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
The instant application, filed 04/26/2022, is a 371 filing of PCT/US2020/054733, filed 10/18/2020 which claims domestic priority to U.S. provisional application no. 62/929,723, filed 11/01/2019.
Amendments and Claim Status
The following amendment filed on 10/02/2025 is acknowledged and entered.
Claims 1, 11, 20, and 21 are amended;
Claims 4, 6, 13, 15, 16, 18, 19, 25, 28, and 29 are cancelled;
Claim 30 is added;
Claims 7, 8, 23, 24, and 26, and 27 remain withdrawn according to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species;
Claims 1-3, 5, 7-12, 14, 17, 20-24, 26, 27, and 30 are pending.
Claims 1-3, 5, 9-12, 14, 17, 20-22, and 30 are under examination.
Information Disclosure Statement
An Information Disclosure Statement has not been received.
Response to arguments
Applicant’s arguments filed 10/02/2025 with respect to the drawing objections and claim rejections under 35 U.S.C. §§ 102 (a) (1), and 103 have been fully considered.
With respect to the claim amendments filed 10/02/2025,
In the reply to the Restriction/Election, filed 06/02/2025, Applicant elected a singular species, compound 52, for examination. In the office action dated 06/02/2025, claims 7, 8, 23, 24, and 26, and 27 were withdrawn according to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species, i.e. Group II a method of treating a bacterial infection and non-elected compounds. In the most recent claim amendment, filed 10/02/2025, Applicant amended claim 1 such that it no longer encompasses the elected species. Specifically, the amendment striking hydrogen from position R3 in a compound of Formula (I), effectively means that the elected species is no longer encompassed by the generic claim (see Figure 1, below). In short, a compound of Formula (I) is no longer under consideration in the instant application as a result of the latest amendments. In addition to the previously withdrawn claims, claims 1-3, 5, 7, 9-12, 14, 17, and 22 as well as new claim 30 are hereby withdrawn from consideration, as being drawn to a non-elected species. At present, only claims 20 and 21 read on the elected species.
Figure 1. Elected species and instantly claimed Formula (I)
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Figure 1. a) Applicant’s elected species :b) instantly claimed Formula (I)
With respect to the objection to the drawings, the inclusion of additional details identifying the relevant data within the figures is sufficient to overcome the rejection.
With respect to the rejection of claims 1-6, 9-12, 14, 17 and 22 rejected under 35 U.S.C. § 102 (a)(1) as being anticipated by Muto and Itai (US 20090239868 A, published September 24, 2009), Applicant has amended the claim to strike Hydrogen from the position of R3, removing the disclosure by Muto from consideration as a prior art for the rejection of claims 1-3, 5, 9-12, 14, 17, and 22. Furthermore, the cancellation of claims 4 and 6 is sufficient to render the rejection over said claims moot. As such, rejection is hereby withdrawn.
With respect to the rejection of claims 1-6, 9-12, 14, 17, and 20-22 are rejected under 35 U.S.C. § 103 as being unpatentable over Wood et al. (US 20090239919 A1, published September 24, 2001), hereinafter Wood, Applicant has amended the claim to strike Hydrogen from the position of R3, removing the disclosure by Wood from consideration as a prior art for the rejection of claims 1-3, 5, 9-12, 14, 17, and 22. Furthermore, the cancellation of claims 4 and 6 is sufficient to render the rejection over said claims moot. In consideration of Applicant’s arguments regarding the remaining claims of 20 and 21, the arguments made by applicant are unconvincing and are insufficient to overcome the rejection. The arguments made by Applicant are herein addressed as follows.
Applicant argues that Wood does not specifically provide examples for every substitution at R3 and R4, and therefore a person of ordinary skill in the art would lack motivation to substitute at these positions.
Applicant’s argument is not persuasive, because a rejection under 35 U.S.C. § 103 is based on rationale which supports the conclusion of obviousness. According to MPEP § 2143, the combination of prior art elements according to known methods to yield predictable results supports the conclusion of obviousness. Wood explicitly teaches that the substituent corresponding to the instantly claimed L4 position of Formula (I) (R4 of the prior art) may be iodine, as disclosed in paragraph [0020]. Thus, Wood affirmatively contemplates iodine substitution at the precise position at issue. The fact that Wood does not exemplify every possible halogen substitution does not negate the express teaching that iodine is an acceptable substituent at this position. A person of ordinary skill in the art is not required to be provided with working examples of every disclosed alternative in order to be motivated to pursue such substitutions, particularly where, as here, the substitution is expressly taught and involves a predictable chemical modification of halogen substitution.
Applicant contends that iodine-substituted organic compounds are uncommon in therapeutic drugs due to concerns regarding metabolic instability and deiodination, and therefore a person of ordinary skill would have avoided iodine substitution.
The argument is found unpersuasive for several reasons. Firstly, Wood discloses a compound virtually identical to the elected species except for the substitution of chlorine versus iodine at the instantly claimed position of L4 in a compound of Formula (I). Secondly, Wood explicitly teaches iodine substitution at the relevant position, which directly contradicts Applicant’s assertion that iodine would have been disfavored unwanted. Where the prior art expressly discloses this substitution, alleging general industry concerns does not negate the motivation to make the substitution as taught within the prior art. As such, the substitution of chlorine for iodine constitutes a single, predictable modification within a disclosed list of alternatives, resulting in a compound that is structurally and functionally similar to the prior art compound. Such a substitution represents a classic case of obvious structural modification with a reasonable expectation of success (see MPEP § 2144.08 II. A. 4. (c)). Furthermore, chlorine and iodine are both halogens, possessing the same number of valence electron count. As recognized by the courts, when compounds are very close in structure, similar properties are normally presumed (see MPEP § 2144.08 (d)). Thus, substitution of chlorine with iodine represents a routine halogen substitution that a person of ordinary skill in the art would have reasonably expected to preserve the core structure and biological activity while potentially modulating electronic properties. Finally, Applicant has not provided evidence that iodine substitution at this position would have been technically infeasible, unpredictable, or contrary to the express teachings of Wood. Generalized concerns regarding metabolic liability do not overcome an express disclosure in the prior art.
Applicant argues that compounds substituted at R3 and R4, including iodine-substituted compound 52 (the elected species), demonstrate “surprisingly” improved adjuvant activity relative to compound 23 (the prior art compound).
For ease of analysis, the extracted data from Table 3 of the instant specification, included in Applicant’s arguments filed 10/02/2025 is reproduced below as Table 1.
Table 1. Comparison of activity of prior art compound with instantly claimed compounds
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Applicant’s argument is found unpersuasive because, the data relied upon by Applicant show, at most, a modest and strain-dependent differences in MIC reduction, of approximately two-fold differences. Such differences fall within the range of expected biological variability, and do not constitute evidence of unexpected results absent statistical analysis or demonstration of quantitatively different property. As is well-recognized in the art, MIC values are logarithmic and discrete measurements, and two-fold shifts are commonly observed due to routine experimental variability, strain-to-strain differences, and minor structural modifications within the chemical series. Such modest changes do not, by themselves, rise to the level of unexpected results absent additional corroborating evidence. In the instant case, Applicant has not provided replicate measurements, statistical analyses (such as standard deviations, confidence intervals, or p-values) or evidence demonstrating that the observed differences exceed normal experimental fluctuation. Moreover, the asserted improvements are shown only for a limited number of individual compounds, and against selected strains, and are therefore not commensurate in scope with the assertion made by Applicant. Evidence limited to a few species cannot rebut a prima fascia case of obviousness encompassing a broader genus (see MPEP § 716.02 (d)).
Closer analysis of the data further demonstrates that any alleged improvement is not uniform across all tested strains. Specifically, for certain AB and KP isolates, instantly claimed compounds 29 or 52 show modestly lower MIC values than the prior art compound 23. For instance, with respect to strains AB 3941 and 3941, the magnitude of difference in activity between the prior art compound 23 and instantly claimed compounds 29 and 52 are limited to approximately two-fold differences, falling squarely within the range of expected biological and experimental variability. In other strains, the activity of the prior art compound 23 is comparable to, or better-performing than that of the instantly claimed compounds 29 and 52 (AB 4119, All KP strains). Specifically, in the case of KP F2210291, the prior art compound 23 performs better than the instantly claimed compounds 29 and 52. This strain-dependent performance indicates that the alleged improvement is, in fact, context-specific rather than intrinsic to the iodine substitution or R3/R4 modification. Such variability undermines Applicant’s assertion that the data reflects a “surprising” or generalizable property of the claimed compounds and of Iodine at position L4. Federal Circuit precedent makes clear that unexpected results must be consistent and reproducible, not sporadic or selectively observed (see MPEP § 716.02 (d)). Contrary to Applicant’s assertion, no strain or compound tested demonstrates a dramatic or “surprising” improvement (such as a ten-fold, i.e. an order of magnitude, or hundred fold, i.e. two orders of magnitude improvement in activity) that would suggest an unexpected biological effect.
