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 .
Response to Arguments
Applicant’s arguments in light of the amendments, filed 02/25/2026, with respect to the rejection(s) of claim(s) under 35 USC 112 have been fully considered and are persuasive with the cancellation of limitations. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of 35 USC 112, 35 USC 102 and 35 USC 103 as described below.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 21 and 31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
With respect to claim 21, the limitation “with a plurality of runs of sample through the spectral flow cytometer,” “through the spectral flow cytometer running a sample,” and “fluorochromes passing through the spectral flow cytometer” is confusing. Firstly, it is unclear if actually running the sample through is part of the method steps. The method steps are only positively reciting calculating steps (generating a matrix, generating a measured sample event vector, etc) without actually positively reciting a step of running the sample through. Secondly, there is an antecedent basis since it is unclear if there are several times that the sample is run through or if all these limitations refer to the same run through. Clarification is required.
With respect to claim 31, the limitation “the measured sample event vector includes N values, and wherein the unmixed sample event vector has N values” is not supported in the specification. In fact, the specification clearly discloses the opposite (P.0154). The specification does disclose the equal N variables in P.0141-142 but for a different embodiment. The embodiment in claim 10 that 19 is dependent upon is the second embodiment, drawn to a Spectral Flow Cytometer in P.0149-0156 rather than the conventional flow cytometer in P.0140-148. Correction required.
All claims dependent on the above noted claims fail to further clarify and support the limitation of a delta function and a compensated spillover matrix and thereby are rejected likewise.
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) 21, 23, 31, and 33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sakai U.S. Patent 8,581,210.
With respect to claim 21, Sakai discloses a fluorescence intensity computing method comprising:
With a plurality of runs of a sample through the spectral flow cytometer, generating a reference matrix of spectral signatures by using a plurality of single stained compensation controls associated with a plurality of antibody capture beads single stained with differing fluorochromes (Figure 3, step (A), Col.6, l 4-6, l 38-40, Figure 4, wavelength distribution coefficients of fluorochrome n, Col.5, l 35-37)
Through the spectral flow cytometer, running a sample with a plurality of differing cells and conjugated antibodies with fluorochromes attached thereto (Figure 3, step (B), Col.2, l 55-60, Col.5, l 35-37)
Generating a measured sample event vector, representing a mixture of differing cells, by measuring fluorescence of the plurality of differing cells with attached fluorochromes passing through the spectral flow cytometer (Figure 4, Measured Fluorescence Intensities PMT1-PMT5, Col.5, l 35-37)
Generating an unmixed sample event vector for the spectral flow cytometer by using the reference matrix and the measured sample event vector to facilitate identification and quantity of types of differing cells within the sample (Figure 3, step (C), Figure 4, unmixed sample event vector = FL1-FL5 True Fluorescence Intensities, Col.2, l 65-Col.3, l 4)
With respect to claim 23, 31, and 33, Sakai discloses all of the limitations as applied to claim 21 above. In addition, Sakai discloses:
23- The unmixed sample even vector equals the measured sample event vector linearly multiplied times the reference matrix (Figure 4, Col.1, l 67- Col.2, l 5)
31- the measured sample event vector includes N values, and wherein the unmixed sample event vector has N values (Figure 4, both have 5)
33- Each single stained compensation control separately generates a differing spectral signature from respective various luminescence of fluorochromes tagged to control particles (Figure 3, (A))
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) 24, 25, 30, 34, 35, 36, 37, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Sakai U.S. Patent 8,581,210.
With respect to claims 24 and 34, Sakai discloses all of the limitations as applied to claim 10 above.
In addition, Sakai discloses:
The number of variables in both the unmixed sample event vector and the measured sample event vector is dependent upon the number of detectors and fluorochromes (Col.3, l 26-46, Col.6, l 31-67, Figure 2, claim 3, unmixed sample event vector = True Fluorescence Intensities FLx, measured sample event vector = Measured Fluorescence Intensities PMTx)
However, Sakai fails to disclose the number of variables in the unmixed sample event vector is less than a number of variables in the measured sample event vector or that the spectral flow cytometer has at least N detectors to measure M fluorochromes where M is less than N.
The situation described in the claim is when there are more detectors than fluorochromes. It would have been obvious to one of ordinary skill in the art at the time of the invention to include more detectors than fluorochromes because it is well known in the art that you need more knowns than unknowns to solve equations. In this case, the number of detectors will result in a number of known spectrum while solving for the different combinations of fluorochromes in the sample. Having a greater number of detectors will allow for easier math but also more information about the particles so that a clearer approximation can be determined for matching the spectral responses to the fluorochromes.
With respect to claim 25, Sakai discloses all of the limitations as applied to claims 21 and 24 above. In addition, Sakai discloses:
Solving for the unmixed sample event vector comprises using a least square algorithm on the measured sample even vector and the reference matrix (Col.8, l 51- Col.9, l 6)
With respect to claim 30, Sakai discloses all of the limitations as applied to claim 10 above. In addition, Sakai discloses:
Each of the single stained compensation controls includes one of: FITC, PE, ECD, PC5, PC7 (Col.2, l 5-10)
However, Sakai fails to disclose the single stained compensation controls include PerCP, PE-Cy7, APC-Cy7, or APC.
These are all well-known fluorescent labels and it would have been obvious to one of ordinary skill in the art at the time of the invention for one of ordinary skill in the art to select from any of the known options based on the source wavelengths and detector’s spectral ranges.
With respect to claims 35, 36, 37, 38, Sakai discloses all of the limitations as applied to claim 34 above. However, Sakai fails to disclose a specific value of N beyond 5.
It would have been obvious to one of ordinary skill in the art at the time of the invention to select the number of detectors, N, based upon the number of wavelengths desired to be detected. The greater variety of fluorochromes will require a greater number of detectors that can catch their responses. Additionally, the more detectors used, the smaller the range they can be focused upon which will minimize the noise. Selecting the exact number will be within ordinary skill in the art as the cost of extra detectors is balanced with the noise level and range of fluorochromes.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA CAROLE BRYANT whose telephone number is (571)272-9787. The examiner can normally be reached on M-F, 12-4 pm.
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/REBECCA C BRYANT/Examiner, Art Unit 2877