DETAILED ACTION
Status of the Application
Claims 15, 18-28 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, 18-20, 23-24, 28, cancellation of claims 16-17 and amendments to the specification as submitted in a communication filed on 10/15/2025 is acknowledged.
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Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Specification
The disclosure was objected to because it contained an embedded hyperlink and/or other form of browser-executable code. In view of Applicant’s amendments, this objection is hereby withdrawn.
Claim Objections
Claim 15 is objected to due to the recitation of “…the substrate oxidizable by the oxidase”. To enhance clarity and to be consistent with commonly used claim language, the term should be amended to recite “…wherein the substrate is oxidizable by the oxidase”. Appropriate correction is required.
Claim 19 is objected to due to the recitation of “…process…characterized in that the concentration of the sulfinic acid….is at least …” . To enhance clarity and to be consistent with commonly used claim language, the term should be amended to recite “…process…wherein the concentration of the sulfinic acid….is at least …” . Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 20, 22-27 remain 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. New grounds of rejection are necessitated by amendment.
Claim 20 (claims 22-26 dependent thereon) is indefinite in the recitation of “wherein the sulfinic acid is…and that the sulfonic acid formed is…(taurine)” for the following reasons. It is unclear as to how the term “and that the sulfonic acid formed is…(taurine)” further limits the claim. If the intended limitation is “wherein the sulfinic acid is…and the sulfonic acid formed is…(taurine)”, the claim should be amended accordingly. Correction is required.
Claim 22 remains indefinite in the recitation of “wherein the hypotaurine is hypotaurine from fermentative production” for the following reasons. The term “fermentative production” is unclear because one cannot determine what is being produced by a fermentation process. Moreover, it is unclear as to how a compound is from a type of production. In addition, even if the intended limitation is hypotaurine produced by a fermentation process, it is unclear if the claimed process requires a fermentation step to produce hypotaurine. Correction is required.
Claim 23 (claims 24-26 dependent thereon) is indefinite in the recitation of “..wherein the hypotaurine is provided to the reaction batch via a culture broth generated from bacterial production of hypotaurine by way of using a bacterial production strain” for the following reasons. While it appears that the claim requires the hypotaurine to be produced by a bacterial strain, it is unclear if the claimed process requires a step where a bacterial strain is cultivated to produce hypotaurine. Correction is required.
Claim 27 is indefinite in the recitation of “…wherein the sulfinic acid is…and that the sulfonic acid formed is cysteic acid” for the following reasons. It is unclear as to how the term “and that the sulfonic acid formed is cysteic acid” further limits the claim. If the intended limitation is …wherein the sulfinic acid is…and the sulfonic acid formed is cysteic acid”, the claim should be amended accordingly. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 15, 18-28 remain 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 the amended claims comply with the written description requirement. Applicant states that claim 15 has been amended to limit the H2O2 generating oxidases and their substrates and also to limit R.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. 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. The claims 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 with or without substituents is structurally diverse and immense. Moreover, the substituents recited encompass an immense number of species since the R group in the substituents recited is undefined. 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 alcohol oxidases that use a primary alcohol as a substrate are H2O2 generating oxidases. 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 remains 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.
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 Example 4 describes in detail what a person skilled in the art would need to know to prepare the claimed strains. Applicant states that the strains can be generated from wild-type E. coli strains which are publicly available.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the teachings of the specification and agrees that E. coli W3110 is publicly available. However, the Examiner disagrees that the specification discloses a method to produce the specific strains required by the claims. While applicant argues that the strains can be generated from wild-type E. coli strains which are publicly available, the issue in the instant case is whether or not the specification provides a repeatable method to obtain the exact strains recited in the claims. The Examiner agrees that one could use a wild type E. coli strain and transform said E. coli strain with a generic plasmid that comprises the gene encoding the rat cysteine dioxygenase of Example 4. However, the claims require two specific strains, E. coli W3110 x pCys-CDOrn-CSADhs and E. coli W3110-ppsA-MHI x pCys-CDOrn-CSADhs. Based on the teachings of the specification, it appears that E. coli W3110 x pCys-CDOrn-CSADhs is a strain obtained by transforming an E. coli K12 W3310 with a plasmid called pCys-CDOrn-CSADhs, and E. coli W3110-ppsA-MHI x pCys-CDOrn-CSADhs is obtained by transforming an E. coli K12 W3310-ppsA-MHI strain with the plasmid called pCys-CDOrn-CSADhs. While the specification provides certain steps that were followed to obtain a plasmid called pCys-CDOrn-CSADhs, the steps provided would not allow one of skill in the art to infer the specific nucleotide sequence of the plasmid called pCys-CDOrn-CSADhs, and the specification fails to provide the specific sequence of the plasmid called pCys-CDOrn-CSADhs so that one of skill in the art can generate it. With regard to the strain E. coli W3110-ppsA-MHI, it is noted that the specification discloses that this strain was isolated from clones that are kanamycin resistant and sucrose sensitive. One of skill in the art would understand that any two or more clones that are kanamycin resistant and sucrose sensitive are not genetically identical. Therefore, the specification fails to disclose how to isolate the specific single clone isolated in Example 4 that Applicant has called E. coli W3110-ppsA-MHI.
