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 (1-10) and new (11-15) claims filed on December 9, 2025. Claims 1-15 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on November 10, 2022 has been considered.
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)).
Claim 11 references the composition of claim 7, however claim 7 is a method of making. For the purposes of applying art, claim 11 is construed to depend from claim 8, a composition claim.
Claim Objections
Claims 1, 10-12, 14 are objected to because of the following informalities:
Claim 1 recite “A compound as” but should read “A compound of”.
Claims 10, 12, 14 recite “comprises” which appears to be a grammatical error and should read “comprising”.
Claim 11 depends from claim 7, but states “the composition of claim 7”. Claim 7 is a method of making claim, not a composition claim (see also Claim Interpretation and 35 USC 112 Rejections below).
Appropriate correction is required.
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 § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 11 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 is a method of treatment and states “the composition of claim 7”, however claim 7 is a method of making claim not a composition. It is unclear what the scope of claim 11 is, what is the composition the claim is referring to?
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.
Claims 1-3, 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018195321 A1 to Aktoudianakis et. al.1
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, 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 2, alternatively, CAS# 2248633-53-4 reads on Formula I-b as described above but 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.
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”).
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 is drawn to a method of making. The closest prior art is Aktoudianakis. Aktoudianakis teaches a method of making compound of instant Formula I-b, such as CAS# 2248633-53-4 (see Aktoudianakis at pp. 546-547, in particular Step 2).
Aktoudianakis
Instant
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Intermediate 1
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Intermediate 2
[above compounds] treated with [1,1’-bis(diphenylphosphino)ferreocene]palladium(II) dichloride and sodium carbonate
providing the compound of Formula I by coupling intermediates 1 and 2 with the existence of Pd(dppf)2Cl2 and Na2CO3.
Step a
The synthetic strategy employed by Aktoudianakis is similar to instant, relying on the reactive groups highlighted in dashed circles to couple the two intermediates in the same reagents (Pd(dppf)2Cl2 and Na2CO3), then later attaching the R3 and R4 groups via reductive amination (see Aktoudianakis at p. 547 Step 3, noted above as gray “R3” and “R4”). The retrosynthesis analysis of Aktoudianakis shows that the coupling is between Rings A-C to D instead of instant Ring A to C-D (compare above gray circled letters of Aktoudianakis with instant rings, see also comparison below).
Comparison of Aktoudianakis Synthetic Strategy and Instant Claim 7 Synthesis
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Put another way, Aktoudianakis and instant claim 7 are completing the same puzzle image by connecting two pieces in the same place, but with different shaped pieces.
However,
No reasonable suggestion or motivation was found in the prior art to modify Aktoudianakis’ synthetic strategy to arrive at instant claim 7.
Conclusion
Claims 4-5, 10-12, 14 are objected to.
Claims 1-3, 8-11 are rejected.
Claims 6-7, 12-15 are allowable.
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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/