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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 19th, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-13 and 21-25, in the reply filed on January 27th, 2026 is acknowledged.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 27th, 2026.
Applicant’s further election of the SEQ ID NOs: 16-17 in the reply filed on January 27th, 2026 is acknowledged and has been applied for examination purposes.
Priority
Applicant's claim under 35 U.S.C. 119(e) for the benefit of prior-filed Provisional Applications 63/050155, 63/135159, and 63/171749 is acknowledged. However, after reviewing the disclosures of 63/050155, 63/135159, and 63/171749, the Examiner finds that they do not adequately support the full scope of the subject matter of claim 21 as currently recited because they do not disclose any kind of method for pooling numerous individual saliva isolated RNA samples, and further adding a binding buffer having a 2X salt concentration compared to the binding buffer claimed earlier in claim 21. Thus, the '155, ‘159, and ‘749 applications do not provide adequate support for the subject matter of claim 21; all claims depending from claim 21 are also unsupported by '155, ‘159, and ‘749. Hence, claims 21-25 are examined as though they had an effective filing date of January 8th, 2011, the filing date of Provisional Application No. 63/135224.
Applicant's claim under 35 U.S.C. 120 for the benefit of prior-filed International Patent Application No. PCT/US2021/041016 filed July 9th, 2021, and Applicant’s further claim under 35 U.S.C. 119(e) for the benefit of prior-filed Provisional U.S. Patent Application No. 63/135224, filed January 8th, 2021, are acknowledged. These applications contain adequate support for the subject matter of claim 21 and further depending claims.
Claim Summary
Claims 1-25 are pending. Claims 14-20 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-13 and 21-25 are under examination and discussed in this Office action.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Pages 100, 101, 109, and 110 of the instant specification). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; 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.
The use of terms such as MagMAX (Page 13 of the instant specification), NucliSENS (Page 35 of the instant specification), and SYNCT Software (Page 44 of the instant specification), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms. It is suggested that the Applicant review the specification for instances of trade names or marks that may need to be properly indicated.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Drawings
It is noted that color drawings have been included in the instant disclosure, and the appropriate paragraph indicating so is included as the first paragraph of the brief description of the drawings section of the specification. However, after review of the provided documentation, it does not appear that the Applicant has paid the appropriate fee set forth in 37 CFR 1.17(h), or that the Applicant has a granted petition filed under 37 CFR 1.84(a)(2). Applicant is suggested to review these potential issues if they wish to have a patent or patent application publication with color drawings available upon request from the Office.
Claim Objections
Claims 1-2, 4, 6, 8, 12-13, 21, and 23 are objected to because of the following informalities:
Claim 1 recites the limitation “one or more patient or individual”. This recitation is awkwardly worded given the plurality of “one or more”, followed by only referring to a single patient or individual. It is suggested to change this recitation to read “one or more patients or individuals”.
Claim 1 further recites the limitation “obtaining one or more small volume saliva sample, wherein the sample is collected in”. This recitation is awkwardly worded given the plurality of “one or more”, followed by only referring to a single sample. It is suggested to change this recitation to read “obtaining one or more small volume saliva samples, wherein a saliva sample of the one or more small volume saliva samples is collected in”.
Claim 1 further recites several instances of “infectious agent RNA, particularly viral RNA”, as well as one instance of “infectious agent, particularly virus”. It is suggested to add an “an” before “infectious agent RNA” or “infectious agent” and an “a” before “viral RNA” or “virus” at the first instance of each phrase or word, followed by the appropriate addition of the word “the” in later recitations.
Claim 2 should have a comma inserted after “claim 1”.
Claim 4 recites the limitation “comprises guanidinine thiocyanate (GSCN), mild detergent, and organic sodium salt”. It is suggested to add an “a” before “mild detergent” and an “an” before “organic sodium salt” for clarity of wording.
Claim 6 recites the limitation “wherein the saliva and lysis/RNA stabilization buffer”. It is suggested to change “the saliva” to “the saliva sample” to establish antecedent basis with the suggested amendment to claim 1 above.
Claim 8 recites the limitation “wherein the protein denaturant or reducing agent is selected from…TCEP (tris(2-carboxymethyl).” To align with the other recitations in the claim, it is suggested to swap the full name of TCEP with the abbreviation, such that the recitation reads “wherein the protein denaturant or reducing agent is selected from… tris(2-carboxymethyl) (TCEP).” Furthermore, tris(2-carboxymethyl) is an incomplete name. The full name of the protein denaturant or reducing agent is tris(2-carboxymethyl) phosphine, and should be appropriately included. However, Applicant is cautioned against adding new matter that is not found in the instant disclosure, given that there is no noted instance of the full name tris(2-carboxymethyl) phosphine found in the instant disclosure.
Claim 12 recites “wherein the saliva and lysis/RNA stabilization buffer”. It is suggested to change “the saliva” to “the saliva sample” to establish antecedent basis with the suggested amendment to claim 1 above.
Claim 13 recites the limitation “selected from phenol extraction, column-based isolation, precipitation, or magnetic bead based purification”. It is suggested to add the appropriate article in front of every option in the Markush group, such that the claim reads “selected from a phenol extraction, a column-based isolation, a precipitation, or a magnetic bead based purification”.
Claim 21 recites the limitation “obtaining one or more small volume saliva sample, wherein the sample is collected in”. This recitation is awkwardly worded given the plurality of “one or more”, followed by only referring to a single sample. It is suggested to change this recitation to read “obtaining one or more small volume saliva samples, where a saliva sample of the one or more small volume saliva samples is collected in”. However, it is noted that there is a further 112(b) rejection of claim 21 related to the recitation of “one or more small volume saliva sample”. Applicant is advised to review both this objection and the 112(b) rejection for issues related to the plurality of samples.
Claim 21 further recites the limitation ““comprising guanidinine thiocyanate (GSCN), mild detergent, and organic sodium salt”. It is suggested to add an “a” before “mild detergent” and an “an” before “organic sodium salt” for clarity of wording.
Claim 21 further recites several instances of “infectious agent RNA, particularly viral RNA”, as well as one instance of “infectious agent, particularly virus”. It is suggested to add an “an” before “infectious agent RNA” or “infectious agent” and an “a” before “viral RNA” or “virus” at the first instance of each phrase or word, followed by the appropriate addition of the word “the” in later recitations.
Claim 21 further recites the limitation “to promote binding of RNA nucleic acid”. The phrase “nucleic acid” is unnecessary given that RNA is the well-known abbreviation for ribonucleic acid. It is suggested to delete the phrase “nucleic acid” from this recitation.
Claim 23 recites the limitation “…wherein the protein denaturant or reducing agent is selected from…TCEP (tris(2-carboxymethyl).” To align with the other recitations in the claim, it is suggested to swap the full name of TCEP with the abbreviation, such that the recitation reads “…wherein the protein denaturant or reducing agent is selected from… tris(2-carboxymethyl) (TCEP).” Furthermore, tris(2-carboxymethyl) is an incomplete name, the full name of the protein denaturant or reducing agent is tris(2-carboxymethyl) phosphine, and should be appropriately included. However, Applicant is cautioned against adding new matter that is not found in the instant disclosure, given that there is no noted instance of the full name tris(2-carboxymethyl) phosphine found in the instant disclosure.
Appropriate correction is required.
Claim Interpretation - 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
The claims contain the following limitations:
Claim 21 recites “binding buffer suitable to promote binding of RNA”.
Thus, the cited limitations are drawn to generic means plus function. However, the limitations are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because a review of the specification yields no limiting definition of the generically claimed means.
If applicant intends to have this limitation interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant should indicate where in the specification the specific structure is indicated.
Claim Interpretation
Claim 21 recites the limitation “(d) adding a binding buffer suitable to promote binding of RNA nucleic acid to a column or magnetic beads” and later “(h) isolating RNA using magnetic beads to generate a reconcentrated pooled RNA sample”. It is noted that while step (d) indicates that the binding buffer is suitable for a column or magnetic beads, there is no reference in claim 21 or its dependent claims 22-25 that a column is a definitive part of the claimed method. Therefore, it is interpreted that a column is not necessary to the method, and that magnetic beads are required.
Claim 25 recites the limitation “wherein a single positive sample can be detected in a pooled RNA sample comprising 96 or 100 individual isolated RNA samples”. It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04. It is also noted that a “wherein” clause, such as that in claim 25, must give “meaning and purpose to the manipulative steps.” See, MPEP § 2111.04. As currently recited, claim 25 does not accomplish this and therefore is interpreted to not further limit the method of claim 21.
Claim Rejections - 35 USC § 112(b)
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 and 21-25 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 1 recites the limitation “…(c) reverse transcribing the RNA to generate cDNA; (d) specifically amplifying any infectious agent RNA, particularly viral RNA, using primers and probes specific for the target infectious agent or virus; and (e) determining the presence and identity of infectious agent RNA, particularly viral RNA, whereby primer amplified nucleic acid for the target infectious agent or virus is identified and characterized.” It is unclear from this recitation, given that cDNA is generated, whether direct amplification of infectious agent RNA, particularly viral RNA, is meant to occur, or if amplification of cDNA produced from infectious agent RNA, particularly viral RNA, is meant to occur. Turning to the specification, there are numerous mentions of converting isolated RNA into cDNA (see paragraphs [00057], [000122], [000123], [000125], [000140]). There are also mentions of direct amplification of isolated RNA (see paragraphs [000140], [000142]). However, further turning to the working examples, it appears all provided methods refer to real-time reverse transcriptase polymerase chain reaction for detection of RNA (see paragraphs [000201], [000202], [000213], [000250], [000309], [000334], [000362]), which as claimed, necessarily produces cDNA. Therefore, it is unclear which nucleic acid is intended to be amplified, the infectious agent RNA, particularly viral RNA, directly or cDNA reverse transcribed from this RNA. For the purpose of compact prosecution, “…(c) reverse transcribing the RNA to generate cDNA; (d) specifically amplifying any infectious agent RNA, particularly viral RNA, using primers and probes specific for the target infectious agent or virus; and (e) determining the presence and identity of infectious agent RNA, particularly viral RNA, whereby primer amplified nucleic acid for the target infectious agent or virus is identified and characterized” will be interpreted to mean that cDNA reverse transcribed from the infectious agent RNA, particularly viral RNA, is specifically amplified using primers and probes, and further used to determine the presence and identity of the infectious agent RNA, particularly viral RNA.
Claim 1 also recites the limitation “the target infectious agent or virus” twice. There is insufficient antecedent basis for this limitation in the claim. There has not been an earlier introduction of “the target infectious agent or virus” in the claim. This is therefore found indefinite.
Claim 1 also recites several instances of “particularly viral RNA”, as well as one instance of “particularly virus”. The word "particularly" renders the claim indefinite because it is unclear whether the limitations following the word (i.e. “viral RNA” or “virus”) are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of compact prosecution, viral RNA and virus will be interpreted to be the intended infectious agent.
Claims 2-13 are also rejected here for their dependence on claim 1 and not further clarifying the identified issues.
Claims 2 and 3 both recite the limitation “the saliva sample”. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which both claim 2 and claim 3 depend, does not introduce “a saliva sample”, but instead “one or more small volume saliva sample” and “the sample”, neither of which establishes basis for “the saliva sample”. This is therefore found indefinite. However, it is noted that in the above claim objection section the suggested amendments may affect later antecedent basis. Applicant is advised to review both the objections and this 112(b) rejection for issues related to antecedent basis.
Claim 4 recites the limitation “mild detergent”. The term “mild” is a relative term which renders the claim indefinite. The term “mild” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For the purpose of compact prosecution, “mild detergent” will be interpreted as detergent.
Claim 5 recites the limitation “sarkosyl in a % range of 0.2% to 0.5%”. It is unclear from this recitation what percentage measurement is intended to be represented given the available options for percentage concentration. This includes (w/v), (v/w), (w/w), or (v/v). Therefore, the claim is found indefinite. However, Applicant is cautioned against adding new matter that is not found in the instant disclosure, given that there is no percentage measurement related to sarkosyl in the instant disclosure noted by the Examiner. For the purpose of compact prosecution, “sarkosyl in a % range of 0.2% to 0.5%” will be interpreted as sarkosyl in a %(w/w) range of 0.2% to 0.5% (w/w).
Claim 8 recites the limitation “wherein the protein denaturant or reducing agent is…TCEP (tris(2-carboxymethyl)”. The abbreviation of TCEP is incomplete given that the “P” of the abbreviation is not defined, and therefore found indefinite. However, Applicant is cautioned against adding new matter that is not found in the instant disclosure, given that there is no noted instance of the full name tris(2-carboxymethyl) phosphine found in the instant disclosure.
Claim 9 recites the limitation “The method of claim 1 for evaluation of coronavirus SARS-CoV-2.” It is unclear from this recitation what aspect of coronavirus SARS-CoV-2 is supposed to be evaluated. The method of claim 1 would suggest it would be infectious agent RNA, and therefore coronavirus SARS-CoV-2 RNA. However, this is not claimed in claim 9, and it is therefore indefinite. For the purpose of compact prosecution, “The method of claim 1 for evaluation of coronavirus SARS-CoV-2” will be interpreted as the method of claim 1, wherein the infectious agent RNA is coronavirus SARS-CoV-2 RNA.
Claim 10 is indefinite given the recitation of Table 1, Table 28, and Table 48. As stated in MPEP 2173.05(s), claims should be complete to themselves and the reference to tables renders the claims incomplete. Claims which recite figures or tables are only permitted in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into a claim. Therefore, the claim is found indefinite.
Regarding claim 11, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 11 recites the broad recitation of less than 500ul, and the claim also recites less than 300ul, less than 250ul, about 200-300ul, less than 200ul, about 100-300ul, about 150-300ul, about 100-250ul, and about 300ul, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For the purpose of compact prosecution, the claimed range will be interpreted as less than 500ul.
Claim 13 recites the limitation “wherein RNA is isolated by a method or system selected from phenol extraction, column-based isolation, precipitation, or magnetic bead based purification.” It is unclear from this recitation whether the Markush group is intended be directed to just a system as claimed, or both a method and a system. For the purpose of compact prosecution, “wherein RNA is isolated by a method or system selected from phenol extraction, column-based isolation, precipitation, or magnetic bead based purification” will be interpreted to mean wherein RNA is isolated by a method selected from phenol extraction, column-based isolation, precipitation, or magnetic bead based purification.
Claim 21 recites the limitation “(a) obtaining one or more small volume saliva sample”. However, as stated in the preamble of the claim and limitation (f), numerous samples are used as a part of the claimed method for pooling RNA for profiling and analysis of infectious agent RNA. Therefore, it is unclear how a single small volume saliva sample is capable of meeting the requirement for numerous samples.
Claim 21 also recites several instances of “particularly viral RNA”, as well as one instance of “particularly virus”. The word "particularly" renders the claim indefinite because it is unclear whether the limitations following the word (i.e. “viral RNA” or “virus”) are part of the claimed invention. See MPEP § 2173.05(d). Claim 22 also suffers from the same issue with relation to the limitation “particularly proteinase K”.
Claim 21 recites the limitations “mild detergent”, “numerous”, “small volume”, and “briefly”. The terms “mild”, “numerous”, “small”, and “briefly” are relative terms which render the claim indefinite. The terms “mild”, “numerous”, “small”, and “briefly” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 21 also recites the limitation "(b) heating the saliva and lysis/RNA stabilization buffer sample". There is insufficient antecedent basis for this limitation in the claim. There has not been an earlier introduction of “the saliva and lysis/RNA stabilization buffer sample” in the claim. This is therefore found indefinite.
Claim 21 also recites the limitation “the heated sample”. There is insufficient antecedent basis for this limitation in the claim. There has not been an earlier introduction of “the heated sample” in the claim. This is therefore found indefinite.
Claim 21 also recites the limitation “isolating RNA to generate numerous individual saliva isolated RNA samples; (f) combining aliquots of numerous individual saliva isolated RNA samples to generate a pooled RNA sample”. It is unclear from this recitation whether the numerous samples are the same as the numerous samples recited in the preamble of the claim. It is further unclear if the two instances of numerous samples in the above recited limitations are referring to the same samples, or different samples. This is therefore found indefinite.
Claim 21 also recites the limitation “the target infectious agent or virus” twice. There is insufficient antecedent basis for this limitation in the claim. There has not been an earlier introduction of “the target infectious agent or virus” in the claim. This is therefore found indefinite.
Also regarding claim 21, the phrase "such as" in step (g) renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 21 also recites the limitation “…(i) reverse transcribing the RNA to generate cDNA; (j) specifically amplifying any infectious agent RNA, particularly viral RNA, using primers and probes specific for the target infectious agent or virus; and (k) determining the presence and identity of infectious agent RNA, particularly viral RNA, whereby primer amplified nucleic acid for the target infectious agent or virus is identified and characterized.” It is unclear from this recitation, given that cDNA is generated, whether direct amplification of infectious agent RNA, particularly viral RNA, is meant to occur, or if amplification of cDNA produced from infectious agent RNA, particularly viral RNA, is meant to occur. Turning to the specification, there are numerous mentions of converting isolated RNA into cDNA (see paragraphs [00057], [000122], [000123], [000125], [000140]). There are also mentions of direct amplification of isolated RNA (see paragraphs [000140], [000142]). However, further turning to the working examples, it appears all provided methods refer to real-time reverse transcriptase polymerase chain reaction for detection of RNA (see paragraphs [000201], [000202], [000213], [000250], [000309], [000334], [000362]), which as claimed, necessarily produces cDNA. Therefore, it is unclear which nucleic acid is intended to be amplified, the infectious agent RNA, particularly viral RNA, directly or cDNA reverse transcribed from this RNA.
Further regarding claim 21, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 21 recites the broad recitation hundreds, and the claim also recites numerous, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 22-25 are also rejected here for their dependence on claim 21 and not further clarifying the identified issues noted above.
Claim 23 recites the limitation “wherein the protein denaturant or reducing agent is…TCEP (tris(2-carboxymethyl)”. The abbreviation of TCEP is incomplete given that the “P” of the abbreviation is not defined, and therefore found indefinite. However, Applicant is cautioned against adding new matter that is not found in the instant disclosure, given that there is no noted instance of the full name tris(2-carboxymethyl) phosphine found in the instant disclosure.
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.
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, 4, 7-11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Yan (Investigation of HGV and TTV infection in sera and saliva from non-hepatitis patients with oral diseases, World Journal of Gastroenterology, October 2002, 8, 857-862; cited on the IDS filed April 19th, 2023), as evidenced by Peters (US 20170327911 A1; cited on the IDS filed April 19th, 2023), in view of Lipkin (US 20230332254 A1, effectively filed February 20th, 2020).
Regarding instant claims 1, 2, and 11, Yan teaches a method for profiling and analysis of infectious agent RNA, particularly viral RNA, of saliva samples from one or more patients or individuals comprising: (a) obtaining one or more small volume saliva samples (Page 858, column 1, Isolation of total RNA and DNA in saliva: 200ul of saliva sample; specific volume pertinent to claims 2 and 11), wherein the sample is collected in or otherwise combined with a buffer comprising guanidinine thiocyanate (GSCN) (Page 858, column 1, Isolation of total RNA and DNA in saliva). As evidenced by Peters, a reagent comprising guanidine isothiocyanate is a stabilization/lysis reagent that also causes instantaneous uncoating of virions and stabilization of RNA (Peters, Page 15, paragraph [0088]; Figure 6A). Therefore, Yan necessarily teaches a lysis/RNA stabilization buffer comprising guanidinine thiocyanate (GSCN), whereby infectious agent, particularly virus, is inactivated and RNA is stabilized. Yan further teaches (b) isolating RNA (Page 858, column 1, Isolation of total RNA and DNA in saliva); (c) reverse transcribing the RNA to generate cDNA (Page 858, column 1 to column 2, RT-nested PCR for HGV RNA detection); (d) specifically amplifying any infectious agent RNA, particularly viral RNA, using primers specific for the target infectious agent or virus (Page 858, columns 1 and 2, RT-Nested PCR for HGV RNA detection); and (e) determining the presence and identity of infectious agent RNA, particularly viral RNA, whereby primer amplified nucleic acid for the target infectious agent or virus is identified and characterized (Page 858, column 2, Examination of amplification products).
Yan does not teach wherein the infectious agent RNA, particularly viral RNA, is amplified with primers and probes specific for the target infectious agent or virus.
Lipkin, in the same field of endeavor, teaches on amplification and detection of infectious agent RNA, particularly viral RNA, with primers and probes specific for the target infectious agent or virus in a saliva sample, and determining the presence and identity of infectious agent RNA, particularly viral RNA (Page 1, paragraphs [0008]-[0009]; Page 12, paragraph [0124]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Yan with the method of Lipkin. Since both Yan and Lipkin are in the same field of endeavor (e.g. analysis of viral RNA), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Yan amplifies viral RNA with specific primers and detects with gel electrophoresis, while Lipkin amplifies viral RNA with specific primers and a detectability labeled probe and detects the labeled probe. A detectably labeled probe would be a simple substitution for gel electrophoresis.
With respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps in claim 1 is an obvious variant of the steps of the cited prior art.
It is further noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed ranges of claims 2 and 11 merely represent routine optimization of the values of the cited prior art. Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel' s arguments in place of evidence in the record.
Regarding instant claim 4, Yan, in view of Lipkin, teaches the method of claim 1. Yan further teaches wherein the lysis/RNA stabilization buffer comprises guanidinine thiocyanate (GSCN), mild detergent and organic sodium salt (i.e., sodium citrate; Page 858, column 1, Isolation of total RNA and DNA in saliva).
Regarding instant claim 7, Yan, in view of Lipkin, teaches the method of claim 1. Yan further teaches wherein a protein denaturant or reducing agent is added to the sample in lysis/RNA stabilization buffer prior to isolating RNA (Page 858, column 1, Isolation of total RNA and DNA in saliva).
As stated above, with respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding instant claim 8, Yan, in view of Lipkin, teaches the method of claim 7. Yan further teaches wherein the protein denaturant or reducing agent is 2-mercaptoethanol (Page 858, column 1, Isolation of total RNA and DNA in saliva).
Regarding instant claim 9, Yan, in view of Lipkin, teaches the method of claim 1. Lipkin further teaches that SARS-CoV-2 is a virus (Page 1, paragraph [0004]), and can be found in saliva samples (Page 12, paragraphs [0122]-[0124]). Therefore, it would be obvious that samples evaluated with the method of Yan could detect SARS-CoV-2. This amounts to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)).
Regarding instant claim 10, Yan, in view of Lipkin teaches the method of claim 9. Lipkin further teaches the probe sequence of SEQ ID. NO:18 (Table 1, nCoV-NP2, Probe, SEQ ID NO:6) and the corresponding primers SEQ ID NOs:16 and 17 (Table 1, nCoV-NF2 and nCoV-NR2, Forward primer and Reverse Primer, SEQ ID NO:4 and SEQ ID NO:5).
Regarding instant claim 13, Yan, in view of Lipkin, teaches the method of claim 1. Yan further teaches wherein RNA is isolated by a phenol extraction (Page 858, column 1, Isolation of total RNA and DNA in saliva).
Claims 3 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Yan (Investigation of HGV and TTV infection in sera and saliva from non-hepatitis patients with oral diseases, World Journal of Gastroenterology, October 2002, 8, 857-862; cited on the IDS filed April 19th, 2023) and Lipkin (US 20230332254 A1, effectively filed February 20th, 2020), as applied to claims 1, 2, 4, 7-11, and 13, and further in view of Sawyer (WO 2021236696 A1, effectively filed May 18th, 2020).
Regarding instant claim 3, Yan, in view of Lipkin teaches the method of claim 1.
Neither reference teaches wherein the saliva sample is combined with an approximately equal amount of lysis/RNA stabilization buffer.
