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 is a national stage entry of PCT/US2022/014375 filed on 01/28/2022, which claims priority to U.S. Provisional Application No. 63/143,627 filed on 01/29/2021.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9) drawn to a viral inhibitor compound comprising formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof in the reply filed on February 9, 2026 is acknowledged. Applicant’s election without traverse of compound 2a having the following structure:
PNG
media_image1.png
284
488
media_image1.png
Greyscale
as a species of a compound of formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof in the reply filed on February 9, 2026 is also acknowledged. Thus Applicant’s elected species of formula I has the following substituents:
X is
PNG
media_image2.png
110
130
media_image2.png
Greyscale
, n is 1, Ro is isobutyl, and Z is CHO.
Claims 3, 4, 10, 13, 19, 22, 25, 27-31 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or group, there being no allowable generic or linking claim.
Claims 1, 2, and 5-9 are currently being examined as they read on the elected species.
Claim Objections
Claim 5 is objected to because of the following informalities: Claim 5 refers to Tables found within the specification.
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
PNG
media_image3.png
18
19
media_image3.png
Greyscale
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.
Claims 1, 2, and 7-9 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.
Claims 1, 2 and 7-9 of the instant application claim a viral inhibitor compound comprising formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof. The use of “comprising” in the preamble of the claim of claim 1 renders the claim indefinite since it is unclear how a viral inhibitor compound can “comprise” formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof. The transitional term “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) (“like the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended.”). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) (“Comprising” is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp. v. CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("comprising” leaves “the claim open for the inclusion of unspecified ingredients even in major amounts”). “The word ‘comprising’ transitioning from the preamble to the body signals that the entire claim is presumptively open-ended.”
In the instant case the use of comprising is unclear because either the viral inhibitor compound is a compound of formula I or it is not. Therefore it is unclear if the viral inhibitor compound is a mixture of unclaimed compounds and compounds of formula I, or if it is a compound of formula I.
For the sake of compact prosecution, claim 1 and dependent claims 2 and 7-9 are being interpreted as “A viral inhibitor compound of formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof” and examined herewith.
Claim 7 is further indefinite since a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation picornavirus-like supercluster, and the claim also recites calciviruses and picornaviruses which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
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 1, 2, and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Jacobson WO 2021/206876 A1.
Claims 1, 2 and 5-9 of the instant application claim a viral inhibitor compound of formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof having the following structure,
PNG
media_image4.png
222
412
media_image4.png
Greyscale
wherein X is the bridged polycyclic cycloalkane
PNG
media_image2.png
110
130
media_image2.png
Greyscale
, n is 1, Ro is isobutyl, and Z is CHO, to form
PNG
media_image1.png
284
488
media_image1.png
Greyscale
.
Jacobson teaches inhibitors of norovirus and coronavirus replication, and methods of treating or preventing norovirus and coronavirus infections by administering the inhibitors to a patient in need of treatment thereof [0001]. Jacobson teaches the compounds can be used in methods of treating viral infections, wherein non-limiting examples of viral infections which can be treated include coronavirus infections, calicivirus infections, and picornavirus infections [00126]-[00133]. Jacobson teaches the treatment of coronaviruses including severe acute respiratory syndrome-related coronavirus (SARS), Middle East respiratory syndrome-related coronavirus (MERS), and SARS-CoV-2 virus (also known as 2019-nCoV, or Wuhan coronavirus), wherein non-limiting examples of coronavirus mediated conditions or coronavirus infections include SARS, MERS, and COVID-19 [00134]-[00142].
Jacobson further teaches the compounds bind to free virus, or inhibits a virus protease, or inhibits both the free virus and protease ([00131] and [00138]).
Jacobson teaches the inhibitors are compounds of Formula (I) having the following structure
PNG
media_image5.png
100
278
media_image5.png
Greyscale
wherein Z is O; RN is H; R2 is C1-6alkylene-C5-8carbocycyl; R3 is C1-6alkyl; n is 0; m is 1; o is 1; R5 is COH; R6 is H ([0007] and claims 1, 2, 13, 18, 21, 22, 27-29, 50-52, 55, 57).
Jacobson teaches the term "carbocycle" (or "carbocyclyl" ) refers to a non-aromatic monocyclic, fused, bridged or spiro ring system whose ring atoms are carbon and which can be saturated or have one or more units of unsaturation [0023]. The carbocycle can have five to eight ring carbon atoms, and in some embodiments, the number of carbon atoms is 5 to 6, and in some embodiments, the number of carbon atoms is 6 [0023]. Jacobson teaches that fused bicyclic ring systems comprise two rings which share two adjoining ring atoms, and bridged bicyclic group comprise two rings which share three or four adjacent ring atoms, and spiro bicyclic ring systems share one ring atom [0023]. Cycloalkyl groups can include cycloalkenyl groups. Specific examples include, but are not limited to, cyclohexyl, cyclopentyl, cyclopropyl, and cyclobutyl [0023].
