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
The present application was filed 01/08/2021 and claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/959,727, filed on 01/10/2020.
Claim Status
Claims 1, 12-16, 20-25, and 27-30 are pending. Claims 1 and 16 are amended; claims 2-11, 17-19, and 26 are cancelled. Claims 1, 12-16, 20-25, and 27-30 are examined below.
Withdrawn rejections
The objection to the specification has been withdrawn due to the amendment of the specification.
Withdrawn rejections
The rejection of claims 1 and 12-15 under 35 U.S.C. 112(b) is withdrawn due to the amendment of claim 1.
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, 12, 14-16, 20-25, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al., US20180229232A1 (PTO-892, 03/30/2023), in view of Tokarska-Rodak et al. (2012) “The serology diagnostic schemes in Borrelia burgdorferi Sensu Lato infections–significance in clinical practice” Book: Lyme Disease, IntechOpen, ISBN 978-953-51-0057-7 , page 79-94 (PTO-892, 03/30/2023), Theel ES (2016) “The Past, Present and (Possible) Future of Serologic Testing for Lyme Disease”, Journal of Clinical Microbiology, 54, 5, pages 1191-1196 (PTO-892, 03/30/2023), and Myers et al., US9390237 (PTO-892, 03/30/2023).
Regarding claim 1, Chang teaches a method of diagnosing a disease or infection by detecting a pathogenic or infectious agent associated with disease or infection in a human subject (Chang, page 12, paragraph [0126], lines 1-11), namely Lyme disease due to B. Burgdorferi (Chang, page 13, paragraph [0134], lines 1-5). Chang further teaches a substrate that has a fluid flow channel and can find use in lateral flow assays to detect and/or discriminate a species of interest in a fluid sample (Chang, page 1, see entire paragraph [0002]). Chang further teaches a lateral flow assay with a plurality of fluid flow channels (Chang, page 2, paragraph [0035], lines 1-2 and Figure 1H), the multiplicity of individual, discrete fluid flow channels on a single substrate (Chang, page 5, paragraph [0078], lines 5-8). Chang also teaches that the test strip described can detect and differentiate IgG and IgM immunoglobulins against a tick-borne infection, namely that of a Borrelia species (Chang, page 13, paragraph [0136], lines 1-3). To this end, Chang further teaches immobilizing a plurality of peptides. The immobilized peptides, according to the teaching of Chang can be any combination of peptides of a panel comprising “IgG antigens,” namely BmpA (p39), p41, p66, VlsE (IR 6) (Chang, page 13, paragraph [0135], lines 17-29) and OspC (p23) (Chang, page 13, paragraph [0134], line 9) and further comprise “IgM antigens,” namely BmpA (p39), p41, VlsE (Chang, page 13, paragraph [0135], lines 18-26) and OspC (p23) (Chang, page 13, paragraph [0134], line 9). Chang further teaches that the plurality of peptides can be the same or different in each of the capture zones and or/label zones (Chang, page 13, paragraph [0135], lines 4-6). As such Chang teaches first and second tier IgG or IgM peptides that do not comprise the same antigen and can be any combination, i.e. can be independently selected.
The specification does not provide a specific or limiting definition for the claim terms “first tier IgG antigens,” “second tier IgG antigens,” “first tier IgM antigens,” and “second tier IgM antigens.” The specification contains a list of exemplary antigens in the table on pages 36-37, but does not clearly delineate or limit which antigens are designated first or second tier. The present claims also fail to clearly identify which of the antigens are first or second tier. The specification states that the “first tier antigens and/or the second tier antigens can be any combination or any number of antigens described herein” ([0129]; see also [0130]). This is interpreted to mean that any of the antigens described in the specification could be considered either first or second tier IgG and/or IgM antigens.
Accordingly, Chang addresses the claims regarding first and second tier antigens, insofar as Chang teaches antigens comprised in the panel as claimed and disclosed, which could be interchangeably interpreted as either first or second tier antigens.
Chang further teaches a device with a single central sample receiving zone that is positioned to distribute the sample to each of a plurality of discrete fluid flow paths, for example, Chang in Figure 2B teaches two fluid flow paths with a central sample introduction port, comprising 4 fluid flow paths each (a central sample introduction port; Chang, page 2, paragraph [0021], lines 1-6 and figure 2B). Chang further teaches a second fluid flow channel that has a fluid flow path that is in a direction opposite from the first fluid flow channel (Chang et al. page 1, see entire paragraph [0018]). Chang further teaches a label zone on the test strip associated with a channel, where a mobilizable anti-human antibody is deposited for detecting infection by a species in the Borrelia genus. Chang further teaches that the anti-human antibody is IgG or IgM. The anti-human IgM antibody is deposited in the label zone of one of the discrete channels in the plurality of fluid flow channels and that the anti-human IgG antibody is deposited in another discrete channel (Chang, page 13, paragraph [0133], lines 19-28). Chang further teaches in Figure 14B a test strip with a single sample receiving zone (126) in communication with a plurality of discrete fluid flow channels where a first portion of the fluid flow channels and a second portion of the fluid flow channels flow in opposing directions and further teaches that each individual flow channel comprises a label zone and test (136) and control (138) zones (Chang, page 8, see entire paragraph [0103] and Figure 14B). Put another way, Chang teaches a test strip with two opposing fluid paths, each comprising a separate label zone and further teaches a test strip with anti-human IgG antibody in one label zone and anti-human IgM antibody in another label zone, opposite each other, one fluid flow path for the detection of IgG antibody and a distinct flow path for the detection of IgM antibody both on a single test strip. Therefore it would have been prima facie obvious to one having ordinary skill in the art that the discrete fluid flow path comprising the anti-human IgG antibody would further comprise IgG antigens and the second distinct flow path comprising anti-human IgM antibody would further comprise IgM antigens. Still further Chang teaches each and every combination of two or more features of the device as long as the features in such combination are not exclusive (Chang, page 2, paragraph [0033], lines 5-7).
