DETAILED ACTION
Claims 28, 30-55, 58-60, 62, and 65 are pending.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/22/2026 has been entered.
Status of Claims
Claims 28, 30-55, 58-60, 62, and 65 are under examination.
Claim Rejections - 35 USC § 103-Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
1.Claims 28, 30-34, 36-55, 62, and 65 are rejected under 35 U.S.C. 103 as being
unpatentable over Pestano et al., (WO 2009/036427 A2) (IDS filed on 07/21/2022) and in view
of Li et al., “Serum thymidine kinase 1 is associated with Gleason score of patients with
prostate carcinoma.” Oncology letters vol. 16,5 (2018): 6171-6180. doi:10.3892/ol.2018.9345
(IDS filed on 07/21/2022).
Pestano teaches a method for predicting patient survival comprising: determining a level of thymidine kinase 1 material in a serum sample or a plasma sample (see page 2 lines 1-3) from a patient diagnosed with prostate cancer using an Enzyme- Linked Immunosorbent Assay (ELISA) kit (see page 41 lines 1-4 “Kd values can, for example, be determined by competitive ELISA (enzyme-linked immunosorbent assay) …”) comprising:
a first monoclonal antibody or a first fragment thereof having specificity for an epitope
selected from the group consisting of:
GEAVAARKLF (SEQ ID NO: 1) of human TK1 (see SEQ ID NO: 6 of Pestano);
at least one of NCPVPGKPGE (SEQ ID NO: 2), PVPGKPGEAV (SEQ ID NO: 3) and NCPVPGKPGEAV (SEQ ID NO: 4) of human TK1 (see SEQ ID NO: 6 of Pestano teaching SEQ ID NOs: 2-4); and
a conformation dependent epitope of human TK1 (see page 41 lines 5-15 “For example peptide fragments of one of the proteins listed in Table 8, such as WNT5A, TKl, or GASl, (e.g., SEQ ID NO: 2, 4 or 6, respectively) can be conjugated to carrier molecules (or nucleic acids encoding such epitopes or conjugated RDPs) can be injected into non-human mammals (such as mice or rabbits, see SEQ ID NO: 6); and
a second monoclonal antibody or a second fragment thereof having specificity for an epitope (see page 22 lines 24-26 “Alternatively, unlabeled primary antibody is used in conjunction with a labeled secondary antibody, comprising antisera, polyclonal antisera or a monoclonal antibody specific for the primary antibody”)
selected from the group consisting of:
GEAVAARKLF (SEQ ID NO: 1) of human TK1 (see SEQ ID NO: 6 of Pestano);
at least one of NCPVPGKPGE (SEQ ID NO: 2), PVPGKPGEAV (SEQ ID NO: 3) and NCPVPGKPGEAV (SEQ ID NO: 4) of human TK1 (see SEQ ID NO: 6 of Pestano); and
a conformation dependent epitope of human TK1 (see SEQ ID NO: 6 of Pestano); and predicting survival of the patient based on the determined level of TK1 protein material in the serum sample or the plasma sample (see page 4 lines 11-21 “Disclosed herein are gene signatures of prostate cancer recurrence, characterized at least in part by altered (e.g., increased or decreased) expression of one or more genes listed in Table 8, which characterizes prostate cancer in subjects afflicted with the disease. For example, gene expression of wingless-type MMTV integration site family member 5 (WNT5A), thymidine kinase 1 (TK1), and growth arrest specific gene 1 ([GAS]) and/or any other gene listed in Table 8 can be used to forecast prostate cancer outcome, e.g., disease recurrence or non-recurrence in patients who have (or are candidates for) prostatectomy. In particular examples, overexpression of WNT5A and TK1 and down-regulation of GAS] indicates an increased likelihood that the prostate cancer will recur, and thus a poor prognosis.”), and
selecting an anti-cancer treatment for the patient based on the predicted survival of the patient, wherein the anti-cancer treatment is selected from the group consisting of prostatectomy, radiation therapy, and androgen deprivation therapy (ADT) (see page 18 lines 9-13, see page 2 lines 22-25 “Treatment options for more aggressive cancers include radical prostatectomy and/or radiation therapy. Androgen- depletion therapy (such as, gonadotropin releasing hormone agonists (e.g., leuprolide, goserelin, etc.) and/or bilateral orchiectomy) is also used, alone or in conjunction with surgery or radiation”) (Instant claim 28).
Pestano teaches wherein determining the concentration of TK1 protein material in the serum sample or the plasma sample comprises: contacting the serum sample or the plasma sample with the first or second monoclonal antibodies or the fragments thereof; and measuring an amount of the second monoclonal antibody or the second fragment thereof bound to the TK1 protein material (see pages 8-9 under “Contact” and “Detect”) (instant claim 30). Pestano teaches correlating the measured amount of antibody or fragment thereof bound to the TK1 material to a level of TK1 material (see page 9 lines 15-20 “For example, use of an antibody specific for a particular protein (e.g., WNT5A, TKI or GASI) permits detection of the of the protein or protein-protein interaction in a sample, such as a sample containing prostate cancer tissue. In another example, use of a probe or primer specific for a particular gene (e.g., WNT5A, TKJ or GAS]) permits detection of the of the desired nucleic acid molecule in a sample, such as a sample containing prostate cancer tissue.”, see page 29 lines 28-31 teaching the use of a second antibody, see page 35 lines 1-8 “A difference in the level of a target protein in the sample (e.g., WNT5A, TKI and GAS 1), relative to the level of the same target protein found an analogous sample from a subject who has not had a recurring prostate cancer, in particular examples indicates that the subject has a poor prognosis.”) (instant claim 31). Pestano teaches correlating the measured amount of the second monoclonal antibody or the second fragment comprises correlating the measured amount of the second antibody or the second fragment thereof to a concentration of TK1 protein material using a pre-defined correlation between measured amount of the second antibody or the second fragment thereof bound to recombinant human TK1 and a concentration of recombinant human TK1 (See claim 1, see page 34 lines 27-31 and page 35 lines 1-8 “The proteins or antibodies forming the array can be directly linked to the support. Alternatively, the proteins or antibodies can be attached to the support by spacers or linkers to the solid support. Changes in protein expression can be detected using, for instance, a protein -specific binding agent, which in some instances is labeled. In certain examples, detecting a change in protein expression includes contacting a protein sample obtained from a prostate cancer sample of a subject with a protein-specific binding agent (which can be for example present on an array); and detecting whether the binding agent is bound by the sample and thereby measuring the levels of the target protein present in the sample. A difference in the level of a target protein in the sample (e.g., WNT5A, TKI and GAS 1), relative to the level of the same target protein found an analogous sample from a subject who has not had a recurring prostate cancer, in particular examples indicates that the subject has a poor prognosis.” See page 38 lines 15-16 “Specific binding reagents include, for example, antibodies or functional fragments or recombinant derivatives thereof.”. See page 11 lines 9-27 under “Specific binding (or obvious derivations of such phase, such as specifically binds, specific for, etc)”) (instant claim 32).
Pestano teaches wherein determining the concentration of TK1 protein material comprises determining, using the ELISA kit, the concentration of TK1 protein material in the serum sample or the plasma sample taken from the patient in connection with diagnosing the patient with metastatic prostate cancer using the antibody or the fragment thereof specifically binding to the serum form of human TK 1 (see claim 1, claim 15, abstract, see page 40 lines 23-31 and page 41 lines 1-5, see page 7 lines 28-30 “Cancer: Malignant neoplasm, for example one that has undergone characteristic anaplasia with loss of differentiation, increased rate of growth, invasion of surrounding tissue, and is capable of metastasis) (instant claims 33-34). Pestano teaches comprising comparing the determined concentration of TK1 protein material in the serum sample or the plasma sample with a threshold value, wherein predicting survival of the patient comprises predicting poor survival of the patient if the determined concentration of TK1 protein material in the serum sample or the plasma sample exceeds the threshold value and otherwise predicting good survival of the patient (see page 4 lines 19-24 “In particular examples, overexpression of WNT5A and TKJ and down-regulation of GAS indicates an increased likelihood that the prostate cancer will recur, and thus a poor prognosis. The disclosed gene signatures may be useful, for example, to screen prostate cancer patients for cancer recurrence, which can aid prognosis and the making of therapeutic decisions in prostate cancer.”, see page 69 lines 10-16 “Similarly, if GAS 1, TKl, and WNT5A expression is similar relative to a value representing GAS 1, TKl, and WNT5A expression in a recurring cancer, this indicates that the subject has a poor prognosis as the cancer is likely to recur. If GAS 1, TKl, and WNT5A expression is similar (e.g., no more than a 2-fold difference) relative to a value representing GASl, TKl, and WNT5A expression in a non - recurring cancer, this indicates that the subject has a good prognosis as the cancer is not likely to recur.”) (instant claims 36 and 48).
