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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/10/2026 has been entered.
Priority
The present application was filed on 12/20/2019. This application claims benefit of U.S. Provisional Patent Application 62/526,051 filed on 06/28/2017.
Status of the claims
Claims 2-6, 12, 24-25, 34-38, and 50-52 are canceled. Claims 14-23, and 26-33 are withdrawn. Claims 1 and 55-58 are amended. Claims 1, 7-11, 13, 49, and 53-58 are examined herein.
Objections/Rejection status
The rejection of claims 1, 7-13, 49, and 53-58 under 35 USC 103 is maintained.
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) 1, 7-11, 49 and 53-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Verschoor (US 20130137598 A1, PTO-892 04/03/2023) in view of SeraCare (Technical Guide for ELISA, 2013).
Regarding claims 1, 49 and 55-57, Verschoor teaches an assay test strip (see Fig.1) comprising:
a flow path configured to receive a fluid sample (see Fig.1: depicting lateral flow immunoassay comprising sample pad, conjugate pad, migration membrane, and absorbent pad; see par.11: lateral flow of sample and reagents occur along a single axis on a test strip format, starting from a sample deposition pad, followed by a conjugate pad and proceeding over a reaction membrane towards a wick that serves as a waste reservoir, and a sample pad is an absorbent pad onto which the test sample is applied), wherein the fluid sample may contain an unlabeled target analyte (see par.12: if the target analyte is also present in the sample it will therefore not bind with the conjugate and will remain unlabeled);
a sample receiving zone coupled to the flow path (sample pad, see Fig.1 and par.11);
a capture zone coupled to the flow path downstream of the sample receiving zone and comprising an immobilized capture agent specific to the analyte of interest (see Fig.1: test line/capture zone on migration/reaction membrane downstream of sample pad; par.11-12: the reaction membrane is typically composed of a hydrophobic nitrocellulose or cellulose acetate membrane onto which anti-target analyte antibodies are immobilized in a line across the membrane as a capture zone or test line).
Verschoor also teaches a complex coupled to the flow path prior to the fluid sample being received on the flow path, wherein the complex is configured to flow in the flow path to the capture zone in the presence of the fluid sample, the complex comprising:
a labeled antibody that specifically binds the analyte of interest, and
the analyte of interest.
See paragraph 12: in a competitive assay, the conjugate pad contains labelled antibodies that are already bound to a target analyte. This means that if the labelled antibody-target analyte complex cannot bind to the analyte in the sample.
Moreover, Verschoor teaches that the complex migrates to the capture zone in the presence of the sample wherein the complex competes with the unlabeled analyte to bind to the immobilized capture agent in the capture zone to generate an optical signal that decreases with increasing concentration of the unlabeled analyte of interest in the sample (see par.12).
Nonetheless, Verschoor is silent to “the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides a dose response curve of the assay test strip comprising about 70 AU for 10 ug/mL unlabeled analyte of interest in the fluid sample, about 38 AU for 60 ug/mL unlabeled analyte of interest in the fluid sample, and about 25 AU for 150 ug/mL unlabeled analyte of interest in the fluid sample” as in claim 1,
“the amount of complex coupled to the flow path comprises between 20-50 ng of analyte of interest” as in claim 49,
“the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides a dose response curve of the assay test strip further comprising about 60 AU for 20 pg/mL unlabeled analyte of interest in the fluid sample” as in claim 55,
“the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides a dose response curve of the assay test strip further comprising about 47 AU for 40 pg/mL unlabeled analyte of interest in the fluid sample” as in claim 56,
“the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides a dose response curve of the assay strip comprises further comprising about 30 AU for 100 pg/mL unlabeled analyte of interest in the fluid sample” as in claim 57.
The limitations “the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides a dose response curve of the assay strip” comprising the relationship between the detecting signal (e.g., 70AU, 38AU, 25AU, 60AU, 47AU, 30AU) and the concentration of analyte (e.g., <10ug/ml, 60ug/ml, 150ug/ml, 20ug/ml, 40ug/ml, 100ug/ml) can be interpreted as setting up a standard curve and determining the optimal coating concentration of the antibody used for capture and the labeled ligand to detect a desired analyte working range (e.g., 10-150 ug/ml as claimed).
