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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 1/28/2026 are acknowledged. Claims 1-2 and 9 are amended; claims 4, 7-8, 10, 13-16, 18-21, 25-26, 28-32, 35-40, 43-44, 46-47 and 49-50 are canceled; claims 1-3, 5-6, 9, 11-12, 17, 22-24, 27, 33-34, 41-42, 45 and 48 are pending; claims 11-12, 17, 22-24, 27, 33-34, 41-42, 45 and 48 are withdrawn; claims 1-3, 5-6 and 9 have been examined on the merits.
Claim Interpretation
Claims 1-3, 5-6 and 9 are drawn to compositions of immobilized enzyme not to a method of producing an immobilized enzyme; hence, limitations drawn to the process of making the compositions are product-by-process limitations. Thus, “wherein the immobilized enzyme comprises an activated cationic polymer and an enzyme covalent-bonded on the activated cationic polymer, wherein the activated cationic polymer is a polyethylene imine (PEI) activated by a crosslinking agent or one or more cofactors, and the cross-linking agent is modified or not modified by a polyol; wherein the polyol comprises polyethylene glycol (PEG); wherein the cross-linking agent comprises glutaraldehyde; the enzyme is selected from the group consisting of: a transaminase, a ketoreductase, a monooxygenase, an ammonia lyase, an ene reductase, an imine reductase, an amino acid dehydrogenase and a nitrilase; wherein a mass ratio of the enzyme and the PEI in the immobilized enzyme is 0.1-1.5:1; wherein the enzyme is a precipitated enzyme or a free enzyme; wherein when the enzyme is the precipitated enzyme, the cross-linking agent is glutaraldehyde, and the activating agent is the glutaraldehyde or a PEG-modified glutaraldehyde; wherein when the enzyme is the free enzyme, the activating agent is one or more cofactors; wherein and a mass ratio of the one or more cofactors and the PEI in the immobilized enzyme is 1-80:120 and wherein the immobilized enzyme is without a carrier support” is interpreted as a product-by-process claim drawn to an immobilized enzyme without a carrier support comprising the enzyme and PEI and optionally, PEG and/or one or more cofactors; wherein the enzyme is crosslinked to the PEI with glutaraldehyde; wherein the mass ratio of the enzyme and the PEI in the immobilized enzyme composition is 0.1-1.5:1; wherein the enzyme is selected from the group consisting of: a transaminase, a ketoreductase, a monooxygenase, an ammonia lyase, an ene reductase, an imine reductase, an amino acid dehydrogenase and a nitrilase; wherein, when present, the mass ratio of the one or more cofactors and the PEI in the immobilized enzyme is 1-80:120.
Claim Rejections - 35 USC § 112
The rejection of claims 1-3, 5-6 and 9 under 35 U.S.C. § 112(b), as set forth at pp. 4-6 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-3, 5-6 and 9 under 35 U.S.C. § 112(a), as set forth at pp. 6-7 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claim 2 under 35 U.S.C. § 112(d), as set forth at pp. 7-8 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 102
The rejection of claims 1-3 under 35 U.S.C. § 102(a)(1) over Hong et al., CN110964710 (Foreign Patent Document 4, IDS, 8/15/2024; herein “Hong”) as set forth at pp. 8-11 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 5 and 9 under 35 U.S.C. § 103(a) over Rozzell, US Patent 4826766 (cite A, PTO-892, 7/9/2025; herein “Rozzell”) as set forth at pp. 11-14 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-3 and 6 under 35 U.S.C. § 103(a) over Hong as set forth at pp. 14-15 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 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.
Claims 1, 3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez-Gallego et al., 2005 (cite U, attached PTO-892; herein “Lopez-Gallego”) in view of Van Pelt et al., WO2018/004341 (cite N, attached PTO-892; herein “Van Pelt”).
Lopez-Gallego discloses an immobilized enzyme without a carrier support, i.e., a crosslinked enzyme aggregate (CLEA; Abst.), comprising the enzyme crosslinked with glutaraldehyde to 600 kDa polyethyleneimine (PEI; pp. 1839-1840, “Materials”) at a 1:1 ratio (p. 1840, “Preparation of CLEA-PEIPEG”, “Preparation of CLEA-PEI”) wherein the immobilized enzyme composition can further comprise 600 Da polyethylene glycol (PEG; pp. 1839-1840, “Materials”; p. 1840, “Preparation of CLEA-PEIPEG”).
Lopez-Gallego differs from claim 1 in that the enzyme is not a transaminase, a ketoreductase, a monooxygenase, an ammonia lyase, an ene reductase, an imine reductase, an amino acid dehydrogenase or a nitrilase. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the enzyme to be a transaminase, a ketoreductase, a lyase, an imine reductase or a nitrilase in view of the disclosure of Van Pelt.
