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 September 17, 2025. The amendment, filed September 17, 2025, is entered, wherein claims 4, 8 – 9, 17, and 19 are amended, claims 1 – 3, 5 – 7, 18, 26 – 31, and 33 – 38 are canceled, and claim 41 is new.
Claims 4, 8 – 17, 19 – 25, 32, and 39 – 41 are pending in this application and are currently examined.
Priority
This application is a national stage application of PCT/CA2021/051688, filed November 25, 2021, which claims benefit of foreign priority document CN202011346141.0, filed November 25, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
4. The objection of claims 1 – 2, 4, 9, and 17 in the previous Office Action, mailed August 6, 2025, is withdrawn in view of the canceled claims and amended claims.
Withdrawn Rejections
5. The rejection of claims 19 – 23 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer, does not reasonably provide enablement for a method to prevent cancer in a subject has been considered and is withdrawn in view of the amended claim 19.
The rejection of claims 19 and 24 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating infections, Alzheimer’s disease (AD), Parkinson’s disease, and multiple sclerosis, does not reasonably provide enablement for a method to prevent these conditions in a subject has been considered and is withdrawn in view of the amended claim 19.
The rejection of claims 1 – 2 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Debien et al. has been considered and is withdrawn in view of the canceled claims 1 – 2.
The rejection of claims 1 – 2 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 102(a)(2) as being anticipated by Lu et al. has been considered and is withdrawn in view of the canceled claims 1 – 2.
The rejection of claim 1 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claim 1 of copending Application No. 17/993,937 has been considered and is withdrawn in view of the canceled claim 1.
Claims 1 – 2, 4, 8 – 9, 17, 19 – 25, 32, and 39 – 40 are rejected in the previous Office Action, mailed August 6, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of U.S. Patent No. 11530234B2. As terminal disclaimer is filed September 17, 2025 and is approved October 10, 2025 and October 20, 2025, the rejection has been withdrawn.
The rejection of claim 1 in the previous Office Action, mailed August 6, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1- 21 of U.S. Patent No. 10881681B2 has been considered and is withdrawn in view of the canceled claim 1.
The following are maintained / modified grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed September 17, 2025, wherein claims 4, 8 – 9, 17, and 19 are amended, claims 1 – 3, 5 – 7, 18, 26 – 31, and 33 – 38 are canceled, and claim 41 is new. Previously cited references have been used to establish the maintained / modified grounds of rejection.
Maintained / Modified 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 4, 8 – 17, 19 – 25, 32, and 39 – 41 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO2020/205538A1) in view of Debien et al. (WO2017/120508A1).
Regarding claims 4, 8 – 17, 19 – 25, 32, and 39 – 41, Liu et al. disclose CD73 inhibitors of the general formula (I) and analogs thereof, pharmaceutical compositions containing these compounds and use of these compounds as therapeutic agents for the treatment of diseases or conditions associated with CD73 activity, such as various cancers (Abstract). Liu et al. provides a compound of formula (I) or a pharmaceutical acceptable salt thereof (page 3, lines 1 – 3):
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In one embodiment, the compound of formula (I) is (page 8, Compound 1):
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However, Liu et al. do not exemplify the structure of the claimed Formula III having the nucleoside core. The exemplified compound differs from the compound of Formula III in the position of G1 and G2. Liu et al. do teach that the position of G1 and G2 can be CRc in formula (I), wherein Rc is hydrogen, and N, respectively (page 3, lines 8 – 9). Said pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier (page 4, lines 26 – 29). The active compounds can be formulated as various dosage forms for oral and parenteral administration (page 12, line 21). Suitable dosage forms include a tablet, aqueous suspension, or emulsion (page 12, lines 25 – 26). The tablet can be uncoated or coated by means of a known technique to mask the taste of the drug or delay the disintegration and absorption of the drug in the gastrointestinal tract, thereby providing sustained release over an extended period (page 12, lines 33 – 34; page 13, lines 1 – 2). The pharmaceutical composition can be in the form of a sterile injectable aqueous solution (page 13, lines 25 – 26). Furthermore, the invention relates to a method for treating a disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, or a pharmaceutical composition thereof, wherein the disease is cancer or immune-related disease (page 11, lines 17 – 22). The cancer may be melanoma, brain tumor, gastric cancer, or breast cancer (page 12, lines 3 – 5). The immune-related disease is Parkinson’s disease (page 12, line 17).
