DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 30-41 in the reply filed on 01/28/2026 is acknowledged.
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 30-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a system for identifying an analyte, does not reasonably provide enablement for a binding reagent, and an analyte. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. An analysis of the Wands factor is performed In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998) (see also MPEP § 2164.01(a) and § 2164.04).
The breadth of the claims: Claim 30 broadly teaches a system for identifying an analyte, and provides how the system is configured to obtain and process signals generated by the analytes, but fails to specify what analytes/proteins and binding reagents/nucleic acid molecules/antibodies are used in conjunction with this system where one of ordinary skill would not be able to successfully use the invention without undue experimentation.
The nature of the invention: The invention draws to a analyte analysis method through binding the analyte with a binding reagent, and denaturing the binding agent to obtain signals indicative of analytes (i.e., polymerase chain reaction (PCR)).
The state of the prior art: Polymerase chain reaction (PCR) is well known in the prior art.
The level of one of ordinary skill: A practitioner who has a master’s level in chemistry.
The level of predictability in the art: The relevant art is unpredictable as there is a wide range of potential proteins and antibodies that could be used in the system.
The amount of direction provided by the inventor: The inventor does not provide sufficient direction in the original specification that one skilled in the art could follow in attempting to use this invention. Specifically, the range of analytes and binding reagents is too broad and is not limited by the claims or specifications to be reasonably used.
The existence of working examples: The specification provided by the instant application does provide two working examples, using interleukin 6 protein and troponin proteins, respectively for quantification. These proteins however are not referenced in the detailed description.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: The amount of experimentation needed based on the content of the disclosure would be substantial and undue in determining which what analyte and binding reagent to use together in this system for analysis.
In conclusion, based on the Wands factor analysis, while the claim does have enablement for a system for identifying an analyte, it fails to enable the specifics of the analyte and binding reagent under scope of enablement.
Additionally, dependent claims 31-41 fail to fulfill the scope of enablement requirement as they do not add any further limitations for carrying out the invention.
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.
Claims 30 and 34-39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lundberg et al. (“Multiplexed Homogeneous Proximity Ligation Assays for High-throughput Protein Biomarker Research in Serological Material”, as cited in the IDS).
Regarding claim 30, Lundberg et al. teaches a system for identifying an analyte (see Abstract, disclosing a high throughput protein biomarker discovery tool), comprising: a detection unit configured to collect and process signals for identification of said analyte (see Abstract, disclosing multiplex proximity ligation assays thereby converts multiple target analytes into real-time PCR amplicons that are individually quantified using microfluidic high-capacity qPCR in nano liter volumes.); and one or more processors operatively coupled to said detection unit (see pg. 3, Experimental Procedures, disclosing real time qPCR reactions were performed either on an ABI 9700 HT Fast (Applied Biosystems) instrument or the BioMarkTM micro fluidic system from Fluidigm. The Fluidigm system is ran by an integrated fluidic circuit controller according to manufacturer’s protocol.), wherein said one or more processors are individually or collectively programmed or otherwise configured to:(i) contact a binding reagent with said analyte, which binding reagent comprises (a) a binding probe having binding specificity for said analyte, and (b) a nucleic acid molecule (see pg. 2, Experimental Procedures, Proximity Probe Preparation, disclosing proximity probes were prepared by linking a single batch of affinity purified polyclonal antibody or matched monoclonal antibody pairs to 3'-hydroxyl free and 5'-phosphate free 40-mer oligonucleotide sequences thereby forming unique amplicons representing each target protein.); (ii) denature at least a portion of said nucleic acid molecule or derivative thereof (see pg. 3, Biomarker Profiling - Multiplex Proximity Ligation Assay, heating and pre-amplification steps performed on connector oligonucleotide.); and (iii) direct said detection unit to detect signals indicative of denaturing of said nucleic acid molecule to identify said analyte (see pg. 4, Fig. 1, disclosing that ligated products are amplified in multiplex using all pre-amplification primers simultaneously. This is followed by quantification of each biomarker by quantitative real time PCR using only the unique primer pair for a given analyte).
Regarding claim 34, Lundberg et al. teaches the system of claim 30, wherein said binding reagent is an antibody. (see Abstract, detector antibody-based probes).
Regarding claim 35, Lundberg et al. teaches the system of claim 30, wherein said analyte is a protein (see Introduction, pg. 1, protein biomarkers).
Regarding claim 36, Lundberg et al. teaches the system of claim 30, further comprising a microfluidic device comprising a plurality of partitions (see pg. 9, Discussion, disclosing quantifying a large number of real-time PCR amplicons using microfluidic nano-liter real time PCR by using the BioMarkTM instrument with a capacity of generating up to 9216 data points in one run (96 samples X 96 assays)).
Regarding claim 37, Lundberg et al. teaches the system of claim 36, wherein said plurality of partitions are configured to partition a mixture comprising said binding reagent (see pg. 2-3, Experiment Procedures, disclosing prior to evaluation of PLA panels, the proximity probes were pooled together with a probe mix. Incubations of sample and proximity-probes totaled 4 μL and was performed in a 96 well plate).
Regarding claim 38, Lundberg et al. teaches the system of claim 37, wherein said detection unit is configured to image one or more partitions of said plurality of partitions (see pg. 9, Discussion, disclosing quantifying a large number of real-time PCR amplicons using microfluidic nano-liter real time PCR by using the BioMarkTM instrument with a capacity of generating up to 9216 data points in one run (96 samples X 96 assays)).
