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 .
DETAILED ACTION
Claims 1-3, 5-7, 9-13, 16, 19-21, 23, 28, and 30-32 are pending and under examination on their merits. Claims 4, 8, 14-15, 17-18, 22, 24-27, 29, and 33-58 are cancelled.
Response to Arguments
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive.
Applicant argues against the rejection of claims under 35 U.S.C. 103 on the grounds that Tao, Lee, and Needles do not teach immersing the molded body in a solution of comprising isopropyl alcohol in addition to ammonium persulfate and water (Arguments, page 11, paragraph 1).
In response, Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439) is relied upon in addition to the Tao, Lee, and Needles in order to meet this claim limitation. Perez-Rigueiro teaches that immersion in water decreases the mechanical properties of silk, whereas immersion in isopropanol increases the stiffness of the fiber. (Abstract). Perez-Rigueiro teaches that although immersion of silk in water decreases the elastic modulus, silk immersed in solvents like isopropanol retains its high elastic modulus (page 8438, right column, bottom paragraph, Table 1, and page 8439, left column, 5. Conclusions, paragraph 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tao, Lee, and Needles by immersing the films in a mixture of ammonium persulfate, water, and isopropanol rather than aqueous ammonium persulfate. The person of ordinary skill in the art would have been motivated to avoid the decrease in mechanical properties of silk associated with immersion in water. The person of ordinary skill in the art would have had a reasonable expectation of success in immersing Tao’s films in aqueous ammonium persulfate mixed with isopropanol.
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.
(New Rection Necessitated by the Amendment) Claims 5, 19-20, and 32 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 5 recites “wherein said recombinant silk in the molded body comprises a crystallinity similar to or less than the crystallinity, before molding, of 18B.” It is unclear whether the comparison is to the recombinant silk before molding, to 18B, to 18B that is not molded, or whether the recombinant silk is 18B and the claim is reciting the effect of molding on crystallinity.
Claim 19 recites “wherein said molded body comprises at least 35% full-length recombinant silk monomers, based on the total amount of recombinant silk protein and impurities in the molded body.” It is unclear whether the plasticizer is considered an impurity or whether “impurities” refers to only recombinant silk monomers that are not full-length.
Claim 20 recites “wherein said molded body comprises recombinant silk monomers, recombinant silk aggregates, and high molecular weight impurities in a total amount of at least 50%, based on the total amount of recombinant silk protein and impurities in the molded body.” It is unclear whether the term “impurities” refers to the plasticizer or the high molecular weight impurities.
Claim 32 recites “wherein said molded body further comprises ammonium persulfate.” It is unclear whether this is the outcome of performing step (e) (i.e. immersing the molded body in a solution comprising ammonium persulfate results in the molded body further comprising ammonium persulfate), or whether claim 32 is further limiting the composition in step (a) that is processed to form the molded body.
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.
The following rejections are necessitated by the amendment.
Claims 1-3, 11, 13, 21, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726) and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439).
Regarding claims 1-3 and 32, Tao teaches compression molding a composition comprising silk fibroin (SF) powder and waterborne polyurethane or WPU (Abstract). WPU is a plasticizer (Abstract). Tao performs compression molding for 10 min under 20 MPa pressure at 110 °C to obtain films (page 640, left column, Preparation of the WPU/SF films). The resulting films were dried further in a ventilated oven at 50 °C and then conditioned at room temperature in a desiccator (page 640, right column, paragraph 1). Both 50°C and room temperature are cooler than 110°C, so Tao teaches cooling the film (“molded body”).
The instant specification defines “recombinant” in [0065] as “a biomolecule, e.g., a gene or protein, that (1) has been removed from its naturally occurring environment, (2) is not associated with all or a portion of a polynucleotide in which the gene is found in nature, (3) is operatively linked to a polynucleotide which it is not linked to in nature, or (4) does not occur in nature.
