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 .
Claim Status
Claims 1-3, 5-9 and 11-21 are pending.
Claims 2, 14 and 17 are withdrawn (see restriction/election below).
Priority
This application is filed 04/16/2024, and claims the benefit of domestic priority as below:
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Information Disclosure Statements
Three IDS(s) received on 07/17/2024, 01/19/2026 and 05/20/2026 have been considered unless marked with a strikethrough. The references which lack an English translation (e.g., English abstract only) have been marked with a strikethrough because their contents could not be adequately reviewed.
Election/Restrictions
Applicant elects the compound 24-a as a species of Formula I, Klebsiella pneumoniae A TCC BAA-1705 infection as a bacterial infection disease, and carbapenem antibiotic as a species of a combinate active beta-lactam antibiotic, with traverse in the reply field on 07/02/2026 is acknowledged.
The applicants argue that the election of species requirement is improper because the compounds of Formula I commonly possess β-lactamase inhibitory activity and, when used in combination with β-lactam antibiotics, can significantly restore or enhance the antibacterial activity.
The argument is considered, however, is not persuasive. Examiner acknowledges that the tested Formula I compounds share a boronated containing framework and the several selected compounds exhibit β-lactamase inhibitory or antibiotic restoring activity. However, common activity alone does not establish that all alternatives are technically interrelated through the same or corresponding special technical feature under PCT Rule 13.2.
Moreover, the common boronated core cannot, by itself, provide the required special technical feature because that core and its β-lactamase inhibitory use are already known in the prior arts. In particular, Koike et al. (US 2023/0038124 A1) discloses the corresponding condensed butonate core in compounds having β-lactamase inhibitory activity and utility in combination with β-lactam antibiotics. Therefore, the common boronated framework does not constitute a contribution over the prior art for purposes of the utility analysis.
Instead, Applicants identify the X-L1 arrangement as the alleged special technical feature. However, Formula I encompasses materially different alternatives of X, L1, L2, L3 and R1. For example, X may be sulfur, sulfoxide, or sulfone; L2 and L3 may include a single bond or structurally district cyclic and acyclic groups; and R1 includes chemically different amino, cycloalkyl, heterocycloalkyl, and heteroaryl groups.
The instant specification reports activity for only selected species within this broader genus. Although the tested compounds generally exhibit the asserted activity, their potency and activity spectrum vary depending on the compound, β-lactamase enzyme, bacterial strain, and co-administered antibiotic. The specification does not provide representative or controlled comparisons showing that the alleged X-L1 arrangement is responsible for the asserted activity throughout the full scope of Formula I, rather than particular combinations of X, L1, L2, L3 and R1.
Accordingly, the evidence may support a common general activity for certain tested species, but the previous known boronated core does not supply a special technical feature, and Applicants have not established that the alleged X-L1 arrangement constitutes the same or corresponding special technical feature throughout the full Formula I genus. Therefore, the election of species requirement is deemed proper under PCT Rule 13.1/13.2and is made FINAL.
Applicant asserts that claims 1-3, 5-9, 11-21 read on the elected species and will be examined on their merits.
If the elected specie is not identified in the prior arts, the elected specie would be allowable if an independent claim were drafted with that specie alone, and Examiner expanded the search to additional species of the genus per MPEP 802.03.
The elected specie was not identified in the art. Examiner expanded his search to a new specie pursuant to MPEP 803.02. The alternative species is identified that would have been obvious to a person of ordinary skill in the art. Thus, the expanded specie reads on claims 1, 3, 5-9, 11-13, 15, 16 and 18-21. Claims 2, 14 and 17 are withdrawn as not reading on the expanded specie. It should be noted that the full scope of claims 2, 14 and 17 have not yet been searched. Accordingly, claims 1, 3, 5-9, 11-13, 15, 16 and 18-21 will be examined on their merits.
With respect to the expanded species, the art is rejected under 35 USC 103 below.
Claim Objections
Claim(s) 1, 3, 5, 6, 8, 12, 13, 16, 18, 19 and 21 is/are objected to because of the following informalities:
Claims 1, 5, 6, 8, and 12 are objected to because “is optionally” should be “optionally”.
Claims 3, and 16 is objected to because the period at the end of the claim is missing.
Claim 12 is objected to because “2,6-diazaspiro[3.4]octyl” is duplicated.
Claim 13 is objected to because “the” should be removed.
Claim 18 is objected to because “a bacterial infection disease” should be “a bacterial infection” or ”a bacterial infectious disease”.
Claim 19 is objected to because “and the pharmaceutically” should be “or the pharmaceutically”.