Regarding claim 39, Lundberg et al. teaches the system of claim 30, further comprising a processing unit configured to amplify said nucleic acid molecule (see Fig. 1, pg. 3-4, Experimental Procedures, Real Time qPCR, disclosing that the qPCR reactions were performed either on an ABI 9700 HT Fast (Applied Biosystems) instrument or the BioMarkTM micro fluidic system from Fluidigm. Pre-amplification and amplification steps performed on ligated products by qPCR.).
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.
Claims 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. as applied to claim 30 above, and further in view of Yoji (JP 2020180892 A, as cited in the IDS).
Regarding claim 31, Lundberg et al. fails to teach the system further comprising a support configured to couple to said analyte.
However, in the analogous art of detection method and reagent kit, Yoji teaches a method for detecting a protein present in a sample using an antigen-antibody reaction. As shown in Fig. 3, the antibody 305 having a recognition site that recognizes the target antigen 301 is bound to the solid phase 306 such as a particle or a substrate (see Yoji, Fig. 3, [0002], [0026]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplexed homogeneous proximity ligation assays of Lundberg et al. by incorporating a supporting substrate that binds the analytes (as taught by Yoji), for the benefit of being able to accurately detect multiple kinds of target substances simultaneously by binding onto a solid surface (see Yoji, Abstract).
Regarding claim 32, Lundberg et al. fails to teach wherein said support comprises a capture agent immobilized on said support, and wherein said capture agent is configured to couple to said analyte.
However, Yoji teaches a method for detecting a protein present in a sample using an antigen-antibody reaction. As shown in Fig. 3, the antibody 305 having a recognition site that recognizes the target antigen 301 is bound to the solid phase 306 such as a particle or a substrate (see Yoji, Fig. 3, [0002], [0026]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multiplexed homogeneous proximity ligation assays of Lundberg et al. by incorporating a supporting substrate that binds the analytes using a capture agent specific to the analyte (as taught by Yoji), for the benefit of being able to accurately detect multiple kinds of target substances simultaneously by binding onto a solid surface (see Yoji, Abstract).
Regarding claim 33, the examiner is interpreting the “capture agent” to be a binding reagent on a solid support as per the specification.
Lundberg et al. fails to teach wherein said capture agent is an antibody.
However, Yoji teaches that for the detection of the target antigen 101, an antibody 108 to which the amplification nucleic acid 106 having the measurement site 104 binds and has a recognition site that recognizes the target antigen 101 (see Yoji, Fig. 1, [0018]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the capture agent on the support structure of Lundberg et al. to incorporate the capture agent being an antibody (as taught by Yoji), for the benefit of being able to accurately detect multiple kinds of target substances simultaneously by binding onto a solid surface (see Yoji, Abstract).
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al..
Regarding claim 40, Lundberg et al. teaches performing multiplex PLA and Real Time qPCR, of the specific steps include heating cycles nucleic acids during incubation, up to 95 oC under specified cycles and time (see Lundberg et al., pg. 3, Biomarker Profiling - Multiplex Proximity Ligation Assay, Real Time qPCR).
While Lundberg et al. fails to explicitly mention using a heating unit configured to for controlled heating of said nucleic acid molecule to denature said nucleic acid molecule, Lundberg teaches a number of controlled temperature cycles performed on nucleic acids, of which is generally meant for denaturing them, which includes heating and cooling of the sample (see Lundberg et al. pg. 3, Experimental Procedures, Biomarker Profiling - Multiplex Proximity Ligation Assay) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to know that heating samples would require a source of heat, especially in PCR, so Lundberg et al. would have to be using a controllable heating element of unit to perform these temperature cycles for denaturing, for the benefit of precision heating following procedure steps in obtaining consistent PCR results (see pg. 3, Experimental Procedures, Biomarker Profiling - Multiplex Proximity Ligation Assay).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. as applied to claim 30 above, and further in view of Velez et al. (“Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling”, as cited in the IDS).
Regarding claim 41, Lundberg et al. teaches denaturing nucleic acid molecules via qPCR processes under the Fluidigm BioMarkTM system, followed by an analysis of data performed by the system (see Lundberg et al., pg. 3, Real Time qPCR, Data Acquisition and Analysis).
Lundberg et al. fails to teach wherein said one or more processors are individually or collectively programmed or otherwise configured to generate a denaturation profile of said nucleic acid molecule, which denaturation profile is usable to identify said analyte.
However, in the analogous art of massively parallel digital high-resolution melt for rapid and absolutely quantitative sequence profiling, Velez et al. teaches high resolution melt (HRM) for heating precision and unwinding post-PCR DNA amplicons in the presence of a fluorescent intercalating dye or sloppy molecular probes. It was proposed to implement HRM into a broad-based profiling technology by preceding it with universal PCR. Universal digital high-resolution melt (U-dHRM) is developed using universal amplification and temperatures calibrated HRM with limiting dilution digital PCR (dPCR) in a 96-well plate format, which can be used for quantitative bacterial profiling (see Velez et al., pg. 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 modify the qPCR system of Lundberg et al. to incorporate profiling of high resolution melts (i.e., denaturing) to be used identification of a target molecule (as taught by Velez et al.), for the benefit of achieving single molecule sensitive detection and absolute quantification of thousands of bacterial DNA molecules in polymicrobial samples in less than four hours (see Velez, pg. 2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tracy C Colena whose telephone number is (571)272-1625. The examiner can normally be reached Mon-Thus 8:00am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRACY CHING-TIAN COLENA/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797