DETAILED ACTION
Status of the Application
Claims 15, 18-25, 27-44 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment of claims 15, 19-20, 22-23, 27, cancellation of claim 26, and addition of claims 29-44 as submitted in a communication filed on 4/21/2026 is acknowledged.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/21/2026 has been entered.
Claims 15, 18-25, 27-44 are at issue and are being examined herein.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claim Objections
Claim 33 is objected to due to the recitation of “…hypotaurine_by”. To enhance clarity and to be consistent with commonly used claim language, the underscore character should be removed and term should be amended to recite “…hypotaurine by”. Appropriate correction is required.
Claim 34 is objected to due to the recitation of “…Escherichia coli-strain” . To enhance clarity and to be consistent with commonly used claim language, the hyphen should be removed and the term should be amended to recite “…Escherichia coli strain” . Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 20, 22-27 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. In view of Applicant’s amendments, this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 15, 18-25, 27-28 remain rejected and new claims 29-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 15 has been amended to limit the substituents of R and that the genus of sulfinic acids and sulfonic acids is now adequately described. According to Applicant, the specification describes a defined chemical scaffold and chemically predictable substituents. Applicant states that all alcohol oxidases with a primary alcohol as a substrate are H2O2 generating oxidases, citing Expasy and Wikipedia as evidence to show that enzymes that use primary alcohols as a substrate and do not produce H2O2 are not classified as alcohol oxidases but rather as alcohol dehydrogenases.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of claims 29-44. The Examiner acknowledges the amendments made to the claims and the limitations added to them. However, the Examiner disagrees with Applicant’s contention that the claims as amended are adequately described.
New claims 29-44 require in part a genus of alcohol oxidases having a primary alcohol as substrate and/or a genus of sulfinic acids having substantial structural variability. New claims 36 and 40 further require a genus of cysteine dioxygenases and cysteine sulfinate decarboxylases having any structure. Neither the specification nor the prior art discloses the structural features required in any enzyme having cysteine dioxygenase activity and cysteine sulfinate decarboxylase activity. No structure/function correlation has been provided that would allow one of skill in the art to determine which proteins have cysteine dioxygenase activity and cysteine sulfinate decarboxylase activity. While the genus of substituents has been reduced, the claims still require the conversion of a genus of sulfinic acids having substantial structural variability. A genus of sulfinic acids having a radical that can be any organic, linear, branched, cyclic, saturated, unsaturated, aromatic or heteroaromatic radical without substituents or with the recited substituents remains structurally diverse and is immense.
With regard to the genus of H2O2 generating oxidases and their corresponding substrates, it is reiterated herein that while the specification discloses a limited number of H2O2 generating oxidases and their corresponding substrates, the specification does not provide the structural elements required in any alcohol oxidase that uses a primary alcohol as a substrate wherein said alcohol oxidase is a H2O2 generating oxidase. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which proteins are alcohol oxidases. While Applicant refers to Expasy and EC 1.1.3.13, it is noted that there are six alcohol oxidases disclosed. See attached entry for EC 1.1.3.13 and the enzymes under the section UniProtKB/Swiss-Prot. The claims are not limited to those alcohol oxidases known in the art but encompasses any enzyme having any structure that has that activity. In addition, while the specification discloses hypotaurine and cysteine sulfinic acid as sulfinic acids that can be oxidized to taurine and cysteic acid, respectively by using hydrogen peroxide as the catalyst, there is no disclosure in the specification or the prior art suggesting that any sulfinic acid having the formula recited in the claims, can be oxidized to its corresponding sulfonic acid using hydrogen peroxide. Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the entire scope of the claims is adequately described by the teachings of the specification and/or the prior art.
Claim 26 was rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. In view of Applicant’s cancellation of claim 26, this rejection is withdrawn.
