The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received March 12, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 4, 8, 10-11, 13, 16-17, 20-21, 24, 28, 31 are canceled. As previously noted, claims 25-27, 29-30 have been withdrawn because they are drawn to non-elected inventions. Claims 1-3, 5-7, 9, 12, 14, 15, 18-19, 22-23, 32 are under consideration.
Priority: This application is a 371 of PCT/SG2021/050205, filed April 13, 2021, which claims benefit to foreign application SG 10202003536S. A copy of the foreign priority document has been received in the instant application on March 16, 2023 and is in the English language.
Objections and Rejections
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-3, 5-7, 9, 12, 14, 15, 18-19, 22-23, 32 are rejected under 35 U.S.C. 103 as being unpatentable over Shuai (2014 Human Hair Keratin Hydrogel: Fabrication, Characterization and Application Thesis, 138 pages; previously cited) in view of Bowden et al. (1984 Eur J Biochem 142: 29-36; previously cited). Shuai discloses a method for forming a keratin-based gel network comprising adding a salt CaCl2 or reducing pH to about 4 using citrate buffer/PBS to a soluble keratin solution (at least p. 61, 66-70, 91). Shuai discloses lyophilized keratin gels (at least p. 68-69). Shuai discloses extracting keratin to obtain the keratin solution for inducing keratin gel formation (at least p. 47-48). Shuai discloses methods for extracting keratin including a dialysis step to obtain a keratin solution (at least p. 11-12, 35). Therefore, Shuai reasonably discloses a method for forming a keratin filament network, comprising dialyzing a solubilized keratin solution in a buffer solution to obtain a purified keratin solution, mixing the purified keratin solution with a salt in an acidic buffer solution, and drying the acidic keratin solution, and forming a keratin filament network. Shuai does not teach dialyzing at a pH of about 2.5 to about 5.5.
Bowden et al. disclose that keratin can also be extracted by soaking the keratin protein source in Tris/HCl, pH 7.5, containing urea and mercaptoethanol (Tum buffer) for 16-24 h at 6º C; homogenized, sonicated, centrifuged, and then where the supernatant is dialyzed against citrate buffer (pH 2.65; citric acid and trisodium citrate) to obtain a keratin solution (p. 30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of the prior art and arrive at the claimed method for forming a keratin filament network, comprising dialyzing a solubilized keratin solution in a buffer solution at a pH 2.5 to about 5.5, the buffer solution comprising citric acid, to obtain a purified keratin solution, mixing the purified keratin solution with a salt in an acidic buffer solution, and drying the acidic keratin solution, and forming a keratin filament network (instant claim 1). The motivation to do so is given by the prior art. Shuai discloses a method for forming a keratin filament network, comprising dialyzing a solubilized keratin solution in a buffer solution to obtain a purified keratin solution, mixing the purified keratin solution with a salt in an acidic buffer solution, and drying the acidic keratin solution, and forming a keratin filament network. Bowden et al. disclose that a keratin solution can also be obtained by dialyzing in a citrate buffer at low pH ~2.65. Therefore, one of ordinary skill would have reasonable motivation to incorporate the acidic dialyzing step of Bowden et al. for the keratin extraction or dialyzing step for obtaining the keratin solution that is mixed with the acidic salt buffer solution in the method of Shuai for forming a keratin filament network because alternative keratin extraction and dialyzing steps are known in the prior art and there is interest in forming materials comprising a keratin-based network. One of ordinary skill would have a reasonable expectation of success because method steps for extracting keratin and forming a keratin-based material are known as disclosed in the prior art.
Regarding instant claims 2, 14-15, Shuai discloses keratin gelation (or formation of a keratin network) is induced by calcium salt or PBS/citrate buffer pH 3 (at least p. 61, 66-70, 91). Therefore, Shuai can be deemed to disclose self-assembly of a keratin filament network when mixing the keratin solution with PBS/citrate buffer pH 3.
Regarding instant claim 3, Bowden et al. disclose a dialysis buffer comprising citrate buffer pH 2.65 (or citric acid) for extracting keratin (p. 30).
Regarding instant claims 3, 5, Bowden et al. disclose subjecting keratin to denaturing and reducing agents (urea and mercaptoethanol) before dialysis with citrate buffer pH 2.65 (p. 30). Shuai also discloses that denaturing agents (urea) can be incorporated into the extraction methods for keratin (p. 11-12). Therefore, it would have been obvious to include a denaturing agent, such as urea, into the citrate buffer pH 2.65 for dialysis of the keratin solution because its incorporation into the citrate buffer pH 2.65 will have the same purpose of producing a keratin solution.
