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 . 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.
Priority
The instant application claims domestic benefit to US provisional application no. 63/316,231 filed on 03/03/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/13/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 08/18/2023 is acknowledged. Claims 3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are amended. Claims 4-10, 12-13, 16-62, 65-66, 68-95, 97, 99-106, 114-117, 119-128, and 130-156 are cancelled.
Accordingly, claims 1-3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are pending and being examined on the merits herein.
Claim Objections
Claims 11 and 67 are objected to because of the following informalities:
Claim 11 recites “… are taken together to form -OC(O)O, -OCHR6O- … “. The conjunction “or” appears to be missing between the two chemical groups, since both recited chemical groups cannot be formed at the same time on the recited compound.
Claim 67 recites “… wherein R7 is C3-C8 carbocyclyl, 4 to 6 membered heterocyclyl containing 1, 2, or 3O.”.
The conjunction “or” appears to be missing between the two chemical groups, since both recited cyclic groups cannot be at the R7 position at the same time on the recited compound.
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 107 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 107 recites “… wherein the compound is a compound of Table 1.”.
MPEP 2173.05(s) recites “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.".
Therefore, claim 107 is indefinite because the claims are not complete in themselves by reciting “a compound of Table 1”.
For purposes of examination, claim 107 is being interpreted as the compound being any one compound listed in Table 1, pages 41-48 in the instant specification.
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.
Claim(s) 1-2, 14-15, 63-64, 96, 107, 113, 118, and 129 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015069939A1 (in IDS filed 08/18/2023) in view of Yates et al. (Antiviral Res., 2018 in PTO-892) and US11541071B1 (in PTO-892, effective filing date of 12/16/2021).
WO’939 teaches a compound of Formula (I) (shown below) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections:
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WO’939 teaches that peumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases including human respiratory syncytial virus (HRSV) (see page 1 lines 10-13). WO’939 teaches that almost all children have an HRSV infection and elderly adults with chronic heart, lung disease or those that are immunosuppressed also have a high risk for developing severe HRSV disease (see page 1 lines 13-16). WO’939 teaches that no vaccine to prevent HRSV infection is currently available, and that a monoclonal antibody palivizum is used for immunoprophylaxis, but its use is restricted to infants at high risk (see page 1 lines 18-23). WO’939 teaches that a nucleoside analog ribavirin is the only approved antiviral agent to treat HRSV but has limited efficacy (see page 1 lines 20-24). Therefore, WO’939 teaches there is a need for new antiviral agents useful for treating Paramyoxviridae viral infections, including Pneumovirinae viral infections such as HRSV, that are effective and have acceptable toxicity profiles (see page lines 1-3). WO’939 teaches that their compounds can be in a pharmaceutical formulation with pharmaceutically acceptable excipients (see page 12 lines 5-6 and page 14 lines 7-10).
WO’939 demonstrates the synthesis of a compound of Formula (I), compound 1, shown below (page 54):
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WO’939 also teaches several other modified nucleoside compounds such as recited in instant claim 30 (page 169) shown below:
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Here, WO’939 demonstrates the modification of the 3’ and 5’-positions on the furanose ring of the nucleoside.
The difference between WO’939 and the claimed invention is that WO’939 does not teach a R3 modification group recited in the instant claims.
Yates teaches the development of nucleoside analogue antiviral drugs and provides several examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics (see Abstract). Yates teaches that nucleosides and nucleotides play important roles in the replication and transcription of genetic information, and, as such, have been utilized for decades for chemotherapy, antiparasitic, antibacterial or antiviral therapeutics (see second paragraph left column page 5). Yates teaches that these analogues possess one
or more modifications that would then lead to the disruption and/or termination of replication (see right column first paragraph page 5). Yates teaches that a combination of many different modifications to the nucleoside has led to the to the development of a wide array of potent nucleoside therapeutics, with complex structures (see right column first paragraph page 5). Yates teaches in Fig. 1 and shown below the sites for potential modifications to nucleoside analogous:
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Yates teaches several modification groups to various positions on the furanose ring of the nucleoside, and further teaches modifications to the 5’ hydroxyl group (see first paragraph under section “5’ Modifications” right column on page 14). Yates teaches that removal or replacement of the 5′-methylene group and/or 5′-hydroxyl group on the nucleoside analogue proved beneficial since these analogues could no longer be phosphorylated and further teaches the toxicity observed with parent analogues such as aristeromycin and neplanocin did not occur with these truncated analogues (see first paragraph under section “5’ Modifications” right column on page 14). Yates teaches that other researchers have also utilized 5’ modification to their advantage in order to decrease overall toxicity of various nucleoside analogues (see first paragraph under section “5’ Modifications” right column on page 14).
Yates also teaches prodrug strategies to improve bioavailability of nucleoside analogues by modifying the 5’ position as shown in Fig. 5 and below with a McGuidan ProTide structure:
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Yates teaches that nucleoside analogue R1479, like many nucleoside analogues, suffered from low bioavailability, and teaches the modification of a tri-isobutyl ester prodrug moiety as shown in Fig. 18 and shown below:
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Yates teaches that the tri-isobutyl ester prodrug moiety increased the antiviral activity compared to the parent analogue R1479 and was efficacious in clinical trials against HCV (see first paragraph left column page 13).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified compound 1 of WO’939 by attaching the isobutyl ester prodrug moiety as disclosed in Yates at the 5’-hydroxyl group position to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside compounds at the 5’ hydroxyl position and specifically teaches the attachment of a isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound to increases its antiviral activity, and WO’939 also teaches several modification groups to the same position. Therefore, an ordinary skilled artisan would have been motivated to modify the 5’hydroxyl group position in order to obtain the advantage of a prodrug form to increase the efficacy of the nucleoside analogue of WO’939.
In regards to instant claims 118 and 128, it would have also been prima facie obvious before the effective filing date of the claimed invention to have used the modified compound as disclosed by the combined teachings of WO’939 and Yates described above for treating a pneumoviridae virus infection. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because WO’939 provides guidance that their compounds are useful as antiviral agents for pneumoviridae virus infection.
Claim(s) 3, 11, 108, and 110-112 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015069939A1 (in IDS filed 08/18/2023) in view of Yates et al. (Antiviral Res., 2018 in PTO-892), as applied to claim 1 above, and further in view of US11541071B1 (in PTO-892, effective filing date of 12/16/2021).
The combined teachings of WO’939 and Yates are as described above and teach the compound recited in instant claim 1 as discussed above.
The combined references, however, do not recite wherein R1 and R2 are taken together to form -OC(O)O- or the compounds recited in instant claims 108, and 110-112.
US’071 teaches various antiviral nucleoside analogues for treating viral infections (see column 1 lines 14-15 and20-35). US’071 teaches that nucleoside analogues mimic endogenous nucleosides, exploiting cellular metabolism and becoming incorporated into both DNA and RNA, and that this property makes nucleoside analogues effective at inhibiting viral replication and stopping cancer cell proliferation (column 1 lines 20-35). US’071 teaches while a number of nucleoside analogues have been developed for the treatment of viral infections, there still exist a need for nucleoside analogues that are more effective in treating viral infections (column 1 lines 20-35). US’071 teaches the viral infection is caused by alphavirus, flavivirus, coronavirus, RSV, influenza virus, Powassan virus, ebola virus, or viruses of filoviridae, orthomyxoviridae, or paramyxoviridae (see column 93 lines 55-59).
US’071 demonstrates the modification of forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as well as the 5’ position alkyl group modifications recited in instant claims 108 and 110-112 shown below (column 139,column 249, and column 311 lines 55-65):
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It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound as disclosed by the combined teachings of WO’939 and Yates described above by forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as demonstrated in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 2’ and 3’ positions, WO’939 also teaches several modification groups to the same positions, and US’071 further demonstrates the specific formation of OC(O)O- at the 2’ and 3’ position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 2’ and 3’ modifications with a reasonable expectation of success.
In regards to instant claims 108 and 111-112, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl ester prodrug moiety as disclosed by the combined teachings of WO’939 and Yates described above with the ester moiety shown at the 5’hydroxl position in either the first, third, or fourth compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a similar isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar ester moieties at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claim 110, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety as disclosed by the combined teachings of WO’939 and Yates described above with the tert-butyl moiety of the second compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a similar isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar tert-butyl ester moiety at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
Claim(s) 67, 98, and 109 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015069939A1 (in IDS filed 08/18/2023) in view of Yates et al. (Antiviral Res., 2018 in PTO-892), as applied to claim 1 above, and further in view of US11638715B2 (in PTO-892, effective filing date of 06/14/2021).
The combined teachings of WO’939 and Yates are as described above and teach the compound recited in instant claim 1 as discussed above. Furthermore, Yates teaches the nucleoside analogue Ara-C, CNDAC, and the prodrug form Sapactiabine shown below in Fig 12:
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Here, Yates teaches the modification of the base in the Sapacitabine to form a prodrug of a parent nucleoside analogue.
The combined references, however, do not recite wherein R7 is 4-6 membered heterocyclyl containing 1, 2, or 3 O as well as the compound recited in instant claim 109.
US’715 teaches several orally-bioavailable nucleoside analogs useful for the treatment of coronavirus infections (see Abstract). US’715 teaches their compounds are also useful for treating other viral infections including Filviridae, Filoviridae, and among others (column 16 lines 6-26). US’715 teaches there is a need for new antiviral nucleoside with improved oral bioavailability for the treatment of coronavirus infections (column 18 lines 14-16). US’715 teaches in some embodiments, prodrugs that are formed using groups attached to functionality, eg. HO-, HS-, HOOC, NHR0, associated with the drug or active compounds, that cleave in vivo (column 293, lines 28-47). US’715 further teaches that prodrugs include but are not limited to carboxylate esters where the group is alkyl, aryl, aralkyl, acycloxyalkyl, alkoaxycarbonyloxyalkyl as well as esters of hydroxyl, thiol, and amines where the group attached is an acyl group, an alkoxycarbonyl, aminocarbonyl, phosphate, or sulfate (column 293, lines 28-47). US’715 teaches that their compounds are prodrugs themselves and are converted into other forms, including the biologically active compound form, when administered to a biological system (column 293 lines 44-47).
US’715 teaches the following compound 257 shown below on column 205:
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Here, compound 205 teaches a 6 membered heterocycyl containing 1 O that is also shown in the compound recited in instant claim 109.
US’715 also teaches compound 141 shown below:
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Here, compound 141 contains an ester moiety modification on the base.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety at the 5’ position as disclosed by the combined teachings of WO’939 and Yates described above with the 6 membered heterocycyl ring as demonstrated in compound 257 of US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ position with an ester prodrug moiety to improve efficacy of the parent nucleoside analogue, and US’715 further demonstrates the specific formation of a 6 membered heterocycyl ring ester moiety at the same 5’ position on similar antiviral nucleoside analogues that also functions as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ modification groups on the ester moiety with a reasonable expectation of success.
In regards to instant claim 98, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the base as disclosed by the combined teachings of WO’939 and Yates described above with the ester moiety shown above in compound 141 of US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds on the base to form prodrugs, and US’715 teaches similar ester moiety modification on the same base on similar antiviral nucleoside analogues that also functions as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of base modification groups to form prodrugs with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 9,388,208 in view of Yates et al. (Antiviral Res., 2018 in PTO-892), US11541071B1 (in PTO-892, effective filing date of 12/16/2021) and US11638715B2 (in PTO-892, effective filing date of 06/14/2021).
The claims of US’208 recite a compound of Formula (I) shown below:
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Here, R4 can be CN and among others, R1 is H or F, R3 and R6 is OH. R5 can be several groups as shown in claim 1. Claim 7 of US’208 recites a method of treating Pneumovirinae virus infection in a human, the method comprising administering to the human a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and Claim 9 recites a pharmaceutically acceptable excipient.
The difference between the claims of US’208 and the claimed invention is that US’208 does not recite the R1-3 modification groups as recited in the instant claims.
The independent teachings of Yates, US’071, and US’715 are as discussed above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 of US’208 by attaching the tri-isobutyl ester prodrug moiety as disclosed in Yates at the 5’-hydroxyl group position to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound to increases its antiviral activity, and US’208 also recites several modification groups to the same position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success and would have been motivated to do so in order to obtain the advantages of a prodrug form to increase the efficacy.
In regards to instant claims 3 and 11, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 as disclosed by the combination of US’208 and Yates described above by forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as demonstrated in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 2’ and 3’ positions, US’208 also recites several modification groups to the same positions, and US’071 further demonstrates the specific formation of OC(O)O- at the 2’ and 3’ position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 2’ and 3’ modifications with a reasonable expectation of success.
In regards to instant claims 108 and 111-112, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the tri-isobutyl ester prodrug moiety as disclosed by the combination of US’208 and Yates described above with the ester moiety shown at the 5’hydroxl position in either the first, third, or fourth compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar ester moieties at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claim 110, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety as disclosed by the combination of US’208 and Yates described above with the tert-butyl moiety of the second compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a similar isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar tert-butyl ester moiety at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claims 67 and 109, it would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety at the 5’ position as disclosed by the combination of US’208 and Yates described above with the 6 membered heterocycyl ring as demonstrated in US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ position to form prodrugs, US’208 also teaches several modification groups to the same positions, and US’715 further demonstrates the specific formation of a 6 membered heterocycyl ring at the same 5’ position on similar antiviral nucleoside analogues that also functions as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ modification groups on the ester moiety with a reasonable expectation of success.
In regards to instant claim 98, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the base as disclosed by the combination of US’208 and Yates described above with the ester moiety shown above in compound 141 of US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds on the base to form prodrugs, and US’715 teaches similar ester moieties at the same base on similar antiviral nucleoside analogues that also function as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of base modification groups to form prodrugs with a reasonable expectation of success.
Claims 1-3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,059,716 in view of Yates et al. (Antiviral Res., 2018 in PTO-892), US11541071B1 (in PTO-892, effective filing date of 12/16/2021) and US11638715B2 (in PTO-892, effective filing date of 06/14/2021).
The claims of US’716 recite a compound of Formula (I) shown below:
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Here, R4 can be CN and among others, R1 is H, R3 and R6 is OH. R5 can be several groups as shown in claim 1. Claim 15 of US’716 recites a method of treating Pneumovirinae virus infection in a human, the method comprising administering to the human a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and Claim 20 recites a pharmaceutically acceptable excipient.
The difference between the claims of US’716 and the claimed invention is that US’716 does not recite the R1-3 modification groups as recited in the instant claims.
The independent teachings of Yates, US’071, and US’715 are as discussed above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 of US’716 by attaching the tri-isobutyl ester prodrug moiety as disclosed in Yates at the 5’-hydroxyl group position to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound to increases its antiviral activity, and US’716 also recites several modification groups to the same position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success and would have been motivated to do so in order to obtain the advantages of a prodrug form to increase the efficacy.
In regards to instant claims 3 and 11, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 as disclosed by the combination of US’716 and Yates described above by forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as demonstrated in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 2’ and 3’ positions, US’716 also recites several modification groups to the same positions, and US’071 further demonstrates the specific formation of OC(O)O- at the 2’ and 3’ position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 2’ and 3’ modifications with a reasonable expectation of success.
In regards to instant claims 108 and 111-112, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the tri-isobutyl ester prodrug moiety as disclosed by the combination of US’716 and Yates described above with the ester moiety shown at the 5’hydroxl position in either the first, third, or fourth compound shown above in US’071to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar ester moieties at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claim 110, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety as disclosed by the combination of US’716 and Yates described above with the tert-butyl moiety of the second compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a similar isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar tert-butyl ester moiety at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claims 67 and 109, it would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety at the 5’ position as disclosed by the combination of US’716 and Yates described above with the 6 membered heterocycyl ring as demonstrated in US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ position to form prodrugs, US’716 also recites several modification groups to the same positions, and US’715 further demonstrates the specific formation of a 6 membered heterocycyl ring at the same 5’ position on similar antiviral nucleoside analogues that also functions as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ modification groups on the ester moiety with a reasonable expectation of success.
In regards to instant claim 98, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the base as disclosed by the combination of US’716 and Yates described above with the ester moiety shown above in compound 141 of US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds on the base to form prodrugs, and US’715 teaches similar ester moieties at the same base on similar antiviral nucleoside analogues that also function as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of base modification groups to form prodrugs with a reasonable expectation of success.
Claims 1-3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,377,761 in view of Yates et al. (Antiviral Res., 2018 in PTO-892), US11541071B1 (in PTO-892, effective filing date of 12/16/2021) and US11638715B2 (in PTO-892, effective filing date of 06/14/2021).
The claims of US’761 recite a compound of Formula (I) shown below:
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476
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Claims 2 and 4 of US’761 recite other 5’ position modification groups. Claim 9 of US’761 recites a method of treating Pneumovirinae virus infection in a human, the method comprising administering to the human a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.
The difference between the claims of US’761 and the claimed invention is that US’761 does not recite the R1-3 modification groups as recited in the instant claims.
The independent teachings of Yates, US’071, and US’715 are as discussed above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 of US’761 by attaching the tri-isobutyl ester prodrug moiety as disclosed in Yates at the 5’-hydroxyl group position to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound to increases its antiviral activity, and US’761 also recites several modification groups to the same position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success and would have been motivated to do so in order to obtain the advantages of a prodrug form to increase the efficacy.
In regards to instant claims 3 and 11, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 as disclosed by the combination of US’761 and Yates described above by forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as demonstrated in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 2’ and 3’ positions, US’761 also recites several modification groups to the same positions, and US’071 further demonstrates the specific formation of OC(O)O- at the 2’ and 3’ position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 2’ and 3’ modifications with a reasonable expectation of success.
In regards to instant claims 108 and 111-112, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the tri-isobutyl ester prodrug moiety as disclosed by the combination of US’761 and Yates described above with the ester moiety shown at the 5’hydroxl position in either the first, third, or fourth compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar ester moieties at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claim 110, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety as disclosed by the combination of US’761 and Yates described above with the tert-butyl moiety of the second compound shown above in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a similar isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound, and US’071 teaches similar tert-butyl ester moiety at the same 5’ hydroxyl group position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success.
In regards to instant claims 67 and 109, it would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the isobutyl moiety at the 5’ position as disclosed by the combination of US’761 and Yates described above by with the 6 membered heterocycyl ring as demonstrated in US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ position to form prodrugs, US’761 also teaches several modification groups to the same positions, and US’715 further demonstrates the specific formation of a 6 membered heterocycyl ring at the same 5’ position on similar antiviral nucleoside analogues that also function as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ modification groups on the ester moiety with a reasonable expectation of success.
In regards to instant claim 98, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the base as disclosed by the combination of US’761 and Yates described above with the ester moiety shown above in compound 141 of US’715 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success Yates provides guidance of modifying nucleoside analogous compounds on the base to form prodrugs, and US’715 teaches similar ester moieties at the same base on similar antiviral nucleoside analogues that also function as a prodrug. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of base modification groups to form prodrugs with a reasonable expectation of success.
Claims 1-3, 11, 14-15, 63-64, 67, 96, 98, 107-113, 118, and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-33 of copending Application No. 18/821,476 (‘476) in view of Yates et al. (Antiviral Res., 2018 in PTO-892), WO2015069939A1 (in IDS filed 08/18/2023), US11541071B1 (in PTO-892, effective filing date of 12/16/2021) and US11638715B2 (in PTO-892, effective filing date of 06/14/2021).
Claims 31-33 of ‘476 recite the following compounds:
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239
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183
243
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229
185
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The difference between the claims of ‘476 and the claimed invention is that ‘476 does not recite the R1-3 modification groups as recited in the instant claims.
The independent teachings of Yates, WO’939, US’071, and US’715 are as discussed above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 of ‘476 by attaching the tri-isobutyl ester prodrug moiety as disclosed in Yates at the 5’-hydroxyl group position to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 5’ hydroxyl position and specifically teaches the attachment of a tri-isobutyl ester prodrug moiety to the 5’ hydroxyl group position on a similar antiviral nucleoside analogue compound to increases its antiviral activity, and ‘476 also recites several modification groups to the same position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 5’ hydroxyl modification groups with a reasonable expectation of success and would have been motivated to do so in order to obtain the advantages of a prodrug form to increase the efficacy.
In regards to claims 118 and 128, it would have also been prima facie obvious before the effective filing date of the claimed invention to have used the modified compound as disclosed by the combination of ‘476 and Yates described above for treating a pneumoviridae virus infection. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because WO’939 provides guidance that their compounds are useful as antiviral agents for pneumoviridae virus infection. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions with a reasonable expectation of success.
In regards to instant claims 3 and 11, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified the compound 1 as disclosed by the combination of ‘476 and Yates described above by forming -OC(O)O- at the 2’ and 3’ position of the furanose ring as demonstrated in US’071 to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Yates provide guidance of modifying nucleoside analogous compounds at the 2’ and 3’ positions, ‘476 also recites several modification groups to the same positions, and US’071 further demonstrates the specific formation of OC(O)O- at the 2’ and 3’ position on similar antiviral nucleoside analogues. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of 2’ and 3’ modifications with a reasonable expectation of success.
In regards to instant claims 108 and 111-112, it would have also been prima facie obvious before the effective filing date of the claimed invention to have substituted the tri-isobutyl ester prodrug moiety as disclosed by the combination of ‘476 and Yates described above with the ester moiety shown at the 5’hydr