Patent Application 15382367 - SYSTEMS AND METHODS FOR POINT-OF-CARE HDL AND

Title: SYSTEMS AND METHODS FOR POINT-OF-CARE HDL AND LDL PARTICLE ASSAY

Application Information

Invention Title: SYSTEMS AND METHODS FOR POINT-OF-CARE HDL AND LDL PARTICLE ASSAY
Application Number: 15382367
Submission Date: 2025-05-14T00:00:00.000Z
Effective Filing Date: 2016-12-16T00:00:00.000Z
Filing Date: 2016-12-16T00:00:00.000Z
National Class: 435
National Sub-Class: 007100
Examiner Employee Number: 78696
Art Unit: 1678
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 1

Cited Patents

The following patents were cited in the rejection:

Office Action Text

DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .

Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/05/25 has been entered. Claims 1 and 13 have been amended. Claims 6-12 remain withdrawn as being directed to non-elected inventions. Claims 2-4 and 14-16 were previously canceled. Accordingly, claims 1, 5, 13 and 17 are under examination.

Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.

The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.

Claims 1, 5, 13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (U.S. 2014/0273270 A1) in view of Badwan et al. (US 2010/0120017) or Ramel et al. (US 2006/0008847) and further in view of Koren et al. (U.S. 6,107,045), Blatt et al. (U.S. 7,476,548), Hu et al. WO 2015/070712 A1), and Fischer-Colbrie et al. (U.S. 2006/0024722).
Wang et al. teach a lateral flow analyte testing system (abstract, [0011]) including one or more test strips (30A, 30B in Fig. 3; 130A, 130B in Fig. 4), thereby reading on first and second lateral flow test strips (see [0029] and Figs. 3-4). The system further includes a sample well “S” [0012], [0015], [0027] that is interconnected with the test strips (see Fig. 4), thereby reading on a dosing area as claimed. Wang et al. further teach a blood collector 70 (i.e., collector for collecting a sample) that is coupled to a sampler body 80 that contains a solution, such that the blood mixes with the solution to form a diluted blood sample which is then placed into the sample well “S”/ dosing area ([0026]-[0027], Figs. 2A-2B). The sampler body 80 thereby reads on the instantly recited “first mixer”. Wang et al. teaches that their devices may be used to measure the concentration of one or more target analytes ((O001], [0008], [0013], claim 1).
Wang et al. further teach that the test strips in their device include a first zone 1, a second zone 2, and a third zone 3. The first zone 1 has colored microparticles, which are configured and adapted to mix with the diluted fluid sample as the fluid sample travels in direction x (i.e., configured to migrate along the test strip; see especially at [0029] and Fig. 3A; and also at [0030], [0032]). Wang et al. therefore teach conjugate and capture reagents in separate rectangular zones of an elongated test strip, thereby reading on “stripes” when this terminology is given its broadest reasonable interpretation. Wang et al. thus teach test strips having conjugate membranes with stripes of colored particles.
Wang et al. further teach that their device may be used to perform an assay format that is competitive a.k.a. inhibitive [0029]. The colored microparticles (in the first zone) can be configured to bind with particular substances in the blood [0029]-[0030].
Wang et al. differs from the claimed invention in failing to teach a sample dosing pad interconnected to the first and second test strips.
Badwan et al. teaches that it is known and conventional in the art to have two test strips share a single sample pad for dosing the sample to the two test strips (e.g. Fig. 6a and para. 0127).
Ramel et al. teaches that it is known and conventional in the art to have two test strips share a single sample pad for dosing the sample to the two test strips (Figs 1 and 3C and para 0026, 0036).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a single sample pad (dosing pad) such as taught by either Badwan et al. or Ramel et al into the device and system of Wang et al because both Badwan et al and Ramel et al show that it is known and conventional in the art to have a single sample pad interconnected to two test strips. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a sample pad such as taught by Badwan et al or Ramel et al into the device and system of Wang et al.
Wang et al., Badwan et al and Ramel et al differs from the claimed invention in that although the reference of Wang teaches that their devices may be used to measure the concentration of one or more target analytes, the reference does not specifically teach testing for LDL-P and HDL-P.
Furthermore, Wang et al. does not specifically teach that the first lateral flow test strip includes a first stripe of colored particles coated with anti Apo A-1 antibody and a second stripe of Apo A antigen or that the second lateral flow test strip includes a first stripe of colored particles coated with anti Apo B-100 antibody and a second stripe of Apo B-100 antigen.
Additionally, Wang et al. while teaching first and second lateral flow test strips with three zones, does not specifically teach that these are made up of a conjugate membrane, a nitrocellulose membrane, and a nylon membrane, in that order. Wang et al. fails to teach the first stripe of colored particles coated with anti Apo A-1 antibody is located in the conjugate membrane and the second stripe of Apo A antigen is located in the nylon membrane.
Lastly, Wang et al. teaches that the sampler body (mixer) contains a “solution” that is mixed with blood to form a diluted blood sample, but does not specifically teach that the solution includes buffers (the reference does not specify the ingredients of the “solution”).
Koren et al. teach antibodies for determining the concentrations of lipoproteins such as HDL and LDL, which are spherical particles (i.e., LDL-P and HDL-P; see abstract; col. 1, lines 1-28; col. 3, lines 12-26; col. 4, lines 52-61).
Koren et al. further teach the clinical importance of measuring HDL and LDL as predictors of coronary heart disease (col. 2, line 20 to col. 7, line 45).
Furthermore, Koren et al. teach using antibodies directed against Apo B-100 in order to detect LDL particles (col. 1, lines 40-42; col. 12, line 44 to col. 13, line 24; col. 19, lines 1-5; Examples 2 and 7) as well as antibodies directed against Apo A-I in order to detect HDL (col. 13, lines 35-42; col. 14, lines 36-49; col. 19, lines 1-5; Example 8).
Blatt et al. also relates to lateral flow test strips for performing immunoassays. The reference teaches a competitive inhibition-type configuration, in which the proximal end of the strip includes a first zone 14 having diffusively immobilized, particle-linked antibody capable of binding sample antigen. Blatt at abstract; col. 5, lines 45-50; col. 13, lines 5-17; col. 16, line 11 to col. 17, line 63; claim 4; Figs. 12 and 15. The first zone 14 is a rectangular section forming part of larger test strip 14, such that the particle-linked antibody present in zone 14 may be said to form a “stripe” of colored particles on the test strip (see, e.g., Fig. 12). Furthermore, the particles may be colloidal gold or colored latex beads (i.e., colored particles; see abstract).
Blatt et al. further teach that the second zone 16 is separate and distinct from the first zone 14, and is located some distance toward the distal end 13 of the bibulous strip, and can be the same or different from the bibulous material of the first zone 14. The second zone 16 includes a bibulous material containing a stripe of non-diffusively immobilized antigen capable of being bound by the particle-linked antibody (ibid; see antigen stripe as shown in Fig. 12).
In this inhibition assay format, application of fluid sample reconstitutes the particle-antibody conjugate, which then migrates laterally through the lateral flow test strip where it becomes bound to the immobilized antigen (i.e., “configured to migrate along the lateral flow test strip”; see, e.g., Blatt et al. at col. 17, lines 41-63; Fig. 15). It is noted that Wang et al. also teach such migration of particle-linked antibodies through the test strip.
Additionally, Blatt et al. also teach that the non-diffusively immobilized antigen can be attached for example to suitable membranes including nylon membranes (col. 16, lines 59-65).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to adapt Wang’s modified multi-test strip system for detecting one or more analytes so as to detect LDL-P and HDL-P as known analytes of clinical importance in order to predict coronary heart disease (as taught by Koren et al.). One skilled in the art would have had a reasonable expectation of success as Wang taught their device for detecting analytes generally and Koren et al. taught that LDL-P and HDL-P can be successfully measured using solid phase immunoassays, which also describes the lateral flow system of Wang.
Accordingly, the ordinary artisan would have found it obvious to employ one test strip for detecting HDL-P and the other test strip for detecting LDL-P in order to detect both of these analytes of recognized clinical importance simultaneously on a single device and using a single sample source.
With respect to the recitation that the first test strip includes a first stripe of particles coated with an Apo A-1 antibody and a second stripe of Apo A antigen, and the second test strip includes a first stripe of particles coated with Apo B-100 antibody and a second stripe of Apo B-100 antibody, Wang et al., as discussed above, do teach that the test strips in their device include a first zone 1, a second zone 2, and a third zone 3. The first zone 1 has colored microparticles, which are configured and adapted to mix with the diluted fluid sample as the fluid sample travels in direction x. See at [0029] and Fig. 3A. Additionally, Wang et al. further teach that their device may be used to perform an assay format that is competitive a.k.a. inhibitive [0029]. The colored microparticles (in the first zone) can be configured to bind with particular substances in the blood [0029]-[0030]. Wang et al. thus teach the test strips having conjugate membranes with stripes of colored particles. However, Wang et al. do not describe in detail the competitive format.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at these features by applying the known competitive inhibition assay format suggested by Wang, and as described in further detail by Blatt et al., in order to detect the analytes LDL-P and HDL-P using the multi-test strip system of Wang et al. In particular, Blatt et al. detail how this assay format employs a first zone of particle-linked antibody capable of binding sample antigen and a second zone having immobilized antigen, where the particle-linked antibody is configured to migrate along the lateral flow test strip as claimed.
When taken together with the teachings of Koren et al. who teach using antibodies directed against Apo B-100 in order to detect LDL particles (col. 1, lines 40-42; col. 12, line 44 to col. 13, line 24; col. 19, lines 1-5; Examples 2 and 7) as well as antibodies directed against Apo A-1 in order to detect HDL (col. 13, lines 35-42; col. 14, lines 36-49; col. 19, lines 1-5; Example 8), it would have been obvious to adapt the system of Wang to the detection of HDL-P and LDL-P by providing particles coated with anti Apo A-1 antibody and anti Apo B-100 antibody as claimed in order to accord with the competitive assay format detailed by Blatt which is taught to be useful in successfully detecting analytes of interest.
Accordingly, in view of the teachings of Koren et al. that antibodies having specificity to Apo A-1 and Apo B-100 antigens are capable of being used in solid phase immunoassays in order to detect HDL and LDL, respectively, it would have been obvious to arrive at the claimed invention by adapting the general assay format of Blatt to the detection of these particular analytes, specifically by using particle-linked Apo A-1 antibodies as the conjugate reagents in the conjugate membrane of the first test strip and particle-linked Apo B-100 antibodies as the conjugate reagents in the conjugate membrane of the second test strip of Wang et al., both configured to migrate along the respective test strips. Thus, the first stripe of particle-linked ApoA-1 antibodies is located in the conjugate membrane of the first test strip and reads on “the first stripe of colored particles coated with anti Apo A-1 antibody is located in the conjugate membrane”.
Put another way, Koren teaches the utility of antibodies directed against Apo A-I and Apo B-100 in order to detect HDL and LDL, respectively, which were antigens of known clinical importance, and it would have been obvious to adapt the system of Wang for detection of these analytes using the well-known assay format as detailed by Blatt (and as also mentioned by Wang). As above, one skilled in the art would have been motivated to do this in order to detect these analytes of recognized clinical importance for prediction of heart disease using the known competitive inhibition assay format.
When adapting the modified system of Wang to the detection of HDL-P and LDL-P in order to predict heart disease as above, it would have been further obvious to use the second zone or the third zone of Wang to provide a zone of immobilized antigen on the test strips (in this case, immobilized HDL-P and LDL-P antigens; Apo A antigens and Apo B-100 antigens) in order to accord with the competitive assay format detailed by Blatt which is taught to be useful in successfully detecting analytes of interest. It would have further been obvious to provide a zone of immobilized antigen on the third zone of the test strips of Wang by selecting from a finite number of ways to incorporate the zone of immobilized antigen into the test strips (e.g., the zone of immobilized antigen can be provided in either the second zone or the third zone which Wang et al. teach as capture zones for conjugates, par. 32).
Blatt et al. (discussed above) also features a test strip made up of multiple zones, in this case a “first zone” 14 containing diffusively immobilized, particle linked antibody capable of binding antigen (see, e.g., col. 13, lines 5-17), thereby also reading on a conjugate membrane. Blatt et al. also instructs that second zone 16 is separate and distinct from the first zone 14, and can be the same or different from the bibulous material of the first zone 14 (col. 13, lines 5-17). Blatt et al. also teach nylon membrane as a suitable material for fabricating test strips (col. 16, lines 59-65).
It would have been further obvious to select nylon membrane for the third zone of Wang et al. as a known material for fabricating test strips, particularly for covalent attachment of antigen (as taught by Blatt et al.), and by applying the known technique of Blatt et al. that the different zones of a test strip may be fabricated separately and may be of different materials. Accordingly, it would have been obvious to arrive at stripes of Apo A antigens and Apo B-100 antigens in first and second nylon membranes as claimed because of the art-recognized suitability of nylon for the purpose of immobilizing antigens on test strips. Thus, the second stripe of Apo A antigens is located on the first nylon membrane and reads on “the second stripe of Apo A antigen is located on the nylon membrane”.
