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 .
This Office Action is in reply to Applicants’ correspondence of 07/30/2026.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
In the reply filed on 10/11/2024 Applicant’s elected without traverse the invention of Group I (claims directed to measurement of CD11b, CD64, CD45 and CD117).
Claim 4 is amended to add the particular marker CD68 to the originally elected combination of markers that is CD45, CD117, CD11b and CD64. As such claim 4 now requires a non-elected combination of elements and is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election of methods directed to the particular combination that is CD45, CD117, CD11b and CD64 made without traverse in the reply filed on 10/11/2024.
Withdrawn Claim Objections
The objection to claim 30, as set forth on pages 2-3 of the Office Action of 04/23/2026, is withdrawn in light of the cancellation of claim 30.
Withdrawn Claim Rejections - 35 USC § 112 – New Matter
The rejection of claims 30-33 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as set forth on pages 3-4 of the Office Action of 04/23/2026, is withdrawn in light of the amendments to the claims.
Withdrawn Claim Rejections - 35 USC § 101
The rejection of claims under 35 U.S.C. 101, as set forth on pages 4-6 of the Office Action of 04/23/2026, is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 103
In the rejection of the amended claims, the breadth of the claimed methods is noted. The amended clams do not require any particular detected amount of the recited CD45, CD117, CD11b and CD64 markers. Nor do the amended claims require the association of any detected amount of the markers with an identification of treatment response (e.g.: refractory; relapse). Additionally it is noted that where the claims are directed to an assessment of markers in a sample form a subject that is “a candidate for treatment with a combination of venetoclax and azacitidine”, there are no particular limitations in the claims for identifying a subject that is “a candidate for treatment”. Where a combination of venetoclax and azacitidine is a known treatment for AML, any subject with AML is properly considered to be “a candidate for treatment with a combination of venetoclax and azacitidine”.
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, 6, 7, 10, 11, 15, 20, 21, 24 and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dunphy et al (2007) in view of Chang et al (2004).
Relevant to the methods of the rejected claims, Dunphy et al teaches flow cytometric immunophenotyping of AML samples (relevant to claim 21). The reference teaches detecting expression levels of CD45, CD117, CD11b and CD64 (e.g.: Table 1; p.749 – Materials and Methods), and teaches the analysis of samples form subjects with FAB classifications of M0, M1, M2, and M5 (relevant to claim 1) and M4 (relevant to claim 2). Further relevant to the side scatter limitations of claims 1 (e.g.: side scatter high) and 2 (i.e.: side scatter medium), the reference teaches that monocyte regions in samples were identified in AML samples by CD45 and side scatter properties (e.g.: p.751, right col) and teaches that in previous studies the monocyte region of leukemic cells are defined as having moderate-to-high side scatter (e.g.: p.749, left col), and teaches analysis of expression in AML blasts (e.g.: Table 1) (relevant to claims 6 and 7). Further relevant to the limitations of claims 1 and 2 as they require complex karyotypes, Dunphy et al teaches that cytogenetic results were available in all of the AML subjects of the analysis, and suggests that a combination of cytomorphology, enzyme cytochemical stains, additional FCI markers, and cytogenetic results can be used for accurate AML subtyping (e.g.: p.753, right col).
Relevant to claims 10, 11 and 15, Dunphy et al teaches the analysis of blood and bone marrow samples taken from pretreatment subjects diagnosed with AML (e.g.: p.749 – Materials and Methods; p.748 – Design).
Dunphy et al does not specifically teach that analyzed samples included complex karyotypes (relevant to claims 1 and 2), or provide the age of subjects (relevant to claims 20), or provide details of any treatment administered to the subject (claims 24 and 26). However, such aspects of analysis included in immunophenotyping AML were known in the prior art and are taught by Chang et al.
Relevant to the methods of the instantly rejected claims, Chang et al teaches methods of analysis of subjects with ages 18-86 years (e.g.: Table 1) (relevant to claim 20), including flow cytometry-based immunophenotyping of leukemic blasts in bone marrow or peripheral blood samples of AML patients with FAB M0, M1, M2, M4 and M4 including the analysis of CD45 with side scatter, CD117 and CD 11b. Relevant to claims 1 and 2 Chang et al teaches cytogenetic features of the samples, and provides that a “complex” karyotype (with five or more independent chromosomal abnormalities) was detected in multiple samples of each FAB classification (e.g.: p.45 – Cytogenetic features; Table 3). Chang et al further teaches that AML subjects are treated with arabinoside (ARA-C) and daunorubicin (DNR) (relevant to claims 24 and 26).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have included the complex karyotype detection of Chang et al in the AML analysis methods of Dunphy et al, or alternatively it would have been obvious to have included the CD64 analysis of Dunphy et al in the analysis of Change et al. Where both Chang et al and Dunphy et al provide for the analysis of various parameters (i.e.: CD markers; FAB classifications; cytogenetics; side scatter) of AML cells for the classification of AML in a subject, the skilled artisan would recognize that using the different parameters known in the prior art in addition to any parameters disclosed in a single reference would provide for a more comprehensive analysis and classification of a subject’s AML. Thus, the use of additional known markers would be the simple substitution of known elements with predictable results. Additionally, the skilled artisan may be motivated to add the methods of Dunphy et al (e.g.: including analysis of CD64) to the methods of Chang et al because Chang et al teaches that analyses including consideration of FAB classification, and Dunphy et al teaches that analysis of CD64 can be useful in distinguishing FAB M5 and FAB M4 AMLs.
Claim(s) 16, 17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dunphy et al (2007) in view of Chang et al (2004), as applied to claims 1, 2, 6, 7, 10, 11, 15, 20, 21, 24 and 36 above, and further in view of Cui et al (2014).
Dunphy et al in view of Chang et al renders obvious the assessment of AML of claim 1, from which instantly rejected claims 16, 17 and 19 depend, including detecting expression levels of CD45, CD117, CD11b and CD64 in a sample that is FAB M5 with a complex karyotype and high side scatter. Further relevant to the instantly rejected claims, Chang et al teaches therapeutic treatment of subjects with anticancer therapy (relevant to claim 19), and relapse of treated subjects (relevant to claim 17).
Dunphy et al in view of Chang et al does not teach the assessment of subjects that have been previously administered an initially therapy (claim 16), but the assessment of AML cells in subjects after treatment, including the use of flow cytometry immunophenotyping to detect leukemia-associated immunophenotypes, including subjects refractory to treatment, was known in the prior art and is taught by Cui et al.
Cui et al teaches the analysis of immunophenotypes (including the use of CD45, CD117, CD11b, and CD64, relevant to the limitations of claim 1) (e.g.: p.637 - Multiparameter flow cytometry). Relevant to the instantly rejected claims, Cui et al teaches the analysis of immunophenotypes in treated subjects that were refractory to treatment and subjects that relapsed (e.g.: Table 2; Figure 2).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have performed the assessments rendered obvious by Dunphy et al in view of Chang et al on samples taken from subjects after treatments. The skilled artisan would have been motivated to perform a post-treatment analysis of subjects, including subject that were refractory to treatment and subjects that relapsed, based on the expressed teachings of Cui et al that leukemia associated immunophenotype assessment can residual disease in refractory/relapsed AMLs, and that the presence of persistent disease can indicate a poor prognosis.
Conclusion
No claim is allowed.
Claim 18 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.
Claim 18 is directed the assessment of AML in a subject comprising the detection of CD45, CD117, CD11b and CD64 in a sample classified as: (i) FAB-M5; complex karyotype; high SSC; or (ii) FAB-M0, FAB-M1, or FAB-M2; complex karyotype; low SSC, where the subject has been previously treated with venetoclax in combination with azacitidine. The prior art does not teach or particularly suggest the required assessment in a subject previously treated with venetoclax in combination with azacitidine, and the instant disclosure teaches that the assessment is particularly relevant to relapse after treatment with venetoclax in combination with azacitidine (e.g.: para 00193 of the specification as filed).
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 STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights