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 .
Status of the Claims
Claims 1-5 are pending and examined herein.
Priority
The present application, filed 12/19/2022, which claims benefit of U.S. Provisional Patent Application 63/321,575, filed 03/18/2022. Claims 1-4 are entitled to the benefit of the 03/18/2022 filing date because the subject matter of those claims is adequately supported by the provisional application. Claim 5, however, is not entitled to the benefit of the 03/18/2022 filing date.
Claim 5 recites that the test kit provides, within five minutes, an indication that less than about 30 pg/mL parathormone is present in the aspirated sample, or that parathormone is present in concentrations from 30 pg/mL to at least about 250 pg/mL, indicating that the sample was likely aspirated from a parathyroid gland. The provisional application describes a qualitative or semiquantitative output exemplified as parathyroid tissue or <250 pg/mL, and separately describes that PTH in excess of 1000 pg/mL presumptively identifies the aspirated tissue as parathyroid. However, the provisional application does not describe 30 pg/mL as a concentration boundary, a concentration interval beginning at 30 pg/mL and extending to at least approximately 250 pg/mL, or the use of that interval to indicate that a sample was likely aspirated from a parathyroid gland.
Accordingly, the provisional application does not reasonably convey to one of ordinary skill in the art that Applicant possessed the subject matter of claim 5 as of 03/18/2022. Therefore, claim 5 is not entitled to the benefit of the provisional filing date and has an effective filing date of 12/19/2022. Claims 1-4 retain an effective filing date of 03/18/2022.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 12/19/2022 are acknowledged and have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: First, limitation (b) recites “binds with the anti-parathyroid on the conjugate.” The phrase is grammatically incomplete because “anti-parathyroid” is used without a noun identifying the material, and “the conjugate” does not clearly identify the relevant structure. Based on the preceding claim language, Applicant may have intended to recite that the sample binds with the nanoparticle-conjugated anti-parathyroid antibody on the conjugate pad. Second, limitation (d) recites “a test line comprising anti-parathyroid.” The term “anti-parathyroid” is used without a noun identifying the claimed component. Based on the Specification and the preceding claim language, Applicant may have intended to recite “a test line comprising an anti-parathyroid antibody.” Appropriate correction is required.
Claim 4 is objected to because of the following informality: Claim 4 recites that the indication is readable “either visually or by digital reader.” The phrase lacks the indefinite article “a” before “digital reader.” Applicant should amend the phrase to recite “either visually or by a digital reader.” Appropriate correction is required.
Claim 5 is objected to because of the following informalities: First, claim 5 recites “providing an indication in said 5 minutes.” For grammatical consistency with the preceding recitation “within 5 minutes,” Applicant should revise the phrase, for example, to recite “providing, within the five minutes, an indication.” Appropriate correction is required. Second, claim 5 recites “less than about 30 pg/mL parathormone is in the aspirated sample.” The phrase is grammatically awkward. Applicant may have intended to recite that the aspirated sample contains less than about 30 pg/mL parathormone. Appropriate correction is required. Third, claim 5 recites “parathormone is present in concentrations of from 30 pg/mL to at least about 250 pg/mL.” The phrase “in concentrations of from” is grammatically improper. Applicant should correct the grammatical form. This objection does not resolve the separate indefiniteness under 35 U.S.C. 112(b) concerning “from 30 pg/mL to at least about 250 pg/mL.”
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 1-5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a third membrane to receive the sample/conjugate mixture.” However, claim 1 does not expressly identify first and second membranes or state that either the sample-receiving pad or the conjugate pad constitutes a numbered membrane. It is therefore unclear what structural relationship or sequence is conveyed by designating the subsequently recited membrane as “a third membrane.” Accordingly, the structural identity and relationship of the recited third membrane are not reasonably certain. For purposes of compact prosecution, “a third membrane” will be interpreted as a membrane positioned downstream from the sample-receiving pad and conjugate pad and configured to receive the sample/conjugate mixture. This interpretation is adopted solely to permit examination on the merits and does not cure the indefiniteness. Appropriate correction is required.
