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 .
Specification
The abstract of the disclosure is objected to because it exceeds 150 words. See MPEP § 608.01(b). The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 1, lines 17-18. 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 disclosure is objected to because the sequence on page 18 needs to be referenced with a sequence identifier. It appears that SEQ ID NO: 1 in the sequence listing filed June 2, 2023 is the identifier for the sequence on page 18. Correction is required.
Claims Summary
Claim 1 is directed to a method for facilitating the detection of target pathogen particles in a test sample. The target pathogen is a virion, a portion of a virion (SARS-CoV-2 (claim 28)), a bacterium, or a cancer cell (claim 27). The method comprises:
Providing one or more support comprising a plurality of support particles (microspheres, or a granular material, having a diameter of about 0.5 to 100 microns, or about 0.5 to 20 microns (claims 18 and 55)) and a flow cytometric apparatus; the one or more support define a support surface; the support surface has a coating of a first set of macromolecular assemblies, each of which selectively bind the target pathogen particles; the arrangement of support particles is preferably a bed or packed conglomeration (claim 14);
Providing a second set of macromolecular assemblies (provided in a liquid (claim 17)), each of which selectively binds the target pathogen particles; each of which comprises at least one fluorophore moiety; each comprise a chimeric protein, one portion of which is adapted to bind selectively to the target pathogen particles and the other portion of which is bound to the fluorophore moiety (claim 26); specifically, one portion of the chimeric protein is selected from an aptamer for the virion, or a receptor for the virion, and each virion is bound to a support particle by the aptamer which binds conformationally with the virion, or by a receptor which binds with a surface protein of the virus (claim 29); one portion of the chimeric protein comprises ACE2 (claim 31); the fluorophore moiety comprises one or more fluorescent nanobeads (claim 32);
Obtaining or providing the test sample to be assayed for the presence of the target pathogen particles therein; the test sample is a liquid (claim 10), or an aerosol of liquid droplets (claim 11); the test sample is in a fluid (claim 16);
Exposing the macromolecular assemblies to the test sample so that target pathogen particles present in the test sample bind to the macromolecular assemblies, thereby producing a multitude of target pathogen particles with a fluorophore coating, distributed over and anchored to said support surface; specifically, the first set of macromolecular assemblies is exposed to the test sample before the second set, so that the anchorage of the target pathogen particles to the support takes place substantially before the binding of the fluorophore moieties (claim 2); a plurality of target pathogen particles become bound to each support, and a multitude of fluorophore moieties are bound to each target pathogen particle (claim 20); each fluorophore comprises a nanobead (claim 21), and each nanobead comprises a multitude of fluorophore molecules (claim 22).
The support comprises a plurality of support particles and a flow cytometric apparatus, through which the support particles are induced to flow sequentially through a focused excitation source, an emitted fluorescence associated with each support particle is detected, and wherein the apparatus is adapted to determine the intensity of fluorescence associated with each support particle. The emissions detected (from each support particle) are integrated to provide a measurement of the amount of target pathogen particles present (claims 9 and 52). The support is immobile when exposed to the test sample (claim 53) with respect to a flow of test sample over the support so as to expose the support to target pathogen particles (claim 54).
The macromolecular assemblies each comprise protein and/or nucleic acids (claim 23). The macromolecular assemblies comprise an aptamer which selectively binds to the target pathogen, or a receptor thereof, and wherein one set of macromolecular assemblies comprises aptamers and the other set comprises receptors of for the target pathogen (claim 24).
One or more binding agents are used to promote or effect binding between the support surface and the first set of macromolecular assemblies and/or wherein one or more binding agents are used to promote or effect binding between the fluorophore moieties and the second set of macromolecular assemblies (claim 33).
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.
Claims 14, 16, 17 and 28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 14 and 28, the phrases "preferably" and “more preferably” render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. See MPEP § 2173.05(d). Dependent claims 16 and 17 are included in this rejection.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 9-11, 14, 16, 17, 18, 20-23, 27, 28, 33 and 52-55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ward et al. (WO 2018/140719 A1, cited in the IDS filed 6/2/2023, “Ward”). The claims are summarized above and correlated with the teachings of the prior art in bold font below. Please note that the limitations in claims 14, 16, 17 and 28 regarding the preferable embodiments, are not necessarily addressed in this rejection (see rejection of claims 14, 16, 17 and 28 for indefiniteness).
Ward discloses magnetic particle-based immunoassay methods for detecting the presence or level of an analyte of interest, e.g., SARS antigen (see paragraph [00150]) in a sample, e.g., bodily fluid, or sputum which is obtained by coughing (see abstract and paragraphs [008], [0017] and [0149] (claims 1, 10, 11, 14, 16, 17, 27 and 28)). Claim 1 of Ward discloses a method comprising contacting the sample with 1) a magnetic conjugate comprising a magnetic particle and a capture moiety that binds the analyte (claim 1, support surface coated with a first set of macromolecular assemblies each binding the target pathogen particles), and 2) a reporter conjugate comprising a reporter, e.g., a fluorophore (see paragraph [005156]), and a reporter binding moiety that binds the analyte (claim 1, second set of macromolecular assemblies each binding the target pathogen particles and having a fluorophore moiety). The two conjugates bind the analyte which is then separated from the sample with a magnetic field, thus detecting the presence or level of the analyte (see Ward’s claim 1). Figure 1A represents Ward’s generic sandwich immunoassay. The method is performed, for example, by exposing the sample to the magnetic conjugates in an assay chamber, followed by exposure to the reporter conjugates (see paragraph [00273]) (claim 2). Fluorescence of the reporter is detected by a photodetector in an analysis chamber, or a FACS apparatus, and quantified (see paragraphs [007], [0056], [0057], [0061], [0099] and [00117]) (claims 1, 9 and 52-54).
The magnetic particle of the magnetic conjugate is about 0.5 to about 100 microns, including values of about 10 and about 50 microns (see paragraph [00121]) (claims 18 and 55). The capture moiety and the reporter binding moiety may be the same or different, selected from a receptor, an aptamer, among other choices of proteins and nucleic acids (see paragraph [0064]) (claim 23). Biocompatible coatings of amine groups or carboxyl groups are disclosed to facilitate coupling of magnetic particles to, for example, capture moieties or reporter binding moieties (see paragraphs [00119]-[00120]) (claim 33). Speaking to claims 20-22, Ward discloses that the reporter comprises a metal nanoparticle, including a plurality of quantum dots (see paragraphs [0011] and [00126]-[00128]). Paragraph [00284] discloses a reporter conjugate comprising a reporter (fluorescent quantum dots). Therefore, the claimed embodiments are anticipated by the prior art.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Ward et al. (WO 2018/140719 A1, cited in the IDS filed 6/2/2023, “Ward”). Claim 24 is directed to an embodiment wherein one set of macromolecular assemblies comprises aptamers and the other set comprises receptors for the target pathogen.
The teachings of Ward are outlined above. Ward teaches that the capture moiety and the reporter binding moiety may be different, selected from a receptor, an aptamer, among other choices (see paragraph [0064]). However, the particular arrangement wherein one set of macromolecular assemblies (Ward’s magnetic conjugates) comprises aptamers and the other set (Ward’s receptor conjugates) comprises receptors for the target pathogen is not set forth. However, it would have been obvious to have used different moieties as suggested by Ward, with a reasonable expectation of success, depending on the type of analyte and binding desired. Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 26, 29, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Ward et al. (WO 2018/140719 A1, cited in the IDS filed 6/2/2023, “Ward”) as applied to claim 1 above, and further in view of Wycoff et al. (US 2022/0002699 A1, priority to 3/7/2020, “Wycoff”). The claims are directed to embodiments wherein the second set of macromolecular assemblies each comprise a chimeric protein, one portion of which is adapted to bind to the target pathogen particles, ACE2, and the other is bound to the fluorophore moiety.
The teachings of Ward are outlined above. Ward suggests targeting SARS (see paragraph [00150]), but SARS-CoV-2 was not known at the time of Ward’s disclosure. It would have been obvious to have applied Ward’s technology to the emerging SARS-CoV-2, given its global impact (see Wycoff, paragraph [0004]). Wycoff discloses ACE2-Fc fusion proteins (chimeric proteins) that bind SARS-CoV-2 spike protein (see abstract). It would have been obvious to have used Wycoff’s fusion protein in Ward’s assay as the reporter binding moiety with a reasonable expectation of success, given that the ACE2-Fc fusion has improved binding to the S protein due to the Fc domain’s effect on presentation of the ACE2 protein (see Wycoff, paragraph [0124]). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672