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 06/05/2025, that the instant application 18/861,291 filed 10/28/2024 is a 371 of PCT/US2023/024103 filed 06/01/2023 which claims benefit of U.S. provisional application 63/347,636 filed 06/01/2022. All of the instant claims have been awarded the effective filing date of 06/01/2022.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/05/2025 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: on p. . Should the structure on the right be labeled “T429”?
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Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See p. 55 of the specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1 and 12 are objected to because of the following informalities:
Claim 1: “and stereoisomers, pharmaceutically acceptable salts thereof” should read “or stereoisomers or pharmaceutically acceptable salts thereof”;
Claim 12: “pharmaceutically composition” should read “pharmaceutical composition”.
For purposes of examination, Examiner clarifies that “pharmaceutically composition” in claim 12 will be interpreted as “pharmaceutical composition”.
Appropriate correction is required.
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 1-17 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 recites “X is selected from… alkylene chain”. This causes confusion as an alkylene chain is divalent, while X is monovalent. Corrected is required. Claims 2-17 require and/or do not clarify the limitation at issue and are also rejected.
Claim 2 recites “wherein the compound of formula (I) comprises a compound of formula (I’)”. 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 term “comprises” is indefinite as it is unclear what other alternatives are within the scope of the claim. Examiner suggests correcting the term “comprises” to “is”.
Claim 5 recites the following structure.
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The structure defines a variable “n” as “n=2”, however, there is no variable “n” depicted in the structure of T425. It is therefore unclear to what “n=2” refers. Correction is required.
Claim 5 recites the following structures.
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The structures are both labeled as “T428”, yet they differ in the identity of the substituent in the X position. This causes confusion as it is unclear how the above compounds are the same. Should the structure on the right be labeled “T429”? Correction is required.
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, 3, and 5 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Sunagawa et al. (US 4742052; 1988; IDS filed 05/05/2025).
Sunagawa et al. discloses the following compounds (col. 18-19).
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Sunagawa et al. discloses that the above compounds were synthesized as the following stereoisomers, respectively (col. 19, lines 33-34; col. 21, lines 6-7).
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The compounds are within the scope of formula (I) wherein m is 0 or 1, A is unsubstituted piperidinyl, and X is H. The compounds of Sunagawa et al. have the stereochemistry of, and are identical to, the following compounds of instant claim 5.
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Examiner additionally notes that the scope of the instant claims includes stereoisomers of the claimed compounds.
Claim(s) 1-3 and 16-17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Townsend et al. (WO 2018071358 A1; 2018).
Townsend et al. discloses the following compounds with in vitro activity against Mycobacterium tuberculosis (p. 35-36).
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The compounds are within the scope of formula (I) wherein m is 0, A is unsubstituted azetidinyl or substituted pyrrolidinyl, and X is an unsubstituted heterocyclic ring or H.
Townsend et al. additionally teaches a method of inhibiting an L,D-transpeptidase comprising incubating the above compounds with L,D-transpeptidases to form adducts (contacting the L,D-transpeptidase with a compound of claim 1) (p. 36-37).
Claim(s) 1-3 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CA (STN; 1984).
CA discloses the compounds RN 85001-00-9, 85000-87-9, and 85000-86-8.
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The compounds are within the scope of formula (I) wherein m is 0, A is azetidinyl or pyrrolidinyl, and X is H. The compounds are also identical to T422, T425, and T426 as in claim 5.
Claim(s) 1-3 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miyadera et al. (JP57176988A; 1982). An English translation of the abstract of Miyadera et al. has been relied on by the Examiner and is attached.
Miyadera et al. discloses the following compound (p. 1105).
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Miyadera et al. further discloses that the compounds are antibacterial agents (Abstract, English translation). The compound is within the scope of formula (I) wherein m is 0, A is azetidinyl, and X is H. The compound is also identical to T422 as in claim 5.
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) 4-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Townsend et al. (WO 2018071358 A1; 2018) as applied to claims 1-3 and 16-17 above, and further in view of Batchelder et al. (Communications Biology; 2020; IDS filed 05/05/2025) and Hugonnet et al. (Science; 2009; IDS filed 05/05/2025).
Townsend et al. discloses as above.
Townsend et al. does not disclose a compound of claim 5. Townsend et al. does not disclose a method of treating a mycobacterial infection in a subject. Townsend et al. does not disclose a composition comprising a compound of formula (I) and one or more antibiotics, or a method of use thereof. These limitations are obvious over Townsend et al. and further in view of Batchelder et al. and Hugonnet et al.
Townsend et al. additionally discloses a method of treating a bacterial infection comprising administering a therapeutically effective amount of a disclosed compound to a subject in need thereof (p. 3, lines 17-19). Townsend et al. discloses administration of the disclosed compounds alone or in combination with one or more antibacterial agents in order to increase inhibition or provide adjunct therapy (p. 11, lines 7-15). Townsend et al. teaches that treating includes that of infectious agents such as M. tuberculosis and M. abscessus (p. 9, lines 14-21).
Batchelder et al. discloses the compound T405, which has the below structure (p. 2, Fig. 1).
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Batchelder et al. discloses that the minimum inhibitory concentration (MIC) of compound T405 is similar to that of current carbapenem (meropenem) used to treat drug-resistant tuberculosis, and has a greater in vitro potency against M. abscessus compared to the β-lactams currently recommended for treatment of infection (p. 2, col. 1, par. 1). Batchelder et al. additionally discloses that combination of T405 with avibactam, a β-lactamase inhibitor, resulted in a reduced frequency of drug resistance in the strain ATCC 19977 (p. 3, col. 1, par. 1; Table 2).
Hugonnet et al. discloses meropenem, an antibiotic part of the carbapenem class of β-lactams, in combination with β-lactamase inhibitor clavulanate exhibits increased potency against strains of M. tuberculosis (Abstract) including 13 drug-resistant strains (p. 1217, par. 1, top of page).
It would have been prima facie obvious for one of ordinary skill in the art to administer compound T405 of Townsend et al. for treatment of M. tuberculosis or M. abscessus infection in a subject. One would have been motivated to do so, with reasonable expectation of success, as new treatments for mycobacterial infections are needed to combat drug resistance and T405 has demonstrated equivalent or greater efficacy against M. tuberculosis or M. abscessus compared to compounds currently administered in the art.
It would have been prima facie obvious for one of ordinary skill in the art to combine compound T405 with another antibiotic such as avibactam or clavulanate. One would have been motivated to do so, with reasonable expectation of success, as combinations of (carbo)penems with β-lactamase inhibitors would be expected to reduce drug resistance by inhibiting the enzyme produced by mycobacteria that metabolizes β-lactam antibiotics, yielding additive or greater results.
Finally, the compound T405 of Townsend et al. renders the following compound of claim 5 prima facie obvious.
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The compounds differ only in the ring structure in the X position, wherein the ring of compound T405 is a five-membered ring (two successive -CH2- groups) and the ring of compound T420 is a six-membered ring (three successive -CH2- groups). Adjacent structural isomers are generally so structurally similar that "without more" such structural similarity could give rise to prima facie obviousness. In re Wilder, 563 F.2d 457, 195 USPQ 426. MPEP 2144.08(II)(A)(4)(c). Moreover, prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.). As such, one of ordinary skill in the art would have been motivated to make the claimed compound in order to produce additional antibacterial agents, and would have had reasonable expectation of success in view of the substantial similarities in the structure and function of compound T405 compared to that of the instant invention.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Miyadera et al. (JP57176988A; 1982) as applied to claims 1-3 and 5 above, and further in view of Sunagawa et al. (US 4742052; 1988; IDS filed 05/05/2025).
Miyadera et al. discloses as above.
Miyadera et al. does not disclose the compound T428 of claim 5. However, this limitation is obvious in view of Sunagawa et al.
Sunagawa et al. discloses the following compounds (col. 18-19).
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Sunagawa et al. discloses that the above compounds were synthesized as the following stereoisomers, respectively (col. 19, lines 33-34; col. 21, lines 6-7).
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Sunagawa et al. teaches synthesizing the former compound wherein the starting material differs from that of the latter compound by having a methylthio group rather than a thio group (col. 18-19). Sunagawa et al. teaches that the compounds are antimicrobial β-lactams.
The compound of Miyadera et al. differs from instantly claimed compound T428 by a single methylene group between the thio and the azetidinyl group. The courts have previously affirmed that the difference between two compounds being a methylene group between a ring and a heteroatom is prima facie obvious. See In re Farkas, 368 F.2d 1016 (C.C.P.A. 1966). Moreover, Sunagawa et al. teaches how to make two β-lactams which only differ by the presence of a methylene between the thio group and the piperidine ring. Absent unexpected results, one of ordinary skill in the art would be apprised that (i) given the similarity in structure and function of the compound of Miyadera et al. and T428, the compounds would be expected to have similar properties; and (ii) one of ordinary skill in the art would be apprised as to how to make T428 in view of Sunagawa et al. in order to arrive at additional antimicrobial compounds.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,084,833 B2 in view of Batchelder et al. (Communications Biology; 2020; IDS filed 05/05/2025) and Hugonnet et al. (Science; 2009; IDS filed 05/05/2025).
The claims of the ‘833 patent are directed toward a compound of formula (Ic) as below.
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Claim 2 further narrows the scope of formula (Ic) to compound T405.
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The compounds are within the scope of instant formula (I) wherein m is 0, A is unsubstituted azetidinyl, and X is an unsubstituted heterocyclic ring.
Claims 3-8 and 11-14 are directed toward methods of treating a bacterial infection, including a bacterial infection caused by M. tuberculosis or M. abscessus, and a method of inhibiting L,D-transpeptidase activity in a subject.
Claims 9-10 and 15 are directed toward pharmaceutical compositions comprising the compound of formula (Ic), or T405, and one or more other antimicrobial compound.
The claims of the ‘833 patent are narrower in scope than or substantially overlap with at least instant claims 1-3, 6-8, 12, and 16-17.
While the claims of the ‘833 patent do not teach a compound of instant claims 4-5, compound T405 and instantly claimed compound T420 differ only in the ring structure in the X position, wherein the ring of compound T405 is a five-membered ring (two successive -CH2- groups) and the ring of compound T420 is a six-membered ring (three successive -CH2- groups). Adjacent structural isomers are generally so structurally similar that "without more" such structural similarity could give rise to prima facie obviousness. In re Wilder, 563 F.2d 457, 195 USPQ 426. MPEP 2144.08(II)(A)(4)(c). Moreover, prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.). As such, one of ordinary skill in the art would have been motivated to make the claimed compound in order to produce additional antibacterial agents, and would have had reasonable expectation of success in view of the substantial similarities in the structure and function of compound T405 compared to that of the instant invention.
Moreover, while the ‘833 patent claims are not directed toward combining the claimed compounds with β-lactams, these limitations are obvious over Batchelder et al. and Hugonnet et al.
Batchelder et al. discloses the compound T405, which has the below structure (p. 2, Fig. 1).
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Batchelder et al. discloses that the minimum inhibitory concentration (MIC) of compound T405 is similar to that of current carbapenem (meropenem) used to treat drug-resistant tuberculosis, and has a greater in vitro potency against M. abscessus compared to the β-lactams currently recommended for treatment of infection (p. 2, col. 1, par. 1). Batchelder et al. additionally discloses that combination of T405 with avibactam, a β-lactamase inhibitor, resulted in a reduced frequency of drug resistance in the strain ATCC 19977 (p. 3, col. 1, par. 1; Table 2).
Hugonnet et al. discloses meropenem, an antibiotic part of the carbapenem class of β-lactams, in combination with β-lactamase inhibitor clavulanate exhibits increased potency against strains of M. tuberculosis (Abstract) including 13 drug-resistant strains (p. 1217, par. 1, top of page).
It would have been prima facie obvious for one of ordinary skill in the art to administer compound T405 of Townsend et al. for treatment of M. tuberculosis or M. abscessus infection in a subject. One would have been motivated to do so, with reasonable expectation of success, as new treatments for mycobacterial infections are needed to combat drug resistance and T405 has demonstrated equivalent or greater efficacy against M. tuberculosis or M. abscessus compared to compounds currently administered in the art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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/MADELINE E BRAUN/Examiner, Art Unit 1624 08/20/2026
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