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, 11-15, 20, and 22-30 are pending in the application.
Claims 1, 13-15, and 20 are withdrawn.
Claims 11-12 and 22-30 are the subject of this office action.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 17 November 2025 has been entered.
Claim Objections
The following claims are objected to because of the following informalities:
In claim 11, the structure of the phrasing “each conjugate pad comprises gold nanoparticles having a size in a range of 10-20 nm and is conjugated with antibodies” appears to indicate that the conjugate pad is conjugated with antibodies rather than the gold nanoparticles being conjugated with antibodies. This should be rephrased for clarification.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
In claim 1: “wherein one reaction membrane is configured to detect VWF and the other reaction membrane is configured to detect FVIII”
This limitation is interpreted under 112(f) because it recites a generic placeholder (“reaction membrane”) linked to a specific recited function (detection of VWF and FVIII) wherein the recited structure of the placeholder is insufficient to enable the recited function (i.e. it is not clear what specific structure or feature of a reaction membrane enables it to detect VWF or FVIII). As such, this limitation is interpreted in light of the structure provided in the instant specification (and its functional equivalents) which indicates that this function is enabled by the provision of a conjugate in the conjugate pad which comprises an anti-analyte antibody conjugated to a detectable label, and the provision of another anti-analyte antibody in a test zone of the reaction membrane (see examples 1-3 in the instant specification).
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112(b)
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 27-28 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.
The recitation of “the membrane” in claim 27 is indefinite because there are multiple “membranes” previously introduced in the claims, such that it is unclear which membrane generic recitation of “the membrane” refers to (i.e. independent claim 11 recites a “reaction membrane” and claim 26 recites a membrane of the conjugation pad. Clarification is required.
Claim 28 is vague regarding “the reaction matrix”. There is no prior introduction of “a reaction matrix” in the claims, therefore there is insufficient antecedent basis for this limitation in the claims.
Claim Rejections - 35 USC § 112(d)
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.
Claim 29 is 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. Claim 29 is directed to a multiplex kit, wherein a kit is defined by its physical features and components, however the claim only limits the type of sample that is used with the claimed kit. Given that a sample is generally collected and applied during the process of using the claimed kit, limitations regarding the sample type used with the claimed kit are a matter of intended use which do not serve to distinguish the claim over the prior art. As such, the limitations of claim 29 which refer only to the type of sample used with the claimed kit do not further limit the kit of the independent claim from which claim 29 depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 11-12 and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Johnsen et al (WO 2015/154090 A1; previously cited) in view of Bahadir et al ((2016). Lateral flow assays: Principles, designs and labels. TrAC Trends in Analytical Chemistry, 82, 286-306.; previously cited), and Sambursky et al (US 2013/0196310 A1).
Regarding claims 11-12 and 28-29, Johnsen teaches a multiplex kit (Par. 25: detection of coagulation factors may comprise detection of multiple factors in a simultaneous multiplexed assay or in assays run in parallel; Par. 86: detection reagents may be packaged in a kit; ) for detection of VWF and FVIII in a plasma sample (Par. 14-15: detection of coagulation factors may comprise detection of VWF and FVIII in a plasma sample). Johnsen teaches that detection of coagulation factors may comprise using primary and secondary antibodies that specifically bind to the coagulation factors and incorporate a detectable label (Par. 86).
Johnsen teaches the kit comprising: a strip (Par. 87) and an instruction/operation manual (Par. 86), wherein the strip may comprise a porous strip which comprises a reaction region which has at least one coagulation factor detection site (Par. 87). Johnsen teaches simultaneous or separate detection of VWF and FVIII through the use of either a multiplex assay or multiple parallel assays for each coagulation factor (Par. 25-26).
Johnsen discloses an invention for the detection of one or more coagulation factors (from a list which explicitly include VWF and FVIII, see Par. 14). Though Johnsen does not explicitly recite the particular combination of detection VWF and FVIII in this list, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have detected VWF and FVIII specifically because the combination is obvious to try from a finite number of identified and predictable combinations, wherein one of ordinary skill in the art would have a reasonable expectation of success in detecting VWF and FVIII because Johnsen teaches that these biomarkers can both be detected alone or in combination by the disclosed invention. Additionally, one would have been motivated to detect VWF and FVIII in particular because they are known in the art to be biomarkers and risk factors associated with clotting diseases and conditions, as evidenced by Martinelli (von Willebrand factor and factor VIII as risk factors for arterial and venous thrombosis. Semin Hematol. 2005 Jan;42(1):49-55.).
Although Johnsen does not specifically teach a photo-strip meter or reader that is capable of directly measuring VWF and FVIII concentrations from a strip, Johnsen discloses that a reader may be used to observe patterns or fluorescence that can be translated into a quantitative measure by a reader or computer system (Par. 85).
Johnsen does not disclose the specific structure of a lateral flow immunoassay strip comprising two sample pads, two conjugate pads, two reaction membranes arranged side by side, and a common absorbent pad extending across distal ends of the two reaction membranes and in fluidic communication with the two reaction membrane, wherein each reaction membrane has a display window, wherein each conjugate pad comprises gold nanoparticles having a size in a range of 10-20nm, wherein the strip is mounted within a plastic cassette.
Bahadir is a literature review of the state of the art in lateral flow assays (LFAs) before the effective filing date of the claimed invention which describes and summarizes the “principles of lateral flow assay, its structure, labels that are used in the construction of LFA and developed LFAs in literature” (Pg. 287, Col. 1, Par. 2). Bahadir teaches typical structure and usage of LFAs and places it in context with the state of the art as of the effective filing date of the claimed invention. Bahadir teaches that the standard lateral flow assay has four parts: a sample pad; a conjugate pad comprising labeled tags conjugated to biorecognition elements; reaction membrane (usually a nitrocellulose membrane with pore size between 5-15 microns) comprising a test line and control line for antigen-antibody interaction or DNA-probe DNA hybridization; and an absorbent pad which absorbs waste (Pg. 287, Col. 1, Par. 1; Pg. 288, Col. 2, Par. 1).
Bahadir further teaches that the conjugate pad comprises analyte-specific antibody that is labeled with a detection reagent (Pg. 289, Col. 1, last Par.). Bahadir teaches the use of gold nanoparticles as a detection reagent in the LFA strip for visualization of signals (Pg. 291, Col. 1, Section 3.1.1.1_ that are in the size range of 10-20nm (Pg. 291, Col. 1, last Par.) as well as a photo strip meter for comparison to directly measure the concentration of analyte on a test strip (Pg. 295, Col. 2, Par. 2).
Thus, Bahadir teaches a lateral flow assay strip comprising a sample pad, a conjugate pad, a reaction membrane, and an absorbent pad, wherein the conjugate pad comprises gold nanoparticles conjugate with analyte-specific antibodies, wherein the gold nanoparticles are in a size range of 10-20nm. Bahadir further teaches that quantitative data from an LFA typically requires an image analyzer or comparison with a color scale card (Pg. 295, Col. 2, Par. 2).
Regarding claim 11, Sambursky teaches a multiplex lateral flow assay kit for the detection of multiple target analytes (Abstract).
Sambursky teaches that the kit comprises a dual use two strip sample analysis device which comprises two lateral flow assay strips, wherein each strip comprises at least one detection zone for at least one different target analyte, wherein each detection zone comprises an immobilized binding partner for its respective target analyte (Par. 21).
Sambursky teaches that each of the two lateral flow assay strips comprises a sample pad, a conjugate pad, a reaction membrane arranged side by side, wherein each reaction membrane has a display window, and a common absorbent pad extending across distal ends to the two reaction membranes and in fluidic communication with the two reaction membranes (Fig. 12; Par. 190: There are two test strips in a housing. The housing may comprise a window located above each sample application zone for applying sample to the device and viewing windows for the detection zone. Each test strip includes a sample application zone, a conjugate zone, a detection zone with a test line comprising immobilized antibodies specific for a respective target analyte, and a common waste pad 860 which is disposed across the distal end of the two test strips).
