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
1. This application is a 371 of PCT/US2022/034411 06/21/2022. This application has PRO 63/310,772 02/16/2022. This application has PRO 63/213,349 06/22/2021.
Claims 1-21 are pending.
Response to Restriction Election
2. Applicant’s election of group I and the species (Example 8) in the reply filed on April 23, 2026 is acknowledged. The election was made without traverse. According to applicants’ representative claims 1-7, 12-14 read on the elected species. As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. Accordingly, claims 8-11, which does not read on the elected species is withdrawn.
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.
3. Claims 1-4, 14 is/are rejected under 35 U.S.C. 103 as being obvious over Brubaker WO 2021146370 A1 (cited on the IDS) in view of Patani Chem. Rev. 1996, 96, 3147-3176.
The applied reference has a common assignee and some inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determination of the scope and content of the prior art
(MPEP 2141.01)
Brubaker teaches compounds that are analogs of the compounds of the instant case that have the same utility. Page 17, teaches compound 13, page 22 compound 27 and page 30 compounds 48 and 49:
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The compounds were potent MAP41K inhibitors with two compounds giving sub nanomolar potency as shown in the Table 3 on Page 267:
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Patani on page 3152 ff. discusses the replacement of amino groups with methyl groups in some drugs, “4. Fluorine and Hydroxyl, Amino, or Methyl Groups as Replacements for Hydrogen (Grimm’s Hydride Displacement Law)”
“N-(Substituted-3-pyridyl)-N -alkylthioureas (19, Figure 13), which have been evaluated as novel potassium channel openers,33 are among the more recent illustrations of the replacement of chlorine with isosteres from Grimm’s Hydride Displacement Law (Table 11). Potassium channel openers cause vasorelaxation in vascular smooth muscle through hyperpolarization of the cell membrane. There is an increased interest in these compounds based on their therapeutic potential in the treatment of cardiovascular diseases. Substitution at the 6-position with monovalent isosteres (-NH2, -CH3, -Cl) results in analogues with similar biological activity. It was observed that substituents with similar biological activity had comparable effective van der Waal’s radii (Table 11).” [Page 3153, col. 1]
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“Table 12 lists the relative potency of a group of bioisosteres which act as inhibitors of thymidylate synthase.”
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“Within this series, it was observed that hydrogen bond donors were more potent than the unsubstituted parent compound. These analogues, however, were less active than compact lipophilic groups in elevating thymidylate synthase inhibition….. In another study aimed at designing cholinergic agents which would be capable of penetrating the central nervous system and displaying high efficacy at the cortical muscarinic receptors, a series of
oxadiazole-based tertiary amines 21 (Figure 15, Table 13) were tested….”
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Ascertainment of the difference between the prior art and the claims
The instant claims differ from the prior art only in the replacement of an amino with a methyl group or H, where in claim 1 R2 is alkyl.
Finding of prima facie obviousness
(MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to use analogs of those of Brubaker to produce the instant invention. Substitution of a monovalent isostere, -NH2, with -CH3 or H results in analogues with similar biological activity. As shown by Patani, these substituents have similar biological activity and comparable effective van der Waal’s radii. The experienced medicinal chemist would be motivated to prepare these compounds on the expectation that such close analogues would have similar properties and upon the routine nature of such experimentation in the art of medicinal chemistry. It would be routine for the chemist to alter the group with known isosteres as shown by Patani in an attempt to increase potency.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was 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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
4. Claims 1-7, 12-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 7, 20-22, 24-27 of copending Application No. 18/572,382 in view of Patani Chem. Rev. 1996, 96, 3147-3176. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the alkyl isosteres where R3 is alkyl. The instant claims are drawn to alkoxy, alkyl amino and isosteres of the ‘382 claims. As Patani explains on page 3155 “B. Divalent Isosteres Divalent isosteres can be classified into two subgroups:… (2) those divalent isosteres where substitution of a different atom results in the alteration of two single bonds such as in the series; C-C-C, C-NH-C, C-O-C, and C-S-C. Both of these types of bioisosteric substitutions have been used extensively in the study of the structure activity relationships of various pharmacologically active agents….As these divalent bioisosteres are attached to two different substituents, the chemical and polar differences are less pronounced. The bond angle or the conformation associated with the use of these divalent bioisosteres may be an important factor associated with retention of biological activity.” It was prima facia obviousness type double patenting at the time the invention was made to make bioisosteres of the claimed compounds.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
5. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID K O'DELL whose telephone number is (571)272-9071. The examiner can normally be reached on Monday - Friday 9:30 - 7:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID K O'DELL/Primary Examiner, Art Unit 1621
Prosecution Insights