Claims 15, 18-25, 27-28 remain rejected and new claims 29-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a process for the synthesis of taurine from hypotaurine, or the synthesis of cysteic acid from cysteine sulfinic acid, wherein said process comprises the conversion of hypotaurine to taurine, or the conversion of cysteic acid from cysteine sulfinic acid, in the presence of (i) a glucose oxidase and glucose, or (ii) a P. pastoris methanol oxidase and methanol, does not reasonably provide enablement for a process for the enzymatic oxidation of any sulfinic acid of the formula H2N-CH(R)-CH2-SO2H to any sulfonic acid of the formula H2N-CH(R)-CH2-SO3H, wherein R can be any organic, linear, branched, cyclic, saturated, unsaturated, aromatic or heteroaromatic radical with or without substituents, by using any alcohol oxidase that uses any primary alcohol as a substrate. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 15 has been amended to limit the substituents of R and that the genus of sulfinic acids and sulfonic acids is now adequately enabled. According to Applicant, the specification describes a defined chemical scaffold and chemically predictable substituents. Applicant states that all alcohol oxidases with a primary alcohol as a substrate are H2O2 generating oxidases, citing Expasy and Wikipedia as evidence to show that enzymes that use primary alcohols as a substrate and do not produce H2O2 are not classified as alcohol oxidases but rather as alcohol dehydrogenases. Applicant states that the specification provides examples for GOX and AOX.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of claims 29-44. The Examiner acknowledges the examples provided by the specification as well as the amendments made to the claims and the limitations added to them. However, the Examiner disagrees with Applicant’s contention that the claims as amended or the new claims are fully enabled.
Claims 29-44 require any alcohol oxidase having a primary alcohol as substrate and/or sulfinic acids having substantial structural variability. New claims 36 and 40 further require cysteine dioxygenases and cysteine sulfinate decarboxylases having any structure. Neither the specification nor the prior art discloses the structural features required in any enzyme having cysteine dioxygenase activity and cysteine sulfinate decarboxylase activity. No structure/function correlation has been provided that would allow one of skill in the art to determine which proteins have cysteine dioxygenase activity and cysteine sulfinate decarboxylase activity. It is reiterated herein that while the genus of substituents has been reduced, the claims still require the conversion of sulfinic acids having substantial structural variability. The sulfinic acids required by the claims have a radical that can be any organic, linear, branched, cyclic, saturated, unsaturated, aromatic or heteroaromatic radical without substituents or with the recited substituents. Thus, the genus of sulfinic acids recited is structurally diverse and is immense.
With regard to the H2O2 generating oxidases required and their corresponding substrates, it is reiterated herein that while the specification discloses a limited number of H2O2 generating oxidases and their corresponding substrates, the specification does not provide the structural elements required in any alcohol oxidase that uses a primary alcohol as a substrate wherein said alcohol oxidase is a H2O2 generating oxidase. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which proteins are alcohol oxidases. As shown in the Expasy entry for EC 1.1.3.13, there are six alcohol oxidases disclosed. See attached Expasy printout. The claims are not limited to those alcohol oxidases known in the art but encompasses any enzyme having any structure that has that activity. In addition, while the specification discloses hypotaurine and cysteine sulfinic acid as sulfinic acids that can be oxidized to taurine and cysteic acid, respectively by using hydrogen peroxide as the catalyst, there is no disclosure in the specification or the prior art suggesting that any sulfinic acid having the formula recited in the claims, can be oxidized to its corresponding sulfonic acid using hydrogen peroxide. It is reiterated herein that while methods of generating or isolating variants of a polypeptide and enzymatic assays were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for (i) an essentially infinite number of proteins to find those that are alcohol oxidases that use a primary alcohol as a substrate, and (ii) an essentially infinite number of sulfinic acids having the formula H2N-CH(R)-CH2-SO2H , wherein R is a radical that can be any organic, linear, branched, cyclic, saturated, unsaturated, aromatic or heteroaromatic radical with or without substituents, to find those that can be oxidized to its corresponding sulfonic acid with hydrogen peroxide.
Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the entire scope of the claims is fully enabled by the teachings of specification and/or the prior art.
Claim Rejections - 35 USC § 103 (AIA )
Claims 15, 18-21, 28 remain rejected and new claims 29-32, 41-44 are rejected under 35 U.S.C. 103 as being unpatentable over Grove (The biosynthesis reaction of hypotaurine to taurine, Thesis, March 2018; University of Central Oklahoma, pages 1-109; cited in the IDS) in view of Kjellander et al. (Biotechnology Letters 35:585-590, 2012), Wong et al. (Applied Microbiology and Biotechnology 78:927-938, 2008), and Waldron et al. (Sports Med 48:1247-1253, 2018).
This rejection has been discussed at length in the prior Office action. It is maintained and further applied to new claims 29-32, 29-32, 41-44 for the reasons of record and those set forth below.
Applicant argues that there is no expectation of success in the prior art. Applicant states that Wong et al. states that H2O2 readily undergoes spontaneous decomposition and that GOX is inactivated by its own reaction product H2O2. Applicant states that an industrial reaction such that that outlined in the disclosed examples, requires high concentrations of H2O2 due to stoichiometry for a long period of time. Applicant states that based on the teachings of Wong et al. these high concentrations of H2O2 would destroy the GOX enzyme, making the process uneconomical and uncontrollable. Therefore, one of skill in the art would have no reasonable expectation of success for high throughput production. Applicant states that in the claimed enzymatic system the high concentrations of H2O2 can only be reached using high amounts of GOX, which makes the process economically unattractive. Applicant states that high concentrations of H2O2 would lead one of skill in the art to expect oxidative damage. Applicant states that the claimed process unexpectedly achieves a molar conversion of >90% at a high starting concentration of 20 g/L hypotaurine (Example 3, Table 5). Applicant states that this is unexpected in light of the issues disclosed by Wong et al., namely enzyme inactivation and the need for equimolar H2O2 concentrations for the desired effect. Applicant states that the claimed process overcomes the instability of H2O2 and GOX inactivation by establishing a balanced one pot system in which the rate of H2O2 generation and the rate of H2O2 consumption are tuned. Applicant states that new claims 29-36 and 43-44 are directed to disclosed embodiments where R is H and the concentration of the sulfinic acid in the reaction batch at the start of the process is at least 10 g/L and the molar yield is at least 90%. Applicant states that Wong et al. and Kjellander et al. teach methods for generating H2O2 but they provide no indication that such systems could operate under the claimed high-performance conditions. Applicant states that the recited % yield and high concentrations recited in the claims are a surprising result in view of the teachings of Wong et al.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of claims 29-32, 41-44. The Examiner acknowledges the amendments made to the claims, the new claims, the teachings of the specification and the prior art. However, the Examiner disagrees with Applicant’s contention that the claimed invention is not obvious over the prior art of record.
New claims 29-32, 41-44 are directed in part to directed in part to a process for the synthesis of taurine (R = H) from hypotaurine (R = H) , wherein said process comprises the conversion of hypotaurine to taurine in the presence of (i) a glucose oxidase or an alcohol oxidase, wherein the glucose oxidase and the alcohol oxidase are H2O2 generating oxidases, and (ii) glucose or an alcohol, wherein the concentration of hypotaurine can be at least 10 g/L at the start of the process and wherein the molar yield of taurine can be at least 90%, wherein the alcohol oxidase can be from P. pastoris and the substrate is methanol, or wherein the glucose oxidase can be from A. niger and the substrate is glucose. Wong et al. teach a glucose oxidase from Aspergillus niger (Abstract).
