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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 8th, 2026 has been entered.
All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed July 8th, 2026, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
Election/Restrictions
Claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, 139 – 141, and 146 – 151 are currently pending in the application. However, due to a restriction requirement mailed July 18th, 2025, claims 146 – 151 are withdrawn from further consideration and claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are being examined on the merits herein.
Claim Objections
Claim 22 is objected to because of the following informalities: spelling error in line 9 of the claim. Line 9 recites “5-(2-aminomethy-henyl)- thien-2-yl,” which should be “5-(2-aminomethy-phenyl)- thien-2-yl.” Appropriate correction is required.
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 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Hillig et. al. ((2019), Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction, PNAS, 116, 2551 – 2560; cited on the IDS dated December 18th, 2023) in view of Li et. al. ((2020), PROTAC**: A Novel Technology for Drug Development, Chemistry Select, 5, 13232 – 13247).
Regarding claims 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141, Hillig et. al. teach that the most-studied guanine nucleotide exchange factor (GEF) for RAS is the protein Son of Sevenless (SOS) for which two human isoforms, SOS1 and SOS2, are known. See page 2551 column 2 paragraph 1. Additionally, Hillig et. al. teach that fragment-based screening, rational design, and high-throughput screening approaches led to identification of small molecules addressing the KRAS–SOS1 interaction, resulting in compounds with moderate micromolar affinity. See page 2551 column 2 paragraph 1. Furthermore, Hillig et. al. teach selective and potent compounds with double-digit nanomolar affinity to SOS1, submicromolar antiproliferative activity in tumor cell lines, and synergistic combination potential with the covalent KRASG12C inhibitor ARS-853. See page 2552 column 1 paragraph 1. Specifically, Hillig et. al. teach compounds 1 of structure
PNG
media_image1.png
140
230
media_image1.png
Greyscale
with an IC50 = 320 nM, compound 15 of structure
PNG
media_image2.png
128
228
media_image2.png
Greyscale
with an IC50 = 170 nM, compound 17 of structure
PNG
media_image3.png
128
270
media_image3.png
Greyscale
with an IC50 = 140 nM, and compound 19 of structure
PNG
media_image4.png
132
274
media_image4.png
Greyscale
with an IC50 = 51 nM. See page 2555 Figure 3 and page 2557 Figure 4. See claim 1 limitation for a compound of Formula (I) where U = Y = -C=; V = X = -C(R4)= where R4 = -OR1a where R1a = CH3; R1 = either H or CH3; R3 = H; R2 = -CH(CH3)-; and Q = substituted thiophene, naphthalene, or substituted benzene, where Qa = bromo, heteroaryl, or aryl. See claim 8 limitation for a compound of formula II where R2a = H; R2b = CH3; and R2c = substituted thiophene, naphthalene, or substituted benzene. See claim 13 limitation for a compound of claim 8 where R2c = substituted thiophene, naphthalene, or substituted benzene. See claim 22 limitation for a compound where R2c is 3 – bromophenyl, napth-1-yl, and 5-(2-aminomethy-phenyl)-thien-2-yl. See claim 76 limitation for a compound of claim 1 where the moiety is : T1
PNG
media_image1.png
140
230
media_image1.png
Greyscale
, T9
PNG
media_image2.png
128
228
media_image2.png
Greyscale
, T10
PNG
media_image3.png
128
270
media_image3.png
Greyscale
, or T12
PNG
media_image4.png
132
274
media_image4.png
Greyscale
. Moreover, Hillig et. al. teach that the IC50 values of these compounds were determined in assay buffer comprising 10 mM HEPES pH 7.4 (AppliChem), 150 mM NaCl (Sigma), 5 mM MgCl2 (Sigma), 1 mM DTT (Thermo Fisher), 0.05% BSA Fraction V pH 7.0 (ICN Biomedicals), 0.0025% (v/v) Igepal (Sigma)]. See page 14 paragraph 3. See claim 141 limitation for a pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
However Hillig et. al. fail to teach a compound of Formula (I) where L is a linker and RE is an E3 ubiquitin ligase binding moiety. See claim 1 limitation. Moreover, Hillig et. al. fail to teach a compound where RE is cereblon (CRBN). See claims 81 and 82 limitation. Furthermore, Hillig et. al. fail to teach a compound where the RE moiety has the structure EC-I which encompasses Formula (EC-V). See claim 83 and 85 limitation. Additionally, Hillig et. al. fail to teach a compound where Z is -CH2- or -C(O)-. See claims 90 – 91. Moreover, Hillig et. al. fail to teach a compound where RE5 = H or F. See claim 92 limitation. Furthermore, Hillig et. al. fail to teach a compound where L =
PNG
media_image5.png
92
108
media_image5.png
Greyscale
and/ or
PNG
media_image6.png
96
106
media_image6.png
Greyscale
. See claim 129 and 139.
Nevertheless, Li et. al. teach that small molecule inhibitors inevitably increase the probability of drug resistance, especially in the late stage of some tumors. See page 13232 column 1 paragraph 1. Li et. al. teach that proteolysis targeting chimeras (PROTACs) can target degrade abnormal proteins by utilizing the ubiquitination-proteasome pathway, which can rapidly and efficiently degrade targets with low concentration and is expected to relieve the drug resistance condition. See page 13232 column 1 paragraph 1. Furthermore, Li et. al. teach that PROTACS are heterobifunctional molecules consisting of three parts: an E3 ligase ligand, a protein of interest (POI) ligand and a chain to connect these ligands (linker). See page 13232 column 1 paragraph 2 and column 2 paragraph 1. Additionally, Li et. al. teach cereblon (CRBN) of structure
PNG
media_image7.png
160
898
media_image7.png
Greyscale
. See page 13234 Table 1. See claims 81 and 82 limitation for a compound where RE is cereblon (CRBN). See claims 83 and 85 limitation for a compound of EC-I which encompasses Formula (EC-V)where Z = -CH2- or -C(O)-; Z1 = Z2 = Z3 = Z4 = -C=; RE1 = RE2 = RE5 = H; m = 1; and AE is a bond. See claim 90 limitation for a compound where Z = -CH2-. See claim 91 limitation for a compound where Z = -C(O)-. See claim 92 limitation for a compound where RE5 = H. Moreover, Li et. al. teach example linkers PROTACS 2, 10 and ARV-825, of structures
PNG
media_image8.png
320
622
media_image8.png
Greyscale
with the circled linkers. See page 13239 Table 2. See claims 129 and 139 for a compound where L =
PNG
media_image5.png
92
108
media_image5.png
Greyscale
and/ or
PNG
media_image6.png
96
106
media_image6.png
Greyscale
.
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify compounds 1, 15, 17, and 19 of Hillig et. al. in view of Li et. al. that is to attach a linker and E3 ligation moiety. One of ordinary skill in the art would have been motivated to make this modification to overcome or reduce the probability of drug resistance in the late stage tumors. One of ordinary skill in the art would have had a reasonable expectation of success because PROTACS can degrade targets with low concentration and thus is expected to relieve the drug resistance condition.
Claims 9 – 11, 23 – 24, 35, 78 – 79, 80 and 84 are rejected under 35 U.S.C. 103 as being unpatentable over Hillig et. al. ((2019), Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction, PNAS, 116, 2551 – 2560; cited on the IDS dated December 18th, 2023) in view of Li et. al. ((2020), PROTAC**: A Novel Technology for Drug Development, Chemistry Select, 5, 13232 – 13247), as applied to claims 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141 above.
The teachings of Hillig et. al. and Li et. al. as they relate to claims 1, 8, and 83, from which claims 9 – 11, 23 – 24, 35, 78 – 79, 80, and 84 depend, are given previously in this office action and are fully incorporated here.