For example Jacobson discloses compound C47 wherein Z is O; each RN is H; R2 is C1-6alkylene-C5-8carbocycyl specifically CH2-cyclohexane; R3 is C1-6alkyl specifically isobutyl; n is 0; m is 1; o is 1; R5 is COH; R6 is H (page 22).
Jacobson does not specifically exemplify a compound wherein the carbocycle is a bicyclic bridged cyclohexyl group.
However, as detailed above, Jacobson discloses compound C47 wherein R2 is C1-6alkylene-C5-8carbocycyl, specifically CH2-cyclohexyl (page 22). Jacobson further specifically teaches that "carbocycle" (or "carbocyclyl" ) refers to a non-aromatic monocyclic, fused, bridged or spiro ring system whose ring atoms are carbon and which can be saturated or have one or more units of unsaturation [0023]. Jacobson teaches that fused bicyclic ring systems comprise two rings which share two adjoining ring atoms, and bridged bicyclic group comprise two rings which share three or four adjacent ring atoms, and spiro bicyclic ring systems share one ring atom [0023]. Thus Jacobson teaches that the monocyclic carbocycle ring may be substituted for a fused bicyclic ring system, a bridged bicyclic group, or a spiro bicyclic ring system, wherein the ring can be cyclohexyl.
Accordingly, prior to the effective filing date of the claimed invention, based on the teachings of Jacobson, it would have been obvious to a person of ordinary skill in the art to select R2 as C1-6alkylene-C5-8carbocycyl, wherein the monocyclic cyclohexane group is substituted for a fused or bridged bicyclic cyclohexane ring system which comprises two rings which share adjoining or adjacent ring atoms. Based on the teachings of Jacobson said substitution would have been seen as an obvious alternative to yield similar and predictable results. Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 1, 2, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Chang U.S. Publication No. 2014/0243341 A1.
Claims 1, 2 and 7-9 of the instant application claim a viral inhibitor compound of formula I, or a prodrug, deuterated form, or pharmaceutically-acceptable salt thereof having the following structure:
PNG
media_image4.png
222
412
media_image4.png
Greyscale
wherein X is a nitrogen-, oxygen-, phosphorus-, or sulfur-containing heterocycle or azetidine, n is 1, Ro is isobutyl, and Z is CHO.
Chang et al. teaches antiviral protease inhibitors, including peptidyl aldehydes, peptidyl a-ketoamides, peptidyl bisulfite salts, and peptidyl heterocycles, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease (abstract). The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus (abstract).
Chang et al. teaches compounds of formula (I) having the following structure:
PNG
media_image6.png
218
286
media_image6.png
Greyscale
wherein Z is selected from the group consisting of aldehydes, ketoamides, bisulfite salts, heterocyclic moieties; R1 is a branched or unbranched alkyl, cycloalkyl, aryl, arylalkyl, alkenyl, alkynyl, natural amino acid side chain, or a combination thereof; Ro is -C(O)R, and R is -OCH2R3 and R3 is a substituted or unsubstituted: aryl, heteroaryl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or saturated heterocycle [0009].
Chang et al. teaches antiviral compounds having broad-spectrum (multivalent) activity against viruses that belong to the picornavirus-like supercluster, including caliciviruses, picornaviruses and coronaviruses [0049]. The compounds effectively target and inhibit viral 3C or 3CL protease activity across multiple virus species, strains, and subtypes, thereby preventing formation of the mature virus and inhibiting virus replication in the host cell [0049]. Coronaviruses include human coronavirus (cause of common cold such as 229E strain), transmissible gastroenteritis virus (TGEV), murine hepatitis virus (MHV), bovine coronavirus (BCV), feline infectious peritonitis virus (FIPV), and severe acute respiratory syndrome coronavirus (SARS-CoV) [0048].
Chang et al. teaches the following compound:
PNG
media_image7.png
270
482
media_image7.png
Greyscale
wherein Z is CHO; R1 is isobutyl; Ro is -C(O)R, and R is -OCH2R3 and R3 is unsubstituted aryl [0051].
Chang et al. does not specifically exemplify a compound wherein R3 which corresponds to X of the instant claims is as claimed in the instant claims.
However, Chang et al. specifically teaches that R3 can be selected as substituted or unsubstituted: aryl group, heteroaryl group, aryloxy group, heteroaryloxy group, arylalkoxy group, heteroarylalkoxy group, or saturated heterocycle (see claim 1 on page 31).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to substitute a heteroaryl group or a saturated heterocycle group for the phenyl group specifically exemplified in Chang et al. with a reasonable expectation of similar success. Thus since Chang et al. teaches that a heteroaryl group or a saturated heterocycle group is a suitable alternative or substitute for an aryl group such as phenyl, an ordinary skilled artisan would have been motivated to substitute a heteroaryl or heterocyclic group for the aryl group to arrive at the instant compounds with a reasonable expectation of predictable results. Accordingly, the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1, 2 and 5-9 are rejected. Claims 3, 4, 10, 13, 19, 22, 25, 27-31 and 34 are withdrawn. Claims 11-12, 14-18, 20-21, 23-24, 26, and 32-33 are canceled. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
Prosecution Insights