Although Chang teaches embodiments comprising a device that has a plurality of fluid flow channels (for example, 3-50 fluid flow paths (Chang, page 2, see entire paragraph [0023]), and teaches embodiments comprising a central sample introduction port (shown in the middle of flow paths, see as cited above), Chang fails to explicitly disclose or describe the claimed embodiment wherein the central sample introduction port is positioned to distribute the sample to a first plurality of at least five fluid flow channels and along a second fluid flow path of at least five fluid flow channels (i.e., 5 on each side of the central port and a first fluid flow path).
However, it would have been prima facie obvious to one having ordinary skill in the art, reading the disclosure of Chang, to arrive at the claimed design, namely comprising a central sample port to distribute the sample along two separate fluid flow paths with at least five individual, discrete fluid flow channels each, because Chang teaches a device with at least 5 fluid flow paths and up to 50, and specifically shows a device with 4 fluid flow paths and a central sample port and further teaches that two or more features, in this case the more than 5 channels and the central sample port, can be combined. The ordinarily skilled artisan reading Chang would readily appreciate the combination of their disclosed embodiments in this case the more than 5 channels and the central sample port, as an obvious matter of design choice, specifically combining the configurations as disclosed because Chang discloses these various designs as shown at Figure 2B and Figures 1G and 1H. Chang further teaches that Figure 2B illustrates a single substrate for multiplex analysis of a fluid sample, where a single common sample receiving zone is in fluid communication with a plurality of flow channels (Chang, page 6, paragraph [0088], lines 1-4; See MPEP 2144.04, the rearrangement of parts has typically been held by the courts as an obvious matter of design choice). In this case, both configurations, comprising a plurality of channels, and providing a port central to the device for bi-directional flow were known and taught by the prior art (Chang), as such the ordinarily skilled artisan, reading Chang, would have found the combination of these elements obvious, as Chang at Figure 2B showing 4 flow paths on either side, appears to be exemplary of the type of design, particularly considering that Chang teach up to 50 channels.
Chang also teaches that a sample is deposited in the sample receiving zone (Chang, page 2, paragraph [0026], lines 5-6), whereby the sample type comprises blood (Chang, page 4, see paragraph [0071]) and is from a person suspected of having an infection (Chang, page 12, paragraph [0129], lines 2-4), such as being infected with a Borrelia species (Chang, page 12, paragraph [0133]). Accordingly, Chang further teaches depositing a sample on a test trip for detection of an infectious agent associated with Lyme disease in order to determine whether a subject has Lyme disease, the test strip having a plurality of discrete fluid flow channels (Chang, page 12, paragraph [0133], lines 1-10).
Chang teaches taking images of the test strip (Chang, paragraph [0141], lines 15-16 and Figure 20C) and further teaches that the test strip is designed for instrument reading and is not intended to be visually read by the human eye (Chang, page 14, paragraph [0140]), but does not expressly teach an image capturing device, nor does Chang teach conducting an analysis of the image by evaluating the signal associated with IgG and IgM first tier antigen with a computer algorithm.
Chang further fails to specifically teach that if the analysis of first tier IgG and IgM indicates presence or possible presence of disease, evaluating the second tier IgG and IgM antigens and if evaluating second tier IgG and IgM indicates presence or possible presence of disease report presence of disease. Chang further fails to teach Applicant’s elected species comprising the entire panel of IgG antigens, specifically Chang fails to teach the peptides p18, p28, p30, p41, p45, p58, p93, p31. Chang further fails to teach Applicant’s elected species comprising the entire panel of IgM antigens, specifically Chang fails to teach the peptides p19 and C10.