Sambursky teaches that the conjugate pad may comprise anti-target analyte antibody conjugated to a gold nanoparticle label (Par. 191-192: conjugate pad comprises an analyte specific binding partner conjugated to a detectable label; Par. 83: detection of the target analyte is achieved in the detection zone where a binding molecule immobilizes the labeled conjugate-analyte complex. Preferably, the label is an optically detectable label. Particularly preferred are direct labels, and more particularly gold labels which can be best recognized by the naked eye).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Johnsen, which teaches a generic strip-based immunoassay, to include a sample pad, conjugate pad, reaction membrane comprising nitrocellulose with pore size between 5-15 microns, and absorbent pad, using gold nanoparticles as the detection reagent as taught by Bahadir because Bahadir teaches that these are standard structural features of a lateral flow assay which are well known in the art, while Johnsen teaches that the disclosed invention may comprise use of any specific immunoassay form known in the art, and specifically discloses methods comprising the use of analyte-specific antibodies and porous membranes, and specifically teaches that POC devices (which would include lateral flow assays) are particularly desirable for the application (Par. 82, 86-87, 78, 57).
Further, one would be particularly motivated to use the gold nanoparticle labels taught by Bahadir in the modified kit of Johnsen in view of Bahadir. Johnsen teaches detection reagents such as, but not limited to, fluorescent labels, dyes, luciferase, and radiolabels. Bahadir teaches that gold nanoparticles as detection labels in LFA have “high chemical stability, large specific area, easy synthesis, low cost, and easy preparation steps. These properties make the analysis time short and provide reliable analysis on-site (Pg. 291, Col. 1, Section 3.1.1.1), and that gold nanoparticles with a diameter of 15nm or less generate a strong color signal, while gold nanoparticles with a diameter larger than 60-70 nm results in self-aggregation and instability (Pg. 291, Col. 1, last Par.). Thus, one would be motivated to use gold nanoparticles with a size in the range of 10-20nm to enable a strong detectable signal, easy synthesis, and low cost while avoiding the issues of aggregation and instability associated with larger nanoparticles.
Bahadir teaches that lateral flow strips may be formatted for detection of a single target analyte or of multiple target analytes on the same strip (Pg. 289, Col. 1, Par. 2; Fig. 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used two lateral flow strips for the detection of VWF and FVIII on two different strips (such that one reaction membrane is configured to detect VWF and the other reaction membrane is configured to detect FVIII) because detection of one analyte per strip allows for simpler device design and allows results for each analyte to be detected to be read separately, such that results are easier and more straightforward to read and interpret.
One of ordinary skill in the art would have a reasonable expectation of success in making these modifications because Bahadir teaches that the lateral flow assay format is well-known in the art for providing detection of target analytes and because Johnsen teaches that the disclosed invention for detection of clotting factors may be performed on a number of different immunoassay formats known to one of ordinary skill in the art.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the kit taught by Johnsen to further include a metered reference chart (i.e. a photo-strip reader) for measuring analyte concentrations from a test strip as taught by Bahadir because such a reference allows a user to obtain quantitative data from the LFA (Pg. 295, Col. 2, Par. 2: quantitative data from an LFA typically requires an image analyzer or comparison with a color scale card), wherein the color scale card disclosed by Bahadir is considered to read on the claimed “photo-strip meter” (see originally filed specification Pg. 14: photo-strip meter (i.e. dilution of the known standard provided with the kit in the form of a photo print). One would be motivated to include such a photo-strip meter for improving quantitative results yielded from an LFA. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both references relate to test strips capable of detecting an analyte using a test matrix via the use of specific antibodies conjugated to a detectable label, and thus are largely variations of the same concept. As a result, the features taught by Bahadir would be expected to improve the generic device disclosed by Johnsen.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the kit of Johnsen in view of Bahadir by combining multiple lateral flow test strips into one cartridge with a common absorbent pad, such that the kit comprises two sample pads, two conjugate pads, two reaction membrane arranged side by side, and a common absorbent pad extending across distal ends of the two reaction membranes and in fluidic communication with the two reaction membranes, wherein each reaction membrane has a display window and wherein the lateral flow strip is mounted within a cassette as taught by Sambursky. Such a combined device with a common absorbent pad would allow measurement of multiple coagulation factors on a single physical device which can be easily handled and which allows a user to run and obtain results from the two strips simultaneously. One would be motivated to modify the kit of Johnsen in view of Bahadir with the multi-strip housing taught by Sambursky for the purpose of accommodating most or all of the assay components and reagents into a single packaging. One would be motivated to apply the common absorbent pad taught by Sambursky because the common absorbent pad would allow for increased absorbent surface area within the same device footprint. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Johnsen in view of Bahadir and Sambursky disclose similar lateral flow assay devices for the detection of multiple target analytes in a patient sample.
