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 I (Claims 1, 2, 4-6, 13, 14, 17, 21, 24, 27, 34, 39, 41, 42, 45, 104, and 125-128) in the reply filed on 6 February 2026 is acknowledged. Applicant further elects the species
PNG
media_image1.png
136
219
media_image1.png
Greyscale
which reads on Claims 1, 2, 4, 5, 14, 17, 21, 34, 39, 41, 42, 45, 104, and 125. A search was performed for the claimed species with no prior art retrieved. The search was expanded to include all options for variables W and Q, with no prior art retrieved. The search was expanded to all variable L and all variable X, with no prior art retrieved. The search was expanded to isomeric forms of Formula (I), with prior art retrieved. The search was then stopped (See STN Search, Search Notes).
Claims 46, 75, 82, 108, 115, 116, 122, and 124 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.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 6 February 2026.
Claims 1, 2, 4-6, 13, 14, 17, 21, 24, 27, 34, 39, 41, 42, 45, 104, and 125-128, submitted on 6 February 2026, represent all claims currently under consideration.
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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The effective filing date is 30 December 2020.
Information Disclosure Statement
Five Information Disclosure Statements (IDSs), submitted on 14 November 2023, 6 March 2024, 3 October 2024, 10 September 2025, and 6 February 2026, are acknowledged and have been considered.
Specification
The Title is objected to because it contains the word “NOVEL”. All patentable inventions are necessarily novel, so such words should not be included in the title (See MPEP § 606). The word “NOVEL” has been deleted from the title. No further action is required on Applicant’s part.
Claim Objections
Claim 125 is objected to under 37 CFR 1.75 as being a substantial duplicate of Claim 45. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 depends on Claim 5, which depends ultimately on Claim 1. Claim 6 claims that variable R’’ is a aryl substituted with different substituents. Claim 1 does not state that variable R’’ can be an optionally substituted aryl, rather it states it can simply be aryl, causing Claim 6 to be broader than Claim 1 and Claim 5. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claims 14, 17, 21, 24, and 27 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 14, 17, 21, 24, and 27 each ultimately depend on Claim 13, which claims that variables W1 through W4 are each CH. Claims 14, 17, 21, 24, and 27 are each broader, and thus do not further limit Claim 13 as these claims state that at least one of variable W1 through W4 is a substituted carbon. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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, 2, 4, 5, 13, 34, 39, 41, and 104 are rejected under 35 U.S.C. 103 as being unpatentable over Phillips (WO 2017/197406; Publication Date: 16 November 2017).
Phillips (See IDS, 14 November 2023) discloses degrommers that have carbon-linked E3 ubiquitin ligase targeting moieties (degrons), which can be linked to a targeting ligand for a protein that has been selected from in vivo degradation, and methods of use and compositions thereof as well as methods of their preparation (Abstract). One compound disclosed is compound 58 (Page 367)
PNG
media_image2.png
198
157
media_image2.png
Greyscale
. This compound has a Kd of between 10 and 50 µM against CRBN-DDB1 (Table 1, Page 367), providing a motivation to select this compound for further modification. This compound has variables X-1- and X2 each as O, one of Q1 N and Q2 as CR with variable R as H, each of W1, W2, W3, and W4 as CR’ with R’ as H, n as 1 (six-membered ring), R as H, and variable L as H. The compounds of the invention as disclosed herein can be administered as a neat chemical, but are more typically administered as a pharmaceutical composition that includes an effective amount of a host, typically a human, in need of such treatment for any of the disorders described herein (Page 212, Lines 17-20).
Compound 58 of Phillips is not identical to the compounds of the examined application; however, it is an isomer of the compounds of Formula (I), having the 2,6-piperidinedione bound to the analogous variable Q2. It would be prima facie obvious to one of ordinary skill in the art to modify Compound 58 by relocating the 2,6-piperidinedione to the location claimed in the compounds of the examined application due to the close chemical structure (See MPEP § 2144.09 I); the compounds of Phillips and those of the examined application are cereblon binding compounds, with Compound 58 demonstrate to be a potent binder of cereblon. The artisan would not expect altering the location of the 2,6-piperidinedione to significantly alter the properties of the resulting compound.
Regarding Claim 2, Compound 58 is drawn in a flat configuration, and thus, embraces all stereoisomeric conformations.
Regarding Claims 34 and 41, the altering the location of the nitrogen from the Q1 location to the Q2 location would not be expected to alter the properties of the resulting compound due to the close chemical structure (See MPEP § 2144.09 I).
Double Patenting
Claims 1, 2, 4-6, 13, 14, 17, 21, 24, 27, 34, 39, 41, 42, and 104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 45, 51, and 103 of copending Application No. 19/154,211 (Amended Claims of 6 August 2025) (‘211) in view of Thornber (Chemical Society Reviews, Issue 4, 1979).