However, the prior art of Hillig et. al. and Li et. al. fail to teach a compound where L-RE is attached at different positions on the ring. See claims 9 – 11, 23 – 24, 35, 78 – 79, and 80 limitation. Moreover, the prior art of Hillig et. al. and Li et. al. fail to teach a where instant AE is attached to the linker at the carbon adjacent to C-RE5. See claim 84 limitation.
Nevertheless, with regards to the limitation of claims 9 – 11, 23 – 24, 35, 78 – 79, and 80, for a compound where L-RE feature is attached at different positions of the rings, given that that only difference between the instant compounds and the combination compound of Hillig et. al. and Li et. al. is the position of the L-RE feature the compounds of both the instant application and combination of Hillig et. al. and Li et. al. are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
Moreover, with regards to the limitation of claim 84, where instant AE is attached to the linker at the carbon adjacent to C-RE5, given that that only difference between the instant compounds and the combination compound of Hillig et. al. and Li et. al.is the position of the AE – L connection, the compounds of both the instant application and the combination compound of Hillig et. al. and Li et. al. are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
Claims 12, and 86 – 89 are rejected under 35 U.S.C. 103 as being unpatentable over Hillig et. al. ((2019), Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction, PNAS, 116, 2551 – 2560; cited on the IDS dated December 18th, 2023) in view of Li et. al. ((2020), PROTAC**: A Novel Technology for Drug Development, Chemistry Select, 5, 13232 – 13247), as applied to claims 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141 above, and further in view of Ali et. al. ((2014), Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, page 150-169; cited in the office action dated March 9th, 2026).
The teachings of Hillig et. al. and Li et. al. as they relate to claims 1, 8, and 83, from which claims 12, and 86 – 89 depend, are given previously in this office action and are fully incorporated here.
However, Hillig et. al. and Li et. al. fail to teach a compound of claim 8 where the compound is a compound of formula (IV)
PNG
media_image9.png
204
306
media_image9.png
Greyscale
where V = -N=. See claim 12 limitation. Moreover, Hillig et. al. and Li et. al. fail to teach a compound of claim 83 where the compound is a compound of formula (EC-VI); (EC-IX); (EC-X), or EC-XII. See claim 86 limitation where RE is a moiety having the structure of Formula (EC-VI)
PNG
media_image10.png
134
418
media_image10.png
Greyscale
. See claim 87 limitation where RE is a moiety having the structure of Formula (EC-IX)
PNG
media_image11.png
132
430
media_image11.png
Greyscale
. See claim 88 limitation where RE is a moiety having the structure of Formula (EC-X)
PNG
media_image12.png
158
386
media_image12.png
Greyscale
. See claim 89 limitation where RE is a moiety having the structure of Formula (EC-XII)
PNG
media_image13.png
152
414
media_image13.png
Greyscale
.
Nevertheless, with regards to the limitation of claim 12, for a compound where L-RE feature is attached at a different position on the ring, given that that only difference between the instant compounds and the combination compound of Hillig et. al. and Li et. al. is the position of the L-RE feature the compounds of both the instant application and combination of Hillig et. al. and Li et. al. are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
Moreover, with regards to the limitation of claim 88, where instant AE is attached to the linker at the carbon adjacent to C-RE5, given that that only difference between the instant compounds and the combination compound of Hillig et. al. and Li et. al.is the position of the AE – L connection, the compounds of both the instant application and the combination compound of Hillig et. al. and Li et. al. are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
Nevertheless, Ali et. al. teach isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules. See page 150 column 1 paragraph 1. Furthermore, Ali et. al. teach that bioisosterism is a well-established technique in modern drug design, extensively studied for modification of drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. See page 150 column 1 paragraph 1. Moreover, Ali et. al. teach that the isosteric replacement approach is a practical and, possibly, better substitutes to recent lead optimization techniques. See page 150 column 1 paragraph 1. Specifically, Ali et. al. teach the idea of Benzene ring equivalents in Table 7 page 158, wherein benzene ring equivalents are
PNG
media_image14.png
132
692
media_image14.png
Greyscale
. See page 158. Thus Ali et. al. suggest
PNG
media_image15.png
200
400
media_image15.png
Greyscale
and
PNG
media_image16.png
200
400
media_image16.png
Greyscale
as known in the prior art ring equivalents to benzene. See claim 12 limitation a compound of claim 8 where the compound is a compound of formula (IV)
PNG
media_image9.png
204
306
media_image9.png
Greyscale
where V from Formula (I) is -N=. See claims 86 – 89 for a compound of claim 83 where the compound is a compound of formula (EC-VI); (EC-IX); (EC-X), or EC-XII.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify compounds 1, 15, 17, and 19 of Hillig et. al. in view of Li et. al. that is to attach a linker and E3 ligation moiety, and in further view of Ali et. al. to use a
PNG
media_image16.png
200
400
media_image16.png
Greyscale
in the R2c position or the AE ring, or to use
PNG
media_image15.png
200
400
media_image15.png
Greyscale
that is, have instant V as a N. One of ordinary skill in the art would have been motivated to make this modification to modify a drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. One or ordinary skill in the art would have had a reason expectation of success because
PNG
media_image15.png
200
400
media_image15.png
Greyscale
and
PNG
media_image16.png
200
400
media_image16.png
Greyscale
as known in the prior art ring equivalents to benzene and are therefore, bioisosteres.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Hillig et. al. ((2019), Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction, PNAS, 116, 2551 – 2560; cited on the IDS dated December 18th, 2023) in view of Li et. al. ((2020), PROTAC**: A Novel Technology for Drug Development, Chemistry Select, 5, 13232 – 13247), as applied to claims 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141 above.
The teachings of Hillig et. al. and Li et. al. as they relate to claim 1, from which claim 77 depends, are given previously in this office action and are fully incorporated here.
However, Hillig et. al. and Li et. al. fail to teach a compound of claim 1, where the moiety is a moiety of a compound having the structure of T44
PNG
media_image17.png
196
248
media_image17.png
Greyscale
. See claim 77 limitation.
Nevertheless, as taught above, Hillig et. al. teach compound 19 of the following structure respectively:
PNG
media_image4.png
132
274
media_image4.png
Greyscale
. See page 2555 Figure 3. Moreover, the only difference between the prior art compound 19 and examined compound T44 is the substituent group attached to the thiophene ring. Furthermore, both prior art compound 19 and examined compound T44 have identical core scaffolds. Thus given that the only difference between the prior art compound 19 and examined compound T44 is the substituent group attached to the thiophene ring both compounds are close structurally. And 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 MPEP 2144.09 (I).
Claim 140 is rejected under 35 U.S.C. 103 as being unpatentable over Hillig et. al. ((2019), Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction, PNAS, 116, 2551 – 2560; cited on the IDS dated December 18th, 2023) in view of Li et. al. ((2020), PROTAC**: A Novel Technology for Drug Development, Chemistry Select, 5, 13232 – 13247), as applied to claims 1, 8, 13, 22, 76, 81 – 83, 85, 90 – 92, 129, 139, and 141 above.
The teachings of Hillig et. al. and Li et. al. as they relate to claim 1, from which claim 140 depends, are given previously in this office action and are fully incorporated here.
However, Hillig et. al. and Li et. al. fail to teach a compound of claim 1, where the compound is 4-((2-(2-(2-(2-((4-(((R)-1-(3-bromophenyl)ethyl)amino)-6-methoxy-2-methylquinazolin-7-yl)oxy)ethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione of structure
PNG
media_image18.png
436
1144
media_image18.png
Greyscale
See claim 140 limitation.
