DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application, Serial No. 17/776,687 was filed on 05/13/2022, and is a 35
U.S.C. 371 national stage entry of PCT Application No. US2020/060374 filed on
11/13/2020, and claims benefit under 35 U.S.C 119 to Provisional Application Serial No.
62/936,038 filed on 11/15/2019.
Status of the Claims
Claims 1-9, 11-38 are pending and are currently under examination. Claim 10 has been canceled.
Applicant’s remarks indicate that claim 16 is canceled but the claim set submitted 10/29/2025 still shows claim 16 as pending. Clarification is required.
Information Disclosure Statement
The IDS filed on 12/8/2025 has been considered.
Withdrawn Rejections
All rejections not reiterated herein below are withdrawn in view of the amendments and arguments.
Claim Objections
Claim 36 is objected to because of the following informalities: the word conjugate in line 7 is misspelled. Appropriate correction is required.
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.
Claim 11 is 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 11 recited analyte related molecule is related to histamine. It is unclear whether this is a positive limitation of the device. Is the analyte-related molecule histamine or a histamine derivatives. What does it mean to be related to histamine? The specification does not disclose any histamine related molecules that may be used on the device.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15-17, 20 and 38 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 15-17 and 38 are directed to the amount of immobilized conjugate in the capture zones and do not further limit claims 1 and 36 from which they depend.
Claim 15, in particular, broadens the scope of claim 1. Amended claim 1 requires the amount of conjugate in the capture zone that is closer to the sample to the sample receiving zone to be lower than an amount of conjugate in a capture zone further from the sample receiving zone which claim 15 broadly recites that the capture zones contain different amount of conjugate.
Claim 17 also appears to contain an error where the location of the capture zone containing lower amount of conjugate is not recited.
Claim 38 depends on claim 36 which requires one or more capture zones each comprising an amount of conjugate where the amount of conjugate in the capture zone closer to the sample receiving zone is lower than the amount of conjugate in the capture zone further from the sample receiving zone. Therefore, claim 38 does not further limit claim 36.
Claim 38 also appears to contain an error where the location of the capture zone containing lower amount of conjugate is not recited. This is confusing.
New Claim Rejections
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 36 and 38 are rejected under 35 U.S.C. 102(a)(1) and 35 USC 102(a)(2) as being anticipated by Saul et al (US 8,709,792).
Saul discloses a lateral flow device and competitive method for using the same comprising a lateral flow membrane having an application pad (sample receiving zone), at least two test areas (capture zone) and a control area. See figure 1 and column 1, lines 35-36 and column 5, lines 35-42. Saul teaches a competitive inhibition test where a receptor for the analyte is labeled with a visible marker. The receptor flows with the sample in the mobile phase to a test zone. The capture agent immobilized in the test zone has affinity to the receptor that is the same or similar to that of the analyte in the test sample such as an analyte analogue. See column 5line 63 through column 6, lines 13. Saul teaches the use of synthetic polypeptides as linkers (i.e. carrier) such as poly-L-lysine, poly-L-glutamic acid and polyethylenimine. See column 7, lines 56-60.
Saul specifically teaches at column 6, lines 13- 60 a method for maximizing binding potential, while maintaining test sensitivity by using multiple test areas, within the test zone, each test area being capable of capturing the receptor. The multiple test areas can each contain the same or similar concentrations of capture agent. Alternatively, the test areas can contain different concentrations of capture agent. For example, the first test area can have a lower concentration of capture agent as compared to the second test area. Such a configuration can accommodate that receptor arrives at the first test area earlier and, therefore, everything else being equal, more binding will tend to occur in the first test area compared to the second. Note that the first test area is defined as the area closer to the sample application zone, and the second test area is the area further away from the sample application zone. See Figure 1 where 1 is the sample application zone, 9 is the first test area, 4 is the second test area and 5 is the control zone. See column 15, lines 42-59.
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.
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 1-5, 8-9, 14-19, 24-30 and 32-38 are rejected under 35 U.S.C. 103 as being unpatentable over Saul et al (USP 8,709,792) in view Hubbell et al (USP 6884628).