Van Pelt discloses that transaminases, ketoreductases, lyases, imine reductases and nitrilases are suitable enzymes for immobilization with CLEA (p. 5, ll. 5-10); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce immobilized transaminases, ketoreductases, lyases, imine reductases and nitrilases by the method of Lopez-Gallego, thus producing the immobilized enzyme compositions of claims 1, 3 and 6; therefore, claims 1, 3 and 6 are prima facie obvious.
Response to Arguments
Applicant's arguments filed 1/28/2026 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on pp. 9-15 regarding the rejections under 35 U.S.C. §§ 112(b), 112(a), 112(d), 102(a)(1) and 103 are moot as the rejections have been withdrawn.
Regarding the rejection of claims 1, 3 and 6 set forth above, the rejection does not rely on any prior art set forth in the prior Office action; hence, the arguments regarding the rejection of claims 1-3 under 35 USC § 102(a)(1) over Hong et al., CN110964710 (Foreign Patent Document 4, IDS, 8/15/2024; herein “Hong”); the rejection of claims 1, 5 and 9 under 35 USC § 103 over Rozzell, US Patent 4826766 (cite A, PTO-892, 7/9/2025; herein “Rozzell”); and the rejection of claims 1-3 and 6 under 35 USC § 103 over Hong are moot.
The rejection set forth above addresses all the limitations of the amended claims.
Claims 1-3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez-Gallego in view of Van Pelt and Hong et al., CN110964710 (Foreign Patent Document 4, IDS, 8/15/2024; herein “Hong”).
The discussion of Lopez-Gallego and Van Pelt regarding claims 1, 3 and 6 set forth in the rejection above is incorporated herein.
Neither Lopez-Gallego nor Van Pelt teach that the transaminase is derived from Chromobacterium violaceum DSM30191; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the transaminase in the immobilized enzyme made obvious by Lopez-Gallego in view of Van Pelt to be derived from Chromobacterium violaceum DSM30191 in view of the disclosure of Hong.
Hong discloses immobilized enzyme compositions wherein the enzyme can be selected from any one of a transaminase, a ketoreductase, a monooxygenase, an ammonia lyase, an alkene reductase, an imine reductase, an amino acid dehydrogenase and a nitrilase [n0010] comprising an activated cationic polymer and an enzyme covalent-bonded on the activated cationic polymer, wherein the activated cationic polymer is a polyethylene imine (PEI) activated by a crosslinking agent wherein the activating agent and crosslinking agent is glutaraldehyde, the PEI has a molecular weight of 3 to 70 kDa, and the mass ratio of the enzyme and the PEI in the immobilized enzyme is 0.42:1 ([n0047], [n0086]).
Hong discloses that the PEI can be contacted with glutaraldehyde (GA) at a mass ratio of 3:1 PEI:GA [n0047], thus producing an activated cationic polymer.
Hong discloses that producing the activated cationic polymer comprises contacting 160 µl of a 50% aqueous solution of glutaraldehyde (~ 80 mg glutaraldehyde) with an appropriate proportion of PEG or PEI [n0086], which [n0047] discloses can be 3 times the mass of the glutaraldehyde for PEI, i.e., 240 mg, of 3 to 70 kDa PEI.
Hong discloses that the activated cationic polymer (described by Hong as a cross-linking agent treated by a high polymer in the Abstract) is contacted with 4 ml of enzyme solution (20-25 mg/ml), thus producing an immobilized enzyme composition comprising an activated cationic polymer and an enzyme covalent-bonded on the activated cationic polymer [n0086]. Thus, the mass ratio of enzyme to PEI in the composition is 100 mg enzyme (4 ml x 25 mg/ml) to 240 mg PEI, which simplifies to 0.42:1.
Hong discloses that the polyol contacted with the cross-linking agent can be polyethylene glycol (PEG) or PEI [n0047] and teaches “In the preferred embodiment described above, glutaraldehyde is treated with a high polymer, PEG or PEI, so that the aldehyde groups of glutaraldehyde covalently bond with the hydroxyl groups of PEG or the amino groups of PEI, ultimately forming a network structure dispersed with aldehyde groups and amino/hydroxyl groups. The functional groups in this network structure bond with the enzyme protein through various mechanisms, including covalent interactions, hydrogen bonding, ionic interactions, and hydrophobic interactions, rather than simply covalent bonding as with glutaraldehyde, which can easily degrade enzyme activity.” [n0048].
