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 .
Status of Claims
Currently, claims 1-5, 7-12, 14-21, and 23-31 are pending in the instant application. Claims 1-2, 13-27, and 29-31 are withdrawn from consideration as being drawn to non-elected inventions. Claims 3-5, 7-12, 14-21, and 28 are currently under examination. All the amendments and arguments in the response dated 5/30/2026 have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are reiterated. They constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments 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Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.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 Objections
Claims 18, 20, and 21 are objected to because of the following informalities: the claims ultimately depend from claim 3 and are grammatically incorrect because they lack the article “the” before each of the signatures. Since all of the genes in the signatures in these claims are already listed in claim 3, the claims should be amended to recite “the” before each signature (it is noted that the article “the” was removed in the 5/30/2026 amendment to address antecedent basis rejections made in the non-final rejection, however, the amendment to claim 3 rendered the antecedent basis issue moot since all of the genes in each signature are listed in the 5/30/2026 amendment to claim 3). For clarity, claim 3 should also be amended to recite the signature for each of a-h. For example, claim 3(a) should be amended to recite “a target gene signature comprising an IFN gamma signaling signature comprising CXCL9, CXCL10, CXCL11, and STAT1; and/or…” Appropriate correction is required.
Maintained Rejections
Claim Rejections - 35 USC § 101
Claims 3-5, 7-12, 14-21, and 28 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 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 determining whether a patient would be a suitable responder to the use of a CD123 X CD3 bispecific molecule to treat a hematological malignancy by evaluating the expression of target genes in one or more target gene signatures, as well as treating the patient with a treatment dosage of the CD123XCD3 bispecific molecule if the patient is determined to be suitable for treatment. However, this recitation is a natural correlation between expression levels of genes and treatment efficacy of a CD123XCD3 bispecific molecule. 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 a number of abstract steps, including: “determining whether a patient would be a suitable responder”, “evaluating expression of one or more target genes”, “identifying said patient as a suitable responder”, “evaluating expression of one or more reference genes”, “evaluating” expression relative to a baseline signature, “comparing expression levels”, “assigning relative expression value”, and “determining” a target gene signature score which read on making mental determinations and comparisons. These are deemed to be abstract ideas because they can occur entirely within the mind. The claims additionally recite steps such as “normalizing” measured raw RNA levels, “averaging the gene expression level”, “log transforming each normalized RNA value”, “multiplying” by a corresponding weight factor, “adding” the weighted RNA values, and “scoring wights and optionally adjustment factors”. These steps are also directed to abstract ideas because they are directed to mathematical formulas and relationships. 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 “evaluating” gene expression levels. Although this broadly encompasses abstract mental activity, such as reading a report that lists expression levels, even if the claim required performing gene expression assays in a laboratory, both situations do 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 9 recites “a method of treating”, the treatment itself is conditional as evidenced by the use of the term “if”.
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, any step of detecting expression levels, encompassed by the term “evaluating”, is generally recited and does 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. Not only is the step of evaluating gene expression 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 and asserts that with regard to step 2A prong two, the method addresses a need and is incredibly valuable as a diagnostic to identify patients particularly amenable to treatment of a hematological malignancy using CD123xCD3 bispecific molecules and also allows a medical professional to only administer the treatment to patients that will respond. This argument has been thoroughly reviewed but was not found persuasive because the claims do not require particular treatment. Claim 3 is directed to identifying patients suitable for treatment, however no actual treatment is required. Claim 3 recites data gathering steps followed by the recitation of a natural correlation. While claim 9 recites “administering a treatment dosage of said CD123xCD3”, it is only required “if” the patient is identified as a suitable responder. No specific treatment is required by the claim “if” the patient is not identified as a responder. Therefore, neither claim integrates the judicial exception because neither claim imposes meaningful limits on the claims by requiring a particular treatment, contrary to the response’s arguments. With regard to step 2B, the response reiterates its arguments for step 2A prong 2 and asserts that the claimed methods amount to significantly more than the JEs. This argument has been thoroughly reviewed but was not found persuasive for the reasons already made of record. The claims generally recite data gathering steps of evaluating expression but 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. Not only is the step of evaluating gene expression 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)). For these reasons and the reasons already made of record, the rejection is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bonvini (Bonvini et al; WO2017/214092; cited in the IDS filed 2/8/2022) teaches administration of flotetuzumab (DART-A; CD123 X CD3 bispecific molecule) to patients with AML. However Bonvini does not teach evaluating the gene expression of any target genes in a cellular sample from a patient prior to treatment, or comparing the gene expression to the gene expression in (i) an individual or a population of patients suffering from AML, (ii) to an individual or population of individuals who did not response to flotetuzumab, or (iii) an individual or population who successfully responded to flotetuzumab, or identifying the patient as a responder based on the gene expression of a target gene or genes.
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 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.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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