DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement(s)
2. The information disclosure statements (IDS) submitted on 12/04/23 and 08/06/24 were filed and entered. The submissions are in compliance with the provisions of 37 CFR 1.97 and have been considered by the Examiner.
Election/Restrictions
3. Applicant's election, with traverse, of Group I, in the reply filed on 10/08/25, is acknowledged. The traversal is on the ground(s) that
Each invention pertains to the same or corresponding special technical feature directed to the claimed test strips, and methods of use thereof, for detecting and/or monitoring treatment of a disease in a subject. Applicant respectfully submits that across the product and method claims, the same assay is used: a metal electrode carrying a capture antibody, then an HRP-labeled detector antibody with TMB/H202, measured by amperometry;
The subject matters described in these claims are not “independent” as defined in MPEP § 803.
4. This is not found persuasive because:
As previously set forth, unity of invention is lacking. Therefore, this argument is not persuasive because the shared technical feature (i.e. a test strip with a capture antibody and electrodes) is not a special technical feature according to PCT Rule 13.2 as it does not make a contribution over the prior art in view of, for example, Mohapatra et al. 2008 (US 2008/0100279) which teaches a test strip for detecting a disease in a subject comprising antibodies, a working electrode and a combination reference and counter electrode (e.g. see abstract; Figures 1 and 4; and the art rejection below). Further, the argument is also not persuasive because it is not commensurate in scope with the claims since that particular antibody and amperometry are not required by the independent claim(s).
Independence is not the metric by which a need for a Restriction Requirement is assessed for a 371 application. Therefore, this argument is not persuasive because unity of invention (or the lack thereof) is the appropriate assessment.
Therefore, the requirement is still deemed proper and is therefore made FINAL.
5. Applicant' s species election of tuberculosis, in the reply filed on 10/02/25, is acknowledged. However, because applicant did not distinctly and specifically point out the supposed errors in the species election requirement, this election has been treated as an election without traverse (MPEP § 818.01(a)). It is noted that claim 12 does not encompass the elected species and thus, has been withdrawn (see below).
Claim Status
6. Claims 1-2, 6-7, 9-13, 15, 17-20, 26, 28-29, 36, and 41-42 are pending. Claims 3-5, 8, 14, 16, 21-25, 27, 30-35, and 37-40 are cancelled. Claims 1, 2, 6, 7, 13, 18-20, and 29 are amended. Claims 12, 18-20, 26, 28-29, 36, and 41-42 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/08/25. Claims 1-2, 6-7, 9-11, 13, 15, and 17 are under examination.
Improper Markush Grouping Rejection
7. Claim 9 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use (emphasis added). A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature; See MPEP § 706.03(y).
In the instant case, the Markush grouping of tuberculosis, COVID-19, HIV, coccidiomycosis, a disease caused by a non-tuberculosis Mycobacterium species, hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E; is improper because the alternatives defined by this Markush grouping do not share both a single structural similarity and a common use for the following reasons. The list includes both diseases (e.g. tuberculosis, coccidiomycosis, a disease caused by a non-tuberculosis species) and etiological agents of diseases (e.g. COVID-19, HIV, and Hepatitis A-E). Further, each disease is an art-recognized condition with different etiologies, symptoms, antigens, patient populations, treatments and/or diagnostics. Therefore, these diseases (and by extension the agents, antigens and antibodies thereof) do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims (although, note that the Restriction Requirement still holds) and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 1-2, 6-7, 9-10, 13, 15, and 17 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The phrase “associated with” in claim 1 (see line 5) is a relative phrase which renders the claim indefinite. The phrase “associated with” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of association is required to be included vs. excluded in the claim scope? Thus, clarification is required to remove scope ambiguity.
