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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Group II, claims 31-105, without traverse, filed November 26, 2025 is acknowledged and has been entered. Claims 1-3, 5-7, 11, 12, 14, 16-21, 26, 29, 30, and 59 have been cancelled. Claims 87-105 have been added. Accordingly, claims 31 and 87-105 are pending and are under examination.
Priority
2. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Based on the Filing Receipt, the present application claims the benefit of Provisional Application Number 63/313,047 filed on 02/23/2022. Accordingly, the effective filing date of this application is February 23, 2022 which is the filing date of Provisional Application Number 63/313,047 from which the benefit of domestic priority is claimed.
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.
3. Claims 31 and 87-105 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 31 in step d) is vague and indefinite in reciting “reference level”, “increased number”, and “decreased number” in all occurrences in the claim because “level”, “increased”, and “decreased” are subjective terms lacking a comparative basis for defining their metes and bounds. Additionally, although the terms “reference level”, “increased”, and “decreased” are generally described, by way of examples, in the specification at paragraphs [0007, 0017, 0028, 0031, 0052-0054, 0057, 0058, 0080, 0081], the teachings fail to provide a specified standard for ascertaining any requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 31 in step d) is further ambiguous in reciting “improved” and “poor” because “improved” and “poor” are subjective terms lacking a comparative basis for defining their metes and bounds. Additionally, although the terms “improved” and “poor” are generally described, by way of examples, in the specification at paragraphs [0080-0083], the teachings fail to provide a specified standard for ascertaining any requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See also claims 102-105.
Claim 31 in step d) is also vague and indefinite in reciting “low frequency” and “high frequency” because “low” and “high” are subjective terms lacking a comparative basis for defining their metes and bounds. Additionally, although the terms “low” and “high” with respect to frequency are generally described, by way of examples, in the specification at paragraph [0083], the teachings fail to provide a specified standard for ascertaining any requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See also claims 102-105.
Claim 92 recites the use of “one or more fluorophore-labeled antibodies specific for one or more cell surface antigens;” however, claim 4 fails to clearly define what method steps encompass this claimed use especially relative to the components recited in claim 31 from which the instant claim depends. In particular, it is unclear what essential structural and/or functional cooperative relationship exists between the “one or more fluorophore-labeled antibodies specific for one or more cell surface antigens” and the blood sample and/or the viable blast-transformed mononuclear cells and viable large granular lymphocytes recited in claim 31. Same analogous comments and problems in claim 92 apply to claim 93.
Claim 93 lacks clear antecedent basis in reciting “the one or more labelled antibodies.” Perhaps, Applicant intends “the one or more fluorophore-labelled antibodies.”
Claim 93 is ambiguous in reciting “the one or more labelled antibodies bind specifically to an antigen selected from …” because it is unclear as to whether the instant “antigen(s)” is the same as the “one or more cell surface proteins” recited in claim 92 from which the instant claim directly depends.
Claim 93 is indefinite in reciting “KIR”, “CTLA-4” and GITR”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 96 is indefinite in reciting, “NK”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 100 is vague and indefinite in reciting “the method further comprising generating a frozen blood sample from a portion of the blood sample” because it is unclear at which point in the method of claim 31 which recites steps a), b), c), d), and e) the instant method step is performed. See also claim 101.
Claim 101 is vague and indefinite in reciting “additional immunological testing/analysis” because “additional” is a subjective term lacking a comparative basis for defining its metes and bounds.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
4. Claims 31, 87, 89-99, and 102-105 are rejected under 35 U.S.C. 103 as being unpatentable over Superti-Furga et al. (US 2017/0356911) in view of Rahul et al. (Large granular lymphocytic leukemia: a brief review. Am J Blood Res 12(1): 17-32 (ePub February 15, 2002)) and Ishiyama et al. (Programmed cell-death 1-expressing CD56-negative nature killer (NK) cell expansion is a hallmark of chronic NK cell activation during dasatnib treatment. Cancer Science 112: 523-536 (2021)- IDS).
Superti-Furga et al. disclose a method of selecting treatment (pharmacoscopy) for a subject diagnosed or identified as having cancer (myeloproliferative disorders: blood cancers, chronic and acute leukemia, lymphoma) or infection (latent virus infections, HIV, inflammatory disorders) (Abstract; [0045, 0093, 0121-0125]; Figure 11). The method comprises: a) contacting a venous whole blood sample from the subject with a cell viability dye (DAPI stain; Invitrogen live/dead fixable 488 dye) [0030, 0035, 0053, 0073]; Figure 11; Example 1; Example 2). Superti-Furga et al. also teach contacting the blood sample with one or more fluorophore-labeled antibodies that bind specifically to one or more cell surface antigens present on the cells in the blood sample. The one or more fluorophore-labeled antibodies maybe one or more of CD4 or CD8, with CD3 for T cells, CD14 (macrophages), and CD19 for B cells [0076, 0077, 0080-0082]. In Example 2, Superti-Furga et al. shows using DAPI, CD11c-APC, CD14-PE, CD19-APC, and CD3-PE (Figure 2). Superti-Furga et al. further teach incubating the blood sample with an antigen (virus) specific for infection for 6-12 hours (encompassed within 6 hours to 3 days) (Example 3; Example 4). The method further comprises b) generating a cell monolayer of the blood sample mixture in a) on a flat plate such as a microscope slide (hemocytometer, cover slide) ([0057, 0061, 0062]; Figure 11). Superti-Furga et al. specifically teach centrifuging the blood sample to concentrate peripheral blood mononucleated cells (PBMC or leukocytes) present in the blood sample into a buffy coat [0027, 0030, 0053, 0057]. The method further comprises c) identifying a number (differential count) of viable blast-transformed (activated) mononuclear cells (viable CD34+pSTAT5+ cells: primary myelofibrosis: blood cancer; myeloproliferative) resulting from cell-cell interactions which occur in the presence of disease such as cancer, infection (T-cell and dendritic cell interaction), and/or inflammatory conditions using microscopic analysis (image cytometry, automated microscope); wherein an increase in the viable CD34+pSTAT5+ blast-transformed mononuclear cells diagnostic of blood cancer (myeloproliferative, progressive to acute myelocytic leukemia (AML)), provides a prognosis of cancer ([0008-0013, 0027, 0030, 0032, 0035, 0073, 0121-0125]; Figure 2B; Figure 8; Figure 11; Example 3). Superti-Furga et al. also teach analyzing sub-cellular, cellular, and single biomarker changes in the PBMCs including cell and nuclear morphology, size, shape, and texture within a patient’s blood sample to allow prediction of clinical therapy and outcomes tailored to individual patients ([0045, 0048-0050, 0096]; Example 3; Example 4).
Superti-Furga et al. differ from the instant invention in failing to teach identifying a subject having an increased number of viable blast-transformed mononuclear cells and/or viable large granular lymphocytes as having an improved prognosis of cancer or infection and selecting the subject for low frequency cancer or infection screening for therapeutic treatment.
Rahul et al. teach large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder of cytotoxic lymphocytes which is associated with autoimmune conditions, is immunophenotypically either T cell lymphocyte or NK cell-derived, and which can be any one of chronic T-cell leukemia, chronic natural killer (NK) lymphocytosis, or aggressive NK LGL leukemia (Abstract; p. 22, right col. to p. 24; Figure 1; Table 4; Table 5). Rahul et al. teach selecting for subjects identified as having improved prognosis of cancer or infection a low frequency (observation only) screening for treatment or selecting for subjects identified as having poor prognosis of cancer or infection a high frequency screening for more aggressive treatment (p. 26-27; Figure 4).
Ishiyama et al. teach that Dasatnib treatment markedly increased the number of LGLs including NK cells in a proportion of Ph leukemia patients, which associates with a better prognosis. In-depth immune profiling of NK cells can predict therapeutic response in these patients (Abstract)
Although Superti-Furga et al., Rahul et al., and Ishiyama et al. differ from the instant invention in failing to teach that the blood sample is a capillary blood sample or a fingerstick blood sample; Applicant admits, by way of disclosure in paragraph [0061], that capillary blood sampling and finger stick blood sampling are standard phlebotomy blood collection techniques that are well-known and conventionally used in the art.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the teachings of Rahul and Ishiyama on LGL and their therapeutic response in cancer treatment into the method of selecting treatment for subjects diagnosed with leukemia or blood cancers as taught by Superti-Furga because both of Rahul and Ishiyama found that LGLs correlate to good or improved prognosis of cancer. One of ordinary skill would have been motivated to have incorporated the teaching of Rahul and Ishiyama into the method of Superti-Furga because the teachings of both of Rahul and Ishiyama in LGL provide avenues that lead to improved prognosis and treatment of blood cancers.
5. Claim 88 is rejected under 35 U.S.C. 103 as being unpatentable over Superti-Furga et al. (US 2017/0356911) in view of Rahul et al. (Am J Blood Res 12(1): 17-32 (ePub February 15, 2002)) and Ishiyama et al. (Cancer Science 112: 523-536 (2021)- IDS) as applied to claims 31 and 87 above; and in further view of Golde et al. (Chronic Myelogenous Leukemia Cell Growth and Maturation in Liquid Culture. Cancer Research 34: 419-423 (February 1974)).
Superti-Furga et al., Rahul et al. and Ishiyama et al. are discussed supra. Superti-Furga et al., Rahul et al., and Ishiyama et al. differ from the instant invention in failing to teach using a cytospin instrument.
Golde et al. teach culturing bone marrow and blood samples from chronic myelogenous leukemia (CML) patients to determine the proliferative and maturational characteristics of the leukemia cells (Abstract). Golde et al. teach pooling the cell culture suspensions, and depositing the leukemia cells on a microscope glass slide using a cytospin instrument (cytofuge) (p. 420, left col.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the teaching of Golde in concentrating PBMC or cancer cells using a cytospin into the method of Superti-Furga as modified by Rahul and Ishiyama because Golde taught that cytospins are well-known and conventionally used in concentrating cells from a cell suspension into microscopic glass slides for microscopic analysis of cells.
6. Claims 100 and 101 are rejected under 35 U.S.C. 103 as being unpatentable over Superti-Furga et al. (US 2017/0356911) in view of Rahul et al. (Am J Blood Res 12(1): 17-32 (ePub February 15, 2002)) and Ishiyama et al. (Cancer Science 112: 523-536 (2021)- IDS) as applied to claim 31 above; and in further view of BioNano Genomics (Whole Blood Collection, Storage, and Shipping Instructions (2020)).
Superti-Furga et al., Rahul et al., and Ishiyama et al. are discussed supra. Superti-Furga et al., Rahul et al., and Ishiyama et al. differ from the instant invention in failing to teach generating a frozen sample from the blood sample and thawing the frozen blood sample and performing additional immunological testing.
BioNano Genomics teaches generating frozen blood samples from a portion of collected EDTA whole blood samples into cryovials with lid gaskets and thawing the frozen blood sample and prior to performing additional immunological analysis or DNA extraction for DNA testing (pp. 2-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the teaching of BioNano in freezing blood samples for storage and transport into the method of Superti-Furga as modified by Rahul and Ishiyama because BioNano taught that freezing and thawing blood samples are a well-known and conventional practice in storing blood samples for future analytical testing of cells and/or analytes in a biological sample.
7. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
December 12, 2025