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 .
Response to Restriction/Election Requirement
Applicant’s election without traverse of Group (I), directed to claims 1-49 and 64-65 in the reply filed on 07/23/2026 is acknowledged. Claims 56-63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Additionally, Applicant’s specie election without traverse of Compound 45 in the reply filed on 07/23/2026 is acknowledged. In Applicant’s response, the elected specie is said to be directed to claims 1, 3, 4, 6, 14, 17-20, 28, 30-34, 37, 40-43, 45-49, and 64-65. However, claim 35 also reads on the elected specie and will be examined in this Office Action. Accordingly, claims 2, 5, 7-13, 15-16, 21-27, 29, 36, 38-39, 44, and 56-63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of the Claims
The status of the claims is as follows:
Claims 1-49 and 56-65 are pending.
Claims 2, 5, 7-13, 15-16, 21-27, 29, 36, 38-39, 44, and 56-63 are withdrawn.
Claims 1, 3-4, 14, 17, 20, 28, 30-35, 37, 40-43, and 45-49 are rejected.
Claims 6, 18-19, and 64 are objected to.
Claim 65 is allowed.
Priority
Acknowledgement is made that Instant Application 18/837,928, filed on 2024, Aug. 13, is a national stage entry of PCT/CA2023/050195, filed on 2023, Feb. 15, which claims priority from Provisional Application 63/268,021, filed on 2022, Feb. 15.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2024, Aug. 13; 2025, Apr. 14, 2025, Jun. 09; 2025, Jul. 24, and 2026, Feb. 20 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
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.
Claim 4 is 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. Specifically, the claim includes the word “preferably”, which is open to multiple interpretations. As a result, the scope of the claim is ambiguous as to whether the preferred limitations are non-limiting preferences or required features. Accordingly, the claim is rejected for lack of clarity and definiteness.
Although claims 5, 7, 11, and 29 are withdrawn from consideration, it should be noted that each claim contains the word “preferably”, rending the respective claim scope ambiguous.
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 (i.e., changing from AIA to pre-AIA ) 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, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1, 3-4, 28, 30-35, 37, 40-41, and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Griffith (US 2004/0157838A1; published 2004, Aug. 12).
Instant claim 1 is directed to a pyrazolopyrimidine compound of Formula I:
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wherein:
R1 and R2 are each independently selected from optionally substituted C6-C10 aryl and optionally substituted C5-C10 heteroaryl;
R3 is selected from optionally substituted C1-C12 alkyl, optionally substituted C1-C12 alkoxy, optionally substituted alkylamino or dialkylamino, optionally substituted C3-C10 cycloalkyl, optionally substituted C3-C10 heterocycloalkyl, optionally substituted C6-C10 aryl, and optionally substituted C5-C10 heteroaryl, optionally substituted -X1-C3-C10 cycloalkyl, optionally substituted -X1-C3-C10 heterocycloalkyl, optionally substituted -X1-C6-C10 aryl, and optionally substituted -X1-C5-C10 heteroaryl;
R4 is selected from NH2, optionally substituted C1-C12 alkoxy, optionally substituted alkylamino or dialkylamino, optionally substituted C3-C10 cycloalkyl, optionally substituted C3-C10 heterocycloalkyl, optionally substituted -X2-C3-C10 cycloalkyl, and optionally substituted -X2-C3-C10 heterocycloalkyl;
X1 is selected from O and NR5, wherein R5 is H or an optionally substituted C1-C6 alkyl; and
X2 is selected from O and NR6, wherein R6 is H or an optionally substituted C1-C6 alkyl;
or an isomer and/or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
Griffith teaches compounds of Formula II that act as a cannabinoid receptor ligand and their uses in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals (abstract):
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.
wherein:
R0 and R1 is an optionally substituted aryl or an optionally substituted heteroaryl;
R2 and R3 are each independently hydrogen, halo, C1-C4 alkyl, halosubstituted C1-C4 alkyl, or C1-C4 alkoxy;
R4 is a group having Formula IIA or Formula IIB
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where:
R4a is hydrogen or C1-C3 alkyl; and
R4b, R4b’, R4f, R4f’, X, Y, and Z, are described elsewhere herein as appropriate.
While Griffith does not teach a single embodiment that encompasses all limitations of instant claim 1, the following pyrazolopyrimidine (“compound I”) is taught as Example 16A-2 (Page 43, paragraph 327):
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Compound I overlaps with instant claim 1 when:
R1 and R2 are each independently selected as optionally substituted C6 aryl; and
R3 is selected as optionally substituted C2 alkoxy.