With regard to the argument that Wong et al. states that H2O2 readily undergoes spontaneous decomposition and that GOX is inactivated by its own reaction product H2O2, it is noted that (i) based on the teachings of Grove, hypotaurine can be converted fully to taurine (100% molar yield) in a reaction catalyzed by H2O2 in two hours, thus indicating that H2O2 is stable enough for the amount of time required for full conversion of hypotaurine to taurine, and (ii) even if the argument is made that GOX can be inactivated by H2O2, there is no evidence that shows that the H2O2 levels present when there is simultaneous generation and consumption of H2O2 are sufficiently high to inactivate GOX, and Wong et al. clearly teach that GOX has been used commercially for the production of H2O2 in several industries, including in processes where the H2O2 produced was simultaneously used in another process, thus showing that GOX was not inactivated at the levels of H2O2 produced. It is reiterated herein that Wong et al. teach that glucose oxidases have been used in food processing and food preservation, including in combination with the lactoperoxidase system. Wong et al. teach that the reaction of glucose oxidase and glucose allows the formation of hydrogen peroxide (H2O2), which is required by the lactoperoxidase system, to be continuously generated and replenished (page 930, left column, Dairy and the lactoperoxidase system). Wong et al. tech teach using glucose oxidase to produce hydrogen peroxide for bleaching (page 934, right column, Other uses and concluding remarks). Therefore, it is abundantly clear that the art, as evidenced by Wong et al., recognizes the use of GOX (glucose oxidase) and glucose for the generation of hydrogen peroxide for a variety of industrial uses.
With regard to the argument that an industrial reaction such that that outlined in the disclosed examples, requires high concentrations of H2O2 due to stoichiometry for a long period of time, it is reiterated herein that Grover teaches that it takes two hours to obtain full conversion of hypotaurine to taurine and that such conversion was obtained with an equimolar mixture of hypotaurine and H2O2. An equimolar mixture simply implies that the reactants are in a molar ratio of 1:1. For example, 0.01 moles of H2O2 and 0.01 moles of hypotaurine. There is no requirement of high concentrations of H2O2 as asserted and the process as claimed do not require a specific concentration of H2O2.
With regard to the arguments that (i) based on the teachings of Wong et al. these high concentrations of H2O2 would destroy the GOX enzyme, making the process uneconomical and uncontrollable, (ii) one of skill in the art would have no reasonable expectation of success for high throughput production, and (iii) the high concentrations of H2O2 can only be reached using high amounts of GOX, which makes the process economically unattractive, it is reiterated herein that there are no high concentrations of H2O2 that would destroy the GOX enzyme because (a) Wong et al. specifically teach that GOX has been used commercially for the production of H2O2 in several industries, including in processes where the H2O2 produced was further used by another system, thus showing that GOX was not inactivated at the levels of H2O2 produced, and (b) having an equimolar mixture of hypotaurine and H2O2 to obtain taurine does not require high concentrations of H2O2 but rather the same molar concentration of hypotaurine and H2O2. An equimolar mixture of hypotaurine and H2O2 does not imply high concentrations of H2O2. It should also be noted that the claims do not require a specific molar concentration of H2O2 and there is no indication in the specification of specific molar concentrations for H2O2 used in the conversion of hypotaurine to taurine.
With regard to the argument that the claimed process unexpectedly achieves a molar conversion of >90% at a high starting concentration of 20 g/L hypotaurine and that this is unexpected in light of the issues disclosed by Wong et al., namely enzyme inactivation and the need for equimolar H2O2 concentrations for the desired effect, it is noted that it is unclear as to how the molar conversion of 90% or higher is unexpected when Grover teaches that an equimolar mixture of hypotaurine and H2O2 would result in 100% molar yield in two hours. Moreover, Grover teaches that 100 mM hypotaurine reacts with 20 mM H2O2 for 20 minutes to produce taurine, thus showing that one could obtain taurine with a mixture that has a molar ratio of H2O2 to hypotaurine which is less than 1 (e.g., 1:5; page 39, lines 15-18). Hypotaurine has a molecular weight of 109 g/mol, thus 20 g/L is equivalent to 183 mM (183 = 20x100/109). Therefore, based on the teachings of Grover, reacting 183 mM hypotaurine with 183 mM H2O2 is expected to produce 100% taurine in 2 hours. Table 5 in Example 3 of the specification discloses that full conversion of 183 mM hypotaurine to taurine took 24 hours. Therefore, it is not believed that the results disclosed in the specification are unexpected based on the teachings of Grove.
