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
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed December 29, 2025. The amendment, filed December 29, 2025, is entered, wherein claims 1, 9, 13 – 19, 24, 26, and 45 are amended and claims 2, 7 – 8, 10 – 12, and 40 – 44 are canceled.
Claims 1, 3 – 6, 9, 13 – 39, and 45 are pending in this application and are currently examined.
Priority
This application is a national stage application of PCT/US2021/036992, filed June 11, 2021, which claims benefit of domestic applications 63/038,856, 63/060,605, and 63/198,856, filed June 14, 2020, August 3, 2020, and November 17, 2020, respectively.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/038,856, 63/060,605, and 63/198,856, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional applications 63/038,856, 63/060,605, and 63/198,856 do not provide support for the limitations of “ 5-aza-2’-deoxycytidine (decitabine)”, “guadecitabine”, “5-fluoro-2’-deoxycytidine”, “zebularine”, “CP-4200”, “RG108”, and “nanaomycin A” recited in claims 4 and 6; “a fixed dose of 10 mg to 1000 mg per day of venetoclax” recited in claim 9; “a fixed dose of 20 mg to 4000 mg per day of the at least one E-selectin antagonist” recited in claim 13; “liquid cancers” recited in claim 14; “solid cancers” recited in claim 15; “colorectal cancer…, and head and neck squamous cell carcinoma’ recited in claim 18; “melanoma, leukemia…., and head and neck squamous cell carcinoma” recited in claim 19; “acute lymphotic leukemia…, and chronic myelogenous leukemia” recited in claim 20; “non-Hodgkin’s lymphoma and Hodgkin’s lymphoma” recited in claim 21; “the myeloma is multiple myeloma” recited in claim 22; “the melanoma is chosen from uveal melanoma and skin melanoma” recited in claim 23; “wherein the subject expresses the gene ST3GAL4 at an expression level greater than that of at least 55% of cancer patients”, “wherein the subject expresses the gene B3GNT5 at an expression level greater than that of at least 55% of cancer patients”, and “wherein the subject expresses the gene FUT7 at an expression level greater than that of at least 55% of cancer patients” recited in claims 28 – 30; claims 31, 33, and 36; “ST3GAL4”, “B3GNT5”, and “FUT7” recited in claims 32 and 37; “one or more E-selectin ligand-forming genes are glycosylation genes” recited in claim 34; “one or more E-selectin-ligand forming genes are chosen from ST3GAL4 and FUT7” recited in claim 35; and “inhibits the metastasis of cancer cells” recited in claim 38. Thus, the priority date of claims 3 – 6, 9, 13 – 15, 18 – 23, 25 – 26, 28 – 38 is June 11, 2021.
Responses to Applicant’s Remarks:
Applicant notes that the effective filing date of a claimed invention is determined on a claim-by-claim basis and not an application-by-application basis. Applicant notes that the claims have been amended, rendering the previous analysis inapplicable to the pending claims. The examiner has considered the amended claims and has adjusted the claim-by-claim analysis as discussed above.
Withdrawn Rejections
4. The rejection of claims 1, 11 – 24, 27 – 30, and 38 – 39 in the previous Office Action, mailed June 30, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Magnani et al. with evidence provided by Nair has been considered and is withdrawn in view of the amended claim 1.
The rejection of claim 1 in the previous Office Action, mailed June 30, 2025, on the ground of nonstatutory double patenting as being unpatentable over claim 40 of copending Application No. 18/630,125 has been considered and is withdrawn in view of the amended claim 1.
The following are maintained / modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed December 29, 2025, wherein claims 1, 9, 13 – 19, 24, 26, and 45 are amended and claims 2, 7 – 8, 10 – 12, and 40 – 44 are canceled. Previously cited references have been used to establish the maintained / modified grounds of rejection.
