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 with traverse of Group 1 as well as species (i) virus and (ii) SARS CoV-2 in the reply filed on 2/06/26 is acknowledged. Applicant’s cancellation of claims 6, 11, 14, 16, and 17 is acknowledged.
The traversal is on the grounds that amendments to the claims have rendered special the shared technical feature over the art of Feng et al. and Ronaghi et al., by requiring that the methods of Group 1 and kit of Group 2 require contacting and incubating to be performed at <65ºC. This is not found persuasive for the following reasons:
The limitation, applied to the kit of Group 2, is an intended use of said kit. As product claims are analyzed with respect to their structure, this intended use does not limit the scope of the claims. Therefore, performance of the contacting and incubating step at <65ºC may not be a shared technical feature between Group 1 and Group 2.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-5, 7-10, 12, 13, 15, 18-21 are currently pending.
Claims 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention(s), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/06/26.
Claims 8-10 have been examined to the extent that they read on the elected organisms (virus). The additionally recited organisms have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Claims 9-10 have been examined to the extent that they read on the elected virus (SARS CoV-2). The additionally recited viruses have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Priority
It is acknowledged that the instant application is a 371 of international PCT Application No. PCT/US2022/019086, filed 3/7/22, and that it claims benefit of provisional 63/160,141, filed 3/12/21. The effective filing date is considered to be 3/12/21.
Claim Objections
Claims 10 and 13 are objected to because of the following informalities: improper grammar and/or typographical errors.
The phrase “an ORF1 a replication protein” either lacks appropriate punctuation (such as commas) or erroneously includes extraneous words, obscuring the meaning of the sentence.
The phrase “a replication protein nucleocapsid protein” either lacks appropriate punctuation (such as commas) or erroneously includes extraneous words, obscuring the meaning of the sentence.
Appropriate correction is required.
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 2, 4, 5, 10, and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is rejected for the recitation of “reverse polymerase chain reaction (RT-PCR).” Claim 1 (on which it depends) specifies that the amplification reaction is an isothermal method, but RT-PCR requires thermal cycling. There is no special definition in the specification for the term ‘isothermal amplification’ which redefines the term to allow for the inclusion of RT-PCR as a species. Therefore, it is unclear what is encompassed by “isothermal amplification” and a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
Claims 2, 4 and 5 are rejected for the recitation of “the amplification reaction” in claims 2 and 4 as lacking antecedent basis. Claim 1 (on which they depend) recites an “isothermal amplification reaction,” and it is unclear if the recitation of “the amplification reaction” refers to the isothermal amplification reaction or some other amplification reaction. Therefore, a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
Claims 10 and 13 are rejected for the recitation of “a primer set to amplify a portion of a gene encoding an ORF1 a replication protein.” It is unclear what is meant by “an ORF1 a replication protein,” given that ORF1 comprises multiple genes that encode for several different proteins involved in replication (e.g. RdRp). For example, does the claim require amplification of any portion of ORF1, or does it restrict the amplification to a portion of a gene comprising only a single gene, or does some other criteria apply? Therefore, a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
Claims 10 and 13 are rejected for the recitation of “a primer set to amplify a portion of a gene encoding a replication protein nucleocapsid protein.” It is unclear what is meant by “a replication protein nucleocapsid protein,” given that replication proteins are in a different genomic region than the nucleocapsid protein, and the claim already requires primers that amplify a portion of a gene encoding “an ORF1 a replication protein.” Therefore, a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 2, 4, 7-9, 12, 15, and 18 are rejected under 35 U.S.C. 103 as unpatentable over the combination of Kellner et al. (published January 20, 2021; Kellner et al. medRxiv 2021.01.19.21250079) and Dey et al. (published Sept 20, 2019; Dey et al. ACS Omega; 4(14):16191-16200). This rejection is further evidenced by Vienna BioCenter (published 2020; accessed from: https://www.rtlamp.org/get-started/rt-lamp-open-access/) and Bearinger et al. (published December 1, 2011; Patent Publication No. US 2011/0294199).
Kellner teaches methods of diagnosing SARS-CoV-2 using assays such as RT-LAMP (pg. 3: Summary).
