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 .
Election/Restrictions
Applicant's election with traverse of Group I, in the reply filed on 10/27/25 is acknowledged. The traversal is on the ground(s) that the amended claims are in compliance with MPEP §806.05(h) in that they are neither a “materially different” product; nor can the product can be used in a “materially different” method. The Group I method cannot be practiced with a materially different system. Every step of the Group I method relies on the unique components of the system of Group II. Without the “anti-CD81-coated substrate,” the EVs cannot be specifically extracted (alternative methods like ultracentrifugation may lead to introducing impurities and thereby causing false positives). Without “LAM/LprG-specific antibody-conjugated nanoparticles,” the target antigens cannot be bound (non-specific nanoparticles fail to recognize LAM/LprG). Further, without a “dark field microscope,” the optical signal of the nanoparticles cannot be detected (note that conventional light microscopes are not sufficient in terms of resolution). Applicant argues that the Group I method is therefore suitable for and specific to a Group II system as claimed, and applicant is unaware of a materially different alternative system. The Group II system also cannot be used in a materially different method. The claimed components in the claims of Group II are tailored exclusively to use in MTB-LAM/LprG detection. The anti-CD81 antibody on the substrate only binds EVs (not other pathogens like SARS-CoV-2 or influenza viruses), the antibody-conjugated nanoparticles only recognize LAM/LprG (not bacterial proteins from Staphylococcus aureus or other species. This is not found persuasive because even though the system (product) may require specific antibodies this product having the antibodies could be used in a materially different process such as sample separation or purification or the system could be used in light studies (NOTE: the recitation “for detecting an MTB-specific antigen” is intended use of the product). The system isn’t exclusive to the method of Group I but clearly the system can be used to specifically bind and separate components from a sample or purify these components from a sample. The requirement is still deemed proper and is therefore maintained.
The amendment filed 10/27/25 is acknowledged and has been entered. Claims 1-2, 8, 10, 15 and 17 have been amended. Claims 6, 12, 16 and 18-22 have been canceled. Claims 8-11 and 13-14 are withdrawn as being directed to non-elected inventions. Accordingly, claims 1-5, 7, 15 and 17 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g. para 0138). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 15 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and/or to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The claims are directed to a naturally occurring correlation between the presence of LAM and LprG and mycobacterium infection.
Step 2A, Prong 2
The additional elements of extracting extracellular vesicles in a bodily fluid sample; mixing antibody-conjuaged nanoparticles and detecting the presence of LAM and/or LprG do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Also, with respect to the recitation “determining the tuberculosis infection status based on the presence of the first and the second MTB-specific antigens…”. The “determining” statement at best articulates the judicial exception, amounting only to a general instruction to apply or use the judicial exception. This could read on mental activity being performed solely in a practitioner’ head, e.g. A mental appreciation of the presence of the recited biomarkers being correlated with MTB. No active method steps are invoked or clearly required; the “determining” statement does not include any activity that would constitute a practical application, i.e. steps that apply, rely on or use the natural principle in a manner such that the claims amount to significantly more that the natural principal itself.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims are recited with a high level of generality and do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. (the active method steps/limitations recited in addition to the judicial exceptions themselves) and do not add significantly more to the judicial exception(s).
As shown by the art below it is well known routine and conventional in the art to extract extracellular vesicles in a bodily fluid sample; mix antibody-conjuaged nanoparticles and detect the presence of LAM and/or LprG
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is indefinite in the recitations “CS-35”, “CS-40” and “A194-01” because the characteristics of these antibodies are not known. The use of CS-35”, “CS-40” and “A194-01” as the sole means of identifying the claimed antibodies renders the claim indefinite because this is merely a laboratory designation that does not clearly define the claimed product, since different laboratories may use the same laboratory designations to define completely distinct cell lines/hybridomas. Amending the claim to recite the appropriate ATCC Accession Numbers would obviate this rejection.
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 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Newman et al (WO 2015/112382)(submitted in the IDS filed 02/14/23) in view of Sun et al (Science Direct, 2017, pages 1-19)(submitted in the IDS filed 02/14/23).
Newman et al discloses methods for detecting an infection or an infectious agent associated disease condition in a subject (e.g. abstract, pages 3-4) based on biomarkers in a bodily fluid sample from the subject. Newman et al discloses that the infection can be mycobacterium tuberculosis (e.g. para’s 0057, 0059). Newman et al discloses the method comprises preparing an exosome preparation (extracellular vesicles) from the bodily fluid and isolating the exosomes by contacting the body fluid with beads coated with one or more antibodies such as anti-CD81 antibodies (2nd antibody/binding agent) (e.g. para’s 0014, 0116, 0127 & page 35). Newman et al discloses and embodiment wherein a binding agent such as an antibody that specifically binds an infectious agent-associated biomarker biomarker is immobilized to a solid support to facilitate washing and subsequent isolation of the complex, prior to contacting the antibody with a sample (e.g. para’s 0014, 0042, 0092). Newman et al discloses contacting complexes with a detection reagent such as an antibody (first antibody) (e.g. para’s 0092-0093).