Sambursky discloses a housing for multiple test strips which comprises display windows for each reaction membrane, but does not specifically teach the material of the housing. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a plastic housing (i.e. plastic cassette) for the invention of Johnsen in view of Bahadir and Sambursky. One would be motivated to use a plastic housing because plastic is a cost effective and widely available material which can be manufactured into a variety of different shapes and configurations for a wide variety of application. Additionally, such a plastic cassette would be durable enough to provide structural support and protection for the enclosed lateral flow strips. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because plastic is a material which is well known in the art and which is commonly used for similar applications.
Regarding the limitation “wherein VWF is detected with 99% specificity and 99% accuracy and FVIII is detected with 98% specificity and 96% accuracy” this is noted as a functional limitation in a product claim, which is not specifically linked to any additional structure that is not previously recited in the instant claim. Since a claim to a kit is defined by its structural features and physical components, prior art which teaches all structural features of the claimed system is understood to be inherently capable of performing the claimed function and is therefore understood to meet the instant claim, regardless of whether the function is explicitly taught in the reference (i.e. because there is no structural or physical distinction between the claimed kit and the kit taught by the prior art, they are assumed to be capable of performing the same functions). See MPEP 2114.
Regarding claim 12, Johnsen in view of Bahadir and Sambursky teaches the kit of claim 11. As discussed above, Bahadir teaches a photo-strip meter for comparison of signal between a provided known standard chart and a test strip to determine the concentration of the target analyte, which was known in the art at the time of filing as a common method for exogenous determination of analyte concentration in a sample (Pg. 295, Col. 2, Par. 2, Fig. 4b). An example of the principle behind a color scale card in which the intensity of a test band is correlated to a known standard concentration is provided in Bahadir Fig. 4b and is reproduced below:
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Regarding claim 30, Bahadir teaches that the disclosed lateral flow strips are configured to detect the analyte of interest within 15 minutes (Table 1). As such, the combination of the cited prior art discussed above which uses the lateral flow strip format and structures taught by Bahadir is understood to be capable of achieving detection within 15 minutes.
Additionally, this limitation of claim 30 is understood to be a functional limitation which is not tied to any particular structure or physical feature which is not previously recited in the claims. Since a claim to a kit is defined by its structural features and physical components, prior art which teaches all structural features of the claimed system is understood to be inherently capable of performing the claimed function and is therefore understood to meet the instant claim, regardless of whether the function is explicitly taught in the reference (i.e. because there is no structural or physical distinction between the claimed kit and the kit taught by the prior art, they are assumed to be capable of performing the same functions). See MPEP 2114.
Claims 22 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Johnsen et al (WO 2015/154090 A1; previously cited) in view of Bahadir et al ((2016). Lateral flow assays: Principles, designs and labels. TrAC Trends in Analytical Chemistry, 82, 286-306.; previously cited), and Sambursky et al (US 2013/0196310 A1) as applied to claim 11 above, and further in view of Zhang et al ((2009). Immunochromatographic lateral flow strip tests. Biosensors and Biodetection: Methods and Protocols: Electrochemical and Mechanical Detectors, Lateral Flow and Ligands for Biosensors, 169-183.; previously cited).
Regarding claims 22 and 26-27, Johnsen in view of Bahadir and Sambursky teaches the kit of claim 11, as described above. Bahadir further teaches that the sample pad comprises a glass fiber membrane (Pg. 287, Col. 2, Par. 2). However, Bahadir is silent as to the thickness of the sample pad and the specific pretreatment with buffer and detergent.