Claim 1 further recites “a control line containing a host animal antibody.” The phrase “host animal antibody” is unclear because it is reasonably susceptible to multiple interpretations. For example, it may reasonably refer to: an antibody produced in or obtained from a host animal, or an antibody directed against antibodies of the host-animal species from which the nanoparticle-conjugated anti-parathyroid antibody was obtained. The claim does not identify the antigenic specificity of the control-line antibody or distinctly define its structural or functional relationship to the nanoparticle-conjugated anti-parathyroid antibody. In particular, claim 1 does not recite the species in which the control-line antibody is produced, the antigen to which the control-line antibody binds, whether the control-line antibody is directed against the nanoparticle-conjugated anti-parathyroid antibody itself, whether it is directed against an immunoglobulin of the species used to produce that anti-parathyroid antibody, or whether it instead binds an unrelated control reagent present in the conjugate pad. Claim 1 also does not recite that the nanoparticle-conjugated anti-parathyroid antibody and the control-line antibody are selected according to a corresponding host-species/anti-host-species relationship, nor does it require that the control-line antibody capture the nanoparticle-conjugated anti-parathyroid antibody to produce the control-line indication. Accordingly, one of ordinary skill in the art would not be reasonably certain of the scope of the claimed “host animal antibody.”
The Specification appears to describe the control-line antibody as an antibody directed against antibodies of the host-animal species associated with the nanoparticle-conjugated anti-parathyroid antibody. However, claim 1 does not expressly recite that relationship. Nor does claim 1 recite that the control-line antibody is an anti-species immunoglobulin antibody, identify the relevant host species, or require binding between the control-line antibody and an antibody generated in that host species. It is therefore unclear whether “host animal antibody” encompasses any antibody produced in or obtained from a host animal, only an antibody directed against antibodies of the host-animal species used to produce the nanoparticle-conjugated anti-parathyroid antibody, or an antibody directed against a separate control component that is unrelated to the anti-parathyroid antibody. These alternatives encompass materially different antibody specificities and control-line architectures, yet the claim does not distinguish among them. For purposes of compact prosecution, “a host animal antibody” will be interpreted broadly as encompassing an antibody produced in or obtained from a host animal, without requiring that the antibody be directed against antibodies of the host species used to generate the nanoparticle-conjugated anti-parathyroid antibody, without requiring any particular antigenic specificity, and without requiring that the control-line antibody directly bind the nanoparticle-conjugated anti-parathyroid antibody. This interpretation is adopted solely to permit examination on the merits and does not resolve or cure the indefiniteness. Appropriate correction is required.
Claim 1 recites “measurement of parathormone in serum PTH,” and claim 5 recites “a delivered sample of serum PTH” and “the serum PTH sample.” However, claim 1 otherwise requires that the immunochromatographic lateral-flow assay cassette receive “a needle aspirated sample from target tissue” and further identifies the tested material as “the liquid aspiration sample of tissue.” The claims do not identify whether the biological sample being tested is serum, tissue fluid obtained by needle aspiration, a tissue aspirate diluted or suspended in another liquid, or a separate serum sample. Because serum and a needle-aspirated target-tissue sample ordinarily identify different biological sample matrices, and the claims do not define the relationship between those samples, one of ordinary skill in the art would not be reasonably certain of the sample to which the claimed measurement and indication requirements apply. For purposes of compact prosecution, the phrases “measurement of parathormone in serum PTH,” “a delivered sample of serum PTH,” and “the serum PTH sample” are interpreted as encompassing a liquid sample obtained by needle aspiration from suspected target tissue, including tissue fluid or an aspirated tissue sample diluted or suspended in a physiologically acceptable liquid, whose PTH concentration is measured by the test kit. This interpretation does not equate tissue aspirate or tissue eluate with serum, but is adopted solely to identify the sample limitation used for examination on the merits. The interpretation does not resolve or cure the indefiniteness. Appropriate correction is required.
