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 .
The preliminary amendment filed 11/14/2022 canceled claims 1-40 and added new claims 41-60.
Claims 41-60 are currently pending in this application.
Specification
The abstract of the disclosure is objected to because the abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
The specification does not include cross-reference to related applications and an incorporation by reference statement regarding an XML filed for “sequence listing” in accordance to 37 CFR 1.77. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 41-60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. There is insufficient written description to demonstrate that applicant was in possession of the device or method that can detect any nucleic acid sequence of interest present in the sample since specific nucleic acid primers required for amplification reaction for detection of a nucleic acid sequence of interest in a sample using RT-LAMP method.
The device claims recite that the “reaction chamber is configured for accommodating …….a reaction mixture adapted for amplification reaction”; the method claims recite that “the amplification reaction is performed using at least one set of primers specific for at least one nucleic acid sequence” and the kit claims recite the reaction mixture comprises at least one set of primers specific for at least one nucleic acid sequence. The specification discloses that “the protocol was developed based on reverse Loop-mediated isothermal amplification (RT-LAMP) for detection of SARS-CoV-2 directly from crude nose and throat swabs (page 8). The specification (pages 67-68) discloses as species a set of SARS-CoV-2 primers (SEQ ID Nos: 1-18) designed by Zhang et al to use in the claimed invention. The specification discloses that any pathogen (viral, bacterial, fungal target DNA) is detected, but no other primers specific to the pathogen are disclosed. The disclosed species of primers are not sufficiently representative of the genus of primers encompassed by the instant claims. Further the loop mediated isothermal amplification (LAMP) employs a specific set of primers that recognize specific sequences in the target DNA (see Notomi 2000). Thus, with the exception of the SARS-CoV-2 specific nucleic acid detection in the sample using RT-LAMP method, the skilled artisan cannot envision that applicants are in possession of the device or assay to detect any nucleic acid of interest in the sample.
Claim Interpretation
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 words “configured for” are not 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.
Within the context of prong (C), examiners may check whether: (1) the specification provides a description sufficient to inform one of ordinary skill in the art that the term denotes structure; (2) general and subject matter specific dictionaries provide evidence that the term has achieved recognition as a noun denoting structure; and/or (3) the prior art provides evidence that the term is an art-recognized structure to perform the claimed function.
The following claim limitations are interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim 41 limitations “configured for enabling delivery of said prepared sample to the reaction module”; “reaction chamber is configured for accommodating therein a respective quantity… reaction mixture” ; and in claim 50 “configured for enabling selective delivery”; in claim 51 “configured for being coupled to the device”, “configured for delivering heat”; in claim 52 “configured for detecting said test parameter” couples the functional language without reciting sufficient structure to achieve the function.
3-prong analysis to determine 35 USC 112 (f) applies-
Regarding prong (A), claims 41, 50, 51 do not use the term “means” or “step” the generic placeholder.
Regarding prong (B), the claims modify the generic placeholder with functional language, specifically “configured for enabling delivery” and “configured for accommodating.” These limitations are wholly functional because they define the specific use.
Regarding prong (C), there is no structural modifier explicitly set forth or implied by the functional language.
Accordingly, claims 41, 50 and 51 limitations do not meet the 3-prong analysis and 35 USC 112 (f) does not apply.
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 41, 50 and 51 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 41, 50 and 51 limitations “configured for enabling delivery of said prepared sample to the reaction module”; “reaction chamber is configured for accommodating therein a respective quantity… reaction mixture” have been evaluated under the three-prong test set forth in MPEP § 2181, subsection I, but the result is inconclusive. Thus, it is unclear whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the term “configured for” which is ambiguous whether it convey structure or function. The boundaries of this claim limitation are ambiguous; therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
In response to this rejection, applicant must clarify whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. Mere assertion regarding applicant’s intent to invoke or not invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph is insufficient. Applicant may:
(a) Amend the claim to clearly invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by reciting “means” or a generic placeholder for means, or by reciting “step.” The “means,” generic placeholder, or “step” must be modified by functional language, and must not be modified by sufficient structure, material, or acts for performing the claimed function;
(b) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, should apply because the claim limitation recites a function to be performed and does not recite sufficient structure, material, or acts to perform that function;
(c) Amend the claim to clearly avoid invoking 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by deleting the function or by reciting sufficient structure, material or acts to perform the recited function; or
(d) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, does not apply because the limitation does not recite a function or does recite a function along with sufficient structure, material or acts to perform that function.
Claim 49 recites “said respective third quantity of said respective reaction mixture” in line 3; said pathogen in line 12 . There is insufficient antecedent basis for these limitation in claim 49 or in claim 41. It is not clear what is considered a respective third reaction mixture.
Claim 50 recites “said respective third quantity of said respective reaction mixture” in lines 2- 3; “said second quantity of at solubizing agent” in lines 14; and “said respective fourth quantity of at least one chaotropic agent” in lines 15. There is insufficient antecedent basis for these limitation in claim 49 or in claim 41.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 53 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (2020).
Claim 53 recites a method for detection and monitoring of at least one nucleic acid sequence of interest in at least one sample.
Zhang discloses rapid detection of SARS-CoV-2 (COVID-19) virus RNA using colorimetric loop-mediated isothermal amplification (LAMP). Regarding the step (a) of the present claim - Zhang teaches that the viral RNA was extracted from deactivated samples (see extraction of viral RNA which includes contacting the sample with a buffer (sample preparation agent)); and regarding step (b) subjecting at least one prepared sample to amplification reaction under isothermal conditions – Zhang teaches LAMP assay on RNA samples from COVID-19 patients. The LAMP assay was performed using LAMP primers (Table 1) targeting fragments of SARS-CoV-2 genome. Zhang teaches colorimetric detection of SARS-CoV-2 nucleic acid in the sample. Zhang also conducted LAMP assay using negative control samples (Figure 4). Zhang teaches that a method for visual detection of LAMP amplification using pH-sensitive dyes. Thus Zhang anticipates claim 53 method.
Claims 41 and 49 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US 2005/0250199 A1 (herein “Anderson”).
Claim 41 recites a device for detection of at least one nucleic acid sequence of interest in at least one sample, comprising a sample module and a reaction module.
Anderson discloses a miniature integrated nucleic acid diagnostic device (0038, 0110). The device is capable of performing sample preparation and sample analysis operation (0038), the device is useful for nucleic acid based diagnostic assay (0038). The device is used to determine the presence or absence of a particular nucleic acid sequence of an infectious agent (a pathogen) within a particular human sample (0200). Anderson teaches that the DNA is extracted from the sample using lysing agents to disrupt the cells and extract the nucleic acids from the cells, followed by treatment of extract with chaotropic salts such as guanidium isothiocyanate or urea to denature any contaminating proteins (0050, 0057, 0202). Anderson teaches that various known amplification reaction methods are suitable to use in the methods and with the device of the invention (0060), and teaches that the nucleic acid based sequence amplification (NASBA) involved isothermal reaction conditions (0061). The device can be used to identify a viral or bacterial pathogen sequence in the sample (0107)
The device comprises a plurality of distinct chambers including a sample preparation chamber, storage chamber and analytical chamber arranged in series, whereby the fluid sample is moved serially through the chambers (0128, 0130, FIG.3).
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In Fig.3, the reaction chamber 202 may be a sample collection chamber (refers to sample module of the present claim), which is adapted for receiving a fluid sample (0131), the sample collection chamber may have reagents for stabilization of the sample (0132); the sample collection chamber is connected via a fluid channel 204 to a second reaction chamber 210 in which extraction of nucleic acids from cells within the sample may be performed (0133); the extraction chamber is fluidly connected via a second fluid channel 208 to amplification chamber 210 (third chamber) (refers to the reaction module of the present claim), which includes the amplification reagents and a controllable heater (adapted for amplification reaction under isothermal conditions 0060, 0061); the amplification chamber is fluidly connected via a fluid channel 212 to an additional reaction chamber 214 and an analytical chamber 218. Thus, the diagnostic device taught by Anderson anticipates the present claim 41.
Regarding claim 49, Anderson teaches that the central chamber functions as a hub for the various operations to be carried out as a whole since the central chamber is fluidly connected to one or more additional reaction and/or storage chambers, and analytical chamber (0140, 0141, 0144). Anderson also teaches that at least one of the chambers is a volumetric chamber to create aliquot of the fluid (0021), which refers to first, second and third quantity of the reaction mixture of the present claim. Regarding c) and d) in claim 49, Anderson teaches that the nucleic acid in a sample is labeled to facilitate detection in subsequent steps. Labeling maybe carried out during amplification (0070) or following amplification (0071). The suitable labels include a variety of known fluorescent labeling groups (0071). Anderson further teaches that following amplification the nucleic acid sequence of interest is detected using a reader device external to the diagnostic device or incorporate the data gathering operation into the diagnostic device itself (0091). Thus, Anderson anticipates claim 49.
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.
Claim 54- 56 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang as applied to claim 53 above, and further in view of Wang (Journal of Virological methods 238(2016) 86-93) and US 2018/0237841 (Stray).
Claims 54-56 depend from claim 53 and further recite that the sample preparation comprises a protease, and further contacting the sample with at least one chaotropic agent.
The teachings of Zhang are as discussed above. Zhang discloses rapid detection of SARS-CoV-2 (COVID-19) virus RNA using colorimetric loop-mediated isothermal amplification (LAMP). Zhang fails to specifically teach that the sample is contacted with a protease and a chaotropic agent. However, the methods for isolating nucleic acids from a biological sample using a protease for lysis of pathogens (i.e., SARS virus), and extraction buffer comprising chaotropic compound guanidine chloride, urea, guanidine thiocyanate to extract nucleic acid are known in the prior art.
Wang in the same field of endeavor teaches rapid detection of zika virus (ZikV) by reverse transcription loop-mediated isothermal amplification (RT-LAMP) (Abstract). Wang teaches that LAMP assay is simple, efficient and robust assay, which can be performed with impure templates and decreasing sample processing times (87, left column). The RT-LAMP reaction was performed at temperatures between 61-65 ◦C (isothermal conditions). Wang teaches that the sample preparation comprises adding proteinase K (a protease) to the biological sample (p.87 right column, p.90). Wang further teaches that the amplification products are observed by the naked eye under natural light by adding calcein fluorescent reagent (a pH sensitive fluorescent dye) (p.88, left column). Similarly, Stray discloses a composition comprising a chaotropic agent for isolating nucleic acids from biological samples (Abstract and claims). The composition for isolating biological sample comprises guanidine chloride (GnCl), guanidine isothiocyante or urea as chaotropic agent. Thus, it would have been obvious to a person skilled in the art before the effective filing date of the claimed invention to include proteinase K (a protease) and guanidine chloride (GnCl) in the sample preparation step of the present claimed method. A person of ordinary skill in the art would have included proteinase K (a protease) and guanidine chloride (GnCl) in the sample preparation step because Wang teaches that LAMP assay decreases sample preparation time and rapid proteolysis treatment was able to extract sufficient quantities of RNA from the biological samples, and further treatment of the nucleic acid extract with GnCl removes any contaminating proteins.
Claims 42-48, 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson as applied to claims 41 and 49 above, and further in view of Wang (Journal of Virological methods 238(2016) 86-93) and Yu (Clinical Chemistry 66:7. 975-986 2020).
