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 .
Election/Restrictions
Applicant’s election without traverse of Group I, and species B, sub-species (c) in the reply filed on May 6, 2026 is acknowledged.
Claim 44 (Group) and claims 27-29, 34, and 35 (species) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions (groups and species), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 6, 2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on May 4, 2023; August 4, 2025; and March 12, 2026 are proper and are being considered by the Examiner.
Drawings
The drawings received on April 3, 2023 are acceptable.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 5, lines 5-8, and page 91, lines 9-10, for example). Applicant is required to peruse the application and delete ALL embedded hyperlink and/or other form of browser-executable codes; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 24-43 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.
Claim 24 is indefinite for the following reasons. Claim 24 recites the preamble of detecting the presence or absence of a virus in a biological sample based on amplifying at least one target nucleic acid derived from the virus without prior nucleic acid purification, but the claim only actively requires single step (A), which is simply providing a virus-inactivated biological sample that is prepared in a composition comprising the biological sample and at least one virus-deactivating substance. Step (B) is an optional pretreatment step; and step (C) subjects an aliquot or all of the optionally pretreated virus-inactivated biological sample. Since step (C) relies on the pretreated sample of step (B) which is optional, steps (B) and (C) become an optional step. However, the intent set out in the preamble cannot be achieved based on this optionality and there is no other breadth of the claim in which the preamble can be achieved. Therefore, the claim is indefinite.
Claim 24 is also indefinite for reciting the phrase, “optionally pretreating” because the phrase does not identify what is being pretreated.
Claim 40 is indefinite for missing a conjunction between elements (iv) and (v). For the purpose of prosecution, the conjunction, “and” has been assumed.
Claim 41 is indefinite for containing limitations followed by the phrase, “such as.” Limitations following the phrase “such as” renders the claim indefinite because it is vague and indefinite whether the limitations are actively required or not.
Claim 42 is indefinite for reciting the phrase, “preferably” because it is unclear under what conditions the limitation is deemed preferred.
Claims 25-43 are indefinite by way of their dependency on claim 24.
Claim Rejections - 35 USC § 102
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 24, 26, 31, 37, 38, 41, and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hasan et al. (PLoS One, July 24, 2020, vol. 15, no. 7, pages 1-9).
With regard to claim 24, Hasan et al. teach a method for detecting the presence of a virus in a biological sample based on amplification of at least one target nucleic acid derived from the virus without prior purification (“we tested a number of commercial and laboratory-developed, specimen pre-treatment procedures to optimize the performance of direct RT-PCR for SARS-CoV-2”, page 2, 1st column), comprising:
providing a virus-inactivated biological sample wherein providing such sample comprises preparing a composition comprising the biological sample and at least one virus-deactivating substance (“[u]sing a human corona virus positive HKU1 (hCoV-HKU1) positive specimen as a surrogate for SARS-CoV-2, we first assed whether specimens can be used directly for RT-qPCR after 2-10 fold dilution with nuclease free water (NFW), simple heat treatment (100oC for 5 min) and centrifugation to remove any insoluble material that may be present in the specimen”, page 4, 4th paragraph; and “pre-treatment conditions showed modest improvement with a non-ionic detergent Tween-201, and further improvement with heating at 65oC for 10 min without centrifugation”, page 4, bottom paragraph); and
subjecting at least an aliquot or all of the sample to an amplification reaction (RT-PCR is an amplification reaction).
With regard to claim 26, Tween-20 is a non-ionic surfactant.
With regard to claim 31, Tween-20 is an alcohol ethoxylate, as admitted by the instant specification2.
With regard to claim 37, the target virus is an RNA virus (hCoV-HKU1).
With regard to claim 38, the sample collected is in either nasopharyngeal swab (NPFS) in viral transport (UVT) medium (page 2, 3rd paragraph).
With regard to claim 41, the method discussed above is for RNA virus (hCoV-HKU1), and employs non-ionic surfactant combination with the sample (Tween-20 that deactivates virus, see above), no pretreatment step (as this is an optional step), amplification involving RT-PCR (see above).
With regard to claim 43, because the same reagent Tween-20 is employed as taught by Applicants, the reduction in viral titire is asserted to be met.
According to In re Best 195 USPQ 430, 1997, the court stated that, “Patent Office can require applicant to prove that prior art products do not necessarily or inherently posses characteristics of his claimed product wherein claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes; burden of proof is on applicant” (pp. 430).
Therefore, Hasan et al. anticipate the invention as claimed.
Claims 24, 25, 37-39, and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Manjula et al. (WO 2009/016652 A1, published February 2009; IDS ref).
With regard to claim 24 and 26, Manjula et al. teach a method of detecting the presence or absence of a virus in a biological sample based on amplifying at least one target nucleic acid derived from the virus without prior nucleic acid purification comprising:
providing a virus-inactivated biological sample, wherein providing such sample comprises preparing a composition comprising the biological sample and at least one virus-deactivating substance (“invention relates to the PCR amplification and detection of nucleic acids from blood, plasma, serum or any other whole microbial cells without nucleic acid isolation … Hepatitis C virus…”, page 1, lines 4-8; also “direct PCR amplification … comprises a buffer salt, a chloride or sulphate containing bivalent ion, a non-ionic detergent, a stabilizer and a sugar alcohol optionally along with a chloride containing monovalent ion and a method for direct PCR amplification of sample”, page 3, lines 8-12); and
subjecting at least an aliquot or all of the biological sample to an amplification reaction and amplifying at least one target nucleic acid (“samples were subjected to PCR … Nonidet-P40-0.5%; sorbitol … appropriate primers”, page 7, line 30 to page 8, line 2).
With regard to claim 25, the amplification reaction also includes gelatin-0.1% and sorbitol (see page 8, line 1), well-known stabilizers that aids amplification against PCR inhibition.
