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 .
Priority
The present application was filed on 12/16/2022. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/EP2021/065880, filed on 06/14/2021, which claims benefit of the foreign Application No. EPO 180205.5, filed on 06/16/2020.
Claim status
Claims 1-15 are pending and examined.
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 1-15 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 “free antigen”, “an antibody”, “free antibody”, “antigen-antibody-complexes”, “capture antibody-antigen complex”, “capture antibody-antigen-tracer antibody complex”. In lines 7-8, claim 1 recites “the capture antibody competes with the antibody for binding to a first epitope on the antigen.” The language of the claim causes confusion because:
it is unclear if the capture antibody bind to which antigen to form a complex, the free antigen in line 1 or the antigen in the antigen-antibody-complexes in line 3;
it is unclear if the “antigen” in the complexes also refers to the “free antigen” which is an analyte of the method;
it is unclear if “the antigen” in line 8 refers to “free antigen” in line 1or an antigen in antigen-antibody-complexes in line 3;
it is unclear if “the antibody” refers to an antibody that can bind to the free antigen as recited in lines 1-2, or any other antibody in serum;
it is unclear if “free antibody” in line 2 is the same or different from an antibody that can be specifically bound to “free antigen” in lines 1-2;
it is unclear if “the free antigen” in step c is the antigen that is still in free form in the solution or the free antigen that is currently in the bound form with the capture and tracer antibodies; it is unclear how the “free antigen” can be detected by “determining the tracer antibody in the capture antibody-antigen-tracer antibody complex” if the free antigen is the antigen that is still in free form in the solution.
Claims 2-6, 12-15 also recite the antibody and/or the antigen. Similar to claim 1, it is unclear if the antibody is “free antibody” or an antibody that can bind to the free antigen , and it is unclear if the antigen is “free antigen” or antigen in the complexes.
All dependent claims are also rejected based on their dependency of the defected parent claims.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 7, 12-13 and 15 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Dysinger (US20190250157).
Regarding claim 1, Dysinger teaches a method for quantitating free (unbound) human C5 complement protein (C5) from a serum sample (see Abstract).
The sample is from a patient treated with eculizumab or ALXN1210 (see par.19). It is noted that eculizumab is an anti-C5 antibody (see par.64), and eculizumab and C5 can form a complex (see par.66: teaching that the anti-C5 antibody is one that binds to a complement C5 protein). The sample comprises free antigen (e.g., unbound human C5), free antibody (e.g., eculizumab) and the antigen-antibody complex (see at least in Abstract, par.139: stating that C5 in the serum sample from a patient treated with eculizumab may be free (unbound) or may be bound to eculizumab).
The method comprises:
applying the undiluted serum sample to a solid phase on which a capture antibody has been immobilized to form a capture antibody-antigen complex (see par.5: teaching that a biotinylated anti-C5 capture antibody binds to streptavidin-coated particles and captures the free (unbound) C5 in the sample; see par.111: teaching that sample should be used at neat if possible because diluted sample may cause disassociation);
wherein the capture antibody competes with the antibody for binding to a first epitope on the antigen (see par.19: teaching that the patient has been treated with eculizumab; par.21: teaching that the biotinylated capture antibody is eculizumab; or pars.63-64 and 139-143: an anti-C5 antibody for use in the methods of this disclosure for treating patients, for use as a capture antibody, and/or for use as a detection antibody, is any anti-human C5 antibody which is eculizumab; since the capture antibody and the therapeutic antibody are the same antibody so it would be obvious for the antibodies compete each other for binding to the same epitope on the antigen);
applying to the solid phase a tracer antibody to form a capture antibody- antigen-tracer antibody complex, wherein the tracer antibody specifically binds to a second epitope on the antigen, wherein the epitope of the tracer antibody is not overlapping with the epitope of the capture antibody on the antigen (see par.5 step c: teaching an AlexaFluor labeled anti-C5 detection antibody is a detection antibody wherein said anti-C5 detection antibody binds C5 at a different epitope from the epitope bound by the capture antibody);
determining the C5 antigen by determining the tracer antibody in the capture antibody-antigen-tracer antibody complex (see par.9: quantitating the captured free C5 using laser-induced fluorescence detection which is from AlexaFluor labeled anti-C5 detection antibody).
Regarding claim 7, Dysinger teaches the method in claim 1. Dysinger teaches antibody can be made in or derived from any of a variety of species, e.g. non-human primates (see par.42).
Regarding claim 12, Dysinger teaches the method in claim 1. Dysinger teaches the antibody is a therapeutic antibody (see par.19: stating that patient has been treated with eculizumab, par.107: stating that Eculizumab is a therapeutic mAb)
Regarding claim 13, Dysinger teaches the method in claim 1. Dysinger teaches that the method further comprises calculating the concentration or amount of free C5 antibody in the sample (see at least par.13 and par.140).
Regarding claim 15, Dysinger teaches the method in claim 1. Dysinger teaches the antigen is human C5 (see Abstract).
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.
Claim(s) 2-4 and 9-11 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Dysinger.
Regarding claim 2, Dysinger teaches the method in claim 1, wherein in step a) the applying is under conditions that at most 10 % of the antibody bound to the antigen are replaced by the capture antibody, wherein in step a) at most 10 % of the antibody bound to the antigen is replaced (see pars.4, 151-152, and 195).
Dysinger teaches a common strategy for overcoming this overestimation in ligand binding assays is to abbreviate sample incubation time and increase the coating reagent concentration by as much as 5 times, thus reducing the opportunity for the capture reagent to pull the bound target from the drug in the matrix (see par.4 and 151). Dysinger teaches that capture antibody and therapeutic antibody are Eculizumab which bind to C5 protein (see pars.19, and 63-64). Based on Biacore or normal ELISA results, approximately 15 % of Eculizumab - C5 complexes dissociate in 60 minutes (see par.108). Dysinger decreases sample incubation in ELISA from 60 - minute to proposed 15 - minute incubation to possibly reduce dissociation (see par.1220). It would be obvious to expect that approximately 3% of Eculizumab - C5 complexes dissociate in this 15 minute incubation.
When using Gyros system, which passes samples along the microstructures in a matter of seconds (e.g., about 6 seconds), it would be obvious to expect that approximately 0.025% of Eculizumab - C5 complexes dissociate in this 6 second incubation. Accordingly, Dysinger teaches that it leaves no time for any bound target in the matrix to dissociate and be bound by the capture antibody by limiting the incubation time between the sample and the capture reagent to about 6 seconds (see pars.152 and 127: teaching that there is almost no time for any bound target in matrix to dissociate and be bound by the drug used as capture antibody). Moreover, Dysinger also increases the concentration of the capture reagent by 10 times to increase the rate of capturing free C5 when shortening incubation time (see Table 6 par.195).
Therefore, the teaching of Dysinger encompasses the conditions that at most 10% of the antibody bound to the antigen are replaced by the capture antibody as recited in claim 2.
Regarding claim 3, Dysinger teaches the method in claim 1. Dysinger teaches:
applying the undiluted serum sample to a solid phase on which a capture antibody has been immobilized to form a capture antibody-antigen complex (see par.5: teaching that a biotinylated anti-C5 capture antibody binds to streptavidin-coated particles and captures the free (unbound) C5 in the sample; see par.111: teaching that sample should be used at neat if possible because diluted sample may cause disassociation);
wherein the capture antibody competes with the antibody for binding to a first epitope on the antigen (see pars.63-64: an anti-C5 antibody for use in the methods of this disclosure for treating patients, for use as a capture antibody, and/or for use as a detection antibody, is any anti-human C5 antibody which is eculizumab);
wherein the sample is incubated in the solid phase for 240 seconds or less. (Dysinger teaches the method uses Gyros system, which uses an affinity flow-through format that eliminates incubations and shortens run times (see par.127). Since the method of Dysinger can eliminate incubation time of the reagents and the sample, which means zero incubation time, it encompasses the limitation of claim 3 which the incubation of the sample and the solid phase is less than 240 seconds.)
