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 .
Election/Restrictions
Applicant's election with traverse of Group IV, encompassed by claim 39 and new claim 63, drawn to a process for preparing a compound of Formula (I), in the reply filed on 06/24/2026, is acknowledged. The traversal is on the ground(s) that the instant claims do make a contribution over the prior art reference used by the Examiner (Berdini et al., cited by Examiner in Restriction Requirement mailed 2/24/2026 ), and argues that the instant synthesis generally avoids impurities (Z-1) and (Z-2), leads to higher yields of desired compounds, and requires less harsh reaction conditions (see Remarks filed 6/24/2026, page 31-32).
This is not found persuasive. The argument that the instant method is a superior method to the prior art method is not enough to overcome the restriction requirement.
The groups of inventions listed in the Restriction Requirement filed 2/24/2026 do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
No Shared Technical Feature or Shared Technical Feature Does Not Make a Contribution over the Prior Art
According to PCT Rule 13.2, unity of invention exists only when there is a shared same
or corresponding special technical feature among the claimed inventions. The "Instructions
Concerning Unity of Invention" (MPEP, Administrative Instructions Under the PCT, Annex B,
Part l(b )) state - "The expression 'special technical features' as defined in Rule 13.2 as meaning
those technical features that define a contribution which each of the inventions, considered as a
whole, makes over the prior art". The unity of invention exists only when the shared same or
corresponding technical feature is a contribution over the art.
No Shared Technical Feature Common
Groups I, II, III, IV, V, X, XI, and XII lack unity of invention because the groups do not share the same or corresponding technical feature. In the instant case, for example, Group I requires preparing a compound of Formula (D) which is not required by Group II, which requires preparing a compound of Formula (J). For example, Group I requires preparing a compound of Formula (D), which is not required by Group V, which requires preparing a compound of Formula (L). This analysis can be applied to all Groups enumerated above. Unity is thus lacking among Groups I, II, III, IV, V, X, XI, and XII.
Shared Technical Feature Does Not Make a Contribution over the Prior Art
Groups III and VI lack unity of invention because even though the inventions of these groups require the technical feature of a compound of Formula (N), this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Berdini (WO 2017/068412 A1, published April 27, 2017). On page 345, lines 1-12, Berdini teaches the synthesis of tert-butyl (R)-2-(3-(5-chloro-2-((oxan-4-yl)amino)pyrimidin-4-yl)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)propanoate, which is the compound of Formula (N), encompassed by Groups III and VI.
Groups IV, VII, VIII, and IX lack unity of invention because even though the inventions of these groups require the technical feature of a compound of Formula (N), this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Berdini (cited above). On page 815, Berdini teaches Examples 1105, or (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-hydroxyphenyl)-2-hydroxyethyl]propanamide, which is the compound of Formula (I), encompassed by Groups IV, VII, VIII, and IX.
Accordingly, unity of invention is considered to be lacking and restriction of the invention in accordance with the rules of unity of invention is considered to be proper.
The requirement is still deemed proper and is therefore made FINAL.
Applicant has elected without traverse the following species:
Chlorinating agent of step (ii): Applicant has elected POCl3;
R2 and R3 of step (iii) = together with the atoms to which they are attached form a 5-membered ring substituted with four methyl groups;
Reagent to remove t-butyl group of step (iv): trifluoroacetic acid.
In the amendment as filed on 06/24/2026, applicants have amended claim 39; cancelled no claims; and added new claim 63. Claims are 1, 9, 13-14, 17, 28-29, 35, 37, 42, 44-45, 47, 51-53, 56, 59 and 62 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Therefore, claims 1, 9, 13-14, 17, 28-29, 35, 37, 39, 42, 44-45, 47, 51-53, 56, 59 and 62-63 are currently pending and claims 39 and 63 are presently under examination.
Priority
The instant application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No 63/209,877, filed June 11, 2021, and U.S. Provisional Application No 63/273,326, filed October 29, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 12/08/2023, 08/05/2024, and 08/12/2024 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Specification
Acknowledgement is made of the drawings received 12/08/2023. These drawings are acceptable.
Claim Objections
Claim 39 is objected to because of the following informality: it is unclear what is the difference between option A or option B of claim 39. The Examiner has combed through them and has not found any distinction. Examiner suggests removal of one of these redundant options. Appropriate correction is required. Examiner notes that, in claim 63, there is a distinction between options A and B. In option A, the reduction of the iminosulfonyl and the ester of Formula (G-1) occurs in one step, while in option B, the reduction of the iminosulfonyl and the ester of Formula (G-1) occurs in two steps.
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.
Claims 39 and 63 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.
Regarding claim 39, the phrase "(e.g. monohydrate)" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 63 is regarded as vague for its recitation of “a reducing agent” in option B, step (v-ii) and again in step (v-iii). Is the same reducing agent used successively? If so, the second recitation of “a reducing agent” should read “the reducing agent of step (v-ii)”. If two different reducing agents are used, Applicant should amend the claim to recite “a first reducing agent” and “a second reducing agent”, respectively.
