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 .
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.
Withdrawn Objections/Rejections
The objections to the specification are withdrawn in response to the amendments.
The objection to claim 1 is withdrawn in response to the amendments. However, a new objection is made in response to the amendments.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/EP2020/067493, filed 06/23/2020. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. EP19182157.8, filed on 06/25/2019 in Europe.
Status of the Claims
Claims 1, 3 and 5-13 are pending; claims 1 and 3 are amended; claims 2, 4 and 14-24 are canceled; claims 11-13 are withdrawn. Claims 1, 3 and 5-10 are examined below.
New Objections
Claim Objections
Claims 1 and 7 are objected to because of the following informalities:
In claim 1 lines 13-14, “dilutions factors” appears to be a typographical error, namely it is suggested that “dilutions factors” read as "dilution
In claim 1 line 19, "and one more dilutions" appears to be a typographical error, namely it is suggested that "and one more dilutions" read as "and one or more dilutions" (emphasis added).
In claim 7 lines 1-2, “the bicomponent method” appears to be a typographical error, namely it is suggested that “the bicomponent method” read as “the bicomponent detection method” as per claim 1.
Appropriate correction is required.
Maintained Rejections
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 1, 3 and 5-10 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 “a method for determining the concentration of an analyte in a sample with an unknown concentration of analyte using a bi-component detection method comprising: a….b….c…d…e…f….”, and in step d. claim 1 recites “applying a bi-component detection method to the sample and the one or more dilutions, wherein the bi-component detection method comprises bringing said two analyte-specific binding components in contact with said analyte to produce a signal that depends on the concentration of bi-component/analyte complexes formed in said sample and one more dilutions”. Therefore, the claim suggests two different bi-component detection methods, one being steps a-f and the other being the wherein clause of step d (bringing said two analyte-specific binding components in contact with said analyte to produce a signal that depends on the concentration of bi-component/analyte complexes formed in said sample and one more dilutions). A person having ordinary skill in the art would not be able to recognize how to perform the claimed method because it is not clear what is encompassed by “a bicomponent detection method” (is it steps a-f or is it the wherein clause of step d?). In this way, it is not clear what is encompassed by the non-bijective reference curve of step e. because it “is a mathematical function reflecting the dependence of a bi-component detection signal on the concentration of analyte”, and “bi-component detection signal” is not clear because the “bi-component detection method” is not clear. Given that there are two possible interpretations to “a bi-component detection method”, there is a questions as to what the metes and bounds of the claim are.
Similarly, claim 3 recites “wherein said non-bijective analyte concentration reference curve provided in step (e) is obtained experimentally by providing a reference sample of known analyte concentration, generating a series of known dilutions of said reference sample and conducting for the reference sample and each known dilution thereof said bi-component detection method…”. Therefore, the claim suggests that the reference curve requires the bi-component detection method. But given that the bi-component detection method has two possible interpretations, i.e. steps a. through f., or the wherein clause of step d, a person having ordinary skill in the art would not be able to recognize how to perform the method of claim 3. Similarly to claim 1 above, dependent claim 3 is not clear because there is a questions as to what the metes and bounds of the claim are.
Also, claim 7 recites “the bi-component method”, claim 8 recites “the bi-component detection method”, and claim 10 recites “the bi-component detection method”. A person having ordinary skill in the art would not be able to recognize how to perform claims 7-8 and 10 because it is not clear what is encompassed by “a bicomponent detection method”/”bi-component method”.
Claim 7 also contains the trademark/trade name ALPHASCREEN (line 6). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a and, accordingly, the identification/description is indefinite.
Claims 5-6 and 9 are included in this rejection because they depend from rejected claim 1 but fail to clarify the scope of patent protection sought.
For these reasons the claims are indefinite.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3 and 5-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea, i.e., mathematical concepts, without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 1 recites “…e. providing a non-bijective analyte concentration reference curve, which is a mathematical function reflecting the dependence of said signal on the concentration of analyte…f. determining the concentration of the analyte using said signal detected in the sample and in the one or more dilutions as a constraining input for a mathematical fit for said non-bijective analyte concentration reference curve at different analyte concentrations”.
Each of the above indicated limitations are drawn to a mathematical concepts, step e. recites “a mathematical function”, which is a mathematical equation and step f. recites “a mathematical fit” which is a mathematical calculation.
