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 .
Claims 1, 4-7, 9-12, 16 and 23 are pending in this application.
Applicant’s amendment to the claims filed 02/10/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 02/10/2026 in response to the non-final rejection mailed on 11/07/2025 are acknowledged and have been fully considered.
Rejections previously applied to claim 8 are withdrawn in view of applicant’s amendment to cancel claim 8.
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, 4-7, 9-12, 16 and new claim 23, drawn to the technical feature of a method of forming a monosaccharide comprising providing a hydrogen source containing hydrogen gas in an aqueous electrolyte solution; providing a carbon dioxide source; forming a reaction mixture by feeding the hydrogen source and the carbon dioxide source into a synthetic reaction vessel containing an aqueous reaction solution, wherein the aqueous reaction solution contains a plurality of photosynthetic enzymes, at least two cofactors including reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenine triphosphate (ATP), and at least one substrate; and forming an amount of the monosaccharide in the synthetic reaction vessel by reacting the hydrogen source, the carbon dioxide source, and the at least one substrate in contact with the plurality of photosynthetic enzymes and the at least two cofactors,
elected in the reply filed 05/10/2024.
Claims 1, 4-7, 9-12, 16 and 23 are being examined on the merits.
Claim Objections
The objection to claim 1 is withdrawn in view of the instant amendments to claim 1.
Claim Rejections - 35 USC § 112(b)
Claims 1, 4-7, 9-12, 16 and 23 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 1 (claims 4-7, 9-12, 16 and 23 dependent therefrom) is indefinite for the phrase “ATP is regenerated using a two-step synthetic enzymatic reaction which comprises polyphosphate kinase (PPK), adenylate kinase (ADK) and AMP phosphotransferase (PPT)”, as it is unclear how three enzymes are being used to catalyze two steps of a reaction. The instant specification at [para 0065] recites this limitation and states that ADK mediates the generation of ATP from two ADP molecules to yield AMP (corresponding to 1 step), then AMP is converted to ADP by PPT using a phosphate group from Poly (Pi)n (corresponding to a 2nd step), and that PPK can generate ATP from ADP and exogenous polyphosphate (corresponding to a 3rd step). Therefore, it is unclear whether the limitation is intended to encompass all three steps and enzymes for ATP regeneration, or whether the limitation is intended to limit the ATP generation to two steps and the corresponding enzymes. If the limitation is intended to limit the ATP generation to two steps and the corresponding enzymes, it is unclear which two enzymes are intended as being encompassed by the noted phrase.
Claim 10 recites the term “about”, which is a relative term which renders the claim indefinite. The term "about" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore the limitation on the upper limit of the voltage range in which hydrolysis it to be performed is rendered indefinite by the use of the term.
Response to remarks. Beginning on page 5 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends the specification defines the two-step process in [para 0065] of the instant specification wherein step 1) comprises one enzyme activity and step 2) comprises the other 2 enzyme activities.
Applicant’s remarks are considered and found not convincing. Applicant’s citation of the two-step process in [para 0065] is part of Example III and does not set forth a special definition of “a two-step process”. As there is no special definition of a two-step process in the specification, and the claims do not recite the specifics of the two-step process, the claim is considered indefinite as one of skill in the art would reasonably conclude the catalysis of three reactions by three separate enzymes to correspond to a three-step process.
Applicant’s amendment to claim 10 to recite “a voltage from -1.5 V to about 5.5 V” is considered indefinite in view of the relative term “about” as stated in the rejection above.
