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 .
Election/Restrictions
Applicant’s election without traverse of Group II, (drawn to a compound that inhibits MLL1-WDR5), in the reply filed on 12/19/2025 is acknowledged.
Claims 1-6, and 70-73 are pending of which claims 1-6 (Group I) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 70-73 have been examined on the merits.
Please note, for clarity of the record, Applicant ’s election of compound of Formula IIIb, as claimed in claim 73:
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Objections
The disclosure is objected to because of the following informalities: for failing to provide a complete and clear disclosure of the claimed subject matter. Specifically, the chemical structure appears incomplete in that portions of the structure and missing and/or improperly defined, resulting in ambiguity as to the precise chemical composition and connectivity (specification page 12, Formula (I) and (III)).
Appropriate correction is required.
Claim Rejections – 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 70 is rejected under 35 U.S.C. 102(a)(l) as being anticipated by Al-Awar US20190112290.
Regarding claim 70, Al-Awar (abstract; page 1) teaches compounds of formula I that inhibit binding between WDR5 and its binding partners, such that can be used as treatment for diseases mediated by WDR5-MLL1 binding, as an example. Al-Awar (page 66, [0935]) teaches the compound can be used to treat brain tumors, thus, it would have been anticipated that the active compound would reach the brain tumor through crossing the blood-brain barrier.
Therefore, claim 70 is anticipated.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 71-73 are rejected under 35 U.S.C. 103 as being unpatentable over Al-Awar et al., US20190112290, as applied to claim 70 above in view of You et al., US 20210139466.
Regarding claim 71-73, while Al-Awar describes the underlying core structure, however, Al-Awar does not explicitly disclose a compound of formula III or IIIb.
You (abstract; page 1), and as applied to claim 70 above, teaches compounds that inhibit MLL1-WDR5 protein-protein interaction. You (page 12, [0061], Example 8) teaches the following compound of Example 8, wherein R10 and R11 together form a 4-alkyl piperazinyl.
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You, however, does not teach a fluoro in the ortho position of the genus phenyl group, as well as
a trimethyl substituents at the piperazinyl ring, as required by the elected species. Nonetheless, You (page 2, [0020]) teaches the composition include “pharmaceutically acceptable salts of compound (I) and its solvates, which all have the same pharmacological functions as that of compound (I).”
Nonetheless, Al-Awar (page 300, [2343]; abstract; page 1) teaches WDRS/MLLl inhibitors with a slightly different genus species that does not contain a triazole. For example, Al-Awar (page 300, [2343]; abstract; page 1) teaches compound of Example 496 containing a -fluoro in the ortho position of the genus phenyl group, as well as a trimethylpiperazinyl, as required by the elected species. Al-Awar (page 409, Table 1) discloses both 1,2 dimethyl piperazinyl and trimethyl-piperazinyl substituents and identifies their contribution to WDR5
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inhibitory activity, thereby establishing that alkyl substitution on the piperazine core is a recognized relevant to the compound potency. In addition, given Table 1 consistently depicts compounds bearing a fluoro substituent at the ortho position of the central phenyl ring, demonstrating that this specific positional placement is significant to the compound inhibitory activity, representing optimization strategy. Thus, a POSITA would have recognized such importance by modifying You’s teachings with the Al-Awar’s disclosure to arrive at the claimed invention. Furthermore, the combined teachings of Al-Awar and You would have also provided a clear motivation to expand the substituent library to include trimetylpiperazinyl analogs and a fluoro substituent in the search for more potent WDR5 inhibitors.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine
grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or
improper timewise extension of the “right to exclude” granted by a patent and to prevent possible
harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where
the conflicting claims are not identical, but at least one examined application claim is not
patentably distinct from the reference claim(s) because the examined application claim is either
anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may
be used to overcome an actual or provisional rejection based on nonstatutory double patenting
provided the reference application or patent either is shown to be commonly owned with the
examined application, or claims an invention made as a result of activities undertaken within the
scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination
under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §
2146 et seq. for applications not subject to examination under the first inventor to file provisions
of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be
accompanied by a reply requesting reconsideration of the prior Office action. Even where the
NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used.
Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or
PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely
online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 70-73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. US12054478.
Although the claims at issue are not identical, they are not patentably distinct from each
other because compounds claimed in US patent '478 are comparable to those of the instant
claims.
For example, claim 1and 3 of the US patent ‘478 recites a method of treating leukemia in a subject by administering a compound of the formula I or a pharmaceutical acceptable salt thereof. The US Patent ‘478 discloses claims analogues compound represented by formula (I) in claims 1 and 3 as the instant claims 70-73. Although the specific species elected in the instant application is not listed in the US Patent ‘478, the structure variations of the species would be considered obvious variants of the genus structure. The claims of the US Patent ‘478 teach
compounds having significant overlap with the instant genus.
This rejection applies to the portions of the claim where a halogen atom is not attached to the ortho position relative to the triazole and the trimethyl substituent to the piperazine group. however, Al-war does teach the a -fluoro in the ortho position of the genus phenyl group, as well as a trimethylpiperazinyl at the piperazinyl ring, as required by the elected species. Al-Awar (page 409, Table 1) discloses both 1,2 dimethyl piperazinyl and trimethyl-piperazinyl substituents and identifies their contribution to WDR5 inhibitory activity, thereby establishing that alkyl substitution on the piperazine core is a recognized relevant to the compound potency. In addition, given Table 1 consistently depicts compounds bearing a fluoro substituent at the ortho position of the central phenyl ring, demonstrating that this specific positional placement is significant to the compound inhibitory activity, representing optimization strategy. Thus, a POSITA would have recognized such importance by modifying US Patent ‘478’s teachings in view of Al-Awar and You’s disclosure to arrive at the instant claimed invention. Furthermore, the combined teachings of US Patent ‘478, Al-Awar and You would have also provided a clear motivation to expand the substituent library to include trimetylpiperazinyl analogs and a fluoro substituent in the search for more potent WDR5 inhibitors, particularly against brain tumor.
Provisional nonstatutory double patenting rejection
Claims 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 11-12, 49-50 and 59-59 of copending Application No. 18/351,439. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in co-pending '439 are comparable to those of the instant claims.
For example, claim 1 drawn to a method of treating cancer in a subject having a tumor; using a composition comprising MLL1-WDR5 protein-protein interaction inhibitor compound of Formula I, and a PD-I inhibitor. Claim 1 of the instant application also teaches compound that inhibits MLL1-WDR5 protein-protein interactions and crosses the blood-brain barrier to treat cancer, as an example. The instant application does not explicitly teach an additional therapeutic agent, a PD-I inhibitor. Claim 48 and 49 of the co-pending '439 recites the method of claim, wherein the compound of Formula I is selected from the following, which is identical to that of instant claim 71 and 72.
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Claim 50 of the co-pending '439 recites the compound of Formula I is Formula (Id), which is identical to that of instant claim 73.
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The instant application teaches compounds of formula I that falls within the genus recited in the claims 1-2, 4, 11-12, and 19 of the co-pending '439. Therefore, it would have been obvious to a POSITA that this known treating cancer compound is encompassed by the claimed genus of the co-pending '439, because both the co-pending '439 band the instant application use the same compound for the same utility.
However, the only distinction between the claims is the additional compound, a PD-1 inhibitor, in the co-pending’ 439. Giving the co-pending claims encompass administration of the same compound of formula I for the same therapeutic benefit, thus the exclusion of an additional agent does not render the instant claims patentably distinct. Since the co-pending and instant claims are directed to the same compound of formula I for the utility, therefore the instant claims are an obvious variation of the cop-pending application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 11-12 and 15-16 of copending Application No. 18/120,318. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in co-pending '318 are comparable to those of the instant claims.
For example, claim 1 drawn to a compound of formula II or a pharmaceutical acceptable salt thereof, wherein the compound is selected from the following
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The claims at issue are not identical, however, they are not patentably distinct from each other because the instant claims disclose the same compound and composition. Therefore, the compound structure would not be novel, and note that the claims are for the same invention or an obvious variant thereof.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Therefore, no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622