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 .
DETAILED ACTION
Applicant preliminary amendment of 9 March 2026, in which claims 5-15 have been amended, and claim 4 has been cancelled, is acknowledged.
Claims 1-3, 5-15 are pending in the instant application.
Claims 7-12, 14 are withdrawn, as being drawn to a non-elected species.
Claims 1-3, 5-6, 13, 15 are being examined herein.
Priority
The instant application is a National Stage entry of International Application No. PCT/US22/72339, filed on 16 May 2022, which claims priority from U.S. Provisional Patent Application 63/202,036, filed on 24 May 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9 March 2026 is acknowledged and considered.
Election/Restrictions
Applicants’ election without traverse of arteether
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as a specific antimalarial endoperoxide compound to be administered in the method, and the election of patients suffering from primary MDS as the patient population suffering from MDS or a subtype of MDS, and from leukemia or subtype of leukemia, if applicable, to be treated, for initial examination, in the Response of 9 March 2026, is acknowledged. Claims 1-3, 5-6, 13, 15 read on the elected species. Claims 7-12, 14 are withdrawn, as being drawn to a non-elected species.
Since Applicant has set forth no arguments against the requirement for restriction/election, the election is considered to be made without traverse, the requirement for restriction/election is maintained and is herein made FINAL.
Claims 1-3, 5-6, 13, 15 have been examined to the extent they read on the elected species, and the following objections and rejections are made below.
Objection to the claims
Claims 7-12, 14, while currently withdrawn, are objected to because of the following informality: they are presented in a non-compliant form. Specifically, the status identifiers for claims 7-12, 14 should read "(Withdrawn)" until such time as examiner rejoins the claims for examination. Appropriate correction is required. See MPEP 714(C).
Claims 6, 8, 10, 12 are objected to because they do not end with a period. Further, there should be a conjunction “and” between the last two structures listed in each of claims 6, 8, 10, 12.
Objection to the Specification
The Specification is objected to because it recites in [0001] the incorrect priority.
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Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-6, 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (Chemico-Biological Interactions 2014, 219, 28-36, cited in IDS).
Wang teaches that artesunate (ART)
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, which is an antimalarial endoperoxide compound of instant claim 1, and is an artemisinin derivative, as in instant claim 5, and is a compound of instant claim 6, is useful in AML and MDS treatment, as in instant claims 1-3, 13.
Wang teaches (page 29, left column, last paragraph) that ART is a useful treatment for MDS that increases apoptosis of the malignant cells. To assess the potential apoptotic effects of ART on malignant bone marrow cells in MDS, the effect of ART treatment was examined on human high-risk MDS cell line SKM-1, primary bone marrow (PBM) MNCs from clinical refractory anemia with excess blasts (RAEB) MDS and MDS AML patients (MDS cells), and PBM stromal cells from clinical rheumatic arthritis and allergic purpura patients without blood diseases (non-MDS cells).
Wang teaches (page 33, left column, point 3.1 under Results) that the ART treatment inhibited SKM-1 cells in a time-and concentration-dependent manner (Fig. 1A), producing IC50 values of 89.92, 4.24, and 1.28l mmol/L for ART treatments of 24, 48, and 72h, respectively.
Wang teaches (page 33, left column, point 3.2) that ART induced apoptosis in SKM-1 cells.
Wang teaches (page 34, left column, last paragraph) that the treatment with ART was shown to induce apoptosis in an MDS cell line, SKM-1 and PBM-MNC cells taken from clinical MDS patients and cultured in vitro.
Wang teaches (page 35, left column, last paragraph) that ART significantly inhibits cell proliferation in both MDS cell line SKM-1 and PBM-MNC cells taken from clinical MDS patients and cultured in vitro, but it has little impact on the proliferation of PBM stromal cells from clinical rheumatic arthritis and allergic purpura patients without blood diseases. In addition, ART inhibits SKM-1cell proliferation through caspase-dependent and-independent mitochondrial apoptotic pathways. These findings provide a rational basis for the use of ART in the treatment of MDS patients with a high risk of AML.
As such, a method of treating MDS in a subject suffering from MDS, and a method for slowing the development of AML in said subject, with ART is anticipated by Wang.
Claims 1-3, 5-6, 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar et al. (Leukemia Research 2017, 59, 124-135, cited in IDS).
Kumar teaches (Abstract) that artesunate (ARTS)
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, which is an antimalarial endoperoxide compound of instant claim 1, and is an artemisinin derivative, as in instant claim 5, and is a compound of instant claim 6, and is an orally bioavailable compound, has the most potent antileukemic activity in AML models and primary patients’ blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82 μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics.
Kumar (page 126, left solumn, last paragraph) tests artemisinin (ARTM)
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, artesunate (ARTS)
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, and dihydroartemisinin (DHA)
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, which are antimalarial endoperoxide compounds of instant claim 1, and are artemisinin or derivatives thereof, as in instant claim 5, and are compounds of instant claim 6, for antiproliferative activity and cytotoxicity against the AML cell lines, MV4-11, MOLM-13, OCI-AML3, NB4 and KG1A (cells lines selected as representative of relatively frequent cytogenetic/molecular subsets of AML). Kumar teaches that among the artimisinins tested, ARTS showed the most anti proliferative activity. The FLT3-ITD+ cell lines MOLM-13 and MV4-11 were the most sensitive to ARTS with IC50 Table 1 IC50 values of 0.82 and 1.1 μM respectively (Table 1).
