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
This application, filed 19 July, 2023, is a national stage application of PCT/US2022/013129, filed 20 January, 2022, which claims the benefit of U.S. provisional application 63/139,638, filed 20 January, 2021.
Information Disclosure Statement
Four information disclosure statements (IDS) submitted on 19 July, 2023; 14 September, 2023; 16 October, 2024; and 16, December, 2025 are acknowledged and have been considered.
Election/Restrictions
Applicant’s election without traverse of Group I (Conjugates and Composition; Claims 1-17 and 32) and of Species DQ-9 (instant Specification, Pg. 93, Para 0269; Claims 1-3, 14-15, 17, and 32), shown below, in the reply filed on 9 February, 2026, is acknowledged.
PNG
media_image1.png
172
316
media_image1.png
Greyscale
The elected species is “a compound of Formula (I), wherein R1 is H, R2 is H, R3 is H, R4 is CH3, R5 is CH3, X is O, Y is H, Z is O-O, Y’ is – Linker – Proteasome inhibitor, wherein the Linker is –(CH2)y-C(=O)-, y is 1 (as in instant Claims 1-3), and wherein the proteasome inhibitor moiety comprises a compound of Formula IV, wherein n is 0, R1’ is CH3 substituted with R3, R3 is heteroaryl (benzofuranyl), Y is
PNG
media_image2.png
70
69
media_image2.png
Greyscale
, and Z1 and Z2 together form a moiety derived from a boronic acid complexing agent” (as in instant Claims 14-15 and 17.)
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 9 February, 2026, in the matter of Application N° 18/262,053. Said documents have been entered on the record.
Claims 18, 20-25, and 27-31 are canceled. Claims 3-7, 10-17, 19, 26, and 32 are amended. No new matter was introduced.
Claims 4-13, 16, 19, and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9 February, 2026.
Thus, Claims 1-3, 14-15, 17, and 32 represent all claims currently under consideration.
Drawings
The drawings are objected to because many of the spectrum related figures (e.g., Figure 4, Figure 5, etc.) are blurry or illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-3, 14-15, 17 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Org. Lett., Vol. 7, No. 8, 2005), hereinafter Liu and further in view of Swinnen et al. (WO 2013/092979 A1), hereinafter Swinnen.
Liu discloses synthesis and cytotoxicity studies of Artemisinin (ART) derivatives, known for antimalarial and other therapeutic activities, using the modular approach “artemisinin + linker + lipophilic alkyl carbon chain” (Liu, Pg. 1562, Introduction) to test efficacy for the ART analogues against the HepG2 cancer cell lines (Liu, Pg. 1563-1564, Tables 1-4.)
PNG
media_image3.png
107
93
media_image3.png
Greyscale
Liu teaches Compound 6a, (Liu, Pg. 1563, Table 1), wherein R is -C2H5, shown top right, which differs from the elected species at the R1’ and Y positions of the Proteasome Inhibitor Moiety, Formula IV (as in instant Claims 14-15, wherein n is 0), shown bottom right, wherein R1’ is H.
PNG
media_image4.png
131
152
media_image4.png
Greyscale
Liu fails to teach R1’ is CH3 substituted with R3, wherein R3 is heteroaryl (benzofuranyl), and Y is
PNG
media_image2.png
70
69
media_image2.png
Greyscale
, and Z1 and Z2 together form a moiety derived from a boronic acid complexing agent.
However, Swinnen discloses alpha-amino boronic acid derivatives as selective immunoproteasome inhibitors, for the treatment of inflammatory and autoimmune diseases, neurodegenerative diseases, and proliferative diseases (‘979, Pg. 1, Lines 3-6.)
PNG
media_image5.png
180
223
media_image5.png
Greyscale
PNG
media_image6.png
208
242
media_image6.png
Greyscale
Swinnen teaches Compound 88 (‘979, Pg. 130, Compound 88), shown top right, which overlaps the instantly claimed -Linker-Proteasome Inhibitor moieties. Further, Swinnen teaches the genus Formula I, shown bottom right, wherein Rb and Rc may be linked to form a 5 or 6 membered-ring containing the oxygen atoms to which they are bond (‘979, Pg. 4, Lines 24-26), which expressly allows for the boronic acid pinacol ester variant at instant Y-Z1/Z2.
Regarding Claim 32, Swinnen teaches pharmaceutical formulations adapted for parenteral administration include aqueous and non-aqueous sterile injection solutions comprising antioxidants, buffers, bacteriostatics and solutes (‘979, Pg. 40, Lines 4-6.)
As Liu teaches conjugates comprising Artemisinin (ART) with the Linker –(CH2)y-C(=O)-, and Swinnen teaches the identical Linker and Proteasome Inhibitor – encompassing the compound of instant Formula IV, wherein n is 0, R1’ is CH3 substituted with R3, R3 is heteroaryl (benzofuranyl), Y is
PNG
media_image2.png
70
69
media_image2.png
Greyscale
, and Z1 and Z2 together form a moiety derived from a boronic acid complexing agent, for shared therapeutic use – it would have been prima facie obvious to a person of ordinary skill in the art to substitute the Proteasome Inhibitor of Swinnen into the conjugate ART – Linker platform of Liu in order to obtain the predictable benefit of improved therapeutic efficacy for the same indication. One would have been motivated to select a known proteosome inhibitor (Swinnen) for use in a known ART conjugate scaffold (Liu) to achieve a predictable improvement in treatment of the same disease (e.g., cancer), with a reasonable expectation that it would yield a functional conjugate suitable of improved treatment of the same disease.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p 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.
/D.M.N./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627