Maintained / Modified / New 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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 – 6, 9, 13 – 23, 27 – 30, 38 – 39, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani et al. (WO2013/096926A1, cited in the previous Office Action mailed June 30, 2025) with evidence provided by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, cited in the previous Office Action mailed June 30, 2025) in view of DiNardo et al. (Blood, 2019, Vol. 133, Issue 1, page 7 – 17, cited in the previous Office Action mailed June 30, 2025).
Regarding claims 1, 3 – 6, 9, 13 – 23, 27 – 30, 38 – 39, and 45, Magnani et al. teach a method for treating a cancer in a subject comprising administering to the subject (a) a compound having a structure of formula (I) and (b) at least one of (i) chemotherapy and (ii) radiotherapy (page 5, lines 15 – 20). The compound of formula (I) is compound 25 (page 21, line 5) or pharmaceutically acceptable salts (page 22, line 5), for example in the form of a salt such as sodium (page 26, line 15):
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The compound may be prepared for pharmaceutical use in a subject, including a human subject (page 49, lines 6 – 7). In general, the amount of the compound described is present in a dose from about 0.01 μg to about 1000 μg per kg weight of the host (page 49, lines 29 – 31). Magnani et al. demonstrates the effectiveness of compound 25 in leukemia animal model, wherein the leukemia is AML and pancreatic cancer animal model (page 63 – 64, Example 3; page 66, Example 5). The method also treats Hodgkin lymphoma, multiple myeloma, and melanoma (page 38, lines 6 – 15). Liquid tumor cells may also adhere to bone marrow, which may further lead to sequestration and quiescence of the tumor cells, resulting in “resistance” of the tumor cells to chemotherapy. Studies have shown that bone marrow contains anatomic regions that comprise specialized endothelium, which expresses the E-selectin. Accordingly, the E-selectin antagonist may be useful for inhibiting metastasis of cancers that comprise either a solid or liquid tumor by inhibiting binding of an E-selectin ligand to E-selectin.
According to Nair, a reference body weight of human is 60 kg. The dosage of the compound would be 60 mg if 1000 μg per kg weight of the host is used, which addresses claim 13. FLT3 mutation or FLT-ITD mutation is known in the art to be the common genetic change in AML. As Magnani et al. teach to treat AML, the patient population will also encompass AML patients with FLT3 or FLT-ITD mutation. For the gene expression level of ST3GAL4, B3GNT5, and FUT7, Magnani et al. do not differentiate the patients, therefore, the disclosure of Magnani et al. encompasses the limitations of claims 28 – 30.
However, Magnani et al. do not teach the method comprising administering at least one hypomethylating agent, such as 5-azacitidine and decitabine, and the venetoclax with a fixed dose of 10 mg to 1000 mg per day.
DiNardo et al. teach that venetoclax in combination with decitabine or azacitidine is reported to be safe and effective in a large, multicenter, phase 1b dose-escalation and expansion study. During dose escalation, oral venetoclax is administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1 – 5, intravenously or azacitidine (75 mg/m2, days 1 – 7, intravenously or subcutaneously) to patients with acute myeloid leukemia (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date to modify the method for treating a cancer, such as AML, in a subject comprising administering to the subject a compound having a structure of formula (I) and at least one of (i) chemotherapy as taught by Magnani et al. with administering venetoclax and decitabine or azacitidine in view of DiNardo et al. to treat AML. It would have been obvious for one of ordinary skill in the art to do this because the drugs are known separately in the prior art for the purpose of treating AML, and it would have been obvious to substitute equivalent drug known to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to modify the method for treating a cancer, such as AML, in a subject comprising administering to the subject a compound having a structure of formula (I) and at least one of (i) chemotherapy as taught by Magnani et al. with administering venetoclax and decitabine or azacitidine in view of DiNardo et al. because it is well known to combine drugs to treat the same disease and further Magnani et al. teach that E-selectin antagonist can be used in combination with other drugs.
Claims 24 – 26 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani et al. (WO2013/096926A1, cited in the previous Office Action mailed June 30, 2025) with evidence provided by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, cited in the previous Office Action mailed June 30, 2025) in view of DiNardo et al. (Blood, 2019, Vol. 133, Issue 1, page 7 – 17, cited in the previous Office Action mailed June 30, 2025) as applied to claims 1, 3 – 24, 27 – 30, 38 – 39, and 45 above, and further in view of Saliba et al. (Cancer Drug Resistance, March 2021, cited in the previous Office Action mailed June 30, 2025).
Regarding claims 24 – 26, the references teach the limitation discussed above.
However, these references do not teach that the subject has acquired resistance to venetoclax, a therapy comprising at least one hypomethylating agent or a combination therapy comprising venetoclax and at least one hypomethylating agent.
Saliba et al. teach that resistance to venetoclax and hypomethylating agents occurs in some patients with AML (Abstract). While some of these mechanisms of resistance can potentially be targeted therapeutically (e.g. FLT3 mutation or even possibly TP53 mutation), others such as monocytic differentiation are more difficult to directly address pharmacologically. Accordingly, targeting a more general mechanism of resistance that is not usually dependent on specific genetic mutations may be clinical utility. AML cells take advantage of stromal-dependent pro-survival signals to create a permissive niche within the bone marrow microenvironment via interactions between upregulated cell surface receptors, including very late antigen-4 (VLA-4), CD44, and E-selectin ligand-1. This niche is favorable for the maintenance and progression of chemotherapy-resistant disease. This mechanism of resistance may be potentially modified or targeted, for example, VLA-4 antibodies and cytarabine improves survival in AML mouse models relative to cytarabine alone.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to expand the patient population as taught by Magnani et al. to cover patients that are resistance to venetoclax and hypomethylating agents in view of Saliba et al. because Saliba et al. suggest that a E-selectin ligand-1 may be the niche that is favorable for the maintenance and progression of chemotherapy-resistant disease. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to expand the patient population as taught by Magnani et al. to cover patients that are resistance to venetoclax and hypomethylating agents in view of Saliba et al. because Saliba et al. suggests that E-selectin ligand-1 is a favorable niche to solving cancer drug resistance.
Claims 31 – 37 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani et al. (WO2013/096926A1, cited in the previous Office Action mailed June 30, 2025) with evidence provided by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, cited in the previous Office Action mailed June 30, 2025) in view of DiNardo et al. (Blood, 2019, Vol. 133, Issue 1, page 7 – 17, cited in the previous Office Action mailed June 30, 2025) as applied to claims 1, 3 – 24, 27 – 30, 38 – 39, and 45 above, and further in view of Liang et al. (OncoTargets and Therapy, 2017, Vol. 10, page 3971 – 3978, cited in the previous Office Action mailed June 30, 2025).
Regarding claims 31 – 37, Magnani et al. teach one of any combination of diagnostic methods, including physical examination, assessment and monitoring of clinical symptoms, and performance of analytical tests and methods may be used for monitoring the health status of the subject (page 40, lines 15 – 18). The cancer patient population most likely to respond to treatment using compounds of formula (I) are patients express a highly active E-selectin or patients with elevated expression of the E-selectin binding ligands (sialyl Lea and sialyl Lex). Magnani et al. disclose that blasts, for example AML blasts, has been used in the observation for CD44 expression. Moreover, mice are engrafted with human AML blasts and treated with compound 25 with other chemotherapeutics in another experiment (page 64, lines 35 – 36). When the AML cells comprised about 10% of cells in the blood, the mice are treated (page 65, lines 1 – 2).
However, Magnani et al. do not teach the method further comprises selecting the subject for treatment when sample from the subject expresses FUT7 gene and selecting the subject for treatment when at least 10% of the blast cells in the sample express FUT7 gene.
