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 .
Status of Application
The Amendments and Remarks filed on 12/18/25 are acknowledged.
Claims 2-3, 5-9, and 11-12 were cancelled.
Claims 1, 4, 13-14, 18, and 21 were amended.
Claims 22-40 were previously withdrawn from consideration.
Claims 1, 4,10, and 13-40 are pending.
Claims 1, 4, 10, and 13-21 are included in the prosecution.
Response to Amendments, Arguments, & Declaration
Objection to the Drawings
In light of the replacement sheets filed on 12/18/25, the objection to the drawings is withdrawn.
Claim Objections
In light of the amendment of claim 21, the objection to this claim is withdrawn.
Rejection of claims under 35 USC § 112(b)
In light of the cancellation of claims 8, 11, and 12, the rejection of these claims under 35 USC § 112(b) is moot. In light of the amendment of claim 1 to delete “components thereof” the rejection of this claim under 35 USC § 112(b) is withdrawn.
Rejection of claims under 35 USC § 112(d)
In light of the cancellation of claims 2 and 6, the rejection of these claims under 35 USC § 112(d) is moot.
Claim Interpretation
The amendment of claim 1 to recite the phrase “in need thereof” is acknowledged.
Rejection of claims under 35 USC § 102(a)(1)
Applicant amended claim 1 to incorporate the subject matter of claims 3 and 9. In light of this amendment, the rejection of claims 1-2, 5-8, and 15-18 under 35 U.S.C. 102(a)(1) as being anticipated by Kirk-Ballard et al. (Nutrition 2014;30(0 0):S21-S25, Pages 1-12 – “Kirk-Ballard”) is withdrawn. Claims 3 and 9 were not previously included in the anticipation rejection.
Rejection of claims under 35 USC § 103 – Kirk-Ballard, Cetin, Ghobrial
Applicant’s arguments (Page 8, filed 12/18/25) regarding the rejection of claims 3-4 and 19-21 under 35 U.S.C. 103 as being unpatentable over Kirk-Ballard in view of Cetin et al. (Nature Communications 2017 Nov 20;8(1):1613 Pages 1-12 – “Cetin”) and Ghobrial et al. (US 2009/0156469 A1 – “Ghobrial”) have been fully considered and are persuasive. Since claim 9 was not previously included in this obviousness rejection, and the subject matter of claim 9 was incorporated into amended claim 1, this rejection is withdrawn.
Rejection of claims under 35 USC § 103 – Kirk-Ballard and Yu
Applicant’s arguments (Page 9, filed 12/18/25) and the Declaration under 37 C.F.R. § 1.130(a) (“the Declaration”) by Elizabeth Floyd (“the Declarant”) (filed 12/18/25) regarding the rejection of claims 9-14 under 35 U.S.C. 103 as being unpatentable over Kirk-Ballard in view of Yu et al. (Journal of Natural Products 2019 Dec 27;82(12):3321-3329 - “Yu”) have been fully considered and are persuasive. The Declarant establishes that Yu is the Applicant’s own work. Therefore, Yu is removed as a prior art reference. Therefore, the obviousness rejection based on Yu is withdrawn.
New ground(s) of rejection
However, upon further consideration of the amended claims, a new ground(s) of rejection is made under 35 USC 103 in view of new supporting reference Obanda et al. (Nutrition 30 (2014) S59-S66).
Since the new grounds of rejection were necessitated by Applicant’s amendment, this action is made FINAL.
Double Patenting
Applicant’s arguments (Page 9, filed 12/18/25) regarding the following double patenting rejections have been fully considered and are persuasive in light of the amendments of the instant claims and the copending applications.
The provisional rejection of claims 1, 6-7, and 15-17 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 and 19-21 of copending Application No. 17/760,093
The provisional rejection of claims 1-2, 6-14, and 18 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 and 5-10 of copending Application No. 17/782,949
Therefore, the provisional double patenting rejections are withdrawn.
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
New Objections & Rejections Necessitated by Amendment
Claim Objections
Claim 1 is objected to because of the following informalities: In claim 1, penultimate line, the term “sakuranenin” should be corrected to recite “sakuranetin.”
Appropriate correction is required.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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, 4, 10, and 13-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kirk-Ballard et al. (Nutrition 2014;30(0 0):S21-S25, Pages 1-12 – “Kirk-Ballard”) in view of Cetin et al. (Nature Communications 2017 Nov 20;8(1):1613 Pages 1-12 – “Cetin”), Ghobrial et al. (US 2009/0156469 A1 – “Ghobrial”), and Obanda et al. (Nutrition 30 (2014) S59-S66 – “Obanda”).
The claimed invention is a method of treating a disease or disorder characterized by aberrations in the ubiquitin proteasome system (UPS), wherein the disease or disorder comprises cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a component of a botanical extract isolated from Artemisia spp., wherein the component comprises DMC-1, DMC-2, davidigenin, sakuranetin, or 6-demethoxycapillarisin or combinations thereof.
Kirk-Ballard discloses a method of treating obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation (Abstract, Page 2, ¶ 2) by administering an extract from Artemisia dracunculus, termed PMI5011, which improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance (Abstract). The method comprises randomly dividing the mice into a control group and a PMl5011-treated group; the PMI5011 treatment group was fed ad libitum the low-fat diet containing 1% (w/w) PMl5011 (Page 3, ¶ 2). As shown in Figure 3 B, the ubiquitin-specific proteases (USP) USP14 and USP19 are up-regulated with muscle atrophy; and PMl5011 consistently decreases the gene expression of Usp14 (Page 4, ¶ 3).
Kirk-Ballard does not expressly teach treating cancer, or the components DMC-1, DMC-2, davidigenin, sakuranetin, or 6-demethoxycapillarisin or combinations thereof.
Cetin teaches that therapeutic advances that have greatly reduced the morbidity and mortality of multiple myeloma include the use of proteasome inhibitors, e.g., bortezomib and carfilzomib (Page 2, Col. 1, 1st ¶). Bortezomib is disclosed as a proteasome inhibitor commonly used as frontline therapy (Page 5, Col. 1, 2nd ¶). Fig. 2 shows that human multiple myeloma ANBL-6 cells rapidly reduce the mass accumulation rate (MAR) upon exposure to proteasome inhibition (Page 3).
Ghobrial teaches that bortezomib, a proteasome inhibitor, inhibits the ubiquitin-26S proteasome pathway, and has become an exciting target in a variety of malignancies, most notably multiple myeloma ([0055]).
Obanda teaches the bioactive compounds of Artemisia dracunculus L. (PMI 5011) (Abstract). Four bioactive compounds previously isolated from PMI 5011 include davidigenin, sakuranetin, DMC-2, and 2’,4-dihydroxy-4’-methoxydihydrochalcone (DMC-1) (Page S60, Col. 2, 2nd ¶, under “Source and characterization of PMI 5011 and active compounds”). Figure 2 shows the structures of the bioactive compounds.
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of regulating ubiquitin-proteasome-mediated protein degradation by administering an extract from Artemisia dracunculus, termed PMI5011, as taught by Kirk-Ballard, in view of the use of proteasome inhibitors, e.g., bortezomib and carfilzomib, for the treatment of multiple myeloma, as taught by Cetin, the inhibition of the ubiquitin-26S proteasome pathway in multiple myeloma by the proteasome inhibitor bortezomib, as taught by Ghobrial, and the bioactive compounds isolated from PMI 5011 which include davidigenin, sakuranetin, DMC-1, and DMC-2, as taught by Obanda, and arrive at the instant invention.
One of ordinary skill in the art would have been motivated to combine the proteasome regulator PMI5011 taught by Kirk-Ballard with the proteasome inhibitors taught by Cetin in the treatment of a cancer such as multiple myeloma because the ubiquitin proteasome pathway in multiple myeloma would have been effectively targeted by ubiquitin proteasome inhibitors such as PMI5011 and bortezomib as taught by Ghobrial ([0055]). There would have been a reasonable expectation of success based on the teaching by Ghobrial ([0055]) unless there is evidence of criticality or unexpected results.