However, Liu et al. do not teach the pharmaceutical composition further comprises at least one additional therapeutic agent and the method further comprising administration of at least one additional therapeutic agent to the subject. Liu et al. do not teach the method comprising administering an effective amount of the compound and an immune checkpoint inhibitor to the subject.
Debien et al. teach compounds and compositions for inhibition of CD73 and pharmaceutical compositions comprising same. The compound may be (page 30, line 22):
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Debien et al. also teach the method of treating a disease mediated by inhibition of CD73 (para. [0004]). The pharmaceutical composition can be used in combination with other therapeutically active agents (para. [0122]) or it may be used in combination with immune checkpoint inhibitors (para. [0148]). The use of the compounds and compositions, as CD73 inhibitors, have been linked to the treatment of a diverse array of disorders, including cancer (para. [0011]). In some embodiments, the cancer is melanoma, brain tumor, breast cancer, and gastric carcinoma (para. [0019]). Inhibition of CD73 may also be important treatment strategy for patients with Parkinson’s disease (para. [0118]).
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 composition comprising exemplified compound of formula (I):
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with the modification of G1 and G2 that are CRc, wherein Rc is hydrogen, and N, respectively as taught by Liu et al. in the use of treating cancer or immune-related disease to a composition further comprising other therapeutically active agents or immune checkpoint agents in view of Debien et al. because Liu et al. teach the substituents that are known in the art, which is further supported by Debien et al. that the modification of the exemplified compound of formula (I) will yield a compound for the same purpose, and Liu et al. and Debien et al. both teach the method of treating the same diseases and the compounds disclosed have the same core structure and are CD73 inhibitors. One would have been motivated to modify the composition comprising the exemplified compound of Formula (I) with said modifications as taught by Liu et al. in the use of treating cancer or immune-related disease to a composition further comprising other therapeutically active agents or immune checkpoint agents in view of Debien et al. because both methods are used to treat the same conditions. Therefore, one of the skill in the art would have had a reasonable expectation of success to modify the composition comprising the exemplified compound of Formula (I) with said modifications as taught by Liu et al. in the use of treating cancer or immune-related disease to a composition further comprising other therapeutically active agents or immune checkpoint agents in view of Debien et al. because Liu et al. teach the exemplified compound of formula (I) with the possible modifications at G1 and G2 that yields a compound for the same purpose, which is supported by Debien et al., and Debien et al. teach the possible pharmaceutical composition comprising CD73 inhibitor and a therapeutically active agent or immune checkpoint inhibitor.Responses to Applicant’s Remarks:
Applicant’s Remarks, filed September 17, 2025, have been fully considered and are found to be not persuasive.
Regarding the claims, Applicant argues that the claimed compounds are structurally distinct from the compounds of the cited references. None of the compounds disclosed by the cited references comprises the structures of the claimed compounds, and there is no teaching or suggestion in Liu et al. and Debien et al. to lead the skilled person to arrive at the claimed compounds. However, the general structure of Liu et al. do teach that G1 is CRc, wherein Rc is hydrogen and G2 is N. One of the skills in the art would have performed a routine experimentation to determine what G1 and G2 is for the optimal treatment characteristics.
Applicant argues that the claimed compounds represent distinct CD73 inhibitors with high inhibition potency. The claimed compounds represent novel CD73 inhibitors with superior potency and PK characteristics, which could not reasonably have been expected by the person of ordinary skill in the art based on the teachings of the cited references. Regarding the unexpected results, Applicant does not provide data and/or results that demonstrate unexpected results because there is no comparison between the claimed invention and the compounds cited in the art. Therefore, the examiner is not able to determine if there is unexpected result.
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 4, 8 – 9, 11, 16 – 17, 19 – 25, 32, and 39 – 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of U.S. Patent No. 10881681B2 in view of Liu et al. (WO2020/205538A1).
Regarding claims 4, 8 – 9, 11, 16 – 17, 19 – 25, 32, and 39 – 41, ‘681B2 teaches a compound of Formula (I), or a pharmaceutically acceptable salt thereof:
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wherein W is oxygen; X is -P(=O)(OR)-, wherein R is a hydrogen; Y is -PO3R2, wherein R is hydrogen; R1 is hydroxyl group; R2 is chlorine; R3 is hydrogen; and R4 is a ring system (claims 1 and 4 – 6). ‘681B2 teaches a compound of Formula IX, or a pharmaceutically acceptable salt thereof:
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wherein R is hydrogen; R1 is hydroxyl group; R2 is chlorine’ and R3, R4, and the nitrogen atom to which they are attached form a fused tricycle structure (claim 8). ‘681B2 teaches (claim 11):
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Moreover, ‘681B2 teaches a pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, wherein the composition may be suitable for oral administration or is injectable (claims 13 – 14). ‘681B2 also teaches a method of treating CD73-associated disease in a subject in need thereof, comprising administering a therapeutically effective amount of the compound to the subject, wherein the disease may be cancer or immune-related disease, such as brain cancer, breast cancer, gastric carcinoma, melanoma, or Parkinson’s disease (claims 15 and 17 – 19). The method further comprises administering at least one additional therapeutic agent to the subject, wherein the at least one additional therapeutic agent is an immune checkpoint inhibitor (claims 19 – 20).
However, ‘681B2 does not teach the R3 and R4 to be
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Liu et al. disclose CD73 inhibitors of the general formula (I) and analogs thereof, pharmaceutical compositions containing these compounds and use of these compounds as therapeutic agents for the treatment of diseases or conditions associated with CD73 activity, such as various cancers (Abstract). Liu et al. provides a compound of formula (I) or a pharmaceutical acceptable salt thereof (page 3, lines 1 – 3):
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In one embodiment, the compound of formula (I) is (page 8, Compound 1):
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The exemplified compound differs from the compound of Formula III in the position of G1 and G2. However, Liu et al. teach in in formula (I) that the position of G1 and G2 can be CRc, wherein Rc is hydrogen, and N, respectively (page 3, lines 8 – 9).
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 NR3R4 as taught by ‘681B2 with
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moiety in the exemplified compound of formula (I) with possible modification at position G1 and G2 in view of Liu et al. to treat the CD73-associated conditions because ‘681B2 teaches that NR3R4 may be replaced with tricyclic structure and Liu et al. teach the exemplified compound with said modifications that has the exact same core structure as the compound of Formula IX and is also a CD73 inhibitor. One would have been motivated to substitute NR3R4 as taught by ‘681B2 with
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moiety in the exemplified compound of formula (I) with possible modification at position G1 and G2 in view of Liu et al. because Liu et al. teach the exemplified compound that can be modified to achieve the same core structure as the compound of Formula IX and, therefore, such modification will yield predictable results. One of the ordinary skill in the art would have a reasonable expectation of success to substitute NR3R4 as taught by ‘681B2 with
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moiety in the exemplified compound of formula (I) with possible modification at position G1 and G2 in view of Liu et al. because such substitution is expected to have the same therapeutic effects.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed September 17, 2025, have been fully considered and are found to be not persuasive.
Regarding Liu et al., Applicant argues that the claimed compounds are structurally distinct from the compounds of the cited references. None of the compounds disclosed by the cited references comprises the structures of the claimed compounds, and there is no teaching or suggestion in Liu et al. to lead the skilled person to arrive at the claimed compounds. This argument has been addressed in the previous responses.
Conclusion
No claim is found to be allowable.
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOI YAN LEE whose telephone number is 571-270-0265. The examiner can normally be reached Monday - Thursday 7:30 - 17:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SCARLETT GOON can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693