DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-18 are pending.
Claims 1, 5-11, 14, and 15 are amended.
Response to Amendments
Applicant’s amendments filed 28 October 2025 are acknowledged.
Drawings
Applicant’s amendment to the drawings is sufficient to overcome the objection of
the drawings. The drawings have been amended to comply with 37 CFR 1.84 (u)(1). The
objection is withdrawn.
Specification
Applicant’s amendment to the specification is sufficient to overcome the
objection of the specification. The specification has been amended to match the
drawings in compliance with 37 CFR 1.84 (u)(1). The objection is withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s amendment to claim 1 is not sufficient to overcome the rejection of claims 1-18 under 35 U.S.C. 103 as being unpatentable over Fremy et al. (US20180273991, hereinafter Fremy) in view of Boyd et al. (“Enzyme-catalysed oxidation of 1,2-disulfides to yield chiral thiosulfinate, sulfoxide and cis-dihydrodiol metabolites”, 26 June 2014, RSC Advances, Vol. 4, Pgs. 27607-27619 and Supplement, hereinafter Boyd) and Netto et al. (“Enzymatic reactions involving the heteroatoms from organic substrates”, 2018, Annals of the Brazilian Academy of Sciences, Vol. 90, 1 Suppl. 1, Pgs. 943-992, hereinafter Netto). The rejection is maintained; however, due solely to the amendment to claim 1 an additional modified ground(s) of rejection is/are provided below.
Response to Arguments
Applicant’s arguments filed 28 October 2025 have been fully considered but they are not persuasive.
Applicant’s argue that Fremy, Boyd, and Netto do not disclose the limitations as recited in amended claim 1. These arguments have been considered but are not persuasive for the reasons set forth in the modified grounds of rejection below and the response to arguments below.
In response to applications arguments on pages 9-10 of the remarks filed on 28 October 2025 that “Fremy teaches the inverse reaction - i.e., an enzymatic process for the preparation of a mercaptan of formula R-SH from disulfides utilizing hydrogen” and “Fremy which relies on hydrogen gas to reduce the disulfide to the target mercaptans, the claimed process proceeds by use of the mercaptan starting material as the hydrogen donor”.
““The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).” See also MPEP 2123.
As stated on pages 7-8 in the previous office action dated 08 July 2025 (hereinafter POA), Fig. 1 of Fremy teaches a batch redox reaction where the reaction cascade includes the reaction of methyl mercaptan associated with methyl disulfide, glutathione associated with GSSG, ethylene mercaptan associated with the aryl disulfide, NADPH associated with NADP+, and the reactions are cyclic in nature, where the reactants are all allowed to contact each other, specifically for methyl mercaptan to contact the dimer GSSG, and regeneration of the disulfides, GSH, GSSG, NADPH, NADP+, see Fig. 1 and Paras. [0048]-[0052];[0067];[0071]. It is well known within the art that the oxidation of a mercaptan and the reduction of a disulfide is a reversible reaction, see below,
PNG
media_image1.png
603
737
media_image1.png
Greyscale
as evidenced by Page 15 of Calvin (Glutathione, “Mercaptans and Disulfides: Some Physics, Chemistry, and Speculation”, November 1953, Proceedings of the Symposium Held at Ridgefield, Connecticut, Pgs. 3-30).
Fremy teaches producing mercaptan from disulfide, see above; but, does not “criticize, discredit, or otherwise discourage” producing disulfide from mercaptan, see Paras. [0064]-[0065] and MPEP 2145 X.D.1. On the contrary, Fremy teaches “dimethyl disulfide (DMDS) may be produced at another site from methyl mercaptan and an oxidizer such as oxygen, sulfur or aqueous hydrogen peroxide solution”, where when DMDS is produced on the site of its use “a process which makes it possible to avoid transporting methyl mercaptan from its site of production by existing industrial routes, to its site of use”, see Paras. [0064]-[0065]. Therefore, Fremy teaches producing both DMDS from methyl mercaptan and methyl mercaptan from DMDS on site throughout the same process.
For the reasons indicated above, applicant’s above arguments are not persuasive.
In response to applications arguments on page 10 of the remarks filed on 28 October 2025 that the “inventors, indeed, have surprisingly found a chemoenzymatic cascade which not only is compatible with the sulfoxide or sulfone production process but also allows the coproduction of a second product of interest, the disulfide”, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious, see Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In addition, “[t]o establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range.” In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960), see MPEP 716.02(d). Applicants have not provided a comparison to the closest prior art and tests inside and outside the chemoenzymatic cascade to support their argument of surprising and unexpected results, see MPEP 716.02(e).
For the reasons indicated above, applicant’s above arguments are not persuasive.
In response to applications arguments on page 10 of the remarks filed on 28 October 2025 that “Fremy teaches the reduction of disulfide starting materials to generate mercaptan products which is the inverse of the claimed invention which co-produces a disulfide from a mercaptan starting material and a sulfoxide or sulfone from a sulfide”; as a result, “modification of the Fremy process, such as by Boyd and Netto, to achieve the claimed invention renders Fremy inoperable for its intended purpose”.
The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), and MPEP 2143.
In this case, as stated above, Fremy does teach the claimed process of producing a disulfide from a mercaptan starting material. Fremy also teaches producing other disulfides and applying the products produced to produce other products, see Paras. [0065];[0067].
“A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention).”, see MPEP 2141.01(a).
In this case, Boyd is in the known prior art field of producing chiral thiosulfinate, sulfoxide and cis-dihydrodiol metabolites by asymmetric sulfoxidation of cyclic 1,2-disulfides, using chemical and enzymatic oxidation methods, such as peroxidase, monooxygenase, dioxygenase, see Abstract, and is applied to teach the same.
Netto is in the known prior art field of enzymatic reactions of heteroatom-containing compounds, such as biocatalyzed reactions involving the heteroatom (S, Se, B, P and Si) from hetero-organic substrates, see Abstract, for example, the sulfides of R1-S-R2, such as dimethyl sulfide, and disulfides, see Pg. 945, Figs. 2-3, 26, 27 and Pg. 963, Col. 1, and is applied to teach the same.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense”, see MPEP 2143 I.E. Since patents are part of the literature of the prior art relevant for all they contain, see MPEP 2123, and Fremy, Boyd, and Netto all teach enzymatic reactions to produce useful compounds from disulfides, a person of ordinary skill in the art has good reason to modify the production of disulfide from mercaptan as taught in Fremy to produce other compounds from the disulfide by relying upon Boyd and Netto before the effective filing date of the claimed invention for knowledge generally available within the enzymatic disulfide art regarding the products produced from the redox reactions, see MPEP 2143 B & G and 2141, for the benefit of utilizing a combination of enzymes to rationalize the unexpectedly wide range of metabolites formed from the disulfide substrate produced, see Boyd, Pg. 27615, Col. 2, First Full Para. and synthesizing relevant hetero-organic derivatives, with special attention to environmental-friendly reactions, such as the regenerative biocatalyzed-transformations, see Netto, Pg. 943, Introduction and Pg. 954, Fig. 14 and MPEP 2141.
For the reasons indicated above, applicant’s above arguments are not persuasive.
Maintained and Modified Rejections Based on Amendments to the Claims in the reply filed on 28 October 2025
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Maintained Rejections – Modified in view of amendment
Claims 1-18 stand rejected in modified form under 35 U.S.C. 103 as being unpatentable over Fremy et al. (US20180273991, hereinafter Fremy), as evidenced by Calvin (Glutathione, “Mercaptans and Disulfides: Some Physics, Chemistry, and Speculation”, November 1953, Proceedings of the Symposium Held at Ridgefield, Connecticut, Pgs. 3-30), in view of Boyd et al. (“Enzyme-catalysed oxidation of 1,2-disulfides to yield chiral thiosulfinate, sulfoxide and cis-dihydrodiol metabolites”, 26 June 2014, RSC Advances, Vol. 4, Pgs. 27607-27619 and Supplement, hereinafter Boyd) and Netto et al. (“Enzymatic reactions involving the heteroatoms from organic substrates”, 2018, Annals of the Brazilian Academy of Sciences, Vol. 90, 1 Suppl. 1, Pgs. 943-992, hereinafter Netto).