Claims 2–5 depend directly or indirectly from claim 1 and therefore incorporate the indefinite limitations “a third membrane,” “a control line containing a host animal antibody,” and the inconsistent identification of the tested sample as both a serum PTH sample and a needle-aspirated target-tissue sample. Accordingly, claims 2–5 are indefinite for the same reasons. Appropriate correction is required.
Claim 5 is further indefinite because it recites that parathormone is present in concentrations “from 30 pg/mL to at least about 250 pg/mL.” The phrase “to at least about 250 pg/mL” is unclear because “to” ordinarily identifies an upper endpoint of a range, whereas “at least” ordinarily identifies an open-ended minimum extending upward from the stated value. The modifier “about” additionally makes the stated value approximate. Accordingly, it is unclear whether the claimed range terminates near 250 pg/mL, extends above approximately 250 pg/mL without a defined upper boundary, or has some other unspecified endpoint greater than approximately 250 pg/mL. For purposes of compact prosecution, “from 30 pg/mL to at least about 250 pg/mL” will be interpreted as encompassing concentrations beginning at 30 pg/mL, extending through approximately 250 pg/mL, and including concentrations above approximately 250 pg/mL. Accordingly, for examination on the merits, approximately 250 pg/mL is treated as a concentration encompassed by the range rather than as a terminal upper boundary. This interpretation does not resolve or cure the indefiniteness. Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claims 1, 2, 4, and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (CN107228944A, refer to English translation provided).
Regarding claim 1, Li teaches a rapid parathormone identification and test kit for locating parathyroid glands and providing quantitative measurement of parathormone by disclosing that immunoassay analyzer combined with parathyroid hormone detection reagents can quantitatively determine the parathyroid hormone content in tissue eluent extracted from tissues during thyroid surgery, and the measurement results are rapid and accurate ([0004], p. 4). Li further discloses that this immunoassay instrument and its reagent kit can be used to identify the parathyroid glands, thereby creating conditions for the protection of the parathyroid glands ([0004], p. 4). Li further discloses that the parathyroid hormone detection kit employs solid-phase immunochromatographic analysis technology and utilizes the double antibody sandwich method ([0035], p. 29).
Regarding the immune-chromatographic lateral-flow assay cassette configured to receive a needle-aspirated sample from target tissue, Li teaches a plastic cartridge and parathyroid hormone test strips contained within the cartridge. The plastic cartridge has a sample application port ([0033], p.26). Li further teaches inserting a syringe into suspected parathyroid tissue, a small amount of tissue fluid is aspirated using negative pressure before withdrawing the needle, and expressly identifies this procedure as the needle aspiration method ([0027], pp. 21-22).
Regarding limitation (a), Li teaches a conjugate pad containing anti-parathyroid antibody conjugated to nanoparticles by disclosing that the chemical coupling pad of the test strip is coated with a colloidal gold-labeled parathyroid hormone secondary antibody and a colloidal gold-labeled streptavidin conjugate, and the parathyroid hormone polypeptide chain in the tissue eluent binds to the gold-labeled antibody-drug conjugate pre-coated on the chemical coupling pad to form an immune complex ([0035, p. 29). Li expressly teaches that the tracer material used in in vitro rapid diagnostic reagents is mainly colloidal gold nanoparticles and that the parathyroid (parathyroid hormone) detection reagent involved in the application has a particle size of about 100nm and has good dispersibility and uniformity ([0045], p. 42). Li further emphasizes that using this large particle colloidal gold to couple with antibodies can greatly improve the detection sensitivity and precision of the product ([0045], p. 42). Thus, the disclosed colloidal gold-labeled parathyroid hormone secondary antibody is an anti-parathyroid antibody conjugated to nanoparticles deposited on the conjugate pad.
Regarding limitation (b), Li teaches that the parathyroid hormone test kit includes a plastic cartridge and parathyroid hormone test strips contained within the cartridge. The plastic cartridge has a sample application port. The parathyroid hormone test strips include a base plate, a sample pad, a chemical coupling pad, a reaction pad, and an absorbent pad. The base plate is elongated, and the sample pad, chemical coupling pad, reaction pad, and absorbent pad are sequentially overlapped and fixed on top of the base plate ([0033], p. 26). Li further teaches that the sample pad is used to receive the sample and is positioned below the sample application port of the plastic cartridge. The tissue eluent is dripped into the sample pad through the sample application port ([0033], pp. 26-27). Furthermore, Li discloses that the tissue eluent on the sample pad travels to the chemically coupled pad under capillary action and binds to the gold-labeled antibody conjugate to form an immune complex ([0033], pp. 26-27), thereby disclosing capillary flow of the aspirated tissue sample into the conjugate pad and formation of the claimed sample/conjugate mixture.
Regarding limitation (c), Li teaches a downstream third membrane receiving the sample/conjugate mixture by disclosing a separate reaction pad made of nitrocellulose membrane ([0034], p. 28), wherein the immune complex continues to travel from the coupling pad to the detection zone of the reaction pad ([0033, p. 27).
Regarding limitation (d), Li teaches that the reaction pad includes a detection zone and a control zone. The detection zone is pre-coated with parathyroid hormone-1 antibody, and the control zone is coated with goat anti-streptavidin antibody, and the immune complex travels to the detection zone of the reaction pad and specifically binds to the parathyroid hormone-1 antibody, thus forming a detection line ([0033], p. 27). Li further teaches that within a certain range, the intensity of the test line color is directly proportional to the parathyroid hormone content in the sample being tested, and that the detection line is scanned and analyzed by an immunoassay analyzer to quantitatively detect the parathyroid hormone content in the tissue eluent ([0035], pp. 30-31). Also, Li teaches that a reading greater than 65 pg/mL is considered positive, and the tissue can be confirmed as parathyroid gland ([0031]-[0032], pp. 24-26).
Regarding limitation (e), as discussed above, Li teaches that the reaction pad includes a control zone coated with goat anti-streptavidin antibody, and that the incompletely reacted immune complex specifically binds to the goat anti-streptavidin antibody to form a control line ([0033], p. 27). Consistent with the compact-prosecution interpretation adopted in the rejection under 35 U.S.C. 112(b), the disclosed goat anti-streptavidin antibody is interpreted as an antibody produced in a host animal and therefore satisfies the recited “control line containing a host animal antibody.”
Regarding claim 2, Li teaches that the immune complex is chromatographically deposited into the detection zone by the capillary action of the membrane. It specifically binds (C-terminal binding) to the parathyroid hormone primary antibody pre-coated in the detection zone and is trapped, aggregating to form the detection line, and that the intensity of the test line color is directly proportional to the parathyroid hormone content in the sample being tested ([0035], p. 30). Li further teaches that if the data obtained by this method is greater than 65 pg/mL, the tissue can be confirmed as parathyroid gland ([0031], p. 25), and a reading greater than 65 pg/mL is considered positive ([0032], pp. 25-26), and data obtained by this method greater than 65 pg/mL were all positive (i.e., confirmed to be parathyroid gland) ([0065], p. 59). Accordingly, the positive readable indication produced by the detection line signifies that the tested sample was taken from a parathyroid gland.
Regarding claim 4, Li teaches that readable indication on the test line is readable visually by disclosing the plastic cartridge having a viewing window allowing observation of the test strips ([0042], pp. 34-35), wherein the intensity of the test line color is directly proportional to the parathyroid hormone content in the sample being tested ([0035], p. 30), thereby permitting visual observation of the detection line. Li further teaches that the readable indication on the test line is readable by a digital reader by disclosing that the detection line and control line are scanned and analyzed by an immunoassay analyzer, and calculations are performed according to the preset parameters of the instrument to quantitatively detect the parathyroid hormone content in the tissue eluent ([0035], p. 31).
Regarding claim 5, Li teaches rapid quantitative detection of parathyroid hormone from needle-aspirated tissue eluent, wherein the test strip is incubated for 3 minutes–12 minutes and a measured concentration greater than 65 pg/mL is positive and confirms that the tissue is parathyroid gland ([0063]–[0065], pp. 58–59). As discussed in the rejection under 35 U.S.C. 112(b), for purposes of compact prosecution, the recited serum PTH is interpreted as encompassing PTH measured in the needle-aspirated tissue-derived liquid sample recited in claim 1, and the phrase from 30 pg/mL to at least about 250 pg/mL is interpreted as encompassing concentrations beginning at 30 pg/mL, extending through approximately 250 pg/mL, and including concentrations above approximately 250 pg/mL. Accordingly, Li expressly discloses the recited testing interval and, under the compact-prosecution interpretation adopted in the rejection under 35 U.S.C. 112(b), discloses the recited concentration alternative of claim 5.
Accordingly, Li discloses, expressly or inherently, each and every limitation of claims 1, 2, 4, and 5. Accordingly, claims 1, 2, 4, and 5 are anticipated under 35 U.S.C. 102.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. in view of Bae et al. (US 8859265 B2).
With respect to the teachings of Li, see the discussion above, which applies equally here. Li directs one of ordinary skill toward ensuring reliable and readily interpretable assay operation because Li emphasizes that the measurement results are rapid and accurate ([0004], p. 4), that the assay is simple to operate and intuitive to judge ([0014], p. 13), and that its disclosed technical objective includes an accurate and highly specific determination that distinguishes parathyroid hormone in tissue eluent from surrounding tissues ([0011], p. 11). Also, as discussed above, Li further provides a quality control area and quality control line as part of its immunochromatographic strip architecture ([0035], pp. 29-31), thereby directing the skilled artisan to known lateral-flow teachings explaining the operational meaning of that control-line response.
However, Li does not expressly teach or specify that a readable indication on the control line indicates that the test was executed correctly even if a positive signal was not exhibited at the test line.
Bae teaches that same missing control-line functionality in an analogous lateral-flow immunoassay device. In particular, Bae teaches that the control line exists for the following two purposes. First, Bae teaches that the control line indicates that the liquid biological sample, i.e. the whole blood sample has been conveyed thereto by capillarity along the pads and the membrane irrespective of a presence or absence of said analyte in said liquid biological sample (col. 10, p. 8; FIG. 3). Bae further states that the control line indicates validity of the test (col. 10, p. 8). Also, Bae teaches the negative-test-line condition by disclosing that if the analyte is not present in the whole blood sample, the colorization will not occur in the test line but in the control line (col. 10, p. 8). Thus, Bae expressly teaches a readable control-line indication showing valid assay execution even when no positive test-line signal appears.
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 parathyroid-hormone lateral-flow kit of Li by configuring and using its disclosed quality-control line according to the control-line functionality expressly taught by Bae, such that formation of the control line indicates valid capillary transport and proper execution of the assay even when insufficient PTH is present to produce a positive test-line signal. Bae provides an express teaching and motivation for the modification by explaining that the control line confirms test validity irrespective of analyte presence and that, in a negative assay, colorization occurs at the control line but not at the test line. The modification would permit the user to distinguish a valid negative PTH result from an invalid assay, thereby furthering Li’s stated objectives of rapid, accurate, and intuitive identification. One of ordinary skill would have had a reasonable expectation of success because both references employ analogous immunochromatographic lateral-flow devices having capillary sample migration, conjugate pads, analyte-dependent test lines, downstream control lines, antibody-based capture reagents, and particulate labels; the modification merely assigns Bae’s known assay-validating function to Li’s already-present control-line structure without altering the PTH-specific detection chemistry or its ordinary operation.
Conclusion
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 28, 2026
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