Detailed Action
The present office action is in response to the reply filed on 02 Apr 2026.
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
Claims 1-3 and 5-10 of the pending application have been examined on the merits. Claims 4 and 11 of the instant application are withdrawn (see “Response to Applicant Elections” below).
Priority
Applicants identify the instant application, Serial #: 18/569,677, filed 13 Dec 2023, as a National Stage Entry of International Patent Application #: PCT/KR2022/009074, filed 24 Jun 2022, which claims priority from U.S. Provisional Application #: 63/214,600, filed 24 Jun 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 13 Dec 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Elections
Applicant’s election without traverse of Group I, claims 1-10, in the reply filed on 02 Apr 2026 is acknowledged. Applicant further elected the following species of Formula (I) in the reply filed 02 Apr 2026:
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A search for the elected species returned prior art.
Claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02 Apr 2026.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 contains a period on pg. 4, line 1 which is not part of an abbreviation or at the end of the claim. See MPEP § 608.01(m). Appropriate correction is required.
Claim Interpretation
Claim 9 is directed towards a “pharmaceutical composition for preventing or treating cancer…” The phrase “for preventing or treating cancer” is an intended use of the invention and is not considered a limitation and is of no significance to the claim construction. See MPEP § 2111.02(II).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 is dependent on claim 9.
Claim 9 is directed towards a “pharmaceutical composition for preventing or treating cancer…” which is not considered part of the claim limitations and is of no significance to the claim construction (see above). Claim 10 limits the types of cancers of claim 9. However, because the phrase, “for preventing or treating cancer” is not significant to claim construction, further limiting the cancers does not further limit the claim itself. Therefore claim 10 fails to further limit claim 9 and is rejected.
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.
Claim(s) 1-3 and 5-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Adkhikari et al. (Nat Chem Biol, 2020, 16:1179-1188; provided in IDS 12/13/23), hereinafter Adkhikari, further in view of Sells et al. (ACS Med Chem Lett, 2015, 6:630-634), hereinafter Sells, Aliagas-Martin et al. (J Med Chem, 2009, 52:3300-3307; provided in IDS 12/13/23), hereinafter Aliagas-Martin, Kargbo (ACS Med Chem Lett, 2019, 10:1251-1252), hereinafter Kargbo, and Goracci et al. (J Med Chem, 2020, 63:11615-11638), hereinafter Goracci.
Applicant has elected Group I, claims 1-10, in the reply filed 02 Apr 2026. In the same reply, applicant elected the single species of Formula (I) below:
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This species reads on claims 1-3 and 5-10. Applicant further claims a pharmaceutical composition where the compound of Formula (I) is the active ingredient (claim 9).
Adhikari teaches that several potent kinase inhibitors of AURORA-A have been developed and that the protein is a priority cancer target (pg. 1179, columns 1-2). One way to target both the catalytic and non-catalytic function is by using bifunctional small molecules called PROTACS which degrade target proteins (pg. 1180, column 1). These bifunctional compounds are made up of an E3-ubiquitin ligase binder attached by a linker to a target protein binding moiety (pg. 1180, column 1). Adhikari teaches several PROTAC compounds including JB170 (below) which uses the E3 ligase-binding moiety of thalidomide attached to alisertib, an AURORA-A inhibitor, by two ethylene glycol molecules and reduces AURORA-A levels by 69% (pg. 1180, column 2; and Fig. 1).
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In order to quantify binding affinity of the PROTAC compounds, Adhikari teaches performing isothermal titration calorimetry measurements and using a composition of JB170, 25 mM HEPES buffer, 200 mM NaCl, 0.5 mM TCEP, and 5% glycerol with JB170 as the tested ingredient (pg. 1192, column 1). While Adhikari teaches the degradation of AURORA-A by a PROTAC molecule with the same E3-ubiquitin ligase binding moiety as the instant claims, Adhikari does not teach the AURORA-A inhibitor or linker of the instantly elected compound.
Sells teaches the discovery of two Aurora A inhibitors, MLN8054 and alisertib, which is the AURORA-A binding moiety of JB170 taught by Adhikari (Abstract; and Fig. 1). Sells teaches that alisertib inhibits Aurora A kinase with an IC50 of 1 nM in HCT116 cells (Table 1). Further, alisertib binds to Aurora A selectively over Aurora B, by comparing phosphorylation of direct substrates Sells shows that alisertib has an IC50 for Aurora A of 7 nM and Aurora B of 1.5 µM (pg. 631, Table 1).
Aliagas-Martin teaches that inhibition of Aurora B produces unstable, polyploid tumor cells which may remain viable, providing a reason to prefer selective inhibition of Aurora A to treat cancer cells (pg. 3300, column 2). The authors further teach Compound 9 (below) which has selective activity against Aurora A over Aurora B (pg. 3302, Scheme 1 and Table 1):
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Compound 9 is the same structure as the PTM structure of the instantly elected compound of Formula (I). Compound 9 inhibits Aurora A with an IC50 of 0.0043 µM and Aurora B with an IC50 of 3.7 µM.
Kargbo teaches compounds to degrade IRAK4 kinases using PROTAC molecules (pg. 1251, column 1). Kargbo teaches the variation of linker group to the IRAK4 binding moiety and the cereblon binding moiety (pg. 1252, columns 1-2). The PROTAC molecules include Example 9 which has the same cereblon binding moiety and linker as the instantly elected compound:
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Goracci teaches that proteolysis targeting chimeras (PROTACS) are hetero-bifunctional molecules that induce a ligand to bind with the protein of interest, another ligand to recruit an E3 ubiquitin ligase, and a linker to concatenate the two ligands (pg. 11615). Goracci teaches that PROTACs can degrade proteins in a catalytic manner and open a new therapeutic modality (pg. 11615, column 2). Goracci teaches that better understanding of ADME properties of PROTACs are needed to better enable rational design of these molecules (pg. 11616, column 1). Goracci teaches a data set of two E3 ligase ligands, nineteen linkers, and four target proteins to gain insight into ADME properties of PROTACs (pg. 11619, column 1; pg. 11621, Fig. 1).
Based on the teaching of Adhikari, Sells, and Aliagas-Martin, a person of ordinary skill in the art would exchange alisertib, the AURORA-A binding moiety of JB170, taught by Adhikari, with Compound 9, taught by Aliagas-Martin, as the AURORA-A binding moiety. The artisan would be motivated to make this exchange because Compound 9 is more selective for Aurora A over Aurora B, as taught by Sells and Aliagas-Martin, and the selective binding of Aurora A is preferred to prevent tumor cells which may be unstable and polyploidy due to inhibition of Aurora B.
Further, based on the teachings of Adhikari, Kargbo, and Goracci, the artisan would modify the PROTAC taught by Adhikari with the E3 ubiquitin ligase moiety and linkers taught by Kargbo to create a rationally designed PROTAC molecule and understand the ADME properties of the compound. By swapping the linker and E3 ubiquitin ligase moiety of the compound taught by Adhikari, Sells, and Aliagas-Martin with the linker and E3 ubiquitin ligase moieties of Kargbo, the artisan would create the instantly elected compound. The artisan would further test the created compounds using isothermal titration calorimetry in a composition of the PROTAC compounds to determine affinity for the target compounds, as taught by Adhikari.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was 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.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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