SeraCare teaches that the complex competes with the unlabeled analyte to bind to the immobilized capture agent in the capture zone to generate an optical signal that decreases with increasing concentration of the unlabeled analyte of interest in the sample (see page 5 col.2: teaching a competitive assay format is that the combination of an unknown amount of analyte introduced from the sample and the reference analyte compete for binding to a limited number of antibody binding sites, see Fig.3: showing the signal decreases with increasing concentration of competitor analyte).
SeraCare teaches that quantitation can be obtained by generating a “standard curve” of concentration of added competitor analyte versus activity. To do this in the format illustrated in Figure 2A, one would add aliquots of known increasing concentrations of analyte to wells containing the solid phase adsorbed analyte. To each of these wells, one would add an aliquot of labeled antibody and generate the curve illustrated in Figure 3 which shows the correlation of detecting signal and concentration of an unlabeled analyte. See page 6 column 1.
SeraCare further teaches the method of optimizing the reagents using for capture or sandwich ELISA format (see page 22-24), wherein the concentration of the capture agent and labeled agent should be determined at the optimal amount (see page 22 col.1 par.5-6). This optimizing process is for identifying at which concentration of capture antibody the detecting signal reaches to saturation, limit of detection, sensitivity and specificity of the assay (see at least page 22 col.1 par.5-6, page 23 col.1 par.1, and page 28 col.2 Limit of Detection).
In the optimizing process, both the capture and detection antibody need to be optimized at several (at least three) concentrations of target (see page 22 col.1 par.6, page 23 Fig.14).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of Verschoor because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of Verschoor can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Verschoor and SeraCare because Verschoor is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
Regarding claim 7, Verschoor and SeraCare teach the invention as discussed above. Verschoor also teaches an optical signal emitted from the complex bound in the capture zone is a maximum optical signal of the dose response curve of the assay test strip when the fluid sample does not comprise analyte of interest (see par.12: teaching that two visible lines in the capture and control zones is a negative result, thereby reading on maximum optical signal when the term is given its broadest reasonable interpretation, e.g., insofar as a visible signal is a maximum optical signal compared to no visible signal or a weak signal).
Regarding claim 8, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches an optical signal emitted from the complex bound in the capture zone is less than the maximum optical signal of the dose response curve of the assay test strip when the fluid sample does comprise analyte of interest (see par. 12, teaching that as the sample migrates along the membrane and reaches the capture zone an excess of unlabeled analyte will bind to the immobilized antibodies and block or outcompete the capture of the conjugate, so that no visible line is produced; a single control line on the membrane is a positive result).
Regarding claim 9, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches the immobilized capture agent comprises an antibody that specifically binds the analyte of interest (see par.11: teaching that the reaction membrane is typically composed of a hydrophobic nitrocellulose or cellulose acetate membrane onto which anti-target analyte antibodies are immobilized in a line across the membrane as a capture zone or test line; see par.12, teaching that sample migrates along the membrane and reaches the capture zone; an excess of unlabeled analyte will bind to the immobilized antibodies and block or outcompete the capture of the conjugate).
Regarding claim 10, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches the complex is integrated onto a surface of the test strip (see par.12, teaching that the conjugate pad contains labelled antibodies that are already bound to a target analyte, or to an analogue of it).
Regarding claim 11, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches the complex is integrated onto the surface of the test strip in a first phase (see par.12, teaching that the conjugate pad contains labelled antibodies that are already bound to a target analyte, or to an analogue of it). While Verschoor does not specifically teach this is accomplished by spraying a solution comprising the complex onto the surface of the strip and drying the solution, these limitations do not impart any additional structure to the test strip. Therefore, this limitation is not patentable weight.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). MPEP 2113.
Regarding claim 53, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches a capture zone or test line where anti-target analyte antibodies are immobilized on lines across the membrane (see in par.11). Also, the lateral flow device taught by Verschoor can include a sample pad, a conjugate pad, a capture zone and, optionally, a control zone (see in par.34). With this teaching above, Verschoor discloses a test device having a single capture line in a capture zone as claimed.
