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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group II, a composition of Formula I, and compound species, KH-1, (page 10 of instant specification) in the reply on 05/06/2026, is acknowledged.
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Applicant did not identify the claims encompassing the elected invention and species as required in the Restriction Requirement mailed on 03/10/2026. It’s noted the elected species does not read on Group II invention, composition comprising a compound according to Formula I
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The examiner called the attorney on the record, Raymond N. Russell to clarify the election response. The attorney filed supplemental response /amendment on 06/08/2026, wherein claim 22 is amended to recite R2 is C1-C6 alkyl group or a phenyl group.
Amended claims 22-23 and 25 read on the elected invention and species.
Claims 1-21, and 26-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claim 24 reciting phenyl group substituted with halogen does not read on the elected species, and withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
The elected species, 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-dione (KH-1) ( CAS# 714261-25-3) , was entered in STN on July 22, 2004 as in ChemBridge library.
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To expedite compact prosecution, the examiner also expanded the search for non-elected species wherein R1 is phenyl, and R2 is C1-C6 alkyl group which are rejected under 35 USC 103 section. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Status of claims
Claims 1-30 are pending.
Claims 1-21, 24 and 26-30 are withdrawn.
Claims 22-23 and 25 and under examination in this Office Action.
Priority
The instant application 18/290,772 filed on 01/20/2024 is a 371 of PCT/US2022/038183 filed July 25, 2022 , which claims priority to U.S. provisional application No. 63/225,082, filed on July 23, 2021.
Information Disclosure Statement
The information disclosure statement submitted 04/25/2024 is in compliance with the provisions of 37 CFR1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Claim Interpretation
Instant claims are directed to composition of compound of Formula I wherein the property of compound does not necessarily contribute to the structural limitation of compound. Instant specification discloses instant elected species, 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-dione (KH-1) is identified as antibacterial agent by screening assay of commercial compound library (See [0006], Fig 1. Example 1, [0082] [0084] ) “Using the LDH assay to measure cellular metabolic activity and cell viability, a subset of the ChemBridge eukaryotic kinase inhibitor/ATP mimetic library was screened for compounds that reduce Salmonella-associated cell death without direct antimicrobial activity against Salmonella in vitro” (See [0082]). “A 3,000-member ATP mimetic library in 96-well plate format was sourced from ChemBridge. The reference compounds 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2-dihydrochromeno[2,3-c] pyrrole-3,9-dione (KH-1), and 2-(4-fluorobenzyl)-1-(3-phenoxyphenyl)-1,2-dihydrochromeno[2,3-c] pyrrole-3,9-dione (KH-1-2) were purchased ChemBridge” (See [0084]).
Please note KH-1 is known compound and the biological activity is the property of active compound. MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Claim Rejections - 35 USC § 112
Claims 22, 23 and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of full scope of composition comprising compound of Formula I. This is a written description rejection, rather than an enablement rejection under 35 U.S.C. 112, first paragraph.
MPEP 2163.02 states “ Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention, and that the invention, in that context, is whatever is now claimed”.
MPEP 2163 II states; “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above)”. While applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. “A representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus” MPEP 2163 II.
Instant specification discloses preparation of known compound KH-1-2. Instant specification does not disclose preparation of any novel compound of Formula I . Instant species does not disclose working example of compound of Formula I comprising R1 is heteroaryl group. Instant specification discloses compound species of instant compound of Formula I are purchased from commercial compound library. For example, 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-dione (KH-1) is identified as antibacterial agent by screening assay of commercial compound library (See [0006], Fig 1. Example 1, [0082] [0084] ). “The work described here details the development of a simple, cell-based high-throughput assay to screen potential host-targeted compounds to control Typhoid fever. Salmonella infection induces macrophage death indicated by the release of lactate dehydrogenase (LDH) in the medium. Using the LDH assay to measure cellular metabolic activity and cell viability, a subset of the ChemBridge eukaryotic kinase inhibitor/ATP mimetic library was screened for compounds that reduce Salmonella-associated cell death without direct antimicrobial activity against Salmonella in vitro” (See [0082]). “A 3,000-member ATP mimetic library in 96-well plate format was sourced from ChemBridge. The reference compounds 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2-dihydrochromeno[2,3-c] pyrrole-3,9-dione (KH-1), and 2-(4-fluorobenzyl)-1-(3-phenoxyphenyl)-1,2-dihydrochromeno[2,3-c] pyrrole-3,9-dione (KH-1-2) were purchased ChemBridge” (See [0084]).
