DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/05/2025 has been entered.
Claims 1, 3, 5-6, 10 and 19-23 are pending in this application.
Applicant’s amendment to the claims filed 12/05/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 12/05/2025 in response to the final rejection mailed on 08/05/2025 and the advisory actions mailed on 10/09/2025 and 10/29/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to claims 1, 3, 5-6, 10 and 23, drawn to the technical feature of an immobilized enzyme composition for the preparation of a hexose comprising at least two of the following enzymes immobilized to at least one carrier or a mixture of carriers: a) a glucan phosphorylase (aGP), phosphoglucomutase (PGM), and optionally 1,4-glucan transferase (4-GT); and b) an enzyme from within a combination of enzymes selected from: (i) phosphoglucoisomerase (PGI), fructose-6-phosphate epimerase (F6PE), and tagatose-6- phosphate phosphatase (T6PP) to prepare tagatose; (ii) PGI, piscose-6-phosphate epimerase (P6PE), and picose-6-phosphate phosphatase (P6PP) to prepare allulose; (iii) PGI, P6PE, allose-6-phosphate isomerase (A6PI), and allose-6-phosphate phosphatase (A6PP) to prepare allose; (iv) PGI, mannose-6-phosphate isomerase (M6PI) or phosphoglucose/phosphomannose isomerase (PGPMI), and mannose 6-phosphate phosphatase (M6PP) to prepare mannose; (v) PGI, F6PE, galactose 6-phosphate isomerase (Gal6PI), and galactose 6-phosphate phosphatase (Gal6PP) to prepare galactose; (vi) PGI and fructose 6-phosphate phosphatase (F6PP) to prepare fructose; (vii) PGI, P6PE, altrose 6-phosphate isomerase (Alt6PI), and altrose 6-phosphate phosphatase (Alt6PP) to prepare altrose; (viii) PGI, F6PE, talose 6-phosphate isomerase (Tal6PI), and talose 6-phosphate phosphatase (Tal6PP) to prepare talose; (ix) PGI, F6PE, sorbose 6-phosphate epimerase (S6PE), and sorbose 6-phosphate phosphatase (S6PP) to prepare sorbose; (x) PGI, F6PE, S6PE, gulose 6-phosphate isomerase (Gul6PI), and gulose 6-phosphate phosphatase (Gul6PP) to prepare gulose; (xi) PGI, F6PE, S6PE, idose 6-phosphate isomerase (16P1), and idose 6-phosphate phosphatase (16PP) to prepare idose; and (xii) inositol 3-phosphate synthase (IPS) and inositol monophosphatase (IMP) to prepare inositol, and
Species (i), the enzymes immobilized to at least one carrier or a mixture of carriers are fructose-6-phosphate epimerase (F6PE), and tagatose-6-phosphate phosphatase (T6PP) to prepare tagatose,
elected without traverse in the reply filed 12/23/2024.
Claims 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 3, 5-6, 10 and 23 are being examined on the merits only to the extent they read on the elected subject matter.
Claim Rejections - 35 USC § 103
The rejection of claims 15 and 25 under 35 U.S.C. 103 as being unpatentable over WO 2017/059278 (cited on the IDS filed 07/30/2024; herein referred to as Bonumose) and Guidini et al. (Biochem Eng J, 2010; 52:137; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as Guidini), and further in view of Garcia-Galan et al. (Adv Synth Catal, 2011, 353:2885; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as Garcia), and
the rejection of claim 26 under 35 U.S.C. 103 as being unpatentable over Bonumose, Guidini and Garcia-Galan et al. (Adv Synth Catal, 2011, 353:2885; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as Garcia), and further in view of Block et al. (Methods Enzymol, 2009, 463:439; cited on the Form PTO-892 mailed 08/05/2025; herein referred to as Block)
are withdrawn in view of the cancelation of claims 15 and 25-26.
Claims 1, 3, 5, 10 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Bonumose in view of Guidini.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 1 is drawn to an immobilized enzyme composition for the preparation of tagatose comprising alpha-glucan phosphorylase (aGP), phosphoglucomutase (PGM), phosphoglucoisomerase (PGI), fructose-6-phosphate epimerase (F6PE), tagatose-phosphate phosphatase (T6PP), and optionally 1,4-glucan transferase (4GT), immobilized to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group.
Bonumose relates to the enzymatic synthesis of d-tagatose [title] which is understood to be a hexose, and discusses the need for an alternative strategy to produce tagatose that is more cost-effective and higher yield than conventional methods [para 5].
Regarding claims 1 and 3 and the limitation of an enzyme composition comprising aGP, PGM, PGI, F6PE, T6PP and 4GT, Bonumose discloses the enzymatic conversion of saccharides to tagatose [para 2] through the conversion of saccharides to glucose-1-phosphate (G1P), converting G1P to glucose-6-phosphate (G6P) with PGM, converting G6P to fructose-6-phosphate (F6P) with PGI, converting F6P to tagatose-6-phosphate (T6P) with an epimerase [para 9] such as fructose-6-phosphate epimerase (F6PE) [para 12], and converting T6P to tagatose catalyzed by a phosphatase [para 8] such as tagatose-6-phosphate phosphatase (T6PP) [para 31]. Bonumose further discloses the saccharides can consist of a starch or derivative which can be prepared by the hydrolysis of starch by 4GT [para 9], and that starch can be hydrolyzed to produce G1P by aGP [para 43]. While Bonumose does not explicitly teach the incorporation of these components into a composition, as Bonumose teaches the use of these enzymes for the production of tagatose, it would have been obvious to combine the enzymes a composition to produce tagatose.
