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
Claims 1-31, 34-37 are pending in the present application.
Election/Restriction
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1-28, drawn to a compound of Formula (I), Formula (IA), Formula (IB), Formula (IA-1A), Formula (IA-1B), Formula (IA-1A1)-Formula (IA-1A5), Formula (IA-1B1)-Formula(IA-1B5), compound of instant claims 23-24, and a pharmaceutical composition comprising the compound of Formula (I), classified in C07D 403/14.
II. Claims 29-30 and 34-37, drawn to a method of treating cancer, as well as a solid cancer with a USP mutation, in a subject in need thereof, classified in A61P 35/00.
III. Claims 31, drawn to a method of treating a USP mediated disorder in a subject, classified in A61P 43/00.
The inventions are independent or distinct, each from the other because:
Inventions I and II are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case the process for using the compounds of Invention (I) as claimed can be practiced with another materially different product (e.g., possible to treat cancer in a subject in need thereof via materially different compounds other than compounds of instant Invention (I)). For example, US 10,648,983 B2 (Filvaroff et al., published on 05/12/2020) teaches a method of treating cancer via administration of compounds of different Formula (I). See abstract, col. 2, compound D and compound E from examples 6.1-6.3, fig. 1A and Table 1.
Inventions I and III are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case the process for using the compounds of Invention (I) as claimed can be practiced with another materially different product (e.g., possible to treat a USP mediated disorder in a subject in need thereof via materially different compounds other than compounds of instant Invention (I)). US 2020/0079776 (Buckmelter et al.; Publication Date: March 12, 2009) teaches compounds of a distinct Formula (I) as “inhibitors of USP1 useful in the treatment of cancers, and other USP1 associated diseases and disorders” (see abstract).
Inventions II and III are directed to related processes. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed have a materially different design and effect (treatment of cancer compared to treatment of USP associated disorders), are mutually exclusive (an infringer to a method of treating cancer would not necessarily be an infringer of a method of treating a USP mediated disorder and similarly in the converse), and the inventions are not obvious variants (the method of treating a USP mediated disorder is not an obvious variant for a method of treating cancer). Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
The inventions have acquired a separate status in the art in view of their different classification.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
This application contains claims directed to the following patentably distinct species a compound of Invention I (i.e., a compound of Formula (I), Formula (IA), Formula (IB), Formula (IA-1A), Formula (IA-1B), Formula (IA-1A1)-Formula (IA-1A5), Formula (IA-1B1)-Formula(IA-1B5), or compound of instant claims 23-24). The species are independent or distinct because of the mutually exclusive characteristics for each potential functional group and permutations of functional groups within the various species of compounds. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, claims 1-31, 34-37 are generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply:
The inventions require different fields of search (searching different groups/subgroups as well as employing different search strategies).
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
During a telephone conversation with Jay Lessler on August 28, 2026 a provisional election was made without traverse to prosecute the invention of Invention I, as well as a species of Example 16 (pictured below), claims 1-2, 4-24, and 27-28. Affirmation of this election must be made by applicant in replying to this Office action.
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As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species of instant formula (I) appears free of the prior art. Therefore, according to MPEP 803.02: should the elected species be found allowable, the examination of the Markush-type claim will be extended. If the examination is extended and a non-elected species found not allowable, the Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration. The examination of the Markush-type claims has been extended to include the species cited below under 35 U.S.C. 102, which are not allowable, as well as the species of instant claim 24, which .
As a non-elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1-2, 4-24, and 27-28 have been examined to the extent that they embrace and are readable on the elected embodiment and the above identified nonelected species. Since the nonelected species has been found not allowable, subject matter not embraced by the elected embodiment or the above identified nonelected species is therefore withdrawn from further consideration.
Claims 3, 25-26, 29-31 and 34-37 withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed applications, IN 202341076811 (filed November 10, 2023), IN 202441000286 (filed January 2, 2024), IN 202441001631 (filed January 9, 2024), IN 202441037320 (filed May 11, 2024), and US PRO 63/690,894 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The instant claims contain several instances where the scope of variables or compounds is broadened relative to the disclosure of the provisional application.
The ‘811 application provides the broadest disclosure for a compound of formula (I) in paragraph 10, pages 4-7. The ‘286 provides the broadest disclosure for a compound of formula (I) in paragraph 10, pages 4-7. The ‘631 application provides the broadest disclosure for a compound of formula (I) in paragraph 10, pages 4-7. The ‘320 application provides the broadest disclosure for a compound of formula (I) in paragraph 10, pages 4-7. The ‘894 application provides the broadest disclosure for a compound of formula (I) in paragraph 10, pages 3-6.
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Formula (I) of instant claim 1.
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Formula (I) of ‘811 application (see page 4 of ‘811 application).
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Formula (I) of ‘286 application (see page 4 of ‘286 application).
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Formula (I) of ‘631 application (see page 4 of ‘631 application).
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Formula (I) of the ‘320 application
(see page 4 of the ‘320 application).
The following differences are noted between the instant claims and the broadest disclosure of the ‘811, ‘286, ‘631, ‘320 and ‘894 applications:
The ‘811 and ‘286 applications disclose a formula (IA) that is distinct from the formula (IA) provided in instant claim 2 (see below).
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Formula (IA) of instant claim 2.
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Formula (IA) of ‘811 application (see page 7 of ‘811 application).
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Formula (IA) of ‘286 application (see page 7 of ‘286 application).
The ‘811 application teaches where “Ring A is selected from a cyclic group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl” in paragraph 16, page 8. The ‘286 application teaches where “Ring A is selected from a cyclic group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl” in paragraph 30, page 9.
Variables Y1-Y3 are not taught by the ‘811 or ‘286 applications (see instant claim 5).
The variable L is not disclosed in Formula (I) of the ‘811 or ‘286 applications (see instant claim 6).
The ’811 application provides further preferable examples of Ring A in paragraph 47, page 13:
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The ‘286 application discloses a similar recitation of preferred moieties for Ring A in paragraph 65, pages 15-16.
The ‘286 application discloses where ring Q of formula (I) including with variables X1-X4 is selected from:
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.
The ‘631 application discloses a recitation of preferred moieties for Ring A including with variables X1, X2, X3 and X4 in paragraph 60, pages 13-14. The ‘320 application discloses a similar recitation of preferred moieties for Ring A including with variables X1, X2, X3 and X4 in paragraph 60, pages 13-14.
See instant claims 7-9 which recite wherein ring A including variables X1, X2, X3 and X4 is independently selected from a group comprising, for example
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which are not disclosed by the ‘811, ‘286, or ‘631 applications.
The variable Rf is not taught by the ‘811 or ‘286 applications (see instant claim 14).
The ‘811, ‘286, ‘631, ‘320 or ‘894 applications do not teach a compound of Formula (IA-1A), Formula (IA-1B), Formula (IA-1Al)-Formula (IA-1A5), or Formula (IA-1Bl)-Formula (IA-1B5) (see instant claims 16-17).
Instant claims 23-24 and 27 contain several compounds which are not disclosed by the ‘811, ‘286 or ‘631 applications including Applicant’s elected species, 2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-N-(4-(1-methyl-4-(trifluoromethyl)-lH-imidazol-2-yl)benzyl)-7H-purin-6-amine, and further compounds such as 2-(2-isopropylphenyl)-N-(4-(1-methyl-4-(trifluoromethyl)-lH-imidazol-2-yl)benzyl)-7Hpurin-6-amine (Example 15) and 2-(4-methoxypyridin-3-yl)-N-(4-(l-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (Example 34). See Table 1 of the ‘811 application , paragraph 49, pages 14-16. See Table 1 of the ‘286 application, paragraph 67, pages 17-20. See Table 1 of the ‘631 application, paragraph 75, pages 18-24.
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For these reasons, the priority date for the purposes of applying prior art for instant claims 4, 10-13, 15, 18-22 and 28 is November 10, 2023; for instant claims 1-2, 5-6 and 14 is January 9, 2024; for instant claims 7-9 and 23-24 and 27 is May 11, 2024; and for claims 16-17 is November 11, 2024.
Information Disclosure Statement
The Information Disclosure Statement(s) filed November 11, 2024 have been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Claim Objections
Claim 17 is objected to because of the following informalities:
In line 2, “(IA-1A4), (IA-1A4),”, should read “(IA-1A4), (IA-1A5),”.
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.
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 4-6, 14 and 18-19 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.
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 4 recites the broad recitation “wherein X1 is CR1 or N; X2 is CR2 or N;·X3 is CR3 or N;·or X4 is CR4 or N”, and the claim also recites “wherein X1 is N; X2 is N; X3 is CH or N; or X4 is CH or N”, which is the narrower statement of the range/limitation.
In the present instance, claim 6 recites the broad recitation wherein L is “absent or selected from substituted or unsubstituted C1-4 alkyl, O, S, -S(=O)p or NRx”, and the claim also recites wherein “L is absent or selected from substituted or unsubstituted C1-4 alkyl”, further wherein L is absent, which is the narrower statement of the range/limitation.
In the present instance, claim 18 recites the broad recitation wherein L1 is “absent or selected from substituted or unsubstituted C1-4 alkyl, O, S, -S(=O)p or NRx”, and the claim also recites wherein L1 is “-NH-, or -O-”, or further wherein L1 is absent, which is the narrower statement of the range/limitation.
In the present instance, claim 19 recites the broad recitation wherein L2 is “absent or selected from substituted or unsubstituted C1-4 alkyl, O, S, -S(=O)p or NRx”, and the claim also recites wherein L2 is “-CH2-, -CH(Me)-”, 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.
Claim 5 recites the following limitations
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There is insufficient antecedent basis for these limitations in the claim. Parent claim 1, from which instant claim 5 depends upon, does not recite the variables Y1, Y2 or Y3 in the definition of a compound of Formula (I). For the purposes of examination, in the interest of compact prosecution, instant claim 5 is interpreted as depending from instant claim 2.
Claim 14 recites the limitation "Rf is selected from hydrogen, […]" in line 2 of instant claim 13. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1, from which instant claim 13 depends upon, does not recite the variable Rf in the definition of a compound of Formula (I). For the purposes of examination, in the interest of compact prosecution, instant claim 14 is interpreted as depending from instant claim 11.
Applicant may amend claims 5 and 14 to depend from claims 2 and 11, respectively, to overcome this aspect of the rejection.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-23 and 27-28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2024/233605 A1 (International filing date: May 8, 2024; Priority to 63/464,888, filed May 8, 2023), alone and as evidenced by US 9,907,807 (Evers et al.).
The prior art teaches the following compound as T-007 on page 350, as well as in claim 76 of WO ‘605 (specifically page 592; see page 119 of the ‘888 application for compound 137).
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Compound T-007 is directed to 2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-6-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methoxy]-7H-purine and corresponds to a compound of instant formula (I) wherein:
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is O (see instant claim 18)
L2 is (CRbRc)n (see instant claim 19)
Rb is H
Rc is H
N is 1
Cy is unsubstituted aryl (phenyl; see instant claim 15)
R is substituted heteroaryl (see instant claim 10-13)
R5 is substituted heteroaryl (see instant claim 20).
Compound T-007 is embraced by instant claims 4-6, 23 and 27. Compound T-007 is embraced by instant claims 7-9 where Ring A including variables X1, X2, X3, and X4 is
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. Compound T-007 is embraced by claim 11 where R is
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substituted with three Rf, wherein one Rf is cyclopropyl, one Rf is hydrogen and the last Rf is methoxy. See also instant claim 14. Compound T-007 is embraced by claim 12 where R is
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. Compound T-007 is embraced by instant claim 13 where R is
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.
Compound T-007 also corresponds to a compound of formula (IA) of instant claim 2 wherein:
Y1 is -N-
Y2 is -CRd
Rd is hydrogen
Y3 is -NRd
Rd is hydrogen
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is O
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heteroaryl.
See instant claim 2.
Compound T-007 also corresponds to a compound of formula (IA-1B) of instant claim 16 wherein:
Y1 is -N-
Y2 is -CRd
Rd is hydrogen
Y3 is -NRd
Rd is hydrogen
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent (see instant claim 6)
L1 is O
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heteroaryl.
Compound T-007 also corresponds to a compound of Formula (IA-1B5) of claim 17 wherein:
X1 is N
X2 is N
L1 is O
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R5 is substituted heteroaryl
Rf is methoxy and cyclopropyl.
Compound T-007 is embraced by claim 21 where R5 is
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substituted by two Ra, where Ra is methyl and trifluoromethyl. Compound T-007 is embraced by claim 22 where R5 is
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Regarding instant claim 28, the prior art discloses preparation and purification in DCM (see paragraph 1111 of WO ‘605 and paragraph 1110 of the priority document) which is deemed to anticipate the instant claim 28 since the evidentiary reference by Evers teaches that alcohols are penetration enhancing agents for topical pharmaceutical compositions (column 9, lines 56-67 of Evers).
Claims 1-2, 4-6, 10-15, 18-21 and 28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2024/041661 A1 (Publication Date: Feb. 29, 2024; International Filing Date: Aug. 28, 2023), alone and as evidenced by US 9,907,807 (Evers et al.).
The prior art teaches the following compound as UB-001 on page 71 of WO ‘661.
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The prior art also discloses a synthesis of UB-001 on page 23.
Compound UB-001 is directed to [6-[4-[[(9-ethyl-2-morpholin-4-ylpurin-6-yl)amino]methyl]phenyl]-2-pyridinyl]methanol and corresponds to a compound of instant formula (I) wherein:
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent (see instant claim 6)
L1 is NRx (see instant claim 18)
Rx is H
L2 is (CRbRc)n (see instant claim 19)
Rb is H
Rc is H
n is 1
Cy1 is unsubstituted aryl (phenyl; see instant claim 15)
R is unsubstituted heterocyclic ring (see instant claim 10-13)
R5 is substituted heteroaryl (see instant claim 20).
Compound UB-001 is embraced by instant claims 4-5.
Compound UB-001 corresponds to a compound of formula (IA) of instant claim 2 wherein:
Y1 is -NRd-
Rd is unsubstituted C2 alkyl
Y2 is -CRd
Rd is hydrogen
Y3 is -N
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is NRx
Rx is H
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heteroaryl.
See instant claim 2.
Compound UB-001 is embraced by claims 11-13 where R is
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. See also instant claim 14, where Rf is hydrogen. Compound UB-001 is embraced by claim 21 where R5 is
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.
Regarding instant claim 28, the prior art discloses purification in methanol (MeOH; see page 23) which is deemed to anticipate the instant claim 28 since the evidentiary reference by Evers teaches that alcohols are penetration enhancing agents for topical pharmaceutical compositions (column 9, lines 56-67 of Evers).
Claims 1-2, 4-6, 10-15, 18-22 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kozicka et al.(Kozicka, Zuzanna, et al. "Design principles for cyclin K molecular glue degraders." Nature Chemical Biology 20.1 (2024): 93-102. Publication Date: September 7, 2023), alone and as evidenced by US 9,907,807 (Evers et al.).
Kozicka et al. teach the following compound as DS21 in Fig. 2 on page 96.
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164
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Kozicka et al. disclose a synthesis of DS21 on page 19 of the Supplemental Information.
Compound DS21 is directed to 9-(1-methyl-1H-pyrazol-4-yl)-2-morpholino-N-(4-(pyridin-2-yl)benzyl)-9H-purin-6-amine and corresponds to a compound of instant formula (I) wherein:
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent (see instant claim 6)
L1 is NRx (see instant claim 18)
Rx is H
L2 is (CRbRc)n (see instant claim 19)
Rb is H
Rc is H
n is 1
Cy1 is unsubstituted aryl (phenyl; see instant claim 15)
R is unsubstituted heterocyclic ring (see instant claim 10-13)
R5 is substituted heteroaryl (see instant claim 20).
Compound DS21 is embraced by instant claims 4-5.
Compound DS21 also corresponds to a compound of formula (IA) of instant claim 2 wherein:
Y1 is -NRd-
Rd is substituted heteroaryl
Y2 is -CRd
Rd is hydrogen
Y3 is -N
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is NRx
Rx is H
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heteroaryl.
See instant claim 2.
Compound DS21 is embraced by claims 11-13 where R is
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61
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. See also instant claim 14, where Rf is hydrogen. Compound DS21 is embraced by claims 21-22 where R5 is
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59
59
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.
Regarding instant claim 28, the prior art discloses preparation of Compound DS21 in dimethylformamide (DMF; see page 19 of the Supplemental Information) which is deemed to anticipate the instant claim 33 since the evidentiary reference by Evers teaches that DMF is a penetration enhancing agent for topical pharmaceutical compositions (column 9, lines 56-67 of Evers).
