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 of Species D (claim 9) from Genus A and Species D (claim 17) from Genus B in the reply filed on 3/7/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The following claims are therefore withdrawn: claims 3, 5-6 and 10-12.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because:
claim 3 recites “SEQ. ID #1”; and
page 17 of Applicant’s specification (as originally submitted) recites SEQ ID #1, #2 and #3, and their respective amino acid sequences; and
page 61 recites amino acid sequences with respective references as “SEQ ID NO://”.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Examiner also notes the following deficiencies.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Examiner notes that the following is insufficient since there is no actual number following “SEQ ID NO:”:
page 61 recites amino acid sequences with respective references as “SEQ ID NO://”.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
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 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 1, 7, 8, 13, 15 and 17-23 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 (and therefore its dependent claims) and claim 23 contains the trademark/trade name Q-card. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a card that can contain the intracellular reaction product, and, accordingly, the identification/description is indefinite.
Examiner notes that Q-card (or the term QMAX Card which is used interchangeably with Q-Card, as noted in paragraph 0028 of Applicant’s specification in the PreGrant publication US 20230021254) is a trademark or trade name since it is used to identify a source of goods, and not the goods themselves. Accordingly, the identification/description is indefinite since the product limitations cannot be ascertained since the trademark or trade name merely identifies the source of the product, and the product is subject to change by the product source. Examiner has not located evidence to the contrary, nor evidence to support that one skilled in the art would be able to ascertain the limitations of a Q-card, and that such limitations are not subject to change by the source of a Q-card.
For examination purposes, since the required limitations of a Q-card cannot be ascertained (for
the reasons set forth above), the term Q-card in the claims is interpreted to be a card.
Moreover, while both independent claims 1 and 23 recite “to form an intracellular reaction product within a closed Q-card”, it is not clear in either claims as to whether a Q-card is actually required by the claims. Both claims recite contacting, but it is not clear what is being contacted with what. It is not clear if the sample is being contacted with the card that must be provided in the claims, or whether the cell is being contacted with the intracellular stain.
Claim 7 recites “wherein at least one disease diagnosis is selected from: a blood cancer, an
infectious disease, an autoimmune disease, a primary immunodeficiency (PID), a genetic disease, a benign urinary tract disease or condition, a urinary tract cancer, or a malignant disease.”
It is not clear if the disease diagnosis is limited to this or can include other disease diagnosis since the term “comprising” or “consisting of” is not used. For examination purposes, the claim will be interpreted to be reciting “comprising”.
Likewise, claim 17 recited “wherein the sample is a fresh crude biological sample selected from a needle biopsy, whole blood, urine, sputum, saliva, a swab sample (e.g., a pap smear), sweat, breath, breast milk, bile, or results from pathological process (such as blister or cyst fluid).”
It is not clear if the sample is limited to these or can include other sample types since the term “comprising” or “consisting of” is not used. For examination purposes, the claim will be interpreted to be reciting “consisting of”.
Also Regarding claim 17, the phrase “e.g.” (i.e., "for example") renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Also regarding claim 17, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim(s) 1, 2, 4, 7-9, 13-23 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 20030170613 (hereinafter “Strauss”).
Applicant’s claim 1 recites:
A method for determining the presence and the quantity of one or more intracellular biomarkers indicative of a disease in a sample containing at least one cell, comprising:
contacting the sample containing at least one cell and an intracellular stain formulation for a targeted intracellular biomarker to form an intracellular reaction product within a closed Q-card [interpreted to be a card] if the targeted intracellular biomarker is present;
imaging the intracellular reaction product with an imager to generate an image of the intracellular reaction product;
analyzing the image to generate an analysis of the intracellular reaction product to determine the presence and the quantity of one or more intracellular biomarker;
and generating at least one disease diagnosis by correlating the determined presence and the quantity of one or more intracellular biomarker measured in the method with a database of correlated biomarker and disease combinations.
Applicant’s claim 23 recites:
A method for correlating a measured intracellular biomarker in a first cell with a measured diseased second cell or an organism having the diseased second cell, comprising: contacting a sample containing at least one cell and an intracellular stain formulation to form an intracellular reaction product within a closed Q-card; imaging the intracellular reaction product with an imager to generate an image of the intracellular reaction product; analyzing the image to generate an analysis of the intracellular reaction product to determine the presence and the quantity of the measured intracellular biomarker; and generating at least one disease diagnosis by correlating the determined presence and the quantity of the measured intracellular biomarker with a database of correlated biomarkers and disease combinations.
The following disclosures by Strauss meets these limitations of Applicant’s independent claims 1 and 23.
The invention provides efficient methods for rapidly and sensitively identifying cellular and viral targets in medical, industrial, and environmental samples. The invention labels targets and then detects them using large area imaging. Diagnostic tests based on the invention can be rapid, ultrasensitive, quantitative, multiplexed, and automated. See abstract.
A test can scan for the presence of five types of upper respiratory viruses (RSV, influenza A, influenza B, parainfluenza, and adenovirus) using five virus-specific monoclonal antibodies. Para. 0063.
Disclosed is detecting M. tuberculosis using non-magnified large area imaging. Para. 0144.
A test scans a sputum sample for the presence of M. tuberculosis, the bacterial pathogen that causes tuberculosis. After heat-fixing a sputum sample to a microscope slide, the sample is incubated with labeled antibodies that specifically bind to M. tuberculosis (anti-MTB Ab). The unbound antibodies are removed leaving only the antibodies that are bound to M. tuberculosis bacteria. The antibodies are labeled with a fluorophore, so that when illuminated with one color of light (the excitation spectrum), they emit a second color (the emission spectrum). Illuminating the slide with the excitation spectrum causes the antibodies, which are localized at the sites where bacteria are fixed to the slide, to emit light in the emission spectrum. The emitted light is focused onto the array of pixels on a CCD chip. Pixels lying beneath a fluorescent bacterium are illuminated and transmit an electronic signal to a computer where it is preserved as an image. Software analyzes the image and the user interface reports the number of bacteria found in the scan. Para. 0145.
A CCD-based imager was used to collect data….The apparatus can detect labeled targets on various detection surfaces (e.g., porous membranes, microscope slides, microtiter dishes, coverslips, and tubes with flat, optically clear, bottoms). The incident light strikes the detection surface inducing fluorescence in the signaling moieties that are bound to targets via category-binding molecules and that are deposited on the optically clear surface. A portion of the emitted fluorescent light is collected by a high-collection efficiency lens system and transmitted to a CCD Camera. Para. 0147.
Combinatorial labeling using multiple signaling moieties (labels) can be used to achieve high signal complexity (i.e., a large number of distinct signal signatures). Each of the three pathogens represented in the diagram are labeled with a distinct combination of quantum dots. Thus, each pathogen emits the distinct coded signal (shown as a colored bar code to the right of the pathogen). The category-binding molecules shown are pathogen-specific oligonucleotide probes that hybridize to genomic DNA. Each probe is conjugated to a fluorescent quantum dot. Many types of category-binding molecules (e.g., antibodies, ligands, PNA probes, etc.) can be used for combinatorial labeling as can other types of signaling moieties (e.g., fluorophores, fluorescent particles, RLS light-scattering particles, etc.). Para. 0151.
Quantitative analysis of the images was carried out by software. (Para. 0167.
In an example, a respiratory sample is scanned for the presence of bacterial pathogen, Mycobacterium tuberculosis. The bacteria are labeled with a fluorescent chemical, a fluorophore, so that they emit light of a specific color (the emission spectrum) when illuminated by a light of a different color (the excitation spectrum). To develop reagents for labeling the bacteria, a category-binding molecule is first chosen. An ideal category-binding molecule would be a monoclonal antibody that binds to M. tuberculosis but to no other type of bacterium or substance that might be present in a respiratory sample. The antibody might, for example, bind specifically to a particular molecular site, a "category-specific binding site," that is found only on the surface of the M. tuberculosis bacterium. Next, the M. tuberculosis-specific category-binding molecule is labeled by conjugation to a fluorophore, e.g., fluorescein. The fluorescein molecule is called the "signaling moiety," as it provides the signal to be detected in the test. Having prepared the category-binding molecule (the anti-M. tuberculosis antibody) labeled with the signaling moiety (fluorescein), diagnostic tests for M. tuberculosis can be performed. Para. 0257.
The invention can identify pathogens in a human bodily fluid sample, such as blood, urine, cerebrospinal fluid, sputum, or feces. Para. 0270.
In some cases, sample preparation is required to make internal category-specific binding sites accessible. This is the case, for example, when category-specific DNA sequences are used to bind to category-specific binding sites on genomic DNA. Target cells must be made permeable to the probes and their genomic DNA must be denatured. When a large number of different types of targets are tested for in the same sample, the sample preparation must be effective for the entire spectrum of targets. Para. 0301.
Detection of the targets labeled with signaling moieties is effected once the complexes are localized in a detection zone. The detection process used depends on the type of signal character of the signaling moieties (e.g., fluorescence, chemiluminescence, or light scattering). Para. 0312.
The CCD camera-based imager can be used for large area imaging using when fluorescence is used as the signal character. The device shown in FIG. 3 can detect labeled targets on various detection surfaces (e.g., microtiter wells, microscope slides, coverslips, and tubes with flat, optically clear, bottoms). The incident light strikes the detection surface inducing fluorescence in the signaling moieties that are bound to targets via category-binding molecules. A portion of the emitted fluorescent light is collected and transmitted to a CCD Camera. The design and construction of the optical train is based on principles and practices known to workers familiar with the art. Para. 0317.
For embodiments of the invention that use imaging detectors, computer software identifies and quantifies the targets. In general the software: (1) corrects for illumination non-uniformity; (2) if necessary, corrects for fluorescence cross-talk through a deconvolution matrix; (3) if necessary, aligns images using registration marks imprinted on the substrate; (4) performs algorithms to distinguish targets from other signals; (5) assigns an identity to each imaged target in the sample; (6) calculates the total number of targets in each category; (7) images and records the sample bar code for sample identification; and (8) automatically saves the output data (including internal standard and sample data), images, and bar code to a database that can be queried via a web browser interface. Commercially available image analysis packages can be used to provide these functions. Software packages for multicolor image analysis can be used. Para. 0331.
In an example utilizing a mixture of the anti-E. coli magnetic and fluorescent particles, wells of a 96-well glass bottom plate were provided and the sample was added. To the wells were added buffer or blood. Fixed E. coli O157:H7 cells were added to three of the wells that contained buffer and three of the wells that contained blood. The wells were sealed using a storage mat (Corning COSTAR, Cat. No. 3080). The samples were incubated with rotation. Para. 0365.
Quantitative analysis of the images was carried out by software that counts the number of fluorescent objects and that integrates the intensity of all of the objects. Para. 0370.
Thus Strauss meets Applicant’s independent claims 1 and 23. Examiner notes that sealed wells (para. 0365) meets Applicant’s claimed “closed Q-card” [see also interpretation of Q-card above under the rejection under 35 USC 112.] Examiner also notes that Strauss in paragraph 331 teaches Applicant’s claimed limitations of “and generating at least one disease diagnosis by correlating the determined presence and the quantity of one or more intracellular biomarker measured in the method with a database of correlated biomarker and disease combinations”.
As to claims 7, 18-21, see discussion of claim 1 above, and see also, for example paragraph 0257 of Strauss disclosing diagnosis of tuberculosis [an infectious disease].
As to claim 8, see paragraph 0331 of Strauss.
As to claims 13 and 15, see discussion of claim 1 above, in which the claimed contact is in one step.
As to claim 17, see Strauss in paragraph 0270 disclosing sputum.
As to claim 22, see Strauss in paragraph 0301 disclosing nucleic acid, and see paragraph 0063 disclosing antibodies.
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.
Claim(s) 2, 4, 9, 14, 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20030170613 (hereinafter “Strauss”).
As to claim 2, Strauss, discussed above, is silent as to the database of the correlated biomarker and disease combinations being based on an extracellular measurement concentration of viral responsive biomarker and the diseased cell.
Likewise, as to claim 4, Strauss is silent as to the database of the correlated biomarker and disease combinations being based on an extracellular measured concentration of a viral biomarker and the diseased cell.
However, it would have been predictable by one skilled in the art that the database correlation can be based on an extracellular measurement concentration of viral responsive biomarker and the diseased cell, given that that result provides the necessary comparison for determining the presence and quantity of the intracellular biomarker measured. Such predictable outcome renders the claimed limitation obvious.
As to claim 9, see discussion of claim 1 above regarding a stain [label] and probe [e.g., antibody]. Moreover, the following disclosure by Strauss implies that a permeabilizer is provided.
In some cases, sample preparation is required to make internal category-specific binding sites accessible. This is the case, for example, when category-specific DNA sequences are used to bind to category-specific binding sites on genomic DNA. Target cells must be made permeable to the probes and their genomic DNA must be denatured. When a large number of different types of targets are tested for in the same sample, the sample preparation must be effective for the entire spectrum of targets. Para. 0301.
While Strauss is silent as to a formulation that comprises the cell permeabilizer (in addition to the stain reagent and probe] and a buffer, combining such reagents into a formulation for use according to Strauss requires ordinary skills, and would have resulted in a predictable outcome in its usage according to the disclosures of Strauss, as they are the disclosed reagents in the assay method, and use of buffers are well known in the assay art.
As to claims 14 and 16, see discussion of Strauss above regarding claim 1. However, Strauss is silent as to one of the recited steps (such as contacting or analyzing) is accomplished in 60 seconds or less. However, this appears to fall within a workable range of the Strauss invention, and as such requires ordinary skills in the art given the general teachings by Strauss of the assays steps.