Bonumose does not teach the immobilization of enzymes to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group.
Guidini relates to the immobilization of enzymes [title] and discusses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability [p 137, col 2, para 1].
Regarding claims 1 and 3 and the limitation of the immobilization of enzymes on at least one carrier or a mixture of carriers, Guidini discloses the immobilization of the enzyme β-galactosidase, which is an important enzyme in the biotechnological process of lactose hydrolysis to form glucose (a hexose) [p 137, col 1, para 1], onto Duolite A568 resin resulting in high enzymatic activity and stability, that was additionally stable across a wide range of pH from 3.5-8.0 [p 138, col 1, para 1], wherein the Duolite A568 resin of Guidini is a weak base anion exchange resin based on cross-linked phenol-formaldehyde polycondensate with tertiary amine functional groups [p 138, col 1, para 4].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Bonumose and Guidini, to immobilize the enzymes of Bonumose using the carrier of Guidini, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to immobilize the enzymes of Bonumose because Guidini discloses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability. One of ordinary skill in the art would have had a reasonable expectation of success because both Bonumose and Guidini relate to the biotechnological production of hexoses.
Regarding claim 5, Bonumose discloses the ratio of enzymes used is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. Bonumose further discloses that 4GT can be added to increase tagatose yields by recycling the degradation products glucose, maltose, and maltotriose into longer maltooligosaccharides which can be phosphorolytically cleaved by aGP to yield G1P [para 55]. In view of the disclosure of Bonumose of the typical ratios of enzymes, one of skill in the art would reasonably conclude the inclusion of 4GT would also typically occur at an equivalent ratio to the other enzymes, which could also be adjusted to optimize yields.
While Bonumose does not teach the claimed limitations of a composition comprising (w/w)%: 10-30% aGP; 0-10% 4-GT; 10-30% PGM; 0.1-10% PGI; 15-35% F6PE; and 25-45% T6PP, wherein the total weight of enzymes in the composition is 100 w/w% as recited in instant claim 5, MPEP 2144.05.II.A states 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. As Bonumose discloses a composition with an equal ratio of each enzyme, one of skill in the art would be motived to alter the ratios of the enzymes to arrive at the claimed (w/w)% of components because Bonumose discloses the ratios of enzymes can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes to optimize yields [para 32].
Regarding claim 10, Bonumose does not teach the limitations of total weight of enzymes relative to carrier being 2.5-12.5%.
Regarding claim 10, Guidini discloses the immobilization of the enzyme β-galactosidase onto Duolite A568 resin, and discloses that 5 g resin was loaded with 10 mL solutions comprising 6.82 to 25.18 g/L enzyme [p 137, col 2, para 2], which corresponds to 1.36-5.04% (w/w) relative to the carrier. According to MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Regarding claim 23, Bonumose discloses the ratio of enzymes used is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. As such, Bonumose is interpreted to disclose the composition comprising equal ratios of the enzymes aGP, PGM, PGI, F6PE and T6PP corresponding to relative weight of each enzyme of approximately 20%, and which is considered to be encompassed by a composition wherein the weight of each enzyme relative to the total weight of the enzymes (w/w)% ranges from 0.1% to 70% as recited in claim 23.
Therefore, the invention of claims 1, 3, 5, 10 and 23 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Bonumose and Guidini as applied to claims 1, 3, 5, 10 and 23 above, and further in view of UniProt Accession No. G8NCC0_9DEIN (2 pages, 04/25/2018; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI1), UniProt Accession No. A0A0P6YKY9_9CHLR (2 pages, 02/28/2018; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI2), UniProt Accession No. Q5SLL6 (3 pages, 02/28/2018; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI3), UniProt Accession No. A0A0P6XN50_9CHLR (1 page, 06/07/2017; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI4), UniProt Accession No. D1C7G9_SPHTD (2 pages, 02/28/2018; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI5), and UniProt Accession No. E8MXP8_ANATU (2 pages, 09/27/2017; cited on the Form PTO-892 mailed 04/07/2025; herein referred to as UNI6).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 6 is drawn to the immobilized enzyme composition of claim 5, wherein:
the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1; the 4-GT if present comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6; the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2; the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3; the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4; and the T6PP comprises SEQ ID NO. 5.
The teachings of Bonumose and Guidini as applied to claims 1, 3, 5, 10 and 23 are discussed above. These references do not teach the sequence limitations of the enzymes recited in the claim.
Regarding claim 6 and the limitation of the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1, UNI1 discloses an alpha-glucan phosphorylase that shares 99.9% sequence identity with SEQ ID NO: 1 [see Appendix A]. As the enzyme of UNI1 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same alpha-glucan phosphorylase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding claim 6 and the limitation of the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2, UNI2 discloses a phosphomutase that shares 100% sequence identity with SEQ ID NO: 2 [see Appendix B]. As the enzyme of UNI2 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucomutase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding claim 6 and the limitation of the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3, UNI3 discloses a glucose-6-phosphate isomerase that shares 100% sequence identity with SEQ ID NO: 3 [see Appendix C]. As the enzyme of UNI3 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucoisomerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding claim 6 and the limitation of the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4, UNI4 discloses an aldolase that shares 100% sequence identity with SEQ ID NO: 4 [see Appendix D]. As the enzyme of UNI4 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same tagatose-6-phosphate phosphatase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding claim 6 and the limitation of the T6PP comprises SEQ ID NO. 5, UNI5 discloses a hydrolase that shares 100% sequence identity with SEQ ID NO: 5 [see Appendix E]. As the enzyme of UNI5 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same fructose-6-phosphate epimerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding claim 6 and the limitation of the 4-GT comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6, UNI6 discloses a 4-alpha-glucanotransferase that shares 100% sequence identity with SEQ ID NO: 6 [see Appendix F]. As the enzyme of UNI6 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same 1,4-glucan transferase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
In view of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined composition of Bonumose and Guidini, by replacing the enzymes of Bonumose with the enzymes of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, respectively, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result.
One of ordinary skill in the art would have recognized that the aGP of Bonumose and the polypeptide of UNI1 are both aGP enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the PGM of Bonumose and the polypeptide of UNI2 are both PGM enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the PGI of Bonumose and the polypeptide of UNI3 are both PGI enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the F6PE of Bonumose and the polypeptide of UNI4 are both F6PE enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the T6PP of Bonumose and the polypeptide of UNI5 are both T6PP enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the 4GT of Bonumose and the polypeptide of UNI6 are both 4GT enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
Thus it would have been obvious to one of ordinary skill in the art to replace the aGP of Bonumose with the polypeptide of UNI1, the PGM of Bonumose with the polypeptide of UNI2, the PGI of Bonumose with the polypeptide of UNI3, the F6PE of Bonumose with the polypeptide of UNI4, the T6PP of Bonumose with the polypeptide of UNI5 are both T6PP enzymes, and the 4GT of Bonumose with the polypeptide of UNI6, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because Bonumose and UNI1 relate to aGP enzymes, Bonumose and UNI2 relate to PGM enzymes, Bonumose and UNI3 relate to PGI enzymes, Bonumose and UNI4 relate to F6PE enzymes, Bonumose and UNI5 relate to T6PP enzymes, and Bonumose and UNI6 relate to 4GT enzymes.
Therefore, the invention of claim 6 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to remarks: beginning on page 4 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends the amended claims focus on a composition that demonstrates an unexpected technical advantage of robust half-life and increased cascade activity rate as shown in Tables 3 and 5 of the instant specification; Applicant further contends one of skill in the art could not have reasonably predicted the performance advantages for producing tagatose at the time of the effective filing date, as Guidini’s disclosed advantages relate to a single enzyme.
Applicant’s remarks are considered and found not convincing.
Applicant’s assertion of an unexpected technical advantage is being considered an allegation of unexpected results. Applicant proffers the results in Tables 3 and 5 of the instant specification, wherein Table 3 corresponds to Example 1 [beginning on para 0035] and Table 5 corresponds to Example 3 [beginning on para 0050].
Example 1 corresponds to the immobilization of 19% aGP (SEQ ID NO: 1), 17% PGM (SEQ ID NO: 2), 3% PGI (SEQ ID NO: 3), 23% F6PE (SEQ ID NO: 4), 35% T6PP (SEQ ID NO: 5), and 3% 4-GT (SEQ ID NO: 6) on 10 resins, 4 of which are identified as phenol-formaldehyde matrix resins, and 1 of which is identified as containing tertiary amine functional groups, at 5% total enzyme weight/carrier. Applicant states in the specification that the cascade activity rate for each carrier-composition preparation is reported in Table 1 relative to the cascade activity rate of the Duolite A548 carrier-composition [para 0047]. As Table 1 only discloses the relationship between the enzymes and their associated UniProt IDs and SEQ ID NOs [see end of para 0021], it is presumed the comparison is made in Table 3 [para 0048]. However, all of the cascade activity rate and half-life data show in Table 3 are reported relative to the composition on Duolite A548, and there is no comparison to the activity rate and half-life of non-immobilized enzyme compositions. Therefore Table 3 does not indicate any advantages over non-immobilized enzyme compositions.
Example 3 (corresponding to Table 5) involves different combinations of enzymes immobilized on different carriers, wherein the enzyme concentrations are the same as in Example 1, and all are immobilized on Duolite A548 resin [para 0050]. As only one sample in Table 5 corresponds to all six enzymes being immobilized, there is only one sample that corresponds to a composition recited in the amended claims, and this one sample displays a 100% relative activity rate, without any indication of what this activity rate is compared with. Therefore Table 5 does not indicate any advantages over non-immobilized enzyme compositions.
MPEP 716.02(b).I states the burden is on applicant to establish results are unexpected and significant. As the data proffered by Applicant is not compared to any non-immobilized enzyme composition, the unexpected advantages of immobilizing the claimed enzyme composition with the claimed resin alleged by Applicant has not been established. Therefore the allegations of unexpected results do not satisfy the requirements of MPEP 716.02(b).I.
MPEP 716.02(b).II states the burden is on applicant to explain proffered data. As Applicant has not explained the proffered data, for example regarding the comparisons of Table 5, the allegations of unexpected results do not satisfy the requirements of MPEP 716.02(b).II.
MPEP 716.02(e) states unexpected results must be compared with the closest prior art. As the proffered data is not compared with any prior art, the allegations of unexpected results do not satisfy the requirements of MPEP 716.02(e).
MPEP 716.02(d) states unexpected results must be commensurate in scope with the claimed invention. The proffered data corresponds to immobilizing a single composition of specific enzymes at fixed enzyme ratios, a fixed total % enzyme weight/carrier, and with only 1 resin disclosed as a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group. The scope of claim 1 encompasses compositions comprising all aGP enzymes, all PGM enzymes, all PGI enzymes, all F6PE enzymes, all T6PP enzymes, all 4-GT enzymes, in all enzyme ratios, immobilized to all weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group, at all % enzyme/carrier weight ratios. The claim scope additionally encompasses compositions that do not include all 4-GT enzymes, as this enzyme is limited as optional. Therefore, the allegation of unexpected results do not satisfy the requirements of MPEP 716.02(d) as they are considered not commensurate in scope with the claims.
For these reasons, Applicant’s allegations of unexpected results are considered insufficient to rebut a prima facie case of obviousness.
Regarding the assertion that one of skill in the art could not have reasonably predicted the performance advantages for producing tagatose at the time of the effective filing date, as Guidini’s disclosed advantages relate to a single enzyme; the performance advantages for producing tagatose alleged by Applicant are considered not convincing for the reasons set forth above.
Applicant states that one of ordinary skill in the art could not have reasonably predicted that the combination of prior art presented in the rejection would yield any performance advantage. Guidini, however, teaches the immobilization of enzymes on a carrier is known to result in advantages over free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability. As Guidini does not restrict the immobilization of enzymes to a carrier to be one enzyme per carrier, one of skill in the art, if interested in utilizing multiple enzymes of for a single purpose such as that disclosed by Bonumose, would be motivated to immobilize multiple enzymes on a single carrier for the reasons given by Guidini.
Applicant contends that performance of immobilized enzymes is unpredictable in the art as evidenced by Homaei et al. (Adv Food Biotechnol, 2016; cited on the IDS filed 07/07/2025) stating “[enzyme immobilization] methods have a number of advantages and drawbacks”, and “adsorption is simple, cheap and effective but frequently reversible; covalent attachment and cross-linking are effective and durable, but expensive and easily worsening the enzyme performance; diffusional problems are inherent in membrane reactor-confinement, entrapment and micro-encapsulations” [page 148, Section 9.4, para 2]. One of skill in the art would similarly recognize that all methods have advantages and disadvantages, and would therefore require some optimization to achieve optimum function. However, the cited disadvantages of Homaei do not all apply to the instant invention, as the claims, as well as combination of cited prior art of record, relate to the immobilization of enzymes on weak anion exchange resin, which corresponds to the entrapment method of immobilization as disclosed by Homaei [page 149, Section 9.4.1, para 1]. Therefore the relevant disadvantage cited by Applicant corresponds with diffusion as evidenced by Homaei. Regarding the arguments that the combination of prior art would not have been able to predict the performance of the claimed immobilized composition, it is noted that the features upon which applicant relies (i.e., performance advantages of the claimed immobilized composition) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims.
Regarding the concepts of predictability used in the Examination process, MPEP 2142 sets forth that “[T]he ultimate determination of patentability is based on the entire record, by a preponderance of evidence, with due consideration to the persuasiveness of any arguments and any evidence properly made of record. In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992)” and “The legal standard of ‘a preponderance of evidence’ requires the evidence to be more convincing than the evidence which is offered in opposition to it”.
The combination of prior art presented in the rejection above is directed to the claimed invention, drawn to an immobilized enzyme composition, and therefore the predictability is based on whether or not elements of the prior art, when combined, would be reasonably expected to successfully produce the claimed immobilized enzyme composition. Guidini teaches a method of immobilizing enzymes to Duolite A548 resin, and provides the motivation to do so that it provides the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability. One of skill in the art considering the disclosure of Homaei, and the disclosures of Bonumose and Guidini, would have a reasonable expectation of success that combining the elements of Bonumose and Guidini as described in the rejection would produce an immobilized enzyme composition based on a preponderance of evidence as described above.
Double Patenting
The rejection of claims 15 and 25 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,138,506 (cited on the Form PTO-892 mailed 04/07/2025) in view of Guidini and Bonumose, and further in view Garcia,
the rejection of claim 26 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,138,506 in view of Guidini, Bonumose and Garcia, and further in view of Block,
the rejection of claims 15 and 25 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,034,988 in view of Bonumose and Guidini, and further in view Garcia, and
the rejection of claim 26 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,034,988 (cited on the Form PTO-892 mailed 04/07/2025) in view of Guidini, Bonumose and Garcia, and further in view of Block
are withdrawn in view of the cancelation of claims 15 and 25-26.
