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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1 – 11 in the reply filed on January 12, 2026 is acknowledged. The traversal is on the grounds that the groups are drawn to a single inventive concept of the immobilized enzyme. This is not found persuasive because immobilized enzymes are known in the art as discussed below.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1 – 13 are pending; claims 12 – 13 are withdraw; claims 1 – 11 have been considered on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 7, 2023 and June 6 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 – 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 and its dependents are drawn to a in immobilized enzyme prepared by a process, however are rendered indefinite for reciting “the five enzymes” as it lacks proper antecedent basis.
Claim 1 is further indefinite for reciting “five enzymes involved in” because the phrase is not adequately defined by the claim language or specification. Since tagatose production may “involves” more than 5 enzymes, it is unclear what applicants regards as “involved.” Applicant may overcome this rejection by deleting “involved in tagatose production”; by deleting “the” prior to the recitation of “five enzymes”; OR deleting “the five enzymes involved in tagatose production:.”
In claim 4, no units are recited for the molecular weight of polyethyleneimine rendering the scope of the claim unclear.
In claim 1, line 6, the recitation of “solutions” appears to lack antecedent basis. It is unclear if the term applies to each of the enzymes, e.g. each in their own solution; or if term applies to the resulting mixture of the enzymes when mixed, e.g., premixing enzymes in a solution. Clarification is required.
In claim 1 line 6, the term “above” is confusing. Applicant may overcome this rejection by deleting the term.
In claim 1 line 7, it is unclear if the term “above solution” refers to the enzyme solution, the calcium chloride solution or the solution resulting from both the enzymes and calcium chloride.
In claim 1, step (4), and claim 10, line 4, the phrase “allowing a reaction” renders the claims indefinite because it is unclear if the phrase intends to encompass unrecited steps that are required to carry out the reaction. Applicant may overcome this rejection by deleting the phrase.
Claim 2 is indefinite for reciting “are used” because it is unclear what the “use” encompasses. Applicant may overcome this rejection by replacing the term with “added,” “included,” or “present.”
In claim 3, line 2, the recitation of “used” renders the claim indefinite because it is unclear what the “use” encompasses. Applicant may overcome this rejection by deleting the term.
In claims 5, 6 and 9, “silicate” lacks proper antecedent basis. Applicant may overcome this rejection by adding “solution” after the term.
In claim 7, “the operations” lacks proper antecedent basis. Applicant may overcome this rejection by deleting “the operations of.”
In claim 9, it is unclear if the calcium carbonate microsphere is referring to the polyethyleneimine-calcium carbonate microsphere of step (2) or the calcium carbonate microsphere of step (1). Clarification is required.
In claim 11, line 2, the phrase “by using” renders the claim indefinite as it is unclear what is included or excluded for the term. Applicant may overcome this rejection by replacing “by using” with “with.”
Claim 11 is further indefinite for reciting “the microsphere obtained above” because the method “obtains” multiple microspheres throughout the process. It is unclear to which microsphere the phrase refers. Clarification is required.
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.
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.
Claims 1 – 11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (IDS 06.06.2025 NPL #2) in view of Neville et al. (2011) and Wichelecki et al. (IDS 06.06.2025 FPD #1).
Regarding claims 1 and 7, Wang teaches gelatin silica microcapsule immobilized enzymes (biomimetic silicon mineralized microcapsules), wherein the microcapsules are prepared by:
combing FateDH (enzymes) and calcium chloride (CaCL2), adding sodium carbonate (Na2CO3) solution, stirring, allowing the samples to settle and centrifuging (solid liquid separation) to collect a solid product (CaCO3 microsphere);
mixing the CaCO3 particles (microsphere) with GelC to create a gel coated CaCO3 particle;
mixing the GelC-CaCO3 particle with sodium metasilicate (Na2SiO3) solution (a silicate solution) to obtain the silicon mineralized particle (microsphere); and
adding EDTA to remove CaCO3 cores, washing and collecting the solid particles (p.943-964).
Wang does not teach the microcapsule or process wherein the enzymes are for producing tagatose. However, Wichelecki teaches immobilized multi-enzyme compositions comprising glucan phosphorylase, phosphoglucomutase, phosphoglucoisomerase, fructose 6 phosphate epimerase (tagatose 6 phosphate 4 epimerase) and tagatose 6 phosphate phosphatase for producing tagatose (abstract, 0003, claims) wherein immobilization of the enzymes provides numerous advantages over their use in free solution. Examples of the advantageous include longer duration of activity, protection of enzyme structural features, multiple cycle reuse, and elimination of the need to remove the enzyme downstream. Wichelecki further teaches that immobilizing the enzymes allow for their use in a stirred tank reactor, a packed bed reactor or a rotating bed reactor which allows for flexibility in scale-up (0014). As such, at the time the claims were filed one of ordinary skill in the art would have been motivated to immobilize the claimed enzymes in the microcapsule of Wang for the documented advantages disclosed by Wichelecki.
Wang does not teach the method wherein polyethyleneimine (PEI) is used. However, at the time the claims were filed, PEI was commonly used in processes for immobilizing enzymes in silicon. In support, Neville teaches PEI can be advantageous in making biosilicate nanoparticles and silicate entrapped enzymes (microcapsules) in that it mimics natural peptides (biomimetic), is stable at room temperature and is inexpensive compared to the natural peptides (abstract). Neville additionally teaches that PEI allows for forming the silicon structures at the same time of enzyme immobilization thereby reducing the number of steps and allows for altering variable such as molecular weight, concentration and type of silicate (p.280). Thus, in following the teachings of Neville, one of ordinary skill in the art would have been motivated to substitute the GelC of Wang with PEI for its well documented advantages over other polymers and with a reasonable expectation for successfully obtaining silicon microcapsule immobilized enzymes.
Regarding claims 2 and 3, Wichelecki further teaches that the weight and ratios between the enzymes may vary, ranging range from 1:1000 to 1000:1, from 1:100 to 100:1 or from 1:50 to 50:1, when comparing any two enzymes in the immobilized composition; and that the weights/rations can be optimized to increase process performance and/or hexose yield (e.g., tagatose) (0019 – 0020). Thus, at the time the claims were filed, one of ordinary skill in the art would have been motivated to optimize the amount and ratio of enzymes as a matter of routine practice and experimentation and as directed by Wichelecki.
Regarding claims 4 and 8, Neville teaches adding 0.1 mM PEI with a molecular weight of 1000 (within the claimed range of 600 – 70000) (p.280). Although Neville does not teach the claimed concentration, the reference states that PEI allows for altering variable such as molecular weight and concentration (p.280). As such, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to optimize the concentration, molecular weights and ratios of PEI as a matter of routine practice and experimentation with a reasonable expectation for successfully preparing an immobilized enzyme.
Regarding claims 5 – 6, Wang does not teach the claimed amount of silicate solution. However, Wang does teach adding 5ml of a 50 mM Na2SiO3 solution (p.964) as an active agent in the methods. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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." MPEP 2144.05(II)(A). Thus, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to optimize the concentration of silicate solution in the methods obtained by the combined teachings as a matter of routine practice and experimentation with a reasonable expectation for successfully preparing an immobilized enzyme.
Regarding claim 9, Wang does not teach the claimed ratio of silicate solution to CaCO3 microspheres. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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." MPEP 2144.05(II)(A). Thus, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to optimize the ratio of silicate solution to microspheres in the methods obtained by the combined teachings as a matter of routine practice and experimentation with a reasonable expectation for successfully preparing an immobilized enzyme.
Regarding claim 10, Wang teaches adding a 1.5L of a 0.33 M CaCl2 solution (within the claimed 0.2 – 0.4 M) with 1.5L, 0.33M NaCO3 (equal volume and equal molar concentrations), stirred (under rotation) for 30 seconds, followed by centrifugation and washing (until no sodium or chlorides ions are removed) (p.963). Although Wang does not teach the specific rotation/centrifugation speeds or deionized water, it would have been well within the purview of one of ordinary skill in the art to optimize these parameters as a matter of routine practice and experimentation.
Regarding claim 11, Wang does not teach the claimed parameters of the EDTA solution and step (4). However, Wang teaches the EDTA is removed by washing with PBS with a pH of 7.0 (p.964). At the time the claims were filed, these parameters would have been well within the purview of one of ordinary skill in the art to optimize these parameters as a matter of routine practice and experimentation, absent evidence of criticality. Generally, differences in concentration, temperature and times will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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." MPEP 2144.05(II)(A). Moreover, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to optimize the ratios of actives, stir times, centrifugation speeds and number of washes as a matter of routine practice and experimentation with a reasonable expectation for successfully preparing an immobilized enzyme.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
No claims are allowed.
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/RUTH A DAVIS/ Primary Examiner, Art Unit 1699