DETAILED ACTION
Claims 1-5 and 7-20 are currently pending. Claims 1-5 and 7-15 are currently under examination.
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 .
Withdrawn Rejections
The prior rejection of claim(s) 1-5 and 12-14 under 35 U.S.C. 103 as being unpatentable over 2020/0181213 is withdrawn in light of Applicant’s amendment for the composite material to comprise antimicrobial urethane oligomer, the modification of the natural silk fibroin is induced by using the antimicrobial urethane oligomer as a casting substrate, which the ‘213 publication does not teach.
Examiner’s Note
Applicant's amendments and arguments filed 12/11/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 12/11/2025, it is noted that claims 1, 7 and 11-12 have been amended and no new matter or claims have been added.
Modified Rejections:
The following rejections are modified based on Applicant’s claim amendments.
Claim(s) 1-5 and 7-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0306411 (previously applied) in view of US 2020/0181213 (previously applied), US 2007/0248566 (previously applied) and US 2012/0015574 (previously applied)
Regarding claim 1, the limitation of silk fibroin composite material comprising a modified silk fibroin that is modified form natural silk fibroin and has an increased content of a beta-sheet is met by the ‘411 publication teaching silk fibroin biocompatible polyurethane membranes using a solvent, which have improved biodegradation, mechanical and vibroacoustic properties (abstract). By including biocompatible polyurethane, it is possible to alter the mechanical characteristics and flexibility of silk fibroin membrane [0011]. Silk fibroin and biocompatible polyurethane is taught ([0014]-[0015]). Silk fibroin is taught to be fabricated to have enhance properties enacted by affecting silk fibroin crystallization behavior in the formation of beta sheets as the stabilizing hydrogen bonded crosslinks in the film [0123]. Fibroin is taught to be dissolved in formic acid and treated with CaCl2 [0125]. The device may comprise multiple layers, wherein at least one layer is comprised of silk fibroin and at least one layer is comprised of biocompatible polyurethane membrane matrix ([0187]-[0188]). Silk fibroin biocompatible polyurethane membrane Is cast, the formation of multiple layers in a membrane ([0217]-[0218]).
The ‘411 publication does not specifically teach the claimed Raman spectroscopy and peak data, 13C-NMR first, second and third peak (claims 1-5, 12-14).
The ‘411 publication does not specifically teach wherein the silk fibroin composite material comprises an antimicrobial urethane oligomer, the modification of the natural silk fibroin is induced by using the antimicrobial urethane oligomer, as a casting substrate (claim 1) prepared by reacting a polyol with an antimicrobial isocyanate (claim 7) having a weight average molecular weight of 100 to 1,000 g/mol (claim 8) wherein the antimicrobial isocyanate compound is a heterocyclic diisocyanate compound comprising a quaternary ammonium salt (claim 9).
The ‘213 publication teaching a plurality of exfoliated silk microfibrils and/or exfoliated silk nanofibrils wherein the micro or nanofibrils (abstract). Fibroin molecules are taught to be into a beta-sheet conformation [0085]. As used herein, the process of annealing involved inducing formation of beta-sheet secondary structure in the silk fibroin of provided micro or nano-fibrils. Increased non-covalent interactions of silk fibroin. Increase beta sheet formation is taught to render the silk fibroin insoluble in an aqueous environment. The conformational change is due to hydrogen-bonding and/or hydrophobic interactions medicated structure shift of silk fibroin to a higher beta sheet content ([0099], [0134]). In some embodiments, an additive such a biocompatible polymer is taught [0122].
Regarding the maximum intensity in the region of 1665 of a spectrum according to Raman spectroscopy, a full width at half maximum of the peak being 10 to 80 cm-1, the first peak, second peak and third peak and Equation 1 and 2 of beta sheet content and toughness of silk fibroin, is met by the ‘213 publication teaching the claimed modified silk fibroin having increased beta sheets, and thus would have the spectroscopy claimed, absent factual evidence to the contrary. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and Applicant’s own disclose supports the suitability of the prior composition as the inventive composition component, the burden is property shifted to Applicant to show otherwise. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to optimize the beta sheets in the silk fibroin as the ‘213 publication teaches generation of secondary structures wherein the structures are mainly beta sheet and included crystallinity into beta sheet conformation wherein the crystallinity content is at least 30% [0100]. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
The ‘566 publication teaches antimicrobial polyisocyanate and derivatives thereof wherein a quaternary amine is added into the polymerization reaction of a polyol and NCO-containing isocyanate/polyisocyanate to form the antimicrobial polyisocyanate. The bactericide will not be released out but will be maintained permanently. Such mechanical contact type antiseptic method can achieve a safe, persistent and environment-friendly antiseptic effect (abstract). The polyol is selected from a group which includes low molecular weight polyols such as ethylene glycol [0023] wherein the n range in the polyisocyante is 1 to 1000 (claim 7). The teaching of low molecular weight leads to an optimizable parameter. “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of molecular weight nonobvious. The antimicrobial polymer is formed A, di isocyanate, B, polyol and C, polyol containing a heterocyclic quaternary ammonium compound (claims 1-4), wherein when reacted will result in the formation of A-C-A structure on a random basis reading on claims 7 and 9.
The ‘574 publication teaches reactive polyurethane emulsion by reacting polyols alone or in combination with at least one of diols with sub-stoichiometric amount of di-isocyanates as to form OH terminated prepolymers (abstract). Antimicrobial agents or biocides employed are quaternary ammonium compounds or pyridium compounds that are capable of addition to isocyanate, preferably OH groups or NH2 groups [0053]. Antimicrobial agent with hexamethylene-diisocyanate Trimer is taught ([0255]-[0256]).
It would have been prima facie obvious to use the methods taught by the ‘213 publication to increase beta sheets in the silk fibroin composite taught by the ‘411 publication because the ‘411 publication teaches silk fibroin having increased beta sheets and to be water insoluble and the ‘213 publication teaches specific methods and reasons to increase beta sheets in a silk fibroin. One of ordinary skill before the filing date of the claimed invention would be motivated to increase the beta sheets as the ‘213 publication teaches the control the solubility of the silk fibrion, at least partially insoluble, and alter crystallinity of the silk fibroin [0098] wherein the ‘411 publication teaches a desire for beta sheet conformation of the silk fibroin.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the antimicrobial polyurethane taught by the ‘566 publication for the polyurethane taught by the ‘411 publication as the ‘411 publication teaches the inclusion of polyurethanes in the silk fibroin membrane and the ‘566 publication teaches a specific polyurethane polymer. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use the polyurethane of the ‘566 publication as the ‘566 publication teaches bactericide will be maintained permanently and is a persistent and environmental-friendly antiseptic (abstract) wherein the ‘411 publication teaches the use of polyurethanes and desires the inclusion of antimicrobial compounds into the biocompatible membrane. Thus one of skill in the art would be motivated to include a compound to maintain antiseptic nature of the implant wherein the effect is maintained long term. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use an isocyanate quaternium ammonium salt as the ‘574 publication teaches it is known to form quaternium isocyante monomers and the ‘566 publication teaches the replacement of the OH functional groups in the quaternary monomer added to the isocyanate compound, thus it would have been prima facie obvious to one of ordinary skill in the art to use known isocyanate terminated monomers to form the antimicrobial polymer base on the teachings of the ‘566 publication and the ‘574 publication. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to optimize the ratio of polyol to isocyanate compound as the ‘566 publication teaches a range of isocyanate included an the ‘574 publication teaches a less than stoichiometric amount of isocyanate used in the polymer formation, thus it would have been prime facie obvious to one of ordinary skilled in the art before the filing date of the claimed invention to optimize the amount of monomers present in the polymer formation. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0306411, US 2020/0181213, US 2007/0248566 and US 2012/0015574 as applied to claims 1-5 and 7-13 above, and further in view of US 2003/0135270 (previously applied).
