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 .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 22 and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural law or abstract idea without significantly more. The claim(s) 22 (and therefore claim 23) recites: “detecting the presence of biomarkers in a sample isolated from a female patient who does not have an infection, wherein said biomarkers comprise…., wherein detection of an elevated presence of the biomarkers compared to a normal control indicates the presence or the risk of bladder cancer in the female patient from whom the sample is isolated, and, in response to detection of an elevated presence of the biomarkers in the sample compared to a normal control directing the female patient for a cystoscopy”. (Emphasis added).
The recited limitations are directed to a correlation (i.e., a correlation between the recited detection and the indication of the presence or risk of bladder cancer) which is a natural law or natural phenomenon, which is a judicial exception.
These judicial exception is not integrated into a practical application for the following reasons.
Applicant’s amended claim 22 recites, in the last three lines, “in response to detection of an elevated presence of the biomarkers in the sample compared to a normal control directing the female patient for a cystoscopy”. This limitation is not tied to the judicial exception such that the judicial exception is integrated into a practical application, since “cystoscopy” is a procedure that encompasses merely another diagnosis or technique to detect a condition, rather than a practical application, such as a treatment tailored to the condition. Also, cystoscopy encompasses a technique for data gathering, and therefore does not add a meaningful limitation to the judicial exception.
The remaining limitations recite detecting the presence of one or more the recited biomarkers in a sample, which are data gathering steps required to use the correlation and therefore do not add a meaningful limitation to the method as they are insignificant extra-solution activity.
Also, the claim(s) 22 and 23 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any other limitations that are not well known, not conventional, and not routine in the art. Examiner notes that use of the particular types of biomarkers (e.g., IL-13 and Midkine) to assess the presence or risk of bladder cancer is the judicial exception itself and therefore cannot constitute additional elements that amount to significantly more than the judicial exception. Also, the step of “determining that a female patient does not have an infection” does not constitute additional elements that amount to significantly more than the judicial exception since it appears well-known that an infection can interfere with an assay for bladder cancer using a urine sample (see discussion of claims 22-23 below) and therefore it would have been desirable to select a patient that does not have an infection.
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.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Van et al., “Validation of the diagnostic utility of urinary midkine for the detection of bladder cancer”, Oncology Letters, 12, 3143-3152, 2016 (hereinafter “Van”) in view of US 20120149043 (hereinafter “Cohen”).
Van discloses that midkine protein levels in urine of bladder cancer (BCa) patients are increased compared to healthy controls (see abstract).
Midkine is readily available in urine (page 3143, right column, second paragraph.)
The analysis of urinary midkine protein revealed significantly elevated midkine concentrations in BCa patients vs controls. Page 3150, left column, last paragraph.
Van discloses that in combination with additional transcriptional or proteomic markers that will recognize low-grade tumors more effectively, midkine may have the potential to contribute to the non-invasive diagnosis and monitoring of BCa (bladder cancer). Page 3151 left column, last paragraph.
Van however does not disclose use of an additional marker that is IL-13.
However, Cohen discloses the following.
“A recent case-control study demonstrated a highly significant difference in mRNA and protein expression of IL-13 between patients with bladder cancer and controls (MalekZadeh et al., 2010; published after the priority date of the present invention).” Para. 0012.
The invention provides methods for diagnosing bladder cancer in a subject, comprising determining the levels of anti-inflammatory cytokines and/or HSPs in a urine sample obtained from the subject. In various embodiments, the methods comprise determining the levels of at least one biomarker selected from the group consisting of IL-6, IL-8, IL-10, IL-13, TGF-.beta., HSP60, HSP70 and HSP90. Para. 0016.
According to one aspect of the present invention, there is provided a method for assessing (or determining) the presence or absence of bladder cancer in a subject, comprising determining the level of at least one biomarker selected from the group consisting of IL-13, IL-10, HSP60, HSP70 and HSP90 in a urine sample obtained from the subject, wherein a significant elevation in the level of the at least one biomarker compared to a control value corresponding to a healthy individual indicates that said subject is afflicted with bladder cancer. In one embodiment, the subject is suspected of having bladder cancer. Each possibility is a separate embodiment of the invention. Para. 0017.
Cohen also suggests detection of more than one biomarker of bladder cancer (see para. 0017-0019, particularly 0019).
Cohen also teaches that determining the levels of a plurality of biomarkers provides a significantly more accurate and reliable assay in discriminating patients and control subjects than each biomarker alone. Para. 0055.
It would have been obvious to one of ordinary skills in the art to combine the teachings and suggestions of Van and Cohen to provide IL-13 as an additional biomarker of bladder cancer, as generally suggested by Cohen, in combination with midkine taught by Van as part of an assay to diagnose bladder cancer, in order to provide a significantly more accurate and reliable assay than one biomarker alone, as suggested by Cohen.
Moreover, it would have been predictable that providing IL-13 as an additional marker of bladder cancer, as taught by Cohen, in the assay taught by Van detecting midkine to diagnose bladder cancer would increase the ability to detect or confirm bladder cancer as each marker is taught by each reference as being elevated in patients with bladder cancer such that they are useful as markers of bladder cancer.
Given that Van and Cohen do not limit the gender of the patient being diagnosed, it would have been obvious that the diagnosis can be performed on a patient that is a female.
Applicant claims (in claim 22, step (i)) also recite determining that the female patient does not have an infection.
Cohen teaches that a urinary tract infection can affect known assays of bladder cancer
biomarkers in urine. Para. 0004.
Cohen also discloses using healthy individuals not afflicted with bladder cancer or genitourinary infection (such as urinary tract infection) (para. 0020).
It would have been obvious to one skilled in the art to determine if the patient has an infection such as a urinary tract infection before performing the assay since it was known that an infection can affect an assay for bladder cancer using biomarkers in urine, as taught by Cohen.
Response to Arguments
Applicant argues that there is no pointer in either documents (Van et al., nor Cohen) to consider the specific combination of midkine and IL-13, especially not in female patients.
Applicant states that Van et al. disclose that midkine could be used “in combination with additional transcriptional or proteomic markers (e.g., keratin 20, hyaluronic acid/hyaluronidase)” to diagnose and monitor bladder cancer, but there is no mention of interleukins, let alone IL-13, thus the skilled person has no motivation to select IL-13 for use in specific combination with midkine. Applicant further states that Cohen identified “a distinct set of antigens” (HSPs and cytokines including IL-13) in urine samples from bladder cancer patients. Applicant that thus there is no reason why the skilled person would depart from the distinct combination taught by Cohen.
However, Examiner notes that Cohen also teaches in general that determining the levels of a plurality of biomarkers provides a significantly more accurate and reliable assay in discriminating patients and control subjects than each biomarker alone. Para. 0055.
More specifically, paragraph 0055 is provided below.
“Thus, the present invention provides compositions, methods and kits for diagnosing genitourinary cancer, particularly bladder cancer and prostate cancer, including for diagnosing bladder cancer stage or grade. While certain reports may have detected specific cytokines and/or HSPs in the urine of BC or CaP patients, the present invention relates to, in certain embodiments, determining the levels of a plurality of biomarkers (e.g. 2, 3, 4, 5 or 6 biomarkers of the invention), thereby providing a significantly more accurate and reliable assay in discriminating patients and control subjects than each biomarker alone.” Para. 0055 (emphasis added).
Thus, it would have been obvious to one of ordinary skills in the art to combine the teachings and suggestions of Van and Cohen to provide IL-13 as an additional biomarker of bladder cancer, as generally suggested by Cohen, in combination with midkine taught by Van as part of an assay to diagnose bladder cancer, in order to provide a significantly more accurate and reliable assay than one biomarker alone, as suggested by Cohen.
Moreover, it would have been predictable that providing IL-13 as an additional marker of bladder cancer, as taught by Cohen, in the assay taught by Van detecting midkine to diagnose bladder cancer would increase the ability to detect or confirm bladder cancer as each marker is taught by each reference as being elevated in patients with bladder cancer such that they are useful as markers of bladder cancer.
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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