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 3, 12, 13, 16, 22, 26, 29, 33-36, 38-41, 43, 44, 50-51, 53-54, 56 and 77 are pending in the application. Preliminary amendment filed 05 May 2026.
Priority
This application claims the benefit of 63/499,166 filed 04/28/2023.
The parent application 63/499,166 to which priority is claimed is seen to provide adequate support under 35 U.S.C. 112 for claims 3, 12, 13, 16, 22, 26, 29, 33-36, 38-41, 43, 44, 50-51, 53-54, 56 and 77 of this application.
Claim Objections
Claims 12, 13, 16, 22, 26, 29, 33-36, 38-41, 43, 44, 50-51, 53-54, 56 are objected to because of the following informalities: Claims 12, 13, 16, 22, 26, 29, 33-36, 38 recite ‘the compound of claim 1’. Claim 1 has been canceled. Claim 39 also recites ‘the compound of any one of claim 1’ which is confusing. Claims 12, 13, 16, 22, 26, 29, 33-36, 38 are examined as drawn to a compound of claim 3, and claims 39 -41, 43, 44, 50-51, 53-54, 56 are examined as drawn to a method of treating a viral infection in a human by administering to the human any one of the compounds of claim 3. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 39-41, 43-44, 50-51, 53-54, and 56 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating a viral infection using any one of the compounds of formula Ia in claim 3, or a pharmaceutically acceptable salt thereof, does not reasonably provide enablement for the prevention of a viral infection as in claim 39 and dependents thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the factors below, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
(A) The breadth of the claims
(B) The level of one of ordinary skill
(C) The amount of direction provided by the inventor
(D) The existence of working examples
(E) The level of predictability in the art
(F) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the Invention
Claims 39 and dependents thereof are drawn to a method of treating or preventing a viral infection in a human via administration to the human any one of the compounds of claim 3. Claim 39 recites compound of claim 1. Claim 1 has been canceled. Claim 41 recites prophylactic agent.
The breadth of the claims
The instant claims are drawn to prevention of a viral infection in a human. According to the definition of prevention at para 0063, prevention encompasses administration of a compound or a pharmaceutically acceptable salt according to the embodiments disclosed herein pre- or post-exposure of the individual to a virus. Prevention also encompasses absolute prevention.
According to American Heritage Dictionary of the English Language, Prophylaxis is prevention of or protective treatment for disease. Therefore, a prophylactic agent is one that prevents a subject from getting infected by a virus.
Any therapy that merely reduces the number or severity of symptoms, or which is effective for a period shorter than the subject’s lifespan is considered to be ineffective at preventing an infection. In general, preventing diseases/disorders linked to an outside stimulus or insult is not possible as any so-called preventive effects of a drug therapy are expected to cease when the drug is cleared from the patient’s system. More generally, prevention of any viral infection in the sense being used herein is not a recognized clinical outcome in the art, as no treatment is perfectly effective.
The amount of direction provided by the inventor
The specification (at page 1) teaches that the present disclosure also provides compounds with combined solubility, stability and permeability properties leading to improved oral bioavailability. No guidance is given suggesting any reason to believe that the administration of the claimed compounds will achieve prevention against a viral infection.
The existence of working examples
Working example A set forth at page 157 in the instant specification is drawn to an assay using A549-hACE2 cell lines and the instant compounds. The examples show the reduction in cell viability of the compounds on SARS-CoV2, and RSV NHBE, which indicates treatment. There are no examples to show that the claimed compounds can prevent a viral infection. There are no correlative prior art procedures disclosed either.
The level of Predictability in the Art
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427.2d 833, 166 USPQ (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary to satisfy the statute.
“Preventing” as recited in the instant claims, is interpreted to mean the complete and total blocking of all symptoms of a disease/disorder (viral infection in the instant case) for an indefinite period of time. Prevention is seen to include the administration of the said compounds to a healthy mammal, and subsequent exposure to conditions that would cause a viral infection wherein the said compounds prevent said exposure from manifesting itself in said mammal so exposed. Any therapy which merely reduces the number or severity of symptoms, or which is effective for a period shorter than the subject’s remaining lifespan, is considered to be ineffective at preventing an infection. In general, preventing an infection linked to an outside stimulus or insult according to the definition of prevention given above is not possible as any so-called preventive effects of a drug therapy are expected to cease when the drug is cleared from the patient’s system. More generally, prevention of a viral infection in the sense being used herein is not a recognized clinical outcome in the art, as no treatment is perfectly effective.
According to the Merck Manual (16th Ed., 1992, pages 183-189) viral infections are also of different types and etiology and require specific therapy. The prior art therefore appears to be silent regarding methods of prevention of a viral infection using a single drug or a particular type of drug as recognized by skilled artisans in the field.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
In view of the information set forth, the instant disclosure is not seen to be sufficient for the method of prevention of a viral infection as recited in the instant claims. One of ordinary skill in the art would have to carry out undue experimentation to practice the instant invention. Thus, the specification fails to provide sufficient support of the broad use of the compounds for treating a viral infection as encompassed by the recitation in the instant claims.
Therefore, in view of the Wands factor and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test the instant compounds for preventive effects against a viral infection in a human as in the instant claims, with no assurance of success.