Here, Tao’s silk fibroin (protein) is recombinant according to the definition (1) of the instant specification because Tao’s silk protein is removed from its naturally occurring environment by chemical processing to remove sericin, also called silk gum (page 640, Materials and Methods, Materials, left column, paragraph 1).
Tao does not teach that the method for producing the films (“molded body”) further comprises immersing the films in a solution comprising ammonium persulfate and isopropyl alcohol (isopropanol).
Lee teaches the effect of various plasticizers and cross-linking agents on the physical properties of protein films (Title). Lee teaches that cross-linking agents are used to improve the tensile strength and water vapor barrier properties of protein films (Introduction, sentence spanning left and right columns).
Lee does not teach that ammonium persulfate is a cross-linking agent.
Needles teaches crosslinking silk fibroin by ammonium peroxydisulfate (synonym for ammonium persulfate): see Abstract. Needles’s solution is aqueous (Title).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to cross-link Tao’s silk films by immersing the films in ammonium persulfate as taught by Needles. The person of ordinary skill in the art would have been motivated by Lee’s teaching that cross-linking improves the mechanical properties of protein films. The person of ordinary skill in the art would have had a reasonable expectation of success given that Needles teaches that ammonium persulfate is capable of crosslinking silk fibroin.
Perez-Rigueiro teaches that immersion in water decreases the mechanical properties of silk, whereas immersion in isopropanol increases the stiffness of the fiber. (Abstract). Perez-Rigueiro teaches that although immersion of silk in water decreases the elastic modulus, silk immersed in solvents like isopropanol retains its high elastic modulus (page 8438, right column, bottom paragraph, Table 1, and page 8439, left column, 5. Conclusions, paragraph 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Tao, Lee, and Needles by immersing the films in a mixture of ammonium persulfate, water, and isopropanol rather than aqueous ammonium persulfate. The person of ordinary skill in the art would have been motivated to avoid the decrease in mechanical properties of silk associated with immersion in water. The person of ordinary skill in the art would have had a reasonable expectation of success in immersing Tao’s films in aqueous ammonium persulfate mixed with isopropanol.
Regarding claim 11, Tao varies the ratio of silk fibroin to WPU (plasticizer) to control properties such as elongation at break (see sentence bridging left and right column on page 640 and Table 2 on page 644). Tao teaches a WPU wt% that includes values overlapping with the range of between 10 and 50%: WPU/SF 70 corresponds to 30% WPU and 70% SF, whereas WPU/SF15 corresponds to WPU 85% and SF 15%.
Regarding claim 13, Tao’s applied pressure of 20 MPa during compression molding (page 640, left column, Preparation of the WPU/SF films) is equivalent to 2900 psi, which is within the claimed range for compression pressure. Therefore, a prima facie case of obviousness exists. See MPEP 2144.05.
Regarding claim 21, Tao’s 10 min duration of compression molding (page 640, left column, Preparation of the WPU/SF films) is a value between 1 and 15 minutes.
Regarding claim 30, Tao does not teach that the composition has an elongation percentage at break of 1 to 4%.
Tao teaches that the elongation at break varies from 17.8% to 882.2% based on the percentage of silk fibroin in the composition (Table 2, page 644 and page 640, line bridging left and right columns).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize by routine experimentation the amount of silk fibroin in the composition in order to achieve the desired elongation at break. The person of ordinary skill in the art would have had a reasonable expectation of success given that Tao teaches the correlation between the amount of silk fibroin in the composition and the resulting property of elongation at break.
Regarding claim 31, Tao teaches that the elongation at break varies from 17.8% to 882.2% based on the percentage of silk fibroin in the composition (Table 2, page 644 and page 640, line bridging left and right columns). 882.2% is within the claimed range of “greater than 20%,” thus a prima facie case of obviousness exists.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439), as applied to claims 1-3, 11, 13, 21, and 30-32 above, further in view of Widmaier (US 2016/0222174 A1).
See discussion of Tao, Lee, Needles, and Perez-Rigueiro above, which is incorporated into this rejection as well.
Claim 5 is interpreted as requiring that the recombinant silk in step a) is 18B (synonym for SEQ ID NO: 1, see [0112] of the specification) and the crystallinity of the recombinant silk after molding is similar to or less than that of 18B before molding.
Regarding claim 5, Tao does not teach that the recombinant silk comprises a crystallinity similar to or less than the crystallinity of 18B before molding.
Regarding claim 6, Tao does not teach that the recombinant silk protein comprises SEQ ID NO: 1.
Widmaier teaches the recombinant silk polypeptide 18B (SEQ ID NO: 1398, which is encoded by nucleic acid SEQ ID NO: 467; [0134], Table 2 on page 18). SEQ ID NO: 1398 of Widmaier is identical to the instant SEQ ID NO: 1 (OA Appendix A of the Non-Final Action mailed on 7/3/2025).
Widmaier teaches the fermentation of recombinant Pichia pastoris to produce the silk polypeptide 18B ([0137] and [139]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace Tao’s silkworm-derived protein with Widmaier’s recombinant silk polypeptide (SEQ ID NO: 1398, identical to the instant SEQ ID NO: 1). The person of ordinary skill in the art would have been motivated to improve the method of Tao by eliminating the need to obtain silkworm cocoons in favor of fermentation to produce SEQ ID NO: 1398. The person of ordinary skill in the art would have had a reasonable expectation of success given that Widmaier teaches that SEQ ID NO: 1398 is a silk-like polypeptide.
Regarding claim 5, Tao teaches that the crystallinity of the films is less than the crystallinity of the silk fibroin powder (“the films consisted of some crystallites embedded in a featureless amorphous matrix,” Fig. 3f, compared to “the SF powder is consisted of very small square-like crystallites,” Fig. 3a; page 641, right column, paragraph 3). Therefore, the person of ordinary skill in the art would have expected that Tao’s compression molding of Widmaier’s recombinant silk polypeptide 18B (the instant SEQ ID NO: 1) mixed with waterborne polyurethane would have resulted in films with crystallinity less than 18B.
Claims 7 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439), and Widmaier (US 2016/0222174 A1), as applied to claims 5-6 above, further in view of Brown et al., Biomacromolecules, 17.12 (2016): 3911-3921).
See discussion of relevant teachings in Tao, Lee, Needles, Perez-Rigueiro, and Widmaier above, which is incorporated into this rejection as well.
Regarding claim 7, Tao does not teach that the recombinant silk is 18B and the molded body has at least 50% full-length 18B monomers as compared to the recombinant silk of the composition in the flowable state.
Regarding claim 19, Tao does not teach that the molded body has at least 35% full-length recombinant silk monomers. Claim 19 is interpreted as requiring that at least 35% of the recombinant silk monomers are full-length within the molded body (i.e. “impurities” are any monomers that are not full length).
Regarding claim 20, Tao does not teach that the molded body has at least 50% total recombinant silk monomers, recombinant silk aggregates, and high molecular weight impurities. Claim 20 is interpreted as requiring that the molded body has at least 50% total recombinant silk monomers, recombinant silk aggregates, and high molecular weight impurities relative to the entire composition comprising the plasticizer.
Brown teaches that the addition of the plasticizer glycerol lowers the glass transition temperature and material stiffness (page 3911, right column, paragraph 1 and page 3916, right column, paragraph 1). Brown teaches that plasticization of silk widens the gap between glass transition and degradation temperatures, creating a workable temperature range where proteins can exist in a rubber transition without degradation , which opens the door for processing applications such as thermal molding that would otherwise not be possible with protein-based materials such as silk (page 3920, Conclusions, paragraph 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount of plasticizer and the thermal molding conditions (e.g. temperature and pressure) in the method of Tao modified by Lee, Needles, Perez-Rigueiro, and Widmaier in order to minimize thermal degradation of the 18B silk polypeptide. The person of ordinary skill in the art would have had a reasonable expectation of success in minimizing thermal degradation based on the teachings of Brown, which suggest that plasticization enables thermal molding of silk polypeptides with minimal thermal degradation. Minimal thermal degradation would have resulted in a molded body with mostly full-length 18B monomers, recombinant silk aggregates, and high molecular weight impurities.
