DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Claims 23-29 are currently pending and have been examined herein.
Claim Rejections - 35 USC § 112
3. 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.
Claims 24-29 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.
Claims 24-29 are rejected over the recitation of the phrase “the method of claim 1”. In the instant case it is noted that claim 1 has been canceled and it is improper for claims to depend from a canceled claim. In order to advance prosecution, these claims have been interpreted to depend from claim 23 which is the only recited independent claim.
Claim Rejections - 35 USC § 101
4. 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 23-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a judicial exception that is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim analysis is set forth below.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The claims recite the following limitations:
-predicting a likelihood of cancer recurrence for the patient based on the expression level of the at least one of UBE2C, THBS2, and MYBPC1.
-normalizing said expression level to obtain a normalized expression level
The instant claims recite abstract ideas.
The “predicting” step broadly encompasses a mental processes. For example, one may “predict” the likelihood of cancer recurrence by thinking about the expression level of the genes. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgment, opinions) are considered to be abstract ideas.
The “normalizing” step could be accomplished by a mathematical calculation. Mathematical concepts are considered to be abstract ideas.
The instant claims recite a law of nature.
The claims recite a correlation between UBE2C, THBS2, and MYBPC1 and prostate cancer recurrence. This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions the claims require measuring or having measured an expression level of an RNA transcript. This step is NOT considered to integrate the judicial exception into a practical application because it merely adds insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exceptions the claims require measuring or having measured an expression level of an RNA transcript. This step does not amount to significantly more because it simply appends well understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
The steps are recited at a high level of generality. Measuring an expression level in a biological sample comprising prostate tissue merely instructs a scientist to use any technique known in the art for detecting expression levels. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine, and conventional activities engaged in by scientists prior to applicants invention and at the time the application was filed.
Additionally the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example see the teachings in the specification at paragraphs 0078-0102.
The prior art also demonstrates the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example Chudin (US Patent 7,914,988 Filed April 2, 2007)
teaches measuring UBE2C expression in prostate cancer tissue using quantitative RT-PCR (col 4 lines 5-14 and 60-64, col 7 lines 20-26, col 15 line 55-58, col 17 line 48-50, Tables 4-5, Claims 1 and 6).
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 102
5. The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claims 23, 26, and 27 are rejected under pre-AIA 35 U.S.C. 102(e) as being anticipated by Chudin (US Patent 7,914,988 Filed April 2, 2007).
Regarding Claim 23 Chudin teaches a method for predicting the probability of relapse of prostate cancer in an individual based on the expression level of one or more “signature genes”. Chudin teaches that UBE2C is a signature gene that is correlated with prostate cancer recurrence. Chudin teaches measuring gene expression in prostate cancer tissue using quantitative RT-PCR (col 4 lines 5-14 and 60-64, col 7 lines 20-26, col 15 line 55-58, col 17 line 48-50, Tables 4-5, Claims 1 and 6). Thus Chudin teaches a method comprising measuring an expression level of an RNA transcript UBE2C in a biological sample comprising prostate tissue obtained from a patient; and predicting a likelihood of cancer recurrence for the patient based on the expression level of UBE2C.
Regarding Claim 26 Chudin teaches a method further comprising generating a report based on the expression level of UBE2C (Claim 5).
Regarding Claim 27 Chudin teaches analysis of 53 samples with TNM Stage II (Table 1). In the instant case Stage II has been interpreted as an early stage prostate cancer because it localized entirely within the prostate gland.
Claim Rejections - 35 USC § 103
6. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
7. Claims 24, 25, and 28 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Chudin (US Patent 7,914,988 Filed April 2, 2007) in view of Nakagawa (PloS ONE May 2008 Vol 3 Issue 5 e2318 pages 1-14).
The teachings of Chudin are presented above.
Chudin does not teach a method further comprising measuring THBS2 and MYBPC1 (clm 24). Chudin does not teach a method further comprising normalizing the expression levels (clm 25). Chudin does not teach a method wherein the biological sample comprises prostate tumor tissue with the primary Gleason pattern for said prostate tumor .
However Nakagawa teaches that they designed a nested-case control study to test the hypothesis that a limited set of RNA expression biomarkers can predict which men with a rising PSA post radical retropubic prostatectomy might benefit from additional clinical intervention (page 2, col 1). Nakagawa teaches that they compared gene expression levels between men that developed systemic progression of prostate cancer after rising PSA versus men without systemic progression of prostate cancer after rising PSA (page 2, col 2). Nakagawa teaches that the block containing the dominant Gleason pattern cancer was selected for RNA analysis. Nakagawa teaches that expression levels were detected by microarray analysis and normalized by fastlo (page 3 col 1-2). Nakagawa teaches that upon univariate analysis of the probe averaged and fastlo normalized data, 68 genes were highly significantly over or under expressed in the SYS cases versus PSA controls. Nakagawa teaches that THBS2 and MYBPC1 are both highly significantly correlated with prostate cancer systemic progression (Table 3 and Fig 1).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of Chudin by further measuring the expression level of THBS2 and MYBPC1 as suggested by Nakagawa. In the instant case both references teaches genes that are correlated with recurrence of prostate cancer. One of skill in the art would have been motivated to measure the expression levels of these genes for the benefit of being able to predict which patients are more likely to experience recurrence and might benefit from additional treatments. Further one of skill in the art would have been motivated to normalize expression levels using fastlo for the benefit of removing technical bias. Finally it would have been obvious to one of ordinary skill in the art at the time the invention was made to have measured the expression levels of the genes in a prostate tumor tissue with the primary Gleason pattern as suggested by Nakagawa. One of skill in the art would have been motivated to obtain tumor tissue with the primary Gleason pattern since this tissue represents the majority of the tumor.
8. Claim 29 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Chudin (US Patent 7,914,988 Filed April 2, 2007) in view of Cheville (Journal of Clinical Oncology Vol 26 No 24 8/20/2008 pages 3930-3936).
The teachings of Chudin are presented above.
Chudin does not teach a method wherein the biological sample comprises prostate tumor tissue with the highest Gleason pattern for the prostate tumor (clm 29).
However Cheville teaches that tumor was collected from the highest Gleason score and gene expression was quantified by RT-PCR (abstract).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of Chudin by determining gene expression levels using biological samples that comprises prostate tumor tissue with the highest Gleason pattern as suggested by Cheville. One of skill in the art would have been motivated to obtain tumor tissue with the highest Gleason pattern since this tissue has the most advanced disease.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached on Monday-Friday, 8:15am-4:45pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached on 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Amanda Haney/
Primary Examiner, Art Unit 1682
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