One of ordinary skill in the art would have been motivated to combine the teachings of Obanda with Kirk-Ballard because both references teach an extract from the same botanical source, i.e., Artemisia dracunculus, termed PMI5011. One of ordinary skill in the art would have found the components davidigenin, sakuranetin, DMC-1, and DMC-2 of PMI 5011 obvious since these are naturally present in Artemisia dracunculus, as taught by Obanda (Abstract, Page S60, Col. 2, 2nd ¶, Fig. 2).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitation of a method of treating a disease or disorder characterized by aberrations in the UPS would have been obvious over the method of treating obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation (Abstract, Page 2, ¶ 2) by administering an extract from Artemisia dracunculus, termed PMI5011, which improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance (Abstract), the PMl5011-treated group which was fed ad libitum the low-fat diet containing 1% (w/w) PMl5011 (Page 3, ¶ 2), and PMl5011 which consistently decreases the gene expression of Usp14 (Figure 3B and Page 4, ¶ 3), as taught by Kirk-Ballard.
Regarding instant claims 1 and 4, the limitations of cancer and multiple myeloma, respectively, would have been obvious over the use of proteasome inhibitors, e.g., bortezomib and carfilzomib (Page 2, Col. 1, 1st ¶), as taught by Cetin, and the inhibition of the ubiquitin-26S proteasome pathway, which is a target in a variety of malignancies, most notably multiple myeloma, by using bortezomib, as taught by Ghobrial ([0055]).
Regarding instant claim 1, the limitations of DMC-1, DMC-2, davidigenin, sakuranetin, or 6-demethoxycapillarisin or combinations thereof would have been obvious over the davidigenin, sakuranetin, DMC-1, and DMC-2 of PMI 5011 which are present in Artemisia dracunculus (Abstract, Page S60, Col. 2, 2nd ¶, Fig. 2), as taught by Obanda.
Regarding instant claim 10, the limitation of the knockout extract (KOE) would have been obvious over the bioactive compounds extracted from Artemisia dracunculus L. (PMI 5011) (Abstract) which contain davidigenin, sakuranetin, DMC-1, and DMC-2 (Page S60, Col. 2, 2nd ¶, under “Source and characterization of PMI 5011 and active compounds”), as taught by Obanda.
Regarding instant claim 13, the limitation of the KOE not comprising DMC-1 or DMC-2 would have been obvious over the bioactive compounds extracted from Artemisia dracunculus L. (PMI 5011) (Abstract) which contain davidigenin and sakuranetin (Page S60, Col. 2, 2nd ¶, under “Source and characterization of PMI 5011 and active compounds”), as taught by Obanda.
Regarding instant claim 14, the limitation of the KOE not comprising DMC-1 and DMC-2 would have been obvious over the bioactive compounds extracted from Artemisia dracunculus L. (PMI 5011) (Abstract) which contain davidigenin and sakuranetin (Page S60, Col. 2, 2nd ¶, under “Source and characterization of PMI 5011 and active compounds”), as taught by Obanda.
Regarding instant claims 15 and 16, the limitations of an alcoholic extract and an ethanolic extract, respectively, would have been obvious over the ethanolic extract of Artemisia dracunculus L. (PMI 5011) (Page S60, Col. 2, 2nd ¶, under “Source and characterization of PMI 5011 and active compounds”), as taught by Obanda.
Regarding instant claim 17, the limitation of the botanical extract modulating the activity of at least one deubiquitinating enzyme (DUB) would have been obvious over the method of using PMI5011 which consistently decreases the gene expression of Usp14 (ubiquitin-specific protease which is a class of deubiquitylating enzymes that reverse the ubiquitin modification of proteins, antagonizing the effect of ubiquitylation and recycling free ubiquitin) (Page 4, 3rd ¶ and Figure 3 B), as taught by Kirk-Ballard.
Regarding instant claim 18, the limitation of the botanical extract orally administered to a subject would have been obvious over the method where the PMI5011 treatment group was fed ad libitum the low-fat diet containing 1% (w/w) PMl5011 (Page 3, ¶ 2), as taught by Kirk-Ballard.
Regarding instant claims 19-21, the limitations of the additional active agents would have been obvious over the use of proteasome inhibitors, e.g., bortezomib and carfilzomib (Page 2, Col. 1, 1st ¶), as taught by Cetin, and the inhibition of the ubiquitin-26S proteasome pathway, which is a target in a variety of malignancies, most notably multiple myeloma, by using bortezomib, as taught by Ghobrial ([0055]).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615