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 .
Priority
This application filed on 06/12/2023, is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/EP2021/086185, filed on 12/16/2021, which claims priority to grand Duchy of Luxembourg application No. LU102333, filed on 12/23/2020, and European patent application EP20215091.8, filed 12/17/2020.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 10/13/2023, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
The premilitary amendment filed on 06/12/2023, that amended claims 3-7, 12, 15, 19, 23, 27, 30, 32, 36, and 37, cancelled claims 8-11, 13-14, 16-18, 20-22, 24-26, 28-29, and 33-35, and added claims 38-42, is acknowledged.
Claims 1-7, 12, 15, 19, 23, 27, 30-32, 36-42 are pending.
Election/Restriction
Applicant’s response filed on 01/20/2026 to Restriction/Election Requirement filed on 12/10/2025, is acknowledged. Applicant elected without traverse Group I drawn to a compound of Formula I and a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt, racemate, diastereomer, enantiomer, ester, carbamate, sulphate, phosphate or prodrug thereof. Claims 1-7, 12, 15, 19, 23, 27, 30-32, 36, and 39-42 read on the elected Group. Claims 37 and 38 of Groups II and III are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse, (S)-1-(2-(3,4-Dichloro-5-methyl-1 H-pyrrole-2-carboxamido)-5-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl) phenyl) pyrrolidin-3-aminium chloride depicted below for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable:
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Claims 1-4, 6-7, 12, 15, 27, 30-32, 36, 39 and 42 read on the elected species. Applicant’s elected species was searched, and determined to be free of the art of record. Pursuant to MPEP § 803.02, the search and examination was extended to the non-elected species discussed below, which new search species falls within the scope of instant claims 1-4, 6-7, 12, 15, 27, 30-32, 36, 39 and 42 (i.e., claims to proper Markush groupings that include both the new search species as well as the originally elected species. MPEP § 803.02(III)(C)(2)). The new search species underlies rejections of these claims pursuant to 35 U.S.C. § 102 and 103. As such, the election of species requirement is maintained as provisional, and claims 5, 19, 23, 37-38, and 40-41 are provisionally withdrawn from consideration pursuant to 37 CFR 1.142(b). See, MPEP § 803.02.
Thus, claims 1-7, 12, 15, 19, 23, 27, 30-32, 36-42 are pending with claims 5, 19, 23, 37-38, and 40-41 are withdrawn from further consideration, and claims 1-4, 6-7, 12, 15, 27, 30-32, 36, 39 and 42 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for “optionally substituted”:
The claims recite optionally substituted alkyl, optionally substituted alkoxy, optionally substituted C3-6 cycloalkyl, etc. The term “optionally substituted” is defines by instant specification as:
Unless otherwise defined, the term "optionally substituted" or "optional substituent" as used herein refers to a group which may or may not be further substituted with 1, 2, 3, 4 or more groups, preferably 1, 2 or 3, more preferably 1 or 2 groups selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, hydroxyl, oxo, C1-6 alkoxy, aryloxy, C1-6 alkoxyaryl, halogen, C1-6 alkylhalogen (such as CF3 and CHF2), C1-6 alkoxyhalogen (such as OCF3 and OCHF2), carboxyl, alkoxycarbonyl, cyano, nitro, amino, mono substituted amino, disubstituted amino, acyl, amides, aminoacyl, substituted amides, disubstituted amides, carbamic acid, carbamates, thiol, alkylthio, thioxo, sulfates, sulfonates, sulfinyl, substituted sulfinyl, sulfonyl, substituted sulfonyl, sulfonylamides, substituted sulfonamides, disubstituted sulfonamides, phosphates, phosphonates, aryl, aryl-C1-6 alkyl, heterocyclyl, heteroaryl and spiro ring systems wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl and spiro ring system and groups containing them may be further optionally substituted. Unless otherwise defined, particularly preferred optional substituents in one case include 1, 2, 3 or 4, preferably 1 or 2 substituents each independently selected from the group consisting of C14 alkyl (particularly methyl), halogen (particularly F), halogeno-C1-3 alkyl (particularly CHF2 and CF3), OH, C1-4 alkoxyl (particularly OСН3), СООН, СООC1-4 alkyl (particularly COOCH3), NH2, NH-C1-4 alkyl (particularly NHCH3), N(C1-4 alkyl)2 (particularly N(CH3)2), NHC(=O)-C1-4 alkyl, NHC(=O)-4-6-membered heterocyclyl, OP(=O)(OR)2(where each R is independently H or C1-4 alkyl), P(=O)(OR)2(where each R is independently H or C1-4 alkyl), C3.6 cycloalkyl (particularly cyclopropyl, cyclobutyl, cyclopenyl and cyclohexyl), phenyl, 4-6-membered heterocylyl (particularly oxetanyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, oxothiazinyl, dioxothiazinyl, thianyl (also known as tetrahydrothiopyranyl), oxothianyl, dioxothianyl, piperidinyl, and piperazinyl) and further where C1. 4alkyl either alone or as part of a substituent group includes methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl and tert-butyl and may be further optionally substituted. [Pg. 36, ln. 10-30].
