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
This application filed on 10/11/2023 is a 35 U.S.C. § 371 National Stage Application of International Application No. PCT/CN2022/086311, filed on 04/12/2022, which claims priority to Chinese Application No. 202110392892.4, filed on 04/12/2021, Chinese Application No. 202110707739.6, filed on 06/24/2021, and Chinese Application No. 202111065912.3, filed on 09/10/2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 03/24/2025 and 07/31/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of Claims
The preliminary amendment filed on 06/11/2026 that amended claims 11-13 and 15, has been acknowledged.
Claims 1-15 are pending.
Election/Restriction
Applicant’s response filed on 06/11/2026 to Restriction/Election Requirement filed on 01/13/2026, is acknowledged. Applicant elected without traverse Group I drawn to a compound of Formula (I), stereoisomers, tautomer’s, N-oxides, hydrate, isotope-substituted derivatives, solvates or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising a compound of Formula (I) and pharmaceutically acceptable carrier. Claims 1-12, and 14-15 read on the elected Group. Claim 13 of Group II is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse, Example 119: 5-(4-((3-ethyl-5-fluoro-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)methyl)piperazin-1-yl)-N,6-dimethylpicolinamide, depicted below for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable:
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Claims 1-12 and 14-15 read on the elected species. Applicant’s elected species was searched, and determined to be free of the art. Pursuant to MPEP § 803.02, the search and examination was extended to the non-elected species discussed below, which new search species falls within the scope of instant claims 1-12 and 14-15 (i.e., claims to proper Markush groupings that include both the new search species as well as the originally elected species. MPEP § 803.02(III)(C)(2)). The new search species underlies rejections of these claims pursuant to 35 U.S.C. § 102. As such, the election of species requirement is maintained as provisional, and claim 13 is provisionally withdrawn from consideration pursuant to 37 CFR 1.142(b). See, MPEP § 803.02.
Thus, claims 1-15 are pending with claim 13 is withdrawn from further consideration, and claims 1-12 and 14-15 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation of “optionally substituted/substituents
Claim 1 recites optionally substituted groups/variables, for example “Cy is selected from a group consisting of an optionally substituted heterocyclic group, an optionally substituted aryl, …”.
The instant specification describes the term “optionally substituted” or the substituents as:
[0031] In this disclosure, unless otherwise described, when substituted, the alkyl, cycloalkyl heterocycloalkyl, alkoxy, heterocycloalkoxy, alkenyl, heterocycloalkenyl, alkynyl, amino, amido, acyloxy, carboxyl, hydroxyl. mercapto, alkylthio sulfonyl, sulfonyl, sulfinyl, aminoacyl, silyl, phosphinecarboxy, phosphono, carbocyclic group, heterocyclic group, aryl or heteroaryl as described in any embodiment herein may be substituted by one or more (such as L. 2, 3, 4,5 or 6) substituents selected from a group consisting of the group consisting of halogen, hydroxyl, carboxyl, amino nitro, cyano, C1-6 amido, C1-6 acyloxy, C1-6 alkoxy, aryloxy, alkylthio, C1-6 alkyl, C1-6 acyl, C1-6 aryl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, heterocyclic or heteroaryl, methylenedioxy, urea group, mercapto group, azide group, carbonyl, alkanesulfonyl, sulfamoyl, dialkylsulfamoyl and alkylsulfinyl, etc. The substituent itself may also be optionally substituted. Preferred substituents include without limitation halogen, hydroxyl, carboxyl, amino, C1-6 amido, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkyl, C1-6 acyl and alkanesulfonyl.
[0032] It should be understood that in each embodiment, when the substituent is a heterocyclic group, aryl or heteroaryl. the number thereof is usually 1.
In view of the specification, the groups can be substituted by absolutely anything, and the substituent can be further substituted by anything. Thus, the term “optionally substituted” is interpreted as any substituent known to skilled artisan in chemistry/organic chemistry.
Specification Objections
The specification is objected to because the text and certain drawings/chemical structures are too faint and/or pixilated to the extent that it will not be transcribable by the publication division in an issued patent. See for example, the chemical structures and the NMR data on page 44, 45, 46, 47, etc. Applicant is required to provide clearer depictions of the unclear text and chemical structures.
