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
Examiner acknowledges that, according to the Filing receipt received 02/03/2025, that the instant application 18/833,489 filed 07/26/2024 is a 371 of PCT/US2023/061619 filed 01/31/2023 which claims benefit of U.S. provisional application 63/267,357 filed 01/31/2022.
However, the limitations of the instant claims are not adequately supported or enabled in the manner provided by 35 U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by 63/267,357. More specifically, the limitations of Formula Ib and the compounds of claim 18 are not taught or suggested in their entirety. Other deficiencies may be present. As such, all the instant claims have been awarded the effective filing date of PCT/US2023/061619 filed 01/31/2023.
Information Disclosure Statement
The Information Disclosure Statement filed on 07/26/2024 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Specification
The disclosure is objected to because of the following informalities: page 65, the structure of Formula II contains an asterisk “*” that is not located on any particular carbon to denote stereochemistry; page 67, the structure of Formula III is unclear as L4 overlaps with the ring and L4 and L3 are positioned such that there is no apparent bond between the two; pages 76-77, 81-86, and 88, the structures in Table 4, 5, 6, and 7 are low resolution such that they are difficult to interpret; the content of pages 71 and 88 are not written in portrait orientation (see 37 CFR 1.52).
Appropriate correction is required.
Claim Objections
Claim 18 is objected to because of the following informalities: the following structures are difficult to interpret due to low resolution.
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Appropriate correction is required.
Claim Rejections – Improper Markush Grouping
Claims 1-3, 8, 11-12, 14, 16-17, and 32-41 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) the species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the Specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
The variable is defined as seen below:
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The claims are drawn to compounds of Formula Ia or Ib, which vary immensely and have no single or common core structure required by their definition. The cyclic structures vary in their degree of saturation, quantity and identity of heteroatoms, and substituents ranging from hydrogen to sulfonyl and aryl groups. Moreover, the variable R2 ranges from hydrogen or halogen to heterocycloalkyl and is linked to Formula Ia or Ib by an alkyl or heteroalkyl chain of variable length. The definitions are so broad that one or ordinary skill in the art could not possibly ascertain a substantial structural feature of Formula Ia or Ib from which a common use would flow. Examiner additionally notes that a search for the broadest scope of the claimed compounds resulted in over a million hits. However, of the extensive scope of compounds claimed by the instant invention, the disclosure only depicts species of compounds wherein X is S; n is 0 or 1; R2 is phenyl, furyl, or benzoxadiazolyl; Y and Z are both nitrogen or both carbon; and the ring containing W1 and W2 or A1-A6 is phenyl, pyridinyl, indolyl, or benzimidazolyl.
Clearly no ‘‘single structural similarity’’ can be seen.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. § 134 and 37 CFR41.31 (a) (1).
Claim Rejections - 35 USC § 112(b)
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 1-3, 8, 11-12, 14, 16-18, and 32-41 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.
Claims 1 and 40 set forth lists of alternatives preceded by “comprise” or “comprises”. Per MPEP 2173.05(h), “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196.” The use of “comprise” or “comprises” is indefinite as it is unclear what other members or alternatives are encompassed by the claim. Claims 2-3, 8, 11-12, 14, 16-18, 32-39, and 41 do not clarify the limitations at issue and are also rejected.
Claim 1 depicts the variables R1(a-b) and R3(a-c). It is unclear whether each of R1(a-b) and R3(a-c) must be present on the structure of Formula Ia or Ib or if they are each optionally present. Additionally, if they must be present, then the valence of the nitrogen bound to R1(a-b) would be violated, as nitrogen can only form 3 bonds. Claims 2-3, 8, 11-12, 14, 16-18, and 32-41 recite and/or do not clarify the limitations at issue and are also rejected.
Claim 1 recites “C3-C7 aryl”, however, neutral C3-C5 and C7 aryl groups are not possible. Claims 2-3, 8, 11-12, 14, 16-18, and 32-41 recite and/or do not clarify the limitations at issue and are also rejected.
Claim 1 recites “; or substituted or unsubstituted C1-C10 alkyl, C3-C7 cycloalkyl… substituted sulfinyloxy”. It is unclear whether the alternatives listed after “substituted or unsubstituted C1-C10 alkyl” can also be substituted or unsubstituted (other than sulfinyloxy, which is explicitly only substituted). For purposes of examination, Examiner has interpreted the claims such that all alternatives listed after C1-C10 alkyl are also substituted or unsubstituted. Claims 2-3, 8, 11-12, 14, 16-18, and 32-41 do not clarify the limitations at issue and are also rejected.