Regarding claims 1, 32 and 36-38, Saul discloses a method and device as discussed above. Saul differs from the instant claims in failing to teach a device where the conjugates are immobilized to the flow matrix via a linker that is not a protein.
Hubbell discloses polymeric coating materials that can be applied to surfaces of substrates for use in analytical and sensing devices to promote specific recognition of the target analyte while minimizing non-specific adsorption of other molecules. See column 1, lines 10-16. Hubbell discloses multifunctional polymer coating including copolymers based on a polycationic or polyanionic backbone with side chains that control interaction with the environment such as poly(ethylene glycol) etc. See column 3, lines 14-65.
Therefore, it would have been obvious to one of ordinary skill in the art at the time the application was filed to modify the device of Saul by using the linkers taught by Hubbell to immobilized the conjugates to the test strip for the advantage of incorporating multifunctional linkers that suppresses non-specific interaction, adsorption or attachment of molecular or ionic components in an analyte solution (Hubbell, column 2, line 61 through column 3, line 14). Hubbell teaches polymer coatings such as PEG are compatible with a variety of different established methods to detect, sense and quantify target molecules, thus, a skilled artisan would have had a reasonable expectation of success in using the polymers taught by Hubbell as linkers for the conjugates in the device of Saul because these linkers are well known in the art and Hubbell specifically teaches how to create surfaces in immunoassay where the polymer is adsorbed to a substrate and an antibody is then chemically coupled to the multifunctional polymer (Hubbell, column 4, line 20-23). Additionally, while Saul doesn’t specifically teach carriers for use with conjugates or capture reagents, Saul does teach the use of carrier, i.e. linkers, such as poly-L-lysine, poly-L-glutamic acid and polyethylenimine to aid in the immobilization of specific binders in at least the control zone of a test strip, therefore, a skilled artisan would have been motivated to use the linkers taught by Saul and Hubbell to aid in the immobilization of recognition molecules for the advantages as detailed by Hubbell.
Regarding claims 2 and 3, Hubbell teaches PEG with molecular weight between 500 and 200,000. See column 6, line 61 through column 7, line 5. While Hubbell does not specifically disclose the length of their PEG, it may be calculated by multiplying the number of repeating ethylene oxide units by the length of each unit (0.28 – 0.36 nm). Therefore, a PEG 500, for example, has approximately 11-12 monomers (each monomer is about 44g/mol). Thus, PEG 500 is about 3.5 – 4.0 nm (35-40 angstrom) which meets the limitation of a linker having a length between 5 and 200 angstroms.
Regarding claim 4, Saul discloses linkers such as poly-L-lysine, poly-L-glutamic acid and polyethylenimine. See column 7, lines 56-60. And Hubbell discloses poly(L-lysine)-g-poly(ethylene glycol) (PEG-g-PLL). See column 3, lines 14-15 and column 4, lines 42-45 and Fig. 1A-1D.
Regarding claim 5, Hubbell discloses in FIG. 1D, a chemical structure of a (PEG-g-PLG) polymer functionalized with biotin at the amino group of the PEG side chains. See column 4, lines 42-45.
Regarding claim 8, Saul discloses the use of antibody as a capture agent. See column 7, lines 36-45.
Regarding claim 9, Saul teaches capture receptor can be labeled with colored particles. See column 2, lines 19-22.
Regarding claim 14, Saul teaches the device comprises a plurality of serially oriented capture zone. See figure 1 and column 1, lines 35-36 and column 5, lines 35-42.
Regarding claim 15, Saul specifically teaches at column 6, lines 13- 60 a device for maximizing binding potential, while maintaining test sensitivity by using multiple test areas, within the test zone, each test area being capable of capturing the receptor. The multiple test areas can each contain the same or similar concentrations of capture agent.
Regarding claims 16 and 17, Saul discloses test areas containing different concentrations of capture agent. For example, the first test area can have a lower concentration of capture agent as compared to the second test area. Such a configuration can accommodate that receptor arrives at the first test area earlier and, therefore, everything else being equal, more binding will tend to occur in the first test area compared to the second. Note that the first test area is defined as the area closer to the sample application zone, and the second test area is the area further away from the sample application zone. See Figure 1 where 1 is the sample application zone, 9 is the first test area, 4 is the second test area and 5 is the control zone. See column 15, lines 42-59.
