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 .
Claims 11-23 are pending in the application. Claims 1-10 have been canceled. Preliminary amendment filed 25 June 2024.
Priority
This application is a 371 of PCT/CN2022/084724 filed 04/01/2022. This application claims foreign priority to CHINA 202210134422.2 filed 02/14/2022, under 35 U.S.C. 119(a)-(d). The certified copy of the priority document has been filed in the instant application.
Claim Objections
Claim 16 is objected to because of the following informalities: In claim 16, at line 1, the term administer should be reworded as ‘administering to’. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 11-23 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al (Cell Research, January 20, 2022, 30, 322-324; cited in IDS filed 06/24/2025) in view of Painter et al (US 2021/0252033 A1), and further in view of Dampalla et al (PNAS, 2021, 118(29), 1-8; cited in IDS filed 06/24/2025).
Li et al teaches that when cells inoculated with SARS-CoV-2 virus and treated with molnupiravir there was a potent dose-dependent inhibition of viral replication based on qRT-PCR quantification. Complete inhibition was achieved at 10mM and higher concentrations (page 1, left col., second full para; method as in claim 16; type of infection as in claims 19-21). Molnupiravir is the second structural formula (the N-hydroxy cytidine derivative) recited in claims 11 and 16 without the deuterium substitution. Nirmatrelvir, which is the key component of Paxlovid, inhibits the main protease of SARS-CoV-2 (page 1, first full para; method of claim 16, type of infections recited in claims 19-21). Nirmatrelvir is the first structural formula recited in claims 11 and 16 without the deuterium substitution. Synergistic activity was observed when a combination of both the active agents was used (page 3, left col., first para).
Li et al does not expressly teach a pharmaceutical composition comprising the deuterated compounds as in claim 11 and their use in the method of treatment as in claim 16, and the limitations of claims 12-15, and 17-23.
Painter et al’s invention relates to N-hydroxycytidine derivatives of formula I, combinations and pharmaceutical compositions, and method of use in treating viral infections like human coronavirus, SARS, MERS or 2019-nCoV infections (paras 0006-0012; 0072-0094):
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Formula I also includes the compound wherein X is CD2, R1 is R6C(=O)- wherein R6 is alkyl (includes isopropyl group as in the second formula in claims 11 and 16), and R2=R3=R4=R5 =H. The compound can also be in the form of a salt, prodrug (para 0041; as in claims 11, 16). The pharmaceutical compositions comprise pharmaceutically acceptable carriers, salts, prodrugs, diluents, binders, lubricants, disintegrants, colorants, stabilizers, and fillers (paras 0319-0336; as in claims 14-15 and 22-23). Another embodiment of the invention is the compounds and the pharmaceutical compositions can be administered in combination with another antiviral (para 0360). Painter also reaches deuterium substitution of the ribose ring (see formulas disclosed at page 37).
Even though Painter does not expressly teach the N-hydroxy cytidine derivative having only one deuterium substitution as in claims 11 and 16, it would be obvious to the artisan to use the compound having the second structural formula with a single deuterium substitution to make a composition and use it in the claimed method of treatment.
Dampalla et al teaches that the 3CL protease is a virus protease encoded by SARS-CoV-2, which is essential for virus replication (Abstract), and make them attractive targets for drug development. In addition to development of vaccines, the concurrent identification of FDA approved drugs that can be repurposed for use against SARS-CoV-2 may accelerate development and implementation of effective counter measures against the virus. For this purpose, Dampalla has synthesized and evaluated deuterated GC376 variants which have enhanced antiviral activity and display efficacy in mouse model of SARS-CoV-2 (page 2, left col, second and third full paras). Compounds 3, 4, 8 and 11 had significantly increased IC50 values (page 2, right col., Table 1 and para below Table 1). The structural formula below the letter B in Table 1 has part of the structural features seen in the first structural formula in claims 11 and 16. The instant active agents are also 3CL protease inhibitors. Therefore, in view of this teaching of Dampalla and that of Painter, one of ordinary skill in the art would have been motivated to deuterate the compounds of Li et al, which are compounds recited in instant claims 11 and 16. The artisan would be motivated to perform adjustments of the site of deuteration in the instant compounds since Painter teaches cytidine derivative with deuteration of the same site as in the second compound in in instant claims 11 and 16, and also deuteration of the ribose ring. This teaching and the teaching that other drugs can be repurposed for use against SARS-CoV-2 will motivate the artisan to make and use the instant compounds, their pharmaceutical compositions and use them in the claimed method of treatment.
Painter teaches unit dosages for its compounds (para 0325). In view of this and the suggestion for a combination treatment for viral infections, the artisan can adjust the amounts as in claims 12-13, and provide the composition in the form of a single dosage unit or as separate dosing units as in claims 17-18.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, deuterated compounds of N-hydroxy cytidine and the other compound as instantly claimed have been suggested in the prior art for treatment of viral infections since they have shown enhanced inhibitory activity. Thus, it is obvious to arrive at the instant compounds, their compositions and use them in the claimed method of treatment.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Product and method improvement is the motivation. Both compounds recited in the instant claims are known in the art for treating viral infections like SARS-CoV-2. Deuterated N-hydroxy cytidine is also suggested for such a treatment. Therefore, one of ordinary skill in the art will be motivated to make the deuterated form of the both compounds taught by Li and their compositions and use them in the claimed method of treatment. The artisan will be motivated to look for other compounds with enhanced activity against the SARS-CoV-2 virus and other related viral infections. The artisan will also use the claimed compounds in a method of treating the other infection recited in claims 19-20. There is a reasonable expectation of success for the same.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
The USPTO Internet website contains Terminal Disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 11-23 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 14-20 and 22-28 of copending Application No. 18/699,969 (‘969) in view of Li et al (Cell Research, January 20, 2022, 30, 322-324; cited in IDS filed 06/24/2025) and further in view of Painter et al (US 2021/0252033 A1) and Dampalla et al (PNAS, 2021, 118(29), 1-8; cited in IDS filed 06/24/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 11 is drawn to a pharmaceutical composition comprising two compounds having the recited structural formulas. Claim 16 is drawn to a method of treating a viral infection in a patient comprising administering the above compounds. Dependent claims 12-16 and 17-23 recite limitations drawn to weight ratio of the two compounds, inclusion of carriers, administration of the two compounds as a single and two separate dosing units, specific viral infections treated.
The copending claims of ‘’969 are drawn to a deuterated cyanide containing compound which is the same as the second formula in instant claims 11 and 16, their pharmaceutical compositions, carrier, method of treating a viral infection in a human and inclusion of the use of another antiviral drug. There is considerable overlap between the instant claims and those of ‘969.
The copending claims of ‘969 differ from the instant claims in that the instant claims are drawn to the use of two compounds whereas ‘969 uses only one.
The teachings of the secondary references are set forth above.
Although the claims of ‘969 teach the use of only one compound, one of ordinary skill in the art would readily recognize that the teachings of ‘969 can be modified in view of the teachings of secondary references to arrive at the instant invention.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Product and method improvement is the motivation. Both compounds recited in the instant claims are known in the art for treating viral infections like SARS-CoV-2. Deuterated N-hydroxy cytidine is also suggested for such a treatment. Therefore, one of ordinary skill in the art will be motivated to make the deuterated form of the both compounds taught by Li and their compositions and use them in the claimed method of treatment. The artisan will be motivated to look for other compounds with enhanced activity against the SARS-CoV-2 virus and other related viral infections.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
1. Pending claims 11-23 are rejected.
2. Claims 1-10 have been canceled.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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