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 .1
Status of Claims
Claims 11-14 are pending, under examination and directed to treatment of a COVID-19 in a subject comprising administering a therapeutically effective amount of compound of I-1 as defined therein, i.e. with a species Compound BS of formula I-1 (see claim 13 and specification page 38, lines 10-11).
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Response to Arguments
Applicant's arguments filed April 20 2026 have been fully considered but they are not persuasive. Applicant’s amendment of claim 13 to overcome its rejection under 35 U.S.C. l 12(b), does not overcome the rejection. The claim remains indefinite as it was amended to depend from itself.
Applicant’s amendment to limit the subject in need to be one suffering from COVID-19 (a SARSCov2 viral infection) does not overcome the rejection of claims 11-13 for lack of full scope of enablement under 35 USC 112(1). See below rejection. Claim 14 was amended to be limited to Compound BS, however, it is not allowable (see below claim objection) because it depends from claims that remain rejected.
Claim Rejections - 35 USC § 112 (2nd Paragraph)
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.
Claim 13 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.
Dependent claim 13 depends from itself. Amendment of claim 13 to recite that it depends from claim 11 will overcome this rejection.
Claim Rejections - 35 USC § 112 - Enablement
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 11-13 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 the compound BS
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to treat COVID 19, does not reasonably provide enablement for the full scope of treat COVID-19 with the full scope of compounds of I-1 as presently claimed, beyond the species compound BS. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claim 11 is directed to a method for treating COVID-19, comprising administering to a subject in need thereof a therapeutically effective amount of a benzisoselenazole derivative of formula (I), or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof,
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wherein R is selected from hydrogen, cyano, hydroxyl, and halogen;
p is 0, 1, 2, 3, or 4;
L is selected from -(CH2)n-, -(CH2)n-O-(CH2)n-, -(CH2)n-S-S-(CH2)m-, -phenyl-(CH2)n-S(O)2-,and -(CH2)n-S(O)2-phenyl-; and
n is an integer from 0 to 12,
m is an integer from 0 to 12.
Claim 12 discloses
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Claim 13 discloses various individual compounds such as (Compound BS). Not included in this scope of enablement rejection is claim 14 limited to Compound BS.
Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set eight forth factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art:
The instant claimed invention is highly unpredictable since a person having ordinary skilled in the art (PHOSITA) recognizes that since the initial identification of the SARS-CoV2 virus in late 2019, the constant evolution of the virus lends to the unpredictability of the treatment of COVID-19. Colson conducted a large-scale genomic surveillance of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic. See Abstract, Colson et al.2 Noting the unpredictability and constantly evolving nature of COVID-19, Colson teaches their analysis recognized almost 62000 SARS-CoV-2 genomes that were sequenced to identify 22225 nucleotide mutations. Id.
Colson cautions with drug therapy of COVID-19, “adding a mutagenic agent can have unintended consequences including the creation of more dangerous SARS-CoV-2 mutants. . . . This evidence should lead us to reflect on the massive use of drugs with a mutagenic effect and on their possible role in selecting drug- resistant mutants but also particularly highly fit mutants and variants as was the case after the use of molnupiravir.” See page 8 column 1. Colson notes that molnupiravir
was associated with the emergence of viruses with mutations selected by the treatment in countries where it had been widely used such as in United States, whereas this was not observed in countries where it had not been used such as in France. . . . In practice, mutagens have an unpredictable effect on the emergence of new viruses and the idea that increasing mutations in a virus during a pandemic is gainful is not necessarily followed by confirmation. Id.
Therefore, the unpredictability of treating COVID-19, due to its ever evolving nature, is a Wands factor against the full scope of enablement of the claimed invention.
The breadth of the claims
The instant claims are broad since they claim any and all compounds of formula I-1 to treat COVID-19 in a subject in need.
Per claim 11, p is defined to be value of up to 4, resulting in compounds substituted at every phenyl ring position with cyano, hydroxyl and halogen, where at best the exemplified one or two substitutions on the phenyl rings.
Further, claim 11 broadly claims n is 0 to 12, which can result in methylenyl linkers up to 24 carbons in length between the two fused rings of formula I-1.