Regarding claim 4 , Dysinger teaches the method in claim 1, wherein the half-life of the complex of the antigen binding site of the antibody specifically binding to the first epitope on the antigen and the antigen is 100 seconds or less.
Dysinger teaches that the method uses Gyros system which uses an affinity flow-through format that eliminates incubations and shortens run times (see par.127). The Gyros system passes samples along the microstructures in a matter of seconds, there may not be an opportunity for back dissociation to occur (see pars.127). Moreover, the required time for a sample to be spun across a microstructure immobilized with a capture reagent is about six seconds, so theoretically there is almost no time for any bound target in the matrix to dissociate and be bound by the drug used as capture antibody (see par.152). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of Dysinger for detecting the analyte, wherein the complex of the antigen binding site of the antibody specifically binds to the first epitope on the antigen and the antigen are 100 seconds or less because the maximum contact time of the analyte and the capture reagent is 6 seconds, which leaves no time for any bound target in matrix as taught by Dysinger.
Regarding claims 9 and 11, Dysinger teaches the method in claim 1, wherein the tracer antibody is incubated with the capture antibody-antigen complex for less than 1200 seconds as recited in claim 9, or wherein the tracer antibody is incubated with the capture antibody-antigen complex for less than 2 seconds as recited in claim 11.
Dysinger teaches that the method uses Gyros system to detect free C5 analyte, where the centrifugal force drives reagents (capture reagents, sample and detection reagents) into columns (see pars.127-128). The Gyros system passes samples along the microstructures in a matter of seconds (see par.127). The Gyros system uses an affinity flow-through format that eliminates incubations and shortens run times (see par.127). Since the method of Dysinger can eliminate incubation time of the reagents and the sample, the incubation time appears to be zero second. The teaching of Dysinger encompasses the limitations of claims 9 and 11, which the incubation of the capture antibody-antigen complex and the tracer antibody is less than 1200 or 2 seconds.
Regarding claim 10, Dysinger teaches the method in claim 1, wherein the method is a nanoliter-scale, microfluidic, affinity flow-through format with laser-induced fluorescence detection and the sample is incubated with the solid phase for 2 seconds or less.
Dysinger teaches that the method uses Gyros system which uses an affinity flow-through format that eliminates incubations and shortens run times. The Gyros platform uses Gyros' proprietary CD technology engineered with highly reproducible nanoliter microfluidics integrated with Gyrolab platforms, which automate immunoassays with parallel processing using laser-induced fluorescence detection. The system is a precise, automated control of centrifugal and capillary forces which steer liquid flow through nanoliter-scale microfluidic structures contained within the CD. See paragraph 127.
Since the method of Dysinger can eliminate incubation time of the reagents and the sample, the incubation time appears to be zero second. The teaching of Dysinger encompasses the limitation of claim 10 which the incubation of the sample and the solid phase is less than 2 seconds.
Claim(s) 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dysinger, as applied in claim 1 above, in view of Tamburini (US20110002931) and Ghayur et al. (US20140308286).
Regarding claim 5, Dysinger teaches the method in claim 1. Dysinger teaches that an anti-C5 antibody for use in the methods for treating patients, for use as a capture antibody, and/or for use as a detection antibody, is any anti-human C5 antibody (see par.63). The capture antibody and the detection antibody can be any anti-C5 antibody, but the detection anti-C5 antibody recognizes a different epitope on C5 as compared to the capture antibody used in the assay (see par.144). The anti-C5 antibody can be a bispecific antibody (see par.75). The teaching of Dysinger encompasses that the antibody for treating patients can be a bispecific antibody.
Dysinger does not teach that the bispecific antibody comprises a first antigen-binding site that specifically binds to the first epitope on the antigen and a second different antigen-binding site that specifically binds the second epitope on the antigen, wherein the tracer antibody competes with the bispecific antibody for binding to the second epitope on the antigen.
Tamburini teaches that bispecific antibodies can bind to two or more different epitopes (see Abstract), e.g., a bispecific antibody can bind to two different epitopes on the same protein or two different epitopes on different proteins (see pars.13-17). The bispecific antibody can be used in a number of diagnostic and/or therapeutic applications (see pars.50, 122, 124, and 126). The bispecific antibody to the same protein is the antibody that can bind to C5a and C5b (see pars.13-17). The bispecific antibody to different proteins is the antibody that can bind to C5a and C5aR, or can bind to C5b and C5L2 (see par.17).
Ghayur teaches methods of making and using multivalent and multispecific binding proteins, e.g., dual variable domain immunoglobulins (DVD-Ig) or multispecific antibodies (see Abstract, pars.11 and 87-88). The multispecific antibodies can be used in a number of diagnostic and/or therapeutic applications (see Abstract, and pars.68 and 310). Ghayur teaches a sandwich immunoassay using DVD-Igs as a capture antibody, a detection antibody, or both (see par.411). For example, one DVD-Ig having a domain that can bind a first epitope on an analyte can be used as a capture antibody and another DVD-Ig having a domain that can bind a second epitope on an analyte can be used as a detection antibody (see par.411).
Dysinger teaches the method of measuring the free C5 in a serum sample of a patient treated with a therapeutic drug by using a sandwich immunoassay, wherein the therapeutic drug, a capture antibody and a detection antibody can be any anti-C5 antibody as discussed above. Tamburini teaches the bispecific anti-C5 antibodies that can be used for therapeutic drug and for diagnostic. Ghayur teaches the sandwich immunoassay using bispecific antibodies as both capture and detection antibody. One embodiment can be given as follow:
a method of measuring the free C5 in a serum sample of a patient treated with a therapeutic drug, e.g., a therapeutic bispecific antibody to C5a and C5b as taught by Tamburini; the serum sample from the patient comprises free C5, bound C5 with bispecific antibody to C5a and C5b and free bispecific antibody to C5a and C5b;
a bispecific antibody to C5a and C5aR is used as a capture antibody as taught by Tamburini and Ghayur;
a bispecific antibody to C5b and C5L2 is used as a detection antibody as taught by Tamburini and Ghayur; the detection antibody is labeled as taught by Dysinger;
wherein C5a is the first epitope of C5 and C5b is the second epitope of C5;
the capture antibody competes with the therapeutic bispecific antibody in the serum sample for binding to the first epitope C5a on C5, the detection antibody competes with the therapeutic bispecific antibody in the serum sample for binding to the second epitope C5b on C5;
determining the C5 antigen by determining the tracer antibody in the capture antibody-antigen-tracer antibody complex as taught by Dysinger.
Therefore, 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 method of Dysinger, by using an antibody to C5a and C5aR as a capture antibody, using an antibody to C5b and C5L2 as a detection antibody, while treating a patient with a bispecific antibody to C5a and C5b of C5 as taught by Ghayur and Tamburini as discussed above to detecting free C5 in the serum of the patient. Since Dysinger is generic to the anti-C5 antibodies used for treating patient, for capture antibody and for detection antibody (see Dysinger par.63), the modification would result in a successfulness of detecting free C5 in the serum of the patient, wherein the serum comprises free C5, bound C5 and free antibodies to C5. The successfulness of the detection assay is also supported by the teaching of Ghayur in paragraph 411.
