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 January 12, 2026. The amendment, filed January 12, 2026, is entered, wherein claims 1, 13 – 14, and 18 are amended, claim 24 is new, claims 9 – 12, 16, and 23 are canceled, and claim 4 is withdrawn.
Claims 1 – 8, 13 – 15, 17 – 22, and 24 are pending in this application and claims 1 – 3, 5 – 8, 13 – 15, 17 – 22, and 24 are currently examined.
Priority
This application is a national stage application of PCT/US21/30402, filed May 3, 2021, which claims benefit of domestic application 63/021,206, filed May 7, 2020.
Withdrawn Rejections
4. The rejection of claims 1 – 3, 5 – 8, 15, and 18 – 22 in the previous Office Action, mailed September 10, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Wu has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 3, 5 – 8, 15, and 17 in the previous Office Action, mailed September 10, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claims 1 – 3, 5 – 12, and 14 – 18 of copending Application No. 17/788,338 has been considered and is withdrawn in view of the amended claim 1.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 January 12, 2026, wherein claims 1, 13 – 14, and 18 are amended, claim 24 is new, claims 9 – 12, 16, and 23 are canceled, and claim 4 is withdrawn. Previously and newly cited references have been used to establish the maintained / modified / new grounds of rejection.
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.
Claims 1 – 3, 5 – 8, 13 – 15, and 17 – 22 are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US7399754B2, cited in the previous Office Action) in view of Daver et al. (Leukemia, 2018, Vol. 32, Issue 5, page 1094 – 1105, cited in the previous Office Action).
Regarding claims 1 – 3, 5 – 8, 13 – 15, and 17 – 22, Wu teaches compounds of formula (A):
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and pharmaceutical compositions comprising the compound of formula (A), methods for treating cancer, and the methods for the synthesis (Abstract). In one embodiment, the compound of formula (A) is (Col. 5, lines 10 – 20):
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The pharmaceutical composition is suitable for treating cancers and the related diseases, and may be used alone or in combination with other anti-cancer drugs (Col. 16, lines 7 – 9), wherein the cancer is lung cancer (Col. 16, line 16). Wu also evaluates the compound using MTT and SRB assays and finds that the compound significantly inhibits the growth of many types of cancers, including leukemia (Col. 34, lines 43 – 47).
However, Wu does not explicitly teach the therapeutic agent is an inhibitor of PD-1 or PD-L1, wherein the inhibitor of PD-1 or PD-L1 is an antibody targeting PD-1 or PD-L1, wherein the antibody targeting PD-1 or PD-L1 is Nivolumab or Atezolizumab. Wu also does not explicitly teach the cancer is acute myeloid leukemia.
Daver et al. teach that Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) (Abstract). A number of trials combining HMAs with PD-1/PD-L1-based therapies have started for treating AML, such as the combination of azacitidine with nivolumab and the combination of azacitidine with atezolizumab (page 1100, Left Col., para. 2).
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 modify the method of treating leukemia as taught by Wu to specifically treating AML because AML is a well-recognized subtype of leukemia. One would have been motivated to modify the method to specifically treating AML because Wu teaches that the claimed compound is effective for treating leukemia and AML falls within the scope of leukemia. It would also have been prima facie obvious for a person of ordinary skill in the art before the effective filling date of the claimed invention to combine the compound of formula (A) as taught by Wu with the antibody targeting PD-1 or PD-L1 in view of Daver et al. to treat leukemia, such as AML, because these drugs are known separately in the prior art for the purpose of treating leukemia, and it would have been obvious to combine them to treat the same disease. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to modify the method of treating leukemia as taught by Wu to specifically treating AML because AML falls within the scope of leukemia. One of the ordinary skill in the art would have had a reasonable expectation of success to combine the compound of formula (A) as taught by Wu with the antibody targeting PD-1 or PD-L1 in view of Daver et al because it is well known to combine drugs to treat the same disease, and further both references teach that the drugs are used in combination.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed January 12, 2026, have been fully considered and are found to be not persuasive.
