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 .
Detailed Action
This office action is in response to applicant’s communication filed on 7/28/26.
In response to the election of species requirement mailed 5/28/26, applicant elected the species of hydrazine in step (ii). Since applicant did not argue the election and did not indicated a traversal of the election, the examiner consider the election without traverse. Claims 8 and 9 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species, namely inorganic acids in step (ii).
As a result, claims 1-7, 10 and 11 are being examined in this Office Action. Claim 1 is generic to the elected species. Should claim 1 be found allowable, claims 8 and 9 will be rejoined. See MPEP § 821.04.
Priority
The applicant claims benefit as follows:
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Objections
The specification is objected to because of the following informalities:
Throughout this office action, a reference to applicant’s specification is directed to applicant’s PGPub: US 20240158335.
Paragraphs [0067], [0072], [0092] and [0116] recite “mmol” where “mol” appears to be intended. For example, paragraph [0067] recites “1.47 g (0.01 mmol) of phtalimide.” However, 1.47 g of phthalimide corresponds to 0.01 mol.
The term “phtalimide” also appears throughout the specification in place of “phthalimide.” Appropriate correction is required.
Claims 1-7, 10 and 11 are objected to because of the following informalities:
Claim 1 recites “Process for preparation of a polyfluoroalkylamine.” This should read “A process for the preparation of a polyfluoroalkylamine.” Claim 1 also recites “Reaction of polyfluoroalkylalcohols of formula (I),” in the plural, while formula (I) is a single compound.
Claim 5 recites that the base is “chosen from” a list of alternatives. Proper Markush format is “selected from the group consisting of.”
Claims 2-7, 10 and 11 recite “The Process according to Claim 1.” The word “Process” should not be capitalized. Appropriate correction is required.
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.
Claims 1-7, 10 and 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 is indefinite because the claim uses two different variables for the same group. Claim 1 defines “RF” as CHF2, CF3, C2F5 or HCF2CF2 in formula (I), and uses “RF” again in formula (IV). However, formula (III) recites “Rf.” The claim never defines “Rf.” It is unclear whether “Rf” is the same group as “RF” or a different group. The metes and bounds of the compound of formula (III) are therefore unclear.
Claim 1 is also indefinite because step (ii) does not recite the product formed. Step (i) recites reacting the alcohol of formula (I) with the imide of formula (II) “to give a compound of formula (III).” Step (ii) recites only the “Reaction of the compound of formula (III) with an acid, base or hydrazine.” Step (ii) has no corresponding “to give” clause. Because the claim recites the product of step (i) but not the product of step (ii), it is unclear whether step (ii) yields the polyfluoroalkylamine of formula (IV) recited in the preamble, or yields a further intermediate that would require additional steps not recited in the claim. Thus the metes and bounds of claim 1 cannot be determined.
Claims 2-7, 10 and 11 depend from claim 1 and are rejected for the same reasons.
Claim 7 is also indefinite because the claim recites “the molar ratio of the base to the imide of formula (II)”. Claim 7 depends on claim 5. Claim 5 recites “in which the acid scavenger in (i) is a base”. Claim 5 depends on claim 1. Claim 1 recites “reaction of the compound of formula (III) with an acid, base or hydrazine.” Thus, both claim 5 and claim 1 recite what appears to be, different bases. It is unclear which “base” claim 7 is referring to. The base in claim 1 or the base in claim 5. For the purposes of examination, the examiner will interpret the base in claim 7 as the same base recited in claim 5. Claim 11 is further indefinite because the claim recites “the molar ratio of acid or hydrazine hydrate to the compound of the formula (III).” Claim 1 recites reacting the compound of formula (III) with “an acid, base or hydrazine.” There is insufficient antecedent basis for “hydrazine hydrate” in the claim. Also, when a base is used in step (ii), the claim recites no acid and no hydrazine hydrate, and it is unclear what ratio is limited. Appropriate correction is required.