Claim Rejections - 35 USC § 103
Claims 1, 4-6, 9, 11-12, 16 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over
Nobles et al. (US 7,803,601; cited on the IDS filed 03/29/2022; herein Nobles) in view of Yagishita et al. (J Biosci Bioeng, 1999, 88:210; cited on the Form PTO-892 mailed 07/12/2024; herein Yagishita), Ortega et al. (J Chem Technol Biotechnol, 1998, 73:7; cited on the Form PTO-892 mailed 02/11/2025; herein referred to as Ortega), Hodgman et al. (Metabolic Eng, 2012, 14:261; cited on the Form PTO-892 mailed 02/11/2025; herein referred to as Hodgman), Greiner et al. (Green Chem, 2003, 5:697; cited on the Form PTO-892 mailed 11/07/2025; herein Greiner) and Resnick et al. (Appl Env Microbiol, 2000, 66:2045; cited on the Form PTO-892 mailed 11/07/2025; herein Resnick), and evidentiary references Ducat et al. (Curr Opin Chem Biol, 2012, 16:337; cited on the Form PTO-892 mailed 01/18/2024; herein Ducat), Mayo et al. (Plant Physiol, 1989, 90:720; cited on the Form PTO-892 mailed 07/12/2024; herein Mayo) and Gibco et al. (Certificate of Analysis BG-11 Media, 1 page, 04/06/2024; cited on the Form PTO-892 mailed 07/12/2024; herein Gibco).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 1 is drawn to a method of forming a monosaccharide comprising:
providing a hydrogen source containing hydrogen gas in an aqueous electrolyte solution;
providing a carbon dioxide source;
forming a cell-free enzyme-based reaction mixture by feeding the hydrogen source and the carbon dioxide source into a synthetic reaction vessel containing an aqueous reaction solution, wherein the aqueous reaction solution contains a plurality of photosynthetic enzymes, at least two cofactors including reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenine triphosphate (ATP), and at least one substrate;
wherein NADPH is regenerated using an electrochemical method and
ATP is regenerated using a 2-step synthetic enzymatic reaction which comprises polyphosphate kinase (PPK), adenylate kinase (ADK) and AMP phosphotransferase (PPT); and
forming an amount of the monosaccharide in the synthetic reaction vessel by reacting the hydrogen source, the carbon dioxide source, and the at least one substrate in contact with the plurality of photosynthetic enzymes and the at least two cofactors,
wherein the synthetic reaction vessel includes an electrochemical cell and a power source; and wherein the hydrogen source is provided by performing hydrolysis of water in the electrochemical cell to produce hydrogen gas;
wherein the plurality of photosynthetic enzymes is immobilized in a hydrogel, and wherein the hydrogel includes alginate or calcium alginate; and
wherein the amount of monosaccharide formed has a concentration in the reaction mixture of 2 mg/ml or greater.
Nobles discusses production and secretion of glucose in photosynthetic prokaryotes [title].
Regarding claim 1 and the limitations of providing a hydrogen source containing hydrogen gas in an aqueous electrolyte solution, providing a carbon dioxide source, and forming a reaction mixture by feeding the hydrogen source and the carbon dioxide source into a synthetic reaction vessel containing an aqueous reaction solution containing a plurality of photosynthetic enzymes, at least two cofactors including NADPH and ATP, and at least one substrate resulting in the production of a monosaccharide, Nobles discloses a scheme of providing CO2, H2O and growth medium components into a photobioreactor [Figure 1], wherein the photobioreactor is a fermentation device suitable for inoculating cyanobacteria for the production of cyanobacteria cells and secreted materials such as cellulose [col 5, lines 4-15], and wherein cellulose is further metabolized via enzymatic hydrolysis to produce monosaccharides [col 6, lines 10-17, and Figure 1]. Nobles describes the cyanobacteria include photosynthetic, nitrogen-fixing facultative heterotrophs, chemoautotrophs, and combinations thereof [col 1, line 67 to col 2, line 3], wherein photosynthetic chemoautotrophs such as Cyanobacteria inherently contain a plurality of photosynthetic enzymes, NADPH and ATP as evidenced by Ducat [Figure 1].
Regarding claim 1 and the limitations of the amount of monosaccharide formed has a concentration in the reaction mixture of from 2 mg/ml or greater, Nobles teaches the removal of glucose from culture supernatant after incubation and subsequent centrifugation [col 11, line 66 to col 12, line 2] wherein the reaction produced 1.37 mg/ml glucose [Table 2].
Nobles does not teach the limitations regarding the electrochemical cell, immobilization of enzymes in hydrogels, forming a cell-free reaction mixture, the electrochemical regeneration of NADPH and a two-step enzymatic reaction to regenerate ATP.
Yagishita discusses photosynthetic electrochemical cells using Synechocystis sp. [title] and discloses the effect of added substrate on the current outputs of electrochemical cells to modulate total sugar content in microbial cells in both light and dark conditions [abstract].
Regarding claim 1 and the limitation of a synthetic reaction vessel that includes an electrochemical cell and a power source, Yagishita teaches the use of an electrochemical cell wherein the anode solution contains Synechocystis sp. with 0.25 mM 2-hydroxy-1,4-naphthoquinone (HNQ) in phosphate buffer, the cathode solution contains 0.1 M ferricyanide in phosphate buffer, and the electrochemical cell is left in an open circuit for 30 min [p 211, col 1, para 4], wherein an open circuit inherently involves the use of a power source.
Regarding claim 1 and the limitation of a hydrogen source provided by performing hydrolysis of water in the electrochemical cell to produce hydrogen gas, Yagishita teaches running the buffer-filled electrochemical cell in an open circuit for 30 minutes [p 211, col 1, para 4], the process of which inherently produces hydrogen gas from the hydrolysis of water.
Greiner relates to the continuous reduction of NADP+ with molecular hydrogen by Pyrococcus furiosus hydrogenase [title], and discusses that hydrogenases can activate H2 [p 697, col 1, para 1] as well as provide a cheap and clean source for the generation and regeneration of NADPH [p 697, col 1, para 3].
Regarding claim 1 and the limitation of regenerating NADPH using an electrochemical method, Greiner teaches a preparation of a cell-free extract of P. furiosus and crude enzyme comprising hydrogenase I [p 698, col 1, para 3] followed by adsorption of the electroactive enzyme onto the surface of an electrode for the continuous reduction of NADP+ to NADPH in the presence of H2 [abstract].
Resnick relates to in vitro ATP regeneration from polyphosphate and AMP by polyphosphate:AMP phosphotransferase and adenylate kinase from Acinetobacter johnsonii 210 [title] and discusses the use of this PPT/ADK system provides an alternative to existing ATP regeneration systems as it uses stabile and inexpensive substrates [abstract].
Regarding claim 1, the limitation of ATP regeneration using a 2-step synthetic enzymatic reaction which comprises polyphosphate kinase (PPK), adenylate kinase (ADK) and AMP phosphotransferase (PPT) is being interpreted as encompassing a two-step synthetic method comprising the corresponding two enzymes to catalyze the two steps. In view of this interpretation, Resnick teaches the two-step reaction scheme of converting polyphosphate (PolyP(n)) and AMP to ADP with the enzyme PPT, and subsequent conversion of ADP or AMP to ATP using the enzyme ADK [Figure 1].
Considering an alternate interpretation where the two-step ATP regeneration encompasses all of the enzymes PPK, ADK, and PPT, in addition to the teaching of Resnick above, Resnick also teaches ATP regeneration from ADP using polyphosphate and the enzyme PPK [p 2045, col 2, para 2].
Hodgman discusses cell-free synthetic biology [title], and describes that cell-free is a powerful approach to harness and expand the capabilities of natural biological systems due to the ability to bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell [abstract].
Regarding claim 1 and the limitation of a cell-free enzyme-based reaction mixture, Hodgman teaches the construction of a cell-free extract harvested from cells in the scheme shown in [Fig. 3], wherein the cell-free extract corresponds to the cell-free enzyme based reaction mixture recited in the claim.
Ortega discusses the stabilization of enzymes entrapped in alginate [title], and describes the immobilization of an enzyme can facilitate a decrease in enzyme consumption as well as an improvement in enzyme stability [p 7, col 1 to col 2, para 1].
Regarding claim 1 and the limitation of the plurality of photosynthetic enzymes immobilized on an alginate or calcium alginate hydrogel, Ortega teaches the immobilization of the enzyme β-glucosidase in alginate gels [p 8, col 1, para 2], wherein the immobilization increased the enzymes thermal stability and half-life [Fig. 3 and Table 1] and its protection against proteolytic degradation [p 11, col 1, para 4]. While Ortega discusses the immobilization of β-glucosidase, which is not a photosynthetic enzyme, one of skill in the art would understand that the principles of enzyme immobilization and its effect on enzyme stability would be applicable to enzymes in any field, such as a photosynthetic enzyme or a plurality thereof.
In view of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick, 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 method of Nobles by using an electrochemical cell, as taught by Yagishita, electrochemically regenerating NADPH, as taught by Greiner, regenerating ATP through a two-step enzymatic process, as taught by Resnick, using a cell-free enzyme mixture as taught by Hodgman, and immobilizing enzymes in a hydrogel, as taught by Ortega, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the method of Nobles by using an electrochemical cell because Yagishita teaches an electrochemical cell with different substrate concentrations can be used to modulate the total sugar content in microbial cells in both light and dark conditions.
One of ordinary skill in the art would have been motivated to electrochemically regenerate NADPH because Greiner teaches electrochemical generation and regeneration of NADPH via hydrogenases can provide a cheap and clean source for NADPH.
One of ordinary skill in the art would have been motivated to regenerate ATP through a two-step enzymatic process because Resnick teaches the use of a two-step enzyme system for ATP regeneration provides an alternative to existing systems as it uses stabile and inexpensive substrates.
One of ordinary skill in the art would have been motivated to use a cell-free enzyme mixture because Hodgman teaches that cell-free is a powerful approach to harness and expand the capabilities of natural biological systems due to the ability to bypass cell walls and remove genetic regulation to enable direct access to the inner workings of the cell.
One of ordinary skill in the art would have been motivated to immobilize enzymes in a hydrogel because Ortega teaches the immobilization of an enzyme can facilitate a decrease in enzyme consumption as well as an improvement in enzyme stability.
One of ordinary skill in the art would have had a reasonable expectation of success because Nobles, Yagishita and Hodgman discuss components for artificial metabolic pathways, and Hodgman, Greiner, Resnick and Ortega discuss methods to optimize enzymatic reactions outside of a cell.
The combination of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick does not explicitly teach or suggest the claim 1 limitation of “the amount of monosaccharide formed has a concentration in the reaction mixture of from 2 mg/ml or greater.” However, MPEP 2112.01(I) states when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the structure of the system of the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick comprises an aqueous electrolyte solution containing a hydrogen gas, a carbon dioxide source, an electrochemical cell and a power source, and a cell-free enzyme reaction mixture comprising a plurality of photosynthetic enzymes, at least two cofactors including reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenine triphosphate (ATP), and at least one substrate, wherein the NADPH is regenerated using an electrochemical method and ATP is regenerated using a two-step synthetic enzymatic reaction which comprises PPK, ADK and PPT, wherein the plurality of photosynthetic enzymes is immobilized in a hydrogel that is substantially identical to the system recited in the claim, the property or function of “the amount of monosaccharide formed has a concentration in the reaction mixture of 2 mg/ml or greater” is presumed to be an inherent property or function of the system of the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick.
Regarding claim 4, Nobles discloses the use of the Cyanobacteria sp. Synechococcus leopoliensis which natively expresses the enzyme ribulose-1,5-bisphosphate carboxylase oxygenase (RUBISCO) as evidenced by Mayo [abstract].
Regarding claims 5-6, Nobles discloses the production of the monosaccharide glucose [Figure 1] which is understood in the art to contain 6 carbon atoms per molecule.
Regarding claim 9, Greiner teaches a preparation of a cell-free extract of P. furiosus and crude enzyme comprising hydrogenase I [p 698, col 1, para 3] followed by adsorption of the electroactive enzyme onto the surface of an electrode for the continuous reduction of NADP+ to NADPH in the presence of H2 [abstract].
Regarding claim 11, Yagishita teaches maintaining photosynthetic reactions with Synechocystis at 25-27 °C in BG-11 media [p 211, col 1, para 2], wherein BG-11 media has a pH ranging 6.7 – 7.5 as evidenced by Gibco. One of skill in the art would be expected to maintain the physiological conditions of the cell-based reaction in a cell-free reaction at least as a starting point, and would be expected to optimize both the temperature and pH ranges to increase reaction efficiency, as it is common in the art to optimize reactions in such a way.
Regarding claim 12, Nobles teaches the removal of glucose from culture supernatant after incubation and subsequent centrifugation [col 11, line 66 to col 12, line 2] wherein the reaction produced 1.37 mg/ml glucose [Table 2]. As the glucose concentrations in [Table 2] were measured from aliquots of cell suspensions [col 12, line 35-37], these measurements are understood to correspond to harvested monosaccharide as recited in the claim. While the combination of the prior art does not teach “the amount of monosaccharide formed from the reaction mixture at a production rate of from 2 mg/mL to 40 mg/mL,” MPEP 2112.01(I) states when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. As the system of the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick is substantially identical to the system recited in the claim, the property or function of “the amount of monosaccharide formed from the reaction mixture at a production rate of from 2 mg/mL to 40 mg/mL” is presumed to be an inherent property or function of the system of the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick.
Regarding claim 16, the method of Yagishita wherein the electrochemical cell is left in an open circuit for 30 min [p 211, col 1, para 4] is understood to use an electrical power source.
Regarding claim 23, Resnick teaches the two-step reaction scheme of converting polyphosphate (PolyP(n)) and AMP to ADP with the enzyme PPT, and subsequent conversion of ADP or AMP to ATP using the enzyme ADK [Figure 1], and also teaches ATP regeneration from ADP using polyphosphate and the enzyme PPK [p 2045, col 2, para 2], which is considered to correspond to ATP regeneration in in a light-independent manner.
Therefore, the invention of claims 1, 4-6, 9, 11-12, 16 and 23 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Nobles in view of Yagishita, Ortega, Hodgman, Greiner and Resnick as applied to claims 1, 4-6, 9, 11-12, 16 and 23 above, and further in view of Fukuzumi et al. (Biochim Biophys Acta, 2016, 1857:604; cited on the Form PTO-892 mailed 07/12/2024; herein Fukuzumi).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 7 is drawn to the method of claim 1, wherein the electrochemical cell includes at least one pair of graphite-based electrodes or at least one photochemical catalyst; or wherein the electrochemical cell contains a carbon nitride catalyst.
The teachings of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick as applied to claims 1, 4-6, 9, 11-12, 16 and 23 are described above. These references do not teach one pair of graphite-based electrodes, or at least one photochemical catalyst, or wherein the electrochemical cell contains a carbon nitride catalyst.
Fukuzumi discusses artificial photosynthesis [title], and discusses methods of harnessing the reduction power of photosystem I (PSI) which normally enables reduction of NADP+ to NADPH, that can be also applied to fuel production via reduction of O2 [abstract].
Regarding claim 7, Fukuzumi teaches that graphite carbon nitride can act as a photocatalyst to catalyze the reduction of O2 [p 6-7, col 2, para 3].
In view of Fukuzumi, 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 method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick by using a carbon nitride catalyst, as taught by Fukuzumi, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick by using a carbon nitride catalyst because Fukuzumi teaches methods of harnessing the reduction power of photosystem I (PSI) which normally enables reduction of NADP+ to NADPH, that can be also applied to fuel production via reduction of O2 using a carbon nitride catalyst. One of ordinary skill in the art would have had a reasonable expectation of success because Nobles, Yagishita and Fukuzumi discuss components for artificial metabolic pathways.
Therefore, the invention of claim 7 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Nobles in view of Yagishita, Ortega, Hodgman, Greiner and Resnick as applied to claims 1, 4-6, 9, 11-12, 16 and 23 above, and further in view of in view of Park et al. (J Phys Chem C, 2009, 113:7935; cited on the Form PTO-892 mailed 07/12/2024; herein Park).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 10 is drawn to the method of claim 1, further comprising feeding the carbon dioxide source into the aqueous reaction solution at a flow rate of from about 80 ml/min to about 110 ml/min, or performing hydrolysis at a voltage of from -1.5 V to about 5.5 V.
The teachings of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick as applied to claims 1, 4-6, 9, 11-12, 16 and 23 are discussed above. These references do not teach a flow rate of CO2 or voltages associated with hydrolysis.
Park discloses electrochemical water splitting [title], and discusses methods of electrochemical water splitting, e.g. electrolysis, for H2 generation that have a negligible carbon footprint compared to the predominant method of steam methane reformation [p 7935, col 1, para 1].
Regarding claim 10, Park teaches a method of producing hydrogen gas at a constant cell voltage of 3.17 V in a cell containing 50 mM NaCl [Figure 6b, and p 7941, col 2, para 2].
In view of Park, 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 method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick by using the voltage of Park to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Nobles, Yagishita, Ortega, Hodgman, Greiner and Resnick by using the voltage of Park, because Park teaches using this voltage in methods for H2 generation that have a negligible carbon footprint compared to the predominant industrial methods. One of ordinary skill in the art would have had a reasonable expectation of success because Nobles, Yagishita and Park discuss systems that carry out hydrolysis.
Therefore, the invention of claim 10 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to remarks: beginning on page 6 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends the present application displays unexpected results with respect to monosaccharide yield which could not be predicted by the prior art; Applicant further contends the rejections of record improperly assume a person of ordinary skill in the art would have had “a finite number of identified, predictable solutions” that would reasonably lead to the claimed invention, and there is no support the invention would have been “obvious to try”; Applicant further contends the combination of prior art would have required substantial experimentation.
Applicant’s response is considered and found not convincing.
Regarding the assertion of improper assumption that a person of ordinary skill in the art would have had “a finite number of identified, predictable solutions” that would reasonably lead to the claimed invention, and that there is no support the invention would have been “obvious to try”: it is unclear which rejection in the previous Office action is being traversed by Applicant’s argument, as the rejections of record do not recite rationales for obviousness that involve “obvious to try” or “a finite number of identified, predictable solutions”.
Regarding the assertion that the combination of prior art would have required substantial experimentation: Applicant additionally states arriving at the invention would require extensive optimization and it therefore would not have been obvious to modify the method of Nobles using the teachings of Yagishita, Grenier, Resnick, Hodgman and Ortega, as the claims disclose 8 different variables including a combination of 10 different photosynthetic enzymes wherein at least 1 of 4 are required, 2 different cofactors, 3 different ATP regenerating enzymes and associated substrates, immobilization of enzymes on a hydrogel, 3 possible lengths of monosaccharide, a temperature range of 30 C, a pH range of 3, a flow rate varying by 30 ml/min and a voltage spanning 6 V, all of which would require extensive optimization and experimentation to result in a functional, reproducible method. As described in the rejection above, each of the limitations of the method were known in the art, including those cited by applicant corresponding to at least one photosynthetic enzyme, the 2 different cofactors, the 3 different ATP regenerating enzymes and associated substrates, the immobilization of enzymes on a hydrogel, and a monosaccharide, temperature, pH, flow rate, and voltage that fall within the claimed ranges (see MPEP 2144.05.I). Therefore the obvious rationale used was the combination of known prior art elements to achieve predictable results as stated above along with the relevant teachings and motivations to combine from each art, as according to MPEP 2141.I, the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. Considering an interpretation that Applicant is arguing against the number of references used in the rejection, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
Regarding Applicant’s allegations of unexpected results, Applicant cites the results of Nobles of a 1.37 mg/ml yield of glucose after 7-14 days of incubation in Table 2 compared with >2 mg/ml yield in 6 hours shown in Figure 3 of the instant application.
MPEP 716.02(b).I states the burden is on Applicant to establish results are unexpected and unobvious and of both statistical and practical significance. Figure 3 corresponds to Example V of the instant specification [para 0070], which offers no description of the data in the Figure aside from the values of “2, 5.8 and 10.6, 18.4 and 39.3 mg/ml after 6, 12, and 24, 36, and 48 hours under the present experimental conditions”, and as such it is unclear whether these data comprise mean values of multiple reactions or what the error bars represent. Assuming data in Figure 3 represents mean and standard deviation, one of ordinary skill in the art would recognize data containing a standard deviation larger than its mean would not be considered significant. As Applicant has not established results are unexpected and unobvious and of both statistical and practical significance, the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(b).I.
MPEP 716.02(b).II states Applicants have the burden of explaining proffered data. As Figure 3 proffered by Applicant corresponds to Example V of the specification which offers no description of the data in the Figure aside from the values of “2, 5.8 and 10.6, 18.4 and 39.3 mg/ml after 6, 12, and 24, 36, and 48 hours under the present experimental conditions”, and offers no description of the present experimental conditions, Applicants have not explained the proffered data, and the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(b).II.
MPEP 716.02(d) states unexpected results must be commensurate in scope with the claimed invention. As Figure 3 proffered by Applicant corresponds to Example V of the specification which offers no description of the data in the Figure aside from the values of “2, 5.8 and 10.6, 18.4 and 39.3 mg/ml after 6, 12, and 24, 36, and 48 hours under the present experimental conditions”, and offers no description of the present experimental conditions, the alleged unexpected results are considered not commensurate in scope with the claimed invention which encompasses:
forming any monosaccharide comprising the steps of:
providing any hydrogen source containing hydrogen gas in any aqueous electrolyte solution;
providing any carbon dioxide source;
forming any cell-free enzyme-based reaction mixture by feeding any hydrogen source and any carbon dioxide source into any synthetic reaction vessel containing any aqueous reaction solution containing a plurality of any photosynthetic enzymes, at least two of any cofactors including reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenine triphosphate (ATP), and at least one of any substrate;
wherein NADPH is regenerated using any electrochemical method and
ATP is regenerated using any 2-step synthetic enzymatic reaction which comprising polyphosphate kinase (PPK), adenylate kinase (ADK) and AMP phosphotransferase (PPT); and
forming an amount of any monosaccharide in any synthetic reaction vessel by reacting any hydrogen source, any carbon dioxide source, and the at least one of any substrate in contact with the plurality of any photosynthetic enzymes and the at least two of any cofactors,
wherein the synthetic reaction vessel includes any electrochemical cell and any power source; and wherein the hydrogen source is provided by performing hydrolysis of water in the electrochemical cell to produce hydrogen gas;
wherein the plurality of any photosynthetic enzymes is immobilized in any hydrogel including alginate or calcium alginate; and
wherein the amount of any monosaccharide formed has a concentration in the reaction mixture of 2 mg/ml or greater.
Therefore the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(d).
For these reasons, Applicant’s allegation of unexpected results is considered insufficient to rebut a prima facie case of obviousness.
Conclusion
Status of the Application:
Claims 1, 4-7, 9-12, 16 and 23 are pending.
Claims 1, 4-7, 9-12, 16 and 23 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656