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 is a 371 of PCT/US2022/022332 filed on 03/29/2022 and claims domestic benefit to US provisional application no. 63/308,435 filed on 02/09/2022 and US provisional application no. 63/167,292 filed on 03/29/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/25/2024 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 09/25/2024 is acknowledged. Claims 1, 3, 20-23, 27, 30, 34-37, and 41 are amended. Claims 4-19, 24-26, 31-33, and 38-40 are cancelled.
Accordingly, claims 1-3, 20-23, 27-30, 34-37, and 41-43 are pending and being examined on the merits herein.
Claim Rejections - 35 USC § 112
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 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating SARS-CoV-2 infection, SARS-CoV-2 infection associated disease or disorder, and partially preventing developing and/or progression of acute respiratory distress syndrome, does not reasonably provide enablement for complete prevention of SARS-CoV-2 infection, SARS-CoV-2 infection associated disease or disorder, or developing / progression of acute respiratory distress syndrome. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples, and
8) The quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, the breadth of the claims, and relative skill level
The invention relates to a method of treating or preventing a SARS-CoV-2 infection or a SARS-CoV-2 infection associated disease or disorder as recited in instant claim 1 as well as further preventing a patient from developing or the progression of acute respiratory distress syndrome as recited in instant claims 36-37 comprising administering the compound of Formula II seen in instant claim 1.
The claims are broad in that they encompass the prevention of SARS-CoV-2 infection and the associated conditions in a subject in need thereof.
The instant specification recites “As used herein, the term “prevent,” “prevention,” or “preventing” refers to any method to partially or completely prevent or delay the onset of one or more signs, symptoms or features of a disease, disorder, and/or condition.” (see paragraph 0070 on page 22).
Therefore, the terms “prevention” or "prevent" are thus interpreted to mean completely preventing one or more signs, symptoms or features of a disease, disorder, and/or condition, indicating that onset never occurs. Furthermore, according to Institute for International Medical Education (IIME, reference included with PTO-892), “prevention” or “prevent” is defined as promoting health, preserving health, and to restore health when it is impaired, and to minimize suffering and distress (see page 16, “Prevention”). IIME further states that “Primary prevention refers to the protection of health by personal and community wide effects, such as preserving good nutritional status, physical fitness, and emotional well-being, immunizing against infectious diseases, and making the environment safe. Secondary prevention can be defined as the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health. Tertiary prevention consists of the measures available to reduce or eliminate long-term”.
The relative skill of those in the art is high, that of an MD or PHD, someone with experience in the recited conditions.
The amount of direction or guidance provided and the presence or absence of working examples
Applicant demonstrates in the Examples (1-7) the in vitro and in vivo antiviral efficacy of the recited compound. Specifically, Applicant demonstrates in Example 7 (paragraphs 343-349) that 5 mg delivery of the recited compound administered three times daily, initiated 8 hours prior to infection with SARS-CoV-2, in a mouse model significantly reduced viral RNA (nsp4) and viral titer in the lung (see paragraph 349, FIG. 8A and FIG 8B).
However, the instant disclosure does not identify a method that could be used by one of ordinary skill in the art to determine that a subject would have predictably developed SARS-CoV-2 without the claimed methods in order to establish that such recited conditions were prevented.
The described example suggests that the recited compounds were effective in treating SARS-CoV-2 and related conditions. However, the example does not demonstrate complete prevention of the recited conditions or a predictable method to identify patients who would have developed the recited conditions.
The state and predictability of the art
There are no art recognized methods that could be used to establish that SARS-CoV-2 and its related conditions were prevented using therapeutic treatment or to identify patients who would predictably develop the recited diseases in order to predictably identify that prevention was achieved using therapeutic approaches. Rather, the art indicates that the recited diseases were not predictable.
Galbadage et al. (in PTO-892) discloses that COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has propagated differently among select nations. Galbadage et al. discloses that this raises questions on whether a full scientific understanding of disease transmission modes has yet to be attained, and thus whether there are more effective ways to prevent its spread (see page 1, first and second paragraph). Galbadage et al. discloses there are no current cures or vaccines for SARS-CoV-2 (see page 3 right column), and further illustrates in Figure 1 (page 2) the different potential modes of transmission of COVID-19.