Liang et al. teach that FUT7 is one of a 1,3-fucosyltransferases family that catalyzes the final fucosylation step in the synthesis of Lewis antigens and generates a unique glycosylated product sialyl Lewis X (sLex) (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the biomarker of sialyl Lex as taught by Magnani et al. with FUT7 in view of Liang et al. because Liang et al. teach that FUT7 is the gene that helps generate sialyl Lex. Based on the relationship provided by Liang et al., it would have been obvious to substitute the biomarker when diagnosing cancer because over-expression of sialyl Lex is directly proportional to more expression of FUT7. Therefore, the substitution will yield predictable results. The references do not explicitly teach the diagnostic test of FUT7 gene in blast cell. One would have been motivated to diagnose AML with blast cells for the expression of FUT7 because Magnani et al. suggests that blast cells may be used to monitor the patients and sialyl Lex is the biomarker of AML and Liang et al. teach that FUT7 will generate sialyl Lex. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to substitute the biomarker of sialyl Lex as taught by Magnani et al. with FUT7 in view of Liang et al. because such substitution to determine whether the patients have AML is predictable.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed December 29, 2025, have been fully considered and are found to be not persuasive.
Regarding the rejection, Applicant mentions that the Office has only provided a generic rationale that it may possible to try to combine previously disclosed treatments with each other or to substitute previously disclosure treatments for one another. Applicant argues that this generic rationale is far from rendering obvious the pending claims because an “obvious to try” rationale may support a conclusion that a claim would have been obvious only where one skilled in the art “is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success”. Applicant argues that the Office has not established that there is “a finite number of identified solutions”, that the Office has failed to establish that the claimed combination would be “predictable”, and that the Office has failed to establish “a reasonable expectation of success”. However, these arguments are not persuasive. The previous rejection is not based on selecting from all possible cancer therapies in general. Instead, the rejection is based on combining known treatment approaches directed to the same disease. Magnani et al. teach the administration of the recited E-selectin antagonist for the treatment of cancer, including AML, and further teach that the antagonist may be administered in combination with other anticancer therapies. DiNardo et al. teach administration of venetoclax in combination with a hypomethylating agent for treatment of AML. Thus, one of ordinary skill in the art would have been motivated to combine the AML treatment approach taught by Magnani et al. with the AML treatment in view of DiNardo et al. to treat the same disease. The Office is not required to demonstrate that the therapeutic effect is predictable. Rather, it is about whether one of ordinary skill in the art would have found it obvious to combine the teachings of the cited references using known methods. Magnani et al. teach the use of the recited E-selectin antagonist in treating cancer, including AML, and further teach to use the recited E-selectin antagonist in combination with other anticancer therapies. DiNardo et al. teach venetoclax-based combination therapy for AML. Therefore, combining the treatment approaches of Magnani et al. and DiNardo et al. will yield predictable results. Furthermore, it is sufficient that one of ordinary skill in the art would have had a reasonable expectation that combining known therapies for the same disease would have been successful for their intended purpose. One of ordinary skill in the art would have had a reasonable expectation of success in combining the AML treatment approach of Magnani et al. with the AML treatment in view of DiNardo et al. because both references teach the treatment for AML and it is known in the art to combine drugs for the same purpose.
Finally, Applicant argues that the combination of Compound A with venetoclax shows surprisingly superior treatment ability in cellular and animal models as compared to either compound A or venetoclax. However, the argument is not persuasive. Claim 1 broadly recites “a method of treating a cancer” and is not limited to AML. The evidence only uses AML as the testing medium. It is clear that the results are not commensurate in scope with the claims.