Thus, the term “optionally substituted” is interpreted consistent with the specification as one of the above groups.
Claim interpretation for “heterocyclyl”:
The claims recite heterocyclyl. The term “heterocyclyl” is defines by instant specification as:
Heterocyclyl is a saturated, partially saturated or unsaturated, optionally substituted monocyclic or bicyclic 10 ring system containing 5 to 10 atoms of which 1, 2, 3 or 4 ring atoms are chosen from nitrogen, sulphur or oxygen, which may, unless otherwise specified, be carbon or nitrogen linked, wherein a -CH2- group can optionally be replaced by a -C(O)-, a ring sulphur atom may be optionally oxidised to form the S-oxide(s), and a ring nitrogen atom may be optionally oxidised to form the N-oxide. Examples and suitable values of the term heterocyclyl are morpholino, morpholinyl, piperidino, piperidyl, pyridyl, pyridyl-N-oxide, pyranyl, pyrrolyl, imidazolyl, thiazolyl, thienyl, 15 dioxolanyl, thiadiazolyl, piperazinyl, isothiazolidinyl, triazolyl, tetrazolyl, pyrrolidinyl, 2-oxazolidinonyl, 5- isoxazolonyl, thiomorpholino, pyrrolinyl, homopiperazinyl, 3,5-dioxapiperidinyl, 3-oxopyrazolin-5-yl, tetrahydropyranyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrazolyl, pyrazolinyl, isoxazolyl, 4-oxopydridyl, 2-oxopyrrolidyl, 4-oxothiazolidyl, furyl, thienyl, oxazolyl, oxadiazolyl, 20 2-[(5-oxo)-[oxa-3,4-diazolyl] and 3-[oxa-2,4-diazolyl]. [Pg. 30, ln. 9-20].
Thus, the term “heterocyclyl” is interpreted consistent with the specification.
Abstract
The Abstract of the disclosure is objected to because the Abstract recites “the present invention relates to compounds having a structure of general formula (I)”. Applicant is reminded of the proper language and format for an abstract of the disclosure. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “p is (independently at each occurrence) 0, 1 or 2”. While Applicant may intend that the parenthetical phrases designate shorthand references, they are superfluous and a better practice is to amend so as to remove the parentheticals to avoid confusion as to whether Applicant improperly intends preferences within the claim. See MPEP § 2173.05(d). Applicant can overcome this objection by amending the claim to remove the parenthesis.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6-7, 12, 15, 27, 30-32, 36, 39 and 42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claim 1 is directed to “an article of manufacture comprising a compound of formula I, that is claimed to have a biological activity as an anti-bacterial agent”. The recitation of prodrug of compounds of formula I is not adequately defined in the instant specification.
