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 .
Priority
This is a continuation application of PCT/U2021/040539 filed on 07/06/2021, and claims benefit to 63/049,074 filed on 7/7/2020 and 63/084502 filed on 9/28/2020.
The limitations “reagent inactivates a pathogen within about 10 seconds without damaging genetic material of said pathogen” in claim 85 and “a viral-inactivating agent for inactivating a virus in said biological sample within 10 seconds” in claim 88 do not find support in the priority provisional applications 63/049,074 and 63/084502. Thus, claims 85 and 88-92 do not benefit the filing date of previously filed 63/049,074 and 63/084502.
Status of Claims
Claims 1-65 were canceled and new claims 66-92 were added by the amendment filed on 8/1/2023. Claims 66-92 are currently pending in this application.
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.
Claims 66-70, 74-85 and 87-91 are rejected under 35 U.S.C. 103 as being unpatentable over US2014/0272921 (Baker) in view of either Kumar et al (Journal of Virological Methods 223 (2015) 13-18) or Tempestilli et al (Clin. Chem Lab Med 2015: 53(12):1967-1973).
The independent claim 66 recites a method for stabilizing a biological sample by a) providing a reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent; and b) contacting the biological sample with said reagent.
The independent claim 88 recites a reagent for stabilizing a biological sample comprising a kosmotrope and a viral-inactivating agent for inactivating a virus in said biological sample within 10 seconds.
Baker teaches methods of generating compositions for stabilization of biological sample (0002). The novel cell viability compositions of Baker comprises at least one kosmotrope, chaotrope, buffer and an apoptosis substrate (0012, 0025). Baker teaches that the kosmotrope is selected from the group consisting of glycerol, aa-Trealose, glucose, dextran or D-Lactose (0016); the chelator is selected from group consisting of EDTA, EGTA or BABTA (0017); the chaotrope is SCN-(sodium thiocyanate), potassium phosphate buffer (0015, 0022, 0028-0029). Baker teaches that the cell viability composition is added to tissue sample (biological sample) (0081) and the tissue sample is stabilized and maintains viable gene expression component up to 72 hours at room temperature (0081 and Examples). Baker teaches that the disclosed reagents stabilize gene expression of target RNA, mRNA and rapid penetration of the reagent components into cells and tissue (0093). Baker teaches that the chaotrope (sodium thiocyanate) maintains the viability of cells and gene expression components (0066). Baker does not teach that the stabilization composition comprises a viral-inactivating agent as in the present claims.
Kumar et al teach methods for safely inactivating Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and potentially other coronaviruses (abstract). Kumar et al teach that the use of Trizol® or Trizol® LS is typical for the isolation and purification of RNA or DNA from virus-infected cells or cell culture supernatants (p.16. left col, and p.17). Kumar et al teach that RNA was extracted from the Trizol® LS treated MERS-CoV virus stock, and it was found that the treatment with Trizol® LS was completely inactivated the virus (Fig.2). The RNA purified from MERS-CoV is not naturally infectious in a cell culture system (p.17 right col.).
Tempestilli et al teach Triton X-100 (non-ionic surfactant also known as octylphenol ethoxylate) can be used to reduce the biohazard (inactivating the virus) in performing laboratory tests on samples from patients with Ebola Virus Disease (Abstract). Tempestilli et al teach that Triton X-100 detergent is used in biomedical laboratories as a mild surfactant for the disruption of cell membranes and release of intracellular materials in a soluble form. Triton X-100 is able to break the protein-protein, protein-lipid and lipid-lipid associations, and denature proteins and other macromolecules. Tempestilli teaches that due to its chemical activity, Triton X-100 is used to inactivate enveloped viruses (p.1968).
Thus, it would have been obvious to a person skilled in the art to use known viral-inactivating agents in the compositions for stabilizing biological sample. A person skilled in the art would have been motivated to include a viral-inactivating agent with the biological sample stabilization composition of Baker since MERS-CoV virus or Ebola virus are enveloped coronavirus with a positive sense RNA genome and highly infectious and fatal to humans. Further the recitation “for inactivating a virus in said biological sample within 10 seconds” in claim 88 is considered as intended use of the viral-inactivating agent. Since Kumar et al and Tempestilli teach viral-inactivating agents claims 66 and 88 are obvious in view of the combined teachings of Baker, Kumar et al or Tempestilli et al.
Claims 67-70, 91 are obvious in view of the teachings in Baker and further in view of Kumar or Tempestilli since the biological sample comprises a protein or nucleic acid (RNA). Further, it would have been obvious to a person skilled in the art to obtain the biological sample via a nasopharyngeal swab since MERS-CoV is a respiratory illness.