Most importantly, the data presented do not rebut the express teachings of Wood of iodine substitution at the position corresponding to L4 in a compound of Formula (I). Where in the prior art contemplates the precise substitution at issue, modest activity differences do not convert an otherwise predictable modification into a nonobvious invention. A person of ordinary skill in the art, having been taught by Wood that Iodine is an acceptable substituent, would reasonably expect compounds bearing such a substitution to retain comparable biological activity, with routine variations in potency, such as the demonstrated two-fold improvement in certain strains.
While Applicant has presented comparative MIC data for the prior art compound, the evidence reflects strain-dependent variation, rather than a surprising or unexpected property sufficient to rebut the obviousness of substituting iodine for chlorine, as expressly taught by Wood.
Thus, all arguments presented by Applicants have been addressed and are found unpersuasive for the reasons presented herein and in the previous non-final rejection. Applicants are reminded that “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
For the reasons set forth above, the rejection of claims 20 and 21 under 35 U.S.C. § 103 are hereby maintained.
With respect to the rejection of claims 1-6, 9-12, 14, 17, and 20 and 21 under 35 U.S.C. § 103 as being unpatentable over Aurora Fine Chemicals, CAS Registry Number: RN 1958429-83-8 [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 1958429-83-8. Entered STN: 24 Jul 2016 ], in view of Meanwell (J. Med. Chem. 2011, 54, 2529–2591, published March 17 2011), Applicant has amended the claim to strike Hydrogen from the position of R3, from consideration as a prior art for the rejection of claims 1-3, 5, 9-12, 14, and 17. Furthermore, the cancellation of claims 4 and 6 is sufficient to render the rejection over said claims moot. In consideration of Applicant’s arguments regarding the remaining claims of 20 and 21, the argument is convincing and the rejection is hereby withdrawn.
With respect to new claim 30, the compound claimed does not read on the elected species, and is therefore withdrawn from consideration, as previously indicated.
Status of Claims
Claims 1-3, 5, 7-12, 14, 17, 20-24, 26, 27, and 30 are pending in the instant application. Claims 1-3, 5, 7-12, 14, 17, 22-24, 26, 27, and 30 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species according to the amendments filed by Applicant on 10/02/2025. Therefore, claims 20 and 21 read on an elected invention and species and are therefore under consideration in the instant application.
Drawings
The drawings filed on 10/02/2025 are found to be in compliance with 37 CFR §§ 1.121 and 1.84, and are hereby accepted.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claims 20 and 21 are rejected under 35 U.S.C. § 103 as being unpatentable over Wood et al. (US 20090239919 A1, published September 24, 2001), hereinafter Wood.
The instant claims are drawn to a compound of Formula (I), specifically Applicant’s elected species, found in Figures 1a and Figure 2 below, as well as a composition thereof.
Wood teaches compounds of Formula (I) [0020]. More specifically, Wood teaches CAS Registry Number: RN 1187819-43-7. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 1187819-43-7, Entered STN: 11 Oct 2009] (according to Figure 4a, below) (claim 1, page 23 and claim 8, page 29).
Although the chemical compound taught by Wood closely resembles the elected species, it fails to teach the compound exactly. Namely, the substitution at position L4 differs between the prior art compound and elected species. Registry number 1187819-43-7 renders obvious the elected species.
Figure 2. Structural comparison the elected species and the prior art compound
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Figure 2. a) Elected species, compound 52; b) CAS Registry Number: RN 1187819-43-7
Regarding wherein R4 of the prior art compound is Chlorine and R4 of the elected species is Iodine, Wood specifically teaches that can be Iodine (page 3, paragraph [0020]). Accordingly, an ordinary skilled artisan would have been specifically motivated to substitute Cl for I with a reasonable expectation of similar results to arrive at the elected species.
Moreover, Chlorine and Iodine are both halogens, having the same number of valence electrons and general electron configurations. Therefore, a person of ordinary skill in the art, prior to the effective filing date of the instant claims, would have been logically motivated to make halogen substitutions. The resulting compounds would have been expected to have similar structural and chemical properties. The courts have stated:
similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close' structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP § 2144.08(d)).
Thus, substitution of Chlorine in the prior art compound for Iodine as in the elected species is considered an obvious substitution. The Iodine substitution at this position would result in a compound of altered electron distribution, while preserving the same core structure, effectively altering the chemical affinity of the prior art compound, with a reasonable expectation of success.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR § 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR § 1.17(a)) pursuant to 37 CFR § 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623