Nevertheless, as taught above, prior art of Hillig et.al. teach compound 15 of structure
PNG
media_image2.png
128
228
media_image2.png
Greyscale
. Moreover, the prior art of Li et. al. teach example linkers in PROTAC ARV-825, of structures
PNG
media_image8.png
320
622
media_image8.png
Greyscale
coupled to the E3 ligase moiety cereblon. Thus the prior art of Hillig et. all and Li et. al. teach the three pieces of examined compound 4-((2-(2-(2-(2-((4-(((R)-1-(3-bromophenyl)ethyl)amino)-6-methoxy-2-methylquinazolin-7-yl)oxy)ethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione. Given that the skill level of one of ordinary skill in the pharmaceutical arts is relatively high, being that of a Ph.D., Pharm. D. or MD it would have been within the purview of such artisan to combine the three portions into synthesize 4-((2-(2-(2-(2-((4-(((R)-1-(3-bromophenyl)ethyl)amino)-6-methoxy-2-methylquinazolin-7-yl)oxy)ethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify compound 15 of Hillig et. al. in view of Li et. al. that is to attach a linker and E3 ligase moiety of ARV-825. One of ordinary skill in the art would have been motivated to make this modification to overcome or reduce the probability of drug resistance in the late stage tumors. One of ordinary skill in the art would have had a reasonable expectation of success because PROTACS can degrade targets with low concentration and thus is expected to relieve the drug resistance condition.
Response to Arguments
Applicant's arguments filed February 3rd, 2026, with regards to prior art rejections of claims 1, 8 – 13, 23 – 24, 34 – 35, 81 – 89, 91 – 92, and 141 have been fully considered and were found to be persuasive. Thus the prior art rejection was modified using Hillig et. al. in view of Li et. al.
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 1, 8, 11, 24, and 141 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 23 of U.S. Patent No. US 12419962 B2 to Erdman et. al. (herein after Erdman‘962).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and the invention of Erdman‘962 direct to a compound of Formula (I)
PNG
media_image19.png
200
400
media_image19.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 4, and 5. See examined claims 1, 8, 11, and 24. Moreover, Erdman‘962 recite a pharmaceutical composition comprising the compound of (reference) claim 1 and a pharmaceutically acceptable excipient. See examined claim 15. See examined claim 141.
Claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, 139, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 23 of U.S. Patent No. US 12419962 B2 to Erdman et. al. (herein after Erdman‘962).
Erdman‘962 recite a compound of Formula (I)
PNG
media_image19.png
200
400
media_image19.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 4, and 5. See examined claims 1, 8, 11, and 24.
However, Erdman‘962 is silent on compounds of Formula (I) where L-RE is attached at different positions on the ring. See examined claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, 139, and 140.
Nevertheless, given that that only difference between the instant compounds and the compounds of Erdman‘962 is the position of the L-RE feature the compounds of both the instant application and copending Erdman‘962 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
Claim 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53, and 139 – 140 of copending Application No. 18/542628 to Chan et. al. (reference application; Chan’628).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and the invention of Erdman‘962 direct to a compound of Formula (I)
PNG
media_image20.png
200
400
media_image20.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. See reference claims 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53. See examined claims 1, 8 – 10, 12, 23, 78 – 79, and 140.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, 16, 95, 105, and 107 of copending Application No. 18/550960 to Chourasia et. al. (Chourasia’960) in view of Boichenko et. al. ((2018), Chemical Ligand Space of Cereblon, ACS Omega, 3, 11163 – 11171; cited in the office action mailed March 9th, 2026).
Chourasia’960 recite a compound of Formula (II)
PNG
media_image21.png
200
400
media_image21.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof where reference R4 is -L-RB where reference RB that is instant RE, is C2-6 fluoroalkyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl. See reference claims 1, 8 – 11, 22 – 23, 40 – 45, and 50 – 53. See examined claims 1, 8 – 10, 12, 23, 78 – 79, and 140.
However, Chourasia’960 fail to recite whether reference RB that is instant RE, is an E3 ubiquitin ligase binding moiety. See examined claim 1.
