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 .
Response to Arguments
Applicant’s arguments, see pp. 7-9, filed 06/11/2026, with respect to the objection to claim 175; the rejection of claims 175-180 and 184-187 under 35 U.S.C. 102; and the rejection of claims 181-183 under 35 U.S.C. 103 have been fully considered and are persuasive. Amendments overcome the rejections. The objection(s)/rejection(s) of 03/11/2026 have been withdrawn.
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.
Claims 175-180 and 184-185 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020069330A2 to Orme et al. (cited in 08/28/2024 IDS; effective filing date 28 September 2018) in view of Zhao et al. “Difluoromethyl 2-Pyridyl Sulfone: A New gem-Difluoroolefination Reagent for Aldehydes and Ketones” Org. Lett., Vol. 12, No. 7, 2010.
Step 1 of Example 32 (p. 121-122, Para. [0542]) is drawn to the synthetic scheme
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. The compound synthesized in step 1 is a compound of formula II wherein Boc is tert-butoxycarbonyl and the starting material is equivalent to a compound of Formula 11a. TBS in the prior art and TBDMS in the instant claims both refer to tert-butyldimethylsilyl. While the intermediate 11b is not explicitly recited in the prior art, it is necessarily formed upon the addition of the difluoroallyl group and prior to deprotection of the alcohol. The reaction utilizes tBuOK in DMF.
Orme et al does not teach the reaction with LiHMDS and THF as claimed.
Zhao et al. is generally drawn to the use of difluoromethyl 2-pyridyl sulfone in the gem-difluoroolefination of aldehydes and ketones:
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(Abstract). A PHOSITA would recognize this reaction as analogous to that employed by Orne et al. Numerous examples are shown (Table 1, Scheme 3). Examples 8 and 13 utilize LiHMDS. Example 10 of scheme 3 uses LiHMDS and THF:
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. A PHOSITA would accordingly recognize LiHMDS and THF as used in Zhao et al. as a suitable equivalent for tBuOK and DMF used in Orme et al, and it therefore would have been obvious to employ the alternative art-recognized suitable base/solvent system of Zhao et al. in the reaction of Orme et al. “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.” In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929).
With respect to claim 178, 2-((difluoromethyl)sulfonyl)pyridine of the prior art is equivalent to difluoromethyl 2-pyridiyl sulfone claimed. With respect to claims 180 and 184, the reaction starts at -50 C and is warmed to room temperature. Accordingly, claims 175, 178, 180 and 184-185 are obvious.
Claims 181-183 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020069330A2 to Orme et al. (cited in 08/28/2024 IDS, effective filing date 28 September 2018) in view of Zhao et al. “Difluoromethyl 2-Pyridyl Sulfone: A New gem-Difluoroolefination Reagent for Aldehydes and Ketones” Org. Lett., Vol. 12, No. 7, 2010 and further in view of Corey et al. “Protection of Hydroxyl Groups as tert-Butyldimethylsilyl Derivatives” JACS 94(17), pp. 6190-6191, August 23, 1972.
Step 1 of Example 32 (p. 121-122, Para. [0542]) is drawn to the synthetic scheme
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.
The compound synthesized in step 1 is a compound of formula II wherein Boc is tert-butoxycarbonyl and the starting material is equivalent to a compound of Formula 11a. TBS in the prior art and TBDMS in the instant claims both refer to tert-butyldimethylsilyl. While the intermediate 11b is not explicitly recited in the prior art, it is necessarily formed upon the addition of the difluoroallyl group and prior to deprotection of the alcohol. The reaction utilizes tBuOK in DMF.
Orme et al does not teach the reaction with LiHMDS and THF as claimed.
Zhao et al. is generally drawn to the use of difluoromethyl 2-pyridyl sulfone in the gem-difluoroolefination of aldehydes and ketones:
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(Abstract). A PHOSITA would recognize this reaction as analogous to that employed by Orne et al. Numerous examples are shown (Table 1, Scheme 3). Examples 8 and 13 utilize LiHMDS. Example 10 of scheme 3 uses LiHMDS and THF:
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. A PHOSITA would accordingly recognize LiHMDS and THF as used in Zhao et al. as a suitable equivalent for tBuOK and DMF used in Orme et al, and it therefore would have been obvious to employ the alternative art-recognized suitable base/solvent system of Zhao et al. in the reaction of Orme et al. “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.” In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929).
Orme et al. does not teach wherein TBDMS deprotection is carried out in a solvent using an organic salt, wherein the organic salt is tetrabutylammonium fluoride, or wherein the solvent is selected from the group consisting of DCM and THF.
Corey et al. discloses
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(p. 6191) which discloses the deprotection of a TBDMS ether with TBAF in THF. Additional examples are taught showing successful protection and deprotection under the same or similar conditions. It would have been obvious to a PHOSITA to substitute the deprotection method taught by Orme et al. with the deprotection method taught by Corey et al. as the method of Corey et al. is a known equivalent for deprotecting TBDMS ethers. There would have been a reasonable expectation of success given that the method is taught to be applicable to numerous compounds containing the TBDMS ether. See MPEP 2144.06(II). Accordingly, claims 181-183 are obvious.
Claim 186 is rejected under 35 U.S.C. 103 as being unpatentable over WO2020069330A2 to Orme et al. (cited in 08/28/2024 IDS; effective filing date 28 September 2018) in view of Wuts et al. “Protection for the Amino Group” in “Greene’s Protective Groups in Organic Synthesis” Fourth Edition, 2007.
The compound
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is synthesized in Example 32 (p. 121-122, Para. [0542]) as an intermediate. Boc (tert-butyloxycarbonyl) is used as an amine protecting group and removed in step 3 of the synthesis of Example 32.
The prior art compound is substituted with Boc and not FMOC, CBZ or trityl as claimed.
Wuts et al. teaches FMOC (p. 711), CBZ (p. 748) and trityl (p. 825) as amine protecting groups. A PHOSITA would accordingly recognize FMOC, CBZ or trityl as taught by Wuts et al. as a suitable equivalent for Boc taught by Orme et al, and it therefore would have been obvious to substitute Boc group of Orme et al. with the art-recognized alternative amine protecting group of Wuts et al. “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.” In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929). Accordingly, claim 186 is obvious.
Conclusion
Claims 168-174 are allowed.
Claims 175, 178 and 180-186 are rejected.
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 JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JED A KUCHARCZK/Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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