Tokarska-Rodak teaches a two-step testing process in serological diagnostics of Lyme disease (Tokarska-Rodak, page 80, lines 2-3). Tokarska-Rodak further teaches that the test for Lyme disease measures antibodies made in response to infection (Tokarska-Rodak, page 80, 2nd paragraph, lines 1-2). Tokarska-Rodak further teaches that the immunoassay tests are characterized by high sensitivity and that the two-step laboratory testing process is designed to eliminate unspecific false positive results (Tokarska-Rodak, page 82, lines 17-23). Tokarska-Rodak further teaches that IgG antigens comprise p18, p30, p31, and p58 (Tokarska-Rodak, page 80, lines 14-17). Tokarska-Rodak teaches that as the infection develops, the immunologic response extends on the increasing number of antigen proteins, comprising p19 and C10. Tokarska-Rodak further teaches that recombinant peptide C10 is used in order to improve the diagnostics of Lyme disease and for a prediction of the duration of the infection (Tokarska-Rodak, page 85, 2nd paragraph, lines 31-34). Tokarska-Rodak further teaches that it is important to include appropriate antigens in tests considering the heterogeneity of the proteins in b. Burgdorferi in Europe (Tokarska-Rodak, page 85, 2nd paragraph , lines 5-7). Tokarska-Rodak further teaches that the use of a broad spectrum of antigens in tier two of the test can contribute to the designation of the severity and dynamics of the immunological response against the used antigens and provide more possibilities in the assessment of the immune reactions in relation to a clinical state of a patient.
Theel teaches B. burgdorferi IgG antigens p28, p45, and p93 (Theel, page 1192, paragraph [0003], lines 17-22) and VlsE/C6 (Theel, page 1193, paragraph [0007], line 4).
Theel also teaches that group of antigens comprising those listed above provide high diagnostic accuracy for Lyme disease patients as endorsed by the CDC (Theel, page 1191, paragraph [0001], lines 7-8). Theel further teaches that IgG reactivity of at least 5 of the 10 antigens provides high diagnostic accuracy for Lyme disease in patients with at least 1 week of symptoms according to a study to determine optimal antigens to detect B. Burgdorferi (Theel, page 1192, paragraph [0002], line 10-15). Theel further teaches that the two tier testing begins with a first-tier screening for IgM and IgG class antibodies using whole cell sonicate and that no further testing is warranted for patients with negative screening results but that a positive or equivocal result in the first-tier assay requires confirmatory testing by B. burgdorferi-specific IgM and IgG analysis to ensure specificity (Theel, page 1192, 3rd paragraph, lines 3-10).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to have modified the method of Chang et al. to add to the panel of antigens detected, additional antigens such as p18, p30, p31, p58, p19 and C10 as taught by Tokarska-Rodak and antigens p28, p45 and p93 as taught by Theel to the immunoassay in order to improve diagnostics/achieve higher diagnostic accuracy (see Tokarska-Rodak and Theel) for Lyme disease and to account for the heterogeneity of the b. Burgdorferi proteins in different regions of the world and also the heterogeneity in the immune response over time of the infection as taught by Tokarska-Rodak. The ordinarily skilled artisan would have been motivated to do so because of the teaching of Tokarska-Rodak that a broad spectrum of antigens can help assess the severity and dynamics of the immune response and provide more possibilities in the assessment of the immune reactions in relation to a clinical state of a patient.
It would have further been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Chang to use a two tier testing method as taught by Theel to first screen patients and exclude those with a negative screening result, i.e. those who do not require further testing and then perform a second tier test in order to confirm the results. One having ordinary skill in the art would be motivated to do so because of the teaching of Theel that the confirmatory testing ensures specificity. Theel further teaches in Figure 1 that in patients with a negative screening test or negative blot and alternate diagnosis should be considered (Theel, page 1192, Figure 1). As such Theel teaches that in patients with negative screening tests or a negative blot after a positive screening test (see Theel, page 1192, flow chart, Figure 1) the diagnosis is not Lyme disease and therefore there is an absence of disease.
The ordinary artisan would have had reasonable expectation of success in having combined the peptides as taught by Chang with those of Tokarska-Rodak and Theel, because all three have shown success diagnosing Lyme disease in patients with an immunoassay using peptides.
Myers teaches a reading device for analyzing the response of a test device, comprising an imaging device for recording images, a software module executed by a processor (computer implemented algorithm) of the reading device to determine one or more test parameters based on the image and for determining a response based on one or more test parameters (conducting an analysis of the image; Myers, column 2, lines 9-19). Myers further teaches that the test strip to be analyzed is based on a lateral flow test device (Myers, column 2, lines 43-44) and that using a generic reader device, such as a mobile phone or tablet computer, obviates the need for expensive and dedicated equipment (Myers, column 1, lines 30-36). Myers further teaches a result may be output to the user, such as a textual output, color indicators, etc. (Myers, column 7, lines 44-47; column 8, lines 26-29; column 5, lines 29-40). Myers further teaches that the test information may comprise output information such as characters indicative of the output “Discharge/Reassure” (Myers, column 5, lines 33-35).
