DETAILED ACTION
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 .
Claims Status
Claims 1, 21, & 23 filed on 10/17/2025 are pending. The cancellation of claims 2, 3, 8, 12, 14, 16, 19, 22, 24, & 25 in the reply filed on 10/17/2025 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 112
Claims 1, 21, & 23 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require detecting the presence or absence of six chromosome interactions in a sample from a human individual to determine whether the individual has aggressive or indolent prostate cancer.
The claims are broadly drawn to six different chromosome interactions. The specification teaches that these interactions allow for distinguishing from subgroups (pg. 4). The specification also teaches that the chromosomal interactions may reflect the status of the region of the chromosome, e.g. if it is being transcribed or repressed in response to change in physiological conditions, and could be caused by changes to the underlying DNA sequence, by environmental factors, DNA methylation, etc. (pg. 6 & 7). In addition, the specification teaches that the chromosomal interactions are detected by generating a ligated nucleic acid (pg. 5)
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. The specification of the instant application provides an example of specific probes for detecting specific chromosomal interactions (e.g. prostate cancer using particular probes) (Example 1; Table 6.a; Table 25.a) but the specification has not provided any guidance as to the critical structures required by term “chromosome interaction” using the detection of the presence of absence of six chromosome interactions. These regions comprise the recitation of particular nucleotides, however, it is not clear what the structures are intending to represent. Depending on the sequence used (e.g. the build in NCBI) and the position that is considered the first nucleotide (e.g. start counting at the first codon or after) the nucleotide numbers would be different. As such the skilled artisan would not be able to determine which detection of these undefined regions would provide functionality of any type of chromosomal interaction.
Next, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features, and functional attributes that would distinguish different members of the claimed genus. In the instant application, the specification provides only specific probes that function to detect particular interactions. The specification of the instant application does not provide characteristics that would allow one to identify any particular detection of any region that would be encompassed by any one of the six chromosome interactions and functionality of any type of interaction of the chromosome that would be encompassed by the breadth of the claims.
In the instant application, because of the lack of analysis regarding the six chromosome interactions and the specific regions that have been brought together by a chromosomal interaction, one of skill in the art cannot envision the detailed chemical structure of the nucleic acid encompassed by the claimed methods, regardless of the complexity or simplicity of the method of isolation or use. Adequate written description requires more than a mere statement that such nucleic acids are part of the inventions and reference to a potential method of detecting chromosomal interactions.
In conclusion, the limited information provided regarding detecting if a chromosome interaction is present or absent in a subgroup of the claimed methods is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the broadly claimed method because the claims encompass a large genus of chromosomal interactions indicative of a prostate cancer subgroup, probes for detecting the chromosomal interactions, and prostate cancer related gene regions included in the chromosomal interactions which are not described in the specification.
Thus, having considered the breadth of the claims and the provisions of the specification, it is concluded that the specification does not provide adequate written description for the claims.
Response to Arguments
The response traverses the rejection. The response asserts that claim 1 as amended describes each chromosome interaction by means of the gene and the position numbers of the two regions of chromosome which come together to form each chromosome interaction, as well as the method which can be used to detect each chromosome interaction. The response also asserts that for each chromosome interaction a probe sequence is also provided in table 6.d which can detect the ligated nucleic acid and therefore provides further sequence information for defining each chromosome interaction. The response also asserts that it is important to understand that the specific chromosome interactions mentioned in claim 1 could only have been identified using the in-house expertise which the scientists at the applicant company have built up over many years and that conceptually speaking identification of chromosome interaction markers is very different to sequencing/investigating a ‘linear genome’ and any sort of ‘brute force’ strategy which seeks to identify all possible chromosome interactions and analyze their relationship with prostate cancer would not be feasible. Finally, the response asserts that applicants identified specific chromosome interactions, developed a means of stabilizing the chromosome interaction (ligation), and created methods for detecting the presence or absence of the chromosome interaction with specific tools or probes for that purpose. These arguments have been thoroughly reviewed but were not found persuasive. First, claim 1, as currently amended, tells the position of the chromosome interaction and not what the chromosome interaction looks like. Further, the probe sequence for each chromosome interaction is listed in table 6.d of the instant specification, however, these specific probe sequences for each chromosome interaction are not required in claim 1 as currently amended. Therefore, the claims as currently amended, do not recite methods for detecting the presence or absence of the chromosome interactions with specific tools or probes and the limited information provided regarding detecting a chromosome interaction is present or absent in a subgroup of the claimed methods is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the broadly claimed method.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Claims 1, 21, & 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding amended claim 1, the recitation of “(a) the chromosome interaction formed on chromosome X in the MIR98 gene between the region of position numbers 53608013 to 53608044 and the region of position numbers 53628991 to 53629022 which relates to aggressive prostate cancer … (f) the chromosome interaction formed on chromosome 11 in the MMP1 gene between the region of position numbers 102661704 to 102661735 and the region of position numbers 102667612 to 102667643 which relates to the presence of prostate cancer” in lines 9-26 of the claim is unclear what type of interaction is being looked for on these formed chromosome interactions as there are only general detection steps and no detection agents recited for the detection of these chromosome interactions. Is the type of interaction being looked for a recombination interaction? For the region of position numbers to be in close proximity to each other? How are these positions interacting with each other?
Claim 21 & 23 are rejected due to their dependence on claim 1.
Claim Rejections - 35 USC § 101
Claims 1, 21, & 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
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. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to processes and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of detecting the presence or absence of six chromosome interactions in a sample from a human individual to determine whether the individual has aggressive or indolent prostate cancer. This recitation is a natural correlation between detection of a presence or absence of a chromosome interaction in a region of the genome and prognosis of a prostate cancer subgroup. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites determining whether the individual has aggressive or indolent prostate cancer and selecting for aggressive prostate cancer or no selecting for aggressive prostate cancer which is a recitation of an abstract idea because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of determining the presence or absence of six chromosome interactions by detecting the presence of a ligated nucleic acid, however, this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
Although the claim 23 recites “administering to the selected individual a therapeutic agent for aggressive prostate cancer”, this step is conditional as if the individual is identified as having aggressive prostate cancer then the individual is selected for aggressive prostate cancer therapy and if the individual is identified as having indolent prostate cancer then the individual is selected for not being given treatment for aggressive prostate cancer. The steps of claim 1 result in the determination of whether or not a chromosomal interaction is present or absent in a prostate cancer subgroup and then selecting a general treatment for the prostate cancer subgroup the individual is identified to have. Accordingly, these generally recited elements are considered nothing more than instructions to apply the law of nature because no particular conditions are required by the step of detecting chromosome interactions. As such, the “administering” step is merely a generalized “treat” limitation with no particularity that integrates the judicial exception into a practical application. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of detecting the chromosome state through presence or absence of a chromosomal interaction are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection. The response asserts that it must be appreciated that the skilled scientist faced with the task of identifying chromosome interactions relevant to prostate cancer is faced with many technical difficulties compared to identifying other types of markers, such as genetic markers, and that the skilled scientist is unlikely to be faced with the task of investigating ‘unknown’ sequences as there is no systematic screening process and no publicly available complete ‘list’ or publicly available comprehensive characterization of chromosome interaction for any genome. The response also asserts that it is important to understand that the specific chromosome interactions mentioned in claim 1 could only have been identified using the in-house expertise which the scientists at the applicant company have built up over many years and that conceptually speaking identification of chromosome interaction markers is very different to sequencing/investigating a ‘linear genome’. The response also asserts it is also important to see that there is no straightforward way of ‘narrowing the search’ to relevant chromosome interactions as while there can be some correlation between chromosome interaction markers and locations of genetic changes, there is no direct systematic correlation which allows the location of a chromosome interaction to be predicted. This argument has been thoroughly reviewed but was not found persuasive as the claims, as currently amended, are not particular to any specific sequence and any particular reagents. In addition, how to detect the chromosome interactions as claimed is not recited in the claims, i.e. there is no specific assay or probes for detection of the chromosome interactions. Further, the steps of cross-linking, cleaving, ligating, and detecting are recited with a high level of generality and, therefore, the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)).
The response also asserts that the applicant’s in-house expertise has developed methods of identifying best targets and that each chromosome interaction in claim 1 has therefore been through a complex screening process is not described in any detail in the prior art. This argument has been thoroughly reviewed but was not found persuasive the claims, as currently amended, are not particular to any specific sequence and any particular reagents. In addition, how to detect the chromosome interactions as claimed is not recited in the claims, i.e. there is no specific assay or probes for detection of the chromosome interactions. Further, the steps of cross-linking, cleaving, ligating, and detecting are recited with a high level of generality that is available in the prior art and, therefore, the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)).
The response also asserts that as a practical reality, if at the priority date a scientist in the field had attempted to identify the chromosome interactions associated with prostate cancer they would not have been able to do so for many reasons including not having a way to obtain a list of the most potentially relevant anchoring sites, not have knowledge to carry out biochemical processing screening high numbers of candidate markers, not know how to carry out successful screening of a sufficient number of patients to provide evaluation of statistically significant markers with sufficient statistical power. The response also asserts that without the applicant’s in-house expertise these are problems which would be close to impossible to overcome based on the knowledge in the field at the priority date. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
The response also asserts that applicants found a way to stabilize chromosome interactions and detect the presence or absence of the six chromosome interactions recited in claim 1 and detection of each chromosome interaction requires formation of a ligated nucleic acid which has a sequence no present in nature. Further, the response asserts that claims 1 and 23 as amended do not merely relate to data gathering or a natural correlation and, therefore, the subject matter of the claims clearly goes beyond a natural or natural phenomenon. This argument has been thoroughly reviewed but was not found persuasive as the claims, as currently amended, is a method for detecting the presence or absence of six chromosome interactions in a sample from a human individual to determine whether the individual has aggressive or indolent prostate cancer which is the recitation of a natural correlation between detection of a presence or absence of a chromosome interaction in a region of the genome and prognosis of a prostate cancer subgroup. In addition, as discussed above, the claims, as currently amended, are not particular to any specific sequence and any particular reagents. In addition, how to detect the chromosome interactions as claimed is not recited in the claims, i.e. there is no specific assay or probes for detection of the chromosome interactions. Further, the steps of cross-linking, cleaving, ligating, and detecting are recited with a high level of generality and, therefore, the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)).
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1, 21, & 23 are rejected.
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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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, 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.
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.
/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682