Claim 3, further limiting the non-bijective analyte concentration reference curve to be “calculated analytically by solving chemical balance, and mass conservation equations” or to be “provided by numerical solutions based upon the provision of dissociation constants for each of the two analyte-specific binding components with the analyte” are further abstract ideas, i.e., mathematical concepts, mathematical calculations.
Claim 10 further limiting the bi-component detection method to comprise “employing an absolute molecular count based analytical method” is an abstract idea, i.e., a mathematical concept, mathematical calculation.
Step 2A, Prong 2
The above discussed steps of “providing…a mathematical function” and “determining the concentration of the analyte using…a mathematical fit” are insufficient themselves to integrate into a practical application because as discussed, these steps themselves are directed to abstract ideas; such steps represent judicial exceptions and not a practical application thereof.
The independent claim recites the limitations/steps “a method for determining the concentration of an analyte in a sample with an unknown concentration of analyte using a bi-component detection method comprising: a. providing the sample with unknown concentration of analyte, b. providing two non-immobilized analyte-specific binding components at known concentrations, c. preparing one or more dilutions of said sample using defined dilutions factors, d. applying a bi-component detection method to the sample and the one or more dilutions, wherein the bi-component detection method comprises bringing said two analyte-specific binding components in contact with said analyte to produce a signal that depends on the concentration of bi-component/analyte complexes formed in said sample and one more dilutions”. However, these steps fail to further amount to a practical application of the indicated judicial exception. Specifically, although, steps a-d amount to producing a signal as recited in steps d-f., steps a-d do not particularly or directly apply, rely on or use the mathematical concepts in steps e-f such that they impose a meaningful limit on the judicial exception. Further, the “providing” steps in a-b, the “preparing” step c. and the “applying” step d., are considered to be insignificant extra-solution activity, as it is a mere data gathering step (necessary in order to gather the data).
Similarly, claim 3 recites “wherein said non-bijective analyte concentration reference curve provided in step (e) is obtained experimentally by providing a reference sample of known analyte concentration, generating a series of known dilutions of said reference sample and conducting for the reference sample and each known dilution thereof said bi-component detection method…” which is insignificant extra-solution activity, as it is a mere data gathering step (necessary in order to gather the data).
Claims 5-6 further limit the “providing” steps a-b, however, these limitations also fail to practically apply the judicial exception. Claims 7-8 and 10 recite “employing a…assay”, however no particular active, wet method steps are recited/performed. Similarly, although claim 9 further limits the method “wherein multiple analytes are determined in parallel” this limitation does not further use, apply or rely on steps e-f as claimed in a meaningful way that would amount to a practical application thereof. Further, these limitations, including those recited at claims 3 and 10, read as limitation merely directed to data gathering for the purpose of performing the method for determining the concentration of an analyte in a sample.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exception; the additional recited claim elements are recited at a high level of generality, and are not, for example limited to any particular testing technique of or platform as claimed.
Furthermore, Laurie et al. (Biotechniques 2013 Vol 55 p. 61-67 Cite No. 11 on IDS filed 12/22/2021) teach a combination of 2 non-immobilized analyte binding components in a method for determining the concentration of an analyte using a droplet digital PCR assay (“[w]e have developed a new assay capable of concurrently measuring the absolute concentration and length of unknown amplifiable DNA templates” page 61 column 3 paragraph 2, “The equation describing the relationship between fluorescence amplitude and amplicon size can be used to calculate the size of any unknown ddPCR template that shares common primer and probe binding sites with the size standards” page 64 column 2 paragraph 3, “As primers and probe are specific to the MiSeq adapter sequences, only adapter-ligated molecules that will be amplifiable on the MiSeq flow cell will be quantified” page 64 column 2 paragraph 4). Laurie also teaches providing the sample with the unknown concentration of analyte (“Eight samples of sheared DNA were ligated…amplified…The amplified libraries were quantified using the ddPCR system” page 4 para. 2) and preparing one or more dilutions of said sample using defined dilutions factors (“The measured concentrations of the eight differently indexed libraries were used to dilute and combine the libraries in a molar ratio of 100:50:10:1 with two libraries at each concentration” page 4 para. 6).
Also, Yu-Tang Wu. Förster Resonance Energy Transfer Immunoassays Using Engineered Proteins for Breast Cancer Biomarker Detection. Biological Physics [physics.bio-ph]. Université Paris Saclay (COmUE), 2018. English. NNT : 2018SACLS340. tel-01909324 (Cite No. 9 of IDS filed 12/22/2021) teaches that employing a proximity-based assay to produce the bi-component/analyte complexes concentration depended signal, wherein the proximity-based assay uses two analyte- specific binding components at known concentrations that produce a detectable signal in dependence of their proximity and/or wherein the bi-component method comprises employing a resonance energy transfer assay is well-understood routine and conventional (“QDs and lanthanide complex as FRET pairs have been developed to detect prostate-specific antigen [Kupstat, Kumke, and Hildebrandt, 2011] and alpha-fetoprotein [Chen et al., 2012] in homogeneous sandwich immunoassay format” page 13 paragraph 1). Wu also suggests providing the sample with the unknown concentration of analyte, and preparing one or more dilutions of said sample using defined dilutions factors (“We demonstrate immediate applicability by the quantification of HER2 in serum containing samples using time-gated LTC-to-QD FRET detection on the clinical benchtop immunoassay analyzer KRYPTOR” page 36 paragraph 1, “we also tested the FRET assays in the sample containing 10%, 20% and 30% of serum (Figure 3.6)” page 42 paragraph 1).
Arkin, Michelle R., et al, “inhibition of Protein-Protein Interactions: Non-Cellular Assay Formats’, (2012) (28 pages)(Cite No. 18 of IDS filed 12/22/2021) teaches that “AlphaScreen™ is bead-based format commercialized by PerkinElmer (http://www.perkinelmer.com) and used to study biomolecular interactions in a microplate format… Like FRET, AlphaScreen is a non-radioactive, homogeneous proximity assay. Binding of two molecules captured on the beads leads to an energy transfer from one bead to the other, ultimately producing a fluorescent signal” (page 14 paragraph 3). Arkin further suggests providing the sample with the unknown concentration of analyte (“AlphaScreen assays have been developed to quantify enzymes, molecular (protein, peptide, small molecule) interactions, as well as DNA and RNA hybridizations” page 15 para. 2) and preparing one or more dilutions of said sample using defined dilutions factors (“choose a protein concentration below the hook point (or saturation point) for your assay” page 15 para. 3).
The specification page 1 last paragraph and page 2 paragraph 1 suggests that FRET, PCA, Alphascreen, and DNA labeled proximity methods for homogeneous assays are well-understood routine and conventional (“Bi-component detection systems are typically exploited in homogeneous assays where two components are applied to produce detection signals. Many of these assays apply a proximity concept and the analyte and the components need to be brought in proximity to produce a signal. Proximity assay technologies such as FRET (fluorescence resonance energy transfer), BRET (bioluminescence resonance energy transfer) (Pfleger, Seeber, &Eidne, 2006), cyan fluorescent protein (CFP) - yellow fluorescent protein (YFP) pair, PCA (protein complementation assays) (Mrell, Ventura, &Avil6s, 2009), Alphascreen (Taouji, Dahan, Bosse, &Chevet, 2009), and DNA labeled proximity methods (PLA - proximity ligation assay, PEA - proximity extension assay) (S6derberg et al., 2006), and a not proximity based assay called emulsion coupling are representative examples of bimolecular (bi-component) detection systems and methods”).
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
Mathematical concepts (calculations and/or equations), which represent abstract ideas, are not themselves patentable. The claims fail to set forth additional steps or elements that would amount to significantly more; the additional steps and elements recited do no more than setting forth the abstract idea(s) with generalized instructions to "apply it". A process of using mathematical calculations and equations would need to integrate the mathematical concepts into the process, as a whole, using additional steps that are not already conventional; and which are sufficient to narrow the scope of the claim so that others are not foreclosed from using the equations/calculations in different applications. Such additional steps could involve, for example, a testing technique or treatment step that would be performed dependent on the outcome, that would not be conventional or routine, so as to ensure that the judicial exception is being practically applied.
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception.
Citation of Pertinent Prior Art
The claims seem to be free of the prior art.