It is reiterated herein that since the strains are essential to the claimed invention, they must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public. The recited strains do not appear to be publicly known and freely available. The specification does not disclose a repeatable process to obtain the specific strains and it is not apparent if the strains are readily available to the public. Accordingly, it is deemed that a deposit of these strains should have been made in accordance with 37 CFR 1.801-1.809.
Claims 15, 18-28 remain 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 H2O2 generating oxidase that is an 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 the claims have been amended to narrow the number of sulfinic acids and H2O2 generating oxidases. Applicant is of the opinion that the amended claims eliminate the need for undue experimentation.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. 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 full scope of the claims as amended is enabled by the teachings of the specification and/or the prior art. As indicated above, the claims require the conversion of sulfinic acids having substantial structural variability in view of the fact that the sulfinic acids have a radical that can be any organic, linear, branched, cyclic, saturated, unsaturated, aromatic or heteroaromatic radical with or without substituents is structurally diverse and immense. Moreover, the substituents recited encompass an immense number of substituents since R is undefined. The claims also require H2O2 generating oxidases which are alcohol oxidases having any structure that use any primary alcohol as a substrate. It is reiterated herein that 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 alcohol oxidases that use a primary alcohol as a substrate are H2O2 generating oxidases. 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.
As previously indicated, 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 H2O2 generating oxidases which 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 the specification and/or the prior art.
Claim Rejections - 35 USC § 103 (AIA )
Claims 15, 18-26, 28 remain 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 for the reasons of record and those set forth below.
Applicant argues that Grove is a Ph.D. thesis that investigates the biochemical mechanism of the conversion of hypotaurine to taurine and that Grove concludes that the conversion is likely non-enzymatic and spontaneous. Applicant states that while Grove shows that hydrogen peroxide can oxidize hypotaurine to taurine, Grove does not teach a method for industrial production. With regard to Wong et al., Applicant argues that while Wong et al.t each that GOX is a well-known tool for applications where the presence of hydrogen peroxide is desired, and that GOX produces hydrogen peroxide from glucose and oxygen, Wong et al. also teach that hydrogen peroxide breaks down spontaneously, and GOX is inactivated by hydrogen peroxide and its enzymatic activity inhibited by the second reaction product gluconic acid. According to Applicant, Grove teaches away from an enzymatic process for the conversion because Grover teaches that no enzyme could be found for the conversion of hypotaurine to taurine. Applicant submits that one of skill in the art would be discouraged from using an enzymatic route for the conversion. Applicant states that there is no motivation to combine the disclosures to achieve an industrially viable process because Grove’s work is purely analytical. Applicant states that Wong et al. do not suggest that the GOX system would be suitable or efficient for driving a stoichiometric, high concentration conversion of a specific substrate like hypotaurine to near completion. Applicant states that there would be no reasonable expectation of success in achieving the claimed process since the invention as disclosed achieves a surprisingly high molar conversion at a high starting concentration of 20 g/L of hypotaurine as shown in Example 6.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the teachings of Grove and Wong et al. as well as the teachings of the specification, including Example 6. However, the Examiner disagrees with Applicant’s contention that the claimed invention is not obvious over the cited prior art.
With regard to the argument that Grove only teaches the reaction that converts hypotaurine to taurine which is catalyzed by hydrogen peroxide and does not teach a method for industrial production, it is noted that Grover teaches the reaction that produces a compound (taurine) which Waldron et al. disclose as being highly desirable because it is one of the primary ingredients in popular energy drinks as well as most meats and seafood. Therefore, it is abundantly clear from the combined teachings of Grove and Waldon et al., that the industrial production of taurine is highly desirable. With regard to the argument that Grove does not teach the enzymatic conversion of hypotaurine to taurine, and that Grove teaches away from an enzymatic process for the conversion because Grover teaches that no enzyme could be found for the conversion of hypotaurine to taurine, it is noted that the conversion of hypotaurine to taurine is catalyzed by hydrogen peroxide. The enzymatic reaction of the claims, Wong et al., and Kjellander is an enzymatic reaction to produce hydrogen peroxide. It is not an enzymatic reaction where hypotaurine is the substrate of an enzyme that catalyzes the direct conversion of hypotaurine to taurine. Therefore, while it is agreed that Grove does not teach an enzyme that generates hydrogen peroxide, or an enzyme that uses hypotaurine as a substrate to produce taurine, it is unclear as to how one of skill in the art could possible conclude that Grove teaches away from the enzymatic production of hydrogen peroxide to produce taurine from hypotaurine if (i) Grove specifically teaches that hydrogen peroxide is required to produce taurine from hypotaurine, (ii) Grove makes no mention of how the hydrogen peroxide for the reaction should be produced, and (iii) Grove does not teach against hydrogen peroxide being produced through an enzymatic reaction. Therefore, contrary to Applicant’s assertions, Grove does not teach away from using hydrogen peroxide produced by an enzymatic reaction.