Nevertheless, Boichenko et. al. teach thalidomide and related IMiDs mediate their effects by binding to the protein cereblon, a substrate receptor of the CRL4A E3 ubiquitin ligase complex. See page 11163 column 1 paragraph 2. Furthermore, Boichenko et. al. teach a variety of E3 ubiquitin ligase binding compounds that are 5 – 6 membered rings containing N and O atoms and are heterocyclic. See Figures 2a-b, Figure 3 and Figure 4 page 11165. Thus Boichenko et. al. suggest E3 ubiquitin ligase binding species that are heterocyclic.
Therefore, it would have been obvious to one of ordinary skill in the art to modify the compound of copending Chourasia’960 to include a heterocyclic ring that in view of Boichenko et. al. is a E3 ubiquitin ligase binding moiety. One of ordinary skill in the art would have made this modification and have reasonable expectation of success to bind to the protein cereblon, a substrate receptor of the CRL4A E3 ubiquitin ligase complex.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 8, 11, 24, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 160 of copending Application No. 19/510087 to Okano et. al. (Okano’087).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and the invention of Okano’087 direct to a compound of Formula (I)
PNG
media_image22.png
158
314
media_image22.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof where R1-4, Re, X, V, U, L, A, and are defined. See reference claims 1, 4, and 5. See examined claims 1, 8, 11, and 24. Additionally, Okano’087 recite a compound of (reference) Formula (I) which encompasses (reference) Formulas and structural limitations as recited in reference claims 14 – 155; and overlap with structural limitations of examined claims 1, 8, 11, and 24. Moreover, Okano’087 recite a pharmaceutical composition comprising the compound of any one of (reference) claims 1 to 155 and a pharmaceutically acceptable excipient. See examined claim 156. See examined claim 141. Furthermore, Okano’087 recite a pharmaceutical composition where dosage forms are recited. See reference claims 157 – 160.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 160 of copending Application No. 19/510087 to Okano et. al. (Okano’087).
Okano’087 direct to a compound of Formula (I)
PNG
media_image22.png
158
314
media_image22.png
Greyscale
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof where R1-4, Re, X, V, U, L, A, and are defined. See reference claims 1, 4, and 5. See examined claims 1, 8, 11, and 24. Additionally, Okano’087 recite a compound of (reference) Formula (I) which encompasses (reference) Formulas and structural limitations as recited in reference claims 14 – 155; and overlap with structural limitations of examined claims 1, 8, 11, and 24.
However, Okano’087 is silent on compounds of Formula (I) where A-L-Re is attached at different positions on the ring. See examined claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, 139, and 140.
Nevertheless, given that that only difference between the instant compounds and the compounds of Okano’087 is the position of the A-L-Re feature the compounds of both the instant application and copending Okano’087 are positional isomers. Therefore compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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 MPEP 2144.09(II).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed July 8th, 2026, with regards to the provisional nonstatutory double patenting (NSDP) and NSDP rejections of examined claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 over claims 1 – 23 of U.S. Patent No. US 12419962 B2 to Erdman et. al. (Erdman‘962); claim 1, 8 – 11, 22 – 23, 40 – 45, 50 – 53, and 139 – 140 of copending Application No. 18/542628 to Chan et. al. (Chan’628); and claim 1, 4, 16, 95, 105, and 107 of copending Application No. 18/550960 to Chourasia et. al. (Chourasia’960) have been fully considered but they are not persuasive.
Applicant states that they will consider filing a terminal disclaimer once the examined claims are otherwise in condition for allowance. See applicant’s remarks page 40 paragraph 2.
The examiner contends that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. (MPEP 804)
Moreover, as filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. (MPEP 804(I)B1). Therefore, the provisional nonstatutory double patenting (NSDP) and NSDP rejections of instant claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are maintained.
Conclusion
Claims 1, 8 – 13, 22 – 24, 34 – 35, 76 – 92, 129, and 139 – 141 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
Prosecution Insights