The MPEP states that for a generic claim can be adequately described if the disclosure presents a sufficient number of representative species in examples that encompass the genus. (MPEP § 2163). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole cover, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. Each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
With respect to the scope of the claims, the full scope includes “an article of manufacture comprising a compound of Formula I, or a pharmaceutically acceptable salt, racemate, diastereomer, enantiomer, ester, carbamate, sulphate, phosphate or prodrug thereof.”
J. Zawilska et al. (Prodrugs: a challenge for the drug development. Pharmacol Rep. 2013; 65(1):1-14), teaches that “Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug.” [Abstract]. Zawilska teaches that “the rationale behind the use of prodrugs is to optimize the absorption, distribution, metabolism, excretion, and unwanted toxicity of the parent drug.” [Pg. 2, col. 1]. Zawilska teaches that there are two main classes of prodrugs, carrier-linked prodrugs (the drug is temporary linked to a carrier that undergoes biotransformation, releasing the parent drug and the carrier), and bioprecursor prodrugs (result from a molecular modification of the drug and transformed metabolically or chemically by hydration or reduction. [Pg. 2, col. 2]. Zawilska teaches the major groups of prodrugs:
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Zawilska teaches that “some esters are not suitable substrates for endogenous esterases, sulfatases or phosphatases, which, in turn, impose unfavorable, too slow kinetics of the prodrug hydrolysis.” [Pg. 4, col. 1, 1st para.]. Zawilska teaches that the prodrug should be easily dissolved in water, and marginally taken up by cells, the drug should be efficiently and rapidly transported, the enzyme should have high intrinsic activity, and enzyme cannot be inactivated by a prodrug or drug. Zawilska teaches that “Despite the remarkable progress made in the field of prodrug design, more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art and take their place in modern pharmacotherapy.” Pg. 11, col. 21st para.].
The instant claims directed to compound of formula I, wherein R1-6 are defined as “optionally substituted” with the substituents includes COOH, C=O, NH, OH, SH, PO(OH)2, etc. (see claim interpretation above). As discussed above by Zawilska, these functional group leads to multiples prodrugs. Additionally, compound of formula I includes multiple sites to which a prodrug moiety could bind. The description does not provide adequate description on the binding moiety, the type of prodrugs (carrier-linked prodrugs or bioprecursor prodrugs), kinetics of the prodrug hydrolysis, or the enzyme-prodrug interaction. See Zawilska above. The specification does not provide answer to question regarding prodrug of compound of formula I, for example, does the metabolism of compound of formula I are well understood, does the prodrug will be active, does the prodrug will introduce any unfavorable interaction, etc. Zawilska teaches that “more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art”
The description does not include a definition of the prodrug that satisfies the functional definition of the genus. "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention."). Problems satisfying the written description requirement for original claims often occur when claim language is generic or functional, or both. Ariad, 593 F.3d at 1349, 94 USPQ2d at 1171 ("The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus."
Comparison of the scope of the claims and the scope of the specification reveals that the scope of the claims is broader than that supported by the specification. There is no guidance in the specification regarding prodrugs. The specification only recites:
In addition to salt forms, the invention provides compounds which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. A prodrug may improve the physical properties of the parent drug and/or it may also improve overall drug efficacy, for example through the reduction of toxicity and unwanted effects of a drug by controlling its absorption, blood levels, metabolic distribution and cellular uptake. [Pg. 67, ln. 1-8].
The generic definition provided in the instant specification do little in discriping a prodrug for compound of formula I because compound of formula I encompass handereds/thousands of species each of which encompasses multiple sites for prodrug binding. The instant specification provides no example for any prodrug of any compound of formula I, let alone, its activity, metabolism, enzymatic interaction, toxicity, etc. BOC Sciences (https://www.bocsci.com/blog/prodrug-activation-strategies-in-drug-discovery/?srsltid=AfmBOor0dyaRkHg4KY8ggdEj09mix1fTx8ZGgnvoIJzT5gtvjX5jYSHE, 2023), teaches that “the design of prodrugs must ensure their ability to degrade and release the parent drug at the appropriate time and site. This requires that the designed prodrugs have suitable chemical stability and enzymatic stability. They should neither degrade before reaching the target site nor remain undegraded for an extended period after entering the target site, as this would hinder their pharmacological effect. Additionally, prodrugs often have distinct chemical structures from the parent drug, which may introduce new toxicities. On one hand, this could result from unexpected metabolism of the prodrug, leading to the formation of unforeseen metabolites. On the other hand, it may occur because inert carriers generated from prodrug cleavage can transform into toxic metabolites, such as formaldehyde and acetaldehyde. Therefore, the comprehensive evaluation of prodrugs should include their physicochemical properties, pharmacological effects, pharmacokinetic properties, and potential toxic reactions.” [Pg. 8]. Thus, in view of BOC Science, claiming prodrug of compound of formula I required more than what provided by instant specification. One skilled in the art cannot, as one can do with a fully described prodrugs, visualize or recognize the identity of the prodrugs of the genus of formula I.
