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 .
CONTINUING DATA
This application is a 371 of PCT/IN2022/050442 05/06/2022
FOREIGN APPLICATIONS
INDIA 202111020678 05/06/2021
Claims 1-13 are pending.
Claim Objections
Claim 9 is objected to because of the following informalities: the end of claim 9 should perhaps read “or combination thereof” instead of only “thereof.” Appropriate correction is required.
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.
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.
Claim1-6 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 Formula 3, which contains a variable Y. Y is defined earlier in claim 1, but the definition appears to be specific to Formula I. The definition given for Y in claim 1 does not appear to apply to Formula 3, which is exemplified in the specification as a compound containing OAc at Y. Claim 1 is unclear because the definition of Y is not provided for Formula 3. For the purpose of search and examination, the definition of Y in Formula 3 is interpreted to be Cl, OAc, SPh, Br, OH, or OMe as given in the priority application. Claims 2-6 depend from claim 1 and incorporate the same limitation by reference, with no clarification on the definition of Y in Formula 3.
Claim 1 recites that Formula 3 is reacted with a substituted nucleobase to obtain Formula 4. In claim 2, the nucleobase is selected from five compounds, four of which do not resemble the nucleobase present in Formula 4. The definition of Formula 4 in claim 1 only encompasses the second nucleobase shown in claim 2. It is unclear how the other nucleobases can be reacted with Formula 3 to achieve Formula 4, because Formula 4 is specific to a particular structure which is different from the recited nucleobases. Furthermore, Formula 4 is a compound wherein the nucleoside base is specifically protected with an OAc group, not “substituted” generally as recited in step i) or substituted with R5 as recited in claim 2. It is unclear how a nucleobase other than the exemplified N-acetyl cytosine can be used to provide Formula 4.
Claims 1 and 6 are unclear because they do not end with a period and so they are incomplete.
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.
Claim(s) 1-2 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Amblard (US 20140235566A1, cited on IDS).
Amblard teaches a process in Scheme 9 wherein a generic compound which could encompass claimed Formula 3 is reacted with a protected pyrimidine base to provide a generic compound which could encompass claimed Formula 4.
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In Example 1, Scheme 14, Amblard teaches a reaction wherein a cytidine derivative is hydroxylated with HO-NH2.HCl.
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Amblard’s method differs from the claimed method because, in Example 1, the position corresponding to R4’ is methyl and not hydrogen as in the current claims.
Amblard also teaches the generic compounds, wherein R4’ can be H. See claim 3.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to modify Amblard’s synthesis to prepare an analog of Amblard’s compound wherein R4’ was H instead of Me. Amblard teaches that R4’ can be H, F, Cl, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2, C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, or NR2;. The skilled artisan would have chosen any of the finite number of variables at R4’ with a reasonable expectation of success because Amblard teaches that any of the variables are appropriate for the R4’ position.
Claim(s) 3-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Amblard (US 20140235566A1, cited on IDS) in view of Beutner (Org. Process Res. Dev. 2019, 23, 2050-2056 and supporting information).
Amblard teaches as set forth above, a reaction wherein claimed step i) is carried out using TMSOTf as a Lewis acid.
Amblard does not teach the reaction using a combination of HMDS and TMSOTf or a different Lewis acid, and is silent about the solvent used in the reaction.
Beutner teaches that the Vorbrüggen reaction is a method for synthesis of nucleosides from anomeric glycosyl esters and nucleobases. The key feature of the reaction is the use of TMSOTf to activate the nucleobase, in the presence of a Lewis acid such as a tin (IV) salt in traditional organic solvent. See page 2050, left column. In Figure 2, the Vorbrüggen reaction is carried out using HMDS and TMSOTf in acetonitrile at 40°C. In Table S3 (in the supporting information), Beutner teaches the use of a number of different Lewis acids, including SnCl4. Page 13 in the supporting information discloses that the reaction is done under nitrogen.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to carry out Amblard’s reaction using a combination of TMSOTf and HDMS, or using SnCl4 as the Lewis acid because the Vorbrüggen reaction is commonly carried out using those same reagents.
Allowable Subject Matter
The closest prior art for claims 7-13 is Vasudevan (Chem. Commun. 2020, 56, 13363, cited on IDS). Vasudevan teaches monoesterification of cytidine using an enzymatic process. See Figure 2. Vasudevan does not teach claimed step ii), diesterification of acetonide protected cytidine in the presence of base. The art of record does not teach or suggest modifying Vasudevan’s method to include diesterification of acetonide protected cytidine in the presence of base.
Conclusion
Claims 1-6 are rejected. Claim 9 is objected to. Claims 7-8 and 10-13 are allowed.
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/LAYLA D BERRY/ Primary Examiner, Art Unit 1693