With regard to claim 37, the target virus is an RNA virus (i.e., hepatitis C, see above).
With regard to claims 38 and 393, the composition comprises a medium that was used for collecting and/or storing the biological sample (“unique buffer system PCR can also be conducted for blood samples that are treated with anticoagulants such as heparin, EDTA”, page 6, lines 22-24) and EDTA is a known nuclease inhibitor as the EDTA binds/sequesters divalent cations which are needed for nuclease functions.
With regard to claim 43, because the same reagent, non-ionic detergent is as claimed, the reduction in viral titire is asserted to be met.
According to In re Best 195 USPQ 430, 1997, the court stated that, “Patent Office can require applicant to prove that prior art products do not necessarily or inherently posses characteristics of his claimed product wherein claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes; burden of proof is on applicant” (pp. 430).
Therefore, Manjula et al. anticipate the invention as claimed.
Claims 24, 26, 37-41, and 43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Golz et al. (WO 2021/204701 A1, published October 14 2021, priority April 2020; IDS ref).
With regard to claims 24 and 26, Golz et al. teach a method of detecting the presence of a virus in a biological sample based on amplifying at least one target nucleic acid derived from the virus without prior nucleic acid purification comprising:
providing a virus-inactivated biological sample, wherein providing such sample comprises preparing a composition comprising the biological sample and at least one virus-deactivating substance (“[a]lthough the method may comprise isolation or purification … of nucleic acids, it has been surprisingly discovered that amplification of target nucleic acids may be accomplished without purification of the nucleic acid beforehand … the lysate of the invention is suitable for direct nucleic acid amplification … qPCR or RT-PCR (including RT-qPCR)”, section [00138]; also lysis buffer includes non-ionic surfactant such as Triton X-1004, see section [0018]); and
pretreating5; and
subjecting at least an aliquot or all of the pretreated biological sample (“a method of amplifying one or more nucleic acids comprising at least one sample with a lysis buffer to produce a lysate, and amplifying at least one nucleic acid in the lysate, wherein the lysis buffer comprises at least one non-ionic surfactant, glycerol and at least one salt” section [0039]).
With regard to claim 37, the method is for amplifying an RNA virus (“method to detect an RNA virus”, section [0082]).
With regard to claim 38, the lysis buffer combination product is stored (“storing the lysate for a period of time before use”, section [00131]).
With regard to claim 39, the artisans also teach contacting the biological composition with a at least one nuclease inhibitor and reducing agent (“[o]n day of usage: 0.1 ml RNAse inhibitor … per 100 ml sample lysis volume”, section [00165]; lysis buffer … may also comprise one or more reducing agents …”, section [00107]).
With regard to claim 40, the sample is contacted with at least one reducing agent and an RNAse inhibitor (“[o]n day of usage: 0.1 ml RNAse inhibitor (NEB M0314L6, 40 U/ml) per 100 ml sample lysis volume”, section [00165]; lysis buffer … may also comprise one or more reducing agents …”, section [00107]; also the buffer includes Triton X-100 and a plurality of such surfactants listed, see section [00102]).
With regard to claim 41, the biological sample is SARS-CoV-2 (“the RNA virus is a coronavirus”, section [0024]) and upon contacting with the above-discussed lysis reagents, the resulting sample is RT-PCR’d with DNAP, an RT, buffers, and substrates necessary in an RT-PCR detection (see section [0003], [0014], [0058], [0069]).
With regard to claim 43, because the same reagent, non-ionic detergent is as claimed, the reduction in viral titire is asserted to be met.
According to In re Best 195 USPQ 430, 1997, the court stated that, “Patent Office can require applicant to prove that prior art products do not necessarily or inherently posses characteristics of his claimed product wherein claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes; burden of proof is on applicant” (pp. 430).
Therefore, Golz et al. anticipate the invention as claimed.
Claim Rejections - 35 USC § 103
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.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Golz et al. (WO 2021/204701 aA1, published October 14 2021, priority April 2020; IDS ref).
The teachings of Golz et al. have been discussed above.
While Golz et al. teach that the biological sample contacted with the lysis buffer is employed in a direct amplification reaction, which is RT-PCR, the artisans do not explicitly teach how much of the sample is included to a total amplification volume (i.e., at least 20%).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine the amount of the sample to be inputted into an amplification mixture which optimizes the amplification reaction by a process involving empirical determination, as such practice had been routinely implemented in the art of molecular diagnostics, yielding no more than a predictable outcome of providing an optimized set of conditions.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Claims 32, 33, and 36 are free of prior art as the prior art does not teach or suggest a method of using seed oil alcohol alkoxylates or 2-ethyl hexanol ethoxylated propoxylated copolymers, iodine-releasing reagent, as quaternary ammonium salts as virus-deactivating agent and combine with a biological sample comprising a virus, wherein the resulting treated sample is amplified without purification.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 July 15, 2026
/YJK/
1 Instant specification, on page 19, lines 24-25, lists Tween-20 as an alcohol ethoxylate that deactivates virucidal activity; see also page 18, lines 34-35, “non-ionic surfactant used as virus-deactivating substance is an alcohol ethoxylate”
2 “the alcohol ethoxylate is a polysorbate … sorbitan monolaurate (Tween® 20)…”, page 19, lines 24-25.
3 “contacting a biological sample with an extraction composition” is not equivalent to an active step of performing an extraction of nucleic acids.
4 Triton X-100 is listed in instant specification as an alcohol ethoxylate, which is a polyoxyethylene alkyl phenyl ether, see page 19, lines 38-40.
5 The step of pretreatment is considered the lysis step as a pretreatment before RT-PCR or PCR step.
6 NEB#M0314 is a 50 kDa recombinant protein.
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