Having analyzed the claims with regard to the written description guidelines, the specification does not disclose a representative number of prodrugs or relate the functional language of “a prodrug that provides for anti-bacterial activity” to sufficiently to describe said prodrugs. Thus, one of ordinary skill in the art would be led to conclude that applicants were not in possession of the invention commensurate with the scope of the claims, at the time the application was filed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 6-7, 12, 36, and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Z. Skok et al. Bioorg Chem. 2020 Sep; 102:104049, “Skok” cited in the IDS dated 10/13/2023).
Skok discloses bacterial topoisomerase inhibitors [Abstract]. Skok discloses compound 18, [Table 1]:
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Skok’s compound 18 anticipates instant claim 1 wherein:
R1 is CH3;
R2 is chloro;
R3 is Chloro;
R4 is H;
R5 is (CH2)mO(CH2)m-5-10-membered heterocycle, wherein m is 0, and the 6-membered heterocycle is piperidine; and
R6 is -CONR6’R6’’, wherein R6’ is H, and R6’’ is alkyl substituted with COOH (see claim interpretation for optionally substituted).
Claims 2, 3, and 4 are met because R1 is CH3, R2 is chloro, and R3 is Chloro.
Claim 6 is met because R4 is H.
Claim 7 is met because R5 is O-piperidine.
Claim 12 is met because R6 is -CONR6’R6’’.
Claim 39 is met because R2 and R3 are Chloro.
With regard to claim 36, Skok discloses inhibition assays, wherein the compound mix in a buffer and water which reads on pharmaceutically acceptable excipient.
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.
Claims 1-4, 6-7, 12, 15, 27, 30-31, 36, 39, and 42 are rejected under 35 U.S.C. 103 as being obvious over B. Tiz et al. Eur. J. Med. Chem. 2019 Apr 1; 167:269-290. doi: 10.1016/j.ejmech.2019.02.004, “Tiz” cited in the IDS dated 10/13/2023).
Tiz teaches DNA gyrase and topoisomerase inhibitors. Tiz teaches construction of the compound as depicted below, [Abstract]:
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In studies on the inhibitory activity against DNA gyrase and topoisomerase IV, Tiz listed compound 9d as the potent inhibitor with an IC50 of 6.9±0.5 nM, [Table 1]:
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Tiz’s compound 9d and 10a only differs in Y of the genus
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, wherein Y of compound 9d (6.9±0.5 nM) is COOH, and Y of compound 10b (48±4 nM) is COOMe. This difference in Y resulted in more than 8 times decrease in potency.
Tiz also teaches compound 50 as the most anti-bacterial and DNA gyrase and topoisomerase IV inhibitor, [Table 2], with minimum inhibitory concentration of 3.13 µM, [Table 6]:
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Tiz’s compounds 46b and 50 only differs in the R2 groups of the genus
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, [Table 2]. R2 of compound 46b (7700 ± 900 nM) is
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, and R2 of compound 50 (77 ± 10 nM) is
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. This difference in the R2 resulted in hundreds times decrease in potency.
One of ordinary skill in the art have access to Tiz studies and looking to prepare a potent anti-bacterial agent, would have been motivated at the time of the invention to modify Tiz’s compound 9d by incorborating the R2 of compound 50 to arrive at the compound below:
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One of ordinary skill in the art would have been motivated to select 1,4-dihydro- tetrazol-5-one as Y, and piperidine as X with reasonable expectation of success because:
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Tiz studies directed to finding potent anti-bacterial agents;
Tiz teaches three different groups as Y and compound 50 with Y as 1,4-dihydro- tetrazol-5-one shows high anti-bacterial potency;
Tiz’s compound 9d with X as piperidine shows higher anti-bacterial inhibition; and
The comparison discussed above between 9d/10b, and 50/46b shows that positions X and Y are crucial in the genus above, and the variables piperidine and 1,4-dihydro- tetrazol-5-one demonstrate high anti-bacterial potency. Thus, one of ordinary skill in the art would reasonably predict to increase the potency with preforming the modification of Tiz compound 9d.
The modified compound
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reads on instant claim 1 wherein:
Skok’s compound 18 anticipates instant claim 1 wherein:
R1 is CH3;
R2 is chloro;
R3 is Chloro;
R4 is H;
R5 is (CH2)mO(CH2)m-5-10-membered heterocycle, wherein m is 0, and the 6-membered heterocycle is piperidine; and
R6 is 5-membered heterocyclyl, 1,4-dihydro- tetrazol-5-one.
Claims 2, 3, and 4 are met because R1 is CH3, R2 is chloro, and R3 is Chloro.
Claim 6 is met because R4 is H.
Claim 7 is met because R5 is O-piperidine.
Claim 12 is met because R6 is 1,4-dihydro- tetrazol-5-one.
Claims 15, 27, 30, and 31 are met because R1 is CH3; R2 is chloro; R3 is Chloro; R4 is H; R5 is O-piperidine; and R6 is 1,4-dihydro- tetrazol-5-one.
Claims 39 and 42 are met because R2 and R3 are Chloro.
With regard to claim 36, Tiz teaches that water solubility of the compound i.e., compound 50 was performed. [Pg. 279, col. 2, last para.]. Water reads on pharmaceutically acceptable excipient.
Objection to Claims
Claim 32 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Allowable Subject Matter
Claim 32 is allowable.
The following is an examiner’s statement of reasons for allowance:
The closest prior art is considered to be Z. Skok et al. Bioorg. Chem. 2020 Sep; 102:104049, “Skok” cited in the IDS dated 10/13/2023).
Skok discloses bacterial topoisomerase inhibitors [Abstract]. Skok discloses compound 18 below, [Table 1]:
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Skok’s compound 18 reads on compounds of claim 32, i.e., 4-(2-(3,4-Dichloro-5-methyl-1 H-pyrrole-2-carboxamido)-5-(5-oxo-4,5-dihydro-1,3,4- oxadiazol-2-yl)phenoxy)piperidin-1-ium chloride (depicted in the Table below), wherein (in claim 32 and Skok’s compound 18): R1 is CH3; R2 is chloro; R3 is Chloro; R4 is H; and R5 is O-piperidine; and differs from the instantly claimed compound of claim 32 in the highlighted circle as depicted in the below table:
[Skok’s compound 18]
[Claim 32 compound]
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In order to arrive at a compound falling within the instantly claimed compounds of claim 32, for example, the compound above, one of ordinary skill in the art would have to modify Skok’s above compound by replacing the highlighted CONHCH(CH3)-COOH group with 1,2,4-oxadiazol-5-one, tetrazole, 1,3,4-oxadiazol-2-one or 1,4-dihydro- tetrazol-5-one, e.g., 1,4-dihydro- tetrazol-5-one above, to arrive at a compound of claim 32. However, Skok’s disclosure does not provide sufficient guidance and motivation to one of ordinary skill in the art to perform the functional modifications to arrive at the instantly claimed compounds of claim 32. Therefore, Skok does not anticipate or render instantly claimed compounds obvious.
Conclusion
Claims 1-4, 6-7, 12, 15, 27, 30-31, 36, 39 and 42 are rejected. Claim 32 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622