With regard to the argument that the claimed process overcomes the instability of H2O2 and GOX inactivation by establishing a balanced one pot system in which the rate of H2O2 generation and the rate of H2O2 consumption are tuned, it is noted that the simultaneous utilization of H2O2 generated by GOX while being produced at an industrial level has been disclosed by Wong et al. Therefore, it is not believed that the one pot system is non-obvious.
With regard to the argument that Wong et al. and Kjellander et al. teach methods for generating H2O2 but they provide no indication that such systems could operate under the claimed high-performance conditions, it is noted that there are no high-performance conditions recited in the claims and Wong et al. specifically teach the use of GOX on an industrial scale for the production of H2O2.
While it is agreed that there is no absolute certainty that the method of Grove, Wong et al., Kjellander et al. and Waldron et al. would result in total conversion, the teachings of Grove strongly suggest that if the catalyst is present (i.e., hydrogen peroxide), the conversion is complete, and the teachings of Wong et al. teach that hydrogen peroxide is produced by combining glucose with glucose oxidase. Therefore, contrary to Applicant’s assertions, it is not believed that the recited % yield and the hypotaurine concentration of 10 g/L recited in the claims are a surprising result in view of the teachings of Wong et al. As such, for the reasons of record and those set above, one of skill in the art would reasonably conclude that the claimed invention is obvious over the prior art of record.
Claims 15, 18-19, 21, 27, 28 remain rejected and new claims 29, 37-39 under 35 U.S.C. 103 as being unpatentable over Tappaz et al. (Neurochemical Research 17(9):849-859, 1992) in view of Luo et al. (Journal of Pharmaceutical Sciences 94(2):304-316, 2005), Kjellander et al. (Biotechnology Letters 35:585-590, 2012), Wong et al. (Applied Microbiology and Biotechnology 78:927-938, 2008), and Waldron et al. (Sports Med 48:1247-1253, 2018).
This rejection has been discussed at length in the prior Office action. It is maintained and further applied to new claims 29, 37-39 for the reasons of record and those set forth below.
Applicant argues that a person of ordinary skill in the art would not have a reasonable expectation of success in combining the cited art as required for a prima facie case of obviousness. Applicant states that H2O2 is a strong and a non-specific oxidant and that one of skill in the art would have serious concerns that H2O2 would not only oxidize the desired sulfinic acid group but also attack other parts of the molecule leading to undesirable side reactions and decomposition. Applicant states that one of skill in the art would anticipate that upon scaling up, non-selective oxidation and side reactions would increase, causing a marked drop in yield and purity. Applicant states that the core of the invention is the creation of a finely balanced one pot system where the rate of H2O2 generation by GOX/AOX is matched to the rate of H2O2 consumption. Applicant states that this kinetic balance there is minimized inactivation of the GOX/AOX enzyme and there is a substantial reduction of undesirable side reactions with the amino acid substrate. According to Applicant, the prior art combination suggests at most a brute-force mixing of components and provides no indication of how to achieve this sensitive kinetic equilibrium to obtain a highly specific reaction on a preparative scale with sustained high yield. Applicant states that achieving the specificity and yield shown in Examples 1A and 2A is surprising and unexpected.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of new claims 29, 37-39. The Examiner acknowledges the amendments made to the claims and the teachings of the prior art. However, the Examiner disagrees with Applicant’s contention that the claimed invention is not obvious over the cited prior art.
New claims 29, 37-39 are directed in part to a process for the synthesis of cysteic acid (R = COOH) from cysteine sulfinic acid (R = COOH), wherein said process comprises the conversion of cysteine sulfinic acid to cysteic acid in the presence of (i) a glucose oxidase or an alcohol oxidase, wherein the glucose oxidase and the alcohol oxidase are H2O2 generating oxidases, and (ii) glucose or an alcohol, and wherein the molar yield of cysteic acid based on the total molar concentration of cysteine sulfinic acid at the start of the reaction is at least 60%.
With regard to the argument that H2O2 is a strong and a non-specific oxidant and that one of skill in the art would have serious concerns that H2O2 would not only oxidize the desired sulfinic acid group but also attack other parts of the molecule leading to undesirable side reactions and decomposition, thus leading one of skill in the art to anticipate that upon scaling-up, non-selective oxidation and side reactions would increase, causing a marked drop in yield and purity, it is noted that there is no evidence in the specification or in the prior art indicating that H2O2 would attack other parts of the sulfinic acid group thus producing undesirable byproducts beyond cysteic acid. It is reiterated herein that Luo et al. teach that cysteine can be converted to cysteic acid by oxidation with hydrogen peroxide to obtain cysteine sulfinic acid, which is then oxidized with hydrogen peroxide to cysteic acid (page 312, right column, Scheme II). There is no mention by Luo et al. of additional reactions associated with cysteine sulfinic acid and H2O2 or the production of byproducts that result from additional reactions associated with cysteine sulfinic acid and H2O2.
With regard to the argument that the core of the invention is the creation of a finely balanced one pot system where the rate of H2O2 generation by GOX/AOX is matched to the rate of H2O2 consumption, such as to minimize inactivation of the GOX/AOX enzyme and reduce undesirable side reactions with the amino acid substrate, it is noted that (i) as explained above, Wong et al. specifically teach that GOX has been used commercially for the production of H2O2 in several industries, including in processes where the H2O2 produced was further used by another system, thus showing that GOX was not inactivated at the levels of H2O2 produced, and (ii) there is no evidence in the prior art suggesting that additional undesirable reactions would take place with cysteine sulfinic acid and H2O2 beyond the production of cysteic acid. In addition, it is reiterated herein that the simultaneous utilization of H2O2 generated by GOX while being produced at an industrial level has been disclosed by Wong et al. Therefore, it is not believed that the one pot system is non-obvious. Thus, for the reasons of record and those set forth above, one would have to conclude that the claimed invention is obvious over the prior art of record.
Claims 22-25, 33-36, 40 are rejected under 35 U.S.C. 103 as being unpatentable over Grove (The biosynthesis reaction of hypotaurine to taurine, Thesis, March 2018; University of Central Oklahoma, pages 1-109; cited in the IDS) in view of Kjellander et al. (Biotechnology Letters 35:585-590, 2012), Wong et al. (Applied Microbiology and Biotechnology 78:927-938, 2008), Waldron et al. (Sports Med 48:1247-1253, 2018) and further in view of Yamakami et al. (WO 2017/213142 published 12/14/2017; cited in the IDS). The Examiner will use an English translation of WO 2017/213142 when referring to specific teachings of Yamakami et al.
Grove et al. teach that hypotaurine can be converted to taurine in a reaction catalyzed by H2O2 , wherein the reaction is equimolar and the complete conversion to taurine is observed in two hours (page 39, last three lines, page 40, lines 1-18). Grove does not teach H2O2 generating oxidases or substrates for these oxidases.
Wong et al. teach that glucose oxidases are enzymes that catalyze the conversion of D-glucose into D-gluconolactone and H2O2 in equimolar amounts (i.e., one mole of glucose would be converted into one mole of H2O2 ; page 927, right column, Introduction). Wong et al. teach that glucose oxidases have been used in food processing and food preservation, including in combination with the lactoperoxidase system. Wong et al. teach that the reaction of glucose oxidase and glucose allows the formation of hydrogen peroxide (H2O2), which is required by the lactoperoxidase system, to be continuously generated and replenished (page 930, left column, Dairy and the lactoperoxidase system). Wong et al. teach using glucose oxidase to produce hydrogen peroxide for bleaching (page 934, right column, Other uses and concluding remarks). Kjellander et al. teach that the generation of hydrogen peroxide can be achieved by glucose oxidase and alcohol oxidases (page 585, right column, Introduction). Kjellander et al. teach the immobilization of an alcohol oxidase from P. pastoris (EC 1.1.3.13; page 586, right column, first line) for steady generation of hydrogen peroxide (Abstract) in the presence of various alcohols including methanol, which was found to be the best substrate (page 588, Table 1, Discussion). Neither Wong et al. nor Kjellander et al. teach taurine or hypotaurine.
