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.
Election/Restrictions
Applicant cancelled claims 1-10 that were subject to the election of species requirement of Aug. 26, 2025. The cancellation of claims 1-10 mooted the previous requirement of invention/species, necessitating the withdrawal of the election requirement. Presently examined claims 11-14 are directed to the treatment of a coronavirus infection in a subject comprising administering a therapeutically effective amount of compound of I-1 as defined therein.
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The below Compound BS is determined to be representative of compounds of formula I-1.
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, which is claimed in claim 13.
This compound is disclosed in the specification as compound BS, at page 38, lines 10-11 and represented by the below structure.
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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.
Claim 13, line 1, recites the limitation that it depends from claim 1. Claim 1 has been canceled. There is insufficient antecedent basis for this limitation. 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 11-14 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 all coronavirus infections with the full scope of compounds of I-1 as presently claimed. 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 coronavirus infections, 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, or4;
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
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.
This species is a compound of formula I-1 where L is –(CH2)n-, where n is 4.
Claim 14 is directed to the method of claim 11, wherein the infection caused by coronaviruses is coronavirus disease 2019 (COVID-19).
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 differences among the coronaviruses, results in unpredictability in the art. More specifically, with regard to SARS-CoV versus SARS-CoV2 viruses, in particular the main protease coronavirus target Mpro 3CLpro protein of both, despite any similarities, there is a known difference in treatment approaches due to different inhibitory effects on the Mpro protein. Lata and Akif2 teach
The main protease Mpro, 3CLpro is an important target from coronaviruses. In spite of having 96% sequence identity among Mpros from SARS-CoV-1 and SARS-CoV-2; the inhibitors used to block the activity of SARS-CoV-1 Mpro so far, were found to have differential inhibitory effect on Mpro of SARS-CoV-2. The possible reason could be due to the difference of few amino acids among the peptidases. See abstract.
Therefore, the unpredictability of treating all coronaviruses with the same agent or agents purported to inhibit the main protease Mpro, 3CLpro coronavirus target, used to block Mpro activity in SARS CoV were found to have a different inhibitory effect on Mpro of SARS CoV2.
The unpredictability of the art in the field of treating coronaviruses 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 the full scope of any coronavirus.
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.
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.
Conclusion and Correspondence
No claims are allowed. 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 Lata and Akif, Comparative protein structure network analysis on 3CLpro from SARS-CoV-1 and SARS-CoV-2 Proteins: Structure, Function, and Bioinformatics Volume 89, Issue 9 pp. 1216-1225 13 May 2021