Regarding claims 1 and 12, Kellner teaches a method for detecting the presence or absence of a target nucleic acid, wherein the target nucleic acids are SARS CoV-2 nucleic acids (pg. 3: Summary). Kellner teaches the method comprising contacting a sample suspected of containing the target nucleic acid (pg. 3, col. 1) with an amplification mixture comprising one or more primer sets to amplify a portion of the target nucleic acid, divalent ions, dNTPs, a dye (pg. 9: RT-LAMP), and a buffer (pg. 3, col. 1). In this case, the buffer is retained in the lysate which is added to the RT-LAMP reaction (pg. 6: RT-LAMP; pg. 10, col 1, 1st par). Although Kellner teaches a Master Mix and not polymerases explicitly, polymerases are used in RT-LAMP, as evidenced by Vienna BioCenter (RT-LAMP Reaction Assembly, see below). In this case, BstLF is the polymerase.
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Kellner teaches incubating the amplification mixture under conditions to perform an isothermal amplification reaction, wherein contacting and incubating are performed at a temperature of less than 65ºC (pg. 10, col. 1, 1st par.). Kellner teaches providing amplified target nucleic acid (in the form of the RT-LAMP product from which colorimetric signal was read: pg. 10, col. 1, 1st par.). Keller does not explicitly teach providing pyrophosphate, but pyrophosphate would be present a natural byproduct of DNA amplification, as evidenced by Bearinger (par. 114).
Kellner teaches a dye which indicates the productions of a metal-pyrophosphate complex and the presence of target nucleic acid in the sample (pg. 6: RT-LAMP). This dye – HNB – demonstrates colorimetric changes as free Mg2+ binds to pyrophosphate generated as a byproduct of amplification, as evidenced by Bearinger (par. 114).
Kellner does not teach an amino-acid functionalized perylene- 3,4:9,10-tetracarboxylic dianhydride (PDI) dye complexed with copper (X-PDI-Cu), wherein amino acid X is selected from aspartic acid, glycyl-l-aspartic acid, and glutamic acid. Kellner does not teach detecting un-complexed X-PDI in in the reaction mixture, wherein un-complexed X- PDI indicates the production of Cu-pyrophosphate and the presence of the target nucleic acid in the sample.
Dey et al. teaches a water-soluble compound suitable for biosensing applications (Abstract).
Regarding claims 1 and 12, Dey teaches an amino-acid functionalized perylene- 3,4:9,10-tetracarboxylic dianhydride (PDI) dye complexed with copper (X-PDI-Cu), wherein amino acid X is selected from aspartic acid, glycyl-l-aspartic acid, and glutamic acid (pg. 16198). Dey teaches detecting un-complexed X-PDI in in the reaction mixture, wherein un-complexed X- PDI indicates the production of Cu-pyrophosphate (pg. 16192, col. 2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Kellner and Dey, in order to utilize a dye effective at a wide range of pH (pH 4-9), with a very low limit of detection (Dey: pg. 16196-8: Conclusions).
Kellner does not explicitly teach an embodiment wherein the sample is a salivary sample, but does teach that the method is compatible with salivary samples (pg. 3, col. 1; pg. 6: RT-LAMP). Given that there are a finite number of solutions (i.e. specimen types) and there is no evidence of unexpected results, it would have been obvious to a person with ordinary skill in the art to try using saliva, in order to analyze a commonly used specimen type (pg. 6: RT-LAMP). This would be desirable as it would allow samples to be collected in a simple, non-invasive manner (pg. 7, 2nd par.).
Regarding claims 2, 4, and 15, Kellner teaches that the amplification reaction is RT-LAMP (pg. 6: RT-LAMP). Although Kellner does not explicitly discuss the amplification mixture comprising a reverse transcriptase, RT-LAMP (or “Reverse Transcription” LAMP) requires the use of reverse transcriptase, as evidenced by Vienna BioCenter (RT-LAMP Reaction Assembly, see above).
Regarding claims 7 and 18, Kellner teaches colorimetric detection and fluorescence detection (pg. 10: 1st par.; pg. 6: RT-LAMP).
Regarding claims 8 and 9, Kellner teaches detecting target nucleic acid from a virus, where the virus is SARS CoV-2 (Summary).