At best, per claim 13 and examples of the specification, Applicant merely exemplified as 12 carbon dodecalkylenyl chain. With regard to the -SO2-phenyl linker, or -S-S- linker between the rings of formula I-1, Applicant merely exemplifies either linker where n is 0 with -SO2-phenyl and at most n is 2, with the -S-S linker. There is no example of a linker with an oxygen moiety.
NOTE, this issue is further exacerbated by the absence of working examples elaborated below. The scope of the 17 species compounds of claim 13 is broader than the scope of 8 compounds of Table 8 of the specification that have demonstrated pharmacological activity. See below, where only Compound BS of claim 13 is demonstrated via working examples to have activity against SARS-CoV-2.
Therefore, the breadth of claims is a Wands factor against the full scope of enablement of the claimed invention.
The amount of direction or guidance presented, and the presence or absence of working examples: It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
Starting at page 35 line 3 of the specification, Biological Example 1 contains Table 9. Table 9 recites IC50 (µg/ml) date for 8 compounds of formula I-1 against a single strain of coronavirus, 2019-nCoV 3CLpro protein as therapeutic target.
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Note that the data of Table 9 to demonstrate an in vitro only fluorescence method screen system to determine activity against 2019-nCoV 3CLpro protein, is not enabling of the full scope of treating all coronaviruses with the full scope of compounds of formula I-1, or all of the species of claim 13.
Biological Example 2 starting at page 36, line 5 of the specification and Table A, note the cytotoxicity of compound BS to cells and inhibition of SARS-CoV2 virus.
See page 38, lines 13-22. While this working example is supportive of treatment of SARS-CoV2 (COVID 19) in a subject in need with compound BS, it does not support the full scope of treating all coronaviruses with the full scope of formula I-1 compounds.
Biological Example 3 starting at page 38, line 16 of the specification, details the cytotoxicity of compound BS (found in claim 13) details a pathological bleomycin induced model in mice, against a dexamethasone control. Tables 1 and 2 of Example 3 note changes in body of mice models (normal control, bleomycin administered model, dexamethasone and mice administered claimed compound BS). The specification states mice administered compound BS were said to be more active than the bleomycin-induced mouse models. See page 45, line 25. Further, in a mouse spleen and lung coefficient model, mice administered compound BS, were demonstrated to have better coefficients results suggesting amelioration of pulmonary (lung) inflammation and fibrosis, as well an inhibitory effect on spleen swelling in mice, when compared to dexamethasone. See page 47, line 25, bridging to page 48, line 12.
Biological Example 3, starting at page 48, line 25, notes after 24 hour and 7 day modeling of BS at certain doses, compound BS made significant improvements to pulmonary ventilation function and acid-base balance in pulmonary fibrosis model mice, in comparison to dexamethasone. See page 51, lines 4-7.
The specification’s Section 6.5, starting page 52, line 18, and Tables 10-11 state and demonstrate reductions of inhibitory effect on inflammatory cells (leucocytes, lymphocytes, monocytes and neutrophils) and proinflammatory factors (NF-KB, TNF-α, IL-1β, IL-2 and IL-6) compared to the positive drug Dex for pulmonary fibrosis. See also Sections 6.6-6.7 and Tables 12-14, noting hydroxyproline content in mouse longs and pulmonary fibrosis modeling with compounds BS.
With regard to the in vivo biological models of Example 3, while they are demonstrative of certain in vivo models of treatment, they are all limited specifically to compound BS and do not take place in coronavirus infected subjects.
The working examples (and lack thereof) are a Wands factor against the full scope of enablement of the claimed invention.
Therefore, in view of the Wands factors as discussed above, particularly the unpredictability of the state of the art, breadth of claims and lack of amount of direction or guidance presented, Applicant fails to enable the full scope of the invention as claimed.
Claim Objections
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion and Correspondence
In summary no claims are allowed. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a 371 of PCT/CN2021/104644 07/06/2021
FOREIGN APPLICATIONS
CHINA 202010373848.4 05/06/2020
2 Colson et al. Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic, Journal of Infection, Volume 88, Issue 5, 2024, 106150,
ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2024.106150.
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