One having an ordinary skill in the art would have been motivated to use bispecific antibody as a therapeutic drug because it is likely to have a longer half-life in blood due to a reduced contribution of antigen-mediated antibody clearance, thereby the bispecific antibody drug can be administered to a human at a much lower dose and/or less frequently than an anti-C5 antibody and can effectively provide the same or greater inhibition of C5 in a human (see Tamburini par.14). One having an ordinary skill in the art would have been motivated to apply the modified method of Dysinger and Ghayur on detecting the free C5 antigen in the serum of the patient treated with the therapeutic bispecific antibody because it would help to monitor disease state, modeling, dosage selection of therapeutic drugs (see Dysinger pars.147-148).
Regarding claim 6, Dysinger, Tamburini and Ghayur teach the method in claim 5. Dysinger teaches wherein the half-life of the complex of the antigen binding site of the bispecific antibody specifically binding to the second epitope on the antigen and the antigen is 20 seconds or less.
Dysinger teaches that the method uses Gyros system which uses an affinity flow-through format that eliminates incubations and shortens run times (see par.127). The Gyros system passes samples along the microstructures in a matter of seconds, there may not be an opportunity for back dissociation to occur (see pars.127). Moreover, the required time for a sample to be spun across a microstructure immobilized with a capture reagent is about six seconds, so theoretically there is almost no time for any bound target in the matrix to dissociate and be bound by the drug used as capture antibody (see par.152).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of Dysinger for detecting the analyte, wherein the half-life of the complex of the antigen binding site of the bispecific antibody specifically binds to the second epitope on the antigen and the antigen are 20 seconds or less because the method eliminates incubation time of the detection reagent and the sample, which means zero incubation time as taught by Dysinger.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dysinger, as applied to claim 1 above, and further in view of Fisher (Factors that impact pharmacokinetic measurements of antibody therapeutics: what is your PK assay telling you?, Bioanalysis (2017) 9(20), 1531–1533).
Regarding claim 8, Dysinger teaches the method in claim 1. Dysinger teaches a method for quantitating free antigen from a serum sample comprising free antigen (i.e., free target), free antibody (i.e., drug) and antigen-antibody complex (see par.139). See discussion of Dysinger in claim 1 above. Dysinger uses drug as a capture reagent for free target, so the capture reagent can set up a dynamic equilibrium with target that is already bound to drug in matrix (see par.3). Due to this equilibrium, it is possible for the assay to overestimate the amount of free target in matrix, thus leading to potentially inaccurate modeling, dosage selection, filing data, and label claims (see par.3). Dysinger teaches that a common strategy for overcoming this overestimation in ligand binding assays is to abbreviate sample incubation time, thus reducing the opportunity for capture reagent to pull bound target from drug in the matrix (see par.4).
Dysinger teaches a modified ELISA Assay Format for improving the detection of a free antigen, wherein the modified assay comprises a decreased incubation time for sample and solid phase, e.g., from 60-minute to proposed 15-minute incubation (see par.120).
Fisher teaches that although in theory an assay could be designed to measure free or total levels of drug, measurement of free drug is technically very challenging because the equilibrium between free and complexed forms of the drug is dynamic and the equilibrium of free/complexed drug can be significantly altered by the choice of assay format (e.g., incubation time and sample dilution) and the turnover rate and the affinity of drug for target and drug levels (see page 1530 Bioanalytical considerations).
Fisher also teaches that it is essential to understand the impact of assay conditions on the specific form of the drug that is being measured and the assay conditions should be optimized to tolerate the expected target levels (see page 1533 par.1). While Fisher’s teaching is about the impact of assay conditions on free drug detection, it would be obvious to apply the teaching to free target detection, because drug and target are two components in the same process and both contribute to the dynamic of equilibrium between free and complexed forms of the drug and target.
While Dysinger and Fisher do not teach the same incubation time as recited in the claim, they suggest that the assay reagents, format and conditions can significantly impact the accuracy of the drug or target detection because they can alter the equilibrium of free/complexed drug in the sample (Dysinger par.3 and Fisher page 1530). Therefore, it would have been obvious to one having ordinary skill in the art to optimize the assay conditions to improve the accuracy of ligand-binding assays, e.g., shortening sample incubation time, thus reducing the opportunity for the capture reagent to pull the bound target from a drug in matrix as suggested by Dysinger and Fisher. It would have been obvious to discover the optimum incubation time for the assay by normal optimization procedures known in the art based on the understanding of the impact of assay conditions on the specific form of the drug or target that is being measured, as suggested by Fisher.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dysinger, as applied to claim 1 above, and further in view of Fetterly et al. (Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data, The Journal of Clinical Pharmacology 53(10) 1020–1027, 2013, IDS filed 09/12/2023), R&D (Human CCL2/MCP-1, DuoSet™ ELISA Development System, 2013, IDS filed 09/12/2023), and Fisher (Factors that impact pharmacokinetic measurements of antibody therapeutics: what is your PK assay telling you?, Bioanalysis (2017) 9(20), 1531–1533).
Regarding claim 14, Dysinger teaches a method for quantitating free (unbound) antigen from a serum sample comprising free antigen, free antibody and antigen-antibody complex (see par.139). See discussion of Dysinger in claim 1 above. Dysinger does not teach the method is used for detecting CCL2.
Fetterly teaches a method for quantitating free (unbound) antigen (e.g., CCL2) from a serum sample comprising free antigen, free antibody (e.g., carlumab) and antigen-antibody complex (e.g., the carlumab–CCL2 complex) to gain a better understanding of the effects of carlumab on free CCL2 and the carlumab–CCL2 complex (see Abstract, page 1021 col.1 par.3 and col.2 par.2). Free serum CCL2 was assayed using a commercial CCL2 ELISA assay kit (see page 1021 col.2 par.2), but the principle of CCL2 detection ELISA was not disclosed. Fetterly teaches that free CCL2 concentrations following carlumab administration were overpredicted.
R&D teaches a sandwich ELISAs commercial kit to measure a free CCL2 comprising: immobilizing a capture antibody to CCL2 on a well, adding sample to the well, adding detection antibody, adding enzyme and substrate to develop signal, thereby determining the concentration of CCL2 (see page 2 col.3). The sandwich assay of R&D encompasses the fact that the capture antibody and the tracer antibody bind to different epitopes on the antigen CCL2.
Fisher teaches that although in theory an assay could be designed to measure free or total levels of drug, measurement of AbT free is technically very challenging because the equilibrium between free and complexed forms of the drug is dynamic and the equilibrium of free/complexed drug can be significantly altered by the choice of assay format (e.g., incubation time and sample dilution) and the turnover rate and the affinity of drug for target and drug levels (see page 1530 Bioanalytical considerations). While Fisher’s teaching is about the impact of assay conditions on free drug detection, it would be obvious to apply the teaching to free target detection, because drug and target are two components in the same process and both contribute to the dynamic of equilibrium between free and complexed forms of the drug and target.
Therefore, 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 method of Dysinger, by replacing the capture and tracer antibody to CCL2 antigen as taught by R&D for detecting free CCL2 in the sample to improve the accuracy of the CCL2 quantitation assay in Fetterly. It is because the method of Dysinger minimizes the alteration of the equilibrium of free/complexed target in the assay by reducing the incubation time and sample dilution to prevent the dissociation of the bound drug, thereby improving the accuracy of free antigen detection (see discussion of Dysinger in claim 1). One having an ordinary skill in the art would have a reasonable expectation of success in combining Dysinger and R&D because the capture and tracer antibodies of R&D are used for detecting antigen in a sandwich immunoassay, which means that they bind to the antigen at different epitopes to make a complex of capture antibody-antigen-tracer antibody. As such, the capture and tracer antibodies of R&D can also be used in the method of Dysinger, which requires the tracer antibody binding to a different epitope from the epitope bound by the capture antibody (see Dysinger par.9).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached Mon-Fri 8:30-6:30 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHAU N.B. TRAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/ Supervisory Patent Examiner, Art Unit 1677 March 30, 2026
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