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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/28/2026 has been entered.
Applicants' arguments filed on 8/28/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1-10 are at issue and present for examination.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 5, 7 and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zonhon Biopharma Inst Inc. and Gensun Inst Biomedicine Co. Ltd. (CN105796507).
Zonhon Biopharma Inst Inc. and Gensun Inst Biomedicine Co. Ltd. (CN105796507) discloses a liquid enzyme preparation comprising a protein deamidase (i.e. asparaginase) and 30w/v% of sorbitol at a pH of 8 (see Table 1) and methods of stabilizing a liquid enzyme preparation comprising a protein deamidase comprising adding sorbitol as an active ingredient to the liquid enzyme preparation of the protein deamidase, the sorbitol being used at a concentration of 30 w/v% or more in the liquid enzyme preparation of the protein deamidase with a pH of 5.5 or more.
Thus, claim(s) 1-3, 5, 7 and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zonhon Biopharma Inst Inc. and Gensun Inst Biomedicine Co. Ltd. (CN105796507).
Claim(s) 1-3, 5, 7 and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zonhon Biopharma Inst Inc. (CN107693796).
Zonhon Biopharma Inst Inc. (CN107693796) discloses a liquid enzyme preparation comprising a protein deamidase (i.e. asparaginase) and 10-50 mg/ml sorbitol at a pH of 5-7 (see pg 4, cl 1-9) and methods of stabilizing a liquid enzyme preparation comprising a protein deamidase comprising adding sorbitol as an active ingredient to the liquid enzyme preparation of the protein deamidase, the sorbitol being used at a concentration of 10-50 mg/ml in the liquid enzyme preparation of the protein deamidase with a pH of 5-7.
Thus, 1-3, 5, 7 and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zonhon Biopharma Inst Inc. (CN107693796).
Claim Rejections - 35 USC § 103
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.
The rejection of claim(s) 1-5, 7-9 under 35 U.S.C. 103 as being unpatentable over Wang et al., US 2020/027598) and Combes et al., Annals of the New York Academy of Sciences, Vol 613, No. 1, pp 559-563, Dec 1990 is withdrawn based upon applicants amendment of the claims that recites “wherein the protein deamidase is an enzyme that exhibits an action of decomposing an amide group-containing side chain of a protein without crosslinking the protein”.
Claim(s) 1-6, 7-9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., US 2020/027598), Yamaguchi et al. (Eur. J. Biochem. Vol 268, pp 1410-1421, 2001) and Combes et al., Annals of the New York Academy of Sciences, Vol 613, No. 1, pp 559-563, Dec 1990 .
This rejection was stated in the previous office action as it applied to previous claims 1-6, 7-9 and 10. In response to the rejection applicants have not amended the claims, but rather traverse the rejection as it applies to the previous claims. For applicants convenience the original rejection is repeated herein.
Wang et al., US 2020/027598 teach a liquid enzyme preparation of transglutaminase and a preparation method thereof, wherein the liquid enzyme preparation is a liquid preparation of transglutaminase EC2.3.2.13, and its components and amounts thereof are as follows: the liquid preparation of transglutaminase has an enzyme activity of 10-1000 u/ml, a water activity regulator is present in an amount of 30-80 w/v %, a redox potential regulator is present in an amount of 0.0075-1 w/v %, a food preservative is present in an amount of 0-0.1 w/v % (a sulfite), and a pH regulator is added to a final volume of 100%. The preparation method thereof comprises purification of an enzyme solution, mixing, sterilization, filling, and obtaining of a final product (see abstract and supporting text). Wang et al. teach the effects of different water activity regulators on the enzyme activity of transglutaminase (Table 5-1 and supporting text) and they teach that sorbitol, malitol, glycerol or any combination thereof was preferred for stabilizing the enzyme activity of transglutaminase.
Yamaguchi et al. teach a protein deamidating enzyme from Chryseobacterium proteolyticum. Yamaguchi et al. teach the isolation and cloning of said protein deamidating enzyme from Chryseobacterium proteolyticum and teach that the enzyme had activity against several proteins including insoluble wheat gluten. Yamaguchi et al. further teach the above enzyme characterization in view of the enzymatic modification of proteins to improve protein functionality for the use of proteins in food ingredients. Yamaguchi et al. teach that the enzyme showed a broad pH optimum between pH 5 and pH 7 (Fig 5A).
Combes et al. teach the stabilizing effect of a number of polyhydric alcohols and they teach that increasing concentrations of sorbitol (36% w/v to 72% w/v) had increased effect on enzyme (lysozyme) stability, and sorbitol was better than numerous other polyhydric alcohols such as xylitol, erythritol, glycerol and ethylene glycol (see Figure 1 and supporting text).
One of skill in the art before the effective filing date would have been motivated to create a liquid enzyme preparation comprising the protein deamidating enzyme from Chryseobacterium proteolyticum as taught by Yamaguchi et al. and 30% (w/v) or more sorbitol as taught by Combes et al. and having a pH of 5.5 or more and a sulfite to maintain/preserve enzyme activity as taught by Wang et al. (enzyme activity of 10-1000 u/ml) of protein deamidating enzyme (claims 1-6) and methods of its use and preparation for enzyme stabilization and prevention of inhibition (claims 7-9) as taught by Wang et al. for its commercial value for improving the color, flavor and taste of products. The motivation for such liquid enzyme preparations and methods of use in enzyme stabilization and inhibition of precipitation are based upon the teachings of Yamaguchi et al., Wang et al. and Combes et al. as above that teach that 30% (w/v) or greater is beneficial in the stabilization of enzymes. One of skill in the art before the effective filing date would have been further motivated to vary the various components of the liquid enzyme preparation such as the sulfite component of 0.1 w/v% to 0.2 w/v% as taught by Wang et al as a means of analyzing and achieving the best stabilized liquid enzyme preparations. The expectation of success is high based upon the high level of skill in the art of protein isolation and stabilization as illustrated by Yamaguchi et al., Wang et al. and Combes et al. who teach all that is required to practice the obvious methods and make the obvious preparations.
Applicants Response
Applicant requests reconsideration of the pending claims on the basis that applicant submits that unexpected effects arising from: (a) the selection of a specific combination of components, and (b) the specific pH range recited in the claims.
Applicant submits that there are unexpected effects arising from the selected combination of components.
Applicant submits that the Examiner relies on Wang and Combes for the claimed feature of "30 w/v% or more of sorbitol", as Wang, which discloses that not only sorbitol but also glycerol may equally be used as a water activity regulator. Applicant submits that compares the effects of sorbitol and glycerol on the retention rate of the enzyme activity of transglutaminase, and demonstrates that glycerol is somewhat superior to sorbitol in terms of the retention rate of enzyme activity.
Applicant submits that the teaching of Wang conflicts with the teaching of Combes, relied upon by the Examiner, that sorbitol "was better than numerous other polyhydric alcohols such as xylitol, erythritol, glycerol and ethylene glycol".
Applicant submits in other words, Wang, which discloses transglutaminase, and Combes, which discloses lysozyme, taken together teach that the polyhydric alcohol that provides activity stability differs depending on the type of enzyme. Applicant submits that accordingly, when applying protein glutaminase, a different enzyme that is disclosed in neither Wang nor Combes, a person skilled in the art would have had no basis to select the teaching of sorbitol in Combes, which discloses lysozyme, while disregarding the advantageous teaching of glycerol in Wang, which discloses transglutaminase.
Applicant submits that in the present specification, as demonstrated by the comparison between glycerin (Comparative Example 4, residual activity 14%) and sorbitol (Example 1, residual activity 45%) at the same concentration, a markedly higher activity stability is obtained through the use of sorbitol. Applicant submits that neither the improvement in activity stability achieved by the selection of sorbitol, nor the remarkable degree of that improvement, could have been predicted from any of the cited references.
Applicant submits that unexpected effects arisie from the selection of the claimed pH range.
Applicant submits that with regard to the presently claimed feature of "a pH of 5.5 or more", the only reference to pH in the Examiner's reasoning is "a broad pH optimum between pH 5 and pH 7", based on Fig. 5A of Yamaguchi et al., which discloses protein glutaminase.
Applicant submits that the pH characteristics shown in Fig. 5A of Yamaguchi, which discloses protein glutaminase, are the pH dependence of activity (closed circles) and the pH stability (open circles). Applicant submits that with regard to pH stability, high stability is obtained at pH 5 (see arrow in the figure). It should also be noted that these pH characteristics do not demonstrate any effect of inhibiting precipitation.
Applicant submits that in Wang, the primary reference disclosing transglutaminase, data concerning activity stability are set out in Table 1 in connection with "stability". Applicant submits that Wang shows that high activity stability is obtained at pH 5.
Applicant submits that in contrast, with the presently claimed liquid enzyme preparation and related methods, which comprise a specific combination of components not disclosed in the cited references, the desired activity stability is not obtained at pH 5 (Comparative Example 8, residual activity 14%), whereas a marked improvement in activity stability is obtained by virtue of the pH being 5.5 or more (Example 1, residual activity 45%).
Applicant submits that since both Yamaguchi et al. and Wang - the only references that refer to pH demonstrate that pH 5 is a pH at which excellent activity stability is assured, a person skilled in the art would not have appreciated the importance of avoiding pH 5.
Applicant submits that accordingly, the fact that such a marked improvement in activity stability is obtained by selecting the claimed pH range could not have been predicted from any of the cited references
Applicants complete argument is acknowledged and has been carefully considered, however, is not found persuasive for the reasons previously made of record and for those reasons repeated herein.
In response to applicants submission that there are unexpected effects arising from the selected combination of components applicants arguments are not found persuasive for the following reasons.
In response to applicants submission that the teaching of Wang conflicts with the teaching of Combes, relied upon by the Examiner, that sorbitol "was better than numerous other polyhydric alcohols such as xylitol, erythritol, glycerol and ethylene glycol", this is not found persuasive in overcoming the rejection on the basis that while the teaching of Wang and Combes may differ slightly as they involve different enzymes and different experimental conditions, they do not conflict. Wang discloses that sorbitol and glycerol may be used interchangeably as they had a similar preservation rate of enzyme activity for transglutaminase (i.e. 81.89% for sorbitol and 85.44% for glycerol). Combes on the other hand teach that sorbitol was better than numerous other polyhydric alcohols such as xylitol, erythritol, glycerol and ethylene glycol (see Figure 1 and supporting text) for lysozyme stability. The data are different but do not conflict.
In response to applicants submission that a person skilled in the art would have had no basis to select the teaching of sorbitol in Combes, which discloses lysozyme, while disregarding the advantageous teaching of glycerol in Wang, which discloses transglutaminase this is not found persuasive on the basis that the ordinary artisan would realize that the effects of the various stabilizers may differ based upon numerous factors including the specific enzyme which is being stabilized. Wang teaches that for the enzyme transglutaminase, sorbitol and glycerol have a similar effect on enzyme activity although glycerol may be a little better (i.e. 81.89% for sorbitol and 85.44% for glycerol relative to 39.31% for the control). Combes et al. teach that increasing concentrations of sorbitol (36% w/v to 72% w/v) had increased effect on enzyme (lysozyme) stability, and sorbitol was better than numerous other polyhydric alcohols such as xylitol, erythritol, glycerol and ethylene glycol (see Figure 1 and supporting text). Thus given the teachings of Wang et al. and Combes et al., one of skill in the art before the effective filing date would have been motivated to create a liquid enzyme preparation comprising the protein deamidating enzyme from Chryseobacterium proteolyticum as taught by Yamaguchi et al. and 30% (w/v) or more sorbitol as taught by Combes et al. and having a pH of 5.5 or more and a sulfite to maintain/preserve enzyme activity as taught by Wang et al. (enzyme activity of 10-1000 u/ml) of protein deamidating enzyme.
Applicants submission that in the present specification, as demonstrated by the comparison between glycerin (Comparative Example 4, residual activity 14%) and sorbitol (Example 1, residual activity 45%) at the same concentration, a markedly higher activity stability is obtained through the use of sorbitol and that the improvement in activity stability achieved by the selection of sorbitol, nor the remarkable degree of that improvement, could have been predicted from any of the cited references, is not found persuasive on the basis that while the skilled artisan would understand that different enymes would have different stability profiles with different components and different stabilizers. Thus the fact that sorbitol acts as a better stabilizer than glycerol for a specific enzyme is not unexpected.
Applicants submission that unexpected effects arise from the selection of the claimed pH range are not found persuasive for the following reasons.
Applicans summary of the results of Yamaguchi et al. and Wang in support of applicants argument is acknowledged.
In response to applicants submission that in contrast to the results of Yamaguchi et al. and Wang the presently claimed liquid enzyme preparation and related methods, which comprise a specific combination of components not disclosed in the cited references, the desired activity stability is not obtained at pH 5 (Comparative Example 8, residual activity 14%), whereas a marked improvement in activity stability is obtained by virtue of the pH being 5.5 or more (Example 1, residual activity 45%) this is not found persuasive as the current claims are drawn to a liquid enzyme preparation comprising a protein deamidase and 30 w/v% or more of sorbitol and having a pH of 5.5 or more, wherein the protein deamidase is an enzyme that exhibits an action of decomposing an amide group-containing side chain of a protein without crosslinking the protein as Yamaguchi et al. teach that the enzyme showed a broad pH optimum between pH 5 and pH 7, which makes a pH of 5.5 or more obvious.
Thus applicants arguments are not found persuasive for the reasons previously stated and for those reasons repeated above.
Further it is noted that whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) Applicants arguments even if deemed persuasive in the results being unexpected are not commensurate in scope with the claims.
Thus, claim(s) 1-6, 7-9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., US 2020/027598), Yamaguchi et al. (Eur. J. Biochem. Vol 268, pp 1410-1421, 2001) and Combes et al., Annals of the New York Academy of Sciences, Vol 613, No. 1, pp 559-563, Dec 1990 .
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
9/23/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
