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 .
Claims Status
Claims 1-22 are pending.
Claims 2, and 6-7, 10 are amended.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-13) in the reply filed on 04/10/2026 is acknowledged.
Applicant’s election without traverse of the following species:
Species Group I: Iodonitrotetrazolium as the tetrazolium compound
Species Group II: polynucleotide as the substrate
Species Group III: NADP+ as the electron transfer mediator
Species Group IV: bacterial enzyme as the supporting enzyme
in the reply filed on 04/10/2026 is acknowledged.
Claims 14-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/10/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/11/2024 is acknowledged. The submissions is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered.
Claim Rejections - 35 USC § 112
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.
Claims 1-13 are 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.
With regards to claim 1 (and claims 2-13 dependent on), the claim recites “exhibits little or no absorbance in the UV/Vis spectrum…” and “exhibits strong absorbance in the UV/Vis spectrum”. The terms “little” and “strong” are relative terms. The terms “little” or “strong” are not defined in the specification and does not provide a standard for defining the requisite degree of “low” or “strong”. Therefore, the claims are rendered indefinite. For the purpose of advancing prosecution, the Examiner is defining the term “little” as being a numerical value for absorbance at a specific wavelength that is less than a higher numerical value for absorbance at the same wavelength.
With regards to claim 1 (and claim 2-13 dependent on), the claim recites “detecting a change in color in the assay composition” and “the color change indicates the effectiveness of the enzyme inhibitor”. The specification does not define what the color change is or what standard value would indicate a color change and how the specific color change would define how effective an inhibitor would be, therefore the claim is rendered indefinite. For the purpose of advancing prosecution, the Examiner is interpreting color change as a general change in color of the tetrazolium compound from oxidized to reduced state.
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 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
With regards to claim 8 (and claims 9-10 dependent on), the claim recites “the assay composition comprises one or more supporting enzymes”. As stated in MPEP 2111.01, during examination the claims must be interpreted as broadly as their terms reasonably allow. A supporting enzyme can be interpreted as any enzyme that can have any activity or function in the assay composition. The specification (paragraph 0040) states that the assay system can include supporting enzymes as may be useful in or more steps of an assay protocol. The specification only gives examples of supporting enzymes such as diaphorase, dehydrogenase, kinase or metalloenzyme and does not provide descriptions of other numerous enzymes that could function as a supporting enzyme in the assay composition. Due to the fact that the specification only discloses diaphorase, dehydrogenase, kinases, and metalloenzymes as potential supporting enzymes and lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 6, 8-9, and 11, 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Adedeji et al. (Antimicrobial Agents and Chemotherapy, Vol. 56., pg. 4718-4728; published September 5, 2012), hereinafter referred to as Adedeji.
With regards to claims 1, 3, 6, 8-9, and 11,13, Adedeji discloses a compound, SSYA10-001 (inhibitor) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA (polynucleotide substrate) unwinding activities of nsp13 (SARS-CoV helicase) (see Abstract, pg. 4718). Adedeji discloses a screening method where helicase activity was measured by incubating the nsp13 (first enzyme) with various concentrations of the inhibitor compound (see right column, first paragraph, pg. 4720). Adedeji further discloses that the screening method includes an assay to assess the effects of the SSYA10-001 inhibitor on cellular viability by incubating cells with various concentrations of inhibitor followed by addition of XTT (tetrazolium, addition of electron transfer mediator as a last step) and after incubation the optical density at 450 nm was read by a plate reader (see left column, last paragraph, pg. 4722). Adejeji discloses that XTT is a tetrazolium salt that is converted by mitochondrial succinate dehydrogenase (supporting enzyme) to a soluble orange-colored formazan product which retains activity only in metabolically live cells (see left column, last paragraph, pg. 4722). Mitochondrial succinate dehydrogenase has the inherent property of an electron transfer mediator as evidenced by Rutter et al. (Mitochondrion, Vol. 10, pg. 393-401, published 2010).
Thus, claims 1, 3, 6, 8-9, and 11, 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Adedeji et al. (Antimicrobial Agents and Chemotherapy, Vol. 56., pg. 4718-4728; published September 5, 2012).
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.
Claims 1-2, 7-9, and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Shivanandappa and Venkatesh (Analytical Biochemistry, Vol. 254., pg. 57-61; published December 1,1997), hereinafter referred to as Shivanandappa, in view of Selinger et al. (British Journal of Obstetrics and Gynaecology, Vol. 95, pg. 596-601; published June 1988), hereinafter referred to as Selinger.