Claims 42, 50 recite the device of claim 41 includes a protease (a sample preparation agent), a solubilizing liquid (a buffer), and one chaotropic agent; and the sample module comprises a sample chamber. The teachings of Anderson are as discussed above. Anderson teaches that the central chamber functions as a hub for the various operations to be carried out as a whole since the central chamber is fluidly connected to one or more additional reaction and/or storage chambers, and analytical chamber (0140, 0141, 0144). Anderson teaches that the fluid sample introduced into the device through the sample inlet 502, which is fluidly connected to a sample collection chamber 504, the sample from the sample collection chamber 504 is transported to a central pumping chamber 508 via fluid channel 506 (FIG.5). From the central pumping chamber the sample maybe transported to reaction storage chambers, reaction chambers or analytical chambers (0140, 0141). Anderson teaches that the opening and closing of the fluid connection between the central pumping chamber and the additional chambers includes a diaphragm pump 516, 518 and 520 (FIG.2) (0140-0144). Anderson further teaches that at least one of the chambers is a volumetric chamber to create aliquot of the fluid (0021), which refers to first, second, third quantity and fourth quantity of the reaction mixture of the present claim. Anderson teaches that the device includes reagents (liquid/lyophilized form) for stabilization of the sample, and pH adjustments (0045), lysing agents, and chaotropic agents (isothiocyanate or urea) (0050). Anderson and Wang teach that the nucleic acid sequence of interest is a pathogen (claim 50).
Claim 50 further recites that the elements (i, ii and iii in e) are optional. Further, regarding the nucleic acid sequence of interest corona virus (CoV) in ii or (SARS) CoV-2 in iii, Yu teaches rapid detection of CoVID-19 coronovirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic method. Yu teaches that LAMP can be coupled with pH indicator present in the reaction mix to read out of the amplification by change in color (975, left column). Yu teaches SARS CoV-2 primer set and the RT-LAMP method conducted at 65 ◦C (middle column). Thus, it would have been obvious to a person skilled in the art to design a system for detecting SARS CoV-2 nucleic acid sequence in the human patient samples. A person skilled in the art would have been motivated to design such system to detect SARS CoV-2 nucleic acid sequence in the human patient sample since Yu teaches that is urgent to develop rapid, accurate and onsite diagnostic methods to effectively identify individuals with early infections, administer timely treatment and control the disease spread.
Anderson fails to teach that the device includes a protease as in the present claim. Anderson specifically does not teach the lysing agent is a protease as in the present claims. However, the use of proteases to disrupt (lyse) the pathogen cells to extract nucleic acid sequences is known prior to the invention. Wang in the same field of endeavor teaches rapid detection of zika virus by reverse transcription loop-mediated isothermal amplification (RT-LAMP) (Abstract). Wang teaches that LAMP assay is simple, efficient and robust assay, which can be performed with impure templates and decreasing sample processing times (87, left column). The RT-LAMP reaction was performed at temperatures between 61-65 ◦C (isothermal conditions). Wang teaches that the sample preparation comprises adding proteinase K (a protease) to the biological sample (p.87 right column, p.90). Wang further teaches that the amplification products are observed by the naked eye under natural light by adding calcein fluorescent reagent (pH sensitive dye) (p.88, left column) (refers to the dye in claim 54). Thus, it would have been obvious to a person skilled in the art before the effective filing date of the claimed invention to include proteinase K (a protease) in the sample preparation chamber of the present claimed method. A person of ordinary skill in the art would have included proteinase K (a protease) during the sample preparation step because Wang teaches that rapid proteolysis treatment was able to extract sufficient quantities of RNA from the biological samples.
Claim 43 recites the sample module configured to include protease prior to the use of the device. Anderson teaches that the appropriate agents used in the sample preparation including the lysing agents are incorporated within the extraction chamber (0050).
Regarding claim 44, Anderson teaches that the device includes several volumetric chambers for the reagents (0113), plurality of reaction chambers, storage chambers and analytical chambers (0128, 0130, 0131, 0134).
Regarding claim 45, Anderson teaches that the chambers of the device are in fluid communication, and the limitations a) or b) are optional.
Regarding claim 46, Anderson teaches that the device includes an inlet port for selectively allowing insertion of the sample into the sample chamber (FIG.5), and the limitations a), b) and c) are optional.
Regarding claims 47, 48, Anderson teaches that the fluid sample introduced into the device through the sample inlet 502, which is fluidly connected to a sample collection chamber 504, the sample from the sample collection chamber 504 is transported to a central pumping chamber 508 via fluid channel 506 (FIG.5). From the central pumping chamber the sample maybe transported to reaction storage chambers, reaction chambers or analytical chambers (0140, 0141).