In the absence of sufficient working example of novel compound of Formula I prepared by the Applicant , the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.
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.
Claims 22-23 and 25 are rejected under 35 U.S.C. 112(b) 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 22 recites “ R¹ is a C₆-C₁₂ alkyl, phenyl, or heteroaryl group, and R² is C₁-C₆ alkyl group or a phenyl group, wherein one or more of the hydrogens of the phenyl group are optionally substituted with a methyl, halogen, -OMe, or -OPh moiety”. Both R1 and R2 recite phenyl group. It’s not clear which phenyl group, in R1 or R2, or both, is further substituted with methyl, halogen, OMe or OPh moiety. Further, R2 is defined as C1-C6 alkyl group or a phenyl group. However the elected species is C3 alkyl further substituted with OH. It’s not clear what groups can the C1-C6 alkyl of R2 be further substituted. Thus, the definition of compound of Formula I is unclear and indefinite. An ordinary skilled in the art would not be appraised of the scope of claim 22.
Claim 23 and 25 are rejected due to dependency on claim 22.
Claim Rejections - 35 USC § 102/103
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 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.
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 22-23 and 25 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over PubChem SID 85839598 / CID 2964603 (Applicant’s IDS dated 04/25/2024, retrieved from https://pubchem.ncbi.nlm.nih.gov/substance/85839598 ).
PubChem 85839598 (CAS# 714261-25-3, PubChem CID 2964603) discloses instant elected species which is available in ChemBridge library since July 22, 2004 according to STN database. As disclosed by instant specification (See [0084]), 2-(3-hydroxypropyl)-1-(3-phenoxyphenyl)-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-dione (KH-1) was purchased from Chembridge.
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As such , instant claimed compound of Formula I comprising diphenyl ether as R1 is known and anticipated by PubChem 85839598 (CAS# 714261-25-3).
Screening compound library for potential targeted therapeutic activity is routine practice in the pharmaceutical industry(See Pyrke 2017, Applicant’s IDS dated 04/25/2024). Once the compound is identified as a hit and its activity confirmed through standard assays, formulating the hit compound with pharmaceutical carrier into a pharmaceutical composition is within the general knowledge and skills of POSA which does not involve inventive step. Accordingly, instant claimed composition is at least prima facie obvious over the known compound PubChem 85839598 (CAS# 714261-25-3) under 35 USC § 103.
Claim Rejections - 35 USC § 103
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 22, 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over PubChem SID 85839598 / CID 2964603 (Applicant’s IDS dated 04/25/2024, retrieved from https://pubchem.ncbi.nlm.nih.gov/substance/85839598 ) in view of Theodorescu et al. (US 9353121 B2, Applicant’s IDS dated 04/25/2024).
PubChem 85839598 discloses a compound having the structure of instant elected species,
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Theodorescu discloses small molecule inhibitors of Ral GTPases as anticancer compound, pharmaceutical composition comprising aforementioned compounds, and method of using the compounds for inhibiting the growth or metastasis of a cancer( See abstract, Col. 2, lines 13; Examples, claims 1-5 ). Theodorescu teaches pharmaceutical composition comprising one or more of the com
pounds of the invention with at least one pharmaceutically acceptable carrier as taught by Remington's Pharmaceutical Sciences (See Col. 12, lines 16-40; claim 4-5).
Theodorescu teaches compounds are identified as hit compound by “in silico” molecular modeling screening followed by assay (See Example 1). Theodorescu explicitly teaches compound species comprising the core structure of 1,2- dihydrochromeno[2,3-c]pyrrole-3,9-dione (See Table 1).
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Screening compound library for potential targeted therapeutic activity is routine practice in the pharmaceutical industry. Once the compound is identified as a hit and its activity confirmed through standard assays, formulating the hit compound with pharmaceutical carrier into a pharmaceutical composition is the routine practice as illustrated by Theodorescu. In view of the structural similarity of Theodorescu compound RLA027 and PubChem 85839598, it would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of instant claimed invention to formulate compound of PubChem 85839598, together with pharmaceutical acceptable carrier into pharmaceutical composition, and arrive at the instant application with reasonable expectation of success. Therefore, instant claimed invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 22, 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Feng et al. ( WO 2020/083855, Applicant’s IDS dated 04/25/2024) in view of PubChem SID 85839598 / CID 2964603 (Deposit date: 18 December 2009, Applicant’s IDS dated 04/25/2024, retrieved from https://pubchem.ncbi.nlm.nih.gov/substance/85839598 ).
Feng discloses a compound of Formula (I), pharmaceutical composition comprising aforementioned compounds as inhibitors of cccDNA for treating Hepatitis B (HBV) infections (See abstract, page 1, lines 2-10; page 3, lines 1-16; Examples 1-52; claims 1-19).
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Feng’s compound wherein m is 0, X is bond, A is CO, is very similar to instant compound of Formula I. Feng also teaches compound species that’s similar to instant compound of Formula I (See Example 51, 52).
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Feng teaches pharmaceutical composition comprising compound of Formula I with pharmaceutically acceptable carrier (See page 17, lines 29-32; page18, lines 1-9, 20-24; claim 13).
PubChem 85839598 discloses a compound of 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-dione. In view of the structural similarity of Feng compound and PubChem 85839598, it would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to explore more 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-dione compounds based on general knowledge of structural similarity, and formulate PubChem 85839598 into pharmaceutical composition, as taught by Feng and arrive at the instant application with reasonable expectation of success. Therefore, instant claimed invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Vydzhak et al. ( hereafter Vydzhak 2008, Russian Journal of General Chemistry, 2008, 78(12), 2391-2397, DOI: 10.1134/s1070363208120165, Synthesis of 2-alkyl-1-aryl-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione derivatives).
Vydzhak 2008 discloses synthesis of 2-alkyl-1-aryl-1,2-dihydrochromeno[2,3-c]pyrrole-
3,9-dione derivatives (See whole article). Vydzhak 2008 discloses 2-alkyl-1-aryl-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione species that are encompassed by instant claimed compound of Formula I, wherein R1 is Ar, R2 is C1-C6 alkyl (See Scheme 1, Table 1; Experimental ).
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Vydzhak 2008 teaches alkyl-1-aryl-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones as potential biologically active substances (See page 2395, left column).
It’s a common practice in the pharmaceutical industry to formulate active compounds together with pharmaceutical carrier into pharmaceutical composition. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to formulate active 2-dihydrochromeno[2,3-c]pyrrole-3,9-diones, together with pharmaceutical carrier into pharmaceutical composition, and arrive at the instant application with reasonable expectation of success. A skilled artisan would be motivated to do so and reasonably expect the composition comprising 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-diones would exhibit biological activity as the active 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-diones compounds. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Vydzhak et al. (hereafter Vydzhak 2010 , Russian Journal of General Chemistry (2010), 80(2), 323-329 , DOI: 10.1134/s1070363210020222, Synthesis of 1-aryl-2-[2-(dimethylamino)ethyl]-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones and their analogs).
Vydzhak 2010 discloses synthesis of 1-aryl-2-[2-(dimethylamino)ethyl]-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones and their analogs (See whole article). Vydzhak 2010 discloses -aryl-2-[2-(dimethylamino)ethyl]-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones that are encompassed by instant claimed compound of Formula I, wherein R1 is Ar, R2 is C1-C6 alkyl (See Scheme 1, Table 1; Experimental ).
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Vydzhak 2010 and incorporated reference (Park 2007, etc. ) teaches activity of 2-aryl(hetero)-1,2-dihydrochromeno[2,3-c]- pyrrol-3 ,9-diones, e.g. 2-(3-morpholin-4-yl-propyl)-1-phenyl-1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-dione, having following structure, exhibited antitumor activity as inhibitor of Hsp90 (See page 323, right column).
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Vydzhak 2010 is silent about pharmaceutical composition comprising 1,2-dihydrochromeno[2,3-c]- pyrrol-3 ,9-diones and pharmaceutical acceptable carrier.
It’s a common practice in the pharmaceutical industry to formulate active compounds together with pharmaceutical carrier into pharmaceutical composition. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention to formulate active 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-diones together with pharmaceutical acceptable carrier into pharmaceutical composition, and arrive at the instant application with reasonable expectation of success. A skilled artisan would be motivated to do so and reasonably expect the composition comprising 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-diones would exhibit biological activity (e.g. antitumor activity) as the active 1,2-dihydrochromeno[2,3-c]-pyrrole-3 ,9-diones compounds.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teaching prior art and general knowledge of pharmaceutical composition. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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