Regarding claim 54, Verschoor and SeraCare teach the invention as discussed above. As discussed in claim 11 above, this claim contains functional language which covers the corresponding structure of the subject matter, e.g., what makes the complex chemically stable on the test strip. Therefore, this limitation is not patentable weight.
Nonetheless, Verschoor teaches that a labeled-analyte is already on the conjugate pad (see in par.12). If the target analyte is also present in the sample, it will therefore not bind with the conjugate and will remain unlabeled (see in par.12). This means that when the labeled-analyte contacts with the target analyte in the sample, it still can’t bind to the target analyte. Thus, the labeled-analyte would be chemically stable until after the fluid sample is applied to the test strip.
Claims 13 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Verschoor in view of SeraCare, as applied in claim 1 above, in view of Qi et al. (Dual-Quantum-Dots-Labeled Lateral Flow Strip Rapidly Quantifies Procalcitonin and C-reactive Protein, Nanoscale Research Letters (2016) 11:167).
Regarding claim 13, Verschoor and SeraCare teach the invention as discussed above. Verschoor teaches the assay strip of claim 1, as detailed above, but fails to specifically teach the analyte of interest comprises C-reactive protein (CRP) and the complex comprises an anti-CRP antibody or fragment thereof bound to the CRP.
Qi discloses a lateral flow assay strip for detecting CRP as the analyte of interest. The detection of CRP in a sample is done by a competitive inhibition method in the strip. See Abstract.
Qi further teaches that a quantum-dot-labeled anti-CRP antibody (QD-Ab2) was used as a detection antibody (see page 3 col.1 par.2). On the lateral flow assay strip, CRP antigen was fixed to form detection line 2, which functions as a capture zone in the claimed device (see page 3 col.1 par.3). When a sample is added onto the sample pad, it rapidly drenches the conjugate pad and dissolves the QD-Ab2. If a target CRP exists in the sample, the QD2-Ab2-CRP is synthesized. Then the sample comprising QD2-Ab2-CRP, extra QD2-Ab2 unreacted flows through the detection line 2, where the QD2-Ab2-CRP does not react with the fixed CRP, while extra QD2-Ab2 is captured by the fixed CRP and QD2-Ab2-fixed CRP is formed. At the end, there is a negative correlation between the fluorescent intensity on detection line 2 and the concentration of CRP. See page 4 column 2 paragraph 2.
From the teaching above, there is a competition between a target analyte in the sample and the target analyte fixed in the test strip for binding to a labeled anti-target antibody. Therefore, Qi’s teaching encompasses the complex comprises an anti-CRP antibody, a label, and the target analyte.
Verschoor and Qi are analogous in terms of a test strip for detecting an analyte based on a competitive method.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the capture agent and the antigen in the complex taught by Verschoor with the known CRP antigen and the labeled anti-CRP antibody taught by Qi into the test strip of Verschoor. By doing that, one having skill in the art can utilize the test strip of Verschoor to detect CRP in the sample because it is great for clinical value to distinguish inflammation, bacterial infection, or viral infection and to provide guidance for the use of antibiotics or other medicines (see Qi Abstract).
One having ordinary skill in the art would have had a reasonable expectation of success in combining Verschoor and Qi because they are analogous in terms of a test strip for detecting an analyte based on a competitive method, and Verschoor is generic with respect to detect an analyte of interest in the sample. Moreover, Verschoor is generic with respect to the analyte and the antibody that can be incorporated into the complex while Qi specifically teaches that the CRP antigen and the labeled anti-CRP antibody can be incorporated into the complex during the detecting procedure.
Regarding claim 58, Verschoor, SeraCare and Qi teach the claimed device as discussed above. Verschoor and Qi teach the device that can detect CRP in a sample comprising the complex that comprises an anti-CRP antibody. See discussion of Verschoor and Qi in claim 13 above.