Regarding claim 74 limitations “the kosmotrope comprises at least a first kosmotrope and a second kosmotrope different from said first kosmotrope”, Baker teaches that the stabilization composition comprises a second kosmotrope, which is different from the first kosmotrope (0076, 0085).
Regarding claim 75, Baker teaches that the first kosmotrope is glycerol and second kosmotrope is aa-trealose (0023, 0076, 0085).
Regarding claim 76, Baker teaches that the chaotrope is sodium isothiocyanate (0022, 0066).
Regarding claims 77 and 78, Baker teaches that the composition comprises a chelator (0012), which is ethylenediaminetetraacetic acid (EDTA) (0023, 0050).
Regarding claim 79, Baker teaches that the stabilization composition comprises DMSO (dimethylsulfoxide) (0023).
Regarding claim 80, Baker teaches that the stabilization composition further comprises potassium phosphate buffer (0023).
Regarding claims 81-84, Kumar et al and Tempestilli et al teach viral inactivating agent comprising a detergent or nonionic surfactant.
Regarding claims 84, 90, Tempestilli et al teaches that Triton™ X-100 (one specific type of octylphenol ethoxylate) (a detergent or non-ionic surfactant) is used to inactivate enveloped viruses (p.1968).
Regarding claim 85, Kumar teaches that Trizol® inactivates virus in cell culture supernatant or infected cells within seconds (p.17). Since the enveloped virus including Ebola virus and coronavirus are highly contagious and fatal to humans, it would have been obvious to a person skilled in the art to use viral-inactivating agents in the stability compositions of Baker that inactivates the virus (pathogen) in the biological sample within about 10 seconds.
Regarding claim 87, the EDTA (chelator) in the composition of Baker enhances stability of the genetic material to enzymatic degradation by a metalloprotease, endonuclease, exonuclease or ribonuclease (0068).
2. Claim 86 is rejected under 35 U.S.C. 103 as being unpatentable over Baker in view of either Kumar et al or Tempestilli et al as applied to claims 66-70, 74-85 and 87-91 above, and further in view of Ettorre et al (The Society for Investigative Dermatology, Inc. 2003. Vol. 121, No.2. pp 328-336) and Silva (Molecules 2020 (publishes 23 February 2020), 25, 991. Pages 1-22).
Claim 86 recites that the stabilizing reagent of claim 66 further comprises 5-Chloro-2-methyl-3(2H)-isothiazolone, 2-methyl-3(2H)-isothiazolone or a combination thereof.
The teachings of Baker, Kumar et al and Tempestilli are as discussed above. The combined teachings of Baker and either Kumar et al or Tempestilli teach the method for stabilizing a biological sample by contacting the biological sample with a stabilizing reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent. The combined teachings of Baker and either Kumar et al or Tempestilli do not teach that the stabilizing reagent further comprises isothiazolinones - 5-Chloro-2-methyl-3(2H)-isothiazolone (or CMI), 2-methyl-3(2H)-isothiazolone (or MI) and/or a combination thereof as in claim 86.
However, it was known in the art the use of isothiazolinones as biocides. Ettorre et al teach that preservatives are an important class of chemicals used to inhibit the growth of pathogenic and nonpathogenic microorganisms in a variety of pharmaceuticals. The combination of 5-Chloro-2-methyl-3(2H)-isothiazolone (CMI) and 2-methyl-3(2H)-isothiazolone (MI) are used in low concentrations against bacteria, fungi and yeast, and a bacterial mutagen (abstract).
Silva et al teach isothiazolinones including MCI and MI are stable and are used at low concentrations as bactericides and fungicides and as preservatives in the industry (Abstract, pages 2, 6, 14 and 16). Silva teaches that isothiazolinones are highly valued by a number of industries (p.6).
Thus, it would have been obvious to a person skilled in the art to include CMI and/or MI in the biological sample stabilizing reagent of Baker since thiazolinones CMI and/or MI are known as a biocide and are widely used in the pharmaceutical industry.
Claims 71-73 and 92 are rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Baker and either Kumar or Tempestilli as applied to claims 66-70, 74-85 and 87-91 above, and further in view of Gorbalenya et al (Nature Microbiology. Vo.5. March 2020.pages 536-544).
Claims 71-73 and 92 recite that the biological sample comprises SARS-CoV-2 or SARS-CoV RNA.
The teachings of Baker, Kumar et al and Tempestilli are as discussed above. The combined teachings of Baker and either Kumar et al or Tempestilli teach the method for stabilizing a biological sample by contacting the biological sample with a stabilizing reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent. The combined teachings of Baker and either Kumar et al or Tempestilli do not teach that the biological sample comprises SARS-CoV-2.
Based on phylogeny, taxonomy and established practice, the CSG (The Coronaviridae Study Group) decided that the coronavirus-associated acute respiratory disease (COVID-19) causing new virus is related to SARS-CoV and designated the new virus as SARS-CoV-2 (Abstract). SARS-CoV-2 is an enveloped single stranded RNA virus. Since both Kumar and Tempestilli teach a reagent that inactivates an enveloped virus, and especially Kumar teaches SARS-CoV inactivating agent, it would have been obvious to a person skilled in the art to include the enveloped virus inactivating agent with the stabilizing composition of Baker to inactivate SARS-CoV-2 or SARS-CoV-2 RNA present in the biological sample.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 66, 67, 70, 74-79 and 88 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 2 of U.S. Patent No. 9,949,474 in view of Tempestilli et al.
The present application and the reference `474 patent share the same inventive entity.
The present application does not benefit from safe harbor provision of 35 USC § 121, since the present application was not filed as a result of restriction requirement made in the `474 patent application.
The independent claim 66 recites a method for stabilizing a biological sample, a) providing a reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent; and b) contacting the biological sample with said reagent.
The independent claim 88 recites a reagent for stabilizing a biological sample comprising a kosmotrope and a viral-inactivating agent.
The reference claim 1 recites producing a cell viability reagent comprising a kosmotrope , a chelator, a chaotrope, an apoptosis substrate and a metabolic modulator.
The reagent produced in reference claim 1 fails to teach a viral-inactivating agent as in the present claim 88 reagent or in the reagent used in the present claim 1. However, Tempestilli in the same field of endeavor teaches that Triton X-100 (viricide) inactivates enveloped viruses including Ebola virus. Tempestilli teaches that Triton X-100 is able to break the protein-protein, protein-lipid and lipid-lipid associations and denature proteins and other macromolecules (p. 1968). Thus, it would have been obvious to a person skilled in the art to include a viral-inactivating agent along with the cell viability reagent of the reference claim 1. Further, it would have been obvious to a person skilled in the art to use the cell viability reagent produced in the reference claim 1 to stabilize and preserve the biological sample.
Claims 67 and 70 are obvious since the tissue sample in the reference claim 1 is obtained from a subject. The tissue sample comprises a protein or nucleic acid.
Claims 74 and 75 are obvious since the reference claim 1 recites that the kosmotrope is α,α-trehalose, and claim 2 recites that the reagent comprises glycerol as a second kosmotrope.
Claim 76 is obvious since the reference claim 1 recites that the chaotrope is sodium thiocyanate.
Claims 77 and 78 are obvious since the reference claim 1 recites that the reagent comprises EDTA as chelator.
Claim 79 is obvious since the reference claim 1 includes DMSO (dimethylsulfoxide) as a metabolic modulator.
Claims 82-84 are obvious since Tempestilli teaches the use of Triton X-100 (a non-ionic surfactant) as a viricide.
Claims 66, 67, 70, 74-79 and 88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of U.S. Patent No. 9,113,623 in view of either Tempestilli et al or Kumar et al.
The present application and the reference `623 patent share the same inventive entity.
The present application does not benefit from safe harbor provision of 35 USC § 121, since the present application was not filed as a result of restriction requirement made in the `623 patent application.
The independent claim 66 recites a method for stabilizing a biological sample, a) providing a reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent; and b) contacting the biological sample with said reagent.
The independent claim 88 recites a reagent for stabilizing a biological sample comprising a kosmotrope and a viral-inactivating agent.
The reference claim 9 recites a cell viability reagent comprising a first and second kosmotrope , a chelator, a chaotrope, an apoptosis substrate and a metabolic modulator.
The reagent produced in reference claim 9 fails to teach a viral-inactivating agent as in the present claim 88 reagent or in the reagent used in the present claim 1. However, Tempestilli in the same field of endeavor teaches that Triton X-100 (viricide) inactivates enveloped viruses including Ebola virus. Tempestilli teaches that Triton X-100 is able to break the protein-protein, protein-lipid and lipid-lipid associations and denature proteins and other macromolecules (p. 1968). Kumar teaches methods for safely inactivating Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and potentially other coronaviruses (abstract) using Trizol® or Trizol® LS (Fig.2, p.16. left col, and p.17). Thus, it would have been obvious to a person skilled in the art to include a viral-inactivating agent along with the cell viability reagent of the reference claim 9. Further, it would have been obvious to a person skilled in the art to use the cell viability reagent of the reference claim 9 to stabilize and preserve the biological sample of the present claim 1.