Sawyer, in the same field of endeavor, teaches on a method of combining a stabilization solution and saliva to detect pathogen nucleic acids, such as those from SARS-CoV-2 (Abstract). Sawyer further teaches combining saliva and stabilization solution in a 1:1 ratio (Page 11, lines 8-9).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Yan, in view of Lipkin, with the saliva to buffer ratio of Sawyer. Since both Yan, in view of Lipkin, and Sawyer are in the same field of endeavor (e.g. methods to analyze viral nucleic acids from saliva), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been obvious the known ratio of Sawyer could have been applied to the method of Yan, in view of Lipkin, with predictable results because the 1:1 ratio of solution to saliva of Sawyer predictably results in stabilization of a saliva sample.
Regarding instant claim 12, Yan, in view of Lipkin, teaches the method of claim 1. Yan teaches on the addition of proteinase K to DNA extraction solution for extraction of DNA from sera (Page 858, column 1, Isolation of total RNA and DNA in sera) and saliva (Page 858, column 1, Isolation of total RNA and DNA in saliva).
Neither reference teaches wherein the saliva and lysis/RNA stabilization buffer is combined with a protease prior to or during RNA isolation, wherein the protease is proteinase K.
Sawyer, in the same field of endeavor, teaches on adding proteinase K to a saliva stabilization solution to inhibit RNases and help preserve virion RNA (Page 23, lines 1-3).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Yan, in view of Lipkin, with the proteinase K of Sawyer. Since both Yan, in view of Lipkin, and Sawyer are in the same field of endeavor (e.g. methods to analyze viral nucleic acids from saliva), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because proteinase K inhibits RNases to preserve virion RNA (Sawyer, Page 23, lines 1-4).
It is further noted that, as stated above, with respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art. Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record”, as also stated above. Thus, Applicant should not merely rely upon counsel's arguments in the place of evidence in the record.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Yan (Investigation of HGV and TTV infection in sera and saliva from non-hepatitis patients with oral diseases, World Journal of Gastroenterology, October 2002, 8, 857-862; cited on the IDS filed April 19th, 2023) and Lipkin (US 20230332254 A1, effectively filed February 20th, 2020), as applied to claims 1, 2, 4, 7-11, and 13, and further in view of Sprenger-Haussels (JP 2008529509 A; both the foreign application and the translation are provided, citations are based on the translation), as evidenced by Synapse (What is the mechanism of Sodium Acetate [online]. Synapse, [2024] [retrieved on April 16th, 2026]. Retrieved from: https://synapse.patsnap.com/article/what-is-the-mechanism-of-sodium-acetate).
Regarding instant claim 5, Yan, in view of Lipkin, teaches the method of claim 1. Yan teaches on using sarkosyl in a % range of 0.2% to 0.5% (Page 858, column 1, Isolation of total RNA and DNA in saliva). Yan also teaches on using sodium acetate as a component of solutions for RNA isolation (Page 858, column 1, Isolation of total RNA and DNA in saliva).
Neither reference teaches wherein the lysis/RNA stabilization buffer has a concentration of components comprising GSCN in the range of 5-6 M, sarkosyl in a % range of 0.2% to 0.5% and sodium acetate (NaAc) at 150mM-200mM, and a pH of 5-6.
Sprenger-Haussels, in the same field of endeavor, teaches on a lysis buffer that comprises chaotropic substances, such as guanidinium thiocyanate, in concentrations ranging from 2M to 7M; alkaline reagents in concentrations ranging from 0.1M to 1M (i.e. from 100mM to 1000mM); and reagents (i.e. detergents), such as sarkosyl, in concentrations ranging from 0.1 to 50wt% (Page 3, paragraph [0018]). Sprenger-Haussels also teaches that suitable concentrations and amounts of lysis reagents vary depending on the system, type of cells, etc. (Page 3, paragraph [0018]). With regard to alkaline reagents, as evidenced by Synapse, sodium acetate solutions are mildly alkaline (Page 1, paragraph 3), and therefore provides evidence for sodium acetate as an alkaline reagent.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Yan, in view of Lipkin, with the component concentrations of Sprenger-Haussels. Since both Yan, in view of Lipkin, and Sprenger-Haussels are in the same field of endeavor (e.g. nucleic acid isolation), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because suitable concentrations and amounts of lysis reagents vary depending on the system, type of cells, etc. (Sprenger-Haussels, Page 3, paragraph [0018]).