Maintained / Modified Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3 – 6, 9, 13 – 23, 25, 27 – 30, 38 – 39, and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 38 of copending Application No. 18/291,884 in view of Magnani et al. (WO2013/096926A1, cited in the previous Office Action mailed June 30, 2025).
a. Regarding claims 1, 3 – 6, 9, 13 – 23, 25, 27 – 30, 38 – 39, and 45, ‘884 teaches a method of treating a cancer in need thereof comprising administering to the subject at least one E-selectin antagonist, wherein the subject is further administered at least one antineoplastic agent, and wherein the at least one E-selectin antagonist is chosen from
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and pharmaceutically acceptable salts thereof (claim 1). The method further comprises administering at least one hypomethylating agent, wherein the hypomethylating agent is 5-azacitidine or decitabine (claims 2 and 4 – 5). The antineoplastic agent is venetoclax (claims 3 and 8). The antineoplastic agent may be a targeted therapy drug or chemotherapeutic agent (claims 7 and 10). The dose of venetoclax is from 10 mg to 1000 mg per day (claim 9). The method comprises administering to the subject a fixed dose of 20 mg to 4000 mg per day of at least one E-selectin antagonist (claim 11). The cancers to be treated may be a solid cancer, liquid cancer (claims 12 – 13), a FLT3 mutated cancer, or FLT3-ITD mutated cancer (claims 14 – 15). The specific cancer to be treated are pancreatic cancer, acute myeloid leukemia, Hodgkin’s lymphoma, multiple myeloma, or uveal melanoma (claims 16 – 22). The subject to be treated has acquired resistance to at least one antineoplastic agent, hypomethylation agent, or the combination of both (claims 23 – 25). The subject to be treated possesses one or more mutational alterations of FLT3 (claim 26). The subject to be treated expresses the gene ST3GAL4, B3GNT5, or FUT7 at an expression level greater than that of at least 55% of cancer patients (claims 27 – 29). The method further comprises selecting the subject to treat through a method comprising (a) determining or having determined the gene expression level of one or more genes in the subject or a sample from the subject; and (b) selecting the subject for treatment when at least 10% of the blast cells from the subject or sample from the subject expresses the one or more genes, wherein the one or more genes are chosen from ST3GAL4, B3GNT5, and FUT7 (claims 30 – 31). The method may further comprise (a) obtaining or having obtained a biological sample comprising blast cells from the subject; (b) performing or having performed an assay on the biological sample to determine the gene expression level of one or more E-selectin ligand-forming genes in the sample; and (c) selecting the subject for treatment when at least 10% of the blast cells in the sample express the one or more E-selectin ligand-forming genes, wherein the E-selectin ligand-forming genes are glycosylation genes or ST3GAL4 and FUT7 (claims 32 – 34). The method may further comprise (a) determining the gene expression level of one or more genes in the subject or a sample from the subject; (b) comparing the gene expression level from (a) to a control sample from a cancer-free subject, a newly diagnosed cancer subject, or a subject diagnosed with the same cancer as the subject; and (c) selecting the subject for treatment when the gene expression level exceeds that in the control sample, wherein the gene are chosen from ST3GAL4, B3GNT5, and FUT7 (claims 35 – 36). The method of the administration inhibits the metastasis of cancer cells (claim 37). The subject is human (claim 38).
However, ‘884 does not teach the E-selectin antagonist to be
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Magnani et al. teach a method for treating a cancer in a subject comprising administering to the subject (a) a compound having a structure of formula (I) and (b) at least one of (i) chemotherapy and (ii) radiotherapy (page 5, lines 15 – 20). The compound of formula (I) is compound 25 (page 21, line 5) or pharmaceutically acceptable salts (page 22, line 5), for example in the form of a salt such as sodium (page 26, line 15):
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The compound may be prepared for pharmaceutical use in a subject, including a human subject (page 49, lines 6 – 7). In general, the amount of the compound described is present in a dose from about 0.01 μg to about 1000 μg per kg weight of the host (page 49, lines 29 – 31). Magnani et al. demonstrates the effectiveness of compound 25 in leukemia animal model, wherein the leukemia is AML and pancreatic cancer animal model (page 63 – 64, Example 3; page 66, Example 5). The method also treats Hodgkin lymphoma, multiple myeloma, and melanoma (page 38, lines 6 – 15). Liquid tumor cells may also adhere to bone marrow, which may further lead to sequestration and quiescence of the tumor cells, resulting in “resistance” of the tumor cells to chemotherapy. Studies have shown that bone marrow contains anatomic regions that comprise specialized endothelium, which expresses the E-selectin. Accordingly, the E-selectin antagonist may be useful for inhibiting metastasis of cancers that comprise either a solid or liquid tumor by inhibiting binding of an E-selectin ligand to E-selectin.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the E-selectin antagonist as taught by ‘884 with
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in view of Magnani et al. to treat cancer. It would have been obvious for one of ordinary skill in the art to do this because both drugs are known separately in the prior art for the purpose of treating cancer, and it would have been obvious to substitute equivalent drug known to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to substitute the E-selectin antagonist as taught by ‘884 with
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in view of Magnani et al. because it is well known to substitute drugs to treat the same disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3 – 6, 9, 14, 18 – 20, and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29, 33, 36, and 40 of copending Application No. 18/630,125 in view of DiNardo et al. (Blood, 2019, Vol. 133, Issue 1, page 7 – 17, cited in the previous Office Action mailed June 30, 2025).
