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
Acknowledgment is made of Applicant's claim for priority from U.S. Provisional Application No. 63/006,000, filed on April, 6, 2020 and U.S. Provisional Application No. 63/030,440, filed on May 27, 2020.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 23, 2026 has been entered.
Response to Amendment
By Applicant’s amendment filed on February 23, 2026 claims 1, 20, 28 and 32 have been amended and new claims 33-37 have been added. Claims 2-8, 10-16, 18-19, 21 and 25-27 were previously cancelled. Claims 1, 9, 17, 20, 22-24 and 28-37 are currently pending.
New claims 36 and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 27, 2023.
Claims 1, 9, 17, 20, 22-24 and 28-35 are currently presented for examination.
Response to Arguments
Due to Applicant’s amendments to the claims, the previous double patenting rejection of claims 17, 20 and 32 over U.S. Patent No. 11,161,841 B2 is hereby withdrawn. These claims now exclude the compounds claimed in or rendered obvious over U.S. Patent No. 11,161,841 B2.
Applicant’s amendments to the claims are not sufficient to overcome the previous double patenting rejection of claims 1, 9, 22-24 and 28-31 over U.S. Patent No. 11,161,841 B2.
The claims currently claim compounds wherein L is
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or
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and PTM is:
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wherein RPTM4C is F.
Claims 1 and 2 of ‘841 claim PTM is
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wherein RPTM4B is chosen from OH, H, -CH2CN, halogen and alkyl and RPTM2 is (C=O)RPTM2’ wherein RPTM2’ is optionally substituted alkene wherein the substituent is halogen. Claim 1 of ‘841 also claims that RPTM1A is optionally substituted such as optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl. Claim 4 of ‘841 specifically claims compounds wherein the RPTM1A is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, wherein the C3-6heterocycloalkyl is piperidine and C1-4alkyl is ethyl. Moreover, claims 9 and 10 of ‘841 claim the linker is
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wherein m and n is 0 such as
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. Furthermore claim 6 of ‘841 claims ULM is
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or
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. Since claim 1 of ‘841 claims that RPTM1A is optionally substituted, a person of ordinary skill in the art would contemplate the linkers claimed in the instant claims
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or
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since these linkers are as taught for RPTM1A which is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl. Thus the claims of ‘841 render obvious 1 or more compounds as claimed in claims 1, 9, 22-24 and 28-31 of the instant application.
For these reasons, the previous double patenting rejection over ‘841 is hereby maintained however, the rejection has been modified as detailed below.
Due to Applicant’s amendments to the claims, the previous rejection under 35 USC 103 of claims 17, 20 and 32 is hereby withdrawn. These claims now exclude the compounds rendered obvious over U.S. Publication No. 2019/0315732 A1.
Applicant’s amendments to the claims are not sufficient to overcome the previous rejection of claims 1, 9, 22-24 and 28-31 under 35 USC 103.
The amendments to the claims are not sufficient to overcome the rejection for the same reasons as detailed above since the rejection under 35 USC 103 over Crew et al. is based upon the publication of U.S. Patent No. 11,161,841 B2 which is U.S. Publication No. 2019/0315732 A1 which is equivalent to WO 2019/195609 A2.
Thus for these reasons, the previous rejection under 35 USC 103 is hereby maintained however, the rejection has been modified as detailed below.
This action is Non-Final.
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, 9, 22-24 and 28-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,161,841 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘841 are overlapping in scope and mutually obvious.
Claims 1, 9, 22-24 and 28-31 of the instant application claim a compound having the following chemical structure PTM-L-VLM wherein PTM is
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, RPTM4C is F, VLM is
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and L is a linker such as
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or
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, for example claim 28 of the instant application claims
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or
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Claims 1-19 of ‘841 claim a bifunctional compound having the chemical structure of PTM-L-ULM wherein ULM is a Von Hippel-Lindau (VHL) ligase-binding moiety (VLM).
Claims 1 and 2 of ‘841 claim PTM is
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wherein RPTM4B is chosen from OH, H, -CH2CN, halogen and alkyl and RPTM2 is (C=O)RPTM2’ wherein RPTM2’ is optionally substituted alkene wherein the substituent is halogen; XPTM is N; RPTM4A is halogen.
Claim 1 of ‘841 also claims that RPTM1A is optionally substituted such as optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl. Claim 4 of ‘841 specifically claims compounds wherein the RPTM1A is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, wherein the C3-6heterocycloalkyl is piperidine and C1-4alkyl is ethyl. Claims 9 and 10 of ‘841 claim the linker is
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wherein m and n is 0 such as
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.
Claim 6 of ‘841 claims ULM is
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wherein R1 is H, or alkyl including ethyl, isopropyl, tert-butyl, etc., and R15 is optionally substituted heteroaryl. Claim 1 of the instant application claims compounds wherein in the same position as R1 of ‘841, the claimed compounds have isopropyl or tert-butyl, and in the same position as R15 of ‘841, the claimed compounds have a substituted heteroaryl group.
The claims of ‘841 do not specifically exemplify a compound wherein the PTM group as claimed contains a halogen substituted vinyl ketone group and wherein the piperazine ring is substituted with -CH2CN or the linker
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or
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.
However, claims 1 and 2 of ‘841 claim PTM is
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wherein RPTM4B is chosen from OH, H, -CH2CN, halogen and alkyl; and RPTM2 is (C=O)RPTM2’ wherein RPTM2’ is optionally substituted alkene wherein the substituent is halogen. Since the only suitable choices for halogen are limited to 4 species, one would clearly envisage selecting F as a halogen with a reasonable expectation of success. Moreover claims 15 and 16 of ‘841 specifically claim compounds wherein RPTM4B is selected as -CH2CN (see for example compounds 499-513 516-523, 534-554 on Table 12 which are specifically claimed in claims 15 and 16 of ‘841).
Accordingly, prior to the effective filing date, it would have been obvious to a person of ordinary skill in the art to substitute the vinyl ketone moieties of PTM with a halogen including F based on claims 1 and 2 of ‘841 which specifically claim that the vinyl ketone group can be substituted with a halogen. Thus a person of ordinary skill in the art following the claims of ‘841 would have been motivated to substitute the vinyl ketone group with a halogen with a reasonable expectation of similar results. Likewise claims 1 and 2 of ‘841 claim that RPTM4B may be chosen as -CH2CN, and thus a person of ordinary skill in the art following the claims of ‘841 would have been motivated to choose -CH2CN for RPTM4B with a reasonable expectation of similar success.
Although ‘841 does not specifically exemplify a linker such as
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or
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, claim 1 of ‘841 specifically teaches that RPTM1A is optionally substituted such as optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl. Since optionally substituted includes substituents especially methyl and halogen, RPTM1A may be substituted with methyl or the halogen, fluorine (see column 118 which defines optionally substituted). Claim 4 of ‘841 specifically claims compounds wherein the RPTM1A is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, wherein the C3-6 heterocycloalkyl is piperidine and C1-4alkyl is ethyl. Moreover, claims 9 and 10 of ‘841 claim the linker is
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wherein m and n is 0 such as
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. Accordingly, an ordinary skilled artisan would have been motivated to select RPTM1A as optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, specifically O-CH2-CH2-piperidine, substituted with methyl or fluorine to arrive at the instant invention. Thus the linker as claimed is rendered obvious over the claims of ‘841.
Thus, the cited claims of the instant application are rendered obvious over the cited claims of ‘841 and thus are not patentably distinct.
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.
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, 9, 22-24 and 28-31 are rejected under 35 U.S.C. 103 as being obvious over Crew et al. U.S. 2019/0315732 A1 (equivalent to WO 2019/195609 A2 provided on IDS).
The applied reference has a common inventor/applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2) and 35 U.S.C. 102(a)(1).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claims 1, 9, 22-24 and 28-31 of the instant application claim a compound having the following chemical structure PTM-L-VLM wherein PTM is
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, RPTM4C is F, VLM is
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and L is a linker such as
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or
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, for example claim 28 of the instant application claims
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as well as compositions thereof.
Claims 1-32 of Crew et al. claim a bifunctional compound having the chemical structure of ULM-L-PTM wherein ULM is a Von Hippel-Lindau (VHL) ligase-binding moiety (VLM).
