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 .
DETAILED ACTION
Status of Claims
1. Claims 1-18 are pending. Claims 1-18 are under examination.
Priority
2. Receipt is acknowledged of certified copies of foreign priority papers required by 37 CFR 1.55, which papers have been placed of record in the file.
3. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119(b) or 365(b), and 37 CFR 1.55 on the basis of the filing dates of foreign application JAPAN 2021-205577 filed 12/17/2021. Based on the filing receipt, the effective filing date of this application is December 17, 2021 which is the filing date of Foreign Application JAPAN 2021-205577 from which the benefit of foreign priority is claimed.
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.
4. Claims 1-18 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.
Claim 1 is ambiguous in reciting “detecting a target particle in the first measurement sample based on the first information and the second information on the first measurement sample, and detecting a background particle in the second measurement sample based on the first information and the second information on the second measurement sample” because it fails to clearly define how each of the first and second information on each of the first and second measurement sample is differentially measured and detected absent a label on a specific component so as to subsequently detect a cell complex that reflects adherence of the T cell and the antigen presenting cell. It appears that the T cell and/or a specific component of the T cell should be specifically labeled. Same analogous comments and problems apply to the next step of “detecting a cell complex….” See also claims 9, 12, and 13.
Claim 1 is vague and indefinite in reciting, “detecting a cell complex in which the T cell and the antigen-presenting cell (APC) adhere to each other in the first measurement sample, the cell complex including a T cell activated by the predetermined antigen, based on a detection result of the target particle and a detection result of the background particle” because it is unclear how the cell complex having the T cell adhered to the APC in the first measurement sample is detected on the basis of the detection results of each of the target particle and the background particle. It appears that differential measurement detection signals between the first measurement sample and the second measurement sample are involved and correlated. See also claim 12.
Claim 9 is ambiguous in reciting “a predetermined molecule or substance in the T cell” because it is unclear, as recited, what is encompassed in the recitation of “molecule” or “substance” that is predetermined relative to the T cell. Additionally, it is unclear how each of the “molecule” and “substance” are intended to be predetermined. Does Applicant intend a selected specific protein or antigen in or on the T cell that may have been activated? See also claim 10.
Claim 12 is vague and indefinite in reciting “the second information is a value based on an optical signal, obtained from an image captured by the imaging flow cytometer” because it is unclear, as recited, what is encompassed in the recitation of “value” relative to “an optical signal” in question, and relative to the “optical information reflecting the particle size” recited in claim 6. In particular, “value” as recited, is a subjective term lacking a comparative basis for defining its metes and bounds.
Claim 13 is vague and indefinite in reciting “a first threshold value corresponding to the first information” and “a second threshold value corresponding to the second information” in all occurrences in the claim because it is unclear what is encompassed in the recitation of “threshold value” corresponding to “the first information” in question, and “threshold value” corresponding to “the second information” in question and further relative to the antecedent basis recitations of “first information” and “second information” in all of their occurrences in claim 1 from which the instant claim depends.
Claim 14 is indefinite in lacking antecedent basis for the recitations of “the number of background particles” and “the number of target particles.”
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 1-10 and 12-18 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Yanagida et al. (US 2018/0292385).
Yanagida et al. disclose a method for detecting an antigen-specific activated T cell in blood sample of a subject (Abstract; Example 1). The method comprises: obtaining (preparing) a first measurement sample (A) by mixing a first separated specimen sample from the blood (biological) sample which contains a T cell (immune cell, T lymphocyte) and an antigen presenting cell (APC) (immune cell, dendritic cell (DC)) and an antigen reagent (immunostimulator) containing a predetermined antigen peptide, wherein a contact or immune synapse is formed between an activated T cell and the APC; and measuring the first measurement sample (A) mixture to obtain a first information (A1) on a particle size (cell size) and a second information (A2) (cell fluorescence signal) on a T cell activation marker (CD28) on the first measurement sample (A) to thereby detect a T cell target particle (measurement target immune T cell) optical signal in the first measurement sample (A) using an imaging flow cytometer (Abstract; [0015, 0017, 0018, 0057, 0058, 0063, 0067, 0072, 0082-0084, 0097, 0099]; Figure 11; Figure 15; Example 1); obtaining a second measurement sample (B) from a second separated specimen sample from the blood sample which contains a T cell and an APC (DC) without or not containing the antigen reagent (without stimulation); and measuring the second measurement sample (B) to obtain a first information (B1) on a particle size (cell size) and a second information (B2) (fluorescence signal) on a T cell activation marker on the second measurement sample (B) to thereby detect a background particle in the second measurement sample (B) for comparison using the imaging flow cytometer ([0018, 0063, 0097, 0099, 0158, 0159]; Example 1; Figure 10; Figure 15); detecting the target T cell particle in the first measurement sample (A) based on the first information (A1) (cell size) and the second information (A2) (fluorescence signal) on the first measurement sample (A); and detecting the background particle in the second measurement sample (B) based on the first information (B1) and the second information (B2) on the second measurement sample (B). The first information is an optical signal reflecting particle size (cell size) by detecting forward light scatter in the scattergram of the target T cell particle (Abstract; [0034]; Example 1; Figure 10; Figure 11; Figure 15). The method further comprises detecting a cell complex (immune synapse) in which the activated T cell and the APC contact and adhere to each other in the first measurement sample, the cell complex including the T cell activated by predetermined antigen-specific peptide (pathogenic bacteria), based on an optical fluorescent signal generated by a labeled predetermined antigen molecule on the activated target T cell particle bound and labeled by a capture body (labeled antibody) and a measured optical signal of the background particle (Abstract; [0015, 0042, 0055-0058, 0065, 0067, 0072, 0076, 0078, 0082-0084, 0097, 0099]; Example 1; Figure 23). The second information (A2) constitutes a surface molecule or antigen (surface antigen localization) (i.e. predetermined molecule) in the activated T cell immune synapse such as CD3, CD28, CD40L, OX40, CTLA4, PD-1, and ICOS [0015, 0017, 0060, 0067, 0072, 0081]. The cell complex is detected by subtracting the number of background particles in the second measurement sample from the number of target T cell particles in the first measurement sample. When the number of cell complexes in (A) is greater than or equal to a predetermined threshold value, it is determined that the blood sample is collected from a subject having an antigen-specific activated T cell with a specific immune response to the predetermined antigen-specific peptide ([0061, 0062, 0067, 0072]; Figure 10).
Yanagida et al. teach that the predetermined antigen in the antigen reagent is an antigenic peptide of a pathogen; wherein the pathogen is Mycobacterium tuberculosis. The antigenic peptide may also be an allergen, an autoantigen, or a cancer antigen [0067, 0072, 0167]. Yanagida et al. specifically teach that the imaging flow cytometer detects and measures an area value of the target T cell particle in an image captured by its imaging unit ([0018, 0042, 0097, 0099]; Figure 9; Figure 11; Figure 18). According to Yanagida et al., the target T cell particle is detected when the first information on the first measurement sample with predetermined antigen-specific stimulation is greater than or equal to a first threshold value corresponding to the first information and the second information on the first measurement sample is greater than or equal to a second threshold value corresponding to the second information. The background particle is detected when the first information on the second measurement sample without or having no predetermined antigen-specific stimulation is greater than or equal to the first threshold value and the second information on the second measurement sample is greater than or equal to the second threshold value corresponding to the second information ([0065, 0101]; Figure 10; Figure 15). Yanagida et al. teach incorporating immune checkpoint costimulatory molecules such as CTLA4 and PD-1 into a third measurement sample containing a T cell and an APC or DC and the antigen reagent and measuring the third measurement sample (C) mixture using the imaging flow cytometer [0081, 0102, 0103].
Accordingly, Yanagida et al. reads on Applicant’s claimed invention.
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.
6. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Yanagida et al. (US 2018/0292385) in view of Habtamu et al. (In vitro analysis of antigen induced T cell-monocyte conjugates by imaging flow cytometry. J Immunol Methods 460: 93-100 (2018)- IDS).
Yanagida et al. is discussed supra. Yanagida et al. differ from the instant invention in failing to teach that the predetermined molecule in the activated T cell is any one of a phosphorylated ERK, NF-B, NFAT, IFN γ or IL-2.
Habtamu et al. teach a method that allows assessing T cell-monocyte interactions associated with immune regulation in tuberculosis infection based on immune synapse formation using imaging flow cytometry (Abstract). Habtamu et al. found that BCG stimulation of immune cells show induced gradual increase in the proportion of conjugated T cells displaying NF-kB translocation to the nucleus. Habtamu et al. further show involvement of IFN-γ and IL-2 cytokines in T cell activation in Mycobacterium tuberculosis (MTB) infection (p. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the teaching of Habmatu in using NF-kB, IFN-γ, and/or IL-2 as predetermined molecules used in determining immune synapse formation that provides detection of antigen-specific activated T cells as taught in the method of Yanagida because Habmatu taught that it allows for simultaneous evaluation of T cell-monocyte immune synapse formation and T cell activation. One of ordinary skill would have had reasonable expectation of success in incorporating the teaching of Habmatu into the method of Yanagida because both of Yanagida and Habmatu teach analogous art in using imaging flow cytometry to detect antigen-specific activation of T cells.
7. No claims are allowed.
Remarks
8. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Abe et al. (US 2021/0082111) teach that the mitochondria and mitochondrial activity state in T cells is involved in activation state of T cells (Abstract; [0046, 0048, 0054, 0055, 0085, 0086]).
Oka et al. (US 2021/0270812) disclose a method of analyzing immune cells including T cells and antigen presenting cells by mixing a whole blood sample containing immune cells with an immunostimulatory to label a target molecule of the activated immune cell and using an imaging flow cytometer to detect an immune synapse formed between the interacting immune cells (Abstract; [0042-0083].
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
February 18, 2026