Claim Rejections – 35 USC 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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 1-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Mo et al. (“One-Pot Substitution of Aliphatic Alcohols Mediated by Sulfuryl Fluoride,” Chem. Eur. J. 2020, 26, 4958-4962, in applicants IDS filed 6/25/24), in view of Epifanov et al. (“One-Pot 1,1-Dihydrofluoroalkylation of Amines Using Sulfuryl Fluoride,” J. Am. Chem. Soc. 2018, 140, 16464-16468, in applicants IDS filed 8/21/23).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Mo et al. teaches a one-pot process for activating an aliphatic alcohol with sulfuryl fluoride (SO2F2) and substituting the activated alcohol with a nucleophile. Mo et al. teaches that the alcohol, the nucleophile and DBU are combined in DMF, and that SO2F2 is bubbled through the solution at room temperature. Mo et al. teaches that nitrogen nucleophiles are effective in this process. (Mo et al., Abstract; page 4958, Scheme 1D)
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Mo et al. teaches reacting the primary alcohol 3-phenyl-1-propanol (1a) with phthalimide in the presence of SO2F2 and DBU to give the corresponding N-alkyl phthalimide 12a. Mo et al. teaches that SO2F2 (4.3 equiv) is bubbled through a solution of the alcohol (1 equiv), DBU (3.5 equiv) and phthalimide (2 equiv) in DMF at room temperature. Mo et al. teaches that 12a is obtained in 90% isolated yield. (Mo et al., page 4960, Table 2)
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Mo et al. teaches that DBU is the optimized base for the phthalimide substitution. Mo et al. teaches that DBU (4 equiv) with phthalimide (2 equiv) gave complete conversion of 1a to 12a in 20 minutes with no detected side products. Mo et al. further teaches that the base serves to quench acid present in the reaction vessel. (Mo et al., page 4959, Table 1, entry 5 and footnote a)
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Mo et al. teaches converting the N-alkyl phthalimide to the corresponding primary amine. Mo et al. teaches treating alcohol 1a with phthalimide, SO2F2 and DBU, and then treating the resulting phthalimide 12a with hydrazine hydrate, to give 3-phenylpropan-1-amine (23a) in 76% yield. Mo et al. teaches isolating the amine as its hydrochloride salt by treatment with 2M HCl in Et2O. (Mo et al., page 4961, Scheme 3; Supporting Information, pages S25-S26)
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Mo et al. further teaches that the high reactivity of the alkyl fluorosulfate intermediate is attenuated by the use of 1,1-dihydrofluoroalcohols, because the fluorine substituents decrease the rate of undesired product formation. Mo et al. teaches that this same reactivity caused the poor yield obtained with an electron rich alcohol. (Mo et al., page 4959; page 4960)
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Mo et al. teaches the two-step conversion of an aliphatic alcohol to a primary amine. The alcohol is reacted with an imide in the presence of SO2F2 and a base to give an N-alkyl imide, and the N-alkyl imide is then reacted with hydrazine.
However, Mo et al. is deficient in the sense that Mo et al. does not teach that the alcohol is a polyfluoroalkylalcohol of formula (I) in which RF is CHF2, CF3, C2F5 or HCF2CF2.
Epifanov et al. cures this deficiency. Epifanov et al. teaches SO2F2-mediated alkylation using 1,1-dihydrofluoroalcohols of the formula RFCH2OH. Epifanov et al. teaches 2,2,2-trifluoroethanol (RF = CF3), 2,2-difluoroethanol (RF = CHF2) and 2,2,3,3,3-pentafluoropropanol (RF = C2F5) as the alcohol. Epifanov et al. teaches bubbling SO2F2 through a solution of the nitrogen nucleophile, the 1,1-dihydrofluoroalcohol and diisopropylethylamine at room temperature to 40° C. Epifanov et al. further teaches that the products are valuable motifs present in many biologically active molecules. (Epifanov et al., Abstract; page 16464; page 16466, Schemes 4 and 5)
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Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention to use the polyfluoroalkylalcohols of Epifanov et al. as the alcohol in the phthalimide substitution process of Mo et al., because both references are directed to SO2F2-mediated activation and substitution of aliphatic alcohols with nitrogen nucleophiles, and both use the same reagents and the same mild conditions. Mo et al. teaches that 1,1-dihydrofluoroalcohols attenuate the reactivity of the alkyl fluorosulfate intermediate and decrease undesired product formation, and identifies that reactivity as a limitation of its own process. One of ordinary skill in the art would therefore have been motivated to use the polyfluoroalkylalcohols of Epifanov et al. in the process of Mo et al., with a reasonable expectation of success. (Mo et al., pages 4959-4960; Epifanov et al., page 16466)
The combination gives the process of claim 1. Reacting the polyfluoroalkylalcohol of formula (I) with phthalimide in the presence of SO2F2 and DBU gives the compound of formula (III), in which R¹ and R² form, together with the carbon atoms to which they are bonded, an unsubstituted six-membered aromatic ring. Reacting the compound of formula (III) with hydrazine gives the polyfluoroalkylamine of formula (IV). (Mo et al., page 4960, Table 2; page 4961, Scheme 3; Epifanov et al., page 16466, Scheme 5)
With regard to claim 2, Epifanov et al. teaches 2,2-difluoroethanol as the 1,1-dihydrofluoroalcohol. Using 2,2-difluoroethanol as the alcohol in the process of Mo et al. gives 2,2-difluoroethyl-1-amine. Therefore claim 2 would have been obvious to one of ordinary skill in the art. (Epifanov et al., page 16466, Scheme 5)