As mentioned in the above 103(a) rejection, all of the limitations of claims 1-5 and 7-13 are taught by the combination of the ‘411 publication, the ‘213 publication, the ‘566 publication and the ‘574 publication.
The combination of references does not specifically teach bioprosthetic (claim 15).
The ‘270 publication teaches heart valve prosthesis device wherein the hearth valve prosthesis is a mechanical hearth valve or a bioprosthetic heart valve. The device contains polyurethane material to improve the hearth valve prosthesis (abstract, [0010], [0019]) wherein the polyurethane is applied to the bioprosthetic heart valve [0036].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the silk fibrion/polyurethane membrane of the ‘411 publication on a bioprosthetic as the ‘411 publication teaches the composition used for heart valves and the ‘270 publication teaches specifically bioprosthetic heart valve. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘411 publication and the ‘270 publication are both directed heart valves which containing polyurethane coatings.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0306411, US 2020/0181213, US 2007/0248566 and US 2012/0015574 as applied to claims 1-5 and 7-13 above, and further in view of CN 111205428.
As mentioned in the above 103(a) rejection, all of the limitations of claims 1-5 and 7-13 are taught by the combination of the ‘411 publication, the ‘213 publication, the ‘566 publication and the ‘574 publication.
The combination of references does not specifically teach wherein the silk fibroin composite material has a toughness of 300 MJ/m3 or more as measured according to STM D882 in a specimen having a size of 40 x 5.0 x 0.4 mm3 (claim 14).
The ‘428 publication teaches polyurethane preparations [0001]. Fibroin is taught to be used that has a toughness of 150 MJ/m that has broad application prospects [0004]. Polyurethane fiber is taught to improve spider silk biomimetic material [0006]. Biomedical materials are taught [0017]. Super tough polyurethane fiber material is taught with a toughness of greater than 150 MJ/m3 [0019].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known toughness of polyurethane as taught by the ‘428 publication for the polyurethane taught by the combination of references as the ‘428 publication teaches known toughness ranges to be used in biomedical applications for polyurethanes and the ‘411 publication teaches polyurethanes use in biomedical application [0010]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the toughness taught by the ‘428 publication for that of the ‘411 publication as the combination of references teaches a fibroins polyurethane structure wherein the fibroin has increased beta structure and the ‘428 publication teaches the toughness for structures have spider silk with beta fold structure and polyurethane materials.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
Applicant argues none of the cited references disclose the technical concept of inducing denaturation of silk fibroin using an antimicrobial urethane as a substrate to induce modification of a natural silk fibroin. None of the cited references teach enhancing beta-sheet formation.
In response, MPEP 2113 - “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The ‘411 publication teaches the use of casting to form the scaffold wherein layers of fibroin and polyurethane are taught ([0187]-[0188], [0217]) and wherein enhanced beta sheets are taught [0099].
Applicant argues the present invention exhibits toughness approximately 50 times superior to that described in the ‘213 publication.
In response, the ‘428 publication teaches polyurethane preparations [0001]. Fibroin is taught to be used that has a toughness of 150 MJ/m that has broad application prospects [0004]. Polyurethane fiber is taught to improve spider silk biomimetic material [0006]. Biomedical materials are taught [0017]. Super tough polyurethane fiber material is taught with a toughness of greater than 150 MJ/m3 [0019].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known toughness of polyurethane as taught by the ‘428 publication for the polyurethane taught by the combination of references as the ‘428 publication teaches known toughness ranges to be used in biomedical applications for polyurethanes and the ‘411 publication teaches polyurethanes use in biomedical application [0010]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the toughness taught by the ‘428 publication for that of the ‘411 publication as the combination of references teaches a fibroins polyurethane structure wherein the fibroin has increased beta structure and the ‘428 publication teaches the toughness for structures have spider silk with beta fold structure and polyurethane materials.
Conclusion
No 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613