Claim 3 is rejected under 35 U.S.C. 103 as unpatentable over Kellner et al. (published January 20, 2021; Kellner et al. medRxiv 2021.01.19.21250079) and Dey et al. (published Sept 20, 2019; Dey et al. ACS Omega; 4(14):16191-16200), as applied to claim 1 above, and in view of Garafutdinov et al. (published August 9, 2020; Int J Biol Macromol. 2020 Oct 15;161:1447-1455). It is noted that the rejection of claim 1 was further evidenced by Vienna BioCenter and Bearinger et al.
Kellner and Dey teach the limitations of claim 1, as discussed above.
Regarding claim 3, Kellner and Dey do not teach the amplification mixture further comprising manganese.
Garafutdinov et al. teaches conditions favorable for polymerases used in isothermal amplification methods (Abstract).
Garafutdinov teaches an amplification mixture comprising manganese (pg. 1454: Conclusion).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Kellner and Dey with the teachings of Garafutdinov, in order to increase the specificity of isothermal amplification in combination with magnesium (Garafutdinov: pg. 1451), or to enhance reverse transcriptase activity (Garafutdinov: pg. 1448, col. 1, 1st par.)
Claim 5 is rejected under 35 U.S.C. 103 as unpatentable over Kellner et al. (published January 20, 2021; Kellner et al. medRxiv 2021.01.19.21250079) and Dey et al. (published Sept 20, 2019; Dey et al. ACS Omega; 4(14):16191-16200), as applied to claims 1 and 4 above, and in view of Thi et al. (published July 27, 2020; Thi et al. Sci Transl Med. 2020 Aug 12;12(556):eabc7075.). It is noted that the rejections of claims 1 and 4 were further evidenced by Vienna BioCenter and Bearinger et al.
Kellner and Dey teach the limitations of claims 1 and 4, as discussed above.
Regarding claim 5, Kellner and Dey do not teach that the method does not include a step of heating to 950C.
Thi et al. teaches methods of diagnosing SARS-CoV-2 using assays such as RT-LAMP (Abstract).
Regarding claim 5, Thi teaches an isothermal amplification method which does not include a step of heating to 95ºC (pg. 10: Swab-to-RT-LAMP assay).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Kellner and Dey with the teachings of Thi, in order to assay specimens without a prior RNA processing step (Thi: pg. 5, col. 2). This would be desirable for simpler point-of-care testing.
Claims 10 and 13 are rejected under 35 U.S.C. 103 as unpatentable over Kellner et al. (published January 20, 2021; Kellner et al. medRxiv 2021.01.19.21250079) and Dey et al. (published Sept 20, 2019; Dey et al. ACS Omega; 4(14):16191-16200), as applied to claims 1, 8, 9 and 12 above, and in view of Zhang et al. (published April 8, 2020; Zhang et al. medRxiv 2020.04.08.20056986). It is noted that the rejections of claims 1 and 12 were further evidenced by Vienna BioCenter and Bearinger et al.
Kellner and Dey teach the limitations of claims 1, 8, 9, and 12, as discussed above.
Regarding claims 10 and 13, Kellner teaches a primer set to amplify a portion of a gene encoding an ORF1a of SARS CoV-2 (pg. 6: RT-LAMP), which can be classified as encoding a replication protein. Kellner also teaches primers targeting the envelope/E gene (pg. 3, col. 1) and the nucleocapsid/N gene (pg. 9: Directed RT-PCR) in RT-qPCR applications.
Kellner does not teach primer sets to amplify a portion of a gene encoding a replication protein, an envelope protein, and a nucleocapsid protein in a single reaction mixture.
Zhang teaches isothermal amplification methods for viral pathogens (Abstract).
Regarding claims 10 and 13, Zhang teaches incorporating primers for multiple SARS CoV-2 gene targets into a single isothermal amplification mixture (Introduction, 2nd par).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Kellner and Dey with the teachings of Zhang, in order to increase confidence of sample positivity (Zhang: Introduction, 2nd par.).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine M Jones whose telephone number is (571)272-2585. The examiner can normally be reached Monday - Friday, 8AM - 4PM.
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/C.M.J./Examiner, Art Unit 1682
/AMANDA HANEY/Primary Examiner, Art Unit 1682