With regard to claims 3 and 4, Mo et al. teaches phthalimide as the nucleophile. Phthalimide is an imide of formula (II) in which R¹ and R² form, together with the carbon atoms to which they are bonded, an unsubstituted six-membered aromatic ring. (Mo et al., page 4959, Table 1; page 4960, Table 2)
With regard to claims 5 and 6, Mo et al. teaches DBU as the base, and Epifanov et al. teaches diisopropylethylamine as the base. DBU and diisopropylethylamine are each recited in claim 5, and DBU is recited in claim 6. (Mo et al., page 4959, Table 1; Epifanov et al., Abstract)
With regard to claim 7, Mo et al. teaches DBU (3.5 equiv) with phthalimide (2 equiv), which is a molar ratio of base to imide of about 1.75:1. Mo et al. also teaches DBU (4 equiv) with phthalimide (2 equiv), which is a molar ratio of 2:1. These ratios fall within the claimed range of from 1:1 to 5:1. (Mo et al., page 4959, Table 1; page 4960, Table 2)
With regard to claim 10, Mo et al. teaches treating the N-alkyl phthalimide with hydrazine hydrate to give the primary amine. (Mo et al., Supporting Information, page S26)
Note that an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Substituting the polyfluoroalkylalcohol of Epifanov et al. for the non-fluorinated alcohol of Mo et al. is the substitution of one known alcohol for another in the same SO2F2-mediated substitution reaction, and yields the predictable result of the corresponding N-polyfluoroalkyl imide.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Mo et al. (“One-Pot Substitution of Aliphatic Alcohols Mediated by Sulfuryl Fluoride,” Chem. Eur. J. 2020, 26, 4958-4962, in applicants IDS filed 6/25/24), in view of Epifanov et al. (“One-Pot 1,1-Dihydrofluoroalkylation of Amines Using Sulfuryl Fluoride,” J. Am. Chem. Soc. 2018, 140, 16464-16468, in applicants IDS filed 8/21/23), and further in view of Lui et al. (US 2012/0190867, pub date Jul. 26, 2012, in applicants IDS filed 8/14/23).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
As discussed above, Mo et al. teaches reacting an aliphatic alcohol with phthalimide in the presence of SO2F2 and DBU, and then treating the resulting phthalimide with hydrazine hydrate to give the primary amine. Epifanov et al. teaches the polyfluoroalkylalcohols of formula (I).
Lui et al. teaches a process for the preparation of 2,2-difluoroethylamine. Lui et al. teaches reacting 2,2-difluoro-1-chloroethane with an imide of formula (II) in the presence of an acid scavenger to give a compound of formula (III), and cleaving the compound of formula (III) with acid, base or hydrazine. Lui et al. teaches that the imide of formula (II) is succinimide or phthalimide. (Lui et al., Abstract; paragraphs [0007] and [0009])
Lui et al. teaches that the molar ratio of acid or hydrazine to the imide of formula (III) lies in the range from approximately 0.8 to approximately 100, preferably from approximately 1 to approximately 20, and particularly preferably from approximately 1.1 to approximately 10. Lui et al. exemplifies treating 10 g (0.046 mol) of 2-(2,2-difluoroethyl)-1H-isoindole-1,3(2H)-dione with 3.16 g (0.063 mol) of hydrazine hydrate in ethanol, which is a molar ratio of about 1.37:1, to give 2,2-difluoroethylamine as the hydrochloride. (Lui et al., paragraphs [0046] and [0069])
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Mo et al. and Epifanov et al. render obvious the process of claim 1, and Mo et al. teaches cleaving the compound of formula (III) with hydrazine hydrate.
However, Mo et al. and Epifanov et al. are deficient in the sense that they do not teach the molar ratio recited in claim 11. Mo et al. treats the phthalimide obtained from 0.6 mmol of alcohol with 0.50 mL of hydrazine hydrate, which is a molar ratio greater than 10:1. (Mo et al., Supporting Information, pages S4 and S26)
Lui et al. cures this deficiency. Lui et al. teaches a preferred molar ratio of hydrazine to the imide of formula (III) of approximately 1.1 to approximately 10, and exemplifies a ratio of about 1.37:1 for the cleavage of 2-(2,2-difluoroethyl)-1H-isoindole-1,3(2H)-dione with hydrazine hydrate. (Lui et al., paragraphs [0046] and [0069])
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention to use the molar ratio of hydrazine taught by Lui et al. in the cleavage step of the process rendered obvious by Mo et al. and Epifanov et al., because Lui et al. and Mo et al. both cleave an N-substituted phthalimide with hydrazine to give the corresponding primary amine, and Lui et al. teaches this ratio for the cleavage of the same compound of formula (III) bearing a polyfluoroalkyl group. (Lui et al., paragraphs [0046] and [0069]; Mo et al., Supporting Information, page S26)
The preferred range taught by Lui et al., approximately 1.1 to approximately 10, lies within the claimed range of from 0.8:1 to 10:1. A prima facie case of obviousness exists where the prior art range lies within, or overlaps, the claimed range. See MPEP § 2144.05. Further, the amount of hydrazine used in the cleavage is a result effective variable that one of ordinary skill in the art would have optimized through routine experimentation in order to achieve complete cleavage while avoiding an unnecessary excess of reagent. (Lui et al., paragraph [0046])
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer Cho Sawyer whose telephone number is (571) 270 1690. The examiner can normally be reached on Monday-Friday 9 AM - 6 PM PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-274-1690.
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/JENNIFER C SAWYER/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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