Regarding claim 18, Saul teaches a control zone having a control zone capture agent immobilized thereon. The control zone capture agent can have affinity to the receptor that is equivalent to the control zone capture agent's affinity to the receptor-analyte complex. When the control zone capture agent has affinity to the receptor that is equivalent to its affinity to the receptor-analyte complex, the signal in the control zone will increase as analyte concentration in the sample increases. See column 2, lines 31-39.
Regarding claim 19, Saul teaches for improved binding to the support, the control ine can also include a protein-protein conjugate with one being the capture agent and the other being a carrier protein such as BSA. See column 7, lines 56-60.
Regarding claim 24, Saul teaches a device comprising a sample receiving zone (Fig. 1, element 1), a labeling zone (Fig. 1, element 7) comprising a diffusively bound capture agent. See column 15, lines 43-59.
Regarding claim 25, Saul teaches the labeling zone is positioned between the sample zone and the capture zones. See Fig. 1 and column 15, lines 43-59.
Regarding claims 26-30, Saul teaches each capture zone independently has a regular shape and are rectangular. See Fig. 1, capture zones 9 and 4 both have the same rectangular shape and can contain the same amount of capture reagent. See column 6, lines 13- 60.
Regarding claims 33-35, Saul teaches combining the detectable signals from the two capture zones to provide a processed signal. See column 2, lines 19-30.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Saul in view of Hubbell as applied to claim 1 above, and further in view of Zhen et al (Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference. NTA-Functionalized Poly(L-lysine)-g-Poly(Ethylene Glycol): A Polymeric Interface for Binding and Stuidying 6xHis-tagged Proteins.)
See the discussion of Saul and Hubbell above.
Zhen discloses the use of poly lysine PEG linkers in binding histidine complexes to a testing matrix surface. Zhen teaches the linker comprises several lysines linked each other and the carboxyl group of the first lysine is linked to the epsilon-amino group of the second lysine, and the carboxyl group of the third lysine is linked to the alpha-amino group of the first or second lysine. See Fig 1. Page 1037.
It would have been obvious to one of ordinary skill in the art at time the application was filed to use the method taught by Zhen to make the PEG polymer for use in the device of Saul and Hubbell because Zhen teaches different grafting ratios may be chosen to impart resistance against non-specific protein adsorption to polymer coated surface and the polymer architecture is readily determined by NMR in terms of both the Lys/PEG and NTA/PEG grafting ratio. A skilled artisan would have had a reasonable expectation of success in choosing the appropriate PEG conjugates for the advantage of providing a non-fouling surface resistant to non-specific protein adsorption, controlled protein orientation and surface density and highly specific, stable, yet reversible tethering of the proteins because Zhen teaches by proper choice of the grafting ratio of lysine units to PEG side chains, excellent resistance against non-specific adsorption of proteins can be achieved. (Zhen, page 1036.)
Claims 11-13 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Saul in view of Hubbell as applied to claim 1 above, and further in view of Peyret et al (Journal of Immunological Methods, 90 (1986) 39-45.)
See the discussion of Saul and Hubbell above. These references differs from the instant invention in failing to teach the use of histamine and its derivatives having imidazole groups as the conjugate.
Peyret discloses competitive radioimmunological assay for histamine using radiolabeled ligand and conjugated histamine, conjugated analogs or unconjugated histamine. (Abstract) Peyret teaches antibody specificity against radiolabeled ligand and conjugated histamine, conjugated analogs or unconjugated histamine and highest affinity of the antibody is to the ligand HA-HD-PPL as it most closely resembled the immunogen histamine. See page 41, Antibody Specificity.
Therefore, it would have been obvious to one of ordinary skill in the art at the time the application was filed to use the radiolabeled ligand, conjugated histamine and conjugated analogs thereof in the device of Saul and Hubbell to detect histamine because Peyret teaches histamine has widespread and diverse roles in biological system and it is important to develop antibodies specific for histamine to detect and measure histamine in biological tissues and fluids. A skilled artisan would have had a reasonable expectation of success in using histamine and is derivatives as the conjugate in a competitive assay because Peyret teaches methods of marking these reagents and antibodies specific to them.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Saul in view of Hubbell as applied to claims 1 and 18 above, and further in view of Thayer et al (USP 6528323).
