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/US2022/018279, filed March 1, 2022, and claims priority benefit of U.S. Provisional Application No. 63/155,441, filed March 2, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 24, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1, 4, 6, 8, 10, 13-16, 22, 26, 28, 31, 32, 35 and 37-42 are currently pending and subject to examination.
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.
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) 1, 4, 6, 8, 10, 13-16, 22, 26, 28, 31, 32, 35 and 37-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ueno & Hoshino (US 2020/0405697 A1, published Dec. 31, 2020) in view of Kohara et al. (Bioorganic & Medicinal Chemistry Letters, Vol. 5, No. 17, pp. 1903-1908, 1995), Tagad et al. (Bioorganic & Medicinal Chemistry, Volume 18, Issue 9, 1 May 2010, Pages 3175-3186) and Ohmoto & Itagaki (US 6,900,207 B2, published May 31, 2005, p. 5228-5235).
Claim 1 is directed towards a compound of formula (I)
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, for example,
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(claim 40).
Ueno teaches highly similar antitumor agents which inhibit ribonucleotide reductase (RNR) having formula
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141
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(Ueno, Specification, paragraph [0022]), for example,
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168
227
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(id., p. 117, ex. 83) and
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198
185
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(id., p. 183, ex. 349).
The compounds of Ueno differ from the instantly claimed compounds in that they have a 1,3,4-oxadiazol-2-one or 1,2,4-oxadiazol-5-one moiety instead of a tetrazole moiety. One of ordinary skill in the art, however, would have a reasonable expectation of success to substitute 1,3,4-oxadiazol-2-one or 1,2,4-oxadiazol-5-one with tetrazole to produce an RNR inhibitor with similar properties because oxadiazolones are well known to be bioisosteres of tetrazole.
For example, Kohara teaches that 1,2,4-oxadiazol-5-one is a bioisostere of tetrazole:
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514
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Kohara, Abstract;
Herein, we demonstrated that the 5-oxo-l,2,4-oxadiazole ring was a novel class of acidic bioisostere of the tetrazole ring. The representative compound, TAK-536 is a new class of potent, orally active and long-acting AII receptor antagonist, which has higher oral bioavailability than CV-11974. Consequently, further chemical modification of TAK-536 was not necessary for improvement of the BA. We believe that a novel class of acidic bioisostere, the 5-oxo1,2,4-oxadiazole ring can be applied to other drug design.
Kohara, p. 1908.
For example, Ohmoto teaches that oxadiazolone is interchangeable with tetrazole in cysteine protease inhibitors:
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128
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Ohmoto, Specification, col. 9; Ohmoto, Specification, col. 13;
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Ohmoto, Specification, col. 129; Ohmoto, Specification, col. 150.
As another example, Tagad teaches 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, 5-thioxo-1,2,4-oxadiazole and 2-thioxo-1,3,4-oxadiazole derivatives have similar BACE1 inhibitory activity to tetrazole derivatives:
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532
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Tagad, p. 3179.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claims 4, 6, 8, 10, 13-14, 22, 28, 31-32, 35, and 37-40 read on the compound
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(claim 40) and thus are prima facie obvious for the reasons given in the rejection of claim 1.
Claim 16 is directed towards the compound of claim 1, wherein ring A is a bicyclic 6- to 10-membered ring optionally substituted with O, S, and N. For example,
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(claim 40).
Ueno teaches a highly similar compound:
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(Ueno, Specification, col. 292-293, ex. 235A).
While compound 235A differs from the instantly claimed compound in that it has a 1,2,4-oxadiazol-5-one moiety instead of a tetrazole moiety, one of ordinary skill in the art would have a reasonable expectation of success to substitute tetrazole for 1,2,4-oxadiazol-5-one because these are well known bioisosteres and the substitution should produce a compound with similar properties.
For example, see the teachings of Kohara, Ohmoto and Tagad above in the rejection of claim 1.
Therefore, claim 16 was prima facie obvious at the time of filing.
Claim 37 is directed towards the compound of claim 1, wherein:
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For example, a compound reading on claim 37 is:
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(claim 40) (RBa is deuterium).
Ueno teaches a similar compound:
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(Ueno, Specification, col. 269-270, ex. 200A).
While compound 200A differs from the instantly claimed compound in that it has a 1,2,4-oxadiazol-5-one moiety instead of a tetrazole moiety, one of ordinary skill in the art would have a reasonable expectation of success to substitute tetrazole for 1,2,4-oxadiazol-5-one because these are well known bioisosteres and the substitution should produce a compound with similar properties.
For example, see the teachings of Kohara, Ohmoto and Tagad above in the rejection of claim 1.
Therefore, claim 37 was prima facie obvious at the time of filing.
Claim 41 is directed towards a pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient.
One of ordinary skill in the art would have a reasonable expectation of success to obtain a pharmaceutical composition comprising a compound of claim 1 because Ueno teaches pharmaceutical compositions comprising structural analogs of the compound of claim 1 and pharmaceutically acceptable excipients:
In yet another embodiment, the present invention provides a pharmaceutical composition comprising the compound of the present invention or a salt thereof and a pharmaceutically acceptable carrier…
With respect to pharmaceutically acceptable carriers, conventional various organic or inorganic carrier substances are used as pharmaceutical materials, and it is formulated as: excipients…
Ueno, Specification, col. 47-48.
Therefore, claim 41 was prima facie obvious at the time of filing.
Claim 42 is directed towards a method of treating cancer in a subject, comprising administering to the subject a compound of claim 1.
One of ordinary skill in the art would have a reasonable expectation of success to treat cancer with the compound of claim 1, because Ueno teaches that structural analogs of the compound of claim 1 can be used to treat cancer:
In yet another embodiment, the present invention comprises administering an effective amount of the compound of the present invention or a salt thereof to a subject to provide an RNR activity suppression method. Further, the present invention comprises administering an effective amount of the compound of the present invention or a salt thereof to a subject to provide a method of treating RNR-related diseases. In a preferred embodiment, a method of treating RNR-related diseases is a method of treating tumors. In the treatment method, the subjects include human or non-human animal in need of the method.
Ueno, Specification, col. 47, lines 43-53.
Ueno demonstrates the anti-cancer effects of the compounds in mice transplanted with a human derived blood cancer line (MV-4-11). For example, Figure 1 shows the effects of these analogs:
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Ueno, Figure 1.
Compare compound 5 with the second compound of claim 40, which differs only by the bioisosteric substitution of tetrazole for 1,3,4-oxadiazol-2-one (they are analogs):
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vs.
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(Instant Claim 40) (Ueno, Specification, col. 177-178, compound 5).
Therefore, claim 42 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629