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439), as applied to claims 1-3, 11, 13, 21, and 30-32 above, further in view of Kaplan (WO 2016/145281 A1; cited on the IDS filed on 9/25/2023).
See discussion of Tao, Lee, Needles, and Perez-Rigueiro above, which is incorporated into this rejection as well.
Regarding claims 9-10, Tao teaches that the plasticizer in the composition is waterborne polyurethane rather than trimethylene glycol.
Kaplan teaches a list of plasticizers including 1,3-propanediol, ([0031]) which is a synonym for trimethylene glycol.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to try replacing waterborne polyurethane with any one of Kaplan’s finite number of plasticizers, such as trimethylene glycol (synonym for 1,3-propanediol). The person of ordinary skill in the art would have had a reasonable expectation of success given that Kaplan teaches that 1,3-propanediol, like waterborne polyurethane, is a plasticizer in a silk fibroin solution (Kaplan Claims).
Further regarding claim 10, Tao does not teach that the amount of trimethylene glycol in the composition is 15%.
However, Tao teaches that the properties of the resulting film depend on the relative amount of plasticizer in the composition: Tao teaches that the elongation at break varies from 17.8% to 882.2% based on the ratio of silk fibroin to plasticizer in the composition (Table 2, page 644 and page 640, line bridging left and right columns).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize by routine experimentation the amount of plasticizer (Kaplan’s 1,3-propanediol) in the composition in order to attain the desired mechanical properties of the film, such as elongation at break. The person of ordinary skill in the art would have had a reasonable expectation of success given that Tao teaches the correlation between the amount of plasticizer in the composition and the resulting property of elongation at break.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439), as applied to claims 1-3, 11, 13, 21, and 30-32 above, further in view of Guo et al. (Nature Materials 19.1 (2020): 102-108).
See discussion of Tao, Lee, Needles, and Perez-Rigueiro above, which is incorporated into this rejection as well.
Regarding claim 12, Tao’s temperature of 110 °C during compression molding (page 640, left column, Preparation of the WPU/SF films) is less than 130 °C.
Guo teaches a thermal molding process for recombinant silk (see Figure 1). The silk powder is first packed in a predesigned aluminum mold, followed by hot pressing at high pressure and densified into bulk silk plates at 125 °C (page 103, right column, bottom paragraph). After hot-pressing, the samples are cooled (page 109, left column, “Hot pressing of ASN”). Guo optimizes the processing temperature of the silk to achieve desired structural properties of the resulting silk plates (Thermal processing of regenerated silk, page 103, right column, bottom paragraph). Guo teaches the effect of processing temperature on the strength of the resulting silk plates (page 105, Physical properties of silk-based bulk materials, left column, top paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize by routine experimentation the temperature of Tao’s compression molding, which Guo suggests controls the strength of the resulting silk product. The person of ordinary skill in the art would have had a reasonable expectation of success in the optimization of the molding temperature through routine experimentation, given that Guo teaches that the processing temperature is a results-effective variable with respect to the strength of the resulting silk product.
Claims 1-2 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hirai (US 2019/0194403 A1) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439) and as evidenced by Xometry (2024, website) and OpenLearn (2025, website).
Regarding claims 1-2, Hirai teaches a method comprising introducing a sample comprising water and a lyophilized powder sample into press molding machine, pressurizing the sample to 31 MPa and heating the sample at 170°C, then cooling the sample to form a molded article ([0093]). The sample comprises recombinant spider silk polypeptide ([0011] and ([0017}). Hirai teaches that the composition is typically in the form of a powder (“flowable state”) and the molded article can be a fused body (molded body in solid form) ([0076]). Hirai teaches that the sample may further comprise an additive such as a plasticizer ([0076]).