Accordingly, Myers contemplates reporting the results of the test, including in the context of reporting a negative test result whereby a patient would be “Discharge[d]” from care and “Reassure[d]” regarding their medical condition.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of diagnosis, as taught by Chang et al., specifically to use the test strip device of Chang by immobilizing a plurality of “IgM antigen” and “IgG antigen” on a test strip, with the method of Theel, comprising identifying a patient as not being infected with Lyme disease in the absence of antibodies to B. burgdorferi antigen. It would have further been obvious to report the results, for example in textual form as taught by Myers comprising “Discharge/Reassure” for a specific result.
More particularly, Chang indicate that detecting reactivity to B. burgdorferi is used to detect Lyme disease, and although Chang does not explicitly state the converse, i.e., that when no reactivity is detected, this would indicate the absence of disease, Theel (which also relates to detection of Lyme) teaches how when all tested antibodies are negative, this would indicate the absence of disease, as does Tokarska-Rodak.
Therefore, it would have been obvious to conclude when performing the methods of Chang that when none of the tested antibodies are detected, that this would indicate the absence of disease (no Lyme infection), and it would have been further obvious to report such absence of disease so that the subject could be discharged from medical care and reassured regarding their Lyme status.
The ordinary skilled artisan would have had reasonable expectation of success in doing so because Chang teaches success measuring antibody response to Lyme disease related antigens using a multiplex lateral flow assay and Theel teaches detecting Lyme specific antibodies using Lyme specific antigen.
It would have further been prima facie obvious to one having ordinary skill in the art before the effective filing date to have modified the method of Chang and Theel to use a reading device, comprising an image capturing device and a processor with a software module (a computer implemented algorithm/system) in order to collect the data from a lateral flow test, because it eliminates the need for expensive and dedicated equipment (Myers).
The ordinarily skilled artisan would have had a reasonable expectation of success, because of the teaching of Chang that the test strip is designed for instrument reading and is not intended to be visually read by the human eye and the teaching of Myers et al., which shows such a device for collecting and analyzing data from a lateral flow test device, such as that of Chang et al. and the cited art.
Regarding claim 12, Chang et al. teaches a method comprising a test strip for detection of an infectious agent associated with Lyme disease (a tick-borne infection; Chang et al., page 12, paragraph [0133], lines 3-5).
Regarding claim 14, see Chang et al. teaching a method of testing human blood, serum or plasma (Chang et al., page 4, paragraph [0071], line 5) comprising a multi-channel lateral flow immunoassay comprising detectable anti-human IgM antibody in the label zone of a discrete fluid flow channel and a detectable anti-human IgG in another discrete fluid flow channel (Chang et al., page 13, paragraph [0133], lines 34-39) and a plurality of peptides immobilized in each capture zone in each of the fluid flow paths, where the plurality of peptides can be the same or different in each capture zone (page 13, paragraph [0135], lines 1-3).
Regarding claim 15, see Chang et al. teaching a method of detecting B. burgdorferi infection (page 13, paragraph [0134], lines 4-5).
Regarding claim 16, Chang teaches a method of detecting presence or absence of an analyte using a device contemplated for use in detection of any pathogenic or infections agent. The analyte indicative of a disease or infection in a disease or infection where discrimination of subtypes aids in diagnosis (method for use in diagnosis; Chang, page 12, ‘III. Methods of Use” and paragraph [0126], lines 1-4). Chang further teaches that the device used in the method is a lateral flow immunoassay device comprising at least 5 individual, discrete fluid flow channels on a single substrate (test strip; Chang, page 5, paragraph [0078], lines 5-8, and Figure 1H) and a plurality of peptides immobilized in the capture zone of each of the fluid flow paths, where the plurality of peptides can be the same or different in each of the capture zones (Chang, page 13, paragraph [0135], lines1-6). Chang further teaches that the antigen in the capture zone is derived from a species in the Borrelia genus, comprising one or more peptide antigens of B. burgdorferi in each of the flow paths on the test strip (Chang, page 13, paragraph [0134], lines 1-7) comprising the antigens BmpA (p39), p41, p66, VlsE (IR6) (Chang, page 13, paragraph [0135], lines 17-22) and OspC (p23) (antigen are selected from a group; Chang, page 13, paragraph [0134], line 9). Chang also teaches that the test strip described can detect and differentiate IgG and IgM immunoglobulins against a tick-borne infection, namely that caused by a Borrelia species (Chang, page 13, paragraph [0136], lines 1-3). Chang further teaches depositing a sample on a test strip (Chang, page 2, paragraph [0020], lines 1-6) and that a sample can be blood, serum, plasma and other types of sample (Chang, page 4, paragraph [0071], line 5). Chang further teaches that the plurality of peptides can be the same or different in each of the capture zones and or/label zones (Chang, page 13, paragraph [0135], lines 4-6). As such Chang teaches first and second tier IgG or IgM peptides that do not comprise the same antigen.
Chang does not specifically teach analyzing the immunoassay with an instrument comprising a processor for execution of an algorithm to evaluate signal associated with IgG and IgM first tier antigen with a computer algorithm. Chang further fails to teach that if the analysis of the first tier IgG and IgM antigens indicates absence of disease, to report absence of disease as in claim 1(a).
As discussed above, the specification and the claims of the present application are silent as to the specific peptides designated tier 1 or tier 2, merely stating that the antigens described (see above) “can be grouped into any number of combinations for a first tier IgG, second tier IgG, first tier IgM and second tier IgM analysis (present application, specification page 37, paragraph [0130], lines 8-11). The claims also do not specify which are specifically tier 1 or 2. The claimed invention merely encompasses a plurality where each is immobilized at a different channel. Further, see as cited above, Chang teaches that the antigens in the various channels can be the same or can be different (from the above citation, Chang, page 13, paragraph [0135], lines1-6).
As discussed previously above, Theel teaches that the two tier testing begins with a first-tier screening for IgM and IgG class antibodies and that no further testing is warranted for patients with negative screening results but that a positive or equivocal result in the first-tier assay requires confirmatory testing by B. burgdorferi-specific IgM and IgG analysis to ensure specificity (Theel, page 1192, 3rd paragraph, lines 3-10).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of diagnosis, as taught by Chang et al., specifically to use the test strip device of Chang by immobilizing a plurality of “IgM antigen” and “IgG antigen” on a test strip, with the two tier testing method as taught by Theel to first screen patients and exclude those with a negative screening result, i.e. those who do not require further testing and then perform a second tier test in order to confirm the results. One having ordinary skill in the art would be motivated to do so because of the teaching of Theel that the confirmatory testing ensures specificity. Theel further teaches in Figure 1 that in patients with a negative screening test or negative blot and alternate diagnosis should be considered (Theel, page 1192, Figure 1). As such Theel teaches that in patients with negative screening tests or a negative blot the diagnosis is not Lyme disease and therefore there is an absence of disease.
The ordinary skilled artisan would have had reasonable expectation of success in doing so because Chang teaches success measuring antibody response to Lyme disease related antigens using a multiplex lateral flow assay and Theel teaches a sandwich immunoassay for the detection of B.burgdorferi derived antigens both assays depending on specific antibody-antigen binding.
Myers teaches a reading device for analyzing the response of a test device, comprising an imaging device for recording images, a software module executed by a processor (computer implemented algorithm) of the reading device to determine one or more test parameters based on the image and for determining a response based on one or more test parameters (conducting an analysis of the image; Myers, column 2, lines 9-19). Myers further teaches that the test strip to be analyzed is based on a lateral flow test device (Myers, column 2, lines 43-44) and that using a generic reader device, such as a mobile phone or tablet computer, obviates the need for expensive and dedicated equipment and provides a quantifiable output (Myers, column 1, lines 30-36).
It would have further been prima facie obvious to one having ordinary skill in the art before the effective filing date to have modified the method of Chang to use a reading device, comprising an image capturing device and a processor with a software module (a computer implemented algorithm/system) in order to collect the data from a lateral flow test, because it allows for the quantification of the data (Myers).
The ordinarily skilled artisan would have had a reasonable expectation of success, because of the teaching of Myers et al., which shows such a device for collecting and analyzing data from a lateral flow test device, such as that of Chang et al. and the cited art.
Regarding claims 20 and 24, Chang teaches a method substantially as claimed. Chang teaches a method comprising a device comprising 2-50 fluid flow paths (Chang, page 2, paragraph [0023], lines 1-2). Chang further teaches a plurality of peptides immobilized in the capture zone of each of the fluid flow paths, where the plurality of peptides can be the same or different in each of the capture zones (Chang, page 13, paragraph [0135], lines1-6). Chang further teaches the group of antigens comprising BmpA (p39), p41, p66, VlsE (region IR6), and OspC (p23) (Chang et al., page 13, see paragraph [0135]).
As discussed previously above in claim 9, Chang fails to teach Applicant’s elected species comprising the entire panel, specifically Chang fails to teach the peptides p18, p28, p30, p41, p45, p58, p93, p31.
Tokarska-Rodak teaches a two-step testing process in serological diagnostics of Lyme disease (Tokarska-Rodak, page 80, lines 2-3). Tokarska-Rodak further teaches that the test for Lyme disease measures antibodies made in response to infection (Tokarska-Rodak, page 80, 2nd paragraph, lines 1-2). Tokarska-Rodak further teaches that the immunoassay tests are characterized by high sensitivity and that the two-step laboratory testing process is designed to eliminate unspecific falsely positive results (Tokarska-Rodak, page 82, lines 17-23). Tokarska-Rodak further teaches that IgG antigens comprise p18, p30, p31, and p58 (Tokarska-Rodak, page 80, lines 14-17). Tokarska-Rodak teaches that as the infection develops, the immunologic response extends on the increasing number of antigen proteins, comprising p19 and C10. Tokarska-Rodak et al. further teaches that recombinant peptide C10 is used in order to improve the diagnostics of Lyme disease and for a prediction of the duration of the infection (Tokarska-Rodak et al., page 85, 2nd paragraph, lines 31-34). Tokarska-Rodak et al. further teaches that it is important to include appropriate antigens in tests considering the heterogeneity of the proteins in b. Burgdorferi in Europe (Tokarska-Rodak et al., page 85, 2nd paragraph , lines 5-7). Tokarska-Rodak further teaches that the use of a broad spectrum of antigens in tier two of the test can contribute to the designation of the severity and dynamics of the immunological response against the used antigens and provide more possibilities in the assessment of the immune reactions in relation to a clinical state of a patient.