Regarding Daver et al., Applicant argues that Daver et al. relate to the combination of checkpoint inhibitors with hypomethylating agents (HMAs) and Daver et al. relies on the mechanism of HMAs to upregulate tumor antigens and expression of PD-L1/PD-L2 for “priming” the immune system for checkpoint blockade.
Regarding the rejection, Applicant argues that, in contrast to Daver et al., Wu discloses kinase inhibitors that operate via phosphorylation pathways rather than the hypomethylation mechanism relied upon by HMAs in Daver et al. Applicant argues that there is no teaching or suggestion that such kinase inhibitors possess the immune “priming” capability attributed to HMAs, and therefore a person of ordinary skill in the art would not have been motivated to substitute the HMAs of Daver et al. with the kinase inhibitors of Wu. Applicant further argues that, absent a shared mechanism or specific teaching, the combination would not have been “obvious to try” with a reasonable expectation of success, and that the success of HMA plus anti-PD-1 therapy does not predict the success of kinase inhibitor plus anti-PD-1 therapy.
However, these arguments are not persuasive. Daver et al. disclose that immune checkpoint inhibitors have shown modest clinical efficacy in the treatment of AML. Daver et al. not only teach a mechanism unique to HMAs, but also broadly teach that immune checkpoint inhibitors may be more effective to administer as a combination approach (Abstract). Thus, Daver et al. teach that immune checkpoint inhibitors show clinical efficacy in the treatment of AML and provide a motivation to combine checkpoint inhibitor with other anti-cancer agents to improve therapeutic efficacy. Wu teaches anti-cancer compounds useful for treating cancer, such as leukemia, and further teaches use in combination with other anti-cancer drugs. The fact that kinase inhibitors and HMAs may act through different biological pathways does not undermine the motivation to combine because the claims do not require that the compound of formula (I) possess the same immune “priming” capability. In view of the combination of Wu and Daver et al., one of ordinary skill in the art would have been motivated to use the compound of formula (A) as taught by Wu with an immune checkpoint inhibitor in view of Daver et al. for treating cancer, such as AML, and would have had a reasonable expectation of success.
Regarding the unexpected results, Applicant argues that the claimed combination exhibits unexpected, synergistic results based on the data presented in Example 1 of the specification. This argument has been considered and it is not persuasive. The evidence relied upon by Applicant is not commensurate in scope with the claims, which encompass a broad genus of compounds of formula (I) and combinations with anti-PD-1 antibodies. The data are limited to a single compound (Compound A) and a specific anti-PD-1 antibody under particular experimental conditions. Such limited evidence is insufficient to establish that the synergistic effect would be expected across the full scope of the claimed invention.
Claims 1 – 3, 5 – 8, 13 – 15, 18 – 22, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US7399754B2, cited in the previous Office Action) in view of Rico (Expert Opinion on Biological Therapy, 2018, Vol. 18, Issue 4, page 449 – 457, Reference included with PTO-892).
b. Regarding claims 1 – 3, 5 – 8, 13 – 15, 18 – 22, and 24, Wu teaches compounds of formula (A):
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and pharmaceutical compositions comprising the compound of formula (A), methods for treating cancer, and the methods for the synthesis (Abstract). In one embodiment, the compound of formula (A) is (Col. 5, lines 10 – 20):
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The pharmaceutical composition is suitable for treating cancers and the related diseases, and may be used alone or in combination with other anti-cancer drugs (Col. 16, lines 7 – 9), wherein the cancer is colon cancer (Col. 16, line 19).
However, Wu does not explicitly teach the therapeutic agent is an inhibitor of PD-1 or PD-L1, wherein the inhibitor of PD-1 or PD-L1 is an antibody targeting PD-1 or PD-L1, wherein the antibody targeting PD-1 or PD-L1 is Pembrolizumab or Atezolizumab.
