DETAILED ACTION
Status of Application
The Examiner acknowledges receipt of the amendments filed on 2/19/2026 wherein claims 1, 5-8, 13 have been amended and claims 3, 4, 10 and 12 have been cancelled.
Claims 1, 2, 5-8 and 13-14 are presented for examination on the merits. The following rejections are made.
Response to Applicants’ Arguments
Applicant’s amendment filed 2/19/2026 overcomes the rejection of claim 1 made by the Examiner under 35 USC 112(b). This rejection has been withdrawn.
Applicant’s arguments filed 2/19/2026 regarding the rejection of claims 1, 2, 5-8 and 13-14 made by the Examiner under 35 USC 103 over Crew et al. (US 2018/0215731) has been considered but is not considered persuasive and is MAINTAINED for the reasons of record in the office action mailed on 11/24/2025.
In regards to the 103 rejection, Applicant asserts the following:
A) The amendments narrow the claims to more narrowly scope the invention to be reflective of the compounds (e.g. compounds 1, 5) that have been discovered to not degrade any native BET bromodomains or any unrelated off targets in MOLT4 cells after 6-hours of treatment. Instead, the compounds of the invention selectively bind mutant BRD but not WT BRD.
In response to A, although the claims have been narrowed, the Examiner is not persuaded that the data provided is demonstrative of unexpected results as there is no comparative data between the compounds deemed obvious. That is, it is unclear if the compounds as claimed (having a methyl substituent) exhibit unexpectedly improved BRD activity relative to similar compounds having a hydrogen substituent. Like the claimed compounds, the prior art compounds possessing a hydrogen exhibit BRD activity. Thus, comparative data between the hydrogen and methyl containing molecules would clarify this question. As to the rest of the structure, the major structural components are obvious as each are described in the specification and claims of the reference application.
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.
Claims 1, 2, 5-8 and 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Crew et al. (US 2018/0215731)
Crew is directed to bifunctional compounds intended to bind a target protein such that the target protein is placed in proximity to a ubiquitin ligase to effect degradation (and inhibition) of that protein. Crew’s bifunctional compounds contain a cereblon ligand and bifunctional compound having the following generic structure: CLM-L-PTM (see claim 2).
CLM is the small molecular cereblon ubiquitin ligase binding moiety and may possess the following structure:
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(see claim 8) (see instant claims 1 and 8). The CLM structure described by Crew overlaps with the degron ligand elected in the response filed 8/7/2025.
PTM is the protein targeting moiety and may possess one of the following structures:
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or
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(where R is a linking group (L); see [0217]) or
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(see [0291] and claim 19). These PTM structures are substantially overlapping with the targeting ligand TL1 structure elected in the response filed 8/7/2025.
L is a linker molecule that connects the CLM and PTM moieties has the generic structure –(AL)q wherein AL may be that of CRL1RL2 where RL1 and RL2 may both be H and q is to be an integer greater than 1 (see claim 9). Thus, an alkyl group of C1 and above is contemplated, e.g.
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, with C2, C5 and C8 alkyl groups being contemplated (see claim 9) (see instant claims 4-7). It is noted that the N of the aforementioned groups is already present on the PTM structure and the O is present on the CLM structure (see above).
Alternative linking groups are contemplated such as those that include PEG such as
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wherein n and o is an integer from between 0-20 (see claim 12). When n or o are independently 0 and 1, the resulting linker would yield a generic structure that overlaps with the structure of instant claim 1. The PEG containing structures of 6 and 7 would have been obvious as well as those structures are broadly provided for by the PEG structure of Crew. It is observed that the modified PEG linker is terminated with an O (of the CLM) and an N (of the PTM) (see instant claim 1).
Other linking groups include those having amide bonds such as
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and
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which overlaps with the linker used in structures 1 and 4 of instant claim 13.
The bifunctional compounds of Crew may be provided as a therapeutic composition comprising a pharmaceutically acceptable carrier (see [0021]) (see instant claim 14).
Crew fails to teach the elected TL1 structure where R is a methyl. It is noted that the PTM structure of Crew possess a H where the elected structure has a methyl (at the arrow):
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.
The modification of Crew’s structure to include a methyl group where Crew provides a hydrogen is considered obvious as methyl and hydrogen are interchangeable and structurally analogous. Absent evidence to the contrary, the modification of Crew’s bifunctional compound to include a methyl where hydrogen is taught would reasonably be expected to possess the same chemical properties as the structure possessing a hydrogen. The obvious modification of Crew’s bifunctional compounds would result in compounds of overlapping structure to those claimed and a reasonable expectation that the modified compounds similarly exhibit the ability to bind target proteins such that the target protein is placed in proximity to a ubiquitin ligase to effect degradation.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Potentially Relevant Prior Art:
Yang et al. (US2022/0117982)
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 extension fee 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 KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611