Hirai does not teach that the method for producing the molded article further comprises immersing the molded article in a solution comprising ammonium persulfate and isopropyl alcohol (isopropanol).
Lee teaches the effect of various plasticizers and cross-linking agents on the physical properties of protein films (Title). Lee teaches that cross-linking agents are used to improve the tensile strength and water vapor barrier properties of protein films (Introduction, sentence spanning left and right columns).
Lee does not teach that ammonium persulfate is a cross-linking agent.
Needles teaches crosslinking silk fibroin by ammonium peroxydisulfate (synonym for ammonium persulfate): see Abstract. Needles’s solution is aqueous (Title).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to cross-link Hirai’s molded article by immersing the articles in ammonium persulfate solution as taught by Needles. The person of ordinary skill in the art would have been motivated by Lee’s teaching that cross-linking improves the mechanical properties of protein films (an extremely thin molded article). The person of ordinary skill in the art would have had a reasonable expectation of success given that Needles teaches that ammonium persulfate is capable of crosslinking silk fibroin.
Perez-Rigueiro teaches that immersion in water decreases the mechanical properties of silk, whereas immersion in isopropanol increases the stiffness of the fiber (Abstract). Perez-Rigueiro teaches that although immersion of silk in water decreases the elastic modulus, silk immersed in solvents like isopropanol retains its high elastic modulus (page 8438, right column, bottom paragraph, Table 1, and page 8439, left column, 5. Conclusions, paragraph 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method of Hirai by immersing the molded article in a mixture of ammonium persulfate, water, and isopropanol rather than aqueous ammonium persulfate. The person of ordinary skill in the art would have been motivated to avoid the decrease in mechanical properties of silk associated with immersion in water. The person of ordinary skill in the art would have had a reasonable expectation of success in immersing Hirai’s molded article in aqueous ammonium persulfate mixed with isopropanol.
Regarding claim 16, Hirai teaches that the molded article has a Vickers hardness of 45 HV or more ([0016]). However, the hardness of 45 HV is attained without the addition of a plasticizer (see page 8, Table 3, and Example 1, [0093])
A Vickers hardness value of 50, is slightly above the hardness of epoxy, as evidenced by OpenLearn (Appendix I, Table of hardness values, Table 3: Typical Vickers hardness numbers for selected materials). The hardness of epoxy by a Shore D (“Type D”) durometer is roughly 75-90, as evidenced by Xometry (page 7, line 3). Therefore, Hirai’s molded article with a hardness of 45 HV (approximately 50) has a hardness within the claimed range of 50 or more. Immersing Hirai’s molded article into a solution comprising ammonium persulfate, water, and isopropanol would have increased the hardness of the molded article by cross-linking the recombinant silk polypeptide, thus increasing hardness (resistance to surface deformation) as measured by a Type D durometer.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Tao et al. (Polymers for Advanced Technologies 23.3 (2012): 639-644) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439), as applied to claims 1-3, 11, 13, 21, and 30-32 above, further in view of Borkner et al. ("Coatings and Films Made of Silk Proteins." (2014)) and Ma (Preventive Nutrition and Food Science 10.2 (2005): 187-190).
See discussion of Tao, Lee, Needles, and Perez-Rigueiro above, which is incorporated into this rejection as well.
Tao does not teach that the method further comprises exposing the film to a relative humidity of at least 50% for at least 24 hours.
Borkner teaches that post-treatment of processed silk proteins can be used to increase beta-sheet content of a silk material resulting in more stable and water insoluble protein materials (2.4. Post-Treatment, bottom paragraph, right column). Borkner teaches that the structural change from alpha-helical and random coil structures to beta-sheets can be induced by many factors, including humidity (page 15616, left column, top paragraph).