Appropriate correction is required.
Rejections 35 U.S.C. 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.
Claims 2-6, 8-9 and 15 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.
Pursuant to 35 U.S.C. 112(b), the claim must apprise one of ordinary skill in the art of its scope so as to provide clear warning to others as to what constitutes infringement. MPEP 2173.02(II); Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000).
The claims recite “preferably”, for example, claim 2 recites “… optionally substituted by 1-5 groups selected from a group consisting of hydroxyl and halogen; preferably, R1 is C1-3 alkyl, halogenated C1-3 alkyl or C3-4 cycloalkyl. The term “preferably” repeated through the claims, including withdrawn claims. As provided in MEMP 2173.05(d), “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made. Claim 9 is rejected as indefinite due to its dependence on a rejected claim 8 and lacking any limitations that cure the ambiguities resulting from the parent claim(s).
Claim 15 recites “… Aldesleukin (recombinant human interleukin-2), sipuleucel-T (prostate cancer therapeutic vaccine)”. The recitation of the parentheses renders the claim indefinite because it is unclear whether the limitations in the parentheses are part of the claimed invention and further limit the anticancer agents or are exemplary of the anticancer agent. See MPEP § 2173.05(d).
Pursuant to 35 U.S.C. 112(b), the claim must apprise one of ordinary skill in the art of its scope so as to provide clear warning to others as to what constitutes infringement. MPEP 2173.02(II); Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000).
In view of compact prosecution, for the purpose of applying prior art, the parenthetic recitations are interpreted as exemplary and as not further limiting the claim.
Claim 15 contains several trade names, including Avastin, Herceptin and Mab Thera. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the claimed therapeutic agents and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112(a) Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-11 and 14-15 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 the claimed invention.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the art that the inventors, at the time the application was filed, had possession of the claimed invention. See MPEP 2143. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filling date of the application, of the specific subject matter claimed. Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Claim I is directed to a compound of Formula (I):
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oxides, hydrates, solvates, isotope-substituted derivatives, or pharmaceutically acceptable salts thereof, or mixtures thereof, or prodrugs thereof, wherein: R1 is selected from a group consisting of an optionally substituted alkyl, an optionally substituted carbocyclic group, an optionally substituted alkenyl and an optionally substituted alkynyl; A1, A2 and A3 are each independently selected from a group consisting of N and CR2; L is selected from a group consisting of bond and alkylene optionally substituted by R3 and/or R4; Cy is selected from a group consisting of an optionally substituted heterocyclic group, an optionally substituted aryl, and an optionally substituted heteroaryl; R2 is selected from a group consisting of hydrogen, halogen, an optionally substituted alkyl, an optionally substituted alkoxy and an optionally substituted carbocyclic group; R3 and R4 are each independently selected from a group consisting of halogen, cyano, an optionally substituted alkyl, an optionally substituted alkoxy, an optionally substituted cycloalkyl, an optionally substituted alkenyl, and an optionally substituted alkynyl; or R3 and R4 together with the attached C form a ring; n is selected from a group consisting of 0, 1 and 2; wherein when n is 1 or 2, the -(CH2)n- is optionally substituted by =0.
The instant specification describes the term “optionally substituted” or the substituents as:
[0031] In this disclosure, unless otherwise described, when substituted, the alkyl, cycloalkyl heterocycloalkyl, alkoxy, heterocycloalkoxy, alkenyl, heterocycloalkenyl, alkynyl, amino, amido, acyloxy, carboxyl, hydroxyl. mercapto, alkylthio sulfonyl, sulfonyl, sulfinyl, aminoacyl, silyl, phosphinecarboxy, phosphono, carbocyclic group, heterocyclic group, aryl or heteroaryl as described in any embodiment herein may be substituted by one or more (such as L. 2, 3, 4,5 or 6) substituents selected from a group consisting of the group consisting of halogen, hydroxyl, carboxyl, amino nitro, cyano, C1-6 amido, C1-6 acyloxy, C1-6 alkoxy, aryloxy, alkylthio, C1-6 alkyl, C1-6 acyl, C1-6 aryl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, heterocyclic or heteroaryl, methylenedioxy, urea group, mercapto group, azide group, carbonyl, alkanesulfonyl, sulfamoyl, dialkylsulfamoyl and alkylsulfinyl, etc. The substituent itself may also be optionally substituted. Preferred substituents include without limitation halogen, hydroxyl, carboxyl, amino, C1-6 amido, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkyl, C1-6 acyl and alkanesulfonyl.