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:
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.
Claim(s) 39 is rejected under 35 U.S.C. 103 as being unpatentable over Berdini et al. (US 2019/0047990 A1, published February 14, 2019, cited on IDS filed 8/05/2024)(hereinafter, ‘Berdini 2019’) and Berdini et al. (WO 2017/068412 A1, published April 27, 2017, cited on IDS filed 12/08/2023)(hereinafter, ‘Berdini 2017’).
Instant claim 39 is drawn to the following synthetic sequence and preparation:
Instant Application:
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Berdini 2019 teaches the following synthetic sequence and preparation:
Berdini 2019:
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Berdini 2019 discloses the step 1 coupling with 2,4,5-trichloropyrimidine (pages 126-127, para [1214-1215], Preparation 94); the step 2 SNAr with 4-aminotetrahydropyran (page 128, para [1223-1224], Preparation 98); the Step 3 boc deprotection (page 128, para [1225-1226], Preparation 99); and lastly, the step 4 amide coupling with (S)-2-amino-(3-fluoro-5-methoxyphenyl)-ethanol (page 481, para [2226-2227], Example 685).
Here, the reference step 3 and step 4 boc removal and amide coupling are the exact same as instant step 4 and step 5. Furthermore, Berdini 2019 also teaches (page 81, para [0722]) a compound of formula (XIX), shown below, “in which “Hal” has been replaced by OH (i.e. the compound is a 4-pyrimidinone)…The hydroxy group on the pyrimidine can then be replaced by chlorine by reaction with a chlorinating agent such as POCl3.”
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Indeed, the instant application employs this teaching and strategy in their revised synthesis of final product, Compound I: Applicants replace “Hal” with hydroxy, followed by replacing the hydroxy with chlorine after SNAr with a nucleophilic amine (Step 1 and Step 2 of Instant Application Scheme above).
Berdini 2019 teaches a first step Suzuki coupling, followed by a second step SNAr. Berdini 2019 does not teach the step 1 SNAr first, followed by chlorination, and then Suzuki coupling, of instant claim 39.
Berdini 2017 teaches (page 231-232, Preparations 120-122) the following synthetic sequence:
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Berdini 2017 teaches the same general sequence employed in the instant application, wherein the SNAr with a nucleophilic amine (reference step 2 above) occurs first, followed by chlorination (reference step 3 above). Following this, the chloropyrimidine substrate is also used in an ensuing Suzuki reaction with an isoindolinone boronic ester (page 417-418, Example 184) in the same manner as instant application.
Berdini 2017 employs a pyrazole as their nucleophilic amine in Step 2 (above), while the instant application employs 4-aminotetrahydropyran. However, the chemical process that is occurring is an expected reaction. The use of a different starting material does not render an obvious, predictable process patentable.
It would have been obvious to a person having ordinary skill in the art before the effective filing
date of the claimed invention to modify the synthetic preparation of Berdini 2019 with the preparation disclosed by Berdini 2017 because it is no more than the simply reversing steps in a multi-step sequence, wherein the reversed steps are taught by Berdini 2017. Moreover, Berdini 2019 also suggests replacement of the halogen with a hydroxy unit, followed by SNAr, and conversion back to halogen.
Thus, said claim is rendered obvious.
Claim(s) 39 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Berdini 2019, Berdini 2017, and Liu et al. (US 2023/0144828 A1, published May 11, 2023, effectively filed April 20, 2020)(hereinafter, ‘Liu’).
The previous 103 rejection is incorporated herein.
Instant claim 63 is directed to the multi-step enantioselective synthesis of compound (J-2), shown below:
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Berdini 2017 discloses (page 672-673) the use of compound (J-2), referred to as “(S)-2-amino-2-3-fluoro-5-methoxyphenyl)-ethanol hydrochloride”. Berdini 2019 does not disclose the instant preparation.
Liu discloses (page 5, Example 1, steps 1-3 through 1-7) the following iminosulfylation and two step reduction sequence to produce vicinal amino alcohol, shown below:
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The preparation of Liu is as follows: condensation of (S)-tert-butylsulfinamide (Ellman’s sulfinamide) onto 1,2-dicarbonyl, reduction with sodium borohydride, reduction with LAH, and last, acid removal of sulfinamide to free amine.
This is the same sequence of steps as instant claim 63, albeit a different starting material is used. It is noted that Liu employs (S)-tert-butylsulfinamide, while instant claim 63 uses (R)-tert-butylsulfinamide. However, stereoisomers are prima facie obvious. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978).
It would have been obvious to a person having ordinary skill in the art before the effective filing
date of the claimed invention to employ the synthetic preparation of Liu to arrive at known compound (J-2) with a reasonable expectation of success. The desired compound (J-2) was known in the prior art, and the synthetic preparation to achieve the desired substitution pattern was also taught in the art.
Thus, said claims are rendered obvious.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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