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 and 21-31 are pending in this application. Claims 2-20 have been cancelled by Applicant.
Duplicate Claims Warning
Applicant is advised that should claims 21-23 be found allowable, claims 25-27 and 29-31 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 21-31 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite because, in Equations 1 and 3, when at least one of R1-10 is a hydrocarbon alkyl chain (such as methyl or ethyl), it is unlikely that deuteration will occur selectively at the indicated positions without giving mixtures of deuterated products at other benzylic positions. In Equation 6 (shown below), when one of R21-23 is aryl and the other two variables are H, it is unlikely that the deuterated product indicated below will be the major product obtained, since benzylic deuteration will be favored, as in Example 29 of the spec. (page 24).
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Further regarding claim 1, claim is indefinite because when applicant states “R21-23 can be connected into aliphatic hydrocarbon rings or aromatic rings”, it is unclear how these three groups can be connected to form an aromatic ring when the carbon alpha to the sulfur is shown as an sp3 carbon. Examiner suggests amending to specify that only two of R21 to R23 connect to form aliphatic or aromatic rings, and that when two of R21-23 are connected to form an aromatic ring, then the other group is absent.
Further regarding claim 1, the claim is indefinite because there is no definition for variable X1 – for the purposes of applying art, it will be assumed that X1 can be C or N (see specification, page 7, top).
Claim 24 is indefinite because it is unclear how selective deuteration of the indicated positions is achieved when any of R36-39- are alkyl groups (e.g. methyl, ethyl). For example, when R39 is an alkyl group, the benzylic C-H bonds will be more easily activated, and therefore, deuteration will be favored at these positions over the positions indicated in equations 13-14 and 16 (see Example 23, page 21 of spec.). Similarly, when R36-39 are H, it is unclear how Applicant intends to stop at mono-deuteration, since multi-deuteration appears to be favored in relevant Examples 38-42 (pages 29-32 of spec.).
Claim 28 is indefinite because, in Equations 8-12, when any of R29-34 is a hydrocarbon alkyl chain (such as ethyl or methyl), it is unlikely that deuteration will occur selectively at the indicated positions without giving mixtures of deuterated products or complete deuteration (see Examples 33-34, page 27 of the spec.).
The Examiner believes inclusion of equations is what is resulting in most of the indefiniteness issues of these claims. The examiner suggests removing these equations from the claims as one possible way to overcome some of these 112(b) rejections.
Furthermore: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 1 recites the broad recitation:
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and the claim also recites:
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which is the narrower statement of the range/limitation.
Claim 24 recites the broad recitation:
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(…)
and the claim also recites:
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which is the narrower statement of the range/limitation.
Claim 24 also recites the broad recitation:
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and the claim also recites:
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which is the narrower statement of the range/limitation.
Claim 28 recites the broad recitation:
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and the claim also recites:
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which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 21-23, 25-27, and 29-31 are rejected for depending upon the limitations of claim 1.
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.
Claims 1, 21-23, 25-27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Angew. Chem. Int. Ed., 2018, 57, 11050 –11054 – previously cited) (“Xu”).
Regarding claim 1, Xu discloses a reaction for toluene (reading on Equation 1 when X1 is C) deuteration with D2 (g) and 5 mol% KH (potassium hydride) (see page 11051, Scheme 2). Xu further discloses their conditions for deuteration with D2 and alkali metal base catalyst, wherein the Lewis acidic alkali metal center (potassium) is demonstrated to interact with H2, HD, or D-2 (page 11053, col. 2, last para.), leading to formation of KH and/ or KD species, which can further undergo Xu’s reaction shown in Schemes 2D and 1B-C; specifically, KH and KD can deprotonate benzylic substrates (“activate benzylic C-H bonds” for deuteration) (page 11052, col. 2, last para.).
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Further regarding claim 1, specifically equations 3, wherein a benzylic position is deuterated, while Xu does not disclose these substrates specifically, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to use Xu’s conditions for the deuteration of benzylic positions. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Xu discloses their conditions for deuteration of the benzylic methyl of toluene, and mentions they are continuing to explore the potential applications of benzylic C-H activation (beyond toluene).
Further regarding claim 1, Xu discloses KN(SiMe3)2 in deuterated benzene scrambled H-D to produce KH, KD, H-N(SiMe3)2, and D-N(SiMe3)2. Xu discloses that these species are in equilibrium with KN(SiMe3)2, H2, D2, and H-D.
Therefore, while Xu doesn’t specifically disclose their deuteration of toluene with KN(SiMe3)2 to produce benzyl potassium, it would have been prima facie obvious to one of ordinary skill to swap KH for KN(SiMe3)2 in Xu’s Scheme 2D reaction, to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Xu’s teachings that KN(SiMe3)2 is capable of activating H-D to generate KH and KD in situ, which can go on to react as shown in their Scheme 2.
Regarding claim 21, 25, and 29, Xu discloses their reaction with 5 mol% KH – thus, in view of the above, it would have been prima facie obvious to perform Xu’s reaction with 5 mol% KN(SiMe3)2.
Regarding claim 22, 26, and 30, Xu discloses their reaction with 5 atm of D2 (same as 5 bar).
