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 .
Status of Claims
Claims 1-13 are pending and have been examined.
Priority
This application 18/249,087 (PGPub: US2023/0384290) was filed 04/14/2023. This application is a 371 of PCT/US2021/55253 filed 10/15/2021, which claims benefit of US Provisional Application 63/092,951 filed 10/16/2020.
Information Disclosure Statement
The Information Disclosure Statement filed 07/19/2023 has been considered by the Examiner.
Claim Objections
Claims 9 and 12 are objected to because of the following informalities:
Claim 9 recites “determining conditions for of the analyte…” and should delete either “for” or “of”.
Claim 12 should correct “where in” to “wherein”.
Appropriate correction is required.
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 5 and 9-10 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 5 recites “the capture agent” and this limitation lacks antecedent basis as no capture agent has been previously recited.
Claim 9 recites “biomolecule production” and it is unclear what biomolecule is being referred to as no biomolecule has previously been mentioned.
Claim 10 is confusing because it recites “diagnosing the analyte” and as a diagnosis usually refers to a condition, it is unclear what the diagnosis of the analyte is intended to be. For further prosecution, the diagnosing term will be interpreted as determining.
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.
Claim(s) 1-2 and 6-12 are rejected under 35 U.S.C. 103 as being unpatentable over Baird et al. (Anal. Chem. 2019, 91, page 2028-2034, IDS) in view of Zane et al. (US 2018/0275118, IDS).
Regarding claim 1, Baird teaches throughout the publication a method of determining cellular response (page 2029, left column, last two paragraphs) comprising:
introducing a complex sample into a microwell, the microwell having a size exclusion filter, the complex sample having an analyte (page 2030, right column, Filtration of Stained Samples);
introducing a stimuli into the microwell (page 2030, right column, Fluorescent Imaging and Cell Counting, filtered cells subjected to automated fluorescent imaging by microscopy);
measuring a response from the analyte (page 2030, right column, Fluorescent Imaging and Cell Counting, images were processed to produce a single stitched image);
analyzing the response (page 2030, right column, Fluorescent Imaging and Cell Counting, stitched images analyzed using software to determine a true cell count).
While Baird does not specifically teach releasing the analyte from the microwell, Zane teaches throughout the publication mass tag analysis for a rare target analyte such as rare cells (abstract). More specifically, Zane teaches that after an interaction between the target and additional molecules, a voltage is provided to the sample to release a droplet from a pore of the microwell, wherein the droplet includes a portion of the sample and the mass spectrometry label (paragraph 0009 and for example, paragraphs 0131-0132, MS label includes an analyte captured by an affinity particle).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the method of Baird, release of the analyte from the microwell as taught by Zane because it would have been desirable to further analyze the presence of the mass spectrometry label that then indicates the presence of the target analyte in the sample (Zane, paragraph 0009). One skilled in the art would have had a reasonable expectation of success in releasing the target cell as taught by Zane within the analysis method of Baird since both methods are focused on the analysis of rare cells and use of MS labels to further analyze the sample.
Regarding claim 2, Baird in view of Zane teach the method further comprising applying a voltage in the microwell, wherein the voltage allows the analyte to exit the microwell via the size exclusion filter, and wherein the analyte comprises cells (Zane, paragraphs 0009 and 0063 and for example, paragraphs 0131-0132, MS label includes an analyte captured by an affinity particle).
Regarding claim 6, Baird teaches the method wherein the analyte is selectively captured in the microwells by an affinity agent prior to exiting the microwell (page 2030, left column, “Immunostaining Procedure”, detection antibody introduced to samples in microwell).
Regarding claim 7, while Baird in view of Zane does not specifically teach the method wherein the response from the analyte is measured before adding the stimuli into the microwell, it would have been obvious to select any order of performing the process steps in the absence of new or unexpected results, see MPEP 2144.
Regarding claim 8, Baird in view of Zane teach the method further comprising measuring molecules and/or biomolecules from the analyte in the presence of one or more compounds to determine the biological activity of the analyte (Baird, page 2031, left column, RNA analysis and page 2032, right column, Compatibility with Transcript Analysis: lysis buffers, primers and probes used to measure specific mRNA).
Regarding claim 9, Baird teaches the method further determining conditions for of the analyte that increases or decreases biomolecule production depending on the response of the analyte (page 2032, right column, Compatibility with Transcript Analysis, CK19 and ACTB mRNA analysis).
Regarding claim 10, Baird teaches the method further comprising diagnosing the analyte depending on the response of the analyte (page 2030, right column, Fluorescent Imaging and Cell Counting, determining a true cell count).
Regarding claim 11, Baird teaches the method wherein the response comprises a signal from a cell (page 2030, right column, Fluorescent Imaging and Cell Counting).
Regarding claim 12, Baird in view of Zane teaches the method wherein a response is measured in the presence of one or more compounds, and wherein the response determines the biological activity of the analyte (Baird, page 2031, left column, RNA analysis and page 2032, right column, Compatibility with Transcript Analysis: lysis buffers, primers and probes used to measure specific mRNA).
Claim(s) 4-5 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Baird et al. (Anal. Chem. 2019, 91, page 2028-2034, IDS) in view of Zane et al. (US 2018/0275118, IDS), as applied to claim 1 above (hereinafter “Modified Baird”) and further in view of Pugia et al. (US 2020/0033335, Pub Date: 01/30/2020).
Regarding claims 4-5, while Modified Baird teaches that voltage is used to release the analyte or tag (Zane, paragraph 0063) and that capture affinity agents (Zane, paragraph 0040) may be cleaved by physical or chemical methods (Zane, paragraphs 0178-0179), the references fail to specifically teach that the affinity agent is connected to a cleavable linkage arm that is connected to the microwell.
Pugia teaches throughout the publication the detection and isolation of target analytes having labels and affinity agents coupled thereto by linker arms (abstract). More specifically, Pugia teaches an analyte detection particle for detection of target analytes present within the microwell. The analyte detection particle includes a base particle, a label and an affinity agent for a target analyte. The label is attached to the base particle by a label linker arm which is coupled to the base particle, and is joined to the label by a label bond that is selectively cleavable to separate the label from the particle. The affinity agent is attached to the base particle by an affinity linker arm which is coupled to the particle, and is joined to the affinity agent by an affinity bond that is selectively cleavable to separate the target analyte from the base particle. At least one of the label bond and the affinity bond is cleavable under conditions which do not cleave the other bond, and which leave the label and/or target analyte viable for analysis (paragraph 0023).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate on the affinity agent released by applied voltage in the method of Modified Baird, a cleavable linkage arm indirectly connected to the microwell as taught by Pugia because it would have been desirable to improve mass label detection limits and sensitivity for analyte detection of labels since it is possible to detect a much lower number of labels (Pugia, paragraphs 0278 and 0280).
Regarding claim 13, while Modified Baird does not explicitly teach the method wherein the released analyte is intact, Pugia teaches that after cleavage of linking arms, the cells remained intact (page 0384). It would have been obvious to one having ordinary skill in the art at the time the invention was filed to allow the cells in the method of Modified Baird to remain intact as taught by Pugia because it would have been desirable to enhance detection capability since the cells could then be used for further analysis (Pugia, paragraph 0384).
Allowable Subject Matter
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
While the prior art teaches the application of voltages to microwells to release the analyte/mass labels for analysis of the analyte (See Baird/Zane above), the prior art fails to specifically teach that the response from the analyte triggers the application of the voltage in the microwell to then allow the analyte to exit via the size exclusion filter. For example, Zane at paragraph 0009 teaches that the voltage is applied to release the sample/MS label through the pore and then the droplet is analyzed for the presence of the MS label to indicate the presence of the target – but it is not taught that the response from the droplet specifically causes the voltage to be applied for subsequent release through the pore to exit the microwell.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677