See the discussion of Saul and Hubbell above. These references differs from the instant invention in failing to teach more than one control zones that are positioned next to a capture zone and where a second control zone comprises an anti-Fc capture agent. Saul and Hubbell also fail to teach a second control zone positioned in series after the capture zones.
Thayer discloses a test strip comprising a sample addition zone, an absorbent zone, one or more test zones and one or more control zones. See column 15, lines 50-56. Thayer teaches in some embodiments, the test zones may also include one or more control zones where one or more control binding agents are immobilized. Control agents capable of binding to the control binding agent may be positioned on the test strip at various locations or added to the test when the assay is being performed. See column 15, lines 60-67. Thayer discloses anti-Fc control agent such as IgG. See column 16, line 25-30.
Given the teachings of Saul, Hubbell and Thayer, it would have been obvious to one of ordinary skill in the art at the time the application was filed to modify the device of Saul as taught by Hubbell and to include more than one control zones as taught by Thayer for the advantages of confirming whether the sample and conjugate buffer have diffused properly with in the test strip and serving as internal standards and allowing analyte measurements results to be compared between different test strips in order to correct strip-to-strip variability. Thayer teaches such correction would be impractical with external controls. Additionally, lot-to-lot and run-to-run variations between different test strips may be minimized by the use of control binding pairs. See Thayer at column 16, lines 4-17. A skilled artisan would have had a reasonable expectation of success in including multiple control zones on a test strip and to use anti-Fc binding agent such as IgG because Thayer teaches the use of multiple control zone to create calibration curve against which a variety of analyte measurement results may be compared is desirable and IgGs are well known and conventional as binding pair partners. Column 16, line 66 through column 17, line 2. Having the test strip possess more than one control zone allows lateral flow assays to have a wider dynamic range than conventional lateral flow assays.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Saul in view of Hubbell as applied to claim 1 above, and further in view of Boehringer (USP 6924153) and Kauvar (US 2005/0124008).
See the discussion of Saul and Hubbell above. These references differ from the instant claim in failing to teach the binding affinity of the analyte to the capture agent is higher than the affinity of the conjugate to the capture agent.
Boehringer teaches the use of a multi-test lane immunometric lateral flow assay to analyze liquid samples for analytes. Boehringer teaches in column 11 line 49 - column 12, line 3 a competitive binding assay comprising binding analyte in a sample to a labelled specific binding pair (SBP) member complementary to the analyte to form an analyte-labelled SBP member complex. Boehringer teaches in column 3, lines 52-59, a first capture zone comprises a second SBP member immobilized therein which is capable of binding the analyte-first SBP member complex with a first affinity, and a second capture zone comprises a third SBP member that is capable of binding the analyte-first SBP member complex with a second affinity. In this aspect, the second affinity is typically different from the first affinity.
While Boehringer discloses binding reagents with different affinities to the analyte and analog, Boehringer does not specifically teach the analyte has a higher binding affinity to the capture agent as compare to the conjugate. However, Kauvar discloses a displacement competitive binding assay where the affinity of the interaction between binding moiety (capture agent) and the analyte is at least one order of magnitude greater than the affinity of the capture agent for the tracer (labeled conjugate). When such a relatively low affinity label has the property that displacement changes an intrinsic property of the molecule, it becomes feasible to assay analytes even in an intracellular environment. See paragraphs [0008] and [0009].
Therefore, it would have been obvious to one having ordinary skill in the art at the time the application was filed to modify the device and method of Hubbell by selecting capture binding reagents having higher affinity to the analyte then to the conjugate for the advantage disclosed by Kauvar, mainly, a versatile method to detect analyte in different environments. The use of capture agents having different binding affinities to the analyte or analyte analog is well-known in the art as disclosed by Hubbell and Kauvar.
A skilled artisan would have a had a reasonable expectation of success in choosing, from a finite list, a capture agent having high affinity to the analyte then to the conjugate for the purpose of having a versatile reagent that may be used in different environments.
Conclusion
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/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 March 16, 2026