Theel teaches B. burgdorferi p28, p45, p93 (Theel, page 1192, paragraph [0003], lines 17-22) and VlsE/C6 (Theel, page 1193, paragraph [0007], line 4).
Theel also teaches that group of antigens comprising those listed above provide high diagnostic accuracy for Lyme disease patients as endorsed by the CDC (Theel, page 1191, paragraph [0001], lines 7-8). Theel further teaches that IgG reactivity of at least 5 of the 10 antigens provides high diagnostic accuracy for Lyme disease in patients with at least 1 week of symptoms according to a study to determine optimal antigens to detect B. Burgdorferi (Theel, page 1192, paragraph [0002], line 10-15).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to have modified the method of Chang et al. to add the antigens listed above as taught by Theel and Tokarska-Rodak in order to achieve a method for testing for Lyme disease with higher diagnostic accuracy, because see as taught by Tokarska-Rodak and Theel, including additional peptides increases diagnostic accuracy and because a broad spectrum of antigens can provide more possibilities in the assessment of the immune reaction in relation to the clinical state of a patient as taught by Tokarska-Rodak.
The ordinarily skilled artisan would have been motivated to add to the panel of Chang in order to detect Lyme disease with higher diagnostic accuracy.
The ordinary artisan would have had reasonable expectation of success in doing so, because both Tokarska-Rodak and Theel teach detecting these antigens improves performance of a diagnostic assay for Lyme disease.
Regarding claim 21, Chang teaches a method substantially as claimed, comprising an immunoassay device with at least 5 fluid flow channels, substantially as claimed. As discussed previously in detail above, Chang further teaches a device with a single central sample receiving zone that is positioned to distribute the sample to each of a plurality of discrete fluid flow paths (Chang, page 2, paragraph [0021], lines 1-6 and figure 2B). Still further Chang teaches each and every combination of two or more features of the device (Chang, page 2, paragraph [0033], lines 5-7).
Although Chang is teaching up to 50 channels, and is teaching central sample port, Chang fails to teach a method comprising a device wherein the central sample introduction port is positioned to distribute the sample to a first plurality of at least five fluid flow channels and along a second fluid flow path of at least five fluid flow channels.
It would have been prima facie obvious to position a central sample port to distribute the sample along two separate fluid flow paths with at least five individual, discrete fluid flow channels each, because Chang teaches a method with a device with at least 5 fluid flow paths and a device with 4 fluid flow paths and a central sample port and further teaches that two or more features, in this case the more than 5 channels and the central sample port, can be combined. See MPEP 2144.04, the rearrangement of parts is a design choice and therefore obvious, see MPEP 2144.04, see reasoning above, the same reasoning applies here.
Regarding claim 22, Chang et al. teaches a method comprising a lateral flow immunoassay device comprising a multiplicity (plurality) of individual, discrete fluid flow channels on a single substrate (Chang et al., page 5, paragraph [0078], lines 5-8). Chang et al. further teaches depositing one or more peptide antigens from B. burgdorferi in each of the flow paths on the test strip (Chang et al., page 13, paragraph [0134], lines 5-7) comprising the IgG antigens BmpA (p39), p41, p66 (Chang et al., page 13, paragraph [0135], lines 17-22) and OspC (p23) (Chang et al., page 13, paragraph [0134], line 9) and the IgM antigens BmpA (p39), p41, VlsE (Chang et al., page 13, paragraph [0135], lines 18-26) and OspC (p23) (Chang et al., page 13, paragraph [0134], line 9). Chang further teaches a plurality of peptides immobilized in the capture zone of each of the fluid flow paths, where the plurality of peptides can be the same or different in each of the capture zones (Chang, page 13, paragraph [0135], lines1-6).
Chang further teaches a label zone on the test strip associated with a channel, where a mobilizable anti-human antibody is deposited for detecting infection by a species in the Borrelia genus. Chang further teaches that the anti-human antibody is IgG or IgM. The anti-human IgM antibody is deposited in the label zone of one of the discrete channels in the plurality of fluid flow channels and that the anti-human IgG antibody is deposited in another discrete channel (Chang, page 13, paragraph [0133], lines 19-28). Chang further teaches in Figure 14B a test strip with a single sample receiving zone (126) in communication with a plurality of discrete fluid flow channels where a first portion of the fluid flow channels and a second portion of the fluid flow channels flow in opposing directions and further teaches that each individual flow channel comprises a label zone and test (136) and control (138) zones (Chang, page 8, see entire paragraph [0103] and Figure 14B). Put another way, Chang teaches a test strip with two opposing fluid paths, each comprising a separate label zone and further teaches a test strip with anti-human IgG antibody in one label zone and anti-human IgM antibody in another label zone, opposite each other. Therefore it would have been prima facie obvious to one having ordinary skill in the art that the discrete fluid flow path comprising the anti-human IgG antibody would further comprise IgG antigens and the second distinct flow path comprising anti-human IgM antibody would further comprise IgM antigens.