Waldron et al. teach that taurine is a sulfur-containing amino acid and is one of the primary ingredients in popular energy drinks and well as most meats and seafood. Waldron et al. teach that taurine is available to facilitate a variety of biological processes that can support endurance exercise performance (page 247, right column, Introduction). Waldron et al. do not teach a glucose oxidase, an alcohol oxidase, glucose or methanol.
Yamakami et al. teach E. coli cells transformed with plasmids that encode a cysteine dioxygenase and a cysteine sulfinate decarboxylase (paragraphs [0155]-[0158]; Table 5; EcoT/pMW-HAS, EcoT/pMW-BTA, EcoT/pMW-GGA, EcoT/pMW-CHX), which is also known as sulfinoalanine decarboxylase as evidenced by Expasy EC 4.1.1.29. Yamamaki et al. teach that these strains accumulate hypotaurine in the fermentation medium and teach that taurine can be produced from this fermentation medium (paragraph [0181]). Yamakami et al. teach that the E. coli cells transformed with nucleic acids that encode a cysteine dioxygenase and a cysteine sulfinate decarboxylase can be E. coli cells genetically modified to be L-cysteine producing cells by suppressing the decomposition of L-cysteine (deregulated cysteine biosynthetic pathway; paragraphs [0047]-[0050]). Yamakami et al. do not teach a glucose oxidase, an alcohol oxidase, glucose or methanol.
Claims 22-25, 33-36, 40 as interpreted are directed in part to a process for the synthesis of taurine from hypotaurine, wherein said process comprises the conversion of hypotaurine to taurine in the presence of (i) a glucose oxidase or an alcohol oxidase, wherein the glucose oxidase and the alcohol oxidase are H2O2 generating oxidases, and (ii) glucose or an alcohol, wherein the method comprises providing a culture broth comprising the hypotaurine, wherein the culture broth comprising the hypotaurine is produced by culturing an E. coli cell that expresses a cysteine dioxygenase and a cysteine sulfinate decarboxylase, wherein the E. coli cell has a deregulated cysteine biosynthetic pathway.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce taurine from hypotaurine in a process catalyzed by hydrogen peroxide, wherein the hydrogen peroxide is provided by the oxidation of glucose by glucose oxidase, or by the oxidation of an alcohol such as methanol by the P. pastoris alcohol oxidase of Kjellander et al., wherein the method comprises providing a hypotaurine-containing culture broth, wherein the culture broth is produced by culturing an E. coli cell that expresses a cysteine dioxygenase and a cysteine sulfinate decarboxylase, wherein the E. coli cell has a deregulated cysteine biosynthetic pathway. Taurine is a well-known compound with several commercial uses as evidenced by Waldron et al. A person of ordinary skill in the art is motivated to produce taurine from hypotaurine in the presence of a glucose oxidase and glucose, or in the presence of methanol and the P. pastoris alcohol oxidase of Kjellander et al. for the benefit of using an enzyme/substrate system that uses relatively inexpensive substrates such as glucose or methanol, which are stable compared to hydrogen peroxide, which is a reactive species. By using glucose/glucose oxidase or methanol/alcohol oxidase, the required catalyst, hydrogen peroxide, is produced in situ. As taught by Wong et al. and Kjellander et al., the use of glucose oxidase/glucose and methanol/alcohol oxidase to generate hydrogen peroxide for processes that require hydrogen peroxide is well known in the art. A person of ordinary skill in the art is motivated to use a hypotaurine-containing culture broth obtained from culturing an E. coli cell that expresses a cysteine dioxygenase and a cysteine sulfinate decarboxylase, wherein the E. coli cell has a deregulated cysteine biosynthetic pathway because hypotaurine is produced by a biological process without the use of chemicals. One of ordinary skill in the art has a reasonable expectation of success at producing hydrogen peroxide for the conversion of hypotaurine to taurine by using glucose oxidase/glucose or methanol/alcohol oxidase because the use of these substrate/enzyme combinations for the production of hydrogen peroxide is well known in the art. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
August 28, 2026
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