Newman et al differs from the instant invention in failing to teach the biomarker is lipoarabinomannan (LAM) and the use of dark field microscopy.
Sun et al teaches the detection of a mycobacterium tuberculosis antigen for distinguishing patients with tuberculosis from healthy subjects and teaches that the antigen to be detected is lipoarabinomannan (LAM) (e.g. page 9). Sun et al teaches that the detection is performed by using dark field microscopy wherein antibody conjugated probes are used in the method (e.g. pgs 1-3, 9). Sun et al teaches that the antibodies can be biotinylated and bound to avidin functionalized gold nanorods (nanoparticles) (e.g. pg 4). Sun et al teaches that this dark-field microscopic analysis is highly useful for a variety of research and biomedical applications (e.g. pg 1) and allows simple and rapid assay quantitation, and may thus serve as a valuable platform for biomarker quantitation in resource-limited settings, where simplicity and robustness are more important than absolute assay sensitivity (e.g. page 3).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the detection of lipoarabinomannan (LAM) and the use of dark-field microscopy such as taught by Sun et al into the method of Newman et al because Sun et al shows that it is known and conventional in the art to detect LAM for the assessment of tuberculosis and that dark-field microscopic analysis is highly useful for a variety of research and biomedical applications and allows simple and rapid assay quantitation, and may thus serve as a valuable platform for biomarker quantitation in resource-limited settings, where simplicity and robustness are more important than absolute assay sensitivity. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating the detection of lipoarabinomannan (LAM) and the use of dark-field microscopy such as taught by Sun et al into the method of Newman et al.
Claims 2, 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Newman et al and Sun et al as applied to claims 1 and 7 above, and further in view of Achkar et al (US 2015/0260714).
See above for the teachings of Newman et al and Sun et al.
Newman et al and Sun et al differ from the instant invention in failing to teach the detection of LprG.
Achkar et al teaches methods for the detection/diagnosis of tuberculosis in patients and teaches a correlation between the presence of LprG and tuberculosis (e.g. para’s 0019, 0028, 0036, 0053, Table 1). Achkar et al teaches the detection of the LprG is achieved with the use of a monoclonal antibody for LprG (e.g. para’s 0019, 0028).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the detection of LprG and the use of antibodies for LprG such as taught by Achkar et al into the modified method of Newman et al because Achkar et al specifically teaches a correlation of the presence of LprG and tuberculosis. Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating the detection of LprG and the use of antibodies for LprG such as taught by Achkar et al into the modified method of Newman et al. Further, one of ordinary skill in the art would understand that additional tests and assessments known to be correlated with tuberculosis would provide a more confident assessment of tuberculosis. It has long been held that it is obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, one of ordinary skill in the art would have a reasonable expectation of success to incorporate the detection of LprG and the use of antibodies for LprG such as taught by Achkar et al into the modified method of Newman et al.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Newman et al and Sun et al as applied to claims 1 and 7 above, and further in view of Sigal et al (Journal of Clinical Microbiology, December 2018, Vol 56; Issue 12, pages 1-21).
See above for the teachings of Newman et al and Sun et al.
Newman et al and Sun et al differ from the instant invention in failing to teach the first antibody for LAM is A194-01.
Sigal et al teaches that it is known and conventional in the art to use an A194-01 antibody for the detection of LAM (e.g. pgs 3, 5-6). Sigal et al teaches that this detection antibody is sensitive and gives 2-5 fold higher signals (e.g. page 6).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate an A194-01 antibody such as taught by Sigal et al into the modified method of Newman et al because Newman et and Sun et al is generic with respect to the antibody for the LAM and Sigal et al shows that this detection antibody is sensitive and gives 2-5 fold higher signals. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating an A194-01 antibody such as taught by Sigal et al into the modified method of Newman et al.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Newman et al and Sun et al as applied to claims 1 and 7 above, and further in view of Diamandis et al (Immunoassay, Chapter 11, The Avidin-Biotin System, pages 237-267, 1996).
See above for the teachings of Newman et al and Sun et al.
Newman et al and Sun et al differ from the instant invention in failing to teach the anti-LAM antibody is biotin functionalized and the particles are avidin-functionalized.
Diamandis et al teaches the use of avidin-biotin system in immunoassay methods. Diamandis et al disclose that antibody can be conjugated with biotin and avidin conjugated with a probe (p. 256-258, Figs 11.6-11.7). Diamandis et al discloses that streptavidin can be substituted for avidin (p. 248). Diamandis et al disclose that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay (p. 237 & 256-258).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate biotin and avidin into the modified method Newman et al because Diamandis et al teaches that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating biotin and avidin into the modified method of Newman et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678