Regarding claim 23, according to the Specification of the present application (paragraph [0129], lines 2-5) the first and second tier IgG antigens can be any combination or number of antigens described in the application, and the claims fail to specifically identify which of the plurality of antigens are identified as first or second tier. The antigens taught by the prior art are the same as presently claimed, as explained previously in detail above (the prior art similarly teaches first and second tier antigens, does teach antigens to IgG, as claimed).
Regarding claim 25, Chang et al. and the cited art above teach a method, comprising an immunoassay device with at least five fluid flow channels, substantially as claimed. Chang further teaches one or more binding members for detection of IgG, wherein the binding members for IgG antibodies comprise a plurality of first-tier and second-tier IgG antigens, such as BmpA (p39), p41, p66, VlsE (region IR6) (Chang et al., page 13, paragraph [0135], lines 17-29) and OspC (p23) (Chang et al., page 13, paragraph [0134], line 9). According to the Specification of the present application (paragraph [0129], lines 2-5) the first and second tier IgG antigens can be any combination or number of antigens described in the application. This comprises the antigens above, namely BmpA (p39), p41, p66, VlsE (region IR6), and OspC.
Regarding claim 28, Chang teaches a method for detecting Lyme disease (Chang, page 13, paragraph [0134], lines 3-4).
Regarding claim 29, Chang teaches a method comprising an in vitro, qualitative assay device, intended for detection of the same targeted antibodies to the same bacterium, the device similarly capable of detection in a sample such as blood (see Chang teaches that the sample type comprises blood, page 4, see paragraph [0071]).
Regarding claim 30, Chang teaches a test strip for detection and differentiation of IgG and IgM immunoglobulins against pathogenic Borrelia species. (Chang, page 13, paragraph [0136], lines 1-3)
Claims 13 is rejected under 35 U.S.C. 103 as being unpatentable over Chang et al., in view of Tokarska-Rodak, Theel ES, Myers et al., and further in view of Wagner B, US20130273572A1, 10/17/2013 (PTO-892, 08/23/2025).
Regarding claim 13, Chang et al. and the cited art above teaches a method of diagnosing disease due to a tick borne infection substantially as claimed.
Chang et al. teaches that the sample can be any material to be tested for the presence of analyte, comprising blood (Chang et al., page 4, see paragraph [0071], and the sample is derived from a person at risk or having Lyme disease (Chang et al., page 12, paragraph [0133], lines 3-5). Chang et al. further teaches that the subject at risk for Lyme disease is at an early stage of infection (Chang et al., page 12, paragraph [0133], line 8). Wagner teaches that “early” infection means that an infection is 2-6 weeks old (Wagner, page 2, paragraph [0026], lines 14-15). It has been previously established in the courts that a prima facie case of obviousness exists where the claimed ranges or amounts overlap or lie inside ranges disclosed by the prior art (see MPEP 2144.05). In the present case, 30 days lies within 2-6 week as taught by Wagner and as such it would have been considered prima facie obvious in view of Wagner to have arrived at the presently claimed 30 days out of the course of routine optimization, in order to assess early stage infection as taught by Chang.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Chang et al., , in view of Tokarska-Rodak, Theel ES, and Myers et al. as applied to claim 16 above and further in view of Egan et al., US20130230844A1, (PTO-892, 03/30/2023).
Regarding claim 27, Chang et al. and the cited art above teach a method substantially as claimed.
However, Chang et al. differs from the instantly claimed invention in that it fails to teach providing with the lateral flow assay, a positive and negative control.
Egan et al. teaches that the device is provided with a positive and a negative sample for assays that require an external positive and/or negative control (Egan et al., page 12, paragraph [0113], lines 1-5). Egan et al. further teaches a test device to which a positive control sample or a negative control sample has been deposited and further that kits provided with the test device can also include any reagents, tubes, pipettes, and swabs for use (Egan, see paragraph [0113]).
It would have been prima facie obvious to one having ordinary skill in the art to have included a positive and negative sample, as an obvious matter of applying a known technique to a known method, namely one would have recognized, that by including the positive/negative control samples, one can assess a positive/negative result of the assay sample. Even though the art does not explicitly teach a container one would have been immediately envisaged because the ordinary artisan would understand that the different reagents, such as positive/negative control samples in a kit would be contained in a container.
Response to Arguments
Applicant's arguments filed 07/11/2025 have been fully considered but they are not persuasive.
