DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, 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 1-33 are pending in the instant invention. According to the Amendments to the Claims, filed January 10, 2024, claims 2-15, 17-24 and 26-33 were amended and claims 34-40 were cancelled.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/EP2021/084734, filed December 8, 2021, which claims priority under 35 U.S.C. § 119(a-d) to International Application No. PCT/CN2020/135294, filed December 10, 2020.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on December 17, 2025, is acknowledged: Group I - claims 1-15. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Moreover, the inventor or joint inventor should further note that claims 16-33 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1-15 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests identifying 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo-[1,5-a]pyrimidine of the formula (VIII).
The following title is suggested: PROCESS FOR THE PREPARATION OF 2-BROMO-4-(3,5-DIFLUOROPHENYL)-4,5,6,7-TETRAHYDRO-[1,2,4]triazolo[1,5-a]PYRIMIDINE.
Appropriate correction is required.
Specification Objection - Abstract
The inventor or joint inventor is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to state the reactions, reagents, and/or process conditions for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine of the formula (VIII). Correction is required. See MPEP § 608.01(b).
The examiner suggests incorporating the reactions, reagents, and/or process conditions for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]-pyrimidine of the formula (VIII) into the abstract, to overcome this objection.
Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
A process for the preparation of a compound of formula (VIII):
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(VIII)
wherein the process comprises the following steps:
(a) reacting a compound of formula (II):
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(II)
with a compound of the following formula:
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,
to provide a compound of formula (III):
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(III);
(b) reacting the compound of formula (III) above with a compound of the following formula:
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,
to provide a compound of formula (IV):
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(IV);
(c) reacting the compound of formula (IV) above with a compound of formula (V):
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(V)
to provide a compound of formula (VI):
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(VI);
(d) reacting the compound of formula (VI) above with an acid selected from the group consisting of hydrobromic acid (HBr), hydrochloric acid (HCl), and trifluoroacetic acid (TFA), to provide a compound of formula (VII):
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(VII);
(e) reacting the compound of formula (VII) above under Mitsunobu conditions using triphenylphosphine in the presence of diethyl azodicarboxylate (DEAD) and a solvent selected from the group consisting of dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and N-methyl-2-pyrrolidone (NMP), to provide a compound of formula (VIII):
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(VIII).
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (a), the reaction is performed in the presence of a solvent selected from the group consisting of dichloromethane (DCM) and tetrahydrofuran (THF).
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (a), the reaction is performed in the presence of a base selected from the group consisting of sodium hydride (NaH), sodium acetate (NaOAc), and potassium acetate (KOAc).
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (b), the reaction is performed in the presence of a solvent selected from the group consisting of dichloromethane (DCM), tetrahydrofuran (THF), and 2-methyltetrahydrofuran (2-MeTHF).
Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (b), the reaction is performed in the presence of a base selected from the group consisting of lithium bis(trimethylsilyl)amide (LiHMDS), sodium bis(trimethylsilyl)amide (NaHMDS), sodium hydride (NaH), sodium hydroxide (KOH), potassium carbonate (K2CO3), and potassium hydroxide (KOH).
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 5, wherein the amount of the base is in the range of from 1.0 equivalent to 2.5 equivalents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (b), the amount of 3,5-difluoroaniline is in the range of from 1.0 equivalent to 2.5 equivalents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (b), the reaction is performed at a temperature in the range of -20 ◦C to 70 ◦C.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (c), the reaction is performed in the presence of a base selected from the group consisting of cesium carbonate (Cs2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), and sodium hydroxide (KOH).
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 9, wherein the amount of the base is in the range of from 2.0 equivalents to 3.0 equivalents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (c), the amount of the compound of formula (V) is in the range of from 1.7 equivalents to 2.26 equivalents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (d), the reaction is performed in the presence of hydrochloric acid (HCl).
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process according to claim 12, wherein the volume of hydrochloric acid (HCl) is in the range of from 1.0 V to 2.0 V.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 1, wherein in step (e), the reaction is performed in the presence of dimethylformamide (DMF).
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process according to claim 14, wherein the volume of dimethylformamide (DMF) is in the range of from 5.0 V to 10.0 V.
Appropriate correction is required. See MPEP § 2173.02.
Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claims 1-15 are rejected under 35 U.S.C. § 112(b) as being incomplete for omitting an essential procedural step, such omission resulting in an indefinite process. See MPEP § 2172.01.
The inventor or joint inventor should note that the omitted essential procedural step in the process for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo-[1,5-a]pyrimidine of the formula (VIII), or a pharmaceutically acceptable salt thereof, as recited in claim 1, is the manipulative step which results in the preparation of a pharmaceutically acceptable salt of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]-pyrimidine of the formula (VIII). The claim fails to explicitly recite a manipulative step which results in the preparation of a pharmaceutically acceptable salt of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine of the formula (VIII). Similarly, the specification fails to provide an adequate standard for ascertaining the requisite degree of a manipulative step which results in the preparation of a pharmaceutically acceptable salt of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine of the formula (VIII). Consequently, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the process for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine of the formula (VIII), or a pharmaceutically acceptable salt thereof, as recited in claim 1, since the essential manipulative step which results in the preparation of a pharmaceutically acceptable salt of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine of the formula (VIII) is omitted.
Similarly, the inventor or joint inventor should further note that [A] claim which omits matter disclosed to be essential to the invention, as described in the specification or in other statements of record, may also be rejected under 35 U.S.C. § 112(a) as not enabling. {See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976); and MPEP § 2164.08(c)}.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claims 1-11 and 13-15 are further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, de-protection, in claim 1, with respect to step (d), is a relative term which renders the claim indefinite. The term, de-protection, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification on page 11, uses open language, such as selected from, to define the term, de-protection, as occurring in the presence of a suitable volume acid selected from HBr, TFA, and HCl; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo-[1,5-a]pyrimidine of the formula (VIII) has been rendered indefinite by the use of the term, de-protection, with respect to step (d).
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claims 1-13 are further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, internal Mitsunobu cyclization, in claim 1, with respect to step (e), is a relative term which renders the claim indefinite. The phrase, internal Mitsunobu cyclization, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification on page 11, uses open language, such as selected from, to define the phrase, internal Mitsunobu cyclization conditions as occurring in the presence of DEAD, PPh3, and a suitable solvent selected from DMSO, NMP, and DMF; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for the preparation of 2-bromo-4-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]-pyrimidine of the formula (VIII) has been rendered indefinite by the use of the phrase, internal Mitsunobu cyclization, with respect to step (e).
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624