Zhang teaches a lateral flow test strip used for the specific detection of analytes (Pg. 169, Par. 1) as an indicator of disease states (Pg. 171, last sentence-Pg. 172, first sentence), comprising the typical constriction of a lateral flow test strip (i.e. “a test strip typically consists of porous materials in four zones containing different reagents: a sample application pad, a conjugate pad containing colloidal gold conjugate, a detection membrane containing narrow absorbed bands of proteins as test and control lines, and an absorbent pad”; Pg. 170, first Par; Fig. 1). Zhang teaches a protocol for the production and preparation of a general lateral flow test strip in which the sample pad and conjugate pad comprises glass fiber (specifically a Millipore glass fiber pad, Cat. No. GFCP203000 which has a thickness of 0.43mm) (Pg. 173, section 2.2). Zhang further teaches that the sample pad is pretreated with buffer and a detergent (namely PBS and Tween 20) (Pg. 176, Section 3.1.5) and the conjugate pad is pretreated with buffer at a pH of 8.0 with the addition of blocking agents (BSA) and detergent (Tween 20) (Pg. 176, Section 3.1.4).
Regarding the wicking time recited in claim 27, the combination of the cited art teaches a kit that is structurally and compositionally consistent with that which is claimed. As a result, absent evidence to the contrary, the kit of the prior art is assumed to be capable of achieving the same wicking time as presently claimed.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the kit taught by Johnsen in view of Bahadir and Sambursky to have used glass fiber having a thickness of 0.43mm for the sample and conjugate pads and pretreat the lateral flow test strip as taught by Zhang because while Johnsen, Bahadir, and Sambursky do not teach the specific treatment of the membranes, it is a consideration in the manufacturing process of lateral flow tests (Zhang, Fig. 3). As Zhang teaches “the general manufacturing process for production of test strips includes the preparation of colloidal gold conjugates, application of reagents onto the membrane and pads, lamination of the membrane, conjugate pad, sample pad, and absorbent pad onto a support backing, cutting the prepared master cards into strips of defined length and width, and strip packaging” (Pg. 172, last Par.; Fig. 3). One would be motivated to modify the kit of Johnsen in view of Bahadir and Sambursky to have used glass fiber for the sample and conjugate pads and pretreat the lateral flow test strip as taught by Zhang to provide an improved version of the base test strip that minimizes nonspecific adsorption, which enhances sensitivity and reproducibility of the lateral flow assay (Bahadir, Pg. 288, Col. 2, Par. 1). One would have a reasonable expectation of success in making this modification because both Johnsen in view of Bahadir and Sambursky and Zhang relate to a lateral flow test strip capable of detecting an analyte in a sample using a reaction membrane via the use of specific antibodies conjugated to a detectable label, and are thus largely variation of the same concept.
Claims 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Johnsen et al (WO 2015/154090 A1; previously cited) in view of Bahadir et al ((2016). Lateral flow assays: Principles, designs and labels. TrAC Trends in Analytical Chemistry, 82, 286-306.; previously cited), Sambursky et al (US 2013/0196310 A1) and Zhang et al ((2009). Immunochromatographic lateral flow strip tests. Biosensors and Biodetection: Methods and Protocols: Electrochemical and Mechanical Detectors, Lateral Flow and Ligands for Biosensors, 169-183.; previously cited). as applied to claims 11 and 22 above, and further in view of Saji et al (WO 2016/156981 A1; previously cited).
Regarding claims 23-24, Johnsen in view of Bahadir, Sambursky, and Zhang teaches the kit of claim 22 as described above. Zhang further teaches that the buffer for pretreating the sample pad is specifically PBS (Pg. 176, Section 3.1.5). Zhang does not specifically teach treatment of the conjugate pad with a buffer that is standardized with blocking agents.
Saji teaches a multiplex lateral flow immunoassay device (Pg. 7, Ln. 15-17) configured to measure the relative or absolute concentration of multiple analytes simultaneously in a sample (e.g. plasma) (Pg. 5, Ln. 27-Pg. 6, Ln. 2). The test strip comprises a sample pad (Pg. 19, Ln. 11-15). A conjugation pad (Pg. 18, Ln. 11-18) containing antibodies that specifically bind to the target antigen (Pg. 16, Ln. 25-30; Pg. 17, Ln. 4-11) wherein the antibody is conjugated to a detectable label (Pg. 17, Ln. 13-16) that comprises a colloidal gold nanoparticle with a mean diameter of 20-25nm (Pg. 18, Ln. 7-9). The strip also comprises a reaction membrane (Pg. 18, Ln. 11-13) and a common absorbent pad that is shared by the multiple lateral flow test paths (Pg. 20, Ln. 10-12). The test strip is fixed in a plastic cassette (Pg. 19, Ln. 20-27).