Claims 1-2, 4-6, 10-15, 18-19 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Monastyrskyi et al.(Monastyrskyi, Andrii, et al. "Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer." Bioorganic & medicinal chemistry 26.3 (2018): 590-602.), alone and as evidenced by US 9,907,807 (Evers et al.).
Monastyrskyi et al. teach the following compound as Compound 56 in Table 4 on page 596.
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383
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Compound 56 is directed to 9-(3-fluorophenyl)-N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-2-morpholin-4-ylpurin-6-amine and corresponds to a compound of formula (I) wherein:
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent (see instant claim 6)
L1 is NRx (see instant claim 18)
Rx is H
L2 is (CRbRc)n (see instant claim 19)
Rb is H
Rc is H
n is 1
Cy1 is unsubstituted aryl (phenyl; see instant claim 15)
R is unsubstituted heterocyclic ring (see instant claim 10-13)
R5 is substituted heterocyclic ring.
Compound 56 is also embraced by instant claims 4-5.
Compound 56 also corresponds to a compound of formula (IA) of instant claim 2 wherein:
Y1 is -NRd-
Rd is substituted aryl
Y2 is -CRd
Rd is hydrogen
Y3 is -N
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is NRx
Rx is H
L2 is (CRbRc)n
Rb is H
Rc is H
N is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heterocyclic ring.
See instant claim 2.
Compound 56 is also embraced by claims 11-13 where R is
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. See also instant claim 14, where Rf is hydrogen.
Regarding instant claim 28, the prior art discloses compound testing in PK studies where compositions comprising compounds of the invention and DMSO (see section 4.5, page 601, right column), which is deemed to anticipate the instant claim 28 since the evidentiary reference by Evers teaches that DMSO is a penetration enhancing agent for topical pharmaceutical compositions (see column 9, lines 56-58 of Evers).
Claims 1-2, 4-6, 10-13, 14-15, 18-22 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2014/121764 (Publication Date: Aug. 14, 2014), alone and as evidenced by US 9,907,807 (Evers et al.).
The prior art teaches the following compound as BP97 on page 71 of WO ‘764.
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Compound BP97 is directed to 9-cyclopentyl-2-piperazin-1-yl-N-[(4-thiophen-2-ylphenyl)methyl]purin-6-amine and corresponds to a compound of instant formula (I) wherein:
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent (see instant claim 6)
L1 is NRx (see instant claim 18)
Rx is H
L2 is (CRbRc)n (see instant claim 19)
Rb is H
Rc is H
n is 1
Cy1 is unsubstituted aryl (phenyl; see instant claim 15)
R is unsubstituted heterocyclic ring (see instant claim 10-13)
R5 is substituted heteroaryl (see instant claim 20).
Compound BP97 is embraced by instant claims 4-5.
Compound BP97 also corresponds to a compound of formula (IA) of instant claim 2 wherein:
Y1 is -NRd-
Rd is unsubstituted cycloalkyl
Y2 is -CRd
Rd is hydrogen
Y3 is -N
X1 is N
X2 is N
X3 is CR3
X4 is CR4
R3 and R4 form a 5-membered unsubstituted ring
L is absent
L1 is NRx
Rx is H
L2 is (CRbRc)n
Rb is H
Rc is H
n is 1
Cy is unsubstituted aryl (phenyl)
R is substituted heteroaryl
R5 is substituted heteroaryl.
See instant claim 2.
Compound BP97 is embraced by claims 11-13 where R is
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56
55
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. See also instant claim 14, where Rf is hydrogen. Compound BP97 is embraced by claims 21-22 where R5 is
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55
69
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Regarding instant claim 28, the prior art discloses where compounds of Table 1 is prepared by Methods of Examples 2, 17, and 21, all which teach preparation in dimethylformamide or crystallization in ethanol (see pages 29-30, 41-42, 45) which is deemed to anticipate the instant claim 33 since the evidentiary reference by Evers teaches that DMF and alcohols are penetration enhancing agents for topical pharmaceutical compositions (column 9, lines 56-67 of Evers).
Allowable Subject Matter
Claim 24 is allowed.
Conclusion
Claims 3, 25-26, 29-31 and 34-37 withdrawn.
Claims 1-2, 4-23 and 27-28 are rejected.
Claim 17 is objected to.
Claim 24 is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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