Borkner does not teach the exact conditions for post-treatment (i.e. exposing the silk materials to a relative humidity of at least 50% for at least 24 hours).
Ma teaches conditioning silk films in an environmental chamber at 50% relative humidity for 2 days (page 188, left column, Film casting and drying paragraph). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to condition the silk films of Tao modified by Lee, Needles, and Perez-Rigueiro per the conditions of Ma in order to improve the stability of the silk films, as suggested by Borkner. The person of ordinary skill in the art would have had a reasonable expectation of success in applying Ma’s conditions to the silk films of Tao to achieve the predictable effect of greater stability.
Claims 1-2 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Hirai (US 2019/0194403 A1) in view of Lee et al. (Preventive Nutrition and Food Science 10.1 (2005): 88-91), Needles (Journal of Applied Polymer Science 11.5 (1967): 719-726), and Perez-Rigueiro et al. (Polymer 41.23 (2000): 8433-8439).
Regarding claims 1-2, Hirai teaches a method comprising introducing a sample comprising water and a lyophilized powder sample into press molding machine, pressurizing the sample to 31 MPa and heating the sample at 170°C, then cooling the sample to form a molded article ([0093]). Hirai teaches that the composition is typically in the form of a powder (“flowable state”) and the molded article can be a fused body (molded body in solid form) ([0076]). The sample comprises a recombinant spider silk polypeptide ([0011] and ([0017}). Hirai teaches that the sample may further comprise an additive such as a plasticizer ([0076]).
Hirai does not teach that the method for producing the molded article further comprises immersing the molded article in a solution comprising ammonium persulfate and isopropyl alcohol (isopropanol).
Lee teaches the effect of various plasticizers and cross-linking agents on the physical properties of protein films (Title). Lee teaches that cross-linking agents are used to improve the tensile strength and water vapor barrier properties of protein films (Introduction, sentence spanning left and right columns).
Lee does not teach that ammonium persulfate is a cross-linking agent.
Needles teaches crosslinking silk fibroin by ammonium peroxydisulfate (synonym for ammonium persulfate): see Abstract. Needles’s solution is aqueous (Title).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to cross-link Hirai’s molded article by immersing the articles in ammonium persulfate solution as taught by Needles. The person of ordinary skill in the art would have been motivated by Lee’s teaching that cross-linking improves the mechanical properties of protein films (an extremely thin molded article). The person of ordinary skill in the art would have had a reasonable expectation of success given that Needles teaches that ammonium persulfate is capable of crosslinking silk fibroin.
Perez-Rigueiro teaches that immersion in water decreases the mechanical properties of silk, whereas immersion in isopropanol increases the stiffness of the fiber. (Abstract). Perez-Rigueiro teaches that although immersion of silk in water decreases the elastic modulus, silk immersed in solvents like isopropanol retains its high elastic modulus (page 8438, right column, bottom paragraph, Table 1, and page 8439, left column, 5. Conclusions, paragraph 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method of Hirai by immersing the molded article in a mixture of ammonium persulfate, water, and isopropanol rather than aqueous ammonium persulfate. The person of ordinary skill in the art would have been motivated to avoid the decrease in mechanical properties of silk associated with immersion in water. The person of ordinary skill in the art would have had a reasonable expectation of success in immersing Hirai’s molded article in aqueous ammonium persulfate mixed with isopropanol.
Regarding claim 28, Hirai teaches that the flexural modulus of the molded article is 7.3 GPa (page 8, Table 3: Example 1, “Three-point bending elastic modulus), which is within the claimed range of 50 MPa or more. Immersing Hirai’s molded article into a solution comprising ammonium persulfate, water, and isopropanol would have increased the flexural modulus of the molded article by cross-linking the recombinant silk polypeptide, thus increasing resistance to bending measured by the flexural modulus.
Conclusion
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 CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657