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
The information disclosure statement (IDS) submitted on 14 July, 2026 is acknowledged and has been considered.
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.
No additions, amendments, or cancellations have been made to the claims filed 2 July, 2024. The issue of new matter is moot.
Claims 4-13, 16, 19, and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.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
A new set of drawings filed 15 June, 2026 has been received and overcomes the previous objection, which is now withdrawn.
Response to Arguments
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues principally that Liu does not individually disclose the claimed proteasome inhibitor moiety and that Swinnen does not individually disclose the claimed artemisinin conjugate (Remarks, Pg 4-5). These arguments do not address the rejection as made. The rejection is not based on either Liu or Swinnen alone disclosing the entirety of the claimed subject matter. Rather, the rejection is based on the combined teachings of Liu and Swinnen.
Liu teaches artemisinin derivatives having an artemisinin moiety joined through a linker, including the recited –(CH2)y-C(=O)- linker arrangement, to a terminal moiety, and further evaluates such derivatives for therapeutic activity against cancer cells. Swinnen teaches boronic-acid-containing proteasome inhibitors, including the selected benzofuranyl-substituted α-amino boronic acid structure and boronic acid complexing-agent forms encompassed by the elected species, for treatment of proliferative and other diseases.
Thus, Liu is relied upon for the artemisinin-linker conjugate framework, while Swinnen is relied upon for the particular proteasome inhibitor moiety absent from Liu. The fact that Liu does not independently disclose the Swinnen proteasome inhibitor (Remarks, Pg. 4), and that Swinnen does not independently disclose an artemisinin conjugate (Remarks, Pg. 5), does not establish error in a rejection premised upon their combined teachings.
A persona of ordinary skill in the art would have had reason to employ the known proteasome inhibitor taught by Swinnen as the terminal therapeutic moiety in the artemisinin-linker conjugate framework taught by Liu. Both references concern therapeutically active compounds applicable to overlapping disease areas, including proliferative diseases. Incorporation of Swinnen’s known proteasome inhibitor into Liu’s known conjugate platform would have represented the use of a known therapeutic component in a known linker-based conjugate arrangement to obtain the predictable therapeutic properties associated with the incorporated components.
Applicant has not identified any teaching in either reference that discourages the proposed combination, any chemical incompatibility that would have prevented formation of the conjugate, or any reason a person of ordinary skill would have expected the resulting conjugate to be inoperative. Nor has Applicant submitted evidence showing that attachment of the Swinnen proteasome inhibitor through the Liu linker would necessarily destroy the therapeutic activity of either component.
Applicant’s argument that Swinnen does not expressly use the term “linker” (Remarks, Pg 5) is likewise unpersuasive. The prior art need not employ Applicant’s terminology where it discloses the relevant structure and connectivity. Swinnen’s disclosure of the complete proteasome inhibitor compounds necessarily discloses the constituent structural portions relied upon in the rejection.
Further, Applicant’s argument that Liu’s unmodified terminal moiety does not itself fall within Formula IV (Remarks, Pg 4) does not address the proposed modification. The rejection does not rely upon Liu’s terminal alkyl moiety as disclosing Formula IV. Rather, Swinnen is relied upon for the Formula IV proteasome inhibitor limitations, which are incorporated into the Liu artemisinin-linker framework in the proposed combination.
The present examination is directed to the elected Group I subject matter and elected Species DQ-9. The relevant inquiry is therefore whether the particular elected conjugate would have been obvious in view of the combined teachings of Liu and Swinnen, not whether either reference independently anticipates the full scope of Applicant’s broader Markush genus.
For the reasons set forth above and in the prior Office action, Applicant’s arguments do not overcome the prima facie case of obviousness. Accordingly, the rejection of Claims 1-3, 14-15, 17 and 32 under 35 U.S.C. § 103 is maintained.
Claim Rejections - 35 USC § 103 (MAINTAINED)
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_image1.png
107
93
media_image1.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_image2.png
131
152
media_image2.png
Greyscale
Liu fails to teach R1’ is CH3 substituted with R3, wherein R3 is heteroaryl (benzofuranyl), and Y is
PNG
media_image3.png
70
69
media_image3.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_image4.png
180
223
media_image4.png
Greyscale
PNG
media_image5.png
208
242
media_image5.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_image3.png
70
69
media_image3.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.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
Prosecution Insights