Claim 21 is objected to because the “or” should be used only once, at the end.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
The rejections under this section are made when the scope of the claimed subject matter is not clear. (See MPEP 2173)
Claims 7 and 19 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 7 recites the limitation "
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" in the middle of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 7 indirectly depends from claim 1 and L1’s definition of claim 1 does not define L1 is R substituted C1-6 alkyl wherein R is the NH2 substituted C1-6 alkyl. Claim 7 does not add a further limitation to the subject matter of claim 1. (see MPEP 608.01(n))
Regarding claim 19, the phrase "other β-lactam antibiotic" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. Claim 19 depends directly or indirectly from claims 1 and 18, and neither claim 1 nor claim 18 previously identifies a β-lactam antibiotic relative to which the recited antibiotics is “other”. Therefore, the reference of “other” and consequently the scope of the limitation, is unclear.
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) 1, 3, 5-9, 11-13, 15, 16 and 18-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Koike et al. (US 2023/0038124 A1, pub'd 02/09/2023, Foreign Priority date 10/25/2019, IDS cited), in view of Hecker et al. (WO 2018/005662 A1, pub'd 01/04/2018, IDS cited).
With respect to independent claim 1, the claim recites that a compound of formula (I), an optical isomer thereof.
Koike teaches 1) substituted condensed ring boronic acid compounds useful as β-lactamase inhibitors (abstract and claim 1); 2) an example of specific spices (Formula 474) that having a boron cyclopropyl substituted hydroxybenzoic acid core and an oxygen linked azetidiny substituent at the corresponding position of the aromatic ring, ring A is azetidine as the corresponding to L2, L3-L4-R5 is -C(O)-C(NH2)-imidazole as the corresponding to -L3-R1 of Formula I (paragraph [1084]); 3) Y is an oxygen atom or a sulfur atom (paragraph 0055) as the corresponding to X of the instant Formula I; 4) a method for treating a bacterial infection, characterized in that a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof (claim 140); and 5) a pharmaceutical composition comprising a β-lactam agent, wherein the pharmaceutical composition is administered with the compound or the pharmaceutically acceptable salt thereof (claim 139). Thus, Koike teaches the principal tricyclic boronic acid pharmacophore, the claimed arrangement, and a method for treating a bacterial infection.
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Instant Formula I Instant compound in claim 16
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Koike’s Formula 6a Koike’s Formula 474
Koike fails to teach L1 of instant Formula I as optionally substituted C1-6 alkyl, and C1-6 heteroalkyl.
Hecker teaches 1) structurally related boronic acid β-lactamase inhibitors (abstract and claim 1 and 12); 2) the Formula Id-I comprising each R1/R4 is hydrogen, R7 is OH, R6 is -COOH, each J/L/M is CR12 wherein R12 is hydrogen, halogen, C1-6 alkoxy, or C1-6 haloalkoxy (paragraph [0024]-[0032]); 3) a variations of R6 may be -COOR wherein R is C1-9 alkyl, -CR10R11OC(O)C1-9alkyl, -CR10R11OC(O)C3-7 carbocyclyl, -CR10R11OC(O)(3 to 7 membered heterocyclyl), or -CR10R11OC(O)C2-8 alkoxyalkyl as the inhibitors in which substituent group are connected through known bond, alkyl, oxygen containing , nitro containing, and carbonyl containing linkages (paragraph [0027]); 4) the compounds show a broad spectrum of inhibitory activity against multiple β-lactamase, including class A, B, C and D enzymes (paragraph [0189]-[0191]); and 5) potentiation of aztreonam and tigemonam against strains expressing class A and class C β-lactamase, potentiation of biapenem against strains expressing KPC and OXA-48 carbapenems, and potentiation of meropenem against Acinetobacter baumannii strains expressing OXA-23 and OXA-72 carbapenems (paragraph [0189], EXAMPLE 26, EXAMPLE 28, and EXAMPLE 29). Thus, Hecker teaches alkyl containing linkages attached to M positions with other variations of linkers at R6 position. Thus, Hecker teaches alkylene groups (i.e., -CH2CH2-) as L1 in instant Formula I, although the halogen in R1 is not the focus here, the discussion is limited to Hecker's linker.
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Hecker’s Formula Id-I Hecker’s compound in claim 36 Instant compound in claim 16
Some of the linkers (e.g., alkyl groups) find in the compounds taught by Hecker could indeed be directly incorporated into the Koike compounds, and other linker groups are attached at positions distinct from the specific bonding sites specified in instant claim 1. However, Hecker’s linker was cited not only to directly incorporate the specific compound described in that literature into the Koike compound, but rather to demonstrate that linkers, including short connecting segments, alkylene groups, and heteroatom-containing linkers, serve as structural variables that enhance the potential of boronic acid-based β-lactamase inhibitors.