Rico teaches that early clinical studies show that atezolizumab is active in numerous malignancies, including metastatic colorectal cancer (mCRC) (page 450, Right Col., para. 2). Rico further teaches that results from early trials using nivolumab and pembrolizumab appear promising, especially in patients with refractory MSI-H/dMMR mCRC (page 455, Left Col., para. 3).
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 combine the compound of formula (A) as taught by Wu with atezolizumab, nivolumab, and pembrolizumab in view of Rico for treating colon cancer because both Wu and Rico teach that the compound of formula (A), atezolizumab, nivolumab, and pembrolizumab are used to treat colon cancer. It would have been obvious for one of ordinary skill in the art to combine the compound of formula (A) as taught by Wu with atezolizumab, nivolumab, and pembrolizumab in view of Rico because the compound of formula (A), atezolizumab, nivolumab, and pembrolizumab are known separately in the prior art for the purpose of treating colon cancer, and it would have been obvious to combine them to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to combine the compound of formula (A) as taught by Wu with atezolizumab, nivolumab, and pembrolizumab in view of Rico for treating colon cancer because it is well known to combine drugs to treat the same disease and further Wu teaches that the compound of formula (A) may be used in combination with other drugs.
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, 5 – 10, 15, and 18 – 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 – 10 and 13 – 16 of U.S. Patent No. 7399754B2 in view of Shtivelman et al. (Oncotarget, 2014, Vol. 5, Issue 6, page 1392 – 1433, Reference included with PTO-892).
Regarding claims 1 – 3, 5 – 10, 15, and 18 – 22, ‘754B2 teaches compounds of the following formula:
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wherein W is C3 cycloalkyl; Y is H; and Q is
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wherein B, E, G, R, T, and M are H (claims 1, 5, and 7 – 8). ‘754B2 teaches that W is cyclopropyl (claims 4 and 6 – 7). In one embodiment, the compound is (claims 9 – 10):
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‘754B2 also teaches a pharmaceutical composition comprising the compound (claim 13) and the pharmaceutical composition is suitable for treating cancers, wherein the cancer is lung cancer (claims 14 – 16).
However, ‘754B2 does not explicitly teach the compound in combination with an immunotherapeutic agent.
Shtivelman et al. teach that lung cancer is the leading cause of cancer death worldwide and there are targeted therapies, such as immune therapies approved or being investigated for the treatment of lung cancer. Shtivelman et al. disclose that immunomodulatory antibodies targeting PD-1 interactions with its ligands showed promising responses in lung cancer.
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 combine the compound as taught by ‘754B2 with the antibody targeting PD-1 in view of Shtivelman et al. to treat lung cancer because these drugs are known separately in the prior art for the purpose of treating lung cancer, and it would have been obvious to combine them to treat the same disease. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the compound as taught by ‘754B2 with the antibody targeting PD-1 in view of Shtivelman et al because it is well known to combine drugs to treat the same disease.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed January 12, 2026, have been fully considered and are found to be not persuasive.
Regarding the unexpected results, Applicant argues that the claimed combination exhibits unexpected, synergistic results based on the data presented in Example 1 of the specification. This argument has been considered and it is not persuasive. The evidence relied upon by Applicant is not commensurate in scope with the claims, which encompass a broad genus of compounds of formula (I) and combinations with anti-PD-1 antibodies. The data are limited to a single compound (Compound A) and a specific anti-PD-1 antibody under particular experimental conditions. Such limited evidence is insufficient to establish that the synergistic effect would be expected across the full scope of the claimed invention.
Claims 1 – 3, 5 – 8, 13 – 15, and 17 – 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of copending Application No. 17/788,338 in view of Daver et al. (Leukemia, 2018, Vol. 32, Issue 5, page 1094 – 1105, cited in the previous Office Action).
b. Regarding claims 1 – 3, 5 – 8, 13 – 15, and 17 – 22, ‘338 teaches a method for treating leukemia in a subject in need thereof, comprising administering the subject an therapeutically effective amount of a compound of formula (I), wherein the compound of formula (I) is (claims 1 – 8)
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‘338 teaches that the leukemia is acute myeloid leukemia (claim 9).
However, ‘338 does not explicitly teach the therapeutic agent is an inhibitor of PD-1 or PD-L1, wherein the inhibitor of PD-1 or PD-L1 is an antibody targeting PD-1 or PD-L1, wherein the antibody targeting PD-1 or PD-L1 is Nivolumab or Atezolizumab.
Daver et al. teach that Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) (Abstract). A number of trials combining HMAs with PD-1/PD-L1-based therapies have started for treating AML, such as the combination of azacitidine with nivolumab and the combination of azacitidine with atezolizumab (page 1100, Left Col., para. 2).
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 combine the compound of formula (I) as taught by ‘338 with atezolizumab and nivolumab in view of Daver for treating AML because both ‘338 and Daver et al. teach that the compound of formula (I), atezolizumab, and nivolumab are used to treat AML. It would have been obvious for one of ordinary skill in the art to combine the compound of formula (I) as taught by ‘338 with atezolizumab and nivolumab in view of Daver et al. because the compound of formula (I), atezolizumab, and nivolumab are known separately in the prior art for the purpose of treating AML, and it would have been obvious to combine them to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to combine the compound of formula (I) as taught by ‘338 with atezolizumab and nivolumab in view of Daver et al. for treating AML because it is well known to combine drugs to treat the same disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 3, 5 – 8, 13 – 15, 18 – 22, and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10 – 17 and 20 of copending Application No. 17/788,338 in view of Rico (Expert Opinion on Biological Therapy, 2018, Vol. 18, Issue 4, page 449 – 457, Reference included with PTO-892).
c. Regarding claims 1 – 3, 5 – 8, 13 – 15, 18 – 22, and 24, ‘338 teaches a method for treating a cancer in a subject in need thereof, comprising administering the subject an therapeutically effective amount of a compound of formula (I) in combination with a chemotherapeutic agent, wherein the compound of formula (I) is (claims 10 – 17)
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‘338 teaches that the cancer is a solid cancer, wherein the solid cancer is colon cancer (claim 20).
However, ‘338 does not explicitly teach that the compound of formula (I) is used in combination with an inhibitor of PD-1 or PD-L1, wherein the inhibitor of PD-1 or PD-L1 is an antibody targeting PD-1 or PD-L1, wherein the antibody targeting PD-1 or PD-L1 is Pembrolizumab or Atezolizumab.
Rico teaches that early clinical studies show that atezolizumab is active in numerous malignancies, including metastatic colorectal cancer (mCRC) (page 450, Right Col., para. 2). Rico further teaches that results from early trials using nivolumab and pembrolizumab appear promising, especially in patients with refractory MSI-H/dMMR mCRC (page 455, Left Col., para. 3).
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 combine the compound of formula (I) as taught by ‘338 with atezolizumab, nivolumab, and pembrolizumab in view of Rico for treating colon cancer because both ‘338 and Rico teach that the compound of formula (I), atezolizumab, nivolumab, and pembrolizumab are used to treat colon cancer. It would have been obvious for one of ordinary skill in the art to combine the compound of formula (I) as taught by ‘338 with atezolizumab, nivolumab, and pembrolizumab in view of Rico because the compound of formula (I), atezolizumab, nivolumab, and pembrolizumab are known separately in the prior art for the purpose of treating colon cancer, and it would have been obvious to combine them to treat the same disease. One of ordinary skill in the art would have had a reasonable expectation of success to combine the compound of formula (I) as taught by ‘338 with atezolizumab, nivolumab, and pembrolizumab in view of Rico for treating colon cancer because it is well known to combine drugs to treat the same disease and further ‘338 teaches that the compound of formula (I) may be used in combination with other drugs.
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
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