DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 17 July 2026. Claims 1, 8, and 10 have been amended. Claim 9 has been cancelled. Claims 15-19 have been withdrawn. Claims 1-8 and 10-14 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/US2021/041123, filed July 9, 2021, which claims priority to U.S. Provisional Application No. 63/050637, filed July 10, 2020.
Withdrawal of Objections:
The objection to claim 8, is withdrawn.
New Rejections Necessitated by Amendment:
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 1-8 and 10-14 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.
The term “stabilized” in claim 1 is a relative term which renders the claim indefinite. The term “stabilized” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what amount of stability, and how this is measured, is required for the leukocytes and erythrocytes to be considered “stabilized.”
Claims 2-8 and 10-14 are included in this rejection, as these claims depend on above-rejected claim 1, and fail to remedy the noted deficiency.
Maintenance/Modification of Rejections Necessitated by Amendment:
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.
Claims 1-8 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bari et al. (IDS; US 2019/0359941; Published Nov. 28, 2019), as evidenced by Beckman Coulter, Inc. (Cytomics FC 500 with CXP Software, Instructions for Use, (Dec. 2009), available online at: qb3.berkeley.edu/wp-content/uploads/2020/07/FC500_Manual_Instructions-for-Use.pdf – Previously Presented), and as evidenced by Stemcell™ Technologies (StemSpan™ SFEM, Accessed 10/9/2026, Available online at: www.stemcell.com/products/stemspan-sfem.html).
With regard to claims 1, 6, 10, and 11, Bari et al. teach a flow cytometry method for the analysis and counting of cells, including hematopoietic stem and progenitor cells and cells that are CD3+ and CD45+ (Abs.; Para. 221), which include T-cells. The method including using a Cytomics FC500 Flow Cytometer and CXP Analysis Software (Beckman Coulter, USA), to analyze an umbilical cord blood or peripheral blood sample, wherein the sample is treated with an imaging reagent comprising recognition elements for CD3, CD34, and CD45 (claim 1; Para. 221-223), which are recognition elements specific for markers on hematopoietic stem cells, hematopoietic progenitor cells, and T-cells. The Cytomics FC500 Flow Cytometer system taught for use in the method of Bari et al. uses sample tubes placed into a carousel (see Beckman Coulter, Inc., p. 1-13 to 1-14), wherein the sample tubes and carousel are a receptacle sample plate and sample preparation area of the flow cytometer.
While a specific step of incubating is not taught, it is taught that the blood sample and imaging reagent comprising the recognition elements for specific markers are brought into contact, where the method provides for the successful analysis of cells from the sample (Para. 222-226). As such, it would have been obvious to an ordinary artisan to incubate the sample with the taught reagent for a time sufficient to provide for the taught analysis. It is further taught that the blood sample is exposed to a lysing reagent to lyse red blood cells in the sample (para. 224-225). The prepared blood sample is analyzed by flow cytometry to obtain counts of viable and total cells that are CD3+, CD34+, and CD45+ (Abs.; Para. 217-218, 222-223; Fig. 2 (7)), which are hematopoietic stem cells, hematopoietic progenitor cells, and T-cells.
The composition comprising the imaging reagent further comprises a viability dye, including 7-aminoactinomycin D (7- AAD) (Para. 222-223). It is further taught that UCB-MNC cultures devoid of small molecules but supplemented with cytokines serve as a control (Para. 216), wherein UCB-MNC includes human red blood cells (erythrocytes) and human white blood cells (leukocytes) (Para. 264, 267), and wherein the erythrocytes and leukocytes in the UCM-MNC are deemed to be “stabilized.” It is noted that UCB-MNC culture media includes StemSpan™ Serum-Free Expansion Media (SFEM) (Para. 216), which is a liquid culture medium (see Stemcell™ Technologies). As such, the method of Bari et al. uses a control that is a liquid preparation of stabilized human leukocytes and erythrocytes.
As Bari et al. render obvious the steps as claimed, including the components as claimed, it would have been routine for one of ordinary skill in the art to utilize the taught steps in an order that provides for the most accurate results depending on the specific blood sample analyzed and desired reagents utilized in each step. Bari et al. teach that cells may be counted using an automated differential hematology cell counter (Para. 217). As such, the method is deemed to be an automated flow cytometric method. Further, as Bari et al. render obvious the method as claimed, including the components as claimed, the method is necessarily an automated flow cytometry method.
With regard to claim 2, Bari et al. render obvious the method as claimed, including the components as claimed. As such, the duplication of the method with additional blood samples would have been obvious to an ordinary artisan desiring to confirm the analysis.
With regard to claims 3-5, Bari et al. teach the use of a reference compound, reference vehicle, and blank control when performing cytometric analysis on the cells with reference markers including CD34 and CD3 (Para. 70, 71, 73, 74, 76, 79, 221; Figs. 8-13, 17), which is conducting the method with a negative control, wherein the negative control is for CD34 or CD3.
With regard to claims 7 and 8 Bari et al. teach that the imaging reagent comprises an FITC or PE fluorescent reporter (Para. 222-223).
With regard to claim 12, Bari et al. teach that the method includes performing flow cytometry using a Cytomics FC500 Flow Cytometer (Beckman Coulter, USA), wherein the Cytomics FC500 Flow Cytometer system taught for use in the method of Bari et al. uses 12 x 75 mm tubes and 24 or 96-well plates for sample analysis (see Art of Record: American Laboratory Trading, p. 3). As Bari et al. teach that the Cytomics FC500 Flow Cytometer is used to perform the method, it would have been obvious to an ordinary artisan to utilize one of the sample tray options usable with the system, including a 96-well microtiter plate.
Claims 1, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Bari et al., as evidenced by Beckman Coulter, Inc., as applied to claim 1 above, and further in view of Rodriguez et al. (IDS; US 6,228,652; Published 2001).
The teaching of Bari et al. as applied to claim 1 have been set forth above.
With regard to claims 13 and 14, Bari et al. do not specifically teach that treating the receptacles with the reagent is performed by an automated pipettor configured to deliver predetermined volumes of the reagent; or that incubating is automated.
Rodriguez et al. teach the use of an automated system for analyzing cells in a whole blood sample (Col. 4, line 19-24). The sample is prepared for analysis in the automated system using a plurality of mixing chambers, where a fluorescent stain is injected into the mixing chamber with the sample in a metered volume (Fig. 2; Col. 11, line 46 to Col. 12, line 2), which is using an automated pipettor to deliver predetermined volumes of reagent. Additionally, incubation for the sample and reagent mixture is automated and conducted for a predetermined period of time (Col. 13, line 14-33).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Bari et al. with Rodriguez et al., because both teach analyzing cells in a blood sample. The use of an automated system for performing analysis of cells in a blood sample, including using an automated pipettor to deliver predetermined volumes of reagent to the sample, and providing automated incubation of the sample with a reagent for a predetermined period of time, is known in the art as taught by Rodriguez et al. The use of automation as taught by Rodriguez et al. would have been expected to predictably and successfully improve the method of Bari et al., by providing an automated system capable of performing the method. Thus, making the method more efficient by eliminating the need for a person to perform each step of the method.
Response to Arguments
Applicant urges that Bari does not teach a step directed to the enumeration (counting) of cells. Further, Bari does not teach the claims as amended, including the limitation that the method uses a control that is a liquid preparation of stabilized human leukocytes and erythrocytes. The noted deficiencies are not remedied by Beckman Coulter, Inc. (evidentiary reference) or Rodriguez.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Bari does not teach a step directed to the enumeration (counting) of cells; as noted in the rejection, Bari teaches that the prepared blood sample is analyzed by flow cytometry to obtain counts of viable and total cells that are CD3+, CD34+, and CD45+ (Abs.; Para. 217-218, 222-223; Fig. 2 (7)), which are hematopoietic stem cells, hematopoietic progenitor cells, and T-cells. For example, Bari specifically recites that “[t]he extracted cells were counted using an automated differential hematology cell counter…” (Para. 217, emphasis added); “[c]ounted UCB-MNC was cryopreserved…” (Para. 216); and in figure 2 “Harvest cells and perform the following assays: TNC count…” (Fig. 2).
With regard to Applicant’s argument that Bari does not teach the limitation that the method uses a control that is a liquid preparation of stabilized human leukocytes and erythrocytes; as noted in rejection above, Bari teaches that UCB-MNC cultures devoid of small molecules but supplemented with cytokines serve as a control (Para. 216), wherein UCB-MNC includes human red blood cells (erythrocytes) and human white blood cells (leukocytes) (Para. 264, 267), and wherein the erythrocytes and leukocytes in the UCM-MNC are deemed to be “stabilized.” It is noted that UCB-MNC culture media includes StemSpan™ Serum-Free Expansion Media (SFEM) (Para. 216), which is a liquid culture medium (see Stemcell™ Technologies). As such, the method of Bari et al. uses a control that is a liquid preparation of stabilized human leukocytes and erythrocytes.
With regard to the evidentiary and secondary references, the noted deficiencies of Bari have been addressed above.
Conclusion
No claims are allowable.
Previously Presented Art of Record:
American Laboratory Trading, Beckman Coulter Cytomics FC500 MPL Flow Cytometer, Accessed: 4/18/2026; Available online at: americanlaboratorytrading.com/lab-equipment-products/beckman-coulter-cytomics-fc-500-mpl-flow-cytometer-19402/?srsltid=AfmBOoq BaRlYK90dI1GYer8aj4ADf-YkOX7neaWTksWRbJQlu1qru9ly (Cytomics FC500 Flow Cytometer system uses 12 x 75 mm tubes and 24 or 96-well plates for sample analysis).
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 JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