With regards to claims 1-2, 7-9, and 11-13, Shivanandappa teaches a colorimetric assay used to asses the activity of the enzyme, 3b-hydroxy-d5-steroid dehydrogenase (screening method). Shivanandappa teaches that the reaction mixture contains the substrate (pregnenolone or dehydroepiandrosterone), NAD (electron transfer mediator), and iodonitrotetrazolium (tetrazolium compound) in 0.1 M Tris pH 7.8. Note that that the current instant application specification recites that the colorimetric agent can include iodonitrotetrazolium chloride (tetrazolium compound). Shivanandappa further teaches the enzyme extract is incubated for 1 h (initiating screening by addition of first enzyme) and absorbance at 490 nm is read in a spectrophotometer (UV-Vis spectrophotometry) (see Abstract, pg. 57). Shivanandappa also teaches that the assay is based on the formation of NADH due to enzymatic oxidation of the steroid alcohol which is coupled to the reduction of the tetrazolium via diaphorase present in the tissues (see left panel, 2nd paragraph, pg. 60). Shivanandappa further teaches that the method is applicable to other NAD or NADP-dependent steroid dehydrogenases (see right panel, last paragraph, pg. 60). Shivanandappa also teaches that graded concentrations of NADH were reacted with iodonitrotetrazolium and color was measured at 490 nm (electron transfer mediator added as final addition) (see Figure 1, pg. 57).
Shivanandappa does not teach the inclusion of an enzyme inhibitor candidate in the assay.
However, Selinger teaches that epostane is a 3b-hydroxy-d5-steroid dehydrogenase inhibitor (see Abstract and left panel, 1st paragraph, pg. 596).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current instant application to modify the enzyme screening assay taught by Shivanandappa by adding the epostane inhibitor to the assay in order to test the efficacy of the epostane inhibitor against the 3b-hydroxy-d5-steroid dehydrogenase enzyme. One of ordinary skill in the art of biochemistry and enzymology would be motivated to do so because the enzyme assay taught by Shivanandappa would be very useful in evaluating the inhibitory efficacy of the epostane inhibitor taught by Selinger. One of ordinary skill in the art of biochemistry and enzymology would have high expectations of success in doing so since Shivanandappa and Selinger teach all the reagents, methods, and protocols needed to carry out the screening.
Thus, claims 1-2, 7-9, and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Shivanandappa and Venkatesh (Analytical Biochemistry, Vol. 254., pg. 57-61; published December 1,1997) in view of Selinger et al. (British Journal of Obstetrics and Gynaecology, Vol. 95, pg. 596-601; published June 1988).
Claims 1, 5, 7-10, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al. (European Patent Application, EP 0924302 A2; published June 6, 2023), hereinafter referred to as Iwata, in view of Wolosker et al. (FEBS Letters, Vol. 392, pg. 274-276; published September 2, 1996), hereinafter referred to as Wolosker.
With regards to claims 1, 5, 7-10, and 12-13, Iwata teaches a test strip assay which can measure creatine kinase activity within a broad measuring range through the measurement of reflected light (screening method). Iwata teaches that the test strip assay comprises a carrier, a dehydrogenase, a diaphorase, NAD or NADP+ (electron transfer mediator), and a water soluble tetrazolium compound. (see Paragraphs, 0010-0011, pg. 2-3). Iwata teaches that the water-soluble tetrazolium compound is soluble in water up to 5 mM or more and it develops a color by its reduction by the action of a diaphorase in the presence of NAD or NADP+ (see paragraph 0016, pg. 3). Iwata further teaches that the diaphorase is produced by Bacillus stearothermophilus (bacterial) (see paragraph 0030, pg. 4). Iwata teaches that creatine kinase solution is spotted on the test strip and reflectance is measured at 30 second intervals (initiating screening method by addition of first enzyme) (see Paragraph 0052, pg. 7).
Iwata does not teach that the test strip assay for creatine kinase activity comprises an enzyme inhibitor candidate.
However, Wolosker teaches that S-nitroglutathione inhibits creatine kinase (see Abstract, pg. 274).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current instant application to modify the screening of the activity of creatine kinase taught by Iwata by adding the S-nitroglutathione inhibitor to the assay in order to test the efficacy of the S-nitrogluathione inhibitor against the creatine kinase. One of ordinary skill in the art of biochemistry and enzymology would be motivated to do so because the enzyme activity screening protocol and assay taught by Iwata would be very useful in evaluating the inhibitory efficacy of the S-nitroglutathione inhibitor taught by Wolosker against the creatine kinase. One of ordinary skill in the art of biochemistry and enzymology would have high expectations of success in doing so since Iwata and Wolosker teach all the reagents, methods, and protocols needed to carry out the screening.
Thus, claims 1, 5, 7-10, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al. (European Patent Application, EP 0924302 A2; published June 6, 2023) in view of Wolosker et al. (FEBS Letters, Vol. 392, pg. 274-276; published September 2, 1996).
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Adedeji et al. (Antimicrobial Agents and Chemotherapy, Vol. 56., pg. 4718-4728; published September 5, 2012), hereinafter referred to as Ajedeji, in view of Habtemariam et al. (Archives of Medical Research, Vol. 51., pg. 733-735; published October 2020), hereinafter referred to as Habtemariam and further in view of White et al. (The Journal of Physical Chemistry Letters, Vol. 11, pg. 9144-9151; published November 5, 2020), hereinafter referred to as White.
With regards to claims 1 and 4, Adedeji teaches a compound, SSYA10-001 (inhibitor) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13 (SARS-CoV helicase) (see Abstract, pg. 4718). Abedeji teaches a screening method where helicase activity was measured by incubating nsp13 with various concentrations of the inhibitor compound. Adedeji further teaches that the screening method includes an assay to assess the effects of the SSYA10-001 inhibitor on cellular viability by incubating cells with various concentrations of inhibitor followed by addition of XTT and after incubation the optical density at 450 nm was read by a plate reader (see left column, last paragraph, pg. 4722). Adejeji teaches that XTT is a teterazolium salt that is converted by mitochondrial succinate dehydrogenase to a soluble orange-colored formazan product which retains activity only in metabolically live cells (see left column, last paragraph, pg. 4722). Mitochondrial succinate dehydrogenase has the inherent property of an electron transfer mediator as evidenced by Rutter et al. (Mitochondrion, Vol. 10, pg. 393-401, published 2010). Abedeji also teaches that given the high homology between SARS-CoV helicase and other coronavirus helicases (~70%), SSAY10-001 may also inhibit several coronaviruses that cause human disease (see left column, pg. 4724).
Adedeji does not specifically teach testing inhibitors of nsp13 against SARS-Cov-2 nsp13.
However, Habtemariam teaches that the discovery of new drugs for treating the new coronavirus, SARS-CoV-2, or repurposing those already in use for other viral infections is possible through understanding of the viral replication cycle (see Abstract, pg. 733). Habtemariam teaches that the close genomic relationship of SARS-CoV-2 and SARS-CoV with 80% nucleotide identity has been a good playground for putting forward similar therapeutic insights (see right column, first paragraph, pg. 733) and that key non-structural proteins such as helicase (nsp13) have been shown to be conserved. Habtemariam further teaches that this means that known therapeutics that target those enzymes even in closely related coronavirus species could have application to SARS-CoV-2 infection (see left column, first paragraph, pg. 734). Habtemariam also teaches that inhibitors of nsp13 activity offer therapeutic option for coronavirus including SARS-CoV-2 and the class of compounds identified with a promise through such a mechanism include benzotriazole and others (see last paragraph, pg. 734).
Habtemariam does not teach the preparation of a SARS-CoV-2 nsp13 protein.
However, White teaches the expression and purification of recombinant SARS-CoV-2 nsp13 protein for use in screening inhibitors against nsp13 (see left column, last paragraph, pg. 9149). White also teaches the identification of potential nsp13 inhibitors using a virtual screen (see left column, pg. 9147).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the current instant application, to modify the screening method of Adedeji by substituting the SARS-CoV nsp13 with the SARS-CoV-2 nsp13 enzyme since Habtemariam teaches that they are conserved and testing the efficacy of the SSYA10-001 inhibitor taught by Adedeji or other potential inhibitors taught by Habtemariam and/or White against SARS-CoV-2 nsp13.. One of ordinary skill in the art of biochemistry and enzymology would be motivated to do so because the screening method taught by Adedeji would be very useful in evaluating the inhibitory efficacy of the potential nsp13 inhibitors taught by Habtemariam and White against the SARS-CoV-2 nsp13 as a potential way of repurposing current coronavirus nsp13 inhibitors. One of ordinary skill in the art of biochemistry and enzymology would have high expectations of success in doing so since Adedeji, Habtemariam, and White teach all the reagents, methods, and protocols needed to carry out the screening method.
Thus, claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Adedeji et al. (Antimicrobial Agents and Chemotherapy, Vol. 56., pg. 4718-4728; published September 5, 2012), in view of Habtemariam et al. (Archives of Medical Research, Vol. 51., pg. 733-735; published October 2020), and further in view of White et al. (The Journal of Physical Chemistry Letters, Vol. 11, pg. 9144-9151; published November 5, 2020).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE T LOUNTOS whose telephone number is (571)272-0502. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/ROBERT B MONDESI/ Supervisory Patent Examiner, Art Unit 1652
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