Furthermore, as stated above, the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Thus, the claimed ranges merely represent routine optimization of the values of the cited prior art.
None of the above cited references as currently presented teach that the lysis/RNA stabilization buffer has a pH of 5-6. However, Yan does teach that the guanidine based buffer is pH 7.0 (Page 858, column 1, Isolation of total RNA and DNA in saliva). As stated above, the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Thus, the claimed ranges merely represent routine optimization of the values of the cited prior art.
Regarding instant claim 6, Yan, in view of Lipkin, teaches the method of claim 1.
Neither reference teaches wherein the saliva and lysis/RNA stabilization buffer are heated briefly for about 10-20 minutes at 65°C prior to isolating RNA.
Sprenger-Haussels, in the same field of endeavor, teaches on heating a lysis buffer comprising detergents and/or chaotropic substances in the range of 37⁰C to 65⁰C (Page 3, paragraph [0019]). Sprenger-Haussels further teaches that incubation time may also be varied from a few minutes to 24 hours, for example 5 minutes to 2 hours (Pages 3-4, paragraph [0020]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Yan, in view of Lipkin, with the component concentrations of Sprenger-Haussels. Since both Yan, in view of Lipkin, and Sprenger-Haussels are in the same field of endeavor (e.g. nucleic acid isolation), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because different incubation conditions are suitable for different lysis systems (Sprenger-Haussels, Page 3, paragraph [0019]).
Furthermore, as stated above, the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, especially with respect to temperature. Thus, the claimed ranges merely represent routine optimization of the values of the cited prior art.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure, more particularly claims 21-25.
Ben-Ami (Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection, Clinical Microbiology and Infection, September 2020, 26, 1248-1253) teaches on pooling of nasopharyngeal swab samples after inactivation by lysis buffer, but prior to isolation of individual samples (Page 1249, column 2, paragraphs 1 and 5). Ben-Ami does not teach on isolating RNA from individual saliva samples with a binding buffer, combining aliquots of the isolated RNA, and then further isolating the pooled RNA using a 2X salt concentration compared to the earlier binding buffer.
Pasomsub (Saliva sample pooling for the detection of SARS‐CoV‐2, Journal of Medical Virology, September 2020, 93, 1506-1511) teaches on pooling RNA specimens extracted from saliva samples in pools of 5 or 10 prior to performing RT-PCR (Page 1506, column 2, paragraph 2 to Page 1507, column 1, paragraph 1). Pasomsub does not teach on isolating RNA from individual saliva samples with a binding buffer, combining aliquots of the isolated RNA, and then further isolating the pooled RNA using a 2X salt concentration compared to the earlier binding buffer.
Lohse (Pooling of samples for testing for SARS-CoV-2 in asymptomatic people, The Lancet Infectious Diseases, November 2020, 20, 1231-1232) teaches on isolating viral RNA from eSwabs, and then pooling RNA from 4 to 30 samples prior to RT-PCR detection of virus (Page 1231, column 3). Lohse does not teach on isolating RNA from individual saliva samples with a binding buffer, combining aliquots of the isolated RNA, and then further isolating the pooled RNA using a 2X salt concentration compared to the earlier binding buffer.
Sun (Saliva as a testing specimen with or without pooling for SARS-CoV-2 detection by multiplex RT-PCR test, medRxiv, November 2020, 1-31, doi.org/10.1101/2020.10.27.20219196) teaches on pooling saliva samples directly (Page 7, paragraph 1), followed by viral RNA extraction (Page 7, paragraph 2) and RT-PCR detection of viral RNA (Page 7, paragraph 3 to Page 8, paragraph 8). Sun does not teach on isolating RNA from individual saliva samples with a binding buffer, combining aliquots of the isolated RNA, and then further isolating the pooled RNA using a 2X salt concentration compared to the earlier binding buffer.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLISON E SCHLOOP/ Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights