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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/29/2025 has been entered.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/KR2019/008465, filed 07/10/2019. Acknowledgement is also made of applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. KR10-2018-0172576, filed on 12/28/2018 in Korea.
Status of the Claims
Claims 1, 3-4, 6-7, and 10 are pending. Claim 1 is amended. Claims 2, 5, and 8-9 are cancelled. Claims 1, 3-4, 6-7, and 10 are examined below.
Withdrawn Rejections
The rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn due to the amendment of the claim.
The rejection of claims 1, 3-4, 6-7, and 10 under 35 U.S.C. 103 is withdrawn due to the amendment of claim 1.
See new grounds of rejection below.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, and 6-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Amended claim 1 recites “wherein the strip is configured to detect a false positive”. Applicant at remarks, page 4, lines 2-3, indicates support for the amendment “in the specification as filed including in the previously pending claims”. However, applicant does not point to a specific portion of the claims or specification and the previous pending claims do not recite a way to detect a false positive pregnancy test. Further, while the instant specification recites that high hCGβcf can interfere and cause false negative errors in pregnancy diagnosis (page 3, see 2nd paragraph) and that the invention can overcome the problem of false negatives (page 13, ‘Advantageous Effects’, line 3 and page 19-20), there is no recitation of a false positive result in the specification. Therefore the amendment is considered new matter.
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, 3-4, and 6-7 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 is indefinite because it recites a “strip configured to detect a false positive”. The recited language fails to specify what the “false positive” refers to. Further, it is unclear how the configuration of the test strip aids in the detection of a false positive pregnancy test. As explained previously in detail above (under 35 U.S.C. 112(a)) there is no recitation of a false positive test in the specification nor how the test is configured to detect said false positive result caused by a variant of hCG comprising a β-core fragment. Applicant argues in the remarks (10/29/2025) that support for the amendment can be found throughout the specification (remarks, page 4) and further that the test strip can provide “a highly accurate pregnancy diagnostic strip that eliminates interference from hCG variants, which exist in high concentration in urine” (remarks, page 6, lines 3-5). The specification provides support for a test strip configured to avoid false negative results which can result from interference of high concentration of hCG variants.
In the interest of compact prosecution, claim 1 will be interpreted to recite a test strip configured to detect a false negative caused by a variant of hCG comprising a β-core fragment.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 6-7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al. KR20160108695A, in view of Chang et al., US7332350B2, Ward et al., WO2018140719, and Nerenz et al. Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG β core fragment: evaluation of 11 devices. Clinical chemistry. 2014 Apr 1;60(4):667-74, as evidenced by MedixMab Hormones, Technical Note, 2020 and Bioventix, Technical Note, 2020.
Regarding claim 1, Jin teaches immunochromatographic strips comprising a detection pad and a conjugate pad (Jin, page 4, ‘E. Preparation of immunochromatographic strips’, line 1). Jin further teaches that the conjugate pad comprises colloidal gold particles and polyclonal anti-hCG as the first anti-chorionic gonadotropin antibody (Jin, page 4, ‘B. Conjugate Making a pad’, lines 1-2). Still further, Jin teaches a detection pad comprising with three analytical lines, using monoclonal anti-human chorionic gonadotropin antibody in one test line and human chorionic gonadotropin second test line (Jin, ‘A. Inspection line, Heterogeneous Inspection line and the formed detection pad making’, lines 2-5). Jin further teaches that the test lines are separated (Jin, page 10, see Figure 4), number 6 is human chorionic gonadotropin antibody immobilized test line and number 7 is human chorionic gonadotropin-immobilized heterogeneous test line (Jin, page 4, last line – page 5, line 8). Jin further teaches that the test strip is provided with a heterogeneous test line (test line comprising human chorionic gonadotropin) to overcome the problem of false negativity due to the hook phenomenon (Jin, page 1, ‘Abstract’, lines 5-7). Jin teaches that in case of the heterogeneous test line, the signal intensity gradually decreases as the concentration in the specimen increases. When the concentration of gonadotropic hormone is low, since the hook phenomenon does not occur in the test line, the concentration of the gonadotropic hormone can be analyzed through the signal intensity of the test line. When the concentration of gonadotropin stimulates further, the intensity of the signal is irregular due to the occurrence of the hook phenomenon in the test line, but it is possible to measure the concentration due to the heterogeneous test line (Jin, page 6, see entire 4th paragraph and table 1).
Jin fails to teach that the first antibody recognizes a β-core fragment site of human chorionic gonadotropin and the second antibody recognizes a different site of hCG, which is not the β-core fragment site of hCG. Jin further fails to teach that hCG or a variant thereof comprises a human chorionic gonadotropin β-core fragment and that the false negative is caused by a variant of hCG comprising a β-core fragment.
Chang teaches a one-step diagnostic device for detecting normal pregnancy and distinguishing it from ectopic pregnancy (Chang, ‘Abstract’, lines 1-3). Chang further teaches the use of an immune-chromatographic method (Chang, column 5, lines 20-21). Chang further teaches antibodies reactive to I-hCG, modified hCG, α-hCG, and β-hCG (Chang, column 5, lines 40-45). Chang further teaches that “modified” hCGs include free β-core fragment (Chang, column 2, lines 37-39). Chang further teaches a test strip comprising an anti-β-hCG monoclonal antibody has been immobilized (Figure 1b, reference numeral 9) and a pad comprising colored particulates having an anti-modified hCG monoclonal antibody bound thereon (Figure 1b, reference numeral 10; Chang, column 4, lines 25-32). Chang further teaches that an ectopic pregnancy can be determined through comparison between the concentrations of normal hCG and modified hCG (Chang, column 3, lines 54-56).
Chang does not teach an antibody recognizing the β-core fragment of hCG or a second antibody that recognizes a different site of hCG.
Ward teaches a method comprising a magnetic particle and a capture moiety configured to bind an analyte of interest, a reporter conjugate comprising a reporter and a reporter binding moiety configured to bind the analyte of interest and detecting the presence, absence, or level of analyte by detecting the reporter (Ward, see entire ‘Abstract’). Ward further teaches that the capture moiety and the reporter binding moiety is an antibody (Ward, page 3, lines 3 and 9-10). Ward further teaches that the terms ‘reporter’ and ‘label’ may be used interchangeably and that the label includes gold particles (Ward, page 38, paragraph [0156], lines 1 and 16-18). Ward further teaches a labeled antibody and a capture antibody bound to a substrate (Ward, page 1/35, Figure 1A) and an exemplary analyte of interest that is hCG (Ward, page 9, line 3). Ward further teaches a labeled first antibody (see Ward, Figure 1A, antibody (b)) that is anti-hCG clone 4F9 and a substrate bound second antibody (see Ward, Figure 1A, antibody (c)) that is anti-hCG clone 5011, which are able to simultaneously bind the analyte (Ward, page 9, paragraph [0032], lines 3-6), which is an important factor for choosing antibodies and a prerequisite for the antibodies to work successfully (Ward, page 18, paragraph [0070], lines 1-2). According to Bioventix Technical Note, clone 4F9 binds intact hCG as well as the β-core fragment (Bioventix Technical Note, ‘ELISA DATA: Epitope Recognition’, see column 3) and according to Medix Technical Note, clone 5011 binds intact hCG, but not the β-core fragment (Medix Technical Note, page 7, ‘Epitopes and specificity, see line 7).
Nerenz teaches that the predominant hCG variant in urine, hCG β core fragment has been demonstrated to cause false-negative results in qualitative point of care hCG devices (immunochromatographic test strips; Nerenz, page 667, ‘Background’, lines 1-4). Nerenz further teaches that hCG immunoreactivity results from intact hCG as well as chemically modified variants, including the core fragment of hCGβ (Nerenz, page 667, 2nd column, lines 1-6). Nerenz further teaches that one-step sandwich assays, including point of care hCG devices may generate weakly positive or negative signal in the presence of high analyte concentration due to excess antigen, known as the hook effect. Nerenz further teaches the phenomenon of a variant hook effect occurs when in addition to intact hCG, one of the antibodies used in the assay recognizes an hCG variant (such as hCG β-core fragment) and the other antibody does not recognize it at all. When the variant is present in high enough concentrations, a false-negative result can occur (Nerenz, page 667-668, 2nd column, see entire 3rd paragraph). Nerenz further teaches that false-negative results because of the presence of high concentrations of hCG β-core fragment, in women with hCG concentrations regularly observed during healthy pregnancy are a clinically significant concern for the healthcare profession (Nerenz, page 672, ‘Discussion’, lines 1-5). Nerenz further teaches that unlike the variant hook effect, the hook effect due to hCG occurs primarily in the presence of pathologically increased hCG such as gestational trophoblastic disease (Nerenz, page 667, 2nd column, 2nd paragraph, lines 11-13).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the test strip of Jin to comprise antibodies to intact and modified hCG (comprising β-core fragment) as taught by Chang and specifically to have applied the antibody clones 4F9 and 5011 of Ward to the invention of Jin, because of the teaching of Ward that they can simultaneously bind hCG and that this is a prerequisite in choosing antibody pairs. One of ordinary skill in the art would have been further motivated to do so because Jin teaches that the immunoassay comprising one test line with anti-hCG antibody and one heterogenous test line comprising hCG allows for the determination of pregnancy even in cases where the hook effect results in a negative first test line due to excess hormone in the sample and the teaching of Nerenz that the hook effect in normal pregnancy can be caused by high, but physiologically normal, levels of hCG β-core fragment whereas very high concentrations of hCG occurs primarily in the presence of pathologically increased hCG. Nerenz teaching that the variant hook effect especially occurs using a test strip where in addition to intact hCG, one of the antibodies used in the assay recognizes an hCG variant and the other antibody does not recognize it at all. Put another way, using an anti-hCG β-core fragment antibody as taught by Ward in the assay of Jin would allow to confirm pregnancy despite a hook effect caused by high, but physiologically normal levels of hCG β-core fragment but not potentially pathologically increased hCG levels.
The ordinary artisan would have a reasonable expectation of success, because Jin teaches an immunoassay with a free labeled antibody specific for hCG and a membrane bound antibody specific for hCG and Ward similarly teaches a free labeled antibody specific for hCG and a complimentary substrate-bound antibody for hCG.
Regarding claim 3, Jin teaches immunochromatographic strips used to diagnose pregnancy detecting human chorionic gonadotropin comprising an antibody bound to a labeling substance such as gold particles, fixed on the conjugate pad. Jin further teaches that when the specimen is developed, it passes through the conjugate pad, a complex of chorionic gonadotropin-anti-human chorionic gonadotropin antibody-gold particles is formed and the complex is bound by the antibody against anti-choroidal gonadotropin immobilized at the test line (Jin, page 3, lines 4-13). Jin further teaches that with increasing amount of human chorionic gonadotropin in the sample the anti-hCG-antibody line increases and the hCG-line decreases (Jin, page 11, see table 1, columns 0-1600).
Regarding claim 4, Jin et al. and the cited art above as applied to claims 2 and 3, also applies to claim 4.
Jin teaches a chromatography strip substantially as claimed.
As discussed previously above, Ward teaches a labeled antibody that binds hCG (clone 4F9; Ward, page 9, paragraph [0032], lines 3-4 & Fig. 1A) and specifically binds normal hCG and the β-core fragment variant of hCG (Bioventix Technical Note, ‘ELISA DATA: Epitope Recognition’, see column 3)) and a second antibody, bound to a substrate that binds hCG (clone 5011; Ward, page 9, paragraph [0032], lines 4-5) and specifically binds normal hCG, but not the β-core fragment variant of hCG (Medix Technical Note, page 7, ‘Epitopes and specificity, see line 7).
As such the combination of the art cited above teaches a chromatography strip wherein normal hCG bound to a labeled reporter is bound to the substrate bound antibody clone 5011 on the test line, but the β-core fragment variant of hCG is not bound to the test line.
Regarding claim 6, Jin teaches colloidal gold particles (Jin, page 4, ‘B. Conjugate Making a pad (conjugate pad)’, line 3).
Regarding claim 7¸ Jin teaches three analytical lines, comprising an anti-mouse immunoglobulin antibody line as a ligand for the control (Jin, page 4, ‘A. Inspection line, heterogeneous inspection line and the formed detection pad making’, lines 7-9).
Regarding claim 10, Jin teaches an immunochromatographic strip for pregnancy test and a Kit using the same (Jin, page 1, see title). Jin further teaches a plastic case, a sample inlet for dropping the sample at the position of the sample pad on the upper part of the case and a result confirmation window for confirming the result of the inspection at the position where the binding agent of the detection pad is fixed (position corresponding to the test line or the control line; Jin, page 2, ‘Description of the drawings’, lines 12-16; see also Figure 5). Jin further teaches inserting the immunochromatographic strip for pregnancy diagnosis into the strip fixing position (guide and strip support) of the plastic lower case (Jin, page 5, ‘F: Case Assembly’, lines 1-3).
Response to Arguments
Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
Applicant argues, starting on page 6, that the strip is configured to detect a false positive caused by a variant of hCG comprising a β-core fragment.
However, as explained previously in detail above and as taught by Nerenz, a variant of hCG comprising a β-core fragment can cause a the variant hook effect which may result in a weakly positive or negative signal (a false negative test result) when in addition to intact hCG, one of the antibodies used in the assay recognizes an hCG variant (such as hCG β-core fragment) and the other antibody does not recognize it at all. Therefore the limitation is interpreted as a strip configured to detect a false negative caused by a β-core fragment of hCG.
Applicant argues that the claimed strip involves a first anti-hCG monoclonal antibody binding to hCG and hCG variants comprising an hCG β core fragment while the second anti-hCG antibody binds to only normal hCG, not variants of hCG and therefore normal hCG is being detected in test line 1 and bare conjugate in test line 2 therefore excluding interference of hCG variants.
Applicant further argues that Jin fails to teach a first antibody recognizing a β-core fragment and a second antibody recognizing a different site of hCG and that it would not be obvious to apply the antibody clones of Ward to the invention of Jin and to modify the test strip of Jin with the anti-variant antibody pair of Chang because Ward and Chang do not remedy the deficiencies of Jin.
Applicant argues that Ward does not teach any sequential detection method using a chromatographic strip and Chang does not teach or suggest a mechanism to exclude a variant of hCG such as the β-core fragment and that instead Chang is concerned with determining ectopic pregnancy.
Applicant further argues that a person of ordinary skill in the art would have no reason or motivation to modify the teachings of Jin to arrive at the present claims.
This argument is not persuasive.
Jin teaches a test strip with two test lines (one comprising antibody and one comprising hCG) in order to avoid false negative pregnancy results due to excess hCG as claimed. Chang teaches a test strip comprising antibodies to hCG and hCG variants and Nerenz provides motivation to apply the antibodies of Ward to the device of Jin, namely the observation that in normal pregnancies the variant hook effect is usually caused by an excess of hCG β-core fragment. As such the combination of Jin and Ward would detect a pregnancy where a physiologically normal level of hCG β-core fragment would otherwise result in a false negative pregnancy test result.
Chang teaches a test strip comprising antibodies to I-hCG, modified hCG, α-hCG, and β-hCG, modified hCG comprising the β-core fragment of hCG and Ward is relied on to teach the antibodies as claimed.
Ward does not teach a sequential detection method, however, Ward does teach a sandwich immunoassay and Chang teaches a lateral flow assay comprising antibodies to normal and modified hCG and therefore one of ordinary skill in the art would have a reasonable expectation of success using the antibody pair of Ward in the test strip as taught by Jin.
Applicant further argues, starting on page 7, last paragraph, that Jin does not suggest determining false positives, let alone provide any reason to modify Jin in view of Ward and Chang but rather Jin is directed to addressing false-negative results caused by the hook effect, Ward does not contemplate a chromatography strip and Jin does not consider antibody specificity thereby indicating a motivation to specifically combine.
This argument is not persuasive.
Neither the specification nor the claims provide a structural limitation or explanation of how the immunochromatography strip as presently claimed is configured to detect a false positive pregnancy test result. Rather, as argued by applicant, the configuration comprising a labeled capture anti-hCG antibody and two test lines, one test comprising another anti-hCG antibody and one test line comprising hCG to bind free labeled anti-hCG antibody, is configured to detect false negative results due to the hook effect and further, when taking into account the teaching of Nerenz, it would be obvious to comprise an anti-β core hCG antibody as the labeled antibody in the test strip because the hook effect can be caused in normal pregnancies by the β core fragment of hCG. It is unclear how this configuration can also detect false positive pregnancy tests because it is further unclear what circumstances may cause the result of a false positive pregnancy test result when using the test strip as claimed.
Applicant further argues on page 8 that the configuration of the strip as claimed and the ability to compare the test lines as recited allows for a highly accurate pregnancy diagnostic strip that eliminates interference from hCG variants, which exist in high concentration in urine. Applicant argues that the test strip allows for quantification of both hCG and the variant.
This argument is not persuasive.
The quantification of both hCG and the variant is not a limitation of the current claims and therefore the argument is not commensurate with the claims.
Applicant further argues on page 9 that in a conventional pregnancy diagnosis kit in which only one test line is present, such as the kit of Jin, false negatives may occur when hCGβcf is present.
This argument is not persuasive.
Jin teaches a pregnancy test strip with two test lines that overcomes the problem of false negativity due to the hook phenomenon.
Applicant further argues that the test kit provides a positive result not only when test line 1 shows color development but also when test line 2 is not visible or less intense than the control line which allows for more accurate pregnancy diagnosis and therefore the test kit is capable of preventing not only false positives but also false negatives.
This argument is not persuasive.
As explained previously in detail above, it is not clear how the test kit as currently claimed detects false positive pregnancy tests and the combination of the prior art teaches a test kit as claimed and is capable of detecting false negative pregnancy test results.
For all the reasons above, the arguments are not persuasive.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEFANIE J KIRWIN whose telephone number is (571)272-6574. The examiner can normally be reached Monday - Friday 7.30 - 4 pm.
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
Prosecution Insights