Pestano teaches determining prostate-specific antigen (PSA) in a body sample from the patient (see page 1 line 31 and page 2 lines 1-3 “Prostate cancer typically is diagnosed with a digital rectal exam ("DRE") and/or prostate specific antigen (PSA) screening. An abnormal finding on DRE and/or an elevated serum PSA level (e.g., >4 ng/ml) can indicate the presence of prostate cancer.”), wherein predicting survival of the patient comprises predicting survival of the patient based on the determined concentration of STK1 protein material in the serum sample or the plasma sample and based on the determined PSA in the body sample (see page 17 lines 5-12 “Other exemplary methods predict the likelihood of prostate progression. Prostate cancer progression means that one or more indices of prostate cancer (e.g., serum PSA levels) show that the disease is advancing independent of treatment. In some examples, prostate cancer progression is marked by rising PSA levels (e.g., greater than 2.0-2.5 ng/mL) and/or by identification of (or increasing numbers of) prostate cancer cells in the blood, prostate biopsy or aspirate, in lymph nodes (e.g., in the pelvis or elsewhere) or at a metastatic site (e.g., muscles that help control urination, the rectum, the wall of the pelvis, in bones or other organs).”, see page 69 lines 10-16 “Similarly, if GAS 1, TKl, and WNT5A expression is similar relative to a value representing GAS 1, TKl, and WNT5A expression in a recurring cancer, this indicates that the subject has a poor prognosis as the cancer is likely to recur. If GAS 1, TKl, and WNT5A expression is similar (e.g., no more than a 2-fold difference) relative to a value representing GASl, TKl, and WNT5A expression in a non-recurring cancer, this indicates that the subject has a good prognosis as the cancer is not likely to recur.”) (instant claim 53). Pestano teaches determining International Society of Urological Pathology (ISUP) Gleason grade group or Gleason score for the patient, wherein predicting survival of the patient comprises predicting survival of the patient based on the determined concentration of TK1 protein material in the serum sample or the plasma sample and based on the determined ISUP Gleason grade group or Gleason score (see page 2 lines 20-21 “Men with a 10-year life expectancy or less who have a low Gleason number and whose tumor has not spread beyond the prostate often are not treated.”, see page 47 lines 15-17 “Tissue sections were stained with hematoxylin and eosin ("H&E") using standard (manual) methods to determine Gleason sum scores, tumor volume, location, and pathologic stage.”, see page 69 lines 10-16 “Similarly, if GAS 1, TKl, and WNT5A expression is similar relative to a value representing GAS 1, TKl, and WNT5A expression in a recurring cancer, this indicates that the subject has a poor prognosis as the cancer is likely to recur. If GAS 1, TKl, and WNT5A expression is similar (e.g., no more than a 2-fold difference) relative to a value representing GASl, TKl, and WNT5A expression in a non-recurring cancer, this indicates that the subject has a good prognosis as the cancer is not likely to recur.”) (instant claim 54).
Pestano teaches determining prostate-specific antigen (PSA) in a body sample from the patient, wherein predicting survival of the patient comprises predicting survival of the patient based on the determined concentration of TK1 protein material in the serum sample or the plasma sample, based on the determined PSA in the body sample (see page 17 “Other exemplary methods predict the likelihood of prostate progression. Prostate cancer progression means that one or more indices of prostate cancer (e.g., serum PSA levels) show that the disease is advancing independent of treatment. In some examples, prostate cancer progression is marked by rising PSA levels (e.g., greater than 2.0-2.5 ng/mL) and/or by identification of (or increasing numbers of) prostate cancer cells in the blood, prostate biopsy or aspirate, in lymph nodes (e.g., in the pelvis or elsewhere) or at a metastatic site (e.g., muscles that help control urination, the rectum, the wall of the pelvis, in bones or other organs).”, see page 69 lines 10-16 “Similarly, if GAS 1, TKl, and WNT5A expression is similar relative to a value representing GAS 1, TKl, and WNT5A expression in a recurring cancer, this indicates that the subject has a poor prognosis as the cancer is likely to recur. If GAS 1, TKl, and WNT5A expression is similar (e.g., no more than a 2-fold difference) relative to a value representing GASl, TKl, and WNT5A expression in a non-recurring cancer, this indicates that the subject has a good prognosis as the cancer is not likely to recur.”) and based on the determined ISUP Gleason grade group or Gleason score (see page 47 lines 15- 17 “Tissue sections were stained with hematoxylin and eosin ("H&E") using standard (manual) methods to determine Gleason sum scores, tumor volume, location, and pathologic stage .”) (instant claim 55). Pestano teaches wherein one of the first monoclonal antibody or first fragment thereof and the second monoclonal antibody or second fragment thereof is immobilized to a solid support or intended to be immobilized to the solid support (see page 31 lines 16-20 “Microarrays include a solid surface (e.g., glass slide) upon which many (e.g., hundreds or even thousands) of specific binding agents (e.g., cDNA probes, mRNA probes, or antibodies) are immobilized. The specific binding agents are distinctly located in an addressable (e.g., grid) format on the array.”) (instant claim 62). Pestano teaches selecting a patient surveillance schedule for the patient based on the predicted survival of the patient (see page 18 lines 9-13 “Taken in the context of the particular subject's medical history, the patient and the caregiver can make better informed decisions of whether or not to treat (e.g., perform surgery, such as prostatectomy) and/or whether or not to provide alternate treatment (such as, external beam radiotherapy, brachytherapy, chemotherapy, or watchful waiting).”) (instant claim 65).
While Pestano teaches that serum levels are taken and measured for those being tested for prostate cancer (see page 2 lines 1-3), Pestano does not explicitly state that the TK1 is from serum.
Li teaches serum TK1 (STK1) is a known biomarker for prostate cancer (see abstract) (instant claims 28, 30-34, 36-55, and 62).
Pestano and Li don’t explicitly teach the various threshold value range of instant claims 37-47 and 49-52. However, Pestano teaches methods of predicting patient survival of prostate cancer using TK1 and Li teaches that serum TK1 is a known biomarker for prostate cancer. Both Pestano and Li teach the benefits of measuring TK1 in individuals to diagnose prostate cancer such that one of ordinary skill would reasonably use any threshold value of this biomarker known to be associated with prostate cancer. Where the general conditions of the claim are taught in the prior art, discovering workable or optimum range requires routine skills in the art. In this case, the general conditions of the claim are taught by the prior art, and the recited duration of measurement falls within a workable or optimum range, and therefore its discovery requires routine skills in the art. Thus, it would have been prima facie obvious at the time of the instant application to determine the workable or optimum threshold range as the discovery requires routine skills in the art (instant claims 37-47 and 49-52).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to consider combining Pestano’s methods of characterizing prostate cancer with Li’s methods of using serum thymidine kinase 1 as a biomarker for prostate cancer. Li provides
motivation by teaching that STK1 is known to be significantly higher in patients with benign
prostatic hyperplasia (BPH) and prostate cancer compared to healthy individuals, and since
STK1 concentration is associated with Gleason scores, it may reduce the number of biopsies
obtained from men with suspected prostate BPH/malignancy by determining STK1
concentration (see page 6178). One of ordinary skill in the art would have been motivated to combine the methods of Pestano and Li as they both teach prostate cancer prognostics. The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
2.Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Pestano and Li as applied to claims 28, 30-34, 36-55, 62, and 65 above and in further view of Stone et al., (WO2015/175692 A1) (IDS filed on 07/21/2022).
The teachings of Pestano and Li as it pertains to claims 28, 30-34, 36-55, 62, and 65 are discussed in the 35 USC 103 rejection above.
Pestano does not teach estimating a hazard ration (HR) for a patient.
Li teaches serum TK1 (STK1) is a known biomarker for prostate cancer (see abstract) (instant claim 35).
Li does not teach estimating a hazard ration (HR) for a patient.
Stone teaches estimating a hazard ratio (HR) for the patient based on the determined concentration of STK protein material in the serum sample or the plasma sample, wherein predicting survival of the patient comprises predicting survival of the patient based on the estimated HR (see [0090] “Such risk may be estimated by applying the hazard ratio for a particular parameter (e.g., CCP score, Combined Score) to that parameter to yield a
patient's relative risk of a particular clinical outcome (e.g., cancer recurrence or cancer-specific
death). In some cases, the hazard ratio represents the relative risk increase per unit of the
parameter. In some of the examples below, for instance, a single unit increase in CCP score
(which represents a doubling of expression) represents a relative risk increased by the multiple
of the hazard ration. Where the hazard ratio is equal to 2, for example, a single unit increase in CCP score corresponds to a doubling of relative risk (i.e., a first patient with a CCP score that is
one unit higher than a second patient has twice the risk of cancer recurrence or cancer-specific
death).”, see [0091] “(3) calculating said patient's risk of cancer recurrence or cancer-specific
death by multiplying the number of increased units of the test value over some reference value
(e.g., average values in a particular population) by the hazard ratio for the value. In some
embodiments, the test value comprises the CCP score or a Combined Score as described
herein and the hazard ration is any of the hazard ratios reported herein.”).
