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
This application is a 371 of PCT/IN2022/050143 (02/18/2022)
And claims foreign priority to INDIA 202141004900 (02/19/2021).
Information Disclosure
An IDS was not filed in this application. Applicant is reminded of the duty of disclosure as per 37 CFR 1.56 and detailed in MPEP § 2000.
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.
Claims 1-12 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 uses the language “Formula (I) …, and its chiral intermediates” which is unclear with respect to whether the process steps required include forming Formula (I) or whether “chiral intermediates” are only required. One of skill in the art would find the phrase used in this manner to claim a process vague and ambiguous such that the scope of the claim is unclear. Thus, the claim and those that depend therefrom are indefinite.
Claims 5, 8, 10, and 12 use lists or Markush groups in a manner which is confusing due to the lack of clear punctuation, use of “and” or “or”, and delineating the beginning and end of groups.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hughes et al. (J. Med. Chem. 2015, 58, 2609−2622) in view of Chao et al. (US 7521558), Nithun et al. (IN201941005368).
Hughes teaches the synthesis of batefenterol (Table 1, compound 12f = 2-Cl-5-methoxy) which is the same compound of claim 1’s Formula (I). Hughes teaches a synthetic process in Scheme 1 including the following:
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Hughes teaches the synthesis of compound 11 above is from reference 13, which is Chao et al. (US 7521558).
Hughes does not teach claim 1d’s step of chiral epoxidation with a chiral sulfide.
Nithun teaches forming a chiral expoxide intermediate in the synthesis of long-acting β2-adrenoceptor agonists (LABAs) such as Indacaterol, Abediterol, and Carmoterol (Ex 3, p. 40):
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One of ordinary skill in the art following the teaching of Hughes would have considered techniques that use chiral intermediates such as Nithun’s intermediate XVIII given the structural similarity of the compounds as well as their related utility as agonist in the same family. One of ordinary skill in the art would consider routine the combination of successful synthetic techniques to improve yield and stereochemistry and incorporated the intermediate into the synthetic scheme of Hughes and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 2, Nithun teaches carbonylation in solvents including 1:1 DMF:THF (p. 24-26):
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and addition of lithium diisopropylamide LDA at 0 to -78C. Nithun also teaches the epoxidation in the presence of KOH (p. 25-26):
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.
Regarding claim 3, one of ordinary skill in the art following the modified teaching of Hughes in view of Nithun would have utilized the same intermediate specifically taught by Chao of Prep 8 (col 24-25) which uses a silyl PG on the hydroxyl in the same manner with the following compound, 8-Benzyloxy-5-[(R)-2-bromo-1-(tert-butyldimethylsilanyloxy)ethyl]-1H-quinolin-2-one:
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And would have performed the same condensation reaction as taught by Chao in Example 3 (col 28-30) analogous to Hughes and arrive at the claimed invention.
Regarding claims 4-12, one of ordinary skill in the art following the combined teaching of the art would consider the same solvent, brominating agents, TBDMS, palladium debenzylation agent, and base as disclosed by the cited art and are routinely used in the art. Furthermore Chao teaches in Preparation 16 forming Biphenyl-2-ylcarbamic Acid 1-[2-(2-Chloro-4- formyl-5-methoxyphenyl-carbamoyl)ethylpiperidin-4-yl ester:
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and Preparation 17 Biphenyl-2-ylcarbamic Acid 1-[2-(4-{(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2- dihydroquinolin-5-yl)ethylaminomethyl}-2-chloro 5-methoxy-phenylcarbamoyl)ethyl]piperidin-4-yl Ester
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With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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