Fremy teaches the claims 1, 2, 5, 6, 8, 9, and 13-15 limitations of a process for coproducing a disulfide, such as GSSG, i.e., glutathione disulfide, and mercaptan, such as H3C-SH, i.e., methyl mercaptan, by an enzymatic redox regeneration reaction of a composition used in order to reduce disulfide, such as H3C-S-S-CH3, i.e., DMDS or dimethyl disulfide, with a peptide, such as glutathione, to mercaptan, such as methyl mercaptan or HS-CH2-CH2-SH, i.e., ethylene mercaptan, by enzymatically creating, such as with glutathione reductase, a dipeptide with a disulfide bridge, such as
PNG
media_image2.png
50
66
media_image2.png
Greyscale
aryl disulfide, i.e., 1,2-Dithietane, see Fig. 1 and Paras. [0045];[0049]-[0053];[0074]-[0091], comprising:
a) preparing a composition M comprising:
1) a sulfide, such as dimethyl disulfide of the formula H3C-S-S-CH3, where R1 is CH3 and R2 is sulfur substituted CH3, see Fig. 1, meeting the specific sulfide formula limitations in claim 9,
2) optionally an oxidizing agent, optionally not included,
3) an organic compound bearing at least one thiol group, such as GSH, i.e., glutathione, see Fig. 1, meeting the specific organic compound limitations in claim 5, in claim 6, and in claim 14,
5) an enzyme D, such as glutathione reductase, see Fig. 1, meeting the specific reductase enzyme limitation in claim 8, and in claim 14, and
6) a cofactor for enzyme D, such as NADPH/NADP+, nicotinamide adenine dinucleotide phosphate reduced form and oxidized form complex, see Fig. 1 and Paras. [0045];[0048]-[0053];[0074]-[0091], meeting most of the step a) composition limitations in claim 1, claim 14, and claim 15 and the specific nicotine cofactor limitations in claim 13;
b) conducting enzymatic reactions of disulfide bridge formation to form a dimer, such as GSSG, see Fig. 1 and Paras. [0045];[0049]-[0053];[0074]-[0091], meeting most of the step b) limitations in claim 1;
c) reducing the dimer GSSG obtained in step b) by reaction with a mercaptan, such as HS-CH2-CH2-SH, i.e., ethylene mercaptan, where R3 is a sulfur substituted linear hydrocarbon, see Fig. 1 and Paras. [0045];[0049]-[0053];[0074]-[0091], meeting the specific mercaptan limitation in claim 2; so as to obtain: the corresponding disulfide
PNG
media_image2.png
50
66
media_image2.png
Greyscale
aryl disulfide, and said organic compound bearing at least one thiol group GSH, as depicted in Fig. 1, the reaction of methyl mercaptan to methyl disulfide, glutathione to GSSG, and ethylene mercaptan to the aryl disulfide are cyclic allowing for the regeneration of the disulfides, GSH, and GSSG, see Fig. 1 and Paras. [0048]-[0052], meeting the step c) limitations in claim 1; and
d) optionally recovering:
the disulfide obtained in step c); and/or
the sulfoxide or the sulfone obtained in step b), optionally not included;
it being possible for said mercaptan to be added in any one of steps a), b) or c), the mercaptans, methyl mercaptan and ethylene mercaptan, i.e., HS-CH2-CH2-SH, are continually created within the mixture, see Fig. 1 and Paras. [0048]-[0052], meeting this optional limitation in claim 1.
Regarding newly amended instant application claim 1, Fremy teaches “dimethyl disulfide (DMDS) may be produced at another site from methyl mercaptan and an oxidizer such as oxygen, sulfur or aqueous hydrogen peroxide solution”, where when DMDS is produced on the site of its use “a process which makes it possible to avoid transporting methyl mercaptan from its site of production by existing industrial routes, to its site of use”, see Paras. [0064]-[0065], i.e., Fremy teaches producing both DMDS from methyl mercaptan and methyl mercaptan from DMDS on site throughout the same process, meeting the producing a disulfide from a mercaptan in newly amended instant application claim 1.
In addition, the instant application claim 1 scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure, see MPEP 2111.04. In this case, the “wherein” clauses drawn to the diameter and the dissolution appear to not give “meaning and purpose to the manipulative steps”, see MPEP 2111.04.
Fremy teaches the claims 3, 4, and 16-18 limitations of a method for regenerating or recycling a cofactor, NADPH to NADP+, by coproducing a disulfide and mercaptan from an enzymatic redox regeneration by reducing disulfide, such as DMDS or dimethyl disulfide, with a peptide, such as glutathione, to mercaptan, such as methyl mercaptan and ethylene mercaptan, by enzymatically creating, such as with glutathione reductase, a dipeptide with a disulfide bridge, such as the aryl disulfide, see Fig. 1 and Paras. [0045];[0048]-[0053];[0071];[0074]-[0091], the method comprising contacting the cofactor with a mercaptan, where as depicted in Fig. 1, the reaction of methyl mercaptan to methyl disulfide, glutathione to GSSG, ethylene mercaptan to the aryl disulfide, and NADPH to NADP+ are cyclic and performed in a batch type reactor allowing for the contact amongst all reactor contents, specifically for methyl mercaptan to contact the dimer GSSG, and regeneration of the disulfides, GSH, GSSG, NADPH, NADP+, see Fig. 1 and Paras. [0048]-[0052];[0067];[0071], meeting the limitations in claim 3, in claim 4, and most of the limitations in claims 16-18.
In addition, it is well known within the art that the oxidation of a mercaptan and the reduction of a disulfide is a reversible reaction, see below,
PNG
media_image1.png
603
737
media_image1.png
Greyscale
as evidenced by Page 15 of Calvin (Glutathione, “Mercaptans and Disulfides: Some Physics, Chemistry, and Speculation”, November 1953, Proceedings of the Symposium Held at Ridgefield, Connecticut, Pgs. 3-30).
Fremy teaches producing mercaptan from disulfide, see above; but, does not “criticize, discredit, or otherwise discourage” producing disulfide from mercaptan, see Paras. [0064]-[0065] and MPEP 2145 X.D.1. On the contrary, Fremy teaches “dimethyl disulfide (DMDS) may be produced at another site from methyl mercaptan and an oxidizer such as oxygen, sulfur or aqueous hydrogen peroxide solution”, where when DMDS is produced on the site of its use “a process which makes it possible to avoid transporting methyl mercaptan from its site of production by existing industrial routes, to its site of use”, see Paras. [0064]-[0065]. Therefore, Fremy teaches producing both DMDS from methyl mercaptan and methyl mercaptan from DMDS on site throughout the same process.
Fremy does not teach:
The claim 1 limitations of coproducing a disulfide and a sulfoxide or a sulfone, a composition M comprising:
4) an enzyme E catalyzing oxidation of said sulfide to sulfoxide or to sulfone;
6) the cofactor is common to both enzyme D and E
step b) conducting enzymatic reactions of sulfide oxidation so as to obtain:
a sulfoxide or a sulfone;
The claim 7 limitation of wherein said enzyme E is an oxidoreductase;
The claim 10 limitations of wherein the radicals R1 and R2 of said sulfide are identical;
The claim 11 limitations of wherein said sulfide is selected from the group consisting of dimethyl sulfide, diethyl sulfide, dipropyl sulfide, dibutyl sulfide, dioctyl sulfide, didodecyl sulfide and tetrahydrothiophene;
The claim 12 limitation of wherein the oxidizing agent is selected from the group consisting of air, oxygen-depleted air, oxygen-enriched air and pure oxygen;
The claim 14 limitation of wherein:
the sulfide is dimethyl sulfide
the enzyme E is a Baeyer-Villiger Monooxygenase (BVMO); and
the cofactor common to the two enzymes E and D is NADP;
The claim 15 limitations of a composition comprising:
2) optionally an oxidizing agent, optionally not included,
4) an enzyme E catalyzing the oxidation of said sulfide to sulfoxide or to sulfone, and
6) a cofactor common to the two enzymes E and D; and,
The claim 16 limitations of the enzymatic oxidation of a sulfide to sulfoxide or to sulfone used in the enzymatic oxidation of a sulfide.