With respect to the recitation that “the first and second lateral flow test strips include a conjugate membrane, a nitrocellulose membrane, and a nylon membrane, in that order”, Wang et al. as above teach that their test strips may include colored microparticles configured to bind with particular substances in the blood, i.e. conjugates ([0012], [0029]-[0033]). Wang et al. also teach that their test strips contain multiple zones. See for example Wang et al. at Fig. 3A, teaching zones 1, 2, and 3. Wang et al. fairly teach a conjugate membrane and the combination of Wang et al., Koren et al., and Blatt et al. as detailed above teach a nylon membrane downstream the conjugate membrane. However, the combination fails to specifically teach the test strips with a nitrocellulose membrane between the conjugate membrane and the nylon membrane such that the test strips include a conjugate membrane, a nitrocellulose membrane, and a nylon membrane, in that order.
However, Blatt et al. (discussed above) also features a test strip made up of multiple zones, in this case a “first zone” 14 containing diffusively immobilized, particle linked antibody capable of binding antigen (see, e.g., col. 13, lines 5-17), thereby also reading on a conjugate membrane. Blatt et al. also instructs that second zone 16 is separate and distinct from the first zone 14, and can be the same or different from the bibulous material of the first zone 14 (col. 13, lines 5-17). Blatt et al. also teach nitrocellulose membrane as a suitable material for fabricating test strips (col. 16, lines 59-65).
It would have been obvious to arrive at the claimed invention by modifying the 3-zone test strips of Wang et al. so as to include a nitrocellulose membrane in addition to the conjugate membrane and the nylon membrane such that the test strips include a conjugate membrane, a nitrocellulose membrane, and a nylon membrane, in that order, by applying the known technique of
Blatt et al. that the different zones of a test strip may be fabricated separately and may be of different materials. Specifically, absent evidence of criticality, one of ordinary skill in the art would have found it obvious to select nitrocellulose as the material for the second zone of Wang et al. by selecting from a finite number of identified, predictable alternatives; namely those materials taught by Blatt et al. as being suitable.
In summary, when adapting the system of Wang and Koren to the detection of LDL-P and HDL-P in order to predict heart disease as above, it would have been obvious to arrive at the claimed invention by applying the known technique of Blatt of detecting analytes through the competitive inhibition assay format, which involves using particle-linked antibodies to the antigen of interest together with immobilized antigen.
One skilled in the art would have had a reasonable expectation of success as Wang already indicates that their device may be used to perform competitive format assays.
Hu et al., similar to Wang et al., also teaches a multi-test strip device in which sample may be introduced to the device using a separate part (“sample collector”) that first mixes/blends the sample with buffer solution prior to introducing the sample onto the test strip device for detection (see, e.g., pages 1-2, 19-21 and 23, Fig. 7). Hu et al. teach that buffer solution is added to samples so as to reduce viscosity and consistency of the samples, thus guaranteeing smooth analysis and detection effectiveness (page 1, paragraph bridging pages 3-4).
While Hu et al. do not specify “buffers” plural, Fischer-Colbrie et al. discuss sample treatment steps that may be performed before subjecting the sample to a solid phase binding assay [0961]. Fischer-Colbrie et al. in particular suggest “addition of one or more buffers or reagents to modify ambient conditions such as pH or ionic strength”.
With respect to the recitation of a mixer including buffers, it would have been obvious to include buffers in the solution contained in the mixer (sampler body 80) of Wang et al. in order to achieve the same purpose, namely to effect dilution of the sample, as well as to reduce viscosity and consistency of the samples, thus guaranteeing smooth analysis and detection effectiveness (as taught by Hu et al.). In particular, although Wang does not specify the ingredients used in their “solution” for mixing with sample, Hu et al. teach that buffer solution is added to samples so as to reduce viscosity and consistency of the samples, thus guaranteeing smooth analysis and detection effectiveness, and Fischer-Colbrie et al. teaches that one may use one or more buffers to treat samples prior to performing solid phase binding assays (which also describes the purpose of the Wang and Hu devices). Accordingly, one skilled in the art would have found it obvious to apply this known technique of including one or more buffers in the sampler body/ mixer in order to achieve the same purpose of diluting the sample prior to testing, as in Wang and Hu, as well as to guarantee smooth analysis and detection effectiveness when detecting LDL-P and HDL-P.
With respect to claim 17, Wang et al. further teach that their lateral flow testing device is an optical device (abstract, [0012]-[0015]), where the multiple test strips are contained in a single cartridge that is designed to be inserted into a meter [0047].