The closest prior art to the claims is Yu-Tang Wu. Biological Physics [physics.bio-ph]. Université Paris Saclay (COmUE), 2018. English. NNT : 2018SACLS340. tel-01909324 (Cite No. 9 of IDS filed 12/22/2021) (“Wu”). Wu teaches a method for determining the concentration of an analyte in a sample with an unknown concentration of analyte using a bi-component detection method (“A competitive homogeneous energy transfer-based immunoassay… FRET signal can be monitored by the extent of donor quenching and acceptor sensitization to estimate the analyte concentration” page 12 paragraph 1). Wu further suggests a. providing the sample with the unknown concentration of analyte (“We demonstrate immediate applicability by the quantification of HER2 in serum containing samples using time-gated LTC-to-QD FRET detection on the clinical benchtop immunoassay analyzer KRYPTOR” page 36 paragraph 1). Wu further teaches b. providing two non-immobilized analyte-specific binding components at known concentrations (“FRET-based immunoassays have been greatly improved…It can directly detect the analyte in the solution, overcoming limitations such as long incubation times, multiple washing steps, nonspecific adsorption on surface upon immobilization” page 12 paragraph 1, “Here, we show that a new class of very small (~6.5 kDa, ~1.0 x 1.5 x 2.5 nm3) albumin-binding domain-derived affinity proteins (ADAPTs) against HER2 [Lindbo et al., 2016, Nilvebrant et al., 2014], … can be applied for advanced LTC-to-QD FRET immunoassays against HER2” page 36 paragraph 1, see Figure 3.6 showing the analyte specific binding components for both the QD (quantum dot) and the LTC (luminescent terbium complexes), “ADAPTs were quantified by absorbance measurement at 280 nm using an extinction coefficient 4 470 M-1 cm-1” page 38 paragraph 1, “Antibody was quantified by absorbance measurements at 280 nm using an extinction coefficient of 1.4 g-1 Lcm-1 (207 200 M-1 cm-1) as provided by the manufacturer” page 38 paragraph 2, “100 µL of a constant assay solution (50 µL of LTC-Pert conjugate with 3nM Pertuzumab and 50 µL of ADAPT-QD conjugate with 1.5 nM of QD)” page 40 para. 1, “50 µL HER2 sample was added to a100 µL solution of 1.5 nM LTC-Pertuzumab and 0.75 nM ADAPT-QD (concentrations of Pertuzumab and QD, respectively)” page 42 para. 2 and page 43 para. 1,), c. preparing one or more dilutions of said sample using defined dilutions factors (““we also tested the FRET assays in the sample containing 10%, 20% and 30% of serum (Figure 3.6)” page 42 paragraph 1). Wu further suggests d. applying the bi-component detection method to the sample and the one or more dilutions (“We demonstrate immediate applicability by the quantification of HER2 in serum containing samples using time-gated LTC-to-QD FRET detection on the clinical benchtop immunoassay analyzer KRYPTOR” page 36 paragraph 1,), and e. providing a non-bijective analyte concentration reference curve for said bi-component detection method which is a mathematical function reflecting the dependence of said signal on the concentration of analyte (“FIGURE 3.7: (A) Calibration curves of LTC-to-QD FRET immunoassay against HER2” page 44 Figure 3.7). Note that although Wu fails to use the language non-bijective, the calibration curve disclosed by Wu inherently addresses a non-bijective function because it shows that different concentrations of an analyte may give rise to the same FRET signal (“All assay curves showed a strong increase of FRET-ratio with increasing HER2 concentration from 0.075 nM to circa 3 nM, after which the curves start to level off and remains at an approximately constant FRET-ratio between 6 and 12 nM HER2” page 42 paragraph 2).
Wu fails to teach step f. determining the concentration of the analyte using said signal detected in the sample and in the one or more dilutions as a constraining input for a mathematical fit for said non-bijective analyte concentration reference curve at different analyte concentration.
The inventive concept of the invention (steps d. and f. of claim 1) seems to be using the signal measured from a sample and a diluted sample as a constraining input for a mathematical fit to a single reference curve to determine the analyte concentration in order to avoid the hook effect.
The art teaches that determining the analyte concentration using a reference curve, taking into account the hook effect, requires the use of either the signal from the undiluted sample or the signal from the diluted sample, but not both.
Yu-Tang Wu. Biological Physics [physics.bio-ph]. Université Paris Saclay (COmUE), 2018. English. NNT : 2018SACLS340. tel-01909324 (Cite No. 9 of IDS filed 12/22/2021) teaches that “[t]he accuracy of an immunoassay may be influenced by sources of interference, which decrease the accuracy. The most predominant is the hook effect, which can be directly seen in the calibration curve (Figure 2.5)… This effect can be avoided by increasing the amount of antibody and reducing the amount of analyte or by sample dilution [Davies, 2013]” (page 11 last paragraph). Wu further teaches “FRET assays in the sample containing 10%, 20% and 30% of serum (Figure 3.6)” (page 42 paragraph 1).
