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 .
DETAILED ACTION
Claims 73-92 are pending in the instant application.
Claims 75, 78, and 90-92 are withdrawn from consideration.
Claims 73, 74, 76, 77, and 79-89 are examined herein.
Priority
The instant application claims benefit of foreign priority to PCTCN2020111722, filed on 27 August 2020, and the benefit of priority to PCT/CN2021/115167, filed on 27 August 2021. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 27 August 2020.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 02 March 2023, 02 March 2023, and 21 October 2025, are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Election/Restrictions
Applicant’s election of Groups I and II, claims 73-89, without traverse, in the reply filed on 21 October 2025 is acknowledged. In addition the specie election of P-221, or 3-(5-(2-(1-(3-(4-(5-acetyl-3-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)piperidin-1-yl)-3-oxopropyl)piperidin-4-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione is acknowledged. The elected specie reads on claims 73, 74, 76, 77, and 79-89. Therefore claims 75, 78, and 90-92 are withdrawn for not reading on the elected group or specie.
As the elected specie is drawn to the genus of Formula 3C1 and Formula 5B, these will be the focus of the below rejection.
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If the elected species is not identified in the art, the search will be expanded to additional species per MPEP 802.03.
Claim Interpretation
Note, P300 is also known as EP300. Thus the terms are interpretated to refer to the same protein and may be used interchangeably throughout the document.
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 73, 74, 76-78, and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 87 and 86 of co-pending Application No. 17434587 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 73, 74, and 76-78, the co-pending application recites a bivalent compound comprising a cyclic-AMP response element binding protein (CBP) and/or adenoviral E1A binding protein of 300 kDa (P300) ligand (CBP/P300 ligand) conjugated to a degradation tag via a linker moiety, or a pharmaceutically acceptable salt thereof, wherein: (I) the CBP/P300 ligand is a moiety of Formula 3U or Formula 3W and (II) the degradation tag is a moiety selected from Formula 5E and Formula 5F and (III) the linker is selected from the group consisting of -(CO)-(CH2)3-7- and -(CH2)1-2(CONH)(CH2)3-7- (claim 86).
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These corresponds to the instant Formulas of 3A1, 3C1, 5B, and 9.
Regarding claim 80, the co-pending application recites A pharmaceutical composition comprising a bivalent compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. (claim 87).
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.
Claims 73, 74, 76, 77, 79-84, and 86-89 is/are rejected under 35 U.S.C. 103 as being unpatentable over Romero et al. (WO2016086200A1; cited by Applicant on 1449 IDS) in view of Qi (WO2020092907A1; cited by Applicant on 1449 IDS) and Liu (WO2020038415A1).
Regarding claim 73, Romero teaches CBP and/or EP300 inhibitors of Formula (I) (claim 1) (pictured below). Formula (I) overlaps with the instant Formula 3C1 (pertaining to the elected species) when:
R1 is a 6 membered heterocycle, optionally substituted
R2 and R3 taken together to form a 10 membered heterocycle, substituted with two groups Re; wherein Re is independently C1 alkyl, substituted with 2 halo, and heteroaryl substituted with C1 alkyl.
R4 is -C(O)-N(Rh)2, wherein Rh is independently hydrogen and C1 alkyl.
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Romero does not teach the CBP/P300 ligand to be conjugated to a degradation tag via a linker.
Qi teaches bifunctional compounds that target EP300 for degradation having the structure of Formula (I) (paragraph [0004]) (pictured below).
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It would be prima facie obvious to one of ordinary skill in the art to substitute the EP300 targeting ligand taught by Qi with the genus of ligands taught by Romero. A skilled artisan would be motivated to link a degradation tag to the compounds of Romero to improve efficacy and protein degradation.
Qi does not teach the linker and degradation tag of the instant claims.
Liu teaches bivalent compounds comprising TRK ligands conjugated to a degradation tag via a linker. Liu teaches the degradation tag of Formulas 5E (claim 48) which overlaps with the instant Formula 5B (pertaining to the elected species) when:
R1 is H
V is CR2; wherein R2 is H
W is CR2; wherein R2 is H
Z is CR2; wherein R2 is H
Y is NR3; wherein R3 is C1 alkyl
Z is CR5R6; wherein R5 is hydrogen and R6 is hydrogen
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Liu teaches the linker of Formula 9A (claim 58) which overlaps with the instant Formula 9 (pertaining to the elected species) when:
A is CO
W is a 6-membered heterocycle
B is null
m is 2
n is 1
R1 is hydrogen
R2 is hydrogen
R3 is hydrogen
R4 is hydrogen
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It would be prima facie obvious to the skilled artist to comine the teachings of Romero, Qi, and Liu to arrive at the instant invention. Qi teaches the structure of an EP300 targeting ligand conjugated to a degron, a type of degradation tag, via a linker. Romero teaches CBP/EP300 ligands of the instant Formula 3C1. Liu teaches the linker and degradation tag of the instant Formula 5B and 9. The skilled artisan would be motivated to make the substitution of the EP300 ligand taught by Romero and the linker and degradation tag taught by Liu into the Formula taught by Qi to improve the drug’s efficacy and protein degradation.
Regarding claim 74, Liu teaches A, which corresponds to the instant AL, to be CO and B which corresponds to the instant BL, to be null (claim 58).
Regarding claims 76, 77, and 79-80 the elected species comprises the recited linker –(CH2)0-3(CO)-(CH2)0-5-RLr-(CH2)0-5–, wherein the linker is –(CO)-(CH2)2 -RLr-(CH2)–, and RLr is a 6-memebered heterocycle. This corresponds to the teaching of Liu’s Formula 9A where A is CO, W is a 6-membered heterocycle, B is null, m is 2, n is 1, R1 is hydrogen, R2 is hydrogen, R3 is hydrogen, and R4 is hydrogen.
Regarding claim 81 and the elected species, Romero teaches the preferred embodiment on page 782 of claim 39 (pictured below) and Liu teaches CPD-246 on page 295. Substituting the oxepane taught by Romero for the linker and degradation tag taught by Qi brings the skilled artisan to the basic components of the instant invention. Substitution of the linker and degradation tag as taught by Liu, for those taught by Qi brings the skilled artisan to the elected species P-221. CPD-246 of Liu shows the degradation tag of the elected species. While Liu does not have a preffered embodiment of the linker of the elected species, Formula 9A does overlap with the isntant Formula 9 for the linker moiety. Liu does provide a long list of possible substituents for the Markish groups of the linker moirty, however Liu does disclose embodiments with elements of the elected specie linker that would guide the skilled artisan to particular substituents in the possible list, such as the piperidinyl group seen in thelinker of the preferred embodiments of CPD-215 and CPD-218 (page 290).
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Regarding claims 82 and 83, Romero teaches a composition of Formula (I) or a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier (claim 65). Qi teaches the same (claim 30).
Regarding claim 84, Romero teaches a method of treating a CBP and or EP300-mediated disorder comprising administering a compound of Formula (I) (claim 68). Qi teaches A method of treating a disease or disorder involving dysregulated EP300 activity, comprising administering a therapeutically effective amount of the bispecific compound of formula (I) (claim 33).
Regarding claims 86 and 87, Romero teaches a method of treating a CBP and or EP300-mediated cancer comprising administering a compound of Formula (I) and a cytotoxic agent (claim79). Qi also teaches administering additional therapuetics (claim 39).
Regarding claim 88, Romero teaches the CBP and or EP300-mediated disease to be prostate cancer, lung cancer, breast cancer, pancreatic cancer, colorectal cancer, and melanoma (claim 70).
Regarding claim 89, Qi teaches administering the EP300 degraders in resistant lines (paragraph [0326]).
Claims 73, 74, 76, 77, and 79-89 is/are rejected under 35 U.S.C. 103 as being unpatentable over Romero et al. (cited above) in view of Qi (cited above) and Liu (cited above) in further view of Giles et al. (Trends Genet.1998;14:178-183; cited by Applicant on 1449 IDS).
The teachings of Romero, Qi, and Liu are disclosed above and incorporated by reference herein.
Regarding claim 85, the combination of teachings above does not teach the CBP-P300-mediated disease arising from CBP/P300 expression, mutation, deletion, and/or fusion.
Giles et al teaches CBP/P300-mediated disease can result from mutations (Figure 4.)
It would be prima facie obvious to one of ordinary skill in the art that a CBP/P300-mediated disease that arises from a mutation, as taught by Giles, can be treated using the same method taught by Romero, Qi, and Liu, though they are silent on the underlying cause of the CBP/P300 mediated disease.
Conclusion
Claims 73, 74, 76, 77, and 79-89 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621