The difference between compound 1 and the instant application is that Griffith fails to teach an embodiment wherein R2 (instant R4) is selected from NH2, optionally substituted C1-C12 alkoxy, optionally substituted alkylamino or dialkylamino, optionally substituted C3-C10 cycloalkyl, optionally substituted C3-C10 heterocycloalkyl, optionally substituted -X2-C3-C10 cycloalkyl, and optionally substituted -X2-C3-C10 heterocycloalkyl.
However, as stated above, Griffith teaches that R2 may be selected as C1-C4 alkoxy. Therefore, it would be obvious to one of ordinary skill in the art to apply the rationale set forth in prong B of the KSR framework to substitute the benzylic –CH2– of Compound I for an –O–, thus forming a C3 alkoxy. The compound thus formed shown as “compound II” below. Said artisan would have been motivated to do so because Griffith teaches a genus that links the alkyl and the alkoxy groups as having similar properties. Therefore, one would have a reasonable expectation of success in making such a substitution.
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Claims 3-4 are directed to compounds of Formula I, wherein R4 is selected from optionally substituted C1-C12 alkoxy, preferably optionally substituted C1-C6 alkoxy, more preferably optionally substituted C1-C4 alkoxy, optionally substituted alkylamino or dialkylamino, optionally substituted C3-C10 cycloalkyl, optionally substituted C3-C10 heterocycloalkyl, optionally substituted -X2-C3-C10 cycloalkyl, and optionally substituted -X2-C3-C10 heterocycloalkyl.
Compound II encompasses the limitations of claims 3-4 when R4 is selected as C3 alkoxy.
Claim 28 is directed to the compounds of Formula I, wherein X1 is absent.
Compound II does not comprise an X1 moiety.
Claims 30-31 are directed to compounds of Formula I, wherein R2 is an optionally substituted C6 aryl or optionally substituted C5-6 heteroaryl, wherein the C6 aryl is of the formula
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. The variables are described herein as necessary.
Griffith teaches compound II is prima facie obvious by applying prong B rationale of the KSR framework. Compound II comprises a C6 aryl in the R2 position, wherein X15, X16, X17, X18, and X19 are each independently selected as CR11 and R11 is selected as halogen (X15) or hydrogen (X16, X17, X18, and X19).
Claims 32-34 are directed to compounds of claim 30, wherein R2 is of the formula ; X15, X16, X17, X18, and X19 are each CR11; wherein X15 is CR11, wherein R11 is selected from halogen and OR9; and wherein X16, X17, X18, and X19 are each CR11, wherein R11 is hydrogen.
Compound II is comprised of a C6 aryl in the R2 position, wherein X15 is selected from CR11 wherein R11 is independently selected as halogen, and X16, X17, X18, and X19 is selected from CR11, wherein R11 is selected as hydrogen.
Claim 35 is directed to compounds of claim 33, wherein the R2 is a 2-methoxyphenyl or 2-chlorophenyl group.
Compound II is comprised of a 2-chlorophenyl group in the R2 position.
Claim 37 is directed to the compound of claim 31, wherein X16 is N or CH.
Compound II is comprised of a C6 aryl in the R2 position, wherein X16 is CH.
Claims 40 and 41 is directed to compounds of Formula 1, wherein R1 is an optionally substituted C6 aryl, wherein R1 is a 4-chlorophenyl group.
Compound II is comprised of an optionally substituted C6 aryl in the R1 position in the form of a 4-chlorophenyl group.
Claim 49 is directed to a pharmaceutical composition comprising compounds of Formula I, together with a pharmaceutically acceptable carrier, diluent, or excipient.
Griffith teaches pharmaceutical compositions comprising a disclosed compound, a pharmaceutically acceptable salt of said compound, or a solvate or hydrate thereof, and a pharmaceutically acceptable excipient, diluent, or carrier (page 63, paragraph 95).
Claim(s) 1, 3, 14, 17, 20, 28, 30-35, 37, 40-43, 45-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shin (US 8,975,264 B2; published 2015, Mar. 10) in view of Griffith.
The teachings of Griffith are discussed above and incorporated herein by reference.
Shin teaches a class of pyrazolo[1,5-a]pyrimidine derivatives of Formula III,
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wherein
R1 and R3 are substituted C6 aryl;
R2 is selected from the group hydrogen, C1-C5 alkyl, haloalkyl, C1-C5 cycloalkyl and C1-C5 alkoxyalkyl; and
R4 and R5 are described herein as needed,
and pharmaceutical compositions thereof for their use as cannabinoid receptor 1 inhibitors (abstract).