Claim 1 recites “R3a-3c is… connected to an R10 by a… alkyl chain” and “each R10 independently comprises H or is… connected to one of R3a-3c by a… alkyl chain”. It is unclear how R3a-3c can connect to R10 if R10 is H or how both “R3a-3c is… connected to an R10 by a… alkyl chain” and “each R10 independently… is… connected to one of R3a-3c by a… alkyl chain” can be true. Claims 2-3, 8, 11-12, 14, 16-18, and 32-41 do not clarify the limitations at issue and are also rejected.
Claim 17 recites “wherein A1-A6 and R3a-3c, if present, form a saturated heterocycle”. It is unclear which of A1-A6 and R3a-3c are intended to be optionally present.
Claims 17 and 18 recite “or any combination thereof”. It is unclear what structure is intended by a “combination” of substituents or compounds.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3, which depends upon claim 1, depicts the following structures.
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Claim 18, which depends upon claim 1, depicts the following structures.
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These structures are not within the scope of claim 1 because R10 and one of R3a-3c are linked by an alkenyl chain rather than an alkyl chain. Claims 3 and 18 therefore fail to incorporate all of the limitations of the claim upon which they depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-2, 8, 14, 16, 32, 36-37, and 39 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Levy et al. (US 2003/0229065 A1; 2003).
Levy et al. discloses the following compounds (p. 257, 259-260, 265). Levy et al. discloses that the compounds were dissolved in a composition additionally comprising 10 mg/mL DMSO stock solution prior to administration to E. coli cells (p. 61, par. [0664] and [0673]).
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The compounds are species of Formula Ia wherein Y and Z are N, R1a-b is optionally substituted alkyl or alkoxy, n is 0 or 1, R2 is optionally substituted phenyl, W1 and W2 are both CH or one of W1 or W2 is N, and the salt is HCl.
Claim(s) 1-2, 8, 14, 16, and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAPLUS (STN; 2006).
CAPLUS discloses RN 883011-58-3.
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The compound is a species of Formula Ia wherein Y and Z are N, R1a-b is alkyl, n is 1, R2 is optionally substituted phenyl, W1 is CH and W2 is N. Claims 36-37 necessarily require the above compound and are also rejected.
Claim(s) 1, 8, 14, 16, 35-37, and 39 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Westwood et al. (Protein & Cell; 2010).
Westwood et al. discloses the following compounds (p. 86, 87).
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The compounds are species of Formula Ia wherein Y and Z are N, R1a-b is H, n is 1 or 2, R2 is optionally substituted phenyl or substituted alkoxy, W1 and W2 are both CH.
Westwood et al. discloses that the compound 4 was dissolved in DMSO prior to administration to mouse macrophages infected with mycobacteria M. bovis, wherein compound 4 was not toxic toward macrophages but enhanced the killing of M. bovis (Figure 6; p. 93 both columns).
Claim(s) 1, 8, 14, and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Page et al. (WO 2014176636 A1; 2014).
Page et al. discloses the following compounds (p. 195).
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The compounds are species of Formula Ia wherein Y and Z are N, R1a-b is H, n is 0 or 1, R2 is substituted phenyl, W1 and W2 are both CH.
Page et al. additionally teaches testing the above compounds for activity against bacteria in culture solution (p. 114, par. [00321]; p. 117, par. [00329]).
Claim(s) 1, 8, 11, 14, 16, 35-37, and 39-40 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Karabanovich et al. (Journal of Medicinal Chemistry; 2019).
Karabanovich et al. discloses the following compounds (p. 8117).
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The compounds are species of Formula Ia wherein Y and Z are N, R1a-b is H, n is 0 or 1, R2 is substituted phenyl, W1 and W2 are both CH. In particular, for compound 9g, R5b and R5c of R2 are chloro.
Karabanovich et al. further discloses administering a composition comprising the compounds and DMSO to drug-sensitive, multidrug-resistant, and extensively drug-resistant strains of M. tuberculosis (p. 8118; p. 8121; Table 1; Table 2; p. 8136). Karabanovich additionally discloses that the compounds are not selective toward mammalian cells (p. 8121, col. 2).
Claim(s) 1, 8, 14, 16-17, and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lasalle et al. (Tetrahedron Letters; 2015).
Lasalle et al. discloses the following compound (p. 1013, Table 2).