Applicant argues, starting on page 9 that the current two tier approach comprises two separate tests with a first tier to rule in infection and a second tier to rule out disease which is currently the gold standard.
Applicant further argues that the claimed method provides for both first tier and second tier analyses in a single test, where all data necessary for both first and second tier test are collected in a single immunoassay and then analyzed sequentially. Applicant argues that the claimed method provides for an immunoassay test strip with antigens for both first and second tier assay, collects an image or evaluates a signal and evaluates the image or signal with an algorithm that evaluates the signal from the first tier antigen first and if positive or equivocal, proceeds to evaluation of the second tier signal. Applicant amended the present claims to recite that if the analysis associated with the plurality of first tier IgG and IgM indicates presence or possible presence of disease and the plurality of second tier IgG and IgM indicates presence of disease, reporting presence of disease or if said evaluating of signal associated with the plurality of second tier IgG antigens and the plurality of second tier IgM antigens indicates absence of disease due to the tick-borne infection, reporting absence of disease.
Applicant argues that a person of ordinary skill would not have been motivated to modify Chang’s disclosure to arrive at the specifically defined invention in the instant claims because reading Chang does not suggest a first-tier and second tier immunoassay as defined in the claims.
This argument is not persuasive.
Chang is relied on to teach the method of detecting multiple antigens with a lateral flow assay. Tokarska-Rodak provides the motivation to modify the method of Chang to do two tier testing because of the teaching that the two-step laboratory testing process is designed to eliminate unspecific false positive results.
Applicant further argues on page 10 that Theel’s testing protocol requires a first test and a subsequent confirmatory test and does not teach or suggest obtaining data for both a first tier and a second tier analysis from a single immunoassay, but rather teaches two tests the second test being performed if the first test is positive or equivocal and one of ordinary skill in the art would not disregard the explicit teaching of Theel, let alone the preferred protocol of the CDC.
This argument is not persuasive.
Chang and the cited art above teach a method of detecting multiple first tier and second tier IgG and IgM antigen on a single lateral flow assay. One having ordinary skill in the art, already in possession of the data needed for both tiers would then be motivated to analyze the results in a two tier fashion as taught by Theel because of the teaching of Theel (as well as Tokarska-Rodak) that the two-tier testing eliminates unspecific false positive results. Theel teaches that the specificities of even new first-tiered only screening assays do not reach that of the two tiered testing algorithm (Theel, page 1194, 2nd paragraph, lines 1-3) and that, overcoming obstacles with the new first tiered screening assays, two sequential enzyme linked immunosorbent assays performed better or equivocal compared to the traditional two tiered algorithm (depending on the patient population tested) at a reduced cost (Theel, page 1194, ‘An Alternative to TTA?’, see entire paragraph).
Applicant further argues starting on page 10 that the combination of the cited art fails to suggest a method involving a single test comprising binding antigens for both a first and second tier test and that the teaching of Chang that the antigens on the immunoassay can be the same or different and that the disclosed antigens detect and differentiate IgG and IgM falls short of suggesting an immunoassay with antigens needed for the first and second tier testing for a tick-borne infection. Applicant further argues that mere mention that antigens can be the same or different does not amount to teaching an immunoassay using antigens needed to obtain data for both first and second tier analysis, let alone specifically the antigens recited in claims 1 and 16.
This argument is not persuasive.
As explained previously in detail above, Chang doesn’t merely mention that antigens can be the same or different, but rather teaches specific IgG and IgM peptides such as IgG antigens BmpA (p39), p41, p66, VlsE (IR 6), and OspC (p23) and “IgM antigens,” such as BmpA (p39), p41, VlsE and that the plurality of peptides can be the same or different in each of the capture zones and or/label zones. Chang and the cited art above further teach and provide motivation to test all the IgG and IgM antigens as claimed. Further, the specification does not provide a specific or limiting definition for the claim terms “first tier IgG antigens,” “second tier IgG antigens,” and therefore Chang teaches an immunoassay with antigens needed to obtain data for both first and second tier.
Applicant further argues that based on the teaching in Theel, that the first and second tier tests are separate, a person of ordinary skill in the art reading Chang would only have been led to use an immunoassay to detect and differentiate IgG and IgM antibodies in the context of a first tier or a second tier test since Theel makes clear that the standard is a two-step testing process. Neither Chang nor Theel alone or in combination provide any guidance that would have led a person of ordinary skill in the art to modify Chang or Theel’s two-test methods without the impermissible benefit of hindsight.
This argument is not persuasive.
The ordinary artisan reading the method of Chang with the ability to detect a multitude of IgG and IgM first and second tier antigens in a single assay would then be motivated by Theel to measure all antigens in a single assay instead of the more labor, reagent, and sample consuming two assays to arrive at the same two tier test data for multiple antigen as Theel, which is the gold standard in detecting Lyme disease. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the present case, the rejection relies only on that which was known to one of ordinary skill, see specifically, the rejection only relies on that which was taught by the prior art.
For all the reasons above the arguments are not persuasive.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Communication
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677