Claim 9 is indefinite because it is unclear what Applicant is trying to encompass with the phrase “…wherein the disease comprises…” followed by both diseases (e.g. tuberculosis, coccidiomycosis, a disease caused by a non-tuberculosis species) and etiological agents of diseases (e.g. COVID-19, HIV, and Hepatitis A-E). Thus, clarification is required to ascertain if the disease is being further limited to a particular disease, or if the target antigen is being further limited to an agent the causes disease. For the purpose of compact prosecution, it is noted that both interpretations will be employed; nevertheless, clarification is required to remove scope ambiguity. Dependent claim 11 clarifies the issue identified and thus has been left out of the rejection.
With regards to claim 13, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Claim 13 recites the broad recitation “mammal”, and the claim also recites “human” which is a narrower statement of the limitation since all humans are, by definition, mammals. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Other dependent claims do not clarify the issues identified above. Consequently, clarification is required to ascertain the metes and bounds of the claims.
Claim Rejections - 35 USC § 102
10. 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.
11. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
12. Claims 1, 2, 6, 7, 9, 10, 13, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mohapatra et al. 2008 (US 2008/0100279).
Mohapatra teaches devices comprising electrochemical sensor strips (i.e. test strips) comprising working and counter electrodes, with and without, a reference electrode, solid substrates, and at least one binding agent, including antibodies, capable of binding a target molecule wherein the binding agent is coupled to the electrode via covalent bonding (see [0018-19, 0046-47, 0065, 0110, 0126, 0142, 0149]; and Figures 1 and 4; meeting limitations found in instant claim 1). Mohapatra teaches the electrode comprises solid support substrates, made of glass, plastics and/or polyamides, covered in a thin layer of metal, including chromium and/or gold (see [0020-23; 0128]; meeting limitations found in instant claims 1, 2, and 7). Mohapatra teaches the surfaces contain reactive groups including carboxyl, amino, hydroxyl, and/or thiols for the attachment of proteins (see [0128]; meeting limitations found in instant claim 6). Mohapatra teaches the target molecule to be detected is for assessing the disease state of a subject (see [0117]; meeting limitations found in the preamble of instant claim 1). Mohapatra teaches the sample may be from a human including samples of blood, saliva and urine (see [0121]; meeting limitations found in instant claim 13). Mohapatra teaches the antibodies are selected by one of ordinary skill in the art and may be specific to a particular antigen (i.e. are not cross-reactive; see [0023]; meeting limitations found in instant claim 10). Mohapatra teaches the targeted biomarker encompass infectious agents, including Bordetella bronchiseptica (i.e. a non-tuberculosis Mycobacterium species) and/or Mycobacterium (i.e. the etiological agent of tuberculosis; see [0119]; meeting the broadest reasonable interpretation of limitations found in claim 9). There does not appear to be any component of the device than cannot be “thrown away”, thus it is the Office’s position that the device per se is disposable, thereby meeting limitations found in instant claim 17.
Accordingly, Mohapatra anticipates the invention as claimed.
Claim Rejections - 35 USC § 103
13. 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.
14. 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.
15. 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.
16. Claims 1, 2, 6, 7, 9, 10, 11, 13, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Mohapatra et al. 2008 (US 2008/0100279) in view of Dahiya et al. 2019 (Detection of Mycobacterium tuberculosis lipoarabinomannan and CRP-10 (Rv3874) from urinary extracellular vesicle of tuberculosis patients by immune-PCR; Pathogen and Disease 77: ftz049; p 1-9).
The teachings of Mohapatra are outlined above. Mohapatra is silent with regards to the particular antibody to use for the detection of mycobacterium. Therefore, the difference between the prior art and the invention is wherein the particular capture antibody is an anti-CFP-10 and/or anti-LAM antibody (see dependent claim 11).
However, Dahiya teaches the use of both CFP-10 and LAM antibodies for sensitive and specific detection of tuberculosis in urine sample from human patients (see abstract; and Table 1). Dahiya teaches both antibodies are useful but the anti-LAM antibody outperformed the anti-CFP-10 antibody (see abstract; and page 4, right column). Dahiya teaches LAM is considered an attractive diagnostic target for urine samples and can discriminated between active TB disease and latent infection (see page 4, right column, discussion). Dahiya teaches the use of monoclonal antibodies and a combination of antibodies to detect a cocktail of antigens including (LAM, CFP-10, and MPT64) will improve accuracy of detection (see page 7, right column). Further, Dahiya teaches tuberculosis is the leading cause of death worldwide from a single infectious agent and thus timely and accurate diagnosis of TB is essential to control the disease (see Introduction, page 1-2).
With regards to the limitation “…wherein the capture antibody has a capture efficiency of at least 50%” in dependent claim 15, it is noted that this limitation does not at a structural element to the device per se and therefore has been interpreted as a functional property of the antibody selected by one of skill in the art (i.e. see the teachings of Mohapatra). Nevertheless, Dahiya teaches the sensitivities attained with LAM and CFP-10 were over 90% (see abstract and page 4, results).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the device for detecting mycobacterium in human-derived samples, including urine, comprising the use of metal-coated, glass or plastic electrodes coupled to antibodies, as taught by Mohapatra, in general, by using anti-LAM and/or anti CFP-10 antibodies, in particular, thereby arriving at the claimed invention, for sensitive and specific detection of tuberculosis, which was the leading cause of death worldwide and accordingly, the timely and accurate diagnosis of TB was recognized as essential to control the disease, as taught by Dahiya. Therefore, each and every element is taught in the prior art and the combination has a beneficial result; however, the combination amounts to no more than a predictable use of prior art elements according to their established functions. The person of ordinary skill in the art would have been motivated to make the modification because the use of these antibodies, in particular the anti-LAM antibodies, would have been recognized as an attractive diagnostic target for urine samples and would have been recognized as having the ability to discriminate between active TB disease and latent infection, as taught by Dahiya. The person of ordinary skill in the art would have had a reasonable expectation of success because Mohapatra had already taught a device having metal-coated, glass or plastic working, reference and/or counter electrodes coupled to antibodies for use in detecting mycobacterium in urine samples, in general and Dahiya had already demonstrated the usefulness of anti-LAM and/or anti-CFP-10 antibodies for sensitive and specific detection of Mycobacterium tuberculosis in the same type of samples, in particular. Therefore, the combination leads to expected results because each element performs the same function as it does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, Mohapatra teaches a device that only differs from the claimed invention by the substitution of a single component (i.e. substitution of the particular antibody used for detection); the substituted element (i.e. the anti-LAM and/or anti-CPF-10 antibodies) were already known and already shown to function as a means to detect Mycobacterium tuberculosis, in the same type of sample, from the same patient population, and therefore no change in the function of the substituted element occurred. Further, one of ordinary skill in the art would be capable of substituting one antibody for another with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Pertinent Art
17. The following prior art, made of record and not relied upon, is considered pertinent to Applicant’s disclosure.
Choudhry et al. 2002 (Detection of Mycobacterium tuberculosis Antigens in Urinary Proteins of Tuberculosis Patients; Eur J Clin Microbiol Infect Dis 21: 1-5) teaches capture and detection anti-CFP antibodies are routinely used to detect Mycobacterium tuberculosis in human urine samples (see abstract; Table 1 and Figure 3). Choudry also teaches sensitive and specific use of the antibodies which do not cross-react with antigens from E. coli, Candida or Saccharomyces (see abstract; and page 2, right column, results) and demonstrated that 22 of 29 (i.e. 75%) samples from sputum-positive TB patients were detected (e.g. see page 4, left column). Therefore, Choudry teaches that one of ordinary skill in the art would recognize anti-CFP antibodies were regularly used to detect Mycobacterium tuberculosis.
Conclusion
18. No claims are allowed.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http: //www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on (571)-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY MAILLE LYONS/Examiner, Art Unit 1645
November 13, 2025