. One would have been motivated to do so since Fu showed that microalgae immobilized on physically crosslinked hydrogel of silk fibroin sustained photosynthetic activity and had significantly increased oxygen producing activity and Vorwald described ionically crosslinked alginate in alginate/fibrous protein IPN to provide tunability and capacity to be shaped in different morphologies and Silva showed alginate/silk fibroin hydrogel to have reduced water uptake. A skilled artisan would have reasonably expected success in that because Vorwald ,Fu and Silva teach hydrogels containing fibrous proteins for cell attachment. Thus, teachings of Vorwald, Fu, Silva and Zhang render claim 3 obvious.
Response to Arguments
Applicant's arguments filed 03/03/2026 have been fully considered but they are not persuasive.
Applicant’s arguments regarding prior art of Ming and Nancharaiah are moot since current rejection does not include references of Ming and Nancharaiah.
In response to Applicant’s arguments (addressing p. 6 of the Remarks) that the prior art on file does not teach the limitation including sonication and swelling rate of the hydrogel, these limitations are addressed in the current modified rejection as described above.
Applicant argues (addressing p. 6-8 of the Remarks) that Vorwald does not disclose silk fibroin or SilMa, Fu utilizes a one component system and does not teach that silk fibroin can stabilize alginate structure, Zhang does not disclose combination of alginate and silk fibroin and obviousness based on cited prior art constitutes improper hindsight reasoning. These arguments are not persuasive because:
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In instant case, Vorwald teaches IPN hydrogel composed of natural polysaccharide, alginate, and natural fibrous protein for cell immobilization (Abstract). Fu discloses that another fibrous protein, silk fibroin, is used for hydrogel preparation for microalgae immobilization and that the resulting hydrogel sustained photosynthetic activity and had significantly increased oxygen producing activity of microalgae (Abstract) providing motivation to replace fibrous protein in Vorwald teaching with silk fibroin and use the alginate/silk fibroin hydrogel for microalgae immobilization. Silva teaches alginate/silk fibroin hydrogel obtained by sonication, points to the role of sonication in increase of silk protein crosslinking (p. 1424, left column, 1st paragraph) and describes that the resulting hydrogel has reduced water uptake properties (p. 1425, left column, 2nd paragraph, Figure 3A) and supports cells viability and proliferation (Abstract) providing motivation to apply sonication treatment to the mixture of alginate and silk fibroin during preparation of IPN microbial hydrogel. Zhang provides bioprinting technique applicable for components of Vorwald, Fu and Silva taught hydrogels (p. 4, left column, 2nd paragraph, p. 7, right column, 2nd paragraph) and indicates that combination of polysaccharide and protein components is used during bioprinting for modulation of their printability, mechanical and biological properties (p. 9, left column, 2nd paragraph) providing motivation to apply bioprinting technique for preparation of hydrogels based on Vorwald, Fu and Silva teachings. Therefore, the combination of prior art of Vorwald, Fu, Silva and Zhang makes claim 1 obvious.
Applicant argues (addressing p. 6-8 of the Remarks) that Vorwald does not provide guidance for microbial immobilization in wastewater treatment, Zhang does not mention wastewater treatment and that the instant claims propose construction of biomimetic EPS-structures microbial carrier, for the first time combining alginate and silk fibroin for microbial immobilization in wastewater treatment. These arguments are not persuasive because:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., wastewater treatment, biomimetic EPS-structures) are not recited in the rejected claim(s). 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). Besides, Fu describes that microalgae are used for wastewater treatment (p. 2734) and suggest silk fibroin hydrogel for environmental application such as air purification (Abstract). That suggests that the alginate/silk fibroin IPN hydrogel based on combination of cited prior art with improved properties over single component silk fibroin hydrogel can be used for microalgae immobilization and wastewater treatment.
Applicant argues (addressing p. 8 of the Remarks) that ultrasound treatment on both alginate and silk fibroin simultaneously forms an interpenetrating network structure and achieves a synergetic effect, that structural stability is achieved with a swelling rate of <20% after 5 days (lower that in comparative examples), that the β-sheet content actually increased by 4.63-6.24% and that microorganisms are uniformly embedded in the gel network without significant shedding or death compared to single alginate or silk fibroin gels. These arguments are not persuasive because:
The combination of prior art renders the instant IPN microbial hydrogel obvious as described above. Silva teaches the features recited by the Applicant, i.e.: (i) the same step of simultaneous ultrasound treatment on the mixture of alginate and silk fibroin (p. 1421, right column, 2nd paragraph), (ii) that sonication provides β-sheet formation in silk fibroin p. 1424, left column, 1st paragraph), (iii) discloses decreased water uptake by the sonicated hydrogel (p. 1425, left column, 2nd paragraph, Figure 3A), and (iv) that alginate/SF hydrogels have significantly increased viability, attachment and proliferation of endothelial cells (Abstract). Even though Silva does not expressly show the synergy in the swelling rate for sonicated alginate/SF hydrogels compared to hydrogels of individual components or not subjected to sonication, such property constitutes a latent property. MPEP 2145(II) states that the “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” In re Baxter Travenol Labs., 952 F.2d 388 (Fed. Cir. 1991). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).” Since the combination of prior art teaches the instant structure of IPN microbial hydrogel and Silva indicates decreased water intake by the sonicated alginate/silk fibroin hydrogels compared to alginate hydrogels, one of ordinary skill in the art would expect the synergistic effect of the swelling rate.
Therefore the 35 U.S.C. 103 rejection is maintained and modified necessitated by amendment of claims.
Conclusion
Np claims are 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 LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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