Claims 67 and 70 are obvious since the tissue sample in the reference claim 9 is obtained from a subject. The tissue sample comprises a protein or nucleic acid.
Claims 74 and 75 are obvious since the reference claim 9 recites that the first kosmotrope is glycerol and the second kosmotrope is α,α-trehalose.
Claim 76 is obvious since the reference claim 9 recites that the chaotrope is sodium thiocyanate.
Claims 77 and 78 are obvious since the reference claim 9 recites that the reagent comprises EDTA as chelator.
Claim 79 is obvious since the reference claim 9 includes DMSO (dimethylsulfoxide) as a metabolic modulator.
Claims 82-84 are obvious since Tempestilli teaches the use of Triton X-100 (a non-ionic surfactant) as a viricide.
Claims 71-73 and 92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of U.S. Patent No.9,113,623 in view of either Kumar or Tempestilli et al and further Gorbalenya et al (Nature Microbiology. Vo.5. March 2020.pages 536-544).
Claims 71-73 and 92 recite that the biological sample comprises SARS-CoV-2.
The teachings of US 9113623, Kumar et al and Tempestilli are as discussed above. The combined teachings of Baker and either Kumar et al or Tempestilli teach a stabilizing a stabilizing reagent comprising a kosmotrope, a chaotrope, a chelator, and a viral-inactivating agent (see Supra). The combined teachings of claim 9 of the `623 patent and either Kumar et al or Tempestilli do not teach that the biological sample comprises SARS-CoV-2.
Based on phylogeny, taxonomy and established practice, the CSG (The Coronaviridae Study Group) decided that the coronavirus-associated acute respiratory disease (COVID-19) causing virus is related to SARS-CoV and designated the new virus as SARS-CoV-2 (Abstract). Since both Kumar and Tempestilli teach a reagent that inactivates an enveloped virus, and especially Kumar teaches SARS-CoV inactivating agent, it would have been obvious to a person skilled in the art to include the enveloped virus inactivating agent with the stabilizing reagent of the reference claim 9 to inactivate SARS-CoV-2 or SARS-CoV-2 RNA present in the biological sample.
Claim 86 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of U.S. Patent No.9,113,623 in view of either Kumar or Tempestilli et al and further Ettorre et al (The Society for Investigative Dermatology, Inc. 2003. Vol. 121, No.2. pp 328-336) and Silva (Molecules 2020 (publishes 23 February 2020), 25, 991. Pages 1-22).
Claim 86 recites that the stabilizing reagent of claim 66 further comprises 5-Chloro-2-methyl-3(2H)-isothiazolone, 2-methyl-3(2H)-isothiazolone or a combination thereof.
The teachings of the reference claim 9, Kumar et al and Tempestilli are as discussed above. The combined teachings of the reference claim 9, and either Kumar et al or Tempestilli teach the method for stabilizing a biological sample by contacting the biological sample with a stabilizing reagent comprising a kosmotrope, a chaotrope and a viral-inactivating agent. The combined teachings of the reference claim 9 and either Kumar et al or Tempestilli do not teach that the stabilizing reagent further comprises isothiazolinones - 5-Chloro-2-methyl-3(2H)-isothiazolone (or CMI), 2-methyl-3(2H)-isothiazolone (or MI) and/or a combination thereof as in claim 86.
However, it was known in the art the use of isothiazolinones as biocides. Ettorre et al teach that preservatives are an important class of chemicals used to inhibit the growth of pathogenic and nonpathogenic microorganisms in a variety of pharmaceuticals. The combination of 5-Chloro-2-methyl-3(2H)-isothiazolone (CMI) and 2-methyl-3(2H)-isothiazolone (MI) are used in low concentrations against bacteria, fungi and yeast, and a bacterial mutagen (abstract).
Silva et al teach isothiazolinones including MCI and MI are stable and are used at low concentrations as bactericides and fungicides and as preservatives in the industry (Abstract, pages 2, 6, 14 and 16). Silva teaches that isothiazolinones are highly valued by a number of industries (p.6).
Thus, it would have been obvious to a person skilled in the art to include CMI and/or MI in the biological sample stabilizing reagent of the reference claim 9 since thiazolinones CMI and/or MI are known as a biocide and are widely used in the pharmaceutical industry.
Conclusion
Claims 66-92 are rejected.
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/Padmashri Ponnaluri/ Primary Examiner
Art Unit 3991