DETAILED ACTION
This office action is in response to applicant’s filing dated November 19, 2025.
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 .
Status of claims
Claims 1 - 14 are pending in the instant application.
Claims 2, 5 – 7 and 9 - 13 remain withdrawn, as being drawn to an unelected invention or species.
Claims under consideration in the instant office action are claims 1, 3, 4, 8 and 14.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on November 19, 2025, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
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 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, 3, 4, 8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Ogiwara et al (WO 2022138944 A1, cited in IDS, filed 06/12/2025 hereinafter Ogiwara) in view of Michaelides et al (WO 2016/044770 A1 cited in IDS, filed 06/12/2025, hereinafter Michaelides).
WO 2022138944 A1 (published on June 30, 2022) is the PCT counterpart to US 2024/0122941 A1 (published April 18, 2024). WO 2022138944 A1 has a 102(a)(1)) date as a result of its June 30, 2022 publication date. Because WO 2022138944 A1 and US 2024/0122941 A1 appear to have identical disclosures, and because the WO document was published in Japanese language designating the United States, the US 2024/0122941 A1, which is the National Stage entry of WO 2022138944 A1, is being used as a translation of WO 2022138944 A1. As such, any reference hereinafter to column and line numbers will be based upon the US publication, but should be interpreted as referring to the corresponding disclosure of the aforementioned WO counterpart.
Instant claims are drawn to a compound of formula:
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(ex.10) or
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(ex. 20) and a pharmaceutical compositions thereof, where the pharmaceutical composition further comprising additional drug such as hormonal therapy agent, chemotherapeutic drug, used in combination with above compound. The claimed compounds show activity against CBP/P300 and can be useful as antitumor agents.
Ogiwara teaches compounds of general formula (1):
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where A is -NH-; B is O; W is phenylene;
Q1 - - - Q2 is -C(R10) 2-(R14)2- where R10 at each occurrence, is independently H or halogen and R14 is hydrogen;
R1 is optionally substituted phenyl or heterocyclyl;
R2a and R2b are each independently hydrogen;
R3a is C1-6 alkyl;
R3b is heterocyclyl;
R4a and R4b are each independently hydrogen;
R6 is optionally substituted pyrazolyl;
R7 is hydrogen;
x and y is 0 ( page 108, [1045] – [1080]).
Ogiwara defines "heterocyclyl", "heterocyclyl group", "heterocycle", "heterocyclic group", "heterocycle", or "heterocyclic group" as non-aryl heterocyclic groups and heteroaryl groups, optionally substituted (page 100, [0957]). "Non-aryl heterocyclic group" defined as a monocyclic nonaromatic heterocycle comprising heteroatoms, such as a nitrogen atom (e.g. azetidinyl) (page 103, [0966]). "Heteroaryl" is defined as aromatic heterocyclic group comprising an atom such as a nitrogen atom (e.g. pyridyl) (page 101, [0962]).
One of the examples, taught by Ogiwara, is compound of formula:
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(page 5, Table 22). The difference in exemplary structure of Ogiwara with structure of Example 10 of instant claims is methyl group instead of N-methyl azetidinyl (see the fragment of molecules with arrow pointing:
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or
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). However, Ogiwara teaches heterocyclyl such as azetidine as a substituent in this part of the structure. The difference between exemplary structure of Ogiwara and instant structure of Example 20 is methyl instead of N-methyl azetidinyl substituent (see the structure above) and R1 is p-fluorophenyl instead of pyridyl substituted with fluorine. However, Ogiwara teaches optionally substituted heteroaryl as R1 of the general structure (1). Ogiwara further teaches a pharmaceutical composition comprising a CBP/P300 inhibitor in combination with anticancer platinum coordination compound (chemotherapeutic agent) a hormone formulation, an angiogenesis inhibitor, an immune checkpoint inhibitor etc. (page 70, [0433]).
Ogiwara does not explicitly teach where “optionally substituted” groups are azetidinyl substituted with -CH3, or where R1 is pyridyl substituted with F. However, Michaelides teaches compounds of general formula (XIIb):
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(page 4, lines 10 – 15) where:
R1 is
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(page 26, lines 5 – 10) or pyridinyl substituted with F (page 140, line 16);
R2a and R2b are each independently H;
R3a is heterocyclyl, optionally substituted with alkyl (page 140, lines 30 – 31)
R3b is trifluoromethyl (page 28, lines 1 – 5); or
R3a and R3b taken together with the carbon to which they are attached form azetidine, optionally substituted with alkyl (page 64, lines 14 – 19);
Q1 - Q2 is -C(R10)2-C(R14)2, where R10, at each occurrence, is independently H, halogen, and R14 is H;
R6 is pyrazolyl (page 30, lines 13 – 14)
x, and y are each independently 0.
Michaelides defies "alkyl" as methyl or ethyl (page 8, lines 12 – 16). "Heterocyclyl" is defined as a stable 3- to 18-membered non-aromatic or aromatic ring radical which consists of two to twelve carbon and from one to six heteroatom ring atoms, such as nitrogen (Page 12, lines 5 – 7). Example of non-aromatic heterocyclyl is azetidinyl.
Thus, prior art teaches compounds of structures having core and substituents corresponding to claimed compounds and useful for the same purpose (p300/CBP inhibitors). The difference between compounds, taught by prior art, and claimed structures is -CH2- group. MPEP 2144.09. I and II states: A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
Thus, since prior art teaches compounds having the same core structure and same of similar substituents in the same position of the molecule, said compounds are being useful for the same purposes (anticancer agent targeting p300/CBP), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine teachings of prior art and arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an improved desired properties of p300/CBP inhibitors with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- Applicant disagrees with the Office’s statement of obviousness because claimed compounds of examples 10 and 20 have a very similar structure, (
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), while Ogiwara teaches compounds of genus structure
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, e.g. example compound
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; however the Office characterized compounds of instant claims and compounds taught by Ogiwara as homologues with the difference in structure -CH2-, which statement is inaccurate;
- even if the methyl group of the Ogiwara compound is replaced with an azetidinyl group, the resulting structure would correspond to structure (b1) shown below and would never correspond to structure (b2), which is the claimed Example 10 compound:
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;
- in Ogiwara, R³ᵃ and R³ᵇ are defined as follows: "R³ᵃ and R³ᵇ, together with the carbon atom to which they are attached, may form arene, cycloalkane, or heterocyclyl.", however, Ogiwara provides no specific examples in which R³ᵃ and R³ᵇ form a ring;
- the term "heterocyclyl may be optionally substituted”, in the absence of any specific disclosure or suggestion regarding such ring structures, a person skilled in the art would have had no motivation to select, from among the numerous possible optionally substituted heterocyclyl groups, the 1-methylazetidine ring substituted with a trifluoromethyl group;
- teachings of Michaelides cited in Office Action do not remedy Ogiwara’ s teachings deficiencies, as Michaelides includes no specific examples in which R³ᵃ and R³ᵇ form a ring;
- "The mere fact that references can be combined or modified does not render the resultant combination obvious unless the results would have been predictable to one of ordinary skill in the art." M.P.E.P. § 2143.01(III), Applicants provide significant evidence demonstrating that the asserted modifications would not have been predictable;
- Applicants demonstrate remarkable antitumor efficacy of the claimed compounds of e.g. Examples 10 and 20 (see the structures above) versus antitumor efficacy of comparative example 1 (
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); where the compounds of example 10 and 20 and comparative example 1 share a common core structure, however, as supported by experimental data, the crucial difference in structure is the fragment
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, which is responsible for the strong antitumor activity of compounds of examples 10 and 20 versus lack of antitumor activity of Comparative Example 1 compound, which does not have this structural feature (comparative example 1
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vs. instant compounds of examples 10 and 20
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);
- the structure of the Ogiwara is the same as the Comparative Example 1 compound at the position attached to the nitrogen in the upper left part of the diagrams presented above; nothing in Ogiwara or Michaelides suggested that the group attached to this position was critical for determining strong antitumor activity or suggested placing an N-methyl azetidinyl at this position.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, instant claims are directed to compounds of formula e.g.:
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(ex.10) or
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(ex. 20), Ogiwara teaches compounds of formula XIIb
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, e.g. compound of formula :
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. The difference in structure of compounds of instant invention and example compound of Ogiwara is
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vs.
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respectfully. Although the example compound of Ogiwara has a methyl group and instantly claimed compounds have N-methyl azetidinyl group in the corresponding part of the molecule, Ogiwara still suggested R3b variable as heterocyclyl, where heterocyclyl can be azetidinyl, optionally substituted. Examiner agrees that Ogiwara’ s teachings regarding structure of R3b are broad, however, Michaelides teaches compounds of formula XIIb
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or formula XVa and XVb:
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, where structure of R3a as heterocyclyl such as azetydinyl, optionally substituted with alkyl such as methyl, and structure of R3b as trifluoromethyl is clearly suggested (see the rejection section above).
Thus, if Michaelides teaches R3a as azetydinyl, optionally substituted with methyl and R3b as trifluoromethyl, then the chemical structures, taught by combined prior art (not Ogiwara’ s teachings only as Applicant mentioned in the arguments), would have fragment
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whereas instantly claimed compounds have structure
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in the corresponding part of the molecule, and where the rest of the elements of the molecule are the same. Hence compounds, taught by combined prior art, appear to be closest homologues (different in -CH2- group) of instantly claimed compounds, and thus presumably possessing similar properties. MPEP 2144.09. I and II states: A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Mentioned by Applicant in the arguments In re Langer case, is not applicable here, as the case discusses the specific example of hindered and unhindered structural elements in chemical reactions, whereas in the instant case structural similarities of molecules and their properties are discussed.
Regarding argument that Michaelides includes no specific examples in which R³ᵃ and R³ᵇ form a ring is not persuasive because, Michaelides teaches example compounds such as:
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(page 492, ex. 718),
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(page 1130, claim 18, N-benzyl-N-[1-(1-methyiazetidin-3-yl)ethyl]-2-{5-[(methylcarbamoyl)amino]-3',5'-dioxo-2,3-dihydrospiro[indene-1,2'-[1,4]ozazolidine]-4'-yl}acetamide) and
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(page 975, ex. 846E). The examples of Michaelides, shown above, have carbocyclic (ex. 718) or heterocyclic (ex. 846E and example with
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fragment) substituents in the same position as instantly claimed compounds, moreover example compounds of Michaelides (e.g. 846E) show azetidinyl and N-methylazetidinyl substituents in the relevant position.
Thus, the combined teachings of prior art recite all the structural elements of the claimed compounds, which indicates that all the properties described by Applicant, such as solubility or pharmacological activities, apparently present, since instantly claimed chemical structures are taught by prior art. MPEP 2112.01.II states: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.")
Considering all said above, the instant invention, as a whole, is obvious over teachings of prior art.
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 1, 3, 4, 8 and 14 as obvious over teachings of Ogiwara and Michaelides is maintained.
Conclusion
Claims 1, 3, 4, 8 and 14 are rejected. No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/E.V.V./Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691