Regarding claim 23, 27, and 31, Xu’s reaction is done under solvent free conditions, as toluene is the reactant and not a solvent in this case.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Angew. Chem. Int. Ed., 2018, 57, 11050 –11054 – previously cited) (“Xu”); as applied to claims 1, 21-23, 25-27, and 29-31; in view of Wenchi et al. (CN109020849A – Pub. Date: Dec. 18th, 2018 – previously cited) (“Wenchi”).
The teachings of Xu are disclosed above and incorporated herein.
While Xu doesn’t teach deuteration of alkyl sulfoxides or sulfates or using a sodium/ potassium hydroxide catalyst; the teachings of Wenchi are relied upon for these disclosures.
Wenchi discloses a method for the preparation of deuterated DMSO (reading on the “Reaction Equation 8” below when R29 is C1 hydrocarbon) with a potassium hydroxide or sodium hydroxide base catalyst and D2O and heating at 90-95 °C for 1-3 h (page 1 of translated document).
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Therefore, regarding claim 28, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to prepare deuterated-DMSO with D2 as a deuterium source, and potassium hydroxide as a base in view of the teachings of Xu and Wenchi. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because of Xu’s disclosure of their conditions for deuteration with D2 and alkali metal base catalyst, wherein the Lewis acidic alkali metal center (such as potassium) is demonstrated to interact with H2, HD, or D-2 (page 11053, col. 2, last para.), leading to formation of KH and/ or KD species, which can further undergo Xu’s reaction shown in Schemes 2D and 1B-C. Further because Wenchi discloses their method of DMSO deuteration with an alkali metal hydroxide catalyst.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Angew. Chem. Int. Ed., 2018, 57, 11050 –11054 – previously cited) (“Xu”); as applied to claims 1, 21-23, 25-27, and 29-31; in view of Salamanca et al. (Eur. J. Org. Chem. 2020, 3206–3212 – previously cited) (“Salamanca”).
The teachings of Xu are disclosed above and incorporated herein.
While Xu doesn’t teach deuteration of fluorobenzene; the teachings of Salamanca are relied upon for these disclosures.
Salamanca teaches the general reaction scheme 1 below (page 3207) for the deuteration of fluorobenzenes (Table 2, page 3208) with D2O and deuterated DMSO as deuterium sources. Salamanca specifically discloses compound 7 as the deuteration product of fluorobenzene under these conditions. Salamanca also teaches deuteration of thiophene and furan under their reaction conditions (see Table 2, entries 11-12; and page 3209, col. 1, para. 4) – “reaction equation 17” when R36-37 are H and X5 is S or O.
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Therefore, regarding claim 24, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to prepare deuterated fluorobenzene 7 with D2 as a deuterium source, and a KN(SiMe3)2 base catalyst in view of the teachings of Xu and Salamanca. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because of Xu’s disclosure of their conditions for deuteration with D2 and KN(SiMe3)2, wherein the Lewis acidic alkali metal center (such as potassium) is demonstrated to interact with H2, HD, or D-2 (page 11053, col. 2, last para.), leading to formation of KH and/ or KD species, which can further undergo Xu’s reaction shown in Schemes 2D and 1B-C. Further because Salamanca discloses their method of fluorobenzene deuteration with an alkali metal base catalyst.
Response to Arguments
Claims/ Claim Objections
Claim amendments are acknowledged and have been entered. No new matter has been introduced. Claim objections have been withdrawn.
Claim Rejections - 35 USC § 112(b)
In view of Applicant canceling previously rejected claims, the 35 USC § 112(b) rejections are rendered moot; however, Applicant amended instant claims by incorporating information from previously rejected claims without resolving the indefiniteness issues pointed out in the non-final rejection filed 01/28/2026. As a result, a new ground of 35 USC § 112(b) rejections have been raised herein, necessitated by claim amendments.
Claim Rejections - 35 USC § 102
Applicant’s arguments, see pages 9-10, filed 01/28/2026, with respect to 35 USC § 102 rejections of the claims have been fully considered and are persuasive. The 35 USC § 102 rejections of the claims have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 01/28/2026 have been fully considered but they are not persuasive. Applicant’s arguments pertaining prior art references cited for the rejections presented herein are summarized below:
Applicant argues instant claims use amine potassium and amine cesium base catalysts, which have better solubility than KH and thus better efficiency, with more selective deuteration of benzyl hydrocarbon bonds with broad substrate compatibility.
Applicant is advised that Xu also discloses the use of amine potassium bases and D2 in their deuteration reaction, thus rendering the instant claims obvious, as presented herein. A person of ordinary skill would have arrived at the instant invention with a reasonable expectation of success in view of Xu.
Applicant argues that Wenchi describes deuteration of DMSO with catalytic KOH, with multiple iterative reactions to achieve satisfactory deuteration and yields. Applicant argues Wenchi provides no guidance or teaching that their reaction works with other sulfur species. Applicant argues the present invention covers reactions with C(sp3)-H bonds as well as C(sp2)-H bonds, while the art only covers C(sp3)-H. Applicant argues the instant choice of base catalyst is cost effective and easily available, and that alkali metal catalysts achieve hydrogen-D exchange. Applicant states they use D2 gas, while Wenchi uses D2O. Applicant argues that Salamanca differs from the instant invention with respects to catalyst and deuterium source.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Xu’s disclosure renders the instant deuteration conditions obvious, and the teachings of Xu in view of Wenchi, or Xu in view of Salamanca render deuteration of DMSO and fluorobenzenes obvious, as presented in this final office action.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Conclusion
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 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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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