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The compound is within the scope of Formula Ib wherein Y is N, Z is CH, n is 1, R1a is phenyl, R2 is substituted phenyl, and A1 is N while A2-6 are CH2. Lasalle et al. further discloses that the compound was synthesized in solution (p. 1013; col. 2).
Claim(s) 1, 12, 14, 16, and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Theoclitou et al. (Journal of Combinatorial Chemistry; 2002).
Theoclitou et al. discloses the following compound (p. 316, Table 1).
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The compound is within the scope of Formula Ia wherein Y is N, Z is CH, n is 1, R1a is substituted phenyl, R2 is furyl substituted by nitro, and W1 and W2 are CH. Theoclitou et al. further discloses that the compound was synthesized in solution (p. 316-317, bridging paragraph).
Claim(s) 1, 3, 8, 14, and 36-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramsbeck et al. (Journal of Medicinal Chemistry; 2013).
Ramsbeck et al. discloses the following compound (p. 6616, Scheme 3a).
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The compound is within the scope of the claims wherein Y and Z are N, X is CH2, n is 1, R2 is phenyl, and R13 is hydrogen. Ramsbeck et al. discloses that the compound was tested in solution for activity against glutaminyl cyclase (Table 3; p. 6624, col. 1).
Examiner notes that claim 3 has been rejected as above under 35 U.S.C. 112(d) for failing to incorporate the limitations of claim 1. For purposes of examination, claim 3 has been rejected under 35 U.S.C. 102 as if it is properly dependent upon claim 1.
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.
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) 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karabanovich et al. (Journal of Medicinal Chemistry; 2019) as applied to claims 1, 8, 11, 14, 16, 35-37, and 39-40 above.
Karabanovich et al. teaches as above. While Karabanovich et al. does not teach treating a bacterial infection in a human subject, this limitation is obvious over Karabanovich et al.
Karabanovich et al. additionally teaches that treatment of multidrug-resistant and extensively drug-resistant forms of tuberculosis requires a wide palette of drugs, but only results in a 55% cure rate due to low efficacy (p. 8116, col. 1). Karabanovich et al. additionally discloses that there is a motivation to identify and develop new compounds to treat tuberculosis that have high antimycobacterial activity (p. 8116, col. 1).
It would have been prima facie obvious for one of ordinary skill in the art to administer the compounds of Karabanovich et al. to a human subject for the treatment of tuberculosis. One would have been motivated to do so in order to provide additional treatments for drug-resistant forms of tuberculosis, and would have had a reasonable expectation of success as the compounds tested by Karabanovich et al. exhibited high selectivity toward tuberculosis cells and were effective in vitro against drug-resistant forms.
Claim(s) 38 and 40-41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. (US 2003/0229065 A1; 2003) as applied to claims 1-2, 8, 14, 16, 32, 36-37, and 39 above.
Levy et al. discloses as above. While Levy et al. does not disclose a composition that is administered orally, by inhalation, parenterally, intravenously, or mucosally; or a method of treating a multidrug-resistant, extensively drug-resistant, or drug-sensitive tuberculosis; or treating a bacterial infection in a human, these limitations are obvious over Levy et al.
Levy et al. further discloses a method for reducing antibiotic resistance of a microbial cell, wherein the microbial cell includes Mycobacterium tuberculosis (claims 1 and 65). Levy et al. discloses that inactivation of MarA overcomes multidrug resistance in mycobacteria (par. [0159]). Levy et al. discloses that microbes include those that are pathogenic to humans (par. [0135]). Levy et al. discloses pharmaceutical compositions that may be administered orally, parenterally, by injection, etc. (par. [0526]).
It would have been prima facie obvious to administer the compounds of Levy et al. to treat multidrug-resistant tuberculosis or to treat a bacterial infection in a human. One would have been motivated to do so, with reasonable expectation of success, as the compounds are disclosed to have activity against MarA (see p. 257, 259-260, 265) and microbes that are pathogenic to humans. One would therefore expect administration of the compounds to a human or multidrug-resistant form of tuberculosis would confer efficacy against a bacterial infection.
It would have been prima facie obvious for one of ordinary skill in the art to formulate a composition for oral, parenteral, or intravenous administration. One would have been motivated to do so, with reasonable expectation of success, in order to determine the best mode of administration. Moreover, absent any unexpected effect, these modes of administration are considered obvious variants of each other in view of Levy et al.
Conclusion
No claims are allowed.
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/MADELINE E BRAUN/Examiner, Art Unit 1624
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