Claims 51 and 52 recite a system for detecting at least one nucleic acid sequence of interest in at least sample comprises the device of claim 50. As shown above, the combined teachings of Anderson and Wang teach the device of claim 50. Further, regarding heating apparatus, Anderson teaches a miniature fluidic system further comprises the device and a controllable heater for thermal cycling of the sample (0135, 0136). The predetermined range of temperatures in (a) and (b) are optional in claims 51 and 52. However, both Anderson and Wang teach controllable heater for amplification reactions.
Regarding method claims 53-54, Anderson teaches extraction and purification of target nucleic acid from the samples by adding agents to lyse the cells, guanidine isothiocyanate (Chaotropic agent) to prepare the sample (Example 1 and 2) (0050, 0191); and subjecting the prepared sample to amplification in amplification chamber under isothermal conditions (0060-0061) for production of amplification product detectable a detectable signal (Example 3).
Anderson does not specifically teach primers for amplification of the nucleic acid sequence under isothermal conditions as required in the present method claims 53-54. The teachings of Wang are as shown above. Wang in the same field of endeavor teaches rapid detection of zika virus (ZIKV) by reverse transcription loop-mediated isothermal amplification (RT-LAMP) (Abstract). The RT-LAMP reaction was performed at temperatures between 61-65 ◦C (isothermal conditions). Wang specifically teaches the RT-LAMP method specific ZIKV primers pairs (outer pair, inner pair and additional loop pair) (Table 1). Thus, it would have been obvious to a person skilled in the art before the effective filing date of the claimed invention to include RT-LAMP specific primers in the method of detection and monitoring nucleic acid sequence of interest.
Additionally, Yu in the same field of endeavor teaches rapid detection of COVID-19 coronovirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic method. Yu teaches that LAMP can be coupled with pH indicator present in the reaction mix to read out of the amplification by change in color (975, left column). Yu teaches SARS CoV-2 primer set and the RT-LAMP method conducted at 65 ◦C (middle column). Thus, it would have been obvious to a person skilled in the art to design a system for detecting SARS CoV-2 nucleic acid sequence in the human patient samples. A person skilled in the art would have been motivated to design such system to detect SARS CoV-2 nucleic acid sequence in the human patient sample since Yu teaches that is urgent to develop rapid, accurate and onsite diagnostic methods to effectively identify individuals with early infections, administer timely treatment and control the disease spread. Thus, a person of ordinary skill in the art would have included RT-LAMP specific primers to detect nucleic acid sequence of interest because Wang teaches that RT-LAMP assay had excellent sensitivity and specificity for detection of ZIKV and can be employed with rapid specimen processing method, offering the possibility for ZIKV (pathogen of claim 54) diagnosis outside of the laboratory and Yu teaches that LAMP combined with reverse transcription allows direct detection of RNA. Further, since Anderson teaches that the device can be used to identify any nucleic acid sequence of interest including in forensic or criminal studies (0110), it would have been obvious to include samples from environmental samples and biological samples in the method of detection of a nucleic acid sequence of interest.
Claims 57-60 recite a kit comprising a) a protease, b) an amplification reaction mixture comprising a set of primers for at least one nucleic acid sequence of interest, c) at least one chaotropic agent. As shown above, the combined teachings of Anderson, Wang and Yu teach the reagents including a protease, a chaotropic agent, amplification primers, pH sensitive detectable label required for detection of a nucleic acid sequence of interest in a sample in a device comprising a sample preparation module and a reaction module. Thus, it would have been obvious to a person skilled in the art collectively include the required reagents in a kit for detecting a nucleic acid sequence of interest (a pathogen i.e., SARS CoV-2) in a human patient sample. Further, it would have been obvious to a person skilled in the art to include a control nucleic acid sequence in the reagent kit such that the reactions are monitored.
Conclusion
Claims 41-60 are rejected.
Future Correspondences
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/Padmashri Ponnaluri/
Primary Patent Examiner
CRU 3991