A. Claims 1 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,138,506 (herein “patent) in view of Guidini.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the patent recites a method of preparing tagatose comprising the use of aGP, PGM, PGI, and claim 3 recites 4GT is added to the process, as well as the use of F6PE and T6PP. While the patent does not explicitly disclose the incorporation of these components into a composition, as the patent discloses the use of these enzymes for the production of tagatose, it would have been obvious to combine the enzymes a composition to produce tagatose.
The claims of the patent do not recite a composition or the immobilization of enzymes to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group.
Guidini relates to the immobilization of enzymes [title] and discusses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability [p 137, col 2, para 1].
Regarding instant claims 1 and 3 and the limitation of immobilizing enzymes on a carrier, Guidini discloses the immobilization of the enzyme β-galactosidase, which is an important enzyme in the biotechnological process of lactose hydrolysis to form glucose (a hexose) [p 137, col 1, para 1], onto Duolite A568 resin resulting in high enzymatic activity and stability, that was additionally stable across a wide range of pH from 3.5-8.0 [p 138, col 1, para 1], wherein the Duolite A568 resin of Guidini is a weak base anion exchange resin based on cross-linked phenol-formaldehyde polycondensate with tertiary amine functional groups [p 138, col 1, para 4].
In view of Guidini, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent by immobilizing the enzymes of the patent on the carrier of Guidini, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to immobilize the enzymes of the patent because Guidini discloses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability. One of ordinary skill in the art would have had a reasonable expectation of success because both the patent and Guidini relate to the biotechnological production of hexoses.
Claims 5, 10 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,138,506 in view of Guidini as applied to claims 1 and 3 above, and further in view of Bonumose.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
The claims of the patent and the disclosure of Guidini as applied to instant claims 1 and 3 are discussed above. The claims of the patent do not recite the weight% of the components of the composition.
Bonumose relates to the enzymatic synthesis of d-tagatose [title] which is understood to be a hexose, and discusses the need for an alternative strategy to produce tagatose that is more cost-effective and higher yield than conventional methods [para 5].
Regarding instant claim 5, Bonumose discloses the ratio of enzymes used in the preparation of tagatose is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. Bonumose further discloses that 4GT can be added to increase tagatose yields by recycling the degradation products glucose, maltose, and maltotriose into longer maltooligosaccharides which can be phosphorolytically cleaved by aGP to yield G1P [para 55]. In view of the disclosure of Bonumose of the typical ratios of enzymes, one of skill in the art would reasonably conclude the inclusion of 4GT would also typically occur at an equivalent ratio to the other enzymes, which could also be adjusted to optimize yields.
While Bonumose does not disclose the claimed limitations of a composition comprising (w/w)%: 10-30% aGP; 0-10% 4-GT; 10-30% PGM; 0.1-10% PGI; 15-35% F6PE; and 25-45% T6PP, wherein the total weight of enzymes in the composition is 100 w/w% as recited in instant claim 5, MPEP 2144.05.II.A states 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. As Bonumose discloses a composition with an equal ratio of each enzyme, one of skill in the art would be motived to alter the ratios of the enzymes to arrive at the claimed (w/w)% of components because Bonumose discloses the ratios of enzymes can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes to optimize yields [para 32].
In view of Bonumose, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined composition of the patent and Guidini by using the enzyme ratios of Bonumose to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to use the enzyme ratios of Bonumose because Bonumose discloses the need for an alternative strategy to produce tagatose that is more cost-effective and higher yield than conventional methods and discloses a method for the enzymatic synthesis of tagatose. One of ordinary skill in the art would have had a reasonable expectation of success because the patent, Guidini and Bonumose relate to the biotechnological production of hexoses.
Regarding instant claim 10, the claims of the patent does not recite the limitations of total weight of enzymes relative to carrier being 2.5-12.5%.
Regarding instant claim 10, Guidini discloses the immobilization of the enzyme β-galactosidase onto Duolite A568 resin, and discloses that 5 g resin was loaded with 10 mL solutions comprising 6.82 to 25.18 g/L enzyme [p 137, col 2, para 2], which corresponds to 1.36-5.04% (w/w) relative to the carrier. According to MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Regarding instant claim 23, Bonumose discloses the ratio of enzymes used is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. As such, Bonumose is interpreted to disclose the composition comprising equal ratios of the enzymes aGP, PGM, PGI, F6PE and T6PP corresponding to relative weight of each enzyme of approximately 20%, and which is considered to be encompassed by a composition wherein the weight of each enzyme relative to the total weight of the enzymes (w/w)% ranges from 0.1% to 70% as recited in instant claim 23.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 10,138,506 in view of Guidini and Bonumose as applied to claims 1, 3, 5, 10 and 23 above, and further in view of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Instant claim 6 is drawn to the immobilized enzyme composition of claim 5, wherein: the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1; the 4-GT comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6; the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2; the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3; the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4; and the T6PP comprises SEQ ID NO. 5.
The claims of the patent and the disclosures of Bonumose and Guidini as applied to instant claims 1, 3, 5, 10 and 23 are discussed above. The claims of the patent do not recite the sequence limitations of the enzymes recited in the claim.
Regarding instant claim 6 and the limitation of the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1, UNI1 discloses an alpha-glucan phosphorylase that shares 99.9% sequence identity with SEQ ID NO: 1 [see Appendix A]. As the enzyme of UNI1 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same alpha-glucan phosphorylase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2, UNI2 discloses a phosphomutase that shares 100% sequence identity with SEQ ID NO: 2 [see Appendix B]. As the enzyme of UNI2 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucomutase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3, UNI3 discloses a glucose-6-phosphate isomerase that shares 100% sequence identity with SEQ ID NO: 3 [see Appendix C]. As the enzyme of UNI3 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucoisomerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4, UNI4 discloses an aldolase that shares 100% sequence identity with SEQ ID NO: 4 [see Appendix D]. As the enzyme of UNI4 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same tagatose-6-phosphate phosphatase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the T6PP comprises SEQ ID NO. 5, UNI5 discloses a hydrolase that shares 100% sequence identity with SEQ ID NO: 5 [see Appendix E]. As the enzyme of UNI5 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same fructose-6-phosphate epimerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the 4-GT comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6, UNI6 discloses a 4-alpha-glucanotransferase that shares 100% sequence identity with SEQ ID NO: 6 [see Appendix F]. As the enzyme of UNI6 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same 1,4-glucan transferase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
In view of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined composition of the patent, Bonumose and Guidini, by replacing the enzymes of the patent with the enzymes of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, respectively, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result.
One of ordinary skill in the art would have recognized that the aGP of the patent and the polypeptide of UNI1 are both aGP enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
One of ordinary skill in the art would have recognized that the PGM of the patent and the polypeptide of UNI2 are both PGM enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
One of ordinary skill in the art would have recognized that the PGI of the patent and the polypeptide of UNI3 are both PGI enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
One of ordinary skill in the art would have recognized that the F6PE of the patent and the polypeptide of UNI4 are both F6PE enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
One of ordinary skill in the art would have recognized that the T6PP of the patent and the polypeptide of UNI5 are both T6PP enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
One of ordinary skill in the art would have recognized that the 4GT of the patent and the polypeptide of UNI6 are both 4GT enzymes, and as such both are capable of being incorporated into such compositions as described by the patent.
Thus it would have been obvious to one of ordinary skill in the art to replace the aGP of the patent with the polypeptide of UNI1, the PGM of the patent with the polypeptide of UNI2, the PGI of the patent with the polypeptide of UNI3, the F6PE of the patent with the polypeptide of UNI4, the T6PP of the patent with the polypeptide of UNI5 are both T6PP enzymes, and the 4GT of the patent with the polypeptide of UNI6, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because the patent and UNI1 relate to aGP enzymes, the patent and UNI2 relate to PGM enzymes, the patent and UNI3 relate to PGI enzymes, the patent and UNI4 relate to F6PE enzymes, the patent and UNI5 relate to T6PP enzymes, and the patent and UNI6 relate to 4GT enzymes.
B. Claims 1, 3, 5, 10 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,034,988 (herein “patent”) in view of Bonumose and Guidini.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the patent recites a method of preparing tagatose comprising the use of PGM, PGI, F6PE and T6PP. While the patent does not explicitly disclose the incorporation of these components into a composition, as the patent discloses the use of these enzymes for the production of tagatose, it would have been obvious to combine the enzymes a composition to produce tagatose.
The claims of the patent do not recite a composition comprising aGP and the immobilization of enzymes to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group.
Bonumose relates to the enzymatic synthesis of d-tagatose [title] which is understood to be a hexose, and discusses the need for an alternative strategy to produce tagatose that is more cost-effective and higher yield than conventional methods [para 5].
Regarding instant claims 1 and 3 and the limitation of an enzyme composition comprising aGP, PGM, PGI and optionally 4GT, Bonumose discloses the enzymatic conversion of saccharides to tagatose [para 2] through the conversion of saccharides to glucose-1-phosphate (G1P), converting G1P to glucose-6-phosphate (G6P) with PGM, converting G6P to fructose-6-phosphate (F6P) with PGI, converting F6P to tagatose-6-phosphate (T6P) with an epimerase [para 9] such as fructose-6-phosphate epimerase (F6PE) [para 12], and converting T6P to tagatose catalyzed by a phosphatase [para 8] such as tagatose-6-phosphate phosphatase (T6PP) [para 31]. Bonumose further discloses the saccharides can consist of a starch or derivative which can be prepared by the hydrolysis of starch by 4GT [para 9], and that starch can be hydrolyzed to produce G1P by aGP [para 43]. While Bonumose does not explicitly disclose the incorporation of these components into a composition, MPEP 2144.06 states it is obvious to combine components disclosed by the prior art to be useful for the same purpose in order to form a composition to be used for the same purpose, such as the production of tagatose as described above.
Guidini relates to the immobilization of enzymes [title] and discusses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability [p 137, col 2, para 1].
Regarding claims 1 and 3 and the limitation of immobilizing enzymes on a carrier, Guidini discloses the immobilization of the enzyme β-galactosidase, which is an important enzyme in the biotechnological process of lactose hydrolysis to form glucose (a hexose) [p 137, col 1, para 1], onto Duolite A568 resin resulting in high enzymatic activity and stability, that was additionally stable across a wide range of pH from 3.5-8.0 [p 138, col 1, para 1], wherein the Duolite A568 resin of Guidini is a weak base anion exchange resin based on cross-linked phenol-formaldehyde polycondensate with tertiary amine functional groups [p 138, col 1, para 4].
In view of Bonumose and Guidini, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent by using the enzymes of Bonumose and immobilizing the enzymes on the carrier of Guidini, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to use the enzymes and immobilize the enzymes because Bonumose discloses the need for an alternative strategy to produce tagatose that is more cost-effective and higher yield than conventional methods and discloses a method for the enzymatic synthesis of tagatose, and Guidini discloses that enzyme immobilization has advantages over the free form enzymes such as the reuse of heterogeneous biocatalyst, cost reduction, possibility of improved process control, continuous operation and increase in stability. One of ordinary skill in the art would have had a reasonable expectation of success because the patent, Bonumose and Guidini relate to the biotechnological production of hexoses.
Regarding instant claim 5, Bonumose discloses the ratio of enzymes used in the preparation of tagatose is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. Bonumose further discloses that 4GT can be added to increase tagatose yields by recycling the degradation products glucose, maltose, and maltotriose into longer maltooligosaccharides which can be phosphorolytically cleaved by aGP to yield G1P [para 55]. In view of the disclosure of Bonumose of the typical ratios of enzymes, one of skill in the art would reasonably conclude the inclusion of 4GT would also typically occur at an equivalent ratio to the other enzymes, which could also be adjusted to optimize yields.
While Bonumose does not disclose the claimed limitations of a composition comprising (w/w)%: 10-30% aGP; 0-10% 4-GT; 10-30% PGM; 0.1-10% PGI; 15-35% F6PE; and 25-45% T6PP, wherein the total weight of enzymes in the composition is 100 w/w% as recited in instant claim 5, MPEP 2144.05.II.A states 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. As Bonumose discloses a composition with an equal ratio of each enzyme, one of skill in the art would be motived to alter the ratios of the enzymes to arrive at the claimed (w/w)% of components because Bonumose discloses the ratios of enzymes can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes to optimize yields [para 32].
Regarding instant claim 10, the claims of the patent does not recite the limitations of total weight of enzymes relative to carrier being 2.5-12.5%.
Regarding instant claim 10, Guidini discloses the immobilization of the enzyme β-galactosidase onto Duolite A568 resin, and discloses that 5 g resin was loaded with 10 mL solutions comprising 6.82 to 25.18 g/L enzyme [p 137, col 2, para 2], which corresponds to 1.36-5.04% (w/w) relative to the carrier. According to MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Regarding instant claim 23, Bonumose discloses the ratio of enzymes used is typically 1:1:1:1:1 (aGP:PGM:PGI:F6PE:T6PP), and to optimize yields the ratios can be adjusted with any number of combinations wherein a particular enzyme may be present in an amount from about 2X to 5X relative to other enzymes [para 32]. As such, Bonumose is interpreted to disclose the composition comprising equal ratios of the enzymes aGP, PGM, PGI, F6PE and T6PP corresponding to relative weight of each enzyme of approximately 20%, and which is considered to be encompassed by a composition wherein the weight of each enzyme relative to the total weight of the enzymes (w/w)% ranges from 0.1% to 70% as recited in instant claim 23.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,034,988 in view of Bonumose and Guidini as applied to claims 1, 3, 5, 10 and 23 above, and further in view of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Instant claim 6 is drawn to the immobilized enzyme composition of claim 5, wherein: the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1; the 4-GT comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6; the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2; the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3; the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4; and the T6PP comprises SEQ ID NO. 5.
The claims of the patent and the disclosures of Bonumose and Guidini as applied to instant claims 1, 3, 5, 10 and 23 are discussed above. The claims of the patent do not recite the sequence limitations of the enzymes recited in the claim.
Regarding instant claim 6 and the limitation of the aGP comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 1, UNI1 discloses an alpha-glucan phosphorylase that shares 99.9% sequence identity with SEQ ID NO: 1 [see Appendix A]. As the enzyme of UNI1 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same alpha-glucan phosphorylase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the PGM comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 2, UNI2 discloses a phosphomutase that shares 100% sequence identity with SEQ ID NO: 2 [see Appendix B]. As the enzyme of UNI2 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucomutase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the PGI comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 3, UNI3 discloses a glucose-6-phosphate isomerase that shares 100% sequence identity with SEQ ID NO: 3 [see Appendix C]. As the enzyme of UNI3 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same phosphoglucoisomerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the F6PE comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 4, UNI4 discloses an aldolase that shares 100% sequence identity with SEQ ID NO: 4 [see Appendix D]. As the enzyme of UNI4 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same tagatose-6-phosphate phosphatase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the T6PP comprises SEQ ID NO. 5, UNI5 discloses a hydrolase that shares 100% sequence identity with SEQ ID NO: 5 [see Appendix E]. As the enzyme of UNI5 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same fructose-6-phosphate epimerase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
Regarding instant claim 6 and the limitation of the 4-GT comprises an amino acid sequence having at least 90% identity with SEQ ID NO. 6, UNI6 discloses a 4-alpha-glucanotransferase that shares 100% sequence identity with SEQ ID NO: 6 [see Appendix F]. As the enzyme of UNI6 shares substantial sequence identity to the claimed polypeptide, it is therefore presumed to have the same 1,4-glucan transferase activity of the polypeptide recited in the claims (see MPEP 2112.01.I).