Boyd relates to producing chiral thiosulfinate, sulfoxide and cis-dihydrodiol metabolites by asymmetric sulfoxidation of cyclic 1,2-disulfides, using chemical and enzymatic oxidation methods, such as peroxidase, monooxygenase, dioxygenase, see Abstract. Boyd teaches the enzymatic oxidation of disulfides 8 to thiosulfonates 9 through use of a composition containing the disulfide, such as where R=R’, i.e., dibutyl disulfide, in an O2 environment, and an enzyme that is a preparation of cyclohexanone monooxygenase, isolated from Acinetobacter calcoaceticus NCIB 9871, thus, cyclohexanone monooxygenase (CYMO)-catalysed sulfoxidation of dialkyl 1,2-disulfides 8a-c and alkylaryl 1,2-disulfide 8e resulted in the formation of the corresponding thiosulfinates 9a, 9b, 9c, and 9e, see All of Pg. 27609, Scheme 3, and Pg. 27611, Col. 2, (iii)-Pg. 27612, Col. 1, Ln. 3, where the mercaptan/thiol 10 is oxidized to produce further disulfide 8d and methyl phenyl sulfide 11, see Pg. 27609, Scheme 3 and Pg. 27610, Col. 1, First Full Para., meeting:
The process for coproducing a disulfide and a sulfoxide or a sulfone in claim 1;
The composition comprising an enzyme E for catalyzing oxidation of said sulfide to sulfoxide or to sulfone in claim 1 and in claim 15;
The specific enzyme E is an oxidoreductase, such as cyclohexanone monooxygenase, which is an oxidoreductase Baeyer-Villiger Monooxygenase (BVMO), as evidenced by Netto Pg. 954, Col. 1 stating “CHMO (cyclohexanone monooxygenase) from Acinetobacter sp. NCIMB 9871”, Pg. 974, Col. 2, First Full Para. stating “Baeyer-Villiger monooxygenases including, PAMO, M446G PAMO, CHMO and HAPMO.”, Pg. 975-Pg. 976, Oxidoreductases, and Pg. 976, Fig. 49 depicting the BVMO is CHMO involved in the oxidoreductase regenerative reaction of NADPH to NADP in claim 7 and in claim 14; and,
The oxidant is O2 in claim 12.
Fremy in view of Boyd do not specifically teach:
The claim 1 limitations of 6) the cofactor is common to both enzyme D and E;
The claim 10 limitations of wherein the radicals R1 and R2 of said sulfide are identical;
The claim 11 limitations of wherein said sulfide is selected from the group consisting of dimethyl sulfide, diethyl sulfide, dipropyl sulfide, dibutyl sulfide, dioctyl sulfide, didodecyl sulfide and tetrahydrothiophene;
The claim 14 limitation of wherein: the sulfide is dimethyl sulfide and the cofactor common to the two enzymes E and D is NADP;
The claim 15 limitations of a composition comprising: 2) optionally an oxidizing agent, optionally not included, and 6) a cofactor common to the two enzymes E and D; and,
The claim 16 limitations of the enzymatic oxidation of a sulfide to sulfoxide or to sulfone used in the enzymatic oxidation of a sulfide.
Netto relates to enzymatic reactions of heteroatom-containing compounds, such as biocatalyzed reactions involving the heteroatom (S, Se, B, P and Si) from hetero-organic substrates, see Abstract, for example, the sulfides of R1-S-R2, such as dimethyl sulfide, see Pg. 945, Figs. 2-3 and Pg. 963, Col. 1, meeting the specific sulfide limitations in claim 10, in claim 11, and in claim 14. Netto teaches a regenerative cofactor oxidoreductase of NADPH to NADP+ with a BVMO, which is CHMO, i.e., NADP is a cofactor for CHMO, see Pg. 954, Col. 1, Pg. 974, Col. 2, First Full Para., and Pg. 976, Fig. 49, and a catalytic cycle for the oxidation of GSH, glutathione, to GSSG, glutathione disulfide, by NADPH and oxygen, i.e., NADP is a cofactor for glutathione, see Pg. 972, Col. 2, Last Para.-Pg. 973, Col. 1, First Para., meeting the cofactor is common to both enzyme D and E in claim 1, in claim 14, and in claim 15.
Netto also teaches an enzymatic oxidation of a sulfide, para-chloro-thioanisole, by recombinant E. coli BL21 to sulfoxide where the cofactor NADPH is regenerated, see Pg. 954, Fig. 14 and Pg. 954, Col. 1, First Full Para.- Col. 2, Last Para., meeting the regenerative enzymatic oxidation of a sulfide to sulfoxide in claim 16.
Fremy does not teach the newly amended instant application claim 1 limitation of producing a sulfoxide or a sulfone from a sulfide.
Boyd is in the known prior art field of producing chiral thiosulfinate, sulfoxide and cis-dihydrodiol metabolites by asymmetric sulfoxidation of cyclic 1,2-disulfides, using chemical and enzymatic oxidation methods, such as peroxidase, monooxygenase, dioxygenase, see Abstract.
Regarding newly amended instant application claim 1, Boyd teaches the enzymatic oxidation of disulfides 8 to thiosulfonates 9 through use of a composition containing the disulfide, such as where R=R’, i.e., dibutyl disulfide, in an O2 environment, and an enzyme that is a preparation of cyclohexanone monooxygenase, isolated from Acinetobacter calcoaceticus NCIB 9871, thus, cyclohexanone monooxygenase (CYMO)-catalyzed sulfoxidation of dialkyl 1,2-disulfides 8a-c and alkylaryl 1,2-disulfide 8e resulted in the formation of the corresponding thiosulfinates 9a, 9b, 9c, and 9e, see All of Pg. 27609, Scheme 3, and Pg. 27611, Col. 2, (iii)-Pg. 27612, Col. 1, Ln. 3. TDO- and NDO-catalyzed sulfoxidations of (a) monosulfide 1, (b) 1,3-disulfide 3 and (c) 1,4-disulfides 6a and 6b, see Pg. 27608, Scheme 1, meeting the producing a sulfoxide or a sulfone from a sulfide in newly amended instant application claim 1.
In reference to the above claims, as stated above, Fremy teaches the claimed process of producing a disulfide from a mercaptan starting material. Fremy also teaches producing other disulfides and applying the products produced to produce other products, see Paras. [0065];[0067]; therefore, modification of Fremy to produce sulfoxides or other compounds from the disulfide does not render Fremy inoperable for its intended purpose.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified Fremy:
To coproduce a disulfide and a sulfoxide by utilizing an additional enzyme, such as CHMO, for the O2 oxidation of the sulfide to a sulfoxide, as taught by Boyd, to obtain the desired sulfoxide with a reasonable predictability of success for the purpose of utilizing a combination of enzymes to rationalize the unexpectedly wide range of metabolites formed from the disulfide substrate produced, see Boyd, Pg. 27615, Col. 2, First Full Para.; and,
To utilize the enzymatic reaction of dimethyl sulfide and to regenerate the cofactor NADP utilized for the enzymatic oxidation of a sulfide to sulfoxide, as taught by Netto, to obtain the desired sulfoxide with a reasonable predictability of success for the purpose of synthesizing relevant hetero-organic derivatives, with special attention to environmental-friendly reactions, such as the regenerative biocatalyzed-transformations, see Netto, Pg. 943, Introduction and Pg. 954, Fig. 14.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense”, see MPEP 2143 I.E. Since patents are part of the literature of the prior art relevant for all they contain, see MPEP 2123, and Fremy, Boyd, and Netto all teach enzymatic reactions to produce useful compounds from disulfides, a person of ordinary skill in the art has good reason to modify the production of disulfide from mercaptan as taught in Fremy to produce other compounds from the disulfide by relying upon Boyd and Netto before the effective filing date of the claimed invention for knowledge generally available within the enzymatic disulfide art regarding the products produced from the redox reactions, see MPEP 2143 B & G and 2141, for the benefit of utilizing a combination of enzymes to rationalize the unexpectedly wide range of metabolites formed from the disulfide substrate produced, see Boyd, Pg. 27615, Col. 2, First Full Para. and synthesizing relevant hetero-organic derivatives, with special attention to environmental-friendly reactions, such as the regenerative biocatalyzed-transformations, see Netto, Pg. 943, Introduction and Pg. 954, Fig. 14 and MPEP 2141.
As stated in Sakraida v. Ag Pro, Inc., 425 U.S. 273, 189 USPQ 449, reh’g denied,
426 U.S. 955 (1976), “[w]hen a work is available in one field of endeavor, design
incentives and other market forces can prompt variations of it, either in the same field
or a different one. If a person of ordinary skill can implement a predictable variation, §
103 likely bars its patentability. For the same reason, if a technique has been used to
improve one device, and a person of ordinary skill in the art would recognize that it
would improve similar devices in the same way, using the technique is obvious unless its
actual application is beyond his or her skill”. See MPEP 2141.
Selection of a known material, such as sulfide substrates, enzymes, and cofactors, based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). See MPEP 2144.07.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the modified ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Y. Lynnette Kelly-O'Neill whose telephone number is (571)270-3456. The examiner can normally be reached Monday-Thursday, 8 a.m. - 6 p.m., EST, with Flex Time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Yen-Ye Goon can be reached at (571) 270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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.
/YO/ Examiner, Art Unit 1692
/FEREYDOUN G SAJJADI/ Supervisory Patent Examiner, Art Unit 1699