Regarding claims 23-24, Saji teaches that the upstream microporous material (i.e. sample pad) is easily pretreated and blockable with BSA to minimize non-specific binding (Pg. 18, Ln. 11-20). Saji does not teach the specific buffer used for application of BSA.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the kit of Johnsen in view of Bahadir, Sambursky, and Zhang to include pretreatment of the sample pad with PBS and BSA as taught by Zhang and Saji. One of ordinary skill in the art would be motivated to pretreat the sample pad with buffer and blocking agent for the purpose of minimizing non-specific binding in the assay, thus improving assay performance. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Johnsen in view of Bahadir, Sambursky, and Zhang and Saji relate to a lateral flow test strip capable of detecting an analyte in a sample using a reaction membrane via the use of specific antibodies conjugated to a detectable label, and are thus largely variation of the same concept.
Regarding claim 25, Zhang further teaches storage of the strip in a sealed package with a desiccant at a temperature of 2-8C (Pg. 177, Section 3.1.9), overlapping the claimed temperature range of 4-10C. While Zhang teaches plastic packaging, Saji alternatively teaches a sealed foil packaging with desiccant for storage (Pg. 47, Ln. 21-23).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Johnsen in view of Bahadir, Sambursky, Zhang, and Saji to use an aluminim pouch containing desiccant and to store at a temperature between 4-10C as taught by Saji and Zhang. One would be motivated to make this modification because the packaging, desiccant, and temperature taught by Saji and Zhang are art-recognized materials and conditions known for the purpose of packaging and storing lateral flow test strips in order to protect the assay and reagents from degradation and to increase the shelf life of the kit. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because the cited references are directed to lateral flow assays and Saji and Zhang teach materials and conditions appropriate for the packaging and storage of lateral flow assays.
Response to Arguments
Applicant’s arguments filed 17 November 2025 have been fully considered.
The previous 103 rejections have been withdrawn in favor of the new grounds of rejection presented above, however, relevant points of Applicant’s arguments against the previous rejection are addressed herein. Applicant argues that the previously cited prior art does not sufficiently teach the amended features of independent claim 11. Specifically, Applicant argues that the Saji reference is insufficient because Saji discloses two test strips with a shared sample pad rather than two test strips with two sample pads as in the amended claim. This argument is not persuasive both because Saji was not relied upon to teach the structure of the sample pad (as this was taught by Bahadir) and because the new ground of rejection presented above also does not rely upon Saji to teach the structure of the sample pads (wherein in the rejection presented above, Bahadir is relied upon to teach the general structure of the lateral flow strips (including the sample pads), while Sambursky is used to teach that two lateral flow test strip can be disposed side by side with a shared absorbent pad and mounted within a housing comprising a display window for each reaction membrane.
Applicant further argues that the cited prior art does not teach the newly added functional limitations regarding simultaneous and differential detection of VWF and FVIII at specifically recited thresholds of specificity and accuracy. As noted in the rejection above, this argument is not persuasive because these are functional limitations within a claim directed to a kit. As such, as long as the prior art teaches all structural features and physical components of the claimed kit, it is assumed to be capable of achieving the recited functions, regardless of whether those functions are explicitly disclosed in the prior art. See MPEP 2114.
Applicant further argues that the claimed combination of fluidic optical and structural features yields an unexpected technical advantage for rapid and accurate differential diagnosis of hemophilia and von Willebrand disease without the need for complex instrumentation, and that this improvement is not a predictable result of combining the teachings of the previously cited prior art. This argument is not persuasive. Applicant has not provided specific recitation or showing of what exactly is unexpectedly improved about the results achieved by the instant invention as compared to the prior art, as rapid detection of protein analytes without the need for complex instrumentation is a common and predictable output of a generic lateral flow device. Additionally, Applicant’s arguments regarding the diagnostic applications of the claimed kit are not persuasive because the instant claims are directed to a kit which is defined and distinguished by its structural features and physical components, and which is not limited to or distinguished by its intended use in the differential diagnosis of hemophilia and von Willebrand disease.
Conclusion
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677