In view of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined composition of the patent, Bonumose and Guidini, by replacing the enzymes of the Bonumose with the enzymes of UNI1, UNI2, UNI3, UNI4, UNI5 and UNI6, respectively, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result.
One of ordinary skill in the art would have recognized that the aGP of Bonumose and the polypeptide of UNI1 are both aGP enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the PGM of Bonumose and the polypeptide of UNI2 are both PGM enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the PGI of the patent and the polypeptide of UNI3 are both PGI enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the F6PE of Bonumose and the polypeptide of UNI4 are both F6PE enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the T6PP of Bonumose and the polypeptide of UNI5 are both T6PP enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
One of ordinary skill in the art would have recognized that the 4GT of Bonumose and the polypeptide of UNI6 are both 4GT enzymes, and as such both are capable of being incorporated into such compositions as described by Bonumose.
Thus it would have been obvious to one of ordinary skill in the art to replace the aGP of Bonumose with the polypeptide of UNI1, the PGM of Bonumose with the polypeptide of UNI2, the PGI of Bonumose with the polypeptide of UNI3, the F6PE of Bonumose with the polypeptide of UNI4, the T6PP of Bonumose with the polypeptide of UNI5 are both T6PP enzymes, and the 4GT of Bonumose with the polypeptide of UNI6, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because Bonumose and UNI1 relate to aGP enzymes, Bonumose and UNI2 relate to PGM enzymes, Bonumose and UNI3 relate to PGI enzymes, Bonumose and UNI4 relate to F6PE enzymes, Bonumose and UNI5 relate to T6PP enzymes, and Bonumose and UNI6 relate to 4GT enzymes.
Response to remarks: beginning on page 6 of Applicant’s response to double patenting rejections; Applicant in summary contends regarding U.S. Patent Nos. 10,138,506 and 11,034,988 that the cited art does not teach or suggest the composition of the amended claims with respect to immobilizing enzymes.
Applicant’s remarks are considered and found not convincing.
Claim 1 of the U.S. Patent No. 10,138,506 recites a method of preparing tagatose comprising the use of aGP, PGM, PGI, and claim 3 recites 4GT is added to the process, as well as the use of F6PE and T6PP. While the patent does not explicitly disclose the incorporation of these components into a composition, as the patent discloses the use of these enzymes for the production of tagatose, it would have been obvious to combine the enzymes a composition to produce tagatose. As the claims of the patent do not recite the immobilization of enzymes to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group, one of skill in the art would have been motivated to modify the claims of the patent in view of the relevant disclosure of Guidini to arrive at the claimed invention as set forth in the rejection above.
Claim 1 of the U.S. Patent No. 11,034,988 recites a method of preparing tagatose comprising the use of PGM, PGI, F6PE and T6PP. While the patent does not explicitly disclose the incorporation of these components into a composition, as the patent discloses the use of these enzymes for the production of tagatose, it would have been obvious to combine the enzymes a composition to produce tagatose. As the claims of the patent do not recite a composition comprising aGP and the immobilization of enzymes to a carrier, wherein the carrier is a weak base anion exchange resin comprising a phenol formaldehyde polycondensate and a tertiary amine functional group, one of skill in the art would have been motivated to modify the claims of the patent in view of the relevant disclosures of Bonumose and Guidini to arrive at the claimed invention as set forth in the rejection above.
Conclusion
Status of the Application:
Claims 1, 3, 5-6, 10 and 19-23 are pending.
Claims 19-22 are withdrawn.
Claims 1, 3, 5-6, 10, and 23 are rejected.
No claim is in condition for allowance.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
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media_image1.png
511
806
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Greyscale
Sequence alignment of SEQ ID NO: 1 with UniProt Accession No. G8NCC0_9DEIN (reference UNI1)
APPENDIX B
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media_image2.png
512
805
media_image2.png
Greyscale
Sequence alignment of SEQ ID NO: 2 with UniProt Accession No. A0A0P6YKY9_CHLR (reference UNI2)
APPENDIX C
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media_image3.png
515
802
media_image3.png
Greyscale
Sequence alignment of SEQ ID NO: 3 with UniProt Accession No. Q5SLL6 (reference UNI3)
APPENDIX D
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media_image4.png
422
819
media_image4.png
Greyscale
Sequence alignment of SEQ ID NO: 4 with UniProt Accession No. A0A0P6XN50_9CHLR (reference UNI4)
APPENDIX E
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media_image5.png
429
807
media_image5.png
Greyscale
Sequence alignment of SEQ ID NO: 5 with UniProt Accession No. D1C7G9_SPHTD (reference UNI5)
APPENDIX F
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media_image6.png
512
806
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Greyscale
Sequence alignment of SEQ ID NO: 6 with UniProt Accession No. E8MXP8_ANATU (reference UNI6)