Claim 1 of ‘211 is drawn to a compound of Formula (I)
PNG
media_image3.png
232
392
media_image3.png
Greyscale
wherein R6 is hydrogen, unsubstituted C1-C4 alkyl, haloalkyl, -OR1, or -N(R1)2; E is CH, CD, CF, C-(C1-C3 alkyl) or N; G is CR1 or N; one of Q1, Q2, Q3, and Q4is CR5 and the other three are each independently N or CR4; each of R1 is independently hydrogen, unsubstituted C1-C4 alkyl, or C1-C4 haloalkyl; each R4 is independently hydrogen, unsubstituted alkyl, haloalkyl, halogen, -CN, -OR1 or -N(R1)2; R5 is selected from
PNG
media_image4.png
160
850
media_image4.png
Greyscale
PNG
media_image5.png
209
912
media_image5.png
Greyscale
; W is CH2 or C=O; Z is C=O, NR1 or C(R2)2; wherein each R2 is independently hydrogen, unsubstituted alkyl, halogen, OR1 or N(R1)2-; V is O or S; each R is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl, or benzyl which are optionally substituted, A is heteroaryl, heterocycloalkyl, cycloalkyl, or cycloalkenyl; B is -SO2NHR or 8-12 membered bicyclic heteroaryl substituted with one or more R8; n is 0 or 1; m is 1 or 2; r is 0 or 1; s is 0 or 1; p is 0-3; and q is 1-4. Claim 45 is drawn to a compound selected from several compounds, including
PNG
media_image6.png
139
318
media_image6.png
Greyscale
and
PNG
media_image7.png
138
404
media_image7.png
Greyscale
. These compounds differ from
PNG
media_image8.png
180
459
media_image8.png
Greyscale
of Claim 42 of the examined application by the presence of -O- instead of -NH- in the alkyl chain connecting the phenyl ring. Claim 51 is drawn to a compound selected from several including
PNG
media_image9.png
133
305
media_image9.png
Greyscale
. This compound differs from
PNG
media_image8.png
180
459
media_image8.png
Greyscale
of Claim 42 of the examined application by the 2,6-piperidinedione ring having an additional nitrogen. Claim 103 is drawn to a pharmaceutical composition comprising a compound of the invention.
‘211 does not teach compounds identical to those of the examined application.
Thornber teaches the concept of bioisosterism, which is the concept wherein groups or molecules which have chemical and physical similarities produce broadly similar biological properties (Page 563). Table 1 (Page 564) lists the classical isosteres, and includes ring equivalents. Such ring equivalents include -CH2- and -N-. These atoms have similar electronic properties and as such, their replacement within a ring system is not expected to significantly alter the properties of that ring. Table 1 also lists bivalent atoms and groups which function as bioisosteres, including -CH2- and -NH- (Table 1, Page 564). These two bivalent atoms have similar electronic properties. Thornber (Chemical Society Reviews, 4, 1979).
‘211 and Thornber are considered analogous to the claimed invention as all are involved in the development and study of biologically active pharmaceutical compounds. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘211 by replacing the -O- in the alkyl chain with -NH-, or substituting the -CH2- in the piperidinedione ring with -N-, as Thornber teaches that these moieties function as bioisosteres of one another. As Thornber teaches that these moieties function as bioisosteres of one another, and the compounds of ‘211 have a similar function as those of the examined application (cereblon binding compounds), the artisan would not expect that these modifications would significantly alter the properties of the resulting compound due to the close chemical structure (See MPEP § 2144.09 I).
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 45 and 125-128 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.
The following is an examiner’s statement of reasons for allowance: There is no prior art which teaches or suggests the compounds of Claim 45 or 125-128. The closest prior art comes from Phillips (WO 2017/197406), Skolnick (WO 2008/153937; Publication Date: 18 December 2008), and Staben (WO 2012/004212; Publication Date: 12 January 2012). Phillips (See IDS, 14 November 2023) is described above and teaches Compound 58. However, there is no teaching, suggestion, or motivation found in Phillips to modify this compound to include alkyl, amino, or nitro moieties around the ring system as claimed, with no reasonable expectation that performing these specific modifications would result in a compound active against cereblon. Skolnick discloses 1-heteroaryl-3-azabicyclo[3.1.0]hexanes and their compositions for the treatment and/or prevention of CNS disorders. Compounds include
PNG
media_image10.png
264
444
media_image10.png
Greyscale
. The compounds of Skolnick require the inclusion of an azabicyclo[3.1.0]hexane, with no teaching, suggestion, or motivation to remove this group to form either a five- or six-membered monocyclic ring system as found in the compounds of the examined application. Staben discloses Hepatitis C virus NS5b polymerase inhibitors such as compound I-2
PNG
media_image11.png
173
299
media_image11.png
Greyscale
, I-3
PNG
media_image12.png
159
281
media_image12.png
Greyscale
, and I-4
PNG
media_image13.png
158
298
media_image13.png
Greyscale
(Pages 22-23). However, these compounds differ in that there is not a 2,6-piperidinedione ring system bound to the central bicyclic heteroaryl ring system. There is no teaching, suggestion, or motivation found in Staben to replace these rings with a 2,6-piperidinedione ring, and no reasonable expectation that performing this substitution would result in a compound effective in inhibiting NS5b polymerase.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1, 2, 4, 5, 6, 13, 14, 17, 21, 24, 27 34, 39, 41, and 104 are rejected.
Claims 45 and 125-128 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM 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, Andrew Kosar can be reached at 571-272-0913. 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.
/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights