DETAILED ACTION
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 .
Priority
The instant application is a 371 National Stage Entry of PCT/CN2021/092482 filed on May 8, 2021 which claims priority to foreign application No. CN202010394259.4 filed on May 11, 2020.
No English Translation
Examiner notes that no certified translation of the Foreign Application CN202010394259.4 (filed May 11, 2020) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Status of Claims
Acknowledgement is made of amended (1-2, 8, 10-12, 14), previously presented (3-7, 9, 13, 15), and new (11-15) claims filed on May 4, 2026. Claims 1-15 are pending in instant application.
Response to Arguments
In light of Applicant’s amendments filed May 4, 2026, the following are withdrawn:
the objections to claims 1, 10-12, 14
the 35 USC 112(b) rejection of claim 11
Applicant's arguments filed May 4, 2025 have been fully considered but they are not persuasive.
Regarding Aktoudiankis (see 5/4/26 Remarks at pp. 16-17), Applicant argues Aktoudianakis species do not read on instant Formula I-b. This is incorrect, Applicant errs in stating the Aktoudianakis ring A substituent is a pyridinyl-substituted alkoxy, whereas the instant claims encompass alkoxy-substituted pyridinyls. Aktoudianakis ring A substituent is a substituted C1-C6 alkoxy, wherein the “substituted” means being substituted by a 5-10 membered heterocyclyl with 1-3 heteroatoms selected from N, S, and O, specifically pyridinyl.
In other words, the instant claims state ring A substituents may be alkoxy-substituted pyridinyls, which is what the prior art teaches.
Applicant has omitted “cyano” as an Rz substituent alternatives. The Aktoudianakis CAS# 2248633-53-4 species is still mappable onto Formula I-b in an anticipatory manner as discussed in the previous Office Action (see 2/3/26 Office Action at p. 6 “Regarding claim 2”) which is applied again below (see 35 USC 102 Rejections). Even if the mapping of CAS# 2248633-53-4 were to fall down to Rz, this is not a marked difference from the core of species taught by Aktoudianakis, and the prior art renders obvious Formula I-b, this has been applied below as a new 35 USC 103 Rejection.
Claim Interpretation
The term “heterocyclyl” in the claims is understood to be any heterocycle, aryl or alkyl (for example, see claim 1 p. 4
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limitations).
At claim 10, the preamble “A PD-1/PD-L1 inhibitor” is understood to recite an intended use that is fully satisfied by the structures set forth in the body of the claim, i.e. a compound of claim 1 (see MPEP § 211.02(II); 2111.04(I)).
Election/Restrictions
The elected species is understood as follows: CAS# 2744297-74-1.
Following extensive search and examination, the originally elected species has been deemed free of the prior art.
Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to a non-elected species. Following extensive search and examination, the non-elected species was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-3, 8-11 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over WO 2018195321 A1 to Aktoudianakis et. al.1
Regarding claims 1-2 and 10, Aktoudianakis teaches Example 396, also known as CAS# 2248633-53-4 (see Aktoudianakis at p. 546).
CAS# 2248633-53-4
Instant I-b
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CAS# 2248633-53-4 reads on Formula I-b when L1 is -O- and A is a substituted 5-12 membered heterocycle, specifically a substituted pyridine substituted with R3 and R1, m is 2, and one R1 is halogen specifically chlorine, one R1 is a substituted C1-C6 alkyl amino (substituted with carboxyl and hydroxy – specifically
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), R3 is
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, n is 2, one L4 is O, one L4 is C1-C4 alkylene specifically methylene, E is a substituted 3-10 membered heterocyclyl specifically pyridine, m is 1 and R5 is CN, Y2 is N and Y1 is S, Z2, Z3 and Z4 are all CRa and Ra is H, R3' is
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and one of Rc and Rb is H and the other is a substituted C1-C8 alkyl, p is 1 and R2' is an unsubstituted C1-C6 alkyl specifically methyl, q is 0, n is 0.
Regarding claim 3, alternatively, CAS# 2248633-53-4 reads on Formula I-b as described above but A is
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and one of X1 and X2 is N and the other is CH, and R1 and R3 are as discussed above.
Regarding claim 8 and a composition, Aktoudianakis claims compositions comprising disclosed compounds and at least one pharmaceutically acceptable excipient (see Aktoudianakis claim 65 and at p. 155 “Pharmaceutical Formulations”).
Regarding claim 9 and a method of treatment, Aktoudianakis claims a method of treating cancer comprising administering a therapeutically effective amount (see Aktoudianakis claim 60).
Further regarding claim 10, Aktoudianakis teaches the disclosed compounds may be used in a method of inhibiting PD-1 or PD-L1 (see Aktoudianakis claim 59), and are PD-1/PD-L1 inhibitors (see Aktoudianakis at pp. 664-670 Table 1).
Regarding claim 11 and a method of treating a disease related to PD-1/PD-L1, Aktoudianakis teaches the disclosed compounds are useful for treating cancer or a condition in a patient that is amendable to treatment by inhibiting PD-1, PD-L1, or the PD-1/PD-L1 interaction (see Aktoudianakis at p. 152 lines 23-30). Aktoudianakis claims compositions comprising disclosed compounds and at least one pharmaceutically acceptable excipient (see Aktoudianakis claim 65 and at p. 155 “Pharmaceutical Formulations”).
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.
Claim(s) 1, 3, 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018195321 A1 to Aktoudianakis et. al.2
Regarding claims 1 and 10, Aktoudianakis teaches Example 396, also known as CAS# 2248633-53-4 (see Aktoudianakis at p. 546).
CAS# 2248633-53-4
Instant I-b
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CAS# 2248633-53-4 reads on Formula I-b when L1 is -O- and A is a substituted 5-12 membered heterocycle, specifically a substituted pyridine substituted with R3 and R1, m is 2 and one R1 is halogen specifically chlorine and one R1 is a substituted C1-C6 alkoxy (substituted with pyridinyl with an Rz substituent), R3 is
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and one of Rc and Rb is H and the other is a substituted C1-C8 alkyl, Y2 is N and Y1 is S, Z2, Z3 and Z4 are all CRa and Ra is H, R3' is
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and one of Rc and Rb is H and the other is a substituted C1-C8 alkyl, p is 1 and R2' is an unsubstituted C1-C6 alkyl specifically methyl, q is 0, n is 0.
Regarding claim 3, alternatively, CAS# 2248633-53-4 reads on Formula I-b as described above but A is
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and one of X1 and X2 is N and the other is CH, and R1 and R3 are as discussed above.
Regarding claim 8 and a composition, Aktoudianakis claims compositions comprising disclosed compounds and at least one pharmaceutically acceptable excipient (see Aktoudianakis claim 65 and at p. 155 “Pharmaceutical Formulations”).
Regarding claim 9 and a method of treatment, Aktoudianakis claims a method of treating cancer comprising administering a therapeutically effective amount (see Aktoudianakis claim 60).
Further regarding claim 10, Aktoudianakis teaches the disclosed compounds may be used in a method of inhibiting PD-1 or PD-L1 (see Aktoudianakis claim 59), and are PD-1/PD-L1 inhibitors (see Aktoudianakis at pp. 664-670 Table 1).
Regarding claim 11 and a method of treating a disease related to PD-1/PD-L1, Aktoudianakis teaches the disclosed compounds are useful for treating cancer or a condition in a patient that is amendable to treatment by inhibiting PD-1, PD-L1, or the PD-1/PD-L1 interaction (see Aktoudianakis at p. 152 lines 23-30). Aktoudianakis claims compositions comprising disclosed compounds and at least one pharmaceutically acceptable excipient (see Aktoudianakis claim 65 and at p. 155 “Pharmaceutical Formulations”).
The prior art differs from the instant claims as follows: Aktoudianakis species CAS# 2248633-53-4 corresponds with Rz is cyano, which is excluded by amended claim 1.
However,
Aktoudianakis teaches Formula VIII (Aktoudianakis claim 1).
Aktoudianakis
Formula VIII
CAS# 2248633-53-4
Instant I-b
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Aktoudianakis teaches Z3 may be RN, and RN may be
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, and L1 may be O, V may be C1 alkyl, L2 may be a bond, and A may be heteroaryl which encompasses pyridine (this leads to the core of CAS# 2248633-53-4, absent the cyano group). Aktoudianakis further teaches this heteroaryl (of CAS# 2248633-53-4’s pyridine) may be optionally substituted (corresponding with instant Rz) with 1 to 4 groups that include halogen, hydroxyl, carboxyl, alkoxy, and alkylamino groups (see Aktoudianakis claim 1 at p. 685).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
The prior art teaches a substantial overlapping species with instant claims, differing only in one substituent choice. The prior art also teaches overlapping acceptable alternative substituents instantly claimed. Accordingly, an artisan would recognize that the cyano-substituted pyridine on CAS# 2248633-53-4 may be exchanged with another suitable substituent such as a halogen, hydroxyl, carboxyl, alkoxy, or alkylamino group.
Furthermore, it is well-within the ordinary skill in art to incorporate an acceptable alternate substituent in lieu of another.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Allowable Subject Matter
Claims 4-7, 12, 13, 14, 15 are free of the prior art.
Claims 4 and 5 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The species of claim 6 appear to be novel, the dependent claims (12-15) are also thus allowable.
Claim 7 closest prior art is discussed in the 2/3/26 Office Action
Conclusion
Claims 4-5, 10-12, 14 are objected to.
Claims 1-3, 8-11 are rejected.
Claims 6-7, 12-15 are 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 SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./ Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Filed April 19, 2018 and published October 25, 2018. Hereinafter Aktoudianakis. Cite No. 1 in the IDS filed 11/10/22/
2 Filed April 19, 2018 and published October 25, 2018. Hereinafter Aktoudianakis. Cite No. 1 in the IDS filed 11/10/22/
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