DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ reply to the November 25, 2025 Office Action, filed February 24, 2026, is acknowledged. Applicants previously canceled claims 1-5 and 8-13 and now cancel claim 7. Applicants amend claim 6, which claim is pending in this application and under examination.
Any objection or rejection of record in the previous Office Action, mailed November 25, 2025, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 6 is 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. This is a new matter rejection necessitated by Applicants’ amendments.
The instant specification, as well as the ‘790 and ‘261 applications, the PCT and British specifications to which the instant application claims priority, as originally filed does not provide support for the invention as now claimed: “wherein the ligated DNA comprises and artificial sequence (i) comprising sequences from the two regions of chromosome, and (ii) which is not the same as any genomic sequence of the individual” (claim 6). The specification does not provide sufficient blazemarks, nor direction for the instant methods encompassing the above-mentioned limitations, as currently recited.
Specifically, the specification does not disclose that the ligated DNA comprises an artificial sequence or that the artificial sequence comprises sequences that are not the same as any genomic sequence of the individual. The specification does not disclose any artificial sequences nor any sequences that are not the same as a genomic sequence of the individual. The specification does ligated DNA.
Thus, the instant claims now recite limitations which were not disclosed in the specification as-filed, and now change the scope of the instant disclosure as-filed. Such limitations recited in the present claims, which did not appear in any of the instant specification, or the ‘790 and ‘261 applications, the PCT and British specifications to which priority is claimed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. § 112.
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.
Claim 6 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. This rejection is maintained, as modified necessitated by Applicants’ amendments.
The claims recite a method of selecting and individual in need of treatment and treating the individual comprising selecting a gene in the individual in which a change in a specific conditional long- range epigenetic chromosomal interaction occurs, determining whether the change in the chromosomal interaction changes a transcription regulating structure comprising CTCF and Pol II, determining whether the change in the epigenetic chromosomal interaction corresponds to a physiological condition, treating an individual in which the change in the chromosomal interaction is found, where the change in the chromosomal interaction has been identified as being present by determining the presence of ligated DNA formed in vitro from the two regions of chromosome in the gene that have come together in the chromosomal interaction, wherein the change in the epigenetic chromosomal interaction leads to an alternative expression from the gene, wherein the physiological condition corresponds to a condition selected from the group consisting of a cardiovascular disorder, an inflammatory condition, an autoimmune disorder, an inflammatory response to an infectious disease, a cancer and an inherited genetic disorder, wherein treating the individual comprises administering to the individual an agent which is therapeutic for the physiological condition. The claims further recite that “the ligated DNA comprises an artificial sequence (i) comprising sequences from the two regions of chromosome, and (ii) which is not the same as any genomic sequence of the individual.”
Step 1 – Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES
The claims recite a method of selecting and treating an individual comprising a series of steps that recite judicial exceptions without additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 2A- Prong One – Does the Claim Recite and Abstract Idea, Law of Nature or Natural Phenomenon? YES
The claims recite a specific conditional long-range epigenetic chromosomal interaction in the gene of an individual and changes in the epigenetic chromosomal interaction corresponding to a physiological condition, wherein monitoring the change in the epigenetic chromosomal interaction comprises ligating together DNA sequences from the regions of chromosomes in the gene that have come together in the chromosomal interaction to thereby make ligated DNA. DNA ligation refers to a judicial exception because DNA ligation occurs naturally within regions of chromosomes coming together evidenced by Timson et al. (“DNA ligases in the repair and replication of DNA” Mutation Research/DNA Repair, Volume 460, Issues 3-4, Year: 2000). “DNA ligases are critical enzymes of DNA metabolism. The reaction they catalyse (the joining of nicked DNA) is required in DNA replication and in DNA repair pathways that require the re-synthesis of DNA” (Abstract). Further, monitoring/detecting is a mental process which is a judicial exception.
Step 2A - Prong Two – Do the Claims Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The additional element of detecting the presence of ligated DNA which corresponds to a chromosomal interaction is noted. Applicant also includes the additional element of treating. The additional element of an artificial sequence which is not the same as any genomic sequence of the individual. These additional elements do not amount to a practical application.
Step 2B – Do the Claims Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The additional element of detecting is considered to be a routine and mere data gathering step. The additional element of treating is considered to be a generic and non-specific form of treating. The claim recites “wherein treating the individual comprises administering to the individual an agent which is therapeutic for the physiological condition.” This is not a specific treatment or method of treating and is not considered to amount to significantly more than the judicial exception.
The claim further recites the additional elements of in vitro crosslinking “regions which form conditional long range chromosomal interactions to form cross linked DNA, isolation of the cross linked DNA, subjecting said cross linked DNA to restriction digestion to form cross linked cleaved DNA ends, and ligating said cross linked cleaved DNA ends to form the ligated DNA. These additional elements are data gathering in nature. All of these additional elements are performed to create the ligated DNA. These additional elements do not amount to significantly more than the judicial exception.
Therefore, the claims are deemed to be patentably ineligible subject matter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1of U.S. Patent No. 10,844,423. This rejection is maintained, as modified by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other.
recite a method of selecting and individual in need of treatment and treating the individual comprising selecting a gene in the individual in which a change in a specific conditional long- range epigenetic chromosomal interaction occurs, determining whether the change in the chromosomal interaction changes a transcription regulating structure comprising CTCF and Pol II, determining whether the change in the epigenetic chromosomal interaction corresponds to a physiological condition, treating an individual in which the change in the chromosomal interaction is found, where the change in the chromosomal interaction has been identified as being present by determining the presence of ligated DNA formed in vitro from the two regions of chromosome in the gene that have come together in the chromosomal interaction, wherein the change in the epigenetic chromosomal interaction leads to an alternative expression from the gene, wherein the physiological condition corresponds to a condition selected from the group consisting of a cardiovascular disorder, an inflammatory condition, an autoimmune disorder, an inflammatory response to an infectious disease, a cancer and an inherited genetic disorder, wherein treating the individual comprises administering to the individual an agent which is therapeutic for the physiological condition.
Claim 1 of the ‘423 patent recites “A method of monitoring a change in a specific conditional long range chromosomal interaction comprising: making a predefined ligated DNA of known identity from a DNA sample from a subject by a chromosome conformation capture (3C) technique comprising the steps of: (i) in vitro crosslinking in the DNA sample specific conditional long range chromosomal interactions between distant regions of a known chromosome locus; (ii) isolating the cross linked DNA from said chromosomal locus; (iii) subjecting said cross linked DNA to restriction digestion with an enzyme that cuts at least once within the chromosomal locus; (iv) ligating said cross linked cleaved DNA ends to form the predefined ligated DNA; (v) amplifying said ligated DNA by PCR using PCR primers that specifically amplify the predefined ligated DNA; - wherein the locus comprises a gene that is regulated by metabolic signaling which leads to an alternative expression from the gene due to a change in chromosome interactions at the locus, and wherein the chromosome interactions are not associated with an inherited genetic disorder, and - wherein the locus is not the B-globin locus, and - wherein the long range chromosomal interactions are not interactions between genes and their regulatory elements.”
Both the instant application and the patent claim the same method steps. The ‘423 patent claims PCR amplification. The ‘423 patent claims a predefined ligated DNA. The ‘423 patent claims the same chromosomal interactions. Therefore, the scope of the ‘423 patent claims and the instant application overlap, and they are deemed to be obvious variants of one another.
Response to Amendments and Arguments
Regarding the rejection under 35 U.S.C. § 101, Applicants’ arguments and amendments have been fully considered, and are not deemed to be persuasive.
Applicants assert that because the ligation of the two regions of chromosome in the gene occurs in vitro and that “the ligated DNA comprises sequences from the two regions of chromosomes and. . . which is not the same as any genomic sequence of the individual” the process is not found in nature. However, this difference is deemed to be irrelevant because the claim, as a whole, is directed to the judicial exception. Just because there is an in vitro step and some sequences are not the same as an individual, this does not provide for integration of judicial exception into a practical application. In addition, because this is a process claim, adding limitations to an artificial sequence and/or sequences that are not obtained from the individual does not provide a practical application of the judicial exception. Using a sequence that is not found in the individual does not change the judicial exception. Because the claims are directed to a method, the method does not provide additional elements to integrate the judicial exception into a practical matter. Specifically, monitoring a change is not something to integrate into a practical application, even where some components employed in the method. Rather, this monitoring is considered to be merely a data gathering step. In addition, although the claims now recite treatment of a condition based upon the change in epigenetic chromosomal interaction, the claims are of a highly general nature and do not provide for any specific treatments of any of the claimed conditions.
Concerning Applicants’ arguments related to Timson, it is noted that processes using ligases that are found in nature in a process to generate artificial sequences does not integrate the judicial exception into a practical application. The method is still a process that employs diagnostic methods without a specific treatment of a specific disease or condition. As such, the method is still directed to a judicial exception, without integration of the judicial exception into a practical application.
Because the claims are still deemed to recite a judicial exception, do not include any additional elements amounting to significantly more than the judicial exception, and do not integrated the judicial exception, this rejection is maintained.
In addition, a new matter rejection under 35 U.S.C. § 112(a)/first paragraph. As noted above, the none of the instant specification and the specifications of each of the applications to which the instant application claims priority disclose or even suggest that an artificial sequence (i) comprising sequences from the two regions of chromosomes, and (ii) which is not the same as any genomic sequence of the individual.” While Applicants point to a specific portion of the specification for support, that portion of the specification fails to disclose an artificial sequence where there are sequences that are not the same as any genomic sequence of the individual.
Regarding the non-statutory double patenting rejection, while Applicants note that they traverse the rejection, they request that the rejection be held in abeyance until such time as there is an indication of otherwise allowable subject matter. Therefore, this rejection is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The closest prior art to this case is Zhao et al. (2006, Nature Genetics, 38: 1341-1347). Zhao teaches a method of identification of epigenetically regulated long range chromosomal interactions by crosslinking interacting chromosomes between known locus of H19 and a number of unknown loci, isolating crosslinked DNA, using restriction enzyme to cut both known and unknown chromosomal locus, ligating crosslinked DNA molecules leading to formation of DNA loops and further analysis of the loops, such analysis involving PCR techniques (see page 1341, last paragraph, and Fig.1).
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 NANCY J LEITH whose telephone number is (313) 446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636