CN1062265168 20180629 (Cite No. 3 of IDS filed 12/22/2021) teaches that “[a]t present, the method for solving the hook effect problem of such project detection is generally performed by diluting the test object or the two-step method” (paragraph 7). CN1062265168 further teaches that “[t]he object of the present invention is to provide a hyperbolic calibration quantitative immunochromatographic detection method, which can directly quantify without diluting the analyte” (paragraph 10).
EP2837937A1·2015-02-18 (Cite No. 4 of IDS filed 12/22/2021) teaches that “homogeneous immunoassays are limited by the high-dose Hook effect… Assay developers and manufacturers usually make every effort to reduce the Hook effect, e.g., by increasing quantity of the antibodies and by reducing the quantity of sample volumes required for the analysis” (paragraph 3). EP2837937A1 further teaches that “[t]he present invention provides an improved method for detecting a prozone phenomenon by analysis of the kinetic data obtained during the sample measurement” (paragraph 20).
A person having ordinary skill in the art before the effective filing date of the claimed invention would have not found the method of claim 1 to be obvious because there is no teaching, suggestion or motivation in the prior art to include steps d. and f. in a method for determining the concentration of an analyte in a sample with an unknown concentration of analyte using a bi-component detection method.
Response to Arguments
Applicant's arguments filed 10/1/2025 have been fully considered but they are not persuasive.
Regarding the 112b rejections, Applicant argues that “[i]n response, claim 1 is amended by reciting a new step a. "providing the sample with the unknown concentration of analyte" and a new step e. of "providing a non-bijective analyte concentration reference curve, which is a mathematical function reflecting the dependence of a bicomponent detection signal on the concentration of analyte"” (page 7 para. 2). However, the new step a. and new step e. fail to clarify the issues of claim 1, i.e. that “the bi-component detection method” recited in the preamble and steps d-e is unclear (see 112b rejection above). Similarly, the argument that “[i]n the context of the presently claimed methods, the term "mathematical function" always refers to the determination of the "non-bijective analyte concentration reference curve" (feature e. of claim 1 ), which represents the signal level of the bi-component assay as a function of the analyte concentration” (page 7 para. 2) does not clarify the indefiniteness of claim 1 as outlined above (see rejection above). Similarly, Applicant further argues that “In response, claim 3 is amended to recite ""wherein said non-bijective analyte concentration reference curve provided in (e) is obtained experimentally by providing a reference sample of known analyte concentration, generating a series of known dilutions of said reference sample and conducting for the reference sample and each known dilution thereof said bi-component detection method ... ". Therefore, the clarifying amendments in claim 1 are incorporated into claim 3” (page 7 para. 3). However, there are no clarifying amendments in claim 1, therefore this argument is not persuasive.
Regarding the 101 rejections, Applicant argues that “[i]n response, claim 1 is amended to more clearly integrate the mathematical concepts into a practical application” (page 7 last paragraph). However, the amendments to claim 1 fail to integrate the judicial exception into a practical application (see rejection above).
Applicant further argues under “Step 2A, Prong 1(Judicial Exception)” that “[w]hile the presently claimed method employs mathematical functions (e.g., in step e. of claim 1), these are not presented as disembodied mathematical concepts. Instead, as is clarified in amended claim 1, the mathematical functions are integral to the specific, practical application of determining the concentration of an analyte in a sample with an unknown concentration of analyte using a bi-component detection method” (page 8 paras. 1-2). However, as stated above, the mathematical functions are themselves not patent eligible. Applicant further argues that “…[t]he claims are thus not directed towards disclosing pure mathematical ideas or concepts, but rather to providing a technical means that allow for the determination of the concentration of the analyte in a sample, using said signal detected in the sample and in the one or more dilutions in order to determine the concentration of an analyte within a sample with an unknown analyte concentration, particularly overcoming the technical problem of the "hook effect"” (page 8 paras. 3-4). However, the claim is directed to at least one judicial exception because the determination of the concentration of the analyte in a sample involves mathematical concepts, i.e. abstract ideas (see rejection above).