[0032] It should be understood that in each embodiment, when the substituent is a heterocyclic group, aryl or heteroaryl. the number thereof is usually 1.
In view of the specification, the groups can be substituted by absolutely anything, and the substituent can be further substituted by anything. Thus, the claims are drawn to millions of compounds structurally different, and each moiety having different structural core. Moreover, the claims include structurally diverse substructures of Formula I, IIa, IIb, IIIa, IIIb, IVa and IVb, all of which are optionally substituted with substituent that are further optionally substituted, see above [0031].
Claim 7, for example, further limits claim 1 by: “wherein Cy is substituted by R5 which is selected from a group consisting of”:
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wherein B1, B2, B3 and B4 are independently selected from a group consisting of N and CR7; R7 is selected from a group consisting of hydrogen, halogen, C1.4 alkyl, C14 alkoxy, halogenated C1. 4 alkyl, halogenated C1.4 alkoxy and -NR'R"; R' and R" are each independently selected from a group consisting of hydrogen, an optionally substituted C1.4 alkyl, an optionally substituted C3-6 cycloalkyl; * indicates the position at which the group is attached to the rest of the compound
Considering that all the variables of Formula (I) can be substituted by absolutely anything, B1-4, R’ R’’ and R7 can be optionally substituted by absolutely anything, claim 7 does not reasonably represent all the species of the claimed genus.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species in examples that encompass the genus. (MPEP § 2163). 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product; however, the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described."). If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or sub-combinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, 1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. Each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high, adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus. "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention."). Problems satisfying the written description requirement for original claims often occur when claim language is generic or functional, or both. Ariad, 593 F.3d at 1349, 94 USPQ2d at 1171 ("The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus."
Comparison of the scope of the claims and the scope of the specification reveals that the scope of the claims is broader than that supported by the specification. The specification provides only 146 species of the millions of structurally different species, all of the provided species (except for compounds 40-47) are falling with the subgenus of Formula IIIa/IIIb. There are no drawings, structural or empirical formulas that sufficiently define the genus of compounds that fulfill the instant claims, to allow one to determine the scope of possible compounds. A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed. The applicants have broadly claimed the compounds of Formula I, IIa, IIb, IIIa, IIIb, IVa and IVb. MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 1-7 are broad and generic, with respect to all possible compounds encompassed by the claims. There is a very large number of structural variations encompassed by the genus of formula (I). The claims lack in written description because the specification lacks sufficient variety of species to reflect this variance in the genus, especially with respect to any groups of variables of Formula I, IIa, IIb, IIIa, IIIb, IVa and IVb can be substituted by absolutely anything, and the substituent can be further substituted by anything. The specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims. Considering the lack of guidance provided in the specification, one of ordinary skill in the art would be led to conclude that applicants were not in possession of the invention commensurate with the scope of the claims, at the time the application was filed, and that one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of claims 1-11 and 14-15.
§ 112(a)- Written Description for claims 1-7, 12, and 14-15 term “prodrug”
Claims 1-12 and 14-15 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 the claimed invention.
The instant claim 1 is directed to “a compound of formula (I), that is claimed to have a biological activity as an inhibitor of PARP activity”. The recitation of prodrug of compounds of formula (I) is not adequately defined in the instant specification.
The MPEP states that for a generic claim can be adequately described if the disclosure presents a sufficient number of representative species in examples that encompass the genus. (MPEP § 2163). 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole cover, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. Each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
With respect to the scope of the claims, the full scope includes “a compound of Formula (I), or stereoisomers, tautomers, N-oxides, hydrates, solvates, isotope-substituted derivatives, or pharmaceutically acceptable salts thereof, or mixtures thereof, or prodrugs thereof, wherein R1 is selected from a group consisting of ….”
Zawilska (J. Zawilska et al. Pharmacol Rep. 2013; 65(1):1-14, “Zawilska” cited in the PTO-892), teaches that “Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug.” [Abstract]. Zawilska teaches that “the rationale behind the use of prodrugs is to optimize the absorption, distribution, metabolism, excretion, and unwanted toxicity of the parent drug.” [Pg. 2, col. 1]. Zawilska teaches that there are two main classes of prodrugs, carrier-linked prodrugs (the drug is temporary linked to a carrier that undergoes biotransformation, releasing the parent drug and the carrier), and bioprecursor prodrugs (result from a molecular modification of the drug and transformed metabolically or chemically by hydration or reduction. [Pg. 2, col. 2]. Zawilska teaches the major groups of prodrugs:
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Zawilska teaches that “some esters are not suitable substrates for endogenous esterases, sulfatases or phosphatases, which, in turn, impose unfavorable, too slow kinetics of the prodrug hydrolysis.” [Pg. 4, col. 1, 1st para.]. Zawilska teaches that the prodrug should be easily dissolved in water, and marginally taken up by cells, the drug should be efficiently and rapidly transported, the enzyme should have high intrinsic activity, and enzyme cannot be inactivated by a prodrug or drug. Zawilska teaches that “Despite the remarkable progress made in the field of prodrug design, more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art and take their place in modern pharmacotherapy.” Pg. 11, col. 21st para.].
The instant claims directed to compounds of formula (I), wherein R1, R2, R3, R4, L, and Cy are defined as “optionally substituted” with the substituents includes amino, amido, acyloxy, carboxyl, hydroxyl. mercapto, alkylthio sulfonyl, sulfonyl, sulfinyl, aminoacyl, silyl, phosphinecarboxy, phosphono, etc. (see claim interpretation above). The substituents, thus includes COOH, C=O, NH, OH, SH, PO(OH)2, etc. As discussed above by Zawilska, these functional group leads to multiples prodrugs. Additionally, compound of formula (I) includes multiple sites to which a prodrug moiety could bind. The description does not provide adequate description on the binding moiety, the type of prodrugs (carrier-linked prodrugs or bio-precursor prodrugs), kinetics of the prodrug hydrolysis, or the enzyme-prodrug interaction. See Zawilska above. The specification does not provide answer to question regarding prodrug of compound of formula (I), for example, does the metabolism of compounds of formula (I) is well understood, does the prodrug will be active, does the prodrug will introduce any unfavorable interaction, etc. Zawilska teaches that “more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art”
The description does not include a definition of the prodrug that satisfies the functional definition of the genus. "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention."). Problems satisfying the written description requirement for original claims often occur when claim language is generic or functional, or both. Ariad, 593 F.3d at 1349, 94 USPQ2d at 1171 ("The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus."
Comparison of the scope of the claims and the scope of the specification reveals that the scope of the claims is broader than that supported by the specification. There is no guidance in the specification regarding prodrugs. The specification only recites:
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The generic definition provided in the instant specification do little in describing a prodrug for compound of formula I because compound of formula I encompass hundreds/thousands of species each of which encompasses multiple sites for prodrug binding. The instant specification provides no example for any prodrug of any compound of formula I, let alone, its activity, metabolism, enzymatic interaction, toxicity, etc. BOC Sciences (https://www.bocsci.com/blog/prodrug-activation-strategies-in-drug-discovery/?srsltid=AfmBOor0dyaRkHg4KY8ggdEj09mix1fTx8ZGgnvoIJzT5gtvjX5jYSHE, 2023), teaches that “the design of prodrugs must ensure their ability to degrade and release the parent drug at the appropriate time and site. This requires that the designed prodrugs have suitable chemical stability and enzymatic stability. They should neither degrade before reaching the target site nor remain undegraded for an extended period after entering the target site, as this would hinder their pharmacological effect. Additionally, prodrugs often have distinct chemical structures from the parent drug, which may introduce new toxicities. On one hand, this could result from unexpected metabolism of the prodrug, leading to the formation of unforeseen metabolites. On the other hand, it may occur because inert carriers generated from prodrug cleavage can transform into toxic metabolites, such as formaldehyde and acetaldehyde. Therefore, the comprehensive evaluation of prodrugs should include their physicochemical properties, pharmacological effects, pharmacokinetic properties, and potential toxic reactions.” [Pg. 8]. Thus, in view of BOC Science, claiming prodrug of compound of formula I required more than what provided by instant specification. One skilled in the art cannot, as one can do with a fully described prodrugs, visualize or recognize the identity of the prodrugs of the genus of formula (I).
Having analyzed the claims with regard to the written description guidelines, the specification does not disclose a representative number of prodrugs or relate the functional language of “a prodrug that provides for anti-bacterial activity” to sufficiently to describe said prodrugs. Thus, one of ordinary skill in the art would be led to conclude that applicants were not in possession of the invention commensurate with the scope of the claims, at the time the application was filed.
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 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.
§ 102 Rejection over Freyne
Claims 1-2, 4-6, and 14-15 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by E. Freyne et al. (US PG-PUB 2011/0028433A1, 02/03/2011, “Freyne” cited in the PTO-892).
Freyne discloses quinazolinone derivatives of formula (I), wherein R1-6 are defined [0017]:
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Freyne further discloses species of formula (I), for example, compound 13, [0086]:
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Freyne’s compound 13 anticipates instant claim 1 compound of Formula (I), wherein:
R1 is alkyl, ethyl;
A1 is CR2, and R2 is H;
A2 is CR2 and R2 is H;
A3 is CR2 and R2 is H;
L is -CH2- substituted with R3 and R4, wherein R3 is cyano and R4 is alkyl, methyl;
Cy is heterocyclic group substituted with chloro; and
n is 1.
Claim 2 is met because R1 is C2 alkyl, ethyl.
Claim 4 is met because R2 is H.
Claim 5 is met because all of A1, A2 and A3 are CR2, and R2 are H.
Claim 6 is met because Cy is heterocyclic group substituted with halogen.
Regarding claim 14, Freyne discloses a pharmaceutical composition comprising a pharmaceutically acceptable carrier and as an active ingredient a therapeutically effective amount of a compound of formula (I), e.g., compound 13. [0108].
Regarding claim 15, Freyne discloses a combination of a compound of formula (I), e.g., compound 13 with another anticancer agent for use as a medicine, wherein the anti-cancer agents include cetuximab, pertuzumab, bevacizumab, etc. [0117], [0129].
§ 102 Rejection over Murata
Claims 1, 3-6, 8 and 14 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by T. Murata et al. (US PG PUB 2015/0141400A1, 05/21/2015, “Murata” cited in the PTO-892)
Murata discloses quinazolinedione derivatives of formula (I), wherein A, Q, R5, R6 and R7 are defined at page 2-3 [0033]:
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Murata discloses compound I-10 as species of formula (I) above, [page 159, [2032]]:
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Murata’s compound I-10 anticipates instant claim 1 compound of Formula (I), wherein:
R1 is alkyl substituted with aryl group, which is substituted with Cl and CH3CH3SO2. Claim 1 recites “optionally substituted alky”, see claim interpterion above of “optionally substituted”;
A1 is CR2, and R2 is H;
A2 is CR2 and R2 is Br;
A3 is CR2 and R2 is Br;
L is -CH2-;
Cy is heterocyclic group, piperazine substituted with tetrahydropyran; and
n is 1 and the –(CH2)n- is substituted with =O.
Claim 3 is met because L is -CH2-.
Claim 4 is met because R2 is Br.
Claim 5 is met because all of A1, A2 and A3 are CR2, and R2 are H, Br and Br, respectively.
Claim 6 is met because Cy is heterocyclic group, piperazine substituted with 4-10 membered heterocyclic group, tetrahydropyran.
Claim 8 is met because R5, as defined in claim 6, is 4-10 membered heterocyclic group, tetrahydropyran. R1, A1-3 and n are met as discussed on claim 1 anticipation above.
Regarding claim 14, Murata discloses that the compound of formula (I), e.g., compound I-10 above are formulated in a pharmaceutically acceptable composition (tablets, powders, fine granules, granules, coated tablets, etc.) with commonly used excipients. [0123].
§ 102 Rejection over Li
Claims 1, 3-7, and 14 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by J. Li et al. (WO 2020/103896A1, 05/28/2020, “Li” cited in the PTO-892).
Li discloses pyrrolo [2, 3-b] pyridine derivative of Formula (I) of formula (I), [page 7, last line- 8]. Li discloses compound 28 as species of formula (I) [page 11]:
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Li’s compound 28 above anticipates instant claim 1 compound of Formula (I), wherein:
R1 is alkyl substituted with methyl and methyl piperidine. Claim 1 recites “optionally substituted alky”, see claim interpterion above of “optionally substituted”;
A1 is CR2, and R2 is H;
A2 is CR2 and R2 is H;
A3 is CR2 and R2 is H;
L is a bond;
Cy is heterocyclic group, substituted with an aryl group, wherein the aryl group is substituted with C(O)N(CH3)2; and
n is 0.
Claim 3 is met because L is a bond.
Claim 4 is met because R2 is H.
Claim 5 is met because all of A1, A2 and A3 are CR2, and R2 are H.
Claim 6 is met because Cy is heterocyclic group, substituted with an aryl group, wherein the aryl group is substituted with C(O)N(CH3)2.
Claim 7 is met because heterocyclic group, substituted with
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, wherein B1, B2, B3, and B4 are CR7 and R7 is H; R’ and R’’ are C1 alkyl, CH3.
Regarding claim 14, Li discloses a pharmaceutical composition comprising compound of formula (I), e.g., compound 28 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. [page 13, 1st para.].
Note: The initial search revealed a very large number of compounds that anticipate the subject-matter of claims 1-6. The cited prior art references were selected to show the anticipation of the claims on the merits, and there are still numerous prior art documents and compounds that anticipate the claimed subject matter. 1
Subject Matter Free of the Prior Art
Claims 9, 10, 11, and 12 are determined to be free of the art of record. However, these claims are not currently allowable, because each of these claims are rejected under § 112(a) and/or 112(b) above. Once the aforementioned § 112 issues are overcome these claims would be allowable.
Reasons for Finding Claims Distinguished Over the Prior Art
The following is an examiner’s statement of reasons for finding claims 9-12 as being free of the prior art:
The closest prior is considered to be T. Murata et al. (US PG PUB 2015/0141400A1, 05/21/2015, “Murata” cited in the PTO-892).
Murata discloses quinazolinedione derivatives of formula (I), wherein A, Q, R5, R6 and R7 are defined at page 2-3 [0033]. Murata discloses compound I-10 as species of formula (I) above, [page 159, [2032]]:
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Murata’s compound I-10 reads on compounds of claims 9, 10, 11 and 12 wherein, A1 is CR2, and R2 is H; A2 is CR2 and R2 is Br; A3 is CR2 and R2 is Br; L is -CH2-; Cy is heterocyclic group, n is 1 and the –(CH2)n- is substituted with =O. However, Murata’s compound I-10 differs from the instant claim compound of claims 9, 10, 11 and 12, for example, compound 1 of claim 12, in the highlighted ovals as depicted in the Table below for facile comparison:
Murata’s compound I-10
Claim 12, 1st Compound
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443
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729
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In order to arrive at a compound, read of claims 9, 10, 11 and 12, for example, compound of claim 12 above, the Murata’s compound I-10 above should be modified by replacing the alkyl substituted with 5‐chloro‐2‐[(ethanesulfonyl)methyl] benzene with unsubstituted alkyl (ethyl), and the highlighted tetrahydropyran should be replace with N‐methylpyridine carboxamide. However, Murata’s disclosure does not provide sufficient guidance and motivation to one of ordinary skill in the art to perform the functional modifications to arrive at instantly claimed compound of claim 12 above. Thus, Murata’s disclosure does not anticipate or render the instantly claimed compound of claims 9, 10, 11 and 12 obvious.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1-8 and 14-15 are rejected. Claim 13 is withdrawn. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1See for example, USPN 7,763,616 B2; WO 2006/088836; USPN 6,413,724 B1; USPN 5,356,904 A; USPN 5,234,928 A; EP 436157A1; USPN 5,296,487; USPN 5,264,438; WO 2008/147864 A2; WO 2018/112842; USPN 4,859,672 A; WO 98/18781; WO 2018/036469 A1; WO 2018/036470 A1; CN 101189238A; JP 2012184205A; CN 1918151; WO 2011/021678; EP 2913330 A1; etc.
Prosecution Insights