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
Amendment Entry
1. Applicant's amendment / response filed July 7, 2026 is acknowledged and has been entered. Claims 31, 92, 93, 96, 100, and 102-105 have been amended. Claims 87, 88, and 101 have been cancelled. Accordingly, claims 31, 89-100, and 102-105 are pending and are under examination.
Withdrawn Rejections / Objections
2. Any objection or rejection not reiterated herein, has been withdrawn.
3. The rejections of claims 87, 88, and 101 are moot in light of Applicant's cancellation of the claims.
4. In light of Applicant’s amendment and arguments, the rejections of claims 31, 89-100, and 102-105 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), and also in further view of BioNano Genomics (Whole Blood Collection, Storage, and Shipping Instructions (2020)), are hereby, withdrawn.
Priority
5. 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.
New Grounds of Rejection
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.
6. Claims 31, 89-99, and 103-105 are rejected under 35 U.S.C. 103 as being unpatentable over Superti-Furga et al. (US 2017/0356911) in view of Weisenthal (US Patent 4,996,145) and in further 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); d) identifying a subject having an increased number of viable CD34+pSTAT5+ blast-transformed mononuclear cells diagnostic of blood cancer (myeloproliferative, progressive to acute myelocytic leukemia (AML)) as compared to viable blast-transformed mononuclear cells in a healthy population, as having an improved prognosis of cancer for selection of tailored clinical therapy ([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 generating a microscope slide from the stained blood sample by performing centrifugation using a cytospin instrument.
Weisenthal discloses a method for detecting the sensitivity of tumor cells to immune effector substances using an assay that distinguishes between living immune cells and dead cells (Abstract; col. 2, line 65 to col. 3, line 18). Weisenthal teaches that a tool that differentiates between improved prognosis or poor prognosis (success or failure) and capable of providing prediction of success of proposed treatment allowing for biological response modification protocol would be valuable in preventing unnecessary ineffective treatment and suffering of individuals and in selecting alternative treatment protocols that have the highest likelihood of success (col. 1, lines 24-33; col. 2, lines 52-63). The method comprises contacting a venous whole blood sample from the subject with a cell viability dyes (Fast Green for tumor cells or Fast Green Nigrosin for hematologic/lymphocytic neoplasm and then counterstained with hematoxylin and eosin (H&E) for tumor cells or Wright Giemsa for hematologic/ lymphocytic neoplasm) and then generating a cell monolayer of the stained blood on a microscope slide (cytospin slide) by centrifugation using a Cytospin instrument (Cytospin I, Cytospin II) (col. 3, line 59; col. 4, lines 22-51). The method further comprises identifying a number (count) of viable blast-transformed activated mononuclear cells and large granular lymphocytes (LGL) resulting from cell-cell interactions which occur in the presence of cancer tumors (Example I, Example II). According to Weisenthal, the method provides advantage in determining the most promising strategies of immune therapy interventions in cancer and other disease states such as infection because immune therapies are very expensive, frequently toxic and only sporadically effective. In vitro prediction of the probable clinical efficacy of immune effector substances and the ability to thereafter monitor patients for acquisition of resistance to such therapies can be used to design modification of treatments to overcome such resistance (col. 2, lines 52-62 and col. 3, lines 43).
Superti-Furga et al. and Weisenthal differ from the instant invention in failing to teach identifying a subject having an increased number of 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 that 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 leukemia patients, which associates with a better prognosis. In-depth immune profiling of NK cells can predict therapeutic response in these patients (Abstract).
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 cytospin technique and instrument as taught by Weisenthal and as modified by 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 Weisenthal taught that the method utilizing cytospin technique has been shown to be highly reliable and successful in providing viable recognizable neoplastic cells, viable blast-transformed mononuclear cells, and viable large transformed granulocyte lymphocytic cells and both of Rahul and Ishiyama also found that LGLs correlate to good or improved prognosis of cancer. One of ordinary skill would have been motivated to have incorporated use of Cytospin instrument as taught by Weisenthal and the teaching of Rahul and Ishiyama into the method of Superti-Furga because Weisenthal showed how the cytospin instrument provides highly reliable successful microscopic cell analysis results and the teachings of both of Rahul and Ishiyama in LGL provide avenues that lead to further improved prognosis and treatment of blood cancers.
Although Superti-Furga et al., Weisenthal, Rahul et al., and Ishiyama et al. do not teach using capillary blood sample collected by fingerstick; Applicant admits, by way of disclosure in paragraph [0061], that capillary blood sample encompasses an obvious variation of blood source conventionally used in the art that is obtained by finger stick phlebotomy which is standard phlebotomy blood collection technique that is 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 substitute the venous blood sample in the method of Superti-Furga as modified by Rahul and Ishiyama with capillary blood sample because capillary blood samples encompass obvious variations of blood samples conventionally used in the art obtained by fingerstick blood collection technique which is well-known and conventionally used in the art.
With respect to the recitation of “selecting and performing screening for a subject identified as having an improved prognosis of cancer or infection as compared to a subject having or decreased number of viable blast-transformed mononuclear cells and decreased number of viable large granular lymphocyte screenings for cancer or infection, a low frequency screening once every year to once every 5 years; and “selecting and performing screening for a subject identified as having a poor prognosis of cancer or infection as compared to a subject having or increased number of viable blast-transformed mononuclear cells and increased number of viable large granular lymphocyte screenings for cancer or infection, high frequency screenings of at least two screenings a year;” generally, differences in time frequency will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such frequence is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. *It would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures.
7. Claim 100 is rejected under 35 U.S.C. 103 as being unpatentable over Superti-Furga et al. (US 2017/0356911) in view of Weisenthal (US Patent 4,996,145) and in further 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., Weisenthal, Rahul et al., and Ishiyama et al. are discussed supra. Superti-Furga et al., Weisenthal, 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 be Weisenthal, 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.
Response to Arguments
8. Applicant’s arguments with respect to claims 31, 89-100, and 102-105 have been considered but are moot in light of the new grounds of rejection necessitated by Applicant’s amendment and because the new grounds of rejection do not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the arguments.
9. No claims are allowed.
10. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
KrishnaMurthy et al. (Comparison of Cell Preparations between Commercially Available Filter Cards of the Cytospin with Custom Made Filter Cards. Journal of Clinical Diagnostic Research 10 (7): EC18-EC20 (2016)) teach that Cytospin technique is successfully used for analysis of body fluids with malignant and non-malignant cells and tissue diagnosis using cell monolayer technique (Abstract; p. EC18, left col.)
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 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.
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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/GAILENE GABEL/Primary Examiner, Art Unit 1678
September 10, 2026
Prosecution Insights