Applicant further argues under “Step 2A of Prong 2 (Practical Application)” (page 8 last paragraph) that “"providing two non-immobilized analyte-specific binding components at known concentrations " This step involves the physical act of preparing and mixing specific chemical components in a solution and performing a physical assay on tangible samples, leading to a molecular interaction of binding components and analyte, thereby generating a signal” (page 9 para. 3). However, as stated above, the step of “providing two non-immobilized analyte-specific binding components at known concentrations” fails to integrate the judicial exception into a practical application as is drawn to data gathering and does not use, rely on, or apply the judicial exception such to amount to a practical application thereof. Similarly, Applicant argues that “Claim 1 further comprises the analysis of a sample at different sample concentrations (step c. 'preparing one or more dilutions of said sample'), comprising concentrations below and above the Hook point, which is a physical manipulation of a sample to create multiple physical samples with varied concentrations… Based on said prepared dilutions of the sample the concentration of the analyte is determined… The objective is thereby also to extend the measurable concentration range… Hence, the 'technical' step of performing a series of dilutions of a sample (without determining the concentration of analyte in advance) and considering each measured value below and above the Hook point, constitutes an advance over prior art methods, which allow only measurements below the hook point, and therefore require an adjustment of analyte concentration in a sample before the final measurements accordingly” (page 9 para. 4-6 and page 10 para. 2). However, as stated in the rejection above, under step 2a prong 2, step c. fails to integrate the judicial exception into a practical application because “preparing one or more dilutions of said sample using defined dilutions factors” is mere data gathering that does not use, rely on, or apply the abstract ideas such to amount to a practical application thereof (see rejection above). Applicant further argues that “steps b., c. and d. in amended claim 1 are not merely "data gathering", as assumed by the Examiner on page 8, but are practical, physical manipulations of chemical and biological materials essential for the subsequent sample analysis. Contrary to the interpretation of the Patent Office, the mathematical step (f) of claim 1 is specifically tailored to interpret the physical signals generated by these physical manipulations within the context of the bi-component detection method that inherently produces non-bijective (bell-shaped) curves, as described in the specification, e.g., in paragraphs [0007], [0045], and [0050]” (page 10 para. 3). However, steps b-d fail to use, rely on, or apply the mathematical equation of step e. or the mathematical calculation of step f such to amount to a practical application thereof. In other words, providing two non-immobilized analyte-specific binding components, preparing one or more dilutions of said sample… and applying the bi-component detection method fail to integrate the mathematical concepts of steps e-f such to amount to a practical application as these are steps drawn to data gathering (see rejection above). Applicant further argues that “Claim 3 specifies how the non-bijective reference curve is obtained… These are concrete methods for establishing the reference curve… Claims 5 and 6 define the types of analytes and binding components to be used… These are tangible biological and chemical entities… Claims 7, 8, and 10 further specify the type of bi-component detection method employed… These are specific biochemical laboratory techniques” (page 10 paras. 4-6). However, although claim 3 is drawn to methods for establishing the reference curve, claims 5-6 are drawn to tangible biological and chemical entities and claims 7-8 and 10 are drawn to specific biochemical laboratory techniques, these claims also fail to use, rely on, or apply the abstract ideas such to amount to a practical application thereof (see rejection above).
Applicant further argues under “Step 2B (Inventive Concept)” that “the Examiner explicitly notes on page 15 that "Wu fails to teach applying the bi-component detection method to the sample, and step f….This deficiency in the cited prior art highlights that the claimed combination of specific physical steps (sample dilutions, applying the presently claimed method) with the mathematical fitting of a non-bijective reference curve to overcome ambiguity and extend dynamic range is not routine or conventional” (page 11 para. 2). However, step f. is directed to the judicial exception and therefore is not patent eligible and “applying the bi-component detection method to the sample” although unclear (see 112b rejection above), can be interpreted as the bringing of two analyte-specific binding components in contact with said analyte to produce a signal that depends on the concentration of bi-component/analyte complexes formed in said sample, which is suggested by Wu, Laurie and Arkin (see rejection above). Note also that the specification page 1 last paragraph and page 2 paragraph 1 also suggests that FRET, PCA, Alphascreen, and DNA labeled proximity methods for homogeneous assays are well-understood routine and conventional, and all of these assays involve the bringing of two analyte-specific binding components in contact with said analyte to produce a signal that depends on the concentration of bi-component/analyte complexes. Finally, sample dilutions are also well-understood, routine and conventional as evidenced by Laurie, Wu and Arkin (see rejection above).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/Fernando Ivich/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678