DETAILED ACTION
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 .
1. The Amendment filed June 18, 2026 in response to the Office Action of April 7, 2026, is acknowledged and has been entered.
The amendment filed June 18, 2026 provides a status identifier of “Canceled” for claim 2 but left the entire claim intact with no strike-through indicating the claim was canceled. For the sake of compact prosecution, Examiner will treat claim 2 as canceled.
Claims 1, 10-16, 59 are pending. Claims 2-9, 17-58, 60-78 are canceled. Claim 1 is amended. Claims 16 and 59 remain withdrawn. Claims 1 and 10-15 are currently being examined.
New Rejections
(necessitated by amendments)
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.
2. Claims 1, 10-12, 14-15 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 recites:
A method of treating glioblastoma in a subject comprising administering to the subject a combination immune checkpoint blockade (ICB) therapy after determining that viable CD45+ CD3- CD68+ myeloid cells in a glioblastoma tumor sample from the subject have low expression of CD73,
wherein the low expression of CD73 is determined based on an absence of, or a frequency or abundance below a threshold of, CD73hi macrophages corresponding to PhenoGraph meta-cluster L8 and/or one or more CD73hi myeloid cell clusters selected from R3, R7, R14, and R17 among the viable CD45+ CD3- CD68+ myeloid cells,
wherein the combination ICB therapy comprises (i) an anti-PD-1 or anti-PDL1 antibody and (ii) an anti-CTLA-4 antibody.
Claim 1 is unclear regarding what the “threshold of CD73hi macrophages corresponding to PhenoGraph meta-cluster L8 and/or one or more CD73hi myeloid cell clusters selected from R3, R7, R14, and R17 among the viable CD45+ CD3- CD68+ myeloid cells” is, therefore the scope of subjects determined to have viable CD45+ CD3- CD68+ myeloid cells with a “low expression of CD73” and receiving combination immune checkpoint blockade therapy is unclear.
The claim is unclear regarding what parameters and single cell data was inputted into PhenoGraph software to produce “meta-cluster L8” and “R3, R7, R14, and R17” cell clusters. PhenoGraph will produce different cell clusters depending on what single cell data is input (sequencing, mass spectrometry, flow cytometry data?), and what parameters are set in the software for cell clustering. Therefore, the resulting cell clusters are variable and the “threshold” of them is unclear.
Claim 1 does not identify what the mathematical threshold or numerical threshold value of cells is. Is it a percentile of the cells, a specific quantity or average amount of cells, or some other value? Given the recited “threshold” of cells is unclear, the scope of subjects determined to have viable CD45+ CD3- CD68+ myeloid cells with a “low expression of CD73” and receiving combination immune checkpoint blockade therapy is unclear.
The assigned names of meta-cluster L8, R3, R7, R14, and R17 do not identify what cell population is being referenced in the claim because these are arbitrary labels given to a resulting cluster of cells after utilizing PhenoGraph. Therefore the meta-cluster L8, R3, R7, R14, and R17 labels render the claim indefinite because the cell populations comprised by those labels is unclear, and the parameters input into PhenoGraph to produce those cell clusters labeled meta-cluster L8, R3, R7, R14, and R17 are unclear based on the claimed method. Therefore, the scope of subjects identified as having low CD73 expression based on a frequency or abundance below a threshold of CD73hi macrophages corresponding to PhenoGraph cluster named meta-cluster L8 and/or one or more of CD73hi myeloid cell clusters named R3 R7, R14, and R17 is unclear.
Although the specification provides an example of applying PhenoGraph cluster analysis to single cell sequencing data from glioblastoma samples, and the claims are read in light of the specification, the limitations of the specification cannot be imported into the claims (MPEP 2111.01).
Dependent claims are rejected for encompassing the rejected limitations of claim 1.
Claim 14 recites the limitation of “wherein the low expression level comprises a normalized level of expression that is determined to be decreased as compared to a control.” The claim is unclear regarding what low expression level it is referring to. “Low expression level” of what – CD45, CD3, CD68, CD73 or something else?
Claim 15 recites “wherein the CD73 expression was detected by an immunoassay”. Which CD73 expression was detected by immunoassay? In the subject tumor sample, the macrophages, or the myeloid cells?
3. Claim 13 is 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 13 depends from claim 2 which is canceled. Therefore, there is insufficient antecedent basis for the limitations in the claim.
4. All other rejections recited in the Office Action mailed April 7, 2026 are hereby withdrawn in view of claim amendments. All of the rejections of claims under 35 USC 103 are withdrawn in view of claim amendments- the cited references do not teach or suggest determining that viable CC54+CD3-CD68+ myeloid cells in a subject’s glioblastoma tumor sample are identified as having low CD73 expression by an absence or frequency/abundance below the claimed threshold of cells corresponding to meta-cluster L8, R3, R7, R14, or R17 and administering combined immune checkpoint blockade to the subject.
5. Conclusion: No claim is allowed.
Conclusion
6. 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.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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