Verschoor also discloses a capture zone coupled to the flow path downstream of the sample receiving zone and comprising an immobilized capture agent specific to the analyte of interest (see Fig.1: test line/capture zone on migration/reaction membrane downstream of sample pad; par.11-12: the reaction membrane is typically composed of a hydrophobic nitrocellulose or cellulose acetate membrane onto which anti-target analyte antibodies are immobilized in a line across the membrane as a capture zone or test line). Therefore, in the case the test strip is used for detecting CRP, the immobilized capture agent is an anti-CRP antibody.
Verschoor also teaches that the capture zone comprises a single capture line (see par.11: the reaction membrane is typically composed of a hydrophobic nitrocellulose or cellulose acetate membrane onto which anti-target analyte antibodies are immobilized in a line across the membrane as a capture zone or test line).
Verschoor does not teach that the assay test strip is configured to be able of detecting CRP concentrations of about 10-150 ug/ml, and not be able to detect CRP concentrations less than 10 ug/mL.
However, the limitations “the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides an assay test strip capable of detecting CRP concentrations of about 10 pg/mL to at least 150 pg/mL, and not cable of detecting CRP concentrations less than 10 pg/mL” can be interpreted as determining the optimal coating concentration of the antibody used for capture and the labeled ligand to detect a desired analyte working range (e.g., 10-150 ug/ml).
SeraCare teaches the step of optimizing the reagents using for capture or sandwich competitive ELISA format (e.g., the concentration of the capture agent and labeled agent) within a desired analyte workable range is a basic process to one having ordinary skill in the art during the assay development. See discussion of SeraCare in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of Verschoor in view of Qi because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of Verschoor can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Verschoor and SeraCare because Verschoor is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 7-11,13, 49 and 53-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 14 and 75 of copending Application No. 16/932,532 (reference application, hereinafter ‘532) in view of SeraCare (Technical Guide for ELISA, 2013). Although the claims at issue are not identical, they are not patentably distinct from each other. Although claim 1 of ‘532 recite a method, the method comprises a lateral flow assay to which the instant claims are directed. Although ‘532 recites structural elements not recited in the instant claims, the instant claims use open claim language “comprising” and therefore do not exclude the presence of additional elements.
Regarding instant claims 1, 49 and 55-57, claim 1 of ‘532 teaches an assay test strip comprising:
a flow path configured to receive a fluid sample;
a sample receiving zone coupled to the flow path;
a capture zone coupled to the flow path downstream of the sample receiving zone and comprising an immobilized capture agent specific to an analyte of interest; and
a complex coupled to the flow path prior to the fluid sample being received on the flow path, wherein the complex is configured to flow in the flow path to the capture zone in the presence of the fluid sample in a second phase, the complex comprising a label, an antibody or a fragment of an antibody that specifically binds the analyte of interest, and the analyte of interest.
Claim 1 of ‘532 further discloses that the first complex competes with the first analyte in the sample to bind to the first immobilized capture agent in the first capture zone. This teaching implies that the complex does not bind to the unlabeled analyte of interest in the sample. Otherwise, if the complex also binds to the unlabeled analyte of interest, the assay does not work properly.
Claim 1 of ‘532 discloses the first signal detected from the first complex bound to the first immobilized capture agent in the first capture zone decreases as the concentration of the first analyte increases in the sample.
Claim 1 of ‘532 does not teach the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides dose response curve of the assay as claimed 55-57, and the amount of complex coupled to the flow path comprises between 20-50 ng of analyte of interest as in claim 49.
However, SeraCare teaches the step of optimizing the reagents using for capture or sandwich competitive ELISA format (e.g., the concentration of the capture agent and labeled agent) within a desired analyte workable range is a basic process to one having ordinary skill in the art during the assay development. See discussion of SeraCare in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of ‘532 because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of ‘532 can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘532 and SeraCare because ‘532 is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
Regarding instant claims 7-8, claim 1 of ‘532 and SeraCare teach the test strip device as discussed above. While ‘532 does not specifically teach the limitations of the instant claims, the limitations do not impart any additional structure to the test strip but are about the function of the test strip. It is noted that functional claim language that is not limited to a specific structure covers all devices that are capable of performing the recited function. Therefore, if the prior art discloses a device that can inherently perform the claimed function. See MPEP 2114. IV.
Regarding instant claim 9, claim 1 of ‘532 and SeraCare teach the immobilized capture agent comprises an antibody or a fragment of an antibody that specifically binds the analyte of interest.
Regarding instant claim 10, claim 1 of ‘532 and SeraCare teach the complex is integrated onto a surface of the test strip.
Regarding instant claim 11, claim 1 of ‘532 and SeraCare teach the complex is integrated onto a surface of the test strip in a first phase. While ‘532 does not specifically teach this is accomplished by spraying a solution comprising the complex onto the surface of the strip and drying the solution, the limitations do not impart any additional structure to the test strip. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). MPEP 2113.
Regarding instant claims 13 and 58, claim 1 of ‘532 and SeraCare teach the analyte of interest is CRP, the complex comprises an anti-CRP antibody, the immobilized capture agent comprises an antibody to CRP, a single capture zone for CRP.
Claims 3 and 75 of ‘532 teaches the test strip can detect CRP concentrations of about 1-999 ug/mL. ‘532 does not teach the test strip is not cable of detecting CRP concentrations less than 10 pg/mL.
However, SeraCare teaches the step of optimizing the reagents using for capture or sandwich competitive ELISA format (e.g., the concentration of the capture agent and labeled agent) within a desired analyte workable range is a basic process to one having ordinary skill in the art during the assay development. See discussion of SeraCare in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of ‘532 because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of ‘532 can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘532 and SeraCare because ‘532 is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
Claims 1, 7-11,13, 49 and 53-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 14, and 74 of copending Application No. 16/932,533 (reference application, hereinafter ‘533) in view of SeraCare (Technical Guide for ELISA, 2013). Although the claims at issue are not identical, they are not patentably distinct from each other. Although claim 1 of ‘533 recite a method, the method comprises a lateral flow assay to which the instant claims are directed.
Regarding instant claims 1, 49 and 55-57, claim 1 of ‘533 teaches an assay test strip comprising:
a flow path configured to receive a fluid sample;
a sample receiving zone coupled to the flow path;
a capture zone coupled to the flow path downstream of the sample receiving zone and comprising an immobilized capture agent specific to an analyte of interest; and
a complex coupled to the flow path in a first phase prior to the fluid sample being received on the flow path, wherein the complex is configured to flow in the flow path to the capture zone in the presence of the fluid sample in a second phase, the complex comprising a label, an antibody or a fragment of an antibody that specifically binds the analyte of interest, and the analyte of interest.
Claim 1 of ‘533 further discloses that the first complex competes with the first analyte in the sample to bind to the first immobilized capture agent in the first capture zone. This teaching implies that the complex does not bind to the unlabeled analyte of interest in the sample. Otherwise, if the complex also binds to the unlabeled analyte of interest, the assay does not work properly.
Claim 1of ‘533 discloses the first signal detected from the first complex bound to the first immobilized capture agent in the first capture zone decreases as the concentration of the first analyte increases in the sample.
Claim 1 of ‘532 does not teach the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone provides dose response curve of the assay as claimed 55-57, and the amount of complex coupled to the flow path comprises between 20-50 ng of analyte of interest as in claim 49.
However, SeraCare teaches the step of optimizing the reagents using for capture or sandwich competitive ELISA format (e.g., the concentration of the capture agent and labeled agent) within a desired analyte workable range is a basic process to one having ordinary skill in the art during the assay development. See discussion of SeraCare in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of ‘533 because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of ‘533 can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘533 and SeraCare because ‘533 is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
Regarding instant claims 7-8, claim 1 of ‘533 and SeraCare teach the test strip device as discussed above. While ‘533 does not specifically teach the limitations of the instant claims, the limitations do not impart any additional structure to the test strip but are about the function of the test strip. It is noted that functional claim language that is not limited to a specific structure covers all devices that are capable of performing the recited function. Therefore, if the prior art discloses a device that can inherently perform the claimed function. See MPEP 2114. IV.