Claim 3 of Crew et al. claims PTM is
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wherein RPTM4B is chosen from OH, H, -CH2CN, halogen and alkyl and RPTM2 is (C=O)RPTM2’ wherein RPTM2’ is optionally substituted alkene wherein the substituent is halogen; XPTM is N; RPTM4A is halogen. Crew et al. teaches that substitution with halogen includes Cl, F, Br and I, preferably F or Cl [0542]. Claim 3 of Crew et al. claims that RPTM1A is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl. Claim 5 of Crew et al. specifically claims compounds wherein the RPTM1A is optionally substituted O-C1-4 alkyl-C3-6heterocycloalkyl, wherein the C3-6heterocycloalkyl is piperidine and C1-4alkyl is ethyl. Claims 22 and 23 of Crew et al. claim the linker is
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wherein m and n is 0 such as
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.
Claim 8 of Crew et al. claims ULM is
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wherein R1 is H, or alkyl including ethyl, isopropyl, tert-butyl, etc., and R15 is optionally substituted heteroaryl. Crew et al. teaches ULM is
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(page 95).
Claim 30 of Crew et al. claim a composition comprising the bifunctional compound of claim 1 and a pharmaceutically acceptable carrier. Claims 31-32 of Crew et al. further claim the pharmaceutical composition further comprising at least one additional bioactive agent wherein the other bioactive agent is an anticancer agent.
Crew et al. does not specifically exemplify a compound wherein the PTM group contains a halogen substituted vinyl ketone group and wherein the piperazine ring is substituted with -CH2CN as claimed in the instant claims and wherein the linker is
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However, Crew et al. teaches that PTM is
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wherein RPTM4B is chosen from OH, H, -CH2CN, halogen and alkyl; and RPTM2 is (C=O)RPTM2’ wherein RPTM2’ is optionally substituted alkene wherein the substituent is halogen. Since the only suitable choices for halogen are limited to 4 species, one would clearly envisage selecting F as a halogen with a reasonable expectation of success. Moreover claims 28 and 29 of Crew et al. specifically claim compounds wherein RPTM4B is selected as -CH2CN (see for example compounds 499-513 516-523, 534-554 on Table 12 which are specifically claimed in claims 28 and 29 of Crew et al.).
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to substitute the vinyl ketone moieties of PTM with a halogen including F based on the teachings of Crew et al. which specifically teaches and claims that the vinyl ketone group can be substituted with a halogen. Thus a person of ordinary skill in the art following the teachings of Crew et al. would have been motivated to substitute the vinyl ketone group with a halogen with a reasonable expectation of similar results. Likewise Crew et al. teaches and claims that RPTM4B may be chosen as -CH2CN, and thus a person of ordinary skill in the art following the teachings of Crew et al. would have been motivated to choose -CH2CN for RPTM4B with a reasonable expectation of similar success.
Although Crew et al. does not specifically exemplify a linker such as
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, claim 1 of Crew et al. specifically teaches that RPTM1A may be selected as optionally substituted O-C1-4alkyl-C3-6 heterocycloalkyl. Since optionally substituted includes substituents especially methyl and halogen, RPTM1A may be substituted with methyl or the halogen, fluorine (see paragraph [0542] which defines optionally substituted). Claim 5 of Crew et al. specifically claims compounds wherein the RPTM1A is optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, wherein the C3-6 heterocycloalkyl is piperidine and C1-4alkyl is ethyl. Moreover, claims 22 and 23 of Crew et al. claim the linker is
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wherein m and n is 0 such as
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. Accordingly, an ordinary skilled artisan would have been motivated to select RPTM1A as optionally substituted O-C1-4alkyl-C3-6heterocycloalkyl, specifically O-CH2-CH2-piperidine, substituted with methyl or fluorine to arrive at the instant invention. Thus the linker as claimed is rendered obvious over the teachings of Crew et al.
Thus, the prior art does not appear to provide sufficient specificity, i.e., involves too much "picking and choosing" to give rise to anticipation. See Coming Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). That being said, it must be remembered that "[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect ....the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected the various combinations of features claimed from within the prior art disclosure as detailed above to arrive at the instantly claimed subject matter.
Thus, the cited claims of the instant application are rendered obvious over the teachings of Crew et al.
Claim Objections
Claims 17, 20 and 32-35 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 2-8, 10-16, 18-19, 21 and 25-27 are cancelled. Claims 1, 9, 22-24 and 28-31 are rejected. Claims 17, 20 and 32-35 are objected. Claims 36 and 37 are withdrawn. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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, Adam C. Milligan can be reached on (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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