Regarding instant claim 6, Bowden et al. disclose a urea concentration of 8 M (p. 30) and Shuai also discloses urea concentrations including 8 M (p. 11-12).
Regarding instant claim 7, it is known that “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 experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. In this instance, the prior art Bowden et al. disclose extracting keratin with a denaturing agent (16-24 h) and then dialyzing in a citrate buffer pH 2.65 (p. 30). Therefore, it would have been obvious to arrive at a dialyzing time of at least two hours to remove residual molecules, including the denaturing agents, by routine optimization.
Regarding instant claim 9, the prior art Bowden et al. disclose extracting keratin with a denaturing agent (16-24 h) where the urea is 8M and then dialyzing in a citrate buffer pH 2.65 (p. 30). As noted above, it would have been obvious to include a denaturing agent, such as urea, into the citrate buffer pH 2.65 for dialysis of the keratin solution because its incorporation into the citrate buffer pH 2.65 will have the same purpose of aiding keratin extraction. MPEP 2144.04 notes that duplicating and/or rearranging parts is obvious. It is further known that “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 experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. It would have been further obvious to repeat the dialysis step with reducing concentrations of the urea by routine optimization because repeating the dialysis step and reducing the concentration of the urea in each subsequent step will still result in keratin extraction.
Regarding instant claims 3, 12, Bowden et al. disclose subjecting keratin to denaturing and reducing agents (urea and mercaptoethanol) before dialysis with citrate buffer pH 2.65 (p. 30), at 2% mercaptoethanol (p. 30). Shuai also discloses that denaturing agents (guanidine) and reducing agent (DTT, Na2S) can be incorporated into the extraction methods for keratin (p. 11-12). Therefore, it would have been obvious to include a reducing agent, such as mercaptoethanol or DTT, into the citrate buffer pH 2.65 for dialysis of the keratin solution because its incorporation into the citrate buffer pH 2.65 will have the same purpose of aiding keratin extraction.
Regarding instant claim 18, Shuai discloses adding the keratin solution to PBS/citrate buffer pH 3 for inducing network formation and monitoring at time intervals from 0 h to 8 hr (p. 26-27).
Regarding instant claim 19, Shuai discloses keratin solutions, including 3 ml of 15 mg/ml, mixed with the PBS/citrate buffer pH 3 for inducing network formation (at least p. 26).
Regarding instant claim 22, Shuai also discloses that denaturing agents (guanidine) and reducing agent (DTT, Na2S) can be incorporated into the extraction methods for keratin before dialysis (p. 11-12). Therefore, it would have been obvious to include an extraction step before the dialysis step in the method for forming a keratin network of Shuai in view of Bowden et al. noted above.
Regarding instant claim 23, Shuai discloses that a source of keratin protein is hair (at least p. 91).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that the Shuai and Bowden et al. references are directed to fundamentally different technical problems in different fields. Applicants assert that Shuai is directed to developing keratin-based hydrogels as cell culture substrates for tissue engineering applications. Applicants assert that Bowden et al. is directed to investigating proteolytic modifications of acidic and basic keratins during terminal differentiation of mouse and human epidermis, not a method of forming any keratin-based material or network.
Applicants’ remarks are not persuasive. In this instance, both the Shuai and Bowden et al. references disclose keratin extraction or purification is needed in order to arrive at a keratin protein for further processing. While Shuai discloses the keratin after extraction is for gel formation and Bowden et al. disclose that the keratin after extraction is for further studies, both Shuai and Bowden et al. disclose the same understanding that keratin extraction is needed in order to obtain keratin protein for further utilization. Therefore, Applicants’ remarks that Shuai and Bowden et al. are directed to different technical problems in different fields are not persuasive. In this instance, Shuai and Bowden et al. disclose the same solution of first extracting keratin to obtain keratin protein.
Applicants assert that Bowden et al.’s use of citrate buffer dialysis at pH 2.65 was not directed to forming a material but rather was one step in an analytical extraction protocol for isolating epidermal keratins for subsequent electrophoretic analysis and peptide mapping (Bowden et al. p. 30). Applicants assert that one of ordinary skill starting from Shuai’s hydrogel fabrication methods would have no reason to look to a 1984 analytical biochemistry paper focused on proteolytic keratin modifications for guidance on how to prepare keratin networks.
Applicants’ remarks are not persuasive. In this instance, Shuai discloses extracting keratin to obtain the keratin solution for inducing keratin gel formation (at least p. 47-48) and that methods for extracting keratin include a dialysis step to obtain a keratin solution (at least p. 11-12, 35). Therefore, it would be obvious that the citrate buffer dialysis at pH 2.65 of Bowden et al. has the same purpose of the dialysis step for extracting keratin in Shuai because Bowden et al. disclose keratin extraction with the citrate buffer dialysis at pH 2.65. MPEP 2144.05 notes that “[W]here 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 experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have been obvious that conditions for extracting keratin known in the prior art, including the citrate buffer dialysis at pH 2.65 of Bowden et al. can be incorporated for the keratin extraction or dialyzing step for obtaining the keratin solution that is mixed with the acidic salt buffer solution in the method of Shuai for forming a keratin filament network because alternative keratin extraction and dialyzing steps are known in the prior art and there is interest in forming materials comprising a keratin-based network.
Applicants assert that moreover, the references address structurally and distinct keratin subfamilies. Applicants assert that Shuai works exclusively with human hair keratins which are “hard” keratins and Bowden et al. work with exclusively epidermal keratins (cytokeratins/soft keratins) from human and mouse stratum corneum and living cell layers. Applicants assert that these are biochemically and structurally distinct protein families and a person of ordinary skill would understand that extraction and processing conditions optimized for epidermal cytokeratins would not necessarily be applicable to hair keratins.
Applicants’ remarks are not persuasive. Bowden et al. disclose that keratins are structural proteins and are also termed prekeratins or cytokeratins (p. 29). Bowden et al. disclose that the keratin proteins extracted from human and mouse epidermis are type II basic and type I acidic keratins (p. 29). Shuai discloses that the keratins present in human hair are also of the type II basic and type I acidic keratins (p. 6-7). Therefore, the keratins disclosed in Bowden et al. and Shuai appear to be from the same keratin family.
Regarding Applicants’ remarks that a person of ordinary skill would understand that extraction and processing conditions optimized for epidermal cytokeratins would not necessarily be applicable to hair keratins, the remarks are not persuasive. In this instance, both hair keratin and the epidermal keratin are being obtained from keratinized cells, and therefore the same type of cells. Therefore, one of ordinary skill would have a reasonable expectation of success that the keratin extraction and processing conditions, including citrate buffer dialysis at pH 2.65 of Bowden et al., can be successfully incorporated into the keratin extraction and dialyzing step for obtaining the keratin solution in the method of Shuai because the same types of proteins are being extracted from the same cell types.
Applicants assert that the office has not provided an articulated reasoning for the 103 rejection.
Applicants’ remarks are not persuasive. MPEP 2141 notes that examples of rationales that may support a conclusion of obviousness include among others: combining prior art elements according to known methods to yield predictable results. It is further known that “[W]here 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 experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. Therefore, it would have been obvious that conditions for extracting keratin known in the prior art, including the citrate buffer dialysis at pH 2.65 of Bowden et al. can be incorporated for the keratin extraction or dialyzing step for obtaining the keratin solution that is mixed with the acidic salt buffer solution in the method of Shuai for forming a keratin filament network because alternative keratin extraction and dialyzing steps are known in the prior art.
Therefore, Applicants’ remarks that the office has not provided an articulated reasoning for the 103 rejection are not found persuasive.
Applicants then assert that Shuai teaches away from dialysis at acidic pH. Applicants assert that Shuai explicitly discloses that keratin undergoes flocculation at lowered pH (Shuai p. 6-7, 63-64). Applicants assert that Shuai further discloses that the gelation process of keratin hydrogel formation involves two stages: keratin flocculation followed by gelation with stabilized keratin flocs. Applicants assert that in fact, Shuai expressly teaches the skilled person to dialyze the soluble keratin solution against deionized water (Shuai p. 21).
