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. Election/Restrictions The restriction requirement and election of species requirements set forth in the office action dated 1/7/2026 are withdrawn. All claims and species are rejoined. Currently, claims 1-18 are pending and under consideration. Claim Objections Claim 7 is objected to because of the following informalities: for grammatical consistency, claim 7 should be amended to recite “wherein … cells are prepared from Hoxb8-immortalized mouse fetal liver progenitor cells”. Appropriate correction is required. 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 8-17 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); s ee 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 methods 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 monitoring a patient for the development or progression of a myeloid malignancy as well as identifying a patient at risk for the development or progression of a myeloid malignancy by detecting a functionally defective variant of DDX41. However, this is a recitation of a natural correlation between variants in DDX41 and myeloid malignancies. 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 “monitoring” and “identifying” steps which are a recitation of an abstract idea because it encompasses observations 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 identifying DDX41 functional variants, 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 claim 17 recites a step of “administering a treatment for the myeloid malignancy”, this limitation is recited at a high level of generality with nor more than a nominal relationship to the exceptions recited. They are considered nothing more than instructions to apply the law of nature because no particular agents are administered. 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. With regard to claim 13, since the claims do not require determining the presence of the variant, the administration of chemotherapy or stem cell transplant is considered a conditional limitation. Although independent claim 8 recites “according to the method of claim 1”, it is not clear from this recitation as to whether the steps of the method of claim 1 are required to be performed or if it merely refers to a mutation that can be identified by the method of claim 1. Since functionally defective DDX41variants, which could be identified by the method steps recited in claim 1 (eg Lys331del as taught in the specification) were known and taught in the prior art, this general recitation is taken as mere data gathering. 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 claims do not recite any particular steps of detecting genetic variants. The generally recited elements in the claim do not 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. Claim Rejections - 35 USC § 112 112(b) 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 8-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. The preamble of claim 8 recites a method of monitoring a patient for the development/progression of a myeloid malignancy and appears to be an independent claim. However the claim also recites “determining the presence or absence of a functionally defective DDX41 variant determined according to the method of claim 1 in a sample from the patient”. It is not clear if claim 8 requires that the steps of claim 1 be performed, or if it merely requires that a DDX41 functional variant that could be determined by the method of claim 1 be determined in claim 8. For example, the Lys331del is a DDX41 functional variant that was known in the prior art, but that applicants have also determined using the method of claim 1. Would determining the presence of the Lys331del in a sample from a patient meet the “determining” limitation in claim 8? Given the ambiguity of the recitation of “according to the method of claim 1”, the metes and bounds of the claimed scope are unclear. The recitation of “such as” in claim 14 is indefinite because it is not clear if the element following this recitation is required or not. 112(d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claims 8-15 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 appears to attempt to be dependent from claim 1 but does not include all of the limitation of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. 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. Claims 8-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by S é bert (Sébert et al; Blood, vol 134, 2019; pages 1441-1444, including supplemental content pages 1-13) . With regard to claims 8, 10, 15, and 16, Sébert teaches determining the presence of the functionally defective DDX41 variant, Lys331del in patients with MDS or AML (see abstract, supplemental table 3 ) . Sébert teaches that this mutation is a causal variant (supplemental table 4). With regard to claims 8 and 11, Sébert teaches the patients were monitored for biological and clinical features of MDS/AML ( page 1441, col 1; “ watchful waiting ” , supplementary table 3). With regard to claim 14, Sébert teaches subjects were over 65 years (see supplemental table 3). With regard to claim 9, Sébert teaches obtaining bone marrow and blood cells (supplemental methods, page 2). With regard to claims 1 2 , 13, 17, and 18, Sébert teaches subjects were treated with AZA, HSCT, and intensive chemotherapy (see supplemental table 3). Double Patenting A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co. , 151 U.S. 186 (1894); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert , 245 F.2d 467, 114 USPQ 330 (CCPA 1957). A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101. Claims 1-18 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim s 1-18 of copending Application No. 19/090,951 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2 :00 PM Eastern Time Zone . 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 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. /JEHANNE S SITTON/ Primary Examiner, Art Unit 1682