Response to Arguments
Applicant's arguments filed 05/05/25 have been fully considered but they are not persuasive.
103 Rejections:
Applicant argues that Wang does not teach “particles coated with anti Apo B-100 antibody.” Koren also does not teach particles coated with an anti Apo B-100 antibody. Koren only teaches these particles immobilized, later to be stained once bound with blood lipoprotein. Applicant states that Koren indicates: “Methods and compositions to determine the concentration of specific lipoproteins and/or apolipoproteins, such as LDL and HDL, which when present at elevated levels in the body are causally related to an increased or decreased risk of CHD have been developed. In the preferred embodiment, blood lipoprotein and/or apolipoprotein molecules in a patient sample are bound to specific antibodies immobilized on specially prepared strips of solid phase material and to the bound lipoprotein and/or apolipoproteins visualized using specific colored staining reagents. The intensity of the color is proportional to the concentration of the lipid component or apolipoprotein component of the lipoprotein circulating in the blood.” (c. 7, 1. 49-61).
Applicant further argues that nowhere do the combined references teach particles coated with an anti Apo B-100 antibody. The Examiner goes on to say that “it would have been obvious to adapt the system of Wang to the detection of HDL-P and LDL-P by providing particles coated with anti Apo A-1 antibody and anti Apo B-1 00 antibody.” However, it is never identified where these particles coated with anti Apo A-1 antibody and anti Apo B-1 00 antibody come from, since Wang does not teach them and Koren does not teach them and the references as a whole do not teach them. A prima facie case has not been articulated. Therefore, the independent claims | and 13, and all claims dependent thereon are patentable.
This argument is not found persuasive because the Examiner has relied upon Wang for teaching the colored particles used in a system for detecting a particular substance in a sample by competitive assay. The examiner then relies upon Koren for teaching that it is known and conventional in the art to use antibodies directed against Apo A-I and Apo B-100 in order to detect HDL and LDL. Thus, one of ordinary skill in the art would be motivated to put the antibodies such as taught by Koren on the colored particles in the modified method of Wang. The applicant is arguing Wang and Koren individually. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).

Conclusion
No claims are allowed.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678