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
Instant application 18/001316 filed on 12/09/2022 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 8, 9, 14, 15, 18, 19, 21, 22, 23, 26, 27, 32, 33, 35, 36, 38, 40, 41and 43 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/09/2022 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/23/2025 is acknowledged.
Claims 26, 27, 32, 33, 35, 36, 38, 40, 41 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/23/2026.
Regarding species election, Applicant’s election without traverse of compound Ia’ in the reply filed on 12/23/2026 is acknowledged.
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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.
Claims 8, 9, 14, 18, 21 and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HENRY (WO-2006/079057-A2) and evidenced by Kainz (Kainz K, Bauer MA, Madeo F, Carmona-Gutierrez D. Fungal infections in humans: the silent crisis. Microb Cell. 2020 Jun 1;7(6):143-145).
Claims Interpretation
The instant claims are directed to a method comprising administering to a subject compound of formula (I) wherein the subject has an infection, or is at risk of developing an infection, with a fungus.
Applying the broadest reasonable interpretation, based on instant specification (see paragraph 69):
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examiner determined that any human is at risk of developing a fungal infection.
As evidenced by Kainz “Fungal infections (FIs) represent an example of such overlooked emerging diseases, accounting for approximately 1.7 million deaths annually [2]. To put these numbers in perspective, tuberculosis is reported to cause 1.5 million deaths/year [3] and malaria around 405,000 deaths/year [4]. The medical impact of FIs, however, goes far beyond these devastating death rates: FIs affect more than one billion people each year, of which more than 150 million cases account for severe and life-threatening FIs. Importantly, the number of cases continues to constantly rise [5]. Thus, FIs are increasingly becoming a global health problem that is associated with high morbidity and mortality rates as well as with devastating socioeconomic consequences [6].
A crucial factor that contributes to the rising number of FIs is the drastic increase of the at-risk population that is specifically vulnerable to FIs, including elderly people, critically ill or immunocompromised patients” (see abstract and the first and second paragraphs).
Since any human is at risk of developing a fungal infection, therefore, and in view of the broadest reasonable interpretation of the claims, the instant claims are interpreted as directed to a method of administering compound of formula (I) to any human subject.
HENRY (WO-2006/079057-A2) teaches the instant elected species (see FIG 9):
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for treatment of infections with M. tuberculosis (see paragraph [0002]).
HENRY teaches and claims:
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HENRY teaches compound #12 (the instant elected species, see FIG 9) works as inhibitor of protein splicing (see title).
Regarding claim 18 and administering one or more additional agents, HENRY teaches that “It is therefore important to keep developing an armamentarium of drugs against a wide range of targets to use in combination with established drugs and replace these when they begin to fail”(see page 1, last paragraph).
Regarding claim 21, HENRY teaches and claims the compounds administered orally (see claim 75):
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Regarding claim 23, the treatments disclosed by HENRY is intended for treatment of humans. A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." In the instant case, one of ordinary skill in the art would at once envisage treatment of all humans including an adult, an infant and a juvenile.
Since HENRY teaches administering the instant elected species to humans for treatment of infections (see paragraph [0002]), thus, as discussed above under claim interpretation, the teachings of HENRY meet all limitations of the instant claims because all humans are at risk of developing an infection, with a fungus.
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.
Claims 8, 9, 14, 15, 18, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li, Z., Fu, B., Green, C. M., Liu, B., Zhang, J., Lang, Y., … Li, H. (2019). Cisplatin protects mice from challenge of Cryptococcus neoformans by targeting the Prp8 intein. Emerging Microbes & Infections, 8(1), 895–908) in view of HENRY (WO-2006/079057-A2).
Li teaches that inhibition of tuberculosis and inhibition of fungal growth may be performed by the same therapeutic agent (cisplatin).
Li teaches (see introduction):
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Li teaches cisplatin against tuberculosis (see page 896, first paragraph):
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Li teaches cisplatin is efficacious at inhibiting intein splicing, thereby blocking the proliferation of M. Tuberculosis (see page 896, first paragraph). Further, Li teaches cisplatin is also efficacious at inhibiting the Prp8 intein containing C. neoformans and C gattii, and can protect mammals from challenge of C. neoformans in vivo (see page 896, third paragraph):
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Li does not teach administering intein splicing inhibitor of formula (I) or the elected species.
The deficiency is cured by HENRY.
HENRY teaches the instant elected species (see FIG 9):
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for treatment of infections with M. tuberculosis (see paragraph [0002]).
HENRY teaches and claims a method for inhibiting protein splicing:
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Further, HENRY teaches that compound #12 (the instant elected species, see FIG 9) works as inhibitor of protein splicing (see title).
It should be noted that tuberculosis is a bacterial infection (see paragraph [0005]).
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Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute cisplatin taught by Li by the inhibitors disclosed by HENRY (including compound #12, the instant elected species) and use the treatment for both fungus (for example, cryptococcus neoformans) and tuberculosis with a reasonable expectation of success. Considering protein splicing is effective in treatments of M. Tuberculosis and infections with C. neoformans and C gattii, a person of ordinary skill in the art would readily predict success using the instant compounds for treatments of infections with a fungus because the instant compounds act by the same mechanism as cisplatin. Therefore, one of ordinary skill would have been motivated to use the inhibitors of protein splicing disclosed by HENRY as inhibitors of protein splicing in treatments of all microbial infections.
The skilled artisan would be motivated to treat fungal infections using the elected species because both cisplatin and the elected species are inhibiting intein splicing (the mechanism of action of cisplatin and the elected species is the same).
Further, regarding instant claim 15, it should be noted that Li teaches, for example, Aspergillus (see introduction).
Regarding claims 18 and 21, Li teaches IFI treatment with combination therapy (see introduction):
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Regarding claim 23, the treatments disclosed by HENRY and Li is intended for treatment of all humans. Given the broadest reasonable interpretation of the phrase “human patient” in HENRY and Li, the examiner interprets that the genus of human patient embodies pediatric human patients and adult human patients, which reads on the present limitations.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Li (Li, Z., Fu, B., Green, C. M., Liu, B., Zhang, J., Lang, Y., … Li, H. (2019). Cisplatin protects mice from challenge of Cryptococcus neoformans by targeting the Prp8 intein. Emerging Microbes & Infections, 8(1), 895–908) in view of HENRY (WO-2006/079057-A2) and further in view of MedlinePlus (Fluconazole: MedlinePlus Drug Information (Revised 12/15/218)).
The teachings of Li and the teachings of HENRY have been discussed above and those teachings are incorporated herein by reference.
The combination of teachings of Li and HENRY is silent about additional agent, fluconazole.
MedlinePlus teaches fluconazole is used to treat fungal infections (see first paragraph):
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Applying KSR prong (A) – Combining prior art elements according to known methods to yield predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the compounds disclosed by HENRY (including compound #12, the instant elected species) with additional agent with a reasonable expectation of success. One of ordinary skill would have been motivated by the teachings of Li to use the inhibitors of protein splicing disclosed by HENRY as inhibitors of protein splicing in treatments of all microbial infections.
Further, MPEP 2144.06 states that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”.
Since fluconazole is used to treat fungal infections, one of ordinary skill in the art would have been motivated to combine fluconazole and the compounds disclosed by HENRY and Li for the same purpose to achieve cumulative therapeutic effect.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
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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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/I.S./Examiner, Art Unit 1621
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621