DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed June 22, 2206. Currently, claims 1-23 are pending. Claims 11-15 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of Group 1, Claims 1-10, 16-23 and PTEN, CDKN1B, BRCA2, MYC in the paper filed June 22, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Improper Markush Rejection
Claim1-10, 16-23 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
Here each species is considered to each of the combinations of CNAs claimed. The species of CHD1 is distinct from PTEN. Similarly, combinations comprising USP10 and CHD1 are distinct from PTEN, CDK1B, BRCA2 and MYC.
The recited alternative species in the groups set forth here do not share a single structural similarity, as each different gene that could be detected is itself located in a separate region of the genome and has its own structure. The genes recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequences with different expression patterns. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with progression of prostate cancer. Accordingly, while the different markers are asserted to have the property of being indicative of progression of prostate cancer, they do not share a single structural similarity.
MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited genes do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the genes will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being associated with progression of prostate cancer.
MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they all have a sugar phosphate backbone. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to the asserted common use of being associated with progression of prostate cancer.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 10, 16-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 10 is directed to a method of classifying the subject as a progressor or non-progressor based on the determination of CNAs.
Claim 16 is also a method for predicting prostate cancer progression with the final step as classifying the subject as a progressor or non-progressor based on the determination of CNAs
Claims 10, 16-23 are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “classifying the subject as a progressor or non-progressor based on the determination of CNAs”) and a law of nature/natural phenomenon (i.e. the natural correlation between the CNA and progressors/non-progressors of prostate cancer).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, Claims 10, 16-23 involve the patent-ineligible concept of an abstract process. Claims 10, 16-23 require performing the step of “classifying the subject as a progressor or a non-progressor”. Neither the specification nor the claims set forth a limiting definition for "classifying" and the claims do not set forth how “classifying” is accomplished. As broadly recited the determining step may be accomplished mentally by thinking about a subject’s CANs and classifying mentally. Thus, the d classifying step constitutes an abstract process idea.
A correlation that preexists in the human is an unpatentable phenomenon. The association between CNAs and progressor or non-progressor status is a law of nature/natural phenomenon. The " classifying " step which tells users of the process to classifying progressor or non-progressor status, amounts to no more than an "instruction to apply the natural law". This classifying step is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The "classifying” step does not require the process user to do anything in light of the correlation. The "classifying" step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and determining copy number alterations, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Claim 10 requires treating the subject with an anticancer agent based on the CNAs of the one or more genes. This treatment step is entirely generic in nature and it not particular to the judicial exception. Furthermore, the claim treats the subject regardless of whether the cancer is high risk or not. Thus, this is not limited in nature.
Accordingly, the claims are directed to judicial exceptions.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The determining copy number alterations in genes is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining Copy number alterations (CNAs) was well known in the art at the time the invention was made. The prior art teaches CNA analysis was performed using commercially available biochips and arrays that comprise the claimed genes. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any method for determining copy number alterations. The claim does not require the use of any particular non-conventional reagents. 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 applicant’s 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 were well known. Specifically, the specification teaches those skilled in the art that methods of preferred ways to detect CNAs were known (para 66).
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.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
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 these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 1-10, 16-23 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 pre-AIA the applicant regards as the invention.
A) The claims are directed to treating the subject “based on the CNAs of the one or more genes” and “classifying the subject as a progressor or a non-progressor based on the determination”. The language “based on” is unclear. It is unclear what based on encompasses. It is unclear how the ordinary artisan would make a determination based on the CNAs. It is unclear whether the determination is “based on” the number of CNAs in the genes, the mere presence of CNAs in the genes or the presence/absence of particular CNAs in the particular genes. The metes and bounds of the claimed invention are unclear and the ordinary artisan would be unable to understand the scope of the claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
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 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.
Claim(s) 1, 5-8, 16, 19-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pollack et al. (US 2006/0263814, November 23, 2006).
Pollack teaches markers of copy number alterations for improved prognostication in prostate cancer. Pollack teaches using array CHG or FISH to sequence and determine single copy number changes in nucleic acid samples (para 24). Pollack teaches that the array CGH and FISH are performed and allow distinct genetic subtypes of prostate cancer to be defined and treatment stratification for patients with prostate cancer (para 55).
With respect to Claims 5, 19, Pollack teaches the sample may be frozen sections or paraffin sections taken from histological purposes (para 38).
With respect to Claims 6-8, 20-22, Pollack teaches analysis of the entire genome, across all genes, including the elected PTEN, CDKN1B, BRCA2 and MYC.
