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
Status of Claim
Claims 1-9 are pending and under examination.
Priority
This instant application 18/836,495 filed on 08/07/2024, is a 371 of PCT/JP2022/005409 filed on 02/10/2022.
Claim Objections
Claims 1-9 are objected to because of the following informalities:
Claim numbers should not be in the bracket.
Claims 2 and 6 recite acronym CDI which should be 1,1’-carbonyldiimidazole. Claim 2 recites “reacted with CDI, borane and concentrated hydrochloric acid in order” followed by “to produce...” is confusing with “in order to produce”. “in order” in claims 2 and 6 should be sequentially which is directed to step-by-step reaction.
Claim 3 recites “the method for producing the compound B according to claim 2”, wherein compound B is not described in claim 2.
Independent claim 6 and 9 recite “wherein TBDMS is defined as above” which is recited in dependent claim 2. The dependency is confusing. The definition of TBDMS should be separately recited in each relevant claims 3, 6, 7 and 9.
Specification
The abstract is objected to because the informalities:
The Abstract recites “ a compound represented by formula (I), a production method thereof, a production intermediate of the same and a method for producing compound B using the compound (I)” It’s not clear what production intermediate can be the same as compound (I).
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Interpretation
Claim 1 is directed to preparation of compound of Formula B comprising Suzuki-Miyaura coupling of bromo-substituted N-arylisoquinolone compound (I) with cyclopropylboronic acid in the presence of a palladium catalyst and a base.
As disclosed by instant spec (page 10), claim 2 and 6 are directed to formation of N-arylisoquinolone compound (I) through multi-step reactions: coupling/condensation by CDI , reduction by BH3-THF, and in-situ double bond formation/deprotection by conc. HCl.
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Claim 3 and 7 are drawn to the same amide formation.
Claim 4 and 8 are drawn to formation of phenylacetic acid compound (III).
Claim 5 and 9 are drawn to intermediate compound (I), (II), (III).
Claim Rejections - 35 USC § 112
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.
Claim 1-4 and 6-8 are 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 1 recites a method for producing a compound B by reacting compound (I) with a cyclopropylboronic acid in the presence of a palladium catalyst and a base, wherein the chemical Formula I recites specific palladium catalyst PdCl2(dppf and specific base K2CO3 .
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites broad limitation of palladium catalyst and then PdCl2(dppf) in Formula I which is the narrower limitation of palladium catalyst. K2CO3 is a narrower limitation of base. Claim 1 is considered indefinite because there is a question or doubt as to whether the feature introduced by narrower language is (a) merely exemplary of palladium catalyst and base, therefore not required, or (b) a required feature of the claims.
Claims 2-4 are rejected due to dependency on claim 1.
Claim 2 and 6 are directed to formation of N-arylisoquinolone compound (I) through multi-step reactions: coupling/condensation by CDI , reduction by BH3-THF, and in-situ double bond formation/deprotection by conc. HCl. However, the wording of claims is unclear as to whether it’s one-pot process or multi-step reactions, with or without isolation of intermediate.
Claim 2 recites “then the compound(I) is subjected to the method:'. It is not clear from the wording of the claim whether the method of claim 2 or the method of claim 1 is being referred to. Claims 3, 4, 7, 8 reciting “then the compound... is subjected to the method:' are rejected due to similar ambiguity. This ambiguity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
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 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:
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.
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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Lou et al. ( Journal of Medicinal Chemistry (2015), Vol. 58, No. 1, pp. 512-516, Applicant’ IDS dated 11/07/2024), in view of Huang et al (Bioorganic & Medicinal Chemistry Letters, 2017, 27(23), 5344-5348 , DOI: 10.1016/j.bmcl.2017.07.064, “The synthesis of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as potent CRTh2 antagonists”).
Lou teaches structure-based drug design of RN 486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis (See whole article).
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Lou teaches synthesis of intermediate 13 ( instant compound B) via sequence from benzoic acid 8: (i) amide coupling with ammonium hydroxide, (ii) Suzuki coupling to give cyclopropane 10, (iii) one-pot procedure of converting primary amide in 10 to bicycle 11 through amidination and base-induced ring closure, (iv) selective Suzuki coupling with 2-bromo-6-chlorobenzaldehyde to yield 12, and (v) reduction of the aldehyde group (See page 513, left column).
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The main difference of instant claim 1 and Lou process is that Suzuki coupling of cyclopropyl moiety occurs after the ring closure/ isoquinolinone formation. It’s well known practice in the art of organic chemistry to explore different intermediate / reagents etc. in different order for preparation of desired product. A skilled artisan would have known to explore Suzuki coupling and ring closure in different order for producing compound B . Thus, claim 1 reciting single-step of Suzuki coupling is not considered inventive in view of Lou and general knowledge of POSA in organic chemistry.
Claim 5 is directed to intermediate compound I in the synthesis of compound B.
The difference of compound I and compound B is bromo verse cyclopropyl moiety. A skilled artisan would have known cyclopropyl moiety could be introduced by Suzuki coupling as taught by Lou. Thus, compound I as intermediate is not considered as inventive in the absence of any pharmacological activity.
Regarding instant claims 2-4 and 6-9, Huang teaches synthetic methods for the preparation of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines,wherein isoquinolinone core could be constructed before the introduction of substitution groups or synthesized through a catalytic intramolecular cyclization reaction with desired substitution groups (See whole article).
Huang teaches formation of isoquinolinone core via phenylacetic acid and phenylacetamide intermediate that’s similar to instantly claimed compound II and III (See Figure 1, Scheme 1 and 2 page 5345 left column ).
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It’s noted Huang compound 1 is very similar to instant claimed compound III. Instant claims differ from Huang process in the substitution and specific reagents (e.g. CDI, etc.). However, the general concept of constructing isoquinolinone core from phenylacetamide was already taught by Huang. A skilled artisan would have known to explore different substitutions / reagents etc. for preparation of desired product. Claims 3, 4, 7 and 8 reciting one step reaction is not considered inventive in view of Huang and general knowledge of POSA in organic chemistry.
Claim 9 is directed to intermediate compound II and III in the synthesis of isoquinolinone core
The difference of instant compound II, III and Huang intermediates are different substitution on the phenyl ring. It’s noted Huang compound 1 is very similar to instant claimed compound III with F as the only difference. The objective of instant compound II, III as intermediate for synthesis of isoquinolinone core is not considered as inventive in the absence of any pharmacological activity.
Lou teaches general process of producing compound B comprising isoquinolinone core. Huang teaches construction of isoquinolinone core via phenylacetamide. It is common practice in the art of organic chemistry to explore different reaction conditions using different intermediate/ reagents etc. for preparation of desired product. Thus, instant invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Berthel et al US 8,299,077 B2. Berthel teaches preparation of 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-phenyl-1H-pyrazin-2-one derivatives as inhibitors of Bruton's tyrosine kinase. Berthel explicitly teaches preparation of instant compound B and intermediates for producing compound B(See Example 249-252).
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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