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 .
Priority
The instant application is a 371 National Stage Entry of PCT/PCT/KR2021/018161 filed on December 2, 2021 which claims priority to foreign application Nos. KR10-2021-0085982 filed on June 30, 2021 and KR10-2020-0167725 December 3, 2020.
Status of Claims
Acknowledgement is made of original (1-14) claims filed on November 3, 2025. Claims 1-14 are pending in instant application. Claims 7, 14 are withdrawn. Claims 1-6, 8-13 are presently examined.
Information Disclosure Statement
The information disclosure statement filed on June 1, 2023 has been considered.
Election/Restrictions
Applicant’s election without traverse of Group I and Compound 1 in the reply filed on November 3, 2025 is acknowledged.
The elected species is understood to be CAS# 2776191-30-9.
The Examiner notes that the ULM, Linker, and GTM moieties of the elected species were not explained in the 11/3/25 Remarks (see 9/8/25 Requirement for Restriction at p. 4). The Examiner has taken the stance that ULM is
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, Linker is
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, and GTM is
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346
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. Accordingly, claim 7 does not read on the elected species (LULM must be -NHCH2CH2OCH2CH2-, LINT must be
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72
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and LGTM must be -CH2O-).
Claim 14 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Claim 14 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 November 3, 2025.
Following extensive search and examination, the elected species was deemed anticipated and/or obvious in view of the prior art as applied below.
Claim Interpretation
At claim 9, the preamble “for degrading GPX4 protein” is understood to recite an intended use that is fully satisfied by the structures set forth in the body of the claim (see MPEP § 211.02(II); 2111.04(I)). Likewise, the dependent claims 10-13 also recite the intended use and are assumed to be satisfied by a composition comprising a compound of claim 1 and an excipient (see also below 35 USC 112(d) Rejection).
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.
Claims 11-13 are 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.
The claims recite intended use without additional structural limitations compared to instant claim 10 (a composition comprising a compound or pharmaceutically acceptable salt of claim 1 and at least one type of pharmaceutically acceptable carrier).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 5-6, 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/140380 A1 to Mainolfi et. al.1
Regarding claim 1, Mainolfi teaches compounds of structure TMB-L-UBM which corresponds with the instant ULM-Linker-GTM.
Limitation
Mainolfi
Instant
Generic Structure
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TBM/GTM
Target binding moiety capable of binding to a targeted protein
GPX4 protein binding moiety
L
Bivalent moiety that connects TBM and UBM
A group that chemically connects ULM and GTM
UBM/ULM
Ubiqutin binding moiety capable of binding to a ubiquitin ligase such as E3 ubiquitin ligase (e.g. cereblon)
CRBN E3 ubiquitin ligase binding moiety
Regarding claims 5-6 and ULM moiety, Mainolfi teaches UBM may be Formula V-a’ (see Mainolfi claim 7 and at p. 92) wherein
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103
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reads on instant ULM Formula A2 when L1 is a covalent bond, X3 is be C(R1)2 and R1 may be H, and Ring B may be an 8-10 membered heteroaryl ring, such as
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(see Mainolfi p. 79 [0143]).
Mainofli Formula V-a’
Instant ULM Formula A2
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103
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81
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Regarding claims 9, 10, 11, 12, 13 and a composition, Mainolfi claims compositions comprising disclosed compounds and an pharmaceutically acceptable carrier, adjuvant, or vehicle (see Mainolfi claim 18). Mainolfi also claims a utility of treating cancer (see Mainolfi at claim 23).
The prior art differs from the instant claims as follows: While instant claims limit GTM to a GPX4 protein binding moiety, Mainolfi broadly designates the TBM moiety as capable of binding a targeted protein.
However,
Regarding GTM, Mainolfi teaches the targeted protein may be GPX4 (see Mainofli at p. 367 [00230]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
An artisan would readily appreciate that the TBM moiety may be a GPX4 protein binding moiety because the prior art suggests GPX4 may be the targeted protein (see MPEP § 2143(I)(E) and (G)).
Furthermore, it is well-within the ordinary skill in art to select a target protein binding moiety for use in targeting a protein as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 2-4, 8, are rejected under 35 U.S.C. 103 as being unpatentable over Mainolfi as applied to claims 1, 5-6, 9-13 above and in further view of Eaton et. al.2
Recall Mainofli teaches corresponding with instant Formula I, including a ULM moiety corresponding with instant Formula A-2.
The prior art differs from the instant claims as follows: Mainolfi (i) does not specify L2 as the instantly elected Linker
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and (ii) does not specify the GPX4 binding moiety to be
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.
However,
Regarding instant Linker, Mainofli exemplifies L2 corresponding with instant Linker may be
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(see Mainolfi at p. 68) which reads on instant Compound 2 Linker (see claim 8), differing by instantly elected Linker only in a repeated OCH2CH2 unit.
Mainolfi Linker Exampler
Instant Compound 2 Linker
Instant Elected Species Linker
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Regarding claims 2, 3, 4, 8 instant GTM, Eaton teaches ML210 which reads on the instantly elected ULM moiety (see Eaton at p. 498 Figure 1) and instant Formula G-1 when R1 is a substituted heteroaryl specifically isoxazole substituted with methyl and NO2 (also reading on instant claim 4 Formula G-2 when M is
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and R4 is methyl), R2 is halogen specifically chloro.
Eaton ML210
Instant Elected GTM
Instant Formula G-2
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding the elected species and linker, per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…homologs…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. Here, the prior art teaches highly similar structural linker homolog of the instantly claimed invention (instant elected linker OCH2CH2 vs Mainolfi OCH2CH2OCH2CH2), wherein such homologs have the same, exact utility as the instantly disclosed treating cancer; accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of cancer, exactly as taught and suggested in view of the prior art. Mainolfi still teaches a linker instantly claimed (see instant Compound 2).
Regarding a structurally defined GPX4 binding moiety, per MPEP § 2143(I)(A), a prima facie case of obviousness exists for combining prior art elements according to known methods to yield predictable results. It would have been obvious to one skilled in the art to incorporate Eaton’s GPX4 targeter ML210 in Mainolfi’s TBM functional group because Mainolfi teaches TBM may be a GPX4 binding moiety.
Furthermore, it is well-within the ordinary skill in art to select a known GPX4 protein-binding compound for use as a GPX4 targeting binding moiety in a known bifunctional compound template for the same purpose as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 1-6, 8-13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Published July 18, 2019. Filed January 14, 2019. Cited in the IDS filed 6/3/23. Hereinafter Mainolfi.
2 Eaton et. al. "Selective covalent targeting of gpx4 using masked nitrile-oxide electrophiles" Nature Chemical Biology 2020, 16, 497-506. DOI: 10.1038/s41589-020-0501-5. Published March 30, 2020. Cited in IDS filed 6/1/23. Hereinafter Eaton.