b. Regarding claims 1, 3 – 6, 9, 14, 18 – 20, and 45, ‘125 teaches a method for treating a cancer and inhibiting infiltration of cancer cells into bone marrow in a subject comprising administering to the subject (a) pharmaceutical composition comprising
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and a pharmaceutically acceptable excipient and (b) at least one of (i) chemotherapy and (ii) radiotherapy (claims 29, 33, 36, and 40).
However, ‘125 does not teach the method comprising administering at least one hypomethylating agent, such as 5-azacitidine and decitabine, and the venetoclax with a fixed dose of 10 mg to 1000 mg per day.
DiNardo et al. teach that venetoclax in combination with decitabine or azacitidine is reported to be safe and effective in a large, multicenter, phase 1b dose-escalation and expansion study. During dose escalation, oral venetoclax is administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1 – 5, intravenously or azacitidine (75 mg/m2, days 1 – 7, intravenously or subcutaneously) to patients with acute myeloid leukemia (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date to modify the method for treating a cancer, such as inhibiting infiltration of cancer cells into bone marrow, in a subject comprising administering to the subject a compound having a structure of formula (I) and at least one of (i) chemotherapy as taught by’125 with administering venetoclax and decitabine or azacitidine in view of DiNardo et al. to treat leukemia, such as AML. It would have been obvious for one of ordinary skill in the art to do this because the drugs are known separately in the prior art for the purpose of treating leukemia, and it would have been obvious to substitute equivalent drug known to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to modify the method for treating a cancer, such as inhibiting infiltration of cancer cells into bone marrow, in a subject comprising administering to the subject a compound having a structure of formula (I) and at least one of (i) chemotherapy as taught by’125 with administering venetoclax and decitabine or azacitidine in view of DiNardo et al. because it is well known to combine drugs to treat the same disease and further ‘125 teaches that E-selectin antagonist can be used in combination with other drugs.
This is a provisional nonstatutory double patenting rejection.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed December 29, 2025, have been fully considered and are found to be not persuasive.
Applicant argues that the instant application has an earlier effective U.S. filing date than the ‘884 application. However, the rejection is consistent with established practice for addressing nonstatutory double patenting. As explained in MPEP 804(II)(B)(5), a later-expiring patent may serve as a proper reference in a one-way obviousness-type double patenting rejection unless the applicant can show that the claims could not have been filed in a single application and that the Office was solely responsible for any delay that caused the reference patent to issue first. In the present case, Applicant does not provide evidence that the Office, rather than Applicant, is solely responsible for any prosecution delay, nor that the claims could not have been presented together. Courts have consistently held that applicant-driven prosecution choices, such as filing multiple applications or continuations, do not warrant application of the two-way test. Therefore, the one-way test applies, and the double patenting rejection over ‘884 remains proper.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the maintained / modified / 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 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.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693