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) 3, 12, 13, 16, 22, 26, 29, 33-36, 38-41, 43, 44, 50-51, 53-54, 56 and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Gupta et al (WO 2024/076951 A2; priority to 63/412.961 filed 04 October 2022; cited in IDS filed 08/15/2024) in view of Chun et al (WO 2022/047065; cited in IDS filed 08/15/2024).
Gupta’s invention provides compounds of formula (IV) wherein X1 and X2 are CH2, and X1 and X2 are O. R1 can be H, -C(=O)(C1-C6)alkyl, -C(=O)CH2Ph, and m and n are 2, 3 or 6 (paras 035, 0038-0041, 0044-0048; page 71, Table 1, compound #1; limitations of claims 3, 12, 16, 22, 26, 29, 33, part of the limitations of claim 35 and 77). When X1 and X2 are O it reads on part of the limitations of claim 3 for R being -C(=O)OR11, and reads on the substitution at the C5’ position of the ribose as in claims 12, 13 and 35. Gupta also teaches some of the substitutions and alkenyl groups as in instant claims 3, 12, 13, 16, 26, 33, 34, 35 and 77 (See page 71, Table 1, compound #’s 2, 4, 6, 8, 13 and 14-double bonds, heteroatom substitution in the chain linking the two carbonyl groups, carbonate linkage, amino substituted ester).
Gupta teaches pharmaceutical compositions of its compounds with a pharmaceutically acceptable excipient (para 0070; page 105, claim 50 of Gupta; as in instant claim 36. Gupta teaches a method of treating a viral infection in a subject in need thereof comprising administering a therapeutically effective amount of a compound of tis embodiment or administering a pharmaceutical composition (para 0078; method of instant claim 39).
The compounds of Gupta can be used in combination with one or more additional therapeutic agents (paras 00132-0244; method as in claim 41). The viral infection that can be treated include coronavirus, SARS-CoV-2 and MERS-CoV infections (page 106, claims 58-60 of Gupta; as in instant claims 43, 50 and 51). One of the embodiments is the treatment of respiratory syncytial virus (para 0077; as in claims 53-54).
Gupta et al does not expressly teach compounds of formula Ia, Ib and Ic wherein L is 2 through 6 -CH2- groups linking the two carbonyl groups in the above compounds and some of the substitutions as in claims 3,12, 13 and 35, does not teach the limitations of claims 38, 40, 44 and 56.
The invention of Chun et al deals with compounds and methods for treating viral infections (Abstract). The compounds have formula I or a pharmaceutically acceptable salt thereof having various substitutions (page 1, para 003-007; page 18, paras 0077-0078, 0080-0129; part of the limitations of claims 3, 12, 13, 16, 22, 26, 29, 33-35). The invention includes pharmaceutical compositions, for example tablets with excipients and formulated for oral and injectable administration (para 0131, 0134, 0148, 0155, 0165; as in claims 36, 38 and 40). The compounds are used in a method of treatment of pneumoviridae, RSV, picornaviridae, Flaviviridae, SARS-CoV-2, MERS infections (paras 0195-0213; as in claims 39, 43, 50, 51-54 and 56).
Chun et al does not teach compounds that have an alky chain linking the two carbonyl groups as in the instant compounds. However, from the teachings of Gupta and Chun, it can be seen that the artisan can arrive at the instant compounds and use them in a method of treating a viral infection in a human. It would be obvious to the artisan to use the compounds in a method of treating zoonotic coronavirus infection as in claim 44. The artisan would also make the compounds having all of the claimed substitutions in view of the combined teachings of Gupta and Chun.
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, compounds having the claimed structural features are known in the art for treating various viral infections. Thus, it is obvious to arrive at the claimed compounds since they are all analogs of the compounds of Gupta, and such compounds are known to be used for treating several viral infections in humans including the ones treated in the instant method.
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.
Obviousness based on similarity of structure and function entails motivation to make the claimed compound in expectation that compounds similar in structure will have similar properties. Where prior art compound essentially brackets the claimed compounds and are well known antiviral agents, one of ordinary skill in the art would be motivated to make the claimed compounds in searching for new antiviral agents. In re Payne, 606 F. 2d 303, 203, USPQ, 245, 254-55 (C.C.P.A. 1979).
Therefore, one of ordinary skill in the art would have reasonably expected that the instant compounds, would have same or substantially similar beneficial therapeutic effects and usefulness in methods for treating viral infections, based on the reasonable expectation that structurally similar species usually have similar properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also Deuel, 51 F.3d at 1558, 34 USPQ2d at 1214, and if the claimed invention and the structurally similar prior art species share any useful property, that will generally be sufficient to motivate an artisan of ordinary skill to make the claimed species. In fact, similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904, as noted in MPEP 2144.
Conclusion
Pending claims 3, 12, 13, 16, 22, 26, 29, 33-36, 38-41, 43, 44, 50-51, 53-54, 56 and 77 are rejected.
Claims 1-2, 4-11, 14-15, 17-21, , 23-25, 27-28, 30-32, , 37, 42, 45-49, 52 and 57-76 have been canceled.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHY KRISHNAN whose telephone number is (571)272-0654. The examiner can normally be reached M-F 8.30am-5pm.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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