Stone teaches STK15 (see table 1 and [0055]), STK12 (see table 1), and STK17 (see
table 1) (instant claim 35).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to consider combining Pestano’s methods of characterizing prostate cancer with Li’s methods of using serum thymidine kinase 1 as a biomarker for prostate cancer, with Stone’s methods of cancer prognosis. Stone provides motivation by teaching that the hazard ratio (HR) is commonly used in the art and is a parameter to yield a patient’s risk of a particular clinical outcome (e.g., cancer recurrence or cancer-specific death) (see [0090]). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
3.Claims 58-60 are rejected under 35 U.S.C. 103 as being unpatentable over Pestano and Li as applied to claims 28, 30-34, 36-55, and 62 above, and in further view of Eriksson et al., (WO 2015094106A1) (IDS filed on 07/21/2022).
The teachings of Pestano and Li as it pertains to claims 28, 30-34, 36-55, and 62 are discussed in the 35 USC 103 rejection above.
Pestano and Li do not teach SEQ ID No’s 5- 19.
Eriksson teaches wherein the first and/or second monoclonal antibody or the first and/or second fragment thereof has a variable heavy (VH) domain complementarity determining region 1 (CDR1) having amino acid sequence SEQ ID NO: 5 (see SEQ ID NO: 6 of ‘106); a VH domain CDR2 having amino acid sequence SEQ ID NO:6 (see SEQ ID NO: 7 of ‘106); a VH domain CDR3 having amino acid sequence SEQ ID NO: 7 (see SEQ ID NO: 8 of ‘106); a variable light (VL) domain CDR1 having amino acid sequence SEQ ID NO: 8 (see SEQ ID NO: 9 of ‘106); a VL domain CDR2 having amino acid sequence SEQ ID NO: 9 (see SEQ ID NO: 10 of ‘106); and a VL domain CDR3 having amino acid sequence SEQ ID NO: 10 (see SEQ ID NO: 11 of ‘106) (instant claim 58).
Eriksson teaches wherein the first and/or second monoclonal antibody or the first and/or second fragment thereof has a variable heavy (VH) domain complementarity determining region 1 (CDR1) having amino acid sequence SEQ ID NO: 5 (see SEQ ID NO: 6 of ‘106); a VH domain CDR2 having amino acid sequence SEQ ID NO: 11 (see SEQ ID NO: 12 of ‘106); a VH domain CDR3 having amino acid sequence SEQ ID NO: 12 (see SEQ ID NO: 13 of ‘106); a variable light (VL) domain CDR1 having amino acid sequence SEQ ID NO: 13 (see SEQ ID NO: 14 ‘106); a VL domain CDR2 having amino acid sequence SEQ ID NO:9 (see SEQ ID NO: 10 of ‘106); and a VL domain CDR3 having amino acid sequence SEQ ID NO: 10 (see SEQ ID NO: 11 of ‘106) (instant claim 59).
Eriksson teaches wherein the first and/or second monoclonal antibody or the first and/or second fragment thereof has a variable heavy (VH) domain complementarity determining region 1 (CDR1) having amino acid sequence SEQ ID NO: 14 (see SEQ ID NO: 15 of ‘106); a VH domain CDR2 having amino acid sequence SEQ ID NO: 15 (see SEQ ID NO: 16 of ‘106); a VH domain CDR3 having amino acid sequence SEQ ID NO: 16 (see SEQ ID NO: 17 of ‘106); a variable light (VL) domain CDR1 having amino acid sequence SEQ ID NO: 17 (see SEQ ID NO: 18 of ‘106); a VL domain CDR2 having amino acid sequence SEQ ID NO: 18 (see SEQ ID NO: 19 of ‘106); and a VL domain CDR3 having amino acid sequence SEQ ID NO: 19 (see SEQ ID NO: 20 of ‘106) (instant claim 60).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to consider combining Pestano and Li’s methods of prostate cancer prognosis with
Eriksson’s teachings of antibodies capable of binding to a serum form of human thymidine
kinase 1. Eriksson provides motivation by teaching that the main reason for choosing an anti-
TK1 antibody that is produced against the C-terminal of TK1 is that the C-terminal region is involved in the cell cycle regulation of TK1 (see page 1 lines 29-30). Eriksson further provides
motivation by teaching that these amino acid sequences have been known in the art to be
amino acid sequences that directly bind to STK1. One of ordinary skill in the art would have
been motivated to combine the methods of Pestano and Eriksson as they both teach cancer
diagnostics and prognostics. The artisan would have had reasonable expectation of success
based on the cumulative disclosures of these prior art references.
Response to Arguments
Applicant's arguments filed 04/22/2026 have been fully considered but they are not persuasive.
On pp. 10-11 applicant argues that Pestano does not teach determining the concentration of STK1 protein maternal in serum or plasma samples.
However, Pestano explicitly states that cancer progression can be determined by serum levels (see page 17 lines 1-2). While Pestano does not explicitly state that Tk1 is from serum, Pestano teaches measuring serum and that Tk1 expression can determine the prognosis of the subject (see page 67 lines 15-21). Further, Li explicitly teaches serum thymidine kinase 1 (STK1).
On p. 11 applicant argues that Pestano does not teach an ELISA kit that is used to determine the concentration of STK1 protein material in a serum or plasma sample. Applicant argues that Pestano merely discloses that Kd values can be determined by competitive ELISA or using surface-plasmon resonance.
However, Pestano does explicitly state the use of an ELISA test (see page 41). While Pestano does teach that Kd values can be determined by an ELISA, Pestano also teaches that antibodies can be used in immunoassay procedures such as an ELISA (see page 41 lines 29-31).
On pp. 11-12 applicant argues that Pestano does not teach SEQ ID Nos: 1-4. Applicant argues that Pestano discloses the amino acid sequence of human Tk1. Applicant argues that Pestano does not disclose the use of a monoclonal antibody, or fragment thereof, having specificity for the epitope as defined in SEQ ID NO: 1, 2, 3, or 4.
However, Pestano teaches instant SEQ ID Nos: 1-4 in SEQ ID No: 6. Further, Pestano teaches that antibodies (monoclonal and/or polyclonal) specific for each protein expression marker are used to detect expression (see page 22). Further, Pestano teaches that serum isolated from immunized animal spleens are used for the production of monoclonal antibodies, such as SEQ ID No: 6 of Pestano (see page 41).
On p. 12 applicant argues that Pestano does not teach predicting survival of the patient based on the determined concentration of STK1 protein material in the serum sample or the plasma sample.
However, Pestano explicitly states that Tk1 expression can indicate poor prognosis (e.g., less than 1- or 2-year survival) (see page 69-70). Thus, Pestano teaches the prediction of survival of a patient based on the concentration of a sample.
On p. 13-16 applicant argues that there is no disclosure in Li that STK1 concentration could be used to predict survival of patients diagnosed with prostate cancer. Applicant argues that Li teaches that STK1 is not suitable to predict the survival of a patient. Applicant argues that Li teaches away from predicting patient survival of a patient diagnosed with prostate cancer because one of the patients from the study died.
However, Li explicitly states that STK activity is a useful took to assess patient prognosis, tumor treatment prognosis, relapse, follow-up and survival (see page 6172). Further, Li explicitly states that STK1 concentration in patients with prostate cancer have been demonstrated to be reliable biomarkers for patient prognosis and survival (see pages 6176-6177). Further, Li does not teach away from predicting the survival of a patient diagnosed with prostate cancer by measuring the concentration of STK1. Li explicitly states that STK1 expression in patients with prostate cancer demonstrates reliable biomarkers for patient survival (see page 6177). Li teaches of the 123 with prostate malignancy, 51 were followed for 5 years, and a total of 98% (50/51) of patients survived the following five years (see page 6174). Li explicitly states that the patient who died at the age of 91, died as a result of type III hypertension, chronic bronchitis, diabetes, coronary heart disease, fatty liver, and multiple cerebral infarctions (see page 6175). Thus, applicants’ argument that the patient’s survival was not properly predicted because a patient died is incorrect. The patient died of other causes, not from prostate cancer. The instant application is a method of predicting patient survival in a patient diagnosed with prostate cancer.
On p. 15-16 applicant argues that one of ordinary skill in the art would not combine Pestano and Li as it is an incorrect combination. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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