Hong discloses that the transaminase can be a transaminase derived from Chromobacterium violaceum DSM30191 or a transaminase derived from Arthrobacter citreus, the ketoreductase can be derived from Acetobacter sp. CCTCC M209061 or Candida macedoniensis AKU4588, the monooxygenase can be a cyclohexanone monooxygenase derived from Brachymonas petroleovorans or Rhodococcus ruber-SD1, the ammonia lyase can be an ammonia lyase derived from Photorhabdus luminescens or Solenostemon scutellarioides, the ene reductase can be derived from Saccharomyces cerevisiae or Chryseobacterium sp. CA49, the imine reductase can be an imine reductase derived from Streptomyces sp. or Bacillus cereus, the amino acid dehydrogenase can be a leucine dehydrogenase derived from Bacillus cereus or a phenylalanine dehydrogenase derived from Bacillus sphaericus and the nitrilase can be a nitrilase derived from Aspergillus niger CBS 513.88 or Neurospora crassa OR74A [n0011-14].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the immobilized enzyme compositions made obvious by Lopez-Gallego in view of Van Pelt wherein the transaminase is a transaminase derived from Chromobacterium violaceum DSM30191 because Lopez-Gallego teaches carrier-free immobilized enzyme compositions comprising PEI and crosslinked with glutaraldehyde (CLEA), Van Pelt discloses that transaminases are suitable for CLEA, and Hong discloses producing immobilized enzyme compositions wherein transaminase derived from Chromobacterium violaceum DSM30191 is crosslinked to PEI with glutaraldehyde; therefore, claim 2 is prima facie obvious.
Response to Arguments
Regarding the rejection set forth above under 35 U.S.C. 103 over Lopez-Gallego in view of Van Pelt and Hong, Hong is relied on for the disclosure that the immobilized transaminase can be Chromobacterium violaceum DSM30191. Applicant does not dispute that Hong discloses that Chromobacterium violaceum DSM30191 can be an immobilized transaminase; hence, the arguments on pp. 10-14 are moot regarding the rejection set forth above.
The rejection set forth above addresses all the limitations of the amended claims.
Claims 1-3, 5-6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez-Gallego in view of Van Pelt, Hong and Rozzell, US Patent 4826766 (cite A, PTO-892, 7/9/2025; herein “Rozzell”).
The discussion of Lopez-Gallego, Van Pelt and Hong regarding claims 1-3 and 6 set forth in the rejection above is incorporated herein.
Lopez-Gallego, Van Pelt and Hong do not disclose having one or more cofactors immobilized with the enzyme; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the immobilized enzymes to further comprise the cofactors for the enzymes in view of the disclosure of Rozzell.
Rozzell is drawn to methods of transamination (Abst.) wherein the enzymes of the process can be immobilized enzymes (col. 9, ll. 7-9) wherein the enzymes can be immobilized on particles impregnated with PEI followed by activation with glutaraldehyde (col. 9, ll. 29-32), i.e., immobilized on an activated cationic polymer (PEI) activated with cross-linker/activating agent glutaraldehyde. Rozzell teaches that immobilization of the enzymes can comprise incubation of the enzyme, the cofactor pyridoxal phosphate (PLP in the instant claims) and the substrate, followed by cross-linking (Example 5, col. 9, ll. 55-68); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the immobilized enzyme compositions made obvious by Lopez-Gallego in view of Van Pelt and Hong, wherein the immobilized enzyme composition further comprises one or more cofactors for the enzyme wherein the cofactor can be PLP.
Rozzell is silent on the mass ratio of the PLP and the PEI in the immobilized enzyme composition; however, the amount of cofactor available to the immobilized enzyme in the immobilized enzyme composition is a result effective variable because the amount of cofactor available to the enzyme would impact the functionality of the immobilized enzyme for enzymes that require a cofactor. Therefore, a person of ordinary skill in the art would find it obvious to vary the amount of cofactor, i.e., PLP, in the immobilized enzyme compositions made obvious by Lopez-Gallego in view of Van Pelt and Hong to get an immobilized enzyme composition that met the perceived need and would arrive at the PLP:PEI ratio of 1-60:100; therefore, claims 1, 5 and 9 are prima facie obvious. See also MPEP 2144.05 II.A. “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%)".
Response to Arguments
Regarding the rejection set forth above under 35 U.S.C. 103 over Lopez-Gallego in view of Van Pelt, Hong and Rozzell, Rozzell is relied on for the disclosure that the cofactors for immobilized enzymes can be immobilized along with the enzyme. Applicant does not dispute that Rozzell discloses that the cofactors for immobilized enzymes can be immobilized along with the enzyme; hence, the arguments on pp. 10-14 are moot regarding the rejection set forth above.
The rejection set forth above addresses all the limitations of the amended claims.
Double Patenting
The rejection of claims 1-3, 5-6 and 9 on the ground of nonstatutory double patenting over claims 1, 4, 7, 11-12 and 14 of U.S. Patent No. 12098239 in view of Hong as set forth at pp. 15-20 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The provisional rejection of claims 1-3 on the ground of nonstatutory double patenting over claims 1-2 of copending Application No. 17/789235 in view of Hong as set forth at pp. 20-22 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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