Applicants’ remarks are not persuasive. In this instance, Shuai expressly discloses that the flocculation (or gelation process) is triggered by mixing keratin solution with PBS/citrate buffer at acidic pH (at least p. 26). Therefore, Shuai discloses that PBS (which contains a salt) is present with the citrate buffer to trigger gelation. Therefore, Shuai does not teach away from dialysis at an acidic pH 2.65 as disclosed in Bowden et al. during keratin extraction.
While Shuai discloses that keratin can be dialyzed against deionized water, at the time of the invention, alternative keratin extraction and dialyzing steps were known in the prior art, including citrate buffer dialysis at pH 2.65 as disclosed in Bowden et al. Bowden et al. disclose that keratin can also be extracted by soaking the keratin protein source in Tris/HCl, pH 7.5, containing urea and mercaptoethanol (Tum buffer) for 16-24 h at 6º C; homogenized, sonicated, centrifuged, and then where the supernatant is dialyzed against citrate buffer (pH 2.65; citric acid and trisodium citrate) to obtain a keratin solution (p. 30).
Bowden et al. disclose that keratin extraction can be successfully extracted by citrate buffer dialysis at pH 2.65.
Therefore, Applicants’ remarks that Shuai teaches away from dialysis at acidic pH are not persuasive.
Regarding Applicants’ remarks that the objective of Bowden et al. was analytical characterization of keratin and that any flocculation or aggregation would not be detrimental to the analytical objectives of Bowden et al., the remarks are not persuasive. Shuai has disclosed that the flocculation or gelation process occurs with salt and citrate buffer; therefore, one of ordinary skill would not have expected flocculation or aggregation during keratin extraction with citrate buffer dialysis at pH 2.65 as disclosed in Bowden et al. since the keratin is being dialyzed just in acidic citrate buffer and not in the presence of salt and citrate buffer.
Applicants assert that there is no reasonable expectation of success.
Applicants’ remarks are not persuasive. As noted above, Bowden et al. disclose that the keratin proteins extracted from human and mouse epidermis are type II basic and type I acidic keratins (p. 29) and Shuai also discloses that the keratins present in human hair are also of the type II basic and type I acidic keratins (p. 6-7). Therefore, the keratins disclosed in Bowden et al. and Shuai appear to be from the same keratin family.
The hair keratin and the epidermal keratin are also being obtained from keratinized cells, and therefore the same type of cells. Therefore, one of ordinary skill would have a reasonable expectation of success that the keratin extraction and processing conditions, including citrate buffer dialysis at pH 2.65 of Bowden et al., can be successfully incorporated into the keratin extraction and dialyzing step for obtaining the keratin solution in the method of Shuai because the same types of keratin proteins are being extracted.
Applicants assert that the claimed “keratin filament network” is structurally distinct from the prior art disclosures. Applicants assert that the specification at page 3 lines 15-18 discloses that as used herein, “keratin filament network” refers to a network of assembled KIFPs. The network may be made up of interconnected KIFPs, etc. Applicants assert that this is fundamentally distinct and different from what Shuai teaches/discloses. Applicants assert that Shuai is directed to forming a hydrogel.
Applicants’ remarks are not persuasive. Instant claim 1 recites that the keratin filament network is formed by mixing the purified keratin (obtained from the dialysis of step i) with a salt in acidic buffer and drying the solution to form the keratin filament network (steps ii and iii).
Shuai discloses the method for forming a keratin-based gel network comprises adding a salt CaCl2 or reducing pH to about 4 using citrate buffer/PBS to a soluble keratin solution, obtained from dialysis (at least p. 61, 66-70, 91) and lyophilizing keratin gels (at least p. 68-69). Therefore, Shuai discloses the same steps recited in the instant claims 1(ii) and 1(iii) for forming a keratin filament network and therefore, Shuai can be deemed to disclose a keratin-based gel network. It is not clear how a keratin gel disclosed in Shuai would not be considered a “keratin filament network” since it comprise keratin proteins in a network which are the same proteins recited in the instant claim.
Regarding Applicants’ remarks that Bowden et al. fail to disclose a keratin filament network, the remarks are not persuasive. The deficiency of Bowden et al. to not teach a keratin filament network is remedied by the teachings of Shuai noted above.
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 this instance, the conditions for extracting keratin proteins and forming a keratin network are known and disclosed in the teachings of the prior art noted above.
Regarding Applicants’ remarks on the dependent claims, the remarks are not persuasive for the reasons noted above and in the 103 rejection.
For at least these reasons, the 103 rejection is maintained.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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