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 .
This is a Final Office Action.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on December 8, 2025 is acknowledged. Group I, drawn to a tricyclic-benzyl-imidazo core compounds of formula (II), embraced by claims 1-19 was elected by Applicant.
Applicant elected the following species, Example 4, paragraph [0150] and the examiner has expanded the search to include the species on the right below:
:
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and
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. Both species read on claims 1-10, 13-17 and 19.
.
Claims 1-20 are pending and claims 1-10, 13-17 and 19 are under consideration. Claims 11, 12 and 18 are withdrawn based on the species election and claim 20 is withdrawn based on the lack of unity.
Specification
The objection to the disclosure because of the title is withdrawn based on the amendments.
Claim Objections
The objection to claims 1, 11 (provisional objection) and 12 (provisional objection) because of the phrase “R6, R7” or “R1, R7” should be replaced with “R6 and R7” or “R1 and R7” is withdrawn based on the amendments.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The rejection of claims 1-10, 13-17 and 19 under AIA 35 U.S.C. 103(a) as being unpatentable over Chakravarty et al. (WO 2018197653) in view of Patani et al. (Chem. Rev. 1996, 96 (8), 3147-3176) and Cambridge MedChem Consulting (2017, <https://www.cambridgemedchemconsulting.com/resources/bioisoteres/carbonyl_bioisosteres.html>, downloaded 12/27/2025, pp. 1-4) is withdrawn.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The two previous 103 rejection have been combined since the rationale for both rejections is the same.
Claims 1-10, 13-17 and 19 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Chakravarty et al. (WO 2018197653) in view of Patani et al. (Chem. Rev. 1996, 96 (8), 3147-3176), and Lu et al. (Chem. Pharm. Bull., 2016, 64(11), 1576-1581).
The present application claims compounds of formula (II), see bottom left, and more specifically the following species in claim 19, page 11:
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164
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.
The reference teaches the following species:
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, see the abstract. The present claims exclude this compound.
The difference between the claimed species and the prior art is the substitution at X and Y, an oxygen (=O) versus Applicant’s oxime on a nitrogen atom (=N-OH).
Lu et al. teach the substitution of =O to an oxime (=N-OH) to a PI3K inhibitor to increase the solubility, kinase inhibition, and cell permeability, see page 1576, right hand column, lines 19-20. See also page 1577, Table 1 and Table 2, for the compounds 4a-4n and 5a-5n. Furthermore, the molecules have the same utility as the presently claimed compounds.
Patani et al. teach that the two groups are bioisosteres of each other and are equivalent, see page 3167, Table 38 and Table 39, compounds 82a and 82b.
Therefore, it would be obvious to a person of ordinary skill in the art to replace =O with =NOH because Patani et al. teach the equivalency of said groups and Lu et al. teach the substitution to improve the properties of a PI3K inhibitor.
Applicant traverses by stating, “Patani and Cambridge MedChem Consulting webpage both describes bioisosteres of carbonyl group among which some imine groups such as =N-OCH3 or =N-OH are listed. It is evident that Patani and Cambridge Cambridge MedChem Consulting webpage merely describes general concept of bioisosteres. No credible arguments and evidences are provided in Patani and Cambridge MedChem Consulting webpage to make one of ordinary skill in the art believe that this teaching is suitable for Chakravarty's GDC-0077 compound and replacing carbonyl group in Chakravarty's GDC-0077 compound with its bioisosteres would result in compounds with retained biological activity.”
This is not persuasive. The Cambridge reference has been removed from the rejection and therefore any traversal regarding said reference is moot. The rejection has been amended to include the rationale in the Lu reference for the substitution. The Patani reference supports the substitution of =O to =NOH.
Applicant further states, “Chakravarty discloses GDC-0077 as a potent PI3K inhibitor. Chakravarty does not disclose how GDC-0077 interacts with PI3K protein, and any structure-activity relationships of GDC-0077 for PI3K inhibition. There are 29 non-hydrogen atoms contained in GDC-0077, and without hindsight one of ordinary skill in the art would not select the carbony groups for modification. It is unknown whether the carbonyl of GDC-0077 is critical for it's biological activity and can be modified or not, so no reasonable expectation of success can be derived that replacing carbonyl group in Chakravarty's GDC-0077 compound with its bioisosteres of imine groups (=N-OCH3 or =N-OH) would result in compounds with retained biological activity.”
This is also unpersuasive. The combination of the references expressly suggests substituting =O for =NOH. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant notes, “The Examiner asserts that Lu et al. teach the substitution of a similar compound at a similar location on the molecule, and the molecules have the same utility as the presently claimed compounds. Applicant respectfully disagrees.” Applicant proceeds to compare the differences in the instantly claimed compounds and the compounds found in the Lu reference.
Applicant is correct. There are many differences between the compounds. However, the reference teaches the substitution of =O to an oxime (=N-OH) to a PI3K inhibitor to increase the solubility, kinase inhibition, and cell permeability, see page 1576, right hand column, lines 19-20.
Applicant contends, “By replacing the carbonyl group with imine group, the present application has achieved at least one unexpected technical effect in terms of PI3Kα subtype selectivity and pharmacokinetic properties, which are supported by the biological data in the present application.
For an example, compounds 3 and 6 of the present application differ from GDC007 merely in the imine group (vs GDC007's carbonyl group) and achieve higher PI3Kα subtype selectivity over PI3Kδ/y compared with GDC007 as shown in the following table (data is cited from table 2 of the present application). It is evident that this unexpected effect is attributed to the replacement of carbonyl with imine group.”
Table 2 is provided below:
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461
641
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.
This is not persuasive. The compounds compared in the table are not the compounds that the obviousness rejection is based over, and therefore, this does not overcome the 103 rejection.
Applicant further contends, “For another example, compound 008 of the present application differs from GDC007 merely in the imine group (vs GDC007's carbonyl group) and achieve higher high exposure, lower clearance rate, and better oral bioavailability compared with GDC007, as shown in the following table (data is cited from table 4 of the present application). It is evident that this unexpected effect is attributed to the replacement of carbonyl with imine group.”
The comparison table is shown below:
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356
649
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.
This is also unpersuasive. The compounds compared in the table are not the compounds that the obviousness rejection is based over, and therefore, this does not overcome the 103 rejection.
MPEP 716.02(D) states, “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). The non-obviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range if one of ordinary skill in the art would be able to determine a trend in the exemplified data which would allow the artisan to reasonably extend the probative value thereof. In re Kollman, 595 F.2d 48, 201 USPQ 193 (CCPA 1979).
Thus, the rejection is maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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