With respect to Claim 16, Pollack teaches indolent subtype I and clinically aggressive subtype II tumors may be determined using 10q23 (PTEN). Thus, Pollack teaches analysis of CNA for the entire gene comprising the elected PTEN, CDKN1B, BRCA2 and MYC genes and classifying the subject as a progressor or aggressive subtype based on this determination.
Claim(s) 1, 5-7, 16, 19-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (2016/0024591, January 28, 2016).
Xu teaches methods for correlating genetic markers with risk of aggressive prostate cancer. Xu teaches analyzing CAN in the MYC gene, PTEN gene wherein the detecting identifies the subject as having increased likelihood of prostate cancer specific death (para 13). Xu teaches when the subject is identified as having increased risk for developing aggressive prostate cancer, treatment may be based on these CNAs (para 29 and 31). Table 2 provides association of DNA copy number changes with PCa-specific death and lists MYC, PTEN, and CDKN1B.
With respect to Claim 5 and 19, Xu teaches formalin-fixed, paraffin-embedded tissues can be used as the source of DNA (para 43).
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.
Claims 1, 5-10, 16-17, 19-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (2016/0024591, January 28, 2016) in view of Seed et al. (Clinical Cancer Research, Vol. 23, No. 20, October 15, 2017).
Xu teaches methods for correlating genetic markers with risk of aggressive prostate cancer. Xu teaches analyzing CAN in the MYC gene, PTEN gene wherein the detecting identifies the subject as having increased likelihood of prostate cancer specific death (para 13). Xu teaches when the subject is identified as having increased risk for developing aggressive prostate cancer, treatment may be based on these CNAs (para 29 and 31). Table 2 provides association of DNA copy number changes with PCa-specific death and lists MYC, PTEN, and CDKN1B.
With respect to Claim 5 and 19, Xu teaches formalin-fixed, paraffin-embedded tissues can be used as the source of DNA (para 43).
Xu does not teach analyzing BRCA2 CNA to determine treatment or aggressiveness of prostate cancer.
However, Seed et al. teaches detection of copy number aberrations (CAN) from tumor biopsies is critically important to the treatment of metastatic prostate cancer. Seed teaches CAN identification using whole-exome sequencing, array comparative genomic hybridization and FISH (abstract). Seed teaches BRCA2, MYC, PTEN may be used (page 6073, col. 2). Seed also teaches paraffin embedded DNA samples to analyze CNAs (page 6071, col. 1).
Therefore, it would have been prima facie obvious at the time the invention was made to have used a set of CNA known to be associated with prostate cancer and progression of prostate cancer. It would have been prima facie obvious to one having ordinary skill int eh art at the time the invention was made to have modified the methods of Xu so as to have surveyed the genes known to have CNA associated with prostate cancer in order to provide a complete picture of CNA status of a patient for known prostate cancer and progression markers. It would have bene prima facie obvious to combine elements, each of which is taught in the prior art to be useful for the same purpose. MPEP 2144.06 provides "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Here all of the elected genes were known in the prior art and duplicated in numerous references to be associated with prostate cancer and CNAs.
Claims 2-4, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (2016/0024591, January 28, 2016) in view of Seed et al. (Clinical Cancer Research, Vol. 23, No. 20, October 15, 2017) as applied to Claims 1, 5-10, 16-17, 19-23 above and further in view of Kader et al. (Genome Medicine, Vol. 8, No. 121, 2016) or Hovelson et al. (Oncotarget, Vol. 8, No. 52, pages 89848-89866, 2017).
Neither Xu nor Seed teach the quantity of genomic DNA used in their method.
However, the art teaches CNA may be detected with samples with low input of genomic DNA. Kader teaches copy number analysis may be performed on FFPE tissues using 5ng of FFPE derived DNA (abstract). Kader teaches 5ng and 20ng input was used for analysis (page 3, col. 1). Kader teaches compared with the standard 100ng input, comparable CN profiles were observed with 5ng or 20ng input DNA with 95% of CN calls being concordant (page 3, col. 2).
Furthermore, Hovelson teaches screening for copy number using ultra low samples of genomic DNA. Hovelson teaches WGA libraries were prepared using 1.73-5.79ng of DNA (page 89861, col. 1).
Therefore, it would have been prima facie obvious at the time the invention was made to have performed methods for detecting CNA as taught by Xu and Seed with low amounts of input DNA. Kader teaches 5ng was comparable to the standard 100ng inputs. Further Hovelson teaches CNA may be detected using as low as 1.73 ng of DNA. Using low amounts of DNA allows small samples to be analyzed.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bartlett et al. (WO2021253134, December 23, 2021) teaches molecular classifiers for prostate cancer. Bartlett discloses analysis of CNAs including CDKN1b, PTEN and MYC.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston 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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
August 31, 2026
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