One example compound of Formula III as disclosed by Shin is Ex. No. 8 (column 37, Table 2. Hereafter referred to as “compound III”)
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.
The difference between compound III and compounds of instantly recited Formula I is that compound fails to teach an embodiment wherein the 5-memebred heteroaryl is comprised of two C6 aryl rings.
However, as stated above, Griffith teaches compound I comprising two C6 aryl rings on the 5-membered heteroaryl of the pyrazolo[1,5-a]pyrimidine core.
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One of ordinary skill in the art would have been motivated to combine the teachings of Shin with the teaching of Griffith because they are both in the same field of endeavor of cannabinoid receptor inhibitors. Furthermore, Griffith teaches the R2 position of Formula III can be C1-C4 alkyl or substituted C6 aryl (most preferably 2-chlorophenyl) (page 2, paragraph 0012), thereby linking both moieties as having similar properties. Accordingly, said skilled artisan would have had a reasonable expectation of success to incorporate a 2-chlorophenyl ring into compound III. The compound thus formed is therefore prima facie obvious and shown below as compound IV
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.
Compound IV encompasses the limitations of instant claims 1 and 3, when
R1, R2, and R3 are all optionally substituted C6 aryl;
R4 is optionally substituted C5 heterocycloalkyl.
Claims 14 and 17 are directed to compounds of Formula I, wherein R3 is an optionally substituted C6 aryl, C5-6 heteroaryl, C4-7 cycloalkyl, or C4-7 heterocycloalkyl group, or a C6 aryl, C5-6heteroaryl, C4-7 cycloalkyl, C4-7 heterocycloalkyl linked to the pyrazolopyrimidine core through X1, wherein the aryl or heteroaryl group is of the formula
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. The variables are described herein as necessary.
Compound IV is comprised of an optionally substituted C6 aryl in the R3 position, wherein X3, X4, X5, X6, and X7 are each independently selected as CR11, wherein X3, X4, X6, and X7 are selected as hydrogen and X5 is selected as optionally substituted C1 alkyl.
Claim 20 is directed to compounds of claim 17, wherein X5 is CR11 and R11 is selected from CN, an optionally substituted C1-6 alkyl group (e.g., CH3, CF3, etc.), and OR9, wherein R9 is an optionally substituted C1-6 alkyl group.
The X5 position on compound IV is substituted with the substituted C1 alkyl group, CF3.
Claim 28 is directed to compounds of Formula I, wherein X1 is absent.
Compound IV is not comprised of an X1 moiety.
Claims 30-31 are directed to compounds of Formula I, wherein R2 is an optionally substituted C6 aryl or optionally substituted C5-6 heteroaryl, wherein the C6 aryl is of the formula
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. The variables are described herein as necessary.
Compound IV comprises a C6 aryl in the R2 position, wherein X15, X16, X17, X18, and X19 are each independently selected as CR11 and R11 is selected as halogen (X15) or hydrogen (X16, X17, X18, and X19).
Claims 32-34 are directed to compounds of claim 30, wherein R2 is of the formula ; X15, X16, X17, X18, and X19 are each CR11; wherein X15 is CR11, wherein R11 is selected from halogen and OR9; and wherein X16, X17, X18, and X19 are each CR11, wherein R11 is hydrogen.
Compound IV is comprised of a C6 aryl in the R2 position, wherein X15 is selected from CR11 wherein R11 is independently selected as halogen, and X16, X17, X18, and X19 is selected from CR11, wherein R11 is selected as hydrogen.
Claim 35 is directed to compounds of claim 33, wherein the R2 is a 2-methoxyphenyl or 2-chlorophenyl group.
Compound IV is comprised of a 2-chlorophenyl group in the R2 position.
Claim 37 is directed to the compound of claim 31, wherein X16 is N or CH.
Compound IV is comprised of a C6 aryl in the R2 position, wherein X16 is CH.
Claims 40 and 41 are directed to compounds of Formula 1, wherein R1 is an optionally substituted C6 aryl, wherein R1 is a 4-chlorophenyl group.
Compound IV is comprised of an optionally substituted C6 aryl in the R1 position in the form of a 4-chlorophenyl group.
Claims 42 and 43 are directed to compounds of Formula I, wherein the compound is selected from Compounds 1 to 78 or Compounds 1 to 77 as defined in the Instant Application, or an isomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
Compound IV above is the same as Compound 4 in the instant specification (page 25).
Shen further teaches compound Ex. No. 1, comprising a 4-OMe phenyl ring on the R3 position (column 36, Table 2).