The teachings of Galbadage demonstrate that complete prevention of SARS-CoV-2 is not predictable due to an incomplete understanding in how this condition spreads and thus difficulties to develop more effective methods to prevent transmission. Furthermore, Galbadage discloses several different modes of transmission, which suggests no predictable method to determine how a patient would develop SARS-CoV-2. Therefore, the complete preventative application against the recited conditions using the recited composition is highly unpredictable in the arts because there was no art recognized method of determining whether a patient would predictably have developed SARS-CoV-2 and, therefore, there is no predictable way to determine that the recited conditions were prevented using the claimed method.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of a predictable method to identify patients who would develop SARS-CoV-2 without treatment, one of ordinary skilled in the art would not be able to predictably use the claimed agent to prevent the recited conditions. Furthermore, the quantity of experimentation to develop a method that could be used to prevent SARS-CoV-2 would be undue because a method to predictably identify a patient who would get the recited conditions does not exist and as described above, one of ordinary skill would have to further develop this method such that the recited method could then be used as a preventative measure against the recited conditions. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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) 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected under 35 U.S.C. 103 as being unpatentable over Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
Zandi teaches the repurposing of nucleoside analogs for the treatment of COVID-19 caused by severe acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see Abstract).
Zandi teaches that SARS-CoV-2 is an enveloped virus with a positive-sense single-stranded RNA genome (see first paragraph on page 1), and further teaches that one of the main druggable targets for coronaviruses (including SARS-CoV-2) is the RNA-dependent RNA polymerase (RdRp) (see second paragraph on page 1). Zandi teaches that this viral polymerase displays similar catalytic mechanisms and some key conserved amino acids in the active site among various positive-sense RNA viruses, and further teaches that nucleoside analogs are a well-established class of antiviral agents for treatment of many human viruses, which include emtricitabine (FTC; HIV-1/HBV [hepatitis B virus]), lamivudine (3TC; HIV-1/HBV), tenofovir disoproxil fumarate (TDF; HIV-1/HBV), tenofovir alafenamide (TAF; HIV/HBV), entecavir (HBV), telbivudine (HBV), and sofosbuvir (HCV [hepatitis C virus]) (see second paragraph on page 1).
Zandi evaluated a defined library of compounds consisting of approved and experimental antiviral nucleoside analogs for their potential in vitro antiviral activity against SARS-CoV-2 and HCoV-OC43 (see third paragraph on page 1), and further shows the structures of the nucleoside analogs tested in Fig. 1 (page 2). Zandi demonstrates in Table 2 on page 4 that compounds 1-3 and 11 along with positive controls (compounds 10 and 17) yielded strong inhibitory effect (>90% virus-yield decrease) from a nontoxic single dose against in vitro replication of SARS-CoV-2 (see last paragraph on page 3).
The difference between Zandi and the claimed invention is that Zandi does not disclose the recited nucleoside compounds of the instant invention.
Townsend teaches pyrrolopyrimidine nucleoside analogs and pharmaceutical compositions thereof as well as methods of treating viral infection and/or viral infection-associated disease or disorder using their compounds.
Townsend teaches their compounds are of Formula II shown below (paragraph 0009):
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471
844
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Townsend teaches several species of the Formula II compound (paragraph 00221) as well as a triphosphate form (Compound 1-TP) (paragraph 0098) shown below:
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758
997
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393
1280
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509
1111
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Here, the above compound 1 and 4 of Townsend is a compound recited in the instant claims, as seen in instant claims 2 and 3 (third compound), and the above compound 1-TP (triphosphate) of Townsend meets the limitation of the active metabolite triphosphate analog recited in instants claims 42-43.
Townsend teaches their compounds are useful for treating various DNA and RNA viruses including norovirus, RSV, hepatitis B and C (HBV and HCV), and among others (see paragraphs 00138-00139). Townsend teaches their compounds can be administered via inhalation or intranasally (paragraph 00187), and further teaches that for administration by inhalation, their compounds are delivered in an aerosol spray such as a nebulizer (paragraph 0189). Townsend also discloses pharmaceutical compositions comprising their compounds with the same routes of administration (paragraph 00191). Townsend teaches that their compounds can be combined with a pharmaceutically acceptable carrier (paragraph 00115). Townsend teaches that their compounds can be administered in combination with an additional antiviral agent (paragraph 00206) as well as with one or more compounds including corticosteroids and among others (paragraph 00207). Townsend discloses metabolites of their compounds (paragraph 0073) as well as prodrug forms of their compounds, which upon in vivo administration, the prodrug is chemically converted to the the biologically, pharmaceutically or therapeutically more active form (paragraph 0068).
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the nucleoside analogs disclosed in Zandi with the nucleoside compounds such as compound 1, 4, or 1-TP disclosed in Townsend for treating COVID-19 caused by SARS-CoV-2. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2, and Townsend discloses several nucleoside analog derivatives that are effective for treating RNA viruses such as RSV, HBV, and HCV. Therefore, an ordinary skilled artisan would have found it obvious to substitute the nucleoside compounds of Zandi with the nucleoside compounds of Townsend for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combined teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combined teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form of the compounds in Townsend, which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combined teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 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, 20-23, 27-30, 34-37, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9,708,359 (‘359) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘359 recite pyrrolopyrimidine nucleosides with a Formula IB structure as shown in claim 1 of ‘359 and further recite a method of treating a viral infection using these nucleoside compounds in claim 21 of ‘359.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘359 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘359 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims that are all useful for the same purpose of treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘359 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘359 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘359 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 with a reasonable expectation of success.
Claims 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 9,701,706 (‘706) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘706 recite pyrrolopyrimidine nucleosides with a Formula II structure as shown in claim 1 of ‘706 and further recite a method of treating a viral infection using these nucleoside compounds in claim 29 of ‘706.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘706 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘706 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims that are all useful for the same purpose of treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘706 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘706 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘706 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 with a reasonable expectation of success.
Claims 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,407,457 (‘457) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘457 recite pyrrolopyrimidine nucleosides with a Formula IB structure as shown in claim 1 of ‘457 and further recite a method of reducing a viral infection using these nucleoside compounds in claim 12 of ‘457.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘457 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘457 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims that are all useful for the same purpose of treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘457 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘457 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘457 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 with a reasonable expectation of success.
Claims 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,941,175 (‘175) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘175 recite pyrrolopyrimidine nucleosides with a formula structure as shown in claim 1 of ‘175 and further recite a method of treating a viral infection using these nucleoside compounds in claim 11 of ‘175.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘175 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘175 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims that are all useful for the same purpose of treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘175 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘175 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘175 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 with a reasonable expectation of success.
Claims 1-3, 20-23, 27-30, 34-37, and 41-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,981,700 (‘700) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘700 recite pyrrolopyrimidine nucleosides as shown in claim 1 of ‘700.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘175 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘700 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims for treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘700 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘700 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘700 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of treating RNA viruses using metabolite forms such as triphosphate of the instant compound as well as forming these active metabolites from a prodrug upon in vivo administration. Therefore, an ordinary skilled artisan could have predictably considered administering an active metabolite by in vivo formation for treating SARS-CoV-2 with a reasonable expectation of success.
Claims 1-3, 20-23, 27-30, 34-37, and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/609,391 (‘391) in view of Zandi et al. (Antimicrobial agents and chemotherapy, 2020 in PTO-892) in view of Townsend et al. (WO2017024310A1 in IDS filed 09/25/2024).
The claims of ‘391 recite pyrrolopyrimidine nucleosides as shown in claim 1 of ‘391.
These pyrrolopyrimidine nucleosides have the same nucleobase structure and overlapping moieties as the instant invention. However, the claims of ‘391 do not recite the compounds of the instant invention for treating SARS-CoV-2.
The independent teachings of Zandi and Townsend are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have arrived at the instant compounds from the claims of ‘391 with guidance from Townsend and further use these compounds for treating SARS-CoV-2 as suggested in Zandi. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provides guidance of the same base pyrrolopyrimidine nucleoside structure as well as guidance for the specific species recited in the instant claims for treating RNA viral infection. Therefore, an ordinary skilled artisan could have predictably arrived at the instant compounds with a reasonable expectation of success. Furthermore, Zandi provides guidance of repurposing known antiviral nucleoside analogs for treating SARS-CoV-2. Therefore, an ordinary skilled artisan would have also found it obvious to substitute these nucleoside compounds for treating SARS-CoV-2 and would have a reasonable expectation of success based on Zandi demonstrating antiviral efficacy for SARS-CoV-2 for similar antiviral nucleoside analogs with same known uses such as treating RSV, HBV, and HCV.
In regards to instant claims 20-23 and 27-30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared a pharmaceutical composition as taught in Townsend for the nucleoside compounds as disclosed by the combination of the claims of ‘391 and the teachings of Zandi and Townsend described above and further administer by intranasal or inhalation via nebulizer as taught in Townsend to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Townsend provide guidance for preparing pharmaceutical compositions of antiviral nucleoside analog compounds as well as administering these nucleoside compounds by intranasal or inhalation.
In regards to instant claims 34-35, it would have also been prima facie obvious before the effective filing date of the claimed invention to have further co-administered an additional agent such as a corticosteroid as taught in Townsend with the nucleoside compounds as disclosed by the combination of the claims of ‘391 and the teachings of Zandi and Townsend described above 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 Townsend provides guidance of effectively co-administering antiviral nucleoside analogs with additional agents for treating RNA viruses. Therefore, an ordinary skilled artisan could have predictably considered co-administration for treating SARS-CoV-2 with a reasonable expectation of success.
In regards to instant claim 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered a prodrug form which would convert to an active metabolite by in vivo formation as disclosed in Townsend for the nucleoside compound as disclosed by the combination of the claims of ‘