The substituent region modified in the Koike compounds and the linker containing region taught by the Hecker are both peripheral to the boronic acid pharmacophore and serve to present a polar substituent to the enzyme environment. Accordingly, one of ordinary skill in the art would have understood that the optimization of substituents attached to a boron containing inhibitor scaffold. It would have been obvious to a PHOSITA at the time of the invention to apply the known linker optimization technique of the Hecker to the corresponding substituent region of the Koike compounds by interposing of the Koike compounds by interposing a short linker encompassed by L1. A person of ordinary skill would have been motivated to make the modification because the Hecker teaches that compounds employing such structural variations provide broad spectrum inhibition across multiple β-lactam antibiotics against resistant bacterial strains. Therefore, the modification would not merely have provided an alternative compound, but would have offered the recognized advantages of improving inhibitor spectrum and potentiating β-lactam activity against resistant bacterial strains.
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Consistently, applying KSR example rationale (C) in the independent claim 1, it would have been prima facie obvious to apply that known technique to the corresponding substituent region of the Koike compounds, with a reasonable expectation of retaining β-lactamase inhibitory activity while predictably modifying substituent presentation. Although its linker at a different position.
With respect to claim 3, the claim recites each R’s variations for the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1.
Koike teaches the Formula 474, as shown the structure above, has a NH2 as a R (paragraph [1084]).
With respect to claims 5-7, the claims recite the variations of L1 for the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1.
Koike fails to teach the variations of L1.
Hecker teaches structurally related boronic acid β-lactamase inhibitors (abstract and claim 1 and 12) and the Formula Id-I comprising each R1/R4 is hydrogen, R7 is OH, R6 is -COOH, each J/L/M is CR12 wherein R12 is hydrogen, halogen, C1-6 alkoxy, or C1-6 haloalkoxy (paragraph [0024]-[0032]). Hecker further teaches alkene linker in the compound as shown above (claim 36).
Therefore, claims 5-7 would have been obvious for the reason stated above with respect claim 1.
With respect to claims 8, 9 and 11, the claims recite variations of L2 and L3 for the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1.
Koike teaches the Formula 474, as shown the structure above, has an azetidinyl group as required in claims 8 and 9, and -C(O)-C(NH2)- as required in claim 11. (paragraph [1084])
With respect to claims 12 and 13, the claims recite variations of R1 for the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1.
Koike teaches the Formula 474, as shown the structure above, has an imidazolyl group as required in claims 12 and 13 (paragraph [1084]).
With respect to claim 15, the claim recites variations of the structural moiety -L1-L2-L3-R1 for the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1.
Koike teaches the Formula 474, as shown the structure above, has
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moiety as -L2-L3-R1 portion.
Koike fails to teach the structural moiety -L1-L2-L3-R1.
Hecker teaches structurally related boronic acid β-lactamase inhibitors (abstract and claim 1 and 12) and the Formula Id-I comprising each R1/R4 is hydrogen, R7 is OH, R6 is -COOH, each J/L/M is CR12 wherein R12 is hydrogen, halogen, C1-6 alkoxy, or C1-6 haloalkoxy (paragraph [0024]-[0032]). Hecker further teaches alkene linker in the compound as shown above (claim 36).
Therefore, claim 15 would have been obvious for the reason stated above with respect claim 1.
With respect to claim 16, the claim recites specific compounds for a compound of the following formula, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.
In view of Koike and Hecker, the compound,
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, would have been obvious as discussed above with respect claim 1. Therefore, claim 16 would have been obvious for the reason stated above with respect claim 1.
With respect to claim 18, the claim recites that a method for treating a bacterial infection disease in a subject in need thereof, comprising administering the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof.
Koike teaches the compounds possess β-lactamase inhibitory activity and are useful as treating or therapeutic agents for bacterial infection (paragraph [1658]-[1659]). Koike further teaches administration of a therapeutically effect amount to a patient in need of treatment. (paragraph [1654])
With respect to claims 19-21, the claims recite that the method further comprises a combination of the compound, the optical isomer thereof, and the pharmaceutically acceptable salt thereof with other β-lactam antibiotic, and β-lactam antibiotic is penicillin, cephalosporin, carbapenem, monocyclic β-lactam antibiotic, or a combination thereof.
Koike teaches administration of the compound (i.e., β-lactamase inhibitors) and therapeutic agent can be administered concurrently or sequentially to a subject being administered therewith (paragraph [1658]), as required in claim 19. Koike further teaches a method for treating a bacterial infection, characterized in that a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof claim 140), and other β-lactam antibiotic including ampicillin as a type of penicillin. (claims 126 and 132), as required in claim 20 and 21.
Conclusion
Claims 1, 3, 5-9, 11-13, 15, 16 and 18-21 are rejected.
Claims 1, 3, 5, 6, 8, 12, 13, 16, 18, 19 and 21 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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