Regarding instant claim 9, claim 1 of ‘533 and SeraCare teach the immobilized capture agent comprises an antibody or a fragment of an antibody that specifically binds the analyte of interest.
Regarding instant claim 10, claim 1 of ‘533 and SeraCare teach the complex is integrated onto a surface of the test strip.
Regarding instant claim 11, claim 1 of ‘533 and SeraCare teach the complex is integrated onto a surface of the test strip in a first phase. While ‘533 does not specifically teach this is accomplished by spraying a solution comprising the complex onto the surface of the strip and drying the solution, the limitations do not impart any additional structure to the test strip. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). MPEP 2113.
Regarding instant claims 13 and 58, claim 1 of ‘533 and SeraCare teach the analyte of interest is CRP, the complex comprises an anti-CRP antibody, the immobilized capture agent comprises an antibody to CRP, a single capture zone for CRP.
Claims 3 and 74 of ‘533 teaches the test strip can detect CRP concentrations of about 1-999 ug/mL. ‘533 does not teach the test strip is not cable of detecting CRP concentrations less than 10 pg/mL.
However, SeraCare teaches the step of optimizing the reagents using for capture or sandwich competitive ELISA format (e.g., the concentration of the capture agent and labeled agent) within a desired analyte workable range is a basic process to one having ordinary skill in the art during the assay development. See discussion of SeraCare in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of SeraCare, pre-defining the amount of complex coupled to the flow path prior to the fluid sample being received on the flow path and the amount of capture agent specific to the analyte of interest immobilized in the capture zone, into the development of a test strip of ‘533 because SeraCare teaches that is a basic concept and protocol to develop a competitive ELISA. By doing that, the test strip of ‘533 can be used to quantify the analyte of interest within a desired workable range with the optimal sensitivity and specificity as taught by SeraCare as discussed above.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘533 and SeraCare because ‘533 is direct to an assay test strip that applies a competitive ELISA, and SeraCare teaches basic concepts for developing and optimizing ELISA format including the competitive assay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process, thus it is obvious to yield a predictable results to one of ordinary skill in the art.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments, in the Remarks filed 03/10/2026 have been fully considered but they are not persuasive.
For the rejection under 35 U.S.C. § 103 of claims 1, 7-11, 49 and 53-57:
Applicant argued that SeraCare does not provide any information on how to achieve the claimed assay with the recited dose response curve for an analyte having concentrations of :S 10 μg/mL, 60 μg/mL and 150 μg/mL. Since SeraCare does not disclose any information regarding optimizing reagents for a competitive assay, either in the context of the ELISA format discussed in SeraCare, or in the context of an assay test strip. SeraCare do not have a single mention of how to optimize the amounts of reagents used in a competitive ELISA.
This argument is not persuasive. SeraCare discloses the background of developing an immunoassay (e.g., ELISA) and discusses some key factors in the process (see page 10 col.1 par.2). SeraCare teaches a method you can use to optimize the concentration of reagents that you will use, some controls to add to ensure that your signal really is signal, and finally some representative protocols to start you off (see page 10 col.1 par.2). Then, SeraCare teaches how to set up a standard curve in a competitive or non-competitive assay (see Fig.3 on page 6 and Fig.6 on page 7). The standard curve is also called a dose response curve of the assay. This teaching encompasses how to optimize the amounts of reagents used in an ELISA. Moreover, the ELISA format or an assay test strip is analogous in terms of immunoassay wherein the analyte of interest is detected by a capture agent and/or a labeled capture agent. Therefore, this teaching also encompasses how to optimize the amounts of reagents used in a test strip.
Applicant argued that SeraCare is clearly directed to a capture/sandwich assay and not a competitive assay.