With regard to the argument that Wong et al. also teach that hydrogen peroxide breaks down spontaneously, and GOX is inactivated by hydrogen peroxide and its enzymatic activity inhibited by the second reaction product gluconic acid, it is noted that Wong et al. also teach that GOX has several industrial applications, including in the food industry, where the production of hydrogen peroxide is desired (Abstract; page 930). 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 uses.
With regard to the argument that Wong et al. do not suggest that the GOX system would be suitable or efficient for driving a stoichiometric, high concentration conversion of a specific substrate like hypotaurine to near completion, and that there is no reasonable expectation of success in achieving the molar conversions disclosed in the specification, it is noted that Grove teaches that the conversion of hypotaurine to taurine catalyzed by hydrogen peroxide is complete in two hours and that the reaction is an equimolar reaction. Therefore, while it is agreed that there is no absolute certainty that the method of Grove and Wong 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, 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 remains rejected 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 for the reasons of record and those set forth below.
Applicant argues that while Kjellander et al. teach that one could enzymatically produce hydrogen peroxide, this does not lead one of skill in the art to expect a constant and high enough level of hydrogen peroxide. Applicant also states that Kjellander et al. that enzymes can be immobilized to allow for repeated and/or extended use, indicating that costly enzyme coupling processes are necessary to create a stable process, which makes an economically feasible process difficult. Applicant claims that the claimed process however shows a stable process at a relevant scale without enzyme immobilization. According to Applicant, Kjellander et al. teach that AOX must first be immobilized to generate hydrogen peroxide.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to the claims and the teachings of Kjellander et al.. However, the Examiner disagrees with Applicant’s contention that the claimed invention is not obvious.
With regard to the argument that while Kjellander et al. teach that one could enzymatically produce hydrogen peroxide, this does not lead one of skill in the art to expect a constant and high enough level of hydrogen peroxide, it is noted that (i) the claims do not require a particular amount of hydrogen peroxide, (ii) Kjellander et al. clearly teach that one way to obtain a steady state generation of hydrogen peroxide is by using a glucose oxidase and an alcohol oxidase (Introduction), (iii) P. pastoris alcohol oxidase offers the best substrate economy since it can produce 2 mols of hydrogen peroxide from 1 mol of methanol (Introduction), (iv) one would adjust the amount of substrate (methanol) and enzyme to produce the desired amount of hydrogen peroxide, and (v) Applicant’s own working examples are carried out in shake flasks.
With regard to the argument that Kjellander et al. teach that AOX must first be immobilized to generate hydrogen peroxide, while it is agreed that Kjellander et al. teach the advantages of immobilizing the P. pastoris alcohol oxidase to generate hydrogen peroxide from alcohols such as methanol, the Examiner has been unable to find any teaching in the art, or by Kjellander et al., indicating that the only way to generate hydrogen peroxide from a reaction catalyzed by AOX in the presence of methanol is by first immobilizing the enzyme.
With regard to the argument that contrary to the teachings of Kjellander et al., the claimed process shows a stable process at a relevant scale without enzyme immobilization, it is noted that the claims as written do not exclude the presence of an immobilized enzyme. The claims simply require obtaining a mixture of the substrate, the enzyme, and sulfinic acid (reaction batch). The enzyme of the claims can be in immobilized form. In addition, even if the argument is made that the claims exclude an immobilized enzyme, it is noted that the fact remains that the prior art, as evidenced by Kjellander et al. teach that, regardless of whether the enzyme is immobilized or free in solution, (i) one way to obtain a steady state generation of hydrogen peroxide is by using a glucose oxidase or an alcohol oxidase (Introduction), and (ii) an alcohol oxidase offers the best substrate economy since it can produce 2 mols of hydrogen peroxide from 1 mol of methanol (Introduction). Therefore, one of skill in the art would have been motivated to use the P. pastoris alcohol oxidase and methanol even if not in immobilized form to produce hydrogen peroxide, and one of skill in the art would have a reasonable expectation of success in obtaining hydrogen peroxide from the reaction catalyzed by the P. pastoris alcohol dehydrogenase disclosed by Kjellander et al.
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.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 date of this final action.
Applicant is advised that any Internet email communication by the Examiner has to be authorized by Applicant in written form. See MPEP § 502.03 (II). Without a written authorization by Applicant in place, the USPTO will not respond via Internet email to any Internet correspondence which contains information subject to the confidentiality requirement as set forth in 35 U.S.C. 122. Sample written authorization language can be found in MPEP § 502.03 (II). An Authorization for Internet Communications in a Patent Application or Request to Withdraw Authorization for Internet Communications form (SB/439) can be found at https://www.uspto.gov/patent/forms/ forms-patent-applications-filed-or-after-september-16-2012, which can be electronically filed.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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
January 20, 2026