For the reasons discussed above, one of ordinary skill in the art would be motivated to combine compound Ex. No. 1 of Shen with the teachings of Griffith to form compound V:
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.
Compound V is the same as Compound 5 in the instant specification (page 26).
Regarding claims 45-48, compound IV and compound V are the same as Compound 4 and Compound 5 from the instant specification (pages 25 and 26, respectively).
Claim 49 is directed to a pharmaceutical composition comprising compounds of Formula I, together with a pharmaceutically acceptable carrier, diluent, or excipient.
Shin teaches, for example, Formulation Example 1 as a pharmaceutical composition comprising a disclosed compound and at least one pharmaceutically acceptable carrier, diluent, or excipient (column 137, lines 5-10).
Claim Objections
Claims 6, 18-19, and 64-65 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. As discussed above, closest prior art to the instant claims is Griffith and Shin in view of Griffith.
Claim 6 is directed to compounds of claim 4, wherein the alkyl or alkoxy on R4 is substituted with at least one of the listed groups.
The closest prior art to the instant claim is compound II, which is prima facie obvious through the teaching of Griffith.
The difference between compound II and the instant claim is that Griffith fails to teach any embodiment wherein the alkoxy substituent on R4 is substituted with any group. Furthermore, Griffith fails to teach a genus wherein the alkoxy substituent in that position may be substituted, so there would be no motivation for a skilled artisan to include any of listed functional groups. Accordingly, claim 6 is free of the prior art.
Claims 18-19 are directed to compounds of claim 17, wherein one of X3, X4, X5, X6, and X7 is N, and wherein X4 is N and X3, X6, and X7 are each CH.
The closest prior art to the instant claims is compound IV, which is prima facie obvious through the teachings of Shin in view of Griffith.
The difference between compound IV and the instant claim is that Shin in view of Griffith fails to teach any embodiment wherein the aryl ring in the R3 position is heteroaryl. Furthermore, Shin fails to teach any genus wherein the aryl ring may be a heteroaryl ring, thus one of ordinary skill in the art would not have had the motivation to use an aryl ring wherein one of X3, X4, X5, X6, and X7 is N, and wherein X4 is N and X3, X6, and X7 are each CH. Accordingly, claims 18-19 are free of the prior art.
Claim 64 is directed to compounds of claim 43, wherein the compound is selected from Compound 8, Compound 15, or Compound 45, or an isomer or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
The closest prior art to the instant claim is compound IV and compound V, which are prima facie obvious through the teachings of Shin in view of Griffith.
The difference between compounds IV and V and the instant claim is discussed in detail above. One of ordinary skill in the art would not have had motivation to substitute the aryl ring as taught by Shin with a heteroaryl ring to arrive at the instantly claimed compounds. Accordingly, claim 64 is free of the prior art.
Allowable Subject Matter
Claim 65 is allowed.
The claim is directed to a compound selected from Compound 8, Compound 15, or Compound 45 (Table 1).
Table 1. Compounds of claim 65.
Compound 8
Compound 15
Compound 45
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The closest prior art to the claimed compounds is compound IV, which is prima facie obvious through the combined teachings of Shin in view of Griffith, and Compound 7A-2 of Griffith (page 40, Table 5, line 1) (Table 2, right).
Table 2. Closest prior art to the compounds of claim 65.
Compound IV
Compound 7A-2
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The difference between compound IV and instant compound 8 is that Shin in view of Griffith comprises only a 4-CF3 aryl ring in the R3 position and fails to teach any embodiment or motivation to substitute the aryl ring for a heteroaryl ring. Accordingly, compound 8 is free of the prior art.
The difference between instant compound 15 and the prior art is that Griffith teaches compound 7A-2, which does not consist of a piperidine in the R3 position that further comprises an SO2CF3 moiety. Substituting the SO2CH3 of compound 7A-2 for the SO2CF3 would in itself be obvious to one of ordinary skill in the art, however compound 7A-2 also fails to teach an embodiment wherein the pyrazolopyrimidine core further comprises an alkyoxy substituent in the R4 position, and further fails to teach a genus wherein the alkoxy substituent may be optionally substituted. Therefore, said skilled artisan would not have found it obvious to make the necessary adjustments to read on the instant compound. Accordingly, compound 15 is free of the prior art.
The difference between compound 45 and the prior art is that Shin in view of Griffith teaches compound IV. The combined teachings fail to teach an embodiment and motivation to substitute the aryl ring for a heteroaryl ring. The combined teachings further fail to teach an alkoxy in the R4 position, and further fails to teach wherein the alkoxy can be further substituted. Accordingly, compound 45 is free of the prior art.
Conclusions
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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