This argument is not persuasive. SeraCare on page 5 teaches the background of capture and direct immunoassay types. SeraCare states that each of the above assay types can be adapted to a competitive or non-competitive format. The distinguishing feature of a competitive assay format is that the combination of an unknown amount of analyte introduced from the sample and the reference analyte compete for binding to a limited number of antibody binding sites (see page 5 col.2). Therefore, while SeraCare does not display a capture competitive assay in Fig.2, the SeraCare optimization method can be used for setting up the standard curve of the competitive assay. It is obvious to one of ordinary skill in the art to select the detecting assay format according to user preference, thereby optimizing the concentration of reagents that the assay requires to ensure that the signal from the assay is an optimal signal.
Applicant argued that the presently claimed assay test strip uses the recited complex to allow for the detection of analytes at high concentrations without the need to dilute the sample. See Specification at paragraphs [0029] and [0082]. SeraCare discloses that when the concentration of analyte is too high, the solution is to "Dilute sample and rerun." See SeraCare at p. 32 "Samples reading above plate reader's ability to discriminate" (emphasis added). Thus, SeraCare teaches away from the claimed invention.
This argument is moot because this limitation is not in the claims.
Applicant argued that SeraCare does not disclose a "complex" or a "capture zone" as recited in currently pending Claim 1. Rather, SeraCare discloses either a "labeled antibody" or "labeled analyte" as shown in Fig. 2 of SeraCare above. Further, SeraCare never mentions test strips, flow paths or capture zones as recited in the presently pending claims, instead focusing on ELISA assays performed in wells such as a 96-well plate.
This argument is not persuasive. Examiner relies on Verschoor for the teaching of the complex, capture zone, flow paths and test strip. Examiner relies on SeraCare for the teaching of setting a dose response curve of the competitive immunoassay. The ELISA format or an assay test strip is analogous in terms of immunoassay wherein the analyte of interest is detected by a capture agent and/or a labeled capture agent. Therefore, the teaching of SeraCare also encompasses how to optimize the amounts of reagents used in a test strip of Verschoor. One having an ordinary skill in the art would have had a reasonable expectation of success in combining Verschoor and SeraCare because Verschoor is direct to an assay test strip that applies a competitive immunoassay, and SeraCare teaches basic concepts for developing and optimizing the immunoassay format. According to SeraCare, pre-determining the amount of capture agent, labeled detector, and correlation of detecting signal and analyte concentration is a part of the competitive assay developing process. Thus, it is obvious to yield predictable results to one of ordinary skill in the art.
For the rejection under 35 U.S.C. § 103 of claims 13 and 58:
Applicant argued that the complex comprising an anti-CRP antibody, a label, and the target analyte is formed after the sample is added to the assay while the claimed complex exists before the sample is added. The Examiner's proposed modification of the assay of Verschoor to incorporate the anti-CRP antibody and CRP capture agent of Qi would not result in the presently claimed assay for at least the reason that the proposed modification would not result in the claimed complex "coupled to the flow path prior to the fluid sample being received on the flow path, wherein the complex is configured to flow in the flow path to the capture zone .... ".
This argument is not persuasive. Examiner relies on Verschoor for the teaching of the complex which is formed before the sample is added (see Verschoor par.12). Examiner relies on Qi for the teaching of CRP detection in a sample by a competitive inhibition method in the strip, wherein the CRP in the sample is detected by using the labeled anti-CRP antibody and the pre-defined CRP antigen in the test.
Examiner proposed that the assay of Verschoor can be modified by substituting the capture agent and the target antigen in the complex taught by Verschoor with the pre-defined CRP antigen and the labeled anti-CRP antibody taught by Qi. By doing that, one having skill in the art can utilize the test strip of Verschoor to detect CRP in the sample because it is great for clinical value to distinguish inflammation, bacterial infection, or viral infection and to provide guidance for the use of antibiotics or other medicines (see Qi Abstract). One having ordinary skill in the art would have had a reasonable expectation of success in combining Verschoor and Qi because they are analogous in terms of a test strip for detecting an analyte based on a competitive method, and Verschoor is generic to detect an analyte of interest in the sample. Moreover, Verschoor is generic with respect to the analyte and the antibody that can be incorporated into the complex, while Qi specifically teaches that the CRP antigen and the labeled anti-CRP antibody can be incorporated into the complex during the detecting procedure.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CHAU N.B. TRAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 18, 2026
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