Kumar teaches (Abstract) that the antileukemic activity of ARTS was further confirmed in MV4-11 and FLT3-ITD+ primary AML cell xenografts as well as MLL-AF9 syngeneic murine AML model where ARTS treatment resulted in significant survival prolongation of treated mice compared to control.
Kumar teaches (Abstract) antileukemic activity of ARTS alone or in combination with conventional chemotherapy or BCL-2 inhibitor, for treatment of AML.
Kumar uses bone marrow samples from MDS patients and AML patients (page 125, left column, point 2.1). Kumar teaches (page 128, right column, point 3.5) that ARTS treatment inhibited colony formation by AML and MDS cells. In order to determine the activity of artimisinins against clonigenic primary AML and MDS cells, the effect of treatment with ARTM, ARTS and DHA on colony forming cells (CFC) in bone marrow CD34+ cells from AML and MDS patients as well as normal controls (n =3) (Fig. 5) was examined. ARTS was the most effective of the artimisinins in suppressing colony formation. ARTS treatment for 48 h prior to plating in methylcellulose resulted in significant inhibition CFU-GM from AML and MDS patients. These data show the activity of ARTS against clonigenic AML and MDS progenitors.
Kumar teaches (page 133, left column, under 4. Discussion) potent antileukemic activity of ARTS in vitro as well as in three different murine models including a xenograft model using primary AML cells. Kumar also teaches in vitro activity of ARTS against primary MDS cells.
As such, a method of treating MDS in a subject suffering from MDS, and a method for treating/slowing the development of AML in said subject, with ARTS is anticipated by Kumar.
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 1-3, 5-6, 13, 15 are rejected under 35 U.S.C. 103 as being unpatentable over Jansen et al. (EP 2,289,554, cited in IDS).
Jansen teaches ([0053]) a method of treating a hematological malignancy such as, for example, acute myelogenous leukemia (also known as acute myeloid leukemia, AML), as in instant claims 2, 3, or myelodysplastic syndrome, as in instant claims 1, 13, comprising administering to a subject in need thereof a composition comprising one or more artemisinin compound.
The artemisinin compound is chosen from the group consisting of dihydroartemisinin, artemisinin, artesunate, artemether, artelinic acid, artenimol and artemotil, although other artemisinin compounds having a sesquiterpene lactone structure are encompassed by the present invention ([0029], page 4). Such compounds are antimalarial endoperoxide compounds of instant claim 1, and are artemisinin derivatives, as in instant claim 5, and are compounds of instant claim 6, namely
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,
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Jansen also teaches [0030] broadly compositions of the invention comprising an artemisinin compound of formula (I)
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Jansen teaches [0035]-[0037] that the compound according to formula (I) is preferably derived from a compound selected from the group consisting of dihydroartemisinin, anhydrodihydroartemisinin and deoxartemisinin; the compound according to formula (I) can be derived from a known intermediate of the biosynthesis of the antimalarial drug artemisinin, i.e., dihydroartemisinin (DHA).
Jansen teaches [0037] that, in case of dihydroartemisinin
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, the 1 position of the initial artemisinin derivative comprises an -OH group allowing covalent coupling of a present moiety to the 1 position, for example, by an esterification reaction or an etherification reaction. The genus of Jansen encompasses ethers, namely artemether or arteether (Applicant’s elected species), which are compounds of instant claim 6.
Jansen specifically teaches ([0042]-[0051], Examples 1-16) compounds of formula (II)-(XVI), which are antimalarial endoperoxide compounds which are artemisinin derivatives, as in instant claims 1-3, 5.
Jansen teaches combination therapy with a pharmaceutical composition comprising thalidomide and one or more artemisinin derivatives as above.
Jansen does not teach treating subtypes of MDS, as in instant claim 15, with an artemisinin derivative.
Bennett (Seminars in Oncology 2005, 32 (Suppl. 5), S3-S10, cited in PTO-892) teaches (Figure 3) classification systems in myelodysplastic syndromes, including (Figure 3, page S6), RA, RARS, RAEB, which are subtypes of MDS in instant claim 15.
It would have been obvious to a person of ordinary skill in the art to use the teachings of Jansen to arrive at the instant invention. The person of ordinary skill in the art would have been motivated to administer an artemisinin derivative taught by Jansen, in a method of treating MDS, or of treating/slowing AML in a patient with MDS, because Jansen teaches a method of treating a hematological malignancy such as, for example, acute myelogenous leukemia (also known as acute myeloid leukemia, AML), as in instant claims 2, 3, or myelodysplastic syndrome, as in instant claims 1, 13, comprising administering to a subject in need thereof a composition comprising one or more artemisinin compound. Thus, the person of ordinary skill in the art would have administered a composition comprising an artemisinin derivative taught by Jansen, in a method of treating MDS, or slowing AML taught by Jansen, with a reasonable expectation of achieving therapeutic effect.
The person of ordinary skill in the art would have been motivated to choose arteether as the artemisinin derivative, because Jansen specifically teaches artemether, which is a direct homolog methyl vs. ethyl ether, of Applicant’s elected species, as an artemisinin compound in a pharmaceutical composition administered in the method. In the absence of unexpected results, stereoisomers are considered obvious variants of each other. "Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties". In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Regarding claim 15, the person of ordinary skill in the art would have been motivated to administer an artemisinin derivative taught by Jansen to treat MDS, ALM, and subtypes of MDS, such as RA, RARS, RAEB, with the expectation that an artemisinin derivative taught by Jansen to treat MDS will be effective to treat MDS and subtypes of MDS.
As such, claims 1-3, 5-6, 13, 15 are rejected as prima facie obvious.
Conclusion
Claims 1-3, 5-6, 13, 15 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S. LUNDGREN can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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