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
This application filed on 04/26/2023 claims the benefit of U.S. Provisional Patent Application No. 63/105,728, filed 10/26/2020 and PCT/US2021/056545 filed on 10/26/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/26/2023 and 08/07/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Election/Restriction
Applicant’s response filed on 10/30/2025 to Restriction/Election Requirement filed on 09/10/2025, is acknowledged. Applicant elected without traverse Group I drawn to a bifunctional compound and a pharmaceutical composition comprising a therapeutically effective amount of the bifunctional compound. Claims 1 and 50 read on the elected Group. Claims 51, 58-72 and newly added claims 73-74 of Group II are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of claims
Amendment and applicant argument submitted on 02/19/2026 have been received and have been carefully considered.
Claim 1 was amended, claim 2 was canceled, and claims 73-74 were added.
Claims 1, 50-51, and 58-74 are pending, claims 51 and 58-74 are withdrawn, and claims 1 and 50 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim 50 recites “A pharmaceutical composition, comprising a therapeutically effective amount of the bifunctional compound …”. The instant specification defines the “therapeutically effective amount” as:
As used herein, the term, "therapeutically effective amount" refers to an amount of a bifunctional compound of the present invention or a pharmaceutically acceptable salt or a stereoisomer thereof, or a composition including a bifunctional compound of the present invention or a pharmaceutically acceptable salt or a stereoisomer thereof, effective in producing the desired therapeutic response in a particular patient suffering from a disease or disorder characterized or mediated by aberrant protein activity. The term "therapeutically effective amount" thus includes the amount of a bifunctional compound of the invention or pharmaceutically acceptable salt or a stereoisomer thereof, that when administered, induces a positive modification in the disease or disorder to be treated, or is sufficient to prevent development or progression of the disease or disorder, or alleviate to some extent, one or more of the symptoms of the disease or disorder being treated in a subject, or which simply kills or inhibits the growth of diseased (e.g., cancer) cells, or reduces the amount of aberrant proteins in diseased cells. [0105].
Thus, claim 50 “therapeutically effective amount” is interpreted consistent with the instant specification.
Withdrawn Claim Rejections - 35 USC § 102
Rejection of claims 1-2 and 50 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by J. Bradner et al. (WO 2018/098280 A1, 05/31/2018), is withdrawn is in view of Applicant’s amendment submitted on 02/19/2026, that cancelled claim 2, and deleted compound DB-3-291 from claim 1.
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.
Claims 1 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Huang, H., et al. Cell Chemical Biology, Volume 25, Issue 1, 18 January 2018, Pages 88-99.e6, “Huang” cited in the IDS dated 04/26/2023).
Huang discloses TL12-186, a heterobifunctional degrader for FLT3 and BTK [Abstract, and page 25, Figure 1]:
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Huang’s compound TL12-186 differs from claim 1 compound SK-3-87 in the region highlighted with the dashed oval as depicted below:
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Huang’s linker includes 2 polyethylene glycol units, whereas claimed compound SK-3-87 includes 3 polyethylene glycol units. However, as provided in MPEP 2144.09, 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). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)
Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups, in instant case -O-CH2CH2) 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) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.).
The presumption of obviousness based on a reference disclosing structurally similar compounds may be overcome where there is evidence showing there is no reasonable expectation of similar properties in structurally similar compounds. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (appellant produced sufficient evidence to establish a substantial degree of unpredictability in the pertinent art area, and thereby rebutted the presumption that structurally similar compounds have similar properties); In re Schechter, 205 F.2d 185, 98 USPQ 144 (CCPA 1953).
A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (affidavit evidence which showed that claimed triethylated compounds possessed anti-inflammatory activity whereas prior art trimethylated compounds did not was sufficient to overcome obviousness rejection based on the homologous relationship between the prior art and claimed compounds); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967) (a 7-fold improvement of activity over the prior art held sufficient to rebut prima facie obviousness based on close structural similarity). However, a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences, in fact, in their respective properties which are determinative of nonobviousness. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, applicant’s recognition of the benefit is not in itself sufficient to distinguish the claimed compound from the prior art. In re Dillon, 919 F.2d 688, 693, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc).
In the instant case, and in view of MPEP 2144.09, the claimed compound and prior art compounds are: homologs, because as stated in the 103 Rejection above, the linker only differs by successive addition of the same chemical group, e.g., by -O-CH2CH2- groups. Please note that the MPEP stated that “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious “; The claimed compound and the prior art compound have very close structural similarities and very similar properties as the claimed compounds and prior art compounds have similar utilities, kinase degrader; and Applicant does not provide evidences of unexpectedly advantageous or superior properties of the claimed compounds over the prior art compounds.
Therefore, Huang’s compound TL12-186 renders instant claim 1 obvious.
With regard to claim 50, Huang teaches that TL12-186 displays potent binding to CRBN (IC50 = 12 nM), [page 5, 1st para., Figure 1]. Huang teaches a composition of compound TL12-186 is DMSO. [Page 14, 1st para.].
Conclusion
Claims 1 and 50 are rejected. No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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